NUCLEIC ACID VACCINES

SEQUENCE LISTING

The instant application contains a Sequence Listing which has been submitted in electronic format via EFS-WEB and is hereby incorporated by reference in its entirety. The Sequence Listing is provided as a file entitled MTX401.xml, created on Jul. 29, 2024, which is 2,628,288 bytes in size.

FIELD OF THE INVENTION

The invention relates to compositions, methods, processes, kits and devices for the selection, design, preparation, manufacture, formulation, and/or use of vaccines, specifically nucleic acid vaccines (NAVs). In particular, the invention relates to compositions, methods, processes, kits and devices for the selection, design, preparation, manufacture, formulation, and/or use of ribonucleic acid (RNA) vaccines, e.g., mRNA vaccines.

BACKGROUND OF THE INVENTION

Vaccination is an effective way to provide prophylactic protection against infectious diseases, including, but not limited to, viral, bacterial, and/or parasitic diseases, such as influenza, AIDS, hepatotisis virus infection, cholera, malaria and tuberculosis, and many other diseases. For example, influenza infections are the seventh leading cause of death in the United States with 200,000 hospitalizations and 40,000 deaths seen in the United States per year and cause about 3-5 million hospitalizations and about 300,000 to 500,000 deaths worldwide per year. Millions of people receive flu vaccines to protect them from seasonal flu each year. Vaccination can also rapidly prevent the spread of an emerging influenza pandemic.

A typical vaccine contains an agent that resembles a weakened or dead form of the disease-causing agent, which could be a microorganism, such as bacteria, virus, fungi, parasites, or one or more toxins and/or one or more proteins, for example, surface proteins, (i.e., antigens) of such a microorganism. The antigen or agent in the vaccine can stimulate the body's immune system to recognize the agent as a foreign invader, generate antibodies against it, destroy it and develop a memory of it. The vaccine-induced memory enables the immune system to act quickly to protect the body from any of these agents that it later encounters.

Vaccine production used in the art e.g., antigen vaccine production, has several stages, including the generation of antigens, antigen purification and inactivation, and vaccine formulation. First, the antigen is generated through culturing viruses in cell lines, growing bacteria in bioreactors, or producing recombinant proteins derived from viruses and bacteria in cell cultures, yeast or bacteria. Recombinant proteins are then purified and the viruses and bacteria are inactivated before they are formulated with adjuvants in vaccines. It has been a challenge to drastically reduce the time and expense associated with current technologies in vaccine development.

Another obstacle to the development of new vaccine is the constant evolution of most infectious agents, such as viruses and bacteria. Viruses often mutate their surface proteins to generate new antigens which can help them skipping the active immune system that has been immunized by vaccines containing the viruses. In contrast, bacteria acquire and mutate key proteins to evade host defense and effective antibiotic applications.

For example, influenza A, B and C viruses are the etiological agents of influenza. Hemagglutinin (HA), the major envelop glycoprotein of influenza A and B viruses, or its homologue, hemagglutinin-esterase (HE) in influenza C virus, is the natural reservoir of the viruses. The rapid evolution of the hemagglutinin (HA) protein of the influenza virus results in the constant emergence of new strains, rendering the adaptive immune response of the host only partially protective to new infections. The biggest challenge for therapy and prophylaxis against influenza and other infections using traditional vaccines is the limitation of vaccines in breadth, providing protection only against closely related subtypes. In addition, today's length of the production process inhibits any fast reaction to develop and produce an adapted vaccine in a pandemic situation.

It is of great interest to develop new vaccines as well as new approaches to combatting infectious disease and infectious agents.

SUMMARY OF THE INVENTION

Described herein are compositions, methods, processes, kits and devices for the selection, design, preparation, manufacture, formulation, and/or use of nucleic acid vaccines (NAVs). In particular, described herein are compositions, methods, processes, kits and devices for the selection, design, preparation, manufacture, formulation, and/or use of nucleic acid vaccines, e.g., RNA vaccines and mRNA vaccines.

The present invention provides compositions, e.g., pharmaceutical compositions, comprising one or more nucleic acid vaccines or NAVs.

The NAVs or NAV compositions or the invention may be designed to comprise one or more nucleic acid molecules, e.g., polynucleotides, which encode one or more wild type or engineered proteins, peptides or polypeptides (e.g., antigens). In some embodiments, the nucleic acid molecule, e.g., polynucleotide, is RNA. In some embodiments the nucleic acid molecule, e.g., polynucleotide, is an mRNA. In some embodiments the NAV or NAV composition comprises a nucleic acid (e.g., a RNA polynucleotide) which is chemically modified. In some embodiments the infectious agent from which the antigen is derived or engineered includes, but is not limited to viruses, bacteria, fungi, protozoa, and/or parasites.

In some embodiments are provided methods of inducing, eliciting, boosting or triggering an immune response in a cell, tissue or organism, comprising contacting said cell, tissue or organism with any of the RNAVs described or taught herein.

Aspects of the invention provide nucleic acid vaccines (NAVs) comprising one or more RNA polynucleotides having an open reading frame encoding a first antigenic polypeptide, formulated within a cationic lipid nanoparticle. Some aspects provide NAVs comprising one or more RNA polynucleotides having an open reading frame encoding a first antigenic polypeptide, formulated in a carrier having a molar ratio of about 20-60% cationic lipid:5-25% non-cationic lipid:25-55% sterol; and 0.5-15% PEG-modified lipid.

In some embodiments, the cationic lipid nanoparticle comprises a cationic lipid, a PEG-modified lipid, a sterol and a non-cationic lipid. In some embodiments, the cationic lipid is selected from the group consisting of 2,2-dilinoleyl-4-dimethylaminoethyl-[1,3]-dioxolane (DLin-KC2-DMA), dilinoleyl-methyl-4-dimethylaminobutyrate (DLin-MC3-DMA), and di((Z)-non-2-en-1-yl) 9-((4-(dimethylamino)butanoyl)oxy)heptadecanedioate (L319). In some embodiments, the cationic lipid nanoparticle has a molar ratio of about 20-60% cationic lipid:about 5-25% non-cationic lipid:about 25-55% sterol; and about 0.5-15% PEG-modified lipid. In some embodiments, the cationic lipid nanoparticle comprises a molar ratio of about 50% cationic lipid, about 1.5% PEG-modified lipid, about 38.5% cholesterol and about 10% non-cationic lipid. In some embodiments, the cationic lipid nanoparticle comprises a molar ratio of about 55% cationic lipid, about 2.5% PEG lipid, about 32.5% cholesterol and about 10% non-cationic lipid. In some embodiments, the cationic lipid is an ionizable cationic lipid and the non-cationic lipid is a neutral lipid, and the sterol is a cholesterol. In some embodiments, the cationic lipid nanoparticle has a molar ratio of 50:38.5:10:1.5 of cationic lipid: cholesterol: PEG2000-DMG:DSPC.

In some embodiments, the cationic lipid nanoparticle has a mean diameter of 50-150 nm. In some embodiments, the cationic lipid nanoparticle has a mean diameter of 80-100 nm. In some embodiments, the vaccine includes 1.5 mg/mL of RNA polynucleotide and 35-45 mg/mL lipids. In some embodiments, the NAV includes about 2 mg/mL of RNA polynucleotide and about 40 mg/mL lipids.

In some embodiments, the open reading frame is codon-optimized. In some embodiments, the first antigenic polypeptide is derived from an infectious agent. In some embodiments, the infectious agent is selected from a member of the group consisting of strains of viruses and strains of bacteria. In some embodiments, the one or more RNA polynucleotides encode a further antigenic polypeptide. In some embodiments, the further RNA polynucleotide comprises at least one chemical modification and a codon-optimized open reading frame, said open reading frame encoding an antigenic polypeptide.

In some embodiments, the one or more antigenic polypeptide is selected from those proteins listed in Tables 6-16, Tables 29-30, or fragments thereof. In some embodiments, the open reading frame of the one or more RNA polynucleotides and/or the open reading frame of the second RNA polynucleotide each, independently, encodes an antigenic polypeptide selected from Tables 6-16, Tables 29-30, or fragments thereof. In some embodiments, each of the open reading frame of the one or more RNA polynucleotides is selected from any of the RNA sequences Table 28, or fragments thereof.

In any of the embodiments provided herein, the infectious agent is a strain of virus selected from the group consisting of adenovirus; Herpes simplex, type 1; Herpes simplex, type 2; encephalitis virus, papillomavirus, Varicella-zoster virus; Epstein-barr virus; Human cytomegalovirus; Human herpes virus, type 8; Human papillomavims; BK virus; JC virus; Smallpox; polio virus; Hepatitis B virus; Human bocavirus; Parvovirus B19; Human astrovirus; Norwalk virus; coxsackievirus; hepatitis A virus; poliovirus; rhinovirus; Severe acute respiratory syndrome virus; Hepatitis C virus; Yellow Fever virus; Dengue virus; West Nile virus; Rubella virus; Hepatitis E virus; Human Immunodeficiency virus (HIV); Influenza virus; Guanarito virus; Junin virus; Lassa virus; Machupo virus; Sabid virus; Crimean-Congo hemorrhagic fever virus; Ebola virus; Marburg virus; Measles virus; Mumps virus; Parainfluenza virus; Respiratory syncytial virus; Human metapneumovirus; Hendra virus; Nipah virus; Rabies virus; Hepatitis D; Rotavirus; Orbivirus; Coltivirus; Banna virus; Human Enterovirus; Hanta virus; West Nile virus; Middle East Respiratory Syndrome Corona Virus; Japanese encephalitis virus; Vesicular exanthernavirus; and Eastern equine encephalitis.

In some embodiments, the virus is a strain of Influenza A or Influenza B or combinations thereof. In some embodiments, the strain of Influenza A or Influenza B is associated with birds, pigs, horses, dogs, humans or non-human primates. In some embodiments, the antigenic polypeptide encodes a hemagglutinin protein or fragment thereof. In some embodiments, the hemagglutinin protein is H1, H2, H3, H4, H5, H6, H7, H8, H9, H10, H11, H12, H13, H14, H15, H16, H17, H18, or a fragment thereof. In some embodiments, the hemagglutinin protein does not comprise a head domain (HAI). In some embodiments, the hemagglutinin protein comprises a portion of the head domain (HAI). In some embodiments, the hemagglutinin protein does not comprise a cytoplasmic domain. In some embodiments, the hemagglutinin protein comprises a portion of the cytoplasmic domain. In some embodiments, the truncated hemagglutinin protein. In some embodiments, the truncated hemagglutinin protein comprises a portion of the transmembrane domain. In some embodiments, the amino acid sequence of the hemagglutinin protein or fragment thereof comprises at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97% 98%, or 99% identify with any of the amino acid sequences provided in Table 6-14. In some embodiments, the virus is selected from the group consisting of H1N1, H3N2, H7N9, and H10N8. In some embodiments, the antigenic polypeptide is selected from those proteins listed in Tables 6-14, or fragments thereof.

In some embodiments, the infectious agent is a strain of bacteria selected from Tuberculosis (Mycobacterium tuberculosis), clindamycin-resistant Clostridium difficile, fluoroquinolon-resistant Clostridium difficile, methicillin-resistant Staphylococcus aureus (MRSA), multidrug-resistant Enterococcus faecalis, multidrug-resistant Enterococcus faecium, multidrug-resistance Pseudomonas aeruginosa, multidrug-resistant Acinetobacter baumannii, and vancomycin-resistant Staphylococcus aureus (VRSA). In some embodiments, the bacteria is Clostridium difficile.

In some embodiments, the NAV is multivalent. In some embodiments, the open reading frame of the one or more RNA polynucleotides encode at least 2, 3, 4, 5, 6, 7, 8, 9 or 10 antigenic polypeptides. In some embodiments, the open reading frame of the one or more RNA polynucleotides encode at least 10, 15, 20 or 50 antigenic polypeptides. In some embodiments, the open reading frame of the one or more RNA polynucleotides encode 2-10, 10-15, 15-20, 20-50, 50-100 or 100-200 antigenic polypeptides.

In some embodiments, the RNA polynucleotide includes a chemical modification and the chemical modification is selected from any of those listed in Tables 22 and 23. In some embodiments, the chemical modification is selected from the group consisting of pseudouridine, N1-methylpseudouridine, 2-thiouridine, 4′-thiouridine, 5-methylcytosine, 2-thio-1-methyl-1-deaza-pseudouridine, 2-thio-1-methyl-pseudouridine, 2-thio-5-aza-uridine, 2-thio-dihydropseudouridine, 2-thio-dihydrouridine, 2-thio-pseudouridine, 4-methoxy-2-thio-pseudouridine, 4-methoxy-pseudouridine, 4-thio-1-methyl-pseudouridine, 4-thio-pseudouridine, 5-aza-uridine, Dihydropseudouridine, 5-methoxyuridine and 2′-O-methyl uridine. In some embodiments, the RNA polynucleotide includes a second chemical modification wherein said second chemical modification is selected from any of those listed in Tables 22 and 23. In some embodiments, the combination of first and second chemical modification is selected from those listed in Table 25.

Other aspects provide a NAV comprising one or more RNA polynucleotides having an open reading frame encoding a first antigenic polypeptide, formulated within a nanoparticle, wherein the nanoparticle has a mean diameter of 50-200 nm. In some embodiments, the nanoparticle has a polydiversity value of less than 0.4. In some embodiments, the nanoparticle has a net neutral charge at a neutral pH. In some embodiments, the nanoparticle has a mean diameter of 80-100 nm. In some embodiments, the nanoparticle is a cationic lipid nanoparticle comprises a cationic lipid, a PEG-modified lipid, a sterol and a non-cationic lipid. In some embodiments, the cationic lipid is selected from the group consisting of 2,2-dilinoleyl-4-dimethylaminoethyl-[1,3]-dioxolane (DLin-KC2-DMA), dilinoleyl-methyl-4-dimethylaminobutyrate (DLin-MC3-DMA), and di((Z)-non-2-en-1-yl) 9-((4-(dimethylamino)butanoyl)oxy)heptadecanedioate (L319).

Other aspects provide NAVs comprising one or more RNA polynucleotides having an open reading frame encoding a first antigenic polypeptide, wherein at least 80% of the uracil in the open reading frame have a chemical modification. In some embodiments, 100% of the uracil in the open reading frame have a chemical modification. In some embodiments, the chemical modification is in the 5-position of the uracil. In some embodiments, the chemical modification is a N1-methyl pseudouridine. In some embodiments, the nucleic acid vaccine is formulated within a cationic lipid complex or cationic lipid nanoparticle.

Yet other aspects provide NAVs comprising one or more RNA polynucleotides having an open reading frame encoding a first antigenic polypeptide, at least one 5′ terminal cap and at least one chemical modification, formulated within a cationic lipid nanoparticle. In some embodiments, the 5′ terminal cap is 7mG(5′)ppp(5′)NlmpNp. In some embodiments, the chemical modification is selected from any of those listed in Tables 22 and 23. In some embodiments, the chemical modification is selected from the group consisting of pseudouridine, N1-methylpseudouridine, 2-thiouridine, 4′-thiouridine, 5-methylcytosine, 2-thio-1-methyl-1-deaza-pseudouridine, 2-thio-1-methyl-pseudouridine, 2-thio-5-aza-uridine, 2-thio-dihydropseudouridine, 2-thio-dihydrouridine, 2-thio-pseudouridine, 4-methoxy-2-thio-pseudouridine, 4-methoxy-pseudouridine, 4-thio-1-methyl-pseudouridine, 4-thio-pseudouridine, 5-aza-uridine. Dihydropseudouridine, 5-methoxyuridine and 2′-O-methyl uridine. In some embodiments, the RNA polynucleotide further comprises a second chemical modification wherein said second chemical modification is selected from any of those listed in Tables 22 and 23. In some embodiments, the combination of first and second chemical modification is selected from those listed in Table 25.

Some aspects provide NAVs comprising one or more RNA polynucleotides having an open reading frame encoding a hemagglutinin protein and a pharmaceutically acceptable carrier or excipient, formulated within a cationic lipid nanoparticle. In some embodiments, the hemagglutinin protein is selected from HA1, HA7 and HA10. In some embodiments, the RNA polynucleotide does not encode F protein. In some embodiments, the RNA polynucleotide further encodes neuraminidase protein. In some embodiments, the hemagglutinin protein is derived from a strain of Influenza A virus or Influenza B virus or combinations thereof. In some embodiments, the Influenza virus is selected from H1N1, H3N2, H7N9, and H10N8.

In some embodiments, the RNA polynucleotide includes a chemical modification and the chemical modification is selected from any of those listed in Tables 22 and 23. In some embodiments, the chemical modification is selected from the group consisting of pseudouridine, N1-methylpseudouridine, 2-thiouridine, 4′-thiouridine, 5-methylcytosine, 2-thio-1-methyl-1-deaza-pseudouridine, 2-thio-1-methyl-pseudouridine, 2-thio-5-aza-uridine, 2-thio-dihydropseudouridine, 2-thio-dihydrouridine, 2-thio-pseudouridine, 4-methoxy-2-thio-pseudouridine, 4-methoxy-pseudouridine, 4-thio-1-methyl-pseudouridine, 4-thio-pseudouridine, 5-aza-uridine, Dihydropseudouridine, 5-methoxyuridine and 2′-O-methyl uridine. In some embodiments, the RNA polynucleotide further comprises a second chemical modification wherein said second chemical modification is selected from any of those listed in Tables 22 and 23. In some embodiments, the combination of first and second chemical modification is selected from those listed in Table 25.

In some embodiments, the RNA polynucleotide comprises SEQ ID NOs 197-392. In some embodiments, the RNA polynucleotide comprises a polynucleotide having at least 80% sequence identity to SEQ ID NOs 197-392. In some embodiments, the RNA polynucleotide comprises a polynucleotide encoding an amino acid sequence having at least 90% sequence identity to SEQ ID NO 941. In some embodiments, the RNA polynucleotide comprises a polynucleotide encoding the amino acid sequence of SEQ ID NO 941. In some embodiments, the RNA polynucleotide comprises a polynucleotide encoding an amino acid sequence having at least 90% sequence identity to SEQ ID NO 946. In some embodiments, the RNA polynucleotide comprises a polynucleotide encoding the amino acid sequence of SEQ ID NO 946. In some embodiments, the RNA polynucleotide comprises a polynucleotide encoding an amino acid sequence having at least 90% sequence identity to SEQ ID NO 1022. In some embodiments, the RNA polynucleotide comprises a polynucleotide encoding the amino acid sequence of SEQ ID NO 1022. In some embodiments, the RNA polynucleotide comprises a polynucleotide encoding an amino acid sequence having at least 90% sequence identity to SEQ ID NO 1023. In some embodiments, the RNA polynucleotide comprises a polynucleotide encoding the amino acid sequence of SEQ ID NO 1023. In some embodiments, the RNA polynucleotide comprises SEQ ID NO 1024. In some embodiments, the RNA polynucleotide comprises a polynucleotide having 80-98% sequence identity to SEQ ID NO 1024. In some embodiments, the RNA polynucleotide comprises SEQ ID NO 1025. In some embodiments, the RNA polynucleotide comprises a polynucleotide having 80-98% sequence identity to SEQ ID NO 1025. In some embodiments, the RNA polynucleotide comprises SEQ ID NO 1026. In some embodiments, the RNA polynucleotide comprises a polynucleotide having 80-98% sequence identity to SEQ ID NO 1026. In some embodiments, the RNA polynucleotide comprises SEQ ID NO 1027. In some embodiments, the RNA polynucleotide comprises a polynucleotide having 80-98% sequence identity to SEQ ID NO 1027.

Aspects of the invention provide nucleic acids comprising 80-95% sequence identity to SEQ ID NO 1027 or SEQ ID NO 1026. Other aspects provide a nucleic acid comprising SEQ ID NO: 395.

Yet other aspects provide a method of inducing an antigen specific immune response in a subject comprising administering any of the vaccines described herein to the subject in an effective amount to produce an antigen specific immune response. In some embodiments, the antigen specific immune response comprises a T cell response. In some embodiments, the antigen specific immune response comprises a B cell response. In some embodiments, the method of producing an antigen specific immune response involves a single administration of the vaccine. In some embodiments, the method further comprises administering a booster dose of the vaccine. In some embodiments, the vaccine is administered to the subject by intradermal or intramuscular injection.

In some embodiments, the booster dose of the vaccine is administered to the subject on day twenty one. In some embodiments, a dosage of between 10 μg/kg and 400 μg/kg of the vaccine is administered to the subject. In some embodiments, a dosage of 25 micrograms of the RNA polynucleotide is included in the vaccine administered to the subject. In some embodiments, a dosage of 100 micrograms of the RNA polynucleotide is included in the vaccine administered to the subject. In some embodiments, a dosage of 400 micrograms of the RNA polynucleotide is included in the vaccine administered to the subject. In some embodiments, the RNA polynucleotide accumulates at a 100 fold higher level in the local lymph node in comparison with the distal lymph node.

Aspects provide methods of preventing or treating influenza viral infection comprising administering to a subject any of the vaccines described herein. In some embodiments, the antigen specific immune response comprises a T cell response. In some embodiments, the antigen specific immune response comprises a B cell response. In some embodiments, the method of producing an antigen specific immune response involves a single administration of the vaccine. In some embodiments, the vaccine is administered to the subject by intradermal or intramuscular injection.

Yet other aspects provide methods of vaccinating a subject comprising administering to the subject a nucleic acid vaccine comprising one or more RNA polynucleotides having an open reading frame encoding a first antigenic polypeptide, wherein the RNA polynucleotide does not include a stabilization element, and wherein an adjuvant is not coformulated or co-administered with the vaccine. In some embodiments, a dosage of between 10 μg/kg and 400 μg/kg of the nucleic acid vaccine is administered to the subject. In some embodiments, the nucleic acid vaccine is administered to the subject by intradermal or intramuscular injection. In some embodiments, the nucleic acid vaccine is administered to the subject on day zero. In some embodiments, a second dose of the nucleic acid vaccine is administered to the subject on day twenty one.

In some embodiments, a dosage of 25 micrograms of the RNA polynucleotide is included in the nucleic acid vaccine administered to the subject. In some embodiments, a dosage of 100 micrograms of the RNA polynucleotide is included in the nucleic acid vaccine administered to the subject. In some embodiments, a dosage of 400 micrograms of the RNA polynucleotide is included in the nucleic acid vaccine administered to the subject. In some embodiments, the RNA polynucleotide accumulates at a 100 fold higher level in the local lymph node in comparison with the distal lymph node.

Aspects of the invention provide a nucleic acid vaccine comprising one or more RNA polynucleotides having an open reading frame encoding a first antigenic polypeptide, wherein the RNA polynucleotide does not include a stabilization element, and a pharmaceutically acceptable carrier or excipient, wherein an adjuvant is not included in the vaccine. In some embodiments, the stabilization element is a histone stem-loop. In some embodiments, the stabilization element is a nucleic acid sequence having decreased GC content relative to wild type sequence.

Aspects of the invention provide NAVs comprising one or more RNA polynucleotides having an open reading frame encoding a first antigenic polypeptide, wherein the RNA polynucleotide is present in the formulation for in vivo administration to a host, which confers an antibody titer superior to the criterion for seroprotection for the first antigen for an acceptable percentage of human subjects. In some embodiments, the antibody titer is a neutralizing antibody titer.

Also provided are NAVs comprising one or more RNA polynucleotides having an open reading frame encoding a first antigenic polypeptide, wherein the RNA polynucleotide is present in a formulation for in vivo administration to a host for eliciting a longer lasting high antibody titer than an antibody titer elicited by an mRNA vaccine having a stabilizing element or formulated with an adjuvant and encoding the first antigenic polypeptide. In some embodiments, the RNA polynucleotide is formulated to produce a neutralizing antibodies within one week of a single administration. In some embodiments, the adjuvant is selected from a cationic peptide and an immunostimulatory nucleic acid. In some embodiments, the cationic peptide is protamine.

Aspects provide NAVs comprising one or more RNA polynucleotides having an open reading frame comprising at least one chemical modification, the open reading frame encoding a first antigenic polypeptide, wherein the RNA polynucleotide is present in the formulation for in vivo administration to a host such that the level of antigen expression in the host significantly exceeds a level of antigen expression produced by an mRNA vaccine having a stabilizing element or formulated with an adjuvant and encoding the first antigenic polypeptide.

Other aspects provide NAVs comprising one or more RNA polynucleotides having an open reading frame comprising at least one chemical modification, the open reading frame encoding a first antigenic polypeptide, wherein the vaccine has at least 10 fold less RNA polynucleotide than is required for an unmodified mRNA vaccine to produce an equivalent antibody titer. In some embodiments, the RNA polynucleotide is present in a dosage of 25-100 micrograms.

Aspects of the invention also provide a unit of use vaccine, comprising between 10 ug and 400 μg of one or more RNA polynucleotides having an open reading frame comprising at least one chemical modification, the open reading frame encoding a first antigenic polypeptide, and a pharmaceutically acceptable carrier or excipient, formulated for delivery to a human subject. In some embodiments, the vaccine further comprises a cationic lipid nanoparticle.

Aspects of the invention provide methods of creating, maintaining or restoring antigenic memory to an influenza strain in an individual or population of individuals comprising administering to said individual or population an antigenic memory booster nucleic acid vaccine comprising (a) at least one RNA polynucleotide, said polynucleotide comprising at least one chemical modification and two or more codon-optimized open reading frames, said open reading frames encoding a set of reference antigenic polypeptides, and (b) optionally a pharmaceutically acceptable carrier or excipient. In some embodiments, the vaccine is administered to the individual via a route selected from the group consisting of intramuscular administration, intradermal administration and subcutaneous administration. In some embodiments, the administering step comprises contacting a muscle tissue of the subject with a device suitable for injection of the composition. In some embodiments, the administering step comprises contacting a muscle tissue of the subject with a device suitable for injection of the composition in combination with electroporation.

Aspects of the invention provide methods of vaccinating a subject comprising administering to the subject a single dosage of between 25 μg/kg and 400 μg/kg of a nucleic acid vaccine comprising one or more RNA polynucleotides having an open reading frame encoding a first antigenic polypeptide in an effective amount to vaccinate the subject.

Aspects provide NAVs comprising one or more RNA polynucleotides having an open reading frame encoding a hemagglutinin protein fragment, wherein the hemagglutinin protein includes only a portion of at least one of: a head domain (HA1), a cytoplasmic domain, or a transmembrane domain. In some embodiments, the hemagglutinin protein is H1, H2, H3, H4, H5, H6, H7, H8, H9, H10, H11, H12, H13, H14, H15, H16, H17, H18. In some embodiments, the hemagglutinin protein does not comprise the head domain (HA1). In some embodiments, the hemagglutinin protein does not comprise the cytoplasmic domain. In some embodiments, the truncated hemagglutinin protein does not comprise the transmembrane domain. In some embodiments, the amino acid sequence of the hemagglutinin protein comprises at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97% 98%, or 99% identify with any of the amino acid sequences provided in Tables 6-16.

In some embodiments, the vaccine is formulated within a cationic lipid complex or cationic lipid nanoparticle. In some embodiments, the polynucleotide comprises at least one 5′ terminal cap and at least one chemical modification.

Aspects also provide any of the vaccines described herein for use in a method of inducing an antigen specific immune response in a subject. In some embodiments, the method comprises administering the vaccine to the subject in an effective amount to produce an antigen specific immune response.

Other aspects provide a use of any of the vaccines described herein in the manufacture of a medicament for use in a method of inducing an antigen specific immune response in a subject, the method comprising administering the vaccine to the subject in an effective amount to produce an antigen specific immune response.

Aspects also provide for any of the vaccines described herein for use in a method of preventing or treating influenza viral infection, the method comprising administering the vaccine to a subject.

Other aspects provide a use any of the vaccines described herein in the manufacture of a medicament for use in a method of preventing or treating influenza viral infection, the method comprising administering the vaccine to a subject.

Other aspects provide nucleic acid vaccines for use in a method of vaccinating a subject wherein the nucleic acid vaccine comprises a first RNA polynucleotide having an open reading frame encoding a first antigenic polypeptide, wherein the RNA polynucleotide does not include a stabilization element, and wherein an adjuvant is not coformulated or co-administered with the vaccine. In some embodiments, the method further comprises administering the vaccine to the subject.

Other aspects provide a use of a nucleic acid vaccine in the manufacture of a medicament for use in a method of vaccinating a subject wherein the nucleic acid vaccine comprises a first RNA polynucleotide having an open reading frame encoding a first antigenic polypeptide, wherein the RNA polynucleotide does not include a stabilization element, and wherein an adjuvant is not coformulated or co-administered with the vaccine. In some embodiments, the method further comprises administering the vaccine to the subject.

Aspects of the invention provide an antigenic memory booster nucleic acid vaccine for use in a method of creating, maintaining or restoring antigenic memory to an influenza strain in an individual or population of individuals. In some embodiments, the antigenic memory booster nucleic acid vaccine comprises (a) at least one RNA polynucleotide, said polynucleotide comprising at least one chemical modification and two or more codon-optimized open reading frames, said open reading frames encoding a set of reference antigenic polypeptides, and (b) optionally a pharmaceutically acceptable carrier or excipient; and wherein the method comprises administering to said individual or population the antigenic memory booster nucleic acid vaccine.

Other aspects provide a use of an antigenic memory booster nucleic acid vaccine in the manufacture of a medicament for use in a method of creating, maintaining or restoring antigenic memory to an influenza strain in an individual or population of individuals, wherein the antigenic memory booster nucleic acid vaccine comprises (a) at least one RNA polynucleotide, said polynucleotide comprising at least one chemical modification and two or more codon-optimized open reading frames, said open reading frames encoding a set of reference antigenic polypeptides, and (b) optionally a pharmaceutically acceptable carrier or excipient; and wherein the method comprises administering to said individual or population the antigenic memory booster nucleic acid vaccine.

Other aspects provide a nucleic acid vaccine for use in a method of vaccinating a subject, wherein the nucleic acid vaccine comprises a first RNA polynucleotide having an open reading frame encoding a first antigenic polypeptide, and wherein the method comprises administering to the subject a single dosage of between 25 μg/kg and 400 μg/kg of the nucleic acid vaccine in an effective amount to vaccinate the subject.

Other aspects provide a use of a nucleic acid vaccine in the manufacture of a medicament for use in a method of vaccinating a subject, wherein the nucleic acid vaccine comprises a first RNA polynucleotide having an open reading frame encoding a first antigenic polypeptide, and wherein the method comprises administering to the subject a single dosage of between 25 μg/kg and 400 μg/kg of the nucleic acid vaccine in an effective amount to vaccinate the subject.

In some embodiments, the NAV polynucleotides may encode one or more polypeptides of an influenza strain as an antigen. Such antigens include, but are not limited to those antigens encoded by the polynucleotides listed in the Tables presented herein. In the table, the GenBank Accession Number or GI Accession Number represents either the complete or partial CDS of the encoded antigen. The NAV polynucleotides may comprise a region of any of the sequences listed in the tables or entire coding region of the mRNA listed. They may comprise hybrid or chimeric regions, or mimics or variants.

The details of various embodiments of the invention are set forth in the description below. Other features, objects, and advantages of the invention will be apparent from the description and the drawings, and from the claims.

BRIEF DESCRIPTION OF THE DRAWINGS

The foregoing and other objects, features and advantages will be apparent from the following description of particular embodiments of the invention, as illustrated in the accompanying drawings in which like reference characters refer to the same parts throughout the different views. The drawings are not necessarily to scale, emphasis instead being placed upon illustrating the principles of various embodiments of the invention.

FIGS. 1A and 1B are schematics of a polynucleotide construct. FIG. 1A is a schematic of a polynucleotide construct taught in commonly owned co-pending U.S. patent application Ser. No. 13/791,922 filed Mar. 9, 2013, the contents of which are incorporated herein by reference. FIG. 1B is a schematic of a linear polynucleotide construct.

FIG. 2 is a schematic of a series of chimeric polynucleotides of the present invention.

FIG. 3 is a schematic of a series of chimeric polynucleotides illustrating various patterns of positional modifications and showing regions analogous to those regions of an mRNA polynucleotide.

FIG. 4 is a schematic of a series of chimeric polynucleotides illustrating various patterns of positional modifications based on Formula I.

FIG. 5 is a is a schematic of a series of chimeric polynucleotides illustrating various patterns of positional modifications based on Formula I and further illustrating a blocked or structured 3′ terminus.

FIGS. 6A and 6B are schematics of circular constructs of the present invention.

FIGS. 7A-7B are schematics of circular constructs of the present invention.

FIGS. 8A-8B are schematics of a circular constructs of the present invention. FIG. 8A shows a circular construct comprising at least one sensor region and a spacer region. FIG. 8B shows a non-coding circular construct.

FIG. 9 is a schematic of a non-coding circular construct of the present invention.

FIG. 10 shows HA neutralization titres of a chemically modified mRNA influenza vaccine in comparison with protein and unmodified mRNA vaccines.

FIG. 11 shows hemagglutinin inhibition titers in mice following vaccination with different doses and formulations of mRNA encoding the hemagglutinin protein of the H1N1 virus.

FIGS. 12A-12D show percent survival of mice after vaccination and challenge with influenza A/PR/8/34 virus. FIG. 12A shows percent survival at 1 week post challenge. FIG. 12B shows percent survival at 2 weeks post challenge. FIG. 12C shows percent survival at 3 weeks post challenge. FIG. 12D shows percent survival at 4 weeks post challenge.

FIG. 13 shows the mean hemagglutination inhibition titers of mice after vaccination and challenge with influenza A/PR/8/34 virus

FIGS. 14A-14C shows CD4 T cell IFNγ cytokine responses. FIG. 14A shows IFNγ production upon H1 protein/peptide stimulation. FIG. 14B shows IFNγ production upon H7 protein/peptide stimulation. FIG. 14C shows IFNγ production upon PMA+ionomycin stimulation.

FIGS. 15A-15D shows IgG production following H1 and H7 protein/peptide stimulation.

FIG. 16 is a graph showing hemagglutinin inhibition titers (HAI) against H10 following administration of the H10N8/N1-methyl pseudouridine/C0 formulation MC3 vaccine at the indicated dosages.

FIG. 17 is a graph showing hemagglutinin inhibition titers (HAI) against H10 following administration of the H10N8/N1-methyl pseudouridine/C1 formulation MC3 vaccine at the indicated dosages.

FIG. 18 is a graph comparing hemagglutinin inhibition titers (HAI) against H7 following administration of 10 μg/dose of the H7N9/C0 formulation compared to the H7N9/C1 formulation.

FIG. 19 is a graph of the mean hemagglutinin inhibition titers (HAI) in serum samples from cynomolgus monkey at various time points prior to and after administration of the indicated formulations and dosages.

FIG. 20 is a graph showing the H7N9 viral load in ferrets challenged at day 21 after receiving a single immunization.

FIGS. 21A-21D present mouse survival and HAI titers in mice challenged with a lethal dose following administration of a single dose of mRNA NAV encoding H7N9. FIG. 21A shows survival at day 7 post challenge. FIG. 21B shows survival at day 21 post challenge. FIG. 21C shows survival at day 84 post challenge. FIG. 21D shows HAI titers.

FIGS. 22-1 through 22-51 show an alignment of amino acid sequences of hemagglutinin proteins from influenza A H7N9 strains relative to a consensus sequence. The sequences, from top to bottom, correspond to SEQ ID NOs: 1020, 8, 13, 7, 98, 99, 100, 96, 89, 92, 24, 29, 90, 57, 42, 27, 78, 74, 95, 30, 31, 32, 25, 39, 38, 35, 36, 37, 82, 91, 83, 104, 93, 94, 178, 133, 134, 132, 135, 136, 173, 175, 174, 73, 70, 33, 34, 41, 40, 76, 75, 72, 79, 80, 86, 105, 77, 11, 12, 4, 164, 150, 151, 171, 152, 165, 121, 166, 167, 156, 157, 168, 143, 169, 144, 145, 122, 113, 117, 119, 138, 137, 146, 147, 148, 158, 159, 160, 161, 162, 62, 129, 130, 141, 123, 124, 176, 125, 182, 183, 179, 180, 184, 181, 185, 186, 187, 188, 189, 190, 193, 177, 140, 49, 47, 48, 97, 50, 51, 191, 195, 196, 128, 131, 170, 111, 112, 118, 108, 120, 109, 107, 26, 106, 52, 53, 28, 192, 45, 46, 6, 44, 43, 126, 19, 21, 20, 59, 54, 71, 102, 10, 101, 2, 58, 23, 55, 5, 22, 103, 153, 154, 155, 172, 142, 114, 115, 116, 127, 149, 163, 139, 194, 110, 17, 81, 3, 85, 87, 88, 84, 61, 60, 1, 9, 14, 15, 16, 64, 63, 66, 65, 67, 68, 69, 18, and 56.

FIGS. 23-1 through 23-14 (SEQ ID NOS: 1021, 967-1019) shows an alignment of amino acid sequences of hemagglutinin proteins from influenza A H10N8 strains relative to a consensus sequence.

DETAILED DESCRIPTION

It is of great interest in the fields of therapeutics, diagnostics, reagents and for biological assays to be able design, synthesize and deliver a nucleic acid, e.g., a ribonucleic acid (RNA) for example, a messenger RNA (mRNA) encoding a peptide or polypeptide of interest inside a cell, whether in vitro, in vivo, in situ or ex vivo, such as to effect physiologic outcomes which are beneficial to the cell, tissue or organ and ultimately to an organism. One beneficial outcome is to cause intracellular translation of the nucleic acid and production of at least one encoded peptide or polypeptide of interest.

Of particular interest, is the ability to design, synthesize and deliver a nucleic acid, e.g., a ribonucleic acid (RNA), for example, a messenger RNA (mRNA), which encodes an antigen, e.g., an antigen derived from an infectious microorganism, for the purpose of vaccination.

Described herein are compositions (including pharmaceutical compositions) and methods for the selection, design, preparation, manufacture, formulation, and/or use of nucleic acid vaccines (NAVs) where at least one component of the NAV is a nucleic acid molecule, e.g., a polynucleotide. In particular, described herein are compositions (including pharmaceutical compositions) and methods for the selection, design, preparation, manufacture, formulation, and/or use of nucleic acid vaccines (NAVs) where at least one component of the NAV is a polynucleotide. In particular, described herein are compositions (including pharmaceutical compositions) and methods for the selection, design, preparation, manufacture, formulation, and/or use of nucleic acid vaccines (NAVs) where at least one component of the NAV is a RNA polynucleotide, e.g., an mRNA polynucleotide which encodes an antigen, e.g., an antigen derived from an infectious microorganism. In certain embodiments, the invention relates to compositions (including pharmaceutical compositions) and methods for the selection, design, preparation, manufacture, formulation, and/or use of ribonucleic acid vaccines (RNAVs) where at least one component of the RNAV is a ribonucleic acid molecule, e.g., a mRNA which encodes an antigen, e.g., an antigen derived from an infectious microorganism. As such the present invention is directed, in part, to polynucleotides, specifically in vitro transcription (IVT) polynucleotides, chimeric polynucleotides and/or circular polynucleotides which may function as a vaccine or component of a vaccine.

Also provided are systems, processes, devices and kits for the selection, design and/or utilization of the NAVs described herein.

According to the present invention, the polynucleotides may be modified in a manner as to avoid the deficiencies of or provide improvements over other polynucleotide molecules of the art.

Although attempts have been made to produce functional RNA vaccines, including mRNA vaccines and self-replicating RNA vaccines, the therapeutic efficacy of these RNA vaccines have not yet been fully established. Quite surprisingly, the inventors have discovered a class of formulations for delivering mRNA vaccines in vivo that results in significantly enhanced, and in many respects synergistic, immune responses including enhanced antigen generation and functional antibody production with neutralization capability. These results are achieved even when significantly lower doses of the mRNA are administered in comparison with mRNA doses used in other classes of lipid based formulations. The formulations of the invention have demonstrated significant unexpected in vivo immune responses sufficient to establish the efficacy of functional mRNA vaccines as prophylactic and therapeutic agents.

The invention involves, in some aspects, the surprising finding that lipid nanoparticle (LNP) formulations significantly enhance the effectiveness of mRNA vaccines, including chemically modified and unmodified mRNA vaccines. The efficacy of mRNA vaccines formulated in LNP was examined in vivo using several distinct viral antigens and in a variety of different animal models. The results presented herein demonstrate the unexpected superior efficacy of the mRNA vaccines formulated in LNP over other mRNA vaccines formulated in other lipid based carriers as well as over protein antigens.

In addition to providing an enhanced immune response, the formulations of the invention generate a more rapid immune response following a single dose of antigen than other mRNA or protein based vaccines tested. A study described herein involved intravenous (IV), intramuscular (IM), or intradermal (ID) vaccination of mice, followed by challenge with a lethal dose of virus. In addition to all of the vaccinated animals surviving the lethal dose, significantly stronger early immune responses were observed (anti-viral activity via virus neutralization assay and HA inhibition (HAI)) in comparison to protein antigen and other lipid based formulations (lipoplex). The data demonstrates that as early as 1 week after vaccination two groups of animals receiving a mRNA-LNP formulation (ID or IM) displayed HAI titers over 40, at 60 and 114, respectively. An HAI titer of greater than 40 is deemed sufficient to protect from a lethal challenge of influenza. The rapid response was unexpected, particularly when compared to the response seen with protein antigen and mRNA vaccines formulated in other lipid carriers (lipoplex), which at one week and even at three weeks following vaccination continued to show ineffective HAI titers of less than 40.

At each of the later time points (3 weeks and 5 weeks), the formulations of the invention continued to provide significantly stronger therapeutic responses than did protein antigen. In fact both chemically unmodified and modified mRNA-LNP formulation administered by IV route had enhanced HAI titers with respect to the protein antigen. By week 3, all of the animals receiving an mRNA-LNP formulation by IM or ID administration displayed HAI activity over 40, as compared to protein antigen, which at one week and three weeks continued to show HAI titers of less than 40. By week 5 a mRNA-LNP formulation administered by ID route had a surprising HAI activity of greater than 10,000, in contrast to the HAI titer of around 400 for protein antigen at that time point. Mice receiving a mRNA-LNP formulation also displayed neutralizing activity of 79-250 (IM) and 250 (ID) by microneutralization assay, in comparison to protein antigen, which had undetectable neutralization activity at that time point. By week 5 following vaccination, five of the six LNP formulated groups showed high neutralizing activity between 789 and 24892. In contrast, the mice vaccinated with protein antigen displayed neutralizing activity in only 3 of 5 mice and ranging only between 79 and 250.

The mRNA-LNP formulations of the invention also produced quantitatively and qualitatively better immune responses than did mRNA vaccines formulated in a different lipid carrier (lipoplex). At week 5 the mRNA-lipoplex vaccine produced HAI titers of 197, in comparison to those achieved by the mRNA-LNP formulations of the invention (HAI titers of 635-10,152). At all other time points and for all of the mRNA-lipoplex vaccines, none of the HAI titers reached the critical level of greater than 40. Additionally, the mRNA-lipoplex vaccines did not result in any detectable neutralizing activity in the microneutralization activity, even as late as five weeks after vaccination.

The data described herein demonstrate that the formulations of the invention produced significant unexpected improvements over both existing protein antigen vaccines and mRNA vaccine formulations, including: 100% rescue from lethal influenza challenge with rapid onset of protective antibody titers after 1 week and high antibody titers, i.e., 50 fold over unmodified mRNA and 20 fold over the protein vaccine.

Additionally, the mRNA-LNP formulations of the invention were superior to other lipid formulations even when the dose of mRNA was significantly lower than in the other lipid formulations. For instance, the data described above was generated using 10 μg of mRNA in the mRNA-LNP formulations in contrast to 80 μg of mRNA in the mRNA-lipoplex formulation.

The formulations of the invention also showed strong efficacy in several non-rodent animal models, including non-human primates. Highly effective vaccination was observed in cynomoglus monkeys and ferrets. Cynomoglus monkeys were vaccinated with various doses of mRNA-LNP formulations (50 μg/dose, 200 μg/dose, 400 μg/dose). Quite surprisingly, the vaccine formulations of the invention at all doses measured significantly reduced viral titers in the lungs of ferrets when exposed to virus just 7 days following single vaccination. Statistically significant increases in antibody titer as measured by HAI and microneutralization were detected as early as 7 days following vaccination and through the entire length of the study (84 days). A single vaccination was able to eliminate all virus in most animals.

The LNP used in the studies described herein has been used previously to deliver siRNA various in animal models as well as in humans. In view of the observations made in association with the siRNA delivery of LNP formulations, the fact that LNP is useful in vaccines is quite surprising. It has been observed that therapeutic delivery of siRNA formulated in LNP causes an undesirable inflammatory response associated with a transient IgM response, typically leading to a reduction in antigen production and a compromised immune response. In contrast to the findings observed with siRNA, the LNP-mRNA formulations of the invention are demonstrated herein to generate enhanced IgG levels, sufficient for prophylactic and therapeutic methods rather than transient IgM responses.

I. Nucleic Acid Vaccines (NAVs)

Nucleic Acid Vaccines (NAVs) of the present invention comprise one or more polynucleotides, e.g., polynucleotide constructs, which encode one or more wild type or engineered antigens. Exemplary polynucleotides, e.g., polynucleotide constructs, include antigen-encoding RNA polynucleotides, e.g., mRNAs. In exemplary aspect, polynucleotides of the invention, e.g., antigen-encoding RNA polynucleotides, may include at least one chemical modification.

NAV compositions of the invention may comprise other components including, but not limited to, tolerizing agents or adjuvants.

Tolerizing Agent or Composition

Where auto-immunity mediated side effects occur, tolerizing mRNA and/or such as any of those taught for example in U.S. Ser. No. 61/892,556 filed Oct. 18, 2013, and PCT/US2014/61104 filed Oct. 17, 2014, the contents of which are incorporated herein by reference in their entirety) are co-administered with the NAV to induce antigen specific tolerance.

Adjuvants

Adjuvants or immune potentiators, may also be administered with or in combination with one or more NAVs.

In one embodiment, an adjuvant acts as a co-signal to prime T-cells and/or B-cells and/or NK cells as to the existence of an infection.

Advantages of adjuvants include the enhancement of the immunogenicity of antigens, modification of the nature of the immune response, the reduction of the antigen amount needed for a successful immunization, the reduction of the frequency of booster immunizations needed and an improved immune response in elderly and immunocompromised vaccinees. These may be co-administered by any route, e.g., intramusculary, subcutaneous, IV or intradermal injections.

Adjuvants useful in the present invention may include, but are not limited to, natural or synthetic. They may be organic or inorganic.

Adjuvants may be selected from any of the classes (1) mineral salts, e.g., aluminium hydroxide and aluminium or calcium phosphate gels; (2) emulsions including: oil emulsions and surfactant based formulations, e.g., microfluidised detergent stabilised oil-in-water emulsion, purified saponin, oil-in-water emulsion, stabilised water-in-oil emulsion; (3) particulate adjuvants, e.g., virosomes (unilamellar liposomal vehicles incorporating influenza haemagluttinin), structured complex of saponins and lipids, polylactide co-glycolide (PLG); (4) microbial derivatives; (5) endogenous human immunomodulators; and/or (6) inert vehicles, such as gold particles; (7) microorganism derived adjuvants; (8) tensoactive compounds; (9) carbohydrates; or combinations thereof.

Adjuvants for DNA nucleic acid vaccines (DNA) have been disclosed in, for example, Kobiyama, et al Vaccines, 2013, 1(3), 278-292, the contents of which are incorporated herein by reference in their entirety. Any of the adjuvants disclosed by Kobiyama may be used in the RNAVs of the present invention.

Other adjuvants which may be utilized in the RNAVs of the present invention include any of those listed on the web-based vaccine adjuvant database, Vaxjo; http://www.violinet.org/vaxjo/ and described in for example Sayers, et al., J. Biomedicine and Biotechnology, volume 2012 (2012), Article ID 831486, 13 pages, the content of which is incorporated herein by reference in its entirety.

Selection of appropriate adjuvants will be evident to one of ordinary skill in the art. Specific adjuvants may include, without limitation, cationic liposome-DNA complex JVRS-100, aluminum hydroxide vaccine adjuvant, aluminum phosphate vaccine adjuvant, aluminum potassium sulfate adjuvant, alhydrogel, ISCOM(s)™, Freund's Complete Adjuvant, Freund's Incomplete Adjuvant, CpG DNA Vaccine Adjuvant, Cholera toxin, Cholera toxin B subunit, Liposomes, Saponin Vaccine Adjuvant, DDA Adjuvant, Squalene-based Adjuvants, Etx B subunit Adjuvant, IL-12 Vaccine Adjuvant, LTK63 Vaccine Mutant Adjuvant, TiterMax Gold Adjuvant, Ribi Vaccine Adjuvant, Montanide ISA 720 Adjuvant, Corynebacterium-derived P40 Vaccine Adjuvant, MPL™ Adjuvant, AS04, AS02, Lipopolysaccharide Vaccine Adjuvant, Muramyl Dipeptide Adjuvant, CRL1005, Killed Corynebacterium parvum Vaccine Adjuvant, Montanide ISA 51, Bordetella pertussis component Vaccine Adjuvant, Cationic Liposomal Vaccine Adjuvant, Adamantylamide Dipeptide Vaccine Adjuvant, Arlacel A, VSA-3 Adjuvant, Aluminum vaccine adjuvant, Polygen Vaccine Adjuvant, Adjumer™, Algal Glucan, Bay R1005, Theramide®, Stearyl Tyrosine, Specol, Algammulin, Avridine®, Calcium Phosphate Gel, CTA 1-DD gene fusion protein, DOC/Alum Complex, Gamma Inulin, Gerbu Adjuvant, GM-CSF, GMDP, Recombinant hIFN-gamma/Interferon-g, Interleukin-1p, Interleukin-2, Interleukin-7, Sclavo peptide, Rehydragel LV, Rehydragel HPA, Loxoribine, MF59, MTP-PE Liposomes, Murametide. Murapalmitine, D-Murapalmitine, NAGO, Non-Ionic Surfactant Vesicles, PMMA, Protein Cochleates, QS-21, SPT (Antigen Formulation), nanoemulsion vaccine adjuvant, AS03, Quil-A vaccine adjuvant, RC529 vaccine adjuvant, LTR1920 Vaccine Adjuvant, E. coli heat-labile toxin, LT, amorphous aluminum hydroxyphosphate sulfate adjuvant, Calcium phosphate vaccine adjuvant, Montanide Incomplete Seppic Adjuvant, Imiquimod, Resiquimod, AF03, Flagellin, Poly(I:C), ISCOMATRIX®, Abisco-100 vaccine adjuvant, Albumin-heparin microparticles vaccine adjuvant. AS-2 vaccine adjuvant, B7-2 vaccine adjuvant, DHEA vaccine adjuvant, Immunoliposomes Containing Antibodies to Costimulatory Molecules, SAF-1, Sendai Proteoliposomes, Sendai-containing Lipid Matrices, Threonyl muramyl dipeptide (TMDP), Ty Particles vaccine adjuvant, Bupivacaine vaccine adjuvant, DL-PGL (Polyester poly (DL-lactide-co-glycolide)) vaccine adjuvant, IL-15 vaccine adjuvant, LTK72 vaccine adjuvant, MPL-SE vaccine adjuvant, non-toxic mutant E112K of Cholera Toxin mCT-E112K, and/or Matrix-S.

Other adjuvants which may be co-administered with the NAVs of the invention include, but are not limited to interferons, TNF-alpha, TNF-beta, chemokines such as CCL21, eotaxin, HMGB1, SA100-8alpha, GCSF, GMCSF, granulysin, lactoferrin, ovalbumin, CD-40L, CD28 agonists, PD-1, soluble PD1, L1 or L2, or interleukins such as IL-1, IL-2, IL-4, IL-6, IL-7, IL-10. IL-12, IL-13, IL-21. IL-23, IL-15, IL-17, and IL-18. These may be administered with the NAV on the same encoded polynucleotide, e.g., polycistronic, or as separate mRNA encoding the adjuvant and antigen.

Valency

NAVs of the present invention may vary in their valency. Valency refers to the number of antigenic components in the NAV or NAV polynucleotide (e.g., RNA polynucleotide) or polypeptide. In some embodiments, the NAVs are monovalent. In some embodiments, the NAVs are divalent. In some embodiments the NAVs are trivalent. In some embodiments the NAVs are multi-valent. Multivalent vaccines may comprise 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, or more antigens or antigenic moieties (e.g., antigenic peptides, etc.). The antigenic components of the NAVs may be on a single polynucleotide or on separate polynucleotides.

Therapeutics

The NAVs of the present invention can be used as therapeutic or prophylactic agents. They are provided for use in medicine and/or for the priming of immune effector cells, e.g., stimulate/transfect PBMCs ex vivo and re-infuse the activated cells. For example, a NAV described herein can be administered to a subject, wherein the polynucleotides is translated in vivo to produce an antigen. Provided are compositions, methods, kits, and reagents for diagnosis, treatment or prevention of a disease or condition in humans and other mammals. The active therapeutic agents of the invention include NAVs, cells containing NAVs or polypeptides translated from the polynucleotides contained in said NAVs.

Provided herein are methods of inducing translation of a polypeptide (e.g., antigen or immunogen) in a cell, tissue or organism using the polynucleotides of the NAVs described herein. Such translation can be in vivo, ex vivo, in culture, or in vitro. The cell, tissue or organism is contacted with an effective amount of a composition containing a NAV which contains a polynucleotide that has at least one a translatable region encoding the polypeptide of interest (e.g., antigen or immunogen).

An “effective amount” of the NAV composition is provided based, at least in part, on the target tissue, target cell type, means of administration, physical characteristics of the polynucleotide (e.g., size, and extent of modified nucleosides) and other components of the NAV, and other determinants. In general, an effective amount of the NAV composition provides an induced or boosted immune response as a function of antigen production in the cell, preferably more efficient than a composition containing a corresponding unmodified polynucleotide encoding the same antigen. Increased antigen production may be demonstrated by increased cell transfection (i.e., the percentage of cells transfected with the NAV), increased protein translation from the polynucleotide, decreased nucleic acid degradation (as demonstrated, e.g., by increased duration of protein translation from a modified polynucleotide), or altered innate immune response of the host cell.

Aspects of the invention are directed to methods of inducing in vivo translation of a polypeptide antigen in a mammalian subject in need thereof. Therein, an effective amount of a NAV composition containing a polynucleotide that has at least one structural or chemical modification and a translatable region encoding the polypeptide (e.g., antigen or immunogen) is administered to the subject using the delivery methods described herein. The polynucleotide is provided in an amount and under other conditions such that the polynucleotide is translated in the cell. The cell in which the polynucleotide is localized, or the tissue in which the cell is present, may be targeted with one or more than one rounds of NAV administration.

In certain embodiments, the administered NAVs comprising polynucleotides directs production of one or more polypeptides that provide a functional immune system-related activity which is substantially absent in the cell, tissue or organism in which the polypeptide is translated. For example, the missing functional activity may be enzymatic, structural, or gene regulatory in nature. In related embodiments, the administered polynucleotides directs production of one or more polypeptides that increases (e.g., synergistically) a functional activity related to the immune system which is present but substantially deficient in the cell in which the polypeptide is translated.

Additionally, the polypeptide antagonizes, directly or indirectly, the activity of a biological moiety present in, on the surface of, or secreted from the cell. Examples of antagonized biological moieties include lipids (e.g., cholesterol), a lipoprotein (e.g., low density lipoprotein), a nucleic acid, a carbohydrate, a protein toxin such as shiga and tetanus toxins, or a small molecule toxin such as botulinum, cholera, and diphtheria toxins. Additionally, the antagonized biological molecule may be an endogenous protein that exhibits an undesirable activity, such as a cytotoxic or cytostatic activity.

The proteins described herein may be engineered for localization within the cell, potentially within a specific compartment such as the cytoplasms or nucleus, or are engineered for secretion from the cell or translocation to the plasma membrane of the cell.

In some embodiments, polynucleotides of the NAVs and their encoded polypeptides in accordance with the present invention may be used for treatment of any of a variety of diseases, disorders, and/or conditions, including but not limited to viral infections (e.g., influenza, HIV, HCV, RSV), parasitic infections or bacterial infections.

The subject to whom the therapeutic agent may be administered suffers from or may be at risk of developing a disease, disorder, or deleterious condition. Provided are methods of identifying, diagnosing, and classifying subjects on these bases, which may include clinical diagnosis, biomarker levels, genome-wide association studies (GWAS), and other methods known in the art.

The agents can be administered simultaneously, for example in a combined unit dose (e.g., providing simultaneous delivery of both agents). The agents can also be administered at a specified time interval, such as, but not limited to, an interval of minutes, hours, days or weeks. Generally, the agents may be concurrently bioavailable, e.g., detectable, in the subject. In some embodiments, the agents may be administered essentially simultaneously, for example two unit dosages administered at the same time, or a combined unit dosage of the two agents. In other embodiments, the agents may be delivered in separate unit dosages. The agents may be administered in any order, or as one or more preparations that includes two or more agents. In a preferred embodiment, at least one administration of one of the agents, e.g., the first agent, may be made within minutes, one, two, three, or four hours, or even within one or two days of the other agent, e.g., the second agent. In some embodiments, combinations can achieve synergistic results, e.g., greater than additive results, e.g., at least 25, 50, 75, 100, 200, 300, 400, or 500% greater than additive results.

Modulation of the Immune Response
Activation of the Immune Response

According to the present invention, the NAVs comprising the polynucleotides disclosed herein, e.g., comprising RNA polynucleotides, may act as a single composition as a vaccine. As used herein, a “vaccine” refers to a composition, for example, a substance or preparation that stimulates, induces, causes or improves immunity in an organism, e.g., an animal organism, for example, a mammalian organism (e.g., a human.) Preferably, a vaccine provides immunity against one or more diseases or disorders in the organism, including prophylactic and/or therapeutic immunity. Exemplary vaccines includes one or more agents that resembles an infectious agent, e.g., a disease-causing microorganism, and can be made, for example, from live, attenuated, modified, weakened or killed forms of disease-causing microorganisms, or antigens derived therefrom, including combinations of antigenic components. In exemplary embodiments, a vaccine stimulates, induces causes or improves immunity in an organism or causes or mimics infection in the organism without inducing any disease or disorder. A vaccine introduces an antigen into the tissues, extracellular space or cells of a subject and elicits an immune response, thereby protecting the subject from a particular disease or pathogen infection. The polynucleotides of the present invention may encode an antigen and when the polynucleotides are expressed in cells, a desired immune response is achieved.

NAVs may be administered prophylactically or therapeutically as part of an active immunization scheme to healthy individuals or early in infection during the incubation phase or during active infection after onset of symptoms.

The NAVs of the present invention may also be administered as a second line treatment after the standard first line treatments such as antibiotics and antivirals have failed to induce passive immunity. In this regard, the NAVs of the present invention are useful in settings where resistance to first line treatments has developed and disease persists and induces chronic disease.

NAVs may be administered as part of a treatment regimen for latent bacterial infections, such as MRSA or Clostridium infections. In this embodiment, one or more polynucleotides are administered which ultimately produce proteins which result in the removal or alterations of the protective shield surrounding a bacterium making the bacterium more susceptible to antibiotic treatment.

In one embodiment, a polynucleotide encoding one or several generic or patient-specific antibiotic resistance genes is administered to a patient, e.g. NDM-1. The polynucleotide is then translated to produce the enzyme in vivo. This production may raise an antibody-mediated immune response to the secreted and/or the intracellular enzyme that neutralized the antibiotic resistance and provides the bacteria susceptible to the clearance by available antibiotics again. Given the broad range of mutations and variants in antibiotic resistance genes, it would be possible to sequence the specific bacteria genes hosted by the patients and design the exact vaccine for the specific variant in the infected patient.

The use of RNA in or as a vaccine overcomes the disadvantages of conventional genetic vaccination involving incorporating DNA into cells in terms of safeness, feasibility, applicability, and effectiveness to generate immune responses. RNA molecules are considered to be significantly safer than DNA vaccines, as RNAs are more easily degraded. They are cleared quickly out of the organism and cannot integrate into the genome and influence the cell's gene expression in an uncontrollable manner. It is also less likely for RNA vaccines to cause severe side effects like the generation of autoimmune disease or anti-DNA antibodies (Bringmann A. et al., Journal of Biomedicine and Biotechnology (2010), vol. 2010, article ID623687). Transfetion with RNA requires only insertion into the cell's cytoplasm, which is easier to achieve than into the nucleus. However, RNA is susceptible to RNase degradation and other natural decomposition in the cytoplasm of cells.

Various attempts to increase the stability and shelf life of RNA vaccines. US 2005/0032730 to Von Der Mulbe et al. discloses improving the stability of mRNA vaccine compositions by increasing G(guanosine)/C(cytosine) content of the mRNA molecules. U.S. Pat. No. 5,580,859 to Felgner et al. teaches incorporating polynucleotide sequences coding for regulatory proteins that binds to and regulates the stabilities of mRNA. While not wishing to be bound by theory, it is believed that the polynucleotides vaccines (NAVs) of the invention will result in improved stability and therapeutic efficacy due at least in part to the specificity, purity and selectivity of the construct designs.

Additionally, certain modified nucleosides, or combinations thereof, when introduced into the polynucleotides of the NAVs of the invention will activate the innate immune response. Such activating molecules are useful as adjuvants when combined with polypeptides and/or other vaccines. In certain embodiments, the activating molecules contain a translatable region which encodes for a polypeptide sequence useful as a vaccine, thus providing the ability to be a self-adjuvant.

In one embodiment, the polynucleotides of the NAVs of the present invention may be used in the prevention, treatment and diagnosis of diseases and physical disturbances caused by infectious agents. The polynucleotide of the present invention may encode at least one polypeptide of interest (antigen) and may be provided to an individual in order to stimulate the immune system to protect against the disease-causing agents. As a non-limiting example, the biological activity and/or effect from an antigen or infectious agent may be inhibited and/or abolished by providing one or more polynucleotides which have the ability to bind and neutralize the antigen and/or infectious agent.

As a non-limiting example, the polynucleotides encoding an immunogen may be delivered to cells to trigger multiple innate response pathways (see International Pub. No. WO2012006377 and US Patent Publication No. US20130177639; herein incorporated by reference in its entirety). As another non-limiting example, the polynucleotides of the NAVs of the present invention encoding an immunogen may be delivered to a vertebrate in a dose amount large enough to be immunogenic to the vertebrate (see International Pub. No. WO2012006372 and WO2012006369 and US Publication No. US20130149375 and US20130177640; the contents of each of which are herein incorporated by reference in their entirety).

A non-limiting list of infectious diseases that the polynucleotide vaccines may treat includes, viral infectious diseases such as AIDS (HIV), HIV resulting in mycobacterial infection, AIDS related Cacheixa, AIDS related Cytomegalovirus infection, HIV-associated nephropathy, Lipodystrophy, AID related cryptococcal meningitis, AIDS related neutropaenia, Pneumocysitis jiroveci (Pneumocystis carinii) infections, AID related toxoplasmosis, hepatitis A, B, C, D or E, herpes, herpes zoster (chicken pox), German measles (rubella virus), yellow fever, dengue fever etc. (flavi viruses), flu (influenza viruses), haemorrhagic infectious diseases (Marburg or Ebola viruses), bacterial infectious diseases such as Legionnaires' disease (Legionella), gastric ulcer (Helicobacter), cholera (Vibrio), E. coli infections, staphylococcal infections, salmonella infections or streptococcal infections, tetanus (Clostridium tetani), protozoan infectious diseases (malaria, sleeping sickness, leishmaniasis, toxoplasmosis, i.e. infections caused by plasmodium, trypanosomes, leishmania and toxoplasma), diphtheria, leprosy, measles, pertussis, rabies, tetanus, tuberculosis, typhoid, varicella, diarrheal infections such as Amoebiasis, Clostridium difficile-associated diarrhea (CDAD), Cryptosporidiosis, Giardiasis, Cyclosporiasis and Rotaviral gastroenteritis, encephalitis such as Japanese encephalitis, Wester equine encephalitis and Tick-borne encephalitis (TBE), fungal skin diseases such as candidiasis, onychomycosis, Tinea captis/scal ringworm, Tinea corporis/body ringworm, Tinea cruris/jock itch, sporotrichosis and Tinea pedis/Athlete's foot, Meningitis such as Haemophilus influenza type b (Hib), Meningitis, viral, meningococcal infections and pneumococcal infection, neglected tropical diseases such as Argentine haemorrhagic fever, Leishmaniasis, Nematode/roundworm infections, Ross river virus infection and West Nile virus (WNV) disease, Non-HIV STDs such as Trichomoniasis, Human papillomavirus (HPV) infections, sexually transmitted chlamydial diseases, Chancroid and Syphilis, Non-septic bacterial infections such as cellulitis, lyme disease, MRSA infection, pseudomonas, staphylococcal infections, Boutonneuse fever, Leptospirosis, Rheumatic fever, Botulism, Rickettsial disease and Mastoiditis, parasitic infections such as Cysticercosis, Echinococcosis, Trematode/Fluke infections, Trichinellosis, Babesiosis, Hypodermyiasis, Diphyllobothriasis and Trypanosomiasis, respiratory infections such as adenovirus infection, aspergillosis infections, avian (H5N1) influenza, influenza, RSV infections, severe acute respiratory syndrome (SARS), sinusitis, Legionellosis, Coccidioidomycosis and swine (H1N1) influenza, sepsis such as bacteraemia, sepsis/septic shock, sepsis in premature infants, urinary tract infection such as vaginal infections (bacterial), vaginal infections (fungal) and gonococcal infection, viral skin diseases such as B19 parvovirus infections, warts, genital herpes, orofacial herpes, shingles, inner ear infections, fetal cytomegalovirus syndrome, foodborn illnesses such as brucellosis (Brucella species). Clostridium perfringens (Epsilon toxin), E. Coli O157:H7 (Escherichia coli), Salmonellosis (Salmonella species), Shingellosis (Shingella), Vibriosis and Listeriosis, bioterrorism and potential epidemic diseases such as Ebola haemorrhagic fever, Lassa fever, Marburg haemorrhagic fever, plague, Anthrax Nipah virus disease, Hanta virus, Smallpox, Glanders (Burkholderia mallei), Melioidosis (Burkholderia pseudomallei), Psittacosis (Chlamydia psittaci). Q fever (Coxiella burnetii), Tularemia (Fancisella tularensis), rubella, mumps and polio.

NAVs of the present invention may be utilized in various settings depending on the prevalence of the infection or the degree or level of unmet medical need. As a non-limiting example, the NAVs of the present invention may be utilized to treat and/or prevent influenza infection, i.e. diseases and conditions related to influenza virus infection (seasonal and pandemic).

Symptoms of the influenza infection include dry cough, fever, chills, myalgias progressing to respiratory failure and the risk of secondary bacterial infections (e.g., MRSA). Seasonal influenza is ubiquitous and consists of three principal strains (A [H1N1], A [H3N2], and B), which are covered by the annual vaccine. Pandemic flu occurs because the viruses' unique reassortment ability allowing antigenic shift as well as transfer between avian and swine flu strains. One emerging concern in Southeast Asia is the pandemic potential of several new strains. Such pandemic outbreaks have a high mortality rate with few available treatments. Anti-virals only provide symptomatic relief and must be given in the first 48 hours.

The NAVs of the present invention have superior properties in that they produce much larger antibody titers, produce responses early than commercially available anti-virals and may be administered after the critical 48 hour period while retaining efficacy.

While not wishing to be bound by theory, the inventors hypothesize that the NAVs of the invention, as mRNA polynucleotides, are better designed to produce the appropriate protein conformation on translation as the NAVs co-opt natural cellular machinery. Unlike traditional vaccines which are manufactured ex vivo and may trigger unwanted cellular responses, the NAVs are presented to the cellular system in a more native fashion. Adding to the superior effects may also involve the formulations utilized which may neither serve to shield nor traffic the NAVs.

According to the present invention, NAVs represent a tailored active vaccine that not only can prevent infection but can limit transmission of influenza.

In some embodiments, the NAVs may be used to prevent pandemic influenza by reacting to emerging new strains with the very rapid NAV-based vaccine production process. In some embodiments, new NAV for treating or prophylactically preventing influenza outbreaks, including for emerging strains (e.g., H10N8), may be produced in less than six weeks, from the time of antigen identification to available vaccine.

In some embodiments a single injection of a single antigen encoding NAV polynucleotide may provide protection for an entire flu season.

The polynucleotides of the NAVs of the invention are not self-replicating RNA. Self-replicating RNA have been described, for instance in US Pub. No. US20110300205 and International Pub. No. WO2011005799 and WO2013055905, the contents of each of which are herein incorporated by reference in their entirety.

In one embodiment, the polynucleotides of the NAVs of the invention may encode amphipathic and/or immunogenic amphipathic peptides.

In on embodiment, a formulation of the polynucleotides of the NAVs of the invention may further comprise an amphipathic and/or immunogenic amphipathic peptide. As a non-limiting example, the polynucleotides comprising an amphipathic and/or immunogenic amphipathic peptide may be formulated as described in US. Pub. No. US20110250237 and International Pub. Nos. WO2010009277 and WO2010009065; each of which is herein incorporated by reference in their entirety.

In one embodiment, the polynucleotides of the NAVs of the invention may be immunostimulatory. As a non-limiting example, the polynucleotides may encode all or a part of a positive-sense or a negative-sense stranded RNA virus genome (see International Pub No. WO2012092569 and US Pub No. US20120177701, each of which is herein incorporated by reference in their entirety). In another non-limiting example, the immunostimultory polynucleotides of the present invention may be formulated with an excipient for administration as described herein and/or known in the art (see International Pub No. WO2012068295 and US Pub No. US20120213812, each of which is herein incorporated by reference in their entirety). The polynucleotides may further comprise a sequence region encoding a cytokine that promotes the immune response, such as a monokine, lymphokine, interleukin or chemokine, such as IL-1, IL-2, IL-3, IL-4, IL-5, IL-6, IL-7, IL-8, IL-9, IL-10, IL-12, INF-α, INF-γ, GM-CFS, LT-α, or growth factors such as hGH.

In one embodiment, the response of the vaccine formulated by the methods described herein may be enhanced by the addition of various compounds to induce the therapeutic effect. As a non-limiting example, the vaccine formulation may include a MHC II binding peptide or a peptide having a similar sequence to a MHC II binding peptide (see International Pub Nos. WO2012027365, WO2011031298 and US Pub No. US20120070493, US20110110965, each of which is herein incorporated by reference in their entirety). As another example, the vaccine formulations may comprise modified nicotinic compounds which may generate an antibody response to nicotine residue in a subject (see International Pub No. WO2012061717 and US Pub No. US20120114677, each of which is herein incorporated by reference in their entirety).

In one embodiment, the effective amount of the polynucleotides of the NAVs of the invention provided to a cell, a tissue or a subject may be enough for immune prophylaxis.

In one embodiment, the polynucleotides of the NAVs of the invention may be administrated with other prophylactic or therapeutic compounds. As a non-limiting example, the prophylactic or therapeutic compound may be an adjuvant or a booster. As used herein, when referring to a prophylactic composition, such as a vaccine, the term “booster” refers to an extra administration of the prophylactic composition. A booster (or booster vaccine) may be given after an earlier administration of the prophylactic composition. The time of administration between the initial administration of the prophylactic composition and the booster may be, but is not limited to, 1 minute, 2 minutes, 3 minutes, 4 minutes, 5 minutes, 6 minutes, 7 minutes, 8 minutes, 9 minutes, 10 minutes, 15 minutes, 20 minutes 35 minutes, 40 minutes, 45 minutes, 50 minutes, 55 minutes, 1 hour, 2 hours, 3 hours, 4 hours, 5 hours, 6 hours, 7 hours, 8 hours, 9 hours, 10 hours, 11 hours, 12 hours, 13 hours, 14 hours, 15 hours, 16 hours, 17 hours, 18 hours, 19 hours, 20 hours, 21 hours, 22 hours, 23 hours, 1 day, 36 hours, 2 days, 3 days, 4 days, 5 days, 6 days, 1 week, 10 days, 2 weeks, 3 weeks, 1 month, 2 months, 3 months, 4 months, 5 months, 6 months, 7 months, 8 months, 9 months, 10 months, 11 months, 1 year, 18 months, 2 years, 3 years, 4 years, 5 years, 6 years, 7 years, 8 years, 9 years, 10 years, 11 years, 12 years, 13 years, 14 years, 15 years, 16 years, 17 years, 18 years, 19 years, 20 years, 25 years, 30 years, 35 years, 40 years, 45 years, 50 years, 55 years, 60 years, 65 years, 70 years, 75 years, 80 years, 85 years, 90 years, 95 years or more than 99 years.

In one embodiment, the polynucleotides of the NAVs of the invention may be administered intranasally similar to the administration of live vaccines. In another aspect the polynucleotide may be administered intramuscularly or intradermally similarly to the administration of inactivated vaccines known in the art.

In one embodiment, the NAVs of the invention may be used to protect against and/or prevent the transmission of an emerging or engineered threat which may be known or unknown.

In another embodiment, the NAVs may be formulated by the methods described herein. In one aspect, the formulation may comprise a NAV or polynucleotide which can have a therapeutic and/or prophylactic effect on more than one disease, disorder or condition. As a non-limiting example, the formulation may comprise polynucleotides encoding an antigen, including but not limited to a protein from an infectious agent such as a viral protein, a parasite protein or a bacterial protein.

In addition, the NAV antibodies of the present invention may be used for research in many applications, such as, but not limited to, identifying and locating intracellular and extracellular proteins, protein interaction, signal pathways and cell biology.

In another embodiment, the NAV may be used in to reduce the risk or inhibit the infection of influenza viruses such as, but not limited to, the highly pathogenic avian influenza virus (such as, but not limited to, H5N1 subtype) infection and human influenza virus (such as, but not limited to, H1N1 subtype and H3N2 subtype) infection. The polynucleotide described herein which may encode any of the protein sequences described in U.S. Pat. No. 8,470,771, the contents of which are herein incorporated by reference in its entirety, may be used in the treatment or to reduce the risk of an influenza infection.

In one embodiment, the NAV may be used to as a vaccine or modulating the immune response against a protein produced by a parasite. Bergmann-Leitner et al. in U.S. Pat. No. 8,470,560, the contents of which are herein incorporated by reference in its entirety, describe a DNA vaccine against the circumsporozoite protein (CSP) of malaria parasites. As a non-limiting example, the polynucleotide may encode the CR2 binding motif of C3d and may be used a vaccine or therapeutic to modulate the immune system against the CSP of malaria parasites.

In one embodiment, the NAV may be used as a vaccine and may further comprise an adjuvant which may enable the vaccine to elicit a higher immune response. As a non-limiting example, the adjuvant could be a sub-micron oil-in-water emulsion which can elicit a higher immune response in human pediatric populations (see e.g., the adjuvanted vaccines described in US Patent Publication No. US20120027813 and U.S. Pat. No. 8,506,966, the contents of each of which are herein incorporated by reference in its entirety).

II. Infectious Agents and Antigens

NAVs of the present invention may be used to protect, treat or cure infection arising from contact with an infectious agent, e.g., microorganism. Infectious agents include bacteria, viruses, fungi, protozoa and parasites.

A. Managing Infection

In one embodiment, provided are methods for treating or preventing a microbial infection (e.g., a bacterial infection) and/or a disease, disorder, or condition associated with a microbial or viral infection, or a symptom thereof, in a subject, by administering a NAV comprising one or more polynucleotide encoding an anti-microbial polypeptide. The administration may be in combination with an anti-microbial agent (e.g., an anti-bacterial agent), e.g., an anti-microbial polypeptide or a small molecule anti-microbial compound described herein. The anti-microbial agents include, but are not limited to, anti-bacterial agents, anti-viral agents, anti-fungal agents, anti-protozoal agents, anti-parasitic agents, and anti-prion agents.

Conditions Associated with Bacterial Infection

Diseases, disorders, or conditions which may be associated with bacterial infections which may be treated using the NAVs of the invention include, but are not limited to one or more of the following: abscesses, actinomycosis, acute prostatitis, Aeromonas hydrophila, annual ryegrass toxicity, anthrax, bacillary peliosis, bacteremia, bacterial gastroenteritis, bacterial meningitis, bacterial pneumonia, bacterial vaginosis, bacterium-related cutaneous conditions, bartonellosis. BCG-oma, botryomycosis, botulism, Brazilian purpuric fever, Brodie abscess, brucellosis, Buruli ulcer, campylobacteriosis, caries, Carrion's disease, cat scratch disease, cellulitis, chlamydia infection, cholera, chronic bacterial prostatitis, chronic recurrent multifocal osteomyelitis, clostridial necrotizing enteritis, combined periodontic-endodontic lesions, contagious bovine pleuropneumonia, diphtheria, diphtheritic stomatitis, ehrlichiosis, erysipelas, piglottitis, erysipelas, Fitz-Hugh-Curtis syndrome, flea-borne spotted fever, foot rot (infectious pododermatitis), Garre's sclerosing osteomyelitis, Gonorrhea, Granuloma inguinale, human granulocytic anaplasmosis, human monocytotropic ehrlichiosis, hundred days' cough, impetigo, late congenital syphilitic oculopathy, legionellosis. Lemierre's syndrome, leprosy (Hansen's Disease), leptospirosis, listeriosis, Lyme disease, lymphadenitis, melioidosis, meningococcal disease, meningococcal septicaemia, methicillin-resistant Staphylococcus aureus (MRSA) infection, Mycobacterium avium-intracellulare (MAI), mycoplasma pneumonia, necrotizing fasciitis, nocardiosis, noma (cancrum oris or gangrenous stomatitis), omphalitis, orbital cellulitis, osteomyelitis, overwhelming post-splenectomy infection (OPSI), ovine brucellosis, pasteurellosis, periorbital cellulitis, pertussis (whooping cough), plague, pneumococcal pneumonia, Pott disease, proctitis, pseudomonas infection, psittacosis, pyaemia, pyomyositis, Q fever, relapsing fever (typhinia), rheumatic fever, Rocky Mountain spotted fever (RMSF), rickettsiosis, salmonellosis, scarlet fever, sepsis, serratia infection, shigellosis, southern tick-associated rash illness, staphylococcal scalded skin syndrome, streptococcal pharyngitis, swimming pool granuloma, swine brucellosis, syphilis, syphilitic aortitis, tetanus, toxic shock syndrome (TSS), trachoma, trench fever, tropical ulcer, tuberculosis, tularemia, typhoid fever, typhus, urogenital tuberculosis, urinary tract infections, vancomycin-resistant Staphylococcus aureus infection, Waterhouse-Friderichsen syndrome, pseudotuberculosis (Yersinia) disease, and yersiniosis

Bacterial Pathogens

The bacterium described herein can be a Gram-positive bacterium or a Gram-negative bacterium. Bacterial pathogens include, but are not limited to, Acinetobacter baumannii, Bacillus anthracis, Bacillus subtilis, Bordetella pertussis, Borrelia burgdorferi, Brucella abortus, Brucella canis, Brucella melitensis, Brucella suis, Campylobacter jejuni, Chlamydia pneumoniae, Chlamydia trachomatis, Chlamydophila psittaci, Clostridium botulinum, Clostridium dilficile, Clostridium perfringens, Clostridium tetani, coagulase Negative Staphylococcus, Corynebacterium diphtheria, Enterococcus faecalis, Enterococcus faecium, Escherichia coli, enterotoxigenic Escherichia coli (ETEC), enteropathogenic E. coli, E. coli O157:H7, Enterobacter sp., Francisella tularensis, Haemophilus influenzae, Helicobacter pylori, Klebsiella pneumoniae, Legionella pneumophila, Leptospira interrogans, Listeria monocytogenes, Moraxella catarralis, Mycobacterium leprae, Mycobacterium tuberculosis, Mycoplasma pneumoniae, Neisseria gonorrhoeae, Neisseria meningitides, Preteus mirabilis, Proteus sps., Pseudomonas aeruginosa, Rickettsia rickettsii, Salmonella typhi, Salmonella typhimurium, Serratia marcesens, Shigella flexneri, Shigella sonnei, Staphylococcus aureus, Staphylococcus epidermidis, Staphylococcus saprophyticus, Streptococcus agalactiae, Streptococcus mutans, Streptococcus pneumoniae, Streptococcus pyogenes, Treponema pallidum, Vibrio cholerae, and Yersinia pestis.

Bacterial pathogens may also include bacteria that cause resistant bacterial infections, for example, clindamycin-resistant Clostridium difficile, fluoroquinolon-resistant Clostridium difficile, methicillin-resistant Staphylococcus aureus (MRSA), multidrug-resistant Enterococcus faecalis, multidrug-resistant Enterococcus faecium, multidrug-resistance Pseudomonas aeruginosa, multidrug-resistant Acinetobacter baumannii, and vancomycin-resistant Staphylococcus aureus (VRSA).

Antibiotic Combinations

In one embodiment, the NAVs of the present invention, e.g., NAVs comprising one or more antigen-encoding polynucleotides of the present invention, may be administered in conjunction with one or more antibiotics.

Antibacterial Agents

Anti-bacterial agents include, but are not limited to, aminoglycosides (e.g., amikacin (AMIKIN®), gentamicin (GARAMYCIN®), kanamycin (KANTREX®), neomycin (MYCIFRADIN®), netilmicin (NETROMYCIN®), tobramycin (NEBCIN®), Paromomycin (HUMATIN®)), ansamycins (e.g., geldanamycin, herbimycin), carbacephem (e.g., loracarbef (LORABID®), Carbapenems (e.g., ertapenem (INVANZ®), doripenem (DORIBAX®), imipenem/cilastatin (PRIMAXIN®), meropenem (MERREM®), cephalosporins (first generation) (e.g., cefadroxil (DURICEF®), cefazolin (ANCEF®), cefalotin or cefalothin (KEFLIN®), cefalexin (KEFLEX®), cephalosporins (second generation) (e.g., cefaclor (CECLOR®), cefamandole (MANDOL®), cefoxitin (MEFOXIN®), cefprozil (CEFZIL®), cefuroxime (CEFTIN®, ZINNAT®)), cephalosporins (third generation) (e.g., cefixime (SUPRAX®), cefdinir (OMNICEF®, CEFDIEL®), cefditoren (SPECTRACEF®), cefoperazone (CEFOBID®), cefotaxime (CLAFORAN®), cefpodoxime (VANTIN®), ceftazidime (FORTAZ®), ceftibuten (CEDAX®), ceftizoxime (CEFIZOX®), ceftriaxone (ROCEPHIN®)), cephalosporins (fourth generation) (e.g., cefepime (MAXIPIME®)), cephalosporins (fifth generation) (e.g., ceftobiprole (ZEFTERA®)), glycopeptides (e.g., teicoplanin (TARGOCID®), vancomycin (VANCOCIN®), telavancin (VIBATIV®)), lincosamides (e.g., clindamycin (CLEOCIN®), lincomycin (LINCOCIN®)), lipopeptide (e.g., daptomycin (CUBICIN®)), macrolides (e.g., azithromycin (ZITHROMAX®, SUMAMED®, ZITROCIN®), clarithromycin (BIAXIN®), dirithromycin (DYNABAC®), erythromycin (ERYTHOCIN®, ERYTHROPED®), roxithromycin, troleandomycin (TAO®), telithromycin (KETEK®), spectinomycin (TROBICIN®)), monobactams (e.g., aztreonam (AZACTAM®)), nitrofurans (e.g., furazolidone (FUROXONE®), nitmfurantoin (MACRODANTIN®, MACROBID®)), penicillins (e.g., amoxicillin (NOVAMOX®, AMOXIL®), ampicillin (PRINCIPEN®), azlocillin, carbenicillin (GEOCILLIN®), cloxacillin (TEGOPEN®), dicloxacillin (DYNAPEN®), flucloxacillin (FLOXAPEN®), mezlocillin (MEZLIN®), methicillin (STAPHCILLIN®), nafcillin (UNIPEN®), oxacillin (PROSTAPHLIN®), penicillin G (PENTIDS®), penicillin V (PEN-VEE-K®), piperacillin (PIPRACIL®), temocillin (NEGABAN®), ticarcillin (TICAR®)), penicillin combinations (e.g., amoxicillin/clavulanate (AUGMENTIN®), ampicillin/sulbactam (UNASYN®), piperacillin/tazobactam (ZOSYN®), ticarcillin/clavulanate (TIMENTIN®)), polypeptides (e.g., bacitracin, colistin (COLY-MYCIN-S®), polymyxin B, quinolones (e.g., ciprofloxacin (CIPRO®, CIPROXIN®, CIPROBAY®), enoxacin (PENETREX®), gatifloxacin (TEQUIN®), levofloxacin (LEVAQUIN®), lomefloxacin (MAXAQUIN®), moxifloxacin (AVELOX®), nalidixic acid (NEGGRAM®), norfloxacin (NOROXIN®), ofloxacin (FLOXIN®, OCUFLOX®), trovafloxacin (TROVAN®), grepafloxacin (RAXAR®), sparfloxacin (ZAGAM®), temafloxacin (OMNIFLOX®)), sulfonamides (e.g., mafenide (SULFAMYLON®), sulfonamidochrysoidine (PRONTOSIL®), sulfacetamide (SULAMYD®, BLEPH-10®), sulfadiazine (MICRO-SULFON®), silver sulfadiazine (SILVADENE®), sulfamethizole (THIOSULFIL FORTE®), sulfamethoxazole (GANTANOL®), sulfanilimide, sulfasalazine (AZULFIDINE®), sulfisoxazole (GANTRISIN®), trimethoprim (PROLOPRIM®), TRIMPEX®), trimethoprim-sulfamethoxazole (co-trimoxazole) (TMP-SMX) (BACTRIM®, SEPTRA®)), tetracyclines (e.g., demeclocycline (DECLOMYCIN®), doxycycline (VIBRAMYCIN®), minocycline (MINOCIN®), oxytetracycline (TERRAMYCIN®), tetracycline (SUMYCIN®, ACHROMYCIN® V, STECLIN®)), drugs against mycobacteria (e.g., clofazimine (LAMPRENE®), dapsone (AVLOSULFON®), capreomycin (CAPASTAT®), cycloserine (SEROMYCIN®), ethambutol (MYAMBUTOL®), ethionamide (TRECATOR®), isoniazid (I.N.H.®), pyrazinamide (ALDINAMIDE®), rifampin (RIFADIN®, RIMACTANE®), rifabutin (MYCOBUTIN®), rifapentine (PRIFTIN®), streptomycin), and others (e.g., arsphenamine (SALVARSAN®), chloramphenicol (CHLOROMYCETIN®), fosfomycin (MONUROL®), fusidic acid (FUCIDIN®), linezolid (ZYVOX®), metronidazole (FLAGYL®), mupirocin (BACTROBAN®), platensimycin, quinupristin/dalfopristin (SYNERCID®), rifaximin (XIFAXAN®), thiamphenicol, tigecycline (TIGACYL®), tinidazole (TINDAMAX®, FASIGYN®)).

Conditions Associated with Viral Infection

In another embodiment, provided are methods for treating or preventing a viral infection and/or a disease, disorder, or condition associated with a viral infection, or a symptom thereof, in a subject, by administering aRNAV comprising one or more polynucleotides encoding an anti-viral polypeptide, e.g., an anti-viral polypeptide described herein in combination with an anti-viral agent, e.g., an anti-viral polypeptide or a small molecule anti-viral agent described herein.

Diseases, disorders, or conditions associated with viral infections which may be treated using the NAVs of the invention include, but are not limited to, acute febrile pharyngitis, pharyngoconjunctival fever, epidemic keratoconjunctivitis, infantile gastroenteritis, Coxsackie infections, infectious mononucleosis, Burkitt lymphoma, acute hepatitis, chronic hepatitis, hepatic cirrhosis, hepatocellular carcinoma, primary HSV-1 infection (e.g., gingivostomatitis in children, tonsillitis and pharyngitis in adults, keratoconjunctivitis), latent HSV-1 infection (e.g., herpes labialis and cold sores), primary HSV-2 infection, latent HSV-2 infection, aseptic meningitis, infectious mononucleosis, Cytomegalic inclusion disease, Kaposi sarcoma, multicentric Castleman disease, primary effusion lymphoma, AIDS, influenza, Reye syndrome, measles, postinfectious encephalomyelitis, Mumps, hyperplastic epithelial lesions (e.g., common, flat, plantar and anogenital warts, laryngeal papillomas, epidermodysplasia verruciformis), cervical carcinoma, squamous cell carcinomas, croup, pneumonia, bronchiolitis, common cold, Poliomyelitis, Rabies, bronchiolitis, pneumonia, influenza-like syndrome, severe bronchiolitis with pneumonia, German measles, congenital rubella, Varicella, and herpes zoster.

Viral Pathogens

Examples of viral infectious agents include, but are not limited to, adenovirus; Herpes simplex, type 1; Herpes simplex, type 2; encephalitis virus, papillomavirus, Varicella-zoster virus; Epstein-barr virus; Human cytomegalovirus; Human herpesvirus, type 8; Human papillomavirus; BK virus; JC virus; Smallpox; polio virus, Hepatitis B virus; Human bocavirus; Parvovirus B19; Human astrovirus; Norwalk virus; coxsackievirus; hepatitis A virus; poliovirus; rhinovirus; Severe acute respiratory syndrome virus; Hepatitis C virus; yellow fever virus; dengue virus; West Nile virus: Rubella virus: Hepatitis E virus; Human immunodeficiency virus (HIV); Influenza virus, type A or B; Guanarito virus; Junin virus; Lassa virus; Machupo virus; Sabis virus; Crimean-Congo hemorrhagic fever virus; Ebola virus; Marburg virus; Measles virus; Mumps virus; Parainfluenza virus; Respiratory syncytial virus; Human metapneumovirus; Hendra virus; Nipah virus; Rabies virus; Hepatitis D; Rotavirus; Orbivirus; Coltivirus; Hantavirus, Middle East Respiratory Coronavirus; Chikungunya virus or Banna virus.

Viral pathogens may also include viruses that cause resistant viral infections.

Antiviral Agents

Exemplary anti-viral agents include, but are not limited to, abacavir (ZIAGEN®), abacavir/lamivudine/zidovudine (Trizivir®), aciclovir or acyclovir (CYCLOVIR®, HERPEX®. ACIVIR®, ACIVIRAX®, ZOVIRAX®, ZOVIR®), adefovir (Preveon®, Hepsera®), amantadine (SYMMETREL®), amprenavir (AGENERASE®), ampligen, arbidol, atazanavir (REYATAZ®), boceprevir, cidofovir, darunavir (PREZISTA®), delavirdine (RESCRIPTOR®), didanosine (VIDEX®), docosanol (ABREVA®), edoxudine, efavirenz (SUSTIVA®, STOCRIN®), emtricitabine (EMTRIVA®), emtricitabine/tenofovir/efavirenz (ATRIPLA®), enfuvirtide (FUZEON®), entecavir (BARACLUDE®, ENNAVIR®), famciclovir (FAMVIR®), fomivirsen (VITRAVENE®), fosamprenavir (LEXIVA®, TELZIR®), foscarnet (FOSCAVIR®), fosfonet, ganciclovir (CYTOVENE®, CYMEVENE®, VITRASERT®), GS 9137 (ELVITEGRAVIR®), imiquimod (ALDARA®, ZYCLARA®, BESELNA®), indinavir (CRIXIVAN®), inosine, inosine pranobex (IMUNOVIR®), interferon type 1, interferon type 11, interferon type III, kutapressin (NEXAVIR®), lamivudine (ZEFFIX®, HEPTOVIR®, EPIVIR®), lamivudinelzidovudine (COMBIVIR®), lopinavir, loviride, maraviroc (SELZENTRY®, CELSENTRI®), methisazone, MK-2048, moroxydine, nelfinavir (VIRACEPT®), nevirapine (VIRAMUNE®), oseltamivir (TAMIFLIU®), peginterferon alfa-2a (PEGASYS®), penciclovir (DENAVIR®), peramivir, pleconaril, podophyllotoxin (CONDYLOX®), raltegravir (ISENTRESS®), ribavirin (COPEGUs®, REBETOL®, RIBASPHERE®, VILONA® AND VIRAZOLE®), rimantadine (FLUMADINE®), ritonavir (NORVIR®), pyramidine, saquinavir (INVIRASE®, FORTOVASE®), stavudine, tea tree oil (melaleuca oil), tenofovir (VIREAD®), tenofovir/emtricitabine (TRUVADA®), tipranavir (APTIVUS®), trifluridine (VIROPTIC®), tromantadine (ViRU-MERZ®), valaciclovir (VALTREX®), valganciclovir (VALCYTE®), vicriviroc, vidarabine, viramidine, zalcitabine, zanamivir (RELENZA®), and zidovudine (azidothymidine (AZT), RETROVIR®, RETROVIS®).

Conditions Associated with Fungal Infections

Diseases, disorders, or conditions associated with fungal infections which may be treated using the NAVs of the invention include, but are not limited to, aspergilloses, blastomycosis, candidasis, coccidioidomycosis, cryptococcosis, histoplasmosis, mycetomas, paracoccidioidomycosis, and tinea pedis. Furthermore, persons with immuno-deficiencies are particularly susceptible to disease by fungal genera such as Aspergillus, Candida, Cryptoccocus, Histoplasma, and Pneumocystis. Other fungi can attack eyes, nails, hair, and especially skin, the so-called dermatophytic fungi and keratinophilic fungi, and cause a variety of conditions, of which ringworms such as athlete's foot are common. Fungal spores are also a major cause of allergies, and a wide range of fungi from different taxonomic groups can evoke allergic reactions in some people.

Fungal Pathogens

Fungal pathogens include, but are not limited to, Ascomycota (e.g., Fusarium oxysporum, Pneumocystis jirovecii, Aspergillus spp., Coccidioides immitis/posadasii, Candida albicans), Basidiomycota (e.g., Filobasidiella neoformans, Trichosporon), Microsporidia (e.g., Encephalitozoon cuniculi, Enterocytozoon bieneusi), and Mucoromycotina (e.g., Mucor circinelloides, Rhizopus oryzae, Lichtheimia corymbifera).

Anti-Fungal Agents

Exemplary anti-fungal agents include, but are not limited to, polyene antifungals (e.g., natamycin, rimocidin, filipin, nystatin, amphotericin B, candicin, hamycin), imidazole antifungals (e.g., miconazole (MICATIN®, DAKTARIN®), ketoconazole (NIZORAL®, FUNGORAL®, SEBIZOLE®), clotrimazole (LOTRIMIN®, LOTRIMIN® AF. CANESTEN®), econazole, omoconazole, bifonazole, butoconazole, fenticonazole, isoconazole, oxiconazole, sertaconazole (ERTACZO®), sulconazole, tioconazole), triazole antifungals (e.g., albaconazole fluconazole, itraconazole, isavuconazole, ravuconazole, posaconazole, voriconazole, terconazole), thiazole antifungals (e.g., abafungin), allylamines (e.g., terbinatine (LAMISIL®), naftifine (NAFTIN®), butenafine (LOTRIMIN® Ultra)), echinocandins (e.g., anidulafungin, caspofungin, micafungin), and others (e.g., polygodial, benzoic acid, ciclopirox, tolnaftate (TINACTIN®, DESENEX®, AFTATE®), undecylenic acid, flucytosine or 5-fluorocytosine, griseofulvin, haloprogin, sodium bicarbonate, allicin).

Conditions Associated with Protozoal Infection

Diseases, disorders, or conditions associated with protozoal infections which may be treated using the NAVs of the invention include, but are not limited to, amoebiasis, giardiasis, trichomoniasis, African Sleeping Sickness, American Sleeping Sickness, leishmaniasis (Kala-Azar), balantidiasis, toxoplasmosis, malaria, Acanthamoeba keratitis, and babesiosis.

Protozoan Pathogens

Protozoal pathogens include, but are not limited to, Entamoeba histolytica, Giardia lambila, Trichomonas vaginalis, Trypanosoma brucei. T. cruzi, Leishmania donovani, Balantidium coli, Toxoplasma gondii, Plasmodium spp., and Babesia microti.

Anti-Protozoan Agents

Exemplary anti-protozoal agents include, but are not limited to, eflornithine, furazolidone (FUROXONE®, DEPENDAL-M®), melarsoprol, metronidazole (FLAGYL®), omidazole, paromomycin sulfate (HUMATIN®), pentamidine, pyrimethamine (DARAPRIM®), and tinidazole (TINDAMAX®, FASIGYN®).

Conditions Associated with Parasitic Infection

Diseases, disorders, or conditions associated with parasitic infections which may be treated using the NAVs of the invention include, but are not limited to, Acanthamoeba keratitis, amoebiasis, ascariasis, babesiosis, balantidiasis, baylisascariasis, chagas disease, clonorchiasis, cochliomyia, cryptosporidiosis, diphyllobothriasis, dracunculiasis, echinococcosis, elephantiasis, enterobiasis, fascioliasis, fasciolopsiasis, filariasis, giardiasis, gnathostomiasis, hymenolepiasis, isosporiasis, katayama fever, leishmaniasis, lyme disease, malaria, metagonimiasis, myiasis, onchocerciasis, pediculosis, scabies, schistosomiasis, sleeping sickness, strongyloidiasis, taeniasis, toxocariasis, toxoplasmosis, trichinosis, and trichuriasis.

Parasitic Pathogens

Parasitic pathogens include, but are not limited to, Acanthamoeba, Anisakis, Ascaris lumbricoides, botfly, Balantidium coli, bedbug, Cestoda, chiggers, Cochliomyia hominivorax, Entamoeba histolytica, Fasciola hepatica, Giardia lamblia, hookworm, Leishmania, Linguatula serrata, liver fluke, Loa loa, Paragonimus, pinworm, Plasmodium falciparum, Schistosoma, Strongyloides stercoralis, mite, tapeworm, Toxoplasma gondii, Trypanosoma, whipworm, Wuchereria bancofti.

Anti-Parasitic Agents

Exemplary anti-parasitic agents include, but are not limited to, antinematodes (e.g., mebendazole, pyrantel pamoate, thiabendazole, diethylcarbamazine, ivermectin), anticestodes (e.g., niclosamide, praziquantel, albendazole), antitrematodes (e.g., praziquantel), antiamoebics (e.g., rifampin, amphotericin B), and antiprotozoals (e.g., melarsoprol, eflornithine, metronidazole, tinidazole).

B. Therapeutic Settings and/or Situations

NAVs of the present invention may be utilized in various settings depending on the prevalence of the infection or the degree or level of unmet medical need. Some applications of the NAVs of the invention are outlined in Table 1.

TABLE 1

Infectious Agents by prevalence and Medical Need

Unmet Need (Infectious Agent Target)

Short term

benign
Short term

Long term
morbidity but
Short term mortality;

Prevalence
sequelae
some treatment
no treatment available

Ubiquitous
HPV, HCV,
Dengue,
seasonal and

UTRIs
Chikungunya,
pandemic influenza,

ETEC and GI
MRSA and TB

bacteria and

S. Pneumo PNA

At risk
VZV, Lyme
Noroviruses,

Klebsiella,

populations
and Chlamydia,
HEV,

Pseudomonas,

N. gonorrhea
CMV, HIV and
Rabies and

and HSV
N. meningitis

C. difficile

Rare
—
VEV
toxin-mediated

disease

diseases, hantavirus,

arborviruses such as

JE, WNV and EEE

Certain abbreviations include:

HPV—Human Papillomavirus;

HCV—Hepatitis C Virus;

HEV—Human Enterovirus;

MERS-CoV: Middle East Respiratory Syndrom Corona Virus;

VZV—Varicella-zoster Virus;

MRSA—Methicillin-resistant Staphareus;

TB—tuberculosis;

WNV—West Nile Virus;

VEV—vesicular exanthema virus;

EEE—Eastern equine encephalitis,

JE—Japanese encephalitis,

ETEC—Enterotoxigenic E. coli.

Influenza (Seasonal and Pandemic)

Symptoms of the flu include dry cough, fever, chills, myalgias progressing to respiratory failure and the risk of secondary bacterial infections (e.g., MRSA). Seasonal influenza is ubiquitous and consists of three principal strains (A [H1N1], A [H3N2], and B), which are covered by the annual vaccine. Pandemic flu occurs because the viruses' unique reassortment ability allowing antigenic shift as well as transfer between avian and swine flu strains. One emerging concern in Southeast Asia is the pandemic potential of several new strains. Such pandemic outbreaks have a high mortality rate with few available treatments. Anti-virals only provide symptomatic relief and must be given in the first 48 hours.

While not wishing to be bound by theory, the inventors hypothesize that the NAVs of the invention, as mRNA polynucleotides, are better designed to produce the appropriate protein conformation on translation as the NAVs co-opt natural cellular machinery. Unlike traditional vaccines which are manufactured ex vivo and may trigger unwanted cellular responses, the NAVs are presented to the cellular system in amore native fashion. Adding to the superior effects may also involve the formulations utilized which may either serve to shield or traffic the NAVs.

According to the present invention, NAVs represent a tailored active vaccine that not only can prevent infection but can limit transmission of influenza.

In some embodiments, the NAVs may be used to prevent pandemic influenza by reacting to emerging new strains with the very rapid NAV-based vaccine production process. In some embodiments, new NAV for treating or prophylactically preventing influenza outbreaks, including for emerging strains (e.g., H7N9 and H10N8), may be produced in less than six weeks, from the time of antigen identification to available vaccine.

In some embodiments a single injection of a single antigen encoding NAV polynucleotide may provide protection for an entire flu season.

Influenza: Maintenance of Antigenic Memory

The NAV compositions of the present invention may also be used to maintain or restore antigenic memory in a subject or population as part of a vaccination plan.

With the speed and versatility of the NAV technology of the present invention, it is now possible to create a vaccination plan that spans both temporal and viral strain space.

In one embodiment, NAV compositions may be created which include polynucleotides that encode one or more flu year antigens. As used herein a flu year antigen is an antigen which is selected from a strain of influenza used as a component of a flu vaccine from a particular year. For example, the influenza A strain, A/Port Chalmers/l/1973(H3N2)-like virus, represents one strain component of the Northern Hemisphere vaccine from 1974-1975.

According to the present invention, a vaccination scheme or plan is developed which allows for not only ongoing vaccination in the current year but antigenic memory booster vaccinations across years, strains, or groups thereof to establish and maintain antigenic memory in a population. In this manner, a population is less likely to succumb to any pandemic or outbreak involving recurrence of older strains or the appearance of antigens from older strains.

Any combination of prior vaccine component strains utilized to create or design an antigenic memory booster vaccine is referred to here as a reference set.

In one embodiment, NAVs which are antigenic memory booster vaccines are administered to boost antigenic memory across a time period of 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 35, 40, 45, 50 or more years.

In one embodiment, NAVs which are antigenic memory booster vaccines are administered to boost antigenic memory for alternating historic years including every other year from the past vaccine component strains relative to a current year. In some embodiments the selection of the vaccine components can be from every 3^rd, 4^th, 5^th, 6^th, 7^th, 8^th, 9^th, 10^thor more years.

In one embodiment. NAVs which are antigenic memory booster vaccines are administered to boost antigenic memory over ten year periods.

In some embodiments NAVs which are antigenic memory booster vaccines are administered to boost antigenic memory and are selected from a number of influenza type A strains as a first selection combined with a selection from a number of influenza type B strains or other strains listed herein. The number of selections of type A or type B may be independently, 1, 2, 1, 4, 5, 6, 7, 8, 9, 10 or more.

In all cases, the antigenic memory booster vaccine strains for antigen encoding in the NAVs may be selected from either the Northern or Southern hemisphere vaccine components independently.

In some embodiments, the NAV booster vaccine may be used in a population either once or periodically to create herd immunity. Such immunity is present when greater than 30% of a population is protected.

The components or strains of influenza which may be utilized in the antigenic memory booster vaccines include, but are not limited to, those in Tables 2-5.

TABLE 2

Influenza vaccine components by year

additional

Northern

B-strain

hemisphere
H1N1
H3N2
B-strain
for QIV

1974-1975
N/A
A/Port
B/HongKong/05/
N/A

Chalmers/1/1973
1972-like virus

(H3N2)-like virus

1975-1976
A/Scotland/840/74-
A/Port
B/HongKong/05/
N/A

like virus
Chalmers/1/1973
1972-like virus

H1N1
(H3N2)-like virus

1976-1977
N/A
A/Victoria/3/75
B/HongKong/05/
N/A

(H3N2)-like virus
1972-like virus

1977-1978
N/A
A/Victoria/3/75
B/HongKong/05/
N/A

(H3N2)-like virus
1972-like virus

1978-1979
A/USSR/90/77
A/Texas/1/77
B/HongKong/05/
N/A

(H1N1)-like virus
(H3N2)-like virus
1972-like virus

1979-1980
A/USSR/90/77
A/Texas/1/77
N/A
N/A

(H1N1)-like virus
(H3N2)-like virus

1980-1981
A/Brazil/11/78
A/Bangkok/01/1979
B/Singapore/222/
N/A

(H1N1)-like virus
(H3N2)-like virus
79-like virus

1981-1982
A/Brazil/11/78
A/Bangkok/01/1979
B/Singapore/222/
N/A

(H1N1)-like virus
(H3N2)-like virus
79-like virus

1982-1983
A/Brazil/11/78
A/Bangkok/01/1979
B/Singapore/222/
N/A

(H1N1)-like virus
(H3N2)-like virus
79-like virus

1983-1984
A/Brazil/11/78
A/Philippines/2/82
B/Singapore/222/
N/A

(H1N1)-like virus
(H3N2)-like virus
79-like virus

1984-1985
A/Chile/1/83
A/Philippines/2/82
B/USSR/100/83-
N/A

(H1N1)-like virus
(H3N2)-like virus
like virus

1985-1986
A/Chile/1/83
A/Philippines/2/82
B/USSR/100/83-
N/A

(H1N1)-like virus
(H3N2)-like virus
like virus

1986-1987
A/Chile/1/83
A/Christchurch/4/
B/Ann Arbor/1/86-
N/A

(H1N1)-like virus
1985(H3N2)-like
like virus

virus and

A/Mississippi/1/85

(H3N2)-like virus

1987-1988
A/Singapore/6/1986
A/Leningrad/360/
N/A
N/A

(H1N1)-like virus
1986(H3N2)-like

strain

1988-1989
A/Singapore/6/1986
A/Sichuan/02/87
B/Beijing/1/87-like
N/A

(H1N1)-like virus
(H3N2)-like virus
rivus

1989-1990
A/Singapore/6/1986
A/Shanghai/11/87
B/Yamagata/16/88-
N/A

(H1N1)-like virus
(H3N2)-like virus
like virus

1990-1991
A/Singapore/6/1986
A/Guizhou/54/89
B/Yamagata/16/88-
N/A

(H1N1)-like virus
(H3N2)-like virus
like virus

1991-1992
A/Singapore/6/1986
A/Beijing/353/89
B/Yamagata/16/88-
N/A

(H1N1)-like virus
(H3N2)-like virus
like virus

1992-1993
N/A
A/Beijing/353/89
B/Yamagata/16/88-
N/A

(H3N2)-like virus
like virus

1993-1994
A/Singapore/6/1986
A/Beijing/32/92
B/Panama/45/90-
N/A

(H1N1)-like virus
(H3N2)-like virus
like virus

1994-1995
A/Singapore/6/1986
A/Shangdong/9/93
B/Panama/45/90-
N/A

(H1N1)-like virus
(H3N2)-like virus
like virus

1995-1996
A/Singapore/6/1986
A/Johannesburg/33/
B/Beijing/184/93-
N/A

(H1N1)-like virus
94(H3N2)-like
virus like virus

1996-1997
A/Singapore/6/1986
A/Wuhan/359/95
B/Beijing/184/93-
N/A

(H1N1)-like virus
(H3N2)-like virus
like virus

1997-1998
A/Bayern/7/95
A/Wuhan/359/95
B/Beijing/184/93-
N/A

(H1N1)-like virus
(H3N2)-like virus
like virus

TABLE 3

Influenza vaccine components by year-Southern Hemisphere

additional

Southern

B-strain for

Hemisphere
H1N1
H3N2
B-strain
QIV

1975
N/A
A/Port
B/HongKong/05/
N/A

Chalmers/1/1973
1972-like virus

(H3N2)-like virus

1976
A/Scotland/840/74-
A/Port
B/HongKong/05/
N/A

like virus
Chalmers/1/1973
1972-like virus

(H1N1)
(H3N2)-like virus

1977
N/A
A/Victoria/3/75
B/HongKong/05/
N/A

(H3N2)-like virus
1972-like virus

1978
N/A
A/Victoria/3/75
B/HongKong/05/
N/A

N(H32)-like virus
1972-like virus

1979
A/USSR/90/77
A/Texas/1/77
B/HongKong/05/
N/A

(H1N1)-like virus
(H3N2)-like virus
1972-like virus

1980
A/USSR/90/77
A/Texas/1/77
N/A
N/A

(H1N1)-like virus
(H3N2)-like virus

1981
A/Brazil/11/78
A/Bangkok/01/1979
B/Singapore/222/
N/A

(H1N1)-like virus
(H3N2)-like virus
79-like virus

1982
A/Brazil/11/78
A/Bangkok/01/1979
B/Singapore/222/
N/A

(H1N1)-like virus
(H3N2)-like virus
79-like virus

1983
A/Brazil/11/78
A/Bangkok/01/1979
B/Singapore/222/
N/A

(H1N1)-like virus
(H3N2)-like virus
79-like virus

1984
A/Brazi1/11/78
A/Philippines/2/82
B/Singapore/222/
N/A

(H1N1)-like virus
(H3N2)-like virus
79-like virus

1985
A/Chile/1/83
A/Philippines/2/82
B/USSR/100/83-
N/A

(H1N1)-like virus
(H3N2)-like virus
like virus

1986
A/Chile/1/83
A/Philippines/2/82
B/USSR/100/83-
N/A

(H1N1)-like virus
(H3N2)-like virus
like virus

1987
A/Chile/1/83
A/Christchurch/4/
B/Ann Arbor/1/86-
N/A

(H1N1)-like virus
1985(H3N2)-like
like virus

virus and

A/Mississippi/1/85

(H3N2)-like virus

1988
A/Singapore/6/1986
A/Leningrad/360/
N/A
N/A

(H1N1)-like virus
1986(H3N2)-like

virus

1989
A/Singapore/6/1986
A/Sichuan/02/87
B/Beijing/1/87-like
N/A

(H1N1)-like virus
(H3N2)-like virus
virus

1990
A/Singapore/6/1986
A/Shanghai/11/87
B/Yamagata/16/88-
N/A

(H1N1)-like virus
(H3N2)-like virus
like virus

1991
A/Singapore/6/1986
A/Guizhou/54/89
B/Yamagata/16/88-
N/A

(H1N1)-like virus
(H3N2)-like virus
like virus

1992
A/Singapore/6/1986
A/Beijing/353/89
B/Yamagata/16/88-
N/A

(H1N1)-like virus
(H3N2)-like virus
like virus

1993
A/Singapore/6/1986
A/Beijing/353/89
B/Yamagata/16/88-
N/A

(H1N1)-like virus
(H3N2)-like virus
like virus

1994
A/Singapore/6/1986
A/Beijing/32/92
B/Panama/45/90-
N/A

(H1N1)-like virus
(H3N2)-like virus
like virus

1995
A/Singapore/6/1986
A/Shangdong/9/93
B/Panama/45/90-
N/A

(H1N1)-like virus
(H3N2)-like virus
like virus

1996
A/Singapore/6/1986
A/Johannesburg/33/
B/Beijing/184/93-
N/A

(H1N1)-like virus
94(H3N2)-like virus
like virus

1997
A/Singapore/6/1986
A/Wuhan/359/95
B/Beijing/184/93-
N/A

(H1N1)-like virus
(H3N2)-like virus
like strain

1998
A/Bayern/7/95
A/Wuhan/359/95
B/Beijing/184/93-
N/A

(H1N1)-like virus
(H3N2)-like virus
like virus

1999
A/Beijing/262/95
A/Sydney/5/97
B/Beijing/184/93-
N/A

(H1N1)-like virus
(H3N2)-like virus
like virus

TABLE 4

Influenza Vaccine components by year-Northern Hemisphere

additional

Northern

B-strain for

hemisphere
H1N1
H3N2
B-strain
QIV

November
A/Beijing/262/95
A/Sydney/5/97
B/Beijing/184/93-
N/A

1998-April
(H1N1)-like virus
(H3N2)-like virus
like virus

1999

November
A/Beijing/262/95
A/Sydney/5/97
B/Beijing/184/93-
N/A

1999-April
(H1N1)-like virus
(H3N2)-like virus
like virus or

2000

B/Shangdong/7/97-

like virus

2000-2001
A/New
A/Moscow/10/99
B/Beijing/184/93-
N/A

Caledonia/20/99
(H3N2)-like virus
like virus

(H1N1)-like virus

2001-2002
A/New
A/Moscow/10/99
B/Sichuan/379/99-
N/A

Caledonia/20/99
(H3N2)-like virus
like virus

(H1N1)-like virus

2002-2003
A/New
A/Moscow/10/99
B/Hong
N/A

Caledonia/20/99
(H3N2)-like virus
Kong/330/2001-

(H1N1)-like virus

like virus

2003-2004
A/New
A/Moscow/10/99
B/Hong
N/A

Caledonia/20/99
(H3N2)-like virus
Kong/330/2001

(H1N1)-like virus

like virus

2004-2005
A/New
A/Fujian/411/2002
B/Shanghai/361/
N/A

Caledonia/20/99
(H3N2)-like virus
2002-like virus

(H1N1)-like virus

2005-2006
A/New
A/California/7/2004
B/Shanghai/361/
N/A

Caledonia/20/99
(H3N2)-like virus
2002-like virus

(H1N1)-like virus

2006-2007
A/New
A/Wisconsin/67/2005
B/Malaysia/2506/
N/A

Caledonia/20/99
(H3N2)-like virus
2004-like virus

(H1N1)-like

2007-2008
A/Solomon
A/Wisconsin/67/2005
B/Malaysia/2506/
N/A

Islands/3/2006
(H3N2)-like virus
2004-like virus

(H1N1)-like virus

2008-2009
A/Brisbane/59/2007
A/Brisbane/10/2007
B/Florida/4/2006-
N/A

(H1N1)-like virus
(H3N2)-like virus
like virus

2009-2010
A/Brisbane/59/2007
A/Brisbane/10/2007
B/Brisbane/60/
N/A

(H1N1)-like virus
(H3N2)-like virus
2008-like virus

2010-2011
A/California/7/2009
A/Perth/16/2009
B/Brisbane/60/
N/A

(H1N1)-like virus
(H3N2)-like virus
2008-like virus

2011-2012
A/California/7/2009
A/Perth/16/2009
B/Brisbane/60/
N/A

(H1N1)-like virus
(H3N2)-like virus
2008-like virus

2012-2013
A/California/7/2009
A/Victoria/361/2011
B/Wisconsin/1/
B/Brisbane/

(H1N1)pdm09-like
(H3N2)-like virus
2010-like virus
60/2008-like

virus

virus

2013-2014
A/California/7/2009
A(H3N2) virus
B/Massachusetts/2/
B/Brisbane/

(H1N1)pdm09-like
antigenically like
2012-like virus
60/2008-like

virus
the cell-propagated

virus

prototype virus

A/Victoria/361/2011

2014-2015
A/California/7/2009
A/Texas/50/2012
B/Massachusetts/2/
B/Brisbane/

(H1N1)pdm09-like
(H3N2)-like virus
2012-like virus
60/2008-like

virus

virus

TABLE 5

Influenza Vaccine components by year-Southern Hemisphere

additional

Southern

B-strain

hemisphere
H1N1
H3N2
B-strain
for QIV

1999
A/Beijing/262/95
A/Sydney/5/97
B/Beijing/184/93-
N/A

(H1N1)-like virus
(H3N2)-like virus
like virus

May-October
A/New
A/Moscow/10/99
B/Beijing/184/93-
N/A

2000
Caledonia/20/99
(H3N2)-like virus
like virus or

(H1N1)-like virus

B/Shangdong/7/97-

like virus

May-October
A/New
A/Moscow/10/99
B/Sichuan/379/99-
N/A

2001
Caledonia/20/99
(H3N2)-like virus
like virus

(H1N1)-like virus

2002
A/New
A/Moscow/10/99
B/Sichuan/379/99-
N/A

Caledonia/20/99
(H3N2)-like virus
like virus

(H1N1)-like virus

2003
A/New
A/Moscow/10/99
B/Hong
N/A

Caledonia/20/99
(H3N2)-like virus
Kong/330/2001-

(H1N1)-like virus

like virus

2004
A/New
A/Fujian/411/2002
B/Hong
N/A

Caledonia/20/99
(H3N2)-like virus
Kong/330/2001-

(H1N1)-like virus

like virus

2005
A/New
A/Wellington/1/
B/Shanghai/361/
N/A

Caledonia/20/99
2004(H3N2)-like
2002-like virus

(H1N1)-like virus
virus

2006
A/New
A/California/7/2004
B/Malaysia/2506/
N/A

Caledonia/20/99
(H3N2)-like virus
2004-like virus

(H1N1)-like virus

2007
A/New
A/Wisconsin/67/
B/Malaysia/2506/
N/A

Caledonia/20/99
2005 (H3N2)-like
2004-like virus

(H1N1)-like
virus

2008
A/Solomon
A/Brisbane/10/2007
B/Florida/4/2006-
N/A

Islands/3/2006
(H3N2)-like virus
like virus

(H1N1)-like virus

2009
A/Brisbane/59/2007
A/Brisbane/10/2007
B/Florida/4/2006-
N/A

(H1N1)-like virus
(H3N2)-like virus
like virus

2010
A/California/7/2009
A/Perth/16/2009
B/Brisbane/60/
N/A

(H1N1)-like virus
(H3N2)-like virus
2008-like virus

2011
A/California/7/2009
A/Perth/16/2009
B/Brisbane/60/
N/A

(H1N1)-like virus
(H3N2)-like virus
2008-like virus

2013
A/California/7/2009
A/Perth/16/2009
B/Brisbane/60/
N/A

(H1N1)pdm09 like
(H3N2)-like virus
2008-like virus

virus

2013
A/California/7/2009
A/Victoria/361/2011
B/Wisconsin/1/
B/Brisbane/

(H1N1)pdm09-like
(H3N2)-like virus
2010-like virus
60/2008-like

virus

virus

2014
A/California/7/2009
A/Texas/50/2012
B/Massachusetts/2/
B/Brisbane/

(H1N1)pdm09-like
(H3N2)-like virus
2012-like virus
60/2008-like

virus

virus

Influenza Antigens

In some embodiments, the NAV polynucleotides may encode one or more polypeptides of an influenza strain as an antigen. Such antigens include, but are not limited to those antigens encoded by the polynucleotides listed in Tables 6-18. In the table, the GenBank Accession Number represents either the complete or partial CDS of the encoded antigen. The NAV polynucleotides may comprise a region of any of the sequences listed in the tables or entire coding region of the mRNA listed. They may comprise hybrid or chimeric regions, or mimics or variants.

Any of the strains referred to in Tables 6-14 may also be used in an antigenic memory booster vaccine as described herein.

TABLE 6

Influenza H1N1 Antigens

GenBank/GI

Strain/Protein
Length
Accession No.

Influenza A virus (A/Bayern/7/95 (H1N1) ) NA
1,459
AJ518104.1

gene for neuraminidase, genomic RNA
bp
GI:31096418

linear

mRNA

Influenza A virus (A/Brazil/11/1978
1,072
X86654.1

(X-71) (H1N1) ) mRNA for hemagglutinin HAI, escape
bp
GI:995549

variant 1
linear

mRNA

Influenza A virus (A/Brazil/11/1978
1,072
X86655,1

(X-71) (H1N1) ) mRNA for hemagglutinin HAI, escape
bp
GI:995550

variant 2
linear

mRNA

Influenza A virus (A/Brazil/11/1978
1,072
X86656.1

(X-71) (H1N1) ) mRNA for hemagglutinin HA1, escape
bp
GI:995551

variant 3
linear

mRNA

Influenza A virus (A/Brazil/11/1978
1,072
X86657.1

(X-71) (H1N1) ) mRNA for hemagglutinin HAI, escape
bp
GI:995552

variant 4
linear

mRNA

Influenza A virus
1,220
AF116575.1

(A/Brevig_Mission/1/18 (H1N1 } ) hemagglutinin
bp
GI:4325017

(HA) MRNA, partial cds
linear

mRNA

Influenza A virus
1,410
AF250356.2

(A/Brevig_Mission/1/18 (H1N1) ) neuraminidase
bp
GI:13260556

(NA) gene, complete cds
linear

mRNA

Influenza A virus (A/Brevig
1,497
AY744935.1

Mission/1/1918 (H1N1) ) nucleoprotein (np)
bp
GI:55273940

mRNA, complete cds
linear

mRNA

Influenza A virus (A/Brevig
2,280
DQ208309.1

Mission/1/1918 (H1N1) ) polymerase PB2 (PB2)
bp
GI:76786704

mRNA, complete cds
linear

mRNA

Influenza A virus (A/Brevig
2,274
DQ208310.1

Mission/1/1918 (H1N1) ) polymerase PB1 (PB1)
bp
GI:76786706

mRNA, complete cds
linear

mRNA

Influenza A virus (A/Brevig
2,151
DQ208311.1

Mission/1/1918 (H1N1) ) polymerase PA (PA)
bp
GI:76786708

mRNA, complete cds
linear

mRNA

Influenza A virus
366 bp
M73975.1

(A/camel/Mongolia/1982 (H1N1) ) hemagglutinin
linear
GI:324242

mRNA, partial cds
mRNA

Influenza A virus
460 bp
M73978.1

(A/camel/Mongolia/1982 (H1N1) ) matrix protein
linear
GI:324402

mRNA, partial cds
mRNA

Influenza A virus
310 bp
M73976.1

(A/camel/Mongolia/1982 (H1N1) ) neuraminidase
linear
GI:324579

(NA) MRNA, partial cds
mRNA

Influenza A Virus A/camel/Mongolia/82 NS1
273 bp
M73977.1

protein mRNA, partial cds
linear
GI:324768

mRNA

Influenza A virus
227 bp
M73974.1

(A/camel/Mongolia/1982 (H1N1) } PA polymerase
linear
GI:324931

mRNA, partial cds
mRNA

Influenza A virus
531 bp
M73973.1

(A/camel/Mongolia/1982 (H1N1) ) PB1 protein
linear
GI:324971

mRNA, partial cds
mRNA

Influenza A Virus (A/camel/Mongolia/82 (H1N1) )
379 bp
M73972.1

polymerase 2 (P2) mRNA, partial cds
linear
GI:324993

mRNA

Influenza A virus (A/chicken/Hong
1,169
U46782.1

Kong/14/1976 (H1N1) ) hemagglutinin precursor
bp
GI:1912328

(HA) MRNA, partial cds
linear

mRNA

Influenza A virus (A/Chonnam/07/2002 (H1N1) )
1,452
AY297141.1

neuraminidase (NA) mRNA, complete cds
bp
GI:31871990

linear

mRNA

Influenza A virus (A/Chonnam/07/2002 (H1N1) )
1,137
AY297154.1

hemagglutinin (HA) mRNA, partial cds
bp
GI:32140347

linear

mRNA

Influenza A virus (A/Chonnam/18/2002 (H1N1) )
1,458
AY297143.1

neuraminidase (NA) mRNA, complete cds
bp
GI:31871994

linear

mRNA

Influenza A virus (A/Chonnam/18/2002 (H1N1) )
1,176
AY297156.1

hemagglutinin (HA) mRNA, partial cds
bp
GI:32140355

linear

mRNA

Influenza A virus (A/Chonnam/19/2002 (H1N1) )
1,458
AY310410.1

neuraminidase (NA) mRNA, complete cds
bp
GI:31872389

linear

mRNA

Influenza A virus (A/Chonnam/19/2002 (H1N1) )
1,167
AY299502.1

hemagglutinin (HA) mRNA, partial cds
bp
GI:32140392

linear

mRNA

Influenza A virus (A/Chonnam/51/2002 (H1N1) )
1,443
AY310412.1

neuraminidase (NA) mRNA, complete cds
bp
GI:31873090

linear

mRNA

Influenza A virus (A/Chonnam/51/2002 (H1N1) )
1,161
AY299498.1

hemagglutinin (HA) mRNA, partial cds
bp
GI:32140384

linear

mRNA

Influenza A virus (A/Chungbuk/50/2002 (H1N1) )
1,425
AY297150.1

neuraminidase (NA) mRNA, partial cds
bp
GI:31872010

linear

mRNA

Influenza A virus (A/Chungbuk/50/2002 (H1N1) )
1,161
AY299506.1

hemagglutinin (HA) mRNA, partial cds
bp
GI:32140400

linear

mRNA

Influenza A virus (A/Denmark/40/2000 (H1N1) )
1,458
AJ518095.1

NA gene for neuraminidase, genomic RNA
bp
GI:31096400

linear

mRNA

Influenza A virus (A/Denver/1/57 (H1N1) )
379 bp
AF305216.1

neuraminidase mRNA, partial cds
linear
GI:10732818

mRNA

Influenza A virus (A/Denver/1/57 (H1N1) )
442 bp
AF305217.1

matrix protein gene, partial cds
linear
GI:10732820

mRNA

Influenza A virus (A/Denver/1/57 (H1N1) )
215 bp
AF305218.1

hemagglutinin gene, partial cds
linear
GI:10732822

mRNA

Influenza A virus
981 bp
U47309.1

(A/duck/Australia/749/80 (H1N1) ) hemagglutinin
linear
GI:1912348

precursor (HA) mRNA, partial cds
mRNA

Influenza A virus
1,777
AF091312.1

(A/duck/Australia/749/80 (H1N1) ) segment 4
bp
GI:4585166

hemagglutinin precursor (HA) mRNA, complete
linear

cds
mRNA

Influenza A virus (A/duck/Bavaria/1/77
1,777
AF091313.1

(H1N1) ) segment 4 hemagglutinin precursor
bp
GI:4585168

(HA) mRNA, complete cds
linear

mRNA

Influenza A virus (A/duck/Bavaria/2/77 (H1N1) )
981 bp
U47308.1

hemagglutinin precursor (HA) mRNA, partial
linear
GI:1912346

cds
mRNA

Influenza A virus (A/duck/Eastern
1,458
EU429749.1

China/103/2003 (H1N1) ) segment 6 neuraminidase
bp
GI:167859463

(NA) mRNA, complete cds
linear

mRNA

Influenza A virus (A/duck/Eastern
1,461
EU429751.1

China/152/2003 (H1N1) ) segment 6 neuraminidase
bp
GI:167859467

(NA) MRNA, complete cds
linear

mRNA

Influenza A virus (A/Duck/Ohio/118C/93
1,410
AF250361.2

(H1N1) ) neuraminidase (NA) gene, complete cds
bp
GI:13260576

linear

mRNA

Influenza A virus (A/Duck/Ohio/175/86 (H1N1) )
1,410
AF250358.2

neuraminidase (NA) gene, complete cds
bp
GI:13260565

linear

mRNA

Influenza A virus (A/Duck/Ohio/194/86 (H1N1) )
1,410
AF250360.2

neuraminidase (NA) gene, complete cds
bp
GI:13260573

linear

mRNA

Influenza A virus (A/Duck/Ohio/30/86 (H1N1) )
1,410
AF250359.2

neuraminidase (NA) gene, complete cds
bp
GI:13260570

linear

mRNA

Influenza A virus strain
1,460
AJ006954.1

A/Fiji/15899/83 (H1N1) mRNA for neuraminidase
bp
GI:4210707

linear

mRNA

Influenza A Virus (A/Fiji/15899/83 (H1N1) )
2,341
AJ564805.1

mRNA for PB2 protein
bp
GI:31442134

linear

mRNA

Influenza A Virus (A/Fiji/15899/83 (H1N1) )
2,113
AJ564807.1

partial mRNA for PBl protein
bp
GI:31442138

linear

mRNA

Influenza A virus (A/FM/1/47 (H1N1) )
1,395
AF250357.2

neuraminidase (NA) gene, complete cds
bp
GI:13260561

linear

mRNA

Influenza A virus (A/goose/Hong
1,091
U46021.1

Kong/8/1976 (H1N1) ) hemagglutinin precursor
bp
GI:1912326

(HA) MRNA, partial cds
linear

mRNA

Influenza A virus (A/goose/Hong
261 bp
U48284.1

Kong/8/1976 (H1N1) ) polymerase (PB1) mRNA,
linear
GI:1912372

partial cds
mRNA

Influenza A virus (A/goose/Hong
1,395
U49093.1

Kong/8/1976 (H1N1) ) nucleoprotein (NP) mRNA,
bp
GI:1912384

partial cds
linear

mRNA

Influenza A virus
1,775
EU382986.1

(A/Guangzhou/1561/2006 (H1N1) ) segment 4
bp
GI:170762603

hemagglutinin (HA) mRNA, complete cds
linear

mRNA

Influenza A virus
1,462
EU382993.1

(A/Guangzhou/1561/2006 (H1N1) ) segment 6
bp
GI:170762617

neuraminidase (NA) mRNA, complete cds
linear

mRNA

Influenza A virus
1,775
EU382987.1

(A/Guangzhou/1684/2006 (H1N1) ) segment 4
bp
GI:170762605

hemagglutinin (HA) mRNA, complete cds
linear

mRNA

Influenza A virus
1,462
EU382994.1

(A/Guangzhou/1684/2006 (H1N1) ) segment 6
bp
GI:170762619

neuraminidase (NA) mRNA, complete cds
linear

mRNA

Influenza A virus (A/Guangzhou/483/2006 (H1N1) ) segment 4
1,775
EU382981.1

hemagglutinin (HA) mRNA, complete cds
bp
GI:170762593

linear

mRNA

Influenza A virus
1,462
EU382988.1

(A/Guangzhou/483/2006 (H1N1) ) segment 6
bp
GI:170762607

neuraminidase (NA) mRNA, complete cds
linear

mRNA

Influenza A virus
1,775
EU382982.1

(A/Guangzhou/506/2006 (H1N1) ) segment 4
bp
GI:170762595

hemagglutinin (HA) mRNA, complete cds
linear

mRNA

Influenza A virus
1,461
EU382989.1

(A/Guangzhou/506/2006 (H1N1) ) segment 6
bp
GI:170762609

neuraminidase (NA) mRNA, complete cds
linear

mRNA

Influenza A virus
1,775
EU382983.1

(A/Guangzhou/555/2006 (H1N1) ) segment 4
bp
GI:170762597

hemagglutinin (HA) mRNA, complete cds
linear

mRNA

Influenza A virus
1,462
EU382990.1

(A/Guangzhou/555/2006 (H1N1) ) segment 6
bp
GI:170762611

neuraminidase (NA) mRNA, complete cds
linear

mRNA

Influenza A virus
1,775
EU382984.1

(A/Guangzhou/657/2006 (H1N1) ) segment 4
bp
GI:170762599

hemagglutinin (HA) mRNA, complete cds
linear

mRNA

Influenza A virus
1,462
EU382991.1

(A/Guangzhou/657/2006 (H1N1) ) segment 6
bp
GI:170762613

neuraminidase (NA) mRNA, complete cds
linear

mRNA

Influenza A virus
1,775
EU382985.1

(A/Guangzhou/665/2006 (H1N1) ) segment 4
bp
GI:170762601

hemagglutinin (HA) mRNA, complete cds
linear

mRNA

Influenza A virus
1,462
EU382992.1

(A/Guangzhou/665/2006 (H1N1) ) segment 6
bp
GI:170762615

neuraminidase (NA) MRNA, complete cds
linear

mRNA

Influenza A virus (A/Gwangju/55/2002 (H1N1) )
1,431
AY297151.1

neuraminidase (NA) mRNA, complete cds
bp
GI:31872012

linear

mRNA

Influenza A virus (A/Gwangju/55/2002 (H1N1) )
1,179
AY299507.1

hemagglutinin (HA) mRNA, partial cds
bp
GI:32140402

linear

mRNA

Influenza A virus (A/Gwangju/57/2002 (H1N1) )
1,446
AY297152.1

neuraminidase (NA) mRNA, complete cds
bp
GI:31872014

linear

mRNA

Influenza A virus (A/Gwangju/57/2002 (H1N1) )
1,167
AY299508.1

hemagglutinin (HA) mRNA, partial cds
bp
GI:32140404

linear

mRNA

Influenza A virus (A/Gwangju/58/2002 (H1N1) )
1,434
AY297153.1

neuraminidase (NA) mRNA, complete cds
bp
GI:31872016

linear

mRNA

Influenza A virus (A/Gwang ju/58/2002 (H1N1) )
1,176
AY299509.1

hemagglutinin (HA) mRNA, partial cds
bp
GI:32140406

linear

mRNA

Influenza A virus (A/Gwangju/90/2002 (H1N1) )
1,446
AY297147.1

neuraminidase : (NA) MRNA, complete cds
bp
GI:31872002

linear

mRNA

Influenza A virus (A/Gwangju/90/2002 (H1N1) )
1,164
AY299499.1

hemagglutinin (HA) mRNA, partial cds
bp
GI:32140386

linear

mRNA

Influenza A virus (A/Hong
1,403
AJ518101.1

Kong/437/2002 (H1N1) ) partial NA gene for
bp
GI:31096412

neuraminidase, genomic RNA
linear

mRNA

Influenza A virus (A/Hong
1,352
AJ518102.1

Kong/747/2001 (H1N1) } partial NA gene for
bp
GI:31096414

neuraminidase, genomic RNA
linear

mRNA

Influenza A virus (A/London/1/1918 (H1N1) )
563 bp
AY184805.1

hemagglutinin (HA) mRNA, partial cds
linear
GI:32395285

mRNA

Influenza A virus (A/London/1/1919 (H1N1) )
563 bp
AY184806.1

hemagglutinin (HA) mRNA, partial cds
linear
GI:32395287

mRNA

Influenza A virus (A/Loygang/4/1957 (H1N1) )
1,565
M76604.1

nucleoprotein mRNA, complete cds
bp
GI:324255

linear

mRNA

Influenza A virus (A/Lyon/651/2001 (H1N1) )
1,318
AJ518103.1

partial NA gene for neuraminidase, genomic
bp
GI:31096416

RNA
linear

mRNA

(A/mallard/Alberta/119/98

Influenza A virus (A/mallard/Alberta/119/98
947 bp
AY664487.1

(H1N1) ) nonfunctional matriz protein mRNA,
linear
GI:51011891

partial sequence
mRNA

Influenza A virus
981 bp
U47310.1

(A/duck/Alberta/35/76 (H1N1) ) hemagglutinin
linear
GI:1912350

precursor (HA) mRNA, partial cds
mRNA

Influenza A virus
1,777
AF091309.1

(A/duck/Alberta/35/76 (H1N1) ) segment 4
bp
GI:4585160

hemagglutinin precursor (HA) mRNA, complete
linear

cds
mRNA

Influenza A virus
1,410
AF250362.2

(A/duck/Alberta/35/76 (H1N1) ) neuraminidase
bp
GI:13260579

(NA) gene, complete cds
linear

mRNA

Influenza A virus
981 bp
U47307.1

(A/mallard/Tennessee/11464/85 (H1N1) )
linear
GI:1912344

hemagglutinin precursor (HA) MRNA, partial
mRNA

cds

Influenza A virus
1,777
AF091311.1

(A/mallard/Tennessee/11464/85 (H1N1) ) segment
bp
GI:4585164

4 hemagglutinin precursor (HA) mRNA, complete
linear

cds
mRNA

Influenza A virus (A/New
294 bp
HQ008884.1

Caledonia/20/1999 (H1N1) ) segment 7 matrix
linear
GI:302566794

protein 2 (M2) MRNA, complete cds
mRNA

Influenza A virus (A/New Jersey/4/1976 (H1N1) )
1,565
M76605.1

nucleoprotein mRNA, complete cds
bp
GI:324581

linear

mRNA

Influenza A virus (A/New Jersey/8/1976 (H1N1) )
1,565
M76606.1

nucleoprotein mRNA, complete cds
bp
GI:324583

linear

mRNA

Influenza A virus (A/New_York/1/18 (H1N1) )
1,220
AF116576.1

hemagglutinin (HA) mRNA, partial cds
bp
GI:4325019

linear

mRNA

Influenza A virus (A/Ohio/3523/1988 (H1N1) )
1,565
M76602.1

nucleoprotein mRNA, complete cds
bp
GI:324889

linear

mRNA

Influenza A virus (A/Pusan/22/2002 (H1N1) )
1,455
AY310411.1

neuraminidase (NA) mRNA, complete cds
bp
GI:31872391

linear

mRNA

Influenza A virus (A/Pusan/22/2002 (H1N1) )
1,149
AY299503.1

hemagglutinin (HA) mRNA, partial cds
bp
GI:32140394

linear

mRNA

Influenza A virus (A/Pusan/23/2002 (H1N1) )
1,440
AY297144.1

neuraminidase (NA) mRNA, complete cds
bp
GI:31871996

linear

mRNA

Influenza A virus (A/Pusan/23/2002 (H1N1) )
1,158
AY297157.1

hemagglutinin (HA) mRNA, partial cds
bp
GI:32140357

linear

mRNA

Influenza A virus (A/Pusan/24/2002 (H1N1) )
1,449
AY297145.1

neuraminidase (NA) mRNA, complete cds
bp
GI:31871998

linear

mRNA

Influenza A virus (A/Pusan/24/2002 (H1N1) )
1,128
AY299494.1

hemagglutinin (HA) mRNA, partial cds
bp
GI:32140376

linear

mRNA

Influenza A virus (A/Pusan/44/2002 (H1N1) )
1,431
AY297148.1

neuraminidase (NA) mRNA, complete cds
bp
GI:31872004

linear

mRNA

Influenza A virus (A/Pusan/44/2002 (H1N1) )
1,167
AY299504.1

hemagglutinin (HA) mRNA, partial cds
bp
GI:32140396

linear

mRNA

Influenza A virus (A/Pusan/45/2002 (H1N1) )
1,434
AY297146.1

neuraminidase (NA) mRNA, complete cds
bp
GI:31872000

linear

mRNA

Influenza A virus (A/Pusan/45/2002 (H1N1) )
1,167
AY299496.1

hemagglutinin (HA) mRNA, partial cds
bp
GI:32140380

linear

mRNA

Influenza A virus (A/Pusan/46/2002 (H1N1) )
1,422
AY310408.1

neuraminidase (NA) MRNA, complete cds
bp
GI:31872385

linear

mRNA

Influenza A virus (A/Pusan/46/2002 (H1N1) )
1,176
AY299497.1

hemagglutinin (HA) MRNA, partial cds
bp
GI:32140382

linear

mRNA

Influenza A virus (A/Pusan/47/2002 (H1N1) )
1,437
AY297149.1

neuraminidase (NA) mRNA, complete cds
bp
GI:31872008

linear

mRNA

Influenza A virus (A/Pusan/47/2002 (H1N1) )
1,170
AY299505.1

hemagglutinin (HA) mRNA, partial cds
bp
GI:32140398

linear

mRNA

Influenza A virus (A/Saudi
789 bp
AJ519463.1

Arabia/7971/2000 (H1N1) ) partial NS1 gene for
linear
GI:31096450

non structural protein 1 and partial NS2 gene
mRNA

for non structural protein 2, genomic RNA

Influenza A virus (A/Seoul/11/2002 (H1N1) )
1,452
AY297142.1

neuraminidase (NA) mRNA, complete cds
bp
GI:31871992

linear

mRNA

Influenza A virus (A/Seoul/11/2002 (H1N1) )
1,176
AY297155.1

hemagglutinin (HA) mRNA, partial cds
bp
GI:32140349

linear

mRNA

Influenza A virus (A/Seoul/13/2002 (H1N1) )
1,452
AY310409.1

neuraminidase (NA) mRNA, complete cds
bp
GI:31872387

linear

mRNA

Influenza A virus (A/Seoul/13/2002 (H1N1) )
1,167
AY299500.1

hemagglutinin (HA) mRNA, partial cds
bp
GI:32140388

linear

mRNA

Influenza A virus (A/Seoul/15/2002 (H1N1) )
1,449
AY297140.1

neuraminidase (NA) mRNA, complete cds
bp
GI:31871988

linear

mRNA

Influenza A virus (A/Seoul/15/2002 (H1N1) )
1,149
AY299501.1

hemagglutinin (HA) mRNA, partial cds
bp
GI:32140390

linear

mRNA

Influenza A virus (A/Seoul/33/2002 (H1N1) )
1,437
AY310407.1

neuraminidase (NA) mRNA, complete cds
bp
GI:31872383

linear

mRNA

Influenza A virus (A/Seoul/33/2002 (H1N1) )
1,167
AY299495.1

hemagglutinin (HA) mRNA, partial cds
bp
GI:32140378

linear

mRNA

Influenza A virus
1,050
Z46437.1

(A/swine/Arnsberg/6554/1979 (H1N1) ) MRNA for
bp
GI:565609

hemagglutinin HA1
linear

mRNA

Influenza A virus
1,595
U46783.1

(A/swine/Beijing/47/1991 (H1N1) ) hemagglutinin
bp
GI:1912330

precursor (HA) mRNA, partial cds
linear

mRNA

Influenza A virus
1,565
U49091.1

(A/swine/Beijing/94/1991 (H1N1) ) nucleoprotein
bp
GI:1912380

(NP) mRNA, complete cds
linear

mRNA

Influenza A virus
1,778
AF091316.1

(A/swine/Belgium/1/83 (H1N1) ) segment 4
bp
GI:4585174

hemagglutinin precursor (HA) mRNA, complete
linear

cds
mRNA

Influenza A virus (A/swine/Cotes
1,116
AM490219.1

d'Armor/0118/2006 (H1N1) ) partial mRNA for
bp
GI:222062898

haemagglutinin precursor (HA1 gene)
linear

mRNA

Influenza A virus (A/swine/Cotes
1,043
AM490223.1

d'Armor/0136_18/2006 (H1N1) ) partial mRNA for
bp
GI:222062906

haemagglutinin precursor (HA1 gene)
linear

mRNA

Influenza A virus (A/swine/Cotes
1,089
AM490220.1

d'Armor/0184/2006 (H1N1) ) partial mRNA for
bp
GI:222062900

haemagglutinin precursor (HAl gene)
linear

mRNA

Influenza A virus (A/swine/Cotes
1,068
AM490221.1

d'Armor/0227/2005 (H1N1) ) partial mRNA for
bp
GI:222062902

haemagglutinin precursor (HA1 gene)
linear

mRNA

Influenza A virus (A/swine/Cotes
1,024
AM490222.1

d'Armor/0250/2006 (H1N1) ) partial mRNA for
bp
GI:222062904

haemagglutinin precursor (HAl gene)
linear

mRNA

Influenza A virus (A/swine/Cotes
1,011
AJ517820.1

d'Armor/736/2001 (H1N1) ) partial HA gene for
bp
GI:38422533

Haemagglutinin, genomic RNA
linear

mRNA

Influenza A virus (A/Swine/England/195852/92
1,410
AF250366.2

(H1N1) ) neuraminidase (NA) gene, complete cds
bp
GI:13260593

linear

mRNA

Influenza A virus PB2 gene for Polymerase 2
2,268
AJ311457.1

protein, genomic RNA, strain
bp
GI:13661037

A/Swine/Finistere/2899/82
linear

mRNA

Influenza A virus PB1 gene for Polymerase 1
2,341
AJ311462.1

protein, genomic RNA, strain
bp
GI:13661047

A/Swine/Finistere/2899/82
linear

mRNA

Influenza A virus PA gene for Polymerase A
2,233
AJ311463.1

protein, genomic RNA, strain
bp
GI:13661049

A/Swine/Finistere/2899/82
linear

mRNA

Influenza A virus
1,002
AJ316059.1

(A/swine/Finistere/2899/82 (H1N1) Ml gene for
bp
GI:20068128

matrix protein 1 and M2 gene for matrix
linear

protein 2, genomic RNA
mRNA

Influenza A virus
864 bp
AJ344037.1

(A/swine/Finistere/2899/82 (H1N1) ) NS1 gene
linear
GI:20068185

for non structural protein 1 and NS2 gene for
mRNA

non structural protein 2, genomic RNA

Influenza A virus
838 bp
X75786.1

(A/swine/Germany/2/1981 (H1N1) ) MRNA for PA
linear
GI:438106

polymerase
mRNA

Influenza A virus
305 bp
Z30277.1

(A/swine/Germany/2/1981 (H1N1) ) MRNA for
linear
GI:530399

neuraminidase (partial)
mRNA

Influenza A virus
1,730
Z30276.1

(A/swine/Germany/2/1981 (H1N1) ) mRNA for
bp
GI:563490

hemagglutinin
linear

mRNA

165. Influenza A virus
1,730
Z46434.1

(A/swine/Germany/8533/1991 (H1N1) ) mRNA for
bp
GI:565611

hemagglutinin precursor
linear

mRNA

Influenza A virus
1,690
AY852271.1

(A/swine/Guangdong/711/2001 (H1N1) )
bp
GI:60327789

nonfunctional hemagglutinin (HA) mRNA,
linear

partial sequence
mRNA

Influenza A virus
1,809
EU163946.1

(A/swine/Haseluenne/IDI2617/03 (H1N1) }
bp
GI:157679548

hemagglutinin mRNA, complete cds
linear

mRNA

Influenza A virus (A/swine/Hokkaido/2/81
981 bp
U47306.1

(H1N1) ) hemagglutinin precursor (HA) mRNA,
linear
GI:1912342

partial cds
mRNA

Influenza A virus (A/swine/Hokkaido/2/81
1,778
AF091306.1

(H1N1) ) segment 4 hemagglutinin precursor
bp
GI:4585154

(HA) mRNA, complete cds
linear

miRNA

Influenza A virus (A/swine/Hong
1,113
U44482.1

Kong/168/1993 (H1N1) ) hemagglutinin precursor
bp
GI:1912318

(HA) MRNA, partial cds
linear

mRNA

Influenza A virus (A/swine/Hong
416 bp
U47817.1

Kong/168/1993 (H1N1) ) neuraminidase (NA) mRNA,
linear
GI:1912354

partial cds
mRNA

Influenza A virus (A/swine/Hong
286 bp
048286,1

Kong/168/1993 (H1N1) ) polymerase (PB2) mRNA,
linear
GI:1912358

partial cds
mRNA

Influenza A virus (A/swine/Hong
379 bp
U48283.1

Kong/168/1993 (H1N1) ) polymerase (PB1) mRNA,
linear
GI:1912370

partial cds
mRNA

Influenza A virus (A/swine/Hong
308 bp
U48850.1

Kong/168/1993 (H1N1 ) ) polymerase (PA) mRNA,
linear
GI:1912376

partial cds
mRNA

Influenza A virus (A/swine/Hong
1,397
U49096.1

Kong/168/1993 (H1N1) ) nucleoprotein (NP) MRNA,
bp
GI:1912390

partial cds
linear

mRNA

Influenza A virus (A/swine/Hong
1,315
U46020.1

Kong/172/1993 (H1N1 ) ) hemagglutinin precursor
bp
GI:1912324

(HA) MRNA, partial cds
linear

mRNA

Influenza A virus (A/swine/Hong
1,113
U45451.1

Kong/176/1993 (H1N1) ) hemagglutinin precursor
bp
GI:1912320

(HA) mRNA, partial cds
linear

mRNA

Influenza A virus (A/swine/Hong
1,330
U45452.1

Kong/273/1994 (H1N1) ) hemagglutinin precursor
bp
GI:1912322

(HA) MRNA, partial cds
linear

mRNA

Influenza A virus (A/swine/Hong
241 bp
U47818.1

Kong/273/1994 (H1N1) ) neuraminidase (NA) MRNA,
linear
GI:1912356

partial cds
mRNA

Influenza A virus (A/swine/Hong
328 bp
048287.1

Kong/273/1994 (H1N1) } polymerase (PB2) mRNA,
linear
GI:1912360

partial cds
mRNA

Influenza A virus (A/swine/Hong
240 bp
U48282.1

Kong/273/1994 (H1N1 ) ) polymerase (PB1) mRNA,
linear
GI:1912368

partial cds
mRNA

Influenza A virus (A/swine/Hong
336 bp
U48851.1

Kong/273/1994 (H1N1 ) } polymerase (PA) MRNA,
linear
GI:1912378

partial cds
mRNA

Influenza A virus (A/swine/Hong
1,422
U49092.1

Kong/273/1994 (H1N1) ) nucleoprotein (NP) mRNA,
bp
GI:1912382

partial cds
linear

mRNA

Influenza A virus
1,761
EU163947.1

(A/swine/IDT/Re230/92hp (H1N1) ) hemagglutinin
bp
GI:157679550

mRNA, complete cds
linear

mRNA

Influenza A virus
1,550
L46849.1

(A/swine/IN/1726/1988 (H1N1) ) nucleoprotein
bp
GI:954755

(segment 5) mRNA, complete cds
linear

mRNA

Influenza A virus (A/swine/Iowa/15/30 (H1N1) )
981 bp
047305.1

hemagglutinin precursor (HA) mRNA, partial
linear
GI:1912340

cds
mRNA

Influenza A virus (A/swine/Iowa/15/30 (H1N1) )
1,778
AF091308.1

segment 4 hemagglutinin precursor (HA) mRNA,
bp
GI:4585158

complete cds
linear

mRNA

Influenza A virus (A/Swine/Iowa/30 (H1N1) )
1,410
AF250364.2

neuraminidase (NA) gene, complete cds
bp
GI:13260586

linear

mRNA

Influenza A virus (A/swine/Iowa/17672/88
981 bp
U47304.1

(H1N1) ) hemagglutinin precursor (HA) mRNA,
linear
GI:1912338

partial cds
mRNA

Influenza A virus
864 bp
AJ519462.1

(A/swine/Italy/3364/00 (H1N1) } partial NS1
linear
GI:31096447

gene for non structural protein 1 and partial
mRNA

NS2 gene for non structural protein 2,

genomic RNA

Influenza A virus (A/swine/Italy-
1,777
AF091315.1

Virus/671/87 (H1N1) ) segment 4 hemagglutinin
bp
GI:4585172

precursor (HA) mRNA, complete cds
linear

mRNA

Influenza A Virus
1,028
Z46436.1

(A/swine/Italy/v. 147/1981 (H1N1) ) MRNA for
bp
GI:854214

hemagglutinin HA1
linear

mRNA

Influenza A virus
1,118
AM490218.1

(A/swine/Morbihan/0070/2005 (H1N1) ) partial
bp
GI:222062896

mRNA for haemagglutinin precursor (HAI gene)
linear

mRNA

Influenza A virus
1,770
L09063.1

(A/swine/Nebraska/1/92 (H1N1) ) HA protein
bp
GI:290722

mRNA, complete cds
linear

mRNA

Influenza A virus
1,550
L11164.1

(A/swine/Nebraska/1/1992 (H1N1) ) segment 5
bp
GI:290724

nucleoprotein (NP) mRNA, complete cds
linear

mRNA

Influenza A virus
981 bp
U46943.1

(A/swine/Netherlands/12/1985 (H1N1) )
linear
GI:1912336

hemagglutinin (HA) mRNA, partial cds
mRNA

Influenza A virus
1,776
AF091317.1

(A/swine/Netherlands/12/85 (H1N1) ) segment 4
bp
GI:4585176

hemagglutinin precursor (HA) mRNA, complete
linear

cds
mRNA

Influenza A virus
539 bp
X75791.1

(A/swine/Netherlands/25/1980 (H1N1) ) mRNA for
linear
GI:438105

nucleoprotein
mRNA

Influenza A virus
981 bp
046942.1

(A/swine/Netherlands/3/1980 (H1N1) )
linear
GI:1912334

hemagglutinin (HA) mRNA, partial cds
mRNA

Influenza A virus
1,778
AF091314.1

(A/swine/Netherlands/3/80 (H1N1) ) segment 4
bp
GI:4585170

hemagglutinin precursor (HA) mRNA, complete
linear

cds
mRNA

Influenza A virus (A/NJ/11/76 (H1N1) )
1,410
AF250363.2

neuraminidase (NA) gene, complete cds
bp
GI:13260583

linear

mRNA

Influenza A virus (A/Swine/Quebec/192/81
1,438
U86144.1

(SwQc81) ) neuraminidase mRNA, complete cds
bp
GI:4099318

linear

mRNA

Influenza A virus (A/Swine/Quebec/5393/91
1,438
U86145.1

(SwQc91) ) neuraminidase mRNA, complete cds
bp
GI:4099320

linear

mRNA

Influenza A virus (A/swine/Schleswig-
1,730
Z46435.1

Holstein/1/1992 (H1N1) ) mRNA for hemagglutinin
bp
GI:854216

precursor
linear

mRNA

Influenza A Virus (A/swine/Schleswig-
1,554
Z46438.1

Holstein/1/1993 (H1N1) ) mRNA for nucleoprotein
bp
GI:854222

linear

mRNA

Influenza A virus
1,778
AF091307.1

(A/swine/Wisconsin/1/61 (H1N1) ) segment 4
bp
GI:4585156

hemagglutinin precursor (HA) mRNA, complete
linear

cds
mRNA

212. Influenza A virus
1,565
M76607.1

(A/swine/Wisconsin/1/1967 (H1N1) )
bp
GI:325086

nucleoprotein mRNA, complete cds
linear

mRNA

Influenza A virus
1,565
M76608.1

(A/swine/Wisconsin/1915/1988 (H1N1) )
bp
GI:325088

nucleoprotein mRNA, complete cds
linear

mRNA

Influenza A virus
1,550
L46850.1

(A/swine/WI/1915/1988 (H1N1) ) nucleoprotein
bp
GI:954757

(segment 5) mRNA, complete cds
linear

mRNA

Influenza A virus
729 bp
AJ532568.1

(A/Switzerland/8808/2002 (H1N1) ) partial ml
linear
GI:31096461

gene for matrix protein 1 and partial m2 gene
miRNA

for matrix protein 2, genomic RNA

Influenza A virus
561 bp
AF362803.1

(A/human/Taiwan/0012/00 (H1N1) ) hemagglutinin
linear
GI:14571975

(HA) mRNA, partial cds
mRNA

Influenza A virus
561 bp
AF362779.1

(A/human/Taiwan/0016/00 (H1N1) ) hemagglutinin
linear
GI:14571927

(HA) mRNA, partial cds
mRNA

Influenza A virus (A/Taiwan/0016/2000 (H1N1) )
303 bp
AY303752.1

polymerase basic protein 1 (PB1) mRNA,
linear
GI:32330993

partial cds
mRNA

Influenza A virus
561 bp
AF362780.1

(A/human/Taiwan/0030/00 (H1N1) ) hemagglutinin
linear
GI:14571929

(HA) mRNA, partial cds
mRNA

Influenza A virus (A/Taiwan/0030/2000 (H1N1) )
303 bp
AY303704.1

polymerase basic protein 1 (PB1) MRNA,
linear
GI:32330897

partial cds
mRNA

Influenza A virus (A/Taiwan/0032/2002 (H1N1) )
494 bp
AY604804.1

hemagglutinin mRNA, partial cds
linear
GI:50727488

mRNA

Influenza A virus (A/Taiwan/0061/2002 (H1N1) )
494 bp
AY604795.1

hemagglutinin mRNA, partial cds
linear
GI:50727470

mRNA

Influenza A virus (A/Taiwan/0069/2002 (H1N1) )
494 bp
AY604803.1

hemagglutinin mRNA, partial cds
linear
GI:50727486

mRNA

Influenza A virus (A/Taiwan/0078/2002 (H1N1) )
494 bp
AY604805.1

hemagglutinin mRNA, partial cds
linear
GI:50727490

mRNA

Influenza A virus (A/Taiwan/0094/2002 (H1N1) )
494 bp
AY604797.1

hemagglutinin mRNA, partial cds
linear
GI:50727474

mRNA

Influenza A virus (A/Taiwan/0116/2002 (H1N1) )
494 bp
AY604796.1

hemagglutinin mRNA, partial cds
linear
GI:50727472

mRNA

Influenza A virus
564 bp
AF362781.1

(A/human/Taiwan/0130/96 (H1N1) ) hemagglutinin
linear
GI:14571931

(HA) mRNA, partial cds
mRNA

Influenza A virus (A/Taiwan/0130/96 (H1N1) )
303 bp
AY303707.1

polymerase basic protein 1 (PB1) mRNA,
linear
GI:32330903

partial cds
mRNA

Influenza A virus
564 bp
AF362782.1

(A/human/Taiwan/0132/96 (H1N1) ) hemagglutinin
linear
GI:14571933

(HA) MRNA, partial cds
mRNA

Influenza A virus (A/Taiwan/0132/96 (H1N1) )
303 bp
AY303708.1

polymerase basic protein 1 (PB1) mRNA,
linear
GI:32330905

partial cds
mRNA

Influenza A virus
564 bp
AF362783.1

(A/human/Taiwan/0211/96 (H1N1) ) hemagglutinin
linear
GI:14571935

(HA) mRNA, partial cds
mRNA

Influenza A virus (A/Taiwan/0211/96 (H1N1) )
303 bp
AY303709.1

polymerase basic protein 1 (PB1) mRNA,
linear
GI:32330907

partial cds
mRNA

Influenza A virus
564 bp
AF362784.1

(A/human/Taiwan/0235/96 (H1N1) ) hemagglutinin
linear
GI:14571937

(HA) mRNA, partial cds
mRNA

Influenza A virus (A/Taiwan/0235/96 (H1N1) )
303 bp
AY303710.1

polymerase basic protein 1 (PB1) mRNA,
linear
GI:32330909

partial cds
mRNA

Influenza A virus
564 bp
AF362785.1

(A/human/Taiwan/0255/96 (H1N1) ) hemagglutinin
linear
GI:14571939

(HA) MRNA, partial cds
mRNA

Influenza A virus (A/Taiwan/0255/96 (H1N1) )
303 bp
AY303711.1

polymerase basic protein 1 (PB1) mRNA,
linear
GI:32330911

partial cds
mRNA

Influenza A virus
564 bp
AF362786.1

(A/human/Taiwan/0337/96 (H1N1) ) hemagglutinin
linear
GI:14571941

(HA) MRNA, partial cds
mRNA

Influenza A virus
564 bp
AF362787.1

(A/human/Taiwan/0342/96 (H1N1) ) hemagglutinin
linear
GI:14571943

(HA) mRNA, partial cds
mRNA

Influenza A virus (A/Taiwan/0342/96 (H1N1) )
303 bp
AY303714.1

polymerase basic protein 1 (PB1) mRNA,
linear
GI:32330917

partial cds
mRNA

Influenza A virus
561 bp
AF362788.1

(A/human/Taiwan/0464/99 (H1N1) ) hemagglutinin
linear
GI:14571945

(HA) mRNA, partial cds
mRNA

Influenza A virus
564 bp
AF362789.1

(A/human/Taiwan/0562/95 (H1N1) ) hemagglutinin
linear
GI:14571947

(HA) mRNA, partial cds
mRNA

Influenza A virus (A/Taiwan/0562/95 (H1N1) )
303 bp
AY303720.1

polymerase basic protein 1 (PB1) mRNA,
linear
GI:32330929

partial cds
mRNA

Influenza A virus
564 bp
AF362790.1

(A/human/Taiwan/0563/95 (H1N1) ) hemagglutinin
linear
GI:14571949

(HA) mRNA, partial cds
mRNA

Influenza A virus (A/Taiwan/0563/95 (H1N1) )
303 bp
AY303721.1

polymerase basic protein 1 (PB1) mRNA,
linear
GI:32330931

partial cds
mRNA

Influenza A virus
564 bp
AF362791.1

(A/human/Taiwan/0657/95 (H1N1) ) hemagglutinin
linear
GI:14571951

(HA) MRNA, partial cds
mRNA

Influenza A virus (A/Taiwan/0657/95 (H1N1) )
303 bp
AY303724.1

polymerase basic protein 1 (PB1) MRNA,
linear
GI:32330937

partial cds
mRNA

Influenza A virus (A/Taiwan/0859/2002 (H1N1) )
494 bp
AY604801.1

hemagglutinin mRNA, partial cds
linear
GI:50727482

mRNA

Influenza A virus
561 bp
AF362792.1

(A/human/Taiwan/0892/99 (H1N1) } hemagglutinin
linear
GI:14571953

(HA) MRNA, partial cds
mRNA

Influenza A virus (A/Taiwan/0983/2002 (H1N1) )
494 bp
AY604800.1

hemagglutinin mRNA, partial cds
linear
GI:50727480

mRNA

Influenza A virus (A/Taiwan/1007/2006 (H1N1) )
507 bp
EU068163.1

hemagglutinin (HA) MRNA, partial cds
linear
GI:158452199

mRNA

Influenza A virus (A/Taiwan/1015/2006 (H1N1) )
507 bp
EU068171.1

hemagglutinin (HA) mRNA, partial cds
linear
GI:158452215

mRNA

Influenza A virus (A/Taiwan/112/1996-1 (H1N1) )
1,176
AF026153.1

haemagglutinin (HA) mRNA, partial cds
bp
GI:2554950

linear

mRNA

Influenza A virus (A/Taiwan/112/1996-2 (H1N1) )
1,176
AF026154.1

haemagglutinin (HA) mRNA, partial cds
bp
GI:2554952

linear

mRNA

Influenza A virus (A/Taiwan/117/1996-1 (H1N1) )
1,176
AF026155.1

haemagglutinin (HA) mRNA, partial cds
bp
GI:2554954

linear

mRNA

Influenza A virus (A/Taiwan/117/1996-2 (H1N1) )
1,176
AF026156.1

haemagglutinin (HA) mRNA, partial cds
bp
GI:2554956

linear

mRNA

Influenza A virus (A/Taiwan/117/1996-3 (H1N1) )
1,176
AF026157.1

haemagglutinin (HA) MRNA, partial cds
bp
GI:2554958

linear

mRNA

Influenza A virus (A/Taiwan/118/1996-1 (H1N1) )
1,176
AF026158.1

haemagglutinin (HA) MRNA, partial cds
bp
GI:2554960

linear

mRNA

Influenza A virus (A/Taiwan/118/1996-2 (H1N1) }
1,176
AF026159.1

haemagglutinin (HA) mRNA, partial cds
bp
GI:2554962

linear

mRNA

Influenza A virus (A/Taiwan/118/1996-3 (H1N1) )
1,176
AF026160.1

haemagglutinin (HA) mRNA, partial cds
bp
GI:2554964

linear

mRNA

Influenza A virus
561 bp
AF362793.1

(A/human/Taiwan/1184/99 (H1N1) ) hemagglutinin
linear
GI:14571955

(HA) mRNA, partial cds
mRNA

Influenza A virus (A/Taiwan/1184/99 (H1N1) )
303 bp
AY303726.1

polymerase basic protein 1 (PB1) MRNA,
linear
GI:32330941

partial cds
mRNA

Influenza A virus
564 bp
AF362794.1

(A/human/Taiwan/1190/95 (H1N1) ) hemagglutinin
linear
GI:14571957

(HA) MRNA, partial cds
mRNA

Influenza A virus (A/Taiwan/1190/95 (H1N1) )
303 bp
AY303727.1

polymerase basic protein 1 (PB1) MRNA,
linear
GI:32330943

partial cds
mRNA

Influenza A virus (A/Taiwan/1523/2003 (H1N1) )
494 bp
AY604808.1

hemagglutinin mRNA, partial cds
linear
GI:50727496

mRNA

Influenza A virus (A/Taiwan/1566/2003 (H1N1) )
494 bp
AY604806.1

hemagglutinin mRNA, partial cds
linear
GI:50727492

mRNA

Influenza A virus (A/Taiwan/1769/96 (H1N1) )
875 bp
AF138710.2

matrix protein Ml (M) mRNA, partial cds
linear
GI:4996871

mRNA

Influenza A virus (A/Taiwan/1906/2002 (H1N1) )
494 bp
AY604799.1

hemagglutinin mRNA, partial cds
linear
GI:50727478

mRNA

Influenza A virus (A/Taiwan/1922/2002 (H1N1) )
494 bp
AY604802.1

hemagglutinin mRNA, partial cds
linear
GI:50727484

mRNA

Influenza A virus (A/Taiwan/2069/2006 (H1N1) )
507 bp
EU068168.1

hemagglutinin (HA) mRNA, partial cds
linear
GI:158452209

mRNA

Influenza A virus (A/Taiwan/2157/2001 (H1N1) )
303 bp
AY303733.1

polymerase basic protein 1 (PB1) mRNA,
linear
GI:32330955

partial cds
mRNA

Influenza A virus (A/Taiwan/2175/2001 (H1N1) )
561 bp
AY303734.1

hemagglutinin (HA) mRNA, partial cds
linear
GI:32330957

mRNA

Influenza A virus
564 bp
AF362795.1

(A/human/Taiwan/2200/95 (H1N1) ) hemagglutinin
linear
GI:14571959

(HA) MRNA, partial cds
mRNA

Influenza A virus (A/Taiwan/2200/95 (H1N1) )
303 bp
AY303737.1

polymerase basic protein 1 (PB1) MRNA,
linear
GI:32330963

partial cds
mRNA

Influenza A virus (A/Taiwan/2966/2006 (H1N1) )
507 bp
EU068170.1

hemagglutinin (HA) mRNA, partial cds
linear
GI:158452213

mRNA

Influenza A virus (A/Taiwan/3168/2005 (H1N1) )
507 bp
EU068174.1

hemagglutinin (HA) mRNA, partial cds
linear
GI:158452221

mRNA

Influenza A virus
561 bp
AF362796.1

(A/human/Taiwan/3355/97 (H1N1) ) hemagglutinin
linear
GI:14571961

(HA) mRNA, partial cds
mRNA

Influenza A virus (A/Taiwan/3355/97 (H1N1) )
303 bp
AY303739.1

polymerase basic protein 1 (PB1) mRNA,
linear
GI:32330967

partial cds
mRNA

Influenza A virus (A/Taiwan/3361/2001 (H1N1) )
303 bp
AY303740.1

polymerase basic protein 1 (PB1) mRNA,
linear
GI:32330969

partial cds
mRNA

Influenza A virus (A/Taiwan/3361/2001 (H1N1) }
561 bp
AY303741.1

hemagglutinin (HA) mRNA, partial cds
linear
GI:32330971

mRNA

Influenza A virus (A/Taiwan/3518/2006 (H1N1) )
507 bp
EU068169.1

hemagglutinin (HA) mRNA, partial cds
linear
GI:158452211

mRNA

Influenza A virus
581 bp
AF362797.1

(A/human/Taiwan/3825/00 (H1N1) ) hemagglutinin
linear
GI:14571963

(HA) mRNA, partial cds
mRNA

Influenza A virus (A/Taiwan/3896/2001 (H1N1) )
303 bp
AY303746.1

polymerase basic protein 1 (PB1) MRNA,
linear
GI:32330981

partial cds
mRNA

Influenza A virus (A/Taiwan/3896/2001 (H1N1) )
561 bp
AY303747.1

hemagglutinin (HA) mRNA, partial cds
linear
GI:32330983

mRNA

Influenza A virus (A/Taiwan/4050/2003 (H1N1) )
494 bp
AY604807.1

hemagglutinin mRNA, partial cds
linear
GI:50727494

mRNA

Influenza A virus (A/Taiwan/4054/2006 (H1N1) )
507 bp
EU068160.1

hemagglutinin (HA) mRNA, partial cds
linear
GI:158452193

mRNA

Influenza A virus
561 bp
AF362798.1

(A/human/Taiwan/4360/99 (H1N1) ) hemagglutinin
linear
GI:14571965

(HA) mRNA, partial cds
mRNA

Influenza A virus (A/Taiwan/4360/99 (H1N1) )
303 bp
AY303748.1

polymerase basic protein 1 (PB1) mRNA,
linear
GI:32330985

partial cds
mRNA

Influenza A virus
561 bp
AF362799.1

(A/human/Taiwan/4415/99 (H1N1) ) hemagglutinin
linear
GI:14571967

(HA) mRNA, partial cds
mRNA

Influenza A virus (A/Taiwan/4415/99 (H1N1) )
303 bp
AY303749.1

polymerase basic protein 1 (PB1) mRNA,
linear
GI:32330987

partial cds
mRNA

Influenza A virus (A/Taiwan/4509/2006 (H1N1) )
507 bp
EU068165.1

hemagglutinin (HA) mRNA, partial cds
linear
GI:158452203

mRNA

Influenza A virus
561 bp
AF362800.1

(A/human/Taiwan/4845/99 (H1N1) ) hemagglutinin
linear
GI:14571969

(HA) mRNA, partial cds
mRNA

Influenza A virus (A/Taiwan/4845/99 (H1N1) )
303 bp
AY303750.1

polymerase basic protein 1 (PB1) MRNA,
linear
GI:32330989

partial cds
mRNA

Influenza A virus
561 bp
AF362801.1

(A/human/Taiwan/4943/99 (H1N1) ) hemagglutinin
linear
GI:14571971

(HA) MRNA, partial cds
mRNA

Influenza A virus (A/Taiwan/5010/2006 (H1N1) )
507 bp
EU068167.1

hemagglutinin (HA) MRNA, partial cds
linear
GI:158452207

mRNA

Influenza A virus
561 bp
AF362802.1

(A/human/Taiwan/5063/99 (H1N1) ) hemagglutinin
linear
GI:14571973

(HA) mRNA, partial cds
mRNA

Influenza A virus (A/Taiwan/5063/99 (H1N1) )
303 bp
AY303751.1

polymerase basic protein 1 (PB1) mRNA,
linear
GI:32330991

partial cds
mRNA

Influenza A virus (A/Taiwan/5084/2006 (H1N1) )
507 bp
EU068166.1

hemagglutinin (HA) mRNA, partial cds
linear
GI:158452205

mRNA

Influenza A virus (A/Taiwan/511/96 (H1N1) )
875 bp
AF138708.2

matrix protein M1 (M) MRNA, partial cds
linear
GI:4996867

mRNA

Influenza A virus (A/Taiwan/557/2006 (H1N1) )
507 bp
EU068156.1

hemagglutinin (HA) mRNA, partial cds
linear
GI:158452185

mRNA

Influenza A virus (A/Taiwan/562/2006 (H1N1) )
507 bp
EU068159.1

hemagglutinin (HA) mRNA, partial cds
linear
GI:158452191

mRNA

Influenza A virus
561 bp
AF362778.1

(A/human/Taiwan/5779/98 (H1N1) ) hemagglutinin
linear
GI:14571925

(HA) mRNA, partial cds
mRNA

Influenza A virus (A/Taiwan/5779/98 (H1N1) )
303 bp
AY303702.1

polymerase basic protein 1 (PB1) MRNA,
linear
GI:32330893

partial cds
mRNA

Influenza A virus (A/Taiwan/6025/2005 (H1N1) )
507 bp
EU068172.1

hemagglutinin (HA) mRNA, partial cds
linear
GI:158452217

mRNA

Influenza A virus (A/Taiwan/607/2006 (H1N1) )
507 bp
EU068157.1

hemagglutinin (HA) mRNA, partial cds
linear
GI:158452187

mRNA

Influenza A virus (A/Taiwan/615/2006 (H1N1) )
507 bp
EU068162.1

hemagglutinin (HA) mRNA, partial cds
linear
GI:158452197

mRNA

Influenza A virus (A/Taiwan/645/2006 (H1N1) )
507 bp
EU068164.1

hemagglutinin (HA) mRNA, partial cds
linear
GI:158452201

mRNA

Influenza A virus (A/Taiwan/680/2005 (H1N1) )
507 bp
EU068173.1

hemagglutinin (HA) mRNA, partial cds
linear
GI:158452219

mRNA

Influenza A virus (A/Taiwan/719/2006 (H1N1) )
507 bp
EU068158.1

hemagglutinin (HA) mRNA, partial cds
linear
GI:158452189

mRNA

Influenza A virus
1,410
EU021285.1

(A/Thailand/CU124/2006 (H3N2) ) neuraminidase
bp
GI:154224724

(NA) mRNA, complete cds
linear

mRNA

Influenza A virus
1,413
EU021265.1

(A/Thailand/CU32/2006 (H1N1) ) neuraminidase
bp
GI:154224704

(NA) MRNA, complete cds
linear

mRNA

Influenza A virus
1,698
EU021264.1

(A/Thailand/CU32/2006 (H1N1) ) hemagglutinin
bp
GI:154224775

(HA) mRNA, complete cds
linear

mRNA

Influenza A virus
1,413
EU021247.1

(A/Thailand/CU41/2006 (H1N1) ) neuraminidase
bp
GI:154224686

(NA) mRNA, complete cds
linear

mRNA

Influenza A virus
1,698
EU021246.1

(A/Thailand/CU41/2006 (H1N1) ) hemagglutinin
bp
GI:154224757

(HA) mRNA, complete cds
linear

mRNA

Influenza A virus
1,413
EU021259.1

(A/Thailand/CU44/2006 (H1N1) ) neuraminidase
bp
GI:154224698

(NA) mRNA, complete cds
linear

mRNA

Influenza A virus
1,698
EU021258.1

(A/Thailand/CU44/2006 (H1N1) ) hemagglutinin
bp
GI:154224769

(HA) mRNA, complete cds
linear

mRNA

Influenza A virus
1,413
EU021255.1

(A/Thailand/CU51/2006 (H1N1) ) neuraminidase
bp
GI:154224694

(NA) mRNA, complete cds
linear

mRNA

Influenza A virus
1,698
EU021254.1

(A/Thailand/CU51/2006 (H1N1) ) hemagglutinin
bp
GI:154224765

(HA) MRNA, complete cds
linear

mRNA

Influenza A virus
1,413
EU021249.1

(A/Thailand/CU53/2006 (H1N1) } neuraminidase
bp
GI:154224688

(NA) mRNA, complete cds
linear

mRNA

Influenza A virus
1,698
EU021248.1

(A/Thailand/CU53/2006 (H1N1) ) hemagglutinin
bp
GI:154224759

(HA) mRNA, complete cds
linear

mRNA

Influenza A virus
1,413
EU021257.1

(A/Thailand/CU57/2006 (H1N1) } neuraminidase
bp
GI:154224696

(NA) mRNA, complete cds
linear

mRNA

Influenza A virus
1,698
EU021256.1

(A/Thailand/CU57/2006 (H1N1) ) hemagglutinin
bp
GI:154224767

(HA) MRNA, complete cds
linear

mRNA

Influenza A virus
1,413
E0021251.1

(A/Thailand/CU67/2006 (H1N1) ) neuraminidase
bp
GI:154224690

(NA) mRNA, complete cds
linear

mRNA

Influenza A virus
1,698
EU021250.1

(A/Thailand/CU67/2006 (H1N1) ) hemagglutinin
bp
GI:154224761

(HA) mRNA, complete cds
linear

mRNA

Influenza A virus
1,413
EU021261.1

(A/Thailand/CU68/2006 (H1N1) ) neuraminidase
bp
GI:154224700

(NA) mRNA, complete cds
linear

mRNA

Influenza A virus
1,698
EU021260.1

(A/Thailand/CU68/2006 (H1N1) ) hemagglutinin
bp
GI:154224771

(HA) mRNA, complete cds
linear

mRNA

Influenza A virus
1,413
EU021263.1

(A/Thailand/CU75/2006 (H1N1) ) neuraminidase
bp
GI:154224702

(NA) MRNA, complete cds
linear

mRNA

Influenza A virus
1,698
EU021262.1

(A/Thailand/CU75/2006 (H1N1) ) hemagglutinin
bp
GI:154224773

(HA) mRNA, complete cds
linear

mRNA

Influenza A virus
1,413
EU021253.1

(A/Thailand/CU88/2006 (H1N1) ) neuraminidase
bp
GI:154224692

(NA) MRNA, complete cds
linear

mRNA

Influenza A virus
1,698
EU021252.1

(A/Thailand/CU88/2006 (H1N1) ) hemagglutinin
bp
GI:154224763

(HA) mRNA, complete cds
linear

MRNA

Influenza A virus
1,565
M76603.1

(A/turkey/England/647/1977 (H1N1) )
bp
GI:325094

nucleoprotein mRNA, complete cds
linear

mRNA

Influenza A virus
1,445
AJ416626.1

(A/turkey/France/87075/87 (H1N1) ) N1 gene for
bp
GI:39840719

neuraminidase, genomic RNA
linear

mRNA

Influenza A virus
394 bp
Z30272.1

(A/turkey/Germany/3/91 (H1N1) ) mRNA for PB2
linear
GI:456652

polymerase (partial)
mRNA

Influenza A virus
97 bp
Z30275.1

(A/turkey/Germany/3/91 (H1N1) ) mRNA for
linear
GI:530398

neuraminidase (UTR)
mRNA

Influenza A virus
264 bp
Z30274.1

(A/turkey/Germany/3/91 (H1N1) ) MRNA for PA
linear
GI:530401

polymerase
mRNA

Influenza A virus
247 bp
Z30273.1

(A/turkey/Germany/3/91 (H1N1) ) mRNA for PBI
linear
GI:530403

polymerase (partial)
mRNA

Influenza A virus
1,038
Z46441,1

(A/turkey/Germany/3/91 (H1N1) ) mRNA for
bp
GI:854218

hemagglutinin HA1
linear

mRNA

Influenza A virus
981 bp
U46941.1

(A/turkey/Minnesota/1661/1981 (H1N1) )
linear
GI:1912332

hemagglutinin (HA) MRNA, partial cds
mRNA

Influenza A virus
1,777
AF091310.1

(A/turkey/Minnesota/1661/81 (H1N1) ) segment 4
bp
GI:4585162

hemagglutinin precursor (HA) MRNA, complete
linear

cds
mRNA

Influenza A virus (A/turkey/North
1,565
M76609.1

Carolina/1790/1988 (H1N1) ) nucleoprotein mRNA,
bp
GI:325096

complete cds
linear

mRNA

Influenza A virus (A/Weiss/43 (H1N1) )
1,410
AF250365.2

neuraminidase (NA) gene, complete cds
bp
GI:13260589

linear

mRNA

Influenza A virus (A/Wilson-Smith/1933 (H1N1) )
1,497
EU330203.1

nucleocapsid protein (NP) mRNA, complete cds
bp
GI:167989512

linear

mRNA

Influenza A virus
241 bp
U47816.1

(A/Wisconsin/3523/1988 (H1N1} ) neuraminidase
linear
GI:1912352

(NA) mRNA, partial cds
mRNA

Influenza A virus
1,565
M76610.1

(A/Wisconsin/3623/1988 (H1N1) ) nucleoprotein
bp
GI:325103

mRNA, complete cds
linear

mRNA

Influenza A virus (A/WI/4754/1994 (H1N1) ) PB1
235 bp
U53156.1

(PB1) mRNA, partial cds
linear
GI:1399590

mRNA

Influenza A virus (A/WI/4754/1994 (H1N1) ) PB2
168 bp
U53158.1

(PB2) mRNA, partial cds
linear
GI:1399594

mRNA

Influenza A virus (A/WI/4754/1994 (H1N1) ) PA
621 bp
U53160.1

(PA) mRNA, partial cds
linear
GI:1399598

mRNA

Influenza A virus (A/WI/4754/1994 (H1N1) )
1,778
U53162.1

hemagglutinin (HA) mRNA, complete cds
bp
GI:1399602

linear

mRNA

Influenza A virus (A/WI/4754/1994 (H1N1) ) NP
200 bp
U53164.1

(NP) mRNA, partial cds
linear
GI:1399606

mRNA

Influenza A virus (A/WI/4754/1994 (H1N1) )
1,458
U53166.1

neuraminidase (NA) mRNA, complete cds
bp
GI:1399610

linear

mRNA

Influenza A virus (A/WI/4754/1994 (H1N1) ) M
1,027
053168.1

(M) mRNA, complete cds
bp
GI:1399614

linear

mRNA

Influenza A virus (A/WI/4754/1994 (H1N1) ) NS
890 bp
U53170.1

(NS) mRNA, complete cds
linear
GI:1399618

mRNA

Influenza A virus (A/WI/4755/1994 (H1N1) ) PB1
203 bp
U53157.1

(PB1) mRNA, partial cds
linear
GI:1399592

mRNA

Influenza A virus (A/WI/4755/1994 (H1N1) ) PB2
173 bp
U53159.1

(PB2) MRNA, partial cds
linear
GI:1399596

mRNA

Influenza A virus (A/WI/4755/1994 (H1N1) ) PA
621 bp
U53161.1

(PA) mRNA, partial cds
linear
GI:1399600

mRNA

Influenza A virus (A/WI/4755/1994 (H1N1) )
1,778
U53163.1

hemagglutinin (HA) mRNA, complete cds
bp
GI:1399604

linear

mRNA

Influenza A virus (A/WI/4755/1994 (H1N1) ) NP
215 bp
U53165.1

(NP) mRNA, partial cds
linear
GI:1399608

mRNA

Influenza A virus (A/WI/4755/1994 (H1N1) )
209 bp
U53167.1

neuraminidase (NA) mRNA, partial cds
linear
GI:1399612

mRNA

Influenza A virus (A/WI/4755/1994 (H1N1) ) M
1,027
U53169.1

(M) mRNA, complete cds
bp
GI:1399616

linear

mRNA

Influenza A virus (A/WI/4755/1994 (H1N1) ) NS
890 bp
U53171.1

(NS) MRNA, complete cds
linear
GI:1399620

mRNA

Influenza A virus (A/WSN/33) segment 5
543 bp
AF306656.1

nucleocapsid protein (NP) MRNA, partial cds
linear
GI:11935089

mRNA

TABLE 7

Influenza H3N2 Antigens

GenBank/GI

Strain/Protein
Length
Accession No.

1. Influenza A virus
1,704 bp
EF614248.1

(A/Aichi/2/1968 (H3N2) ) hemagglutinin
linear
GI:148910819

(HA) mRNA, complete cds
mRNA

2. Influenza A virus
1,698 bp
EF614249.1

(A/Aichi/2/1968 (H3N2) ) hemagglutinin
linear
GI:148910821

(HA) mRNA, partial cds
mRNA

3. Influenza A virus
1,698 bp
EF614250.1

(A/Aichi/2/1968 (H3N2) ) hemagglutinin
linear
GI:148910823

(HA) mRNA, partial cds
mRNA

4. Influenza A virus
1,698 bp
EF614251.1

(A/Aichi/2/1968 (H3N2) ) hemagglutinin
linear
GI:148910825

(HA) mRNA, partial cds
mRNA

5. Influenza A virus
1,032 bp
U48444.1

(A/Akita/1/1995 (H3N2) )
linear
GI:1574989

haemagglutinin mRNA, partial cds
mRNA

6. Influenza A virus
1,041 bp
Z46392.1

(A/Beijing/32/1992 (H3N2) ) mRNA for
linear
GI:609020

haemagglutinin
mRNA

7. Influenza A virus
987 bp
AF501516.1

(A/Canada/33312/99 (H3N2) )
linear
GI:21314288

hemagglutinin (HA) mRNA, partial cds
mRNA

8. Influenza A virus
987 bp
AF297094.1

(A/Charlottesville/10/99 (H3N2) )
linear
GI:11228917

hemagglutinin mRNA, partial cds
mRNA

9. Influenza A virus
987 bp
AF297096.1

(A/Charlottesville/49/99 (H3N2) )
linear
GI:11228921

hemagglutinin mRNA, partial cds
mRNA

10. Influenza A virus
987 bp
AF297097.1

(A/Charlottesville/69/99 (H3N2) )
linear
GI:11228923

hemagglutinin mRNA, partial cds
mRNA

11. Influenza A virus
987 bp
AF297095.1

(A/Charlottesville/73/99 (H3N2) )
linear
GI:11228919

hemagglutinin mRNA, partial cds
mRNA

12. Influenza A virus
1,041 bp
Z46393.1

(A/England/1/1993 (H3N2) ) mRNA for
linear
GI:609024

haemagglutinin
mRNA

13. Influenza A virus
1,041 bp
Z46394.1

(A/England/247/1993 (H3N2) ) mRNA for
linear
GI:609025

haemagglutinin
mRNA

14. Influenza A virus
1,041 bp
Z46395.1

(A/England/269/93 (H3N2) ) MRNA for
linear
GI:609027

haemagglutinin
mRNA

15. Influenza A virus
1,041 bp
Z46396.1

(A/England/284/1993 (H3N2) ) mRNA for
linear
GI:609029

haemagglutinin
mRNA

16. Influenza A virus
1,041 bp
Z46397.1

(A/England/286/1993 (H3N2) ) mRNA for
linear
GI:609031

haemagglutinin
mRNA

17. Influenza A virus
1,041 bp
Z46398.1

(A/England/289/1993 (H3N2) ) mRNA for
linear
GI:609033

haemagglutinin
mRNA

18. Influenza A virus
1,041 bp
Z46399.1

(A/England/328/1993 (H3N2) ) mRNA for
linear
GI:609035

haemagglutinin
mRNA

19. Influenza A virus
1,041 bp
Z46400.1

(A/England/346/1993 (H3N2) ) mRNA for
linear
GI:609037

haemagglutinin
mRNA

20. Influenza A virus
1,041 bp
Z46401.1

(A/England/347/1993 (H3N2) ) mRNA for
linear
GI:609039

haemagglutinin
mRNA

21. Influenza A virus
1,091 bp
AF201875.1

(A/England/42/72 (H3N2) )
linear
GI:6470274

hemagglutinin mRNA, partial cds
mRNA

22. Influenza A virus
1,041 bp
Z46402.1

(A/England/471/1993 (H3N2) ) mRNA for
linear
GI:609041

haemagglutinin
mRNA

23. Influenza A virus
1,041 bp
Z46403.1

(A/England/67/1994 (H3N2) ) mRNA for
linear
GI:609043

haemagglutinin
mRNA

24. Influenza A virus
1,041 bp
Z46404.1

(A/England/68/1994 (H3N2) ) mRNA for
linear
GI:609045

haemagglutinin
mRNA

25. Influenza A virus
1,041 bp
Z46405.1

(A/England/7/1994 (H3N2) ) mRNA for
linear
GI:609047

haemagglutinin
mRNA

28. Influenza A virus
1,041 bp
Z46406.1

(A/Guangdong/25/1993 (H3N2) ) MRNA for
linear
GI:609049

haemagglutinin
mRNA

29. Influenza A virus (A/Hong
1,091 bp
AF201874.1

Kong/1/68 (H3N2) ) hemagglutinin mRNA,
linear
GI:6470272

partial cds
mRNA

30. Influenza A virus (A/Hong
1,041 bp
Z46407.1

Kong/1/1994 (H3N2) ) MRNA for
linear
GI:609051

haemagglutinin
mRNA

31. Influenza A virus (A/Hong
1,762 bp
AF382319.1

Kong/1143/99 (H3N2) ) hemagglutinin
linear
GI:14487957

mRNA, complete cds
mRNA

32. Influenza A virus (A/Hong
1,762 bp
AF382320.1

Kong/1143/99 (H3N2) ) hemagglutinin
linear
GI:14487959

mRNA, complete cds
mRNA

33. Influenza A virus (A/Hong
1,466 bp
AF382329.1

Kong/1143/99 (H3N2) ) neuraminidase
linear
GI:14487977

mRNA, complete cds
mRNA

34. Influenza A virus (A/Hong
1,466 bp
AF382330.1

Kong/1143/99 (H3N2) ) neuraminidase
linear
GI:14487979

mRNA, complete cds
mRNA

35. Influenza A virus (A/Hong
1,762 bp
AY035589.1

Kong/1144/99 (H3N2) ) hemagglutinin
linear
GI:14486403

mRNA, complete cds
mRNA

36. Influenza A virus (A/Hong
1,762 bp
AF382321.1

Kong/1144/99 (H3N2) ) hemagglutinin
linear
GI:14487961

mRNA, complete cds
mRNA

37. Influenza A virus (A/Hong
1,762 bp
AF382322.1

Kong/1144/99 (H3N2) ) hemagglutinin
linear
GI:14487963

mRNA, complete cds
mRNA

38. Influenza A virus (A/Hong
1,466 bp
AF382331.1

Kong/1144/99 (H3N2) ) neuraminidase
linear
GI:14487981

mRNA, complete cds
mRNA

39. Influenza A virus (A/Hong
1, 466 bp
AF382332.1

Kong/1144/99 (H3N2) ) neuraminidase
linear
GI:14487983

mRNA, complete cds
mRNA

40. Influenza A virus (A/Hong
1,762 bp
AY035590.1

Kong/1179/99 (H3N2) ) hemagglutinin
linear
GI:14486405

mRNA, complete cds
mRNA

41. Influenza A virus (A/Hong
1,762 bp
AF382323.1

Kong/1179/99 (H3N2) ) hemagglutinin
linear
GI:14487965

mRNA, complete cds
mRNA

42. Influenza A virus (A/Hong
1,762 bp
AF382324.1

Kong/1179/99 (H3N2) ) hemagglutinin
linear
GI:14487967

mRNA, complete cds
mRNA

43. Influenza A virus (A/Hong
1,762 bp
AY035591.1

Kong/1180/99 (H3N2) ) hemagglutinin
linear
GI:14486407

mRNA, complete cds
mRNA

44. Influenza A virus (A/Hong
1,762 bp
AF382325.1

Kong/1180/99 (H3N2) ) hemagglutinin
linear
GI:14487969

mRNA, complete cds
mRNA

45. Influenza A virus (A/Hong
1,762 bp
AF382326.1

Kong/1180/99 (H3N2) ) hemagglutinin
linear
GI:14487971

mRNA, complete cds
mRNA

46. Influenza A virus (A/Hong
1,762 bp
AF382327.1

Kong/1182/99 (H3N2) ) hemagglutinin
linear
GI:14487973

mRNA, complete cds
mRNA

47. Influenza A virus (A/Hong
1,762 bp
AF382328.1

Kong/1182/99 (H3N2) ) hemagglutinin
linear
GI:14487975

mRNA, complete cds
mRNA

48. Influenza A virus (A/Hong
1,041 bp
Z46408.1

Kong/2/1994 (H3N2) ) mRNA for
linear
GI:609055

haemagglutinin
mRNA

49. Influenza A virus (A/Hong
1,041 bp
Z46410.1

Kong/23/1992 (H3N2) ) mRNA for
linear
GI:609053

haemagglutinin
mRNA

50. Influenza A virus (A/Hong
1,041 bp
Z46409.1

Kong/34/1990 (H3N2) ) mRNA for
linear
GI:609057

haemagglutinin
mRNA

51. Influenza A virus
1,041 bp
Z46397.1

(A/England/286/1993 (H3N2) ) mRNA for
linear
GI:609031

haemagglutinin
mRNA

52. Influenza A virus
1,041 bp
Z46398.1

(A/England/289/1993 (H3N2) } mRNA for
linear
GI:609033

haemagglutinin
mRNA

53. Influenza A virus
1,041 bp
Z46399.1

(A/England/328/1993 (H3N2) ) mRNA for
linear
GI:609035

haemagglutinin
mRNA

54. Influenza A virus
1,041 bp
Z46400.1

(A/England/346/1993 (H3N2) ) mRNA for
linear
GI:609037

haemagglutinin
mRNA

55. Influenza A virus
1,041 bp
Z46401.1

(A/England/347/1993 (H3N2) ) mRNA for
linear
GI:609039

haemagglutinin
mRNA

56. Influenza A virus
1,091 bp
AF201875.1

(A/England/42/72 (H3N2) )
linear
GI:6470274

hemagglutinin mRNA, partial cds
mRNA

57. Influenza A virus
1,041 bp
Z46402.1

(A/England/471/1993 (H3N2) ) mRNA for
linear
GI:609041

haemagglutinin
mRNA

58. Influenza A virus
1,041 bp
Z46403.1

(A/England/67/1994 (H3N2) ) mRNA for
linear
GI:609043

haemagglutinin
mRNA

59. Influenza A virus
1,041 bp
Z46404.1

(A/England/68/1994 (H3N2) ) mRNA for
linear
GI:609045

haemagglutinin
mRNA

60. Influenza A virus
1,041 bp
Z46405.1

(A/England/7/1994 (H3N2) ) mRNA for
linear
GI:609047

haemagglutinin
mRNA

63. Influenza A virus
1,032 bp
U48442.1

(A/Guandong/28/1994 (H3N2) )
linear
GI:1574985

haemagglutinin mRNA, partial cds
mRNA

64. Influenza A virus
1,041 bp
Z46406.1

(A/Guangdong/25/1993 (H3N2) ) mRNA for
linear
GI:609049

haemagglutinin
mRNA

65. Influenza A virus
1,032 bp
U48447.1

(A/Hebei/19/1995 (H3N2) )
linear
GI:1574995

haemagglutinin mRNA, partial cds
mRNA

66. Influenza A virus
1,032 bp
U48441.1

(A/Hebei/41/1994 (H3N2) )
linear
GI:1574983

haemagglutinin mRNA, partial cds
mRNA

67. Influenza A virus (A/Hong
1,091 bp
AF201874.1

Kong/1/68 (H3N2) ) hemagglutinin mRNA,
linear
GI:6470272

partial cds
mRNA

68. Influenza A virus (A/Hong
1,041 bp
Z46407.1

Kong/1/1994 (H3N2) ) mRNA for
linear
GI:609051

haemagglutinin
mRNA

69. Influenza A virus (A/Hong
1,762 bp
AY035588.1

Kong/1143/99 (H3N2) ) hemagglutinin
linear
GI:14486401

mRNA, complete cds
mRNA

70. Influenza A virus (A/Hong
1,762 bp
AF382319.1

Kong/1143/99 (H3N2) ) hemagglutinin
linear
GI:14487957

mRNA, complete cds
mRNA

71. Influenza A virus (A/Hong
1,762 bp
AF382320.1

Kong/1143/99 (H3N2) ) hemagglutinin
linear
GI:14487959

mRNA, complete cds
mRNA

72. Influenza A virus (A/Hong
1,466 bp
AF382329.1

Kong/1143/99 (H3N2) ) neuraminidase
linear
GI:14487977

mRNA, complete cds
mRNA

73. Influenza A virus (A/Hong
1,466 bp
AF382330.1

Kong/1143/99 (H3N2) ) neuraminidase
linear
GI:14487979

mRNA, complete cds
mRNA

74. Influenza A virus (A/Hong
1,762 bp
AY035589.1

Kong/1144/99 (H3N2) ) hemagglutinin
linear
GI:14486403

mRNA, complete cds
mRNA

75. Influenza A virus (A/Hong
1,762 bp
AF382321.1

Kong/1144/99 (H3N2) ) hemagglutinin
linear
GI:14487961

mRNA, complete cds
mRNA

76. Influenza A virus (A/Hong
1,762 bp
AF382322.1

Kong/1144/99 (H3N2) ) hemagglutinin
linear
GI:14487963

mRNA, complete cds
mRNA

77. Influenza A virus (A/Hong
1,466 bp
AF382331.1

Kong/1144/99 (H3N2) ) neuraminidase
linear
GI:14487981

mRNA, complete cds
mRNA

78. Influenza A virus (A/Hong
1,466 bp
AF382332.1

Kong/1144/99 (H3N2) ) neuraminidase
linear
GI:14487983

mRNA, complete cds
mRNA

79. Influenza A virus (A/Hong
1,762 bp
AY035590.1

Kong/1179/99 (H3N2) ) hemagglutinin
linear
GI:14486405

mRNA, complete cds
mRNA

80. Influenza A virus (A/Hong
1,762 bp
AF382323.1

Kong/1179/99 (H3N2) ) hemagglutinin
linear
GI:14487965

mRNA, complete cds
mRNA

81. Influenza A virus (A/Hong
1,762 bp
AF382324.1

Kong/1179/99 (H3N2) ) hemagglutinin
linear
GI:14487967

mRNA, complete cds
mRNA

82. Influenza A virus (A/Hong
1,762 bp
AY035591.1

Kong/1180/99 (H3N2) ) hemagglutinin
linear
GI:14486407

mRNA, complete cds
mRNA

83. Influenza A virus (A/Hong
1,762 bp
AF382325.1

Kong/1180/99 (H3N2) ) hemagglutinin
linear
GI:14487969

mRNA, complete cds
mRNA

84. Influenza A virus (A/Hong
1,762 bp
AF382326.1

Kong/1180/99 (H3N2) ) hemagglutinin
linear
GI:14487971

mRNA, complete cds
mRNA

85. Influenza A virus (A/Hong
1,762 bp
AY035592.1

Kong/1182/99 (H3N2) ) hemagglutinin
linear
GI:14486409

mRNA, complete cds
mRNA

86. Influenza A virus (A/Hong
1,762 bp
AF382327.1

Kong/1182/99 (H3N2) ) hemagglutinin
linear
GI:14487973

mRNA, complete cds
mRNA

87. Influenza A virus (A/Hong
1,762 bp
AF382328.1

Kong/1182/99 (H3N2) ) hemagglutinin
linear
GI:14487975

mRNA, complete cds
mRNA

88. Influenza A virus (A/Hong
1,041 bp
Z46408.1

Kong/2/1994 (H3N2) ) mRNA for
linear
GI:609055

haemagglutinin
mRNA

89. Influenza A virus (A/Hong
1,041 bp
Z46410.1

Kong/23/1992 (H3N2) ) mRNA for
linear
GI:609053

haemagglutinin
mRNA

90. Influenza A virus (A/Hong
1,041 bp
Z46409.1

Kong/34/1990 (H3N2) ) mRNA for
linear
GI:609057

haemagglutinin
mRNA

91. Influenza A virus
987 bp
AF501534.1

(A/Indiana/28170/99 (H3N2) )
linear
GI:21314324

hemagglutinin (HA) mRNA, partial cds
mRNA

92. Influenza A virus
529 bp
AY961997.1

(A/Kinmen/618/03 (H3N2) )
linear
GI:68138151

hemagglutinin (HA) mRNA, partial cds
mRNA

93. Influenza A virus
383 bp
AY973325.1

(A/Kinmen/618/03 (H3N2) )
linear
GI:70673206

neuraminidase (NA) mRNA, partial cds
mRNA

94. Influenza A virus
882 bp
AY986986.1

(A/Kinmen/618/03 (H3N2) )
linear
GI:70728099

nucleoprotein (NP) mRNA, partial cds
mRNA

95. Influenza A virus
545 bp
AY962017.1

(A/Kinmen/621/03 (H3N2) )
linear
GI:68138191

hemagglutinin (HA) MRNA, partial cds
mRNA

96. Influenza A virus
386 bp
AY973326.1

(A/Kinmen/621/03 (H3N2) )
linear
GI:70673208

neuraminidase (NA) mRNA, partial cds
mRNA

97. Influenza A virus
882 bp
AY986987.1

(A/Kinmen/621/03 (H3N2) )
linear
GI:70728101

nucleoprotein (NP) MRNA, partial cds
mRNA

98. Influenza A virus
786 bp
AY962008.1

(A/Kinmen/639/04 (H3N2) )
linear
GI:68138173

hemagglutinin (HA) mRNA, partial cds
mRNA

99. Influenza A virus
381 bp
AY973327.1

(A/Kinmen/639/04 (H3N2) )
linear
GI:70673210

neuraminidase (NA) MRNA, partial cds
mRNA

100. Influenza A virus
882 bp
AY986988.1

(A/Kinmen/639/04 (H3N2) )
linear
GI:70728103

nucleoprotein (NP) MRNA, partial cds
mRNA

101. Influenza A virus
596 bp
AY962004.1

(A/Kinmen/641/04 (H3N2) )
linear
GI:68138165

hemagglutinin (HA) mRNA, partial cds
mRNA

102. Influenza A virus
785 bp
AY973328.1

(A/Kinmen/641/04 (H3N2) )
linear
GI:70673212

neuraminidase (NA) mRNA, partial cds
mRNA

103. Influenza A virus
576 bp
AY962001.1

(A/Kinmen/642/04 (H3N2) )
linear
GI:68138159

hemagglutinin (HA) mRNA, partial cds
mRNA

104. Influenza A virus
580 bp
AY973329.1

(A/Kinmen/642/04 (H3N2) )
linear
GI:70673214

neuraminidase (NA) mRNA, partial cds
mRNA

105. Influenza A virus
882 bp
AY986989.1

(A/Kinmen/642/04 (H3N2) )
linear
GI:70728105

nucleoprotein (NP) mRNA, partial cds
mRNA

106. Influenza A virus
789 bp
AY962009.1

(A/Kinmen/645/04 (H3N2) )
linear
GI:68138175

hemagglutinin (HA) MRNA, partial cds
mRNA

107. Influenza A virus
581 bp
AY973330.1

(A/Kinmen/645/04 (H3N2) )
linear
GI:70673216

neuraminidase (NA) mRNA, partial cds
mRNA

108. Influenza A virus
981 bp
AY986990.1

(A/Kinmen/645/04 (H3N2) )
linear
GI:70728107

nucleoprotein (NP) MRNA, partial cds
mRNA

109. Influenza A virus
2,341 bp
U62543.1

(A/LosAngeles/2/1987 (H3N2) )
linear
GI:1480737

polymerase protein basic 2 (PB2)
mRNA

mRNA, complete cds

110. Influenza A virus
1,041 bp
Z46411.1

(A/Madrid/252/1993 (H3N2) ) mRNA for
linear
GI:609067

haemagglutinin
mRNA

111. Influenza A virus
987 bp
AF501531.1

(A/Michigan/22568/99 (H3N2) )
linear
GI:21314318

hemagglutinin (HA) mRNA, partial cds
mRNA

112. Influenza A virus
987 bp
AF501518.1

(A/Michigan/22692/99 (H3N2) )
linear
GI:21314292

hemagglutinin (HA) mRNA, partial cds
mRNA

113. Influenza A virus
754 bp
AJ519454.1

(A/Moscow/10/99 (H3N2) ) partial NS1
linear
GI:31096423

gene for non structural protein 1
mRNA

and partial NS2 gene for non

structural protein 2, genomic RNA

114. Influenza A virus
987 bp
AY138518.1

(A/ningbo/17/2002 (H3N2) )
linear
GI:24895178

hemagglutinin (HA) mRNA, partial cds
mRNA

115. Influenza A virus
987 bp
AY138517.1

(A/ningbo/25/2002 (H3N2) )
linear

hemagglutinin (HA) MRNA, partial cds
mRNA
GI:24895169

116. Influenza A virus
1,765 bp
V01103.1

(A/NT/60/68/29C (H3N2) ) mRNA for
linear
GI:60800

haemagglutinin (HA1 and HA2 genes)
mRNA

117. Influenza A virus
1,701 bp
DQ059385.1

(A/Oklahoma/323/03 (H3N2) )
linear
GI:66933143

hemagglutinin mRNA, complete cds
mRNA

118. Influenza A virus
1,410 bp
DQ059384.2

(A/Oklahoma/323/03 (H3N2) )
linear

neuraminidase mRNA, complete cds
mRNA
GI:75859981

119. Influenza A virus
766 bp
AJ519458.1

(A/Panama/2007/99 (H3N2) ) partial NS1
linear
GI:31096435

gene for non structural protein 1
mRNA

and partial NS2 gene for non

structural protein 2, genomic RNA

120. Influenza A virus
987 bp
AF501526.1

(A/Pennsalvanya/20109/99 (H3N2) )
linear
GI:21314308

hemagglutinin (HA) mRNA, partial cds
mRNA

121. Influenza A virus
1,091 bp
AF233691.1

(A/Philippines/2/82 (H3N2) )
linear
GI:7331124

hemagglutinin mRNA, partial cds
MRNA

122. Influenza A virus
767 bp
AY962000.1

(A/Pingtung/303/04 (H3N2) )
linear
GI:68138157

hemagglutinin (HA) mRNA, partial cds
mRNA

123. Influenza A virus
783 bp
AY973331.1

(A/Pingtung/303/04 (H3N2) )
linear
GI:70673218

neuraminidase (NA) mRNA, partial cds
mRNA

124. Influenza A virus
928 bp
AY986991.1

(A/Pingtung/303/04 (H3N2) )
linear
GI:70728109

nucleoprotein (NP) mRNA, partial cds
mRNA

125. Influenza A virus
788 bp
AY961999.1

(A/Pingtung/313/04 (H3N2) )
linear
GI:68138155

hemagglutinin (HA) mRNA, partial cds
mRNA

126. Influenza A virus
787 bp
AY973332.1

(A/Pingtung/313/04 (H3N2) )
linear
GI:70673220

neuraminidase (NA) mRNA, partial cds
mRNA

127. Influenza A virus
882 bp
AY986992.1

(A/Pingtung/313/04 (H3N2) )
linear
GI:70728111

nucleoprotein (NP) mRNA, partial cds
mRNA

128. Influenza A virus (A/ruddy
927 bp
AY664458.1

turnstone/Delaware/142/99 (H3N2) )
linear
GI:51011862

nonfunctional matrix protein mRNA,
mRNA

partial sequence

129. Influenza A virus
1,041 bp
Z46413.1

(A/Scotland/142/1993 (H3N2) ) mRNA for
linear
GI:609059

haemagglutinin
mRNA

130. Influenza A virus
1,041 bp
Z46414.1

(A/Scotland/160/1993 (H3N2) ) mRNA for
linear
GI:609061

haemagglutinin
mRNA

131. Influenza A virus
1,041 bp
Z46416.1

(A/Scotland/173/1993 (H3N2) ) mRNA for
linear
GI:609063

haemagglutinin
mRNA

132. Influenza A virus
1,041 bp
Z46415.1

(A/Scotland/174/1993 (H3N2) ) mRNA for
linear
GI:609065

haemagglutinin
mRNA

133. Influenza A virus
1,041 bp
Z46412.1

(A/Scotland/2/1993 (H3N2) ) mRNA for
linear
GI:609069

haemagglutinin
mRNA

134. Influenza A virus
1,032 bp
U48439.1

(A/Sendai/c182/1994 (H3N2) )
linear
GI:1574979

haemagglutinin mRNA, partial cds
mRNA

135. Influenza A virus
1,032 bp
048445.1

(A/Sendai/c373/1995 (H3N2) )
linear
GI:1574991

haemagglutinin mRNA, partial cds
mRNA

136. Influenza A virus
1,032 bp
048440.1

(A/Sendai/c384/1994 (H3N2) )
linear
GI:1574981

haemagglutinin mRNA, partial cds
mRNA

137. Influenza A virus
1,041 bp
246417.1

(A/Shangdong/9/1993 (H3N2) ) mRNA for
linear
GI:609071

haemagglutinin
mRNA

138. Influenza A virus
987 bp
L19416.1

(A/Shanghai/11/1987/x99aE high yield
linear
GI:348117

reassortant (H3N2) ) hemagglutinin
mRNA

(HA) MRNA, partial cds

139. Influenza A virus
2,280 bp
AF225514.1

(A/sw/Shizuoka/110/97 (H3N2) )
linear
GI:27462098

polymerase basic 2 (PB2) mRNA,
mRNA

complete cds

140. Influenza A virus
2,274 bp
AF225518.1

(A/sw/Shizuoka/110/97 (H3N2) )
linear
GI:27462106

polymerase basic 1 (PB1) mRNA,
mRNA

complete cds

141. Influenza A virus
2,151 bp
AF225522.1

(A/sw/Shizuoka/110/97 (H3N2) )
linear
GI:27462114

polymerase acidic (PA) mRNA,
mRNA

complete cds

142. Influenza A virus
1,497 bp
AF225534.1

(A/sw/Shizuoka/110/97 (H3N2) )
linear
GI:27462146

nucleoprotein (NP) mRNA, complete
mRNA

cds

143. Influenza A virus
1,410 bp
AF225538.1

(A/sw/Shizuoka/110/97 (H3N2) )
linear
GI:27462154

neuraminidase (NA) mRNA, complete
mRNA

cds

144. Influenza A virus
984 bp
AF225542.1

(A/sw/Shizuoka/110/97 (H3N2) )
linear
GI:27462162

hemagglutinin (HA1) mRNA, partial
mRNA

cds

145. Influenza A virus
2,280 bp
AF225515.1

(A/sw/Shizuoka/115/97 (H3N2) )
linear
GI:27462100

polymerase basic 2 (PB2) MRNA,
mRNA

complete cds

146. Influenza A virus
2,274 bp
AF225519.1

(A/sw/Shizuoka/115/97 (H3N2) )
linear
GI:27462108

polymerase basic 1 (PB1) mRNA,
mRNA

complete cds

147. Influenza A virus
2,151 bp
AF225523.1

(A/sw/Shizuoka/115/97 (H3N2) )
linear
GI:27462116

polymerase acidic (PA) mRNA,
mRNA

complete cds

148. Influenza A virus
1,497 bp
AF225535.1

(A/sw/Shizuoka/115/97 (H3N2) )
linear
GI:27462148

nucleoprotein (NP) mRNA, complete
mRNA

cds

149. Influenza A virus
1,410 bp
AF225539.1

(A/sw/Shizuoka/115/97 (H3N2) )
linear
GI:27462156

neuraminidase (NA) mRNA, complete
mRNA

cds

150. Influenza A virus
984 bp
AF225543.1

(A/sw/Shizuoka/115/97 (H3N2) )
linear
GI:27462164

hemagglutinin (HA1) MRNA, partial
mRNA

cds

151. Influenza A virus
2,280 bp
AF225516.1

(A/sw/Shizuoka/119/97 (H3N2) )
linear
GI:27462102

polymerase basic 2 (PB2) MRNA,
mRNA

complete cds

152. Influenza A virus
2,274 bp
AF225520.1

(A/sw/Shizuoka/119/97 (H3N2) )
linear
GI:27462110

polymerase basic 1 (PB1) mRNA,
mRNA

complete cds

153. Influenza A virus
2,151 bp
AF225524.1

(A/sw/Shizuoka/119/97 (H3N2) )
linear
GI:27462118

polymerase acidic (PA) mRNA,
mRNA

complete cds

154. Influenza A virus
1,497 bp
AF225536.1

(A/sw/Shizuoka/119/97 (H3N2) )
linear
GI:27462150

nucleoprotein (NP) mRNA, complete
mRNA

cds

155. Influenza A virus
1,410 bp
AF225540.1

(A/sw/Shizuoka/119/97 (H3N2) )
linear
GI:27462158

neuraminidase (NA) mRNA, complete
mRNA

cds

156. Influenza A virus
984 bp
AF225544.1

(A/sw/Shizuoka/119/97 (H3N2) )
linear
GI:27462166

hemagglutinin (HA1) mRNA, partial
mRNA

cds

159. Influenza A virus
1,410 bp
EU163948.1

(A/swine/Bakum/IDT1769/2003 (H3N2) )
linear
GI:157679552

neuraminidase mRNA, complete cds
mRNA

163. Influenza A virus
1,738 bp
AY857957.1

(A/swine/Fujian/668/01 (H3N2) )
linear
GI:58042507

nonfunctional hemagglutinin mRNA,
mRNA

complete sequence

164. Influenza A virus PB2 gene for
2,280 bp
AJ311459.1

Polymerase 2 protein, genomic RNA,
linear
GI:13661041

strain A/Swine/Italy/1523/98
mRNA

165. Influenza A virus PB1 gene for
2,274 bp
AJ311460.1

Polymerase 1 protein, genomic RNA,
linear
GI:13661043

strain A/Swine/Italy/1523/98
mRNA

166. Influenza A virus
821 bp
AJ344024.1

(A/swine/Italy/1523/98 (H3N2) ) NS1
linear
GI:20068146

gene for non structural protein 1
mRNA

and NS2 gene for non structural

protein 2, genomic RNA

167. Influenza A virus
1,465 bp
EU163949.1

(A/swine/Re220/92hp (H3N2) )
linear
GI:157679554

neuraminidase mRNA, complete cds
mRNA

168. Influenza A virus
2,280 bp
AF225517.1

(A/sw/Shizuoka/120/97 (H3N2) )
linear
GI:27462104

polymerase basic 2 (PB2) mRNA,
mRNA

complete cds

169. Influenza A virus
2,274 bp
AF225521.1

(A/sw/Shizuoka/120/97 (H3N2) )
linear
GI:27462112

polymerase basic 1 (PB1) MRNA,
mRNA

complete cds

170. Influenza A virus
2,151 bp
AF225525.1

(A/sw/Shizuoka/120/97 (H3N2) )
linear
GI:27462120

polymerase acidic (PA) MRNA,
mRNA

complete cds

171. Influenza A virus
1,497 bp
AF225537.1

(A/sw/Shizuoka/120/97 (H3N2) )
linear
GI:27462152

nucleoprotein (NP) mRNA, complete
mRNA

cds

172. Influenza A virus
1,410 bp
AF225541.1

(A/sw/Shizuoka/120/97 (H3N2) )
linear
GI:27462160

neuraminidase (NA) mRNA, complete
mRNA

cds

173. Influenza A virus
984 bp
AF225545.1

(A/sw/Shizuoka/120/97 (H3N2) )
linear
GI:27462168

hemagglutinin (HA1) MRNA, partial
mRNA

cds

174. Influenza A virus
1,762 bp
AY032978.1

(A/Switzerland/7729/98 (H3N2) )
linear
GI:14161723

hemagglutinin mRNA, complete cds
mRNA

175. Influenza A virus
1,762 bp
AF382318.1

(A/Switzerland/7729/98 (H3N2) )
linear
GI:14487955

hemagglutinin mRNA, complete cds
mRNA

176. Influenza A virus
528 bp
AY962011.1

(A/Tainan/704/03 (H3N2) )
linear
GI:68138179

hemagglutinin (HA) mRNA, partial cds
mRNA

177. Influenza A virus
384 bp
AY973333.1

(A/Tainan/704/03(H3N2) )
linear
GI:70673222

neuraminidase (NA) mRNA, partial cds
mRNA

178. Influenza A virus
882 bp
AY986993.1

(A/Tainan/704/03 (H3N2) )
linear
GI:70728113

nucleoprotein (NP) mRNA, partial cds
mRNA

179. Influenza A virus
519 bp
AY962012.1

(A/Tainan/712/03 (H3N2) )
linear
GI:68138181

hemagglutinin (HA) MRNA, partial cds
mRNA

180. Influenza A virus
383 bp
AY973334.1

(A/Tainan/712/03 (H3N2) )
linear
GI:70673224

neuraminidase (NA) mRNA, partial cds
mRNA

181. Influenza A virus
882 bp
AY986994.1

(A/Tainan/712/03 (H3N2) )
linear
GI:70728115

nucleoprotein (NP) mRNA, partial cds
mRNA

182. Influenza A virus
784 bp
AY962005.1

(A/Tainan/722/03 (H3N2) )
linear
GI:68138167

hemagglutinin (HA) MRNA, partial cds
mRNA

183. Influenza A virus
592 bp
AY973335.1

(A/Tainan/722/03 (H3N2) )
linear
GI:70673226

neuraminidase (NA) mRNA, partial cds
mRNA

184. Influenza A virus
936 bp
AY986995.1

(A/Tainan/722/03 (H3N2) )
linear
GI:70728117

nucleoprotein (NP) MRNA, partial cds
mRNA

185. Influenza A virus
788 bp
AY961998.1

(A/Taipei/407/03 (H3N2) )
linear
GI:68138153

hemagglutinin (HA) mRNA, partial cds
mRNA

186. Influenza A virus
787 bp
AY973336.1

(A/Taipei/407/03 (H3N2) )
linear
GI:70673228

neuraminidase (NA) mRNA, partial cds
mRNA

187. Influenza A virus
882 bp
AY986996.1

(A/Taipei/407/03 (H3N2) )
linear
GI:70728119

nucleoprotein (NP) mRNA, partial cds
mRNA

188. Influenza A virus
787 bp
AY962007.1

(A/Taipei/416/03 (H3N2) )
linear
GI:68138171

hemagglutinin (HA) mRNA, partial cds
mRNA

189. Influenza A virus
782 bp
AY973337.1

(A/Taipei/416/03 (H3N2) )
linear
GI:70673230

neuraminidase (NA) mRNA, partial cds
mRNA

190. Influenza A virus
882 bp
AY986997.1

(A/Taipei/416/03 (H3N2) )
linear
GI:70728121

nucleoprotein (NP) MRNA, partial cds
mRNA

191. Influenza A virus
297 bp
AY303703.1

(A/Taiwan/0020/98 (H3N2) ) polymerase
linear

basic protein 1 (PB1) mRNA, partial cds
mRNA
GI:32330895

192. Influenza A virus
791 bp
AY604817.1

(A/Taiwan/0040/2003(H3N2) )
linear
GI:50727514

hemagglutinin mRNA, partial cds
mRNA

193. Influenza A virus
297 bp
AY303705.1

(A/Taiwan/0045/98 (H3N2) ) polymerase
linear
GI:32330899

basic protein 1 (PB1) mRNA, partial cds
mRNA

194. Influenza A virus
844 bp
AF362820.1

(A/human/Taiwan/0095/96 (H3N2) )
linear
GI:15055140

hemagglutinin (HA) mRNA, partial cds
mRNA

195. Influenza A virus
791 bp
AY604828.1

(A/Taiwan/0097/2003(H3N2) )
linear
GI:50727536

hemagglutinin mRNA, partial cds
mRNA

196. Influenza A virus
297 bp
AY303706.1

(A/Taiwan/0104/2001 (H3N2) )
linear
GI:32330901

polymerase basic protein 1 (PB1)
mRNA

mRNA, partial cds

197. Influenza A virus
844 bp
AF362805.1

(A/human/Taiwan/0118/98 (H3N2) )
linear
GI:15055110

hemagglutinin (HA) mRNA, partial cds
mRNA

198. Influenza A virus
791 bp
AY604823.1

(A/Taiwan/0122/2003(H3N2) )
linear
GI:50727526

hemagglutinin mRNA, partial cds
mRNA

199. Influenza A virus
844 bp
AF362806.1

(A/human/Taiwan/0149/00 (H3N2) )
linear
GI:15055112

hemagglutinin (HA) mRNA, partial cds
mRNA

200. Influenza A virus
297 bp
AY303712.1

(A/Taiwan/0275/2000 (H3N2) )
linear
GI:32330913

polymerase basic protein 1 (PB1)
mRNA

mRNA, partial cds

201. Influenza A virus
844 bp
AY303713.1

(A/Taiwan/0275/2000 (H3N2) )
linear
GI:32330915

hemagglutinin (HA) mRNA, partial cds
mRNA

202. Influenza A virus
844 bp
AF362807.1

(A/human/Taiwan/0293/98 (H3N2) )
linear
GI:15055114

hemagglutinin (HA) mRNA, partial cds
mRNA

203. Influenza A virus
297 bp
AY303715.1

(A/Taiwan/0346/98 (H3N2) ) polymerase
linear
GI:32330919

basic protein 1 (PB1) mRNA, partial
mRNA

cds

204. Influenza A virus
297 bp
AY303716.1

(A/Taiwan/0379/2000 (H3N2) )
linear
GI:32330921

polymerase basic protein 1 (PB1)
mRNA

mRNA, partial cds

205. Influenza A virus
844 bp
AY303717.1

(A/Taiwan/0379/2000 (H3N2) )
linear
GI:32330923

hemagglutinin (HA) mRNA, partial cds
mRNA

206. Influenza A virus
791 bp
AY625729.1

(A/Taiwan/0388/2001 (H3N2) )
linear
GI:50604415

hemagglutinin (HA) mRNA, partial cds
mRNA

207, Influenza A virus
844 bp
AF362808.1

(A/human/Taiwan/0389/99 (H3N2) )
linear
GI:15055116

hemagglutinin (HA) mRNA, partial cds
mRNA

208. Influenza A virus
844 bp
AF362809.1

(A/human/Taiwan/0423/98 (H3N2) )
linear
GI:15055118

hemagglutinin (HA) mRNA, partial cds
mRNA

209. Influenza A virus
297 bp
AY303718.1

(A/Taiwan/0423/98 (H3N2) ) polymerase
linear
GI:32330925

basic protein 1 (PB1) mRNA, partial
mRNA

cds

210. Influenza A virus
844 bp
AF362810.1

(A/human/Taiwan/0464/98 (H3N2) )
linear
GI:15055120

hemagglutinin (HA) mRNA, partial cds
mRNA

211. Influenza A virus
297 bp
AY303719.1

(A/Taiwan/0464/98 (H3N2) ) polymerase
linear
GI:32330927

basic protein 1 (PB1) mRNA, partial
mRNA

cds

212. Influenza A virus
791 bp
AY625730.1

(A/Taiwan/0568/2001 (H3N2) )
linear
GI:50604440

hemagglutinin (HA) MRNA, partial cds
mRNA

213. Influenza A virus
791 bp
AY604822.1

(A/Taiwan/0570/2003 (H3N2) )
linear
GI:50727524

hemagglutinin mRNA, partial cds
mRNA

214. Influenza A virus
791 bp
AY604827.1

(A/Taiwan/0572/2003 (H3N2) )
linear
GI:50727534

hemagglutinin mRNA, partial cds
mRNA

215. Influenza A virus
791 bp
AY604821.1

(A/Taiwan/0578/2003 (H3N2) )
linear
GI:50727522

hemagglutinin mRNA, partial cds
mRNA

216. Influenza A virus
791 bp
AY604820.1

(A/Taiwan/0583/2003(H3N2) )
linear
GI:50727520

hemagglutinin mRNA, partial cds
mRNA

217. Influenza A virus
297 bp
AY303722.1

(A/Taiwan/0646/2000 (H3N2) )
linear
GI:32330933

polymerase basic protein 1 (PB1)
mRNA

mRNA, partial cds

218. Influenza A virus
844 bp
AY303723.1

(A/Taiwan/0646/2000 (H3N2) )
linear
GI:32330935

hemagglutinin (HA) MRNA, partial cds
mRNA

219. Influenza A virus
844 bp
AF362811.1

(A/human/Taiwan/0830/99 (H3N2) )
linear
GI:15055122

hemagglutinin (HA) mRNA, partial cds
mRNA

220. Influenza A virus
791 bp
AY625731.1

(A/Taiwan/0964/2001 (H3N2) )
linear
GI:50604469

hemagglutinin (HA) MRNA, partial cds
mRNA

221. Influenza A virus
844 bp
AF362812.1

(A/human/Taiwan/1008/99 (H3N2) )
linear
GI:15055124

hemagglutinin (HA) mRNA, partial cds
mRNA

222. Influenza A virus
297 bp
AY303725.1

(A/Taiwan/1008/99 (H3N2) ) polymerase
linear
GI:32330939

basic protein 1 (PB1) mRNA, partial
mRNA

cds

223. Influenza A virus
750 bp
EU068138.1

(A/Taiwan/1219/2004 (H3N2) )
linear
GI:158452149

hemagglutinin (HA) MRNA, partial cds
mRNA

224. Influenza A virus
750 bp
EU068125.1

(A/Taiwan/1315/2005 (H3N2) )
linear
GI:158452123

hemagglutinin (HA) mRNA, partial cds
mRNA

225. Influenza A virus
750 bp
EU068153.1

(A/Taiwan/1511/2004 (H3N2) )
linear
GI:158452179

hemagglutinin (HA) mRNA, partial cds
mRNA

226. Influenza A virus
750 bp
EU068119.1

(A/Taiwan/1533/2003(H3N2) )
linear
GI:158452111

hemagglutinin (HA) mRNA, partial cds
mRNA

227. Influenza A virus
844 bp
AF362813.1

(A/human/Taiwan/1537/99 (H3N2) )
linear
GI:15055126

hemagglutinin (HA) MRNA, partial cds
mRNA

228. Influenza A virus
297 bp
AY303728.1

(A/Taiwan/1537/99 (H3N2) ) polymerase
linear
GI:32330945

basic protein 1 (PB1) mRNA, partial
mRNA

cds

229. Influenza A virus
791 bp
AY604826.1

(A/Taiwan/1566/2003 (H3N2) )
linear
GI:50727532

hemagglutinin mRNA, partial cds
mRNA

230. Influenza A virus
791 bp
AY604819.1

(A/Taiwan/1568/2003 (H3N2) )
linear
GI:50727518

hemagglutinin mRNA, partial cds
mRNA

231. Influenza A virus
750 bp
EU068116.1

(A/Taiwan/158/2003 (H3N2) )
linear
GI:158452105

hemagglutinin (HA) mRNA, partial cds
mRNA

232. Influenza A virus
875 bp
AF138709.2

(A/Taiwan/1600/96 (H3N2) ) matrix
linear
GI:4996869

protein M1 (M) mRNA, partial cds
mRNA

233. Influenza A virus
750 bp
EU068117.1

(A/Taiwan/1613/2003 (H3N2) )
linear
GI:158452107

hemagglutinin (HA) MRNA, partial cds
mRNA

234. Influenza A virus
750 bp
EU068148.1

(A/Taiwan/1651/2004 (H3N2) )
linear
GI:158452169

hemagglutinin (HA) mRNA, partial cds
mRNA

235. Influenza A virus
844 bp
AF362814.1

(A/human/Taiwan/1748/97 (H3N2) )
linear
GI:15055128

hemagglutinin (HA) MRNA, partial cds
mRNA

236. Influenza A virus
297 bp
AY303729.1

(A/Taiwan/1748/97 (H3N2) ) polymerase
linear
GI:32330947

basic protein 1 (PB1) mRNA, partial
mRNA

cds

237. Influenza A virus
872 bp
AF138707.2

(A/Taiwan/179/96 (H3N2) ) matrix
linear
GI:4996865

protein M1 (M) mRNA, partial cds
mRNA

238. Influenza A virus
750 bp
EU068139.1

(A/Taiwan/1817/2004 (H3N2) )
linear
GI:158452151

hemaqqlutinin (HA) MRNA, partial cds
mRNA

239. Influenza A virus
750 bp
EU068154.1

(A/Taiwan/1904/2003 (H3N2) )
linear
GI:158452181

hemagglutinin (HA) mRNA, partial cds
mRNA

240. Influenza A virus
750 bp
EU068155.1

(A/Taiwan/1921/2003(H3N2) )
linear
GI:158452183

hemagglutinin (HA) MRNA, partial cds
mRNA

241. Influenza A virus
844 bp
AF362815.1

(A/human/Taiwan/1986/96 (H3N2) )
linear
GI:15055130

hemagglutinin (HA) mRNA, partial cds
mRNA

242. Influenza A virus
297 bp
AY303730.1

(A/Taiwan/1990/96 (H3N2) ) polymerase
linear
GI:32330949

basic protein 1 (PB1) mRNA, partial
mRNA

cds

243. Influenza A virus
844 bp
AY303731.1

(A/Taiwan/1990/96 (H3N2) )
linear
GI:32330951

hemagglutinin (HA) MRNA, partial cds
mRNA

244. Influenza A virus
861 bp
AF139938.1

(A/Taiwan/20/98 (H3N2) ) H3
linear
GI:4972940

hemagglutinin (HA) mRNA, partial cds
mRNA

245. Influenza A virus
392 bp
AF140627.1

(A/Taiwan/20/98 (H3N2) ) N2
linear
GI:4972988

neuraminidase (NA) MRNA, partial cds
mRNA

246. Influenza A virus
875 bp
AF138715.2

(A/Taiwan/20/98 (H3N2) ) matrix
linear
GI:4996879

protein M1 (M) mRNA, partial cds
mRNA

247. Influenza A virus
844 bp
AF362816.1

(A/human/Taiwan/2031/97 (H3N2) )
linear
GI:15055132

hemagglutinin (HA) mRNA, partial cds
mRNA

248. Influenza A virus
861 bp
AF139937.1

(A/Taiwan/2034/96 (H3N2) ) H3
linear
GI:4972938

hemagglutinin (HA) MRNA, partial cds
mRNA

249. Influenza A virus
392 bp
AF140620.1

(A/Taiwan/2034/96 (H3N2) ) N2
linear
GI:4972974

neuraminidase (NA) mRNA, partial cds
mRNA

250. Influenza A virus
297 bp
AY303732.1

(A/Taiwan/2034/96 (H3N2) ) polymerase
linear
GI:32330953

basic protein 1 (PB1) mRNA, partial
mRNA

cds

251. Influenza A virus
791 bp
AY604818.1

(A/Taiwan/2040/2003(H3N2) )
linear
GI:50727516

hemagglutinin mRNA, partial cds
mRNA

252. Influenza A virus
750 bp
EU068131.1

(A/Taiwan/2072/2006(H3N2) )
linear
GI:158452135

hemagglutinin (HA) mRNA, partial cds
mRNA

253. Influenza A virus
861 bp
AF139934.1

(A/Taiwan/21/98 (H3N2) ) H3
linear
GI:4972932

hemagglutinin (HA) mRNA, partial cds
mRNA

254. Influenza A virus
392 bp
AF140624.1

(A/Taiwan/21/98 (H3N2) ) N2
linear
GI:4972982

neuraminidase (NA) MRNA, partial cds
mRNA

255. Influenza A virus
875 bp
AF138716.2

(A/Taiwan/21/98 (H3N2) ) matrix
linear
GI:4996881

protein M1 (M) mRNA, partial cds
mRNA

256. Influenza A virus
861 bp
AF139932.1

(A/Taiwan/2191/96(H3N2) ) H3
linear
GI:4972928

hemagglutinin (HA) MRNA, partial cds
mRNA

257. Influenza A virus
392 bp
AF140622.1

(A/Taiwan/2191/96 (H3N2) ) N2
linear
GI:4972978

neuraminidase (NA) mRNA, partial cds
mRNA

258. Influenza A virus
875 bp
AF138711.3

(A/Taiwan/2191/96 (H3N2) ) matrix
linear
GI:156147502

protein MI (M) MRNA, partial cds
mRNA

259. Influenza A virus
861 bp
AF139936.1

(A/Taiwan/2192/96 (H3N2) ) H3
linear
GI:4972936

hemagglutinin (HA) MRNA, partial cds
mRNA

260. Influenza A virus
392 bp
AF140626.1

(A/Taiwan/2192/96 (H3N2) ) N2
linear
GI:4972986

neuraminidase (NA) mRNA, partial cds
mRNA

261. Influenza A virus
297 bp
AY303735.1

(A/Taiwan/2195/96 (H3N2) ) polymerase
linear
GI:32330959

basic protein 1 (PB1) mRNA, partial
mRNA

cds

262. Influenza A virus
844 bp
AY303736.1

(A/Taiwan/2195/96 (H3N2) )
linear
GI:32330961

hemagglutinin (HA) mRNA, partial cds
mRNA

263. Influenza A virus
875 bp
AF138718.2

(A/Taiwan/224/98 (H3N2) ) matrix
linear
GI:4996885

protein Ml (M) mRNA, partial cds
mRNA

264. Influenza A virus
844 bp
AF362817.1

(A/human/Taiwan/2548/99 (H3N2) )
linear
GI:15055134

hemagglutinin (HA) MRNA, partial cds
mRNA

265. Influenza A virus
750 bp
EU068120.1

(A/Taiwan/268/2005 (H3N2) )
linear
GI:158452113

hemagglutinin (HA) mRNA, partial cds
mRNA

266. Influenza A virus
750 bp
EU068149.1

(A/Taiwan/3008/2004 (H3N2) )
linear
GI:158452171

hemagglutinin (HA) mRNA, partial cds
mRNA

267. Influenza A virus
750 bp
EU068152.1

(A/Taiwan/3075/2003 (H3N2) )
linear
GI:158452177

hemagglutinin (HA) mRNA, partial cds
mRNA

268. Influenza A virus
940 bp
AF362818.1

(A/human/Taiwan/3083/00 (H3N2) )
linear
GI:15055136

hemagglutinin (HA) mRNA, partial cds
mRNA

269. Influenza A virus
791 bp
AY604811.1

(A/Taiwan/3131/2002 (H3N2) )
linear
GI:50727502

hemagglutinin mRNA, partial cds
mRNA

270. Influenza A virus
750 bp
EU068145.1

(A/Taiwan/3154/2004 (H3N2) )
linear
GI:158452163

hemagglutinin (HA) mRNA, partial cds
mRNA

271. Influenza A virus
750 bp
EU068141.1

(A/Taiwan/3187/2004 (H3N2) )
linear
GI:158452155

hemagglutinin (HA) MRNA, partial cds
mRNA

272. Influenza A virus
750 bp
EU068134.1

(A/Taiwan/3245/2004 (H3N2) )
linear
GI:158452141

hemagglutinin (HA) mRNA, partial cds
mRNA

273. Influenza A virus
750 bp
EU068133.1

(A/Taiwan/3294/2005 (H3N2) )
linear
GI:158452139

hemagglutinin (HA) mRNA, partial cds
mRNA

274. Influenza A virus
861 bp
AF139935.1

(A/Taiwan/3351/97(H3N2) ) H3
linear
GI:4972934

hemagglutinin (HA) mRNA, partial cds
mRNA

275. Influenza A virus
392 bp
AF140625.1

(A/Taiwan/3351/97 (H3N2) ) N2
linear
GI:4972984

neuraminidase (NA) mRNA, partial cds
mRNA

276. Influenza A virus
875 bp
AF138713.2

(A/Taiwan/3351/97 (H3N2) ) matrix
linear
GI:4996875

protein M1 (M) MRNA, partial cds
mRNA

277. Influenza A virus
297 bp
AY303738.1

(A/Taiwan/3351/97 (H3N2) ) polymerase
linear
GI:32330965

basic protein 1 (PB1) mRNA, partial
mRNA

cds

278. Influenza A virus
750 bp
EU068132.1

(A/Taiwan/3387/2005 (H3N2) )
linear
GI:158452137

hemagglutinin (HA) mRNA, partial cds
mRNA

279. Influenza A virus
297 bp
AY303742.1

(A/Taiwan/3396/97 (H3N2) ) polymerase
linear
GI:32330973

basic protein 1 (PB1) mRNA, partial
mRNA

cds

280. Influenza A virus
844 bp
AY303743.1

(A/Taiwan/3396/97 (H3N2) )
linear
GI:32330975

hemagglutinin (HA) mRNA, partial cds
mRNA

281. Influenza A virus
861 bp
AF139930.1

(A/Taiwan/3427/97 (H3N2) ) H3
linear
GI:4972924

hemagglutinin (HA) MRNA, partial cds
mRNA

282. Influenza A virus
392 bp
AF140619.1

(A/Taiwan/3427/97 (H3N2) ) N2
linear
GI:4972972

neuraminidase (NA) MRNA, partial cds
mRNA

283. Influenza A virus
861 bp
AF139940.1

(A/Taiwan/346/98 (H3N2) ) H3
linear
GI:4972944

hemagglutinin (HA) mRNA partial cds
mRNA

284. Influenza A virus
392 bp
AF140787.1

(A/Taiwan/346/98 (H3N2) ) N2
linear
GI:4972992

neuraminidase (NA) mRNA, partial cds
mRNA

285. Influenza A virus
875 bp
AF138719.2

(A/Taiwan/346/98 (H3N2) ) matrix
linear
GI:4996887

protein Ml (M) mRNA, partial cds
mRNA

286. Influenza A virus
942 bp
AF362819.1

(A/human/Taiwan/3460/00 (H3N2) )
linear
GI:15055138

truncated hemagglutinin (HA) mRNA,
mRNA

partial cds

287. Influenza A virus
861 bp
AF139933.1

(A/Taiwan/3469/97 (H3N2) ) H3
linear
GI:4972930

hemagglutinin (HA) mRNA, partial cds
mRNA

288. Influenza A virus
392 bp
AF140623.1

(A/Taiwan/3469/97 (H3N2) ) N2
linear
GI:4972980

neuraminidase (NA) mRNA, partial cds
mRNA

289. Influenza A virus
875 bp
AF138714.2

(A/Taiwan/3469/97 (H3N2) ) matrix
linear
GI:4996877

protein M1 (M) mRNA, partial cds
mRNA

290. Influenza A virus
297 bp
AY303744.1

(A/Taiwan/3503/97 (H3N2) ) polymerase
linear
GI:32330977

basic protein 1 (PB1) mRNA, partial
mRNA

cds

291. Influenza A virus
844 bp
AY303745.1

(A/Taiwan/3503/97 (H3N2) )
linear
GI:32330979

hemagglutinin (HA) mRNA, partial cds
mRNA

292. Influenza A virus
919 bp
AF138712.1

(A/Taiwan/3513/96 (H3N2) ) matrix
linear
GI:4928900

protein M1 (M) mRNA, partial cds
mRNA

293. Influenza A virus
861 bp
AF139931.1

(A/Taiwan/3513/97 (H3N2) ) H3
linear
GI:4972926

hemagglutinin (HA) MRNA, partial cds
mRNA

294. Influenza A virus
392 bp
AF140621.1

(A/Taiwan/3513/97 (H3N2) ) N2
linear
GI:4972976

neuraminidase (NA) mRNA, partial cds
mRNA

295. Influenza A virus
791 bp
AY604814.1

(A/Taiwan/3744/2002 (H3N2) )
linear
GI:50727508

hemagglutinin mRNA, partial cds
mRNA

296. Influenza A virus
940 bp
AF362804.1

(A/human/Taiwan/3760/00 (H3N2) )
linear
GI:15055108

hemagglutinin (HA) mRNA, partial cds
mRNA

297. Influenza A virus
561 bp
AY303747.1

(A/Taiwan/3896/2001 (H1N1) )
linear
GI:32330983

hemagglutinin (HA) MRNA, partial cds
mRNA

298. Influenza A virus
791 bp
AY604825.1

(A/Taiwan/4050/2003(H3N2) )
linear
GI:50727530

hemagglutinin mRNA, partial cds
mRNA

299. Influenza A virus
791 bp
AY604824.1

(A/Taiwan/4063/2003 (H3N2) )
linear
GI:50727528

hemagglutinin mRNA, partial cds
mRNA

300. Influenza A virus
750 bp
EU068137.1

(A/Taiwan/41/2004 (H3N2) )
linear
GI:158452147

hemagglutinin (HA) MRNA, partial cds
mRNA

301. Influenza A virus
861 bp
AF139939.1

(A/Taiwan/45/98 (H3N2) ) H3
linear
GI:4972942

hemagglutinin (HA) mRNA, partial cds
mRNA

302. Influenza A virus
392 bp
AF140628.1

(A/Taiwan/45/98 (H3N2) ) N2
linear
GI:4972990

neuraminidase (NA) mRNA, partial cds
mRNA

303. Influenza A virus
875 bp
AF138717.2

(A/Taiwan/45/98 (H3N2) ) matrix
linear
GI:4996883

protein Ml (M) mRNA, partial cds
mRNA

304. Influenza A virus
750 bp
EU068114.1

(A/Taiwan/4548/2003 (H3N2) )
linear
GI:158452101

hemagglutinin (HA) mRNA, partial cds
mRNA

305. Influenza A virus
791 bp
AY604813.1

(A/Taiwan/4673/2002 (H3N2) )
linear
GI:50727506

hemagglutinin mRNA, partial cds
mRNA

306. Influenza A virus
791 bp
AY604812.1

(A/Taiwan/4680/2002(H3N2) )
linear
GI:50727504

hemagglutinin mRNA, partial cds
mRNA

307. Influenza A virus
750 bp
EU068136.1

(A/Taiwan/4735/2004 (H3N2) )
linear
GI:158452145

hemagglutinin (HA) MRNA, partial cds
mRNA

308. Influenza A virus
750 bp
EU068142.1

(A/Taiwan/4829/2005 (H3N2) )
linear
GI:158452157

hemagglutinin (HA) mRNA, partial cds
mRNA

309. Influenza A virus
750 bp
EU068130.1

(A/Taiwan/4836/2005 (H3N2) )
linear
GI:158452133

hemagglutinin (HA) mRNA, partial cds
mRNA

310. Influenza A virus
750 bp
EU068143.1

(A/Taiwan/4865/2005(H3N2) )
linear
GI:158452159

hemagglutinin (HA) mRNA, partial cds
mRNA

311. Influenza A virus
750 bp
EU068121.1

(A/Taiwan/4883/2005 (H3N2) )
linear
GI:158452115

hemagglutinin (HA) mRNA, partial cds
mRNA

312. Influenza A virus
791 bp
AY604809.1

(A/Taiwan/4938/2002 (H3N2) )
linear
GI:50727498

hemagglutinin mRNA, partial cds
mRNA

313. Influenza A virus
791 bp
AY604815.1

(A/Taiwan/4954/2002 (H3N2) )
linear
GI:50727510

hemagglutinin mRNA, partial cds
mRNA

314. Influenza A virus
791 bp
AY604810.1

(A/Taiwan/4963/2002 (H3N2) )
linear
GI:50727500

hemagglutinin mRNA, partial cds
mRNA

315. Influenza A virus
750 bp
EU068122.1

(A/Taiwan/4987/2005 (H3N2) )
linear
GI:158452117

hemagglutinin (HA) mRNA, partial cds
mRNA

316. Influenza A virus
750 bp
EU068127.1

(A/Taiwan/4990/2005 (H3N2) )
linear
GI:158452127

hemagglutinin (HA) mRNA, partial cds
mRNA

317. Influenza A virus
750 bp
EU068118.1

(A/Taiwan/5/2003 (H3N2) )
linear
GI:158452109

hemagglutinin (HA) mRNA, partial cds
mRNA

318. Influenza A virus
791 bp
AY604816.1

(A/Taiwan/5153/2002 (H3N2) )
linear
GI:50727512

hemagglutinin mRNA, partial cds
MRNA

319. Influenza A virus
750 bp
EU068128.1

(A/Taiwan/5267/2005 (H3N2) )
linear
GI:158452129

hemagglutinin (HA) mRNA, partial cds
mRNA

320. Influenza A virus
750 bp
EU068146.1

(A/Taiwan/556/2004 (H3N2) )
linear
GI:158452165

hemagglutinin (HA) MRNA, partial cds
mRNA

321. Influenza A virus
750 bp
EU068126.1

(A/Taiwan/5694/2005(H3N2) )
linear
GI:158452125

hemagglutinin (HA) mRNA, partial cds
mRNA

322. Influenza A virus
750 bp
EU068147.1

(A/Taiwan/587/2004 (H3N2) )
linear
GI:158452167

hemagglutinin (HA) mRNA, partial cds
mRNA

323. Influenza A virus
750 bp
EU068151.1

(A/Taiwan/592/2004 (H3N2) )
linear
GI:158452175

hemagglutinin (HA) MRNA, partial cds
mRNA

324. Influenza A virus
791 bp
AY604829.1

(A/Taiwan/7099/2003 (H3N2) )
linear
GI:50727538

hemagglutinin mRNA, partial cds
mRNA

325. Influenza A virus
791 bp
AY604830.1

(A/Taiwan/7100/2003(H3N2) )
linear
GI:50727540

hemagglutinin mRNA, partial cds
mRNA

326. Influenza A virus
750 bp
EU068150.1

(A/Taiwan/7196/2003 (H3N2) )
linear
GI:158452173

hemagglutinin (HA) MRNA, partial cds
mRNA

327. Influenza A virus
750 bp
EU068135.1

(A/Taiwan/7568/2004 (H3N2) )
linear
GI:158452143

hemagglutinin (HA) mRNA, partial cds
mRNA

328. Influenza A virus
750 bp
EU068144.1

(A/Taiwan/7601/2005 (H3N2) )
linear

hemagglutinin (HA) mRNA, partial cds
mRNA
GI:158452161

329. Influenza A virus
750 bp
EU068124.1

(A/Taiwan/7681/2005(H3N2) )
linear
GI:158452121

hemagglutinin (HA) mRNA, partial cds
mRNA

330. Influenza A virus
750 bp
E0068123.1

(A/Taiwan/7702/2005 (H3N2) )
linear
GI:158452119

hemagglutinin (HA) mRNA, partial cds
mRNA

331. Influenza A virus (A/Taiwan/7873/2005 (H3N2) )
750 bp
EU068129.1

hemagglutinin (HA) mRNA, partial cds
linear
GI:158452131

mRNA

332. Influenza A virus
750 bp
EU068115.1

(A/Taiwan/8/2003 (H3N2) )
linear
GI:158452103

hemagglutinin (HA) mRNA, partial cds
mRNA

333. Influenza A virus
750 bp
EU068140.1

(A/Taiwan/93/2004 (H3N2) )
linear
GI:158452153

hemagglutinin (HA) mRNA, partial cds
mRNA

334. Influenza A virus
528 bp
AY962016.1

(A/Taoyuan/108/02 (H3N2) )
linear
GI:68138189

hemagglutinin (HA) mRNA partial cds
mRNA

335. Influenza A virus
754 bp
AY973338.1

(A/Taoyuan/108/02 (H3N2) )
linear
GI:70673232

neuraminidase (NA) mRNA, partial cds
mRNA

336. Influenza A virus
882 bp
AY986998.1

(A/Taoyuan/108/02 (H3N2) )
linear
GI:70728123

nucleoprotein (NP) mRNA, partial cds
mRNA

337. Influenza A virus
1,410 bp
EU021285.1

(A/Thailand/CU124/2006 (H3N2) )
linear
GI:154224724

neuraminidase (NA) MRNA, complete
mRNA

cds

338. Influenza A virus
1,701 bp
EU021284.1

(A/Thailand/CU124/2006 (H3N2) )
linear
GI:154224795

hemagglutinin (HA) MRNA, complete
mRNA

cds

339. Influenza A virus
1,410 bp
EU021275.1

(A/Thailand/CU228/2006 (H3N2) )
linear
GI:154224714

neuraminidase (NA) mRNA, complete
mRNA

cds

340. Influenza A virus
1,701 bp
EU021274.1

(A/Thailand/CU228/2006 (H3N2) )
linear
GI:154224785

hemagglutinin (HA) mRNA, complete
mRNA

cds

341. Influenza A virus
1,347 bp
EU021267.1

(A/Thailand/CU23/2006 (H3N2) )
linear
GI:154224706

neuraminidase (NA) MRNA, partial cds
mRNA

342. Influenza A virus
1,701 bp
EU021266.1

(A/Thailand/CU23/2006 (H3N2) )
linear
GI:154224777

hemagglutinin (HA) mRNA, complete
mRNA

cds

343. Influenza A virus
1,410 bp
E0021283.1

(A/Thailand/CU231/2006 (H3N2) )
linear
GI:154224722

neuraminidase (NA) MRNA, complete
mRNA

cds

344. Influenza A virus
1,701 bp
EU021282.1

(A/Thailand/CU231/2006 (H3N2) )
linear
GI:154224793

hemagglutinin (HA) mRNA, complete
mRNA

cas

345. Influenza A virus
1,410 bp
EU021279.1

(A/Thailand/CU259/2006 (H3N2) )
linear
GI:154224718

neuraminidase (NA) MRNA, complete
mRNA

cds

346. Influenza A virus
1,701 bp
EU021278.1

(A/Thailand/CU259/2006 (H3N2) )
linear
GI:154224789

hemagglutinin (HA) mRNA, complete
mRNA

cds

347. Influenza A virus
1, 410 bp
EU021281.1

(A/Thailand/CU260/2006 (H3N2) )
linear
GI:154224720

neuraminidase (NA) mRNA, complete
mRNA

cds

348. Influenza A virus
1,129 bp
EU021280.1

(A/Thailand/CU260/2006 (H3N2) )
linear
GI:154224791

hemagglutinin (HA) mRNA, partial cds
mRNA

349. Influenza A virus
1,410 bp
EU021271.1

(A/Thailand/CU272/2007 (H3N2) )
linear
GI:154224710

neuraminidase (NA) MRNA, complete
mRNA

cds

350. Influenza A virus
1,701 bp
EU021270.1

(A/Thailand/CU272/2007 (H3N2) )
linear
GI:154224781

hemagglutinin (HA) MRNA, complete
mRNA

cds

351. Influenza A virus
1,410 bp
EU021273.1

(A/Thailand/CU280/2007 (H3N2) )
linear
GI:154224712

neuraminidase (NA) mRNA, complete
mRNA

cds

352. Influenza A virus
1,701 bp
EU021272.1

(A/Thailand/CU280/2007 (H3N2) )
linear
GI:154224783

hemagglutinin (HA) mRNA, complete
mRNA

cds

353. Influenza A virus
1,410 bp
EU021277.1

(A/Thailand/CU282/2007 (H3N2) )
linear
GI:154224716

neuraminidase (NA) MRNA, complete
mRNA

cds

354. Influenza A virus
1,701 bp
EU021276.1

(A/Thailand/CU282/2007 (H3N2) )
linear
GI:154224787

hemagglutinin (HA) mRNA, complete
mRNA

cds

355. Influenza A virus
1,413 bp
EU021265.1

(A/Thailand/CU32/2006 (H1N1) )
linear
GI:154224704

neuraminidase (NA) mRNA, complete
mRNA

cds

361. Influenza A virus
1,410 bp
EU021269.1

(A/Thailand/CU46/2006 (H3N2} )
linear
GI:154224708

neuraminidase (NA) mRNA, complete
mRNA

cds

362. Influenza A virus
1,701 bp
EU021268.1

(A/Thailand/CU46/2006 (H3N2) )
linear
GI:154224779

hemagglutinin (HA) mRNA, complete
mRNA

cds

377. Influenza A virus
987 bp
U77837.1

(A/Tottori/849AM1AL3/1994 (H3N2) )
linear
GI:2992515

hemagglutinin (HA) mRNA, partial cds
mRNA

378. Influenza A virus
987 bp
U77833.1

(A/Tottori/849AM2/1994 (H3N2) )
linear
GI:2992507

hemagglutinin (HA) mRNA, partial cds
mRNA

379. Influenza A virus
987 bp
U77839.1

(A/Tottori/849AM2AL3/1994 (H3N2) )
linear
GI:2992519

hemagglutinin (HA) mRNA, partial cds
mRNA

380. Influenza A virus
987 bp
U77835.1

(A/Tottori/849AM4/1994 (H3N2) )
linear
GI:2992511

hemagglutinin (HA) MRNA, partial cds
mRNA

382. Influenza A virus
987 bp
U77834.1

(A/Tottori/872AM2/1994 (H3N2) )
linear
GI:2992509

hemagglutinin (HA) mRNA, partial cds
mRNA

383. Influenza A virus
987 bp
U77840.1

(A/Tottori/872AM2AL3/1994 (H3N2) )
linear
GI:2992521

hemagglutinin (HA) MRNA, partial cds
mRNA

384. Influenza A virus
987 bp
U77836.1

(A/Tottori/872AM4/1994 (H3N2) )
linear
GI:2992513

hemagglutinin (HA) MRNA, partial cds
mRNA

385. Influenza A virus
987 bp
U77832.1

(A/Tottori/872K4/1994 (H3N2) )
linear
GI:2992505

hemagglutinin (HA) mRNA, partial cds
mRNA

386. Influenza A virus (A/United
987 bp
AF501529.1

Kingdom/26554/99 (H3N2) )
linear
GI:21314314

hemagglutinin (HA) mRNA, partial cds
mRNA

387. Influenza A virus (A/United
987 bp
AF501527.1

Kingdom/34300/99 (H3N2) )
linear
GI:21314310

hemagglutinin (HA) mRNA, partial cds
mRNA

388. Influenza A virus
987 bp
AF501533.1

(A/Utah/20997/99 (H3N2) )
linear
GI:21314322

hemagglutinin (HA) mRNA, partial cds
mRNA

389. Influenza A virus
1,565 bp
AF072545.1

(A/Victoria/3/75) segment 5
linear
GI:4218933

nucleoprotein mRNA, complete cds
mRNA

390. Influenza A virus
1,762 bp
AF017270.2

(A/Vienna/47/96M (H3N2) )
linear
GI:14286338

hemagglutinin (HA) MRNA, complete
mRNA

cds

391. Influenza A virus
1,762 bp
AF017272.2

(A/Vienna/47/96V (H3N2) )
linear
GI:15004991

hemagglutinin (HA) mRNA, complete
mRNA

cds

392. Influenza A virus
1,069 bp
AF017271.1

(A/Vienna/81/96V (H3N2) )
linear
GI:2407251

hemagglutinin (HA) MRNA, partial cds
mRNA

393. Influenza A virus
987 bp
AF501532.1

(A/Virginia/21712/99 (H3N2) }
linear
GI:21314320

hemagglutinin (HA) mRNA, partial cds
mRNA

394. Influenza A virus
987 bp
AF501515.1

(A/Virginia/21716/99 (H3N2) )
linear
GI:21314286

hemagglutinin (HA) mRNA, partial cds
mRNA

395. Influenza A virus
987 bp
AF501530.1

(A/Virginia/21735/99 (H3N2) )
linear
GI:21314316

hemagglutinin (HA) mRNA, partial cds
mRNA

396. Influenza A virus
987 bp
AF501524.1

(A/Virginia/21743/99 (H3N2) )
linear
GI:21314304

hemagglutinin (HA) MRNA, partial cds
mRNA

397. Influenza A virus
987 bp
AF501519.1

(A/Virginia/21754/99 (H3N2) )
linear
GI:21314294

hemagglutinin (HA) mRNA, partial cds
mRNA

398. Influenza A virus
987 bp
AF501523.1

(A/Virginia/21799/99 (H3N2) )
linear
GI:21314302

hemagglutinin (HA) MRNA, partial cds
mRNA

399. Influenza A virus
987 bp
AF501525.1

(A/Virginia/21817/99 (H3N2) )
linear
GI:21314306

hemagglutinin (HA) mRNA, partial cds
mRNA

400. Influenza A virus
987 bp
AF501520.1

(A/Virginia/21822/99 (H3N2) )
linear
GI:21314296

hemagglutinin (HA) MRNA, partial cds
mRNA

401. Influenza A virus
987 bp
AF501528.1

(A/Virginia/21828/99 (H3N2) }
linear
GI:21314312

hemagglutinin (HA) mRNA, partial cds
mRNA

402. Influenza A virus
987 bp
AF501517.1

(A/Virginia/21833/99 (H3N2) )
linear
GI:21314290

hemagglutinin (HA) mRNA, partial cds
mRNA

403. Influenza A virus
987 bp
AF501522.1

(A/Virginia/21845/99 (H3N2) )
linear
GI:21314300

hemagglutinin (HA) MRNA, partial cds
mRNA

404. Influenza A virus
987 bp
AF501535.1

(A/Virginia/21847/99 (H3N2) )
linear
GI:21314326

hemagglutinin (HA) mRNA, partial cds
mRNA

405. Influenza A virus
987 bp
AF501521.1

(A/Virginia/G1/99 (H3N2) )
linear
GI:21314298

hemagglutinin (HA) mRNA, partial cds
mRNA

406. Influenza A virus
755 bp
AY973339.1

(A/Yilan/508/03 (H3N2) ) neuraminidase
linear
GI:70673234

(NA) mRNA, partial cds
mRNA

407. Influenza A virus
882 bp
AY986999.1

(A/Yilan/508/03 (H3N2) ) nucleoprotein
linear
GI:70728125

(NP) mRNA, partial cds
mRNA

408. Influenza A virus
740 bp
AY962015.1

(A/Yilan/513/03 (H3N2) ) hemagglutinin
linear
GI:68138187

(HA) mRNA, partial cds
mRNA

409. Influenza A virus
396 bp
AY973340.1

(A/Yilan/513/03 (H3N2) ) neuraminidase
linear
GI:70673236

(NA) mRNA, partial cds
mRNA

410. Influenza A virus
882 bp
AY987000.1

(A/Yilan/513/03 (H3N2) ) nucleoprotein
linear
GI:70728127

(NP) mRNA, partial cds
mRNA

411. Influenza A virus
511 bp
AY962010.1

(A/Yilan/515/03 (H3N2) ) hemagglutinin
linear
GI:68138177

(HA) MRNA, partial cds
mRNA

412. Influenza A virus
394 bp
AY973341.1

(A/Yilan/515/03 (H3N2) ) neuraminidase
linear
GI:70673238

(NA) mRNA, partial cds
mRNA

413. Influenza A virus
882 bp
AY987001.1

(A/Yilan/516/03 (H3N2) ) nucleoprotein
linear
GI:70728129

(NP) MRNA, partial cds
mRNA

414. Influenza A virus
530 bp
AY962006.1

(A/Yilan/518/03 (H3N2} ) hemagglutinin
linear
GI:68138169

(HA) mRNA, partial cds
mRNA

415. Influenza A virus
397 bp
AY973342.1

(A/Yilan/518/03 (H3N2) ) neuraminidase
linear
GI:70673240

(NA) mRNA, partial cds
mRNA

416. Influenza A virus
882 bp
AY987002.1

(A/Yilan/518/03 (H3N2) ) nucleoprotein
linear
GI:70728131

(NP) mRNA, partial cds
mRNA

417. Influenza A virus
777 bp
AY962002.1

(A/Yilan/538/04 (H3N2) ) hemagglutinin
linear
GI:68138161

(HA) mRNA, partial cds
mRNA

418. Influenza A virus
783 bp
AY973343.1

(A/Yilan/538/04 (H3N2) ) neuraminidase
linear
GI:70673242

(NA) mRNA, partial cds
mRNA

419. Influenza A virus
882 bp
AY987003.1

(A/Yilan/538/04 (H3N2) ) nucleoprotein
linear
GI:70728133

(NP) mRNA, partial cds
mRNA

420. Influenza A virus
788 bp
AY962003.1

(A/Yilan/549/04 (H3N2) ) hemagglutinin
linear
GI:68138163

(HA) mRNA, partial cds
mRNA

421. Influenza A virus
779 bp
AY973344.1

(A/Yilan/549/04 (H3N2) ) neuraminidase
linear
GI:70673244

(NA) mRNA, partial cds
mRNA

422. Influenza A virus
882 bp
AY987004.1

(A/Yilan/549/04 (H3N2) ) nucleoprotein
linear
GI:70728135

(NP) MRNA, partial cds
mRNA

423. Influenza A virus
776 bp
AY962013.1

(A/Yilan/557/04 (H3N2) ) hemagglutinin
linear
GI:68138183

(HA) mRNA, partial cds
mRNA

424. Influenza A virus
796 bp
AY973345.1

(A/Yilan/557/04 (H3N2) ) neuraminidase
linear
GI:70673246

(NA) mRNA, partial cds
mRNA

425. Influenza A virus
882 bp
AY987005.1

(A/Yilan/557/04 (H3N2) ) nucleoprotein
linear
GI:70728137

(NP) mRNA, partial cds
mRNA

426. Influenza A virus
753 bp
AY962014.1

(A/Yilan/566/04 (H3N2) ) hemagglutinin
linear
GI:68138185

(HA) MRNA, partial cds
mRNA

427. Influenza A virus
808 bp
AY973346.1

(A/Yilan/566/04 (H3N2) ) neuraminidase
linear
GI:70673248

(NA) mRNA, partial cds
mRNA

428. Influenza A virus
882 bp
AY987006.1

(A/Yilan/566/04 (H3N2) ) nucleoprotein
linear
GI:70728139

(NP) mRNA, partial cds
mRNA

429. Influenza A virus
987 bp
AY138513.1

(A/zhe jiang/06/99 (H3N2) )
linear
GI:24895131

hemagglutinin (HA) mRNA, partial cds
mRNA

430. Influenza A virus
987 bp
AY138515.1

(A/zhejiang/10/98 (H3N2) )
linear
GI:24895149

hemagglutinin (HA) MRNA, partial cds
mRNA

431. Influenza A virus
987 bp
AY138516.1

(A/zhejiang/11/2002 (H3N2) )
linear
GI:24895159

hemagglutinin (HA) mRNA, partial cds
mRNA

432. Influenza A virus
987 bp
AY138514.1

(A/zhejiang/12/99 (H3N2) )
linear
GI:24895141

hemagglutinin-like (HA) mRNA,
mRNA

partial sequence

433. Influenza A virus
987 bp
AY138519.1

(A/zhejiang/8/2002 (H3N2) )
linear
GI:24895188

hemagglutinin (HA) MRNA, partial cds
mRNA

434. Influenza A virus H3N2 strain
840 bp
U65670.1

A/Akita/1/94 nonstructural protein 1
linear
GI:3929405

and nonstructural protein 2 mRNAs,
mRNA

complete cds

435. Influenza A virus H3N2 strain
840 bp
U65671.1

A/Akita/1/95 nonstructural protein 1
linear
GI:3929408

and nonstructural protein 2 mRNAS,
mRNA

complete cds

436. Influenza A virus H3N2 strain
840 bp
U65673.1

A/Shiga/20/95 nonstructural protein
linear
GI:3929411

1 and nonstructural protein 2 mRNAs,
mRNA

complete cds

437. Influenza A virus H3N2 strain
840 bp
U65674.1

A/Miyagi/69/95 nonstructural protein
linear
GI:3929414

1 and nonstructural protein 2 mRNAs,
mRNA

complete cds

438. Influenza A virus H3N2 strain
840 bp
U65672.1

A/Hebei/19/95 nonstructural protein
linear
GI:6468319

1 and nonstructural protein 2 mRNAs,
mRNA

complete cds

A/Aichi/69/1994 (H3N2) haemagglutinin

U48446.1

A/Bangkok/1/1979 (H3N2)

AF201843.1

hemagglutinin (HA)

A/Beijing/353/89 (H3) hemagglutinin

U97740.1

(HA)

A/Beijing/353/1989 (H3N2)

Z46391.1

haemagglutinin

A/chicken/Singapore/2002 (H3N2) M2

EU014143.1

protein

A/Christ Hospital/231/82 (H3N2) )

U77830.1

hemagglutinin (HA)

A/duck/Eastern China/36/2002 (H3N2)

EU429701.1

segment 6 neuraminidase (NA)

A/duck/Eastern China/160/2003 (H3N2)

EU429732.1

segment 6 neuraminidase (NA)

A/duck/Eastern China/848/2003 (H3N2)

EU429721.1

segment 6 neuraminidase (NA)

A/duck/Eastern China/770/2003 (H3N2)

EU429736.1

segment 6 neuraminidase (NA)

A/duck/Eastern China/855/2003 (H3N2)

EU429737.1

segment 6 neuraminidase (NA)

A/duck/Eastern China/875/2003 (H3N2)

EU429738.1

segment 6 neuraminidase (NA)

A/duck/Eastern China/901/2003 (H3N2)

EU429739.1

segment 6 neuraminidase (NA)

A/duck/Eastern China/866/2003 (H3N2)

EU429756.1

segment 6 neuraminidase (NA)

A/duck/Eastern China/857/2003 (H3N2)

EU429761.1

segment 6 neuraminidase (NA)

A/duck/Eastern China/852/2003 (H3N2)

EU429767.1

segment 6 neuraminidase (NA)

A/duck/Eastern China/838/2003 (H3N2)

EU429720.1

segment 6 neuraminidase (NA)

A/duck/Eastern China/6/2004 (H3N2)

EU429745.1

segment 6 neuraminidase (NA)

A/duck/Eastern China/03/2005 (H3N2)

EU429781.1

segment 6 neuraminidase (NA)

A/duck/Eastern China/02/2006 (H3N2)

EU429769.1

segment 6 neuraminidase (NA)

A/duck/Eastern China/04/2006 (H3N2)

EU429770.1

segment 6 neuraminidase (NA)

A/duck/Eastern China/21/2006 (H3N2)

EU429771.1

segment 6 neuraminidase (NA)

A/duck/Eastern China/23/2006 (H3N2)

EU429772.1

segment 6 neuraminidase (NA)

A/duck/Eastern China/31/2006 (H3N2)

EU429773.1

segment 6 neuraminidase (NA)

A/duck/Eastern China/35/2006 (H3N2)

EU429768.1

segment 6 neuraminidase (NA)

A/duck/Eastern China/42/2006 (H3N2)

EU429774.1

segment 6 neuraminidase (NA)

A/duck/Eastern China/53/2006 (H3N2)

EU429775.1

segment 6 neuraminidase (NA)

A/duck/Eastern China/60/2006 (H3N2)

EU429776.1

segment 6 neuraminidase (NA)

A/duck/Eastern China/62/2006 (H3N2)

EU429784.1

segment 6 neuraminidase (NA)

A/duck/Eastern China/63/2006 (H3N2)

EU429777.1

segment 6 neuraminidase (NA)

A/duck/Eastern China/142/2006 (H3N2)

EU429742.1

segment 6 neuraminidase (NA)

A/Dunedin/4/1973 (H3N2)

AF201842.1

hemagglutinin (HA)

TABLE 8

Influenza H5N1 Antigens

1. Influenza A virus
827 bp
AM503036.1

(A/chicken/Burkina
linear
GI: 147846308

Faso/01.03/2006(H5N1)) mRNA for non-
mRNA

structural protein (ns gene)

2. Influenza A virus
990 bp
AM503007.1

(A/chicken/Burkina
linear
GI: 147846250

Faso/13.1/2006(H5N1)) partial mRNA
mRNA

for matrix protein 1 (m1 gene)

3. Influenza A virus
1,529 bp
AM503029.1

(A/chicken/Burkina
linear
GI: 147846294

Faso/13.1/2006(H5N1)) mRNA for
mRNA

nucleoprotein (np gene)

4. Influenza A virus
827 bp
AM503037.1

(A/chicken/Burkina
linear
GI: 147846310

Faso/13.1/2006(H5N1)) mRNA for non-
mRNA

structural protein (ns gene)

5. Influenza A virus
2,169 bp
AM503046.1

(A/chicken/Burkina
linear
GI: 147846328

Faso/13.1/2006(H5N1)) partial mRNA
mRNA

for polymerase (pa gene)

6. Influenza A virus
2,259 bp
AM503056.1

(A/chicken/Burkina
linear
GI: 147846348

Faso/13.1/2006(H5N1)) partial mRNA
mRNA

for polymerase basic protein 1 (pb1

gene)

7. Influenza A virus
2,315 bp
AM503067.1

(A/chicken/Burkina
linear
GI: 147846859

Faso/13.1/2006(H5N1)) partial mRNA
mRNA

for polymerase basic protein 2 (pb2

gene)

8. Influenza A virus
1,736 bp
DQ023145.1

(A/chicken/China/1/02(H5N1))
linear
GI: 66775624

hemagglutinin (HA) mRNA, complete cds
mRNA

9. Influenza A virus
1,509 bp
DQ023146.1

(A/chicken/China/1/02(H5N1))
linear
GI: 66775626

nucleoprotein (NP) mRNA, complete cds
mRNA

10. Influenza A virus
1,379 bp
DQ023147.1

(A/chicken/China/1/02(H5N1))
linear
GI: 66775628

neuraminidase (NA) mRNA, complete cds
mRNA

11. Influenza A virus
999 bp
DQ650660.1

(A/chicken/Crimea/04/2005(H5N1))
linear
GI: 109692767

matrix protein (M) mRNA, complete cds
mRNA

12. Influenza A virus
850 bp
DQ650662.1

(A/chicken/Crimea/04/2005(H5N1))
linear
GI: 109692771

nonstructural protein (NS) mRNA,
mRNA

complete cds

13. Influenza A virus
994 bp
DQ650664.1

(A/chicken/Crimea/08/2005(H5N1))
linear
GI: 109692775

matrix protein (M) mRNA, complete cds
mRNA

14. Influenza A virus
1,532 bp
DQ650666.1

(A/chicken/Crimea/08/2005(H5N1))
linear
GI: 109692779

nucleoprotein (NP) mRNA, complete cds
mRNA

15. Influenza A virus
850 bp
DQ650667.1

(A/chicken/Crimea/08/2005(H5N1))
linear
GI: 109692781

nonstructural protein (NS) mRNA,
mRNA

complete cds

16. Influenza A virus
2,208 bp
DQ650668.1

(A/chicken/Crimea/08/2005(H5N1))
linear
GI: 109692783

polymerase acidic protein (PA) mRNA,
mRNA

complete cds

17. Influenza A virus
2,305 bp
DQ650670.1

(A/chicken/Crimea/08/2005(H5N1))
linear
GI: 109692787

polymerase basic protein 2 (PB2)
mRNA

mRNA, complete cds

18. Influenza A virus
1,015 bp
DQ676838.1

(A/chicken/Dovolnoe/03/2005(H5N1))
linear
GI: 108782527

hemagglutinin (HA) mRNA, partial cds
mRNA

20. Influenza A virus
2,341 bp
DQ366327.1

(A/chicken/Guangxi/12/2004(H5N1))
linear
GI: 86753731

polymerase PB2 mRNA, complete cds
mRNA

21. Influenza A virus
2,341 bp
DQ366328.1

(A/chicken/Guangxi/12/2004(H5N1))
linear
GI: 86753741

polymerase PB1 mRNA, complete cds
mRNA

22. Influenza A virus
2,233 bp
DQ366329.1

(A/chicken/Guangxi/12/2004(H5N1)) PA
linear
GI: 86753751

protein mRNA, complete cds
mRNA

23. Influenza A virus
1,565 bp
DQ366331.1

(A/chicken/Guangxi/12/2004(H5N1))
linear
GI: 86753771

nucleocapsid mRNA, complete cds
mRNA

24. Influenza A virus
1,027 bp
DQ366333.1

(A/chicken/Guangxi/12/2004(H5N1))
linear
GI: 86753791

matrix protein mRNA, complete cds
mRNA

25. Influenza A virus (A/chicken/Hong
1,718 bp
AF057291.1

Kong/258/97(H5N1)) hemagglutinin
linear
GI: 3068720

mRNA, complete cds
mRNA

26. Influenza A virus (A/chicken/Hong
1,318 bp
AF057292.1

Kong/258/97(H5N1)) neuraminidase
linear
GI: 3068722

mRNA, partial cds
mRNA

27. Influenza A virus (A/chicken/Hong
1,508 bp
AF057293.1

Kong/258/97(H5N1)) nucleoprotein
linear
GI: 3068724

mRNA, complete cds
mRNA

28. Influenza A virus (A/Chicken/Hong
1,726 bp
AF082034.1

Kong/728/97(H5N1)) hemagglutinin H5
linear
GI: 4240435

mRNA, complete cds
mRNA

29. Influenza A virus (A/Chicken/Hong
1,726 bp
AF082035.1

Kong/786/97(H5N1)) hemagglutinin H5
linear
GI: 4240437

mRNA, complete cds
mRNA

30. Influenza A virus (A/chicken/Hong
1,726 bp
AF082036.1

Kong/915/97(H5N1)) hemagglutinin H5
linear
GI: 4240439

mRNA, complete cds
mRNA

31. Influenza A virus (A/chicken/Hong
1,091 bp
AF082037.1

Kong/990/97(H5N1)) hemagglutinin H5
linear
GI: 4240441

mRNA, partial cds
mRNA

32. Influenza A virus
1,002 bp
DQ676835.1

(A/chicken/Krasnodar/01/2006(H5N1))
linear
GI: 108782521

matrix protein 1 (M) mRNA, complete
mRNA

cds

33. Influenza A virus
850 bp
DQ676837.1

(A/chicken/Krasnodar/01/2006(H5N1))
linear
GI: 108782525

nonstructural protein (NS) mRNA,
mRNA

complete cds

34. Influenza A virus
1,754 bp
DQ449632.1

(A/chicken/Kurgan/05/2005(H5N1))
linear
GI: 90289625

hemagglutinin (HA) mRNA, complete cds
mRNA

35. Influenza A virus
1,002 bp
DQ449633.1

(A/chicken/Kurgan/05/2005(H5N1))
linear
GI: 90289627

matrix protein 1 (M) mRNA, complete
mRNA

cds

36. Influenza A virus
1,373 bp
DQ449634.1

(A/chicken/Kurgan/05/2005(H5N1))
linear
GI: 90289629

neuraminidase (NA) mRNA, complete cds
mRNA

37. Influenza A virus
1,540 bp
DQ449635.1

(A/chicken/Kurgan/05/2005(H5N1))
linear
GI: 90289631

nucleoprotein (NP) mRNA, complete cds
mRNA

38. Influenza A virus
850 bp
DQ449636.1

(A/chicken/Kurgan/05/2005(H5N1))
linear
GI: 90289633

nonstructural protein (NS) mRNA,
mRNA

complete cds

39. Influenza A virus
2,208 bp
DQ449637.1

(A/chicken/Kurgan/05/2005(H5N1))
linear
GI: 90289635

polymerase acidic protein (PA) mRNA,
mRNA

complete cds

40. Influenza A virus
2,316 bp
DQ449638.1

(A/chicken/Kurgan/05/2005(H5N1))
linear
GI: 90289637

polymerase basic protein 1 (PB1)
mRNA

mRNA, complete cds

41. Influenza A virus
2,316 bp
DQ449639.1

(A/chicken/Kurgan/05/2005(H5N1))
linear
GI: 90289646

polymerase basic protein 2 (PB2)
mRNA

mRNA, complete cds

42. Influenza A virus
184 bp
EU447276.1

(A/chicken/Lobzenko/01/2008(H5N1))
linear
GI: 168998217

hemagglutinin (HA) mRNA, partial cds
mRNA

43. Influenza A virus
1,002 bp
DQ676831.1

(A/chicken/Mahachkala/05/2006(H5N1))
linear
GI: 108782513

matrix protein 1 (M) mRNA, complete
mRNA

cds

44. Influenza A virus
850 bp
DQ676833.1

(A/chicken/Mahachkala/05/2006(H5N1))
linear
GI: 108782517

nonstructural protein (NS) mRNA,
mRNA

complete cds

45. Influenza A virus
1,531 bp
AM503030.1

(A/chicken/Nigeria/AB13/2006(H5N1))
linear
GI: 147846296

mRNA for nucleoprotein (np gene)
mRNA

46. Influenza A virus
827 bp
AM503040.1

(A/chicken/Nigeria/AB13/2006(H5N1))
linear
GI: 147846316

mRNA for non-structural protein (ns
mRNA

gene)

47. Influenza A virus
2,169 bp
AM503051.1

(A/chicken/Nigeria/AB13/2006(H5N1))
linear
GI: 147846338

partial mRNA for polymerase (pa gene)
mRNA

48. Influenza A virus
2,259 bp
AM503060.1

(A/chicken/Nigeria/AB13/2006(H5N1))
linear
GI: 147846845

partial mRNA for polymerase basic
mRNA

protein 1 (pb1 gene)

49. Influenza A virus
2,315 bp
AM503071.1

(A/chicken/Nigeria/AB13/2006(H5N1))
linear
GI: 147846867

partial mRNA for polymerase basic
mRNA

protein 2 (pb2 gene)

70. Influenza A virus (A/chicken/Hong
1,055 bp
DQ250158.1

Kong/3123.1/2002(H5N1)) neuraminidase
linear
GI: 82412012

(NA) mRNA, partial cds
mRNA

75. Influenza A virus
1,754 bp
DQ676834.1

(A/chicken/Krasnodar/01/2006(H5N1))
linear
GI: 108782519

hemagglutinin (HA) mRNA, complete cds
mRNA

78. Influenza A virus
1,373 bp
DQ676836.2

(A/chicken/Krasnodar/01/2006(H5N1))
linear
GI: 115520953

neuraminidase (NA) mRNA, complete cds
mRNA

91. Influenza A virus
184 bp
EU447276.1

(A/chicken/Lobzenko/01/2008(H5N1))
linear
GI: 168998217

hemagglutinin (HA) mRNA, partial cds
mRNA

92. Influenza A virus
1,683 bp
DQ676830.1

(A/chicken/Mahachkala/05/2006(H5N1))
linear
GI: 108782511

hemagglutinin (HA) mRNA, complete cds
mRNA

94. Influenza A virus
1,373 bp
DQ676832.1

(A/chicken/Mahachkala/05/2006(H5N1))
linear
GI: 108782515

neuraminidase (NA) mRNA, complete cds
mRNA

96. Influenza A virus
433 bp
DQ096567.1

(A/chicken/Malaysia/01/2004(H5N1))
linear
GI: 69145364

neuramidase (NA) mRNA, partial cds
mRNA

97. Influenza A virus
1,722 bp
AM503002.1

(A/chicken/Nigeria/AB13/2006(H5N1))
linear
GI: 147846240

partial mRNA for hemagglutinin (ha
mRNA

gene)

98. Influenza A virus
1,329 bp
AM503020.1

(A/chicken/Nigeria/AB13/2006(H5N1))
linear
GI: 147846276

partial mRNA for neuraminidase (na
mRNA

gene)

105. Influenza A virus
1,719 bp
AM503003.1

(A/chicken/Nigeria/AB14/2006(H5N1))
linear
GI: 147846242

partial mRNA for hemagglutinin (ha
mRNA

gene)

106. Influenza A virus
953 bp
AM503011.1

(A/chicken/Nigeria/AB14/2006(H5N1))
linear
GI: 147846258

partial mRNA for matrix protein 1 (m1
mRNA

gene)

107. Influenza A virus
1,343 bp
AM503025.1

(A/chicken/Nigeria/AB14/2006(H5N1))
linear
GI: 147846286

partial mRNA for neuraminidase (na
mRNA

gene)

108. Influenza A virus
827 bp
AM503041.1

(A/chicken/Nigeria/AB14/2006(H5N1))
linear
GI: 147846318

mRNA for non-structural protein (ns
mRNA

gene)

109. Influenza A virus
2,169 bp
AM503054.1

(A/chicken/Nigeria/AB14/2006(H5N1))
linear
GI: 147846344

partial mRNA for polymerase (pa gene)
mRNA

110. Influenza A virus
2,259 bp
AM503061.1

(A/chicken/Nigeria/AB14/2006(H5N1))
linear
GI: 147846847

partial mRNA for polymerase basic
mRNA

protein 1 (pb1 gene)

111. Influenza A virus
2,315 bp
AM503072.1

(A/chicken/Nigeria/AB14/2006(H5N1))
linear
GI: 147846869

partial mRNA for polymerase basic
mRNA

protein 2 (pb2 gene)

112. Influenza A virus
1,548 bp
AM503034.2

(A/chicken/Nigeria/AB14/2006(H5N1))
linear
GI: 149773117

mRNA for nucleoprotein (np gene)
mRNA

113. Influenza A virus
1,342 bp
AM503022.1

(A/chicken/Nigeria/BA210/2006(H5N1))
linear
GI: 147846280

partial mRNA for neuraminidase (na
mRNA

gene)

114. Influenza A virus
1,321 bp
AM503021.1

(A/chicken/Nigeria/BA211/2006(H5N1))
linear
GI: 147846278

partial mRNA for neuraminidase (na
mRNA

gene)

115. Influenza A virus
2,315 bp
AM503073.1

(A/chicken/Nigeria/BA211/2006(H5N1))
linear
GI: 147846871

partial mRNA for polymerase basic
mRNA

protein 2 (pb2 gene)

116. Influenza A virus
1,717 bp
AM503004.1

(A/chicken/Nigeria/FA4/2006(H5N1))
linear
GI: 147846244

partial mRNA for hemagglutinin (ha
mRNA

gene)

117. Influenza A virus
989 bp
AM503013.1

(A/chicken/Nigeria/FA4/2006(H5N1))
linear
GI: 147846262

partial mRNA for matrix protein 1 (m1
mRNA

gene)

118. Influenza A virus
1,321 bp
AM503026.1

(A/chicken/Nigeria/FA4/2006(H5N1))
linear
GI: 147846288

partial mRNA for neuraminidase (na
mRNA

gene)

119. Influenza A virus
827 bp
AM503045.1

(A/chicken/Nigeria/FA4/2006(H5N1))
linear
GI: 147846326

mRNA for non-structural protein (ns
mRNA

gene)

120. Influenza A virus
2,169 bp
AM503055.1

(A/chicken/Nigeria/FA4/2006(H5N1))
linear
GI: 147846346

partial mRNA for polymerase (pa gene)
mRNA

121. Influenza A virus
2,259 bp
AM503064.1

(A/chicken/Nigeria/FA4/2006(H5N1))
linear
GI: 147846853

partial mRNA for polymerase basic
mRNA

protein 1 (pb1 gene)

122. Influenza A virus
2,224 bp
AM503074.1

(A/chicken/Nigeria/FA4/2006(H5N1))
linear
GI: 147846873

partial mRNA for polymerase basic
mRNA

protein 2 (pb2 gene)

123. Influenza A virus
1,717 bp
AM502998.1

(A/chicken/Nigeria/FA6/2006(H5N1))
linear
GI: 147846232

partial mRNA for hemagglutinin (ha
mRNA

gene)

124. Influenza A virus
965 bp
AM503012.1

(A/chicken/Nigeria/FA6/2006(H5N1))
linear
GI: 147846260

partial mRNA for matrix protein 1 (m1
mRNA

gene)

125. Influenza A virus
1,327 bp
AM503023.1

(A/chicken/Nigeria/FA6/2006(H5N1))
linear
GI: 147846282

partial mRNA for neuraminidase (na
mRNA

gene)

126. Influenza A virus
1,543 bp
AM503031.1

(A/chicken/Nigeria/FA6/2006(H5N1))
linear
GI: 147846298

mRNA for nucleoprotein (np gene)
mRNA

127. Influenza A virus
2,169 bp
AM503052.1

(A/chicken/Nigeria/FA6/2006(H5N1))
linear
GI: 147846340

partial mRNA for polymerase (pa gene)
mRNA

128. Influenza A virus
2,259 bp
AM503063.1

(A/chicken/Nigeria/FA6/2006(H5N1))
linear
GI: 147846851

partial mRNA for polymerase basic
mRNA

protein 1 (pb1 gene)

129. Influenza A virus
1,710 bp
AM502999.1

(A/chicken/Nigeria/FA7/2006(H5N1))
linear
GI: 147846234

partial mRNA for hemagglutinin (ha
mRNA

gene)

130. Influenza A virus
1,001 bp
AM503009.1

(A/chicken/Nigeria/FA7/2006(H5N1))
linear
GI: 147846254

partial mRNA for matrix protein 1 (m1
mRNA

gene)

131. Influenza A virus
1,331 bp
AM503018.1

(A/chicken/Nigeria/FA7/2006(H5N1))
linear
GI: 147846272

partial mRNA for neuraminidase (na
mRNA

gene)

132. Influenza A virus
1,531 bp
AM503035.1

(A/chicken/Nigeria/FA7/2006(H5N1))
linear
GI: 147846306

mRNA for nucleoprotein (np gene)
mRNA

133. Influenza A virus
827 bp
AM503042.1

(A/chicken/Nigeria/FA7/2006(H5N1))
linear
GI: 147846320

mRNA for non-structural protein (ns
mRNA

gene)

134. Influenza A virus
2,169 bp
AM503049.1

(A/chicken/Nigeria/FA7/2006(H5N1))
linear
GI: 147846334

partial mRNA for polymerase (pa gene)
mRNA

135. Influenza A virus
2,259 bp
AM503057.1

(A/chicken/Nigeria/FA7/2006(H5N1))
linear
GI: 147846350

partial mRNA for polymerase basic
mRNA

protein 1 (pb1 gene)

136. Influenza A virus
2,315 bp
AM503068.1

(A/chicken/Nigeria/FA7/2006(H5N1))
linear
GI: 147846861

partial mRNA for polymerase basic
mRNA

protein 2 (pb2 gene)

137. Influenza A virus
1,714 bp
AM503001.1

(A/chicken/Nigeria/IF10/2006(H5N1))
linear
GI: 147846238

partial mRNA for hemagglutinin (ha
mRNA

gene)

138. Influenza A virus
990 bp
AM503010.1

(A/chicken/Nigeria/IF10/2006(H5N1))
linear
GI: 147846256

partial mRNA for matrix protein 1 (m1
mRNA

gene)

139. Influenza A virus
1,332 bp
AM503024.1

(A/chicken/Nigeria/IF10/2006(H5N1))
linear
GI: 147846284

partial mRNA for neuraminidase (na
mRNA

gene)

140. Influenza A virus
827 bp
AM503044.1

(A/chicken/Nigeria/IF10/2006(H5N1))
linear
GI: 147846324

mRNA for non-structural protein (ns
mRNA

gene)

141. Influenza A virus
2,169 bp
AM503053.1

(A/chicken/Nigeria/IF10/2006(H5N1))
linear
GI: 147846342

partial mRNA for polymerase (pa gene)
mRNA

142. Influenza A virus
2,259 bp
AM503059.1

(A/chicken/Nigeria/IF10/2006(H5N1))
linear
GI: 147846843

partial mRNA for polymerase basic
mRNA

protein 1 (pb1 gene)

143. Influenza A virus
2,315 bp
AM503069.1

(A/chicken/Nigeria/IF10/2006(H5N1))
linear
GI: 147846863

partial mRNA for polymerase basic
mRNA

protein 2 (pb2 gene)

144. Influenza A virus
1,550 bp
AM503033.2

(A/chicken/Nigeria/IF10/2006(H5N1))
linear
GI: 149773115

mRNA for nucleoprotein (np gene)
mRNA

145. Influenza A virus
1,719 bp
AM503005.1

(A/chicken/Nigeria/OD8/2006(H5N1))
linear
GI: 147846246

partial mRNA for hemagglutinin (ha
mRNA

gene)

146. Influenza A virus
989 bp
AM503014.1

(A/chicken/Nigeria/OD8/2006(H5N1))
linear
GI: 147846264

partial mRNA for matrix protein 1 (m1
mRNA

gene)

147. Influenza A virus
1,720 bp
AM503000.1

(A/chicken/Nigeria/OD9/2006(H5N1))
linear
GI: 147846236

partial mRNA for hemagglutinin (ha
mRNA

gene)

148. Influenza A virus
988 bp
AM503015.1

(A/chicken/Nigeria/OD9/2006(H5N1))
linear
GI: 147846266

partial mRNA for matrix protein 1 (m1
mRNA

gene)

149. Influenza A virus
1,330 bp
AM503019.1

(A/chicken/Nigeria/OD9/2006(H5N1))
linear
GI: 147846274

partial mRNA for neuraminidase (na
mRNA

gene)

150. Influenza A virus
1,531 bp
AM503032.1

(A/chicken/Nigeria/OD9/2006(H5N1))
linear
GI: 147846300

mRNA for nucleoprotein (np gene)
mRNA

151. Influenza A virus
827 bp
AM503043.1

(A/chicken/Nigeria/OD9/2006(H5N1))
linear
GI: 147846322

mRNA for non-structural protein (ns
mRNA

gene)

152. Influenza A virus
2,169 bp
AM503050.1

(A/chicken/Nigeria/OD9/2006(H5N1))
linear
GI: 147846336

partial mRNA for polymerase (pa gene)
mRNA

153. Influenza A virus
2,259 bp
AM503058.1

(A/chicken/Nigeria/OD9/2006(H5N1))
linear
GI: 147846841

partial mRNA for polymerase basic
mRNA

protein 1 (pb1 gene)

154. Influenza A virus
2,315 bp
AM503070.1

(A/chicken/Nigeria/OD9/2006(H5N1))
linear
GI: 147846865

partial mRNA for polymerase basic
mRNA

protein 2 (pb2 gene)

155. Influenza A virus
1,768 bp
X07869.1

(A/chicken/Scotland/59(H5N1)) mRNA
linear
GI: 60482

for haemagglutinin precursor
mRNA

156. Influenza A virus
1,445 bp
AJ416625.1

(A/chicken/Scotland/59(H5N1)) N1 gene
linear
GI: 39840717

for neuraminidase, genomic RNA
mRNA

161. Influenza A virus
1,497 bp
DQ208502.1

(A/chicken/zz/02/2004(H5N1))
linear
GI: 77158587

nucleoprotein mRNA, complete cds
mRNA

162. Influenza A virus (A/common
1,707 bp
EF110519.1

coot/Switzerland/V544/2006(H5N1))
linear
GI: 119394676

hemagglutinin (HA) gene, complete cds
mRNA

163. Influenza A virus (A/domestic
1,735 bp
EU190482.1

goose/Pavlodar/1/2005(H5N1))
linear
GI: 158516739

hemagglutinin (HA) mRNA, complete cds
mRNA

164. Influenza A virus
1,401 bp
EU429750.1

(A/duck/Eastern China/145/2003(H5N1))
linear
GI: 167859465

segment 6 neuraminidase (NA) mRNA,
mRNA

complete cds

165. Influenza A virus
1,407 bp
EU429731.1

(A/duck/Eastern China/150/2003(H5N1))
linear
GI: 167859427

segment 6 neuraminidase (NA) mRNA,
mRNA

complete cds

166. Influenza A virus
1,398 bp
EU429783.1

(A/duck/Eastern China/22/2005(H5N1))
linear
GI: 167859531

segment 6 neuraminidase (NA) mRNA,
mRNA

complete cds

167. Influenza A virus
1,398 bp
60429747.1

(A/duck/Eastern China/304/2002(H5N1))
linear
GI: 167859459

segment 6 neuraminidase (NA) mRNA,
mRNA

complete cds

168. Influenza A virus
1,401 bp
EU429727.1

(A/duck/Eastern China/318/2002(H5N1))
linear
GI: 167859419

segment 6 neuraminidase (NA) mRNA,
mRNA

complete cds

169. Influenza A virus
1,399 bp
EU429778.1

(A/duck/Eastern China/37/2006(H5N1))
linear
GI: 167859521

segment 6 neuraminidase (NA) mRNA,
mRNA

complete cds

170. Influenza A virus
1,398 bp
EU429757.1

(A/duck/Eastern China/40/2005(H5N1))
linear
GI: 167859479

segment 6 neuraminidase (NA) mRNA,
mRNA

complete cds

171. Influenza A virus
1,398 bp
EU429779.1

(A/duck/Eastern China/48/2006(H5N1))
linear
GI: 167859523

segment 6 neuraminidase (NA) mRNA,
mRNA

complete cds

172. Influenza A virus
1,398 bp
EU429763.1

(A/duck/Eastern China/51/2005(H5N1))
linear
GI: 167859491

segment 6 neuraminidase (NA) mRNA,
mRNA

complete cds

173. Influenza A virus
1,398 bp
EU429758.1

(A/duck/Eastern China/54/2005(H5N1))
linear
GI: 167859481

segment 6 neuraminidase (NA) mRNA,
mRNA

complete cds

174. Influenza A virus
1,398 bp
EU429764.1

(A/duck/Eastern China/58/2005(H5N1))
linear
GI: 167859493

segment 6 neuraminidase (NA) mRNA,
mRNA

complete cds

175. Influenza A virus
1,398 bp
EU429759.1

(A/duck/Eastern China/59/2005(H5N1))
linear
GI: 167859483

segment 6 neuraminidase (NA) mRNA,
mRNA

complete cds

176. Influenza A virus
1,398 bp
EU429765.1

(A/duck/Eastern China/89/2005(H5N1))
linear
GI: 167859495

segment 6 neuraminidase (NA) mRNA,
mRNA

complete cds

177. Influenza A virus
1,399 bp
EU429785.1

(A/duck/Eastern China/89/2006(H5N1))
linear
GI: 167859535

segment 6 neuraminidase (NA) mRNA,
mRNA

complete cds

178. Influenza A virus
1,398 bp
EU429717.1

(A/duck/Eastern China/97/2001(H5N1))
linear
GI: 167859399

segment 6 neuraminidase (NA) mRNA,
mRNA

complete cds

179. Influenza A virus
2,281 bp
AY585504.1

(A/duck/Fujian/01/2002(H5N1))
linear
GI: 47156226

polymerase basic protein 2 (PB2)
mRNA

mRNA, complete cds

180. Influenza A virus
760 bp
AY585378.1

(A/duck/Fujian/01/2002(H5N1)) matrix
linear
GI: 47156310

protein mRNA, complete cds
mRNA

181. Influenza A virus
1,357 bp
AY585399.1

(A/duck/Fujian/01/2002(H5N1))
linear
GI: 47156352

neuraminidase (NA) mRNA, complete cds
mRNA

182. Influenza A virus
1,497 bp
AY585420.1

(A/duck/Fujian/01/2002(H5N1))
linear
GI: 47156394

nucleoprotein (NP) mRNA, complete cds
mRNA

183. Influenza A virus
686 bp
AY585441.1

(A/duck/Fujian/01/2002(H5N1))
linear
GI: 47156436

nonstructural protein 1 (NS1) mRNA,
mRNA

partial cds

184. Influenza A virus
2,281 bp
AY585505.1

(A/duck/Fujian/13/2002(H5N1))
linear
GI: 47156228

polymerase basic protein 2 (PB2)
mRNA

mRNA, complete cds

185. Influenza A virus
761 bp
AY585379.1

(A/duck/Fujian/13/2002(H5N1)) matrix
linear
GI: 47156312

protein mRNA, complete cds
mRNA

186. Influenza A virus
1,357 bp
AY585400.1

(A/duck/Fujian/13/2002(H5N1))
linear
GI: 47156354

neuraminidase (NA) mRNA, complete cds
mRNA

187. Influenza A virus
1,499 bp
AY585421.1

(A/duck/Fujian/13/2002(H5N1))
linear
GI: 47156396

nucleoprotein (NP) mRNA, complete cds
mRNA

188. Influenza A virus
685 bp
AY585442.1

(A/duck/Fujian/13/2002(H5N1))
linear
GI: 47156438

nonstructural protein 1 (NS1) mRNA,
mRNA

partial cds

189. Influenza A virus
2,281 bp
AY585506.1

(A/duck/Fujian/17/2001(H5N1))
linear
GI: 47156230

polymerase basic protein 2 (PB2)
mRNA

mRNA, complete cds

190. Influenza A virus
759 bp
AY585380.1

(A/duck/Fujian/17/2001(H5N1)) matrix
linear
GI: 47156314

protein mRNA, complete cds
mRNA

191. Influenza A virus
1,418 bp
AY585401.1

(A/duck/Fujian/17/2001(H5N1))
linear
GI: 47156356

neuraminidase (NA) mRNA, complete cds
mRNA

192. Influenza A virus
1,498 bp
AY585422.1

(A/duck/Fujian/17/2001(H5N1))
linear
GI: 47156398

nucleoprotein (NP) mRNA, complete cds
mRNA

193. Influenza A virus
686 bp
AY585443.1

(A/duck/Fujian/17/2001(H5N1))
linear
GI: 47156440

nonstructural protein 1 (NS1) mRNA,
mRNA

complete cds

194. Influenza A virus
2,281 bp
AY585507.1

(A/duck/Fujian/19/2000(H5N1))
linear
GI: 47156232

polymerase basic protein 2 (PB2)
mRNA

mRNA, complete cds

195. Influenza A virus
760 bp
AY585381.1

(A/duck/Fujian/19/2000(H5N1)) matrix
linear
GI: 47156316

protein mRNA, complete cds
mRNA

196. Influenza A virus
1,355 bp
AY585402.1

(A/duck/Fujian/19/2000(H5N1))
linear
GI: 47156358

neuraminidase (NA) mRNA, complete cds
mRNA

197. Influenza A virus
1,498 bp
AY585423.1

(A/duck/Fujian/19/2000(H5N1))
linear
GI: 47156400

nucleoprotein (NP) mRNA, complete cds
mRNA

198. Influenza A virus
687 bp
AY585444.1

(A/duck/Fujian/19/2000(H5N1))
linear
GI: 47156442

nonstructural protein 1 (NS1) mRNA,
mRNA

complete cds

199. Influenza A virus
2,281 bp
AY585508.1

(A/duck/Guangdong/01/2001(H5N1))
linear
GI: 47156234

polymerase basic protein 2 (PB2)
mRNA

mRNA, complete cds

200. Influenza A virus
760 bp
AY585382.1

(A/duck/Guangdong/01/2001(H5N1))
linear
GI: 47156318

matrix protein mRNA, complete cds
mRNA

201. Influenza A virus
1,414 bp
AY585403.1

(A/duck/Guangdong/01/2001(H5N1))
linear
GI: 47156360

neuraminidase (NA) mRNA, complete cds
mRNA

202. Influenza A virus
1,497 bp
AY585424.1

(A/duck/Guangdong/01/2001(H5N1))
linear
GI: 47156402

nucleoprotein (NP) mRNA, complete cds
mRNA

203. Influenza A virus
687 bp
AY585445.1

(A/duck/Guangdong/01/2001(H5N1))
linear
GI: 47156444

nonstructural protein 1 (NS1) mRNA,
mRNA

complete cds

204. Influenza A virus
2,280 bp
AY585509.1

(A/duck/Guangdong/07/2000(H5N1))
linear
GI: 47156236

polymerase basic protein 2 (PB2)
mRNA

mRNA, complete cds

205. Influenza A virus
759 bp
AY585383.1

(A/duck/Guangdong/07/2000(H5N1))
linear
GI: 47156320

matrix protein mRNA, complete cds
mRNA

206. Influenza A virus
1.,417 bp
AY585404.1

(A/duck/Guangdong/07/2000(H5N1))
linear
GI: 47156362

neuraminidase (NA) mRNA, complete cds
mRNA

207. Influenza A virus
1,497 bp
AY585425.1

(A/duck/Guangdong/07/2000(H5N1))
linear
GI: 47156404

nucleoprotein (NP) mRNA, complete cds
mRNA

208. Influenza A virus
690 bp
AY585446.1

(A/duck/Guangdong/07/2000(H5N1))
linear
GI: 47156446

nonstructural protein 1 (NS1) mRNA,
mRNA

partial cds

209. Influenza A virus
2,281 bp
AY585510.1

(A/duck/Guangdong/12/2000(H5N1))
linear
GI: 47156238

polymerase basic protein 2 (PB2)
mRNA

mRNA, complete cds

210. Influenza A virus
760 bp
AY585384.1

(A/duck/Guangdong/12/2000(H5N1))
linear
GI: 47156322

matrix protein mRNA, complete cds
mRNA

211. Influenza A virus
1,359 bp
AY585405.1

(A/duck/Guangdong/12/2000(H5N1))
linear
GI: 47156364

neuraminidase (NA) mRNA, complete cds
mRNA

212. Influenza A virus
1,498 bp
AY585426.1

(A/duck/Guangdong/12/2000(H5N1))
linear
GI: 47156406

nucleoprotein (NP) mRNA, complete cds
mRNA

213. Influenza A virus
685 bp
AY585447.1

(A/duck/Guangdong/12/2000(H5N1))
linear
GI: 47156448

nonstructural protein 1 (NS1) mRNA,
mRNA

partial cds

214. Influenza A virus
2,281 bp
AY585511.1

(A/duck/Guangdong/22/2002(H5N1))
linear
GI: 47156240

polymerase basic protein 2 (PB2)
mRNA

mRNA, complete cds

215. Influenza A virus
760 bp
AY585385.1

(A/duck/Guangdong/22/2002(H5N1))
linear
GI: 47156324

matrix protein mRNA, complete cds
mRNA

216. Influenza A virus
1,412 bp
AY585406.1

(A/duck/Guangdong/22/2002(H5N1))
linear
GI: 47156366

neuraminidase (NA) mRNA, complete cds
mRNA

217. Influenza A virus
1,499 bp
AY585427.1

(A/duck/Guangdong/22/2002(H5N1))
linear
GI: 47156408

nucleoprotein (NP) mRNA, complete cds
mRNA

218. Influenza A virus
682 bp
AY585448.1

(A/duck/Guangdong/22/2002(H5N1))
linear
GI: 47156450

nonstructural protein 1 (NS1) mRNA,
mRNA

complete cds

219. Influenza A virus
2,281 bp
AY585512.1

(A/duck/Guangdong/40/2000(H5N1))
linear
GI: 47156242

polymerase basic protein 2 (PB2)
mRNA

mRNA, complete cds

220. Influenza A virus
760 bp
AY585386.1

(A/duck/Guangdong/40/2000(H5N1))
linear
GI: 47156326

matrix protein mRNA, complete cds
mRNA

221. Influenza A virus
1,401 bp
AY585407.1

(A/duck/Guangdong/40/2000(H5N1))
linear
GI: 47156368

neuraminidase (NA) mRNA, partial cds
mRNA

222. Influenza A virus
1,499 bp
AY585428.1

(A/duck/Guangdong/40/2000(H5N1))
linear
GI: 47156410

nucleoprotein (NP) mRNA, complete cds
mRNA

223. Influenza A virus
689 bp
AY585449.1

(A/duck/Guangdong/40/2000(H5N1))
linear
GI: 47156452

nonstructural protein 1 (NS1) mRNA,
mRNA

partial cds

224. Influenza A virus
2,281 bp
AY585513.1

(A/duck/Guangxi/07/1999(H5N1))
linear
GI: 47156244

polymerase basic protein 2 (PB2)
mRNA

mRNA, complete cds

225. Influenza A virus
760 bp
AY585387.1

(A/duck/Guangxi/07/1999(H5N1)) matrix
linear
GI: 47156328

protein mRNA, complete cds
mRNA

226. Influenza A virus
1,421 bp
AY585408.1

(A/duck/Guangxi/07/1999(H5N1))
linear
GI: 47156370

neuraminidase (NA) mRNA, complete cds
mRNA

227. Influenza A virus
1,501 bp
AY585429.1

(A/duck/Guangxi/07/1999(H5N1))
linear
GI: 47156412

nucleoprotein (NP) mRNA, complete cds
mRNA

228. Influenza A virus
687 bp
AY585450.1

(A/duck/Guangxi/07/1999(H5N1))
linear
GI: 47156454

nonstructural protein 1 (NS1) mRNA,
mRNA

partial cds

229. Influenza A virus
875 bp
DQ366342.1

(A/duck/Guangxi/13/2004(H5N1))
linear
GI: 86753723

nonstructural protein 1 mRNA,
mRNA

complete cds

230. Influenza A virus
2,341 bp
DQ366335.1

(A/duck/Guangxi/13/2004(H5N1))
linear
GI: 86753733

polymerase PB2 mRNA, complete cds
mRNA

231. Influenza A virus
2,341 bp
DQ366336.1

(A/duck/Guangxi/13/2004(H5N1))
linear
GI: 86753743

polymerase PB1 mRNA, complete cds
mRNA

232. Influenza A virus
2,233 bp
DQ366337.1

(A/duck/Guangxi/13/2004(H5N1)) PA
linear
GI: 86753753

protein mRNA, complete cds
mRNA

233. Influenza A virus
1,776 bp
DQ366338.1

(A/duck/Guangxi/13/2004(H5N1))
linear
GI: 86753763

hemagglutinin mRNA, complete cds
mRNA

234. Influenza A virus
1,565 bp
DQ366339.1

(A/duck/Guangxi/13/2004(H5N1))
linear
GI: 86753773

nucleocapsid mRNA, complete cds
mRNA

235. Influenza A virus
1,378 bp
DQ366340.1

(A/duck/Guangxi/13/2004(H5N1))
linear
GI: 86753783

neuraminidase mRNA, complete cds
mRNA

236. Influenza A virus
1,027 bp
DQ366341.1

(A/duck/Guangxi/13/2004(H5N1)) matrix
linear
GI: 86753793

protein mRNA, complete cds
mRNA

237. Influenza A virus
2,281 bp
AY585514.1

(A/duck/Guangxi/22/2001(H5N1))
linear
GI: 47156246

polymerase basic protein 2 (PB2)
mRNA

mRNA, complete cds

238. Influenza A virus
757 bp
AY585388.1

(A/duck/Guangxi/22/2001(H5N1)) matrix
linear
GI: 47156330

protein mRNA, partial cds
mRNA

239. Influenza A virus
1,414 bp
AY585409.1

(A/duck/Guangxi/22/2001(H5N1))
linear
GI: 47156372

neuraminidase (NA) mRNA, complete cds
mRNA

240. Influenza A virus
1,498 bp
AY585430.1

(A/duck/Guangxi/22/2001(H5N1))
linear
GI: 47156414

nucleoprotein (NP) mRNA, complete cds
mRNA

241. Influenza A virus
687 bp
AY585451.1

(A/duck/Guangxi/22/2001(H5N1))
linear
GI: 47156456

nonstructural protein 1 (NS1) mRNA,
mRNA

complete cds

242. Influenza A virus
2,281 bp
AY585515.1

(A/duck/Guangxi/35/2001(H5N1))
linear
GI: 47156248

polymerase basic protein 2 (PB2)
mRNA

mRNA, complete cds

243. Influenza A virus
760 bp
AY585389.1

(A/duck/Guangxi/35/2001(H5N1)) matrix
linear
GI: 47156332

protein mRNA, complete cds
mRNA

244. Influenza A virus
1,414 bp
AY585410.1

(A/duck/Guangxi/35/2001(H5N1))
linear
GI: 47156374

neuraminidase (NA) mRNA, complete cds
mRNA

245. Influenza A virus
1,498 bp
AY585431.1

(A/duck/Guangxi/35/2001(H5N1))
linear
GI: 47156416

nucleoprotein (NP) mRNA, complete cds
mRNA

246. Influenza A virus
685 bp
AY585452.1

(A/duck/Guangxi/35/2001(H5N1))
linear
GI: 47156458

nonstructural protein 1 (NS1) mRNA,
mRNA

complete cds

247. Influenza A virus
2,281 bp
AY585516.1

(A/duck/Guangxi/50/2001(H5N1))
linear
GI: 47156250

polymerase basic protein 2 (PB2)
mRNA

mRNA, complete cds

248. Influenza A virus
760 bp
AY585398.1

(A/duck/Guangxi/50/2001(H5N1)) matrix
linear
GI: 47156350

protein mRNA, complete cds
mRNA

249. Influenza A virus
1,354 bp
AY585411.1

(A/duck/Guangxi/50/2001(H5N1))
linear
GI: 47156376

neuraminidase (NA) mRNA, complete cds
mRNA

250. Influenza A virus
1,498 bp
AY585432.1

(A/duck/Guangxi/50/2001(H5N1))
linear
GI: 47156418

nucleoprotein (NP) mRNA, complete cds
mRNA

251. Influenza A virus
686 bp
AY585453.1

(A/duck/Guangxi/50/2001(H5N1))
linear
GI: 47156460

nonstructural protein 1 (NS1) mRNA,
mRNA

complete cds

252. Influenza A virus
2,281 bp
AY585517.1

(A/duck/Guangxi/53/2002(H5N1))
linear
GI: 47156252

polymerase basic protein 2 (PB2)
mRNA

mRNA, complete cds

253. Influenza A virus
760 bp
AY585390.1

(A/duck/Guangxi/53/2002(H5N1)) matrix
linear
GI: 47156334

protein mRNA, complete cds
mRNA

254. Influenza A virus
1,361 bp
AY585412.1

(A/duck/Guangxi/53/2002(H5N1))
linear
GI: 47156378

neuraminidase (NA) mRNA, complete cds
mRNA

255. Influenza A virus
1,498 bp
AY585433.1

(A/duck/Guangxi/53/2002(H5N1))
linear
GI: 47156420

nucleoprotein (NP) mRNA, complete cds
mRNA

256. Influenza A virus
687 bp
AY585454.1

(A/duck/Guangxi/53/2002(H5N1))
linear
GI: 47156462

nonstructural protein 1 (NS1) mRNA,
mRNA

partial cds

257. Influenza A virus
1,754 bp
DQ449640.1

(A/duck/Kurgan/08/2005(H5N1))
linear
GI: 90289674

hemagglutinin (HA) mRNA, complete cds
mRNA

258. Influenza A virus
1,002 bp
DQ449641.1

(A/duck/Kurgan/08/2005(H5N1)) matrix
linear
GI: 90289689

protein 1 (M) mRNA, complete cds
mRNA

259. Influenza A virus
1,373 bp
DQ449642.1

(A/duck/Kurgan/08/2005(H5N1))
linear
GI: 90289708

neuraminidase (NA) mRNA, complete cds
mRNA

260. Influenza A virus
1,540 bp
DQ449643.1

(A/duck/Kurgan/08/2005(H5N1))
linear
GI: 90289731

nucleoprotein (NP) mRNA, complete cds
mRNA

261. Influenza A virus
850 bp
DQ449644.1

(A/duck/Kurgan/08/2005(H5N1))
linear
GI: 90289739

nonstructural protein (NS) mRNA,
mRNA

complete cds

262. Influenza A virus
2,208 bp
DQ449645.1

(A/duck/Kurgan/08/2005(H5N1))
linear
GI: 90289756

polymerase acidic protein (PA) mRNA,
mRNA

complete cds

263. Influenza A virus
2,316 bp
DQ449646.1

(A/duck/Kurgan/08/2005(H5N1))
linear
GI: 90289774

polymerase basic protein 1 (PB1)
mRNA

mRNA, complete cds

264. Influenza A virus
2,316 bp
DQ449647.1

(A/duck/Kurgan/08/2005(H5N1))
linear
GI: 90289783

polymerase basic protein 2 (PB2)
mRNA

mRNA, complete cds

266. Influenza A virus
2,281 bp
AY585518.1

(A/duck/Shanghai/08/2001(H5N1))
linear
GI: 47156254

polymerase basic protein 2 (PB2)
mRNA

mRNA, complete cds

267. Influenza A virus
760 bp
AY585391.1

(A/duck/Shanghai/08/2001(H5N1))
linear
GI: 47156336

matrix protein mRNA, complete cds
mRNA

268. Influenza A virus
1,357 bp
AY585413.1

(A/duck/Shanghai/08/2001(H5N1))
linear
GI: 47156380

neuraminidase (NA) mRNA, complete cds
mRNA

269. Influenza A virus
1,498 bp
AY585434.1

(A/duck/Shanghai/08/2001(H5N1))
linear
GI: 47156422

nucleoprotein (NP) mRNA, complete cds
mRNA

270. Influenza A virus
685 bp
AY585455.1

(A/duck/Shanghai/08/2001(H5N1))
linear
GI: 47156464

nonstructural protein 1 (NS1) mRNA,
mRNA

partial cds

271. Influenza A virus
2,281 bp
AY585519.1

(A/duck/Shanghai/13/2001(H5N1))
linear
GI: 47156256

polymerase basic protein 2 (PB2)
mRNA

mRNA, complete cds

272. Influenza A virus
760 bp
AY585392.1

(A/duck/Shanghai/13/2001(H5N1))
linear
GI: 47156338

matrix protein mRNA, complete cds
mRNA

273. Influenza A virus
1,417 bp
AY585414.1

(A/duck/Shanghai/13/2001(H5N1))
linear
GI: 47156382

neuraminidase (NA) mRNA, complete cds
mRNA

274. Influenza A virus
1,499 bp
AY585435.1

(A/duck/Shanghai/13/2001(H5N1))
linear
GI: 47156424

nucleoprotein (NP) mRNA, complete cds
mRNA

275. Influenza A virus
685 bp
AY585456.1

(A/duck/Shanghai/13/2001(H5N1))
linear
GI: 47156466

nonstructural protein 1 (NS1) mRNA,
mRNA

complete cds

276. Influenza A virus
2,281 bp
AY585520.1

(A/duck/Shanghai/35/2002(H5N1))
linear
GI: 47156258

polymerase basic protein 2 (PB2)
mRNA

mRNA, complete cds

277. Influenza A virus
760 bp
AY585393.1

(A/duck/Shanghai/35/2002(H5N1))
linear
GI: 47156340

matrix protein mRNA, complete cds
mRNA

278. Influenza A virus
1,363 bp
AY585415.1

(A/duck/Shanghai/35/2002(H5N1))
linear
GI: 47156384

neuraminidase (NA) mRNA, complete cds
mRNA

279. Influenza A virus
1,498 bp
AY585436.1

(A/duck/Shanghai/35/2002(H5N1))
linear
GI: 47156426

nucleoprotein (NP) mRNA, complete cds
mRNA

280. Influenza A virus
685 bp
AY585457.1

(A/duck/Shanghai/35/2002(H5N1))
linear
GI: 47156468

nonstructural protein 1 (NS1) mRNA,
mRNA

partial cds

281. Influenza A virus
2,281 bp
AY585521.1

(A/duck/Shanghai/37/2002(H5N1))
linear
GI: 47156260

polymerase basic protein 2 (PB2)
mRNA

mRNA, complete cds

282. Influenza A virus
760 bp
AY585394.1

(A/duck/Shanghai/37/2002(H5N1))
linear
GI: 47156342

matrix protein mRNA, complete cds
mRNA

283. Influenza A virus
1,361 bp
AY585416.1

(A/duck/Shanghai/37/2002(H5N1))
linear
GI: 47156386

neuraminidase (NA) mRNA, complete cds
mRNA

284. Influenza A virus
1,497 bp
AY585437.1

(A/duck/Shanghai/37/2002(H5N1))
linear
GI: 47156428

nucleoprotein (NP) mRNA, complete cds
mRNA

285. Influenza A virus
685 bp
AY585458.1

(A/duck/Shanghai/37/2002(H5N1))
linear
GI: 47156470

nonstructural protein 1 (NS1) mRNA,
mRNA

partial cds

286. Influenza A virus
2,282 bp
AY585522.1

(A/duck/Shanghai/38/2001(H5N1))
linear
GI: 47156262

polymerase basic protein 2 (PB2)
mRNA

mRNA, complete cds

287. Influenza A virus
760 bp
AY585395.1

(A/duck/Shanghai/38/2001(H5N1))
linear
GI: 47156344

matrix protein mRNA, complete cds
mRNA

288. Influenza A virus
1,355 bp
AY585417.1

(A/duck/Shanghai/38/2001(H5N1))
linear
GI: 47156388

neuraminidase (NA) mRNA, complete cds
mRNA

289. Influenza A virus
1,499 bp
AY585438.1

(A/duck/Shanghai/38/2001(H5N1))
linear
GI: 47156430

nucleoprotein (NP) mRNA, complete cds
mRNA

290. Influenza A virus
692 bp
AY585459.1

(A/duck/Shanghai/38/2001(H5N1))
linear
GI: 47156472

nonstructural protein 1 (NS1) mRNA,
mRNA

partial cds

291. Influenza A virus
875 bp
DQ354059.1

(A/duck/Sheyang/1/2005(H5N1))
linear
GI: 87128643

nonstructural protein (NS) mRNA,
mRNA

complete cds

292. Influenza A virus
1,748 bp
DQ861291.1

(A/duck/Tuva/01/2006(H5N1))
linear
GI: 112820195

hemagglutinin (HA) mRNA, complete cds
mRNA

293. Influenza A virus
991 bp
DQ861292.1

(A/duck/Tuva/01/2006(H5N1)) matrix
linear
GI: 112820197

protein 1 (M1) mRNA, complete cds
mRNA

294. Influenza A virus
1,364 bp
DQ861293.1

(A/duck/Tuva/01/2006(H5N1))
linear
GI: 112820199

neuraminidase (NA) mRNA, complete cds
mRNA

295. Influenza A virus
1,531 bp
DQ861294.1

(A/duck/Tuva/01/2006(H5N1))
linear
GI: 112820201

nucleoprotein (NP) mRNA, complete cds
mRNA

296. Influenza A virus
842 bp
DQ861295.1

(A/duck/Tuva/01/2006(H5N1))
linear
GI: 112820203

nonstructural protein (NS) mRNA,
mRNA

complete cds

297. Influenza A virus
890 bp
DQ366310.1

(A/duck/Vietnam/1/2005(H5N1))
linear
GI: 86753715

nonstructural protein 1 mRNA,
mRNA

complete cds

298. Influenza A virus
2,341 bp
DQ366303.1

(A/duck/Vietnam/1/2005(H5N1))
linear
GI: 86753725

polymerase PB2 mRNA, complete cds
mRNA

299. Influenza A virus
2,341 bp
DQ366304.1

(A/duck/Vietnam/1/2005(H5N1))
linear
GI: 86753735

polymerase PB1 mRNA, complete cds
mRNA

300. Influenza A virus
2,233 bp
DQ366305.1

(A/duck/Vietnam/1/2005(H5N1)) PA
linear
GI: 86753745

protein mRNA, complete cds
mRNA

301. Influenza A virus
1,779 bp
DQ366306.1

(A/duck/Vietnam/1/2005(H5N1))
linear
GI: 86753755

hemagglutinin mRNA, complete cds
mRNA

302. Influenza A virus
1,565 bp
DQ366307.1

(A/duck/Vietnam/1/2005(H5N1))
linear
GI: 86753765

nucleocapsid mRNA, complete cds
mRNA

303. Influenza A virus
1,401 bp
DQ366308.1

(A/duck/Vietnam/1/2005(H5N1))
linear
GI: 86753775

neuraminidase mRNA, complete cds
mRNA

304. Influenza A virus
1,027 bp
DQ366309.1

(A/duck/Vietnam/1/2005(H5N1)) matrix
linear
GI: 86753785

protein mRNA, complete cds
mRNA

305. Influenza A virus
890 bp
DQ366326.1

(A/duck/Vietnam/8/05(H5N1))
linear
GI: 86753719

nonstructural protein 1 mRNA,
mRNA

complete cds

306. Influenza A virus
2,341 bp
DQ366319.1

(A/duck/Vietnam/8/05(H5N1))
linear
GI: 86753729

polymerase PB2 mRNA, complete cds
mRNA

307. Influenza A virus
2,341 bp
DQ366320.1

(A/duck/Vietnam/8/05(H5N1))
linear
GI: 86753739

polymerase PB1 mRNA, complete cds
mRNA

308. Influenza A virus
2,233 bp
DQ366321.1

(A/duck/Vietnam/8/05(H5N1)) PA
linear
GI: 86753749

protein mRNA, complete cds
mRNA

309. Influenza A virus
1,779 bp
DQ366322.1

(A/duck/Vietnam/8/05(H5N1))
linear
GI: 86753759

hemagglutinin mRNA, complete cds
mRNA

310. Influenza A virus
1,565 bp
DQ366323.1

(A/duck/Vietnam/8/05(H5N1))
linear
GI: 86753769

nucleocapsid mRNA, complete cds
mRNA

311. Influenza A virus
1,401 bp
DQ366324.1

(A/duck/Vietnam/8/05(H5N1))
linear
GI: 86753779

neuraminidase mRNA, complete cds
mRNA

312. Influenza A virus
1,027 bp
DQ366325.1

(A/duck/Vietnam/8/05(H5N1)) matrix
linear
GI: 86753789

protein mRNA, complete cds
mRNA

313. Influenza A virus
876 bp
DQ354060.1

(A/duck/Yangzhou/232/2004(H5N1))
linear
GI: 87128645

nonfunctional nonstructural protein
mRNA

(NS) mRNA, complete sequence

314. Influenza A virus
2,281 bp
AY585523.1

(A/duck/Zhejiang/11/2000(H5N1))
linear
GI: 47156264

polymerase basic protein 2 (PB2)
mRNA

mRNA, complete cds

315. Influenza A virus
760 bp
AY585396.1

(A/duck/Zhejiang/11/2000(H5N1))
linear
GI: 47156346

matrix protein mRNA, complete cds
mRNA

316. Influenza A virus
1,352 bp
AY585418.1

(A/duck/Zhejiang/11/2000(H5N1))
linear
GI: 47156390

neuraminidase (NA) mRNA, complete cds
mRNA

317. Influenza A virus
1,498 bp
AY585439.1

(A/duck/Zhejiang/11/2000(H5N1))
linear
GI: 47156432

nucleoprotein (NP) mRNA, complete cds
mRNA

318. Influenza A virus
687 bp
AY585460.1

(A/duck/Zhejiang/11/2000(H5N1))
linear
GI: 47156474

nonstructural protein 1 (NS1) mRNA,
mRNA

partial cds

319. Influenza A virus
2,281 bp
AY585524.1

(A/duck/Zhejiang/52/2000(H5N1))
linear
GI: 47156266

polymerase basic protein 2 (PB2)
mRNA

mRNA, complete cds

320. Influenza A virus
760 bp
AY585397.1

(A/duck/Zhejiang/52/2000(H5N1))
linear
GI: 47156348

matrix protein mRNA, complete cds
mRNA

321. Influenza A virus
1,423 bp
AY585419.1

(A/duck/Zhejiang/52/2000(H5N1))
linear
GI: 47156392

neuraminidase (NA) mRNA, complete cds
mRNA

322. Influenza A virus
1,499 bp
AY585440.1

(A/duck/Zhejiang/52/2000(H5N1))
linear
GI: 47156434

nucleoprotein (NP) mRNA, complete cds
mRNA

323. Influenza A virus
686 bp
AY585461.1

(A/duck/Zhejiang/52/2000(H5N1))
linear
GI: 47156476

nonstructural protein 1 (NS1) mRNA,
mRNA

complete cds

324. Influenza A virus (A/Egypt/0636-
1,749 bp
EF382359.1

NAMRU3/2007(H5N1)) hemagglutinin
linear
GI: 124244205

(HA) mRNA, complete cds
mRNA

325. Influenza A virus
1,707 bp
EF110518.1

(A/goosander/Switzerland/V82/06
linear
GI: 119394674

(H5N1)) hemagglutinin (HA) gene,
mRNA

complete cds

326. Influenza A virus
1,707 bp
AF148678.1

(A/goose/Guangdong/1/96/(H5N1))
linear
GI: 5007022

hemagglutinin mRNA, complete cds
mRNA

327. Influenza A virus
1,779 bp
DQ201829.1

(A/Goose/Huadong/1/2000(H5N1))
linear
GI: 76786306

hemagglutinin (HA) mRNA, complete cds
mRNA

328. Influenza A virus
1,458 bp
DQ201830.1

(A/Goose/Huadong/1/2000(H5N1))
linear
GI: 76786308

neuraminidase (NA) mRNA, complete cds
mRNA

329. Influenza A virus
2,287 bp
EF446768.1

(A/goose/Hungary/2823/2/2007(H5N1))
linear
GI: 126428373

polymerase PB1 (PB1) mRNA, partial
mRNA

cds

330. Influenza A virus
2,274 bp
EF446769.1

(A/goose/Hungary/2823/2/2007(H5N1))
linear
GI: 126428375

polymerase PB2 (PB2) mRNA, partial
mRNA

cds

331. Influenza A virus
2,175 bp
EF446770.1

(A/goose/Hungary/2823/2/2007(H5N1))
linear
GI: 126428377

polymerase PA (PA) mRNA, complete cds
mRNA

332. Influenza A virus
1,735 bp
EF446771.1

(A/goose/Hungary/2823/2/2007(H5N1))
linear
GI: 126428379

hemagglutinin (HA) mRNA, complete cds
mRNA

333. Influenza A virus
1,473 bp
EF446772.1

(A/goose/Hungary/2823/2/2007(H5N1))
linear
GI: 126428381

nucleocapsid protein (NP) mRNA,
mRNA

partial cds

334. Influenza A virus
1,311 bp
EF446773.1

(A/goose/Hungary/2823/2/2007(H5N1))
linear
GI: 126428383

neuraminidase (NA) mRNA, partial cds
mRNA

335. Influenza A virus
971 bp
EF446774.1

(A/goose/Hungary/2823/2/2007(H5N1))
linear
GI: 126428385

matrix protein 1 (M1) mRNA, partial
mRNA

cds

336. Influenza A virus
795 bp
EF446775.1

(A/goose/Hungary/2823/2/2007(H5N1))
linear
GI: 126428387

nonstructural protein 1 (NS1) mRNA,
mRNA

partial cds

337. Influenza A virus
2,277 bp
EF446776.1

(A/goose/Hungary/3413/2007(H5N1))
linear
GI: 126428389

polymerase PB1 (PB1) mRNA, partial
mRNA

cds

338. Influenza A virus
2,274 bp
EF446777.1

(A/goose/Hungary/3413/2007(H5N1))
linear
GI: 126428391

polymerase PB2 (PB2) mRNA, partial
mRNA

cds

339. Influenza A virus
2,163 bp
EF446778.1

(A/goose/Hungary/3413/2007(H5N1))
linear
GI: 126428393

polymerase PA (PA) mRNA, partial cds
mRNA

340. Influenza A virus
1,722 bp
EF446779.1

(A/goose/Hungary/3413/2007(H5N1))
linear
GI: 126428395

hemagglutinin (HA) mRNA, complete cds
mRNA

341. Influenza A virus
1,463 bp
EF446780.1

(A/goose/Hungary/3413/2007(H5N1))
linear
GI: 126428397

nucleocapsid protein (NP) mRNA,
mRNA

partial cds

342. Influenza A virus
1,289 bp
EF446781.1

(A/goose/Hungary/3413/2007(H5N1))
linear
GI: 126428399

neuraminidase (NA) mRNA, partial cds
mRNA

343. Influenza A virus
955 bp
EF446782.1

(A/goose/Hungary/3413/2007(H5N1))
linear
GI: 126428401

matrix protein 1 (M1) mRNA, partial
mRNA

cds

344. Influenza A virus
805 bp
EF446783.1

(A/goose/Hungary/3413/2007(H5N1))
linear
GI: 126428403

nonstructural protein 1 (NS1) mRNA,
mRNA

complete cds

345. Influenza A virus
877 bp
DQ354061.1

(A/goose/jiangsu/131/2002(H5N1))
linear
GI: 87128646

nonfunctional nonstructural protein
mRNA

(NS) mRNA, complete sequence

346. Influenza A virus
875 bp
DQ354062.1

(A/goose/Jiangsu/220/2003(H5N1))
linear
GI: 87128647

nonstructural protein (NS) mRNA,
mRNA

complete cds

347. Influenza A virus
1,754 bp
DQ676840.1

(A/goose/Krasnoozerka/627/2005(H5N1))
linear
GI: 108782531

hemagglutinin (HA) mRNA, complete cds
mRNA

348. Influenza A virus
1,530 bp
DQ676841.1

(A/goose/Krasnoozerka/627/2005(H5N1))
linear
GI: 108782533

nucleoprotein (NP) mRNA, complete cds
mRNA

349. Influenza A virus
850 bp
DQ676842.1

(A/goose/Krasnoozerka/627/2005(H5N1))
linear
GI: 108782535

nonstructural protein (NS) mRNA,
mRNA

complete cds

350. Influenza A virus
890 bp
DQ366318.1

(A/goose/Vietnam/3/05(H5N1))
linear
GI: 86753717

nonstructural protein 1 mRNA,
mRNA

complete cds

351. Influenza A virus
2,341 bp
DQ366311.1

(A/goose/Vietnam/3/05(H5N1))
linear

polymerase PB2 mRNA, complete cds
mRNA
GI: 86753727

352. Influenza A virus
2,341 bp
DQ366312.1

(A/goose/Vietnam/3/05(H5N1))
linear
GI: 86753737

polymerase PB1 mRNA, complete cds
mRNA

353. Influenza A virus
2,233 bp
DQ366313.1

(A/goose/Vietnam/3/05(H5N1)) PA
linear
GI: 86753747

protein mRNA, complete cds
mRNA

354. Influenza A virus
1,779 bp
DQ366314.1

(A/goose/Vietnam/3/05(H5N1))
linear
GI: 86753757

hemagglutinin mRNA, complete cds
mRNA

355. Influenza A virus
1,565 bp
DQ366315.1

(A/goose/Vietnam/3/05(H5N1))
linear
GI: 86753767

nucleocapsid mRNA, complete cds
mRNA

356. Influenza A virus
1,401 bp
DQ366316.1

(A/goose/Vietnam/3/05(H5N1))
linear
GI: 86753777

neuraminidase mRNA, complete cds
mRNA

357. Influenza A virus
1,027 bp
DQ366317.1

(A/goose/Vietnam/3/05(H5N1)) matrix
linear
GI: 86753787

protein mRNA, complete cds
mRNA

358. Influenza A virus
1,700 bp
AF082043.1

(A/gull/Pennsylvania/4175/83(H5N1))
linear
GI: 4240453

hemagglutinin H5 mRNA, partial cds
mRNA

360. Influenza A virus
1,388 bp
AF028708.1

(A/HongKong/156/97(H5N1))
linear
GI: 2865377

neuraminidase mRNA, complete cds
mRNA

361. Influenza A virus
1,741 bp
AF028709.1

(A/HongKong/156/97(H5N1))
linear
GI: 2865379

hemagglutinin mRNA, complete cds
mRNA

362. Influenza A virus
1,549 bp
AF028710.1

(A/HongKong/156/97(H5N1))
linear
GI: 2865381

nucleoprotein mRNA, complete cds
mRNA

363. Influenza A virus (A/hooded
1,451 bp
AM503028.1

vulture/Burkina Faso/1/2006(H5N1))
linear
GI: 147846292

partial mRNA for nucleoprotein (np
mRNA

gene)

364. Influenza A virus (A/hooded
827 bp
AM503038.1

vulture/Burkina Faso/1/2006(H5N1))
linear
GI: 147846312

mRNA for non-structural protein (ns
mRNA

gene)

365. Influenza A virus (A/hooded
2,169 bp
AM503047.1

vulture/Burkina Faso/1/2006(H5N1))
linear
GI: 147846330

partial mRNA for polymerase (pa gene)
mRNA

366. Influenza A virus (A/hooded
1,686 bp
AM503065.1

vulture/Burkina Faso/1/2006(H5N1))
linear
GI: 147846855

partial mRNA for polymerase basic
mRNA

protein 1 (pb1 gene)

367. Influenza A virus (A/hooded
977 bp
AM503006.1

vulture/Burkina Faso/2/2006(H5N1))
linear
GI: 147846248

partial mRNA for matrix protein 1 (m1
mRNA

gene)

368. Influenza A virus (A/hooded
1,336 bp
AM503017.1

vulture/Burkina Faso/2/2006(H5N1))
linear
GI: 147846270

partial mRNA for neuraminidase (na
mRNA

gene)

369. Influenza A virus (A/hooded
1,499 bp
AM503027.1

vulture/Burkina Faso/2/2006(H5N1))
linear
GI: 147846290

partial mRNA for nucleoprotein (np
mRNA

gene)

370. Influenza A virus (A/hooded
827 bp
AM503039.1

vulture/Burkina Faso/2/2006(H5N1))
linear
GI: 147846314

mRNA for non-structural protein (ns
mRNA

gene)

371. Influenza A virus (A/hooded
2,169 bp
AM503048.1

vulture/Burkina Faso/2/2006(H5N1))
linear
GI: 147846332

partial mRNA for polymerase (pa gene)
mRNA

372. Influenza A virus (A/hooded
2,259 bp
AM503062.1

vulture/Burkina Faso/2/2006(H5N1))
linear
GI: 147846849

partial mRNA for polymerase basic
mRNA

protein 1 (pb1 gene)

373. Influenza A virus (A/hooded
2,315 bp
AM503066.1

vulture/Burkina Faso/2/2006(H5N1))
linear
GI: 147846857

partial mRNA for polymerase basic
mRNA

protein 2 (pb2 gene)

374. Influenza A virus
294 bp
EU014135.1

(A/Indonesia/CDC177/2005(H5N1)) M2
linear
GI: 151336850

protein mRNA, complete cds
mRNA

375. Influenza A virus
294 bp
EU014138.1

(A/Indonesia/CDC298/2005(H5N1)) M2
linear
GI: 151336856

protein mRNA, complete cds
mRNA

376. Influenza A virus
294 bp
EU014136.1

(A/Indonesia/CDC485/2006(H5N1)) M2
linear
GI: 151336852

protein mRNA, complete cds
mRNA

377. Influenza A virus
294 bp
EU014134.1

(A/Indonesia/CDC530/2006(H5N1)) M2
linear
GI: 151336848

protein mRNA, complete cds
mRNA

378. Influenza A virus
294 bp
EU014133.1

(A/Indonesia/CDC535/2006(H5N1)) M2
linear
GI: 151336846

protein mRNA, complete cds
mRNA

379. Influenza A virus
294 bp
EU014132.1

(A/Indonesia/CDC540/2006(H5N1)) M2
linear
GI: 151336844

protein mRNA, complete cds
mRNA

380. Influenza A virus
294 bp
EU014137.1

(A/Indonesia/CDC561/2006(H5N1)) M2
linear
GI: 151336854

protein mRNA, complete cds
mRNA

381. Influenza A virus
294 bp
EU014139.1

(A/Indonesia/CDC60/2005(H5N1)) M2
linear
GI: 151336858

protein mRNA, complete cds
mRNA

382. Influenza A virus
996 bp
U79453.1

(A/mallard/Wisconsin/428/75(H5N1))
linear
GI: 1840071

hemagglutinin mRNA, partial cds
mRNA

383. Influenza A virus
441 bp
JN157759.1

(A/ostrich/VRLCU/Egypt/2011(H5N1))
linear
GI: 338223304

segment 4 hemagglutinin (HA) mRNA,
mRNA

partial cds

384. Influenza A virus
875 bp
DQ354063.1

(A/quail/yunnan/092/2002(H5N1))
linear
GI: 87128649

nonstructural protein (NS) mRNA,
mRNA

complete cds

385. Influenza A virus
1,472 bp
AB241613.1

(A/R(Turkey/Ontario/7732/66-
linear
GI: 82581222

Bellamy/42)(H5N1)) HA mRNA for
mRNA

hemagglutinin, partial cds

386. Influenza A virus
1,350 bp
AY679513.1

(A/Thailand/LFPN-2004/2004(H5N1))
linear
GI: 50843945

neuraminidase mRNA, complete cds
mRNA

387. Influenza A virus
1,704 bp
AY679514.1

(A/Thailand/LFPN-2004/2004(H5N1))
linear
GI: 50843949

hemagglutinin mRNA, complete cds
mRNA

388. Influenza A virus
534 bp
DQ017251.1

(A/tiger/Thailand/CU-T4/04(H5N1))
linear
GI: 65329524

polymerase basic protein 2 (PB2)
mRNA

mRNA, partial cds

389. Influenza A virus
582 bp
DQ017252.1

(A/tiger/Thailand/CU-T5/04(H5N1))
linear
GI: 65329536

polymerase basic protein 2 (PB2)
mRNA

mRNA, partial cds

390. Influenza A virus
564 bp
DQ017253.1

(A/tiger/Thailand/CU-T6/04(H5N1))
linear
GI: 65329553

polymerase basic protein 2 (PB2)
mRNA

mRNA, partial cds

391. Influenza A virus
582 bp
DQ017254.1

(A/tiger/Thailand/CU-T8/04(H5N1))
linear
GI: 65329568

polymerase basic protein 2 (PB2)
mRNA

mRNA, partial cds

392. Influenza A virus
1,695 bp
EF441263.1

(A/turkey/England/250/2007(H5N1))
linear
GI: 129307104

hemagglutinin (HA) mRNA, partial cds
mRNA

393. Influenza A virus
943 bp
EF441264.1

(A/turkey/England/250/2007(H5N1))
linear
GI: 129307106

matrix protein (M) mRNA, partial cds
mRNA

394. Influenza A virus
812 bp
EF441265.1

(A/turkey/England/250/2007(H5N1))
linear
GI: 129307109

nonstructural protein 1 (NS1) mRNA,
mRNA

complete cds

395. Influenza A virus
2,185 bp
EF441266.1

(A/turkey/England/250/2007(H5N1))
linear
GI: 129307111

polymerase PA (PA) mRNA, complete cds
mRNA

396. Influenza A virus
2,272 bp
EF441267.1

(A/turkey/England/250/2007(H5N1))
linear
GI: 129307113

polymerase PB2 (PB2) mRNA, partial
mRNA

cds

397. Influenza A virus
1,396 bp
EF441268.1

(A/turkey/England/250/2007(H5N1))
linear
GI: 129307115

nucleocapsid (NP) mRNA, partial cds
mRNA

398. Influenza A virus
2,288 bp
EF441269.1

(A/turkey/England/250/2007(H5N1))
linear
GI: 129307117

polymerase PB1 (PB1) mRNA, partial
mRNA

cds

399. Influenza A virus
1,276 bp
EF441270.1

(A/turkey/England/250/2007(H5N1))
linear
GI: 129307119

neuraminidase (NA) mRNA, partial cds
mRNA

A/chicken/Burkina

AM503016.1

Faso/13.1/2006(H5N1) neuraminidase

(NA)

A/chicken/Crimea/04/2005(H5N1)

DQ650661.1

neuraminidase (NA)

A/chicken/Crimea/04/2005(H5N1)

DQ650659.1

hemagglutinin

A/chicken/Crimea/08/2005(H5N1)

DQ650669.1

polymerase basic protein 1 (PB1)

A/chicken/Crimea/08/2005(H5N1)

DQ650665.1

neuraminidase (NA)

A/chicken/Crimea/08/2005(H5N1)

DQ650663.1

hemagglutinin (HA)

A/chicken/Guangxi/12/2004(H5N1)

DQ366334.1

nonstructural protein 1

A/chicken/Guangxi/12/2004(H5N1)

DQ366332.1

neuraminidase

A/chicken/Guangxi/12/2004(H5N1)

DQ366330.1

hemagglutinin

A/duck/Kurgan/08/2005(H5N1)

DQ449643.1

nucleoprotein (NP)

TABLE 9

Other Influenza A Antigens(H1N*, H2N*, H3N*)

GenBank/GI

Accession

Strain/Protein
Length
Nos.

H1N*

Influenza A virus (A/duck/Hong
1,402 bp
U49097.1

Kong/193/1977(H1N2)) nucleoprotein (NP)
linear mRNA
GI: 1912392

mRNA, partial cds

Influenza A virus (A/duck/Hong
258 bp
U48285.1

Kong/193/1977(H1N2)) polymerase (PB1)
linear mRNA
GI: 1912374

mRNA, partial cds

Influenza A virus
795 bp
AJ519455.1

(A/England/2/2002(H1N2)) partial NS1 gene
linear mRNA
GI: 31096426

for non structural protein 1 and partial

NS2 gene for non structural protein 2,

genomic RNA

Influenza A virus (A/England/3/02(H1N2))
384 bp
AJ489497.1

partial mRNA for nucleoprotein (np gene)
linear mRNA
GI: 27526856

Influenza A virus (A/England/3/02(H1N2))
442 bp
AJ489488.1

partial mRNA for polymerase subunit 2
linear mRNA
GI: 27526838

(pb2 gene)

Influenza A virus (A/England/5/02(H1N2))
384 bp
AJ489498.1

partial mRNA for nucleoprotein (np gene)
linear mRNA
GI: 27526858

Influenza A virus (A/England/5/02(H1N2))
442 bp
AJ489489.1

partial mRNA for polymerase subunit 2
linear mRNA
GI: 27526840

(pb2 gene)

Influenza A virus (A/England/57/02(H1N2))
384 bp
AJ489499.1

partial mRNA for nucleoprotein (np gene)
linear mRNA
GI: 27526860

Influenza A virus (A/England/57/02(H1N2))
442 bp
AJ489492.1

partial mRNA for polymerase subunit 2
linear mRNA
GI: 27526846

(pb2 gene)

Influenza A virus
384 bp
AJ489496.1

(A/England/691/01(H1N2)) partial mRNA for
linear mRNA
GI: 27526854

nucleoprotein (np gene)

Influenza A virus (A/England/73/02(H1N2))
384 bp
AJ489500.1

partial mRNA for nucleoprotein (np gene)
linear mRNA
GI: 27526862

Influenza A virus (A/England/73/02(H1N2))
442 bp
AJ489493.1

partial mRNA for polymerase subunit 2
linear mRNA
GI: 27526848

(pb2 gene)

Influenza A virus (A/England/90/02(H1N2))
384 bp
AJ489501.1

partial mRNA for nucleoprotein (np gene)
linear mRNA
GI: 27526864

Influenza A virus (A/England/90/02(H1N2))
442 bp
AJ489490.1

partial mRNA for polymerase subunit 2
linear mRNA
GI: 27526842

(pb2 gene)

Influenza A virus (A/England/97/02(H1N2))
384 bp
AJ489502.1

partial mRNA for nucleoprotein (np gene)
linear mRNA
GI: 27526866

Influenza A virus (A/England/97/02(H1N2))
442 bp
AJ489491.1

partial mRNA for polymerase subunit 2
linear mRNA
GI: 27526844

(pb2 gene)

Influenza A virus
384 bp
AJ489494.1

(A/England/627/01(H1N2)) partial mRNA for
linear mRNA
GI: 27526850

nucleoprotein (np gene)

Influenza A virus
442 bp
AJ489485.1

(A/England/627/01(H1N2)) partial mRNA for
linear mRNA
GI: 27526832

polymerase subunit 2 (pb2 gene)

Influenza A virus
442 bp
AJ489487.1

(A/England/691/01(H1N2)) partial mRNA for
linear mRNA
GI: 27526836

polymerase subunit 2 (pb2 gene)

Influenza A virus (A/Egypt/96/2002(H1N2))
747 bp
AJ519457.1

partial NS1 gene for non structural
linear mRNA
GI: 31096432

protein 1 and partial NS2 gene for non

structural protein 2, genomic RNA

Influenza A virus (A/Israel/6/2002(H1N2))
773 bp
AJ519456.1

partial NS1 gene for non structural
linear mRNA
GI: 31096429

protein 1 and partial NS2 gene for non

structural protein 2, genomic RNA

Influenza A virus (A/Saudi
772 bp
AJ519453.1

Arabia/2231/2001(H1N2)) partial NS1 gene
linear mRNA
GI: 31096420

for non structural protein 1 and partial

NS2 gene for non structural protein 2,

genomic RNA

Influenza A virus
384 bp
AJ489495.1

(A/Scotland/122/01(H1N2)) partial mRNA
linear mRNA
GI: 27526852

for nucleoprotein (np gene)

Influenza A virus
442 bp
AJ489486.1

(A/Scotland/122/01(H1N2)) partial mRNA
linear mRNA
GI: 27526834

for polymerase subunit 2 (pb2 gene)

Influenza A virus
832 bp
AY861443.1

(A/swine/Bakum/1832/2000(H1N2))
linear mRNA
GI: 57791765

hemagglutinin (HA) mRNA, partial cds

Influenza A virus
467 bp
AY870645.1

(A/swine/Bakum/1832/2000(H1N2))
linear mRNA
GI: 58042754

neuraminidase mRNA, partial cds

Influenza A virus (A/swine/Cotes
1,039 bp
AM503547.1

d'Armor/0040/2007(H1N2)) segment 4
linear mRNA
GI: 225578611

partial mRNA

Influenza A virus (A/swine/Cotes
1,136 bp
AM490224.3

d'Armor/0136_17/2006(H1N2)) partial mRNA
linear mRNA
GI: 222062921

for haemagglutinin precursor (HA1 gene)

Influenza A virus
1,778 bp
AF085417.1

(A/swine/England/72685/96(H1N2))
linear mRNA
GI: 3831770

haemagglutinin precursor, mRNA, complete

cds

Influenza A virus
1,778 bp
AF085416.1

(A/swine/England/17394/96(H1N2))
linear mRNA
GI: 3831768

haemagglutinin precursor, mRNA, complete

cds

Influenza A virus
1,778 bp
AF085415.1

(A/swine/England/690421/95(H1N2))
linear mRNA
GI: 3831766

haemagglutinin precursor, mRNA, complete

cds

Influenza A virus
1,778 bp
AF085414.1

(A/swine/England/438207/94(H1N2))
linear mRNA
GI: 3831764

haemagglutinin precursor, mRNA, complete

cds

Influenza A virus
1,427 bp
AY129157.1

(A/Swine/Korea/CY02/02(H1N2))
linear mRNA
GI: 24286064

neuraminidase (NA) mRNA, complete cds

Influenza A virus
952 bp
AY129158.1

(A/Swine/Korea/CY02/02(H1N2)) matrix
linear mRNA
GI: 24286066

protein (M) mRNA, complete cds

Influenza A virus
1,542 bp
AY129159.1

(A/Swine/Korea/CY02/02(H1N2))
linear mRNA
GI: 24286069

nucleoprotein (NP) mRNA, complete cds

Influenza A virus
842 bp
AY129160.1

(A/Swine/Korea/CY02/02(H1N2))
linear mRNA
GI: 24286081

nonstructural protein (NS) mRNA, complete

cds

Influenza A virus
2,165 bp
AY129161.1

(A/Swine/Korea/CY02/02(H1N2)) polymerase
linear mRNA
GI: 24286087

acidic protein 2 (PA) mRNA, complete cds

Influenza A virus
2,274 bp
AY129162.1

(A/Swine/Korea/CY02/02(H1N2)) polymerase
linear mRNA
GI: 24286096

subunit 1 (PB1) mRNA, complete cds

Influenza A virus
2,334 bp
AY129163.1

(A/Swine/Korea/CY02/02(H1N2)) polymerase
linear mRNA
GI: 24286100

subunit 2 (PB2) mRNA, complete cds

Influenza A virus
1,778 bp
AF085413.1

(A/swine/Scotland/410440/94(H1N2))
linear mRNA
GI: 3831762

haemagglutinin precursor, mRNA, complete

cds

Influenza A virus (A/swine/Spain/80598-
291 bp
EU305436.1

LP4/2007(H1N2)) matrix protein 2 (M2)
linear mRNA
GI: 168830657

mRNA, partial cds

Influenza A virus
975 bp
AJ517813.1

(A/Switzerland/3100/2002(H1N2)) partial
linear mRNA
GI: 38422519

HA gene for Haemagglutinin, genomic RNA

Influenza A virus (A/duck/Hong
1,387 bp
U49095.1

Kong/717/1979(H1N3)) nucleoprotein (NP)
linear mRNA
GI: 1912388

mRNA, partial cds

Influenza A virus (A/duck/Hong
265 bp
U48281.1

Kong/717/1979(H1N3)) polymerase (PB1)
linear mRNA
GI: 1912366

mRNA, partial cds

Influenza A virus (A/herring gull/New
971 bp
AY664422.1

Jersey/780/86(H1N3)) nonfunctional
linear mRNA
GI: 51011826

matrix protein mRNA, partial sequence

Influenza A virus
997 bp
AY664426.1

(A/mallard/Alberta/42/77(H1N6))
linear mRNA
GI: 51011830

nonfunctional matrix protein mRNA,

partial sequence

Influenza A virus
1,020 bp
U85985.1

(A/swine/England/191973/92(H1N7)) matrix
linear mRNA
GI: 1835733

protein M1 mRNA, complete cds

Influenza A virus
1,524 bp
U85987.1

(A/swine/England/191973/92(H1N7))
linear mRNA
GI: 1835737

nucleoprotein mRNA, complete cds

Influenza A virus
1,458 bp
085988.1

(A/swine/England/191973/92(H1N7))
linear mRNA
GI: 1835739

neuraminidase mRNA, complete cds

Influenza A virus
1,698 bp
U85986.1

(A/swine/England/191973/92(H1N7))
linear mRNA
GI: 1835735

haemagglutinin HA mRNA, partial cds

H2N*

Influenza A virus (A/ruddy
917 bp
AY664465.1

turnstone/Delaware/81/93(H2N1))
linear mRNA
GI: 51011869

nonfunctional matrix protein mRNA,

partial sequence

Influenza A virus (A/ruddy
968 bp
AY664429.1

turnstone/Delaware/34/93(H2N1))
linear mRNA
GI: 51011833

nonfunctional matrix protein mRNA,

partial sequence

Influenza A virus
925 bp
AY664466.1

(A/Shorebird/Delaware/122/97(H2N1))
linear mRNA
GI: 51011870

nonfunctional matrix protein mRNA,

partial sequence

Influenza A virus
958 bp
AY664454.1

(A/shorebird/Delaware/138/97(H2N1))
linear mRNA
GI: 51011858

nonfunctional matrix protein mRNA,

partial sequence

Influenza A virus
958 bp
AY664457.1

(A/shorebird/Delaware/111/97(H2N1))
linear mRNA
GI: 51011861

nonfunctional matrix protein mRNA,

partial sequence

Influenza A virus
979 bp
AY664442.1

(A/shorebird/Delaware/24/98(H2N1))
linear mRNA
GI: 51011846

nonfunctional matrix protein mRNA,

partial sequence

Influenza virus type
2,233 bp
M81579.1

A/Leningrad/134/17/57(H2N2) PA RNA,
linear mRNA
GI: 324935

complete cds

Influenza A virus (STRAIN A/MALLARD/NEW
2,151 bp
AJ243994.1

YORK/6750/78) partial mRNA for PA protein
linear mRNA
GI: 5918195

Influenza A virus (A/X-7 (F1)/(H2N2))
1,467 bp
M11205.1

neuraminidase mRNA, complete cds
linear mRNA
GI: 323969

Influenza A virus
1,009 bp
AY664425.1

(A/mallard/Alberta/77/77(H2N3))
linear mRNA
GI: 51011829

nonfunctional matrix protein mRNA,

partial sequence

Influenza A virus
968 bp
AY664447.1

(A/mallard/Alberta/226/98(H2N3))
linear mRNA
GI: 51011851

nonfunctional matrix protein mRNA,

partial sequence

Influenza A virus (A/sanderling/New
846 bp
AY664477.1

Jersey/766/86(H2N7)) nonfunctional
linear mRNA
GI: 51011881

matrix protein mRNA, partial sequence

Influenza A virus (A/laughing gull/New
907 bp
AY664471.1

Jersey/798/86(H2N7)) nonfunctional
linear mRNA
GI: 51011875

matrix protein mRNA, partial sequence

Influenza A virus (A/herring
960 bp
AY664440.1

gull/Delaware/471/1986(H2N7))
linear mRNA
GI: 51011844

nonfunctional matrix protein mRNA,

partial sequence

Influenza A virus (A/ruddy
1,011 bp
AY664423.1

turnstone/Delaware/142/98(H2N8))
linear mRNA
GI: 51011827

nonfunctional matrix protein mRNA,

partial sequence

Influenza A virus
906 bp
AY664473.1

(A/pintail/Alberta/293/77(H2N9))
linear mRNA
GI: 51011877

nonfunctional matrix protein mRNA,

partial sequence

Influenza A virus (A/blue-winged
961 bp
AY664449.1

teal/Alberta/16/97(H2N9)) nonfunctional
linear mRNA
GI: 51011853

matrix protein mRNA, partial sequence

Influenza A virus (A/Laughing gull/New
952 bp
AY664437.1

Jersey/75/85(H2N9)) nonfunctional matrix
linear mRNA
GI: 51011841

protein mRNA, partial sequence

Influenza A virus
959 bp
AY664450.1

(A/mallard/Alberta/205/98(H2N9))
linear mRNA
GI: 51011854

nonfunctional matrix protein mRNA,

partial sequence

H3N*

Influenza A virus (A/duck/Eastern
1,458 bp
EU429755.1

China/267/2003(H3N1)) segment 6
linear mRNA
GI: 167859475

neuraminidase (NA) mRNA, complete cds

Influenza A virus (A/duck/Eastern
1,458 bp
EU429754.1

China/253/2003(H3N1)) segment 6
linear mRNA
GI: 167859473

neuraminidase (NA) mRNA, complete cds

Influenza A virus (A/duck/Eastern
1,458 bp
E0429753.1

China/252/2003(H3N1)) segment 6
linear mRNA
GI: 167859471

neuraminidase (NA) mRNA, complete cds

Influenza A virus (A/duck/Eastern
1,458 bp
EU429752.1

China/243/2003(H3N1)) segment 6
linear mRNA
GI: 167859469

neuraminidase (NA) mRNA, complete cds

Influenza A virus (A/duck/Eastern
1,458 bp
EU429734.1

China/262/2003(H3N1)) segment 6
linear mRNA
GI: 167859433

neuraminidase (NA) mRNA, complete cds

Influenza A virus (A/duck/Eastern
1,459 bp
EU429733.1

China/233/2003(H3N1)) segment 6
linear mRNA
GI: 167859431

neuraminidase (NA) mRNA, complete cds

Influenza A virus (A/duck/Eastern
1,458 bp
EU429723.1

China/213/2003(H3N1)) segment 6
linear mRNA
GI: 167859411

neuraminidase (NA) mRNA, complete cds

Influenza A virus (A/duck/Eastern
1,458 bp
EU429719.1

China/341/2003(H3N1)) segment 6
linear mRNA
GI: 167859403

neuraminidase (NA) mRNA, complete cds

Influenza A virus (A/duck/Eastern
1,458 bp
EU429718.1

China/01/2002(H3N1)) segment 6
linear mRNA
GI: 167859401

neuraminidase (NA) mRNA, complete cds

Influenza A virus
1,013 bp
AY664434.1

(A/mallard/Alberta/22/76(H3N6))
linear mRNA
GI: 51011838

nonfunctional matrix protein mRNA,

partial sequence

Influenza A virus
970 bp
AY664443.1

(A/mallard/Alberta/199/99(H3N6))
linear mRNA
GI: 51011847

nonfunctional matrix protein mRNA,

partial sequence

Influenza A virus
922 bp
AY664461.1

(A/shorebird/Delaware/222/97(H3N6))
linear mRNA
GI: 51011865

nonfunctional matrix protein mRNA,

partial sequence

Influenza A virus (A/Duck/Hokkaido/8/80
984 bp
AF079570.1

(H3N8)) hemagglutinin precursor, mRNA,
linear mRNA
GI: 3414978

partial cds

Influenza A virus (A/Duck/Hokkaido/8/80
1,497 bp
AF079571.1

(H3N8)) nucleoprotein mRNA, complete cds
linear mRNA
GI: 3414980

Influenza A virus
1,461 bp
EU429797.1

(A/duck/Ukraine/1/1963(H3N8)) segment 6
linear mRNA
GI: 167859559

neuraminidase (NA) mRNA, complete cds

(A/duck/Eastern

Influenza A virus (A/duck/Eastern
1,460 bp
EU429698.1

China/19/2004(H3N8)) segment 6
linear mRNA
GI: 167859361

neuraminidase (NA) mRNA, complete cds

Influenza A virus (A/duck/Eastern
1,460 bp
EU429700.1

China/90/2004(H3N8)) segment 6
linear mRNA
GI: 167859365

neuraminidase (NA) mRNA, complete cds

Influenza A virus (A/duck/Eastern
1,460 bp
EU429787.1

China/18/2005(H3N8)) segment 6
linear mRNA
GI: 167859539

neuraminidase (NA) mRNA, complete cds

Influenza A virus (A/duck/Eastern
1,460 bp
EU429788.1

China/119/2005(H3N8)) segment 6
linear mRNA
GI: 167859541

neuraminidase (NA) mRNA, complete cds

Influenza A virus
1,061 bp
AF197246.1

(A/equine/Argentina/1/96(H3N8))
linear mRNA
GI: 6651512

hemagglutinin precursor (HA1) mRNA,

partial cds

Influenza A virus
1,061 bp
AF197245.1

(A/equine/Argentina/2/94(H3N8))
linear mRNA
GI: 6651510

hemagglutinin precursor (HA1) mRNA

partial cds

Influenza A virus
1,061 bp
AF197244.1

(A/equine/Argentina/1/95(H3N8))
linear mRNA
GI: 6651508

hemagglutinin precursor (HA1) mRNA,

partial cds

Influenza A virus HA partial gene for
1,026 bp
AJ223194.1

haemagglutinin, genomic RNA, strain
linear mRNA
GI: 2780201

A/equine/Berlin/3/89(H3N8)

Influenza A virus HA partial gene for
1,006 bp
AJ223195.1

haemagglutinin, genomic RNA, strain
linear mRNA
GI: 2780203

A/equine/Berlin/4/89(H3N8)

Influenza A virus
1,061 bp
AF197242.1

(A/equine/Florida/1/94(H3N8))
linear mRNA
GI: 6651504

hemagglutinin precursor (HA1) mRNA,

partial cds

Influenza A virus
695 bp
AY328471.1

(A/equine/Grobois/1/98(H3N8))
linear mRNA
GI: 32966577

nonstructural protein NS1 mRNA, complete

cds

Influenza A virus (A/equi
473 bp
AY919314.1

2/Gotland/01(H3N8)) hemagglutinin HA1
linear mRNA
GI: 60250543

subunit mRNA, partial cds

Influenza A virus
1,763 bp
U58195.1

(A/eq/Kentucky/81(H3N8)) hemagglutinin
linear mRNA
GI: 1377873

mRNA, complete cds

Influenza A virus
1,061 bp
AF197247.1

(A/equine/Kentucky/9/95(H3N8))
linear mRNA
GI: 6651514

hemagglutinin precursor (HA1) mRNA,

partial cds

Influenza A virus
1,061 bp
AF197248.1

(A/equine/Kentucky/1/96(H3N8))
linear mRNA
GI: 6651516

hemagglutinin precursor (HA1) mRNA,

partial cds

Influenza A virus
1,061 bp
AF197249.1

(A/equine/Kentucky/1/97(H3N8))
linear mRNA
GI: 6651518

hemagglutinin precursor (HA1) mRNA,

partial cds

Influenza A virus
1,061 bp
AF197241.1

(A/equine/Kentucky/1/98(H3N8))
linear mRNA
GI: 6651502

hemagglutinin precursor (HA1) mRNA,

partial cds

Influenza A virus
1,497 bp
AY383753.1

(A/equine/Santiago/85(H3N8))
linear mRNA
GI: 37223511

nucleoprotein mRNA, complete cds

Influenza A virus
1,698 bp
AY383755.1

(A/equine/Santiago/85(H3N8))
linear mRNA
GI: 37223515

hemagglutinin mRNA, complete cds

Influenza A virus
1,413 bp
AY383754.1

(A/equine/Santiago/85(H3N8))
linear mRNA
GI: 37223513

neuraminidase mRNA, complete cds

Influenza A virus
1,061 bp
AF197243.1

(A/equine/Saskatoon/1/90(H3N8))
linear mRNA
GI: 6651506

hemagglutinin precursor (HA1) mRNA,

partial cds

Influenza A virus
1,010 bp
AY664432.1

(A/mallard/Alberta/114/97(H3N8))
linear mRNA
GI: 51011836

nonfunctional matrix protein mRNA,

partial sequence

Influenza A virus
961 bp
AY664489.1

(A/mallard/Alberta/167/98(H3N8))
linear mRNA
GI: 51011893

nonfunctional matrix protein mRNA,

partial sequence

Influenza A virus
970 bp
AY664445.1

(A/pintail/Alberta/37/99(H3N8))
linear mRNA
GI: 51011849

nonfunctional matrix protein mRNA,

partial sequence

Influenza A virus
922 bp
AY664455.1

(A/sanderling/Delaware/65/99(H3N8))
linear mRNA
GI: 51011859

nonfunctional matrix protein mRNA,

partial sequence

TABLE 10

Other Influenza A Antigens (H4N*-H13N*)

GenBank

Strain/Protein
Access No.

H4N*

A/chicken/Singapore/1992(H4N1) M2 protein
EU014144.1

A/mallard/Alberta/47/98(H4N1) nonfunctional matrix protein
AY664488.1

A/duck/Hong Kong/412/1978(H4N2) polymerase (PB1)
U48279.1

A/mallard/Alberta/300/77 (H4N3) nonfunctional matrix protein
AY664480.1

A/Duck/Czechoslovakia/56(H4N6) segment 4 hemagglutinin
AF290436.1

A/duck/Eastern China/376/2004(H4N6) segment 6neuraminidase (NA)
EU429792.1

A/duck/Eastern China/01/2007(H4N6) segment 6 neuraminidase (NA)
EU429790.1

A/duck/Eastern China/216/2007(H4N6) segment 6 neuraminidase (NA)
EU429789.1

A/duck/Eastern China/166/2004(H4N6) segment 6 neuraminidase (NA)
EU429746.1

A/duck/Eastern China/02/2003(H4N6) segment 6 neuraminidase (NA)
EU429713.1

A/duck/Eastern China/160/2002(H4N6) segment 6 neuraminidase (NA)
EU429706.1

A/mallard/Alberta/111/99(H4N6) nonfunctional matrix protein
AY664482.1

A/mallard/Alberta/213/99 (H4N6) nonfunctional matrix protein
AY664460.1

A/mallard/Alberta/30/98 (H4N6) nonfunctional matrix protein
AY664484.1

A/blue-winged teal/Alberta/96/76 (H4N8) nonfunctional matrix protein
AY664420.1

H5N*

A/chicken/Florida/25717/1993(H5N2) hemagglutinin
U05332.1

A/chicken/Hidalgo/26654-1368/1994(H5N2) hemagglutinin (HA)
U37172.1

A/chicken/Jalisco/14585-660/1994(H5N2) hemagglutinin (HA)
U37181.1

A/chicken/Mexico/26654-1374/1994(H5N2) hemagglutinin (HA)
U37173.1

A/chicken/Mexico/31381-3/1994(H5N2) hemagglutinin (HA)
U37176.1

A/chicken/Mexico/31381-6/1994(H5N2) hemagglutinin (HA)
U37175.1

A/chicken/Mexico/31381-4/1994(H5N2) hemagglutinin (HA)
U37174.1

A/chicken/Mexico/31381-5/1994(H5N2) hemagglutinin (HA)
U37169.1

A/chicken/Mexico/31381-8/1994(H5N2) hemagglutinin (HA)
U37170.1

A/Chicken/Mexico/31381-Avilab/94(H5N2)hemagglutinin (HA)
L46585.1

A/chicken/Mexico/31382-1/1994(H5N2)hemagglutinin (HA)
U37168.1

A/chicken/Mexico/31381-2/1994(H5N2) hemagglutinin (HA)
U37167.1

A/chicken/Mexico/31381-1/1994(H5N2) hemagglutinin (HA)
U37166.1

A/chicken/Mexico/31381-7/1994(H5N2) hemagglutinin (HA)
U37165.1

A/chicken/Pennsylvania/13609/1993(H5N2) hemagglutinin
U05331.1

A/chicken/Pennsylvania/1/1983(H5N2) hemagglutinin esterase precursor
M18001.1

A/chicken/Pennsylvania/1370/1983(H5N2) hemagglutinin esterase precursor
M10243.1

A/Chicken/Puebla/8623-607/94(H5N2) hemagglutinin (HA)
L46586.1

A/chicken/Puebla/14586-654/1994(H5N2) hemagglutinin (HA)
U37180.1

A/chicken/Puebla/14585-622/1994(H5N2) hemagglutinin (HA)
U37179.1

A/chicken/Puebla/8623-607/1994(H5N2)hemagglutinin (HA)
U37178.1

A/chicken/Puebla/8624-604/1994(H5N2) hemagglutinin (HA)
U37177.1

A/Chicken/Queretaro/14588-19/95(H5N2) hemagglutinin (HA)
L46587.1

A/chicken/Queretaro/7653-20/95(H5N2) hemagglutinin (HA)
U79448.1

A/chicken/Queretaro/26654-1373/1994(H5N2) hemagglutinin (HA)
U37171.1

A/chicken/Queretaro/14588-19/1994(H5N2)hemagglutinin (HA)
U37182.1

A/chicken/Singapore/98(H5N2) matrix protein 2 (M2)
EF682127.1

A/chicken/Taiwan/1209/03(H5N2) hemagglutinin protein (HA)
AY573917.1

A/chicken/Taiwan/1209/03(H5N2) neuraminidase
AY573918.1

A/duck/Eastern China/64/2004(H5N2) segment 6 neuraminidase (NA)
EU429791.1

A/duck/Eastern China/264/2002(H5N2) segment 6 neuraminidase (NA)
EU429744.1

A/duck/Eastern China/01/2001(H5N2) segment 6 neuraminidase (NA)
EU429728.1

A/duck/Eastern China/06/2000(H5N2) segment 6 neuraminidase (NA)
EU429722.1

A/duck/Hong Kong/342/78(H5N2) matrix protein 1 (M) and matrix protein 2 (M)
DQ107452.1

A/duck/Hong Kong/342/78(H5N2) hemagglutinin precursor
U20475.1

A/duck/Michigan/80(H5N2) hemagglutinin 1 chain
U20474.1

A/duck/Michigan/80(H5N2) hemagglutinin
U79449.1

A/duck/MN/1564/81(H5N2) matrix protein 1 (M) and matrix protein 2 (M)
DQ107467.1

A/duck/Mongolia/54/2001(H5N2) hemagglutinin (HA)
AB241614.2

A/duck/Primorie/2621/01(H5N2) hemagglutinin (HA)
AJ621811.3

A/duck/Primorie/2621/01(H5N2)nucleoprotein (NP )
AJ621812.1

A/duck/Primorie/2621/01(H5N2) nonstructural protein (NS)
AJ621813.1

A/duck/Pennsylvania/84(H5N2) hemagglutinin 1chain
U20473.1

A/duck/Potsdam/1402-6/86(H5N2) hemagglutinin H5
AF082042.1

A/emu/Texas/39442/93(H5N2) hemaglutinin
U28920.1

A/emu/Texas/39442/93(H5N2) hemaglutinin
U28919.1

A/mallard/Alberta/645/80(H5N2) matrix protein 1 (M) and matrix protein 2 (M)
DQ107471.1

A/mallard/AR/1C/2001(H5N2) matrix protein 1 (M) and matrix protein 2 (M)
DQ107463.1

A/mallard/NY/189/82(H5N2) matrix protein 1 (M) and matrix protein 2 (M)
DQ107465.1

A/mallard/MN/25/80(H5N2) matrix protein 1 (M) and matrix protein 2 (M)
DQ107473.1

A/mallard/MI/18/80(H5N2) matrix protein 1 (M) and matrix protein 2 (M)
DQ107470.1

A/mallard/Ohio/345/88(H5N2) hemagglutinin
U79450.1

A/parrot/CA/6032/04(H5N2) polymerase basic protein 2 (PB2)
DQ256390.1

A/parrot/CA/6032/04(H5N2) polymerase basic protein 1 (PB1)
DQ256389.1

A/parrot/CA/6032/04(H5N2) matrix protein (M)
DQ256384.2

A/parrot/CA/6032/04(H5N2) hemagglutinin (HA)
DQ256383.1

A/parrot/CA/6032/04(H5N2) neuraminidase (NA)
DQ256385.1

A/parrot/CA/6032/04(H5N2) polymerase basic protein 2 (PB2)
DQ256390.1

A/parrot/CA/6032/04(H5N2) nucleoprotein (NP)
DQ256386.1

A/parrot/CA/6032/04(H5N2)) polymerase (PA)
DQ256388.1

A/ruddy turnstone/Delaware/244/91 (H5N2) nonfunctional matrix protein
AY664474.1

A/ruddy turnstone/Delaware/244/91 (H5N2)
U05330.1

A/turkey/Colorado/72(H5N2) hemagglutinin 1 chain (HA)
U20472.1

A/turkey/England/N28/73 (H5N2) hemagglutinin
AY500365.1

A/turkey/TX/14082/81(H5N2) matrix protein 1 (M) and matrix protein 2 (M)
DQ107464.1

A/turkey/MN/1704/82(H5N2)) matrix protein 1 (M) and matrix protein 2 (M)
DQ107472.1

A/turkey/Minnesota/10734/95(H5N2)) hemagglutinin
U79455.1

A/turkey/Minnesota/3689-1551/81(H5N2) hemagglutinin
U79454.1

A/chicken/Singapore/1997(H5N3) M2 protein
EU014141.1

A/duck/Hokkaido/299/04(H5N3) hemagglutinin (HA)
AB241626.1

A/duck/Hokkaido/193/04(H5N3) hemagglutinin (HA)
AB241625.1

A/duck/Hokkaido/101/04(H5N3) hemagglutinin (HA)
AB241624.1

A/duck/Hokkaido/447/00(H5N3) hemagglutinin (HA)
AB241620.1

A/duck/Hokkaido/69/00(H5N3) hemagglutinin (HA)
AB241619.1

A/duck/Hong Kong/205/77(H5N3) hemagglutinin H5
AF082038.1

A/duck/Hong Kong/698/79(H5N3) hemagglutinin H5
AF082039.1

A/duck/Hong Kong/308/78(H5N3) matrix protein 1 (M) and matrix protein 2 (M)
DQ107457.1

A/duck/Hong Kong/825/80(H5N3) matrix protein 1 (M) and matrix protein 2 (M)
DQ107455.1

A/duck/Hong Kong/820/80(H5N3) matrix protein 1 (M) and matrix protein 2 (M)
DQ107453.1

A/duck/Hong Kong/205/77(H5N3) matrix protein 1 (M) and matrix protein 2 (M)
DQ107456.1

A/Duck/Ho Chi Minh/014/78(H5N3) segment 4 hemagglutinin
AF290443.1

A/duck/Jiangxi/6151/2003(H5N3) matrix protein 1 (M) and matrix protein 2 (M)
DQ107451.1

A/duck/Malaysia/F119-3/97(H5N3) hemagglutinin
AF303057.1

A/duck/Miyagi/54/76(H5N3)hemagglutinin (HA)
AB241615.1

A/duck/Mongolia/596/01(H5N3) hemagglutinin HA)
AB241622.1

A/duck/Mongolia/500/01(H5N3)hemagglutinin (HA)
AB241621.1

A/duck/Primorie/2633/01(H5N3) matrix protein (M1)
AJ621810.1

A/duck/Primorie/2633/01(H5N3)nucleoprotein (NP)
AJ621808.1

A/duck/Primorie/2633/01(H5N3)hemagglutinin (HA )
AJ621807.1

A/duck/Primorie/2633/01(H5N3)nucleoprotein (NP)
AJ621809.1

A/goose/Hong Kong/23/78(H5N3) matrix protein 1 (M) and matrix protein 2 (M)
DQ107454.1

A/mallard/Wisconsin/169/75(H5N3) hemagglutinin
U79452.1

A/swan/Hokkaido/51/96(H5N3)hemagglutinin (HA)
AB241617.1

A/swan/Hokkaido/4/96(H5N3) hemagglutinin (HA)
AB241616.1

A/turkey/CA/6878/79(H5N3) matrix protein 1 (M) and matrix protein 2 (M)
DQ107469.1

A/tern/South Africa/61(H5N3) hemagglutinin precursor (HA)
U20460.1

A/gull/Delaware/5/2000(H5N4) matrix protein 1 (M) and matrix protein 2 (M)
DQ107459.1

A/gull/Delaware/4/2000(H5N4) matrix protein 1 (M) and matrix protein 2 (M)
DQ107458.1

A/shorebird/Delaware/109/2000(H5N4) matrix protein 1 (M)
DQ107460.1

A/shorebird/Delaware/243/2000(H5N4) matrix protein 1 (M) and matrix protein 2
DQ107462.1

(M)

A/shorebird/Delaware/230/2000(H5N4) matrix protein 1 (M) and matrix protein 2
DQ107461.1

(M)

A/mallard/Wisconsin/34/75(H5N6) hemagglutinin
U79451.1

A/duck/Potsdam/2216-4/1984(H5N6) hemagglutinin H5
AF082041.1

A/shorebird/Delaware/207/98 (H5N8) nonfunctional matrix protein
AY664456.1

A/shorebird/Delaware/27/98 (H5N8) nonfunctional matrix protein
AY664453.1

A/herring gull/Delaware/281/98 (H5N8) nonfunctional matrix protein
AY664452.1

A/mallard/Ohio/556/1987(H5N9) hemagglutinin (HA)
U67783.2

A/turkey/Wisconsin/68(H5N9) hemagglutinin
U79456.1

H6N*

A/blue-winged teal/Alberta/685/82(H6N1) matrix protein 1 (M) and matrix protein
DQ107448.1

2 (M)

A/chicken/Taiwan/7-5/99(H6N1) nucleocapsid protein (NP)
AF261750.1

A/chicken/Taiwan/7-5/99(H6N1) matrix protein
AF262213.1

A/chicken/Taiwan/7-5/99(H6N1) nonstructural protein
AF262212.1

A/chicken/Taiwan/7-5/99(H6N1) polymerase (PA)
AF262211.1

A/chicken/Taiwan/7-5/99(H6N1) polymerase subunit PB1
AF262210.1

A/chicken/Taiwan/7-5/99(H6N1) nucleocapsid protein (NP)
AF261750.1

A/chicken/Taiwan/ns2/99(H6N1) segment 4 hemagglutinin (HA1)
AF310985.1

A/chicken/Taiwan/na3/98(H6N1) segment 4 hemagglutinin (HA1)
AF310984.1

A/chicken/Taiwan/7-5/99(H6N1) segment 4 hemagglutinin (HA1)
AF310983.1

A/duck/Hong Kong/D73/76(H6N1) matrix protein 1 (M) and matrix protein 2 (M)
DQ107432.1

A/duck/Taiwan/9/23-3/2000(H6N1) matrix protein 1 (M) and matrix protein 2 (M)
DQ107407.1

A/pheasant/Hong Kong/FY479/2000(H6N1) matrix protein 1 (M) and matrix
DQ107409.1

protein 2 (M)

A/pheasant/Hong Kong/SSP44/2002(H6N1) matrix protein 1 (M) and matrix
DQ107412.1

protein 2 (M)

A/quail/Hong Kong/YU421/2002(H6N1) matrix protein 1 (M) and matrix protein 2
DQ107414.1

(M)

A/avian/NY/17150-7/2000(H6N2) matrix protein 1 (M) and matrix protein 2 (M)
DQ107423.1

A/chicken/CA/285/2003(H6N2) matrix protein 1 (M) and matrix protein 2 (M)
DQ107429.1

A/chicken/CA/375TR/2002(H6N2) matrix protein 1 (M) and matrix protein 2 (M)
DQ107428.1

A/chicken/CA/203/2003(H6N2) matrix protein 1 (M) and matrix protein 2 (M)
DQ107426.1

A/chicken/NY/101250-7/2001(H6N2) matrix protein 1 (M) and matrix protein 2
DQ107419.1

(M)

A/chicken/CA/625/2002(H6N2) matrix protein 1 (M) and matrix protein 2 (M)
DQ107418.1

A/Chicken/California/0139/2001(H6N2)nucleoprotein (NP)
AF474070.1

A/Chicken/California/650/2000(H6N2) nucleoprotein (NP)
AF474069.1

A/Chicken/California/9420/2001(H6N2) neuraminidase N2 (N2)
AF474048.1

A/Chicken/California/9174/2001 (H6N2) neuraminidase N2 (N2)
AF474047.1

A/Chicken/California/8892/2001(H6N2)neuraminidase N2 (N2)
AF474046.1

A/Chicken/California/6643/2001(H6N2) neuraminidase N2 (N2)
AF474045.1

A/Chicken/California/1316/2001(H6N2)neuraminidase N2 (N2)
AF474044.1

A/Chicken/California/0139/2001(H6N2) neuraminidase N2 (N2)
AR474043.1

A/Chicken/California/1002/2000(H6N2) neuraminidase N2 (N2)
AF474042.1

A/Chicken/California/650/2000(H6N2) neuraminidase N2 (N2)
AF474041.1

A/Chicken/California/465/2000(H6N2) neuraminidase N2 (N2)
AF474040.1

A/Chicken/California/431/2000(H6N2) neuraminidase N2 (N2)
AF474039.1

A/Chicken/California/6643/2001 (H6N2) hemagglutinin H6 (H6)
AF474035.1

A/Chicken/California/431/2000(H6N2) hemagglutinin H6 (H6)
AF474029.1

A/Chicken/California/9420/2001(H6N2) hemagglutinin H6 (H6)
AF474038.1

A/Chicken/California/9174/2001 (H6N2) hemagglutinin H6 (H6)
AF474037.1

A/Chicken/California/8892/2001(H6N2) hemagglutinin H6 (H6)
AF474036.1

A/Chicken/California/1316/2001 (H6N2) hemagglutinin H6 (H6)
AF474034.1

A/Chicken/California/0139/2001(H6N2) hemagglutinin H6 (H6)
AF474033.1

A/Chicken/California/1002/2000(H6N2) hemagglutinin H6 (H6)
AF474032.1

A/Chicken/California/650/2000(H6N2) hemagglutinin H6 (H6)
AF474031.1

A/Chicken/California/465/2000(H6N2) hemagglutinin H6 (H6)
AF474030.1

A/cornish cross/CA/139/2001(H6N2) matrix protein 1 (M) and matrix protein 2
DQ107424.1

(M)

A/duck/Eastern China/164/2002(H6N2) segment 6 neuraminidase (NA)
EU429762.1

A/duck/Eastern China/729/2003(H6N2) segment 6 neuraminidase (NA)
EU429760.1

A/duck/Eastern China/262/2002(H6N2) segment 6 neuraminidase (NA)
EU429743.1

A/duck/Eastern China/74/2006(H6N2) segment 6 neuraminidase (NA)
EU429741.1

A/duck/Eastern China/161/2002(H6N2) segment 6 neuraminidase (NA)
EU429740.1

A/duck/Hong Kong/960/80(H6N2)) matrix protein 1 (M) and matrix protein 2 (M)
DQ107435.1

A/duck/Hong Kong/D134/77(H6N2)) matrix protein 1 (M) and matrix protein 2
DQ107433.1

(M)

A/duck/CA/10221/2002(H6N2) matrix protein 1 (M) and matrix protein 2 (M)
DQ107421.1

A/duck/Shantou/5540/2001(H6N2) matrix protein 1 (M) and matrix protein 2 (M)
DQ107431.1

A/guinea fowl/Hong Kong/SSP99/2002(H6N2) matrix protein 1 (M) and matrix
DQ107413.1

protein 2 (M)

A/mallard/NY/016/83(H6N2) matrix protein 1 (M) and matrix protein 2 (M)
DQ107449.1

A/mallard/NY/046/83(H6N2) matrix protein 1 (M) and matrix protein 2 (M)
DQ107450.1

A/pintail/Alberta/644/81(H6N2) matrix protein 1 (M) and matrix protein 2 (M)
DQ107445.1

A/quail/Hong Kong/SF792/2000(H6N2) matrix protein 1 (M) and matrix protein 2
DQ107410.1

(M)

A/ruddy turnstone/Delaware/106/98 (H6N2) nonfunctional matrix protein
AY664439.1

A/Shorebird/Delaware/127/97(H6N2) nonfunctional matrix protein
AY664467.1

A/shorebird/Delaware/124/2001(H6N2) matrix protein 1 (M) and matrix protein 2
DQ107417.1

(M)

A/shorebird/Delaware/208/2001(H6N2) matrix protein 1 (M) and matrix protein 2
DQ107427.1

(M)

A/turkey/CA/527/2002(H6N2) matrix protein 1 (M) and matrix protein 2 (M)
DQ107420.1

A/turkey/CA/1623CT/2002(H6N2) matrix protein 1 (M) and matrix protein 2 (M)
DQ107425.1

A/turkey/MN/836/80(H6N2) matrix protein 1 (M) and matrix protein 2 (M)
DQ107440.1

A/turkey/MN/735/79(H6N2) matrix protein 1 (M) and matrix protein 2 (M)
DQ107437.1

A/chicken/Hong Kong/17/77(H6N4)) matrix protein 1 (M) and matrix protein 2
DQ107436.1

(M)

A/chicken/Hong Kong/CSW106/2001(H6N4) matrix protein 1 (M) and matrix
DQ107406.1

protein 2 (M)

A/gull/Delaware/18/2000(H6N4) matrix protein 1 (M) and matrix protein 2 (M)
DQ107415.1

A/pheasant/Hong Kong/CSW2573/2001(H6N4) matrix protein 1 (M) and matrix
DQ107411.1

protein 2 (M)

A/quail/Hong Kong/CSW106/2001(H6N4) matrix protein 1 (M) and matrix protein
DQ107430.1

2 (M)

A/Shorebird/Delaware/194/98(H6N4) nonfunctional matrix protein
AY664424.1

A/shorebird/Delaware/259/2000(H6N4) matrix protein 1 (M) and matrix protein 2
DQ107416.1

(M)

A/shearwater/Australia/1/1972(H6N5) segment 6 neuraminidase (NA)
EU429794.1

A/shearwater/Australia/1/1972(H6N5) polymerase A (PA)
L25832.1

A/pintail/Alberta/1040/79(H6N5) matrix protein 1 (M) and matrix protein 2 (M)
DQ107439.1

A/blue-winged teal/MN/993/80(H6N6)) matrix protein 1 (M) and matrix protein 2
DQ107441.1

(M)

A/duck/NY/83779/2002(H6N6) matrix protein 1 (M) and matrix protein 2 (M)
DQ107422.1

A/duck/MN/1414/81(H6N6) matrix protein 1 (M) and matrix protein 2 (M)
DQ107444.1

A/mallard/Alberta/289/82(H6N6) matrix protein 1 (M) and matrix protein 2 (M)
DQ107447.1

A/mallard duck/MN/1041/80(H6N6) matrix protein 1 (M) and matrix protein 2 (M)
DQ107442.1

A/pintail/Alberta/189/82(H6N6) matrix protein 1 (M) and matrix protein 2 (M)
DQ107446.1

A/sanderling/Delaware/1258/86(H6N6) nonfunctional matrix protein
AY664436.1

A/blue-winged teal/Alberta/368/78(H6N8)) matrix protein 1 (M) and matrix
DQ107438.1

protein 2 (M)

A/ruddy turnstone/Delaware/105/98 (H6N8) nonfunctional matrix protein
AY664428.1

A/domestic duck/NY/81(H6N8)) matrix protein (M)
DQ107443.1

A/duck/Eastern China/163/2002(H6N8) segment 6 neuraminidase (NA)
EU429786.1

A/duck/Hong Kong/D182/77(H6N9) matrix protein 1 (M) and matrix protein 2 (M)
DQ107434.1

A/chicken/Hong Kong/SF3/2001(H6) matrix protein 1 (M) and matrix protein 2
DQ107408.1

(M)

H7N*

A/African starling/England/983/79(H7N1) neuraminidase (N1)
AJ416629.1

A/Afri.Star./Eng-Q/938/79(H7N1) hemagglutinin precurosr
AF149295.1

A/chicken/Italy/1067/99(H7N1) matrix protein 1 (M1)
AJ416630.1

A/chicken/Italy/1067/99(H7N1) neuraminidase (N1)
AJ416627.1

A/chicken/Italy/4575/99 (H7N1) hemagglutinin (HA)
AJ493469.1

A/chicken/Italy/13474/99(H7N1) haemagglutinin (HA)
AJ491720.1

A/chicken/Italy/445/1999(H7N1)
AX537385.1

A/Chicken/Italy/267/00(H7N1) hemagglutinin (HA)
AJ493215.1

A/Chicken/Italy/13489/99(H7N1) hemagglutinin (HA)
AJ493214.1

A/Chicken/Italy/13307/99(H7N1) hemagglutinin (HA)
AJ493212.1

A/chicken/Singapore/1994(H7N1) M2 protein
EU014140.1

A/duck/Hong Kong/301/78(H7N1) matrix protein 1 (M) and matrix protein 2 (M)
DQ107475.1

A/Hong Kong/301/78(H7N1) hemagglutinin (HA)
AY672090.1

A/fowl plaguq virus/Rostock/34 (H7N1) NP protein
AJ243993.1

A/fowl plaguq virus/Rostock/34 (H7N1) PA protein
AJ243992.1

A/fowl plaguq virus/Rostock/34 (H7N1) PB2 protein
AJ243991.1

A/fowl plaguq virus/Rostock/34 (H7N1) PB1 protein
AJ243990.1

A/ostrich/South Africa/5352/92(H7N1) hemagglutinin precursor (HA)
U20458.1

A/rhea/North Carolina/39482/93(H7N1) hemagglutinin precursor (HA)
U20468.1

A/turkey/Italy/3775/99 (H7N1) hemagglutinin (HA)
AJ493472.1

A/turkey/Italy/4603/99 (H7N1) hemagglutinin (HA)
AJ493471.1

A/turkey/Italy/4602/99 (H7N1) hemagglutinin (HA)
AJ493470.1

A/turkey/Italy/4169/99 (H7N1) hemagglutinin (HA)
AJ493468.1

A/turkey/Italy/4073/99 (H7N1) hemagglutinin (HA)
AJ493467.1

A/turkey/Italy/3889/99 (H7N1) hemagglutinin (HA)
AJ493466.1

A/turkey/Italy/12598/99(H7N1) haemagglutinin (HA)
AJ489520.1

A/turkey/Italy/4580/99(H7N1) haemagglutinin (HA)
AJ416628.1

A/Turkey/Italy/335/00(H7N1) haemagglutinin (HA)
AJ493217.1

A/Turkey/Italy/13468/99(H7N1) haemagglutinin (HA)
AJ493216.1

A/Turkey/Italy/13467/99(H7N1) haemagglutinin (HA)
AJ493213.1

A/chicken/CT/9407/2003(H7N2) matrix protein 1 (M) and matrix protein 2 (M)
DQ107478.1

A/chicken/NY/116124/2003(H7N2) matrix protein 1 (M) and matrix protein 2 (M)
DQ107479.1

A/chicken/PA/143586/2002(H7N2) matrix protein 1 (M) and matrix protein 2 (M)
DQ107477.1

A/duck/Hong Kong/293/78(H7N2) matrix protein 1 (M) and matrix protein 2 (M)
DQ107474.1

A/duck/Hong Kong/293/78(H7N2) hemagglutinin precursor (HA)
U20461.1

A/laughing gull/Delaware/2838/87 (H7N2) nonfunctional matrix protein
AY664427.1

A/pheasant/NJ/30739-9/2000(H7N2) matrix protein 1 (M) and matrix protein 2 (M)
DQ107481.1

A/ruddy turnstone/Delaware/130/99 (H7N2) onfunctional matrix protein
AY664451.1

A/unknown/149717-12/2002(H7N2) matrix protein 1 (M) and matrix protein 2 (M)
DQ107480.1

A/unknown/NY/74211-5/2001(H7N2) matrix protein 1 (M) and matrix protein 2
DQ107476.1

(M)

A/unknown/149717-12/2002(H7N2) matrix protein 1 (M) and matrix protein 2(M)
DQ107480.1

A/unknown/NY/74211-5/2001(H7N2) matrix protein 1(M) and matrix protein 2
DQ107476.1

(M)

A/chicken/British Columbia/CN7-3/04 (H7N3) hemagglutinin (HA)
AY644402.1

A/chicken/British Columbia/CN7-3/04 (H7N3) matrix protein (M1)
AY677732.1

A/chicken/Italy/270638/02(H7N3) hemagglutinin (HA)
EU158111.1

A/gadwall/MD/3495/83(H7N3) matrix protein 1 (M) and matrix protein 2 (M)
DQ107488.1

A/mallard/Alberta/22/2001(H7N3) matrix protein 1 (M) and matrix protein 2 (M)
DQ107482.1

A/mallard/Alberta/699/81(H7N3) matrix protein 1 (M) and matrix protein 2 (M)
DQ107487.1

A/pintail/Alberta/25/2001(H7N3) matrix protein 1 (M) and matrix protein 2 (M)
DQ107483.1

A/Quail/Arkansas/16309-7/94 (H7N3) hemagglutinin protein subunit 1 precursor
AF072401.1

(HA1)

A/ruddy turnstone/New Jersey/65/85(H7N3) nonfunctional matrix protein
AY664433.1

A/turkey/England/63(H7N3) hemagglutinin precursor (HA)
U20462.1

A/Turkey/Colorado/13356/91 (H7N3) hemagglutinin protein subunit 1 precursor
AF072400.1

(HAI)

A/turkey/MN/1200/80(H7N3)) matrix protein 1 (M) and matrix protein 2 (M)
DQ107486.1

A/turkey/MN/1818/82(H7N3) matrix protein 1 (M) and matrix protein 2 (M)
DQ107489.1

A/turkey/Minnesota/1237/80(H7N3) hemagglutinin precursor (HA)
U20466.1

A/turkey/TX/1/79(H7N3) matrix protein 1 (M) and matrix protein 2 (M)
DQ107484.1

A/Turkey/Oregon/71(H7N3) hemagglutinin
AF497557.1

A/Turkey/Utah/24721-10/95 (H7N3) hemagglutinin protein subunit 1 precursor
AF072402.1

(HA1)

A/softbill/South Africa/142/92(H7N4) hemagglutinin precursor (HA)
U20464.1

A/ruddy turnstone/Delaware/2770/87 (H7N5) nonfunctional matrix protein
AY664476.1

A/chicken/Brescia/1902(H7N7) hemagglutinin 1 chain (HA)
U20471.1

A/chicken/Jena/1816/87(H7N7) hemagglutinin precursor (HA)
U20469.1

A/chicken/Leipzig/79(H7N7) hemagglutinin precursor (HA)
U20459.1

A/duck/Heinersdorf/S495/6/86(H7N7) hemagglutinin precursor (HA)
U20465.1

A/equine/Prague/1/56 (H7N7) neuraminidase
U85989.1

A/equine/Santiago/77(H7N7) nucleoprotein
AY383752.1

A/equine/Santiago/77(H7N7) neuraminidase
AY383757.1

A/equine/Santiago/77(H7N7) hemagglutinin
AY383756.1

A/FPV/Weybridge(H7N7) matrix protein
M38299.1

A/goose/Leipzig/187/7/1979(H7N7) hemagglutinin
L43914.1

A/goose/Leipzig/192/7/1979(H7N7) hemagglutinin
L43915.1

A/goose/Leipzig/137/8/1979(H7N7) hemagglutinin
L43913.1

A/ruddy turnstone/Delaware/134/99 (H7N7) nonfunctional matrix protein
AY664468.1

A/seal/Mass/1/80 H7N7 recombinant
S73497.1

A/swan/Potsdam/63/6/81(H7N7) hemagglutinin precursor (HA)
U20467.1

A/tern/Potsdam/342/6/79(H7N7) hemagglutinin precursor (HA)
U20470.1

A/pintail/Alberta/121/79(H7N8) matrix protein 1 (M) and matrix protein 2 (M)
DQ107485.1

A/Turkey/Minnesota/38429/88(H7N9) hemagglutinin
AF497551.1

H8N*

A/turkey/Ontario/6118/1968(H8N4) segment 6 neuraminidase (NA)
EU429793.1

A/Mallard Duck/Alberta/357/84(H8N4) segment 4 hemagglutinin (HA1)
AF310988.1

A/Pintail Duck/Alberta/114/79(H8N4) segment 4 hemagglutinin (HA1)
AF310987.1

A/duck/Eastern China/01/2005(H8N4) segment 6 neuraminidase (NA)
EU429780.1

A/Red Kont/Delaware/254/94(H8N4) segment 4 hemagglutinin (HA1)
AF310989.1

H9N*

A/chicken/Amioz/1527/03(H9N2) nucleoprotein
DQ116511.1

A/chicken/Amioz/1527/03(H9N2) neuraminidase
DQ116081.1

A/chicken/Amioz/1527/03(H9N2) hemagglutinin
DQ108911.1

A/chicken/Alonim/1953/104(H9N2) hemagglutinin
DQ108928.1

A/chicken/Alonim/1552/03(H9N2) hemagglutinin
DQ108914.1

A/chicken/Alonim/1552/03(H9N2) nucleoprotein
DQ116514.1

A/chicken/Alonim/1965/04(H9N2) hemagglutinin
DQ108929.1

A/Chicken/Anhui/1/98(H9N2) hemagglutinin (HA)
AF461511.1

A/Chicken/Beijing/1/95(H9N2) nonfunctional matrix protein
AF536719.1

A/Chicken/Beijing/1/95(H9N2) nucleoprotein (NP)
AF536699.1

A/Chicken/Beijing/1/95(H9N2) nonfunctional nonstructural protein
AF536729.1

A/Chicken/Beijing/1/95(H9N2) segment 6 neuraminidase (NA)
AF536709.1

A/Chicken/Beijing/2/97(H9N2) nucleoprotein (NP)
AF536700.1

A/Chicken/Beijing/2/97(H9N2) nonfunctional matrix protein
AF536720.1

A/Chicken/Beijing/2/97(H9N2) nonfunctional nonstructural protein
AF536730.1

A/Chicken/Beijing/2/97(H9N2) segment 6 neuraminidase (NA)
AF536710.1

A/Chicken/Beijing/1/97(H9N2) hemagglutinin (HA)
AF461530.1

A/Chicken/Beijing/3/99(H9N2) nonfunctional matrix protein
AF536721.1

A/Chicken/Beijing/3/99(H9N2) nucleoprotein (NP)
AF536701.1

A/Chicken/Beijing/3/99(H9N2) nonfunctional nonstructural protein
AF536731.1

A/Chicken/Beijing/3/99(H9N2) segment 6 neuraminidase (NA)
AF536711.1

A/chicken/Beit Alfa/1282/03(H9N2)hemagglutinin
DQ104476.1

A/chicken/Beit-Aran/29/05(H9N2) hemagglutinin
DQ108931.1

A/chicken/Bnei Darom/1557/03(H9N2) hemagglutinin
DQ108915.1

A/chicken/Ein Habsor/1808/04(H9N2) hemagglutinin
DQ108925.1

A/Chicken/Gangxi/2/00(H9N2) hemagglutinin (HA)
AF461514.1

A/Chicken/Gangxi/1/00(H9N2) hemagglutinin (HA)
AF461513.1

A/chicken/Gan Shomron/1465/03(H9N2) hemagglutinin
DQ104480.1

A/chicken/Gan Shomron/1292/03(H9N2) hemagglutinin
DQ104478.1

A/chicken/Gan_Shomron/1465/03(H9N2) nucleoprotein
DQ116506.1

A/chicken/Gan_Shomron/1465/03(H9N2) neuraminidase
DQ116077.1

A/chicken/Gan Shomron/1543/04(H9N2) nucleoprotein
DQ116512.1

A/chicken/Gan Shomron/1543/04(H9N2) hemagglutinin
DQ108912.1

A/Chicken/Guangdong/97(H9N2) nonfunctional matrix protein
AF536722.1

A/Chicken/Guangdong/97(H9N2) nucleoprotein (NP)
AF536702.1

A/Chicken/Guangdong/97(H9N2) nonfunctional nonstructural protein
AF536732.1

A/Chicken/Guangdong/97(H9N2) segment 6 neuraminidase (NA)
AF536712.1

A/Chicken/Gansu/1/99(H9N2) hemagglutinin (HA)
AF461512.1

A/chicken/Gujrat/India/3697/2004(H9N2) polymerase basic 2 (PB2)
DQ979865.1

A/chicken/Haryana/India/2424/2004(H9N2) polymerase basic 2 (PB2)
DQ979862.1

A/Chicken/Henan/98(H9N2) nonfunctional matrix protein
AF536726.1

A/Chicken/Henan/98(H9N2) nucleoprotein (NP)
AF536706.1

A/Chicken/Henan/98(H9N2) nonfunctional nonstructural protein
AF536736.1

A/Chicken/Henan/2/98(H9N2) hemagglutinin (HA)
AF461517.1

A/Chicken/Henan/1/99(H9N2) hemagglutinin (HA)
AF461516.1

A/Chicken/Henan/98(H9N2) segment 6 neuraminidase (NA)
AF536716.1

A/Chicken/Hebei/1/96(H9N2) nonfunctional matrix protein
AF536723.1

A/Chicken/Hebei/1/96(H9N2) segment 6 nonfunctional neuraminidase protein
AF536713.1

A/Chicken/Hebei/1/96(H9N2) nucleoprotein (NP)
AF536703.1

A/Chicken/Hebei/1/96(H9N2) nonfunctional nonstructural protein
AF536733.1

A/Chicken/Hebei/1/96(H9N2) segment 6 nonfunctional neuraminidase protein
AF536713.1

A/Chicken/Hebei/2/00(H9N2) hemagglutinin (HA)
AF461531.1

A/Chicken/Hebei/2/98(H9N2) nonfunctional matrix protein
AF536724.1

A/Chicken/Hebei/2/98(H9N2) nucleoprotein (NP)
AF536704.1

A/Chicken/Hebei/2/98(H9N2) nonfunctional nonstructural protein
AF536734.1

A/Chicken/Hebei/2/98(H9N2) segment 6 neuraminidase (NA)
AF536714.1

A/Chicken/Hebei/1/00(H9N2) hemagglutinin (HA)
AF461515.1

A/Chicken/Hebei/3/98(H9N2) nucleoprotein (NP)
AF536705.1

A/Chicken/Hebei/3/98(H9N2) nonfunctional matrix protein
AF536725.1

A/Chicken/Hebei/3/98(H9N2) nonfunctional onstructural protein
AF536735.1

A/Chicken/Hebei/3/98(H9N)) segment 6 neuraminidase (NA)
AF536715.1

A/chicken/Hong Kong/FY313/2000(H9N2) matrix protein 1 (M) and matrix
DQ107508.1

protein 2 (M)

A/chicken/Hong Kong/WF208/2001(H9N2) matrix protein 1 (M) and matrix
DQ107513.1

protein 2 (M)

A/chicken/Hong Kong/NT471/2002(H9N2) matrix protein 1 (M) and matrix
DQ107514.1

protein 2 (M)

A/chicken/Hong Kong/WF2/99(H9N2) hemagglutinin
AY206677.1

A/chicken/Iarah/1376/03(H9N2) nucleoprotein
DQ116504.1

A/chicken/Iarah/1376/03(H9N2) neuraminidase
DQ116075.1

A/chicken/Iarah/1376/03(H9N2) hemagglutinin
DQ108910.1

A/chicken/India/2793/2003(H9N2) hemagglutinin (HA)
AY336597.1

A/chicken/Iran/101/1998(H9N2) matrix protein 2 (M2)
EU477375.1

A/Chicken/Jiangsu/1/99(H9N)) hemagglutinin (HA)
AF461509.1

A/Chicken/Jiangsu/2/98(H9N2) hemagglutinin (HA)
AF461510.1

A/chicken/Kfar Monash/636/02(H9N2) hemagglutinin
DQ104464.1

A/chicken/Kalanit/1966/06.12.04(H9N2) hemagglutinin
DQ108930.1

A/chicken/Kalanit/1946/04(H9N2) hemagglutinin
DQ108927.1

A/chicken/Korea/S4/2003(H9N2) matrix protein 1 (M) and matrix protein 2 (M)
DQ107517.1

A/Chicken/Korea/MS96/96(H9N2) matrix protein 1 and 2 (M)
AF203788.1

A/Chicken/Korea/MS96/96(H9N2) neuraminidase subtype 2
AF203786.1

A/Chicken/Korea/MS96/96(H9N2) nucleoprotein
AF203787.1

A/Chicken/Liaoning/99(H9N2) nonfunctional matrix protein
AF536727.1

A/Chicken/Liaoning/1/00(H9N2) hemagglutinin (HA)
AF461518.1

A/Chicken/Liaoning/99(H9N2) nucleoprotein (NP)
AF536707.1

A/Chicken/Liaoning/99(H9N2) nonfunctional matrix protein
AF536727.1

A/Chicken/Liaoning/99(H9N2) nonfunctional onstructural protein
AF536737.1

A/Chicken/Liaoning/2/00(H9N2) hemagglutinin (HA)
AF461519.1

A/chicken/Liaoning/99(H9N2) segment 6 neuraminidase (NA)
AF536717.1

A/chicken/Mudanjiang/0823/2000(H9N2) nucleoprotein (NP)
AY496851.1

A/Chicken/Mudanjiang/0823/2000 (H9N2) nonstructural protein
AY631868.1

A/Chicken/Mudanjiang/0823/00 (H9N2) hemagglutinin (HA)
AY513715.1

A/chicken/Mudanjiang/0823/2000(H9N2) matrix protein (M1)
AY496852.1

A/chicken/Mudanjiang/0823/2000(H9N2) nucleoprotein (np)
AY496851.1

A/chicken/Maale HaHamisha/90658/00(H9N2) hemagglutinin
DQ104472.1

A/chicken/Maanit/1477/03(H9N2) hemagglutinin
DQ104483.1

A/chicken/Maanit/1291/03(H9N2) hemagglutinin
DQ104477.1

A/chicken/Maanit/1275/03(H9N2) hemagglutinin
DQ104457.1

A/chicken/Maanit/1477/03(H9N2) nucleoprotein
DQ116508.1

A/chicken/Netohah/1373/03 (H9N2) nucleoprotein
DQ116503.1

A/chicken/Netohah/1373/03 (H9N2) neuraminidase
DQ116074.1

A/chicken/Netobah/1373/03 (H9N2) hemagglutinin
DQ108909.1

A/chicken/Neve Ilan/1504/03(H9N2) hemagglutinin
DQ104484.1

A/chicken/Neve_Ilan/1504/03(H9N2) nucleoprotein
DQ116509.1

A/chicken/Neve_Ilan/1504/03(H9N2) neuraminidase
DQ116079.1

A/chicken/Orissa/India/2317/2004(H9N2) polymerase basic 2 (PB2)
DQ979861.1

A/chicken/Pardes-Hana-Carcur/1475/03(H9N2) hemagglutinin
DQ104482.1

A/chicken/Pardes-Hana-Carcur/1475/03(H9N2) neuraminidase
DQ116078.1

A/chicken/Saar/1456/03(H9N2) hemagglutinin
DQ104479.1

A/chicken/Sde_Uziahu/1747/04(H9N2) neuraminidase
DQ116068.1

A/chicken/Sede Uzziyyahu/1651/04(H9N2) hemagglutinin
DQ108923.1

A/chicken/Sde Uziahu/1747/04(H9N2)
DQ108905.1

A/chicken/Singapore/1998(H9N2) M2 protein
EU014142.1

A/chicken/Singapore/1998(H9N2) M2 protein
EU014142.1

A/Chicken/Shandong/98(H9N2) nonfunctional matrix protein
AF536728.1

A/Chicken/Shandong/1/98(H9N2) hemagglutinin (HA)
AF461520.1

A/Chicken/Shandong/98(H9N2) nucleoprotein (NP)
AF536708.1

A/Chicken/Shandong/98(H9N2) nonfunctional nonstructural protein
AF536738.1

A/Chicken/Shandong/98(H9N2) segment 6 neuraminidase (NA)
AF536718.1

A/Chicken/Shandong/2/99(H9N2) hemagglutinin (HA)
AF461521.1

A/chicken/Shandong/1/02(H9N2) neuraminidase (NA)
AY295761.1

A/Chicken/Shanghai/F/98(H9N2) hemagglutinin
AF461532.1

A/Chicken/Shanghai/1/02(H9N2) hemagglutinin
AY281745.1

A/Chicken/Shanghai/2/99(H9N2)) hemagglutinin (HA)
AF461522.1

A/Chicken/Shanghai/3/00(H9N2)) hemagglutinin (HA)
AF461523.1

A/Chicken/Shanghai/F/98(H9N2) hemagglutinin (HA)
AY743216.1

A/Chicken/Shanghai/4-2/01(H9N2) hemagglutinin (HA)
AF461525.1

A/Chicken/Shanghai/4-1/01(H9N2) hemagglutinin (HA)
AF461524.1

A/Chicken/Shanghai/4/01(H9N2) hemagglutinin (HA)
AY083841.1

A/Chicken/Shanghai/3/01(H9N2) hemagglutinin HA)
AY083840.1

A/chicken/Talmei_Elazar/1304/03(H9N2)nucleoprotein
DQ116530.1

A/chicken/Talmei_Elazar/1304/03(H9N2) neuraminidase
DQ116072.1

A/Chicken/Tianjing/2/96(H9N2) hemagglutinin
AF461527.1

A/Chicken/Tianjing/1/96(H9N2) hemagglutinin (HA)
AF461526.1

A/chicken/Tel Adashim/811/01 (H9N2) hemagglutinin
DQ104467.1

A/chicken/Tel Adashim/811/01 (H9N2) nucleoprotein
DQ116527.1

A/ck/Tel_Adashim/811/01(H9N2) neuraminidase
DQ116064.1

A/chicken/Tel Adashim/812/01 (H9N2) nucleoprotein
DQ116528.1

A/chicken/Tel Adashim/812/01 (H9N2) hemagglutinin
DQ104468.1

A/ck/Tel_Adashim/812/01(H9N2) neuraminidase
DQ116065.1

A/chicken/Tel Adashim/786/01 (H9N2) nucleoprotein
DQ116524.1

A/chicken/Tel Adashim/809/01 (H9N2) hemagglutinin
DQ104465.1

A/chicken/Tel Adashim/809/01 (H9N2) nucleoprotein
DQ116525.1

A/chicken/Tel Adashim/1469/03 (H9N2) nucleoprotein
DQ116507.1

A/chicken/Tel Adashim/1469/303(H9N2) hemagglutinin
DQ104481.1

A/chicken/Tel Adashim/1506/03 (H9N2) neuraminidase
DQ116080.1

A/chicken/Tel Adashim/1506/03(H9N2) hemagglutinin
DQ104474.1

A/chicken/Tel Adashim/1506/03 (H9N2) nucleoprotein
DQ116510.1

A/chicken/Tel Adashim/1332/03(H9N2) nucleoprotein
DQ116501.1

A/chicken/Tel Adashim/1321/03(H9N2) nucleoprotein
DQ116500.1

A/chicken/Tel Adashim/1332/03(H9N2) hemagglutinin
DQ108907.1

A/chicken/Tel Adashim/1321/03(H9N2) hemagglutinin
DQ108906.1

A/chicken/Telmond/1308/03(H9N2) nucleoprotein
DQ116499.1

A/chicken/Telmond/1308/03(H9N2) neuraminidase
DQ116073.1

A/chicken/Telmond/1308/03(H9N2) hemagglutinin
DQ108921.1

A/chicken/Tzrofa/1568/04(H9N2) nucleoprotein
DQ116519.1

A/chicken/Tzrofa/1568/04(H9N2) hemagglutinin
DQ108919.1

A/chicken/UP/India/2544/2004(H9N2) polymerase basic 2 (PB2)
DQ979864.1

A/chicken/UP/India/2543/2004(H9N2) polymerase basic 2 (PB2)
DQ979863.1

A/chicken/Wangcheng/4/2001(H9N2) nucleoprotein
AY268949.1

A/chicken/Y sodot/1362/03(H9N2) nucleoprotein
DQ116502.1

A/chicken/Y sodot/1362/03(H9N2) hemagglutinin
DQ108908.1

A/Chicken/Yunnan/2/00(H9N2) hemagglutinin (HA)
AF461529.1

A/Chicken/Yunnan/1/99(H9N2) hemagglutinin (HA)
AF461528.1

A/duck/Eastern China/01/2000(H9N2) segment 6 neuraminidase (NA)
EU429725.1

A/duck/Eastern China/48/2001(H9N2) segment 6 neuraminidase (NA)
EU429707.1

A/duck/Eastern China/66/2003(H9N2) segment 6 neuraminidase (NA)
EU429699.1

A/duck/Eastern China/80/2004(H9N2) segment 6 neuraminidase (NA)
EU429726.1

A/duck/Hong Kong/448/78(H9N2) matrix protein 1 (M) and matrix protein 2 (M)
DQ107494.1

A/duck/Hong Kong/448/78(H9N2) hemagglutinin precursor
AY206673.1

A/duck/Hong Kong/366/78(H9N2) hemagglutinin precursor
AY206674.1

A/duck/Hong Kong/784/79(H9N2)) matrix protein 1(M) and matrix protein 2 (M)
DQ107496.1

A/duck/Hong Kong/702/79(H9N2) matrix protein 1 (M) and matrix protein 2 (M)
DQ107495.1

/duck/Hong Kong/702/79(H9N2) hemagglutinin precursor
AY206672.1

A/duck/Hong Kong/610/79(H9N2) hemagglutinin precursor
AY206680.1

A/duck/Hong Kong/552/79(H9N2) hemagglutinin precursor
AY206679.1

A/duck/Hong Kong/644/79(H9N2) hemagglutinin precursor
AY206678.1

A/duck/Korea/S13/2003(H9N2) matrix protein 1 (M) and matrix protein 2 (M)
DQ107518.1

A/duck/Nanchang/4-361/2001(H9N2) matrix protein 1 (M) and matrix protein 2
DQ107511.1

(M)

A/duck/NY/83793/2002(H9N2) matrix protein 1 (M) and matrix protein 2 (M)
DQ107499.1

A/goose/MN/5733-1243/80(H9N2) matrix protein 1 (M) and matrix protein 2 (M)
DQ107492.1

A/geese/Tel Adashim/829/01(H9N2) hemagglutinin
DQ104469.1

A/geese/Tel Adasbim/830/01(H9N2 hemagglutinin
DQ104470.1

A/ostrich/Esbkol/1436/03(H9N2) neuraminidase
DQ116076.1

A/ostrich/Eshkol/1436/03(H9N2) nucleoprotein
DQ116505.1

A/pigeon/Hong Kong/WF286/2000(H9N2) matrix protein 1 (M) and matrix protein
DQ107509.1

2 (M)

A/quail/Hong Kong/YU415/2002(H9N2) matrix protein 1 (M) and matrix protein 2
DQ107516.1

(M)

A/quail/Hong Kong/SSP225/2001(H9) matrix protein 1 (M) and matrix protein 2
DQ107512.1

(M)

A/quail/Hong Kong/YU1495/2000(H9N2) matrix protein 1 (M) and matrix protein
DQ107510.1

2 (M)

A/quail/Hong Kong/A28945/88(H9N2) hemagglutinin precursor
AY206675.1

A/shorebird/Delaware/276/99 (H9N2) nonfunctional matrix protein
AY664464.1

A/shorebird/Delaware/113/2001(H9N2) matrix protein 1 (M) and matrix protein 2
DQ107505.1

(M)

A/silky chicken/Hong Kong/WF266/2002(H9N2) matrix protein 2 (M) and matrix
DQ107515.1

protein 1 (M)

A/shorebird/Delaware/77/2001(H9N2) matrix protein 1 (M) and matrix protein 2
DQ107497.1

(M)

A/guinea fowl/Hong Kong/WF10/99(H9N2) hemagglutinin precursor
AY206676.1

A/swine/Hangzhou/1/2006(H9N2) nucleocapsid protein (NP)
DQ907704.1

A/swine/Hangzhou/1/2006(H9N2)) matrix protein 1 (M1)
EF055887.1

A/swine/Hangzhou/1/2006(H9N2)) nonstructural protein 1 (NS1)
DQ823385.1

A/Sw/ShanDong/1/2003(H9N2) hemagglutinin (HA)
AY294658.1

A/turkey/CA/6889/80(H9N2) matrix protein 1 (M) and matrix protein 2 (M)
DQ107491.1

A/turkey/TX/28737/81(H9N2) matrix protein 1 (M) and matrix protein 2 (M)
DQ107493.1

A/turkey/MN/511/78(H9N2) matrix protein 1 (M) and matrix protein 2 (M)
DQ107490.1

A/turkey/Beit Herut/1267/03(H9N2) hemagglutinin
DQ104485.1

A/turkey/Beit HaLevi/1009/02(H9N2) hemagglutinin
DQ104473.1

A/turkey/Beit Herut/1265/03(H9N2) hemagglutinin
DQ104456.1

A/turkey/Beit_HaLevi/1562/03(H9N2) nucleoprotein
DQ116515.1

A/turkey/Beit_HaLevi/1566/04(H9N2) nucleoprotein
DQ116517.1

A/turkey/Beit_HaLevi/1562/03(H9N2) neuraminidase
DQ116083.1

A/turkey/Beit_HaLevi/1566/04(H9N2) neuraminidase
DQ116084.1

A/turkey/Beit_Herut/1267/03(H9N2) neuraminidase
DQ116070.1

A/turkey/Beit_Herut/1265/03(H9N2) neuraminidase
DQ116069.1

A/turkey/Beit HaLevi/1566/04(H9N2) hemagglutinin
DQ108917.1

A/turkey/Bezat/89/05(H9N2) hemagglutinin
DQ108922.1

A/turkey/Brosh/1276/03(H9N2) hemagglutinin
DQ104458.1

A/turkey/Brosh/1276/03(H9N2) neuraminidase
DQ116071.1

A/turkey/Emek Hefer/1272/03(H9N2) hemagglutinin
DQ104475.1

A/turkey/Ein Habsor/1804/04(H9N2) hemagglutinin
DQ108924.1

A/turkey/Ein Tzurim/1172/02(H9N2) hemagglutinin
DQ104451.1

A/turkey/Ein Tzurim/1738/04(H9N2) hemagglutinin
DQ108920.1

A/turkey/Ein_Tzurim/1738/04(H9N2) neuraminidase
DQ116085.1

A/turkey/Gyvat Haim Ehud/1544/03(H9N2)hemagglutinin
DQ108913.1

A/turkey/Givat Haim/810/01 (H9N2) hemagglutinin
DQ104466.1

A/turkey/Givat Haim/810/01 (H9N2) nucleoprotein
DQ116526.1

A/turkey/Givat Haim/868/02(H9N2) hemagglutinin
DQ104471.1

A/turkey/Givat Haim/622/02(H9N2) hemagglutinin
DQ104462.1

A/turkey/Givat_Haim/965/02(H9N2) nucleoprotein
DQ116498.1

A/turkey/Gyvat_Haim_Ehud/1544/03(H9N2) nucleoprotein
DQ116513.1

A/turkey/Gyvat_Haim_Ehud/1544/03(H9N2) neuraminidase
DQ116082.1

A/tk/Givat_Haim/810/25.12.01(H9N2) neuraminidase
DQ116063.1

A/turkey/Givat_Haim/622/02(H9N2)) neuraminidase
DQ116060.1

A/turkey/Givat_Haim/965/02(H9N2) neuraminidase
DQ116057.1

A/turkey/Hod_Ezyon/699/02(H9N2) neuraminidase
DQ116062.1

A/turkey/Mishmar Hasharon/619/02 (H9N2) hemagglutinin
DQ104461.1

A/turkey/Mishmar_Hasharon/619/02(H9N2) neuraminidase
DQ116059.1

A/turkey/Kfar_Vitkin/616/02(H9N2) neuraminidase
DQ116058.1

A/turkey/Kfar Vitkin/616/02 (H9N2) hemagglutinin
DQ104460.1

A/turkey/Kfar Vitkin/615/02 (H9N2)hemagglutinin
DQ104459.1

A/turkey/Kfar Vitkin/615/02 (H9N2) nucleoprotein
DQ116520.1

A/turkey/Kfar_Vitkin/616/02(H9N2)) nucleoprotein
DQ116521.1

A/turkey/Kfar Warburg/1224/03(H9N2) hemagglutinin
DQ104455.1

A/tk/Kfar_Vitkin/615/02(H9N)) neuraminidase
DQ116067.1

A/turkey/Mishmar_Hasharon/619/02(H9N2) nucleoprotein
DQ116522.1

A/turkey/Naharia/1013/02(H9N2) hemagglutinin
DQ104449.1

A/turkey/Nahalal/1547/04(H9N2) hemagglutinin
DQ108932.1

A/turkey/Neve Ilan/90710/00 (H9N2) nucleoprotein
DQ116529.1

A/tk/Neve_Ilan/90710/00(H9N2) neuraminidase
DQ116066.1

A/turkey/Qevuzat_Yavne/1242/03(H9N2) neuraminidase
DQ116086.1

A/turkey/Sapir/1199/02(H9N2) hemagglutinin
DQ104452.1

A/turkey/Shadmot Dvorah/1567/04(H9N2) nucleoprotein
DQ116518.1

A/turkey/Sbadmot Dvorah/1567/04(H9N2) hemagglutinin
DQ108918.1

A/turkey/Tzur Mosbe/1565/04(H9N2) nucleoprotein
DQ116516.1

A/turkey/Tzur Moshe/1565/04(H9N2) hemagglutinin
DQ108916.1

A/turkey/Yedidia/625/02 (H9N2) hemagglutinin
DQ104463.1

A/turkey/Yedidia/625/02 (H9N2) nucleoprotein
DQ116523.1

A/turkey/Yedidia/625/02 (H9N2) neuraminidase
DQ116061.1

A/turkey/Yedidia/911/02(H9N2) hemagglutinin
DQ104448.1

A/turkey/Avigdor/1215/03(H9N2) hemagglutinin
DQ104454.1

A/turkey/Avigdor/1209/03(H9N2) hemagglutinin
DQ104453.1

A/turkey/Avichail/1075/02(H9N2) hemagglutinin
DQ104450.1

A/turkey/Avigdor/1920/04(H9N2) hemagglutinin
DQ108926.1

A/pintail/Alberta/49/2003(H9N5) matrix protein 1 (M) and matrix protein 2 (M)
DQ107498.1

A/red knot/Delaware/2552/87 (H9N5) nonfunctional matrix protein
AY664472.1

A/duck/Hong Kong/147/77(H9N6) hemagglutinin precursor
AY206671.1

A/shorebird/Delaware/270/2001(H9N7) matrix protein 1 (M) and matrix protein 2
DQ107504.1

(M)

A/shorebird/Delaware/277/2000(H9N7) matrix protein 1 (M) and matrix protein 2
DQ107507.1

(M)

A/shorebird/Delaware/275/2001(H9N7)) matrix protein 2 (M) and matrix protein 1
DQ107506.1

(M)

A/ruddy turnstone/Delaware/116/98 (H9N8) nonfunctional matrix protein
AY664435.1

A/shorebird/Delaware/141/2002(H9N9) matrix protein 1 (M) and matrix protein 2
DQ107503.1

(M)

A/ruddy turnstone/Delaware/103/2002(H9N9) matrix protein 1 (M) and matrix
DQ107502.1

protein 2 (M)

A/shorebird/Delaware/29/2002(H9N9) matrix protein 1 (M) and matrix protein 2
DQ107501.1

(M)

A/shorebird/Delaware/18/2002(H9N9) matrix protein 1 (M) and matrix protein 2
DQ107500.1

(M)

A/ruddy turnstone/Delaware/259/98 (H9N9) nonfunctional matrix protein
AY664469.1

H10N*

A/duck/Eastern China/527/2003(H10N3) segment 6 neuraminidase (NA)
EU429716.1

A/duck/Eastern China/495/2003(H10N3) segment 6 neuraminidase (NA)
EU429715.1

A/duck/Eastern China/372/2003(H10N3) segment 6 neuraminidase (NA)
EU429714.1

A/duck/Eastern China/488/2003(H10N3) segment 6 neuraminidase (NA)
EU429712.1

A/duck/Eastern China/453/2002(H10N3) segment 6 neuraminidase (NA)
EU429711.1

A/duck/Eastern China/412/2003(H10N3) segment 6 neuraminidase (NA)
EU429710.1

A/duck/Eastern China/404/2003(H10N3) segment 6 neuraminidase (NA)
EU429709.1

A/duck/Eastern China/397/2003(H10N3) segment 6 neuraminidase (NA)
EU429708.1

A/duck/Eastern China/502/2003(H10N3) segment 6 neuraminidase (NA)
EU429705.1

A/duck/Eastern China/395/2003(H10N3) segment 6 neuraminidase (NA)
EU429704.1

A/duck/Eastern China/356/2003(H10N3) segment 6 neuraminidase (NA)
EU429703.1

A/duck/Eastern China/368/2003(H10N3) segment 6 neuraminidase (NA)
EU429702.1

A/chicken/Singapore/1993(H10N5) M2 protein
EU014145.1

A/red knot/Delaware/2561/87 (H10N5) nonfunctional matrix protein
AY664441.1

A/chicken/Germany/N/1949(H10N7) segment 6 neuraminidase (NA)
EU429796.1

A/ruddy turnstone/Delaware/2764/87 (H10N7) nonfunctional matrix protein
AY664462.1

A/mallard/Alberta/71/98 (H10N7) nonfunctional matrix protein
AY664485.1

A/mallard/Alberta/90/97 (H10N7) nonfunctional matrix protein
AY664446.1

A/mallard/Alberta/110/99(H10N7) nonfunctional matrix protein
AY664481.1

A/mallard/Alberta/297/77 (H10N7) nonfunctional matrix protein
AY664430.1

A/mallard/Alberta/223/98 (H10N8) nonfunctional matrix protein
AY664486.1

H11N*

A/ruddy turnstone/New Jersey/51/85 (H11N1) nonfunctional matrix protein
AY664479.1

A/duck/Nanchang/1749/1992(H11N2) nucleoprotein (NP)
U49094.1

A/duck/Hong Kong/62/1976(H11N2) polymerase (PB1)
U48280.1

A/duck/Yangzhou/906/2002(H11N2) hemagglutinin
DQ080993.1

A/shorebird/Delaware/86/99 (H11N2) nonfunctional matrix protein
AY664463.1

A/ruddy turnstone/Delaware Bay/2762/1987(H11N2)polymerase PB2 (PB2)
CY126279.1

A/ruddy turnstone/Delaware/2762/87 (H11N2) nonfunctional matrix protein
AY664459.1

A/ruddy turnstone/Delaware Bay/2762/1987(H11N2) polymerase PB1 (PB1) and
CY126278.1

PB1-F2 protein (PB1-F2)

A/ruddy turnstone/Delaware/2589/87 (H11N4) nonfunctional matrix protein
AY664478.1

A/duck/England/1/1956(H11N6) segment 6 neuraminidase (NA)
EU429795.1

A/mallard/Alberta/125/99 (H11N6) nonfunctional matrix protein
AY664483.1

A/duck/Memphis/546/1974(H11N9) segment 6 neuraminidase (NA)
EU429798.1

A/mallard/Alberta/122/99 (H11N9) nonfunctional matrix protein
AY664444.1

H12N*

A/Mallard Duck/Alberta/342/83(H12N1) segment 4 hemagglutinin (HA1)
AF310991.1

A/ruddy turnstone/Delaware/67/98(H12N4) nonfunctional matrix protein
AY664470.1

A/Ruddy Turnstone/Delaware/67/98(H12N4) segment 4 hemagglutinin (HA1)
AF310990.1

A/mallard/Alberta/52/97 (H12N5) nonfunctional matrix protein
AY664448.1

A/mallard/Alberta/223/77 (H12N5) nonfunctional matrix protein
AY664431.1

A/Laughing Gull/New Jersey/171/92(H12N5) segment 4 hemagglutinin (HA1)
AF310992.1

A/ruddy turnstone/Delaware/265/98 (H12N8) nonfunctional matrix protein
AY664438.1

H13N*

A/herring gull/New Jersey/782/86 (H13N2) nonfunctional matrix protein
AY664475.1

A/shorebird/Delaware/224/97 (H13N6) nonfunctional matrix protein
AY664421.1

Other

A/PR/8/34 (H1N1) x A/England/939/69 (H3N2) PB1 protein
AJ564806.1

A/PR/8/34 (H1N1) x A/England/939/69 (H3N2)PB2 protein
AJ564804.1

A/duck/Czechslovakia/56(H4N6) x A/USSR/90/77(H1N1)) neuraminidase (NA)
EU643639.1

A/duck/Czechslovakia/56(H4N6) x A/USSR/90/77(H1N1)) neuraminidase (NA)
EU643638.1

A/duck/Ukraine/63(H3N8) x A/USSR/90/77(H1N1)) neuraminidase (NA)
EU643637.1

A/duck/Ukraine/63(H3N8) x A/USSR/90/77(H1N1)) neuraminidase (NA)
EU643636.1

RCB1-XXI: A/USSR/90/77(H1N1)xA/Duck/Czechoslov 56 (H4N6) segment 4
AF290438.1

hemagglutinin

RCB1: A/USSR/90/77(H1N1)xA/Duck/Czechoslov 56 (H4N6) hemagglutinin
AF290437.1

PX14-XIII (A/USSR/90/77(H1N1)xA/Pintail Duck/Primorie/695/76(H2N3))
AF290442.1

segment 4 hemagglutinin

PX14(A/USSR/90/77(H1N1)xA/Pintail Duck/Primorie/695/76(H2N3)) segment 4
AF290441.1

hemagglutinin

PX8-XIII(A/USSR/90/77(H1N1)xA/Pintail Duck/Primorie/695/76(H2N3))

segment 4 hemagglutinin

PX8(A/USSR/90/77(H1N1)xA/Pintail Duck/Primorie/695/76(H2N3)) segment 4
AF290439.1

hemagglutinin

A/swine/Schleswig-Holstein/1/93 hemagglutinin (HA)
U72669.1

A/swine/England/283902/93 hemagglutinin (HA)
U72668.1

A/swine/England/195852/92 hemagglutinin (HA)
U72667.1

A/swine/England/117316/86 hemagglutinin (HA)
U72666.1

A/turkey/Germany/2482/90) hemagglutinin (HA)
U96766.1

TABLE 11

Influenza B Antigens

GenBank Access

Strain/Protein
No.

B/Daeku/47/97 hemagglutinin
AF521237.1

B/Daeku/45/97 hemagglutinin
AF521236.1

B/Daeku/10/97 hemagglutinin
AF521221.1

B/Daeku/9/97 hemagglutinin
AF521220.1

B/Gyeonggi/592/2005 neuraminidase
DQ231543.1

B/Gyeonggi/592/2005 hemagglutinin
DQ231538.1

B/Hong Kong/5/72 neuraminidase
AF305220.1

B/Hong Kong/5/72 hemagglutinin
AF305219.1

B/Hong Kong/157/99 hemagglutinin
AF387503.1

B/Hong Kong/157/99 hemagglutinin
AF387502.1

B/Hong Kong/156/99 hemagglutinin
AF387501.1

B/Hong Kong/156/99 hemagglutinin
AF387500.1

B/Hong Kong/147/99 hemagglutinin
AF387499.1

B/Hong Kong/147/99 hemagglutinin
AF387498.1

B/Hong Kong/110/99 hemagglutinin
AF387497.1

B/Hong Kong/110/99 hemagglutinin
AF387496.1

B/Incheon/297/2005 hemagglutinin
DQ231539.1

B/Incheon/297/2005 neuraminidase
DQ231542.1

B/Lee/40 polymerase protein (PB1)
D00004.1

B/Michigan/22572/99 hemagglutinin
AY129961.1

B/Michigan/22723/99 hemagglutinin (HA)
AY112992.1

B/Michigan/22631/99 hemagglutinin (HA)
AY112991.1

B/Michigan/22587/99 hemagglutinin (HA)
AY112990.1

B/New York/20139/99 hemagglutinin
AY129960.1

B/Panama/45/90 nucleoprotein
AF005739.1

B/Panama/45/90 polymerase (PA)
AF005738.1

B/Panama/45/90 polymerase (PB2)
AF005737.1

B/Panama/45/90 polymerase (PB1)
AF005736.1

B/Pusan/250/99 hemagglutinin
AF521218.1

B/Pusan/255/99 hemagglutinin
AF521226.1

B/Pusan/270/99 hemagglutinin
AF521219.1

B/Pusan/285/99 hemagglutinin
AF521217.1

B/Riyadh/01/2007 segment 8 nuclear export protein
GU135839.1

(NEP) and non structural protein 1 (NS1)

B/Seoul/6/88 hemagglutinin
AF521238.1

B/Seoul/12/88 hemagglutinin
AF521239.1

B/Seoul/1/89 hemagglutinin
AF521230.1

B/Seoul/37/91 hemagglutinin
AF521229.1

B/Seoul/38/91 hemagglutinin
AF521227.1

B/Seoul/40/91 hemagglutinin
AF521235.1

B/Seoul/41/91 hemagglutinin
AF521228.1

B/Seoul/13/95 hemagglutinin
AF521225.1

B/Seoul/12/95 hemagglutinin
AF521223.1

B/Seoul/17/95 hemagglutinin
AF521222.1

B/Seoul/21/95 hemagglutinin
AF521224.1

B/Seoul/16/97 hemagglutinin
AF521233.1

B/Seoul/19/97 hemagglutinin
AF521231.1

B/Scoul/28/97 hemagglutinin
AF521234.1

B/Seoul/31/97 hemagglutinin
AF521232.1

B/Seoul/232/2004 neuraminidase
DQ231541.1

B/Seoul/1163/2004 neuraminidase
DQ231540.1

B/Seoul/1163/2004 hemagglutinin
DQ231537.1

B/Sichuan/379/99 hemagglutinin (HA)
AF319590.1

B/Sichuan/38/2000 hemagglutinin (HA)
AF319589.1

B/South Carolina/25723/99 hemagglutinin
AY129962.1

B/Switzerland/4291/97 hemagglutinin
AF387505.1

B/Switzerland/4291/97 hemagglutinin
AF387504.1

B/Taiwan/21706/97 nonstructural protein 1 (NS1)
AF492479.1

B/Taiwan/21706/97 hemagglutinin (HA)
AF026162.1

B/Taiwan/3143/97 nonstructural protein 1 (NS1)
AF492478.1

B/Taiwan/3143/97 haemagglutinin (HA)
AF026161.1

B/Taiwan/2026/99 nonstructural protein 1 (NS1)
AF492481.1

B/Taiwan/2026/99 hemagglutinin
AY604741.1

B/Taiwan/2027/99 nonstructural protein 1 (NS1)
AF492480.1

B/Taiwan/2027/99 hemagglutinin
AY604742.1

B/Taiwan/1243/99 nonstructural protein NS1(NS1)
AF380504.1

B/Taiwan/1243/99 hemagglutinin
AY604740.1

B/Taiwan/2195/99 hemagglutinin
AY604743.1

B/Taiwan/2195/99 nonstructural protein 1 (NS1)
AF492482.1

B/Taiwan/1293/2000 nonstructural protein NS1(NS1)
AF380509.1

B/Taiwan/1293/00 hemagglutinin
AY604746.1

B/Taiwan/1293/2000 hemagglutinin (HA)
AF492477.1

B/Taiwan/1265/2000 nonstructural protein NS1 (NS1)
AF380508.1

B/Taiwan/1265/00 hemagglutinin
AY604745.1

B/Taiwan/4184/2000 nonstructural protein NS1 (NS1)
AF380507.1

B/Taiwan/4184/00 hemagglutinin (HA)
AY604750.1

B/Taiwan/31511/2000 nonstructural protein NS1 (NS1)
AF380505.1

B/Taiwan/31511/00 hemagglutinin (HA)
AY604748.1

B/Taiwan/12192/2000 hemagglutinin
AY604747.1

B/Taiwan/41010/00 hemagglutinin (HA)
AY604749.1

B/Taiwan/41010/2000 nonstructural protein NS1 (NS1)
AF380506.1

B/Taiwan/0409/00 hemagglutinin (HA)
AY604744.1

B/Taiwan/202/2001 nonstructural protein 1 (NS1)
AF380512.1

B/Taiwan/202/2001 hemagglutinin (HA)
AF366076.1

B/Taiwan/11515/2001 nonstructural protein 1 (NS1)
AF380511.1

B/Taiwan/11515/01 hemagglutinin
AY604754.1

B/Taiwan/11515/2001 hemagglutinin (HA)
AF366075.1

B/Taiwan/1103/2001 nonstructural protein NS1 (NS1)
AF380510.1

B/Taiwan/1103/01 hemagglutinin
AY604755.1

B/Taiwan/114/2001 hemagglutinin (HA), HA-4 allele
AF492476.1

B/Taiwan/2805/2001 hemagglutinin (HA)
AF400581.1

B/Taiwan/2805/01 hemagglutinin (HA)
AY604752.1

B/Taiwan/0114/01 hemagglutinin (HA)
AY604753.1

B/Taiwan/0202/01 hemagglutinin (HA)
AY604751.1

B/Taiwan/4119/02 hemagglutinin (HA)
AY604778.1

B/Taiwan/4602/02 hemagglutinin (HA)
AY604777.1

B/Taiwan/1950/02 hemagglutinin (HA)
AY604776.1

B/Taiwan/1949/02 hemagglutinin (HA)
AY604775.1

B/Taiwan/1584/02 hemagglutinin (HA)
AY604774.1

B/Taiwan/1561/02 hemagglutinin (HA)
AY604773.1

B/Taiwan/1536/02 hemagglutinin (HA)
AY604772.1

B/Taiwan/1534/02 hemagglutinin (HA)
AY604771.1

B/Taiwan/1503/02 hemagglutinin (HA)
AY604770.1

B/Taiwan/1502/02 hemagglutinin (HA)
AY604769.1

B/Taiwan/1013/02 hemagglutinin (HA)
AY604768.1

B/Taiwan/0993/02 hemagglutinin (HA)
AY604766.1

B/Taiwan/0932/02 hemagglutinin (HA)
AY604765.1

B/Taiwan/0927/02 hemagglutinin (HA)
AY604764.1

B/Taiwan/0880/02 hemagglutinin (HA)
AY604763.1

B/Taiwan/0874/02 hemagglutinin (HA)
AY604762.1

B/Taiwan/0730/02 hemagglutinin (HA)
AY604761.1

B/Taiwan/0722/02 hemagglutinin (HA)
AY604760.1

B/Taiwan/0702/02 hemagglutinin (HA)
AY604759.1

B/Taiwan/0654/02 hemagglutinin (HA)
AY604758.1

B/Taiwan/0600/02 hemagglutinin (HA)
AY604757.1

B/Taiwan/0409/02 hemagglutinin (HA)
AY604756.1

B/Taiwan/0879/02 nonfunctional hemagglutinin
AY604767.1

B/Taiwan/3532/03 hemagglutinin (HA)
AY604794.1

B/Taiwan/2551/03 hemagglutinin (HA)
AY604793.1

B/Taiwan/1618/03 hemagglutinin (HA)
AY604792.1

B/Taiwan/1574/03 hemagglutinin (HA)
AY604791.1

B/Taiwan/1013/03 hemagglutinin (HA)
AY604790.1

B/Taiwan/0833/03 hemagglutinin (HA)
AY604789.1

B/Taiwan/0735/03 hemagglutinin (HA)
AY604788.1

B/Taiwan/0699/03 hemagglutinin (HA)
AY604787.1

B/Taiwan/0684/03 hemagglutinin (HA)
AY604786.1

B/Taiwan/0616/03 hemagglutinin (HA)
AY604785.1

B/Taiwan/0615/03 hemagglutinin (HA)
AY604784.1

B/Taiwan/0610/03 hemagglutinin (HA)
AY604783.1

B/Taiwan/0576/03 hemagglutinin (HA)
AY604782.1

B/Taiwan/0569/03 hemagglutinin (HA)
AY604781.1

B/Taiwan/0562/03 hemagglutinin (HA)
AY604780.1

B/Taiwan/0002/03 hemagglutinin (HA)
AY604779.1

B/Taiwan/773/2004 hemagglutinin (HA)
EU068195.1

B/Taiwan/187/2004 hemagglutinin (HA)
EU068194.1

B/Taiwan/3892/2004 hemagglutinin (HA)
EU068193.1

B/Taiwan/562/2004 hemagglutinin (HA)
EU068191.1

B/Taiwan/234/2004 hemagglutinin (HA)
EU068188.1

B/Taiwan/4897/2004 hemagglutinin (HA)
EU068186.1

B/Taiwan/8579/2004 hemagglutinin (HA)
EU068184.1

B/Taiwan/184/2004 hemagglutinin (HA)
EU068183.1

B/Taiwan/647/2005 hemagglutinin (HA)
EU068196.1

B/Taiwan/877/2005 hemagglutinin (HA)
EU068198.1

B/Taiwan/521/2005 hemagglutinin (HA)
EU068189.1

B/Taiwan/1064/2005 hemagglutinin (HA)
EU068192.1

B/Taiwan/3722/2005 hemagglutinin (HA)
EU068197.1

B/Taiwan/5049/2005 hemagglutinin (HA)
EU068190.1

B/Taiwan/5011/2005 hemagglutinin (HA)
EU068187.1

B/Taiwan/4659/2005 hemagglutinin (HA)
EU068185.1

B/Taiwan/25/2005 hemagglutinin (HA)
EU068182.1

B/Taiwan/1037/2005 hemagglutinin (HA)
EU068181.1

B/Taiwan/62/2005 hemagglutinin (HA)
EU068180.1

B/Taiwan/591/2005 hemagglutinin (HA)
EU068179.1

B/Taiwan/649/2005 hemagglutinin (HA)
EU068178.1

B/Taiwan/4554/2005 hemagglutinin (HA)
EU068177.1

B/Taiwan/987/2005 hemagglutinin (HA)
EU068176.1

B/Taiwan/2607/2006 hemagglutinin (HA)
EU068175.1

B/Vienna/1/99 hemagglutinin
AF387495.1

B/Vienna/1/99 hemagglutinin
AF387494.1

B/Vienna/1/99 hemagglutinin
AF387493.1

B/Vienna/1/99 hemagglutinin
AF387492.1

TABLE 12

Influenza C Antigens

GenBank

Strain/Protein
Access No.

C/JHB/1/66) hemagglutinin-esterase-fusion
AY880247.1

protein (HEF) mRNA, complete cds.

STRAIN C/ANN ARBOR/1/50) persistent variant
AF102027.1

segment 7 non-structural protein 1 (NS1) mRNA, complete cds

(STRAIN C/ANN ARBOR/1/50) wild type segment 7 non-structural protein 1
AF102026.1

(NS1) mRNA, complete cds

(C/JHB/1/66) hemagglutinin-esterase-fusion protein (HEF) mRNA, complete cds
AY880247.1

(STRAIN C/BERLIN/1/85) mRNA for basic polymerase 2 precursor
X55992.1

TABLE 13

H7 Hemagglutinin Amino Acid Sequences

SEQ
Accession No/

ID NO
Strain/Protein
Amino Acid Sequence

1
AAM19228
ACVLVEAKGDKICLGHHAVVNGTKVNTLTEKGIEVVNAT

A/turkey/
ETVETANIGKICTQGKRPTDLGQCGLLGTLIGPPQCDQFLE

Minnesota/
FESDLIIERREGNDVCYPGKFTNEESLRQILRGSGGIDKESM

38429/1988
GFTYSGIITNGATSACRRSGSSFYAEMKWLLSNSDNAAFP

1988// HA
QMTKSYRNPRNKPALIVWGIHHSGSTTEQTKLYGSGNKLI

20335017
TVESSKYQQSFTPSPGARPQVNGESGRIDFHWMLLDPNDT

VTFTFNGAFIAPDRASFFKGESLGVQSDVPLDSSCGGDCFH

SGGTIVSSLPFQNINPRTVGKCPRYVKQPSLLLATGMRNVP

ENPKTRGLFGAIAGFIEKDGGSHYG

2
AAY46211
MNTQILVFALVAIPINADKICLGHHAVSNGTKVNTLTERG

A/mallard/
VEVVNATETVERTNVPRICSRGKRTVDLGQCGLLGTITGP

Sweden/91/2002
PQCDQFLEFSADLIIERREGSDVCYPGKFVNEEALRQILRES

2002// HA
GGIDKETMGFTYSGIRTNGAPSACRRSGSSFYAEMKWLLS

66394828
NTDNAAFPQMTKSYKNTRNDPALIIWGIHHSGSTTEQTKL

YGSGNKLITVGSSNYQQSFVPSPGARPQVNGQSGRIDFHW

LILNPNDTVTFSFNGAFIAPDRASFLRGKSMGIQSGVQIDA

NCEGDCYHSGGTIISNLPFQNINSRAVGKCPRYVKQESLLL

ATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGWYGFRH

QNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELID

NEFTEVEKQIGNVINWTRDSMTEVWSYNAELLVAMENQH

TIDLADSEMNKLYERVRRQLRENAEEDGTGCFEIFHKCDD

DCMASIRNNTYDHSKYREEAMQNRIQIDPVKLSSGYKDVI

LWFSFGASCFILLAIAMGLVFMCVKNGNMRCTICI

3
ABI84694
MNTQILVFIACVLVEAKGDKICLGHHAVVNGTKVNTLTE

A/turkey/
KGIEVVNATETVETANIGKICTQGKRPTDLGQCGLLGTLIG

Minnesota/
PPQCDQFLEFESDLIIERREGNDVCYPGKFTNEESLRQILRG

1/1988
SGGIDKESMGFTYSGIRTNGATSACRRSGSSFYAEMKWLL

1988/07/13 HA
SNSDNAAFPQMTKSYRNPRNKPALIVWGIHHSGSTTEQTK

115278573
LYGSGNKLITVGSSKYQQSFTPSPGARPQVNGQSGRIDFH

WMLLDPNDTVTFTFNGAFIAPDRASFFKGESLGVQSDVPL

DSSCGGDCFHSGGTIVSSLPFQNINPRTVGKCPRYVKQPSL

LLATGMRNVPENPKTRGLFGAIAGFIENGWEGLIDGWYGF

KHQNAQGEGTAADYKSTQSAIDQITGKLNRLIDKTNQQFE

LIDNEFSEIEQQIGNVINWTRDSMTEVWSYNAELLVAMEN

QHTIDLADSEMNKLYERVRRQLRENAEEDGTGCFEIFHKC

DDQCMESIRNNTYDHAQYRAESLQNRIQIDPVKLSSGYKD

IILWFSFGASCFLLLAIAMGLVFICIKNGNMRCTICI

4
ABS89409
MNTQILALIACMLIGAKGDKICLGHHAVANGTKVNTLTER

A/blue-winged
GIEVVNATETVETANIKKICTQGKRPTDLGQCGLLGTLIGP

teal/Ohio/566/
PQCDQFLEFDTDLIIERREGTDVCYPGKFTNEESLRQILRGS

2006 2006// HA
GGIDKESMGFTYSGIRTNGATSACRRSGSSFYAEMKWLLS

155016324
NSDNAAFPQMTKSYRNPRNKPALIIWGVHHSGSATEQTKL

YGSGNKLITVGSSKYQQSFTPSPGARPQVNGQSGRIDFHW

LLLDPNDTVTFTFNGAFIAPDRASFFRGESLGVQSDVPLDS

GCEGDCFHSGGTIVSSLPFQNINPRTVGKCPRYVKQTSLLL

ATGMRNVPENPKTRGLFGAIAGFIENGWEGLIDGWYGFR

HQNAQGEGTAADYKSTQSAIDQITGKLNRLIDKTNQQFEL

IDNEFSEIEQQIGNVINWTRDSMTEVWSYNAELLVAMENQ

HTIDLADSEMNKLYERVRKQLRENAEEDGTGCFEIFHKCD

DQCMESIRNNTYDHTQYRTESLQNRIQIDPVRLSSGYKDII

LWFSFGASCFLLLAIAMGLVFICIKNGNMRCTICI

5
ACD03594
MNTQILAFIACMLVGVRGDKICLGHHAVANGTKVNTLTE

A/ruddy
KGIEVVNATETVESANIKKICTQGKRPTDLGQCGLLGTLIG

turnstone/DE/
PPQCDQFLEFDSDLIIERREGTDVCYPGKFTNEESLRQILRG

1538/2000 2000//
SGGIDKESMGFTYSGIRTNGATSACRRLGSSFYAEMKWLL

HA 187384848
SNSDNAAFPQMTKSYRNPRNKPALIIWGVHHSGSANEQT

KLYGSGNKLITVGSSKYQQSFTPSPGARPQVNGQSGRIDF

HWLLLDPNDTVTFTFNGAFIAPDRASFFRGESLGIQSDVPL

DSSCGGDCFHSGGTIVSSLPFQNINPRTVGKCPRYVKQTSL

LLATGMRNVPENPKTRGLFGAIAGFIENGWEGLIDGWYGF

RHQNAQGEGTAADYKSTQSAIDQITGKLNRLIDKTNQQFE

LMDNEFNEIEQQIGNVINWTRDSMTEVWSYNAELLVAME

NQHTIDLADSEMNKLYERVRKQLRENAEEDGTGCFEIFHK

CDDQCMESIRNNTYDHTQYRTESLQNRIQIDPVKLSSGYK

DIILWFSFGASCFLLLAIAMGLIFICIKNGNMRCTICI

6
BAH22785
MNTQILVEALVAIPTNADKICLGHHAVSNGTKVNTLTER

A/duck/Mongolia/
GVEVVNATETVERTNIPRICSKGKRTVDLGQCGLLGTITGP

119/2008
PQCDQFLEFSADLIIERREGSDVCYPGKFVNEEALRQILRES

2008// HA
GGIGKETMGFTYSGIRTNGATSACRRSGSSFYAEMKWLLS

223717820
NTDNAAFPQMTKSYKNTRKDPALIIWGIHHSGSTTEQTKL

YGSGNKLITVGSSNYQQSFVPSPGARPQVNGQSGRIDFHW

LMLNPNDTVTFSFNGAFIAPDRASFLRGKSMGIQSGVQVD

ANCEGDCYHNGGTIISNLPFQNINSRTVGKCPRYVKQESLL

LATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGWYGFR

HQNAQGEGTAADYKSTQSAIDQITGKLNRLIERTNQQFELI

DNEFTEVEKQIGNVINWTRDSMTEVWSYNAELLVAMENQ

HTIDLADSEMNKLYERVKRQLRENAEEDGTGCFEIFHKCD

DDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLSNGYKD

VILWFSFGASCFILLAIAMGLVFICVKNGNMRCTICI

7
CAY39406
MNTQILVFALVAIIPTNADKICLGHHAVSNGTKVNTLTER

A/Anas
GVEVVNATETVERTNVPRICSKGKRTVDLGQCGLLGTITG

crecca/Spain/
PPQCDQFLEFSADLIIERREGSDVCYPGKFVNEEALRQILRE

1460/2008
SGGIDKETMGFTYSGIRTNGATSACRRSGSSFYAEMKWLL

2008/01/26 HA
SNTDNAAFPQMTKSYKNTRKDPALIIWGIHHSGSTTEQTK

254674376
LYGSGSKLITVGSSNYQQSFVPSPGARPQVNGQSGRIDFH

WLMLNPNDTVTFSFNGAFIAPDRASFLRGKSMGIQSGVQV

DANCEGDCYHSGGTIISNLPFQNINSRAVGKCPRYVKQES

LMLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGWY

GFRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQ

FELIDNEFTEVEKQIGNVINWTRDSITEVWSYNAELLVAM

ENQHTIDLADSEMNKLYERVKRQLRENAEEDGTGCFEIFH

KCDDDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLSSG

YKDVILWFSFGASCFILLAIAMGLVFICVKNGNMRCTICI

8
ACX53683
MNIQILVFALVAHIPTNADKICLGHHAVSNGTKVNTLTERG

A/goose/Czech
VEVVNATETVERTNVPRICSKGKRTVDLGQCGLLGTITGP

Republic/1848-
PQCDQFLEFSADLIIERRGGSDVCYPGKFVNEEALRQILRE

K9/2009
SGGIDKETMGFTYSGIRTNGATSACRRSGSSFYAEMKWLL

2009/02/04 HA
SNTDNAAFPQMTKSYKNTRKDPALIIWGIHHSGSTTEQTK

260907763
LYGSGSKLITVGSSNYQQSFVPSPGARPQVNGQSGRIDFH

WLMLNPNDTVTFSFNGAFIAPDRASFLKGKSMGIQSGVQV

DANCEGDCYHSGGTIISNLPFQNINSRAVGKCPRYVKQES

LMLATGMKNVPELPKGRGLFGAIAGFIENGWEGLIDGWY

GFRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQ

FELIDNEFTEVEKQIGNVINWTRDSMTEVWSYNAELLVA

MENQHTIDLADSEMNKLYERVKRQLRENAEEDGTGCFEIF

HKCDDDCMASIRNNTYDHSKYREEAMQNRIQINPVKLSS

GYKDVILWFSFGASCFILLAIAMGLVFICVKNGNMRCTICI

9
ACZ48625
MNTQILVFIACVLVEAKGDKICLGHHAVVNGTKVNTLTE

A/turkey/
KGIEVVNATETVETANIGKICTQGKRPTDLGQCGLLGTLIG

Minnesota/
PPQCDQFLEFESDLIIERREGNDVCYPGKFTNEESLRQILRG

38429/1988
SGGIDKESMGFTYSGIRTNGATSACRRSGSSFYAEMKWLL

1988// HA
SNSDNAAFPQMTKSYRNPRNKPALIVWGIHHSGSTTEQTK

269826341
LYGSGNKLITVGSSKYQQSFTPSPGARPQVNGQSGRIDFH

WMLLDPNDTVTFTFNGAFIAPDRASFFKGESLGVQSDVPL

DSSCGGDCFHSGGTIVSSLPFQNINPRTVGKCPRYVKQPSL

LLATGMRNVPENPKTRGLFGAIAGFIENGWEGLIDGWYGF

KHQNAQGEGTAADYKSTQSAIDQITGKLNRLIDKTNQQFE

L

10
ADC29485
STQSAIDQITGKLNRLIEKTNQQFELIDNEFTEVEKQIGNVI

A/mallard/Spain/
NWTRDSMTEVWSYNAELLVAMENQHTIDLADSEMNKLY

08.00991.3/2005
ERVKRQLRENAEEDGTGCFEIFHKCDDDCMASIRNNTYD

2005/11/ HA
HSKYREEAMQNRIQIDPVKLSSGYKDVILWFSFGASCFILL

284927336

11
ADK71137
MNTQILALIACMLIGAKGDKICLGHHAVANGTKVNTLTER

A/blue-winged
GIEVVNATETVETANIKKICTQGKRPTDLGQCGLLGTLIGP

teal/Guatemala/
PQCDQFLEFDADLIIERREGTDVCYPGKFTNEESLRQILRG

CIP049-01/2008
SGGIDKESMGFTYSGIRTNGATSACRRSGSSSYAEMKWLL

2008/02/07 HA
SNSDNAAFPQMTKSYRNPRNKPALIIWGVHHSGSATEQTK

301333785
LYGSGNKLITVGSSKYQQSFTPSPGTRPQVNGQSGRIDFH

WLLLDPNDTVTFTFNGAFIAPDRASFLRGKSLGIQSDVPLD

SGCEGDCFHSGGTIVSSLPFQNINPRTVGKCPRYVKQTSLL

LATGMRNVPENPKTRGLFGAIAGFIENGWEGLIDGWYGF

RHQNAQGEGTAADYKSTQSAIDQITGKLNRLIDKTNQHFE

LIDNEFSEIEQQIGNVINWTRDSMTEVWSYNAELLVAMEN

QHTIDLADSEMNKLYERVRKQLRENAEEDGTGCFEIFHKC

DDQCMESIRNNTYDHTQYRTESLQNRIQIDPVKLSSGYKDI

ILWFSFGASCFLLLAIAMGLVFICIKNGNMRCTICI

12
ADK71148
MNTQILALIACMLIGAKGDKICLGHHAVANGTKVNTLTER

A/blue-winged
GIEVVNXTETVETANIKKICTHGKRPTDLGQCGLLGTLIGP

teal/Guatemala/
PQCDRFLEFDADLIIERREGTDVCYPGKFTNEESLRQILRGS

CIP049-02/2008
GGIDKESMGFTYSGIRTNGATSACRRSGSSFYAEMKWLLS

2008/03/05 HA
NSDNAAFPQMTKSYRNPRNKPALIIWGVHHSGSATEQTKL

301333804
YGSGNKLITVGSSKYQQSFTPSPGTRPQVNGQSGRIDFHW

LLLDPNDTVTFTFNGAFIAPDRASFLRGKSLGIQSDVPLDS

GCEGDCFHSGGTIVSSLPFQNINPRTVGKCPRYVKQTSLLL

ATGMRNVPENPKTRGLFGAIAGFIENGWEGLIDGWYGFR

HQNAQGEGTAADYKSTQSAIDQITGKLNRLIDKTNQQFEL

IDNEFSEIEQQIGNVINWTRDSMTEVWSYNAELLVAMENQ

HTIDLADSEMNKLYERVRKQLRENAEEDGTGCFEIFHKCD

DQCMESIRNNTYDHTQYRTESLQNRIQIDPVKLSSGYKDII

LWFSFGASCFLLLAIAMGLVFICIKNGNMRCTICI

13
ADN34727
MNIQILVFALVAIPTNADKICLGHHAVSNGTKVNTLTERG

A/goose/Czech
VEVVNATETVERTNVPRICSKGKRTVDLGQCGLLGTITGP

Republic/1848-
PQCDQFLEFSADLIIERRGGSDVCYPGKFVNEEALRQILRE

T14/2009
SGGIDKETMGFTYSGIRTNGXTSACRRSGSSFYAEMKWLL

2009/02/04 HA
SNTDNAAFPQMTKSYKNTRKDPALIIWGIHHSGSTTEQTK

307141869
LYGSGSKLITVGSSNYQQSFVPSPGARPQVNGQSGRIDFH

WLMLNPNDTVTFSFNGAFIAPDRASFLKGKSMGIQSGVQV

DANCEGDCYHSGGTIISNLPFQNINSRAVGKCPRYVKQES

LMLATGMKNVPELPKGRGLFGAIAGFIENGWEGLIDGWY

GFRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQ

FELIDNEFTEVEKQIGNVINWTRDSMTEVWSYNAELLVA

MENQHTIDLADSEMNKLYERVKRQLRENAEEDGTGCFEIF

HKCDDDCMASIRNNTYDHSKYREEAMQNRIQINPVKLSS

GYKDVILWFSFGASCFILLAIAMGLVFICVKNGNMRCTICI

14
AEK84760
PAFIAPDRASFLRGKSMGIQSGVQVDASCEGDCYHSGGTII

A/wild
SNLPFQNINSRAVGKCPRYVKQESLMLATGMKNVPELPK

bird/Korea/A14/
GRGLFGAIAGFIENGWEGLIDGWYGFRHQNAQGEGTAAD

2011 2011/02/
YKSTQSAIDQITGKLNRLIEKTNQQFELIDNEFTEVEKQIGN

HA 341610308
VINWTRDSMTEVWSYNAELLVAMENQHTIDLADSEMNK

LYERVRRQLRENAEEDGTGCFEIFHKCDDDCMASIRNNTY

DHSKYREEAMQNRIQIDPVKLSSGYKDVILWFSFGASCFIL

LAIAMGLVFICVKNGNMRCTICI

15
AEK84761
ILVFALVAIIPTNANKIGLGHHAVSNGTKVNTLTERGVEVF

A/wild
NATETVERTNVPRICSKGKKTVDLGQCGLRGTITGPPQCD

bird/Korea/A3/
QFLKFSPDLIIERQKGSDVCYPGKFVNEKPLRQILRESGGID

2011 2011/02/
KETMGFAYNGIKTNGPPIACRKSGSSFYAKMKWLLSNTD

HA 341610310
KAAFPQMTKSYKNTRRNPALIVWGIHHSGSTTKQTKLYGI

GSNLITVGSSNYQQSFVPSPGARPQVNGQSGRIDFHWLILN

PNDTVTFSFNGAFIPPDRASFLRGKSMGIQSGVQVDASCEG

DCYHSGGTIISNLPFQNINSRAVGKCPRYVKQESLMLATG

MKNVPELPKGKGLFGAIAGFIENGWEGLIDGWYGFRHQN

AQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELIDNE

FTEVEKQIGNVINWTRDSMTEVWSYNAELLVAMENQHTI

DLADSEMNKLYERVRRQLRENAEEDGTGCFEIFHKCDDD

CMASIRNNTYDHSKYREEAMQNRIQIDPVKLSSGYKDVIL

WFSFGASCFILLAIAMGLVFICVKNGNMRCTICI

16
AEK84763
ILVFALVAIPTNANKIGLGHHAVSNGTKVNTLTERGVEFF

A/wild
NATETVEPTNVPRICSKGKKTVDLGQCGLLGTITGPPQCD

bird/Korea/A9/
QFLEFSADLIIERREGSDVCYPGKFVNEKALRQILRESGGID

2011 2011/02/
KETMGFAYSGIKTNGPPIACRKSGSSFYAKMKWLLSNTDK

HA 341610314
AAFPQMTKSYKNIRRDPALIVWGIHHSGSTTKQTNLYGIG

SNLITVGSSNYQQSFVPSPGARPQVNGQSGRIDFHWLILNP

NDTVTFIFNGAFIAPDRASFLIGKSMGIQSGVQVDASCEGD

CYHSGGTIISNLPFQNINSRAVGKCPRYVKQESLMLATGM

KNVPELPKGRGLFGAIAGFIENGWEGLIDGWYGFRHQNA

QGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELIDNEF

TEVEKQIGNVINWTRDSMTEVWSYNAELLVAMENQHTID

LADSEMNKLYERVRRQLRENAEEDGTGCFEIFHKCDDDC

MASIRNNTYDHSKYREEAMQNRIQIDPVKLSSGYKDVILW

FSFGASCFILLAIAMGLVFICVKNGNMRCTICI

17
AEK84765
LVFALVAIIPTNADKICLGHHAVSNGTKVNTLTERGVEVV

A/spot-billed
NATETVERTNVPRICSKGKRTVDLGQCGLLGTITGPPQCD

duck/Korea/447/
QFLEFSADLIIERREGSDVCYPGKFVNEEALRQILRESGGID

2011 2011/04/
KETMGFTYSGIRTNGATSACRRSGSSFYAEMKWLLSNTD

HA 341610318
NAAFPQMTKSYKNTRRDPALIVWGIHHSGSTTEQTKLYGS

GSKLITVGSSNYQQSFVPSPGARPQVNGQSGRIDFHWLILN

PNDTVTFSFNGAFIAPDRASFLRGKSMGIQSGVQVDASCE

GDCYHSGGTIISNLPFQNINSRAVGKCPRYVKQESLMLAT

GMKNVPEPPKGRGLFGAIAGFIENGWEGLIDGWYGFRHQ

NAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELIDN

EFTEVEKQIGNVINWTRDSMTEVWSYNAELLVAMENQHT

IDLADSEMNKLYERVRRQLRENAEEDGTGCFEIFHKCDDD

CMARIRNNTYDHSKYREEAMQNRIQIDPVKLSSGYKDVIL

WFSFGASCFILLAIAMGLVFICVKNGNMRCTICI

18
AEM98291
SILVFALVAIIPTNADKICLGHHAVSNGTKVNTLTERGVEV

A/wild
VNATETVERTNVPRICSKGKRTVDLGQCGLLGTITGPPQC

duck/Mongolia/
DQFLEFSADLIIERREGSDVCYPGKFVNEEALRQILRESGGI

1-241/2008
DKETMGFTYSGIRTNGATSACRRSGSSFYAEMKWLLSNT

2008/04/ HA
DNAAFPQMTKSYKNTRKDPALIIWGIHHSGSTTEQTKLYG

344196120
SGSKLITVGSSNYQQSFVPSPGARPQVNGQSGRIDFHWLM

LNPNDTVTFSFNGAFIAPDRASFLRGKSMGIQSGVQVDAN

CEGDCYHSGGSIISNLPFQNINSRAVGKCPRYVKQESLML

ATGMKNVPELPKGRGLFGAIAGFIENGWEGLIDGWYGFR

HQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELI

DNEFTEVEKQIGNVINWTRDSMTEVWSYNAELLVAMENQ

HTIDLADSEMNKLYERVKRQLRENAEEDGTGCFEIFHKCD

DDCMASIRNNTYDHSKYREEAMQNRIQINPVKLSSGYKD

VILWFSFGASCFILLAIAMGLVFICVKNGNMRCTI

19
AFM09439
QILAFIACMLIGAKGDKICLGHHAVANGTKVNTLTERGIE

A/emperor
VVNATETVETVNIKKICTQGKRPTDLGQCGLLGTLIGPPQC

goose/Alaska/
DQFLEFDADLIIERRKGTDVCYPGKFTNEESLRQILRGSGGI

44063-061/2006
DKESMGFTYSGIRTNGATSACRRSGSSFYAEMKWLLSNSD

2006/05/23 HA
NAAFPQMTKSYRNPRNKPALIWGVHHSGSATEQTKLYGS

390535062
GNKLITVGSSKYQQSFVPSPGARPQVNGQSGRIDFHWLLL

DPNDTVTFTFNGAFIAPERASFFRGESLGVQSDVPLDSGCE

GDCFHSGGTIVSSLPFQNINPRTVGKCPRYVKQTSLLLATG

MRNVPENPKTRGLFGAIAGFIENGWEGLIDGWYGFRHQN

AQGEGTAADYKSTQSAIDQITGKLNRLIDKTNQQFELIDNE

FSEIEQQIGNVINWTRDSMTEVWSYNAELLVAMENQHTID

LADSEMNKLYERVRKQLRENAEEDGTGCFEIFHKCDDQC

MESIRNNTYDHTQYRTESLQNRIQINPVKLSSGYKDIILWF

SFGASCFLLLAIAMGLVFICIKNGNMRCTICI

20
AFV33945
MNTQILALIACMLIGAKGDKICLGHHAVANGTKVNTLTER

A/guinea
RIEVVNATETVETANIKKICTQGKRPTDLGQCGLLGTLIGP

fowl/Nebraska/
PQCDQFLEFDADLIIERREGTDVCYPGKFTNEESLRQILRG

17096-1/2011
SGGIDKESMGFTYSGIRTNGATSACRRSGSSFYAEMKWLL

2011/04/05 HA
SNSNNAAFPQMTKSYRNPRNKPALIVWGVHHSGSATEQT

409676820
KLYGSGSKLITVGSSKYQQSFTPSPGARPQVNGQSGRIDFH

WLLLDPNDTVTFTFNGAFIAPDRASFFRGESLGVQSDVPL

DSGCEGDCFHKGGTIVSSLPFQNINPRTVGKCPRYVKQTSL

LLATGMRNVPENPKTRGLFGAIAGFIENGWEGLIDGWYGF

RHQNAQGEGTAADYKSTQSAIDQITGKLNRLIDKTNQQFE

LIDNEFSEIEQQIGNVINWTRDSMTEIWSYNAELLVAMEN

QHTIDLADSEMNKLYERVRKQLRENAEEDGTGCFEIFHKC

DDQCMESIRNNTYDHTQYRAESLQNRIQIDPVKLSSGYKD

IILWFSFGASCFLLLAIAMGLVFICIKNGNMRCTICI

21
AFV33947
MNTQILALIACMLIGAKGDKICLGHHAVANGTKVNTLTER

A/goose/Nebraska/
GIEVVNATETVETANIKKICTQGKRPTDLGQCGLLGTLIGP

17097-
PQCDQFLEFDADLIIERREGTDVCYPGKFTNEESLRQILRG

4/2011
SGGIDKESMGFTYSGIRTNGATSACRRSGSSFYAEMKWLL

2011/04/05 HA
SNSDNAAFPQMTKSYRNPRNKPALIVWGVHHSASATEQT

409676827
KLYGSGSKLITVGSSKYQQSFTPSPGARPQVNGQSGRIDFH

WLLLDPNDTVTFTFNGAFIAPDRASFFRGESLGVQSDVPL

DSGCEGDCFHKGGTIVSSLPFQNINPRTVGKCPRYVKQTSL

LLATGMRNVPENPKTRGLFGAIAGFIENGWEGLIDGWYGF

RHQNAQGEGTAADYKSTQSAIDQITGKLNRLIDKTNQQFE

LIDNEFSEIEQQIGNVINWTRDSMTEIWSYNAELLVAMEN

QHTIDLADSEMNKLYERVRKQLRENAEEDGTGCFEIFHKC

DDQCMESIRNNTYDHTQYRAESLQNRIQIDPVKLSSGYKD

IILWFSFGASCFLLLAIAMGLVFICIKNGNMRCTICI

22
AFX85260
MNTQILAFIACMLIGINGDKICLGHHAVANGTKVNTLTER

A/ruddy
GIEVVNATETVETANIKRICTQGKRPIDLGQCGLLGTLIGPP

turnstone/
QCDQFLEFDSDLIERREGTDVCYPGKFTNEESLRQILRGS

Delaware
GGIDKESMGFTYSGIRTNGATSACIRLGSSFYAEMKWLLS

Bay/220/1995
NSDNAAFPQMTKSYRNPRNKPALIWGVHHSGSANEQTK

1995/05/21 HA
LYGSGNKLITVGSSKYQQSFTPSPGARPQVNGQSGRIDFH

423514912
WLLLDPNDTVTFTFNGAFIAPDRASFFRGESLGVQSDVPL

DSSCGGDCFHSGGTIVSSLPFQNINPRTVGRCPRYVKQTSL

LLATGMKNVPENPKTRGLFGAIAGFIENGWEGLIDGWYG

FRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIDKTNQQF

ELIDNEFNEIEQQIGNVINWTRDSMTEVWSYNAELLVAME

NQHTIDLADSEMNKLYERVRKQLRENAEEDGTGCFEIFHK

CDDQCMESIRNNTYDHTQYRTESLQNRIQIDPVKLSSGYK

DIILWFSFGASCFLLLAIAMGLVFICIKNGNMRCTICI

23
AGE08098
MNTQILTLIACMLIGAKGDKICLGHHAVANGTKVNTLTER

A/northern
GIEVVNATETVETANIKKICTQGKRPTDLGQCGLLGTLIGP

shoverl/
PQCDQFLEFDADLIIERREGTDVCYPGKFTNEESLRQILRG

Mississippi/
SGGIDKESMGFTYSGIRTNGATSACRRSGSSFYAEMKWLL

11OS145/2011
SNSDNAAFPQMTKSYRNPRNKPALIWGVHHSGSATEQTK

2011/01/08
LYGSGNKLITVGSSKYQQSFTPSPGARPQVNGQSGRIDFH

HA 444344488
WLLLDPNDTVTFTFNGAFIAPDRASFFRGESLGVQSDVPL

DSGCEGDCFHNGGTIVSSLPFQNINPRTVGKCPRYVKQTSL

LLATGMRNVPENPKTRGLFGAIAGFIENGWEGLIDGWYGF

RHQNAQGEGTAADYKSTQSAIDQITGKLNRLIDKTNQQFE

LIDNEFSEIEQQIGNVINWTRDSMTEVWSYNAELLVAMEN

QHTIDLADSEMNKLYERVRKQLRENAEEDGTGCFEIFHKC

DDQCMESIRNNTYDHTQYRAESLQNRIQIDPVKLSSGYKD

IILWFSFGASCFLLLAIAMGLVFICIKNGNMRCTICI

24
AGI60301
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERG

A/Hangzhou/1/
VEVVNATETVERTNIPRICSKGKRTVDLGQCGLLGTITGPP

2013 2013/03/24
QCDQFLEFSADLIIERREGSDVCYPGKFVNEEALRQILRES

HA 475662454
GGIDKEAMGFTYSGIRTNGATSACRRSGSSFYAEMKWLLS

NTDNAAFPQMTKSYKNTRKSPALIVWGIHHSVSTAEQTKL

YGSGNKLVTVGSSNYQQSFVPSPGARPQVNGISGRIDFHW

LMLNPNDTVTFSFNGAFIAPDRASFLRGKSMGIQSGVQVD

ANCEGDCYHSGGTIISNLPFQNIDSRAVGKCPRYVKQRSLL

LATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGWYGFR

HQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELI

DNEFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQ

HTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFHKCD

DDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLSSGYKD

VILWFSFGASCFILLAIVMGLVFICVKNGNMRCTICI

25
AGI60292
MNTQILVFALIAIIPANADKICLGHHAVSNGTKVNTLTERG

A/Shanghai/
VEVVNATETVERTNIPRICSKGKRTVDLGQCGLLGTITGPP

4664T/2013
QCDQFLEFSADLIIERREGSDVCYPGKFVNEEALRQILRES

2013/03/05 HA
GGIDKEAMGFTYSGIRTNGATSACRRSGSSFYAEMKWLLS

476403560
NTDNAAFPQMTKSYKNTRKSPALIVWGIHHSVSTAEQTKL

YGSGNKLVTVGSSNYQQSFVPSPGARPQVNGLSGRIDFH

WLMLNPNDTVTFSFNGAFIAPDRASFLRGKSMGIQSGVQV

DANCEGDCHHSGGTIISNLPFQNIDSRAVGKCPRYVKQRS

LLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGWYG

FRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQF

ELIDNEFNEVEKQIGNVINWIRDSITEVWSYNAELLVAME

NQHTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFHK

CDDDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLSSGY

KDVILWFSFGASCFILLAIVMGLVFICVKNGNMRCTICI

26
AGJ72861
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERG

A/chicken/
GEVVNATETVERTNIPRICSKGKKTVDLGQGGPRGTITGPP

Zhejiang/DTID-
QCDQFLEFSADLIMERREGSDVCYPGKFVNEEALRQILRES

ZJU01/2013
GGIDKEAMGFTYSGIRTNGATSACRRSGSSFYAEMKWLLS

2013/04/ HA
NTDNAAFPQMTKSYKNTRKSPALIVWGIHHSVSTAEQTKL

479280294
YGSGNKLVTVGSSNYQQSFVPSPGARPQVNGQSGRIDFH

WLMLNPNDTVTFSFNGAFIAPDRASFLRGKSMGIQSGVQV

DANCEGDCYHSGGTIISNLPFQNIDSRAVGKCPRYVKQRS

LLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGWYG

FRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQF

ELIDNEFNEVEKQIGNVINWTRDSITEVWSYNAELLVAME

NQHTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFHK

CDDDCMASINNTYDHSKYREEAMQNRIQIDPVKLSSGY

KDVILWFSFGASCFILLAIVMGLVFICVKNGNMRCTICI

27
AGJ73503
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERG

A/Nanjing/1/2013
VEVVNATETVERTNIPRICSKGKMTVDLGQCGLLGTITGPP

2013/03/28
QCDQFLEFSADLIIERREGSDVCYPGKFVNEEALRQILRES

HA 479285761
GGIDKEAMGFTYSGIRTNGATSACRRSGSSFYAEMKWLLS

NTDNAAFPQMTKSYKNTRKSPALIVWGIHHSVSTAEQTKL

YGSGNKLVTVGSSNYQQSFVPSPGARPQVNGLSGRIDFH

WLMLNPNDTVTFSFNGAFIAPDRASFLRGKSMGIQSGVQV

DANCEGDCYHSGGTIISNLPFQNIDSRAVGKCPRYVKQRS

LLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGWYG

FRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQF

ELIDNEFNEVEKQIGNVINWTRDSITEVWSYNAELLVAME

NQHTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFHK

CDDDCMASINNTYDHSKYREEAMQNRIQIDPVKLSSGY

KDVILWFSFGASCFILLAIVMGLVFICVKNGNMRCTICI

28
BAN16711
MNTQVLVFALMAIIPTNADKICLGHHAVSNGTKVNTLTER

A/duck/Gunma/
GVEVVNATETVERTNVPRICSKGKRTVDLGQCGLLGTITG

466/2011 2011//
PPQCDQFLEFSADLIIERREGSDVCYPGKFVNEEALRQILRE

HA 482661571
SGGIDKETMGFTYSGIRTNGTTSACRRSGSSFYAEMKWLL

SNTDNAAFPQMTKSYKNTRRDPALIAWGIHHSGSTTEQTK

LYGSGSKLITVGSSNYQQSFVPSPGARPQVNGQSGRIDFH

WLILNPNDTVTFSFNGAFIAPDRASFLRGKSMGIQSGVQV

DASCEGDCYHSGGTIISNLPFQNINSRAVGKCPRYVKQESL

MLATGMKNVPELPKGRGLFGAIAGFIENGWEGLIDGWYG

FRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQF

ELIDNEFTEVEKQIGNVINWTRDSMTEVWSYNAELLVAM

ENQHTIDLADSEMNKLYERVRRQLRENAEEDDTGCFEIFH

KCDDDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLSSG

YKDVILWFSFGASCFILLAIAMGLVFICVKNGNMRCTICI

29
AGK84857
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERG

A/Hangzhou/2/
VEVVNATETVERTNIPRICSKGKRTVDLGQCGLLGTITGPP

2013 2013/04/01
QCDQFLEFSADLIIERREGSDVCYPGKFVNEEALRQILRES

HA 485649824
GGIDKEAMGFTYSGIRTNGATSACRRSGSSFYAEMKWLLS

NTDNAAFPQITKSYKNTRKSPALIVWGIHHSVSTAEQTKL

YGSGNKLVTVGSSNYQQSFVPSPGARPQVNGLSGRIDFH

WLMLNPNDTVTFSFNGAFIAPDRASFLRGKSMGIQSGVQV

DANCEGDCYHSGGTIISNLPFQNIDSRAVGKCPRYVKQRS

LLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGWYG

FRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQF

ELIDNEFNEVEKQIGNVINWIRDSITEVWSYNAELLVAME

NQHTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFHK

CDDDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLSSGY

KDVILWFSFGASCFILLAIVMGLVFICVKNGNMRCTICI

30
AGL44438
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERG

A/Shanghai/02/
VEVVNATETVERTNIPRICSKGKRTVDLGQCGLLGTITGPP

2013 2013/03/05
QCDQFLEFSADLIIERREGSDVCYPGKFVNEEALRQILRES

HA 496493389
GGIDKEAMGFTYSGIRTNGATSACRRSGSSFYAEMKWLLS

NTDNAAFPQMTKSYKNTRKSPALIVWGIHHSVSTAEQTKL

YGSGNKLVTVGSSNYQQSFVPSPGARPQVNGLSGRIDFH

WLMLNPNDTVTFSFNGAFIAPDRASFLRGKSMGIQSGVQV

DANCEGDCYHSGGTIISNLPFQNIDSRAVGKCPRYVKQRS

LLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGWYG

FRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQF

ELIDNEFNEVEKQIGNVINWIRDSITEVWSYNAELLVAME

NQHTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFHK

CDDDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLSSGY

KDVILWFSFGASCFILLAIVMGLVFICVKNGNMRCTICI

31
AGL33692
GMIDGWYGFRHQNAQGEGTAADYKSTQSAIDQITGKLNR

A/Shanghai/
LIEKTNQQFELIDNEFTEVEKQIGNVINWTRDSITEVWSYN

4655T/2013
AELLVAMENQHTIDLADSEMDKLYERVKRQLRENAEEDG

2013/02/26 HA
TGCFEIFHKCDDDCMASIRNNTYDHSKYREEAMQNRIQID

491874175
PVKLSSGYKDVILWFSFGASCFILLAIAMGLVFICVKNGN

MRCTICI

32
AGL33693
GMIDGWYGFRHQNAQGEGTAADYKSTQSAIDQITGKLNR

A/Shanghai/
LIEKTNQQFELIDNEFNEVEKQIGNVINWTRDSITEVWSYN

4659T/2013
AELLVAMENQHTIDLADSEMDKLYERVKRQLRENAEEDG

2013/02/27 HA
TGCFEIFHKCDDDCMASIRNNTYDHSKYREEAMQNRIQID

491874186
PVKLSSGYKDVILWFSFGASCFILLAIVMGLVFICVKNGN

MRCTICI

33
AGL95088
VFALIAIIPTNADKICLGHHAVSNGTKVNTLTERGVEVVN

A/Taiwan/
ATETVERTNIPRICSKGKRTVDLGQCGLLGTITGPPQCDQF

S02076/2013
LEFSADLIIERREGSDVCYPGKFVNEEALRQILRESGGIDKE

2013/04/22 HA
AMGFTYSGIRTNGATSACRRSGSSFYAEMKWLLSNTDNA

501485301
AFPQMTKSYKNTRKSPALIVWGIHHSVSTAEQTKLYGSGN

KLVTVGSSNYQQSFVPSPGARPQVNGLSGRIDFHWLMLNP

NDTVTFSFNGAFIAPDRASFLRGKSMGIQSGVQVDANCEG

DCYHSGGTIISNLPFQNIDSRAVGKCPRYVKQRSLLLATG

MKNVPEIPKGRGLFGAIAGFIENGWEGLIDGWYGFRHQN

AQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELIDNE

FNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQHTID

LADSEMDKLYERVKRQLRENAEEDGTGCFEIFHKCDDDC

MASIRNNTYDHSKYREEAMQNRIQIDPVKLSSGYKDVILW

FSFGASCFILLAIVMGLVFICVKNGNMR

34
AGL95098
LVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERGVEVVN

A/Taiwan/
ATETVERTNIPRICSKGKRTVDLGQCGLLGTITGPPQCDQF

T02081/2013
LEFSADLIIERREGSDVCYPGKFVNEEALRQILRESGGIDKE

2013/04/22 HA
AMGFTYSGIRTNGATSACRRSGSSFYAEMKWLLSNTDNA

501485319
AFPQMTKSYKNTRKSPALIVWGIHHSVSTAEQTKLYGSGN

KLVTVGSSNYQQSFVPSPGARPQVNGLSGRIDFHWLMLNP

NDTVTFSFNGAFIAPDRASFLRGKSMGIQSGVQVDANCEG

DCYHSGGTIISNLPFQNIDSRAVGKCPRYVKQRSLLLATG

MKNVPEIPKGRGLFGAIAGFIENGWEGLIDGWYGFRHQN

AQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELIDNE

FNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQHTID

LADSEMDKLYERVKRQLRENAEEDGTGCFEIFHKCDDDC

MASIRNNTYDHSKYREEAMQNRIQIDPVKLSSGYKDVILW

FSFGASCFILLAIVMGLVFICVKNGNMRCT

35
AGM53883
GFRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQ

A/Shanghai/
FELIDNEFNEVEKQIGNVINWTRDSITEVWSYNAELLVAM

5083T/2013
ENQHTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFH

2013/04/20 HA
KCDDDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLSSG

507593986
YKDVILWFSFGASCFILLAIVMGLVFICVKNGNMRCT

36
AGM53884
AQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELIDNE

A/Shanghai/
FNEVEKQIGNVINWIRDSITEVWSYNAELLVAMENQHTID

5180T/2013
LADSEMDKLYERVKRQLRENAEEDGTGCFEIFHKCDDDC

2013/04/23 HA
MASIRNNTYDHSKYREEAMQNRIQIDPVKLSSGYKDVILW

507593988
FSFGASCFILLAIVMGLVFICVKNGNMRCTICI

37
AGM53885
QNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELID

A/Shanghai/
NEFNEVEKQIGNVINWIRDSITEVWSYNAELLVAMENQH

5240T/2013
TIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFHKCDD

2013/04/25 HA
DCMASIRNNTYDHSKYREEAMQNRIQIDPVKLSSGYKDVI

507593990
LWFSFGASCFILLAIVMGLVFICVKNGNMRCT

38
AGM53886
NAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELIDN

A/Shanghai/
EFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQHTI

4842T/2013
DLADSEMDKLYERVKRQLRENAEEDGTGCFEIFHKCDDD

2013/04/13 HA
CMASIRNNTYDHSKYREEAMQNRIQIDPVKLSSGYKDVIL

507593992
WFSFGASCFILLAIVMGLVFICVKNGNMRCT

39
AGM53887
NAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELIDN

A/Shanghai/
EFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQHTI

4701T/2013
DLADSEMDKLYERVKRQLRENAEEDGTGCFEIFHKCDDD

2013/04/06 HA
CMASIRNNTYDHSKYREEAMQNRIQIDPVKLSSGYKDVIL

507593994
WFSFGASCFILLAIVMGLVFICVKNGNMRCTIC

40
AGN69462
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERG

A/Wuxi/2/2013
VEVVNATETVERTNIPRICSKGKRTVDLGQCGLLGTITGPP

2013/03/31 HA
QCDQFLEFSADLIIERREGSDVCYPGKFVNEEALRQILRES

511105778
GGIDKEAMGFTYSGIRTNGSTSACRRSGSSFYAEMKWLLS

NTDNAAFPQMTKSYKNTRKSPALIVWGIHHSVSTAEQTKL

YGSGSKLVTVGSSNYQQSFVPSPGARPQVNGLSGRIDFHW

LMLNPNDTVTFSFNGAFIAPDRASFLRGKSMGIQSGVQVD

ANCEGDCYHSGGTHISNLPFQNIDSRAVGKCPRYVKQRSLL

LATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGWYGFR

HQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELI

DNEFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQ

HTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFHKCD

DDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLSSGYKD

VILWFSFGASCFILLAIVMGLVFICVKNGNMRCTICI

41
AGN69474
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERG

A/Wuxi/1/2013
VEVVNATETVERTNIPRICSKGKRTVDLGQCGLLGTITGPP

2013/03/31 HA
QCDQFLEFSADLHIERREGSDVCYPGKFVNEEALRQILRES

511105798
GGIDKEAMGFTYSGIRTNGATSACRRSGSSFYAEMKWLLS

NTDNAAFPQMTKSYKNTRKSPALIVWGIHHSVSTAEQTKL

YGSGNKLVTVGSSNYQQSFVPSPGARPQVNGLSGRIDFH

WLMLNPNDTVTFSFNGAFIAPDRASFLRGKSMGIQSGVQV

DANCEGDCYHSGGTHISNLPFQNIDSRAVGKCPRYVKQRS

LLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLINGWYG

FRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQF

ELIDNEFNEVEKQIGNVINWIRDSITEVWSYNAELLVAME

NQHTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFHK

CDDDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLSSGY

KDVILWFSFGASCFILLAIVMGLVFICVKNGNMRCTICI

42
AGO51387
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERG

A/Jiangsu/2/
VEVVNATETVERTNIPRICSKGKMTVDLGQCGLLGTITGPP

2013 2013/04/20
QCDQFLEFSADLIIERREGSDVCYPGKFVNEEALRQILRES

HA 514390990
GGIDKEAMGFTYSGIRTNGATSACRRSGSSFYAEMKWLLS

NTDNAAFPQMTKSYKNTRKSPALIVWGIHHSVSTAEQTKL

YGSGNKLVTVGSSNYQQSFVPSPGARPQVNGLSGRIDFH

WLMLNPNDTVTFSFNGAFIAPDRASFLRGKSMGIQSGVQV

DANCEGDCYHSGGTIISNLPFQNIDSRAVGKCPRYVKQRS

LLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGWYG

FRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQF

ELIDNEFNEVEKQIGNVINWTRDSITEVWSYNAELLVAME

NQHTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFHK

CDDDCMASIRNNTYDHSKYRXEAMXBXIQIDPVKLSSGY

KDVXJWFSFGASCFILLAIVMGLVFICVKNGNMRCTICI

43
BAN59726
MNTQILVFALVAIIPTNADKICLGHHAVSNGTKVNTLTER

A/duck/Mongolia/
GVEVVNATETVERTNIPRICSKGKRTVDLGQCGLLGTITGP

147/2008
PQCDQFLEFSADLIIERREGSDVCYPGKFVNEEALRQILRES

2008/08/29 HA
GGIGKETMGFTYSGIRTNGATSACRRSRSSFYAEMKWLLS

519661951
NTDNAAFPQMTRSYKNTRKDPALIIWGIHHSGSTTEQTKL

YGSGNKLITVGSSNYQQSFVPSPGARPQVNGQSGRIDFHW

LMLNPNDTVTFSFNGAFIAPDRASFLRGKSMGIQSGVQVD

ANCEGDCYHNGGTIISNLPFQNINSRTVGKCPRYVKQESLL

LATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGWYGFR

HQNAQGEGTAADYKSTQSAIDQITGKLNRLIERTNQQFELI

DNEFTEVEKQIGNVINWTRDSMTEVWSYNAELLVAMENQ

HTIDLADSEMNKLYERVKRQLRENAEEDGTGCFEIFHKCD

DDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLSNGYKD

VILWFSFGASCFILLAIAMGLVFICVKNGNMRCTICI

44
BAN59727
MNTQILVFALVAIIPTNADKICLGHHAVSNGTKVNTLTER

A/duck/Mongolia/
GVEVVNATETVERINVPRICSKGKRTVDLGQCGLLGTITG

129/2010
PPQCDQFLEFSADLIIERREGSDVCYPGKFVNEEALRQILRE

2010// HA
SGGIDKETMGFTYSGIRTNGATSACRRSGSSFYAEMKWLL

519661954
SNTDNAAFPQMTKSYKNTRKDPALIIWGIHHSGSTTEQTK

LYGSGSKLITVGSSNYQQSFVPSPGARPQVNGQSGRIDFH

WLMLNPNDTVTFSFNGAFIAPDRASFLRGKSMGIQSGVQV

DASCEGDCYHSGGTIISNLPFQNINSRAVGKCPRYVKQESL

MLATGMKNVPELPKGRGLFGAIAGFIENGWEGLIDGWYG

FRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQF

ELIDNEFTEVEKQIGNVINWTRDSMTEVWSYNAELLVAM

ENQHTIDLADSEMNKLYERVKRQLRENAEEDGTGCFEIFH

KCDDDCMASIRNNTYDHSKYREEAMQNRIQINPVKLSSG

YKDVILWFSFGASCFILLAIAMGLVFICVKNGNMRCTICI

45
AGQ80952
MNTQILVFALVAIIPTNADKICLGHHAVSNGTKVNTLTER

A/duck/Jiangxi/
GVEVVNATETVERTSIPRICSKGKRAVDLGQCGLLGTITGP

3096/2009
PQCDQFLEFSADLIIERREGSDVCYPGKFVNEEALRQILRES

2009// HA
GGIDKETMGFTYSGIRTNGATSACRRSGSSFYAEMKWLLS

523788794
NTDNAAFPQTTKSYKNTRKDPALIIWGIHHSGSTTEQTKL

YGSGNKLITVGSSNYQQSFVPSPGARPQVNGQSGRIDFHW

LMLNPNDTVTFSFNGAFIAPDRASFLRGKSMGIQSGVQVD

ANCEGDCYHNGGTIISNLPFQNINSRAVGKCPRYVKQESL

LLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGWYGF

RHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQFE

LIDNEFTEVERQIGNVINWTRDSMTEVWSYNAELLVAME

NQHTIDLADSEMNKLYERVRRQLRENAEEDGTGCFEIFHK

CDDDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLSSGY

KDVILWFSFGASCFILLAIAMGLVFICVKNGNMRCTICI

46
AGQ80989
MNTQILVFALVAHIPTNADKICLGHHAVSNGTKVNTLTER

A/duck/Jiangxi/
GVEVVNATETVERTSIPRICSKGKRAVDLGQCGLLGTITGP

3257/2009
PQCDQFLEFSADLIIERREGSDVCYPGKFVNEEALRQILRES

2009// HA
GGIDKETMGFTYSGIRTNGATSACRRSGSSFYAEMKWLLS

523788868
NTDNAAFPQTTKSYKNTRKDPALIIWGIHHSGSTTEQTKL

YGSGNKLITVGXSNYQQSFVPSPGARPQVNGQSGRIDFHW

LMLNPNDTVTFSFNGAFIAPDRASFLRGKSMGIQSGVQVD

ANCEGDCYHNGGTIISNLPFQNINSRAVGKCPRYVKQESL

LLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGWYGF

RHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQFE

LIDNEFTEVERQIGNVINWTRDSMTEVWSYNAELLVAME

NQHTIDLADSEMNKLYERVRRQLRENAEEDGTGCFEIFHK

CDDDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLSSGY

KDVILWFSFGASCFILLAIAMGLVFICVKNGNMRCTICI

47
AGQ81043
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERG

A/chicken/Rizhao/
VEVVNATETVERTNIPRICSKGKRTVDLGQCGLLGTITGPP

515/2013
QCDQFLEFSADLIIERREGSDVCYPGKFVNEEALRQILRES

2013// HA
GGIDKEEMGFTYSGIRTNGATSACRRSGSSFYAEMKWLLS

523788976
NTDNAAFPQMTKSYKNTRKSPALIVWGIHHSVSTAEQTKL

YGSGNKLVTVGSSNYQQSFVPSPGARPQVNGLSGRIDFH

WLMLNPNDTVTFSFNGAFIAPDRASFLRGKSMGIQSGVQV

DANCEGDCYHSGGTIISNLPFQNIDSRAVGKCPRYVKQRS

LLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGWYG

FRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQF

ELIDNEFNEVEKQIGNVINWTRDSITEVWSYNAELLVAME

NQHTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFHK

CDDDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLSSGY

KDVILWFSFGASCFILLAIVMGLVFICVKNGNMRCTICI

48
AGR33894
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERG

A/chicken/Rizhao/
VEVVNATETVERTNIPRICSKGKRTVDLGQCGLLGTITGPP

719b/2013
QCDQFLEFSADLIIERREGSDVCYPGKFVNEEALRQILRES

2013// HA
GGIDKEAMGFTYSGIRTNGATSACRRSGSSFYAEMKWLLS

524845213
NTDNAAFPQMTKSYKNTRKSPALIVWGIHHSVSTAEQTKL

YGSGNKLVTVGSSNYQQSFVPSPGARPQVNGLSGRIDFH

WLMLNPNDTVTFSFNGAFIAPDRASFLRGKSMGIQSGVQV

DANCEGDCYHSGGTHISNLPFQNIDSRAVGKCPRYVKQRS

LLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGWYG

FRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQF

ELIDNEFNEVEKQIGNVINWTRDSITEVWSYNAELLVAME

NQHTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFHK

CDDDCMASIRNNTYDRSKYREEAMQNRXXXXXXXXXXX

XKDVILWFSFGASCFILLAIVMGLVFICVKNGNMRCTICI

49
AGR49399
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERG

A/chicken/Jiangxi/
VEVVNATETVERTNIPRICSKGKRTVDLGQCGLLGTITGPP

SD001/2013
QCDQFLEFSADLIIERREGSDVCYPGKFVNEEALRQILRKS

2013/05/03 HA
GGIDKEAMGFTYSGIRTNGATSACRRSGSSFYAEMKWLLS

525338528
NTDNAAFPQMTKSYKNTRKSPALIVWGIHHSVSTAEQTKL

YGSGNKLVTVGSSNYQQSFVPSPGARPQVNGLSGRIDFH

WLMLNPNDTVTFSFNGAFIAPDRASFLRGKSMGIQSGVQV

DANCEGDCYHSGGTIISNLPFQNIDSRAVGKCPRYVKQRS

LLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGWYG

FRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQF

ELIDNEFNEVEKQIGNVINWIRDSITEVWSYNAELLVAME

NQHTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFHK

CDDDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLSSGY

KDVILWFSFGASCFILLAIVMGLVFICVKNGNMRCTICI

50
AGR49495
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERG

A/chicken/Shanghai/
VEVVNATETVERTNIPRICSKGKMTVDLGQCGLLGTITGPP

S1358/2013
QCDQFLEFSADLIIERREGSDVCYPGKFVNEEALRQILRES

2013/04/03
GGIDKEAMGFTYSGIRTNGATSACRRSGSSFYAEMKWLLS

HA 525338689
NTDNAAFPQMTKSYKNTRKSPALIVWGIHHSVSTAEQTKL

YGSGNKLVTVGSSNYQQSFVPSPGARPQVNGLSGRIDFH

WLMLNPNDTVTFSFNGAFIAPDRASFLRGKSMGIQSGVQV

DANCEGDCYHSGGTIISNLPFQNIDSRAVGKCPRYVKQRS

LLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGWYG

FRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQF

ELIDNEFNEVEKQIGNVINWTRDSITEVWSYNAELLVAME

NQHTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFHK

CDDDCMASIKNNTYDHSKYREEAMQNRIQIDPVKLSSGY

KDVILWFSFGASCFILLAIVMGLVFICVKNGNMRCTICI

51
AGR49506
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERG

A/chicken/Shanghai/
VEVVNATETVERTNIPRICSKGKRTVDLGQCGLLGTITGPP

S1410/2013
QCDQFLEFSADLIIERREGSDVCYPGKFVNEEALRQILRES

2013/04/03
GGIDKEAMGFTYSGIRTNGATSACRRSGSSFYAEMKWLLS

HA 525338708
NTDNAAFPQMTKSYKNTRKSPALIVWGIHHSVSTAEQTKL

YGSGNKLVTVGSSNYQQSFVPSPGARPQVNGQSGRIDFH

WLMLNPNDTVTFSFNGAFIAPDRASFLRGKSMGIQSGVQV

DANCEGDCYHSGGTIISNLPFQNIDSRAVGKCPRYVKQRS

LLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGWYG

FRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQF

ELIDNEFNEVEKQIGNVINWIRDSITEVWSYNAELLVAME

NQHTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFHK

CDDDCMASINNTYDHSKYREEAMQNRIQIDPVKLSSGY

KDVILWFSFGASCFILLAIVMGLVFICVKNGNMRCTICI

52
AGR49554
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERG

A/chicken/Zhejiang/
VEVVNATETVERTNIPRICSKGKRTVDLGQCGLLGTITGPP

SD033/2013
QCDQFLEFSADLIIERREGSDVCYPGKFVNEEALRQILRES

2013/04/11 HA
GGIDKEAMGFTYSGIRTNGATSACRRSGSSFYAEMKWLLS

525338789
NTDNAAFPQMTKSYKNTRKSPALIVWGIHHSVSTAEQTKL

YGSGNKLVTVGSSNYQQSFVPSPGARPQVNGLSGRIDFH

WLMLNPNDTVTFSFNGAFIAPDRASFLRGKSMGIQSGVQV

DANCEGDCYHSGGTIISNLPFQNIDSRAVGKCPRYVKQRS

LLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGWYG

FRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQF

ELIDNEFNEVEKQIGNVINWTRDSITEVWSYNAELLVAME

NQHTIDLADSEMDKLYERVRRQLRENAEEDGTGCFEIFHK

CDDDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLSSGY

KDVILWFSFGASCFILLAIVMGLVFICVKNGNMRCTICI

53
AGR49566
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERG

A/duck/Anhui/
VEVVNATETVERTNIPRICSKGKRTVDLGQCGLLGTITGPP

SC702/2013
QCDQFLEFSADLIIERREGSDVCYPGKFVNEEALRQILRES

2013/04/16 HA
GGIDKEAMGFTYSGIRTNGATSACRRSGSSFYAEMKWLLS

525338809
NTDNAAFPQMTKSYKNTRKSPALIVWGIHHSVSTAEQTKL

YGSGNKLVTVGSSNYQQSFVPSPGARPQVNGLSGRIDFH

WLMLNPNDTVTFSFNGAFIAPDRASFLRGKSMGIQSGVQV

DANCEGDCYHSGGTIISNLPFQNIDNRAVGKCPRYVKQRS

LLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGWYG

FRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQF

ELIDNEFNEVEKQIGNVINWIRDSITEVWSYNAELLVAME

NQHTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFHK

CDDDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLSSGY

KDVILWFSFGASCFILLAIVMGLVFICVKNGNMRCTICI

54
AGR49722
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERG

A/homing
VEVVNATETVERTNIPRICSKGKRTVDLGQCGLLGTITGPP

pigeon/Jiangsu/
QCDQFLEFSADLIIERREGSDVCYPGKFVNEEALRQILRES

SD184/2013
GGIDKEAMGFTYSEIRTNGATSACRRSGSSFYAEMKWLLS

2013/04/20 HA
NTDNAAFPQMTKSYKNTRKSPALIVWGIHHSVSTAEQTKL

525339071
YGSGNKLVTVGSSNYQQSFVPSPGARPQVNGQSGRIDFH

WLMLNPNDTVTFSFNGAFIAPDRASFLRGKSMGIQSGVQV

DANCEGDCYHSGGTIISNLPFQNIDSRAVGKCPRYVKQRS

LLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGWYG

FRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQF

ELIDNEFNEVEKQIGNVINWTRDSITEVWSYNAELLVAME

NQHTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFHK

CDDDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLSSGY

KDVILWFSFGASCFILLAIVMGLVFICVKNGNMRCTICI

55
AGR49734
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERG

A/pigeon/Shanghai/
VEVVNATETVERTNIPRICSKGKRTVDLGQCGLLGTITGPP

S1069/2013
QCDQFLEFSADLIIERREGSDVCYPGKFVNEEALRQILRES

2013/04/02 HA
GGIDKEAMGFTYSGIRTNGATSACRRSGSSFYAEMKWLLS

525339091
NTDNAAFPQMTKSYKNTRKSPALIVWGIHHSVSTAEQTKL

YGSGNKLVTVGSSNYQQSFVPSPGARPQVNGLSGRIDFH

WLMLNPNDTITFSFNGAFIAPDRASFLRGKSMGIQSGVQV

DANCEGDCYHSGGTIISNLPFQNIDSRAVGKCPRYVKQRS

LLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGWYG

FRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQF

ELIDNEFNEVEKQIGNVINWIRDSITEVWSYNAELLVAME

NQHTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFHK

CDDDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLSSGY

KDVILWFSFGASCFILLAIVMGLVFICVKNGNMRCTICI

56
AGR49770
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERG

A/wild
VEVVNATETVERTNIPRICSKGKKTVDLGQCGLLGTITGPP

pigeon/Jiangsu/
QCDQFLEFSADLIIERREGSDVCYPGKFVNEEALRQILRES

SD001/2013
GGIDKEAMGFTYSGIRTNGATSACRRSGSSFYAEMKWLLS

2013/04/17 HA
NTDNAAFPQMTKSYKNTRKSPALIVWGIHHSVSTAEQTKL

525339151
YGSGNKLVTVGSSNYQQSFVPSPGARPQVNGQSGRIDFH

WLMLNPNDTVTFSFNGAFIAPDRASFLRGKSMGIQSGVQV

DANCEGDCYHSGGTIISNLPFQNIDSRAVGKCPRYVKQRS

LLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGWYG

FRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQF

ELIDNEFNEVEKQIGNVINWTRDSITEVWSYNAELLVAME

NQHTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFHK

CDDDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLSSGY

KDVILWFSFGASCFILLAIVMGLVFICVKNGNMRCTICI

57
AGY41893
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERG

A/Huizhou/01/
VEVVNATETVERTNIPRICSKGKKTVDLGQCGLLGTITGPP

2013 2013/08/08
QCDQFLEFSADLIIERREGSDVCYPGKFVNEEALRQILRES

HA 552049496
GGIDKEAMGFTYSGIRANGATSACRRSGSSFYAEMKWLL

SNTDNAAFPQMTKSYKNTRKSPALIVWGIHHSVSTAEQTK

LYGSGNKLVTVGSSNYQQSFVPSPGARPQVNGLSGRIDFH

WLMLNPNDTVTFSFNGAFIAPDRASFLRGKSMGIQSGVQV

DADCEGDCYHSGGTIISNLPFQNIDSRAVGKCPRYVKQRS

LLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGWYG

FRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQF

ELIDNEFNEVEKQIGNVINWTRDSITEVWSYNAELLVAME

NQHTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFHK

CDDDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLSSGY

KDVILWFSFGASCFILLAIVMGLVFICVKNGNMRCTICI

58
AGY42258
FALVAIIPINADKICLGHHAVSNGTKVNTLTERGVEVVNA

A/mallard/Sweden/
TETVERTNVPRICSRGKRTVDLGQCGLLGTIXGPPQCDQFL

91/2002
EFSADLIIERREGSDVCYPGKFVNEEALRQILRESGGIDKET

2002/12/12 HA
MGFTYSGIRTNGAXSACRRSGSSFYAEMKWLLSNTDNAA

552052155
FPQMTKSYKNTRNDPALIIWGIHHSGSTTEQTKLYGSGNK

LITVGSSNYQQSFVPSPGARPQVNGQSGRIDFHWLILNPND

TVTFSFNGAFIAPDRASFLRGKSMGIQSGVQIDANCEGDC

YHSGGTHISNLPFQNINSRAVGKCPRYVKQESLLLATGMK

NVPEIPKGRGLFGAIAGFIENGWEGLIDGWYGFRHQNAQG

EGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELIDNEFTE

VEKQIGNVINWTRDSMTEVWSYNAELLVAMENQHTIDLA

DSEMNKLYERVRRQLRENAEEDGTGCFEIFHKCDDDCMA

SIRNNTYDHSKYREEAMQNRIQIDPVKLSSGYKDVILWFSF

GASCFILLAIAMGLVFMCVKNGNMRCTICI

59
AHA11441
MNTQILALIACMLIGAKGDKICLGHHAVANGTKVNTLTER

A/guinea
GIEVVNATETVETANIKKICTQGKRPTDLGQCGLLGTLIGP

fowl/Nebraska/
PQCDQFLEFDADLIIERREGTDVCYPGKFTNEESLRQILRG

17096/2011
SGGIDKESMGFTYSGIRTNGATSACRRSGSSFYAEMKWLL

2011/04/10 HA
SNSNNAAFPQMTKSYRNPRNKPALIVWGVHHSGSATEQT

557478572
KLYGSGSKLITVGSSKYQQSFTPSPGARPQVNGQSGRIDFH

WLLLDPNDTVTFTFNGAFIAPDRASFFRGESLGVQSDVPL

DSGCEGDCFHKGGTIVSSLPFQNINPRTVGKCPRYVKQTSL

LLATGMRNVPENPKTRGLFGAIAGFIENGWEGLIDGWYGF

RHQNAQGEGTAADYKSTQSAIDQITGKLNRLIDKTNQQFE

LIDNEFSEIEQQIGNVINWTRDSMTEIWSYNAELLVAMEN

QHTIDLADSEMNKLYERVRKQLRENAEEDGTGCFEIFHKC

DDQCMESIRNNTYDHTQYRAESLQNRIQIDPVKLSSGYKD

IILWFSFGASCFLLLAIAMGLVFICIKNGNMRCTICI

60
AHA11452
MNTQILALIACMLVGTKGDKICLGHHAVANGTKVNTLTE

A/turkey/Minnesota/
RGIEVVNATETVETANIKKICTQGKRPTDLGQCGLLGTLIG

32710/2011
PPQCDQFLEFDADLIIERREGTDVCYPGKFTNEEPLRQILR

2011/07/12 HA
GSGGIDKESMGFTYSGIRTNGATSTCRRSGSSFYAEMKWL

557478591
LSNSNNAAFPQMTKSYRNPRNKPALIVWGVHHSGSATEQ

TKLYGSGSKLITVGSSKYQQSFTPSPGARPQVNGQSGRIDF

HWLLLDPNDTVTFTFNGAFIAPDRASFFRGESLGVQSDVP

LDSGCEGDCFHKGGTIVSSLPFQNINPRTVGKCPRYVKQTS

LLLATGMRNVPENPKTRGLFGAIAGFIENGWEGLIDGWY

GFRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIDKTNQQ

FEMIDNEFSEIEQQIGNVINWTRDSMTEIWSYNAELLVAM

ENQHTIDLADSEMNKLYERVRKQLRENAEEDGTGCFEIFH

KCDDQCMESIRNNTYDHTQYRAESLQNRIQIDPVKLSSGY

KDIILWFSFGASCFLLLAIAMGLVFICIKNGNMRCTICI

61
AHA11461
MNTQILALIACMLVGTKGDKICLGHHAVANGTKVNTLTE

A/turkey/Minnesota/
RGIEVVNATETVETANIKKICTQGKRPTDLGQCGLLGTLIG

31900/2011
PPQCDQFLEFDADLIIERREGTDVCYPGKFTNEEPLRQILR

2011/07/05 HA
GSGGIDKESMGFTYSGIRTNGATSTCRRSGSSFYAEMKWL

557478606
LSNSNNAAFPQMTKSYRNPRNKPALIVWGVHHSGSATEQ

TKLYGSGSKLITVGSSKYQQSFTPSPGARPQVNGQSGRIDF

HWLLLDPNDTVTFTFNGAFIAPDRASFFRGESLGVQSDVP

LDSGCEGDCFHKGGTIVSSLPFQNINPRTVGKCPRYVKQTS

LLLATGMRNVPENPKTRGLFGAIAGFIENGWEGLIDGWY

GFRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIDKTNQQ

FELIDNEFSEIEQQIGNVINWTRDSMTEIWSYNAELLVAME

NQHTIDLADSEMNKLYERVRKQLRENAEEDGTGCFEIFHK

CDDQCMESIRNNTYDHTQYRAESLQNRIQIDPVKLSSGYK

DIILWFSFGASCFLLLAIAMGLVFICIKNGNMRCTICI

62
AHK10585
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERG

A/chicken/Guangdong/
VEVVNATETVERTNIPRICSKGKKTVDLGQCGLLGTITGPP

G1/2013
QCDQFLEFSADLIIERREGSDVCYPGKFVNEEALRQILRES

2013/05/05 HA
GGIDKEAMGFTYSGIRTNGATSACRRSGSSFYAEMKWLLS

587680636
NTDNAAFPQMTKSYKNTRKSPALIVWGIHHSVSTAEQTKL

YGSGNKLVTVGSSNYQQSFVPSPGARPQVNGLSGRIDFH

WLMLNPNDTVTFSFNGAFIAPDRASFLRGKSMGIQSGVQV

DANCEGDCYHSGGTIISNLPFQNIDSRAVGKCPRYVKQRS

LLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGWYG

FRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQF

ELIDNEFNEVEKQIGNVINWIRDSITEVWSYNAELLVAME

NQHTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFHK

CDDDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLSSGY

KDVILWFSFGASCFILLAIVMGLVFICVKNGNMRCTICI

63
AGG53366
MNTQILVFALVAIIPTNADKICLGHHAVSNGTKVNTLTER

A/wild
GVEVVNATETVERTNVPRICSKGKRTVDLGQCGLLGTITG

duck/Korea/
PPQCDQFLEFSADLIIERREGSDVCYPGKFVNEEALRQILRE

CSM42-34/2011
SGGIDKETMGLTYSGIRTNGATSACRRSGSSFYAEMKWLL

2011/03/ HA
SNTDNAAFPQMTKSYKNTRRDPALIVWGIHHSGSSTEQTK

459252887
LYGSGSKLITVGSSNYQQSFVPSPGARPQVNGQSGRIDFH

WLILNPNDTVTFSFNGAFIAPDRASFLRGKSMGIQSGVQV

DASCEGDCYHSGGTIISNLPFQNINSRAVGKCPRYVKQESL

MLATGMKNVPELPKGRGLFGAIAGFIENGWEGLIDGWYG

FRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQF

ELIDNEFTEVEKQIGNVINWTRDSMTEVWSYNAELLVAM

ENQHTIDLADSEMNKLYERVRRQLRENAEEDGTGCFEIFH

KCDDDCMASIRNNTYDHSKYREEAMQNRIQIDPVRLSSG

YKDVILWFSFGASCFILLAIAMGLVFICVKNGNMRCTICI

64
AGG53377
MNTQILVFALVAIIPTNADKICLGHHAVSNGTKVNTLTER

A/wild
GVEVVNATETVERTNVPRICSKGKRTVDLGQCGLLGTITG

duck/Korea/
PPQCDQFLEFSADLIIERREGSDVCYPGKFVNEEALRQILRE

CSM42-1/2011
SGGIDKETMGLTYSGIRTNGATSACRRSGSSFYAEMKWLL

2011/03/ HA
SNTDNAAFPQMTKSYKNTRRDPALIVWGIHHSGSSTEQTK

459252925
LYGSGSKLITVGSSNYQQSFVPSPGARPQVNGQSGRIDFH

WLILNPNDTVTFSFNGAFIAPDRASFLRGKSMGIQSGVQV

DASCEGDCYHSGGTIISNLPFQNINSRAVGKCPRYVKQESL

MLATGMKNVPELPKGRGLFGAIAGFIENGWEGLIDGWYG

FRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQF

ELIDNEFTEVEKQIGNVINWTRDSMTEVWSYNAELLVAM

ENQHTIDLADSEMNKLYERVRRQLRENAEEDGTGCFEIFH

KCDDDCMASIRNNTYDHSKYREEAMQNRIQIDPVRLSSG

YKDVILWFSFGASCFILLAIAMGLVFICVKNGNMRCT

65
AGG53399
MNTQILVFALVAIIPTNADKICLGHHAVSNGTKVNTLTER

A/wild
GVEVVNATETVERTNVPRICSKGKRTVDLGQCGLLGTITG

duck/Korea/
PPQCDQFLEFSADLIIERREGSDVCYPGKFVNEEALRQILRE

MHC39-26/2011
SGGIDKETMGFTYSGIRTNGATSACRRSGSSFYAEMKWLL

2011/03/ HA
SNTDNAAFPQMTKSYKNTRRDPALIVWGIHHSGSTTEQTK

459253005
LYGSGSKLITVGSSNYQQSFVPSPGARPQVNGQSGRIDFH

WLILNPNDTVTFSFNGAFIAPDRASFLRGKSMGIQSGVQV

DASCEGDCYHSGGTHISNLPFQNINSRAVGKCPRYVKQESL

MLATGMKNVPEPPKGRGLFGAIAGFIENGWEGLIDGWYG

FRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQF

ELIDNEFTEVEKQIGNVINWTRDSMTEVWSYNAELLVAM

ENQHTIDLADSEMNKLYERVRRQLRENAEEDGTGCFEIFH

KCDDDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLSSG

YKDVILWFSFGASCFILLAIAMGLVFICVKNGNMRCTICI

66
AGG53432
MNTQILVFALVAIIPTNADKICLGHHAVSNGTKVNTLTER

A/wild
GVEVVNATETVERTNVPRICSKGKRTVDLGQCGLLGTITG

duck/Korea/
PPQCDQFLEFSADLIIERREGSDVCYPGKFVNEEALRQILRE

MHC35-41/2011
SGGIDKETMGFTYSGIRTNGATSACRRSGSSFYAEMKWLL

2011/03/ HA
SNTDNAAFPQMTKSYKNTRRDPALIVWGIHHSGSTTEQTK

459253136
LYGSGSKLITVGSSNYQQSFVPSPGARPQVNGQSGRIDFH

WLILNPNDTVTFSFNGAFIAPDRASFLRGKSMGIQSGVQV

DASCEGDCYHSGGTIISNLPFQNINSRAVGKCPRYVKQESL

MLATGMKNVPEPPKGRGLFGAIAGFIENGWEGLIDGWYG

FRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQF

ELIDNEFTEVEKQIGNVINWTRDSMTEVWSYNAELLVAM

ENQHTIDLADSEMNKLYERVRRQLRENAEEDGTGCFEIFH

KCDDDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLSSG

YKDVILWFSFGASCFILLAIAMGLVFICVKNGNMRCT

67
AGG53476
MNTQILVFALVAIPTNADKICLGHHAVSNGTKVNTLTER

A/wild
GVEVVNATETVERTNVPRICSKGKRTVDLGQCGLLGTITG

duck/Korea/
PPQCDQFLEFSADLIIERREGSDVCYPGKFVNEEALRQILRE

SH19-27/2010
SGGIDKETMGFTYSGIRTNGATSACRRSGSSFYAEMKWLL

2010/12/ HA
SNTDNAAFPQMTKSYKNTRRDPALIVWGIHHSGSTTEQTK

459253257
LYGSGSKLITVGSSNYQQSFVPSPGARPQVNGQSGRIDFH

WLILNPNDTVTFSFNGAFIAPDRASFLRGKSMGIQSGVQV

DASCEGDCYHSGGTIISNLPFQNINSRAVGKCPRYVKQESL

MLATGMKNVPELPKGRGLFGAIAGFIENGWEGLIDGWYG

FRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQF

ELIDNEFTEVEKQIGNVINWTRDSMTEVWSYNAELLVAM

ENQHTIDLADSEMNKLYERVRRQLRENAEEDGTGCFEIFH

KCDDDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLSSG

YKDVILWFSFGASCFILLAIAMGLVFICVKNGNMRCTI

68
AGG53487
MNTQILVFALVAIPTNADKICLGHHAVSNGTKVNTLTER

A/wild
GVEVVNATETVERTNVPRICSKGKRTVDLGQCGLLGTITG

duck/Korea/
PPQCDQFLEFSADLIIERREGSDVCYPGKFVNEEALRQILRE

SH19-50/2010
SGGIDKETMGFTYSGIRTNGATSACRRSGSSFYAEMKWLL

2010/01/ HA
SNTDNAAFPQMTKSYKNTRRDPALIVWGIHHSGSTTEQTK

459253278
LYGSGSKLITVGSSNYQQSFVPSPGARPQVNGQSGRIDFH

WLILNPNDTVTFSFNGAFIAPDRASFLRGKSMGIQSGVQV

DASCEGDCYHSGGTIISNLPFQNINSRAVGKCPRYVKQESL

MLATGMKNVPELPKGRGLFGAIAGFIENGWEGLIDGWYG

FRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQF

ELIDNEFTEVEKQIGNVINWTRDSMTEVWSYNAELLVAM

ENQHTIDLADSEMNKLYERVRRQLRENAEEDGTGCFEIFH

KCDDDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLSSG

YKDVILWFSFGASCFILLAIAMGLVFICVKNGNMRCTICI

69
AGG53520
QILVFALVAIIPTNADKICLGHHAVSNGTKVNTLTERGVEV

A/wild
VNATETVERTNVPRICSKGKRTVDLGQCGLLGTITGPPQC

duck/Korea/
DQLLEFSADLIIERREGTDVCYPGKFVNEEALRQILRESGGI

SH20-27/2008
EKETMGFTYSGIRTNGATSACRRSGSSFYAEMKWLLSNTD

2008/12/ HA
NAAFPQMTKSYKNTRKDPALIIWGIHHSGSTTEQTKLYGS

459253409
GSKLITVGSSNYQQSFVPSPGARPQVNGQSGRIDFHWLML

NPNDTVTFSFNGAFIAPDRASFLRGKSMGIQSGVQVDANC

EGDCYHSGGTIISNLPFQNINSRAVGKCPRYVKQESLMLA

TGMKNVPELPKGRGLFGAIAGFIENGWEGLIDGWYGFRH

QNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELID

NEFTEVEKQIGNVINWTRDSMTEVWSYNAELLVAMENQH

TIDLADSEMNKLYERVKRQLRENAEEDGTGCFEIFHKCDD

DCMASIRNNTYDHSKYREEAMQNRIQINPVKLSSGYKDVI

LWFSFGASCFILLAIAMGLVFICVKNGNMR

70
AGL43637
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERG

A/Taiwan/1/2013
VEVVNATETVERTNIPRICSKGKRTVDLGQCGLLGTITGPP

2013// HA
QCDQFLEFSADLIIERREGSDVCYPGKFVNEEALRQILRES

496297389
GGIDKEAMGFTYSGIRTNGATSACRRSGSSFYAEMKWLLS

NTDNAAFPQMTKSYKNTRKSPALIVWGIHHSVSTAEQTKL

YGSGNKLVTVGSSNYQQSFVPSPGARPQVNGPSGRIDFHW

LMLNPNDTVTFSFNGAFIAPDRASFLRGKSMGIQSGVQVD

ANCEGDCYHSGGTIINNLPFQNIDSRAVGKCPRYVKQRSL

LLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGWYGF

RHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQFE

LIDNEFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMEN

QHTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFHKC

DDDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLSSGYK

DVILWFSFGASCFILLAIVMGLVFICVKNGNMRCTICI

71
AGL97639
IACMLVGAKGDKICLGHHAVANGTKVNTLTERGIEVVNA

A/mallard/
TETVETANIKKLCTQGKRPTDLGQCGLLGTLIGPPQCDQFL

Minnesota/AI09-
EFDADLIIERREGTDVCYPGKFTNEESLRQILRGSGGIDKES

3770/2009
MGFTYSGIRTNGATSACRRSGSSFYAEMKWLLSNSDNAA

2009/09/12 HA
FPQMTKSYRNPRNKPALIWGVHHSGSATEQTKLYGSGNK

505555371
LITVGSSKYQQSFTPSPGARPQVNGQSGRIDFHWLLLDPN

DTVTFTFNGAFIAPDRASFFRGESLGVQSDVPLDSGCEGDC

FHSGGTIVSSLPFQNINPRTVGKCPRYVKQTSLLLATGMRN

VPENPKTRGLFGAIAGFIENGWEGLIDGWYGFRHQNAQG

EGTAADYKSTQSAIDQITGKLNRLIDKTNQQFELIDNEFSEI

EQQIGNVINWTRDSMTELWSYNAELLVAMENQHTIDLAD

SEMNKLYERVRKQLRENAEEDGTGCFEIFHKCDDQCMESI

RNNTYDHTQYRTESLQNRIQIDPVKLS

72
AGO02477
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERG

A/Xuzhou/1/2013
VEVVNATETVERTNIPRICSKGKRTVDLGQCGLLGTITGPP

2013/04/25
QCDQFLEFSADLIERREGSDVCYPGKFVNEEALRQILRES

HA 512403688
GGIDKEAMGFTYSGIRTNGATSACRRSGSSFYAEMKWLLS

NTDNAAFPQMTKSYKNTRKSPALIVWGIHHSVSTAEQTKL

YGSGSKLVTVGSSNYQQSFVPSPGARPQVNGLSGRIDFHW

LMLNPNDTVTFSFNGAFIAPDRASFLRGKSMGIQSGVQVD

ANCEGDCYHSGGTIISNLPFQNIDSRAVGKCPRYVKQRSLL

LATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGWYGFR

HQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELI

DNEFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQ

HTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFHKCD

DDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLSSGYKD

VILWFSFGASCFILLAIVMGLVFICVKSRNMRCTICI

73
AGR84942
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERG

A/Suzhou/5/2013
VEVVNATETVERTNIPRICSKGKRTVDLGQCGLLGTITGPP

2013/04/12
QCDQFLEFSADLIIERREGSDVCYPGKFVNEEALRQILRES

HA 526304561
GGIDKEAMGFTYSGIRTNGATSACRRSGSSFYAEMKWLLS

NTDNAAFPQMTKSYKNTRKSPALIVWGIHHSVSTAEQTKL

YGSGSKLVTVGSSNYQQSFVPSPGARPQVNGLSGRIDFHW

LMLNPNDTVTFSFNGAFIAPDRASFLRGKSMGIQSGVQVD

ANCEGDCYHSGGTIISNLPFQNIDSRAVGKCPRYVKQRSLL

LATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGWYGFR

HQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELI

DNEFNEVEKQIGNVINWIRDSITEVWSYNAELLVAMENQ

HTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFHKCD

DDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLSSGYKD

VILWFSFGASCFILLAIVMGLVFICVKNGNMRCTICI

74
AGR84954
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERG

A/Nanjing/6/2013
VEVVNATETVERTNIPRICSKGKRTVDLGQCGLLGTITGPP

2013/04/11
QCDQFLEFSADLIIERREGSDVCYPGKFVNEEALRQILRES

HA 526304594
GGIDKEAMGFTYSGIRTNGATSACRRSGSSFYAEMKWLLS

NTDNAAFPQMTKSYKNTRKSPALIVWGIHHSVSTAEQTKL

YGSGNKLVTVGSSNYQQSFVPSPGARPQVNGLSGRIDFH

WLMLNPNDTVTFSFNGAFIAPDRASFLRGKSMGIQSGVQV

DANCEGDCYHSGGTHISNLPFQNIDSRAVGKCPRYVKQRS

LLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGWYG

FRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQF

ELIDNEFNEVEKQIGNVINWIRDSITEVWSYNAELLVAME

NQHTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFHK

CDDDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLSSGY

KDVILWFSFGASCFILLAIVMGLVFICVKNRNMRCTICI

75
AGR84978
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERG

A/Wuxi/4/2013
VEVVNATETVERTNIPRICSKGKKTVDLGQCGLLGTITGPP

2013/04/07 HA
QCDQFLEFSADLIIERREGSDVCYPGKFVNEEALRQILRES

526304656
GGIDKEAMGFTYSGIRTNGATSACRRSGSSFYAEMKWLLS

NTDNAAFPQMTKSYKNTRKSPALIVWGIHHSVSTAEQTKL

YGSGNKLVTVGSSNYQQSFVPSPGARPQVNGLSGRIDFH

WLMLNPNDTVTFSFNGAFIAPDRASFLRGKSMGIQSGVQV

DANCEGDCYHSGGTIISNLPFQNIDSRAVGKCPRYVKQRS

LLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGWYG

FRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQF

ELIDNEFNEVEKQIGNVINWIRDSITEVWSYNAELLVAME

NQHTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFHK

CDDDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLSSGY

KDVILWFSFGASCFILLAIVMGLVFICVKSRNMRCTICI

76
AGR84990
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERG

A/Wuxi/3/2013
VEVVNATETVERTNIPRICSKGKRTVDLGQCGLLGTITGPP

2013/04/07 HA
QCDQFLEFSADLIIERREGSDVCYPGKFVNEEALRQILRES

526304688
GGIDKEAMGFTYSGIRTNGATSACRRSGSSFYAEMKWLLS

NTDNAAFPQMTKSYKNTRKSPALIVWGIHHSVSTAEQTKL

YGSGNKLVTVGSSNYQQSFVPSPGARPQVNGLSGRIDFH

WLMLNPNDTVTFSFNGAFIAPDRASFLRGKSMGIQSGVQV

DANCEGDCYHSGGTIISNLPFQNIDSRAVGKCPRYVKQRS

LLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGWYG

FRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQF

ELIDNEFNEVEKQIGNVINWTRDSITEVWSYNAELLVAME

NQHTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFHK

CDDDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLSSGY

KDVILWFSFGASCFILLAIVMGLVFICVKSRNMRCTICI

77
AGR85002
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERG

A/Zhenjiang/1/
VEVVNATETVERTNIPRICSKGKMTVDLGQCGLLGTITGPP

2013 2013/04/07
QCDQFLEFSADLIIERREGSDVCYPGKFVNEEALRQILRES

HA 526304708
GGIDKEAMGFTYSGIRTNGATSACRRSGSSFYAEMKWLLS

NTDNAAFPQMTKSYKNTRKSPALIVWGIHHSVSTAEQTKL

YGSGNKLVTVGSSNYQQSFVPSPGARPQVNGLSGRIDFH

WLMLNPNDTVTFSFNGAFIAPDRASFLRGKSMGIQSGVQV

DANCEGDCYHSGGTIISNLPPQNIDSRAVGKCPRYVKQRS

LLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGWYG

FRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQF

ELIDNEFNEVEKQIGNVINWTRDSITEVWSYNAELLVAME

NQHTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFHK

CDDDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLSSGY

KDVILWFSFGASCFILLAIVMGLVFICVKSRNKRCTICI

78
AGR85026
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERG

A/Nanjing/2/2013
VEVVNATETVERTNIPRICSKGKMTVDLGQCGLLGTITGPP

2013/04/05
QCDQFLEFSADLIIERREGSDVCYPGKFVNEEALRQILRES

HA 526304762
GGIDKEAMGFTYSGIRTNGATSACRRSGSSFYAEMKWLLS

NTDNAAFPQMTKSYKNTRKSPALIVWGIHHSVSTAEQTKL

YGSGNKLVTVGSSNYQQSFVPSPGARPQVNGLSGRIDFH

WLMLNPNDTVTFSFNGAFIAPDRASFLRGKSMGIQSGVQV

DANCEGDCYHSGGTIISNLPFQNIDSRAVGKCPRYVKQRS

LLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGWYG

FRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQF

ELIDNEFNEVEKQIGNVINWTRDSITEVWSYNAELLVAME

NQHTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFHK

CDDDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLSSGY

KDVILWFSFGASCFILLAIVMGLVFICVKSRNMRCTICI

79
AGU02230
LVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERGGEVVN

A/Zhejiang/
ATETVERTNIPRICSKGKRTVDLGQCGLRGTITGPPQCDQF

DTID-ZJU05/2013
LEFSADLIIERREGSDVCYPGKFVNEEALRQILRESGGIDKE

2013/04/ HA
AMGFTYSGIRTNGATSACRRSGSSFYAEMKWLLSNTDNA

532808765
AFPQMTKSYKNTRKSPALIVWGIHHSVSTAEQTKLYGSGN

KLVTVGSSNYQQSFVPSPGARPQVNGLSGRIDFHWLMLNP

NDTVTFSFNGAFIAPDRASFLRGKSMGIQSGVQVDANCEG

DCYHSGGTIISNLPFQNIDSRAVGKCPRYVKQRSLLLATG

MKNVPEIPKGRGLFGAIAGFIENGWEGLIDGWYGFRHQN

AQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELIDNE

FNEVEKQIGNVINWIRDSITEVWSYNAELLVAMENQHTID

LADSEMDKLYERVKRQLRENAEEDGTGCFEIFHKCDDDC

MASIRNNTYDHSKYREEAMQNRIQIDPVKLSSGYKDVILW

FSFGASCFILLAIVMGLVFICVKNGNMRCT

80
AGU02233
FALIAIIPTNADKICLGHHAVSNGTKVNTLTERGGEVVNAT

A/Zhejiang/DTID-
ETVERTNFPRICSKGKRTVDLGQCGLRGTITGPPQCDQFLE

ZJU08/2013
FSADLIIERREGSDVCYPGKFVNEEALRQILRESGGIDKEA

2013/04/ HA
MGFTYSGIRTNGATSACRRSGSSFYAEMKWLLSNTDNAA

532808788
FPQMTKSYKNTRKSPALIVWGIHHSVSTAEQTKLYGSGNK

LVTVGSSNYQQSFVPSPGARPQVNGLSGRIDFHWLMLNPN

DTVTFSFNGAFIAPDRASFLRGKSMGIQSGVQVDANCEGD

CYHSGGTIISNLPFQNIDSRAVGKCPRYVKQRSLLLATGM

KNVPEIPKGRGLFGAIAGFIENGWEGLIDGWYGFRHQNAQ

GEGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELIDNEFN

EVEKQIGNVINWTRDSITEVWSYNAELLVAMENQHTIDLA

DSEMDKLYERVKRQLRENAEEDGTGCFEIFHKCDDDCMA

SIRNNTYDHSKYREEAMQNRIQIDPVKLSSGYKDVILWFSF

GASCFILLAIVMGLVFICVKNGNMRCT

81
AGW82588
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERG

A/tree
VEVVNATETVERTNIPRICSKGKRTVDLGQCGLLGTITGPP

sparrow/Shanghai/
QCDQFLEFSADLIIERREGSDVCYPGKFVNEEALRQILRES

01/2013
GGIDKEAMGFTYSGIRTNGATSACRRSGSSFYAEMKWLLS

2013/05/09 HA
NTDNAAFPQMTKSYKNTRKSPALIVWGIHHSVSTAEQTKL

546235348
YGSGNKLVTVGSSNYQQSFVPSPGARPQVNGLSGRIDFH

WLMLNPNDTVTFSFNGAFIAPDRASFLRGKSMGIQSGVQV

DANCEGDCYHSGGTIISNLPFQNIDSRAVGKCPRYVKQRS

LLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGWYG

FRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQF

ELIDNEFNEVEKQIGNVINWTRDSITEVWSYNAELLVAME

NQHTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFHK

CDDDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLSSGY

KDVILWFSFGASCFILLAIVMGLVFICVKNGNMRCTIGI

82
AGW82600
ALIAIIPTNADKICLGHHAVSNGTKVNTLTERGVEVVNATE

A/Shanghai/
TVERTNIPRICSKGKRTVDLGQCGLLGTITGPPQCDQFLEF

CN01/2013
SADLIIERREGSDVCYPGKFVNEEALRQILRESGGIDKEAM

2013/04/11 HA
GFTYSGIRTNGATSACRRSRSSFYAEMKWLLSNTDNAAFP

546235368
QMTKSYKNTRKSPALIVWGIHHSVSTAEQTKLYGSGNKL

VTVGSSNYQQSFVPSPGARPQVNGLSGRIDFHWLMLNPN

DTVTFSFNGAFIAPDRASFLRGKSMGIQSGVQVDANCEGD

CYHSGGTIMSNLPFQNIDSRAVGKCPRYVKQRSLLLATGM

KNVPEIPKGRGLFGAIAGFIENGWEGLIDGWYGFRHQNAQ

GEGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELIDNEFN

EVEKQIGNVINWTRDSITEVWSYNAELLVAMENQHTIDLA

DSEMDKLYERVKRQLRENAEEDGTGCFEIFHKCDDDCMA

SIRNNTYDHSKYREEAMQNRIQIDPVKLSSGYKDVILWFSF

GASCFILLAIVMGLVFICVKNGNMRCTICI

83
AGW82612
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERG

A/Shanghai/JS01/
VEVVNATETVERTNIPRICSKGKRTVDLGQCGLLGTITGPP

2013
QCDQFLEFSADLIIERREGSDVCYPGKFVNEEALRQILRES

2013/04/03 HA
GGIDKEAMGFTYSGIRTNGATSACRRSGSSFYAEMKWLLS

546235388
NTDNAAFPQMTKSYKNTRKNPALIVWGIHHSGSTAEQTK

LYGSGNKLVTVGSSNYQQSFAPSPGARTQVNGQSGRIDFH

WLMLNPNDTVTFSFNGAFIAPDRASFLRGKSMGIQSGVQV

DADCEGDCYHSGGTIISNLPFQNIDSRAVGKCPRYVKQRS

LLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGWYG

FRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQF

ELIDNEFTEVEKQIGNVINWTRDSITEVWSYNAELLVAME

NQHTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFHK

CDDDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLSSGY

KDVILWFSFGASCFILLAIAMGLVFICVKNGNMRCTICI

84
AHA11472
MNTQILALIACMLIGAKGDKICLGHHAVANGTKVNTLTER

A/turkey/Minnesota/
GIEVVNATETVETANVKKICTQGKRPTDLGQCGLLGTLIG

31676/2009
PPQCDQFLEFDADLIIERREGTDVCYPGKFTNEESLRQILR

2009/12/08 HA
GSGGIDKESMGFTYSGIRTNGETSACRRSGSSFYAEMKWL

557478625
LSNSNNAAFPQMTKSYRNPRDKPALIIWGVHHSGSATEQT

KLYGSGNKLITVGSSKYQQSFTPSPGARPQVNGQSGRIDF

HWLLLDPNDTVTFTFNGAFIAPDRASFFRGESLGVQSDVP

LDSGCEGDCFHSGGTIVSSLPFQNINPRTVGKCPRYVKQTS

LLLATGMRNVPEKPKTRGLFGAIAGFIENGWEGLIDGWY

GFRHQNAQGEGTAADYKSTQSAIDQITNKLNRLIDKTNQQ

FELIDNEFSEIEQQIGNVINWTRDSMTEVWSYNAELLVAM

ENQHTIDLADSEMNKLYERVRKQLRENAEEDGTGCFEIFH

KCDDQCMESIRNNTYDHTQYRKESLQNRIQIDPVKLSSGY

KDIILWFSFGASCFLLLAIAMGLVFICIKNGNMRCTICI

85
AHA11483
MNTQILALIACMLIGAKGDKICLGHHAVANGTKVNTLTER

A/turkey/Minnesota/
GIEVVNATETVETANVKKICTQGKRPTDLGQCGLLGTLIG

14135-2/
PPQCDQFLEFDADLIIERREGTDVCYPGKFTNEESLRQILR

2009
GSGGIDKESMGFTYSGIRTNGATSACRRSGSSFYAEMKWL

2009/08/07 HA
LSNSNNAAFPQMTKSYRNPRDKPALIIWGVHHSGSATEQT

557478644
KLYGSGNKLITVGSSKYQQSFTPSPGARPQVNGQSGRIDF

HWLLLDPNDTVTFTFNGAFIAPDRASFFRGESLGVQSDVP

LDSGCEGDCFHSGGTIVSSLPFQNINPRTVGKCPRYVKQTS

LLLATGMRNVPEKPKTRGLFGAIAGFIENGWEGLIDGWY

GFRHQNAQGEGTAADYKSTQSAIDQITSKLNRLIDKTNQQ

FELIDNEFSEIEQQIGNVINWTRDSMTEVWSYNAELLVAM

ENQHTIDLADSEMNKLYERVRKQLRENAEEDGTGCFEIFH

KCDDQCMESIRNNTYDHTQYRKESLQNRIQIDPVKLSSGY

KDIILWFSFGASCFLLLAIAMGLVFICIKNGNMRCTICI

86
AHA11500
TQILVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERGVE

A/Zhejiang/DTID-
VVNATETVERTNIPRICSKGKRTVDLGQCGLLGTITGPPQC

ZJU10/2013
DQFLEFSADLIIERREGSDVCYPGKFVNEEALRQILRESGGI

2013/10/14 HA
DKEAMGFTYSGIRTNGATSACRRSGSSFYAEMKWLLSNT

557478676
DNAAFPQMTKSYKNTRKSPALIVWGIHHSVSTAEQTKLY

GSGNKLVTVGSSNYQQSFVPSPGARPPVNGLSGRIDFHWL

MLNPNDTVTFSFNGAFIAPDRASFLRGKSMGIQSGVQVDA

NCEGDCYHSGGTIISNLPFQNIDSRAVGKCPRYVKQRSLLL

ATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGWYGFRH

QNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELID

NEFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQH

TIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFHKCDD

DCMASIRNNTYDHSKYREEAMQNRIQIDPVKLSSGYKDVI

LWFSFGASCFILLAIVMGLVFICVKN

87
AHA57050
MNTQILALIACMLIGAKGDKICLGHHAVANGTKVNTLTER

A/turkey/Minnesota/
GIEVVNATETVETANVKKICTQGKRPTDLGQCGLLGTLIG

14659/2009
PPQCDQFLEFDADLIIERREGTDVCYPGKFTNEESLRQILR

2009/08/12 HA
GSGGIDKESMGFTYSGIRTNGATSACRRSGSSFYAEMKWL

558484427
LSNSNNAAFPQMTKSYRNPRDKPALIWGVHHSGSATEQT

KLYGSGNKLITVGSSKYQQSFTPSPGARPQVNGQSGRIDF

HWLLLDPNDTVTFTFNGAFIAPDRASFFRGESLGVQSDVP

LDSGCEGDCFHSGGTIVSSLPFQNINPRTVGKCPRYVKQTS

LLLATGMRNVPEKPKTRGLFGAIAGFIENGWEGLIDGWY

GFRHQNAQGEGTAADYKSTQSAIDQITSKLNRLIDKTNQQ

FELIDNEFSEIEQQIGNVINWTRDSMTEVWSYNAELLVAM

ENQHTIDLADSEMNKLYERVRKQLRENAEEDGTGCFEIFH

NCDDQCMESIRNNTYDHTQYRKESLQNRIQIDPVKLSSGY

KDIILWFSFGASCFLLLAIAMGLVFICIKNGNMRCTICI

88
AHA57072
MNTQILALIACMLIGAKGDKICLGHHAVANGTKVNTLTER

A/turkey/Minnesota/
GIEVVNATETVETANVKKICTQGKRPTDLGQCGLLGTLIG

18421/2009
PPQCDQFLEFDADLIIERREGTDVCYPGKFTNEESLRQILR

2009/09/09 HA
GSGGIDKESMGFTYSGIRTNGATSACRRSGSSFYAEMKWL

558484465
LSNSNDAAFPQMTKSYRNPRDKPALIWGVHHSGSATEQT

KLYGSGNKLITVGSSKYQQSFTPSPGARPQVNGQSGRIDF

HWLLLDPNDTVTFTFNGAFIAPDRASFFRGESLGVQSDVP

LDSGCEGDCFHSGGTIVSSLPFQNINPRTVGKCPRYVKQTS

LLLATGMRNVPEKPKTRGLFGAIAGFIENGWEGLIDGWY

GFRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIDKTNQQ

FELIDNEFSEIEQQIGNVINWTRDSMTEVWSYNAELLVAM

ENQHTIDLADSEMNKLYERVRKQLRENAEEDGTGCFEIFH

KCDDQCMESIRNNTYDHTQYRKESLQNRIQIDPVKLSSGY

KDIILWFSFGASCFLLLAIAMGLVFICIKNGNMRCTICI

89
AHD25003
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERG

A/Guangdong/02/
VEVVNATETVERTNIPRICSKGKKTVDLGQCGLLGTITGPP

2013 2013/10/
QCDQFLEFSADLIIERREGSDVCYPGKFVNEEALRQILRES

HA 568260567
GGIDKEAMGFTYSGIRANGATSACRRSGSSFYAEMKWLL

SNTDNAAFPQMTKSYKNTRKSPALIVWGIHHSVSTAEQTK

LYGSGNKLVTVGSSNYQQSFVPSPGARPQVNGLSGRIDFH

WLMLNPNDTVTFSFNGAFIAPDRASFLRGKSMGIQSGVQV

DANCEGDCYHSGGTIISNLPFQNIDSRAVGKCPRYVKQRS

LLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGWYG

FRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQF

ELIDNEFNEVEKQIGNVINWTRDSITEVWSYNAELLVAME

NQHTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFHK

CDDDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLSSGY

KDVILWFSFGASCFILLAIVMGLVFICVKNGNM

90
AHF20528
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERG

A/Hong
VEVVNATETVERTNIPRICSKGKRTVDLGQCGLLGTITGPP

Kong/470129/
QCDQFLEFSADLIIERREGSDVCYPGKFVNEEALRQILRES

2013 2013/11/30
GGIDKEAMGFTYSGIRANGATSACRRSGSSFYAEMKWLL

HA 570933555
SNTDNAAFPQMTKSYKNTRKSPALIVWGIHHSVSTAEQTK

LYGSGNKLVTVGSSNYQQSFVPSPGARPQVNGLSGRIDFH

WLMLNPNDTVTFSFNGAFIAPDRASFLRGKSMGIQSGVQV

DANCEGDCYHSGGTIISSLPFQNIDSRAVGKCPRYVKQRSL

LLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGWYGF

RHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQFE

LIDNEFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMEN

QHTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFHKC

DDDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLSSGYK

DVILWFSFGASCFILLAIVMGLVFICVKNGNMRCTICI

91
AHF20568
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERG

A/Shanghai/
VEVVNATETVERTNIPRICSKGKRTVDLGQCGLLGTITGPP

CN02/2013
QCDQFLEFSADLIIERREGSDVCYPGKFVNEEALRQILRES

2013/04/02 HA
GGIDKEAMGFTYSGIRTNGATSACRRSGSSFYAEMKWLLS

570933626
NTDNAAFPQMTKSYKNTRKSPALIVWGIHHSVSTAEQTKL

YGSGNKLVTVGSSNYQQSFVPSPGARPQVNGLSGRIDFH

WLMLNPNDTVTFSFNGAFIAPDRASFLRGKSMGIQSGVQV

DANCEGDCYHSGGTIMSNLPFQNIDSRAVGKCPRYVKQR

SLLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGWY

GFRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQ

FELIDNEFNEVEKQIGNVINWTRDSITEVWSYNAELLVAM

ENQHTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFH

KCDDDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLSSG

YKDVILWFSFGASCFILLAIVMGLVFICVKNGNMRCTICI

92
AHH25185
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERG

A/Guangdong/
VEVVNATETVERTNIPRICSKGKKTVDLGQCGLLGTITGPP

04/2013
QCDQFLEFSADLIIERREGSDVCYPGKFVNEEALRQILRES

2013/12/16 HA
GGIEKEAMGFTYSGIRANGATSACRRSGSSFYAEMKWLLS

576106234
NTDNAAFPQMTKSYKNTRKSPALIVWGIHHSVSTAEQTKL

YGSGNKLVTVGSSNYQQSFVPSPGARPQVNGLSGRIDFH

WLMLNPNDTVTFSFNGAFIAPDRASFLRGKSMGIQSGVQV

DANCEGDCYHSGGTHISNLPFQNIDSRAVGKCPRYVKQRS

LLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGWYG

FRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQF

ELIDNEFNEVEKQIGNVINWTRDSITEVWSYNAELLVAME

NQHTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFHK

CDDDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLSSGY

KDVILWFSFGASCFILLAIVMGLVFICVKNGNMRCTICI

93
AHJ57411
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERG

A/Shanghai/PD-
VEVVNATETVERTNIPRICSKGKRTVDLGQCGLLGTITGPP

01/2014
QCDQFLEFSADLHIERREGSDVCYPGKFVNEEALRQILRES

2014/01/17 HA
GGIDKEAMGFTYSGIRTNGATSACRRSGSSFYAEMKWLLS

585478041
NTDNAAFPQMTKSYKNTRKSPALIVWGIHHSVSTAEQTKL

YGSGNKLVTVGSSNYQQSFVSSPGARPQVNGLSGRIDFH

WLMLNPNDTVTFSFNGAFIAPDRASFLRGKSMGIQSGVQV

DANCKGDCYHSGGTIISNLPFQNIDSRAVGKCPRYVKQRS

LLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGWYG

FRHQNAQGEGTAADYKSTQSAIDQITGKLNRIIEKTNQQFE

LIDNEFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMEN

QHTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFHKC

DDDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLSSGYK

DVILWFSFGASCFILLAIVMGLVFICVKNGNMRCTICI

94
AHJ57418
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERG

A/Shanghai/PD-
VEVVNATETVERTNIPRICSKGKRTVDLGQCGLLGTITGPP

02/2014
QCDQFLEFSADLIIERREGSDICYPGKFVNEEALRQILRESG

2014/01/17 HA
GIDKEAMGFTYSGIRTNGATSACRRSGSSFYAEMKWLLSN

585478256
TDNAAFPQMTKSYKNTRKSPALIVWGIHHSVSTAEQTKLY

GSGNKLVTVGSSNYQQSFVPSPGARPQVNGLSGRIDFHWL

MLNPNDTVTFSFNGAFIAPDRASFLKGKSMGIQSGVQVDA

NCEGDCYHSGGTIISNLPFQNIDSRAVGKCPRYVKQRSLLL

ATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGWYGFRH

QNAQGEGTAADYKSTQSAIDQITGKLNRIIEKTNQQFELID

NEFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQH

TIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFHKCDD

DCMASIRNNTYDHSKYREEAMQNRIQIDPVKLSSGYKDVI

LWFSFGASCFILLAIVMGLVFICVKNGNMRCTICI

95
AHK10800
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERG

A/Shanghai/01/
VEVVNATETVERTNIPRICSKGKRTVDLGQCGLLGTITGPP

2014 2014/01/03
QCDQFLEFSADLIIERREGSDVCYPGKFVNEEALRQILRES

HA 587681014
GGIDKEAMGFTYSGIRTNGATSACRRSGSSFYAEMKWLLS

NTDNAAFPQMTKSYKNTRKSPALIVWGIHHSVSTAEQTKL

YGSGNKLVTVGSSNYQQSFVPSPGARPQVNGLSGRIDFH

WLMLNPNDTVTFSFNGAFIAPDRASFLRGKSMGIQSGVQV

DANCEGDCYHSGGTIISNLPFQNIDSRAVGKCPRYVKQRS

LLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGWYG

FRHQNAQGEGTAADYKSTQSAIDQITGKLNRIIEKTNQQFE

LIDNEFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMEN

QHTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFHKC

DDDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLSSGYK

DVILWFSFGASCFILLAIVMGLVFICVKNGNMRCTICI

96
AHM24224
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERG

A/Beijing/3/
VEVVNATETVERTNIPRICSKGKRTVDLGQCGLLGTITGPP

2013 2013/04/16
QCDQFLEFSADLIIERREGSDVCYPGKFVKEEALRQILRES

HA 594704802
GGIDKEAMGFTYSGIRTNGATSACRRSGSSFYAEMKWLLS

NTDNAAFPQMTKSYKNTRKSPALIVWGIHHSVSTAEQTKL

YGSGNKLVTVGSSNYQQSFVPSPGARPQVNGLSGRIDFH

WLMLNPNDTVTFSFNGAFIAPDRASFLRGKSMGIQSGVQV

DANCEGDCYHSGGTIISNLPFQNIDSRAVGKCPRYVKQRS

LLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGWYG

FRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQF

ELIDNEFNEVEKQIGNVINWTRDSITEVWSYNAELLVAME

NQHTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFHK

CDDDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLSSGY

KDVILWFSFGASCFILLAIVMGLVFICVKNGNMRCTICI

97
AHN96472
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERG

A/chicken/
VEVVNATETVERTNIPRICSKGKKTVDLGQCGLLGTITGPP

Shanghai/PD-CN-
QCDQFLEFSADLIIERREGSDVCYPGKFVNEEALRQILRES

02/2014
GGIDKEAMGFTYSGIRTNGATSACRRSGSSFYAEMKWLLS

2014/01/21 HA
NTDNAAFPQMTKSYKNTRKSPALIVWGIHHSVSTAEQTKL

602701641
YGSGNKLVTVGSSNYQQSFVPSPGARPQVNGLSGRIDFH

WLMLNPNDTVTFSFNGAFIAPDRASFLRGKSMGIQSGVQV

DANCEGDCYHSGGTIISNLPFQNIDSRAVGKCPRYVKQKS

LLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGWYG

FRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQF

ELIDNEFNEVEKQIGNVINWTRDSITEVWSYNAELLVAME

NQHTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFHK

CDDDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLSSGY

KDVILWFSFGASCFILLAIVMGLVFICVKNGNMRCTICI

98
AHZ39686
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERG

A/Anhui/
VEVVNATETVERTNIPRICSKGKRTVDLGQCGLLGTITGPP

DEWH72-01/2013
QCDQFLEFSADLIIERREGSDVCYPGKFVNEEALRQILRES

2013// HA
GGIDKEAMGFTYSGIRTNGATSACRRSGSSFYAEMKWLLS

632807036
NTDDAAFPQMTKSYKNTRKSPALIVWGIHHSVSTAEQTKL

YGSGNKLVTVGSSNYQQSFVPSPGARPQVNGLSGRIDFH

WLMLNPNDTVTFSFNGAFIAPDRASFLRGKSMGIQSGVQV

DANCEGDCYHSGGTIISNLPFQNIDSRAVGKCPRYVKQRS

LLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGWYG

FRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQF

ELIDNEFNEVEKQIGNVINWIRDSITEVWSYNAELLVAME

NQHTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFHK

CDDDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLSSGY

KDVILWFSFGASCFILLAIVMGLVFICVKNGNMRCTICI

99
AHZ39710
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERG

A/Anhui/
VEVVNATETVERTNIPRICSKGKRTVDLGQCGLLGTITGPP

DEWH72-03/2013
QCDQFLEFSADLIIERREGSDVCYPGKFVNEEALRQILRES

2013// HA
GGIDKEAMGFTYSGIRTDGATSACRRSGSSFYAEMKWLLS

632807076
NTDDAAFPQMTKSYKNTRKSPALIVWGIHHSVSTAEQTKL

YGSGNKLVTVGSSNYQQSFVPSPGARPQVNGLSGRIDFH

WLMLNPNDTVTFSFNGAFIAPDRASFLRGKSMGIQSGVQV

DANCEGDCYHSGGTIISNLPFQNIDSRAVGKCPRYVKQRS

LLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGWYG

FRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQF

ELIDNEFNEVEKQIGNVINWIRDSITEVWSYNAELLVAME

NQHTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFHK

CDDDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLSSGY

KDVILWFSFGASCFILLAIVMGLVFICVKNGNMRCTICI

100
AHZ39746
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERG

A/Anhui/
VEVVNATETVERTNIPRICSKGKRTVDLGQCGLLGTITGPP

DEWH72-06/2013
QCDQFLEFSADLIIERREGSDVCYPGKFVNEEALRQILRES

2013// HA
GGIDKEAMGFTYSGIRTNGATSACRRSGSSFYAEMKWLLS

632807136
NTDNAAFPQMTKSYKNTRKSPALIVWGIHHSVSTAEQTKL

YGSGNKLVTVGSSNYQQSFVPSPGERPQVNGLSGRIDFHW

LMLNPNDTVTFSFNGAFIAPDRASFLRGKSMGIQSGVQVD

ANCEGDCYHSGGTHISNLPFQNIDSRAVGKCPRYVKQRSLL

LATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGWYGFR

HQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELI

DNEFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQ

HTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFHKCD

DDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLSSGYKD

VILWFSFGASCFILLAIVMGLVFICVKNGNMRCTICI

101
AHZ41929
MNTQILVFALVAIPINADKICLGHHAVSNGTKVNTLTERG

A/mallard/Sweden/
VEVVNATETVERTNVPRICSRGKRTVDLGQCGLLGTITGP

1621/2002
PQCDQFLEFSADLIIERREGSDVCYPGKFVNEEALRQILRES

2002/12/12 HA
GGIDKETMGFTYSGIRTNGATSACRRSGSSFYAEMKWLLS

632810949
NTDNAAFPQMTKSYKNTRNDPALIIWGIHHSGSTTEQTKL

YGSGNKLITVGSSNYQQSFVPSPGARPQVNGQSGRIDFHW

LILNPNDTVTFSFNGAFIAPDRASFLRGKSMGIQSGVQIDA

NCEGDCYHSGGTIISNLPFQNINSRAVGKCPRYVKQESLLL

ATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGWYGFRH

QNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELID

NEFTEVEKQIGNVINWTRDSMTEVWSYNAELLVAMENQH

TIDLADSEMNKLYERVRRQLRENAEEDGTGCFEIFHKCDD

DCMASIRNNTYDHSKYREEAMQNRIQIDPVKLSSGYKDVI

LWFSFGASCFILLAIAMGLVFMCVKNGNMRCTICI

102
AHZ42537
MNTQILAFIACMLVGAKGDKICLGHHAVANGTKVNTLTE

A/mallard/
RGIEVVNATETVETANIKKLCTQGKRPTDLGQCGLLGTLI

Minnesota/A109-
GPPQCDQFLEFDADLIIERREGTDVCYPGKFTNEESLRQIL

3770/2009
RGSGGIDKESMGFTYSGIRTNGATSACRRSGSSFYAEMKW

2009/09/12 HA
LLSNSDNAAFPQMTKSYRNPRNKPALIWGVHHSGSATEQ

632811964
TKLYGSGNKLITVGSSKYQQSFTPSPGARPQVNGQSGRIDF

HWLLLDPNDTVTFTFNGAFIAPDRASFFRGESLGVQSDVP

LDSGCEGDCFHSGGTIVSSLPFQNINPRTVGKCPRYVKQTS

LLLATGMRNVPENPKTRGLFGAIAGFIENGWEGLIDGWY

GFRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIDKTNQQ

FELIDNEFSEIEQQIGNVINWTRDSMTELWSYNAELLVAM

ENQHTIDLADSEMNKLYERVRKQLRENAEEDGTGCFEIFH

KCDDQCMESIRNNTYDHTQYRTESLQNRIQIDPVKLSSGY

KDIILWFSFGASCFLLLAIAMGLVFICIKNGNMRCTICI

103
AHZ42549
MNTQILAFIACMLVGVRGDKICLGHHAVANGTKVNTLTE

A/ruddy
KGIEVVNATETVESANIKKICTQGKRPTDLGQCGLLGTLIG

turnstone/
PPQCDQFLEFDSDLIIERREGTDVCYPGKFTNEESLRQILRG

Delaware/AI00-
SGGIDKESMGFTYSGIRTNGATSACRRLGSSSFYAEMKWL

1538/2000
LSNSDNAAFPQMTKSYRNPRNKPALIIWGVHHSGSANEQT

2000/05/20 HA
KLYGSGNKLITVGSSKYQQSFTPSPGARPQVNGQSGRIDF

632811984
HWLLLDPNDTVTFTFNGAFIAPDRASFFRGESLGIQSDVPL

DSSCGGDCFHSGGTIVSSLPFQNINPRTVGKCPRYVKQTSL

LLATGMRNVPENPKTRGLFGAIAGFIENGWEGLIDGWYGF

RHQNAQGEGTAADYKSTQSAIDQITGKLNRLIDKTNQQFE

LMDNEFNEIEQQIGNVINWTRDSMTEVWSYNAELLVAME

NQHTIDLADSEMNKLYERVRKQLRENAEEDGTGCFEIFHK

CDDQCMESIRNNTYDHTQYRTESLQNRIQIDPVKLSSGYK

DIILWFSFGASCFLLLAIAMGLIFICIKNGNMRCTICI

104
AID70634
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERG

A/Shanghai/
VEVVNATETVERTNIPRICSKGKRTVDLGQCGLLGTITGPP

Mix1/2014
QCDQFLEFSADLIIERREGSDVCYPGKFVNEEALRQILRES

2014/01/03 HA
GGIDKEAMGFTYSGIRTNGATSACRRSGSSFYAEMKWLLS

660304650
NTDNAAFPQMTKSYKNTRKSPALIVWGIHHSVSTAEQTKL

YGSGNKLVTVGSSNYQQSFVPSPGARPQVNGLSGRIDFH

WLMLNPNDTVTFSFNGAFIAPDRASFLRGKSMGIQSGVQV

DANCEGDCYHSGGTIISNLPFQNIDSRAVGKCPRYVKQRS

LLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGWYG

FRHQNAQGEGTAADYKSTQSAIDQITGKLNRIIEKTNQQFE

LIDNEFNEVEKQISNVINWIRDSITEVWSYNAELLVAMEN

QHTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFHKC

DDDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLSSGYK

DVILWFSFGASCFILLAIVMGLVFICVKNGNMRCTICI

105
AIN76383
MNTQILVFALIAIVPTNADKICLGHHAVSNGTKVNTLTER

A/Zhejiang/
GVEVVNATETVERTNIPRICSKGKKTVDLGQCGLLGTITGP

LS01/2014
PQCDQFLEFSADLIIERREGSDVCYPGKFVNEEALRQILRES

2014/02/08 HA
GGIDKEAMGFTYSGIRTNGTTSACRRSGSSFYAEMKWLLS

684694637
NTDNAAFPQMTKSYKNTRKSPALIVWGIHHSVSTAEQTKL

YGSGNKLVTVGSSNYQQSFVPSPGARPQVNGLSGRIDFH

WLMLNPNDTVTFSFNGAFIAPDRASFLRGKSMGIQSGVQV

DANCEGDCYHSGGTIISNLPFQNIDSRAVGKCPRYVKQKS

LLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGWYG

FRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQF

ELIDNEFNEVEKQIGNVINWTRDSITEVWSYNAELLVAME

NQHTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFHK

CDDDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLSSGY

KDVILWFSFGASCFILLAIVMGLVFICVKNGNMRCTICI

106
AIU46619
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERG

A/chicken/
VEVVNATETVERTNIPRICSKGKRTVDLGQCGLLGTITGPP

Zhejiang/DTID-
QCDQFLEFSADLIIERREGSDVCYPGKFVNEEALRQILRES

ZJU06/2013
GGIDKEAMGFTYSGIRTNGATSACRRSGSSFYAEMKWLLS

2013/12/ HA
NTDNAAFPQMTKSYKNTRKSPALIVWGIHHSVSTAEQTKL

699978931
YGSGNKLVTVGSSNYQQSFVPSPGARPQVNGLSGRIDFH

WLMLNPNDTVTFSFNGAFIAPDRASFLRGKSMGIQSGVEV

DANCEGDCYHSGGTIISNLPFQNIDSRAVGKCPRYVKQRS

LLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGWYG

FRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQF

ELIDNEFNEVEKQIGNVINWTRDSITEVWSYNAELLVAME

NQHTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFHK

CDDDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLSSGY

KDVILWFSFGASCFILLAIVMGLVFICVKNGNMRCTICI

107
AIU47013
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERG

A/chicken/
VEVVNATETVERTNIPRICSKGKRTVDLGQCGLLGTITGPP

Suzhou/040201H/
QCDQFLEFSADLIIERREGSDVCYPGKFVNEEALRQILRES

2013 2013/04/ HA
GGIDKEAMGFTYSGIRTNGATSACRRSGSSFYAEMKWLLS

699979673
NTDNAAFPQMTKSYKNTRKSPALIVWGIHHSVSTAEQTKL

YGSGNKLVTVGSSNYQQSFVPSPGARPQVNGLSGRIDFH

WLMLNPNDTVTFSFNGAFIAPDRASFLRGKSMGIQSGVQV

DANCEGDCYHSGGTIISNLPFQNIDSRAVGKCPRYVKQRS

LLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGWYG

FRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQF

ELIDNEFNEVEKQIGNVINWTRDSITEVWSYNAELLVAME

NQHTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFHK

CDDDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLSSGY

KDMILWFSFGASCFILLAIVMGLVFICVKNGNMRCTICI

108
AJJ90490
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERG

A/chicken/
VEVVNATETVERTNIPRICSKGKKTVDLGQCGLLGTITGPP

Shenzhen/742/2013
QCDQFLEFSADLIIERREGSDVCYPGKFVNEEALRQILRES

2013/12/10 HA
GGIDKEAMGFTYSGIRANGATSACRRSGSSFYAEMKWLL

755178094
SNTDNAAFPQMTKSYKNTRRSPALIVWGIHHSVSTAEQTK

LYGSGNKLVTVGSSNYQQSFVPSPGARPQVNGLSGRIDFH

WLMLNPNDTVTFSFNGAFIAPDRASFLRGKSMGIQSGVQV

DANCEGDCYHSGGTIISNLPFQNIDSRAVGKCPRYVKQRS

LLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGWYG

FRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQF

ELIDNEFNEVEKQIGNVINWIRDSITEVWSYNAELLVAME

NQHTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFHK

CDDDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLSSGY

KDVILWFSFGASCFILLAIVMGLVFICVKNGNMRCTICI

109
AJJ90526
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERG

A/chicken/
VEVVNATETVERTNIPRICSKGKKTVDLGQCGLLGTITGPP

Shenzhen/898/2013
QCDQFLEFSADLIIERREGSDICYPGKFVNEEALRQILRESG

2013/12/09 HA
GIDKEAMGFTYSGIRANGATSACKRSGSSFYAEMKWLLS

755178154
NTDNAAFPQMTKSYKNTRKSPALIVWGIHHSVSTAEQTKL

YGSGNKLVTVGSSNYQQSFVPSPGARPQVNGLSGRIDFH

WLMLNPNDTVTFSFNGAFIAPDRASFLRGKSMGIQSGVQV

DANCEGDCYHSGGTIISSLPFQNIDSRAVGKCPRYVKQRSL

LLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGWYGF

RHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQFE

LIDNEFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMEN

QHTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFHKC

DDDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLSRGYK

DVILWFSFGASCFILLAIVMGLVFICVKNGNMRCTICI

110
AJJ90538
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERG

A/silkie
VEVVNATETVERTNIPRICSKGKKTVDLGQCGLLGTITGPP

chicken/Shenzhen/
QCDQFLEFSADLIIERREGSDVCYPGKFVNEEALRQILRES

918/2013
GGIDKEAMGFTYSGIRANGATSACRRSGSSFYAEMKWLL

2013/12/09 HA
SNTDNAAFPQMTKSYKNTRKSPALIVWGIHHSVSTAEQTK

755178174
LYGSGNKLVTVGSSNYQQSFVPSPGARPQVNGLSGRIDFH

WLMLNPNDTVTFSFNGAFIAPDRASFLRGKSMGIQSGVQV

DANCEGDCYHSGGTIISNLPFQNIDSRAVGKCPRYVKQRS

LLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGWYG

FRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQF

ELIDNEFNEVEKQIGNVINWIRDSITEVWSYNAELLVAME

NQHTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFHK

CDDDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLSSGY

KDVILWFSFGASCFILLAIVMGLVFICVKNGNMRCTICI

111
AJJ90576
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERG

A/chicken/Shenzhen/
VEVVNATETVERTNIPRICSKGKKTVDLGQCGLLGTITGPP

1665/2013
QCDQFLEFSADLIIERREGSDICYPGKFVNEEALRQILRESG

2013/12/12 HA
GIDKEAMGFTYSGIRANGATSACKRSGSSFYAEMKWLLS

755178238
NTDNAAFPQMTKSYKNTRKSPALIVWGIHHSVSTAEQTKL

YGSGNKLVTVGSSNYQQSFVPSPGARPQVNGLSGRIDFH

WLMLNPNDTVTFSFNGAFIAPDRASFLRGKSMGIQSGVQV

DANCEGDCYHSGGTIISNLPFQNIDSRAVGKCPRYVKQRS

LLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGWYG

FRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQF

ELIDNEFNEVEKQIGNVINWTRDSITEVWSYNAELLVAME

NQHTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFHK

CDDDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLSRGY

KDVILWFSFGASCFILLAIVMGLVFICVKNGNMRCTICI

112
AJJ90588
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERG

A/chicken/Shenzhen/
VEVVNATETVERTNIPRICSKGKKTVDLGQCGLLGTITGPP

2110/2013
QCDQFLEFSADLIIERREGSDVCYPGKFVNEEALRQILRES

2013/12/13 HA
GGIDKEAMGFTYSGIRANGATSACRRSGSSFYAEMKWLL

755178258
SNTDNAAFPQMTKSYKNTRRSPALIVWGIHHSVSTAEQTK

LYGSGNKLVTVGSSNYQQSFVPSPGARPQVNGLSGRIDFH

WLMLNPNDTVTFSFNGAFIAPDRASFLRGKSIGIQSGVQV

DANCEGDCYHSGGTIISNLPFQNIDSRAVGKCPRYVKQRS

LLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGWYG

FRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQF

ELIDNEFNEVEKQIGNVINWTRDSITEVWSYNAELLVAME

NQHTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFHK

CDDDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLSSGY

KDVILWFSFGASCFILLAIVMGLVFICVKNGNMRCTICI

113
AJJ90661
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERG

A/chicken/Dongguan/
VEVVNATETVERTNIPRICSKGKKTVDLGQCGLLGTITGPP

2912/2013
QCDQFLEFSADLIIERREGSDVCYPGKFVNEEALRQILRES

2013/12/18 HA
GGIDKEAMGFTYSGIRANGATSACRRSGSSFYAEMKWLL

755178380
SNTDNAAFPQMTKSYKNTRKSPALIVWGIHHSVSTAEQTK

LYGSGNKLVTVGSSNYQQSFVPSPGARPQVNGLSGRIDFH

WLMLNPNDTVTFSFNGAFIAPDRASFLRGKSMGIQSGVQV

DANCEGDCYHSGGTHISNLPFQNIDSRAVGKCPRYVKQRS

LLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGWYG

FRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQF

ELIDNEFNEVEKQIGNVINWTRDSITEVWSYNAELLVAME

NQHTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFHK

CDNDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLSSGY

KDVILWFSFGASCFILLAIVMGLVFICVKNGNMRCTICI

114
AJJ90673
MNTQILVFALTAIIPTNADKICLGHHAVSNGTKVNTLTERG

A/silkie
VEVVNATETVERTNIPRICSKGKKTVDLGQCGLLGTITGPP

chicken/Dongguan/
QCDQFLEFSADLIIERREGSDVCYPGKFVNEEALRQILRES

3049/2013
GGIDKEAMGFTYSGIRANGATSACRRSGSSFYAEMKWLL

2013/12/18 HA
SNTDNAAFPQMTKSYKNTRKSPALIVWGIHHSVSTAEQTK

755178400
LYGSGNKLVTVGSSNYQQSFVPSPGARPQVNGLSGRIDFH

WLMLNPNDTVTFSFNGAFIAPDRASFLRGKSMGIQSGVQV

DANCEGDCYHSGGTIISNLPFQNIDSRAVGKCPRYVKQRS

LLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGWYG

FRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQF

ELIDNEFNEVEKQIGNVINWTRDSITEVWSYNAELLVAME

NQHTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFHK

CDNDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLSSGY

KDVILWFSFGASCFILLAIVMGLVFICVKNGNMRCTICI

115
AJJ90795
MNTQILVFALIAIIPTNADKICLGHHAVPNGTKVNTLTERG

A/silkie
VEVVNATETVERTNIPRICSKGKKTVDLGQCGLLGTITGPP

chicken/Dongguan/
QCDQFLEFSADLIIERREGSDVCYPGKFVNEEALRQILRES

3281/2013
GGIDKEAMGFTYSGIRANGATSACRRSGSSFYAEMKWLL

2013/12/18 HA
SNTDNAAFPQMTKSYKNTRKSPALIVWGIHHSVSTAEQTK

755178604
LYGSGNKLVTVGSSNYQQSFVPSPGARPQVNGLSGRIDFH

WLMLNPNDTVTFSFNGAFIAPDRASFLRGKSMGIQSGVQV

DANCEGDCYHSGGTIISNLPFQNIDSRAVGKCPRYVKQRS

LLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGWYG

FRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQF

ELIDNEFNEVEKQIGNVINWTRDSITEVWSYNAELLVAME

NQHTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFHK

CDDDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLSSGY

KDVILWFSFGASCFILLAIVMGLVFICVKNGNMRCTICI

116
AJJ90891
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERG

A/silkie
VEVVNATETVERTNIPRICSKGKKTVDLGQCGLLGTITGPP

chicken/Dongguan/
QCDQFLEFSADLIIERREGSDVCYPGKFVNEEALRQILRES

3520/2013
GGIDKEAMGFTYSGIRANGATSACRRSGSSFYAEMKWLL

2013/12/19 HA
SNTDNAAFPQMTKSYKNTRKXPALIVWGIHHSVSTAEQT

755178764
KLYGSGNKLVTVGSSNYQQSFVPSPGARPQVNGLSGRIDF

HWLMLNPNDTVTFSFNGAFIAPDRASFLRGKSMGIQSGVQ

VDANCEGDCYHSGGTIISNLPFQNIDSRAVGKCPRYVKQR

SLLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGWY

GFRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQ

FELIDNEFNEVEKQIGNVINWIRDSITEVWSYNAELLVAM

ENQHTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFH

KCDNDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLSSG

YKDVILWFSFGASCFILLAIVMGLVFICVKNGNMRCTICI

117
AJJ90951
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERG

A/chicken/
VEVVNATETVERTNIPRICSKGKKTVDLGQCGLLGTITGPP

Dongguan/3544/2013
QCDQFLEFSADLIIERREGSDVCYPGKFVNEEALRQILRES

2013/12/19 HA
GGIDKEAMGFTYSGIRANGATSACRRSGSSFYAEMKWLL

755178864
SNTDNAAFPQMTKSYRNTRKSPALIVWGIHHSVSTAEQTK

LYGSGNKLVTVGSSNYQQSFVPSPGARPQVNGLSGRIDFH

WLMLNPNDTVTFSFNGAFIAPDRASFLRGKSMGIQSGVQV

DANCEGDCYHSGGTIISNLPFQNIDSRAVGKCPRYVKQRS

LLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGWYG

FRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQF

ELIDNEFNEVEKQIGNVINWTRDSITEVWSYNAELLVAME

NQHTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFHK

CDDDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLSSGY

KDVILWFSFGASCFILLAIVMGLVFICVKNGNMRCTICI

118
AJJ91035
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERG

A/chicken/
VEVVNATETVERTNIPRICSKGKKTVDLGQCGLLGTITGPP

Shenzhen/3780/2013
QCDQFLEFSADLIIERREGSDVCYPGKFVNEEALRQILRES

2013/12/19 HA
GGIDKEAMGFTYSGIRANGATSACRRSGSSFYAEMKWLL

755179004
SNTDNAAFPQMTKSYKNTRRSPALIVWGIHHSVSTAEQTK

LYGSGNKLVTVGSSNYQQSFVPSPGARPQVNGLSGRIDFH

WLMLNPNDTVTFSFNGAFIAPDRASFLRGKSMGIQSGVQV

DANCEGDCYHSGGTIISNLPFQNIDNRAVGKCPRYVKQRS

LLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGWYG

FRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQF

ELIDNEFNEVEKQIGNVINWTRDSITEVWSYNAELLVAME

NQHTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFHK

CDDDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLSSGY

KDVILWFSFGASCFILLAIVMGLVFICVKNGNMRCTICI

119
AJJ91155
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERG

A/chicken/
VEVVNATETVERTNIPRICSKGKKTVDLGQCGLLGTITGPP

Dongguan/4037/2013
QCDQFLEFSADLIIERREGSDVCYPGKFVNEEALRQILRES

2013/12/19 HA
GGIDKEAMGFTYSGIRANGATSACRRSGSSFYAEMKWLL

755179204
SNTDNAAFPQMTKSYKNTRKSPALIVWGIHHSVSTAEQTK

LYGSGNKLVTVGSSNYQQSFVPSPGARPQVNGLSGRIDFH

WLMLNPNDTVTFSFNGAFIAPDRASFLRGKSMGIQSGVQV

DANCEGDCYHSGGTHISNLPFQNIDSRAVGKCPRYVKQRS

LLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGWYG

FRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQF

ELIDNEFNEVEKQIGNVINWTRDSITEVWSYNAELLVAME

NQHTIDLADSEMNKLYERVKRQLRENAEEDGTGCFEIFHK

CDDDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLSSGY

KDVILWFSFGASCFILLAIVMGLVFICVKNGNMRCTICI

120
AJJ92005
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERG

A/chicken/
VEVVNATETVERTNIPRICSKGKKTVDLGQCGLLGTITGPP

Shenzhen/801/2013
QCDQFLEFSADLIIERREGSDVCYPGKFVNEEALRQILRES

2013/12/09 HA
GGIDKEAMGFTYSGIRANGATSACRRSGSSFYAEMKWLL

755180629
SNTDNAAFPQMTKSYKNTRKSPALIVWGIHHSVSTAEQTK

LYGSGNKLVTVGSSNYQQSFVPSPGARPQVNGLSGRIDFH

WLMLNPNDTVTFSFNGAFIAPDRASFLRGKSMGIQSGVQV

DANCEGDCYHSGGTIISNLPFQNIDSRAVGKCPRYVKQRS

LLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGWYG

FRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQF

ELIDNEFNEVEKQIGNVINWTRDSITEVWSYNAELLVAME

NQHTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFHK

CDDDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLSRGY

KDVILWFSFGASCFILLAIVMGLVFICVKNGNMRCTICI

121
AJJ94254
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERG

A/chicken/Dongguan/
VEVVNATETVERTNIPRICSKGKKTVDLGQCGLLGTITGPP

1374/2014
QCDQFLEFSADLIIERREGSDVCYPGKFVNEEALRQILRES

2014/02/21 HA
GGIDKEAMGFTYSGIRTNGATSACRRSGSSFYAEMKWLLS

755184382
NTDNAAFPQMTKSYKNTRKSPALIVWGIHHSVSTAEQTKL

YGSGNKLVTVGSSNYQQSFVPSPGARPQVNGLSGRIDFH

WLMLNPNDTVTFSFNGAFIAPERASFLRGKSMGIQSGVQV

DANCEGDCYHSGGTHISNLPFQNIDSRAVGKCPRYVKQRS

LLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGWYG

FKHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQF

ELIDNEFNEVETQIGNVINWTRDSITEVWSYNAELLVAME

NQHTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFHK

CDDDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLSSGY

KDVILWFSFGASCFILLAIVMGLVFICVKNGNMRCTICI

122
AJJ94606
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERG

A/chicken/
VEVVNATETVERTNIPRICSKGKKTVDLGQCGLLGTITGPP

Dongguan/191/2014
QCDQFLEFSADLIIERREGSDVCYPGKFVNEEALRQILRKS

2014/02/20 HA
GGIDKEAMGFTYSGIRTNGATSACRRSGSSFYAEMKWLLS

755184968
NTDNAAFPQMTKSYKNTRKSPAIIVWGIHHSVSTAEQTKL

YGSGNKLVTVGSSNYQQSFVPSPGARPQVNGLSGRIDFH

WLMLNPNDTVTFSFNGAFIAPDRASFLRGKSMGIQSGVQV

DADCEGDCYHSGGTHISNLPFQNIDSRAVGKCPRYVKQRS

LLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGWYG

FRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQF

ELIDNEFNEVEKQIGNVINWTRDSITEVWSYNAELLVAME

NQHTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFHK

CDDDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLSSGY

KDVILWFSFGASCFILLAIVMGLVFICVKNGNMRCTICI

123
AJJ96552
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERG

A/chicken/Jiangxi/
VEVVNATETVERTNIPRICSKGKKTIDLGQCGLLGTITGPP

12206/2014
QCDQFLEFSADLIIERREGSDVCYPGKFVNEEALRQILRES

2014/03/16 HA
GGIDKEAMGFTYSGIRTNGATSACRRSGSSFYAEMKWLLS

755188219
NTDNAAFPQMTKSYKNTRKSPALIVWGIHHSVSTAEQTKL

YGSGNKLVTVGSSNYQQSFVPSPGARPQVNGLSGRIDFH

WLMLNPNDTVTFSFNGAFIAPDRASFLRGKSMGIQSGVQV

DANCEGDCYHSGGTIISNLPFQNIDSRAVGKCPRYVKQKS

LLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGWYG

FRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQF

ELIDNEFNEVEKQIGNVINWTRDSITEVWSYNAELLVAME

NQHTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFHK

CDDDCMASIRNNTYDHNKYREEAMQNRIQIDPVKLSSGY

KDVILWFSFGASCFILLAIVMGLVFICVKNGNMRCTICI

124
AJJ96684
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKINTLTERG

A/chicken/Jiangxi/
VEVVNATETVERTNIPRICSKGKKTVDLGQCGLLGTITGPP

13207/2014
QCDQFLEFSADLIIERREGSDVCYPGKFVNEEALRQILRES

2014/03/30 HA
GGIDKEAMGFTYSGIRTNGATSACRRSGSSFYAEMKWLLS

755188439
NTDNAAFPQMTKSYKNTRKSPALIVWGIHHSVSTAEQTKL

YGSGNKLVTVGSSNYQQSFVPSPGARPQVNGLSGRIDFH

WLMLNPNDTVTFSFNGAFIAPDRASFLRGKSMGIQSGVQV

DANCEGDCYHSGGTIISNLPFQNIDSRAVGKCPRYVKQKS

LLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGWYG

FRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQF

ELIDNEFNEVEKQIGNVINWTRDSITELWSYNAELLVAME

NQHTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFHK

CDDDCMASINNTYDHSKYREEAMQNRIQIDPVKLSSGY

KDVILWFSFGASCFILLAIVMGLVFICVKNGNMRCTICI

125
AJJ96732
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERG

A/chicken/Jiangxi/
VEVVNATETVERTNIPRICSKGKKTVDLGQCGLLGTITGPP

13223/2014
QCDQFLEFSADLIIERREGSDVCYPGKFVNEEALRQILRES

2014/03/30 HA
GGIDKEAMGFTYSGIRTNGATSACRRSGSSFYAEMKWLLS

755188519
NTDNAAFPQMTKSYKNTRKSPALIVWGIHHSVSTAEQTKL

YGSGNKLVTVGSSNYQQSFVPSPGARPQVNGLSGRIDFH

WLMLNPNDTVTFSFNGAFIAPDRASFLRGKSMGIQSGVQV

DANCEGDCYHSGGTIISNLPFQNIDSRAVGKCPRYVKQKS

LLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGWYG

FRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQF

ELIDNEFNEVEKQIGNVINWTRDSITELWSYNAELLVAME

NQHTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFHK

CDDDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLSSGY

KDVILWFSFGASCFILLAIVMGLVFICVKNGNMRCTICI

126
AJK00354
MNTQILVFALVAIPTNADKICLGHHAVSNGTKVNTLTER

A/duck/Zhejiang/
GVEVVNATETVERTNIPRICSKGKKTVDLGQCGLLGTITGP

LS02/2014
PQCDQFLEFSADLIVERREGSDVCYPGKFVNEEALRQILRE

2014/01/12 HA
SGGIDKEAMGFTYSGIRTNGATSACRRSGSSFYAEMKWLL

755194469
SNTDNAAFPQMTKSYKNTRKDPALIIWGIHHSGSTTEQTK

LYGSGNKLITVGSSNYQQSFVPSPGARPLVNGQSGRIDFH

WLMLNPNDTVTFSFNGAFIAPDRASFLRGKSMGIQSGVQV

DANCEGDCYHSGGTIISNLPFQNINSRAVGKCPRYVKQES

LLLATGMKNVPEVPKGRGLFGAIAGFIENGWEGLIDGWY

GFRHQNAQGEGTAADYKSTQSAIDQVTGKLNRLIEKTNQ

QFELIDHEFTEVEKQIGNVINWTRDSMTEVWSYNAELLVA

MENQHTIDLADSEMNKLYERVKRQLRENAEEDGTGCFEIF

HKCDNDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLSS

GYKDVILWFSFGASCFILLAIVMGLVFICVKNGNMRCTICI

127
AJJ91264
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERG

A/silkie
VEVVNATETVERTNIPRICSKGKKTVDLGQCGLLGTITGPP

chicken/Dongguan/
QCDQFLEFSADLIIERREGSDVCYPGKFVNEEALRQILRES

4129/2013
GGIDKEAMGFTYSGIRANGATSACRRSGSSFYAEMKWLL

2013/12/19 HA
SNTDNAAFPQMTKSYKNTRKSPALIVWGIHHSVSTAEQTK

755179386
LYGSGNKLVTVGSSNYQQSFVPSPGARPQVNGLSGRIDFH

WLMLNPNDTVTFSFNGAFIAPDRASFLRGKSMGIQSGVQV

DANCEGDCYHSGGTHISNLPFQNIDSRAVGKCPRYVKQRS

LLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGWYG

FRHQNAQGEGTAADYKSTQSAIDQITGKLNRLMEKTNQQ

FELIDNEFNEVEKQIGNVINWIRDSITEVWSYNAELLVAM

ENQHTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFH

KCDDDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLSSG

YKDVILWFSFGASCFILLAIVMGLVFICVKNGNMRCTICI

128
AJJ91314
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERG

A/chicken/
VEVVNATETVERTNIPRICSKGKRTVDLGQCGLLGTITGPP

Shaoxing/2417/2013
QCDQFLEFSADLIIERREGSDVCYPGKFVNEEALRQILRES

2013/10/20 HA
GGIDKEAMGFTYSGIRTNGATSACRRSGSSFYAEMKWLLS

755179470
NTDNAAFPQMTKSYKNTRKSPALIVWGIHHSVSTAEQTKL

YGSGNKLVTVGSSNYQQSFVPSPGARPPVNGLSGRIDFHW

LMLNPNDTVTFSFNGAFIAPDRASFLRGKSMGIQSGVQVD

ANCEGDCYHSGGTIISNLPFQNIDSRAVGKCPRYVKQRSLL

LATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGWYGFR

HQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELI

DNEFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQ

HTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFHKCD

DDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLSSGYKD

VILWFSFGASCFILLAIVMGLVFICVKNGNMRCTICI

129
AJJ91402
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERG

A/chicken/Huzhou/
VEVVNATETVERTNIPRICSKGKRTVDLGQCGLLGTITGPP

4045/2013
QCDQFLEFSADLIIERREGSDVCYPGKFVNEEALRQILRES

2013/10/24 HA
GGIDKEAMGFTYSGIRTNGATSACRRSGSSFYAEMKWLLS

755179618
NTDNAAFPQMTKSYKNTRKSPALIVWGIHHSVSTAEQTKL

YGSGNKLVTVGSSNYQQSFVPSPGARPQVNGLSGRIDFH

WLMLNPNDTVTFSFNGAFIAPDRASFLRGKSMGIQSGVQV

DANCEGDCYHSGGTHISNLPFQNIDSRAVGKCPRYVKQRS

LLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGWYG

FRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQF

ELIDNEFNEVEKQIGNVINWTRDSITELWSYNAELLVAME

NQHTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFHK

CDDDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLSSGY

KEVILWFSFGASCFILLAIVMGLVFICVKNGNMRCTICI

130
AJJ91476
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERG

A/chicken/Huzhou/
VEVVNATETVERTNIPRICSKGKRTVDLGQCGLLGTITGPP

4076/2013
QCDQFLEFSADLIIERREGSDVCYPGKFVNEEALRQILRKS

2013/10/24 HA
GGIDKEAMGFTYSGIRTNGATSACRRSGSSFYAEMKWLLS

755179743
NTDNAAFPQMTKSYKNTRKSPALIVWGIHHSVSTAEQTKL

YGSGNKLVTVGSSNYQQSFVPSPGARPQVNGLSGRIDFH

WLMLNPNDTVTFSFNGAFIAPDRASFLRGKSMGIQSGVQV

DANCEGDCYHSRGTIISNLPFQNIDSRAVGKCPRYVKQRS

LLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGWYG

FRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQF

ELIDNEFNEVEKQIGNVINWTRDSITEVWSYNAELLVAME

NQHTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFHK

CDDDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLSSGY

KDVILWFSFGASCFILLAIVMGLVFICVKNGNMRCTICI

131
AJJ91725
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERG

A/chicken/
VEVVNATETVERTNIPRICSKGKRTVDLGQCGLLGTITGPP

Shaoxing/5201/2013
QCDQFLEFSADLIIERREGSDVCYPGKFVNEEALRQILRES

2013/10/28 HA
GGIDKEAMGFTYSGIRTNGATSACRRSGSSFYAEMKWLLS

755180161
NTDNAAFPQMTKSYKNTRKSPALIVWGIHHSVSTAEQTKL

YGSGNKLVTVGSSNYQQSFVPSPGARPQVNGLSGRIDFH

WLMLNPNDTVTFSFNGAFIAPDRASFLRGKSMGIQSGVQV

DANCEGDCYHSGGTIISNLPFQNIDSRAVGKCPRYVKQRS

LLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGWYG

FRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQF

ELIDNEFNEVEKQIGNVINWTRDSITELWSYNAELLVAME

NQHTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFHK

CDDDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLSSGY

KDVILWFSFGASCFILLAIVMGLVFICVKNGNMRCTICI

132
AJJ91885
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERG

A/Shenzhen/
VEVVNATETVERTNIPRICSKGKKTVDLGQCGLLGTITGPP

SP4/2014
QCDQFLEFSADLIIERREGSDVCYPGKFVNEEALRQILRES

2014/01/16 HA
GGIDKEAMGFTYSGIRANGVTSACRRSGSSFYAEMKWLL

755180429
SNTDNAAFPQMTKSYKNTRKSPALIVWGIHHSVSTAEQTK

LYGSGNKLVTVGSSNYQQSFVPSPGARPQVNGLSGRIDFH

WLMLNPNDTVTFSFNGAFIAPDRASFLRGKSMGIQSGVQV

DANCEGDCYHSGGTIISNLPFQNIDSRAVGKCPRYVKQRS

LLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGWYG

FRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQF

ELIDNEFNEVEKQIGNVINWTRDSITEVWSYNAELLVAME

NQHTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFHK

CDDDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLSRGY

KDVILWFSFGASCFILLAIVMGLVFICVKNGNMRCTICI

133
AJJ91909
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERG

A/Shenzhen/
VEVVNATETVERTNIPRICSKGKKTVDLGQCGLLGTITGPP

SP26/2014
QCDQFLEFSADLIIERREGSDICYPGKFVNEEALRQILRESG

2014/01/20 HA
GIDKEAMGFTYSGIRANGATSACKRSGSSFYAEMKWLLS

755180469
NTDNAAFPQMTKSYKNTRKSPALIVWGIHHSVSTAEQTKL

YGSGNKLVTVGSSNYQQSFVPSPGARPQVNGLSGRIDFH

WLMLNPNDTVTFSFNGAFIAPDRASFLRGKSMGIQSGVQV

DANCEGDCYHSGGTIISSLPFQNIDSRAVGKCPRYVKQRSL

LLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGWYGF

RHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQFE

LIDNEFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMEN

QHTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFHKC

DDGCMASIRNNTYDHSKYREEAMQNRIQIDPVKLSRGYK

DVILWFSFGASCFILLAIVMGLVFICVKNGNMRCTICI

134
AJJ91945
MNTQILAFALIAIIPTNADKICLGHHAVSNGTKVNTLTERG

A/Shenzhen/
VEVVNATETVERTNIPRICSKGKKTVDLGQCGLLGTITGPP

SP38/2014
QCDQFLEFSADLIIERREGSDVCYPGKFVNEEALRQILRES

2014/01/22 HA
GGIDKEAMGFTYSGIRANGATSACRRSGSSFYAEMKWLL

755180529
SNTDNAAFPQMTKSYKNTRKSPALIVWGIHHSVSTAEQTK

LYGSGNKLVTVGSSNYQQSFVPSPGARPQVNGLSGRIDFH

WLMLNPNDTVTFSFNGAFIAPDRASFLRGKSMGIQSGVQV

DANCEGDCYHSGGTIISNLPFQNIDSRAVGKCPRYVKQRS

LLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIGGWYG

FRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQF

ELIDNEFNEVEKQIGNVINWIRDSITEVWSYNAELLVAME

NQHTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFHK

CDDDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLSSGY

KDVILWFSFGASCFILLAIVMGLVFICVKNGNMRCTICI

135
AJJ91957
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERG

A/Shenzhen/
VEVVNATETVERTNIPRICSKGKRTVDLGQCGLLGTITGPP

SP44/2014
QCDQFLEFSADLIIERREGSDVCYPGKFVNEEALRQILRES

2014/01/23 HA
GGIDKEAMGFTYSGIRANGTTSACRRSGSSFYAEMKWLLS

755180549
NTDNAAFPQMTKSYKNTRKSPALIVWGIHHSVSTAEQTKL

YGSGNKLVTVGSSNYQQSFVPSPGARPQVNGLSGRIDFH

WLMLNPNDTVTFSFNGAFIAPDRASFLRGKSMGIQSGVQV

DANCEGDCYHSGGTIISSLPFQNIDSRAVGKCPRYVKQRSL

LLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGWYGF

RHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQFE

LIDNEFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMEN

QHTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFHKC

DDDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLSSGYK

DVILWFSFGASCFILLAIVMGLVFICVKNGNMRCTICI

136
AJJ91969
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERG

A/Shenzhen/
VEVVNATETVERTNIPRICSKGKKTVDLGQCGLLGTITGPP

SP48/2014
QCDQFLEFSADLIIERREGSDVCYPGKFVNEEALRQILRES

2014/01/23 HA
GGIDKEAMGFTYSGIRTNGATSACRRSGSSFYAEMKWLLS

755180569
NTDNAAFPQMTKSYKNTRKSPALIVWGIHHSVSTAEQTKL

YGSGNKLVTVGSSNYQQSFVPSPGARPQVNGLSGRIDFH

WLMLNPNDTVTFSFNGAFIAPDRASFLRGKSMGIQSGVQV

DANCEGDCYHSGGTIISNLPFQNIDSRAVGKCPRYVKQRS

LLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGWYG

FRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQF

ELIDNEFNEVETQIGNVINWTRDSITEVWSYNAELLVAME

NQHTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFHK

CDDDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLSSGY

KDVILWFSFGASCFILLAIVMGLVFICVKNGNMRCTICI

137
AJJ91993
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERG

A/chicken/
VEVVNATETVERTNIPRICSKGKKTVDLGQCGLLGTITGPP

Dongguan/4119/2013
QCDQFLEFSADLIIERREGSDVCYPGKFVNEEALRQILRES

2013/12/19 HA
GGIDKEAMGFTYSGIRANGATSACRRSGSSFYAEMKWLL

755180609
SNTDNAAFPQMTKSYKNTRKSPALIVWGIHHSVSTAEQTK

LYGSGNKLVTVGSSNYQQSFVPSPGARPQVNGLSGRIDFH

WLMLNPNDTVTFSFNGAFIAPDRASFLRGKSMGIQSGVQV

DANCEGDCYHSGGTIISNLPFQNIDSRAVGKCPRYVKQRS

LLLATGMKNVPEIPKGRGLLGAIAGFIENGWEGLIDGWYG

FRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQF

ELIDNEFNEVEKQIGNVINWTRDSITEVWSYNAELLVAME

NQHTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFHK

CDDDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLSSGY

KDVILWFSFGASCFTLLAIVMGLVFICVKNGNMRCTICI

138
AJJ92031
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERG

A/chicken/
VEVVNATETVERTNIPRICSKGKKTVDLGQCGLLGTITGPP

Dongguan/4064/2013
QCDQFLEFSADLIIERREGSDVCYPGKFVNEEALRQILRES

2013/12/19 HA
GGIDKEAMGFTYSGIRANGATSACRRSGSSFYAEMKWLL

755180672
SNTDNAAFPQMTKSYKNTRKSPALIVWGIHHSVSTAEQTK

LYGSGNKLVTVESSNYQQSFVPSPGARPQVNGLSGRIDFH

WLMLNPNDTVTFSENGAFIAPDRASFLRGKSMGIQSGVQV

DANCEGDCYHSGGTIISNLPFQNIDSRAVGKCPRYVKQRS

LLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGWYG

FRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQF

ELIDNEFNEVEKQIGNVINWTRDSITEVWSYNAELLVAME

NQHTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFHK

CDDDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLSSGY

KDVILWFSFGASCFILLAIVMGLVFICVKNGNMRCTICI

139
AJJ92967
MNTQILVFALIAIVPTNADKICLGHHAVSNGTKVNTLTER

A/silkie
GVEVVNATETVERTNIPRICSKGKKTVDLGQCGLLGTITGP

chicken/Jiangxi/
PQCDQFLEFSADLIIERREGSDVCYPGKFVNEEALRQILRES

9469/2014
GGIDKEAMGFTYSGIRTNGVTSACRRSGSSFYAEMKWLLS

2014/02/16 HA
NTDNAAFPQMTKSYKNTRKSPALIVWGIHHSVSTAEQTKL

755182232
YGSGNKLVTVGSSNYQQSFVPSPGARPQVNGLSGRIDFH

WLMLNPNDTVTFSFNGAFIAPDRASFLRGKSMGIQSGVQV

DANCEGDCYHSGGTIISNLPFQNIDSRAVGKCPRYVKQKS

LLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGWYG

FRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQF

ELIDNEFNEVEKQIGNVINWTRDSITEVWSYNAELLVAME

NQHTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFHK

CDDDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLSSGY

KDVILWFSFGASCFILLAIVMGLVFICVKNGNMRCTICI

140
AJJ93027
MNTQILVFALIAIVPTNADKICLGHHAVSNGTKVNTLTER

A/chicken/Jiangxi/
GVEVVNATETVERTNIPRICSKGKKTVDLGQCGLLGTITGP

9558/2014
PQCDQFLEFSADLIIERREGSDVCYPGKFVKEEALRQILRES

2014/02/16 HA
GGIDKEAMGFTYSGIRTNGVTSACRRSGSSFYAEMKWLLS

755182332
NTDNAAFPQMTKSYKNTRKSPALIVWGIHHSVSTAEQTKL

YGSGNKLVTVGSSNYQQSFVPSPGARPQVNGLSGRIDFH

WLMLNPNDTVTFSFNGAFIAPDRASFLRGKSMGIQSGVQV

DANCEGDCYHSGGTHISNLPFQNIDSRAVGKCPRYVKQKS

LLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGWYG

FRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQF

ELIDNEFNEVEKQIGNVINWTRDSITEVWSYNAELLVAME

NQHTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFHK

CDDDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLSSGY

KDVILWFSFGASCFILLAIVMGLVFICVKNGNMRCTICI

141
AJJ93051
MNTQILVFALIAIVPTNADKICLGHHAVSNGTKVNTLTER

A/chicken/Jiangxi/
GVEVVNATETVERTNIPRICSKGKKTVDLGQCGLLGTITGP

10573/2014
PQCDQFLEFSADLIIERREGSDVCYPGKFVNEEALRQILRES

2014/02/18 HA
GGIDKEAMGFTYSGIRTNGVTSACRRSGSSFYAEMKWLLS

755182372
NTDDAAFPQMTKSYKNTRKSPALIVWGIHHSVSTAEQTKL

YGSGNKLVTVGSSNYQQSFVPSPGARPQVNGLSGRIDFH

WLMLNPNDTVTFSFNGAFIAPDRASFLRGKSMGIQSGVQV

DANCEGDCYHSGGTHISNLPFQNIDSRAVGKCPRYVKQKS

LLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGWYG

FRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQF

ELIDNEFNEVEKQIGNVINWTRDSITEVWSYNAELLVAME

NQHTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFHK

CDDDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLSSGY

KDVILWFSFGASCFILLAIVMGLVFICVKNGNMRCTICI

142
AJJ93845
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERG

A/silkie
VEVVNATETVERTNIPRICSKGKKTVDLGQCGLLGTITGPP

chicken/Dongguan/
QCDQFLEFSADLIIERREGSDVCYPGKFVNEEALRQILRES

157/2014
GGIDKEAMGFTYSGIRANGATSACRRSGSSFYAEMKWLL

2014/02/20 HA
SNTDNAAFPQMTKSYKNTRKSPALIVWGIHHSVSTAEQTK

755183695
LYGSGNKLVTVGSSNYQQSFVPSPGARPQVNGLSGRIDFH

WLMLNPNDTVTFSFNGAFIAPDRASFLRGKSMGIQSGVQV

DANCEGDCYHSGGTIISNLPFQNIDSRAVGKCPRYVKQKS

LLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGWYG

FRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQF

ELIDNEFNEVEKQIGNVINWTRDSITEVWSYNAELLVAME

NQHTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFHK

CDNDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLSSGY

KDVILWFSFGASCFILLAIVMGLVFICVKNGNMRCTICI

143
AJJ93857
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERG

A/chicken/Dongguan/
VEVVNATETVERTNIPRICSKGKKTVDLGQCGLLGTITGPP

169/2014
QCDQFLEFSADLIIERREGSDVCYPGKFVNEEALRQILRKS

2014/02/20 HA
GGIDKEAMGFTYSGIRTNGATSACMRSGSSFYAEMKWLL

755183715
SNTDNAAFPQMTKSYKNTRKSPAIIVWGIHHSVSTAEQTK

LYGSGNKLVTVGSSNYQQSFVPSPGARPQVNGLSGRIDFH

WLMLNPNDTVTFSFNGAFIAPDRASFLRGKSMGIQSGVQV

DADCEGDCYHSGGTIISNLPFQNIDSRAVGKCPRYVKQRS

LLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGWYG

FRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQF

ELIDNEFNEVEKQIGNVINWIRDSITEVWSYNAELLVAME

NQHTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFHK

CDDDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLSSGY

KDVILWFSFGASCFILLAIVMGLVFICVKNGNMRCTICI

144
AJJ93869
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERG

A/chicken/
VEVVNATETVERTNIPRICSKGKKTVDLGQCGLLGTVTGP

Dongguan/173/2014
PQCDQFLEFSADLIIERREGSDVCYPGKFVNEEALRQILRES

2014/02/20 HA
GGIDKEAMGFTYSGIRANGATSACRRSGSSFYAEMKWLL

755183735
SNTDNAAFPQMTKSYKNTRKSPALIVWGIHHSVSTAEQTK

LYGSGNKLVTVGSSNYQQSFVPSPGARPQVNGLSGRIDFH

WLMLNPNDTVTFSFNGAFIAPDRASFLRGKSMGIQSGVQV

DANCEGDCYHSGGTIISNLPFQNIDSRAVGKCPRYVKQKS

LLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGWYG

FRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQF

ELIDNEFNEVEKQIGNVINWTRDSITEVWSYNAELLVAME

NQHTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFHK

CDNDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLSSGY

KDVILWFSFGASCFILLAIVMGLVFICVKNGNMRCTICI

145
AJJ93881
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERG

A/chicken/
VEVVNATETVERTNIPRICSKGKKTVDLGQCGLLGTVTGP

Dongguan/189/2014
PQCDQFLEFSADLIIERREGSDVCYPGKFVNEEALRQILRES

2014/02/20 HA
GGIDKEAMGFTYSGIRANGATSACRRSGSSFYAEMKWLL

755183755
SNTDNAAFPQMTKSYKNTRKSPALIVWGIHHSVSTAEQTK

LYGSGNKLVTVGSSNYQQSFVPSPGARPQVNGLSGRIDFH

WLMLNPNDTVTFSFNGAFIAPDRASFLRGKSMGIQSGVQV

DANCEGDCYHSGGTIISNLPFQNIDSRAVGKCPKYVKQKS

LLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGWYG

FRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQF

ELIDNEFNEVEKQIGNVINWTRDSITEVWSYNAELLVAME

NQHTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFHK

CDNDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLSSGY

KDVILWFSFGASCFILLAIVMGLVFICVKNGNMRCTICI

146
AJJ93907
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERG

A/chicken/
VEVVNATETVERTNIPRICSKGKKTVDLGQCGLLGTITGPP

Dongguan/449/2014
QCDQFLEFSADLIIERREGSDVCYPGKFVNEEALRQILRES

2014/02/20 HA
GGIDKEAMGFTYSGIRANGATSACRRSGSSFYAEMKWLL

755183799
SNTDNAAFPQMTKSYKNTRKSPALIVWGIHHSVSTAEQTK

LYGSGNKLVTVGSSNYQQSFVPSPGARPQVNGLSGRIDFH

WLMLNPNDTVTFSFNGAFIAPERASFLRGKSMGIQSGVQV

DANCEGDCYHSGGTIISNLPFQNIDSRAVGKCPRYVKQRS

LLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGWYG

FRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQF

ELIDNEFNEVEKQIGNVINWTRDSITEVWSYNAELLVAME

NQHTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFHK

CDDDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLSSGY

KDVILWFSFGASCFILLAIVMGLVFICVKNGNMRCTICI

147
AJJ93931
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERG

A/chicken/
VEVVNATETVERTNIPRICSKGKKTVDLGQCGLLGTITGPP

Dongguan/536/2014
QCDQFLEFSADLIIERREGSDVCYPGKFVNEEALRQILRKS

2014/02/20 HA
GGIDKEAMGFTYSGIRTNGATSACRRSGSSFYAEMKWLLS

755183839
NTDNAAFPQMTKSYKNTRKSPAIIVWGIHHSVSTAEQTKL

YGSGNKLVTVGSSNYQQSFVPSPGARPQVNGLSGRIDFH

WLMLNPNDTVTFSFNGAFIAPDRASFLRGKSMGIQSGVQV

DADCEGDCYHSGGTIISKLPFQNIDSRAVGKCPRYVKQRS

LLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGWYG

FRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQF

ELIDNEFNEVEKQIGNVINWTRDSITEVWSYNAELLVAME

NQHTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFHK

CDDDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLSSGY

KDVILWFSFGASCFILLAIVMGLVFICVKNGNMRCTICI

148
AJJ93943
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERG

A/chicken/
VEVVNATETVERTNIPRICSKGKKTVDLGQCGLLGTITGPP

Dongguan/568/2014
QCDQFLEFSADLIIERREGSDVCYPGKFVNEEALRQILRES

2014/02/20 HA
GGIEKEAMGFTYSGIRANGATSACRRSGSSFYAEMKWLLS

755183859
NTDNAAFPQMTKSYKNTRKSPALIVWGIHHSVSTAEQTKL

YGSGNKLVTVGSSNYQQSFVPSPGARPQVNGLSGRIDFH

WLMLNPNDTVTFSFNGAFIAPDRASFLRGKSMGIQSGVQV

DANCEGDCYHSGGTHISNLPFQNIDSRAVGKCPRYVKQRS

LLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGWYG

FRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQF

ELIDNEFNEVEKQIGNVINWTRDSITEVWSYNAELLVAME

NQHTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFHK

CDDDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLSGGY

KDVILWFSFGASCFILLAIVMGLVFICVKNGNMRCTICI

149
AJJ93979
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERG

A/silkie
VEVVNATETVERTNIPRICSKGKKTVDLGQCGLLGTVTGP

chicken/Dongguan/
PQCDQFLEFSADLIIERREGSDVCYPGKFVNEEALRQILRES

656/2014
GGIDKEAMGFTYSGIRANGATSACRRSGSSFYAEMKWLL

2014/02/20 HA
SNTDNAAFPQMTKSYKNTRKSPALIVWGIHHSVSTAEQTK

755183919
LYGSGNKLVTVGSSNYQQSFVPSPGARPQVNGLSGRIDFH

WLMLNPNDTVTFSFNGAFIAPDRASFLRGKSMGIQSGVQV

DANCEGDCYHSGGTIISNLPFQNIDSRAVGKCPRYVKQKS

LLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGWYG

FRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQF

GLIDNEFNEVEKQIGNVINWTRDSITEVWSYNAELLVAME

NQHTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFHK

CDNDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLSSGY

KDVILWFSFGASCFILLAIVMGLVFICVKNGNMRCTICI

150
AJJ94134
MNTQILVLALIAIIPTNADKICLGHHAVSNGTKVNTLTERG

A/chicken/
VEVVNATETVERTNIPRICSKGKKTVDLGQCGLLGTITGPP

Dongguan/1051/2014
QCDQFLEFSADLIIERREGSDVCYPGKFVNEEALRQILRKS

2014/02/21 HA
GGIDKEAMGFTYSGIRTNGATSACRRSGSSFYAEMKWLLS

755184182
NTDNAAFPQMTKSYKNTRKSPAIIVWGIHHSVSTAEQTKL

YGSGNKLVTVGSSNYQQSFVPSPGARPQVNGLSGRIDFH

WLMLNPNDTVTFSFNGAFIAPDRASFLRGKSMGIQSGVQV

DADCEGDCYHSGGTIISNLPFQNIDSRAVGKCPRYVKQRS

LLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGWYG

FRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQF

ELIDNEFNEVEKQIGNVINWTRDSITEVWSYNAELLVAME

NQHTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFHK

CDDDCMASIRNNTYDHSKYREEAMQNRIQIDPVXLSXGY

KDVILWFSFGASCFILLAIVMGLVFICVKNGNMRCTICI

151
AJJ94158
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERG

A/chicken/
VEVVNATETVERTNIPRICSKGKKTVDLGQCGLLGTITGPP

Dongguan/1075/2014
QCDQFLEFSADLIIERREGSDVCYPGKFVNEEALRQILRES

2014/02/21 HA
GGIDKEAMGFTYSGIRTNGATSACRRSGSSFYAEMKWLLS

755184222
NTDNAAFPQMTKSYKNTRKSPALIVWGIHHSVSTAEQTKL

YGSGNKLVTVGSSNYQQSFVPSPGARPQVNGLSGRIDFH

WLMLNPNDTVTFSFNGAFIAPERASFLRGKSMGIQSGVQV

DANCEGDCYHSGGTIISNLPFQNIDSRAVGKCPRYVKQRS

LLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGWYG

FKHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQF

ELIDNEFNEVETQIGNVINWTRDSITEVWSYNAELLVAME

NQHTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFHK

CDDDCMASIRNNTYDHSKYRGEAMQNRIQIDPVKLSSGY

KDVILWFSFGASCFILLAIVMGLVFICVKNGNMRCTICI

152
AJJ94182
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERG

A/chicken/
VEVVNATETVERTNIPRICSKGKKTVDLGQCGLLGTITGPP

Dongguan/1177/2014
QCDQFLEFSADLIIERREGSDVCYPGKFVNEEALRQILRES

2014/02/21 HA
GGIDKEAMGFTYSGIRTNGATSACKRSGSSFYAEMKWLLS

755184262
NTDNAAFPQMTKSYKNTRKSPALIVWGIHHSVSIAEQTKL

YGSGNKLVTVGSSNYQQSFVPSPGARPQVNGLSGRIDFH

WLMLNPNDTVTFSFNGAFIAPDRASFLRGKSMGIQSGVQV

DANCEGDCYHSGGTIISNLPFQNIDSRAVGKCPRYVKQKS

LLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGWYG

FRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQF

ELIDNEFNEVEKQIGNVINWTRDSITEVWSYNAELLVAME

NQHTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFHK

CDDDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLSSGY

KDVILWFSFGASCFILLAIVMGLVFICVKNGNMRCTICI

153
AJJ94194
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERG

A/silkie
VEVVNATETVERTNIPRICSKGKKTIDLGQCGLLGTITGPP

chicken/
QCDQFLEFSADLIIERREGSDVCYPGKFVNEEALRQILRES

Dongguan/1264/2014
GGIDKEAMGFTYSGIRTNGATSACRRSGSSFYAEMKWLLS

2014/02/21 HA
NTDNAAFPQMTKSYKNTRKSPALIVWGIHHSVSTAEQTKL

755184282
YGSGNKLVTVGSSNYQQSFVPSPGARPQVNGLSGRIDFH

WLMLNPNDTVTFSFNGAFIAPERASFLRGKSMGIQSGVQV

DANCEGDCYHSGGTIISNLPFQNIDSRAVGKCPRYVKQRS

LLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGWYG

FKHQNAQGEGTAADYKSTQSAIDQVTGKLNRLIEKTNQQ

FELIDNEFNEVETQIGNVINWTRDSITEVWSYNAELLVAM

ENQHTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFH

KCDDDCMASIRNNTYDHSKYRGEAMQNRIQIDPVKLSSG

YKDVILWFSFGASCFMLLAIVMGLVFICVKNGNMRCTICI

154
AJJ94206
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERG

A/silkie
VEVVNATETVERTNIPRICSKGKKTVDLGQCGLLGTITGPP

chicken/Dongguan/
QCDQFLEFSADLIIERREGSDVCYPGKFVNEEALRQILRES

1268/2014
GGIDKEAMGFTYSGIRANGATSACRRSGSSFYAEMKWLL

2014/02/21 HA
SNTDNAAFPQMTKSYKNTRKSPALIVWGIHHSVSTAEQTK

755184302
LYGSGNKLVTVGSSNYQQSFVPSPGARPQVNGLSGRIDFH

WLMLNPNDTVTFSFNGAFIAPERASFLRGKSMGIQSGVQV

DANCEGDCYHSGGTHISDLPFQNIDSRAVGKCPRYVKQRS

LLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGWYG

FRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQF

ELIDNEFNEVEKQIGNVINWTRDSITEVWSYNAELLVAME

NQHTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFHK

CDDDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLSSGY

KDVILWFSFGASCFILLAIVMGLVFICVKNGNMRCTICI

155
AJJ94344
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERG

A/silkie
VEVVNSTETVERTNIPRICSKGKKTVDLGQCGLLGTITGPP

chicken/Dongguan/
QCDQFLEFSADLIIERREGSDVCYPGKFVNEEALRQILRKS

1451/2014
GGIDKEAMGFTYSGIRTNGATSACRRSGSSFYAEMKWLLS

2014/02/21 HA
NTDNAAFPQMTKSYKNTRKSPAIIVWGIHHSVSTAEQTKL

755184532
YGSGNKLVTVGSSNYQQSFVPSPGARPQVNGLSGRIDFH

WLMLNPNDTVTFSFNGAFIAPDRASFLRGKSMGIQSGVQV

DADCEGDCYHSGGTIISNLPFQNIDSRTVGKCPRYVKQRSL

LLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGWYGF

RHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQFE

LIDNEFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMEN

QHTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFHKC

DDDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLSSGYK

DVILWFSFGASCFILLAIVMGLVFICVKNGNMRCTICI

156
AJJ94356
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERG

A/chicken/
VEVVNATETVERTNIPRICSKGKKTVDLGQCGLLGTITGPP

Dongguan/1456/2014
QCDQFLEFSADLIIERREGSDVCYPGKFVNEEALRQILRES

2014/02/21 HA
GGIDKEAMGFTYSGIRTNGATSACRRSGSSFYAEMKWLLS

755184552
NTDNAAFPQMTKSYKNTRKSPALIVWGIHHSVSTAEQTKL

YGSGNKLVTVGSSNYQQSFVPSPGARPQVNGLSGRIDFH

WLMLNPNDTVTFSFNGAFIAPERASFLRGKSMGIQSGVQV

DANCEGDCYHSGGTIISNLPFQNIDSRAVGKCPRYVKQRS

LLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGWYG

FRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQF

ELIDNEFNEVETQIGNVINWIRDSITEVWSYNAELLVAME

NQHTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFHK

CDDDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLSSGY

KDVILWFSFGASCFILLAIVMGLVFICVKNGNMRCTICI

157
AJJ94396
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERG

A/chicken/
VEVVNATETVERTNIPRICSKGKKTVDLGQCGLLGTITGPP

Dongguan/1494/2014
QCDQFLEFSADLIIERREGSDVCYPGKFVNEEALRQILRES

2014/02/21 HA
GGIDKEAMGFTYSGIRANGATSACRRSGSSFYAEMKWLL

755184618
SNTDNAAFPQMTKSYKNTRKSPALIVWGIHHSVSTAEQTK

LYGSGNKLVTVGSSNYQQSFVPSPGARPQVNGLSGRIDFH

WLMLNPNDTVTFSFNGAFIAPDRASFLRGKSMGIQSGVQV

DANCEGDCYHSGGTHISNLPFQNIDSRAVGKCPRYVKQRS

LLLATGMKNVPETPKGRGLFGAIAGFIENGWEGLIDGWY

GFRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQ

FELIDNEFNEVEKQIGNVINWTRDSITEVWSYNAELLVAM

ENQHTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFH

KCDNDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLSSG

YKDVILWFSFGASCFILLAIVMGLVFICVKNGNMRCTICI

158
AJJ94754
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERG

A/chicken/
VEVVNATETVERTNIPRICSKGKKTVDLGQCGLLGTITGPP

Dongguan/748/2014
QCDQFLEFSADLIIERREGSDVCYPGKFVNEEALRQILRES

2014/02/20 HA
GGIEKEAMGFTYSGIRANGATSACRRSGSSFYAEMKWLLS

755185215
NTDNAAFPQMTKSYKNTRKSPALIVWGIHHSVSNAEQTK

LYGSGNKLVTVGSSNYQQSFVPSPGARPQVNGLSGRIDFH

WLMLNPNDTVTFSFNGAFIAPDRASFLRGKSMGIQSGVQV

DANCEGDCYHSGGTIISNLPFQNIDSRAVGKCPRYVKQRS

LLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGWYG

FRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQF

ELIDNEFNEVEKQIGNVINWTRDSITEVWSYNAELLVAME

NQHTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFHK

CDDDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLSGGY

KDVILWFSFGASCFILLAIVMGLVFICVKNGNMRCTICI

159
AJJ94838
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERG

A/chicken/
VEVVNATETVERTNIPRICSKGKKTVDLGQCGLLGTITGPP

Dongguan/835/2014
QCDQFLEFSADLIIERREGSDVCYPGKFVNEEALRQILRES

2014/02/20 HA
GGIDKEAMGFTYSGIRANGATSACRRSGSSFYAEMKWLL

755185356
SNTDNAAFPQMTKSYKNTRKSPALIVWGIHHSASTAEQTK

LYGSGNKLVTVGSSNYQQSFVPSPGARPQVNGLSGRIDFH

WLMLNPNDTVTFSFNGAFIAPDRASFLRGKSMGIQSGVQV

DANCEGDCYHSGGTIISNLPFQNIDSRAVGKCPRYVKQKS

LLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGWYG

FRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQF

ELIDNEFNEVEKQIGNVINWTRDSITEVWSYNAELLVAME

NQHTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFHK

CDNDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLSSGY

KDVILWFGFGASCFILLAIVMGLVFICVKNGNMRCTICI

160
AJJ94862
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERG

A/chicken/
VEVVNATETVERTNIPRICSKGKKTVDLGQCGLLGTITGPP

Dongguan/843/2014
QCDQFLEFSADLIIERREGSDVCYPGKFVNEEALRQILRES

2014/02/20 HA
GGIEKEAMGFTYSGIRTNGATSACRRSGSSFYAEMKWLLS

755185396
NTDNAAFPQMTKSYKNTRKSPALIVWGIHHSVSTAEQTKL

YGSGNKLVTVGSSNYQQSFVPSPGARPQVNGLSGRIDFH

WLMLNPNDTVTFSFNGAFIAPDRASFLRGKSMGIQSGVQV

DANCEGDCYHSGGTIISNLPFQNIDSRAVGKCPRYVKQRS

LLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGWYG

FRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQF

ELIDNEFNEVEKQIGNVINWTRDSITEVWSYNAELLVAME

NQHTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFHK

CDDDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLSGGY

KDVILWFSFGASCFILLAIVMGLVFICVKNGNMRCTICI

161
AJJ94886
MNTQILAFALIAIIPTNADKICLGHHAVSNGTKVNTLTERG

A/chicken/
VEVVNATETVERTNIPRICSKGKKTVDLGQCGLLGTITGPP

Dongguan/851/2014
QCDQFLEFSADLIIERREGSDVCYPGKFVNEEALRQILRES

2014/02/20 HA
GGIDKEAMGFTYSGIRANGATSACRRSGSSFYAEMKWLL

755185436
SNTDNAAFPQMTKSYKNTRKSPALIVWGIHHSVSTAEQTK

LYGSGNKLVTVGSSNYQQSFVPSPGARPQVNGLSGRIDFH

WLMLNPNDTVTFSFNGAFIAPDRASFLRGKSMGIQSGVQV

DANCEGDCYHSGGTIISNLPFQNIDSRAVGKCPRYVKQRS

LLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGWYG

FRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQF

ELIDNEFNEVEKQIGNVINWTRDSITEVWSYNAELLVAME

NQHTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFHK

CDNDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLSSGY

KDVILWFSFGASCFILLAIVMGLVFICVKNGNMRCTICI

162
AJJ94910
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERG

A/chicken/
VEVVNATETVERTNIPRICSKGKKTVDLGQCGLLGTITGPP

Dongguan/874/2014
QCDQFLEFSADLIIERREGSDVCYPGKFVNEEALRQILRES

2014/02/20 HA
GGIDKEAMGFTYSGIRANGATSACRRSGSSFYAEMKWLL

755185476
SNTDNAAFPQMTKSYKNTRKSPALIVWGIHHSASTAEQTK

LYGSGNKLVTVGSSNYQQSFVPSPGARPQVNGLSGRIDFH

WLMLNPNDTVTFSFNGAFIAPDRASFLRGKSMGIQSGVQV

DANCEGDCYHSGGTIISNLPFQNIDSRAVGKCPRYVKQKS

LLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGWYG

FRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQF

ELIDNEFNEVEKQIGNVINWIRDSITEVWSYNAELLVAME

NQHTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFHK

CDNDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLSSGY

KDVILWFSFGASCFILLAIVMGLVFICVKNGNMRCTICI

163
AJJ94959
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERG

A/silkie
VEVVNATETVERTNIPRICSKGKKTVDLGQCGLLGTITGPP

chicken/Dongguan/
QCDQFLEFSADLIIERREGSDVCYPGKFVNEEALRQILRES

967/2014
GGIDKEAMGFTYSGIRANGATSACXRSGSSFYAEMKWLL

2014/02/21 HA
SNTDNAAFPQMTKSYKNTRKSPALIVWGIHHSVSTAEQTK

755185558
LYGSGNKLVTVGSSNYQQSFVPSPGARPQVNGLSGRIDFH

WLMLNPNDTVTFSFNGAFIAPDRASFLRGKSMGIQSGVQV

DANCEGDCYHSGGTIISNLPFQNIDSRAVGKCPRYVKQRS

LLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGWYG

FRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQF

ELIDNEFNEVEKQIGNVINWIRDSITEVWSYNAELLVAME

NQHTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFHK

CDNDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLSSGY

KDVILWFSFGASCFILLAIVMGLVFICVKNGNMRCTICI

164
AJJ95048
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERG

A/chicken/
VEVVNATETVERTNIPRICSKGKRTVDLGQCGLLGTITGPP

Dongguan/1009/2014
QCDQFLEFSADLIIERREGSDVCYPGKFVNEEALRQILRES

2014/02/21 HA
GGIDKEAMGFTYSGIRANGATSACRRSGSSFYAEMKWLL

755185708
SNTDNAAFPQMTKSYKNTRKSPALIVWGIHHSVSTAEQTK

LYGSGNKLVTVGSSNYQQSFVPSPGARPQVNGLSGRIDFH

WLMLNPNDTVTFSFNGAFIAPDRASFLRGKSMGIQSGVQV

DANCEGDCYHSGGTIISNLPFQNIDSRAVGKCPRYVKQRS

LLLATGMKNVPETPKGRGLFGAIAGFIENGWEGLIDGWY

GFRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQ

FELIDNEFNEVEKQIGNVINWIRDSITEVWSYNAELLVAM

ENQHTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFH

KCDNDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLSSG

YKDVILWFSFGASCFILLAIVMGLVFICVKNGNMRCTICI

165
AJJ95171
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERG

A/chicken/
VEVVNATETVERTNIPRICSKGKKTVDLGQCGLLGTITGPP

Dongguan/1314/2014
QCDQFLEFSADLIIERREGSDVCYPGKFVNEEALRQILRES

2014/02/21 HA
GGIDKEAMGFTYSGIRTNGATSACRRSGSSFYAEMKWLLS

755185913
NTDNAAFPQMTKSYKNTRKSPALIVWGIHHSVSTAEQTKL

YGSGNKLVTVGSSNYQQSFVPSPGARPQVNGLSGRIDFH

WLMLNPNDTVTFNFNGAFIAPERASFLRGKSMGIQSGVQV

DANCEGDCYHSGGTIISNLPFQNIDSRAVGKCPRYVKQRS

LLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGWYG

FKHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQF

ELIDNEFNEVETQIGNVINWIRDSITEVWSYNAELLVAME

NQHTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFHK

CDDDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLSSGY

KDVILWFSFGASCFILLAIVMGLVFICVKNGNMRCTICI

166
AJJ95227
MNTQILVEALIAIIPTNADKICLGHHAVSNGTKVNTLTERG

A/chicken/
VEVVNATETVERTNIPRICSKGKKTVDLGQCGLLGTITGPP

Dongguan/1382/2014
QCDQFLEFSADLIIERREGSDICYPGKFVNEEALRQILRESG

2014/02/21 HA
GIDKEAMGFTYSGIRANGATSACRRSGSSFYAEMKWLLS

755186006
NTDNAAFPQMTKSYKNTRKSPALIVWGIHHSVSTAEQTKL

YGSGNKLVTVGSSNYQQSFVPSPGARPQVNGLSGRIDFH

WLMLNPNDTVTFSENGAFIAPERASFLRGKSMGIQSGVQV

DANCEGDCYHSGGTIISNLPFQNIDSRAVGKCPRYVKQRS

LLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGWYG

FRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQF

ELIDNEFNEVEKQIGNVINWTRDSITEVWSYNAELLVAME

NQHTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFHK

CDDDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLSSGY

KDVILWFSFGASCFILLAIVMGLVFICVKNGNMRCTICI

167
AJJ95251
MNTQILVEALIAIIPTNADKICLGHHAVSNGTKVNTLTERG

A/chicken/
VEVVNATETVERTNIPRICSKGKKTVDLGQCGLLGTITGPP

Dongguan/1401/2014
QCDQFLEFSADLIIERREGSDVCYPGKFVNEEALRQILRES

2014/02/21 HA
GGIDKEAMGFTYSGIRTNGATSACRRSGSSFYAEMKWLLS

755186046
NTDNAAFPQMTKSYKNTRKSPALIVWGIHHSVSTAEQTKL

YGSGNKLVTVGSSNYQQSFVPSPGARPQVNGLSGRIDFH

WLMLNPNDTVTFSFNGAFIAPDRASFLRGKSMGIQSGVQV

DANCEGDCYHSGGTHISNLPFQNIDSRAVGKCPRYVKQRS

LLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGWYG

FRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQF

ELIDNEFNEVETQIGNVINWIRDSITEVWSYNAELLVAME

NQHTIDLADSEMDKLYKRVKRQLRENAEEDGTGCFEIFH

KCDDDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLSSG

YKDVILWFSFGASCFILLAIVMGLVFICVKNGNMRCTICI

168
AJJ95346
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERG

A/chicken/
VEVVNATETVERTNIPRICSKGKKTVDLGQCGLLGTITGPP

Dongguan/1548/2014
QCDQFLEFSADLIIERREGSDVCYPGKFVNEEALRQILRES

2014/02/21 HA
GGIDKEAMGFTYSGIRTNGATSACRRSGSSFYAEMKWLLS

755186206
NTDNAAFPQMTKSYKNTRKSPALIVWGIHHSVSTAEQTKL

YGSGNKLVTVGSSNYQQSFVPSPGARPQVNGLSGRIDFH

WLMLNPNDTVTFSFNGAFIAPDRASFLRGKSMGIQSGVQV

DANCEGDCYHSGGTHISNLPFQNIDSRAVGKCPRYVKQRS

LLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGWYG

FRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQF

ELIDNEFNEVETQIGNVINWIRDSITEVWSYNAELLVAME

NQHTIDLADSEMDKLYKRVKRQLRENAEEDGTGCFEIFH

KCDDDCMASIRNNTYDHNKYREEAMQNRIQIDPVKLSSG

YKDVILWFSFGASCFILLAIVMGLVFICVKNGNMRCTICI

169
AJJ95382
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERG

A/chicken/
VEVVNATETVERTNIPRICSKGKKTVDLGQCGLLGTITGPP

Dongguan/1690/2014
QCDQFLEFSADLIIERREGSDVCYPGKFVNEEALRQILRKS

2014/02/21 HA
GGIDKEAMGFTYSGIRTNGATSACRRSGSSFYAEMKWLLS

755186266
NTDNAAFPQMTKSYKNTRKSPAIIVWGIHHSVSTAEQTKL

YGSGNKLVTVGSSNYQQSFVPSPGARPQVNGLSGRIDFH

WLMLNPNDTVTFSFNGAFIAPDRASFLRGKSIGIQSGVQV

DADCEGDCYHSGGTIISNLPFQNIDSRAVGKCPRYVKQRS

LLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGWYG

FRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQF

ELIDNEFNEVEKQIGNVINWTRDSITEVWSYNAELLVAME

NQHTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFHK

CDDDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLSSGY

KDVILWFSFGASCFILLAIVMGLVFICVKNGNMRCTICI

170
AJJ95464
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERG

A/chicken/
VEVVNATETVERTNIPRICSKGKKTVDLGQCGLLGTITGPP

Shenzhen/138/2014
QCDQFLEFSADLIIERREGSDVCYPGKFVNEEALRQILRES

2014/02/19 HA
GGIDKEAMGFTYSGIRTNGATSACRRSGSSFYAEMKWLLS

755186404
NTDNAAFPQMTKSYKNTRKSPALIVWGIHHSVSTAEQTKL

YGSGNKLVTVGSSNYQQSFVPSPGARPQVNGLSGRIDFH

WLMLNPNDTVTFSFNGAFIAPERASFLRGKSMGIQSGVQV

DANCEGDCYHSGGTIISNLPFQNIDSRAVGKCPRYVKQRS

LLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGWYG

FKHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQF

ELIDNEFNEVETQIGNVINWTRDSITEVWSYNAELLVAME

NQHTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFHK

CDDDCMASIRNNTYDHSKYRGEAMQNRIQIDPVKLSSGY

KDVILWFSFGASCFMLLAIVMGLVFICVKNGNMRCTICI

171
AJJ95572
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERG

A/chicken/
VEVVNATETVERTNIPRICSKGKRTVDLGQCGLLGTITGPP

Dongguan/1100/2014
QCDQFLEFSADLIIERREGSDVCYPGKFVNEEALRQILRES

2014/02/21 HA
GGIEKEAMGFTYSGIRANGATSACRRSGSSFYAEMKWLLS

755186584
NTDNAAFPQMTKSYKNTRKSPALIVWGIHHSVSTAEQTKL

YGSGNKLVTVGSSNYQQSFVPSPGARPQVNGLSGRIDFH

WLMLNPNDTVTFSFNGAFIAPDRASELRGKSMGIQSGVQV

DANCEGDCYHSGGTIISNLPFQNIDSRAVGKCPRYVKQRS

LLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGWYG

FRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQF

ELIDNEFNEVEKQIGNVINWTRDSITEVWSYNAELLVAME

NQHTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFHK

CDDDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLSGGY

KDVILWFSFGASCFILLAIVMGLVFICVKNGNMRCTICI

172
AJJ95584
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERG

A/silkie
VEVVNATETVERTNIPRICSKGKRTVDLGQCGLLGTITGPP

chicken/Dongguan/
QCDQFLEFSADLIIERREGSDVCYPGKFVNEEALRQILRES

1519/2014
GGIDKEAMGFTYSGIRTNGATSACRRSGSSFYAEMKWLLS

2014/02/21 HA
NTDNAAFPQMTKSYKNTRKSPALIVWGIHHSVSTAEQTKL

755186604
YGSGNKLVTVGSSNYQQSFVPSPGARPQVNGLSGRIDFH

WLMLNPNDTVTFSFNGAFIAPERASFLRGKSMGIQSGVQV

DANCEGDCYHSGGTIISNLPFQNIDSRAVGKCPRYVKQRS

LLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGWYG

FKHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQF

ELIDNEFNEVETQIGNVINWTRDSITEVWSYNAELLVAME

NQHTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFHK

CDDDCMASIRNNTYDHSKYRGEAMQNRIQIDPVKLSSGY

KDVILWFSFGASCFMLLAIVMGLVFICVKNGNMRCTICI

173
AJJ95596
MNTQILAFALIAIIPTNADKICLGHHAVSNGTKVNTLTERG

A/Shenzhen/
VEVVNATETVERTNIPRICSKGKKTVDLGQCGLLGTITGPP

SP58/2014
QCDQFLEFSADLIIERREGSDVCYPGKFVNEEALRQILRES

2014/01/25 HA
GGIDKEAMGFTYSGIRANGATSACRRSGSSFYAEMKWLL

755186624
SNTDNAAFPQMTKSYKNTRKSPALIVWGIHHSVSTAEQTK

LYGSGNKLVTVGSSNYQQSFVPSPGARPQVNGLSGRIDFH

WLMLNPNDTVTFSFNGAFIAPDRASFLRGKSMGIQSGVQV

DANCEGDCYHSGGTHISNLPFQNIDSRAVGKCPRYVKQRS

LLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGWYG

FRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQF

ELIDNEFNEVEKQIGNVINWTRDSITEVWSYNAELLVAME

NQHTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFHK

CDDDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLSSGY

KDVILWFSFGASCFILLAIVMGLVFICVKNGNMRCTICI

174
AJJ95620
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERG

A/Shenzhen/
VEVVNATETVERTNIPRICSKGKKTVDLGQCGLLGTITGPP

SP75/2014
QCDQFLEFSADLIIERREGSDVCYPGKFVNEEALRQILRES

2014/02/15 HA
GGIDKEAMGFTYSGIRTNGSTSACRRSGSSFYAEMKWLLS

755186664
NTDNAAFPQMTKSYKNTRKSPALIVWGIHHSVSTAEQTKL

YGSGNKLVTVGSSNYQQSFVPSPGARPQVNGLSGRIDFH

WLMLNPNDTVTFSFNGAFIAPDRASFLRGKSMGIQSGVQV

DANCEGDCYHSGGTHISNLPFQNIDSRAVGKCPRYVKQRS

LLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGWYG

FRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQF

ELIDNEFNEVETQIGNVINWTRDSITEVWSYNAELLVAME

NQHTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFHK

CDDDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLSSGY

KDVILWFSFGASCFILLAVVMGLVFICVKNGNMRCTICI

175
AJJ95632
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERG

A/Shenzhen/
VEVVNATETVERTNIPRICSKGKKTVDLGQCGLLGTITGPP

SP62/2014
QCDQFLEFSADLIIERREGSDVCYPGKFVNEEALRQILRES

2014/02/05 HA
GGIDKEAMGFTYSGIRTNGATSACRRSGSSFYAEMKWLLS

755186684
NTDNATFPQMTKSYKNTRKSPALIIWGIHHSVSTAEQTKL

YGSGNKLVTVGSSNYQQSFVPSPGARPQVNGLSGRIDFH

WLMLNPNDTVTFSFNGAFIAPDRASFLRGKSMGIQSGVQV

DANCEGDCYHSGGTIISNLPFQNIDSRAVGKCPRYVKQRS

LLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGWYG

FRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQF

ELIDNEFNEVETQIGNVINWIRDSITEVWSYNAELLVAME

NQHTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFHK

CDDDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLSSGY

KDVILWFSFGASCFILLAIVMGLVFICVKNGNMRCTICI

176
AJJ96720
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERG

A/chicken/Jiangxi/
VEVVNATETVERTTIPRICSKGKKTVDLGQCGLLGTITGPP

13220/2014
QCDQFLEFSADLIIERREGSDVCYPGKFVNEEALRQILRES

2014/03/30 HA
GGIDKEAMGFTYSGIRTNGATSACRRSGSSFYAEMKWLLS

755188499
NTDNAAFPQMTKSYKNTRKSPALIVWGIHHSVSTAEQTKL

YGSGNKLVTVGSSNYQQSFVPSPGARPQVNGLSGRIDFH

WLMLNPNDTVTFSFNGAFIAPDRASFLRGKSMGIQSGVQV

DANCEGDCYHSRGTIISNLPFQNIDSRAVGKCPRYVKQKS

LLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGWYG

FRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQF

ELIDNEFNEVEKQIGNVINWIRDSITEVWSYNAELLVAME

NQHTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFHK

CDDDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLSSGY

KDVILWFSFGASCFILLAIVMGLVFICVKNGNMRCTICI

177
AJJ96817
MNTQILVFALIAIVPTNADKICLGHHAVSNGTKVNTLTER

A/chicken/Jiangxi/
GVEVVNATEIVERTNIPRICSKGKKTVDLGQCGLLGTITGP

9513/2014
PQCDQFLEFSADLIIERREGSDVCYPGKFVNEEALRQILRES

2014/02/16 HA
GGIDKEAMGFTYSGIRTNGVTSACRRSGSSFYAEMKWLLS

755188661
NTDNAAFPQMTKSYKNTRKSPALIVWGIHHSVSTAEQTKL

YGSGNKLVTVGSSNYQQSFVPSPGARPQVNGLSGRIDFH

WLMLNPNDTVTFSFNGAFIAPDRASFLRGKSMGIQSGVQV

DANCEGDCYHSGGTIISNLPFQNIDSRAVGKCPRYVKQKS

LLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGWYG

FRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQF

ELIDNEFNEVEKQIGNVINWTRDSITEVWSYNAELLVAME

NQHTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFHK

CDDDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLSSGY

KDVILWFSFGASCFILLAIVMGLVFICVKNGNMRCTICI

178
AJJ96841
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERG

A/Shenzhen/
VEVVNATETVERTNIPRICSKGKKTVDLGQCGLLGTITGPP

SP139/2014
QCDQFLEFSADLIIERREGSDVCYPGKFVNEEALRQILRKS

2014/04/02 HA
GGIDKEAMGFTYSGIRTNGATSTCRRSGSSFYAEMKWLLS

755188701
NTDNAAFPQMTKSYKNTRKSPAIIVWGIHHSVSTAEQTKL

YGSGNKLVTVGSSNYQQSFVPSPGARPQVNGLSGRIDFH

WLMLNPNDTVTFSFNGAFIAPDRACFLRGKSMGIQSGVQ

VDADCEGDCYHSGGTIISNLPFQNIDSRAVGKCPRYVKQR

SLLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGWY

GFRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQ

FELIDNEFNEVERQIGNVINWTRDSITEVWSYNAELLVAM

ENQHTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFH

KCDDDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLSSG

YKDVILWFSFGASCFILLAIVMGLVFICVKNGNMRCTICI

179
AJJ96889
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERG

A/chicken/Jiangxi/
VEVVNATETVERTXIPRICSKGKKTVDLGQCGLLGTITGPP

13496/2014
QCDQFLEFSADLIIERREGSDVCYPGKFVNEEALRQILRES

2014/04/11 HA
GGIDKXAMGFTYSGIRTNGATSACRRSGSSFYAEMKWLL

755188781
SNTDNAAFPQMTKSYKNTRKSPALIVWGIHHSVSTAEQTK

LYGSGNKLVTVGSSNYQQSFVPSPGARPQVNGLSGRIDFH

WLMLNPNDTVTFSFNGAFIAPDRASFLRGKSMGIQSGVQV

DANCEGDCYHSXGTIISNLPFQNIDSRAVGKCPRYVKQKS

LLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGWYG

FRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQF

ELIDNEFNEVEKQIGNVINWTRDSITEVWSYNAELLVAME

NQHTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFHK

CDDDCMASINNTYDHSKYREEAMQNRIQIDPVKLSSGY

KDVILWFSFGASCFILLAIVMGLVFICVKNGNMRCTICI

180
AJJ96901
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERG

A/chicken/Jiangxi/
VEVVNATETVERTNIPRICSKGKKTVDLGQCGLLGTITGPP

13502/2014
QCDQFLEFSADLIIERREGSDVCYPGKFVNEEALRQILRES

2014/04/11 HA
GGIDKEAMGFTYSGIRTNGATSACRRSGSSFYAEMKWLLS

755188801
NTDNAAFPQMTKSYKNTRKSPALIVWGIHHSVSTAEQTKL

YGSGNKLVTVGSSNYQQSFVPSPGARPQVNGLSGRIDFH

WLMLNPNDTVTFSFNGAFIAPDRASFLRGKSMGIQSGVQV

DANCEGDCYHSXGTIISNLPFQNIDSRAVGKCPRYVKQKS

LLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGWYG

FRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQF

ELIDNEFNEVEKQIGNVINWIRDSITELWSYNAELLVAME

NQHTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFHK

CDDDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLSSGY

KDVILWFSFGASCFILLAIVMGLVFICVKNGNMRCTICI

181
AJJ96925
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERG

A/chicken/Jiangxi/
VEVVNATETVERTNIPRICSKGKRTVDLGQCGLLGTITGPP

13513/2014
QCDQFLEFSADLIIERREGSDVCYPGKFVNEEALRQILRES

2014/04/11 HA
GGIDKEAMGFTYNGIRTNGATSACRRSGSSFYAEMKWLL

755188841
SNTDNAAFPQMTKSYKNTRKSPAIIVWGIHHTVSTAEQTK

LYGSGNKLVTVGSSNYQQSFVPSPGARPQVNGLSGRIDLH

WLMLNPNDTVTFSFNGAFIAPDRASFLRGKSMGIQSGVQV

DANCEGDCYHSGGTIISNLPFQNIDSRAVGKCPRYVKQRS

LLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGWYG

FRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIAKTNQQF

ELIDNEFNEVEKQIGNVINWTRDSITEVWSYNAELLVAME

NQHTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFHK

CDDDCMASIRNNTYDHRKYREEAMQNRIQIDPVKLSSGY

KDVILWFSFGASCFILLAIVMGLVFICVKNGNMRCTICI

182
AJJ97267
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERG

A/chicken/Jiangxi/
VEVVNATETVERTNIPRICSKGKRTVDLGQCGLLGTITGPP

13252/2014
QCDQFLEFSADLIIERREGSDVCYPGKFVNEEALRQILRES

2014/03/30 HA
GGIDKEAMGFTYSGIRTNGATSACRRSGSSFYAEMKWLLS

755189411
NTDNAAFPQMTKSYKNTRKSPALIVWGIHHSVSTAEQTKL

YGSGNKLVTVGSSNYQQSFVPSPGARPQVNGLSGRIDFH

WLMLNPNDTVTFSFNGAFIAPDRASFLRGKSMGIQSGVQV

DANCEGDCYHSGGTHISNLPFQNIDSRAVGKCPRYVKQKS

LLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGWYG

FRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQF

ELIDNEFNEVEKQIGNVINWTRDSITELWSYNAELLVAME

NQHTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFHK

CDDDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLSSGY

KDVILWFSFGASCFILLAIVMGLVFICVKNGNMRCTICI

183
AJJ97291
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERG

A/chicken/Jiangxi/
VEVVNATETVERTNIPRICSKGKRTVDLGQCGLLGTITGPP

13493/2014
QCDQFLEFSADLIIERREGSDVCYPGKFVNEEALRQILRES

2014/04/06 HA
GGIDKEAMGFTYNGIRTNGATSACRRSGSSFYAEMKWLL

755189451
SNTDNAAFPQMTKSYKNTRKSPAIIVWGIHHSVSTAEQTK

LYGSGNKLVTVGSSNYQQSFVPSPGARPQVNGLSGRIDFH

WLMLNPNDTVTFSFNGAFIAPDRASFLRGKSMGIQSGVQV

DANCEGDCYHSGGTHISNLPFQNIDSRAVGKCPRYVKQRS

LLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGWYG

FRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIAKTNQQF

ELIDNEFNEVEKQIGNVINWIRDSITEVWSYNAELLVAME

NQHTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFHK

CDDDCMASIRNNTYDHRKYREEAMQNRIQIDPVKLSSGY

KDVILWFSFGASCFILLAIVMGLVFICVKNGNMRCTICI

184
AJJ97331
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERG

A/chicken/Jiangxi/
VEVVNATETVERTNIPRICSKGKRTVDLGQCGLLGTITGPP

13512/2014
QCDQFLEFSADLIIERREGSDVCYPGKFVNEEALRQILRES

2014/04/06 HA
GGIDKEAMGFTYNGIRTNGATSACRRSGSSFYAEMKWLL

755189517
SNTDNAAFPQMTKSYKNTRKSPAIIVWGIHHSVSTAEQTK

LYGSGNKLVTVGSSNYQQSFVPSPGARPQVNGLSGRIDFH

WLMLNPNDTVTFSFNGAFIAPDRASFLRGKSIGIQSGVQV

DANCEGDCYHSGGTHISNLPFQNIDSRAVGKCPRYVKQRS

LLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGWYG

FRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIAKTNQQF

ELIDNEFNEVEKQIGNVINWTRDSITEVWSYNAELLVAME

NQHTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFHK

CDDDCMASIRNNTYDHRKYREEAMQNRIQIDPVKLSSGY

KDVILWFSFGASCFILLAIVMGLVFICVKNGNMRCTICI

185
AJJ97373
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERG

A/chicken/Jiangxi/
VEVVNATETVERTNIPRICSKGKRTVDLGQCGLLGTITGPP

13521/2014
QCDQFLEFSADLIIERREGSDVCYPGKFVNEEALRQILRES

2014/04/06 HA
GGIDKEAMGFTYNGIRTNGATSACRRSGSSFYAEMKWLL

755189587
SNTDNAAFPQMTKSYKNTRKSPAIIVWGIHHSVSTAEQTK

LYGSGNKLVTVGSSNYQQSFVPSPGARPQVNGLSGRIDFH

WLMLNPNDTVTFSFNGAFIAPXRASFLRGKSXGIQSGVQV

DANCEGDCYHSGGTHISNLPFQNIDSRAVGKCPRYVKQRS

LLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGWYG

FRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIAKTNQQF

ELIDNEFNEVEKQIGNVINWTRDSITEVWSYNAELLVAME

NQHTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFHK

CDDDCMASIRNNTYDHRKYREEAMQNRIQIDPVKLSSGY

KDVILWFSFGASCFILLAIVMGLVFICVKNGNMRCTICI

186
AJJ97443
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERG

A/chicken/Jiangxi/
VEVVNATETVERTTIPRICSKGKRTVDLGQCGLLGTITGPP

13530/2014
QCDQFLEFSADLIIERREGSDVCYPGKFVNEEALRQILRES

2014/04/06 HA
GGIDKEAMGFTYSGIRTNGATSACRRSGSSFYAEMKWLLS

755189702
NTDNAAFPQMTKSYKNTRKSPALIVWGIHHSVSTAEQTKL

YGSGNKLVTVGSSNYQQSFVPSPGARPQVNGLSGRIDFH

WLMLNPNDTVTFSFNGAFIAPDRASFLRGKSMGIQSGVQV

DANCEGDCYHSRGTIISNLPFQNIDSRAVGKCPRYVKQKS

LLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGWYG

FRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQF

ELIDNEFNEVEKQIGNVINWTRDSITEVWSYNAELLVAME

NQHTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFHK

CDDDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLSSGY

KDVILWFSFGASCFILLAIVMGLVFICVKNGNMRCTICI

187
AJJ97582
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERG

A/chicken/Jiangxi/
VEVVNATETVERTNIPRICSKGKRTVDLGQCGLLGTITGPP

14023/2014
QCDQFLEFSADLIIERREGSDVCYPGKFVNEEALRQILRES

2014/04/13 HA
GGIDKEAMGFTYSGIRTNGATSACRRSGSSFYAEMKWLLS

755189933
NTDNAAFPQMTKSYKNTRKSPAIIVWGIHHSVSTAEQTKL

YGSGNKLVTVGSSNYQQSFVPSPGARPQVNGLSGRIDFH

WLMLNPNDTVTFSFNGAFIAPDRASFLRGKSMGIQSGVQV

DANCEGDCYHSGGTHISNLPFQNIDSRAVGKCPRYVKQRS

LLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGWYG

FRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIAKTNQQF

ELIDNEFNEVEKQIGNVINWTRDSITEVWSYNAELLVAME

NQHTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFHK

CDDDCMASIRNNTYDHRKYREEAMQNRIQIDPVKLSSGY

KDVILWFSFGASCFILLAIVMGLVFICVKNGNMRCTICI

188
AJJ97697
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERG

A/chicken/Jiangxi/
VEVVNATETVERTNIPRICSKGKKTVDLGQCGLLGTITGPP

14517/2014
QCDQFLEFSADLIIERREGSDVCYPGKFVNEEALRQILRES

2014/04/20 HA
GGIDKEAMGFTYSGIRTNGATSACRRSGSSFYAEMKWLLS

755190125
NTDNAAFPQMTKSYKNTRKSPALIVWGIHHSVSTAEQTKL

YGSGNKLVTVGSSNYQQSFVPSPGARPQVNGLSGRIDFH

WLMLNPNDTVTFSFNGAFIAPDRASFLRGKSMGIQSGVQV

DANCDGDCYHSGGTIISNLPFQNIDSRAVGKCPRYVKQKS

LLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGWYG

FRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQF

ELIDNEFNEVEKQIGNVINWIRDSITELWSYNAELLVAME

NQHTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFHK

CDDDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLSSGY

KDVILWFSFGASCFILLAIVMGLVFICVKNGNMRCTICI

189
AJJ97709
MNTQILVFALIAIIPANADKICLGHHAVSNGTKVNTLTERG

A/chicken/Jiangxi/
VEVVNATETVERTNIPRICSKGKRTVDLGQCGLLGTITGPP

14518/2014
QCDQFLEFSADLIIERREGSDVCYPGKFVNEEALRQILRES

2014/04/20 HA
GGIDKEAMGFTYNGIRTNGATSACRRSGSSFYAEMKWLL

755190145
SNTDNAAFPQMTKSYKNTRKSPAIIVWGIHHSVSTAEQTK

LYGSGNKLVTVGSSNYQQSFVPSPGARPQVNGLSGRIDFH

WLMLNPNDTVTFSFNGAFIAPDRASFLRGKSMGIQSGVQV

DANCEGNCYHSGGTIISNLPFQNIDSRAVGKCPRYVKQRS

LLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGWYG

FRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIAKTNQQF

ELIDNEFNEVEKQIGNVINWIRDSITEVWSYNAELLVAME

NQHTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFHK

CDDDCMASIRNNTYDHRKYREEAMQNRIQIDPVKLSSGY

KDVILWFSFGASCFILLAIVMGLVFICVKNGNMRCTICI

190
AJJ97745
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERG

A/chicken/Jiangxi/
VEVVNATETVERTNIPRICSKGKKTVDLGQCGLLGTITGPP

14554/2014
QCDQFLEFSADLIIERREGSDVCYPGKFVNEEALRQILRES

2014/04/20 HA
GGIDKEAMGFTYSGIRTNGATSACRRSGSSFYAEMKWLLS

755190205
NTDNAAFPQMTKSYKNTRKSPALIVWGIHHSVSTAEQTKL

YGSGNKLVTVGSSNYQQSFVPSPGARPQVNGLSGRIDFH

WLMLNPNDTVTFSFNGAFIAPDRASFLRGKSMGIQSGVQV

DANCEGDCYHSGGTIISNLPFQNIDSRAVGKCPRYVKQKS

LLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGWYG

FRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQF

ELMDNEFNEVEKQIGNVINWIRDSITELWSYNAELLVAM

ENQHTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFH

KCDDDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLSSG

YKDVILWFSFGASCFILLAIVMGLVFICVKNGNMRCTICI

191
AJJ97757
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERG

A/chicken/Shantou/
VEVVNATETVERTNIPRICSKGKKTVDLGQCGLLGTITGPP

2537/2014
QCDQFLEFSADLIIERREGSDVCYPGKFVNEEALRQILRKS

2014/04/16 HA
GGIDKEAMGFTYSGIRTNGATSACRRSGSSFYAEMKWLLS

755190225
NTDNAAFPQMTKSYKNTRKSPAIIVWGIHHSVSTAEQTKL

YGSGNKLVTVGSSNYQQSFVPSPGARPQVNGLSGRIDFH

WLMLNPNDTVTFSFNGAFIAPDRASFLRGKSMGIQSGVQV

DADCEGDCYHSGGTIISNLPFQNIDSRAVGKCPRYVKQRS

LLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGWYG

FKHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQF

ELIDNEFNEVEKQIGNVINWTRDSITEVWSYNAELLVAME

NQHTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFHK

CDDDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLSSGY

KDVILWFSFGASCFILLAIVMGLVFICVKNGNMRCTICI

192
AJJ97841
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERG

A/duck/Jiangxi/
VEVVNATETVERTNIPRICSKGKRTVDLGQCGLLGTITGPP

15044/2014
QCDQFLEFSADLIIERREGSDVCYPGKFVNEEALRQILRES

2014/04/27 HA
GGIDKEAMGFTYSGIRTNGATSACRRSGSSFYAEMKWLLS

755190365
NTDNAAFPQMTKSYKNTRKSPAIIVWGIHHSVSTAEQTKL

YGSGNKLVTVGSSNYQQSFVPSPGARPQVNGLSGRIDFH

WLMLNPNDTVTFSENGAFIAPDRASFLRGKSMGIQSGVQV

DANCEGDCYHSGGTIISNLPFQNIDSRAVGKCPRYVKQRS

LLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGWYG

FRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIAKTNQQF

ELIDNEFNEVEKQIGNVINWTRDSITEVWSYNAELLVAME

NQHTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFHK

CDDDCMASIRNNTYDHRKYREEAMQNRIQIDPVRLSSGY

KDVILWFSFGASCFILLAIVMGLVFICVKNGNMRCTICI

193
AJJ97899
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERG

A/chicken/Jiangxi/
VEVVNATETVERTNIPRICSKGKRTVDLGQCGLLGTITGPP

15524/2014
QCDQFLEFSADLIIERREGSDVCYPGKFVNEEALRQILRES

2014/05/05 HA
GGIDKEAMGFTYSGIRTNGATSACRRSGSSFYAEMKWLLS

755190462
NTDNAAFPQMTKSYKNTRKSPAIIVWGIHHSVSTAEQTKL

YGSGNKLVTVGSSNYQQSFVPSPGARPQVNGLSGRIDFH

WLMLNPNDTVTFSFNGAFIAPDRASFLRGKSMGIQSGVQV

DANCEGDCYHSGGTIISNLPFQNIDSRAVGKCPRYVKQRS

LLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGWYG

FRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIAKTNQQF

ELIDNEFNEVEKQIGNVINWTRDSITEVWSYNAELLVAME

NQHTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFHK

CDDDCMASIRNNTYDHRKYREEAMQNRIQIDPVKLSSGY

KDVILWFSFGASCFILLAIVMGLVFMCVKNGNMRCTICI

194
AJJ97925
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERG

A/silkie
VEVVNATETVERTNIPRICSKGKKTVDLGQCGLLGTITGPP

chicken/Shantou/
QCDQFLEFSADLIIERREGSDVCYPGKFVNEEALRQILRKS

2050/2014
GGIDKEAMGFTYSGIRTNGATSACRRSGSSFYAEMKWLLS

2014/03/25 HA
NTDNAAFPQMTKSYKNTRKSPAIIVWGIHHSVSTAEQTKL

755190506
YGSGNKLVTVGSSNYQQSFVPSPGARPQVNGLSGRIDFH

WLMLNPNDTVTFSFNGAFIAPDRASFLRGKSMGIQSGVQV

DADCEGDCYHSGGTHISNLPFQNIDSRAVGKCPRYVKQRS

LLLATGMKNVPEVPKGRGLFGAIAGFIENGWEGLIDGWY

GFRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQ

FELIDNEFNEVEKQIGNVINWTRDSITEVWSYNAELLVAM

ENQHTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFH

KCDDDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLSSG

YKDVILWFSFGASCFILLAIVMGLVFICVKNGNMRCTICI

195
AJJ97973
MNTQILVFALISIIPTNADKICLGHHAVSNGTKVNTLTERG

A/chicken/Shantou/
VEVVNATETVERTNIPRICSKGKKTVDLGQCGLLGTITGPP

4325/2014
QCDQFLEFSADLIIERREGSDVCYPGKFVNEEALRQILRKS

2014/07/01 HA
GGIDKEAMGFTYSGIRTNGVTSACRRSGSSFYAEMKWLLS

755190586
NTDNAAFPQMTKSYKNTRKSPAIIVWGIHHSVSTAEQTKL

YGSGNKLVTVGSSNYQQSFVPSPGARPQVNGLSGRIDFH

WLMLNPNDTVTFSFNGAFIAPDRASFLRGKSMGIQSGVQV

DADCEGDCYHSGGTIISNLPFQNIDSRAVGKCPRYVKQRS

LLLATGMKNVPEVPKGRGLFGAIAGFIENGWEGLIDGWY

GFRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQ

FELIDNEFNEVEKQIGNVINWTRDSITEVWSYNAELLVAM

ENQHTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFH

KCDDDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLSSG

YKDVILWFSFGASCFILLAIVMGLVFICVKNGNMRCTICI

196
AJJ97998
MNTQILVFALIAIVPTNADKICLGHHAVSNGTKVNTLTER

A/chicken/Shantou/
GVEVVNATETVERTNIPRICSKGKKTVDLGQCGLLGTITGP

4816/2014
PQCDQFLEFSADLIIERREGSDVCYPGKFVNEEALRQILRES

2014/07/22 HA
GGIDKEAMGFTYSGIRTNGATSACRRSGSSFYAEMKWLLS

755190628
NTDNAAFPQMTKSYKNTRKSPALIVWGIHHSVSTAEQTKL

YGSGNKLVTVGSSNYQQSFVPSPGARPQVNGLSGRIDFH

WLMLNPNDTVTFSFNGAFIAPDRASFLRGKSMGIQSGVQV

DANCEGDCYHSGGTIISNLPFQNIDSRAVGKCPRYVKOKS

LLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGWYG

FRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQF

ELVDNEFNEVEKQIGNVINWTRDSITEVWSYNAELLVAM

ENQHTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFH

KCDDDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLSSG

YKDVILWFSFGASCFILLAIVMGLVFICVKNGNMRCTICI

TABLE 14

H10 Hemagglutinin Amino Acid Sequences

SEQ ID
Accession No/

NO
Strain/Protein
Amino Acid Sequence

197
AAM19228
ACVLVEAKGDKICLGHHAVVNGTKVNTLTEKGIEVVNAT

A/turkey/Minnesota/
ETVETANIGKICTQGKRPTDLGQCGLLGTLIGPPQCDQFLE

38429/19881988//
FESDLIIERREGNDVCYPGKFTNEESLRQILRGSGGIDKESM

HA
GFTYSGIITNGATSACRRSGSSFYAEMKWLLSNSDNAAFP

20335017
QMTKSYRNPRNKPALIVWGIHHSGSTTEQTKLYGSGNKLI

TVESSKYQQSFTPSPGARPQVNGESGRIDFHWMLLDPNDT

VTFTFNGAFIAPDRASFFKGESLGVQSDVPLDSSCGGDCFH

SGGTIVSSLPFQNINPRTVGKCPRYVKQPSLLLATGMRNVP

ENPKTRGLFGAIAGFIEKDGGSHYG

198
AAY46211
MNTQILVFALVAIIPINADKICLGHHAVSNGTKVNTLTERG

A/mallard/Sweden/
VEVVNATETVERTNVPRICSRGKRTVDLGQCGLLGTITGP

91/20022002//
PQCDQFLEFSADLIIERREGSDVCYPGKFVNEEALRQILRES

HA
GGIDKETMGFTYSGIRTNGAPSACRRSGSSFYAEMKWLLS

66394828
NTDNAAFPQMTKSYKNTRNDPALIIWGIHHSGSTTEQTKL

YGSGNKLITVGSSNYQQSFVPSPGARPQVNGQSGRIDFHW

LILNPNDTVTFSFNGAFIAPDRASFLRGKSMGIQSGVQIDA

NCEGDCYHSGGTIISNLPFQNINSRAVGKCPRYVKQESLLL

ATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGWYGFRH

QNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELID

NEFTEVEKQIGNVINWTRDSMTEVWSYNAELLVAMENQH

TIDLADSEMNKLYERVRRQLRENAEEDGTGCFEIFHKCDD

DCMASIRNNTYDHSKYREEAMQNRIQIDPVKLSSGYKDVI

LWFSFGASCFILLAIAMGLVFMCVKNGNMRCTICI

199
ABI84694A/
MNTQILVFIACVLVEAKGDKICLGHHAVVNGTKVNTLTE

turkey/Minnesota/
KGIEVVNATETVETANIGKICTQGKRPTDLGQCGLLGTLIG

1/19881988/
PPQCDQFLEFESDLIIERREGNDVCYPGKFTNEESLRQILRG

07/13 HA
SGGIDKESMGFTYSGIRTNGATSACRRSGSSFYAEMKWLL

115278573
SNSDNAAFPQMTKSYRNPRNKPALIVWGIHHSGSTTEQTK

LYGSGNKLITVGSSKYQQSFTPSPGARPQVNGQSGRIDFH

WMLLDPNDTVTFTFNGAFIAPDRASFFKGESLGVQSDVPL

DSSCGGDCFHSGGTIVSSLPFQNINPRTVGKCPRYVKQPSL

LLATGMRNVPENPKTRGLFGAIAGFIENGWEGLIDGWYGF

KHQNAQGEGTAADYKSTQSAIDQITGKLNRLIDKTNQQFE

LIDNEFSEIEQQIGNVINWTRDSMTEVWSYNAELLVAMEN

QHTIDLADSEMNKLYERVRRQLRENAEEDGTGCFEIFHKC

DDQCMESIRNNTYDHAQYRAESLQNRIQIDPVKLSSGYKD

ILWFSFGASCELLLAIAMGLVFICIKNGNMRCTICI

200
ABS89409
MNTQILALIACMLIGAKGDKICLGHHAVANGTKVNTLTER

A/blue-winged
GIEVVNATETVETANIKKICTQGKRPTDLGQCGLLGTLIGP

teal/Ohio/566/
PQCDQFLEFDTDLIIERREGTDVCYPGKFTNEESLRQILRGS

2006 2006//HA
GGIDKESMGFTYSGIRTNGATSACRRSGSSFYAEMKWLLS

155016324
NSDNAAFPQMTKSYRNPRNKPALIWGVHHSGSATEQTKL

YGSGNKLITVGSSKYQQSFTPSPGARPQVNGQSGRIDFHW

LLLDPNDTVTFTFNGAFIAPDRASFFRGESLGVQSDVPLDS

GCEGDCFHSGGTIVSSLPFQNINPRTVGKCPRYVKQTSLLL

ATGMRNVPENPKTRGLFGAIAGFIENGWEGLIDGWYGFR

HQNAQGEGTAADYKSTQSAIDQITGKLNRLIDKTNQQFEL

IDNEFSEIEQQIGNVINWTRDSMTEVWSYNAELLVAMENQ

HTIDLADSEMNKLYERVRKQLRENAEEDGTGCFEIFHKCD

DQCMESIRNNTYDHTQYRTESLQNRIQIDPVRLSSGYKDII

LWFSFGASCFLLLAIAMGLVFICIKNGNMRCTICI

201
ACD03594
MNTQILAFIACMLVGVRGDKICLGHHAVANGTKVNTLTB

A/ruddy
KGIEVVNATETVESANIKKICTQGKRPTDLGQCGLLGTLIG

turnstone/DE/
PPQCDQFLEFDSDLIIERREGTDVCYPGKFTNEESLRQILRG

1538/2000 2000//
SGGIDKESMGFTYSGIRTNGATSACRRLGSSFYAEMKWLL

HA 187384848
SNSDNAAFPQMTKSYRNPRNKPALIIWGVHHSGSANEQT

KLYGSGNKLITVGSSKYQQSFTPSPGARPQVNGQSGRIDF

HWLLLDPNDTVTFTFNGAFIAPDRASFFRGESLGIQSDVPL

DSSCGGDCFHSGGTIVSSLPFQNINPRTVGKCPRYVKQTSL

LLATGMRNVPENPKTRGLFGAIAGFIENGWEGLIDGWYGF

RHQNAQGEGTAADYKSTQSAIDQITGKLNRLIDKTNQQFE

LMDNEFNEIEQQIGNVINWTRDSMTEVWSYNAELLVAME

NQHTIDLADSEMNKLYERVRKQLRENABEDGTGCFEIFHK

CDDQCMESIRNNTYDHTQYRTESLQNRIQIDPVKLSSGYK

DIILWFSFGASCFLLLAIAMGLIFICIKNGNMRCTICI

202
BAH22785
MNTQILVFALVAIIPTNADKICLGHHAVSNGTKVNTLTER

A/duck/Mongolia/
GVEVVNATETVERTNIPRICSKGKRTVDLGQCGLLGTITGP

119/2008
PQCDQFLEFSADLIIERREGSDVCYPGKFVNEEALRQILRES

2008//HA
GGIGKETMGFTYSGIRTNGATSACRRSGSSFYAEMKWLLS

223717820
NTDNAAFPQMTKSYKNTRKDPALIIWGIHHSGSTTEQTKL

YGSGNKLITVGSSNYQQSFVPSPGARPQVNGQSGRIDFHW

LMLNPNDTVTFSFNGAFIAPDRASFLRGKSMGIQSGVQVD

ANCEGDCYHNGGTHISNLPFQNINSRTVGKCPRYVKQESLL

LATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGWYGFR

HQNAQGEGTAADYKSTQSAIDQITGKLNRLIERTNQQFELI

DNEFTEVEKQIGNVINWTRDSMTEVWSYNAELLVAMENQ

HTIDLADSEMNKLYERVKRQLRENAEEDGTGCFEIFHKCD

DDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLSNGYKD

VILWFSFGASCFILLAIAMGLVFICVKNGNMRCTICI

203
CAY39406
MNTQILVFALVAIIPTNADKICLGHHAVSNGTKVNTLTER

A/Anas
GVEVVNATETVERTNVPRICSKGKRTVDLGQCGLLGTITG

crecca/Spain/
PPQCDQFLEFSADLIIERREGSDVCYPGKFVNEEALRQILRE

1460/2008
SGGIDKETMGFTYSGIRTNGATSACRRSGSSFYAEMKWLL

2008/01/26 HA
SNTDNAAFPQMTKSYKNTRKDPALIWGIHHSGSTTEQTK

254674376
LYGSGSKLITVGSSNYQQSFVPSPGARPQVNGQSGRIDFH

WLMLNPNDTVTFSFNGAFIAPDRASFLRGKSMGIQSGVQV

DANCEGDCYHSGGTIISNLPFQNINSRAVGKCPRYVKQES

LMLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGWY

GFRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQ

FELIDNEFTEVEKQIGNVINWIRDSITEVWSYNAELLVAM

ENQHTIDLADSEMNKLYERVKRQLRENAEEDGTGCFEIFH

KCDDDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLSSG

YKDVILWFSFGASCFILLAIAMGLVFICVKNGNMRCTICI

204
ACX53683
MNIQILVFALVAIPTNADKICLGHHAVSNGTKVNTLTERG

A/goose/Czech
VEVVNATETVERTNVPRICSKGKRTVDLGQCGLLGTITGP

Republic/1848-
PQCDQFLEFSADLIIERRGGSDVCYPGKFVNEEALRQILRE

K9/2009
SGGIDKETMGFTYSGIRTNGATSACRRSGSSFYAEMKWLL

2009/02/04 HA
SNTDNAAFPQMTKSYKNTRKDPALIIWGIHHSGSTTEQTK

260907763
LYGSGSKLITVGSSNYQQSFVPSPGARPQVNGQSGRIDFH

WLMLNPNDTVTFSENGAFIAPDRASFLKGKSMGIQSGVQV

DANCEGDCYHSGGTIISNLPFQNINSRAVGKCPRYVKQES

LMLATGMKNVPELPKGRGLFGAIAGFIENGWEGLIDGWY

GFRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQ

FELIDNEFTEVEKQIGNVINWTRDSMTEVWSYNAELLVA

MENQHTIDLADSEMNKLYERVKRQLRENAEEDGTGCFEIF

HKCDDDCMASIRNNTYDHSKYREEAMQNRIQINPVKLSS

GYKDVILWFSFGASCFILLAIAMGLVFICVKNGNMRCTICI

205
ACZ48625
MNTQILVFIACVLVEAKGDKICLGHHAVVNGTKVNTLTE

A/turkey/Minnesota/
KGIEVVNATETVETANIGKICTQGKRPTDLGQCGLLGTLIG

38429/1988
PPQCDQFLEFESDLIIERREGNDVCYPGKFTNEESLRQILRG

1988//HA
SGGIDKESMGFTYSGIRTNGATSACRRSGSSFYAEMKWLL

269826341
SNSDNAAFPQMTKSYRNPRNKPALIVWGIHHSGSTTEQTK

LYGSGNKLITVGSSKYQQSFTPSPGARPQVNGQSGRIDFH

WMLLDPNDTVTFTFNGAFIAPDRASFFKGESLGVQSDVPL

DSSCGGDCFHSGGTIVSSLPFQNINPRTVGKCPRYVKQPSL

LLATGMRNVPENPKTRGLFGAIAGFIENGWEGLIDGWYGF

KHQNAQGEGTAADYKSTQSAIDQITGKLNRLIDKTNQQFE

L

206
ADC29485
STQSAIDQITGKLNRLIEKTNQQFELIDNEFTEVEKQIGNVI

A/mallard/Spain/
NWTRDSMTEVWSYNAELLVAMENQHTIDLADSEMNKLY

08.00991.3/2005
ERVKRQLRENAEEDGTGCFEIFHKCDDDCMASIRNNTYD

2005/11/ HA
HSKYREEAMQNRIQIDPVKLSSGYKDVILWFSFGASCFILL

284927336

207
ADK71137
MNTQILALIACMLIGAKGDKICLGHHAVANGTKVNTLTER

A/blue-winged
GIEVVNATETVETANIKKICTQGKRPTDLGQCGLLGTLIGP

teal/Guatemala/
PQCDQFLEFDADLIIERREGTDVCYPGKFTNEESLRQILRG

CIP049-01/2008
SGGIDKESMGFTYSGIRTNGATSACRRSGSSSYAEMKWLL

2008/02/07 HA
SNSDNAAFPQMTKSYRNPRNKPALIIWGVHHSGSATEQTK

301333785
LYGSGNKLITVGSSKYQQSFTPSPGTRPQVNGQSGRIDFH

WLLLDPNDTVTFTFNGAFIAPDRASFLRGKSLGIQSDVPLD

SGCEGDCFHSGGTIVSSLPFQNINPRTVGKCPRYVKQTSLL

LATGMRNVPENPKTRGLFGAIAGFIENGWEGLIDGWYGF

RHQNAQGEGTAADYKSTQSAIDQITGKLNRLIDKTNQHFE

LIDNEFSEIEQQIGNVINWTRDSMTEVWSYNAELLVAMEN

QHTIDLADSEMNKLYERVRKQLRENAEEDGTGCFEIFHKC

DDQCMESIRNNTYDHTQYRTESLQNRIQIDPVKLSSGYKDI

ILWFSFGASCFLLLAIAMGLVFICIKNGNMRCTICI

208
ADK71148
MNTQILALIACMLIGAKGDKICLGHHAVANGTKVNTLTER

A/blue-winged
GIEVVNXTETVETANIKKICTHGKRPTDLGQCGLLGTLIGP

teal/Guatemala/
PQCDRFLEFDADLIIERREGTDVCYPGKFTNEESLRQILRGS

CIP049-02/2008
GGIDKESMGFTYSGIRTNGATSACRRSGSSFYAEMKWLLS

2008/03/05 HA
NSDNAAFPQMTKSYRNPRNKPALIIWGVHHSGSATEQTKL

301333804
YGSGNKLITVGSSKYQQSFTPSPGTRPQVNGQSGRIDFHW

LLLDPNDTVTFTFNGAFIAPDRASFLRGKSLGIQSDVPLDS

GCEGDCFHSGGTIVSSLPFQNINPRTVGKCPRYVKQTSLLL

ATGMRNVPENPKTRGLFGAIAGFIENGWEGLIDGWYGFR

HQNAQGEGTAADYKSTQSAIDQITGKLNRLIDKTNQQFEL

IDNEFSEIEQQIGNVINWTRDSMTEVWSYNAELLVAMENQ

HTIDLADSEMNKLYERVRKQLRENAEEDGTGCFEIFHKCD

DQCMESIRNNTYDHTQYRTESLQNRIQIDPVKLSSGYKDII

LWFSFGASCFLLLAIAMGLVFICIKNGNMRCTICI

209
ADN34727
MNIQILVFALVAIIPTNADKICLGHHAVSNGTKVNTLTERG

A/goose/Czech
VEVVNATETVERTNVPRICSKGKRTVDLGQCGLLGTITGP

Republic/1848-
PQCDQFLEFSADLIIERRGGSDVCYPGKFVNEEALRQILRE

T14/2009
SGGIDKETMGFTYSGIRTNGXTSACRRSGSSFYAEMKWLL

2009/02/04 HA
SNTDNAAFPQMTKSYKNTRKDPALIIWGIHHSGSTTEQTK

307141869
LYGSGSKLITVGSSNYQQSFVPSPGARPQVNGQSGRIDFH

WLMLNPNDTVTFSFNGAFIAPDRASFLKGKSMGIQSGVQV

DANCEGDCYHSGGTIISNLPFQNINSRAVGKCPRYVKQES

LMLATGMKNVPELPKGRGLFGAIAGFIENGWEGLIDGWY

GFRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQ

FELIDNEFTEVEKQIGNVINWTRDSMTEVWSYNAELLVA

MENQHTIDLADSEMNKLYERVKRQLRENAEEDGTGCFEIF

HKCDDDCMASIRNNTYDHSKYREEAMQNRIQINPVKLSS

GYKDVILWFSFGASCFILLAIAMGLVFICVKNGNMRCTICI

210
AEK84760
PAFIAPDRASFLRGKSMGIQSGVQVDASCEGDCYHSGGTII

A/wild
SNLPFQNINSRAVGKCPRYVKQESLMLATGMKNVPELPK

bird/Korea/A14/
GRGLFGAIAGFIENGWEGLIDGWYGFRHQNAQGEGTAAD

2011 2011/02/
YKSTQSAIDQITGKLNRLIEKTNQQFELIDNEFTEVEKQIGN

HA 341610308
VINWTRDSMTEVWSYNAELLVAMENQHTIDLADSEMNK

LYERVRRQLRENAEEDGTGCFEIFHKCDDDCMASIRNNTY

DHSKYREEAMQNRIQIDPVKLSSGYKDVILWFSFGASCFIL

LAIAMGLVFICVKNGNMRCTICI

211
AEK84761
ILVFALVAUPTNANKIGLGHHAVSNGTKVNTLTERGVEVF

A/wild
NATETVERTNVPRICSKGKKTVDLGQCGLRGTITGPPQCD

bird/Korea/A3/
QFLKFSPDLIIERQKGSDVCYPGKFVNEKPLRQILRESGGID

2011 2011/02/
KETMGFAYNGIKTNGPPIACRKSGSSFYAKMKWLLSNTD

HA 341610310
KAAFPQMTKSYKNTRRNPALIVWGIHHSGSTTKQTKLYGI

GSNLITVGSSNYQQSFVPSPGARPQVNGQSGRIDFHWLILN

PNDTVTFSFNGAFIPPDRASFLRGKSMGIQSGVQVDASCEG

DCYHSGGTIISNLPFQNINSRAVGKCPRYVKQESLMLATG

MKNVPELPKGKGLFGAIAGFIENGWEGLIDGWYGFRHQN

AQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELIDNE

FTEVEKQIGNVINWTRDSMTEVWSYNAELLVAMENQHTI

DLADSEMNKLYERVRRQLRENAEEDGTGCFEIFHKCDDD

CMASIRNNTYDHSKYREEAMQNRIQIDPVKLSSGYKDVIL

WFSFGASCFILLAIAMGLVFICVKNGNMRCTICI

212
AEK84763
ILVFALVAIIPTNANKIGLGHHAVSNGTKVNTLTERGVEFF

A/wild
NATETVEPTNVPRICSKGKKTVDLGQCGLLGTITGPPQCD

bird/Korea/A9/
QFLEFSADLIIERREGSDVCYPGKFVNEKALRQILRESGGID

2011 2011/02/
KETMGFAYSGIKTNGPPIACRKSGSSFYAKMKWLLSNTDK

HA 341610314
AAFPQMTKSYKNIRRDPALIVWGIHHSGSTTKQTNLYGIG

SNLITVGSSNYQQSFVPSPGARPQVNGQSGRIDFHWLILNP

NDTVTFIFNGAFIAPDRASFLIGKSMGIQSGVQVDASCEGD

CYHSGGTIISNLPFQNINSRAVGKCPRYVKQESLMLATGM

KNVPELPKGRGLFGAIAGFIENGWEGLIDGWYGFRHQNA

QGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELIDNEF

TEVEKQIGNVINWTRDSMTEVWSYNAELLVAMENQHTID

LADSEMNKLYERVRRQLRENAEEDGTGCFEIFHKCDDDC

MASIRNNTYDHSKYREEAMQNRIQIDPVKLSSGYKDVILW

FSFGASCFILLAIAMGLVFICVKNGNMRCTICI

213
AEK84765
LVFALVAIIPTNADKICLGHHAVSNGTKVNTLTERGVEVV

A/spot-billed
NATETVERTNVPRICSKGKRTVDLGQCGLLGTITGPPQCD

duck/Korea/447/
QFLEFSADLIERREGSDVCYPGKFVNEEALRQILRESGGID

2011 2011/04/
KETMGFTYSGIRTNGATSACRRSGSSFYAEMKWLLSNTD

HA 341610318
NAAFPQMTKSYKNTRRDPALIVWGIHHSGSTTEQTKLYGS

GSKLITVGSSNYQQSFVPSPGARPQVNGQSGRIDFHWLILN

PNDTVTFSFNGAFIAPDRASFLRGKSMGIQSGVQVDASCE

GDCYHSGGTIISNLPFQNINSRAVGKCPRYVKQESLMLAT

GMKNVPEPPKGRGLFGAIAGFIENGWEGLIDGWYGFRHQ

NAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELIDN

EFTEVEKQIGNVINWTRDSMTEVWSYNAELLVAMENQHT

IDLADSEMNKLYERVRRQLRENAEEDGTGCFEIFHKCDDD

CMARIRNNTYDHSKYREEAMQNRIQIDPVKLSSGYKDVIL

WFSFGASCFILLAIAMGLVFICVKNGNMRCTICI

214
AEM98291
SILVFALVAIIPTNADKICLGHHAVSNGTKVNTLTERGVEV

A/wild
VNATETVERTNVPRICSKGKRTVDLGQCGLLGTITGPPQC

duck/Mongolia/
DQFLEFSADLIIERREGSDVCYPGKFVNEEALRQILRESGGI

1-241/2008
DKETMGFTYSGIRTNGATSACRRSGSSFYAEMKWLLSNT

2008/04/HA
DNAAFPQMTKSYKNTRKDPALIIWGIHHSGSTTEQTKLYG

344196120
SGSKLITVGSSNYQQSFVPSPGARPQVNGQSGRIDFHWLM

LNPNDTVTFSFNGAFIAPDRASFLRGKSMGIQSGVQVDAN

CEGDCYHSGGSIISNLPFQNINSRAVGKCPRYVKQESLML

ATGMKNVPELPKGRGLFGAIAGFIENGWEGLIDGWYGFR

HQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELI

DNEFTEVEKQIGNVINWTRDSMTEVWSYNAELLVAMENQ

HTIDLADSEMNKLYERVKRQLRENAEEDGTGCFEIFHKCD

DDCMASINNTYDHSKYREEAMQNRIQINPVKLSSGYKD

VILWFSFGASCFILLAIAMGLVFICVKNGNMRCTI

215
AFM09439
QILAFIACMLIGAKGDKICLGHHAVANGTKVNTLTERGIE

A/emperor
VVNATETVETVNIKKICTQGKRPTDLGQCGLLGTLIGPPQC

goose/Alaska/
DQFLEFDADLIIERRKGTDVCYPGKFTNEESLRQILRGSGGI

44063-061/2006
DKESMGFTYSGIRTNGATSACRRSGSSFYAEMKWLLSNSD

2006/05/23 HA
NAAFPQMTKSYRNPRNKPALIWGVHHSGSATEQTKLYGS

390535062
GNKLITVGSSKYQQSFVPSPGARPQVNGQSGRIDFHWLLL

DPNDTVTFTFNGAFIAPERASFFRGESLGVQSDVPLDSGCE

GDCFHSGGTIVSSLPFQNINPRTVGKCPRYVKQTSLLLATG

MRNVPENPKTRGLFGAIAGFIENGWEGLIDGWYGFRHQN

AQGEGTAADYKSTQSAIDQITGKLNRLIDKTNQQFELIDNE

FSEIEQQIGNVINWTRDSMTEVWSYNAELLVAMENQHTID

LADSEMNKLYERVRKQLRENAEEDGTGCFEIFHKCDDQC

MESIRNNTYDHTQYRTESLQNRIQINPVKLSSGYKDIILWF

SFGASCELLLAIAMGLVFICIKNGNMRCTICI

216
AFV33945
MNTQILALIACMLIGAKGDKICLGHHAVANGTKVNTLTER

A/guinea
RIEVVNATETVETANIKKICTQGKRPTDLGQCGLLGTLIGP

fowl/Nebraska/
PQCDQFLEFDADLIIERREGTDVCYPGKFTNEESLRQILRG

17096-1/2011
SGGIDKESMGFTYSGIRTNGATSACRRSGSSFYAEMKWLL

2011/04/05 HA
SNSNNAAFPQMTKSYRNPRNKPALIVWGVHHSGSATEQT

409676820
KLYGSGSKLITVGSSKYQQSFTPSPGARPQVNGQSGRIDFH

WLLLDPNDTVTFTFNGAFIAPDRASFFRGESLGVQSDVPL

DSGCEGDCFHKGGTIVSSLPFQNINPRTVGKCPRYVKQTSL

LLATGMRNVPENPKTRGLFGAIAGFIENGWEGLIDGWYGF

RHQNAQGEGTAADYKSTQSAIDQITGKLNRLIDKTNQQFE

LIDNEFSEIEQQIGNVINWTRDSMTEIWSYNAELLVAMEN

QHTIDLADSEMNKLYERVRKQLRENAEEDGTGCFEIFHKC

DDQCMESIRNNTYDHTQYRAESLQNRIQIDPVKLSSGYKD

IILWFSFGASCFLLLAIAMGLVFICIKNGNMRCTICI

217
AFV33947
MNTQILALIACMLIGAKGDKICLGHHAVANGTKVNTLTER

A/goose/Nebraska/
GIEVVNATETVETANIKKICTQGKRPTDLGQCGLLGTLIGP

17097-4/2011
PQCDQFLEFDADLIIERREGTDVCYPGKFTNEESLRQILRG

2011/04/05 HA
SGGIDKESMGFTYSGIRTNGATSACRRSGSSFYAEMKWLL

409676827
SNSDNAAFPQMTKSYRNPRNKPALIVWGVHHSASATEQT

KLYGSGSKLITVGSSKYQQSFTPSPGARPQVNGQSGRIDFH

WLLLDPNDTVTFTFNGAFIAPDRASFFRGESLGVQSDVPL

DSGCEGDCFHKGGTIVSSLPFQNINPRTVGKCPRYVKQTSL

LLATGMRNVPENPKTRGLFGAIAGFIENGWEGLIDGWYGF

RHQNAQGEGTAADYKSTQSAIDQITGKLNRLIDKTNQQFE

LIDNEFSEIEQQIGNVINWTRDSMTEIWSYNAELLVAMEN

QHTIDLADSEMNKLYERVRKQLRENABEDGTGCFEIFHKC

DDQCMESIRNNTYDHTQYRAESLQNRIQIDPVKLSSGYKD

IILWFSFGASCELLLAIAMGLVFICIKNGNMRCTICI

218
AFX85260
MNTQILAFIACMLIGINGDKICLGHHAVANGTKVNTLTER

A/ruddy
GIEVVNATETVETANIKRICTQGKRPIDLGQCGLLGTLIGPP

turnstone/Delaware
QCDQFLEFDSDLIIERREGTDVCYPGKFTNEESLRQILRGS

Bay/220/1995
GGIDKESMGFTYSGIRTNGATSACIRLGSSFYAEMKWLLS

1995/05/21 HA
NSDNAAFPQMTKSYRNPRNKPALIWGVHHSGSANEQTK

423514912
LYGSGNKLITVGSSKYQQSFTPSPGARPQVNGQSGRIDFH

WLLLDPNDTVTFTFNGAFIAPDRASFFRGESLGVQSDVPL

DSSCGGDCFHSGGTIVSSLPFQNINPRTVGRCPRYVKQTSL

LLATGMKNVPENPKTRGLFGAIAGFIENGWEGLIDGWYG

FRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIDKTNQQF

ELIDNEFNEIEQQIGNVINWTRDSMTEVWSYNAELLVAME

NQHTIDLADSEMNKLYERVRKQLRENAEEDGTGCFEIFHK

CDDQCMESIRNNTYDHTQYRTESLQNRIQIDPVKLSSGYK

DIILWFSFGASCFLLLAIAMGLVFICIKNGNMRCTICI

219
AGB08098
MNTQILTLIACMLIGAKGDKICLGHHAVANGTKVNTLTER

A/northern
GIEVVNATETVETANIKKICTQGKRPTDLGQCGLLGTLIGP

shoverl/Mississippi/
PQCDQFLEFDADLIIERREGTDVCYPGKFTNEESLRQILRG

11OS145/2011
SGGIDKESMGFTYSGIRTNGATSACRRSGSSFYAEMKWLL

2011/01/08
SNSDNAAFPQMTKSYRNPRNKPALIIWGVHHSGSATEQTK

HA 444344488
LYGSGNKLITVGSSKYQQSFTPSPGARPQVNGQSGRIDFH

WLLLDPNDTVTFTFNGAFIAPDRASFFRGESLGVQSDVPL

DSGCEGDCFHNGGTIVSSLPFQNINPRTVGKCPRYVKQTSL

LLATGMRNVPENPKTRGLFGAIAGFIENGWEGLIDGWYGF

RHQNAQGEGTAADYKSTQSAIDQITGKLNRLIDKTNQQFE

LIDNEFSEIEQQIGNVINWTRDSMTEVWSYNAELLVAMEN

QHTIDLADSEMNKLYERVRKQLRENAEEDGTGCFEIFHKC

DDQCMESIRNNTYDHTQYRAESLQNRIQIDPVKLSSGYKD

IILWFSFGASCFLLLAIAMGLVFICIKNGNMRCTICI

220
AGI60301
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERG

A/Hangzhou/1/
VEVVNATETVERTNIPRICSKGKRTVDLGQCGLLGTITGPP

2013 2013/03/24
QCDQFLEFSADLIIERREGSDVCYPGKFVNEEALRQILRES

HA 475662454
GGIDKEAMGFTYSGIRTNGATSACRRSGSSFYAEMKWLLS

NTDNAAFPQMTKSYKNTRKSPALIVWGIHHSVSTAEQTKL

YGSGNKLVTVGSSNYQQSFVPSPGARPQVNGISGRIDFHW

LMLNPNDTVTFSFNGAFIAPDRASFLRGKSMGIQSGVQVD

ANCEGDCYHSGGTHISNLPFQNIDSRAVGKCPRYVKQRSLL

LATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGWYGFR

HQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELI

DNEFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQ

HTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFHKCD

DDCMASINNTYDHSKYREEAMQNRIQIDPVKLSSGYKD

VILWFSFGASCFILLAIVMGLVFICVKNGNMRCTICI

221
AGI60292
MNTQILVEALIAIIPANADKICLGHHAVSNGTKVNTLTERG

A/Shanghai/466
VEVVNATETVERTNIPRICSKGKRTVDLGQCGLLGTITGPP

4T/2013
QCDQFLEFSADLIIERREGSDVCYPGKFVNEEALRQILRES

2013/03/05 HA
GGIDKEAMGFTYSGIRTNGATSACRRSGSSFYAEMKWLLS

476403560
NTDNAAFPQMTKSYKNTRKSPALIVWGIHHSVSTAEQTKL

YGSGNKLVTVGSSNYQQSFVPSPGARPQVNGLSGRIDFH

WLMLNPNDTVTFSENGAFIAPDRASFLRGKSMGIQSGVQV

DANCEGDCHHSGGTIISNLPFQNIDSRAVGKCPRYVKQRS

LLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGWYG

FRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQF

ELIDNEFNEVEKQIGNVINWTRDSITEVWSYNAELLVAME

NQHTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFHK

CDDDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLSSGY

KDVILWFSFGASCFILLAIVMGLVFICVKNGNMRCTICI

222
AGJ72861
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERG

A/chicken/Zhejiang/
GEVVNATETVERTNIPRICSKGKKTVDLGQGGPRGTITGPP

DTID-ZJU01/2013
QCDQFLEFSADLIMERREGSDVCYPGKFVNEEALRQILRES

2013/04/ HA
GGIDKEAMGFTYSGIRTNGATSACRRSGSSFYAEMKWLLS

479280294
NTDNAAFPQMTKSYKNTRKSPALIVWGIHHSVSTAEQTKL

YGSGNKLVTVGSSNYQQSFVPSPGARPQVNGQSGRIDFH

WLMLNPNDTVTFSFNGAFIAPDRASFLRGKSMGIQSGVQV

DANCEGDCYHSGGTHISNLPFQNIDSRAVGKCPRYVKQRS

LLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGWYG

FRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQF

ELIDNEFNEVEKQIGNVINWTRDSITEVWSYNAELLVAME

NQHTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFHK

CDDDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLSSGY

KDVILWFSFGASCFILLAIVMGLVFICVKNGNMRCTICI

223
AGJ73503
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERG

A/Nanjing/1/2013
VEVVNATETVERTNIPRICSKGKMTVDLGQCGLLGTITGPP

2013/03/28
QCDQFLEFSADLIIERREGSDVCYPGKFVNEEALRQILRES

HA 479285761
GGIDKEAMGFTYSGIRTNGATSACRRSGSSFYAEMKWLLS

NTDNAAFPQMTKSYKNTRKSPALIVWGIHHSVSTAEQTKL

YGSGNKLVTVGSSNYQQSFVPSPGARPQVNGLSGRIDFH

WLMLNPNDTVTFSFNGAFIAPDRASFLRGKSMGIQSGVQV

DANCEGDCYHSGGTHISNLPFQNIDSRAVGKCPRYVKQRS

LLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGWYG

FRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQF

ELIDNEFNEVEKQIGNVINWTRDSITEVWSYNAELLVAME

NQHTIDLADSEMDKLYERVKRQLRENABEDGTGCFEIFHK

CDDDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLSSGY

KDVILWFSFGASCFILLAIVMGLVFICVKNGNMRCTICI

224
BAN16711
MNTQVLVFALMAIPTNADKICLGHHAVSNGTKVNTLTER

A/duck/Gunma/
GVEVVNATETVERTNVPRICSKGKRTVDLGQCGLLGTITG

466/2011 2011//
PPQCDQFLEFSADLIIERREGSDVCYPGKFVNEEALRQILRE

HA 482661571
SGGIDKETMGFTYSGIRTNGTTSACRRSGSSFYAEMKWLL

SNTDNAAFPQMTKSYKNTRRDPALIAWGIHHSGSTTEQTK

LYGSGSKLITVGSSNYQQSFVPSPGARPQVNGQSGRIDFH

WLILNPNDTVTFSFNGAFIAPDRASFLRGKSMGIQSGVQV

DASCEGDCYHSGGTIISNLPFQNINSRAVGKCPRYVKQESL

MLATGMKNVPELPKGRGLFGAIAGFIENGWEGLIDGWYG

FRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQF

ELIDNEFTEVEKQIGNVINWTRDSMTEVWSYNAELLVAM

ENQHTIDLADSEMNKLYERVRRQLRENAEEDDTGCFEIFH

KCDDDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLSSG

YKDVILWFSFGASCFILLAIAMGLVFICVKNGNMRCTICI

225
AGK84857
MNTQILVEALIAIIPTNADKICLGHHAVSNGTKVNTLTERG

A/Hangzhou/2/
VEVVNATETVERTNIPRICSKGKRTVDLGQCGLLGTITGPP

2013 2013/04/01
QCDQFLEFSADLIHIERREGSDVCYPGKFVNEEALRQILRES

HA 485649824
GGIDKEAMGFTYSGIRTNGATSACRRSGSSFYAEMKWLLS

NTDNAAFPQITKSYKNTRKSPALIVWGIHHSVSTAEQTKL

YGSGNKLVTVGSSNYQQSFVPSPGARPQVNGLSGRIDFH

WLMLNPNDTVTFSFNGAFIAPDRASFLRGKSMGIQSGVQV

DANCEGDCYHSGGTIISNLPFQNIDSRAVGKCPRYVKQRS

LLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGWYG

FRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQF

ELIDNEFNEVEKQIGNVINWTRDSITEVWSYNAELLVAME

NQHTIDLADSEMDKLYERVKRQLRENABEDGTGCFEIFHK

CDDDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLSSGY

KDVILWFSFGASCFILLAIVMGLVFICVKNGNMRCTICI

226
AGL44438
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERG

A/Shanghai/02/
VEVVNATETVERTNIPRICSKGKRTVDLGQCGLLGTITGPP

2013 2013/03/05
QCDQFLEFSADLIIERREGSDVCYPGKFVNEEALRQILRES

HA 496493389
GGIDKEAMGFTYSGIRTNGATSACRRSGSSFYAEMKWLLS

NTDNAAFPQMTKSYKNTRKSPALIVWGIHHSVSTAEQTKL

YGSGNKLVTVGSSNYQQSFVPSPGARPQVNGLSGRIDFH

WLMLNPNDTVTFSFNGAFIAPDRASFLRGKSMGIQSGVQV

DANCEGDCYHSGGTIISNLPFQNIDSRAVGKCPRYVKQRS

LLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGWYG

FRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQF

ELIDNEFNEVEKQIGNVINWTRDSITEVWSYNAELLVAME

NQHTIDLADSEMDKLYERVKRQLRENABEDGTGCFEIFHK

CDDDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLSSGY

KDVILWFSFGASCFILLAIVMGLVFICVKNGNMRCTICI

227
AGL33692
GMIDGWYGFRHQNAQGEGTAADYKSTQSAIDQITGKLNR

A/Shanghai/465
LIEKTNQQFELIDNEFTEVEKQIGNVINWTRDSITEVWSYN

5T/2013
AELLVAMENQHTIDLADSEMDKLYERVKRQLRENAEEDG

2013/02/26 HA
TGCFEIFHKCDDDCMASIRNNTYDHSKYREEAMQNRIQID

491874175
PVKLSSGYKDVILWFSFGASCFILLAIAMGLVFICVKNGN

MRCTICI

228
AGL33693
GMIDGWYGFRHQNAQGEGTAADYKSTQSAIDQITGKLNR

A/Shanghai/465
LIEKTNQQFELIDNEFNEVEKQIGNVINWTRDSITEVWSYN

9T/2013
AELLVAMENQHTIDLADSEMDKLYERVKRQLRENAEEDG

2013/02/27 HA
TGCFEIFHKCDDDCMASIRNNTYDHSKYREEAMQNRIQID

491874186
PVKLSSGYKDVILWFSFGASCFILLAIVMGLVFICVKNGN

MRCTICI

229
AGL95088
VFALIAIIPTNADKICLGHHAVSNGTKVNTLTERGVEVVN

A/Taiwan/S020
ATETVERTNIPRICSKGKRTVDLGQCGLLGTITGPPQCDQF

76/2013
LEFSADLIIERREGSDVCYPGKFVNEEALRQILRESGGIDKE

2013/04/22 HA
AMGFTYSGIRTNGATSACRRSGSSFYAEMKWLLSNTDNA

501485301
AFPQMTKSYKNTRKSPALIVWGIHHSVSTAEQTKLYGSGN

KLVTVGSSNYQQSFVPSPGARPQVNGLSGRIDFHWLMLNP

NDTVTFSFNGAFIAPDRASFLRGKSMGIQSGVQVDANCEG

DCYHSGGTIISNLPFQNIDSRAVGKCPRYVKQRSLLLATG

MKNVPEIPKGRGLFGAIAGFIENGWEGLIDGWYGFRHQN

AQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELIDNE

FNEVEKQIGNVINWIRDSITEVWSYNAELLVAMENQHTID

LADSEMDKLYERVKRQLRENAEEDGTGCFEIFHKCDDDC

MASIRNNTYDHSKYREEAMQNRIQIDPVKLSSGYKDVILW

FSFGASCFILLAIVMGLVFICVKNGNMR

230
AGL95098
LVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERGVEVVN

A/Taiwan/T020
ATETVERTNIPRICSKGKRTVDLGQCGLLGTITGPPQCDQF

81/2013
LEFSADLIIERREGSDVCYPGKFVNEEALRQILRESGGIDKE

2013/04/22 HA
AMGFTYSGIRTNGATSACRRSGSSFYAEMKWLLSNTDNA

501485319
AFPQMTKSYKNTRKSPALIVWGIHHSVSTAEQTKLYGSGN

KLVTVGSSNYQQSFVPSPGARPQVNGLSGRIDFHWLMLNP

NDTVTFSFNGAFIAPDRASFLRGKSMGIQSGVQVDANCEG

DCYHSGGTIISNLPFQNIDSRAVGKCPRYVKQRSLLLATG

MKNVPEIPKGRGLFGAIAGFIENGWEGLIDGWYGFRHQN

AQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELIDNE

FNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQHTID

LADSEMDKLYERVKRQLRENAEEDGTGCFEIFHKCDDDC

MASIRNNTYDHSKYREEAMQNRIQIDPVKLSSGYKDVILW

FSFGASCFILLAIVMGLVFICVKNGNMRCT

231
AGM53883
GFRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQ

A/Shanghai/508
FELIDNEFNEVEKQIGNVINWTRDSITEVWSYNAELLVAM

3T/2013
ENQHTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFH

2013/04/20 HA
KCDDDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLSSG

507593986
YKDVILWFSFGASCFILLAIVMGLVFICVKNGNMRCT

232
AGM53884
AQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELIDNE

A/Shanghai/518
FNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQHTID

0T/2013
LADSEMDKLYERVKRQLRENAEEDGTGCFEIFHKCDDDC

2013/04/23 HA
MASIRNNTYDHSKYREEAMQNRIQIDPVKLSSGYKDVILW

507593988
FSFGASCFILLAIVMGLVFICVKNGNMRCTICI

233
AGM53885
QNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELID

A/Shanghai/524
NEFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQH

0T/2013
TIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFHKCDD

2013/04/25 HA
DCMASIRNNTYDHSKYREEAMQNRIQIDPVKLSSGYKDVI

507593990
LWFSFGASCFILLAIVMGLVFICVKNGNMRCT

234
AGM53886
NAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELIDN

A/Shanghai/484
EFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQHTI

2T/2013
DLADSEMDKLYERVKRQLRENAEEDGTGCFEIFHKCDDD

2013/04/13 HA
CMASIRNNTYDHSKYREEAMQNRIQIDPVKLSSGYKDVIL

507593992
WFSFGASCFILLAIVMGLVFICVKNGNMRCT

235
AGM53887
NAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELIDN

A/Shanghai/470
EFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQHTI

1T/2013
DLADSEMDKLYERVKRQLRENAEEDGTGCFEIFHKCDDD

2013/04/06 HA
CMASIRNNTYDHSKYREEAMQNRIQIDPVKLSSGYKDVIL

507593994
WFSFGASCFILLAIVMGLVFICVKNGNMRCTIC

236
AGN69462
MNTQILVFALIAUPTNADKICLGHHAVSNGTKVNTLTERG

A/Wuxi/2/2013
VEVVNATETVERTNIPRICSKGKRTVDLGQCGLLGTITGPP

2013/03/31 HA
QCDQFLEFSADLIIERREGSDVCYPGKFVNEBALRQILRES

511105778
GGIDKEAMGFTYSGIRTNGSTSACRRSGSSFYAEMKWLLS

NTDNAAFPQMTKSYKNTRKSPALIVWGIHHSVSTAEQTKL

YGSGSKLVTVGSSNYQQSFVPSPGARPQVNGLSGRIDFHW

LMLNPNDTVTFSFNGAFIAPDRASFLRGKSMGIQSGVQVD

ANCEGDCYHSGGTIISNLPFQNIDSRAVGKCPRYVKQRSLL

LATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGWYGFR

HQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELI

DNEFNEVEKQIGNVINWIRDSITEVWSYNAELLVAMENQ

HTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFHKCD

DDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLSSGYKD

VILWFSFGASCFILLAIVMGLVFICVKNGNMRCTICI

237
AGN69474
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERG

A/Wuxi/1/2013
VEVVNATETVERTNIPRICSKGKRTVDLGQCGLLGTITGPP

2013/03/31 HA
QCDQFLEFSADLIIERREGSDVCYPGKFVNEBALRQILRES

511105798
GGIDKEAMGFTYSGIRTNGATSACRRSGSSFYAEMKWLLS

NTDNAAFPQMTKSYKNTRKSPALIVWGIHHSVSTAEQTKL

YGSGNKLVTVGSSNYQQSFVPSPGARPQVNGLSGRIDFH

WLMLNPNDTVTFSFNGAFIAPDRASFLRGKSMGIQSGVQV

DANCEGDCYHSGGTHISNLPFQNIDSRAVGKCPRYVKQRS

LLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLINGWYG

FRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQF

ELIDNEFNEVEKQIGNVINWTRDSITEVWSYNAELLVAME

NQHTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFHK

CDDDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLSSGY

KDVILWFSFGASCFILLAIVMGLVFICVKNGNMRCTICI

238
AGO51387
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERG

A/Jiangsu/2/2013
VEVVNATETVERTNIPRICSKGKMTVDLGQCGLLGTITGPP

2013/04/20
QCDQFLEFSADLIIERREGSDVCYPGKFVNEEALRQILRES

HA 514390990
GGIDKEAMGFTYSGIRTNGATSACRRSGSSFYAEMKWLLS

NTDNAAFPQMTKSYKNTRKSPALIVWGIHHSVSTAEQTKL

YGSGNKLVTVGSSNYQQSFVPSPGARPQVNGLSGRIDFH

WLMLNPNDTVTFSFNGAFIAPDRASFLRGKSMGIQSGVQV

DANCEGDCYHSGGTHISNLPFQNIDSRAVGKCPRYVKQRS

LLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGWYG

FRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQF

ELIDNEFNEVEKQIGNVINWTRDSITEVWSYNAELLVAME

NQHTIDLADSEMDKLYERVKRQLRENABEDGTGCFEIFHK

CDDDCMASIRNNTYDHSKYRXEAMXBXIQIDPVKLSSGY

KDVXJWFSFGASCFILLAIVMGLVFICVKNGNMRCTICI

239
BAN59726
MNTQILVFALVAIPTNADKICLGHHAVSNGTKVNTLTER

A/duck/Mongolia/
GVEVVNATETVERTNIPRICSKGKRTVDLGQCGLLGTITGP

147/2008
PQCDQFLEFSADLIIERREGSDVCYPGKFVNEEALRQILRES

2008/08/29 HA
GGIGKETMGFTYSGIRTNGATSACRRSRSSFYAEMKWLLS

519661951
NTDNAAFPQMTRSYKNTRKDPALIWGIHHSGSTTEQTKL

YGSGNKLITVGSSNYQQSFVPSPGARPQVNGQSGRIDFHW

LMLNPNDTVTFSFNGAFIAPDRASFLRGKSMGIQSGVQVD

ANCEGDCYHNGGTIISNLPFQNINSRTVGKCPRYVKQESLL

LATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGWYGFR

HQNAQGEGTAADYKSTQSAIDQITGKLNRLIERTNQQFELI

DNEFTEVEKQIGNVINWTRDSMTEVWSYNAELLVAMENQ

HTIDLADSEMNKLYERVKRQLRENAEEDGTGCFEIFHKCD

DDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLSNGYKD

VILWFSFGASCFILLAIAMGLVFICVKNGNMRCTICI

240
BAN59727
MNTQILVFALVAIPTNADKICLGHHAVSNGTKVNTLTER

A/duck/Mongolia/
GVEVVNATETVERINVPRICSKGKRTVDLGQCGLLGTITG

129/2010
PPQCDQFLEFSADLHIERREGSDVCYPGKFVNEEALRQILRE

2010//HA
SGGIDKETMGFTYSGIRTNGATSACRRSGSSFYAEMKWLL

519661954
SNTDNAAFPQMTKSYKNTRKDPALIIWGIHHSGSTTEQTK

LYGSGSKLITVGSSNYQQSFVPSPGARPQVNGQSGRIDFH

WLMLNPNDTVTFSFNGAFIAPDRASFLRGKSMGIQSGVQV

DASCEGDCYHSGGTHISNLPFQNINSRAVGKCPRYVKQESL

MLATGMKNVPELPKGRGLFGAIAGFIENGWEGLIDGWYG

FRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQF

ELIDNEFTEVEKQIGNVINWTRDSMTEVWSYNAELLVAM

ENQHTIDLADSEMNKLYERVKRQLRENAEEDGTGCFEIFH

KCDDDCMASIRNNTYDHSKYREEAMQNRIQINPVKLSSG

YKDVILWFSFGASCFILLAIAMGLVFICVKNGNMRCTICI

241
AGQ80952
MNTQILVFALVAIIPTNADKICLGHHAVSNGTKVNTLTER

A/duck/Jiangxi/
GVEVVNATETVERTSIPRICSKGKRAVDLGQCGLLGTITGP

3096/2009
PQCDQFLEFSADLIIERREGSDVCYPGKFVNEEALRQILRES

2009//HA
GGIDKETMGFTYSGIRTNGATSACRRSGSSFYAEMKWLLS

523788794
NTDNAAFPQTTKSYKNTRKDPALIIWGIHHSGSTTEQTKL

YGSGNKLITVGSSNYQQSFVPSPGARPQVNGQSGRIDFHW

LMLNPNDTVTFSFNGAFIAPDRASFLRGKSMGIQSGVQVD

ANCEGDCYHNGGTIISNLPFQNINSRAVGKCPRYVKQESL

LLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGWYGF

RHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQFE

LIDNEFTEVERQIGNVINWTRDSMTEVWSYNAELLVAME

NQHTIDLADSEMNKLYERVRRQLRENAEEDGTGCFEIFHK

CDDDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLSSGY

KDVILWFSFGASCFILLAIAMGLVFICVKNGNMRCTICI

242
AGQ80989
MNTQILVFALVAIIPTNADKICLGHHAVSNGTKVNTLTER

A/duck/Jiangxi/
GVEVVNATETVERTSIPRICSKGKRAVDLGQCGLLGTITGP

3257/2009
PQCDQFLEFSADLIIERREGSDVCYPGKFVNEEALRQILRES

2009//HA
GGIDKETMGFTYSGIRTNGATSACRRSGSSFYAEMKWLLS

523788868
NTDNAAFPQTTKSYKNTRKDPALIIWGIHHSGSTTEQTKL

YGSGNKLITVGXSNYQQSFVPSPGARPQVNGQSGRIDFHW

LMLNPNDTVTFSFNGAFIAPDRASFLRGKSMGIQSGVQVD

ANCEGDCYHNGGTHISNLPFQNINSRAVGKCPRYVKQESL

LLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGWYGF

RHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQFE

LIDNEFTEVERQIGNVINWTRDSMTEVWSYNAELLVAME

NQHTIDLADSEMNKLYERVRRQLRENAEEDGTGCFEIFHK

CDDDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLSSGY

KDVILWFSFGASCFILLAIAMGLVFICVKNGNMRCTICI

243
AGQ81043
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERG

A/chicken/Rizhao/
VEVVNATETVERTNIPRICSKGKRTVDLGQCGLLGTITGPP

515/2013
QCDQFLEFSADLIIERREGSDVCYPGKFVNEEALRQILRES

2013//HA
GGIDKEEMGFTYSGIRTNGATSACRRSGSSFYAEMKWLLS

523788976
NTDNAAFPQMTKSYKNTRKSPALIVWGIHHSVSTAEQTKL

YGSGNKLVTVGSSNYQQSFVPSPGARPQVNGLSGRIDFH

WLMLNPNDTVTFSFNGAFIAPDRASFLRGKSMGIQSGVQV

DANCEGDCYHSGGTHISNLPFQNIDSRAVGKCPRYVKQRS

LLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGWYG

FRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQF

ELIDNEFNEVEKQIGNVINWTRDSITEVWSYNAELLVAME

NQHTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFHK

CDDDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLSSGY

KDVILWFSFGASCFILLAIVMGLVFICVKNGNMRCTICI

244
AGR33894
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERG

A/chicken/Rizhao/
VEVVNATETVERTNIPRICSKGKRTVDLGQCGLLGTITGPP

719b/2013
QCDQFLEFSADLIIERREGSDVCYPGKFVNEEALRQILRES

2013// HA
GGIDKEAMGFTYSGIRTNGATSACRRSGSSFYAEMKWLLS

524845213
NTDNAAFPQMTKSYKNTRKSPALIVWGIHHSVSTAEQTKL

YGSGNKLVTVGSSNYQQSFVPSPGARPQVNGLSGRIDFH

WLMLNPNDTVTFSFNGAFIAPDRASFLRGKSMGIQSGVQV

DANCEGDCYHSGGTHISNLPFQNIDSRAVGKCPRYVKQRS

LLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGWYG

FRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQF

ELIDNEFNEVEKQIGNVINWTRDSITEVWSYNAELLVAME

NQHTIDLADSEMDKLYERVKRQLRENABEDGTGCFEIFHK

CDDDCMASIRNNTYDRSKYREEAMQNRXXXXXXXXXXX

XKDVILWFSFGASCFILLAIVMGLVFICVKNGNMRCTICI

245
AGR49399
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERG

A/chicken/Jiangxi/
VEVVNATETVERTNIPRICSKGKRTVDLGQCGLLGTITGPP

SD001/2013
QCDQFLEFSADLIIERREGSDVCYPGKFVNEEALRQILRKS

2013/05/03 HA
GGIDKEAMGFTYSGIRTNGATSACRRSGSSFYAEMKWLLS

525338528
NTDNAAFPQMTKSYKNTRKSPALIVWGIHHSVSTAEQTKL

YGSGNKLVTVGSSNYQQSFVPSPGARPQVNGLSGRIDFH

WLMLNPNDTVTFSFNGAFIAPDRASFLRGKSMGIQSGVQV

DANCEGDCYHSGGTHISNLPFQNIDSRAVGKCPRYVKQRS

LLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGWYG

FRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQF

ELIDNEFNEVEKQIGNVINWTRDSITEVWSYNAELLVAME

NQHTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFHK

CDDDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLSSGY

KDVILWFSFGASCFILLAIVMGLVFICVKNGNMRCTICI

246
AGR49495
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERG

A/chicken/Shanghai/
VEVVNATETVERTNIPRICSKGKMTVDLGQCGLLGTITGPP

S1358/2013
QCDQFLEFSADLIIERREGSDVCYPGKFVNEEALRQILRES

2013/04/03
GGIDKEAMGFTYSGIRTNGATSACRRSGSSFYAEMKWLLS

HA 525338689
NTDNAAFPQMTKSYKNTRKSPALIVWGIHHSVSTAEQTKL

YGSGNKLVTVGSSNYQQSFVPSPGARPQVNGLSGRIDFH

WLMLNPNDTVTFSFNGAFIAPDRASFLRGKSMGIQSGVQV

DANCEGDCYHSGGTHISNLPFQNIDSRAVGKCPRYVKQRS

LLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGWYG

FRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQF

ELIDNEFNEVEKQIGNVINWTRDSITEVWSYNAELLVAME

NQHTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFHK

CDDDCMASIKNNTYDHSKYREEAMQNRIQIDPVKLSSGY

KDVILWFSFGASCFILLAIVMGLVFICVKNGNMRCTICI

247
AGR49506
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERG

A/chicken/Shanghai/
VEVVNATETVERTNIPRICSKGKRTVDLGQCGLLGTITGPP

S1410/2013
QCDQFLEFSADLIIERREGSDVCYPGKFVNEBALRQILRES

2013/04/03
GGIDKEAMGFTYSGIRTNGATSACRRSGSSFYAEMKWLLS

HA 525338708
NTDNAAFPQMTKSYKNTRKSPALIVWGIHHSVSTAEQTKL

YGSGNKLVTVGSSNYQQSFVPSPGARPQVNGQSGRIDFH

WLMLNPNDTVTFSENGAFIAPDRASFLRGKSMGIQSGVQV

DANCEGDCYHSGGTHISNLPFQNIDSRAVGKCPRYVKQRS

LLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGWYG

FRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQF

ELIDNEFNEVEKQIGNVINWTRDSITEVWSYNAELLVAME

NQHTIDLADSEMDKLYERVKRQLRENABEDGTGCFEIFHK

CDDDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLSSGY

KDVILWFSFGASCFILLAIVMGLVFICVKNGNMRCTICI

248
AGR49554
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERG

A/chicken/Zbejiang/
VEVVNATETVERTNIPRICSKGKRTVDLGQCGLLGTITGPP

SD033/2013
QCDQFLEFSADLIIERREGSDVCYPGKFVNEEALRQILRES

2013/04/11 HA
GGIDKBAMGFTYSGIRTNGATSACRRSGSSFYAEMKWLLS

525338789
NTDNAAFPQMTKSYKNTRKSPALIVWGIHHSVSTAEQTKL

YGSGNKLVTVGSSNYQQSFVPSPGARPQVNGLSGRIDFH

WLMLNPNDTVTFSFNGAFIAPDRASFLRGKSMGIQSGVQV

DANCEGDCYHSGGTIISNLPFQNIDSRAVGKCPRYVKQRS

LLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGWYG

FRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQF

ELIDNEFNEVEKQIGNVINWIRDSITEVWSYNAELLVAME

NQHTIDLADSEMDKLYERVRRQLRENAEEDGTGCFEIFHK

CDDDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLSSGY

KDVILWFSFGASCFILLAIVMGLVFICVKNGNMRCTICI

249
AGR49566
MNTQILVEALIAIIPTNADKICLGHHAVSNGTKVNTLTERG

A/duck/Anhui/
VEVVNATETVERTNIPRICSKGKRTVDLGQCGLLGTITGPP

SC702/2013
QCDQFLEFSADLIIERREGSDVCYPGKFVNEEALRQILRES

2013/04/16 HA
GGIDKEAMGFTYSGIRTNGATSACRRSGSSFYAEMKWLLS

525338809
NTDNAAFPQMTKSYKNTRKSPALIVWGIHHSVSTAEQTKL

YGSGNKLVTVGSSNYQQSFVPSPGARPQVNGLSGRIDFH

WLMLNPNDTVTFSFNGAFIAPDRASFLRGKSMGIQSGVQV

DANCEGDCYHSGGTIISNLPFQNIDNRAVGKCPRYVKQRS

LLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGWYG

FRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQF

ELIDNEFNEVEKQIGNVINWTRDSITEVWSYNAELLVAME

NQHTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFHK

CDDDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLSSGY

KDVILWFSFGASCFILLAIVMGLVFICVKNGNMRCTICI

250
AGR49722
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERG

A/homing
VEVVNATETVERTNIPRICSKGKRTVDLGQCGLLGTITGPP

pigeon/Jiangsu/
QCDQFLEFSADLIIERREGSDVCYPGKFVNEEALRQILRES

SD184/2013
GGIDKEAMGFTYSEIRTNGATSACRRSGSSFYAEMKWLLS

2013/04/20 HA
NTDNAAFPQMTKSYKNTRKSPALIVWGIHHSVSTAEQTKL

525339071
YGSGNKLVTVGSSNYQQSFVPSPGARPQVNGQSGRIDFH

WLMLNPNDTVTFSFNGAFIAPDRASFLRGKSMGIQSGVQV

DANCEGDCYHSGGTHISNLPFQNIDSRAVGKCPRYVKQRS

LLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGWYG

FRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQF

ELIDNEFNEVEKQIGNVINWTRDSITEVWSYNAELLVAME

NQHTIDLADSEMDKLYERVKRQLRENABEDGTGCFBIFHK

CDDDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLSSGY

KDVILWFSFGASCFILLAIVMGLVFICVKNGNMRCTICI

251
AGR49734
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERG

A/pigeon/Shanghai/
VEVVNATETVERTNIPRICSKGKRTVDLGQCGLLGTITGPP

S1069/2013
QCDQFLEFSADLIIERREGSDVCYPGKFVNEEALRQILRES

2013/04/02 HA
GGIDKEAMGFTYSGIRTNGATSACRRSGSSFYAEMKWLLS

525339091
NTDNAAFPQMTKSYKNTRKSPALIVWGIHHSVSTAEQTKL

YGSGNKLVTVGSSNYQQSFVPSPGARPQVNGLSGRIDFH

WLMLNPNDTITFSFNGAFIAPDRASFLRGKSMGIQSGVQV

DANCEGDCYHSGGTIISNLPFQNIDSRAVGKCPRYVKQRS

LLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGWYG

FRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQF

ELIDNEFNEVEKQIGNVINWTRDSITEVWSYNAELLVAME

NQHTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFHK

CDDDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLSSGY

KDVILWFSFGASCFILLAIVMGLVFICVKNGNMRCTICI

252
AGR49770
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERG

A/wild
VEVVNATETVERTNIPRICSKGKKTVDLGQCGLLGTITGPP

pigeon/Jiangsu/
QCDQFLEFSADLIIERREGSDVCYPGKFVNEEALRQILRES

SD001/2013
GGIDKEAMGFTYSGIRTNGATSACRRSGSSFYAEMKWLLS

2013/04/17 HA
NTDNAAFPQMTKSYKNTRKSPALIVWGIHHSVSTAEQTKL

525339151
YGSGNKLVTVGSSNYQQSFVPSPGARPQVNGQSGRIDFH

WLMLNPNDTVTFSFNGAFIAPDRASFLRGKSMGIQSGVQV

DANCEGDCYHSGGTHISNLPFQNIDSRAVGKCPRYVKQRS

LLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGWYG

FRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQF

ELIDNEFNEVEKQIGNVINWTRDSITEVWSYNAELLVAME

NQHTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFHK

CDDDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLSSGY

KDVILWFSFGASCFILLAIVMGLVFICVKNGNMRCTICI

253
AGY41893
MNTQILVEALIAIIPTNADKICLGHHAVSNGTKVNTLTERG

A/Huizhou/01/
VEVVNATETVERTNIPRICSKGKKTVDLGQCGLLGTITGPP

2013 2013/08/08
QCDQFLEFSADLIIERREGSDVCYPGKFVNEEALRQILRES

HA 552049496
GGIDKEAMGFTYSGIRANGATSACRRSGSSFYAEMKWLL

SNTDNAAFPQMTKSYKNTRKSPALIVWGIHHSVSTAEQTK

LYGSGNKLVTVGSSNYQQSFVPSPGARPQVNGLSGRIDFH

WLMLNPNDTVTFSENGAFIAPDRASFLRGKSMGIQSGVQV

DADCEGDCYHSGGTHISNLPFQNIDSRAVGKCPRYVKQRS

LLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGWYG

FRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQF

ELIDNEFNEVEKQIGNVINWTRDSITEVWSYNAELLVAME

NQHTIDLADSEMDKLYERVKRQLRENABEDGTGCFEIFHK

CDDDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLSSGY

KDVILWFSFGASCFILLAIVMGLVFICVKNGNMRCTICI

254
AGY42258
FALVAIIPINADKICLGHHAVSNGTKVNTLTERGVEVVNA

A/mallard/Sweden/
TETVERTNVPRICSRGKRTVDLGQCGLLGTIXGPPQCDQFL

91/2002
EFSADLIIERREGSDVCYPGKFVNEEALRQILRESGGIDKET

2002/12/12 HA
MGFTYSGIRTNGAXSACRRSGSSFYAEMKWLLSNTDNAA

552052155
FPQMTKSYKNTRNDPALIIWGIHHSGSTTEQTKLYGSGNK

LITVGSSNYQQSFVPSPGARPQVNGQSGRIDFHWLILNPND

TVTFSFNGAFIAPDRASFLRGKSMGIQSGVQIDANCEGDC

YHSGGTIISNLPFQNINSRAVGKCPRYVKQESLLLATGMK

NVPEIPKGRGLFGAIAGFIENGWEGLIDGWYGFRHQNAQG

EGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELIDNEFTE

VEKQIGNVINWTRDSMTEVWSYNAELLVAMENQHTIDLA

DSEMNKLYERVRRQLRENAEEDGTGCFEIFHKCDDDCMA

SIRNNTYDHSKYREEAMQNRIQIDPVKLSSGYKDVILWFSF

GASCFILLAIAMGLVFMCVKNGNMRCTICI

255
AHA11441
MNTQILALIACMLIGAKGDKICLGHHAVANGTKVNTLTER

A/guinea
GIEVVNATETVETANIKKICTQGKRPTDLGQCGLLGTLIGP

fowl/Nebraska/
PQCDQFLEFDADLIIERREGTDVCYPGKFTNEESLRQILRG

17096/2011
SGGIDKESMGFTYSGIRTNGATSACRRSGSSFYAEMKWLL

2011/04/10 HA
SNSNNAAFPQMTKSYRNPRNKPALIVWGVHHSGSATEQT

557478572
KLYGSGSKLITVGSSKYQQSFTPSPGARPQVNGQSGRIDFH

WLLLDPNDTVTFTFNGAFIAPDRASFFRGESLGVQSDVPL

DSGCEGDCFHKGGTIVSSLPFQNINPRTVGKCPRYVKQTSL

LLATGMRNVPENPKTRGLFGAIAGFIENGWEGLIDGWYGF

RHQNAQGEGTAADYKSTQSAIDQITGKLNRLIDKTNQQFE

LIDNEFSEIEQQIGNVINWTRDSMTEIWSYNAELLVAMEN

QHTIDLADSEMNKLYERVRKQLRENAEEDGTGCFEIFHKC

DDQCMESIRNNTYDHTQYRAESLQNRIQIDPVKLSSGYKD

IILWFSFGASCFLLLAIAMGLVFICIKNGNMRCTICI

256
AHA11452
MNTQILALIACMLVGTKGDKICLGHHAVANGTKVNTLTE

A/turkey/Minnesota/
RGIEVVNATETVETANIKKICTQGKRPTDLGQCGLLGTLIG

32710/2011
PPQCDQFLEFDADLIIERREGTDVCYPGKFTNEEPLRQILR

2011/07/12 HA
GSGGIDKESMGFTYSGIRTNGATSTCRRSGSSFYAEMKWL

557478591
LSNSNNAAFPQMTKSYRNPRNKPALIVWGVHHSGSATEQ

TKLYGSGSKLITVGSSKYQQSFTPSPGARPQVNGQSGRIDF

HWLLLDPNDTVTFTFNGAFIAPDRASFFRGESLGVQSDVP

LDSGCEGDCFHKGGTIVSSLPFQNINPRTVGKCPRYVKQTS

LLLATGMRNVPENPKTRGLFGAIAGFIENGWEGLIDGWY

GFRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIDKTNQQ

FEMIDNEFSEIEQQIGNVINWTRDSMTEIWSYNAELLVAM

ENQHTIDLADSEMNKLYERVRKQLRENAEEDGTGCFEIFH

KCDDQCMESIRNNTYDHTQYRAESLQNRIQIDPVKLSSGY

KDIILWFSFGASCFLLLAIAMGLVFICIKNGNMRCTICI

257
AHA11461
MNTQILALIACMLVGTKGDKICLGHHAVANGTKVNTLTE

A/turkey/Minne
RGIEVVNATETVETANIKKICTQGKRPTDLGQCGLLGTLIG

sota/31900/2011
PPQCDQFLEFDADLIIERREGTDVCYPGKFTNEEPLRQILR

2011/07/05 HA
GSGGIDKESMGFTYSGIRTNGATSTCRRSGSSFYAEMKWL

557478606
LSNSNNAAFPQMTKSYRNPRNKPALIVWGVHHSGSATEQ

TKLYGSGSKLITVGSSKYQQSFTPSPGARPQVNGQSGRIDF

HWLLLDPNDTVTFTFNGAFIAPDRASFFRGESLGVQSDVP

LDSGCEGDCFHKGGTIVSSLPFQNINPRTVGKCPRYVKQTS

LLLATGMRNVPENPKTRGLFGAIAGFIENGWEGLIDGWY

GFRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIDKTNQQ

FELIDNEFSEIEQQIGNVINWTRDSMTEIWSYNAELLVAME

NQHTIDLADSEMNKLYERVRKQLRENAEEDGTGCFEIFHK

CDDQCMESIRNNTYDHTQYRAESLQNRIQIDPVKLSSGYK

DIILWFSFGASCFLLLAIAMGLVFICIKNGNMRCTICI

258
AHK10585
MNTQILVEALIAIIPTNADKICLGHHAVSNGTKVNTLTERG

A/chicken/
VEVVNATETVERTNIPRICSKGKKTVDLGQCGLLGTITGPP

Guangdong/G1/2013
QCDQFLEFSADLIIERREGSDVCYPGKFVNEEALRQILRES

2013/05/05 HA
GGIDKEAMGFTYSGIRTNGATSACRRSGSSFYAEMKWLLS

587680636
NTDNAAFPQMTKSYKNTRKSPALIVWGIHHSVSTAEQTKL

YGSGNKLVTVGSSNYQQSFVPSPGARPQVNGLSGRIDFH

WLMLNPNDTVTFSFNGAFIAPDRASFLRGKSMGIQSGVQV

DANCEGDCYHSGGTHISNLPFQNIDSRAVGKCPRYVKQRS

LLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGWYG

FRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQF

ELIDNEFNEVEKQIGNVINWIRDSITEVWSYNAELLVAME

NQHTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFHK

CDDDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLSSGY

KDVILWFSFGASCFILLAIVMGLVFICVKNGNMRCTICI

259
AGG53366
MNTQILVFALVAIIPTNADKICLGHHAVSNGTKVNTLTER

A/wild
GVEVVNATETVERTNVPRICSKGKRTVDLGQCGLLGTITG

duck/Korea/
PPQCDQFLEFSADLIIERREGSDVCYPGKFVNEEALRQILRE

CSM42-34/2011
SGGIDKETMGLTYSGIRTNGATSACRRSGSSFYAEMKWLL

2011/03/HA
SNTDNAAFPQMTKSYKNTRRDPALIVWGIHHSGSSTEQTK

459252887
LYGSGSKLITVGSSNYQQSFVPSPGARPQVNGQSGRIDFH

WLILNPNDTVTFSENGAFIAPDRASFLRGKSMGIQSGVQV

DASCEGDCYHSGGTIISNLPFQNINSRAVGKCPRYVKQESL

MLATGMKNVPELPKGRGLFGAIAGFIENGWEGLIDGWYG

FRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQF

ELIDNEFTEVEKQIGNVINWTRDSMTEVWSYNAELLVAM

ENQHTIDLADSEMNKLYERVRRQLRENABEDGTGCFEIFH

KCDDDCMASIRNNTYDHSKYREEAMQNRIQIDPVRLSSG

YKDVILWFSFGASCFILLAIAMGLVFICVKNGNMRCTICI

260
AGG53377
MNTQILVFALVAIIPTNADKICLGHHAVSNGTKVNTLTER

A/wild
GVEVVNATETVERTNVPRICSKGKRTVDLGQCGLLGTITG

duck/Korea/
PPQCDQFLEFSADLIIERREGSDVCYPGKFVNEEALRQILRE

CSM42-1/2011
SGGIDKETMGLTYSGIRTNGATSACRRSGSSFYAEMKWLL

2011/03/HA
SNTDNAAFPQMTKSYKNTRRDPALIVWGIHHSGSSTEQTK

459252925
LYGSGSKLITVGSSNYQQSFVPSPGARPQVNGQSGRIDFH

WLILNPNDTVTFSFNGAFIAPDRASFLRGKSMGIQSGVQV

DASCEGDCYHSGGTIISNLPFQNINSRAVGKCPRYVKQESL

MLATGMKNVPELPKGRGLFGAIAGFIENGWEGLIDGWYG

FRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQF

ELIDNEFTEVEKQIGNVINWTRDSMTEVWSYNAELLVAM

ENQHTIDLADSEMNKLYERVRRQLRENABEDGTGCFEIFH

KCDDDCMASIRNNTYDHSKYREEAMQNRIQIDPVRLSSG

YKDVILWFSFGASCFILLAIAMGLVFICVKNGNMRCT

261
AGG53399
MNTQILVFALVAIIPTNADKICLGHHAVSNGTKVNTLTER

A/wild
GVEVVNATETVERTNVPRICSKGKRTVDLGQCGLLGTITG

duck/Korea/
PPQCDQFLEFSADLHIERREGSDVCYPGKFVNEEALRQILRE

MHC39-26/2011
SGGIDKETMGFTYSGIRTNGATSACRRSGSSFYAEMKWLL

2011/03/HA
SNTDNAAFPQMTKSYKNTRRDPALIVWGIHHSGSTTEQTK

459253005
LYGSGSKLITVGSSNYQQSFVPSPGARPQVNGQSGRIDFH

WLILNPNDTVTFSFNGAFIAPDRASFLRGKSMGIQSGVQV

DASCEGDCYHSGGTIISNLPFQNINSRAVGKCPRYVKQESL

MLATGMKNVPEPPKGRGLFGAIAGFIENGWEGLIDGWYG

FRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQF

ELIDNEFTEVEKQIGNVINWTRDSMTEVWSYNAELLVAM

ENQHTIDLADSEMNKLYERVRRQLRENAEEDGTGCFEIFH

KCDDDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLSSG

YKDVILWFSFGASCFILLAIAMGLVFICVKNGNMRCTICI

262
AGG53432
MNTQILVFALVAIIPTNADKICLGHHAVSNGTKVNTLTER

A/wild
GVEVVNATETVERTNVPRICSKGKRTVDLGQCGLLGTITG

duck/Korea/
PPQCDQFLEFSADLIIERREGSDVCYPGKFVNEEALRQILRE

MHC35-41/2011
SGGIDKETMGFTYSGIRTNGATSACRRSGSSFYAEMKWLL

2011/03/HA
SNTDNAAFPQMTKSYKNTRRDPALIVWGIHHSGSTTEQTK

459253136
LYGSGSKLITVGSSNYQQSFVPSPGARPQVNGQSGRIDFH

WLILNPNDTVTFSFNGAFIAPDRASFLRGKSMGIQSGVQV

DASCEGDCYHSGGTIISNLPFQNINSRAVGKCPRYVKQESL

MLATGMKNVPEPPKGRGLFGAIAGFIENGWEGLIDGWYG

FRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQF

ELIDNEFTEVEKQIGNVINWTRDSMTEVWSYNAELLVAM

ENQHTIDLADSEMNKLYERVRRQLRENABEDGTGCFEIFH

KCDDDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLSSG

YKDVILWFSFGASCFILLAIAMGLVFICVKNGNMRCT

263
AGG53476
MNTQILVFALVAIIPTNADKICLGHHAVSNGTKVNTLTER

A/wild
GVEVVNATETVERTNVPRICSKGKRTVDLGQCGLLGTITG

duck/Korea/
PPQCDQFLEFSADLIIERREGSDVCYPGKFVNEEALRQILRE

SH19-27/2010
SGGIDKETMGFTYSGIRTNGATSACRRSGSSFYAEMKWLL

2010/12/HA
SNTDNAAFPQMTKSYKNTRRDPALIVWGIHHSGSTTEQTK

459253257
LYGSGSKLITVGSSNYQQSFVPSPGARPQVNGQSGRIDFH

WLILNPNDTVTFSFNGAFIAPDRASFLRGKSMGIQSGVQV

DASCEGDCYHSGGTIISNLPFQNINSRAVGKCPRYVKQESL

MLATGMKNVPELPKGRGLFGAIAGFIENGWEGLIDGWYG

FRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQF

ELIDNEFTEVEKQIGNVINWTRDSMTEVWSYNAELLVAM

ENQHTIDLADSEMNKLYERVRRQLRENAEEDGTGCFEIFH

KCDDDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLSSG

YKDVILWFSFGASCFILLAIAMGLVFICVKNGNMRCTI

264
AGG53487
MNTQILVFALVAIPTNADKICLGHHAVSNGTKVNTLTER

A/wild
GVEVVNATETVERTNVPRICSKGKRTVDLGQCGLLGTITG

duck/Korea/
PPQCDQFLEFSADLIIERREGSDVCYPGKFVNEEALRQILRE

SH19-50/2010
SGGIDKETMGFTYSGIRTNGATSACRRSGSSFYAEMKWLL

2010/01/HA
SNTDNAAFPQMTKSYKNTRRDPALIVWGIHHSGSTTEQTK

459253278
LYGSGSKLITVGSSNYQQSFVPSPGARPQVNGQSGRIDFH

WLILNPNDTVTFSFNGAFIAPDRASFLRGKSMGIQSGVQV

DASCEGDCYHSGGTIISNLPFQNINSRAVGKCPRYVKQESL

MLATGMKNVPELPKGRGLFGAIAGFIENGWEGLIDGWYG

FRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQF

ELIDNEFTEVEKQIGNVINWTRDSMTEVWSYNAELLVAM

ENQHTIDLADSEMNKLYERVRRQLRENAEEDGTGCFEIFH

KCDDDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLSSG

YKDVILWFSFGASCFILLAIAMGLVFICVKNGNMRCTICI

265
AGG53520
QILVFALVAIIPTNADKICLGHHAVSNGTKVNTLTERGVEV

A/wild
VNATETVERTNVPRICSKGKRTVDLGQCGLLGTITGPPQC

duck/Korea/
DQLLEFSADLIIERREGTDVCYPGKFVNEEALRQILRESGGI

SH20-27/2008
EKETMGFTYSGIRTNGATSACRRSGSSFYAEMKWLLSNTD

2008/12/HA
NAAFPQMTKSYKNTRKDPALIWGIHHSGSTTEQTKLYGS

459253409
GSKLITVGSSNYQQSFVPSPGARPQVNGQSGRIDFHWLML

NPNDTVTFSFNGAFIAPDRASFLRGKSMGIQSGVQVDANC

EGDCYHSGGTIISNLPFQNINSRAVGKCPRYVKQESLMLA

TGMKNVPELPKGRGLFGAIAGFIENGWEGLIDGWYGFRH

QNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELID

NEFTEVEKQIGNVINWTRDSMTEVWSYNAELLVAMENQH

TIDLADSEMNKLYERVKRQLRENAEEDGTGCFEIFHKCDD

DCMASIRNNTYDHSKYREEAMQNRIQINPVKLSSGYKDVI

LWFSFGASCFILLAIAMGLVFICVKNGNMR

266
AGL43637
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERG

A/Taiwan/1/
VEVVNATETVERTNIPRICSKGKRTVDLGQCGLLGTITGPP

2013 2013//HA
QCDQFLEFSADLIIERREGSDVCYPGKFVNEEALRQILRES

496297389
GGIDKEAMGFTYSGIRTNGATSACRRSGSSFYAEMKWLLS

NTDNAAFPQMTKSYKNTRKSPALIVWGIHHSVSTAEQTKL

YGSGNKLVTVGSSNYQQSFVPSPGARPQVNGPSGRIDFHW

LMLNPNDTVTFSFNGAFIAPDRASFLRGKSMGIQSGVQVD

ANCEGDCYHSGGTIINNLPFQNIDSRAVGKCPRYVKQRSL

LLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGWYGF

RHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQFE

LIDNEFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMEN

QHTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFHKC

DDDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLSSGYK

DVILWFSFGASCFILLAIVMGLVFICVKNGNMRCTICI

267
AGL97639
IACMLVGAKGDKICLGHHAVANGTKVNTLTERGIEVVNA

A/mallard/Minnesota/
TETVETANIKKLCTQGKRPTDLGQCGLLGTLIGPPQCDQFL

AI09-3770/2009
EFDADLIIERREGTDVCYPGKFTNEESLRQILRGSGGIDKES

2009/09/12 HA
MGFTYSGIRTNGATSACRRSGSSFYAEMKWLLSNSDNAA

505555371
FPQMTKSYRNPRNKPALIWGVHHSGSATEQTKLYGSGNK

LITVGSSKYQQSFTPSPGARPQVNGQSGRIDFHWLLLDPN

DTVTFTFNGAFIAPDRASFFRGESLGVQSDVPLDSGCEGDC

FHSGGTIVSSLPFQNINPRTVGKCPRYVKQTSLLLATGMRN

VPENPKTRGLFGAIAGFIENGWEGLIDGWYGFRHQNAQG

EGTAADYKSTQSAIDQITGKLNRLIDKTNQQFELIDNEFSEI

EQQIGNVINWTRDSMTELWSYNAELLVAMENQHTIDLAD

SEMNKLYERVRKQLRENAEEDGTGCFEIFHKCDDQCMESI

RNNTYDHTQYRTESLQNRIQIDPVKLS

268
AGO02477
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERG

A/Xuzhou/1/
VEVVNATETVERTNIPRICSKGKRTVDLGQCGLLGTITGPP

2013 2013/04/25
QCDQFLEFSADLIIERREGSDVCYPGKFVNEEALRQILRES

HA 512403688
GGIDKEAMGFTYSGIRTNGATSACRRSGSSFYAEMKWLLS

NTDNAAFPQMTKSYKNTRKSPALIVWGIHHSVSTAEQTKL

YGSGSKLVTVGSSNYQQSFVPSPGARPQVNGLSGRIDFHW

LMLNPNDTVTFSFNGAFIAPDRASFLRGKSMGIQSGVQVD

ANCEGDCYHSGGTIISNLPFQNIDSRAVGKCPRYVKQRSLL

LATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGWYGFR

HQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELI

DNEFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQ

HTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFHKCD

DDCMASINNTYDHSKYREEAMQNRIQIDPVKLSSGYKD

VILWFSFGASCFILLAIVMGLVFICVKSRNMRCTICI

269
AGR84942
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERG

A/Suzhou/5/2013
VEVVNATETVERTNIPRICSKGKRTVDLGQCGLLGTITGPP

2013/04/12
QCDQFLEFSADLIIERREGSDVCYPGKFVNEEALRQILRES

HA 526304561
GGIDKEAMGFTYSGIRTNGATSACRRSGSSFYAEMKWLLS

NTDNAAFPQMTKSYKNTRKSPALIVWGIHHSVSTAEQTKL

YGSGSKLVTVGSSNYQQSFVPSPGARPQVNGLSGRIDFHW

LMLNPNDTVTFSFNGAFIAPDRASFLRGKSMGIQSGVQVD

ANCEGDCYHSGGTIISNLPFQNIDSRAVGKCPRYVKQRSLL

LATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGWYGFR

HQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELI

DNEFNEVEKQIGNVINWIRDSITEVWSYNAELLVAMENQ

HTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFHKCD

DDCMASINNTYDHSKYREEAMQNRIQIDPVKLSSGYKD

VILWFSFGASCFILLAIVMGLVFICVKNGNMRCTICI

270
AGR84954
MNTQILVEALIAIIPTNADKICLGHHAVSNGTKVNTLTERG

A/Nanjing/6/2013
VEVVNATETVERTNIPRICSKGKRTVDLGQCGLLGTITGPP

2013/04/11
QCDQFLEFSADLIIERREGSDVCYPGKFVNEEALRQILRES

HA 526304594
GGIDKEAMGFTYSGIRTNGATSACRRSGSSFYAEMKWLLS

NTDNAAFPQMTKSYKNTRKSPALIVWGIHHSVSTAEQTKL

YGSGNKLVTVGSSNYQQSFVPSPGARPQVNGLSGRIDFH

WLMLNPNDTVTFSFNGAFIAPDRASFLRGKSMGIQSGVQV

DANCEGDCYHSGGTIISNLPFQNIDSRAVGKCPRYVKQRS

LLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGWYG

FRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQF

ELIDNEFNEVEKQIGNVINWTRDSITEVWSYNAELLVAME

NQHTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFHK

CDDDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLSSGY

KDVILWFSFGASCFILLAIVMGLVFICVKNRNMRCTICI

271
AGR84978
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERG

A/Wuxi/4/2013
VEVVNATETVERTNIPRICSKGKKTVDLGQCGLLGTITGPP

2013/04/07 HA
QCDQFLEFSADLIIERREGSDVCYPGKFVNEEALRQILRES

526304656
GGIDKEAMGFTYSGIRTNGATSACRRSGSSFYAEMKWLLS

NTDNAAFPQMTKSYKNTRKSPALIVWGIHHSVSTAEQTKL

YGSGNKLVTVGSSNYQQSFVPSPGARPQVNGLSGRIDFH

WLMLNPNDTVTFSFNGAFIAPDRASFLRGKSMGIQSGVQV

DANCEGDCYHSGGTHISNLPFQNIDSRAVGKCPRYVKQRS

LLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGWYG

FRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQF

ELIDNEFNEVEKQIGNVINWTRDSITEVWSYNAELLVAME

NQHTIDLADSEMDKLYERVKRQLRENABEDGTGCFEIFHK

CDDDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLSSGY

KDVILWFSFGASCFILLAIVMGLVFICVKSRNMRCTICI

272
AGR84990
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERG

A/Wuxi/3/2013
VEVVNATETVERTNIPRICSKGKRTVDLGQCGLLGTITGPP

2013/04/07 HA
QCDQFLEFSADLIIERREGSDVCYPGKFVNEEALRQILRES

526304688
GGIDKEAMGFTYSGIRTNGATSACRRSGSSFYAEMKWLLS

NTDNAAFPQMTKSYKNTRKSPALIVWGIHHSVSTAEQTKL

YGSGNKLVTVGSSNYQQSFVPSPGARPQVNGLSGRIDFH

WLMLNPNDTVTFSENGAFIAPDRASFLRGKSMGIQSGVQV

DANCEGDCYHSGGTIISNLPFQNIDSRAVGKCPRYVKQRS

LLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGWYG

FRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQF

ELIDNEFNEVEKQIGNVINWTRDSITEVWSYNAELLVAME

NQHTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFHK

CDDDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLSSGY

KDVILWFSFGASCFILLAIVMGLVFICVKSRNMRCTICI

273
AGR85002
MNTQILVEALIAIIPTNADKICLGHHAVSNGTKVNTLTERG

A/Zhenjiang/1/
VEVVNATETVERTNIPRICSKGKMTVDLGQCGLLGTITGPP

2013 2013/04/07
QCDQFLEFSADLIIERREGSDVCYPGKFVNEEALRQILRES

HA 526304708
GGIDKEAMGFTYSGIRTNGATSACRRSGSSFYAEMKWLLS

NTDNAAFPQMTKSYKNTRKSPALIVWGIHHSVSTAEQTKL

YGSGNKLVTVGSSNYQQSFVPSPGARPQVNGLSGRIDFH

WLMLNPNDTVTFSFNGAFIAPDRASFLRGKSMGIQSGVQV

DANCEGDCYHSGGTIISNLPFQNIDSRAVGKCPRYVKQRS

LLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGWYG

FRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQF

ELIDNEFNEVEKQIGNVINWTRDSITEVWSYNAELLVAME

NQHTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFHK

CDDDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLSSGY

KDVILWFSFGASCFILLAIVMGLVFICVKSRNKRCTICI

274
AGR85026
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERG

A/Nanjing/2/
VEVVNATETVERTNIPRICSKGKMTVDLGQCGLLGTITGPP

2013 2013/04/05
QCDQFLEFSADLIIERREGSDVCYPGKFVNEEALRQILRES

HA 526304762
GGIDKEAMGFTYSGIRTNGATSACRRSGSSFYAEMKWLLS

NTDNAAFPQMTKSYKNTRKSPALIVWGIHHSVSTAEQTKL

YGSGNKLVTVGSSNYQQSFVPSPGARPQVNGLSGRIDFH

WLMLNPNDTVTFSFNGAFIAPDRASFLRGKSMGIQSGVQV

DANCEGDCYHSGGTHISNLPFQNIDSRAVGKCPRYVKQRS

LLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGWYG

FRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQF

ELIDNEFNEVEKQIGNVINWTRDSITEVWSYNAELLVAME

NQHTIDLADSEMDKLYERVKRQLRENABEDGTGCFEIFHK

CDDDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLSSGY

KDVILWFSFGASCFILLAIVMGLVFICVKSRNMRCTICI

275
AGU02230
LVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERGGEVVN

A/Zhejiang/
ATETVERTNIPRICSKGKRTVDLGQCGLRGTITGPPQCDQF

DTID-ZJU05/2013
LEFSADLIIERREGSDVCYPGKFVNEEALRQILRESGGIDKE

2013/04/ HA
AMGFTYSGIRTNGATSACRRSGSSFYAEMKWLLSNTDNA

532808765
AFPQMTKSYKNTRKSPALIVWGIHHSVSTAEQTKLYGSGN

KLVTVGSSNYQQSFVPSPGARPQVNGLSGRIDFHWLMLNP

NDTVTFSFNGAFIAPDRASFLRGKSMGIQSGVQVDANCEG

DCYHSGGTIISNLPFQNIDSRAVGKCPRYVKQRSLLLATG

MKNVPEIPKGRGLFGAIAGFIENGWEGLIDGWYGFRHQN

AQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELIDNE

FNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQHTID

LADSEMDKLYERVKRQLRENAEEDGTGCFEIFHKCDDDC

MASIRNNTYDHSKYREEAMQNRIQIDPVKLSSGYKDVILW

FSFGASCFILLAIVMGLVFICVKNGNMRCT

276
AGU02233
FALIAIIPTNADKICLGHHAVSNGTKVNTLTERGGEVVNAT

A/Zhejiang/
ETVERTNFPRICSKGKRTVDLGQCGLRGTITGPPQCDQFLE

DTID-ZJU08/2013
FSADLIIERREGSDVCYPGKFVNEEALRQILRESGGIDKEA

2013/04/HA
MGFTYSGIRTNGATSACRRSGSSFYAEMKWLLSNTDNAA

532808788
FPQMTKSYKNTRKSPALIVWGIHHSVSTAEQTKLYGSGNK

LVTVGSSNYQQSFVPSPGARPQVNGLSGRIDFHWLMLNPN

DTVTFSFNGAFIAPDRASFLRGKSMGIQSGVQVDANCEGD

CYHSGGTIISNLPFQNIDSRAVGKCPRYVKQRSLLLATGM

KNVPEIPKGRGLFGAIAGFIENGWEGLIDGWYGFRHQNAQ

GEGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELIDNEFN

EVEKQIGNVINWIRDSITEVWSYNAELLVAMENQHTIDLA

DSEMDKLYERVKRQLRENAEEDGTGCFEIFHKCDDDCMA

SIRNNTYDHSKYREEAMQNRIQIDPVKLSSGYKDVILWFSF

GASCFILLAIVMGLVFICVKNGNMRCT

277
AGW82588
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERG

A/tree
VEVVNATETVERTNIPRICSKGKRTVDLGQCGLLGTITGPP

sparrow/Shanghai/
QCDQFLEFSADLIIERREGSDVCYPGKFVNEEALRQILRES

01/2013
GGIDKEAMGFTYSGIRTNGATSACRRSGSSFYAEMKWLLS

2013/05/09 HA
NTDNAAFPQMTKSYKNTRKSPALIVWGIHHSVSTAEQTKL

546235348
YGSGNKLVTVGSSNYQQSFVPSPGARPQVNGLSGRIDFH

WLMLNPNDTVTFSENGAFIAPDRASFLRGKSMGIQSGVQV

DANCEGDCYHSGGTHISNLPFQNIDSRAVGKCPRYVKQRS

LLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGWYG

FRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQF

ELIDNEFNEVEKQIGNVINWTRDSITEVWSYNAELLVAME

NQHTIDLADSEMDKLYERVKRQLRENABEDGTGCFEIFHK

CDDDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLSSGY

KDVILWFSFGASCFILLAIVMGLVFICVKNGNMRCTIGI

278
AGW82600
ALIAIIPTNADKICLGHHAVSNGTKVNTLTERGVEVVNATE

A/Shanghai/
TVERTNIPRICSKGKRTVDLGQCGLLGTITGPPQCDQFLEF

CN01/2013
SADLIIERREGSDVCYPGKFVNEEALRQILRESGGIDKEAM

2013/04/11 HA
GFTYSGIRTNGATSACRRSRSSFYAEMKWLLSNTDNAAFP

546235368
QMTKSYKNTRKSPALIVWGIHHSVSTAEQTKLYGSGNKL

VTVGSSNYQQSFVPSPGARPQVNGLSGRIDFHWLMLNPN

DTVTFSFNGAFIAPDRASFLRGKSMGIQSGVQVDANCEGD

CYHSGGTIMSNLPFQNIDSRAVGKCPRYVKQRSLLLATGM

KNVPEIPKGRGLFGAIAGFIENGWEGLIDGWYGFRHQNAQ

GEGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELIDNEFN

EVEKQIGNVINWTRDSITEVWSYNAELLVAMENQHTIDLA

DSEMDKLYERVKRQLRENAEEDGTGCFEIFHKCDDDCMA

SIRNNTYDHSKYREEAMQNRIQIDPVKLSSGYKDVILWFSF

GASCFILLAIVMGLVFICVKNGNMRCTICI

279
AGW82612
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERG

A/Shanghai/
VEVVNATETVERTNIPRICSKGKRTVDLGQCGLLGTITGPP

JS01/2013
QCDQFLEFSADLIIERREGSDVCYPGKFVNEEALRQILRES

2013/04/03 HA
GGIDKEAMGFTYSGIRTNGATSACRRSGSSFYAEMKWLLS

546235388
NTDNAAFPQMTKSYKNTRKNPALIVWGIHHSGSTAEQTK

LYGSGNKLVTVGSSNYQQSFAPSPGARTQVNGQSGRIDFH

WLMLNPNDTVTFSFNGAFIAPDRASFLRGKSMGIQSGVQV

DADCEGDCYHSGGTHISNLPFQNIDSRAVGKCPRYVKQRS

LLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGWYG

FRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQF

ELIDNEFTEVEKQIGNVINWTRDSITEVWSYNAELLVAME

NQHTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFHK

CDDDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLSSGY

KDVILWFSFGASCFILLAIAMGLVFICVKNGNMRCTICI

280
AHA11472
MNTQILALIACMLIGAKGDKICLGHHAVANGTKVNTLTER

A/turkey/Minnesota/
GIEVVNATETVETANVKKICTQGKRPTDLGQCGLLGTLIG

31676/2009
PPQCDQFLEFDADLIIERREGTDVCYPGKFTNEESLRQILR

2009/12/08 HA
GSGGIDKESMGFTYSGIRINGETSACRRSGSSFYAEMKWL

557478625
LSNSNNAAFPQMTKSYRNPRDKPALIIWGVHHSGSATEQT

KLYGSGNKLITVGSSKYQQSFTPSPGARPQVNGQSGRIDF

HWLLLDPNDTVTFTFNGAFIAPDRASFFRGESLGVQSDVP

LDSGCEGDCFHSGGTIVSSLPFQNINPRTVGKCPRYVKQTS

LLLATGMRNVPEKPKTRGLFGAIAGFIENGWEGLIDGWY

GFRHQNAQGEGTAADYKSTQSAIDQITNKLNRLIDKTNQQ

FELIDNEFSEIEQQIGNVINWTRDSMTEVWSYNAELLVAM

ENQHTIDLADSEMNKLYERVRKQLRENAEEDGTGCFEIFH

KCDDQCMESIRNNTYDHTQYRKESLQNRIQIDPVKLSSGY

KDIILWFSFGASCELLLAIAMGLVFICIKNGNMRCTICI

281
AHA11483
MNTQILALIACMLIGAKGDKICLGHHAVANGTKVNTLTER

A/turkey/Minnesota/
GIEVVNATETVETANVKKICTQGKRPTDLGQCGLLGTLIG

14135-2/2009
PPQCDQFLEFDADLIIERREGTDVCYPGKFTNEESLRQILR

2009/08/07 HA
GSGGIDKESMGFTYSGIRTNGATSACRRSGSSFYAEMKWL

557478644
LSNSNNAAFPQMTKSYRNPRDKPALIIWGVHHSGSATEQT

KLYGSGNKLITVGSSKYQQSFTPSPGARPQVNGQSGRIDF

HWLLLDPNDTVTFTFNGAFIAPDRASFFRGESLGVQSDVP

LDSGCEGDCFHSGGTIVSSLPFQNINPRTVGKCPRYVKQTS

LLLATGMRNVPEKPKTRGLFGAIAGFIENGWEGLIDGWY

GFRHQNAQGEGTAADYKSTQSAIDQITSKLNRLIDKTNQQ

FELIDNEFSEIEQQIGNVINWTRDSMTEVWSYNAELLVAM

ENQHTIDLADSEMNKLYERVRKQLRENAEEDGTGCFEIFH

KCDDQCMESIRNNTYDHTQYRKESLQNRIQIDPVKLSSGY

KDIILWFSFGASCFLLLAIAMGLVFICIKNGNMRCTICI

282
AHA11500
TQILVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERGVE

A/Zhejiang/
VVNATETVERTNIPRICSKGKRTVDLGQCGLLGTITGPPQC

DTID-ZJU10/2013
DQFLEFSADLIIERREGSDVCYPGKFVNEEALRQILRESGGI

2013/10/14 HA
DKEAMGFTYSGIRTNGATSACRRSGSSFYAEMKWLLSNT

557478676
DNAAFPQMTKSYKNTRKSPALIVWGIHHSVSTAEQTKLY

GSGNKLVTVGSSNYQQSFVPSPGARPPVNGLSGRIDFHWL

MLNPNDTVTFSFNGAFIAPDRASFLRGKSMGIQSGVQVDA

NCEGDCYHSGGTIISNLPFQNIDSRAVGKCPRYVKQRSLLL

ATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGWYGFRH

QNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELID

NEFNEVEKQIGNVINWIRDSITEVWSYNAELLVAMENQH

TIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFHKCDD

DCMASIRNNTYDHSKYREEAMQNRIQIDPVKLSSGYKDVI

LWFSFGASCFILLAIVMGLVFICVKN

283
AHA57050
MNTQILALIACMLIGAKGDKICLGHHAVANGTKVNTLTER

A/turkey/Minnesota/
GIEVVNATETVETANVKKICTQGKRPTDLGQCGLLGTLIG

14659/2009
PPQCDQFLEFDADLIIERREGTDVCYPGKFTNEESLRQILR

2009/08/12 HA
GSGGIDKESMGFTYSGIRTNGATSACRRSGSSFYAEMKWL

558484427
LSNSNNAAFPQMTKSYRNPRDKPALIIWGVHHSGSATEQT

KLYGSGNKLITVGSSKYQQSFTPSPGARPQVNGQSGRIDF

HWLLLDPNDTVTFTFNGAFIAPDRASFFRGESLGVQSDVP

LDSGCEGDCFHSGGTIVSSLPFQNINPRTVGKCPRYVKQTS

LLLATGMRNVPEKPKTRGLFGAIAGFIENGWEGLIDGWY

GFRHQNAQGEGTAADYKSTQSAIDQITSKLNRLIDKTNQQ

FELIDNEFSEIEQQIGNVINWTRDSMTEVWSYNAELLVAM

ENQHTIDLADSEMNKLYERVRKQLRENAEEDGTGCFEIFH

NCDDQCMESIRNNTYDHTQYRKESLQNRIQIDPVKLSSGY

KDIILWFSFGASCFLLLAIAMGLVFICIKNGNMRCTICI

284
AHA57072
MNTQILALIACMLIGAKGDKICLGHHAVANGTKVNTLTER

A/turkey/Minnesota/
GIEVVNATETVETANVKKICTQGKRPTDLGQCGLLGTLIG

18421/2009
PPQCDQFLEFDADLIIERREGTDVCYPGKFTNEESLRQILR

2009/09/09 HA
GSGGIDKESMGFTYSGIRTNGATSACRRSGSSFYAEMKWL

558484465
LSNSNDAAFPQMTKSYRNPRDKPALIIWGVHHSGSATEQT

KLYGSGNKLITVGSSKYQQSFTPSPGARPQVNGQSGRIDF

HWLLLDPNDTVTFTFNGAFIAPDRASFFRGESLGVQSDVP

LDSGCEGDCFHSGGTIVSSLPFQNINPRTVGKCPRYVKQTS

LLLATGMRNVPEKPKTRGLFGAIAGFIENGWEGLIDGWY

GFRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIDKTNQQ

FELIDNEFSEIEQQIGNVINWTRDSMTEVWSYNAELLVAM

ENQHTIDLADSEMNKLYERVRKQLRENAEEDGTGCFEIFH

KCDDQCMESIRNNTYDHTQYRKESLQNRIQIDPVKLSSGY

KDIILWFSFGASCFLLLAIAMGLVFICIKNGNMRCTICI

285
AHD25003
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERG

A/Guangdong/
VEVVNATETVERTNIPRICSKGKKTVDLGQCGLLGTITGPP

02/2013 2013/10/
QCDQFLEFSADLIIERREGSDVCYPGKFVNEEALRQILRES

HA 568260567
GGIDKEAMGFTYSGIRANGATSACRRSGSSFYAEMKWLL

SNTDNAAFPQMTKSYKNTRKSPALIVWGIHHSVSTAEQTK

LYGSGNKLVTVGSSNYQQSFVPSPGARPQVNGLSGRIDFH

WLMLNPNDTVTFSENGAFIAPDRASFLRGKSMGIQSGVQV

DANCEGDCYHSGGTIISNLPFQNIDSRAVGKCPRYVKQRS

LLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGWYG

FRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQF

ELIDNEFNEVEKQIGNVINWTRDSITEVWSYNAELLVAME

NQHTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFHK

CDDDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLSSGY

KDVILWFSFGASCFILLAIVMGLVFICVKNGNM

286
AHF20528
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERG

A/Hong
VEVVNATETVERTNIPRICSKGKRTVDLGQCGLLGTITGPP

Kong/470129/
QCDQFLEFSADLIIERREGSDVCYPGKFVNEEALRQILRES

2013 2013/11/30
GGIDKEAMGFTYSGIRANGATSACRRSGSSFYAEMKWLL

HA 570933555
SNTDNAAFPQMTKSYKNTRKSPALIVWGIHHSVSTAEQTK

LYGSGNKLVTVGSSNYQQSFVPSPGARPQVNGLSGRIDFH

WLMLNPNDTVTFSFNGAFIAPDRASFLRGKSMGIQSGVQV

DANCEGDCYHSGGTIISSLPFQNIDSRAVGKCPRYVKQRSL

LLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGWYGF

RHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQFE

LIDNEFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMEN

QHTIDLADSEMDKLYERVKRQLRENABEDGTGCFEIFHKC

DDDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLSSGYK

DVILWFSFGASCFILLAIVMGLVFICVKNGNMRCTICI

287
AHF20568
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERG

A/Shanghai/
VEVVNATETVERTNIPRICSKGKRTVDLGQCGLLGTITGPP

CN02/2013
QCDQFLEFSADLIIERREGSDVCYPGKFVNEEALRQILRES

2013/04/02 HA
GGIDKEAMGFTYSGIRTNGATSACRRSGSSFYAEMKWLLS

570933626
NTDNAAFPQMTKSYKNTRKSPALIVWGIHHSVSTAEQTKL

YGSGNKLVTVGSSNYQQSFVPSPGARPQVNGLSGRIDFH

WLMLNPNDTVTFSFNGAFIAPDRASFLRGKSMGIQSGVQV

DANCEGDCYHSGGTIMSNLPFQNIDSRAVGKCPRYVKQR

SLLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGWY

GFRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQ

FELIDNEFNEVEKQIGNVINWIRDSITEVWSYNAELLVAM

ENQHTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFH

KCDDDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLSSG

YKDVILWFSFGASCFILLAIVMGLVFICVKNGNMRCTICI

288
AHH25185
MNTQILVEALIAIIPTNADKICLGHHAVSNGTKVNTLTERG

A/Guangdong/
VEVVNATETVERTNIPRICSKGKKTVDLGQCGLLGTITGPP

04/2013
QCDQFLEFSADLIIERREGSDVCYPGKFVNEEALRQILRES

2013/12/16 HA
GGIEKEAMGFTYSGIRANGATSACRRSGSSFYAEMKWLLS

576106234
NTDNAAFPQMTKSYKNTRKSPALIVWGIHHSVSTAEQTKL

YGSGNKLVTVGSSNYQQSFVPSPGARPQVNGLSGRIDFH

WLMLNPNDTVTFSFNGAFIAPDRASFLRGKSMGIQSGVQV

DANCEGDCYHSGGTHISNLPFQNIDSRAVGKCPRYVKQRS

LLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGWYG

FRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQF

ELIDNEFNEVEKQIGNVINWTRDSITEVWSYNAELLVAME

NQHTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFHK

CDDDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLSSGY

KDVILWFSFGASCFILLAIVMGLVFICVKNGNMRCTICI

289
AHJ57411
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERG

A/Shanghai/
VEVVNATETVERTNIPRICSKGKRTVDLGQCGLLGTITGPP

PD-01/2014
QCDQFLEFSADLIIERREGSDVCYPGKFVNEEALRQILRES

2014/01/17 HA
GGIDKEAMGFTYSGIRTNGATSACRRSGSSFYAEMKWLLS

585478041
NTDNAAFPQMTKSYKNTRKSPALIVWGIHHSVSTAEQTKL

YGSGNKLVTVGSSNYQQSFVSSPGARPQVNGLSGRIDFH

WLMLNPNDTVTFSFNGAFIAPDRASFLRGKSMGIQSGVQV

DANCKGDCYHSGGTIISNLPFQNIDSRAVGKCPRYVKQRS

LLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGWYG

FRHQNAQGEGTAADYKSTQSAIDQITGKLNRIIEKTNQQFE

LIDNEFNEVEKQIGNVINWIRDSITEVWSYNAELLVAMEN

QHTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFHKC

DDDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLSSGYK

DVILWFSFGASCFILLAIVMGLVFICVKNGNMRCTICI

290
AHJ57418
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERG

A/Shanghai/
VEVVNATETVERTNIPRICSKGKRTVDLGQCGLLGTITGPP

PD-02/2014
QCDQFLEFSADLIIERREGSDICYPGKFVNEEALRQILRESG

2014/01/17 HA
GIDKEAMGFTYSGIRTNGATSACRRSGSSFYAEMKWLLSN

585478256
TDNAAFPQMTKSYKNTRKSPALIVWGIHHSVSTAEQTKLY

GSGNKLVTVGSSNYQQSFVPSPGARPQVNGLSGRIDFHWL

MLNPNDTVTFSFNGAFIAPDRASFLKGKSMGIQSGVQVDA

NCEGDCYHSGGTIISNLPFQNIDSRAVGKCPRYVKQRSLLL

ATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGWYGFRH

QNAQGEGTAADYKSTQSAIDQITGKLNRIIEKTNQQFELID

NEFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQH

TIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFHKCDD

DCMASIRNNTYDHSKYREEAMQNRIQIDPVKLSSGYKDVI

LWFSFGASCFILLAIVMGLVFICVKNGNMRCTICI

291
AHK10800
MNTQILVEALIAIIPTNADKICLGHHAVSNGTKVNTLTERG

A/Shanghai/01/
VEVVNATETVERTNIPRICSKGKRTVDLGQCGLLGTITGPP

2014 2014/01/03
QCDQFLEFSADLIIERREGSDVCYPGKFVNEEALRQILRES

HA 587681014
GGIDKEAMGFTYSGIRTNGATSACRRSGSSFYAEMKWLLS

NTDNAAFPQMTKSYKNTRKSPALIVWGIHHSVSTAEQTKL

YGSGNKLVTVGSSNYQQSFVPSPGARPQVNGLSGRIDFH

WLMLNPNDTVTFSFNGAFIAPDRASFLRGKSMGIQSGVQV

DANCEGDCYHSGGTHISNLPFQNIDSRAVGKCPRYVKQRS

LLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGWYG

FRHQNAQGEGTAADYKSTQSAIDQITGKLNRIIEKTNQQFE

LIDNEFNEVEKQIGNVINWIRDSITEVWSYNAELLVAMEN

QHTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFHKC

DDDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLSSGYK

DVILWFSFGASCFILLAIVMGLVFICVKNGNMRCTICI

292
AHM24224
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERG

A/Beijing/3/
VEVVNATETVERTNIPRICSKGKRTVDLGQCGLLGTITGPP

2013 2013/04/16
QCDQFLEFSADLIIERREGSDVCYPGKFVKEEALRQILRES

HA 594704802
GGIDKEAMGFTYSGIRTNGATSACRRSGSSFYAEMKWLLS

NTDNAAFPQMTKSYKNTRKSPALIVWGIHHSVSTAEQTKL

YGSGNKLVTVGSSNYQQSFVPSPGARPQVNGLSGRIDFH

WLMLNPNDTVTFSFNGAFIAPDRASFLRGKSMGIQSGVQV

DANCEGDCYHSGGTIISNLPFQNIDSRAVGKCPRYVKQRS

LLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGWYG

FRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQF

ELIDNEFNEVEKQIGNVINWTRDSITEVWSYNAELLVAME

NQHTIDLADSEMDKLYERVKRQLRENABEDGTGCFEIFHK

CDDDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLSSGY

KDVILWFSFGASCFILLAIVMGLVFICVKNGNMRCTICI

293
AHN96472
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERG

A/chicken/Shanghai/
VEVVNATETVERTNIPRICSKGKKTVDLGQCGLLGTITGPP

PD-CN-
QCDQFLEFSADLIIERREGSDVCYPGKFVNEEALRQILRES

02/2014
GGIDKEAMGFTYSGIRTNGATSACRRSGSSFYAEMKWLLS

2014/01/21 HA
NTDNAAFPQMTKSYKNTRKSPALIVWGIHHSVSTAEQTKL

602701641
YGSGNKLVTVGSSNYQQSFVPSPGARPQVNGLSGRIDFH

WLMLNPNDTVTFSFNGAFIAPDRASFLRGKSMGIQSGVQV

DANCEGDCYHSGGTIISNLPFQNIDSRAVGKCPRYVKQKS

LLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGWYG

FRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQF

ELIDNEFNEVEKQIGNVINWTRDSITEVWSYNAELLVAME

NQHTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFHK

CDDDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLSSGY

KDVILWFSFGASCFILLAIVMGLVFICVKNGNMRCTICI

294
AHZ39686
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERG

A/Anhui/DEWH72-
VEVVNATETVERTNIPRICSKGKRTVDLGQCGLLGTITGPP

01/2013
QCDQFLEFSADLIIERREGSDVCYPGKFVNEEALRQILRES

2013//HA
GGIDKEAMGFTYSGIRTNGATSACRRSGSSFYAEMKWLLS

632807036
NTDDAAFPQMTKSYKNTRKSPALIVWGIHHSVSTAEQTKL

YGSGNKLVTVGSSNYQQSFVPSPGARPQVNGLSGRIDFH

WLMLNPNDTVTFSFNGAFIAPDRASFLRGKSMGIQSGVQV

DANCEGDCYHSGGTIISNLPFQNIDSRAVGKCPRYVKQRS

LLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGWYG

FRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQF

ELIDNEFNEVEKQIGNVINWTRDSITEVWSYNAELLVAME

NQHTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFHK

CDDDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLSSGY

KDVILWFSFGASCFILLAIVMGLVFICVKNGNMRCTICI

295
AHZ39710
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERG

A/Anhui/
VEVVNATETVERTNIPRICSKGKRTVDLGQCGLLGTITGPP

DEWH72-03/2013
QCDQFLEFSADLIIERREGSDVCYPGKFVNEEALRQILRES

2013//HA
GGIDKEAMGFTYSGIRTDGATSACRRSGSSFYAEMKWLLS

632807076
NTDDAAFPQMTKSYKNTRKSPALIVWGIHHSVSTAEQTKL

YGSGNKLVTVGSSNYQQSFVPSPGARPQVNGLSGRIDFH

WLMLNPNDTVTFSFNGAFIAPDRASFLRGKSMGIQSGVQV

DANCEGDCYHSGGTIISNLPFQNIDSRAVGKCPRYVKQRS

LLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGWYG

FRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQF

ELIDNEFNEVEKQIGNVINWTRDSITEVWSYNAELLVAME

NQHTIDLADSEMDKLYERVKRQLRENABEDGTGCFEIFHK

CDDDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLSSGY

KDVILWFSFGASCFILLAIVMGLVFICVKNGNMRCTICI

296
AHZ39746
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERG

A/Anhui/DEWH72-
VEVVNATETVERTNIPRICSKGKRTVDLGQCGLLGTITGPP

06/2013
QCDQFLEFSADLIIERREGSDVCYPGKFVNEEALRQILRES

2013//HA
GGIDKEAMGFTYSGIRTNGATSACRRSGSSFYAEMKWLLS

632807136
NTDNAAFPQMTKSYKNTRKSPALIVWGIHHSVSTAEQTKL

YGSGNKLVTVGSSNYQQSFVPSPGERPQVNGLSGRIDFHW

LMLNPNDTVTFSFNGAFIAPDRASFLRGKSMGIQSGVQVD

ANCEGDCYHSGGTHISNLPFQNIDSRAVGKCPRYVKQRSLL

LATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGWYGFR

HQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELI

DNEFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQ

HTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFHKCD

DDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLSSGYKD

VILWFSFGASCFILLAIVMGLVFICVKNGNMRCTICI

297
AHZ41929
MNTQILVEALVAIPINADKICLGHHAVSNGTKVNTLTERG

A/mallard/Sweden/
VEVVNATETVERTNVPRICSRGKRTVDLGQCGLLGTITGP

1621/2002
PQCDQFLEFSADLIIERREGSDVCYPGKFVNEEALRQILRES

2002/12/12 HA
GGIDKETMGFTYSGIRTNGATSACRRSGSSFYAEMKWLLS

632810949
NTDNAAFPQMTKSYKNTRNDPALIIWGIHHSGSTTEQTKL

YGSGNKLITVGSSNYQQSFVPSPGARPQVNGQSGRIDFHW

LILNPNDTVTFSFNGAFIAPDRASFLRGKSMGIQSGVQIDA

NCEGDCYHSGGTIISNLPFQNINSRAVGKCPRYVKQESLLL

ATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGWYGFRH

QNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELID

NEFTEVEKQIGNVINWTRDSMTEVWSYNAELLVAMENQH

TIDLADSEMNKLYERVRRQLRENAEEDGTGCFEIFHKCDD

DCMASIRNNTYDHSKYREEAMQNRIQIDPVKLSSGYKDVI

LWFSFGASCFILLAIAMGLVFMCVKNGNMRCTICI

298
AHZ42537
MNTQILAFIACMLVGAKGDKICLGHHAVANGTKVNTLTE

A/mallard/Minnesota/
RGIEVVNATETVETANIKKLCTQGKRPTDLGQCGLLGTLI

AI09-3770/2009
GPPQCDQFLEFDADLIIERREGTDVCYPGKFTNEESLRQIL

2009/09/12 HA
RGSGGIDKESMGFTYSGIRTNGATSACRRSGSSFYAEMKW

632811964
LLSNSDNAAFPQMTKSYRNPRNKPALIIWGVHHSGSATEQ

TKLYGSGNKLITVGSSKYQQSFTPSPGARPQVNGQSGRIDF

HWLLLDPNDTVTFTFNGAFIAPDRASFFRGESLGVQSDVP

LDSGCEGDCFHSGGTIVSSLPFQNINPRTVGKCPRYVKQTS

LLLATGMRNVPENPKTRGLFGAIAGFIENGWEGLIDGWY

GFRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIDKTNQQ

FELIDNEFSEIEQQIGNVINWTRDSMTELWSYNAELLVAM

ENQHTIDLADSEMNKLYERVRKQLRENAEEDGTGCFEIFH

KCDDQCMESIRNNTYDHTQYRTESLQNRIQIDPVKLSSGY

KDIILWFSFGASCFLLLAIAMGLVFICIKNGNMRCTICI

299
AHZ42549
MNTQILAFIACMLVGVRGDKICLGHHAVANGTKVNTLTE

A/ruddy
KGIEVVNATETVESANIKKICTQGKRPTDLGQCGLLGTLIG

turnstone/Delaware/
PPQCDQFLEFDSDLIIERREGTDVCYPGKFTNEESLRQILRG

A100-1538/2000
SGGIDKESMGFTYSGIRTNGATSACRRLGSSSFYAEMKWL

2000/05/20 HA
LSNSDNAAFPQMTKSYRNPRNKPALIIWGVHHSGSANEQT

632811984
KLYGSGNKLITVGSSKYQQSFTPSPGARPQVNGQSGRIDF

HWLLLDPNDTVTFTFNGAFIAPDRASFFRGESLGIQSDVPL

DSSCGGDCFHSGGTIVSSLPFQNINPRTVGKCPRYVKQTSL

LLATGMRNVPENPKTRGLFGAIAGFIENGWEGLIDGWYGF

RHQNAQGEGTAADYKSTQSAIDQITGKLNRLIDKTNQQFE

LMDNEFNEIEQQIGNVINWTRDSMTEVWSYNAELLVAME

NQHTIDLADSEMNKLYERVRKQLRENAEEDGTGCFEIFHK

CDDQCMESIRNNTYDHTQYRTESLQNRIQIDPVKLSSGYK

DIILWFSFGASCFLLLAIAMGLIFICIKNGNMRCTICI

300
AID70634
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERG

A/Shanghai/
VEVVNATETVERTNIPRICSKGKRTVDLGQCGLLGTITGPP

Mix1/2014
QCDQFLEFSADLIIERREGSDVCYPGKFVNEEALRQILRES

2014/01/03 HA
GGIDKEAMGFTYSGIRTNGATSACRRSGSSFYAEMKWLLS

660304650
NTDNAAFPQMTKSYKNTRKSPALIVWGIHHSVSTAEQTKL

YGSGNKLVTVGSSNYQQSFVPSPGARPQVNGLSGRIDFH

WLMLNPNDTVTFSFNGAFIAPDRASFLRGKSMGIQSGVQV

DANCEGDCYHSGGTHISNLPFQNIDSRAVGKCPRYVKQRS

LLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGWYG

FRHQNAQGEGTAADYKSTQSAIDQITGKLNRIIEKTNQQFE

LIDNEFNEVEKQISNVINWIRDSITEVWSYNAELLVAMEN

QHTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFHKC

DDDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLSSGYK

DVILWFSFGASCFILLAIVMGLVFICVKNGNMRCTICI

301
AIN76383
MNTQILVFALIAIVPTNADKICLGHHAVSNGTKVNTLTER

A/Zhejiang/
GVEVVNATETVERTNIPRICSKGKKTVDLGQCGLLGTITGP

LS01/2014
PQCDQFLEFSADLIIERREGSDVCYPGKFVNEEALRQILRES

2014/02/08 HA
GGIDKBAMGFTYSGIRTNGTTSACRRSGSSFYAEMKWLLS

684694637
NTDNAAFPQMTKSYKNTRKSPALIVWGIHHSVSTAEQTKL

YGSGNKLVTVGSSNYQQSFVPSPGARPQVNGLSGRIDFH

WLMLNPNDTVTFSFNGAFIAPDRASFLRGKSMGIQSGVQV

DANCEGDCYHSGGTIISNLPFQNIDSRAVGKCPRYVKQKS

LLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGWYG

FRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQF

ELIDNEFNEVEKQIGNVINWTRDSITEVWSYNAELLVAME

NQHTIDLADSEMDKLYERVKRQLRENABEDGTGCFEIFHK

CDDDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLSSGY

KDVILWFSFGASCFILLAIVMGLVFICVKNGNMRCTICI

302
AIU46619
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERG

A/chicken/
VEVVNATETVERTNIPRICSKGKRTVDLGQCGLLGTITGPP

Zbejiang/DTID-
QCDQFLEFSADLIIERREGSDVCYPGKFVNEEALRQILRES

ZJU06/2013
GGIDKEAMGFTYSGIRTNGATSACRRSGSSFYAEMKWLLS

2013/12/HA
NTDNAAFPQMTKSYKNTRKSPALIVWGIHHSVSTAEQTKL

699978931
YGSGNKLVTVGSSNYQQSFVPSPGARPQVNGLSGRIDFH

WLMLNPNDTVTFSFNGAFIAPDRASFLRGKSMGIQSGVEV

DANCEGDCYHSGGTIISNLPFQNIDSRAVGKCPRYVKQRS

LLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGWYG

FRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQF

ELIDNEFNEVEKQIGNVINWTRDSITEVWSYNAELLVAME

NQHTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFHK

CDDDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLSSGY

KDVILWFSFGASCFILLAIVMGLVFICVKNGNMRCTICI

303
AIU47013
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERG

A/chicken/Suzhou/
VEVVNATETVERTNIPRICSKGKRTVDLGQCGLLGTITGPP

040201H/2013
QCDQFLEFSADLIIERREGSDVCYPGKFVNEEALRQILRES

2013/04/ HA
GGIDKEAMGFTYSGIRTNGATSACRRSGSSFYAEMKWLLS

699979673
NTDNAAFPQMTKSYKNTRKSPALIVWGIHHSVSTAEQTKL

YGSGNKLVTVGSSNYQQSFVPSPGARPQVNGLSGRIDFH

WLMLNPNDTVTFSFNGAFIAPDRASFLRGKSMGIQSGVQV

DANCEGDCYHSGGTIISNLPFQNIDSRAVGKCPRYVKQRS

LLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGWYG

FRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQF

ELIDNEFNEVEKQIGNVINWTRDSITEVWSYNAELLVAME

NQHTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFHK

CDDDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLSSGY

KDMILWFSFGASCFILLAIVMGLVFICVKNGNMRCTICI

304
AJJ90490
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERG

A/chicken/Shenzhen/
VEVVNATETVERTNIPRICSKGKKTVDLGQCGLLGTITGPP

742/2013
QCDQFLEFSADLIIERREGSDVCYPGKFVNEEALRQILRES

2013/12/10 HA
GGIDKEAMGFTYSGIRANGATSACRRSGSSFYAEMKWLL

755178094
SNTDNAAFPQMTKSYKNTRRSPALIVWGIHHSVSTAEQTK

LYGSGNKLVTVGSSNYQQSFVPSPGARPQVNGLSGRIDFH

WLMLNPNDTVTFSFNGAFIAPDRASFLRGKSMGIQSGVQV

DANCEGDCYHSGGTIISNLPFQNIDSRAVGKCPRYVKQRS

LLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGWYG

FRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQF

ELIDNEFNEVEKQIGNVINWTRDSITEVWSYNAELLVAME

NQHTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFHK

CDDDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLSSGY

KDVILWFSFGASCFILLAIVMGLVFICVKNGNMRCTICI

305
AJJ90526
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERG

A/chicken/Shenzhen/
VEVVNATETVERTNIPRICSKGKKTVDLGQCGLLGTITGPP

898/2013
QCDQFLEFSADLIIERREGSDICYPGKFVNEEALRQILRESG

2013/12/09 HA
GIDKEAMGFTYSGIRANGATSACKRSGSSFYAEMKWLLS

755178154
NTDNAAFPQMTKSYKNTRKSPALIVWGIHHSVSTAEQTKL

YGSGNKLVTVGSSNYQQSFVPSPGARPQVNGLSGRIDFH

WLMLNPNDTVTFSFNGAFIAPDRASFLRGKSMGIQSGVQV

DANCEGDCYHSGGTIISSLPFQNIDSRAVGKCPRYVKQRSL

LLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGWYGF

RHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQFE

LIDNEFNEVEKQIGNVINWIRDSITEVWSYNAELLVAMEN

QHTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFHKC

DDDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLSRGYK

DVILWFSFGASCFILLAIVMGLVFICVKNGNMRCTICI

306
AJJ90538
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERG

A/silkie
VEVVNATETVERTNIPRICSKGKKTVDLGQCGLLGTITGPP

chicken/Shenzhen/
QCDQFLEFSADLIIERREGSDVCYPGKFVNEEALRQILRES

918/2013
GGIDKEAMGFTYSGIRANGATSACRRSGSSFYAEMKWLL

2013/12/09 HA
SNTDNAAFPQMTKSYKNTRKSPALIVWGIHHSVSTAEQTK

755178174
LYGSGNKLVTVGSSNYQQSFVPSPGARPQVNGLSGRIDFH

WLMLNPNDTVTFSFNGAFIAPDRASFLRGKSMGIQSGVQV

DANCEGDCYHSGGTIISNLPFQNIDSRAVGKCPRYVKQRS

LLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGWYG

FRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQF

ELIDNEFNEVEKQIGNVINWTRDSITEVWSYNAELLVAME

NQHTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFHK

CDDDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLSSGY

KDVILWFSFGASCFILLAIVMGLVFICVKNGNMRCTICI

307
AJJ90576
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERG

A/chicken/Shenzhen/
VEVVNATETVERTNIPRICSKGKKTVDLGQCGLLGTITGPP

1665/2013
QCDQFLEFSADLIIERREGSDICYPGKFVNEEALRQILRESG

2013/12/12 HA
GIDKEAMGFTYSGIRANGATSACKRSGSSFYAEMKWLLS

755178238
NTDNAAFPQMTKSYKNTRKSPALIVWGIHHSVSTAEQTKL

YGSGNKLVTVGSSNYQQSFVPSPGARPQVNGLSGRIDFH

WLMLNPNDTVTFSFNGAFIAPDRASFLRGKSMGIQSGVQV

DANCEGDCYHSGGTIISNLPFQNIDSRAVGKCPRYVKQRS

LLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGWYG

FRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQF

ELIDNEFNEVEKQIGNVINWTRDSITEVWSYNAELLVAME

NQHTIDLADSEMDKLYERVKRQLRENABEDGTGCFEIFHK

CDDDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLSRGY

KDVILWFSFGASCFILLAIVMGLVFICVKNGNMRCTICI

308
AJJ90588
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERG

A/chicken/Shenzhen/
VEVVNATETVERTNIPRICSKGKKTVDLGQCGLLGTITGPP

2110/2013
QCDQFLEFSADLIIERREGSDVCYPGKFVNEEALRQILRES

2013/12/13 HA
GGIDKEAMGFTYSGIRANGATSACRRSGSSFYAEMKWLL

755178258
SNTDNAAFPQMTKSYKNTRRSPALIVWGIHHSVSTAEQTK

LYGSGNKLVTVGSSNYQQSFVPSPGARPQVNGLSGRIDFH

WLMLNPNDTVTFSENGAFIAPDRASFLRGKSIGIQSGVQV

DANCEGDCYHSGGTIISNLPFQNIDSRAVGKCPRYVKQRS

LLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGWYG

FRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQF

ELIDNEFNEVEKQIGNVINWTRDSITEVWSYNAELLVAME

NQHTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFHK

CDDDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLSSGY

KDVILWFSFGASCFILLAIVMGLVFICVKNGNMRCTICI

309
AJJ90661
MNTQILVEALIAIIPTNADKICLGHHAVSNGTKVNTLTERG

A/chicken/Dongguan/
VEVVNATETVERTNIPRICSKGKKTVDLGQCGLLGTITGPP

2912/2013
QCDQFLEFSADLIIERREGSDVCYPGKFVNEEALRQILRES

2013/12/18 HA
GGIDKEAMGFTYSGIRANGATSACRRSGSSFYAEMKWLL

755178380
SNTDNAAFPQMTKSYKNTRKSPALIVWGIHHSVSTAEQTK

LYGSGNKLVTVGSSNYQQSFVPSPGARPQVNGLSGRIDFH

WLMLNPNDTVTFSFNGAFIAPDRASFLRGKSMGIQSGVQV

DANCEGDCYHSGGTHISNLPFQNIDSRAVGKCPRYVKQRS

LLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGWYG

FRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQF

ELIDNEFNEVEKQIGNVINWTRDSITEVWSYNAELLVAME

NQHTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFHK

CDNDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLSSGY

KDVILWFSFGASCFILLAIVMGLVFICVKNGNMRCTICI

310
AJJ90673
MNTQILVFALTAIIPTNADKICLGHHAVSNGTKVNTLTERG

A/silkie
VEVVNATETVERTNIPRICSKGKKTVDLGQCGLLGTITGPP

chicken/Dongguan/
QCDQFLEFSADLIIERREGSDVCYPGKFVNEEALRQILRES

3049/2013
GGIDKEAMGFTYSGIRANGATSACRRSGSSFYAEMKWLL

2013/12/18 HA
SNTDNAAFPQMTKSYKNTRKSPALIVWGIHHSVSTAEQTK

755178400
LYGSGNKLVTVGSSNYQQSFVPSPGARPQVNGLSGRIDFH

WLMLNPNDTVTFSFNGAFIAPDRASFLRGKSMGIQSGVQV

DANCEGDCYHSGGTIISNLPFQNIDSRAVGKCPRYVKQRS

LLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGWYG

FRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQF

ELIDNEFNEVEKQIGNVINWTRDSITEVWSYNAELLVAME

NQHTIDLADSEMDKLYERVKRQLRENABEDGTGCFEIFHK

CDNDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLSSGY

KDVILWFSFGASCFILLAIVMGLVFICVKNGNMRCTICI

311
AJJ90795
MNTQILVFALIAIIPTNADKICLGHHAVPNGTKVNTLTERG

A/silkie
VEVVNATETVERTNIPRICSKGKKTVDLGQCGLLGTITGPP

chicken/Dongguan/
QCDQFLEFSADLIIERREGSDVCYPGKFVNEEALRQILRES

3281/2013
GGIDKEAMGFTYSGIRANGATSACRRSGSSFYAEMKWLL

2013/12/18 HA
SNTDNAAFPQMTKSYKNTRKSPALIVWGIHHSVSTAEQTK

755178604
LYGSGNKLVTVGSSNYQQSFVPSPGARPQVNGLSGRIDFH

WLMLNPNDTVTFSENGAFIAPDRASFLRGKSMGIQSGVQV

DANCEGDCYHSGGTIISNLPFQNIDSRAVGKCPRYVKQRS

LLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGWYG

FRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQF

ELIDNEFNEVEKQIGNVINWTRDSITEVWSYNAELLVAME

NQHTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFHK

CDDDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLSSGY

KDVILWFSFGASCFILLAIVMGLVFICVKNGNMRCTICI

312
AJJ90891
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERG

A/silkie
VEVVNATETVERTNIPRICSKGKKTVDLGQCGLLGTITGPP

chicken/Dongguan/
QCDQFLEFSADLIIERREGSDVCYPGKFVNEEALRQILRES

3520/2013
GGIDKEAMGFTYSGIRANGATSACRRSGSSFYAEMKWLL

2013/12/19 HA
SNTDNAAFPQMTKSYKNTRKXPALIVWGIHHSVSTAEQT

755178764
KLYGSGNKLVTVGSSNYQQSFVPSPGARPQVNGLSGRIDF

HWLMLNPNDTVTFSFNGAFIAPDRASFLRGKSMGIQSGVQ

VDANCEGDCYHSGGTIISNLPFQNIDSRAVGKCPRYVKQR

SLLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGWY

GFRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQ

FELIDNEFNEVEKQIGNVINWTRDSITEVWSYNAELLVAM

ENQHTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFH

KCDNDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLSSG

YKDVILWFSFGASCFILLAIVMGLVFICVKNGNMRCTICI

313
AJJ90951
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERG

A/chicken/Dongguan/
VEVVNATETVERTNIPRICSKGKKTVDLGQCGLLGTITGPP

3544/2013
QCDQFLEFSADLIIERREGSDVCYPGKFVNEEALRQILRES

2013/12/19 HA
GGIDKEAMGFTYSGIRANGATSACRRSGSSFYAEMKWLL

755178864
SNTDNAAFPQMTKSYRNTRKSPALIVWGIHHSVSTAEQTK

LYGSGNKLVTVGSSNYQQSFVPSPGARPQVNGLSGRIDFH

WLMLNPNDTVTFSFNGAFIAPDRASFLRGKSMGIQSGVQV

DANCEGDCYHSGGTHISNLPFQNIDSRAVGKCPRYVKQRS

LLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGWYG

FRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQF

ELIDNEFNEVEKQIGNVINWTRDSITEVWSYNAELLVAME

NQHTIDLADSEMDKLYERVKRQLRENABEDGTGCFEIFHK

CDDDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLSSGY

KDVILWFSFGASCFILLAIVMGLVFICVKNGNMRCTICI

314
AJJ91035
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERG

A/chicken/Shenzhen/
VEVVNATETVERTNIPRICSKGKKTVDLGQCGLLGTITGPP

3780/2013
QCDQFLEFSADLIIERREGSDVCYPGKFVNEEALRQILRES

2013/12/19 HA
GGIDKEAMGFTYSGIRANGATSACRRSGSSFYAEMKWLL

755179004
SNTDNAAFPQMTKSYKNTRRSPALIVWGIHHSVSTAEQTK

LYGSGNKLVTVGSSNYQQSFVPSPGARPQVNGLSGRIDFH

WLMLNPNDTVTFSFNGAFIAPDRASFLRGKSMGIQSGVQV

DANCEGDCYHSGGTIISNLPFQNIDNRAVGKCPRYVKQRS

LLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGWYG

FRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQF

ELIDNEFNEVEKQIGNVINWTRDSITEVWSYNAELLVAME

NQHTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFHK

CDDDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLSSGY

KDVILWFSFGASCFILLAIVMGLVFICVKNGNMRCTICI

315
AJJ91155
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERG

A/chicken/Dongguan/
VEVVNATETVERTNIPRICSKGKKTVDLGQCGLLGTITGPP

4037/2013
QCDQFLEFSADLIIERREGSDVCYPGKFVNEEALRQILRES

2013/12/19 HA
GGIDKEAMGFTYSGIRANGATSACRRSGSSFYAEMKWLL

755179204
SNTDNAAFPQMTKSYKNTRKSPALIVWGIHHSVSTAEQTK

LYGSGNKLVTVGSSNYQQSFVPSPGARPQVNGLSGRIDFH

WLMLNPNDTVTFSENGAFIAPDRASFLRGKSMGIQSGVQV

DANCEGDCYHSGGTHISNLPFQNIDSRAVGKCPRYVKQRS

LLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGWYG

FRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQF

ELIDNEFNEVEKQIGNVINWIRDSITEVWSYNAELLVAME

NQHTIDLADSEMNKLYERVKRQLRENAEEDGTGCFEIFHK

CDDDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLSSGY

KDVILWFSFGASCFILLAIVMGLVFICVKNGNMRCTICI

316
AJJ92005
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERG

A/chicken/Shenzhen/
VEVVNATETVERTNIPRICSKGKKTVDLGQCGLLGTITGPP

801/2013
QCDQFLEFSADLIIERREGSDVCYPGKFVNEEALRQILRES

2013/12/09 HA
GGIDKEAMGFTYSGIRANGATSACRRSGSSFYAEMKWLL

755180629
SNTDNAAFPQMTKSYKNTRKSPALIVWGIHHSVSTAEQTK

LYGSGNKLVTVGSSNYQQSFVPSPGARPQVNGLSGRIDFH

WLMLNPNDTVTFSFNGAFIAPDRASFLRGKSMGIQSGVQV

DANCEGDCYHSGGTIISNLPFQNIDSRAVGKCPRYVKQRS

LLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGWYG

FRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQF

ELIDNEFNEVEKQIGNVINWTRDSITEVWSYNAELLVAME

NQHTIDLADSEMDKLYERVKRQLRENABEDGTGCFEIFHK

CDDDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLSRGY

KDVILWFSFGASCFILLAIVMGLVFICVKNGNMRCTICI

317
AJJ94254
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERG

A/chicken/Dongguan/
VEVVNATETVERTNIPRICSKGKKTVDLGQCGLLGTITGPP

1374/2014
QCDQFLEFSADLIIERREGSDVCYPGKFVNEEALRQILRES

2014/02/21 HA
GGIDKEAMGFTYSGIRTNGATSACRRSGSSFYAEMKWLLS

755184382
NTDNAAFPQMTKSYKNTRKSPALIVWGIHHSVSTAEQTKL

YGSGNKLVTVGSSNYQQSFVPSPGARPQVNGLSGRIDFH

WLMLNPNDTVTFSFNGAFIAPERASFLRGKSMGIQSGVQV

DANCEGDCYHSGGTIISNLPFQNIDSRAVGKCPRYVKQRS

LLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGWYG

FKHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQF

ELIDNEFNEVETQIGNVINWIRDSITEVWSYNAELLVAME

NQHTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFHK

CDDDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLSSGY

KDVILWFSFGASCFILLAIVMGLVFICVKNGNMRCTICI

318
AJJ94606
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERG

A/chicken/Dongguan/
VEVVNATETVERTNIPRICSKGKKTVDLGQCGLLGTITGPP

191/2014
QCDQFLEFSADLIIERREGSDVCYPGKFVNEEALRQILRKS

2014/02/20 HA
GGIDKEAMGFTYSGIRTNGATSACRRSGSSFYAEMKWLLS

755184968
NTDNAAFPQMTKSYKNTRKSPAIIVWGIHHSVSTAEQTKL

YGSGNKLVTVGSSNYQQSFVPSPGARPQVNGLSGRIDFH

WLMLNPNDTVTFSFNGAFIAPDRASFLRGKSMGIQSGVQV

DADCEGDCYHSGGTHISNLPFQNIDSRAVGKCPRYVKQRS

LLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGWYG

FRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQF

ELIDNEFNEVEKQIGNVINWTRDSITEVWSYNAELLVAME

NQHTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFHK

CDDDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLSSGY

KDVILWFSFGASCFILLAIVMGLVFICVKNGNMRCTICI

319
AJJ96552
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERG

A/chicken/Jiangxi/
VEVVNATETVERTNIPRICSKGKKTIDLGQCGLLGTITGPP

12206/2014
QCDQFLEFSADLIIERREGSDVCYPGKFVNEEALRQILRES

2014/03/16 HA
GGIDKEAMGFTYSGIRTNGATSACRRSGSSFYAEMKWLLS

755188219
NTDNAAFPQMTKSYKNTRKSPALIVWGIHHSVSTAEQTKL

YGSGNKLVTVGSSNYQQSFVPSPGARPQVNGLSGRIDFH

WLMLNPNDTVTFSFNGAFIAPDRASFLRGKSMGIQSGVQV

DANCEGDCYHSGGTIISNLPFQNIDSRAVGKCPRYVKQKS

LLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGWYG

FRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQF

ELIDNEFNEVEKQIGNVINWTRDSITEVWSYNAELLVAME

NQHTIDLADSEMDKLYERVKRQLRENABEDGTGCFEIFHK

CDDDCMASIRNNTYDHNKYREEAMQNRIQIDPVKLSSGY

KDVILWFSFGASCFILLAIVMGLVFICVKNGNMRCTICI

320
AJJ96684
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKINTLTERG

A/chicken/Jiangxi/
VEVVNATETVERTNIPRICSKGKKTVDLGQCGLLGTITGPP

13207/2014
QCDQFLEFSADLIIERREGSDVCYPGKFVNEEALRQILRES

2014/03/30 HA
GGIDKEAMGFTYSGIRTNGATSACRRSGSSFYAEMKWLLS

755188439
NTDNAAFPQMTKSYKNTRKSPALIVWGIHHSVSTAEQTKL

YGSGNKLVTVGSSNYQQSFVPSPGARPQVNGLSGRIDFH

WLMLNPNDTVTFSFNGAFIAPDRASFLRGKSMGIQSGVQV

DANCEGDCYHSGGTIISNLPFQNIDSRAVGKCPRYVKQKS

LLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGWYG

FRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQF

ELIDNEFNEVEKQIGNVINWTRDSITELWSYNAELLVAME

NQHTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFHK

CDDDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLSSGY

KDVILWFSFGASCFILLAIVMGLVFICVKNGNMRCTICI

321
AJJ96732
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERG

A/chicken/Jiangxi/
VEVVNATETVERTNIPRICSKGKKTVDLGQCGLLGTITGPP

13223/2014
QCDQFLEFSADLIIERREGSDVCYPGKFVNEEALRQILRES

2014/03/30 HA
GGIDKEAMGFTYSGIRTNGATSACRRSGSSFYAEMKWLLS

755188519
NTDNAAFPQMTKSYKNTRKSPALIVWGIHHSVSTAEQTKL

YGSGNKLVTVGSSNYQQSFVPSPGARPQVNGLSGRIDFH

WLMLNPNDTVTFSFNGAFIAPDRASFLRGKSMGIQSGVQV

DANCEGDCYHSGGTIISNLPFQNIDSRAVGKCPRYVKQKS

LLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGWYG

FRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQF

ELIDNEFNEVEKQIGNVINWTRDSITELWSYNAELLVAME

NQHTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFHK

CDDDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLSSGY

KDVILWFSFGASCFILLAIVMGLVFICVKNGNMRCTICI

322
AJK00354
MNTQILVFALVAIIPTNADKICLGHHAVSNGTKVNTLTER

A/duck/Zhejiang/
GVEVVNATETVERTNIPRICSKGKKTVDLGQCGLLGTITGP

LS02/2014
PQCDQFLEFSADLIVERREGSDVCYPGKFVNEEALRQILRE

2014/01/12 HA
SGGIDKEAMGFTYSGIRTNGATSACRRSGSSFYAEMKWLL

755194469
SNTDNAAFPQMTKSYKNTRKDPALIWGIHHSGSTTEQTK

LYGSGNKLITVGSSNYQQSFVPSPGARPLVNGQSGRIDFH

WLMLNPNDTVTFSFNGAFIAPDRASFLRGKSMGIQSGVQV

DANCEGDCYHSGGTHISNLPFQNINSRAVGKCPRYVKQES

LLLATGMKNVPEVPKGRGLFGAIAGFIENGWEGLIDGWY

GFRHQNAQGEGTAADYKSTQSAIDQVTGKLNRLIEKTNQ

QFELIDHEFTEVEKQIGNVINWTRDSMTEVWSYNAELLVA

MENQHTIDLADSEMNKLYERVKRQLRENAEEDGTGCFEIF

HKCDNDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLSS

GYKDVILWFSFGASCFILLAIVMGLVFICVKNGNMRCTICI

323
AJJ91264
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERG

A/silkie
VEVVNATETVERTNIPRICSKGKKTVDLGQCGLLGTITGPP

chicken/Dongguan/
QCDQFLEFSADLIIERREGSDVCYPGKFVNEEALRQILRES

4129/2013
GGIDKEAMGFTYSGIRANGATSACRRSGSSFYAEMKWLL

2013/12/19 HA
SNTDNAAFPQMTKSYKNTRKSPALIVWGIHHSVSTAEQTK

755179386
LYGSGNKLVTVGSSNYQQSFVPSPGARPQVNGLSGRIDFH

WLMLNPNDTVTFSFNGAFIAPDRASFLRGKSMGIQSGVQV

DANCEGDCYHSGGTIISNLPFQNIDSRAVGKCPRYVKQRS

LLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGWYG

FRHQNAQGEGTAADYKSTQSAIDQITGKLNRLMEKTNQQ

FELIDNEFNEVEKQIGNVINWTRDSITEVWSYNAELLVAM

ENQHTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFH

KCDDDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLSSG

YKDVILWFSFGASCFILLAIVMGLVFICVKNGNMRCTICI

324
AJJ91314
MNTQILVEALIAIIPTNADKICLGHHAVSNGTKVNTLTERG

A/chicken/Shaoxing/
VEVVNATETVERTNIPRICSKGKRTVDLGQCGLLGTITGPP

2417/2013
QCDQFLEFSADLIIERREGSDVCYPGKFVNEEALRQILRES

2013/10/20 HA
GGIDKEAMGFTYSGIRTNGATSACRRSGSSFYAEMKWLLS

755179470
NTDNAAFPQMTKSYKNTRKSPALIVWGIHHSVSTAEQTKL

YGSGNKLVTVGSSNYQQSFVPSPGARPPVNGLSGRIDFHW

LMLNPNDTVTFSFNGAFIAPDRASFLRGKSMGIQSGVQVD

ANCEGDCYHSGGTIISNLPFQNIDSRAVGKCPRYVKQRSLL

LATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGWYGFR

HQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQFELI

DNEFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMENQ

HTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFHKCD

DDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLSSGYKD

VILWFSFGASCFILLAIVMGLVFICVKNGNMRCTICI

325
AJJ91402
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERG

A/chicken/Huzhou/
VEVVNATETVERTNIPRICSKGKRTVDLGQCGLLGTITGPP

4045/2013
QCDQFLEFSADLIIERREGSDVCYPGKFVNEEALRQILRES

2013/10/24 HA
GGIDKEAMGFTYSGIRTNGATSACRRSGSSFYAEMKWLLS

755179618
NTDNAAFPQMTKSYKNTRKSPALIVWGIHHSVSTAEQTKL

YGSGNKLVTVGSSNYQQSFVPSPGARPQVNGLSGRIDFH

WLMLNPNDTVTFSFNGAFIAPDRASFLRGKSMGIQSGVQV

DANCEGDCYHSGGTHISNLPFQNIDSRAVGKCPRYVKQRS

LLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGWYG

FRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQF

ELIDNEFNEVEKQIGNVINWTRDSITELWSYNAELLVAME

NQHTIDLADSEMDKLYERVKRQLRENABEDGTGCFEIFHK

CDDDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLSSGY

KEVILWFSFGASCFILLAIVMGLVFICVKNGNMRCTICI

326
AJJ91476
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERG

A/chicken/Huzhou/
VEVVNATETVERTNIPRICSKGKRTVDLGQCGLLGTITGPP

4076/2013
QCDQFLEFSADLIIERREGSDVCYPGKFVNEEALRQILRKS

2013/10/24 HA
GGIDKEAMGFTYSGIRTNGATSACRRSGSSFYAEMKWLLS

755179743
NTDNAAFPQMTKSYKNTRKSPALIVWGIHHSVSTAEQTKL

YGSGNKLVTVGSSNYQQSFVPSPGARPQVNGLSGRIDFH

WLMLNPNDTVTFSFNGAFIAPDRASFLRGKSMGIQSGVQV

DANCEGDCYHSRGTIISNLPFQNIDSRAVGKCPRYVKQRS

LLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGWYG

FRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQF

ELIDNEFNEVEKQIGNVINWTRDSITEVWSYNAELLVAME

NQHTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFHK

CDDDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLSSGY

KDVILWFSFGASCFILLAIVMGLVFICVKNGNMRCTICI

327
AJJ91725
MNTQILVEALIAIIPTNADKICLGHHAVSNGTKVNTLTERG

A/chicken/Shaoxing/
VEVVNATETVERTNIPRICSKGKRTVDLGQCGLLGTITGPP

5201/2013
QCDQFLEFSADLIIERREGSDVCYPGKFVNEEALRQILRES

2013/10/28 HA
GGIDKEAMGFTYSGIRTNGATSACRRSGSSFYAEMKWLLS

755180161
NTDNAAFPQMTKSYKNTRKSPALIVWGIHHSVSTAEQTKL

YGSGNKLVTVGSSNYQQSFVPSPGARPQVNGLSGRIDFH

WLMLNPNDTVTFSFNGAFIAPDRASFLRGKSMGIQSGVQV

DANCEGDCYHSGGTIISNLPFQNIDSRAVGKCPRYVKQRS

LLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGWYG

FRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQF

ELIDNEFNEVEKQIGNVINWIRDSITELWSYNAELLVAME

NQHTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFHK

CDDDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLSSGY

KDVILWFSFGASCFILLAIVMGLVFICVKNGNMRCTICI

328
AJJ91885
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERG

A/Shenzhen/SP4/
VEVVNATETVERTNIPRICSKGKKTVDLGQCGLLGTITGPP

2014
QCDQFLEFSADLIIERREGSDVCYPGKFVNEEALRQILRES

2014/01/16 HA
GGIDKEAMGFTYSGIRANGVTSACRRSGSSFYAEMKWLL

755180429
SNTDNAAFPQMTKSYKNTRKSPALIVWGIHHSVSTAEQTK

LYGSGNKLVTVGSSNYQQSFVPSPGARPQVNGLSGRIDFH

WLMLNPNDTVTFSFNGAFIAPDRASFLRGKSMGIQSGVQV

DANCEGDCYHSGGTHISNLPFQNIDSRAVGKCPRYVKQRS

LLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGWYG

FRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQF

ELIDNEFNEVEKQIGNVINWTRDSITEVWSYNAELLVAME

NQHTIDLADSEMDKLYERVKRQLRENABEDGTGCFEIFHK

CDDDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLSRGY

KDVILWFSFGASCFILLAIVMGLVFICVKNGNMRCTICI

329
AJJ91909
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERG

A/Shenzhen/SP26/
VEVVNATETVERTNIPRICSKGKKTVDLGQCGLLGTITGPP

2014
QCDQFLEFSADLIIERREGSDICYPGKFVNEEALRQILRESG

2014/01/20 HA
GIDKEAMGFTYSGIRANGATSACKRSGSSFYAEMKWLLS

755180469
NTDNAAFPQMTKSYKNTRKSPALIVWGIHHSVSTAEQTKL

YGSGNKLVTVGSSNYQQSFVPSPGARPQVNGLSGRIDFH

WLMLNPNDTVTFSENGAFIAPDRASFLRGKSMGIQSGVQV

DANCEGDCYHSGGTIISSLPFQNIDSRAVGKCPRYVKQRSL

LLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGWYGF

RHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQFE

LIDNEFNEVEKQIGNVINWIRDSITEVWSYNAELLVAMEN

QHTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFHKC

DDGCMASIRNNTYDHSKYREEAMQNRIQIDPVKLSRGYK

DVILWFSFGASCFILLAIVMGLVFICVKNGNMRCTICI

330
AJJ91945
MNTQILAFALIAIIPTNADKICLGHHAVSNGTKVNTLTERG

A/Shenzhen/SP38/
VEVVNATETVERTNIPRICSKGKKTVDLGQCGLLGTITGPP

2014
QCDQFLEFSADLIIERREGSDVCYPGKFVNEEALRQILRES

2014/01/22 HA
GGIDKEAMGFTYSGIRANGATSACRRSGSSFYAEMKWLL

755180529
SNTDNAAFPQMTKSYKNTRKSPALIVWGIHHSVSTAEQTK

LYGSGNKLVTVGSSNYQQSFVPSPGARPQVNGLSGRIDFH

WLMLNPNDTVTFSFNGAFIAPDRASFLRGKSMGIQSGVQV

DANCEGDCYHSGGTHISNLPFQNIDSRAVGKCPRYVKQRS

LLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIGGWYG

FRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQF

ELIDNEFNEVEKQIGNVINWTRDSITEVWSYNAELLVAME

NQHTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFHK

CDDDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLSSGY

KDVILWFSFGASCFILLAIVMGLVFICVKNGNMRCTICI

331
AJJ91957
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERG

A/Shenzhen/SP44/
VEVVNATETVERTNIPRICSKGKRTVDLGQCGLLGTITGPP

2014
QCDQFLEFSADLIIERREGSDVCYPGKFVNEEALRQILRES

2014/01/23 HA
GGIDKEAMGFTYSGIRANGTTSACRRSGSSFYAEMKWLLS

755180549
NTDNAAFPQMTKSYKNTRKSPALIVWGIHHSVSTAEQTKL

YGSGNKLVTVGSSNYQQSFVPSPGARPQVNGLSGRIDFH

WLMLNPNDTVTFSFNGAFIAPDRASFLRGKSMGIQSGVQV

DANCEGDCYHSGGTHISSLPFQNIDSRAVGKCPRYVKQRSL

LLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGWYGF

RHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQFE

LIDNEFNEVEKQIGNVINWIRDSITEVWSYNAELLVAMEN

QHTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFHKC

DDDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLSSGYK

DVILWFSFGASCFILLAIVMGLVFICVKNGNMRCTICI

332
AJJ91969
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERG

A/Shenzhen/SP48/
VEVVNATETVERTNIPRICSKGKKTVDLGQCGLLGTITGPP

2014
QCDQFLEFSADLIIERREGSDVCYPGKFVNEEALRQILRES

2014/01/23 HA
GGIDKEAMGFTYSGIRTNGATSACRRSGSSFYAEMKWLLS

755180569
NTDNAAFPQMTKSYKNTRKSPALIVWGIHHSVSTAEQTKL

YGSGNKLVTVGSSNYQQSFVPSPGARPQVNGLSGRIDFH

WLMLNPNDTVTFSFNGAFIAPDRASFLRGKSMGIQSGVQV

DANCEGDCYHSGGTIISNLPFQNIDSRAVGKCPRYVKQRS

LLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGWYG

FRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQF

ELIDNEFNEVETQIGNVINWIRDSITEVWSYNAELLVAME

NQHTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFHK

CDDDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLSSGY

KDVILWFSFGASCFILLAIVMGLVFICVKNGNMRCTICI

333
AJJ91993
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERG

A/chicken/Dongguan/
VEVVNATETVERTNIPRICSKGKKTVDLGQCGLLGTITGPP

4119/2013
QCDQFLEFSADLIIERREGSDVCYPGKFVNEEALRQILRES

2013/12/19 HA
GGIDKEAMGFTYSGIRANGATSACRRSGSSFYAEMKWLL

755180609
SNTDNAAFPQMTKSYKNTRKSPALIVWGIHHSVSTAEQTK

LYGSGNKLVTVGSSNYQQSFVPSPGARPQVNGLSGRIDFH

WLMLNPNDTVTFSFNGAFIAPDRASFLRGKSMGIQSGVQV

DANCEGDCYHSGGTIISNLPFQNIDSRAVGKCPRYVKQRS

LLLATGMKNVPEIPKGRGLLGAIAGFIENGWEGLIDGWYG

FRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQF

ELIDNEFNEVEKQIGNVINWTRDSITEVWSYNAELLVAME

NQHTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFHK

CDDDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLSSGY

KDVILWFSFGASCFTLLAIVMGLVFICVKNGNMRCTICI

334
AJJ92031
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERG

A/chicken/Dongguan/
VEVVNATETVERTNIPRICSKGKKTVDLGQCGLLGTITGPP

4064/2013
QCDQFLEFSADLIIERREGSDVCYPGKFVNEEALRQILRES

2013/12/19 HA
GGIDKEAMGFTYSGIRANGATSACRRSGSSFYAEMKWLL

755180672
SNTDNAAFPQMTKSYKNTRKSPALIVWGIHHSVSTAEQTK

LYGSGNKLVTVESSNYQQSFVPSPGARPQVNGLSGRIDFH

WLMLNPNDTVTFSFNGAFIAPDRASFLRGKSMGIQSGVQV

DANCEGDCYHSGGTHISNLPFQNIDSRAVGKCPRYVKQRS

LLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGWYG

FRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQF

ELIDNEFNEVEKQIGNVINWTRDSITEVWSYNAELLVAME

NQHTIDLADSEMDKLYERVKRQLRENABEDGTGCFEIFHK

CDDDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLSSGY

KDVILWFSFGASCFILLAIVMGLVFICVKNGNMRCTICI

335
AJJ92967
MNTQILVFALIAIVPTNADKICLGHHAVSNGTKVNTLTER

A/silkie
GVEVVNATETVERTNIPRICSKGKKTVDLGQCGLLGTITGP

chicken/Jiangxi/
PQCDQFLEFSADLIIERREGSDVCYPGKFVNEEALRQILRES

9469/2014
GGIDKEAMGFTYSGIRTNGVTSACRRSGSSFYAEMKWLLS

2014/02/16 HA
NTDNAAFPQMTKSYKNTRKSPALIVWGIHHSVSTAEQTKL

755182232
YGSGNKLVTVGSSNYQQSFVPSPGARPQVNGLSGRIDFH

WLMLNPNDTVTFSFNGAFIAPDRASFLRGKSMGIQSGVQV

DANCEGDCYHSGGTIISNLPFQNIDSRAVGKCPRYVKQKS

LLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGWYG

FRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQF

ELIDNEFNEVEKQIGNVINWTRDSITEVWSYNAELLVAME

NQHTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFHK

CDDDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLSSGY

KDVILWFSFGASCFILLAIVMGLVFICVKNGNMRCTICI

336
AJJ93027
MNTQILVEALIAIVPTNADKICLGHHAVSNGTKVNTLTER

A/chicken/Jiangxi/
GVEVVNATETVERTNIPRICSKGKKTVDLGQCGLLGTITGP

9558/2014
PQCDQFLEFSADLIIERREGSDVCYPGKFVKEEALRQILRES

2014/02/16 HA
GGIDKEAMGFTYSGIRTNGVTSACRRSGSSFYAEMKWLLS

755182332
NTDNAAFPQMTKSYKNTRKSPALIVWGIHHSVSTAEQTKL

YGSGNKLVTVGSSNYQQSFVPSPGARPQVNGLSGRIDFH

WLMLNPNDTVTFSFNGAFIAPDRASFLRGKSMGIQSGVQV

DANCEGDCYHSGGTIISNLPFQNIDSRAVGKCPRYVKQKS

LLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGWYG

FRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQF

ELIDNEFNEVEKQIGNVINWTRDSITEVWSYNAELLVAME

NQHTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFHK

CDDDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLSSGY

KDVILWFSFGASCFILLAIVMGLVFICVKNGNMRCTICI

337
AJJ93051
MNTQILVFALIAIVPTNADKICLGHHAVSNGTKVNTLTER

A/chicken/Jiangxi/
GVEVVNATETVERTNIPRICSKGKKTVDLGQCGLLGTITGP

10573/2014
PQCDQFLEFSADLIIERREGSDVCYPGKFVNEEALRQILRES

2014/02/18 HA
GGIDKBAMGFTYSGIRTNGVTSACRRSGSSFYAEMKWLLS

755182372
NTDDAAFPQMTKSYKNTRKSPALIVWGIHHSVSTAEQTKL

YGSGNKLVTVGSSNYQQSFVPSPGARPQVNGLSGRIDFH

WLMLNPNDTVTFSENGAFIAPDRASFLRGKSMGIQSGVQV

DANCEGDCYHSGGTHISNLPFQNIDSRAVGKCPRYVKQKS

LLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGWYG

FRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQF

ELIDNEFNEVEKQIGNVINWTRDSITEVWSYNAELLVAME

NQHTIDLADSEMDKLYERVKRQLRENABEDGTGCFEIFHK

CDDDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLSSGY

KDVILWFSFGASCFILLAIVMGLVFICVKNGNMRCTICI

338
AJJ93845
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERG

A/silkie
VEVVNATETVERTNIPRICSKGKKTVDLGQCGLLGTITGPP

chicken/Dongguan/
QCDQFLEFSADLIIERREGSDVCYPGKFVNEEALRQILRES

157/2014
GGIDKEAMGFTYSGIRANGATSACRRSGSSFYAEMKWLL

2014/02/20 HA
SNTDNAAFPQMTKSYKNTRKSPALIVWGIHHSVSTAEQTK

755183695
LYGSGNKLVTVGSSNYQQSFVPSPGARPQVNGLSGRIDFH

WLMLNPNDTVTFSFNGAFIAPDRASFLRGKSMGIQSGVQV

DANCEGDCYHSGGTIISNLPFQNIDSRAVGKCPRYVKQKS

LLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGWYG

FRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQF

ELIDNEFNEVEKQIGNVINWTRDSITEVWSYNAELLVAME

NQHTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFHK

CDNDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLSSGY

KDVILWFSFGASCFILLAIVMGLVFICVKNGNMRCTICI

339
AJJ93857
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERG

A/chicken/Dongguan/
VEVVNATETVERTNIPRICSKGKKTVDLGQCGLLGTITGPP

169/2014
QCDQFLEFSADLIIERREGSDVCYPGKFVNEEALRQILRKS

2014/02/20 HA
GGIDKEAMGFTYSGIRTNGATSACMRSGSSFYAEMKWLL

755183715
SNTDNAAFPQMTKSYKNTRKSPAIIVWGIHHSVSTAEQTK

LYGSGNKLVTVGSSNYQQSFVPSPGARPQVNGLSGRIDFH

WLMLNPNDTVTFSFNGAFIAPDRASFLRGKSMGIQSGVQV

DADCEGDCYHSGGTHISNLPFQNIDSRAVGKCPRYVKQRS

LLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGWYG

FRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQF

ELIDNEFNEVEKQIGNVINWTRDSITEVWSYNAELLVAME

NQHTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFHK

CDDDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLSSGY

KDVILWFSFGASCFILLAIVMGLVFICVKNGNMRCTICI

340
AJJ93869
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERG

A/chicken/Dongguan/
VEVVNATETVERTNIPRICSKGKKTVDLGQCGLLGTVTGP

173/2014
PQCDQFLEFSADLIIERREGSDVCYPGKFVNEEALRQILRES

2014/02/20 HA
GGIDKEAMGFTYSGIRANGATSACRRSGSSFYAEMKWLL

755183735
SNTDNAAFPQMTKSYKNTRKSPALIVWGIHHSVSTAEQTK

LYGSGNKLVTVGSSNYQQSFVPSPGARPQVNGLSGRIDFH

WLMLNPNDTVTFSFNGAFIAPDRASFLRGKSMGIQSGVQV

DANCEGDCYHSGGTIISNLPFQNIDSRAVGKCPRYVKQKS

LLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGWYG

FRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQF

ELIDNEFNEVEKQIGNVINWTRDSITEVWSYNAELLVAME

NQHTIDLADSEMDKLYERVKRQLRENABEDGTGCFEIFHK

CDNDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLSSGY

KDVILWFSFGASCFILLAIVMGLVFICVKNGNMRCTICI

341
AJJ93881
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERG

A/chicken/Dongguan/
VEVVNATETVERTNIPRICSKGKKTVDLGQCGLLGTVTGP

189/2014
PQCDQFLEFSADLIIERREGSDVCYPGKFVNEEALRQILRES

2014/02/20 HA
GGIDKEAMGFTYSGIRANGATSACRRSGSSFYAEMKWLL

755183755
SNTDNAAFPQMTKSYKNTRKSPALIVWGIHHSVSTAEQTK

LYGSGNKLVTVGSSNYQQSFVPSPGARPQVNGLSGRIDFH

WLMLNPNDTVTFSFNGAFIAPDRASFLRGKSMGIQSGVQV

DANCEGDCYHSGGTIISNLPFQNIDSRAVGKCPKYVKQKS

LLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGWYG

FRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQF

ELIDNEFNEVEKQIGNVINWTRDSITEVWSYNAELLVAME

NQHTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFHK

CDNDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLSSGY

KDVILWFSFGASCFILLAIVMGLVFICVKNGNMRCTICI

342
AJJ93907
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERG

A/chicken/Dong
VEVVNATETVERTNIPRICSKGKKTVDLGQCGLLGTITGPP

guan/449/2014
QCDQFLEFSADLIIERREGSDVCYPGKFVNEEALRQILRES

2014/02/20 HA
GGIDKEAMGFTYSGIRANGATSACRRSGSSFYAEMKWLL

755183799
SNTDNAAFPQMTKSYKNTRKSPALIVWGIHHSVSTAEQTK

LYGSGNKLVTVGSSNYQQSFVPSPGARPQVNGLSGRIDFH

WLMLNPNDTVTFSFNGAFIAPERASFLRGKSMGIQSGVQV

DANCEGDCYHSGGTIISNLPFQNIDSRAVGKCPRYVKQRS

LLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGWYG

FRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQF

ELIDNEFNEVEKQIGNVINWTRDSITEVWSYNAELLVAME

NQHTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFHK

CDDDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLSSGY

KDVILWFSFGASCFILLAIVMGLVFICVKNGNMRCTICI

343
AJJ93931
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERG

A/chicken/
VEVVNATETVERTNIPRICSKGKKTVDLGQCGLLGTITGPP

Dongguan/536/2014
QCDQFLEFSADLIIERREGSDVCYPGKFVNEEALRQILRKS

2014/02/20 HA
GGIDKEAMGFTYSGIRTNGATSACRRSGSSFYAEMKWLLS

755183839
NTDNAAFPQMTKSYKNTRKSPAIIVWGIHHSVSTAEQTKL

YGSGNKLVTVGSSNYQQSFVPSPGARPQVNGLSGRIDFH

WLMLNPNDTVTFSFNGAFIAPDRASFLRGKSMGIQSGVQV

DADCEGDCYHSGGTIISKLPFQNIDSRAVGKCPRYVKQRS

LLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGWYG

FRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQF

ELIDNEFNEVEKQIGNVINWTRDSITEVWSYNAELLVAME

NQHTIDLADSEMDKLYERVKRQLRENABEDGTGCFEIFHK

CDDDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLSSGY

KDVILWFSFGASCFILLAIVMGLVFICVKNGNMRCTICI

344
AJJ93943
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERG

A/chicken/Dongguan/
VEVVNATETVERTNIPRICSKGKKTVDLGQCGLLGTITGPP

568/2014
QCDQFLEFSADLIIERREGSDVCYPGKFVNEEALRQILRES

2014/02/20 HA
GGIEKEAMGFTYSGIRANGATSACRRSGSSFYAEMKWLLS

755183859
NTDNAAFPQMTKSYKNTRKSPALIVWGIHHSVSTAEQTKL

YGSGNKLVTVGSSNYQQSFVPSPGARPQVNGLSGRIDFH

WLMLNPNDTVTFSFNGAFIAPDRASFLRGKSMGIQSGVQV

DANCEGDCYHSGGTIISNLPFQNIDSRAVGKCPRYVKQRS

LLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGWYG

FRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQF

ELIDNEFNEVEKQIGNVINWTRDSITEVWSYNAELLVAME

NQHTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFHK

CDDDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLSGGY

KDVILWFSFGASCFILLAIVMGLVFICVKNGNMRCTICI

345
AJJ93979
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERG

A/silkie
VEVVNATETVERTNIPRICSKGKKTVDLGQCGLLGTVTGP

chicken/Dongguan/
PQCDQFLEFSADLIIERREGSDVCYPGKFVNEEALRQILRES

656/2014
GGIDKEAMGFTYSGIRANGATSACRRSGSSFYAEMKWLL

2014/02/20 HA
SNTDNAAFPQMTKSYKNTRKSPALIVWGIHHSVSTAEQTK

755183919
LYGSGNKLVTVGSSNYQQSFVPSPGARPQVNGLSGRIDFH

WLMLNPNDTVTFSFNGAFIAPDRASFLRGKSMGIQSGVQV

DANCEGDCYHSGGTIISNLPFQNIDSRAVGKCPRYVKQKS

LLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGWYG

FRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQF

GLIDNEFNEVEKQIGNVINWTRDSITEVWSYNAELLVAME

NQHTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFHK

CDNDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLSSGY

KDVILWFSFGASCFILLAIVMGLVFICVKNGNMRCTICI

346
AJJ94134
MNTQILVLALIAIIPTNADKICLGHHAVSNGTKVNTLTERG

A/chicken/Dongguan/
VEVVNATETVERTNIPRICSKGKKTVDLGQCGLLGTITGPP

1051/2014
QCDQFLEFSADLIIERREGSDVCYPGKFVNEEALRQILRKS

2014/02/21 HA
GGIDKEAMGFTYSGIRTNGATSACRRSGSSFYAEMKWLLS

755184182
NTDNAAFPQMTKSYKNTRKSPAIIVWGIHHSVSTAEQTKL

YGSGNKLVTVGSSNYQQSFVPSPGARPQVNGLSGRIDFH

WLMLNPNDTVTFSFNGAFIAPDRASFLRGKSMGIQSGVQV

DADCEGDCYHSGGTHISNLPFQNIDSRAVGKCPRYVKQRS

LLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGWYG

FRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQF

ELIDNEFNEVEKQIGNVINWTRDSITEVWSYNAELLVAME

NQHTIDLADSEMDKLYERVKRQLRENABEDGTGCFEIFHK

CDDDCMASIRNNTYDHSKYREEAMQNRIQIDPVXLSXGY

KDVILWFSFGASCFILLAIVMGLVFICVKNGNMRCTICI

347
AJJ94158
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERG

A/chicken/Dongguan/
VEVVNATETVERTNIPRICSKGKKTVDLGQCGLLGTITGPP

1075/2014
QCDQFLEFSADLIIERREGSDVCYPGKFVNEEALRQILRES

2014/02/21 HA
GGIDKEAMGFTYSGIRTNGATSACRRSGSSFYAEMKWLLS

755184222
NTDNAAFPQMTKSYKNTRKSPALIVWGIHHSVSTAEQTKL

YGSGNKLVTVGSSNYQQSFVPSPGARPQVNGLSGRIDFH

WLMLNPNDTVTFSFNGAFIAPERASFLRGKSMGIQSGVQV

DANCEGDCYHSGGTIISNLPFQNIDSRAVGKCPRYVKQRS

LLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGWYG

FKHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQF

ELIDNEFNEVETQIGNVINWIRDSITEVWSYNAELLVAME

NQHTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFHK

CDDDCMASIRNNTYDHSKYRGEAMQNRIQIDPVKLSSGY

KDVILWFSFGASCFILLAIVMGLVFICVKNGNMRCTICI

348
AJJ94182
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERG

A/chicken/Dongguan/
VEVVNATETVERTNIPRICSKGKKTVDLGQCGLLGTITGPP

1177/2014
QCDQFLEFSADLIIERREGSDVCYPGKFVNEEALRQILRES

2014/02/21 HA
GGIDKEAMGFTYSGIRTNGATSACKRSGSSFYAEMKWLLS

755184262
NTDNAAFPQMTKSYKNTRKSPALIVWGIHHSVSIAEQTKL

YGSGNKLVTVGSSNYQQSFVPSPGARPQVNGLSGRIDFH

WLMLNPNDTVTFSFNGAFIAPDRASFLRGKSMGIQSGVQV

DANCEGDCYHSGGTIISNLPFQNIDSRAVGKCPRYVKQKS

LLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGWYG

FRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQF

ELIDNEFNEVEKQIGNVINWTRDSITEVWSYNAELLVAME

NQHTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFHK

CDDDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLSSGY

KDVILWFSFGASCFILLAIVMGLVFICVKNGNMRCTICI

349
AJJ94194
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERG

A/silkie
VEVVNATETVERTNIPRICSKGKKTIDLGQCGLLGTITGPP

chicken/Dongguan/
QCDQFLEFSADLIIERREGSDVCYPGKFVNEEALRQILRES

1264/2014
GGIDKEAMGFTYSGIRTNGATSACRRSGSSFYAEMKWLLS

2014/02/21 HA
NTDNAAFPQMTKSYKNTRKSPALIVWGIHHSVSTAEQTKL

755184282
YGSGNKLVTVGSSNYQQSFVPSPGARPQVNGLSGRIDFH

WLMLNPNDTVTFSFNGAFIAPERASFLRGKSMGIQSGVQV

DANCEGDCYHSGGTIISNLPFQNIDSRAVGKCPRYVKQRS

LLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGWYG

FKHQNAQGEGTAADYKSTQSAIDQVTGKLNRLIEKTNQQ

FELIDNEFNEVETQIGNVINWIRDSITEVWSYNAELLVAM

ENQHTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFH

KCDDDCMASIRNNTYDHSKYRGEAMQNRIQIDPVKLSSG

YKDVILWFSFGASCFMLLAIVMGLVFICVKNGNMRCTICI

350
AJJ94206
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERG

A/silkie
VEVVNATETVERTNIPRICSKGKKTVDLGQCGLLGTITGPP

chicken/Dongguan/
QCDQFLEFSADLIIERREGSDVCYPGKFVNEEALRQILRES

1268/2014
GGIDKEAMGFTYSGIRANGATSACRRSGSSFYAEMKWLL

2014/02/21 HA
SNTDNAAFPQMTKSYKNTRKSPALIVWGIHHSVSTAEQTK

755184302
LYGSGNKLVTVGSSNYQQSFVPSPGARPQVNGLSGRIDFH

WLMLNPNDTVTFSENGAFIAPERASFLRGKSMGIQSGVQV

DANCEGDCYHSGGTIISDLPFQNIDSRAVGKCPRYVKQRS

LLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGWYG

FRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQF

ELIDNEFNEVEKQIGNVINWIRDSITEVWSYNAELLVAME

NQHTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFHK

CDDDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLSSGY

KDVILWFSFGASCFILLAIVMGLVFICVKNGNMRCTICI

351
AJJ94344
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERG

A/silkie
VEVVNSTETVERTNIPRICSKGKKTVDLGQCGLLGTITGPP

chicken/Dongguan/
QCDQFLEFSADLIIERREGSDVCYPGKFVNEEALRQILRKS

1451/2014
GGIDKEAMGFTYSGIRTNGATSACRRSGSSFYAEMKWLLS

2014/02/21 HA
NTDNAAFPQMTKSYKNTRKSPAIIVWGIHHSVSTAEQTKL

755184532
YGSGNKLVTVGSSNYQQSFVPSPGARPQVNGLSGRIDFH

WLMLNPNDTVTFSFNGAFIAPDRASFLRGKSMGIQSGVQV

DADCEGDCYHSGGTHISNLPFQNIDSRTVGKCPRYVKQRSL

LLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGWYGF

RHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQFE

LIDNEFNEVEKQIGNVINWTRDSITEVWSYNAELLVAMEN

QHTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFHKC

DDDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLSSGYK

DVILWFSFGASCFILLAIVMGLVFICVKNGNMRCTICI

352
AJJ94356
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERG

A/chicken/Dongguan/
VEVVNATETVERTNIPRICSKGKKTVDLGQCGLLGTITGPP

1456/2014
QCDQFLEFSADLIIERREGSDVCYPGKFVNEEALRQILRES

2014/02/21 HA
GGIDKEAMGFTYSGIRTNGATSACRRSGSSFYAEMKWLLS

755184552
NTDNAAFPQMTKSYKNTRKSPALIVWGIHHSVSTAEQTKL

YGSGNKLVTVGSSNYQQSFVPSPGARPQVNGLSGRIDFH

WLMLNPNDTVTFSENGAFIAPERASFLRGKSMGIQSGVQV

DANCEGDCYHSGGTHISNLPFQNIDSRAVGKCPRYVKQRS

LLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGWYG

FRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQF

ELIDNEFNEVETQIGNVINWIRDSITEVWSYNAELLVAME

NQHTIDLADSEMDKLYERVKRQLRENABEDGTGCFBIFHK

CDDDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLSSGY

KDVILWFSFGASCFILLAIVMGLVFICVKNGNMRCTICI

353
AJJ94396
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERG

A/chicken/Dongguan/
VEVVNATETVERTNIPRICSKGKKTVDLGQCGLLGTITGPP

1494/2014
QCDQFLEFSADLIIERREGSDVCYPGKFVNEEALRQILRES

2014/02/21 HA
GGIDKEAMGFTYSGIRANGATSACRRSGSSFYAEMKWLL

755184618
SNTDNAAFPQMTKSYKNTRKSPALIVWGIHHSVSTAEQTK

LYGSGNKLVTVGSSNYQQSFVPSPGARPQVNGLSGRIDFH

WLMLNPNDTVTFSFNGAFIAPDRASFLRGKSMGIQSGVQV

DANCEGDCYHSGGTHISNLPFQNIDSRAVGKCPRYVKQRS

LLLATGMKNVPETPKGRGLFGAIAGFIENGWEGLIDGWY

GFRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQ

FELIDNEFNEVEKQIGNVINWIRDSITEVWSYNAELLVAM

ENQHTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFH

KCDNDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLSSG

YKDVILWFSFGASCFILLAIVMGLVFICVKNGNMRCTICI

354
AJJ94754
MNTQILVEALIAIIPTNADKICLGHHAVSNGTKVNTLTERG

A/chicken/Dong
VEVVNATETVERTNIPRICSKGKKTVDLGQCGLLGTITGPP

guan/748/2014
QCDQFLEFSADLIIERREGSDVCYPGKFVNEEALRQILRES

2014/02/20 HA
GGIEKEAMGFTYSGIRANGATSACRRSGSSFYAEMKWLLS

755185215
NTDNAAFPQMTKSYKNTRKSPALIVWGIHHSVSNAEQTK

LYGSGNKLVTVGSSNYQQSFVPSPGARPQVNGLSGRIDFH

WLMLNPNDTVTFSENGAFIAPDRASFLRGKSMGIQSGVQV

DANCEGDCYHSGGTHISNLPFQNIDSRAVGKCPRYVKQRS

LLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGWYG

FRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQF

ELIDNEFNEVEKQIGNVINWTRDSITEVWSYNAELLVAME

NQHTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFHK

CDDDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLSGGY

KDVILWFSFGASCFILLAIVMGLVFICVKNGNMRCTICI

355
AJJ94838
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERG

A/chicken/Dongguan/
VEVVNATETVERTNIPRICSKGKKTVDLGQCGLLGTITGPP

835/2014
QCDQFLEFSADLIIERREGSDVCYPGKFVNEEALRQILRES

2014/02/20 HA
GGIDKEAMGFTYSGIRANGATSACRRSGSSFYAEMKWLL

755185356
SNTDNAAFPQMTKSYKNTRKSPALIVWGIHHSASTAEQTK

LYGSGNKLVTVGSSNYQQSFVPSPGARPQVNGLSGRIDFH

WLMLNPNDTVTFSENGAFIAPDRASFLRGKSMGIQSGVQV

DANCEGDCYHSGGTIISNLPFQNIDSRAVGKCPRYVKQKS

LLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGWYG

FRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQF

ELIDNEFNEVEKQIGNVINWTRDSITEVWSYNAELLVAME

NQHTIDLADSEMDKLYERVKRQLRENABEDGTGCFEIFHK

CDNDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLSSGY

KDVILWFGFGASCFILLAIVMGLVFICVKNGNMRCTICI

356
AJJ94862
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERG

A/chicken/Dongguan/
VEVVNATETVERTNIPRICSKGKKTVDLGQCGLLGTITGPP

843/2014
QCDQFLEFSADLIIERREGSDVCYPGKFVNEEALRQILRES

2014/02/20 HA
GGIEKEAMGFTYSGIRTNGATSACRRSGSSFYAEMKWLLS

755185396
NTDNAAFPQMTKSYKNTRKSPALIVWGIHHSVSTAEQTKL

YGSGNKLVTVGSSNYQQSFVPSPGARPQVNGLSGRIDFH

WLMLNPNDTVTFSFNGAFIAPDRASFLRGKSMGIQSGVQV

DANCEGDCYHSGGTIISNLPFQNIDSRAVGKCPRYVKQRS

LLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGWYG

FRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQF

ELIDNEFNEVEKQIGNVINWTRDSITEVWSYNAELLVAME

NQHTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFHK

CDDDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLSGGY

KDVILWFSFGASCFILLAIVMGLVFICVKNGNMRCTICI

357
AJJ94886
MNTQILAFALIAIIPTNADKICLGHHAVSNGTKVNTLTERG

A/chicken/Dongguan/
VEVVNATETVERTNIPRICSKGKKTVDLGQCGLLGTITGPP

851/2014
QCDQFLEFSADLIIERREGSDVCYPGKFVNEEALRQILRES

2014/02/20 HA
GGIDKEAMGFTYSGIRANGATSACRRSGSSFYAEMKWLL

755185436
SNTDNAAFPQMTKSYKNTRKSPALIVWGIHHSVSTAEQTK

LYGSGNKLVTVGSSNYQQSFVPSPGARPQVNGLSGRIDFH

WLMLNPNDTVTFSENGAFIAPDRASFLRGKSMGIQSGVQV

DANCEGDCYHSGGTHISNLPFQNIDSRAVGKCPRYVKQRS

LLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGWYG

FRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQF

ELIDNEFNEVEKQIGNVINWTRDSITEVWSYNAELLVAME

NQHTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFHK

CDNDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLSSGY

KDVILWFSFGASCFILLAIVMGLVFICVKNGNMRCTICI

358
AJJ94910
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERG

A/chicken/Dongguan/
VEVVNATETVERTNIPRICSKGKKTVDLGQCGLLGTITGPP

874/2014
QCDQFLEFSADLIIERREGSDVCYPGKFVNEEALRQILRES

2014/02/20 HA
GGIDKEAMGFTYSGIRANGATSACRRSGSSFYAEMKWLL

755185476
SNTDNAAFPQMTKSYKNTRKSPALIVWGIHHSASTAEQTK

LYGSGNKLVTVGSSNYQQSFVPSPGARPQVNGLSGRIDFH

WLMLNPNDTVTFSFNGAFIAPDRASFLRGKSMGIQSGVQV

DANCEGDCYHSGGTIISNLPFQNIDSRAVGKCPRYVKQKS

LLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGWYG

FRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQF

ELIDNEFNEVEKQIGNVINWTRDSITEVWSYNAELLVAME

NQHTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFHK

CDNDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLSSGY

KDVILWFSFGASCFILLAIVMGLVFICVKNGNMRCTICI

359
AJJ94959
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERG

A/silkie
VEVVNATETVERTNIPRICSKGKKTVDLGQCGLLGTITGPP

chicken/Dongguan/
QCDQFLEFSADLIIERREGSDVCYPGKFVNEEALRQILRES

967/2014
GGIDKEAMGFTYSGIRANGATSACXRSGSSFYAEMKWLL

2014/02/21 HA
SNTDNAAFPQMTKSYKNTRKSPALIVWGIHHSVSTAEQTK

755185558
LYGSGNKLVTVGSSNYQQSFVPSPGARPQVNGLSGRIDFH

WLMLNPNDTVTFSFNGAFIAPDRASFLRGKSMGIQSGVQV

DANCEGDCYHSGGTIISNLPFQNIDSRAVGKCPRYVKQRS

LLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGWYG

FRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQF

ELIDNEFNEVEKQIGNVINWTRDSITEVWSYNAELLVAME

NQHTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFHK

CDNDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLSSGY

KDVILWFSFGASCFILLAIVMGLVFICVKNGNMRCTICI

360
AJJ95048
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERG

A/chicken/Dongguan/
VEVVNATETVERTNIPRICSKGKRTVDLGQCGLLGTITGPP

1009/2014
QCDQFLEFSADLIIERREGSDVCYPGKFVNEEALRQILRES

2014/02/21 HA
GGIDKEAMGFTYSGIRANGATSACRRSGSSFYAEMKWLL

755185708
SNTDNAAFPQMTKSYKNTRKSPALIVWGIHHSVSTAEQTK

LYGSGNKLVTVGSSNYQQSFVPSPGARPQVNGLSGRIDFH

WLMLNPNDTVTFSENGAFIAPDRASFLRGKSMGIQSGVQV

DANCEGDCYHSGGTHISNLPFQNIDSRAVGKCPRYVKQRS

LLLATGMKNVPETPKGRGLFGAIAGFIENGWEGLIDGWY

GFRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQ

FELIDNEFNEVEKQIGNVINWTRDSITEVWSYNAELLVAM

ENQHTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFH

KCDNDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLSSG

YKDVILWFSFGASCFILLAIVMGLVFICVKNGNMRCTICI

361
AJJ95171
MNTQILVEALIAIIPTNADKICLGHHAVSNGTKVNTLTERG

A/chicken/Dongguan/
VEVVNATETVERTNIPRICSKGKKTVDLGQCGLLGTITGPP

1314/2014
QCDQFLEFSADLIIERREGSDVCYPGKFVNEEALRQILRES

2014/02/21 HA
GGIDKEAMGFTYSGIRTNGATSACRRSGSSFYAEMKWLLS

755185913
NTDNAAFPQMTKSYKNTRKSPALIVWGIHHSVSTAEQTKL

YGSGNKLVTVGSSNYQQSFVPSPGARPQVNGLSGRIDFH

WLMLNPNDTVTFNFNGAFIAPERASFLRGKSMGIQSGVQV

DANCEGDCYHSGGTHISNLPFQNIDSRAVGKCPRYVKQRS

LLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGWYG

FKHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQF

ELIDNEFNEVETQIGNVINWIRDSITEVWSYNAELLVAME

NQHTIDLADSEMDKLYERVKRQLRENABEDGTGCFEIFHK

CDDDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLSSGY

KDVILWFSFGASCFILLAIVMGLVFICVKNGNMRCTICI

362
AJJ95227
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERG

A/chicken/Dongguan/
VEVVNATETVERTNIPRICSKGKKTVDLGQCGLLGTITGPP

1382/2014
QCDQFLEFSADLIIERREGSDICYPGKFVNEEALRQILRESG

2014/02/21 HA
GIDKEAMGFTYSGIRANGATSACRRSGSSFYAEMKWLLS

755186006
NTDNAAFPQMTKSYKNTRKSPALIVWGIHHSVSTAEQTKL

YGSGNKLVTVGSSNYQQSFVPSPGARPQVNGLSGRIDFH

WLMLNPNDTVTFSFNGAFIAPERASFLRGKSMGIQSGVQV

DANCEGDCYHSGGTIISNLPFQNIDSRAVGKCPRYVKQRS

LLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGWYG

FRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQF

ELIDNEFNEVEKQIGNVINWTRDSITEVWSYNAELLVAME

NQHTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFHK

CDDDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLSSGY

KDVILWFSFGASCFILLAIVMGLVFICVKNGNMRCTICI

363
AJJ95251
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERG

A/chicken/Dong
VEVVNATETVERTNIPRICSKGKKTVDLGQCGLLGTITGPP

guan/1401/2014
QCDQFLEFSADLIIERREGSDVCYPGKFVNEEALRQILRES

2014/02/21 HA
GGIDKEAMGFTYSGIRTNGATSACRRSGSSFYAEMKWLLS

755186046
NTDNAAFPQMTKSYKNTRKSPALIVWGIHHSVSTAEQTKL

YGSGNKLVTVGSSNYQQSFVPSPGARPQVNGLSGRIDFH

WLMLNPNDTVTFSFNGAFIAPDRASFLRGKSMGIQSGVQV

DANCEGDCYHSGGTIISNLPFQNIDSRAVGKCPRYVKQRS

LLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGWYG

FRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQF

ELIDNEFNEVETQIGNVINWTRDSITEVWSYNAELLVAME

NQHTIDLADSEMDKLYKRVKRQLRENAEEDGTGCFEIFH

KCDDDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLSSG

YKDVILWFSFGASCFILLAIVMGLVFICVKNGNMRCTICI

364
AJJ95346
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERG

A/chicken/Dongguan/
VEVVNATETVERTNIPRICSKGKKTVDLGQCGLLGTITGPP

1548/2014
QCDQFLEFSADLIIERREGSDVCYPGKFVNEBALRQILRES

2014/02/21 HA
GGIDKEAMGFTYSGIRTNGATSACRRSGSSFYAEMKWLLS

755186206
NTDNAAFPQMTKSYKNTRKSPALIVWGIHHSVSTAEQTKL

YGSGNKLVTVGSSNYQQSFVPSPGARPQVNGLSGRIDFH

WLMLNPNDTVTFSFNGAFIAPDRASFLRGKSMGIQSGVQV

DANCEGDCYHSGGTHISNLPFQNIDSRAVGKCPRYVKQRS

LLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGWYG

FRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQF

ELIDNEFNEVETQIGNVINWIRDSITEVWSYNAELLVAME

NQHTIDLADSEMDKLYKRVKRQLRENAEEDGTGCFEIFH

KCDDDCMASIRNNTYDHNKYREEAMQNRIQIDPVKLSSG

YKDVILWFSFGASCFILLAIVMGLVFICVKNGNMRCTICI

365
AJJ95382
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERG

A/chicken/Dongguan/
VEVVNATETVERTNIPRICSKGKKTVDLGQCGLLGTITGPP

1690/2014
QCDQFLEFSADLIIERREGSDVCYPGKFVNEEALRQILRKS

2014/02/21 HA
GGIDKEAMGFTYSGIRTNGATSACRRSGSSFYAEMKWLLS

755186266
NTDNAAFPQMTKSYKNTRKSPAIIVWGIHHSVSTAEQTKL

YGSGNKLVTVGSSNYQQSFVPSPGARPQVNGLSGRIDFH

WLMLNPNDTVTFSFNGAFIAPDRASFLRGKSIGIQSGVQV

DADCEGDCYHSGGTIISNLPFQNIDSRAVGKCPRYVKQRS

LLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGWYG

FRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQF

ELIDNEFNEVEKQIGNVINWTRDSITEVWSYNAELLVAME

NQHTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFHK

CDDDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLSSGY

KDVILWFSFGASCFILLAIVMGLVFICVKNGNMRCTICI

366
AJJ95464
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERG

A/chicken/Shenzhen/
VEVVNATETVERTNIPRICSKGKKTVDLGQCGLLGTITGPP

138/2014
QCDQFLEFSADLIIERREGSDVCYPGKFVNEEALRQILRES

2014/02/19 HA
GGIDKEAMGFTYSGIRTNGATSACRRSGSSFYAEMKWLLS

755186404
NTDNAAFPQMTKSYKNTRKSPALIVWGIHHSVSTAEQTKL

YGSGNKLVTVGSSNYQQSFVPSPGARPQVNGLSGRIDFH

WLMLNPNDTVTFSFNGAFIAPERASFLRGKSMGIQSGVQV

DANCEGDCYHSGGTIISNLPFQNIDSRAVGKCPRYVKQRS

LLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGWYG

FKHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQF

ELIDNEFNEVETQIGNVINWIRDSITEVWSYNAELLVAME

NQHTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFHK

CDDDCMASIRNNTYDHSKYRGEAMQNRIQIDPVKLSSGY

KDVILWFSFGASCFMLLAIVMGLVFICVKNGNMRCTICI

367
AJJ95572
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERG

A/chicken/Dongguan/
VEVVNATETVERTNIPRICSKGKRTVDLGQCGLLGTITGPP

1100/2014
QCDQFLEFSADLIIERREGSDVCYPGKFVNEEALRQILRES

2014/02/21 HA
GGIEKEAMGFTYSGIRANGATSACRRSGSSFYAEMKWLLS

755186584
NTDNAAFPQMTKSYKNTRKSPALIVWGIHHSVSTAEQTKL

YGSGNKLVTVGSSNYQQSFVPSPGARPQVNGLSGRIDFH

WLMLNPNDTVTFSFNGAFIAPDRASFLRGKSMGIQSGVQV

DANCEGDCYHSGGTIISNLPFQNIDSRAVGKCPRYVKQRS

LLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGWYG

FRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQF

ELIDNEFNEVEKQIGNVINWTRDSITEVWSYNAELLVAME

NQHTIDLADSEMDKLYERVKRQLRENABEDGTGCFBIFHK

CDDDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLSGGY

KDVILWFSFGASCFILLAIVMGLVFICVKNGNMRCTICI

368
AJJ95584
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERG

A/silkie
VEVVNATETVERTNIPRICSKGKRTVDLGQCGLLGTITGPP

chicken/Dongguan/
QCDQFLEFSADLIIERREGSDVCYPGKFVNEEALRQILRES

1519/2014
GGIDKEAMGFTYSGIRTNGATSACRRSGSSFYAEMKWLLS

2014/02/21 HA
NTDNAAFPQMTKSYKNTRKSPALIVWGIHHSVSTAEQTKL

755186604
YGSGNKLVTVGSSNYQQSFVPSPGARPQVNGLSGRIDFH

WLMLNPNDTVTFSFNGAFIAPERASFLRGKSMGIQSGVQV

DANCEGDCYHSGGTIISNLPFQNIDSRAVGKCPRYVKQRS

LLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGWYG

FKHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQF

ELIDNEFNEVETQIGNVINWIRDSITEVWSYNAELLVAME

NQHTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFHK

CDDDCMASIRNNTYDHSKYRGEAMQNRIQIDPVKLSSGY

KDVILWFSFGASCFMLLAIVMGLVFICVKNGNMRCTICI

369
AJJ95596
MNTQILAFALIAIIPTNADKICLGHHAVSNGTKVNTLTERG

A/Shenzhen/SP58/
VEVVNATETVERTNIPRICSKGKKTVDLGQCGLLGTITGPP

2014
QCDQFLEFSADLIIERREGSDVCYPGKFVNEEALRQILRES

2014/01/25 HA
GGIDKEAMGFTYSGIRANGATSACRRSGSSFYAEMKWLL

755186624
SNTDNAAFPQMTKSYKNTRKSPALIVWGIHHSVSTAEQTK

LYGSGNKLVTVGSSNYQQSFVPSPGARPQVNGLSGRIDFH

WLMLNPNDTVTFSFNGAFIAPDRASFLRGKSMGIQSGVQV

DANCEGDCYHSGGTIISNLPFQNIDSRAVGKCPRYVKQRS

LLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGWYG

FRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQF

ELIDNEFNEVEKQIGNVINWTRDSITEVWSYNAELLVAME

NQHTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFHK

CDDDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLSSGY

KDVILWFSFGASCFILLAIVMGLVFICVKNGNMRCTICI

370
AJJ95620
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERG

A/Shenzhen/SP75/
VEVVNATETVERTNIPRICSKGKKTVDLGQCGLLGTITGPP

2014
QCDQFLEFSADLIIERREGSDVCYPGKFVNEEALRQILRES

2014/02/15 HA
GGIDKEAMGFTYSGIRTNGSTSACRRSGSSFYAEMKWLLS

755186664
NTDNAAFPQMTKSYKNTRKSPALIVWGIHHSVSTAEQTKL

YGSGNKLVTVGSSNYQQSFVPSPGARPQVNGLSGRIDFH

WLMLNPNDTVTFSFNGAFIAPDRASFLRGKSMGIQSGVQV

DANCEGDCYHSGGTHISNLPFQNIDSRAVGKCPRYVKQRS

LLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGWYG

FRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQF

ELIDNEFNEVETQIGNVINWTRDSITEVWSYNAELLVAME

NQHTIDLADSEMDKLYERVKRQLRENABEDGTGCFEIFHK

CDDDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLSSGY

KDVILWFSFGASCFILLAVVMGLVFICVKNGNMRCTICI

371
AJJ95632
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERG

A/Shenzhen/SP62/
VEVVNATETVERTNIPRICSKGKKTVDLGQCGLLGTITGPP

2014
QCDQFLEFSADLIIERREGSDVCYPGKFVNEEALRQILRES

2014/02/05 HA
GGIDKEAMGFTYSGIRTNGATSACRRSGSSFYAEMKWLLS

755186684
NTDNATFPQMTKSYKNTRKSPALIIWGIHHSVSTAEQTKL

YGSGNKLVTVGSSNYQQSFVPSPGARPQVNGLSGRIDFH

WLMLNPNDTVTFSFNGAFIAPDRASFLRGKSMGIQSGVQV

DANCEGDCYHSGGTIISNLPFQNIDSRAVGKCPRYVKQRS

LLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGWYG

FRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQF

ELIDNEFNEVETQIGNVINWIRDSITEVWSYNAELLVAME

NQHTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFHK

CDDDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLSSGY

KDVILWFSFGASCFILLAIVMGLVFICVKNGNMRCTICI

372
AJJ96720
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERG

A/chicken/Jiangxi/
VEVVNATETVERTTIPRICSKGKKTVDLGQCGLLGTITGPP

13220/2014
QCDQFLEFSADLIIERREGSDVCYPGKFVNEEALRQILRES

2014/03/30 HA
GGIDKEAMGFTYSGIRTNGATSACRRSGSSFYAEMKWLLS

755188499
NTDNAAFPQMTKSYKNTRKSPALIVWGIHHSVSTAEQTKL

YGSGNKLVTVGSSNYQQSFVPSPGARPQVNGLSGRIDFH

WLMLNPNDTVTFSFNGAFIAPDRASFLRGKSMGIQSGVQV

DANCEGDCYHSRGTIISNLPFQNIDSRAVGKCPRYVKQKS

LLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGWYG

FRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQF

ELIDNEFNEVEKQIGNVINWTRDSITEVWSYNAELLVAME

NQHTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFHK

CDDDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLSSGY

KDVILWFSFGASCFILLAIVMGLVFICVKNGNMRCTICI

373
AJJ96817
MNTQILVFALIAIVPTNADKICLGHHAVSNGTKVNTLTER

A/chicken/Jiangxi/
GVEVVNATEIVERTNIPRICSKGKKTVDLGQCGLLGTITGP

9513/2014
PQCDQFLEFSADLIIERREGSDVCYPGKFVNEEALRQILRES

2014/02/16 HA
GGIDKEAMGFTYSGIRTNGVTSACRRSGSSFYAEMKWLLS

755188661
NTDNAAFPQMTKSYKNTRKSPALIVWGIHHSVSTAEQTKL

YGSGNKLVTVGSSNYQQSFVPSPGARPQVNGLSGRIDFH

WLMLNPNDTVTFSFNGAFIAPDRASFLRGKSMGIQSGVQV

DANCEGDCYHSGGTIISNLPFQNIDSRAVGKCPRYVKQKS

LLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGWYG

FRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQF

ELIDNEFNEVEKQIGNVINWTRDSITEVWSYNAELLVAME

NQHTIDLADSEMDKLYERVKRQLRENABEDGTGCFEIFHK

CDDDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLSSGY

KDVILWFSFGASCFILLAIVMGLVFICVKNGNMRCTICI

374
AJJ96841
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERG

A/Shenzhen/SP139/
VEVVNATETVERTNIPRICSKGKKTVDLGQCGLLGTITGPP

2014
QCDQFLEFSADLIIERREGSDVCYPGKFVNEEALRQILRKS

2014/04/02 HA
GGIDKEAMGFTYSGIRTNGATSTCRRSGSSFYAEMKWLLS

755188701
NTDNAAFPQMTKSYKNTRKSPAIIVWGIHHSVSTAEQTKL

YGSGNKLVTVGSSNYQQSFVPSPGARPQVNGLSGRIDFH

WLMLNPNDTVTFSFNGAFIAPDRACFLRGKSMGIQSGVQ

VDADCEGDCYHSGGTIISNLPFQNIDSRAVGKCPRYVKQR

SLLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGWY

GFRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQ

FELIDNEFNEVERQIGNVINWIRDSITEVWSYNAELLVAM

ENQHTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFH

KCDDDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLSSG

YKDVILWFSFGASCFILLAIVMGLVFICVKNGNMRCTICI

375
AJJ96889
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERG

A/chicken/Jiangxi/
VEVVNATETVERTXIPRICSKGKKTVDLGQCGLLGTITGPP

13496/2014
QCDQFLEFSADLIIERREGSDVCYPGKFVNEEALRQILRES

2014/04/11 HA
GGIDKXAMGFTYSGIRTNGATSACRRSGSSFYAEMKWLL

755188781
SNTDNAAFPQMTKSYKNTRKSPALIVWGIHHSVSTAEQTK

LYGSGNKLVTVGSSNYQQSFVPSPGARPQVNGLSGRIDFH

WLMLNPNDTVTFSFNGAFIAPDRASFLRGKSMGIQSGVQV

DANCEGDCYHSXGTHISNLPFQNIDSRAVGKCPRYVKQKS

LLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGWYG

FRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQF

ELIDNEFNEVEKQIGNVINWTRDSITEVWSYNAELLVAME

NQHTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFHK

CDDDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLSSGY

KDVILWFSFGASCFILLAIVMGLVFICVKNGNMRCTICI

376
AJJ96901
MNTQILVEALIAIIPTNADKICLGHHAVSNGTKVNTLTERG

A/chicken/Jiangxi/
VEVVNATETVERTNIPRICSKGKKTVDLGQCGLLGTITGPP

13502/2014
QCDQFLEFSADLIIERREGSDVCYPGKFVNEEALRQILRES

2014/04/11 HA
GGIDKEAMGFTYSGIRTNGATSACRRSGSSFYAEMKWLLS

755188801
NTDNAAFPQMTKSYKNTRKSPALIVWGIHHSVSTAEQTKL

YGSGNKLVTVGSSNYQQSFVPSPGARPQVNGLSGRIDFH

WLMLNPNDTVTFSFNGAFIAPDRASFLRGKSMGIQSGVQV

DANCEGDCYHSXGTHISNLPFQNIDSRAVGKCPRYVKQKS

LLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGWYG

FRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQF

ELIDNEFNEVEKQIGNVINWTRDSITELWSYNAELLVAME

NQHTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFHK

CDDDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLSSGY

KDVILWFSFGASCFILLAIVMGLVFICVKNGNMRCTICI

377
AJJ96925
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERG

A/chicken/Jiangxi/
VEVVNATETVERTNIPRICSKGKRTVDLGQCGLLGTITGPP

13513/2014
QCDQFLEFSADLIIERREGSDVCYPGKFVNEEALRQILRES

2014/04/11 HA
GGIDKEAMGFTYNGIRTNGATSACRRSGSSFYAEMKWLL

755188841
SNTDNAAFPQMTKSYKNTRKSPAIIVWGIHHTVSTAEQTK

LYGSGNKLVTVGSSNYQQSFVPSPGARPQVNGLSGRIDLH

WLMLNPNDTVTFSFNGAFIAPDRASFLRGKSMGIQSGVQV

DANCEGDCYHSGGTIISNLPFQNIDSRAVGKCPRYVKQRS

LLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGWYG

FRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIAKTNQQF

ELIDNEFNEVEKQIGNVINWTRDSITEVWSYNAELLVAME

NQHTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFHK

CDDDCMASIRNNTYDHRKYREEAMQNRIQIDPVKLSSGY

KDVILWFSFGASCFILLAIVMGLVFICVKNGNMRCTICI

378
AJJ97267
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERG

A/chicken/Jiangxi/
VEVVNATETVERTNIPRICSKGKRTVDLGQCGLLGTITGPP

13252/2014
QCDQFLEFSADLIIERREGSDVCYPGKFVNEEALRQILRES

2014/03/30 HA
GGIDKEAMGFTYSGIRTNGATSACRRSGSSFYAEMKWLLS

755189411
NTDNAAFPQMTKSYKNTRKSPALIVWGIHHSVSTAEQTKL

YGSGNKLVTVGSSNYQQSFVPSPGARPQVNGLSGRIDFH

WLMLNPNDTVTFSENGAFIAPDRASFLRGKSMGIQSGVQV

DANCEGDCYHSGGTIISNLPFQNIDSRAVGKCPRYVKQKS

LLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGWYG

FRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQF

ELIDNEFNEVEKQIGNVINWTRDSITELWSYNAELLVAME

NQHTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFHK

CDDDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLSSGY

KDVILWFSFGASCFILLAIVMGLVFICVKNGNMRCTICI

379
AJJ97291
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERG

A/chicken/Jiangxi/
VEVVNATETVERTNIPRICSKGKRTVDLGQCGLLGTITGPP

13493/2014
QCDQFLEFSADLIIERREGSDVCYPGKFVNEEALRQILRES

2014/04/06 HA
GGIDKEAMGFTYNGIRTNGATSACRRSGSSFYAEMKWLL

755189451
SNTDNAAFPQMTKSYKNTRKSPAIIVWGIHHSVSTAEQTK

LYGSGNKLVTVGSSNYQQSFVPSPGARPQVNGLSGRIDFH

WLMLNPNDTVTFSFNGAFIAPDRASFLRGKSMGIQSGVQV

DANCEGDCYHSGGTIISNLPFQNIDSRAVGKCPRYVKQRS

LLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGWYG

FRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIAKTNQQF

ELIDNEFNEVEKQIGNVINWTRDSITEVWSYNAELLVAME

NQHTIDLADSEMDKLYERVKRQLRENABEDGTGCFEIFHK

CDDDCMASIRNNTYDHRKYREEAMQNRIQIDPVKLSSGY

KDVILWFSFGASCFILLAIVMGLVFICVKNGNMRCTICI

380
AJJ97331
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERG

A/chicken/Jiangxi/
VEVVNATETVERTNIPRICSKGKRTVDLGQCGLLGTITGPP

13512/2014
QCDQFLEFSADLIIERREGSDVCYPGKFVNEEALRQILRES

2014/04/06 HA
GGIDKEAMGFTYNGIRTNGATSACRRSGSSFYAEMKWLL

755189517
SNTDNAAFPQMTKSYKNTRKSPAIIVWGIHHSVSTAEQTK

LYGSGNKLVTVGSSNYQQSFVPSPGARPQVNGLSGRIDFH

WLMLNPNDTVTFSFNGAFIAPDRASFLRGKSIGIQSGVQV

DANCEGDCYHSGGTIISNLPFQNIDSRAVGKCPRYVKQRS

LLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGWYG

FRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIAKTNQQF

ELIDNEFNEVEKQIGNVINWTRDSITEVWSYNAELLVAME

NQHTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFHK

CDDDCMASIRNNTYDHRKYREEAMQNRIQIDPVKLSSGY

KDVILWFSFGASCFILLAIVMGLVFICVKNGNMRCTICI

381
AJJ97373
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERG

A/chicken/Jiangxi/
VEVVNATETVERTNIPRICSKGKRTVDLGQCGLLGTITGPP

13521/2014
QCDQFLEFSADLIIERREGSDVCYPGKFVNEEALRQILRES

2014/04/06 HA
GGIDKEAMGFTYNGIRTNGATSACRRSGSSFYAEMKWLL

755189587
SNTDNAAFPQMTKSYKNTRKSPAIIVWGIHHSVSTAEQTK

LYGSGNKLVTVGSSNYQQSFVPSPGARPQVNGLSGRIDFH

WLMLNPNDTVTFSFNGAFIAPXRASFLRGKSXGIQSGVQV

DANCEGDCYHSGGTIISNLPFQNIDSRAVGKCPRYVKQRS

LLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGWYG

FRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIAKTNQQF

ELIDNEFNEVEKQIGNVINWTRDSITEVWSYNAELLVAME

NQHTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFHK

CDDDCMASIRNNTYDHRKYREEAMQNRIQIDPVKLSSGY

KDVILWFSFGASCFILLAIVMGLVFICVKNGNMRCTICI

382
AJJ97443
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERG

A/chicken/Jiangxi/
VEVVNATETVERTTIPRICSKGKRTVDLGQCGLLGTITGPP

13530/2014
QCDQFLEFSADLIIERREGSDVCYPGKFVNEEALRQILRES

2014/04/06 HA
GGIDKEAMGFTYSGIRTNGATSACRRSGSSFYAEMKWLLS

755189702
NTDNAAFPQMTKSYKNTRKSPALIVWGIHHSVSTAEQTKL

YGSGNKLVTVGSSNYQQSFVPSPGARPQVNGLSGRIDFH

WLMLNPNDTVTFSFNGAFIAPDRASFLRGKSMGIQSGVQV

DANCEGDCYHSRGTIISNLPFQNIDSRAVGKCPRYVKQKS

LLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGWYG

FRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQF

ELIDNEFNEVEKQIGNVINWTRDSITEVWSYNAELLVAME

NQHTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFHK

CDDDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLSSGY

KDVILWFSFGASCFILLAIVMGLVFICVKNGNMRCTICI

383
AJJ97582
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERG

A/chicken/Jiangxi/
VEVVNATETVERTNIPRICSKGKRTVDLGQCGLLGTITGPP

14023/2014
QCDQFLEFSADLIIERREGSDVCYPGKFVNEEALRQILRES

2014/04/13 HA
GGIDKEAMGFTYSGIRTNGATSACRRSGSSFYAEMKWLLS

755189933
NTDNAAFPQMTKSYKNTRKSPAIIVWGIHHSVSTAEQTKL

YGSGNKLVTVGSSNYQQSFVPSPGARPQVNGLSGRIDFH

WLMLNPNDTVTFSFNGAFIAPDRASFLRGKSMGIQSGVQV

DANCEGDCYHSGGTHISNLPFQNIDSRAVGKCPRYVKQRS

LLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGWYG

FRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIAKTNQQF

ELIDNEFNEVEKQIGNVINWTRDSITEVWSYNAELLVAME

NQHTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFHK

CDDDCMASIRNNTYDHRKYREEAMQNRIQIDPVKLSSGY

KDVILWFSFGASCFILLAIVMGLVFICVKNGNMRCTICI

384
AJJ97697
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERG

A/chicken/Jiangxi/
VEVVNATETVERTNIPRICSKGKKTVDLGQCGLLGTITGPP

14517/2014
QCDQFLEFSADLIIERREGSDVCYPGKFVNEEALRQILRES

2014/04/20 HA
GGIDKEAMGFTYSGIRTNGATSACRRSGSSFYAEMKWLLS

755190125
NTDNAAFPQMTKSYKNTRKSPALIVWGIHHSVSTAEQTKL

YGSGNKLVTVGSSNYQQSFVPSPGARPQVNGLSGRIDFH

WLMLNPNDTVTFSENGAFIAPDRASFLRGKSMGIQSGVQV

DANCDGDCYHSGGTIISNLPFQNIDSRAVGKCPRYVKQKS

LLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGWYG

FRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQF

ELIDNEFNEVEKQIGNVINWTRDSITELWSYNAELLVAME

NQHTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFHK

CDDDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLSSGY

KDVILWFSFGASCFILLAIVMGLVFICVKNGNMRCTICI

385
AJJ97709
MNTQILVFALIAIIPANADKICLGHHAVSNGTKVNTLTERG

A/chicken/Jiangxi/
VEVVNATETVERTNIPRICSKGKRTVDLGQCGLLGTITGPP

14518/2014
QCDQFLEFSADLIIERREGSDVCYPGKFVNEEALRQILRES

2014/04/20 HA
GGIDKEAMGFTYNGIRTNGATSACRRSGSSFYAEMKWLL

755190145
SNTDNAAFPQMTKSYKNTRKSPAIIVWGIHHSVSTAEQTK

LYGSGNKLVTVGSSNYQQSFVPSPGARPQVNGLSGRIDFH

WLMLNPNDTVTFSFNGAFIAPDRASFLRGKSMGIQSGVQV

DANCEGNCYHSGGTIISNLPFQNIDSRAVGKCPRYVKQRS

LLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGWYG

FRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIAKTNQQF

ELIDNEFNEVEKQIGNVINWTRDSITEVWSYNAELLVAME

NQHTIDLADSEMDKLYERVKRQLRENABEDGTGCFBIFHK

CDDDCMASIRNNTYDHRKYREEAMQNRIQIDPVKLSSGY

KDVILWFSFGASCFILLAIVMGLVFICVKNGNMRCTICI

386
AJJ97745
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERG

A/chicken/Jiangxi/
VEVVNATETVERTNIPRICSKGKKTVDLGQCGLLGTITGPP

14554/2014
QCDQFLEFSADLIIERREGSDVCYPGKFVNEEALRQILRES

2014/04/20 HA
GGIDKEAMGFTYSGIRTNGATSACRRSGSSFYAEMKWLLS

755190205
NTDNAAFPQMTKSYKNTRKSPALIVWGIHHSVSTAEQTKL

YGSGNKLVTVGSSNYQQSFVPSPGARPQVNGLSGRIDFH

WLMLNPNDTVTFSFNGAFIAPDRASFLRGKSMGIQSGVQV

DANCEGDCYHSGGTIISNLPFQNIDSRAVGKCPRYVKQKS

LLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGWYG

FRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQF

ELMDNEFNEVEKQIGNVINWTRDSITELWSYNAELLVAM

ENQHTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFH

KCDDDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLSSG

YKDVILWFSFGASCFILLAIVMGLVFICVKNGNMRCTICI

387
AJJ97757
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERG

A/chicken/Shantou/
VEVVNATETVERTNIPRICSKGKKTVDLGQCGLLGTITGPP

2537/2014
QCDQFLEFSADLIIERREGSDVCYPGKFVNEEALRQILRKS

2014/04/16 HA
GGIDKEAMGFTYSGIRTNGATSACRRSGSSFYAEMKWLLS

755190225
NTDNAAFPQMTKSYKNTRKSPAIIVWGIHHSVSTAEQTKL

YGSGNKLVTVGSSNYQQSFVPSPGARPQVNGLSGRIDFH

WLMLNPNDTVTFSFNGAFIAPDRASFLRGKSMGIQSGVQV

DADCEGDCYHSGGTHISNLPFQNIDSRAVGKCPRYVKQRS

LLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGWYG

FKHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQF

ELIDNEFNEVEKQIGNVINWTRDSITEVWSYNAELLVAME

NQHTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFHK

CDDDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLSSGY

KDVILWFSFGASCFILLAIVMGLVFICVKNGNMRCTICI

388
AJJ97841
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERG

A/duck/Jiangxi/
VEVVNATETVERTNIPRICSKGKRTVDLGQCGLLGTITGPP

15044/2014
QCDQFLEFSADLIIERREGSDVCYPGKFVNEEALRQILRES

2014/04/27 HA
GGIDKEAMGFTYSGIRTNGATSACRRSGSSFYAEMKWLLS

755190365
NTDNAAFPQMTKSYKNTRKSPAIIVWGIHHSVSTAEQTKL

YGSGNKLVTVGSSNYQQSFVPSPGARPQVNGLSGRIDFH

WLMLNPNDTVTFSENGAFIAPDRASFLRGKSMGIQSGVQV

DANCEGDCYHSGGTIISNLPFQNIDSRAVGKCPRYVKQRS

LLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGWYG

FRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIAKTNQQF

ELIDNEFNEVEKQIGNVINWTRDSITEVWSYNAELLVAME

NQHTIDLADSEMDKLYERVKRQLRENABEDGTGCFBIFHK

CDDDCMASIRNNTYDHRKYREEAMQNRIQIDPVRLSSGY

KDVILWFSFGASCFILLAIVMGLVFICVKNGNMRCTICI

389
AJJ97899
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERG

A/chicken/Jiangxi/
VEVVNATETVERTNIPRICSKGKRTVDLGQCGLLGTITGPP

15524/2014
QCDQFLEFSADLIIERREGSDVCYPGKFVNEEALRQILRES

2014/05/05 HA
GGIDKEAMGFTYSGIRTNGATSACRRSGSSFYAEMKWLLS

755190462
NTDNAAFPQMTKSYKNTRKSPAIIVWGIHHSVSTAEQTKL

YGSGNKLVTVGSSNYQQSFVPSPGARPQVNGLSGRIDFH

WLMLNPNDTVTFSFNGAFIAPDRASFLRGKSMGIQSGVQV

DANCEGDCYHSGGTIISNLPFQNIDSRAVGKCPRYVKQRS

LLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGWYG

FRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIAKTNQQF

ELIDNEFNEVEKQIGNVINWIRDSITEVWSYNAELLVAME

NQHTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFHK

CDDDCMASIRNNTYDHRKYREEAMQNRIQIDPVKLSSGY

KDVILWFSFGASCFILLAIVMGLVFMCVKNGNMRCTICI

390
AJJ97925
MNTQILVFALIAIIPTNADKICLGHHAVSNGTKVNTLTERG

A/silkie
VEVVNATETVERTNIPRICSKGKKTVDLGQCGLLGTITGPP

chicken/Shantou/
QCDQFLEFSADLIIERREGSDVCYPGKFVNEEALRQILRKS

2050/2014
GGIDKEAMGFTYSGIRTNGATSACRRSGSSFYAEMKWLLS

2014/03/25 HA
NTDNAAFPQMTKSYKNTRKSPAIIVWGIHHSVSTAEQTKL

755190506
YGSGNKLVTVGSSNYQQSFVPSPGARPQVNGLSGRIDFH

WLMLNPNDTVTFSENGAFIAPDRASFLRGKSMGIQSGVQV

DADCEGDCYHSGGTHISNLPFQNIDSRAVGKCPRYVKQRS

LLLATGMKNVPEVPKGRGLFGAIAGFIENGWEGLIDGWY

GFRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQ

FELIDNEFNEVEKQIGNVINWTRDSITEVWSYNAELLVAM

ENQHTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFH

KCDDDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLSSG

YKDVILWFSFGASCFILLAIVMGLVFICVKNGNMRCTICI

391
AJJ97973
MNTQILVFALISIIPTNADKICLGHHAVSNGTKVNTLTERG

A/chicken/Shantou/
VEVVNATETVERTNIPRICSKGKKTVDLGQCGLLGTITGPP

4325/2014
QCDQFLEFSADLIIERREGSDVCYPGKFVNEEALRQILRKS

2014/07/01 HA
GGIDKBAMGFTYSGIRTNGVTSACRRSGSSFYAEMKWLLS

755190586
NTDNAAFPQMTKSYKNTRKSPAIIVWGIHHSVSTAEQTKL

YGSGNKLVTVGSSNYQQSFVPSPGARPQVNGLSGRIDFH

WLMLNPNDTVTFSFNGAFIAPDRASFLRGKSMGIQSGVQV

DADCEGDCYHSGGTHISNLPFQNIDSRAVGKCPRYVKQRS

LLLATGMKNVPEVPKGRGLFGAIAGFIENGWEGLIDGWY

GFRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQ

FELIDNEFNEVEKQIGNVINWTRDSITEVWSYNAELLVAM

ENQHTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFH

KCDDDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLSSG

YKDVILWFSFGASCFILLAIVMGLVFICVKNGNMRCTICI

392
AJJ97998
MNTQILVFALIAIVPTNADKICLGHHAVSNGTKVNTLTER

A/chicken/Shantou/
GVEVVNATETVERTNIPRICSKGKKTVDLGQCGLLGTITGP

4816/2014
PQCDQFLEFSADLIIERREGSDVCYPGKFVNEEALRQILRES

2014/07/22 HA
GGIDKEAMGFTYSGIRTNGATSACRRSGSSFYAEMKWLLS

755190628
NTDNAAFPQMTKSYKNTRKSPALIVWGIHHSVSTAEQTKL

YGSGNKLVTVGSSNYQQSFVPSPGARPQVNGLSGRIDFH

WLMLNPNDTVTFSFNGAFIAPDRASFLRGKSMGIQSGVQV

DANCEGDCYHSGGTIISNLPFQNIDSRAVGKCPRYVKQKS

LLLATGMKNVPEIPKGRGLFGAIAGFIENGWEGLIDGWYG

FRHQNAQGEGTAADYKSTQSAIDQITGKLNRLIEKTNQQF

ELVDNEFNEVEKQIGNVINWTRDSITEVWSYNAELLVAM

ENQHTIDLADSEMDKLYERVKRQLRENAEEDGTGCFEIFH

KCDDDCMASIRNNTYDHSKYREEAMQNRIQIDPVKLSSG

YKDVILWFSFGASCFILLAIVMGLVFICVKNGNMRCTICI

TABLE 15

Examples of Wild type Hemagglutinin Antigens

SEQ

ID
Protein/

NO
Strain
Nucleic Acid Sequence

393
H1
AGCAAAAGCAGGGGAAAATAAAAACAACCAAAATGAAGGCAAACCTACTGGTCCTG

TTATGTGCACTTGCAGCTGCAGATGCAGACACAATATGTATAGGCTACCATGCGAA

CAATTCAACCGACACTGTTGACACAGTGCTCGAGAAGAATGTGACAGTGACACACT

CTGTTAACCTGCTCGAAGACAGCCACAACGGAAAACTATGTAGATTAAAAGGAATA

GCCCCACTACAATTGGGGAAATGTAACATCGCCGGATGGCTCTTGGGAAACCCAGA

ATGCGACCCACTGCTTCCAGTGAGATCATGGTCCTACATTGTAGAAACACCAAACT

CTGAGAATGGAATATGTTATCCAGGAGATTTCATCGACTATGAGGAGCTGAGGGAG

CAATTGAGCTCAGTGTCATCATTCGAAAGATTCGAAATATTTCCCAAAGAAAGCTC

ATGGCCCAACCACAACACAACCAAAGGAGTAACGGCAGCATGCTCCCATGCGGGGA

AAAGCAGTTTTTACAGAAATTTGCTATGGCTGACGGAGAAGGAGGGCTCATACCCA

AAGCTGAAAAATTCTTATGTGAACAAGAAAGGGAAAGAAGTCCTTGTACTGTGGGG

TATTCATCACCCGTCTAACAGTAAGGATCAACAGAATATCTATCAGAATGAAAATG

CTTATGTCTCTGTAGTGACTTCAAATTATAACAGGAGATTTACCCCGGAAATAGCA

GAAAGACCCAAAGTAAGAGATCAAGCTGGGAGGATGAACTATTACTGGACCTTGCT

AAAACCCGGAGACACAATAATATTTGAGGCAAATGGAAATCTAATAGCACCAAGGT

ATGCTTTCGCACTGAGTAGAGGCTTTGGGTCCGGCATCATCACCTCAAACGCATCA

ATGCATGAGTGTAACACGAAGTGTCAAACACCCCTGGGAGCTATAAACAGCAGTCT

CCCTTTCCAGAATATACACCCAGTCACAATAGGAGAGTGCCCAAAATACGTCAGGA

GTGCCAAATTGAGGATGGTTACAGGACTAAGGAACATTCCGTCCATTCAATCCAGA

GGTCTATTTGGAGCCATTGCCGGTTTTATTGAAGGGGGATGGACTGGAATGATAGA

TGGATGGTACGGTTATCATCATCAGAATGAACAGGGATCAGGCTATGCAGCGGATC

AAAAAAGCACACAAAATGCCATTAACGGGATTACAAACAAGGTGAACTCTGTTATC

GAGAAAATGAACATTCAATTCACAGCTGTGGGTAAAGAATTCAACAAATTAGAAAA

AAGGATGGAAAATTTAAATAAAAAAGTTGATGATGGATTTCTGGACATTTGGACAT

ATAATGCAGAATTGTTAGTTCTACTGGAAAATGAAAGGACTCTGGATTTCCATGAC

TCAAATGTGAAGAATCTGTATGAGAAAGTAAAAAGCCAATTAAAGAATAATGCCAA

AGAAATCGGAAATGGATGTTTTGAGTTCTACCACAAGTGTGACAATGAATGCATGG

AAAGTGTAAGAAATGGGACTTATGATTATCCCAAATATTCAGAAGAGTCAAAGTTG

AACAGGGAAAAGGTAGATGGAGTGAAATTGGAATCAATGGGGATCTATCAGATTCT

GGCGATCTACTCAACTGTCGCCAGTTCACTGGTGCTTTTGGTCTCCCTGGGGGCAA

TCAGTTTCTGGATGTGTTCTAATGGATCTTTGCAGTGCAGAATATGCATCTGAGAT

TAGAATTTCAGAAATATGAGGAAAAACACCCTTGTTTCTACT

394
H7
AGCGAAAGCAGGGGATACAAAATGAACACTCAAATCCTGGTATTCGCTCTGATTGC

GATCATTCCAACAAATGCAGACAAAATCTGCCTCGGACATCATGCCGTGTCAAACG

GAACCAAAGTAAACACATTAACTGAAAGAGGAGTGGAAGTCGTCAATGCAACTGAA

ACAGTGGAACGAACAAACATCCCCAGGATCTGCTCAAAAGGGAAAAGGACAGTTGA

CCTCGGTCAATGTGGACTCCTGGGGACAATCACTGGACCACCTCAATGTGACCAAT

TCCTAGAATTTTCAGCCGATTTAATTATTGAGAGGCGAGAAGGAAGTGATGTCTGT

TATCCTGGGAAATTCGTGAATGAAGAAGCTCTGAGGCAAATTCTCAGAGAATCAGG

CGGAATTGACAAGGAAGCAATGGGATTCACATACAGTGGAATAAGAACTAATGGAG

CAACCAGTGCATGTAGGAGATCAGGATCTTCATTCTATGCAGAAATGAAATGGCTC

CTGTCAAACACAGATGATGCTGCATTCCCGCAGATGACTAAGTCATATAAAAATAC

AAGAAAAAGCCCAGCTCTAATAGTATGGGGGATCCATCATTCCGTATCAACTGCAG

AGCAAACCAAGCTATATGGGAGTGGAAACAAACTGGTGACAGTTGGGAGTTCTAAT

TATCAACAATCTTTTGTACCGAGTCCAGGAGCGAGACCACAAGTTAATGGTCTATC

TGGAAGAATTGACTTTCATTGGCTAATGCTAAATCCCAATGATACAGTCACTTTCA

GTTTCAATGGGGCTTTCATAGCTCCAGACCGTGCAAGCTTCCTGAGAGGAAAATCT

ATGGGAATCCAGAGTGGAGTACAGGTTGATGCCAATTGTGAAGGGGACTGCTATCA

TAGTGGAGGGACAATAATAAGTAACTTGCCATTTCAGAACATAGATAGCAGGGCAG

TTGGAAAATGTCCGAGATATGTTAAGCAAAGGAGTCTGCTGCTAGCAACAGGGATG

AAGAATGTTCCTGAGATTCCAAAGGGAAGAGGCCTATTTGGTGCTATAGCGGGTTT

CATTGAAAATGGATGGGAAGGCCTAATTGATGGTTGGTATGGTTTCAGACACCAGA

ATGCACAGGGAGAGGGAACTGCTGCAGATTACAAAAGCACTCAATCGGCAATTGAT

CAAATAACAGGAAAATTAAACCGGCTTATAGAAAAAACCAACCAACAATTTGAGTT

GATAGACAATGAATTCAATGAGGTAGAGAAGCAAATCGGTAATGTGATAAATTGGA

CCAGAGATTCTATAACAGAAGTGTGGTCATACAATGCTGAACTCTTGGTAGCAATG

GAGAACCAGCATACAATTGATCTGGCTGATTCAGAAATGGACAAACTGTACGAACG

AGTGAAAAGACAGCTGAGAGAGAATGCTGAAGAAGATGGCACTGGTTGCTTTGAAA

TATTTCACAAGTGTGATGATGACTGTATGGCCAGTATTAGAAATAACACCTATGAT

CACAGCAAATACAGGGAAGAGGCAATGCAAAATAGAATACAGATTGACCCAGTCAA

ACTAAGCAGCGGCTACAAAGATGTGATACTTTGGTTTAGCTTCGGGGCATCATGTT

TCATACTTCTAGCCATTGTAATGGGCCTTGTCTTCATATGTGTAAAGAATGGAAAC

ATGCGGTGCACTATTTGTATATAAGTTTTGGAAAAAAACACCCTTGTTTCTAC

395
H10
ATGTACAAAATAGTAGTGATAATCGCGCTCCTTGGAGCTGTGAAAGGTCTTGATAA

AATCTGTCTAGGACATCATGCAGTGGCTAATGGGACCATCGTAAAGACTCTCACAA

ACGAACAGGAAGAGGTAACCAACGCTACTGAAACAGTGGAGAGTACAGGCATAAAC

AGATTATGTATGAAAGGAAGAAAACATAAAGACCTGGGCAACTGCCATCCAATAGG

GATGCTAATAGGGACTCCAGCTTGTGATCTGCACCTTACAGGGATGTGGGACACTC

TCATTGAACGAGAGAATGCTATTGCTTACTGCTACCCTGGAGCTACTGTAAATGTA

GAAGCACTAAGGCAGAAGATAATGGAGAGTGGAGGGATCAACAAGATAAGCACTGG

CTTCACTTATGGATCTTCCATAAACTCGGCCGGGACCACTAGAGCGTGCATGAGGA

ATGGAGGGAATAGCTTTTATGCAGAGCTTAAGTGGCTGGTATCAAAGAGCAAAGGA

CAAAACTTCCCTCAGACCACGAACACTTACAGAAATACAGACACGGCTGAACACCT

CATAATGTGGGGAATTCATCACCCTTCTAGCACTCAAGAGAAGAATGATCTATATG

GAACACAATCACTGTCCATATCAGTCGGGAGTTCCACTTACCGGAACAATTTTGTT

CCGGTTGTTGGAGCAAGACCTCAGGTCAATGGACAAAGTGGCAGAATTGATTTTCA

CTGGACACTAGTACAGCCAGGTGACAACATCACCTTCTCACACAATGGGGGCCTGA

TAGCACCGAGCCGAGTTAGCAAATTAATTGGGAGGGGATTGGGAATCCAATCAGAC

GCACCAATAGACAATAATTGTGAGTCCAAATGTTTTTGGAGAGGGGGTTCTATAAA

TACAAGGCTTCCCTTTCAAAATTTGTCACCAAGAACAGTGGGTCAGTGTCCTAAAT

ATGTGAACAGAAGAAGCTTGATGCTTGCAACAGGAATGAGAAACGTACCAGAACTA

ATACAAGGGAGAGGTCTATTTGGTGCAATAGCAGGGTTTTTAGAGAATGGGTGGGA

AGGAATGGTAGATGGCTGGTATGGTTTCAGACATCAAAATGCTCAGGGCACAGGCC

AGGCCGCTGATTACAAGAGTACTCAGGCAGCTATTGATCAAATCACTGGGAAACTG

AATAGACTTGTTGAAAAAACCAATACTGAGTTCGAGTCAATAGAATCTGAGTTCAG

TGAGATCGAACACCAAATCGGTAACGTCATCAATTGGACTAAGGATTCAATAACCG

ACATTTGGACTTATCAGGCTGAGCTGTTGGTGGCAATGGAGAACCAGCATACAATC

GACATGGCTGACTCAGAGATGTTGAATCTATATGAAAGAGTGAGGAAACAACTAAG

GCAGAATGCAGAAGAAGATGGGAAAGGATGTTTTGAGATATATCATGCTTGTGATG

ATTCATGCATGGAGAGCATAAGAAACAACACCTATGACCATTCACAGTACAGAGAG

GAAGCTCTTTTGAACAGATTGAATATCAACCCAGTGACACTCTCTTCTGGATATAA

AGACATCATTCTCTGGTTTAGCTTCGGGGCATCATGTTTTGTTCTTCTAGCCGTTG

TCATGGGTCTTTTCTTTTTCTGTCTGAAGAATGGAAACATGCGATGCACAATCTGT

ATTTAG

TABLE 16

Codon Optimized Sequences Encoding H1 Hemagglutinin

Seq

ID

No.
Nucleotide sequence

396
ATGAAGGCAAACCTCTTAGTCCTTCTCTGCGCACTGGCCGCTGCCGACGCAGATACCATA

TGTATCGGTTATCACGCCAATAACTCTACCGATACAGTCGATACGGTGCTTGAGAAAAAC

GTCACCGTGACTCATAGCGTGAACCTGCTCGAGGACTCCCATAACGGTAAGCTATGCCGA

CTAAAGGGCATCGCCCCCCTGCAGCTGGGGAAATGCAACATCGCTGGCTGGTTGTTAGGT

AATCCCGAATGCGATCCACTGCTGCCCGTGAGATCCTGGTCTTACATCGTCGAAACCCCT

AACTCTGAAAATGGCATCTGCTATCCGGGAGACTTTATTGACTATGAGGAGCTCCGAGAA

CAGCTGAGCTCAGTATCCAGCTTTGAACGCTTCGAAATTTTTCCAAAGGAATCCAGCTGG

CCAAACCATAACACGAATGGCGTCACAGCCGCATGCAGCCACGAGGGAAAGAGCAGCTTT

TATAGGAACCTTCTGTGGTTGACGGAAAAAGAGGGAAGTTATCCCAAACTTAAAAACAGC

TATGTGAATAAAAAGGGCAAGGAGGTCTTGGTACTTTGGGGAATCCATCACCCTCCAAAC

AGTAAGGAACAACAAAATCTGTACCAGAATGAAAATGCATACGTGTCCGTGGTTACATCT

AATTACAACCGACGGTTTACTCCCGAGATCGCCGAGCGACCGAAAGTTCGCGACCAGGCC

GGGAGGATGAACTATTATTGGACGTTGCTGAAACCCGGTGACACAATTATCTTTGAGGCA

AATGGTAATCTTATCGCCCCGATGTACGCATTCGCACTGTCGCGCGGATTTGGCAGTGGG

ATTATAACCAGTAACGCATCTATGCATGAATGCAACACAAAGTGCCAGACTCCTTTAGGC

GCTATAAACTCTTCTTTGCCCTATCAGAATATACACCCAGTGACCATCGGCGAGTGTCCA

AAGTACGTACGCAGCGCCAAGCTCCGAATGGTTACAGGCCTCAGAAATAACCCCAGTATC

CAGAGCCGCGGCTTATTCGGGGCGATCGCTGGATTTATTGAGGGGGGCTGGACGGGAATG

ATAGATGGGTGGTACGGCTACCATCATCAGAATGAGCAGGGTAGCGGCTATGCGGCCGAC

CAGAAAAGCACCCAGAACGCTATCAACGGTATAACCAATAAAGTGAACACTGTGATCGAA

AAAATGAACATACAGTTCACTGCCGTGGGAAAGGAATTCAACAAACTGGAAAAAAGGATG

GAAAATCTTAACAAAAAAGTGGATGACGGGTTTTTGGACATTTGGACATACAATGCCGAA

CTGCTGGTTCTGCTGGAGAACGAAAGGACACTGGACTTTCACGATTCCAACGTCAAGAAT

CTCTATGAAAAAGTGAAGTCCCAATTGAAAAACAACGCCAAGGAGATCGGTAATGGGTGC

TTTGAGTTCTATCACAAGTGTGACAACGAGTGCATGGAGAGCGTTAGGAACGGCACATAC

GATTACCCAAAATATTCTGAGGAGTCTAAGTTGAACAGAGAGAAGGTCGATGGCGTTAAA

CTGGAAAGCATGGGAATTTACCAGATCCTTGCCATCTACTCCACCGTGGCCTCCTCCCTT

GTGCTGCTGGTGTCGCTGGGGGCCATCTCCTTTTGGATGTGCTCCAATGGTTCACTGCAA

TGTCGAATCTGCATC

397
ATGAAGGCTAACCTCCTAGTGCTGCTCTGTGCCTTGGCGGCTGCGGATGCTGACACCATT

TGCATTGGGTACCACGCCAATAATTCAACCGATACTGTCGACACCGTGTTGGAGAAGAAT

GTGACCGTGACTCATTCCGTGAACCTTCTTGAAGATTCGCACAACGGGAAGCTGTGTCGA

CTCAAAGGCATCGCGCCTCTACAGTTGGGCAAATGTAACATCGCTGGGTGGCTGCTCGGG

AACCCAGAATGTGATCCTTTGCTGCCAGTGAGATCGTGGTCATACATTGTGGAGACCCCC

AATTCAGAGAACGGGATATGCTACCCAGGTGACTTTATCGATTATGAGGAACTTCGGGAA

CAACTGTCTTCAGTGTCGTCATTTGAGCGTTTCGAGATCTTTCCCAAAGAGTCCTCGTGG

CCAAACCACAACACTAACGGCGTTACTGCCGCCTGCTCACATGAAGGAAAGAGCTCATTC

TACAGAAACCTGTTGTGGCTCACCGAGAAGGAGGGGAGTTATCCCAAGTTGAAAAACAGT

TATGTTAACAAGAAGGGCAAAGAAGTGTTAGTCCTGTGGGGAATCCACCACCCACCGAAT

TCTAAAGAGCAGCAGAATCTATATCAGAACGAGAACGCCTATGTGTCAGTTGTAACTTCA

AATTACAACCGCAGGTTTACTCCTGAAATCGCGGAGCGCCCGAAAGTGCGTGATCAGGCT

GGACGTATGAATTACTACTGGACTTTGCTAAAACCTGGCGACACCATCATTTTCGAAGCT

AACGGCAATCTCATTGCGCCGATGTACGCCTTTGCTCTCTCTAGGGGGTTCGGGTCTGGG

ATCATTACCAGCAATGCTTCCATGCACGAGTGTAATACAAAGTGCCAGACTCCCCTCGGC

GCGATTAATAGCTCGCTCCCCTACCAAAACATACACCCAGTGACAATTGGCGAGTGCCCT

AAATATGTGCGCTCTGCTAAGTTACGTATGGTGACGGGCCTAAGAAACAACCCCTCAATT

CAGAGCAGGGGGCTGTTCGGAGCTATTGCAGGTTTCATCGAAGGGGGCTGGACAGGGATG

ATCGACGGCTGGTATGGGTATCACCACCAGAACGAACAGGGATCCGGCTATGCTGCCGAT

CAGAAATCAACACAAAATGCAATCAATGGCATCACTAACAAAGTGAATACCGTAATTGAG

AAGATGAACATACAGTTTACCGCTGTCGGTAAAGAATTCAACAAGCTGGAGAAACGGATG

GAGAATCTGAACAAGAAAGTCGATGATGGCTTCTTGGATATCTGGACCTATAATGCTGAG

TTACTTGTGCTCTTGGAAAACGAGCGTACTCTCGACTTTCATGATTCAAATGTCAAGAAT

CTGTATGAAAAGGTAAAGTCCCAGCTAAAAAACAATGCCAAGGAGATCGGGAATGGCTGC

TTTGAATTCTACCACAAATGCGATAATGAGTGCATGGAGTCGGTGAGGAACGGAACCTAC

GATTACCCAAAATATAGCGAGGAATCAAAACTGAACAGAGAGAAGGTGGATGGTGTGAAG

CTGGAATCCATGGGTATCTACCAGATCCTCGCCATCTATTCAACTGTGGCTAGTTCCCTG

GTGCTGCTCGTGAGCCTTGGTGCAATCTCCTTCTGGATGTGTTCCAACGGGTCATTGCAG

TGTAGGATCTGCATA

398
ATGAAGGCTAACTTGCTGGTCTTGCTTTGCGCGCTGGCCGCTGCTGACGCCGACACCATC

TGTATTGGGTATCATGCTAACAACTCCACGGATACCGTGGATACAGTGTTGGAAAAAAAT

GTTACAGTTACTCATTCGGTGAACCTGCTGGAGGACTCTCACAATGGGAAGCTGTGCAGG

CTCAAAGGTATCGCTCCGCTCCAACTAGGCAAATGTAATATTGCCGGCTGGCTGTTAGGA

AACCCAGAGTGTGACCCTCTCTTACCCGTGAGATCTTGGTCCTACATCGTCGAGACCCCC

AACAGCGAAAACGGAATTTGTTATCCCGGAGACTTCATAGATTATGAGGAGCTGCGCGAA

CAGCTCTCTTCTGTTAGCTCTTTTGAGCGTTTTGAGATCTTTCCTAAAGAGAGTTCATGG

CCCAACCACAATACCAACGGAGTGACAGCCGCATGCTCCCATGAAGGGAAGTCTAGCTTC

TATAGAAATCTTCTGTGGCTGACTGAAAAAGAAGGATCTTACCCCAAGTTGAAGAATTCT

TATGTGAACAAAAAGGGCAAAGAGGTGTTGGTACTCTGGGGCATTCATCACCCACCTAAT

TCAAAGGAGCAGCAAAACCTTTATCAAAACGAGAATGCCTATGTTAGCGTCGTCACTTCT

AATTATAACCGGAGATTCACCCCGGAGATAGCGGAACGCCCCAAGGTTCGGGATCAGGCT

GGCCGCATGAATTACTACTGGACCCTCCTAAAACCTGGCGACACCATAATCTTCGAAGCA

AATGGCAACCTGATCGCACCTATGTACGCCTTTGCGCTGTCTAGGGGATTCGGCTCGGGC

ATTATTACCAGTAATGCCTCAATGCACGAGTGTAATACAAAATGCCAGACCCCTCTGGGA

GCCATTAATTCTAGTCTGCCTTATCAGAATATTCATCCTGTGACCATTGGCGAATGTCCG

AAATATGTTAGATCCGCAAAGCTGCGAATGGTTACCGGACTTCGCAACAACCCCTCTATA

CAAAGCCGCGGACTCTTTGGAGCAATCGCTGGCTTCATTGAGGGTGGCTGGACGGGCATG

ATCGATGGGTGGTACGGATACCATCATCAGAACGAGCAGGGAAGCGGATATGCCGCAGAC

CAAAAATCTACTCAGAACGCTATTAACGGAATTACCAACAAAGTCAACACAGTTATCGAG

AAAATGAATATTCAGTTCACCGCAGTTGGTAAGGAATTTAACAAACTGGAGAAACGAATG

GAGAACTTGAACAAGAAGGTCGACGATGGCTTCTTAGACATCTGGACATATAATGCCGAA

CTGTTGGTCCTCCTGGAGAACGAGAGAACCTTGGACTTTCACGACTCTAACGTGAAGAAT

CTTTACGAGAAGGTGAAGTCCCAACTGAAGAATAATGCAAAAGAGATCGGAAACGGCTGT

TTTGAGTTCTACCACAAGTGCGACAATGAGTGCATGGAGAGCGTGCGGAATGGGACATAT

GATTATCCCAAGTATAGTGAAGAAAGCAAGCTGAATCGAGAAAAGGTTGACGGAGTGAAG

CTGGAGAGCATGGGGATCTACCAGATCTTAGCAATTTATAGCACAGTGGCTTCTTCCCTT

GTGTTGCTGGTCTCGCTGGGAGCTATCAGCTTTTGGATGTGCAGCAACGGAAGTCTGCAG

TGCCGCATTTGCATT

399
ATGAAAGCCAACCTGTTGGTGCTGTTATGCGCGCTGGCAGCCGCAGATGCTGATACTATC

TGTATCGGATACCATGCCAATAACAGCACCGATACCGTGGATACTGTGTTAGAGAAGAAT

GTGACAGTGACGCATTCAGTAAACCTCCTCGAGGACAGTCATAATGGAAAACTGTGTAGG

CTCAAGGGTATAGCTCCGCTGCAGCTGGGCAAGTGTAACATCGCTGGGTGGCTGCTGGGC

AACCCTGAATGCGATCCCCTGTTGCCCGTTCGGAGTTGGTCTTACATCGTGGAGACCCCA

AACTCTGAGAACGGAATTTGTTACCCCGGTGACTTTATCGATTACGAGGAATTGCGGGAG

CAGCTTAGCTCAGTGTCTTCATTTGAACGGTTTGAAATCTTTCCCAAGGAAAGCAGCTGG

CCCAATCATAATACTAACGGCGTGACTGCCGCTTGTTCCCACGAAGGCAAGAGCTCCTTC

TACAGAAATCTGCTTTGGTTGACAGAGAAAGAGGGCAGCTATCCAAAGCTGAAGAACAGT

TATGTGAATAAGAAGGGCAAGGAGGTCCTGGTTCTTTGGGGGATCCATCATCCCCCTAAT

AGTAAGGAGCAGCAGAACTTATACCAGAATGAGAATGCCTACGTCAGCGTTGTCACCTCA

AACTATAACCGGCGATTTACACCCGAAATTGCCGAACGTCCCAAGGTCCGCGACCAAGCC

GGGCGTATGAACTACTATTGGACACTTCTGAAACCTGGGGACACAATAATTTTCGAAGCC

AACGGTAACTTAATCGCTCCCATGTACGCTTTCGCTCTCAGCAGGGGCTTCGGCAGCGGC

ATTATCACTTCCAATGCGTCCATGCATGAATGTAATACGAAGTGCCAGACCCCTCTCGGT

GCCATAAACTCTTCTCTCCCCTACCAGAACATTCACCCTGTCACCATAGGAGAATGCCCA

AAGTATGTCCGGTCGGCAAAGTTGAGGATGGTTACGGGCCTGCGTAACAACCCTTCTATA

CAGTCTAGGGGCCTGTTCGGAGCAATCGCCGGCTTCATCGAAGGAGGCTGGACTGGGATG

ATCGATGGCTGGTACGGCTATCATCACCAGAATGAGCAGGGCTCAGGTTATGCAGCCGAT

CAGAAGTCCACACAGAACGCTATTAACGGGATAACGAACAAGGTGAACACCGTCATTGAA

AAGATGAACATTCAGTTTACAGCCGTTGGAAAAGAGTTCAACAAACTGGAAAAGCGGATG

GAGAACCTGAACAAAAAGGTGGACGATGGATTTCTGGATATTTGGACATATAACGCCGAG

CTGCTGGTACTCCTTGAGAACGAGCGTACGCTTGACTTTCATGACAGTAACGTGAAGAAT

CTGTACGAGAAGGTCAAAAGCCAGCTGAAGAACAATGCCAAAGAAATTGGGAACGGGTGT

TTCGAATTCTACCACAAGTGTGACAATGAATGCATGGAGAGTGTTCGGAACGGAACCTAC

GACTATCCTAAATATTCTGAGGAGTCCAAGCTGAATCGGGAAAAGGTTGACGGGGTGAAA

CTGGAGAGTATGGGAATCTACCAGATCCTGGCTATTTACTCCACAGTCGCTTCCTCTCTC

GTCTTGTTGGTGTCCCTTGGTGCCATCTCATTTTGGATGTGTTCTAATGGTTCTCTTCAG

TGCCGAATCTGTATA

400
ATGAAAGCTAACCTTCTCGTATTGCTCTGCGCTTTGGCTGCAGCCGATGCCGATACGATT

TGCATCGGATACCACGCAAATAACAGCACTGACACTGTGGACACGGTACTGGAAAAGAAT

GTTACCGTGACACACTCCGTCAACCTGCTCGAGGACTCCCACAACGGAAAGTTGTGTAGG

CTTAAAGGTATCGCCCCTCTACAGTTAGGGAAGTGCAACATCGCAGGGTGGTTGTTAGGA

AACCCCGAATGTGACCCACTCCTGCCTGTGCGCTCTTGGAGCTATATTGTGGAAACCCCG

AATAGCGAAAACGGAATTTGTTACCCTGGCGACTTTATCGATTATGAAGAGCTCCGAGAG

CAACTGAGCAGCGTGTCCAGCTTTGAGCGATTTGAAATATTCCCCAAAGAGAGTTCCTGG

CCCAACCATAACACTAACGGAGTGACCGCTGCATGTTCGCACGAAGGCAAATCGAGTTTT

TACCGGAACCTGCTTTGGCTCACCGAGAAGGAAGGAAGTTATCCCAAACTCAAAAATTCA

TACGTGAATAAAAAGGGTAAGGAGGTGCTGGTGCTGTGGGGAATCCACCATCCTCCAAAC

AGCAAGGAACAACAGAATCTCTACCAGAATGAGAACGCCTATGTGAGCGTGGTAACCTCC

AACTACAATCGGCGGTTCACTCCTGAGATCGCCGAGCGCCCGAAGGTCCGGGATCAAGCA

GGTCGAATGAACTACTACTGGACCCTGCTGAAGCCAGGTGATACTATCATTTTCGAGGCT

AATGGAAACCTGATTGCGCCTATGTACGCTTTCGCCCTGTCTAGGGGGTTTGGGTCCGGT

ATCATCACGTCTAACGCTTCAATGCATGAATGCAACACGAAGTGTCAGACCCCGCTTGGC

GCCATAAACAGCTCCCTCCCCTACCAGAACATTCACCCCGTCACCATAGGCGAGTGTCCC

AAGTACGTGCGGTCAGCCAAGTTGCGGATGGTAACGGGCCTCCGGAATAATCCAAGTATA

CAATCCCGAGGACTTTTCGGGGCAATCGCGGGCTTCATTGAGGGGGGATGGACCGGCATG

ATTGATGGATGGTACGGTTACCACCACCAGAACGAGCAGGGCAGTGGATATGCCGCTGAC

CAGAAGAGCACTCAGAACGCAATTAATGGCATCACCAATAAGGTGAACACCGTCATTGAG

AAGATGAACATCCAGTTTACGGCAGTAGGCAAGGAGTTTAACAAGCTGGAGAAACGTATG

GAAAACCTGAATAAGAAAGTGGACGACGGGTTTTTGGATATTTGGACATATAACGCCGAA

CTCCTCGTGCTGCTCGAGAATGAAAGAACATTAGACTTTCACGATAGTAACGTGAAAAAC

CTGTATGAAAAGGTCAAATCCCAGCTAAAGAACAACGCCAAAGAGATCGGCAATGGCTGT

TTTGAGTTTTACCACAAGTGTGATAATGAATGCATGGAAAGTGTTCGGAACGGAACCTAC

GATTATCCAAAATACTCGGAGGAGTCCAAACTGAATAGAGAGAAGGTGGACGGCGTCAAA

CTAGAGAGTATGGGTATCTATCAGATACTTGCGATCTACTCAACCGTCGCCAGCTCCTTA

GTACTTCTCGTCAGCCTCGGTGCTATCTCCTTTTGGATGTGTAGTAACGGCAGTCTGCAG

TGTCGGATATGCATC

401
ATGAAGGCTAACCTGTTGGTGCTCCTATGTGCCCTGGCCGCTGCAGATGCTGACACAATC

TGCATTGGGTATCATGCAAACAACTCCACCGACACTGTTGACACAGTTTTGGAAAAGAAC

GTGACAGTCACTCACAGCGTAAACCTCCTGGAAGACTCACACAATGGGAAGTTATGTCGG

CTGAAGGGCATAGCCCCATTGCAACTGGGCAAGTGCAATATAGCGGGGTGGCTTCTCGGC

AACCCGGAATGCGACCCCCTGTTGCCCGTACGCAGCTGGAGTTACATTGTGGAGACGCCC

AATTCCGAGAATGGCATCTGTTACCCGGGCGATTTCATAGATTACGAAGAACTGCGGGAG

CAGCTCTCCTCCGTTTCCTCGTTCGAACGGTTCGAGATTTTCCCTAAAGAATCATCATGG

CCTAATCACAATACAAATGGCGTGACGGCCGCATGCTCACACGAGGGCAAGTCCAGCTTT

TACAGAAATCTCCTGTGGCTGACGGAGAAGGAAGGAAGCTACCCTAAGCTTAAGAATAGC

TATGTAAACAAAAAGGGGAAGGAGGTGCTGGTTCTCTGGGGGATTCATCATCCGCCAAAT

AGTAAGGAACAGCAGAACCTTTACCAGAATGAGAATGCATACGTCTCTGTGGTCACGTCT

AACTACAATCGGCGCTTCACACCCGAGATCGCTGAACGGCCCAAAGTCCGGGACCAAGCC

GGACGAATGAATTACTACTGGACCCTTTTGAAGCCCGGCGATACCATTATCTTCGAAGCG

AACGGGAACCTGATAGCTCCCATGTACGCCTTTGCTCTCAGTAGGGGATTCGGCTCCGGC

ATTATTACCTCTAATGCTTCTATGCACGAGTGCAACACAAAATGTCAGACTCCGCTCGGT

GCCATCAACAGTTCGTTGCCATACCAGAATATACACCCCGTCACTATCGGGGAATGTCCT

AAATACGTGAGGAGCGCCAAACTCAGGATGGTCACTGGACTCAGGAATAATCCAAGCATC

CAGTCGAGGGGCTTATTCGGAGCAATTGCTGGCTTCATCGAAGGCGGGTGGACTGGCATG

ATCGATGGATGGTATGGGTACCACCACCAGAACGAACAAGGTAGCGGATATGCCGCTGAC

CAGAAATCAACACAAAACGCCATCAACGGTATTACCAACAAGGTTAACACTGTTATTGAG

AAGATGAATATCCAATTTACCGCCGTAGGGAAGGAGTTTAATAAGTTGGAGAAACGTATG

GAGAATCTGAACAAGAAAGTTGACGACGGATTTCTGGACATCTGGACCTACAACGCCGAG

CTGTTAGTGCTGTTGGAAAATGAGAGAACCCTTGACTTCCATGATAGCAACGTGAAAAAC

CTATATGAAAAGGTCAAGTCCCAGCTGAAGAACAATGCAAAGGAAATAGGCAATGGCTGC

TTCGAGTTTTATCATAAATGCGACAACGAATGTATGGAAAGCGTCCGAAACGGCACTTAT

GACTATCCCAAATATAGCGAAGAGTCAAAGCTGAATCGGGAAAAGGTGGACGGGGTCAAG

CTCGAGTCAATGGGGATCTACCAGATTCTTGCAATCTATTCCACAGTGGCGTCTTCCCTC

GTGCTGCTGGTTAGTCTCGGCGCCATATCATTTTGGATGTGCAGCAATGGCTCCCTGCAG

TGTCGGATCTGTATC

402
ATGAAGGCGAACTTGCTGGTCCTGTTGTGCGCTTTAGCTGCTGCGGATGCCGATACAATC

TGTATCGGGTATCACGCAAACAACAGTACAGATACCGTGGATACAGTTCTCGAGAAGAAT

GTCACTGTTACGCACAGTGTAAACCTGCTGGAGGACAGTCACAATGGGAAGCTGTGCCGG

CTAAAGGGCATTGCGCCACTACAGCTCGGCAAGTGCAATATTGCGGGGTGGTTATTGGGT

AACCCCGAATGCGACCCACTATTGCCAGTGCGCTCTTGGTCGTACATCGTCGAAACCCCC

AATTCAGAAAATGGCATTTGCTACCCAGGGGATTTTATAGACTACGAAGAGTTACGAGAA

CAATTAAGTAGTGTTTCTTCCTTTGAGCGATTCGAGATTTTCCCCAAGGAGAGTTCTTGG

CCCAACCATAACACAAATGGAGTGACTGCCGCATGCTCACACGAGGGCAAATCATCCTTT

TATAGAAACCTGCTTTGGCTGACTGAAAAGGAGGGGAGTTACCCGAAGCTTAAAAACTCC

TATGTGAACAAGAAGGGCAAGGAAGTGCTGGTCCTGTGGGGGATCCACCACCCACCCAAC

TCCAAAGAGCAACAGAACCTCTACCAGAACGAGAATGCGTATGTGAGCGTGGTGACAAGT

AACTATAATCGAAGGTTCACTCCCGAGATAGCAGAGCGTCCAAAAGTGCGAGATCAAGCC

GGCCGAATGAACTACTATTGGACCTTACTGAAACCCGGCGATACCATCATATTCGAAGCT

AACGGCAATCTCATAGCTCCTATGTACGCTTTCGCTTTGAGTAGAGGTTTCGGATCTGGA

ATTATAACATCTAATGCATCAATGCACGAGTGCAATACTAAATGCCAGACCCCTCTTGGT

GCTATCAACTCTAGTTTACCCTATCAGAACATCCACCCTGTGACGATAGGAGAGTGTCCC

AAGTATGTGCGCTCCGCTAAGCTTAGAATGGTCACCGGGCTTCGGAACAACCCTTCAATC

CAAAGTCGAGGGCTTTTTGGCGCTATCGCTGGCTTCATCGAAGGCGGTTGGACAGGTATG

ATCGATGGTTGGTACGGCTACCATCATCAGAACGAGCAGGGGTCTGGTTATGCGGCCGAC

CAAAAATCTACTCAGAATGCCATCAACGGGATCACAAATAAGGTAAACACTGTGATTGAG

AAGATGAACATCCAGTTTACTGCAGTGGGAAAGGAGTTTAACAAACTGGAGAAACGTATG

GAAAACCTAAACAAAAAAGTGGACGACGGATTCTTAGACATTTGGACATACAACGCCGAG

CTGCTCGTGCTGCTTGAGAATGAGCGGACACTCGACTTCCACGACAGCAACGTGAAGAAC

CTATACGAAAAGGTCAAGAGCCAGCTCAAGAATAACGCGAAGGAGATTGGAAACGGCTGC

TTCGAGTTCTACCATAAGTGCGATAACGAATGTATGGAGTCTGTTCGGAATGGCACTTAC

GACTACCCAAAGTATAGCGAGGAATCTAAGCTCAACCGAGAGAAGGTGGATGGAGTGAAA

TTAGAGTCAATGGGAATTTATCAGATTCTGGCCATCTACTCAACAGTTGCGAGCTCGTTA

GTGCTGCTTGTCTCACTGGGCGCGATTAGTTTTTGGATGTGCAGTAATGGGTCCCTCCAG

TGTCGCATCTGCATT

403
ATGAAGGCCAACTTGCTGGTGTTACTATGTGCTCTCGCCGCCGCCGATGCCGATACTATT

TGCATTGGCTATCACGCCAACAATAGTACGGACACCGTGGACACTGTCCTGGAAAAAAAT

GTCACCGTCACCCATTCTGTGAATCTCCTAGAGGATTCTCATAACGGCAAGCTGTGCCGG

CTTAAAGGAATCGCTCCCTTGCAGCTTGGGAAGTGCAATATCGCCGGCTGGCTCCTTGGA

AACCCGGAGTGTGATCCATTGCTCCCTGTCAGAAGCTGGAGCTATATCGTTGAGACCCCG

AACAGTGAGAATGGCATCTGTTACCCCGGAGATTTCATTGATTACGAGGAGCTGCGCGAA

CAGCTCAGCTCAGTCTCTAGTTTCGAGCGATTTGAGATCTTCCCCAAGGAGTCTAGCTGG

CCAAATCATAACACCAACGGAGTGACAGCCGCCTGTAGCCATGAAGGGAAAAGCAGCTTC

TACCGAAATTTGCTGTGGCTAACTGAGAAAGAGGGGAGTTATCCTAAGCTCAAAAACAGC

TATGTGAACAAGAAGGGGAAAGAAGTCCTGGTGTTGTGGGGCATCCACCATCCCCCAAAT

AGCAAGGAACAGCAGAACCTTTACCAGAACGAGAATGCATACGTGAGCGTCGTAACATCC

AATTATAACAGACGGTTCACACCCGAGATAGCCGAACGGCCAAAAGTGAGGGACCAGGCC

GGAAGGATGAATTACTATTGGACTCTCTTAAAGCCAGGCGACACCATTATATTTGAGGCA

AACGGAAACTTGATTGCGCCAATGTACGCATTCGCACTGTCACGGGGATTCGGATCCGGG

ATTATCACGTCCAATGCATCGATGCATGAGTGCAACACCAAGTGTCAGACCCCACTGGGA

GCCATCAATTCCAGCTTGCCCTATCAGAACATTCACCCCGTGACTATAGGAGAGTGCCCT

AAATATGTCCGCAGCGCCAAACTGCGAATGGTTACCGGCCTGCGCAACAATCCTTCGATC

CAGTCACGGGGCCTGTTCGGGGCCATAGCTGGCTTCATTGAGGGGGGATGGACCGGTATG

ATTGATGGGTGGTACGGCTACCACCATCAGAACGAGCAGGGTTCAGGCTACGCGGCTGAC

CAGAAATCCACTCAGAACGCTATCAATGGCATCACAAACAAGGTCAATACTGTTATAGAA

AAAATGAATATCCAATTCACTGCTGTGGGTAAAGAGTTTAACAAGCTGGAGAAAAGAATG

GAAAATCTGAACAAAAAAGTGGATGACGGCTTCTTGGATATCTGGACATACAACGCTGAA

CTTCTGGTGCTGTTGGAAAACGAAAGGACTCTGGATTTCCACGATTCCAACGTGAAAAAT

CTCTACGAAAAAGTTAAGTCCCAACTGAAGAATAACGCGAAGGAGATCGGAAACGGATGC

TTTGAGTTCTATCATAAGTGTGATAATGAGTGTATGGAATCAGTTAGAAACGGTACGTAC

GATTACCCAAAATACTCCGAAGAGTCTAAGCTGAATCGCGAGAAAGTCGATGGGGTCAAA

CTCGAATCCATGGGAATTTACCAGATCTTAGCTATTTACAGTACAGTGGCCAGCTCTCTT

GTCTTACTGGTGTCACTTGGCGCGATTAGTTTCTGGATGTGCTCCAATGGCAGCCTCCAG

TGTCGGATTTGCATA

404
ATGAAGGCCAACCTGCTTGTACTGCTATGCGCCTTGGCTGCTGCAGACGCCGACACAATT

TGCATCGGCTATCATGCCAACAATTCTACAGATACAGTGGACACTGTGCTGGAGAAAAAC

GTTACTGTCACTCATAGCGTTAATCTCCTCGAGGACTCTCACAATGGAAAACTCTGTCGT

CTGAAAGGCATCGCGCCACTGCAGTTGGGTAAATGTAATATCGCCGGCTGGTTGTTGGGC

AACCCCGAATGTGACCCCCTCCTCCCAGTGAGGTCCTGGTCTTATATCGTAGAGACACCT

AATTCGGAGAATGGAATTTGTTACCCTGGCGACTTCATAGACTATGAGGAACTGAGGGAG

CAGCTTTCTTCTGTGAGTTCTTTTGAAAGATTTGAGATCTTCCCTAAAGAATCATCTTGG

CCCAACCATAATACCAACGGCGTTACAGCAGCCTGTTCCCACGAGGGCAAGTCGAGTTTC

TACAGGAATTTGTTATGGCTGACTGAGAAAGAGGGGTCTTATCCAAAGCTGAAAAACAGC

TATGTCAACAAGAAAGGCAAAGAGGTTTTGGTGCTGTGGGGAATCCATCACCCACCAAAC

TCGAAGGAACAGCAAAATCTTTACCAAAACGAAAATGCATACGTATCAGEGGTTACTAGC

AATTATAATCGGCGCTTTACGCCAGAGATTGCCGAAAGACCTAAGGTGAGAGACCAAGCA

GGAAGGATGAATTACTACTGGACACTACTGAAACCAGGCGATACTATCATTTTTGAGGCC

AACGGAAACCTGATCGCACCCATGTACGCCTTCGCACTGTCGCGGGGTTTTGGGTCTGGC

ATCATCACCTCAAATGCCAGCATGCATGAGTGCAATACTAAATGCCAAACACCTTTAGGT

GCCATTAATAGCTCACTCCCCTACCAGAACATCCATCCAGTAACTATCGGGGAGTGTCCC

AAGTACGTGCGATCTGCAAAACTGAGGATGGTCACTGGTTTGCGCAACAATCCCTCTATC

CAGTCAAGGGGCCTATTTGGCGCAATTGCGGGCTTTATCGAGGGAGGGTGGACGGGTATG

ATTGACGGATGGTACGGCTACCACCACCAGAATGAACAGGGTTCGGGGTACGCGGCAGAT

CAGAAGAGTACTCAGAACGCAATTAATGGTATAACTAATAAGGTCAACACCGTAATTGAA

AAAATGAATATCCAATTCACAGCTGTTGGGAAAGAATTTAACAAACTGGAGAAGAGGATG

GAGAATCTCAATAAGAAGGTTGATGACGGCTTTCTCGATATCTGGACTTACAATGCTGAG

CTGCTAGTTCTGCTCGAGAACGAACGGACACTCGATTTTCACGATTCCAACGTTAAAAAC

CTGTACGAAAAGGTCAAATCTCAGCTGAAGAATAATGCTAAGGAAATTGGTAATGGCTGT

TTCGAATTTTATCATAAATGTGATAATGAGTGCATGGAAAGTGTCCGTAACGGCACCTAC

GATTATCCAAAGTATAGCGAGGAAAGCAAGCTTAATCGTGAAAAAGTAGATGGCGTGAAG

CTGGAAAGTATGGGCATATATCAGATCCTGGCCATATACAGTACTGTTGCCTCCAGTCTA

GTTTTACTGGTATCCCTCGGAGCTATCTCATTCTGGATGTGTAGCAATGGCAGCCTTCAG

TGCCGTATCTGTATA

405
ATGAAAGCTAACCTGCTAGTTCTACTTTGTGCCCTTGCCGCTGCCGACGCTGACACCATC

TGCATAGGGTACCACGCTAACAACAGTACTGACACAGTGGATACCGTTCTTGAAAAGAAC

GTCACCGTAACTCACTCTGTGAATTTGCTCGAGGATTCACACAATGGGAAACTCTGCAGA

CTGAAAGGAATTGCTCCACTTCAGTTGGGCAAGTGTAACATCGCTGGCTGGCTGCTTGGG

AATCCGGAGTGCGACCCATTGCTGCCTGTGCGCAGTTGGAGCTACATTGTGGAGACCCCC

AACAGCGAGAATGGCATCTGTTATCCCGGAGATTTCATCGACTACGAGGAGCTCCGAGAA

CAATTATCCTCTGTGTCTAGTTTCGAACGGTTTGAGATCTTTCCCAAAGAATCAAGCTGG

CCCAACCACAACACAAACGGTGTGACAGCAGCATGCAGTCATGAGGGCAAGTCGTCCTTC

TATAGGAATCTGCTGTGGCTTACTGAGAAGGAGGGTAGCTACCCGAAACTCAAGAACTCC

TACGTCAATAAGAAGGGCAAAGAGGTGTTAGTCTTGTGGGGAATACACCACCCACCCAAC

TCTAAAGAGCAACAAAACCTGTACCAGAACGAAAACGCCTACGTCTCCGTAGTAACCTCA

AATTATAACAGACGCTTTACGCCCGAGATCGCAGAGCGCCCCAAGGTCAGGGACCAGGCA

GGGAGAATGAACTACTATTGGACTTTGTTGAAGCCCGGAGACACAATTATCTTCGAGGCG

AATGGCAATCTGATTGCCCCCATGTACGCTTTTGCACTGTCCCGCGGTTTTGGTTCCGGC

ATCATAACTTCCAACGCATCGATGCACGAATGTAACACCAAATGTCAGACACCATTGGGC

GCCATAAACTCCAGTCTCCCATATCAAAATATCCACCCAGTCACAATCGGGGAATGTCCT

AAATACGTGAGGTCAGCAAAGCTTAGGATGGTCACGGGACTGCGCAACAATCCCTCAATA

CAGTCCAGAGGGCTTTTCGGAGCCATAGCCGGCTTCATCGAAGGCGGCTGGACTGGGATG

ATCGATGGCTGGTATGGGTATCATCACCAGAATGAGCAGGGCTCCGGCTATGCTGCCGAT

CAGAAATCCACACAGAACGCTATCAATGGGATAACTAACAAAGTTAACACCGTGATTGAG

AAGATGAACATACAATTTACTGCAGTGGGAAAGGAGTTCAACAAACTGGAGAAGCGGATG

GAGAACTTAAATAAAAAGGTGGATGACGGCTTCCTGGACATCTGGACTTATAACGCTGAA

CTGTTGGTACTGCTTGAGAATGAGCGGACCCTCGACTTTCACGACTCAAACGTGAAGAAT

CTCTATGAGAAGGTAAAATCCCAGTTGAAAAACAACGCCAAGGAGATCGGGAATGGCTGC

TTTGAATTTTACCACAAGTGCGACAATGAGTGTATGGAAAGTGTGCGCAACGGAACATAT

GACTATCCTAAATATAGTGAAGAGTCCAAACTGAACCGTGAAAAGGTGGATGGGGTGAAA

CTCGAGTCCATGGGAATCTACCAAATCCTCGCCATTTATTCAACCGTGGCAAGCAGCCTC

GTGCTACTGGTCAGTCTCGGCGCGATTTCTTTCTGGATGTGCTCCAACGGGTCACTGCAG

TGTCGCATATGCATC

406
ATGAAGGCGAACCTCCTTGTGCTTCTCTGCGCTCTCGCAGCTGCTGATGCAGACACGATT

TGCATAGGGTATCATGCAAACAATAGTACAGACACTGTGGACACCGTGCTGGAGAAAAAC

GTGACTGTCACGCACTCAGTTAATCTTTTGGAGGACTCCCATAATGGAAAACTGTGCAGA

CTTAAGGGGATCGCACCCCTGCAGTTAGGCAAGTGTAATATAGCCGGGTGGCTTCTGGGG

AACCCAGAATGTGACCCACTGTTACCTGTGCGAAGCTGGTCTTACATAGTGGAGACGCCA

AATTCTGAGAACGGCATCTGTTACCCTGGGGACTTTATTGATTATGAGGAACTCCGGGAA

CAACTCTCGAGCGTTAGCAGCTTCGAAAGGTTTGAAATTTTTCCCAAGGAATCTTCATGG

CCTAACCACAACACTAACGGTGTGACGGCTGCTTGCTCACATGAGGGAAAGTCCAGTTTC

TATAGGAACCTGTTGTGGCTGACTGAGAAAGAAGGCAGCTACCCAAAGCTGAAGAACTCT

TACGTTAACAAAAAAGGCAAGGAAGTGTTAGTACTGTGGGGTATCCACCACCCACCAAAC

AGCAAGGAGCAGCAGAACTTGTACCAGAACGAAAATGCCTACGTCAGTGTTGTCACATCA

AACTACAATAGAAGATTTACGCCAGAAATTGCCGAAAGGCCAAAGGTGCGGGACCAAGCT

GGGCGGATGAACTATTATTGGACCCTTCTGAAGCCGGGAGACACGATCATATTCGAAGCA

AACGGGAATCTGATCGCTCCGATGTACGCCTTCGCACTCAGCCGGGGTTTTGGATCAGGG

ATCATCACATCTAACGCCTCTATGCATGAATGTAACACGAAGTGCCAGACTCCTCTAGGC

GCTATCAACTCTAGCTTACCCTACCAGAATATACATCCCGTCACCATCGGCGAGTGTCCT

AAGTATGTGCGCAGCGCCAAACTGCGGATGGTGACTGGCCTGAGAAATAATCCGTCCATC

CAGTCAAGAGGGCTGTTTGGAGCAATCGCCGGCTTCATTGAAGGGGGCTGGACAGGTATG

ATTGATGGTTGGTACGGATACCACCATCAGAATGAACAGGGGAGTGGCTACGCAGCAGAT

CAAAAGTCGACACAAAACGCGATAAACGGAATCACAAACAAGGTCAATACCGTGATTGAA

AAGATGAATATTCAGTTCACCGCCGTCGGCAAAGAATTTAACAAGCTTGAGAAACGTATG

GAAAATCTCAATAAGAAAGTTGACGACGGTTTCTTAGACATCTGGACCTATAACGCAGAA

CTGCTGGTGCTACTGGAAAACGAGAGAACCCTTGATTTCCATGATAGCAACGTGAAAAAC

CTTTACGAGAAAGTTAAGAGTCAGCTCAAAAACAATGCTAAAGAAATCGGAAACGGCTGC

TTCGAGTTTTATCATAAGTGCGACAATGAGTGTATGGAGAGTGTTCGAAACGGGACATAT

GATTACCCGAAGTATTCAGAGGAGAGCAAACTCAATCGCGAAAAAGTTGATGGTGTGAAG

CTGGAATCTATGGGCATCTACCAGATACTGGCCATCTACTCAACAGTGGCAAGTTCTCTG

GTATTGCTCGTTTCCCTGGGAGCTATCTCCTTCTGGATGTGTTCGAACGGCTCACTTCAG

TGTAGGATTTGCATA

407
ATGAAGGCCAACCTGTTGGTTCTCTTGTGTGCTCTGGCAGCCGCAGACGCTGACACTATT

TGTATCGGATACCACGCCAATAATAGTACTGACACCGTTGACACAGTACTTGAGAAGAAC

GTGACAGTAACCCACTCAGTGAACCTCCTTGAGGATAGCCACAATGGAAAATTATGTAGA

CTTAAGGGTATCGCTCCCCTCCAGCTGGGCAAATGTAATATTGCCGGCTGGCTACTGGGG

AATCCGGAATGTGATCCTCTCCTGCCAGTCCGATCATGGAGTTATATAGTAGAAACTCCA

AATAGCGAGAATGGAATTTGTTACCCCGGCGATTTTATTGACTACGAAGAGCTCCGAGAA

CAGCTCAGTTCAGTGTCTTCATTCGAACGGTTTGAAATCTTCCCAAAAGAATCCTCATGG

CCCAATCACAACACTAACGGGGTCACGGCAGCATGCAGCCACGAAGGGAAGTCGTCTTTC

TACCGAAATCTCCTGTGGCTGACCGAGAAAGAGGGTTCGTACCCCAAGCTCAAGAATTCT

TACGTTAACAAGAAGGGGAAGGAAGTACTTGTGCTGTGGGGTATACACCATCCACCTAAT

TCCAAAGAGCAGCAGAACCTGTATCAAAACGAAAATGCATACGTCAGCGTGGTTACAAGT

AACTACAACAGGCGCTTTACCCCAGAGATCGCCGAGAGGCCTAAGGTTCGGGATCAGGCC

GGGAGAATGAACTACTATTGGACTCTCCTCAAGCCCGGTGACACAATAATCTTCGAGGCC

AATGGAAATCTTATAGCACCGATGTATGCCTTCGCACTGTCACGCGGGTTTGGCTCAGGC

ATTATAACATCTAACGCTAGTATGCATGAGTGCAATACCAAGTGCCAGACCCCACTGGGT

GCAATCAACAGCTCCTTGCCTTACCAGAACATACACCCAGTCACTATTGGCGAGTGCCCG

AAATACGTACGCTCTGCCAAGCTGCGTATGGTCACCGGACTCCGCAATAACCCCAGTATC

CAAAGCCGAGGTTTGTTTGGCGCTATTGCTGGATTCATTGAAGGAGGCTGGACGGGAATG

ATTGACGGGTGGTACGGCTATCATCATCAGAATGAGCAAGGGTCAGGTTACGCCGCCGAC

CAGAAGAGTACACAGAATGCAATCAACGGAATAACCAATAAGGTCAACACCGTCATCGAA

AAGATGAATATCCAGTTCACGGCAGTGGGAAAGGAATTCAATAAGCTAGAAAAACGCATG

GAGAATCTCAACAAGAAGGTTGACGATGGGTTTCTGGATATCTGGACATACAACGCTGAG

CTGCTTGTGCTGCTGGAGAACGAGAGGACACTGGACTTCCACGACTCTAATGTCAAGAAT

CTTTATGAAAAAGTCAAATCCCAGCTCAAAAATAATGCAAAGGAGATCGGAAATGGCTGC

TTCGAATTCTACCACAAGTGTGACAACGAGTGCATGGAGTCTGTGCGGAACGGAACCTAC

GACTATCCAAAGTATTCTGAGGAATCAAAACTCAATCGAGAGAAAGTTGATGGGGTAAAA

CTGGAATCTATGGGGATTTACCAGATCCTGGCCATCTACTCCACAGTGGCTAGTTCCTTG

GTTCTGTTGGTGTCTCTAGGTGCGATCTCCTTCTGGATGTGTTCCAATGGGAGTCTTCAA

TGTCGAATCTGCATA

408
ATGAAGGCAAATTTGCTTGTTTTACTGTGTGCTTTGGCTGCGGCTGATGCCGACACCATA

TGCATCGGTTACCACGCTAATAACAGCACCGACACAGTGGATACGGTGCTGGAGAAAAAT

GTGACCGTAACTCACAGTGTGAACCTGCTTGAGGACAGCCACAACGGTAAGCTCTGCCGT

CTGAAAGGAATCGCCCCGCTGCAATTGGGAAAGTGCAACATTGCTGGCTGGCTCCTGGGT

AATCCTGAGTGTGACCCGCTGCTGCCCGTGCGAAGCTGGTCCTACATCGTGGAGACTCCA

AACTCAGAGAACGGGATCTGTTACCCTGGAGATTTTATAGACTATGAAGAGCTAAGGGAA

CAATTGTCGTCTGTCAGTTCCTTTGAACGGTTCGAGATTTTCCCAAAGGAGTCCAGTTGG

CCTAATCATAATACCAATGGTGTCACTGCTGCATGTAGTCACGAAGGCAAGTCCTCATTT

TATCGGAATTTGCTGTGGCTGACTGAGAAGGAGGGCAGCTATCCGAAGTTGAAGAATTCA

TACGTTAATAAAAAAGGTAAGGAAGTGCTTGTCCTTTGGGGCATTCATCATCCCCCTAAC

AGTAAGGAACAGCAGAATCTCTACCAGAACGAGAACGCATACGTGTCCGTGGTTACTAGT

AATTACAATAGGAGGTTCACACCAGAGATTGCGGAACGGCCTAAAGTCCGGGATCAGGCC

GGTAGAATGAACTATTATTGGACTTTGCTGAAACCCGGAGACACAATCATATTCGAAGCT

AATGGTAACCTGATTGCTCCTATGTACGCATTCGCTCTGTCCCGTGGCTTCGGCTCCGGG

ATTATCACCTCTAATGCTAGCATGCACGAGTGTAACACCAAATGCCAGACCCCACTCGGG

GCGATTAACAGCAGCCTCCCATACCAGAACATTCATCCCGTTACTATAGGCGAGTGCCCA

AAATATGTTCGGTCTGCAAAACTGCGGATGGTGACGGGGCTGCGAAATAACCCTTCAATA

CAGAGTAGGGGGCTGTTCGGAGCAATAGCTGGTTTTATTGAGGGCGGATGGACTGGCATG

ATCGATGGCTGGTATGGATACCATCACCAAAACGAGCAAGGATCTGGTTATGCAGCGGAC

CAGAAGTCAACTCAGAATGCCATTAACGGCATTACTAATAAAGTTAATACCGTTATTGAA

AAGATGAACATTCAGTTTACCGCCGTAGGGAAGGAGTTTAACAAGCTTGAAAAGCGCATG

GAGAACCTCAACAAGAAAGTGGATGATGGGTTCCTTGACATCTGGACATATAACGCCGAA

TTACTAGTGCTTTTGGAAAACGAAAGAACACTGGATTTCCATGACTCCAATGTGAAGAAT

TTATATGAAAAGGTCAAAAGTCAGCTCAAGAATAATGCAAAGGAAATCGGCAATGGTTGC

TTCGAATTTTACCATAAGTGTGACAACGAGTGTATGGAGAGTGTAAGGAATGGGACATAC

GATTACCCAAAGTATAGCGAGGAATCAAAGCTGAACAGAGAGAAAGTGGACGGCGTGAAA

TTGGAGTCCATGGGGATCTACCAGATTCTGGCGATCTATAGCACCGTCGCCAGCAGCTTG

GTCTTGCTGGTATCTCTCGGGGCCATTTCCTTTTGGATGTGTTCAAATGGGAGCCTCCAA

TGTAGAATCTGTATC

409
ATGAAAGCCAATCTACTGGTGTTGCTCTGTGCCCTGGCTGCTGCCGATGCTGACACGATA

TGTATCGGCTACCACGCAAACAACTCCACCGATACAGTTGATACCGTGCTCGAAAAGAAT

GTCACCGTAACACATAGCGTGAACCTTTTGGAGGATTCGCACAACGGTAAGCTGTGTCGT

TTAAAGGGCATCGCCCCTCTTCAGCTGGGAAAATGCAATATTGCGGGCTGGTTGCTCGGT

AACCCCGAGTGTGACCCTCTGCTCCCCGTGCGTAGTTGGTCATATATTGTGGAGACACCC

AATAGCGAGAATGGAATTTGTTACCCCGGGGACTTTATCGATTACGAAGAGCTGCGGGAA

CAACTGTCTAGTGTCAGCTCGTTCGAACGCTTTGAGATTTTCCCAAAAGAGAGCTCCTGG

CCCAACCATAACACTAACGGGGTGACTGCTGCCTGTTCCCATGAGGGGAAGTCTAGTTTT

TACCGAAATCTGCTGTGGCTAACGGAGAAAGAGGGCTCTTATCCAAAGCTAAAGAATAGT

TACGTAAACAAGAAAGGAAAAGAGGTGCTCGTTCTCTGGGGCATTCATCACCCACCAAAC

TCCAAGGAGCAGCAGAATCTGTATCAGAATGAAAACGCCTACGTATCCGTGGTGACAAGC

AACTACAACAGGCGATTCACGCCCGAGATCGCCGAGCGGCCTAAAGTGAGGGATCAGGCT

GGCAGGATGAACTACTATTGGACGCTGCTGAAGCCAGGGGATACTATTATTTTTGAGGCG

AACGGAAACTTAATTGCCCCCATGTACGCATTTGCGCTCTCCAGAGGATTCGGCTCTGGA

ATCATCACGTCAAACGCTAGCATGCACGAGTGTAATACAAAGTGTCAGACCCCACTGGGG

GCAATCAATAGCAGCTTACCTTACCAAAACATCCATCCAGTGACTATCGGTGAATGCCCG

AAGTACGTAAGGTCCGCAAAGCTGAGAATGGTGACGGGCCTCAGAAATAACCCTAGTATA

CAGAGTCGTGGCCTGTTTGGGGCCATTGCTGGATTTATCGAAGGAGGGTGGACCGGAATG

ATAGACGGCTGGTATGGCTACCACCACCAGAATGAGCAGGGATCTGGGTACGCTGCTGAT

CAGAAGAGCACGCAGAACGCCATTAACGGCATAACCAACAAGGTGAATACAGTCATCGAA

AAAATGAACATACAGTTTACAGCAGTTGGGAAAGAATTCAACAAACTGGAGAAGAGGATG

GAAAACTTGAACAAAAAAGTCGATGACGGGTTTCTCGACATCTGGACTTACAACGCCGAG

CTGCTTGTGTTACTGGAGAACGAAAGGACACTCGACTTTCACGACTCTAACGTGAAGAAT

CTTTATGAGAAAGTGAAAAGCCAACTGAAAAACAATGCCAAAGAAATTGGTAACGGCTGC

TTCGAGTTTTACCATAAGTGTGACAACGAGTGTATGGAATCAGTCCGCAACGGTACCTAC

GACTATCCAAAATACTCTGAAGAATCAAAGCTGAATAGGGAGAAGGTGGACGGCGTTAAA

TTGGAGAGCATGGGCATTTATCAAATCCTTGCCATTTATTCGACAGTGGCCTCCTCTTTA

GTGCTCTTAGTGTCCCTGGGCGCCATCAGTTTCTGGATGTGTAGTAACGGCTCACTCCAA

TGTCGAATTTGCATT

410
ATGAAAGCGAACCTCCTGGTTTTATTGTGCGCACTTGCCGCTGCTGATGCAGACACCATC

TGTATTGGGTATCACGCGAACAATTCGACCGACACGGTCGATACAGTGCTTGAGAAAAAT

GTGACTGTAACACATTCCGTGAATCTCCTCGAAGACAGCCATAACGGGAAGCTTTGCAGG

CTTAAGGGGATTGCACCGCTGCAGCTCGGGAAATGTAATATAGCCGGGTGGCTATTAGGG

AACCCGGAGTGCGACCCTTTGCTTCCAGTGAGGTCCTGGTCATATATTGTCGAGACCCCA

AATTCAGAAAACGGGATCTGTTACCCCGGCGACTTCATTGACTACGAAGAGCTGAGGGAA

CAATTAAGTTCTGTCTCCTCTTTTGAACGGTTTGAGATATTCCCAAAAGAGTCCTCCTGG

CCCAATCATAACACGAATGGCGTGACAGCTGCGTGTAGCCATGAAGGGAAGAGCAGTTTC

TACAGGAATCTTCTTTGGTTAACAGAAAAAGAAGGTAGTTATCCGAAACTGAAAAACAGC

TACGTAAATAAAAAAGGCAAGGAGGTCCTGGTGTTGTGGGGCATTCATCACCCTCCCAAT

AGCAAGGAACAGCAGAATCTCTATCAGAATGAAAACGCCTATGTCAGCGTTGTTACTAGC

AACTACAACCGGCGGTTTACCCCCGAAATTGCTGAGCGACCCAAAGTTCGCGATCAGGCC

GGTCGGATGAATTACTACTGGACCCTTCTGAAGCCTGGCGACACCATTATTTTTGAGGCC

AACGGCAACCTAATTGCCCCAATGTATGCATTCGCCCTGAGCCGAGGTTTTGGAAGTGGC

ATAATCACGTCCAATGCCTCTATGCACGAATGCAACACCAAGTGCCAGACACCCCTTGGC

GCTATCAACTCTTCTCTACCTTATCAGAACATCCATCCCGTTACTATTGGGGAGTGCCCC

AAATACGTCCGGTCTGCTAAACTTCGGATGGTGACAGGCCTCCGCAATAATCCTTCGATT

CAAAGTCGGGGCCTGTTTGGTGCAATCGCCGGGTTCATTGAGGGAGGGTGGACTGGCATG

ATCGACGGTTGGTATGGGTACCACCATCAGAACGAACAAGGCAGTGGGTACGCTGCCGAT

CAGAAAAGCACCCAGAATGCTATCAACGGCATTACGAACAAGGTGAACACTGTGATAGAG

AAGATGAACATCCAGTTCACTGCTGTCGGTAAAGAGTTTAACAAACTTGAAAAAAGAATG

GAGAACCTCAATAAAAAGGTGGACGATGGTTTCCTGGATATATGGACATATAACGCCGAA

CTACTTGTGCTCTTGGAAAATGAACGGACACTGGACTTCCACGACTCTAATGTGAAAAAT

TTATATGAGAAAGTGAAGTCACAGCTCAAGAATAACGCGAAGGAAATTGGCAACGGGTGT

TTCGAGTTCTATCATAAGTGCGACAATGAGTGCATGGAATCAGTTCGAAATGGAACCTAT

GACTATCCAAAGTACTCAGAAGAGAGTAAACTGAACCGGGAGAAAGTCGACGGAGTCAAG

CTCGAATCTATGGGTATTTATCAGATTCTGGCCATCTACAGCACAGTCGCTTCTTCTCTT

GTACTGCTGGTTTCTTTGGGCGCAATCTCTTTCTGGATGTGCTCAAACGGGAGCCTGCAG

TGCCGGATCTGCATC

411
ATGAAGGCTAATCTGTTAGTACTTTTATGTGCACTTGCCGCAGCTGACGCGGATACGATC

TGCATTGGGTACCATGCCAACAACAGTACCGACACCGTCGATACCGTTTTGGAAAAGAAT

GTGACCGTGACCCACAGCGTCAACCTTCTCGAGGATAGTCACAATGGGAAACTCTGTCGG

CTGAAAGGCATAGCTCCTCTGCAGCTCGGAAAATGTAACATCGCCGGCTGGTTATTGGGG

AACCCCGAATGCGATCCCCTCCTCCCAGTAAGGTCTTGGTCCTATATCGTGGAAACACCT

AACAGCGAGAATGGCATCTGCTACCCCGGGGACTTCATTGATTACGAAGAACTAAGAGAA

CAACTGTCGAGTGTGAGTAGTTTCGAAAGATTTGAAATATTCCCTAAGGAGTCAAGTTGG

CCCAATCACAACACGAACGGCGTTACGGCAGCGTGCTCCCATGAAGGGAAATCAAGCTTC

TATAGAAATCTGCTCTGGCTAACAGAAAAGGAGGGCTCATACCCAAAGTTGAAGAACTCC

TACGTCAATAAAAAAGGTAAGGAAGTATTGGTCCTGTGGGGGATCCATCACCCCCCAAAT

TCGAAAGAGCAACAGAACCTTTATCAGAATGAGAATGCTTACGTTAGCGTAGTTACGAGC

AACTATAATCGGCGATTCACACCCGAGATTGCTGAGAGACCTAAGGTGAGAGATCAGGCA

GGTCGGATGAACTACTACTGGACTCTTCTAAAGCCCGGCGATACTATAATCTTTGAGGCT

AACGGCAATCTGATTGCCCCTATGTATGCTTTCGCATTGTCCAGAGGTTTTGGGAGTGGG

ATCATCACGAGCAATGCCAGTATGCATGAGTGTAACACTAAATGTCAGACACCCTTAGGG

GCTATCAACAGTTCTCTTCCCTATCAGAATATCCACCCAGTAACCATCGGAGAATGCCCT

AAATACGTCAGATCTGCAAAACTCAGGATGGTGACTGGCCTCAGAAATAACCCCAGTATA

CAGAGCAGAGGTTTATTCGGGGCGATCGCTGGCTTTATAGAAGGAGGCTGGACGGGCATG

ATTGACGGCTGGTATGGCTATCATCATCAGAATGAACAGGGCAGCGGTTACGCAGCCGAC

CAGAAGAGCACACAAAACGCTATTAACGGAATCACCAACAAGGTGAATACAGTCATTGAA

AAAATGAATATTCAATTCACTGCAGTCGGAAAGGAATTCAACAAACTGGAAAAAAGGATG

GAGAATCTCAACAAAAAAGTCGACGACGGGTTCCTGGATATCTGGACATACAATGCCGAA

CTCCTCGTCCTGCTCGAGAATGAGCGGACCCTTGATTTCCACGATTCCAATGTCAAGAAC

CTTTACGAGAAGGTGAAATCCCAGTTAAAGAATAACGCCAAAGAGATTGGCAATGGGTGC

TTCGAATTTTATCACAAGTGCGACAACGAGTGTATGGAAAGCGTCAGAAATGGCACCTAC

GACTATCCTAAATATTCAGAAGAGTCTAAACTGAATAGGGAAAAAGTCGACGGCGTCAAG

CTTGAGTCTATGGGGATATATCAGATTCTTGCGATTTATTCAACTGTCGCATCCTCCCTC

GTTCTGCTCGTGTCCCTGGGCGCAATCTCATTCTGGATGTGCTCTAATGGTTCATTGCAG

TGTCGCATCTGTATC

412
ATGAAGGCAAACCTGCTGGTTCTTCTGTGTGCATTAGCCGCGGCCGACGCCGATACAATA

TGTATCGGATACCACGCAAATAACAGCACCGACACCGTTGACACAGTGCTTGAGAAAAAC

GTGACCGTGACACACAGTGTGAATCTGCTAGAGGACTCCCATAACGGGAAGCTGTGCCGG

TTGAAGGGAATCGCTCCGCTGCAGTTGGGCAAATGCAATATTGCTGGGTGGCTGTTAGGT

AACCCTGAATGCGATCCACTCCTCCCTGTACGTTCTTGGTCGTATATAGTGGAAACTCCC

AATAGCGAAAATGGTATTTGTTATCCTGGGGATTTCATAGATTACGAAGAGCTGCGCGAA

CAGCTCAGCTCTGTGAGCTCTTTCGAGCGCTTCGAAATATTCCCCAAGGAGTCCAGTTGG

CCCAACCACAATACCAACGGCGTTACCGCAGCCTGTAGCCACGAGGGCAAGTCCAGCTTT

TACCGCAACCTCTTGTGGTTGACCGAAAAGGAGGGAAGCTATCCGAAACTCAAGAACAGC

TACGTCAATAAAAAAGGCAAGGAGGTACTAGTGCTGTGGGGCATCCACCACCCTCCAAAT

AGTAAAGAGCAGCAGAATCTGTATCAGAACGAAAACGCGTATGTCTCAGTTGTGACAAGC

AATTACAACCGCAGGTTCACTCCGGAGATAGCTGAAAGACCCAAAGTACGGGATCAGGCT

GGGCGAATGAACTACTACTGGACACTACTCAAACCAGGTGACACCATTATTTTCGAAGCA

AATGGCAATTTGATCGCACCCATGTACGCATTTGCCTTGTCCCGGGGGTTCGGCTCCGGC

ATTATTACGTCTAACGCATCTATGCACGAGTGCAACACGAAATGCCAGACTCCCCTGGGG

GCCATAAACTCAAGCCTGCCATATCAGAACATCCACCCGGTCACCATCGGCGAGTGCCCC

AAATACGTCCGCTCAGCTAAACTCAGGATGGTCACGGGCCTCAGAAATAATCCTAGCATT

CAGTCTCGCGGTCTGTTTGGCGCCATCGCAGGCTTCATTGAAGGGGGCTGGACCGGAATG

ATCGATGGGTGGTACGGGTATCATCACCAGAACGAGCAAGGCAGTGGCTATGCTGCCGAT

CAGAAATCAACCCAGAATGCGATTAACGGAATAACTAACAAGGTGAACACCGTCATTGAG

AAGATGAATATTCAGTTCACGGCCGTCGGAAAGGAGTTTAACAAGCTCGAAAAGCGCATG

GAGAACCTGAACAAGAAGGTAGATGATGGCTTCCTGGACATTTGGACCTACAATGCTGAG

CTCCTCGTCTTGCTGGAGAATGAACGGACTCTCGACTTCCACGATTCCAACGTTAAGAAT

TTATATGAGAAAGTGAAGAGTCAACTTAAAAACAACGCGAAGGAAATCGGTAATGGCTGC

TTTGAGTTCTACCATAAGTGTGATAACGAGTGTATGGAAAGCGTGCGAAATGGGACTTAT

GACTACCCTAAGTATTCGGAAGAATCTAAACTGAATAGAGAGAAGGTGGATGGGGTGAAG

CTCGAATCTATGGGGATTTACCAGATCTTGGCTATCTATTCGACAGTGGCTTCCAGTCTT

GTCCTACTGGTGTCTCTTGGCGCCATTTCCTTCTGGATGTGCTCCAACGGATCTCTGCAG

TGCCGCATCTGTATA

413
ATGAAGGCAAATTTGTTAGTCTTGTTGTGCGCTCTGGCCGCTGCAGATGCAGACACCATC

TGTATCGGGTATCACGCAAATAATTCCACAGATACAGTGGACACCGTTCTCGAGAAAAAC

GTCACCGTGACCCATAGCGTGAACCTTCTCGAGGACTCTCACAACGGTAAATTATGCAGG

CTTAAGGGAATAGCTCCCCTGCAACTTGGTAAGTGCAATATAGCAGGATGGCTCCTGGGC

AACCCAGAATGTGACCCGCTACTGCCAGTGAGGAGCTGGTCTTACATCGTCGAAACGCCT

AACTCCGAAAACGGGATCTGTTATCCTGGCGATTTCATTGATTATGAAGAGTTACGGGAG

CAGTTATCAAGCGTGTCGAGCTTCGAAAGGTTTGAGATCTTCCCTAAGGAGTCAAGTTGG

CCGAACCACAACACGAATGGCGTCACAGCCGCATGTTCCCATGAAGGGAAGTCCTCTTTC

TATCGGAATCTTTTGTGGCTAACGGAGAAGGAGGGATCCTATCCTAAGCTTAAAAACTCC

TACGTAAACAAAAAGGGCAAGGAGGTCTTAGTACTGTGGGGCATACACCACCCACCTAAC

TCAAAGGAGCAGCAGAACCTTTATCAGAATGAAAATGCTTACGTCTCGGTGGTGACCAGC

AACTACAACAGACGCTTCACGCCGGAAATTGCCGAGAGACCAAAGGTAAGGGATCAAGCC

GGTCGAATGAATTACTATTGGACCTTATTGAAACCCGGGGACACCATCATATTTGAAGCT

AACGGCAATTTGATCGCTCCAATGTACGCGTTTGCCCTTTCCCGCGGGTTCGGTTCTGGG

ATCATAACCTCTAACGCTTCCATGCATGAATGTAACACAAAGTGCCAGACTCCATTAGGG

GCCATTAATAGCAGTTTACCTTATCAAAATATCCACCCAGTCACTATCGGAGAGTGCCCA

AAATACGTGAGGAGCGCGAAATTGAGGATGGTGACAGGCCTTCGGAACAATCCCTCTATC

CAGAGCAGAGGACTGTTTGGCGCAATTGCTGGGTTTATAGAGGGGGGATGGACCGGCATG

ATTGACGGATGGTACGGATACCATCATCAGAATGAGCAGGGAAGTGGATATGCTGCAGAC

CAAAAGTCAACTCAGAATGCTATTAATGGTATCACCAACAAGGTGAACACAGTCATAGAA

AAGATGAACATCCAGTTTACCGCCGTTGGGAAGGAATTTAACAAGCTGGAAAAAAGGATG

GAGAATCTCAATAAAAAGGTAGACGATGGGTTCCTTGATATTTGGACTTACAATGCTGAG

CTGTTAGTCCTACTAGAAAATGAGAGAACCCTTGACTTTCACGACTCCAACGTTAAAAAC

TTATACGAGAAAGTGAAATCCCAATTAAAGAATAACGCGAAAGAGATCGGCAACGGGTGT

TTCGAATTCTATCACAAATGCGACAACGAATGCATGGAGTCTGTGAGGAATGGGACTTAT

GATTATCCCAAGTATTCAGAGGAGTCTAAACTGAATCGAGAAAAAGTGGACGGAGTAAAG

CTGGAGTCCATGGGCATATATCAAATCCTCGCCATCTATTCCACAGTCGCCTCCTCCCTT

GTTTTGTTGGTTTCCCTTGGTGCGATCAGTTTTTGGATGTGCTCTAACGGGTCCCTACAG

TGCCGAATTTGTATT

414
ATGAAAGCTAATCTTCTCGTGCTACTGTGCGCCTTAGCAGCTGCCGACGCTGATACCATC

TGTATAGGCTATCATGCCAATAACTCCACAGACACCGTTGATACTGTGCTTGAGAAGAAT

GTGACGGTAACCCACAGCGTTAATCTCCTTGAGGACAGCCATAATGGCAAACTGTGTCGG

CTGAAGGGAATCGCTCCCCTACAATTGGGAAAATGCAACATTGCAGGATGGTTGTTAGGA

AACCCAGAATGCGACCCTCTACTGCCAGTGCGCAGCTGGAGTTACATTGTTGAAACACCT

AACAGCGAAAATGGTATTTGCTACCCTGGGGATTTCATAGATTACGAGGAGTTAAGAGAG

CAGCTGTCCAGTGTGTCTTCCTTCGAAAGGTTTGAAATCTTCCCAAAGGAGTCCTCATGG

CCCAACCACAACACGAATGGCGTCACAGCTGCCTGTTCACACGAGGGTAAGTCAAGTTTT

TATAGGAACTTGCTTTGGTTAACCGAAAAAGAGGGAAGCTACCCAAAGCTGAAAAATAGC

TACGTGAATAAAAAGGGCAAAGAGGTGCTGGTGCTATGGGGTATCCATCATCCGCCAAAC

AGCAAAGAGCAGCAAAACCTGTACCAGAACGAAAATGCCTACGTGTCTGTTGTGACGAGC

AACTACAACCGTAGATTTACCCCGGAAATCGCAGAGCGGCCGAAGGTGCGCGATCAGGCG

GGACGTATGAATTACTATTGGACATTGCTTAAGCCCGGAGACACAATTATTTTCGAAGCT

AACGGGAATCTCATTGCCCCAATGTATGCTTTCGCACTGAGCCGAGGCTTTGGGAGCGGC

ATCATCACAAGTAATGCTAGCATGCATGAGTGCAATACCAAGTGTCAAACGCCTCTGGGC

GCAATCAATTCCAGTTTACCATATCAGAACATTCATCCAGTCACCATCGGGGAGTGCCCT

AAATATGTAAGGTCTGCTAAACTGCGGATGGTCACTGGTCTCCGCAACAATCCATCTATC

CAGAGCCGGGGTTTGTTCGGAGCTATTGCTGGATTTATAGAGGGGGGCTGGACGGGGATG

ATTGATGGCTGGTACGGCTATCACCATCAGAACGAACAGGGCAGCGGCTACGCTGCAGAC

CAAAAAAGTACTCAGAACGCTATTAATGGCATTACCAACAAGGTTAACACTGTGATTGAG

AAGATGAACATCCAGTTCACTGCGGTAGGAAAGGAATTCAACAAACTTGAGAAGCGGATG

GAAAATCTCAACAAGAAGGTAGACGATGGGTTCCTAGATATATGGACCTATAATGCCGAG

CTCTTGGTCTTGTTAGAAAACGAGCGGACCTTAGACTTCCATGATAGCAACGTGAAAAAC

CTGTACGAGAAAGTGAAGAGCCAGTTAAAGAATAACGCTAAGGAAATCGGAAACGGGTGC

TTTGAGTTCTACCATAAGTGTGACAATGAGTGTATGGAATCTGTGCGTAACGGGACCTAC

GACTACCCCAAATATTCTGAGGAATCAAAACTAAATCGAGAGAAGGTAGACGGCGTGAAG

TTAGAATCTATGGGTATCTATCAAATCCTGGCTATATACTCAACCGTGGCCTCATCCCTA

GTTCTCCTGGTATCCCTCGGCGCCATCTCTTTCTGGATGTGCAGCAACGGCTCTCTCCAG

TGTCGCATTTGCATC

415
ATGAAGGCCAATTTGCTGGTGTTGTTGTGTGCTCTGGCAGCAGCCGATGCTGACACTATC

TGCATCGGCTACCATGCCAACAATAGTACCGATACTGTGGACACTGTGTTAGAGAAGAAC

GTGACAGTCACTCACTCAGTAAACTTGCTGGAGGATAGCCATAATGGCAAACTCTGTCGC

CTCAAGGGCATCGCCCCTCTGCAGCTGGGAAAATGCAACATTGCTGGATGGCTGCTGGGG

AACCCGGAATGCGACCCGCTGCTCCCCGTGAGATCCTGGAGTTATATAGTTGAAACTCCC

AACAGTGAGAACGGGATATGTTATCCTGGCGACTTCATTGACTACGAGGAGCTGCGCGAA

CAGCTCTCTAGCGTATCTTCGTTTGAACGTTTCGAAATATTTCCCAAGGAATCTTCTTGG

CCAAATCACAATACCAACGGAGTCACGGCGGCCTGCTCGCACGAGGGGAAGAGTTCCTTT

TATCGCAACCTACTGTGGCTCACCGAGAAGGAGGGTTCCTACCCCAAGCTGAAAAACAGC

TATGTGAACAAAAAAGGCAAAGAAGTCTTGGTACTGTGGGGCATTCATCACCCACCCAAC

AGCAAGGAACAGCAGAACCTGTATCAAAATGAAAATGCTTACGTCTCCGTTGTGACATCA

AACTACAACAGACGGTTCACCCCTGAAATTGCTGAGAGGCCTAAGGTCAGGGACCAGGCC

GGGCGGATGAATTACTACTGGACACTGCTGAAGCCGGGAGACACGATTATCTTCGAAGCA

AACGGCAATCTGATCGCCCCAATGTACGCGTTTGCTCTTTCTCGGGGATTTGGCTCTGGG

ATCATTACCTCTAATGCATCCATGCACGAATGCAACACCAAATGTCAGACCCCACTAGGC

GCTATTAATAGTTCCCTGCCCTATCAGAATATCCACCCGGTGACCATCGGCGAATGTCCT

AAATATGTGCGGAGTGCCAAGCTGAGGATGGTCACTGGCTTACGTAACAATCCCTCAATT

CAGAGCCGGGGCCTCTTTGGAGCAATCGCTGGATTCATCGAGGGGGGTTGGACCGGAATG

ATCGACGGCTGGTACGGATATCATCACCAGAATGAACAAGGGTCTGGCTACGCCGCCGAC

CAAAAATCTACCCAAAACGCTATTAATGGGATTACCAATAAGGTGAACACTGTAATAGAA

AAAATGAATATTCAGTTTACTGCCGTTGGAAAGGAATTCAATAAGCTGGAGAAACGTATG

GAGAATCTGAACAAGAAGGTAGATGACGGATTCCTGGACATCTGGACCTATAATGCAGAA

TTGCTCGTTCTGCTTGAAAATGAGCGCACACTGGACTTTCATGACTCTAACGTCAAAAAT

CTGTATGAAAAGGTCAAGTCCCAGCTGAAAAATAATGCGAAAGAGATTGGGAACGGATGT

TTCGAATTCTACCACAAGTGTGACAACGAATGCATGGAGTCCGTACGGAACGGCACGTAC

GACTACCCAAAATATTCTGAGGAAAGCAAGCTGAATAGAGAAAAGGTCGATGGGGTGAAA

CTGGAGAGTATGGGAATCTATCAGATTCTCGCCATCTACTCCACTGTCGCCAGCTCCTTG

GTACTTCTTGTTAGCTTGGGAGCCATATCATTCTGGATGTGCTCCAATGGATCCCTCCAA

TGCAGAATCTGCATC

416
ATGAAAGCTAACCTTTTGGTGCTGCTCTGTGCCCTGGCAGCTGCCGATGCCGATACCATC

TGTATCGGCTACCATGCTAATAATAGTACAGACACAGTGGACACCGTTCTGGAGAAAAAT

GTCACCGTGACACATAGCGTGAACTTGCTGGAGGATTCTCACAACGGGAAGCTGTGCCGT

CTGAAAGGGATTGCCCCTCTTCAGCTCGGTAAATGCAACATCGCCGGGTGGCTGCTAGGC

AATCCAGAGTGTGATCCCCTGCTGCCGGTGAGAAGCTGGAGCTACATCGTGGAGACACCC

AACTCCGAAAATGGCATTTGCTACCCCGGCGATTTCATCGACTACGAAGAACTGCGGGAG

CAGCTGTCGTCTGTGAGCTCCTTCGAGAGATTCGAGATCTTTCCAAAAGAAAGCAGTTGG

CCCAATCACAATACCAACGGCGTGACCGCTGCATGTAGTCACGAGGGCAAGAGCTCATTC

TATAGAAACCTGTTGTGGCTGACAGAGAAGGAGGGGAGCTATCCCAAACTGAAGAATTCC

TATGTGAATAAAAAGGGGAAGGAGGTTCTGGTATTATGGGGCATCCATCATCCTCCTAAC

AGCAAAGAGCAGCAAAACCTTTATCAGAACGAGAATGCCTATGTATCGGTTGTTACCAGC

AATTATAATCGGAGGTTTACCCCAGAGATAGCTGAGCGTCCAAAAGTGAGAGACCAAGCT

GGCCGGATGAATTACTATTGGACCCTCCTCAAACCGGGCGATACCATCATTTTCGAAGCC

AATGGCAACTTAATAGCGCCCATGTATGCTTTTGCCCTTTCGAGGGGATTTGGATCAGGT

ATCATCACAAGCAACGCATCAATGCACGAGTGTAACACTAAGTGTCAGACTCCACTCGGG

GCAATTAACAGCAGCCTACCTTACCAGAACATCCACCCCGTGACGATTGGAGAGTGTCCC

AAGTACGTAAGGTCAGCCAAGCTCAGGATGGTTACAGGGCTGCGAAATAACCCCTCTATT

CAGTCAAGGGGCTTGTTCGGCGCCATCGCCGGGTTTATCGAGGGCGGCTGGACCGGAATG

ATCGACGGATGGTATGGCTACCATCACCAGAACGAACAAGGGTCTGGCTATGCTGCGGAT

CAGAAGTCAACACAGAATGCTATAAATGGTATCACGAATAAGGTAAATACAGTCATTGAA

AAGATGAATATCCAGTTTACGGCCGTTGGGAAGGAGTTCAACAAGCTTGAAAAGAGAATG

GAAAATCTGAATAAAAAAGTGGACGACGGCTTTTTGGATATCTGGACATATAACGCGGAG

CTGCTAGTGCTCCTGGAAAACGAGCGGACTCTTGACTTTCACGATTCCAACGTCAAGAAC

CTCTATGAAAAGGTTAAATCACAATTGAAGAATAATGCTAAGGAGATTGGCAATGGGTGC

TTTGAGTTCTACCATAAGTGTGACAACGAATGTATGGAGTCAGTCCGGAACGGTACTTAC

GATTACCCCAAGTATTCGGAAGAGTCAAAGTTGAATAGAGAAAAAGTCGACGGCGTGAAA

CTCGAGTCTATGGGCATTTACCAGATCCTTGCGATTTATAGCACCGTCGCCAGTAGCTTG

GTACTCCTAGTATCTCTGGGTGCAATCTCCTTTTGGATGTGTTCTAACGGCAGCTTACAG

TGCAGGATCTGCATT

417
ATGAAAGCTAACTTGCTTGTGTTGTTGTGCGCTTTGGCCGCTGCCGACGCCGACACTATT

TGCATCGGGTATCACGCCAATAATTCCACAGATACCGTCGATACCGTGCTCGAGAAGAAC

GTGACCGTCACTCACTCAGTGAACCTTCTGGAGGACTCCCATAACGGGAAGCTCTGTAGG

TTGAAAGGAATCGCCCCACTGCAGCTTGGTAAATGCAATATAGCCGGTTGGCTGCTGGGA

AACCCTGAGTGCGACCCACTCCTCCCCGTACGGTCTTGGAGCTACATCGTGGAGACGCCA

AATTCCGAGAATGGAATCTGTTATCCCGGCGACTTTATCGATTATGAGGAGTTGCGCGAG

CAGCTGAGTTCAGTTTCATCCTTTGAACGGTTCGAGATTTTTCCAAAAGAGTCTAGCTGG

CCTAATCATAATACCAATGGGGTTACAGCCGCTTGCTCACATGAGGGGAAGTCCAGTTTC

TATAGGAACCTGCTTTGGCTGACCGAGAAAGAGGGCTCCTATCCAAAGCTCAAGAACAGC

TATGTAAATAAGAAAGGCAAGGAAGTGTTGGTCCTGTGGGGCATACACCACCCTCCCAAC

TCGAAGGAGCAGCAAAACCTATACCAGAACGAGAATGCCTACGTCAGCGTGGTCACTAGC

AATTACAATAGAAGGTTCACACCCGAAATTGCTGAGCGGCCGAAAGTGAGAGACCAGGCA

GGACGAATGAACTACTATTGGACCCTGCTGAAGCCCGGGGATACAATCATTTTCGAGGCG

AACGGGAACCTCATTGCCCCCATGTACGCTTTTGCCCTCAGCAGAGGCTTTGGGTCTGGT

ATAATCACCAGTAACGCTAGCATGCATGAATGTAATACCAAGTGCCAGACACCCTTAGGG

GCCATTAACTCATCTCTCCCATATCAGAACATACATCCTGTGACCATCGGTGAATGCCCG

AAATACGTAAGGAGCGCAAAATTAAGGATGGTGACCGGTCTTAGGAACAATCCATCCATT

CAGTCTCGAGGGCTTTTCGGCGCCATTGCTGGATTCATAGAAGGCGGATGGACAGGCATG

ATCGATGGATGGTACGGTTATCACCACCAGAATGAGCAGGGGTCGGGCTACGCTGCCGAT

CAGAAGTCTACCCAAAATGCCATCAATGGCATAACCAACAAGGTGAACACAGTTATCGAG

AAAATGAACATACAGTTTACTGCAGTGGGAAAGGAGTTCAACAAACTGGAGAAACGAATG

GAGAACTTGAATAAAAAAGTCGACGACGGCTTCCTTGATATTTGGACTTATAATGCCGAG

CTTTTAGTCCTGTTAGAGAATGAACGTACATTGGACTTCCACGATAGCAACGTAAAGAAC

CTCTATGAGAAAGTGAAAAGTCAGCTAAAAAATAATGCCAAAGAGATCGGGAATGGTTGT

TTCGAGTTTTATCACAAGTGTGATAATGAGTGCATGGAGTCTGTGAGAAACGGCACGTAC

GATTACCCTAAGTATTCTGAGGAGAGTAAGTTAAATCGCGAGAAAGTTGATGGTGTGAAG

CTTGAGTCAATGGGCATCTACCAGATCCTGGCCATCTACTCCACCGTGGCGTCTTCTCTG

GTGCTGCTTGTTAGCCTGGGTGCTATCTCCTTCTGGATGTGTTCTAACGGCTCCCTGCAG

TGTAGGATTCTGCATC

418
ATGAAAGCAAATCTGCTGGTGTTGCTGTGTGCCCTGGCTGCCGCAGACGCAGATACCATC

TGTATCGGCTATCACGCTAATAACAGTACAGACACTGTGGATACTGTTCTCGAGAAGAAC

GTCACTGTGACCCACTCAGTAAATTTACTCGAAGACAGTCACAACGGCAAGTTGTGTAGA

CTCAAAGGCATTGCCCCTCTCCAGCTGGGAAAGTGCAACATTGCTGGATGGCTCCTGGGG

AACCCCGAATGTGATCCGCTTTTGCCTGTGAGAAGCTGGTCCTACATAGTAGAAACCCCA

AACTCCGAAAATGGTATTTGCTATCCGGGCGATTTTATAGATTATGAAGAATTAAGGGAG

CAGTTGTCTTCCGTGTCCTCCTTCGAACGCTTCGAAATCTTCCCCAAAGAGAGTTCCTGG

CCAAACCATAATACTAACGGGGTGACAGCGGCTTGCTCTCACGAAGGAAAATCTTCCTTC

TACCGGAACCTGCTTTGGTTGACCGAGAAGGAGGGCAGTTACCCGAAATTGAAAAATAGT

TACGTTAATAAGAAAGGGAAGGAAGTCCTGGTGTTATGGGGTATTCATCACCCCCCAAAC

AGCAAGGAGCAGCAAAATTTGTACCAGAACGAGAATGCGTACGTGAGTGTGGTCACCAGT

AATTACAACCGGAGGTTTACCCCCGAGATCGCAGAACGCCCGAAAGTACGGGACCAGGCA

GGGAGGATGAATTACTATTGGACTCTTTTAAAGCCCGGGGATACCATCATCTTTGAGGCA

AACGGTAACCTCATAGCTCCCATGTACGCCTTCGCCCTGAGCCGCGGTTTCGGCAGTGGC

ATTATAACCTCTAACGCCAGCATGCACGAATGTAACACTAAATGTCAGACCCCTCTCGGC

GCCATTAATAGCAGTCTCCCTTACCAAAATATCCACCCCGTTACCATTGGCGAGTGTCCA

AAATACGTAAGGTCCGCAAAACTGCGCATGGTGACTGGACTGAGAAACAATCCCTCTATT

CAGTCGAGGGGACTATTCGGAGCCATCGCTGGGTTTATCGAAGGGGGATGGACTGGAATG

ATCGATGGTTGGTACGGGTACCACCACCAGAACGAGCAAGGCTCAGGGTATGCCGCAGAC

CAGAAGAGTACCCAGAACGCCATCAACGGTATCACTAATAAGGTGAATACCGTCATCGAG

AAGATGAATATCCAGTTTACCGCTGTGGGCAAAGAGTTTAATAAGCTGGAAAAGCGCATG

GAGAACCTGAATAAGAAGGTTGACGACGGCTTCCTCGATATTTGGACTTATAACGCCGAG

CTGCTCGTTCTCCTCGAAAATGAACGCACCCTTGACTTTCACGATTCAAACGTCAAGAAT

CTGTATGAGAAGGTGAAGAGCCAGCTGAAGAATAACGCGAAGGAAATCGGGAACGGTTGT

TTCGAATTTTACCACAAGTGCGATAATGAGTGCATGGAGAGCGTGCGAAATGGCACATAT

GACTATCCTAAGTACAGCGAGGAAAGTAAACTCAACAGAGAAAAGGTTGATGGCGTCAAG

CTCGAGTCAATGGGGATTTACCAGATTCTGGCCATCTATAGTACTGTGGCTTCCTCTCTG

GTTTTGCTCGTTTCACTGGGAGCCATTTCTTTCTGGATGTGTTCGAACGGATCCCTCCAA

TGCAGGATTTGTATT

419
ATGAAAGCAAATCTGCTCGTCCTCCTGTGCGCTCTTGCAGCCGCCGACGCCGACACCATA

TGCATTGGATATCATGCTAACAACTCAACAGACACCGTGGACACTGTCCTAGAAAAAAAC

GTGACCGTGACACACTCGGTCAATCTGTTAGAAGACAGCCATAACGGGAAGCTGTGCCGA

CTCAAGGGAATAGCCCCCCTGCAGCTGGGCAAGTGCAATATCGCCGGGTGGCTCCTCGGC

AACCCTGAGTGCGATCCCTTGCTTCCAGTTAGAAGTTGGTCCTATATCGTCGAAACTCCT

AACTCAGAGAATGGAATTTGCTATCCCGGAGATTTCATCGACTACGAAGAGCTCAGAGAG

CAACTTTCCAGTGTGTCAAGTTTCGAACGCTTTGAAATCTTCCCAAAGGAATCTTCATGG

CCCAACCACAATACGAATGGAGTGACCGCCGCCTGTAGTCACGAGGGAAAAAGTAGCTTC

TACCGCAATCTTTTGTGGCTGACCGAGAAGGAAGGAAGCTACCCAAAGCTGAAGAACTCC

TACGTGAACAAAAAAGGTAAGGAGGTCCTGGTGCTGTGGGGGATTCACCATCCCCCTAAC

AGTAAGGAGCAGCAAAATCTCTACCAGAACGAGAACGCTTACGTATCTGTTGTGACTTCT

AATTATAACAGGAGGTTCACGCCAGAAATTGCTGAGAGGCCAAAGGTCAGGGACCAGGCT

GGGCGCATGAACTACTACTGGACCCTGCTAAAGCCTGGTGACACTATCATCTTTGAGGCC

AATGGAAATTTAATTGCACCCATGTACGCATTTGCCCTATCGCGCGGGTTCGGGAGGGGG

ATAATTACCTCCAACGCATCGATGCATGAGTGCAACACAAAATGTCAAACACCTCTCGGG

GCCATTAACAGCTCCCTCCCCTATCAGAATATTCACCCGGTAACAATCGGTGAATGTCCT

AAGTACGTACGCTCCGCCAAGCTGAGGATGGTAACCGGTCTGCGGAATAATCCTAGCATC

CAGTCCCGGGGTCTTTTCGGCGCCATCGCAGGTTTTATAGAAGGGGGCTGGACTGGTATG

ATCGATGGATGGTACGGGTACCATCACCAAAATGAGCAAGGTTCGGGGTACGCAGCAGAC

CAGAAATCAACCCAAAATGCCATTAACGGAATTACAAATAAGGTTAACACCGTTATCGAA

AAGATGAATATCCAGTTTACAGCCGTAGGGAAAGAATTTAATAAGCTCGAGAAGCGGATG

GAAAACCTGAACAAGAAAGTGGATGACGGGTTCCTTGACATCTGGACTTATAATGCAGAG

CTATTAGTGCTGCTGGAGAACGAACGTACCCTGGATTTCCATGATTCAAACGTCAAAAAT

CTTTATGAGAAAGTTAAGTCCCAGCTCAAGAATAATGCGAAGGAAATCGGCAACGGGTGT

TTCGAATTCTATCACAAGTGCGATAACGAATGCATGGAGAGCGTTAGAAACGGCACCTAT

GACTACCCCAAGTACAGCGAAGAGTCTAAGCTGAACCGGGAAAAGGTCGACGGTGTGAAA

CTGGAATCCATGGGCATTTACCAGATCCTCGCTATTTACTCGACAGTCGCAAGTAGCCTG

GTGCTTTTGGTTTCTCTCGGCGCAATCTCATTCTGGATGTGCTCCAACGGATCCCTCCAG

TGTCGCATCTGTATC

420
ATGAAAGCTAACCTGCTGGTCCTTCTGTGCGCTCTCGCAGCAGCAGATGCGGACACCATC

TGCATAGGATACCATGCTAATAATTCCACAGACACTGTGGACACAGTGCTGGAAAAGAAT

GTAACGGTGACCCACAGCGTTAACTTGCTGGAGGATAGCCACAATGGTAAGCTTTGTCGT

TTGAAAGGGATCGCACCCCTGCAGTTGGGCAAATGTAATATCGCCGGGTGGCTCCTGGGC

AACCCGGAGTGCGACCCTTTGCTGCCCGTGCGGAGTTGGTCATACATTGTGGAAACTCCT

AACAGTGAGAATGGTATTTGCTATCCTGGGGACTTCATTGACTATGAAGAACTTCGCGAA

CAGTTATCTAGCGTGTCTAGCTTTGAACGCTTTGAGATCTTCCCAAAGGAGAGTAGTTGG

CCTAACCATAACACCAACGGGGTCACAGCGGCCTGTTCGCACGAAGGCAAGTCCAGCTTT

TATCGCAATCTGCTGTGGTTGACAGAGAAGGAGGGATCATACCCGAAGCTGAAAAATTCC

TACGTGAACAAGAAGGGCAAAGAAGTACTGGTGTTATGGGGCATTCACCACCCACCAAAT

AGCAAAGAGCAGCAGAACCTTTATCAGAACGAGAACGCCTACGTGAGCGTTGTTACGAGT

AATTACAACCGCCGATTTACTCCCGAGATTGCGGAAAGGCCGAAGGTGAGAGACCAGGCA

GGCCGCATGAACTATTACTGGACACTCCTGAAGCCTGGTGACACAATAATCTTCGAAGCT

AACGGCAACCTGATAGCCCCAATGTACGCCTTTGCCCTAAGTAGAGGTTTCGGCTCTGGA

ATTATTACGTCTAACGCCAGCATGCACGAGTGTAACACTAAATGCCAAACCCCACTAGGT

GCTATTAACTCGTCTCTGCCGTACCAGAATATCCACCCAGTAACGATTGGAGAGTGCCCT

AAATATGTGCGATCAGCAAAGCTTAGAATGGTGACTGGGTTACGCAACAATCCCTCTATT

CAGTCCCGCGGCCTGTTTGGGGCGATAGCCGGATTCATCGAAGGGGGCTGGACGGGCATG

ATTGACGGCTGGTATGGGTATCATCATCAGAACGAACAGGGATCAGGATACGCAGCTGAC

CAAAAATCCACGCAGAACGCCATCAACGGGATCACGAATAAAGTGAATACAGTGATCGAG

AAAATGAACATTCAGTTCACGGCAGTTGGAAAAGAGTTCAACAAACTTGAGAAGAGGATG

GAGAACCTGAATAAAAAGGTGGACGACGGATTCCTGGATATATGGACTTACAATGCCGAA

CTACTCGTCCTACTGGAAAATGAGCGAACGCTGGACTTCCATGATTCGAATGTCAAGAAT

CTGTATGAAAAGGTCAAGTCCCAGCTGAAAAATAATGCTAAAGAGATAGGCAACGGGTGT

TTCGAGTTTTACCATAAGTGCGATAATGAATGTATGGAGTCCGTGCGAAACGGTACTTAC

GACTACCCAAAATACTCAGAGGAGTCCAAACTCAACAGGGAGAAAGTGGACGGGGTTAAG

CTGGAAAGTATGGGTATTTATCAGATCCTGGCCATCTATTCTACAGTTGCATCTTCTCTA

GTGCTGCTGGTATCTCTGGGCGCAATATCTTTTTGGATGTGTTCAAATGGGAGCCTGCAG

TGCCGGATTTGTATC

421
ATGAAAGCAAATCTTCTGGTGTTACTGTGTGCTTTGGCAGCAGCCGATGCTGACACCATA

TGTATTGGCTATCACGCAAACAATTCAACCGACACAGTCGACACCGTCCTCGAAAAGAAC

GTTACCGTGACCCACTCAGTGAACCTCCTCGAGGACTCCCATAATGGCAAGCTGTGTAGG

TTAAAGGGGATCGCCCCACTGCAGTTGGGAAAGTGTAATATTGCTGGGTGGCTTCTGGGT

AACCCCGAATGCGATCCACTCCTCCCCGTTCGCAGCTGGAGTTACATTGTTGAAACCCCA

AACAGCGAGAACGGTATCTGTTACCCAGGAGATTTTATTGATTACGAGGAGTTACGAGAA

CAACTGTCCTCAGTGAGTTCTTTTGAAAGGTTTGAGATATTCCCTAAAGAGAGCAGCTGG

CCGAATCATAACACCAATGGGGTGACTGCAGCTTGCTCCCACGAGGGGAAGTCCTCCTTC

TATCGCAATCTGTTGTGGCTCACCGAAAAGGAGGGATCATATCCGAAGTTGAAAAATAGC

TACGTTAATAAGAAGGGAAAAGAGGTGCTGGTGCTGTGGGGAATCCATCATCCACCTAAT

TCCAAGGAGCAACAGAATCTATACCAAAACGAAAATGCTTACGTTTCTGTGGTGACCTCA

AATTATAACCGCCGCTTCACTCCAGAGATCGCTGAGCGACCAAAAGTGCGGGACCAAGCC

GGCAGAATGAATTACTATTGGACCTTGCTGAAACCCGGAGACACCATAATTTTTGAAGCC

AATGGGAACCTGATTGCCCCTATGTACGCCTTCGCCCTGTCTAGGGGTTTCGGCAGCGGG

ATCATAACATCTAACGCAAGCATGCACGAATGTAATACCAAGTGTCAGACCCCTCTGGGA

GCCATTAATTCCAGTCTCCCATACCAGAACATCCACCCCGTTACCATTGGGGAGTGTCCG

AAATACGTTAGAAGTGCCAAATTACGAATGGTGACAGGATTGCGGAACAACCCCAGCATC

CAGAGCAGAGGCCTATTTGGCGCCATCGCAGGATTCATCGAAGGCGGATGGACCGGAATG

ATCGACGGATGGTACGGGTATCACCACCAGAATGAACAGGGGTCGGGTTACGCCGCCGAC

CAGAAATCTACCCAGAATGCCATTAATGGGATAACAAACAAGGTCAACACCGTGATTGAG

AAGATGAATATACAGTTTACTGCCGTCGGCAAAGAGTTTAATAAACTGGAAAAGCGAATG

GAAAACCTGAACAAGAAAGTCGACGATGGGTTCCTGGATATCTGGACATACAACGCTGAG

TTGCTCGTGCTGCTCGAGAATGAGAGAACCTTGGACTTTCACGATTCAAACGTAAAAAAC

TTATACGAAAAAGTCAAGAGTCAGCTGAAAAATAATGCCAAGGAAATCGGGAACGGATGC

TTTGAGTTCTATCACAAGTGCGACAATGAGTGTATGGAATCCGTTAGGAACGGGACATAC

GATTACCCAAAATACTCCGAGGAGAGCAAGTTAAACAGAGAAAAAGTTGACGGAGTGAAA

CTAGAGTCCATGGGTATTTACCAGATCCTGGCCATTTATTCTACCGTCGCGTCATCACTG

GTACTCCTTGTCTCCCTTGGAGCGATATCCTTCTGGATGTGTTCCAACGGCTCCCTTCAG

TGCCGAATCTGCATT

422
ATGAAGGCTAATCTTCTGGTGTTACTGTGCGCCCTGGCTGCCGCCGACGCCGACACCATC

TGCATTGGTTATCACGCTAATAACTCGACGGATACAGTGGATACTGTACTGGAAAAGAAC

GTGACAGTCACCCACAGTGTTAACCTGCTCGAGGATAGTCACAATGGCAAGTTGTGCAGG

CTGAAGGGGATCGCTCCCCTGCAACTCGGCAAGTGTAATATCGCCGGCTGGCTTTTAGGC

AACCCCGAGTGCGACCCCCTACTGCCCGTTAGGTCCTGGAGCTACATCGTGGAAACTCCT

AACAGCGAGAACGGCATCTGCTATCCTGGGGACTTCATCGATTACGAAGAGCTCCGGGAA

CAGCTCTCTTCCGTGAGCTCCTTTGAGAGATTTGAGATCTTCCCTAAGGAATCGTCCTGG

CCTAACCACAATACAAATGGCGTGACAGCTGCCTGTTCACACGAAGGGAAAAGTTCCTTC

TATAGGAATCTGCTGTGGCTGACAGAGAAAGAGGGCTCTTATCCTAAATTAAAGAACTCC

TACGTGAACAAGAAGGGTAAAGAGGTCTTAGTGCTGTGGGGCATTCACCATCCCCCCAAT

TCCAAGGAGCAGCAAAATCTGTACCAGAACGAGAACGCTTATGTGTCCGTCGTTACTTCT

AACTATAATAGGCGTTTCACCCCGGAGATTGCTGAGAGGCCTAAGGTACGGGACCAGGCC

GGTAGAATGAATTACTACTGGACACTACTTAAGCCAGGTGACACAATCATCTTTGAGGCA

AACGGAAACCTAATCGCTCCAATGTATGCATTTGCCCTGAGCCGCGGATTCGGTAGCGGA

ATTATCACCAGCAATGCCTCTATGCACGAGTGCAATACTAAGTGTCAGACTCCTTTGGGA

GCGATCAACTCCAGCTTGCCATACCAAAACATTCACCCGGTGACTATTGGTGAATGCCCC

AAGTACGTGCGGTCTGCAAAACTGAGAATGGTTACCGGACTCCGGAATAACCCTAGTATA

CAGTCTAGGGGGCTCTTTGGAGCCATTGCAGGTTTCATCGAAGGCGGCTGGACCGGCATG

ATCGACGGATGGTATGGTTATCACCACCAAAACGAGCAGGGATCAGGATATGCTGCAGAT

CAAAAATCTACTCAAAATGCAATAAACGGTATCACCAATAAGGTGAACACCGTAATCGAA

AAAATGAACATCCAGTTTACAGCCGTGGGCAAGGAGTTTAATAAGCTGGAGAAACGCATG

GAGAACCTCAATAAGAAGGTTGACGATGGATTCCTGGACATCTGGACGTATAATGCCGAG

CTCCTGGTACTGCTCGAGAATGAACGAACCCTCGACTTCCATGATAGCAACGTGAAGAAC

TTATATGAGAAGGTGAAGTCACAACTGAAAAACAATGCTAAGGAAATAGGCAACGGATGT

TTTGAATTCTACCACAAGTGTGACAACGAATGTATGGAATCGGTGAGGAATGGGACATAT

GACTACCCCAAGTACTCGGAAGAAAGTAAGCTTAATAGGGAGAAGGTGGACGGCGTGAAA

CTCGAGAGCATGGGGATTTACCAAATCCTAGCAATCTATTCCACAGTTGCTTCTTCTCTG

GTGCTCCTTGTGTCACTTGGGGCGATTTCGTTCTGGATGTGCTCAAACGGGAGCCTCCAG

TGCCGGATCTGCATC

423
ATGAAGGCAAACCTGCTGGTCCTGCTCTGCGCACTGGCCGCGGCAGACGCCGACACAATC

TGCATAGGCTATCACGCAAATAACAGTACTGACACCGTCGATACAGTCCTGGAGAAAAAC

GTGACTGTGACCCACAGCGTAAATCTGCTGGAAGACAGCCACAATGGAAAATTGTGCAGA

TTGAAAGGAATAGCACCCCTGCAATTGGGGAAATGTAATATTGCCGGATGGCTGCTCGGC

AACCCCGAATGCGACCCGCTGCTGCCCGTCCGGTCTTGGAGTTATATCGTTGAGACACCG

AACTCCGAGAATGGTATCTGCTATCCGGGCGACTTCATCGACTATGAGGAACTCAGAGAG

CAGCTGTCATCTGTGTCTTCATTCGAGCGTTTCGAGATTTTCCCAAAGGAGTCATCGTGG

CCCAACCATAACACAAACGGAGTCACGGCAGCATGCTCTCACGAAGGGAAAAGCTCTTTC

TACCGCAACCTGCTCTGGTTGACTGAGAAAGAGGGGTCTTACCCCAAACTTAAGAACAGC

TACGTGAACAAGAAGGGCAAGGAGGTCTTGGTACTGTGGGGCATCCATCACCCACCTAAT

AGTAAAGAGCAACAAAACCTATACCAGAACGAGAACGCATACGTGTCAGTAGTCACCTCT

AATTACAACAGGCGGTTTACACCAGAGATAGCTGAGCGGCCAAAGGTCCGGGACCAGGCA

GGCAGGATGAACTACTATTGGACTTTGTTAAAGCCTGGAGACACCATCATCTTTGAGGCT

AACGGGAATCTGATTGCTCCCATGTATGCTTTTGCACTTTCCAGAGGCTTTGGATCCGGT

ATTATCACATCGAATGCGTCCATGCATGAGTGTAACACTAAGTGTCAAACACCACTCGGC

GCAATCAATTCTTCACTTCCTTATCAAAATATTCACCCCGTGACCATCGGCGAGTGCCCC

AAGTATGTCAGGAGCGCTAAGCTGCGGATGGTGACAGGGTTGAGGAATAATCCTTCAATT

CAGTCGAGGGGATTATTCGGTGCCATCGCGGGATTCATTGAGGGGGGGTGGACAGGAATG

ATAGACGGGTGGTATGGTTACCACCATCAGAACGAGCAGGGGTCAGGCTACGCCGCTGAC

CAAAAATCCACCCAAAATGCCATCAATGGAATCACAAATAAGGTAAATACAGTGATCGAA

AAAATGAACATTCAATTCACAGCTGTCGGAAAGGAGTTCAATAAGCTTGAGAAACGAATG

GAGAACTTAAATAAAAAAGTTGACGACGGTTTCCTGGACATTTGGACATACAACGCAGAA

CTGCTCGTTTTACTAGAGAACGAACGGACGCTGGACTTTCATGATTCTAACGTAAAGAAC

TTGTACGAGAAGGTGAAAAGCCAGCTTAAAAATAACGCCAAAGAAATCGGAAACGGCTGC

TTCGAATTCTACCACAAATGTGATAACGAGTGCATGGAGAGCGTGAGGAATGGGACATAT

GACTATCCCAAATATTCTGAAGAGTCAAAACTGAATCGGGAAAAGGTCGATGGTGTCAAA

CTGGAGTCTATGGGCATCTATCAGATACTGGCAATCTACTCCACCGTGGCCAGCAGTCTC

GTGCTGCTGGTGAGCCTGGGCGCAATAAGCTTCTGGATGTGCTCAAACGGAAGCCTGCAA

TGTAGGATTTGTATC

424
ATGAAGGCCAATCTCCTGGTGCTGTTGTGCGCACTGGCAGCGGCGGATGCAGATACAATA

TGTATCGGATATCACGCAAATAACAGCACAGATACAGTGGACACCGTGCTGGAGAAGAAT

GTGACTGTGACGCATAGTGTTAACCTCTTGGAAGATAGCCACAATGGCAAGCTGTGTCGC

TTGAAGGGAATCGCCCCCCTGCAGCTCGGGAAATGCAATATCGCGGGATGGCTTCTGGGT

AACCCTGAATGCGACCCGCTGCTGCCCGTGCGCTCATGGTCATACATTGTGGAGACACCT

AATTCAGAGAATGGGATTTGCTATCCTGGGGACTTTATCGATTACGAGGAACTGAGAGAG

CAGCTATCTTCAGTTAGTTCCTTCGAACGATTCGAGATCTTTCCAAAGGAGAGTAGCTGG

CCCAATCATAACACTAACGGAGTGACCGCCGCGTGCAGCCACGAGGGCAAATCCTCATTT

TACCGAAACCTGTTATGGCTCACAGAAAAGGAGGGGTCTTACCCGAAGCTGAAAAACTCT

TATGTGAACAAGAAGGGGAAAGAGGTGTTAGTTCTGTGGGGCATTCACCACCCTCCAAAT

TCCAAGGAACAACAAAACCTTTACCAAAACGAGAATGCATATGTCTCGGTCGTGACGTCG

AACTATAATAGAAGATTTACCCCCGAGATTGCTGAACGACCCAAGGTGAGAGATCAGGCG

GGAAGAATGAACTATTACTGGACCTTGCTCAAACCGGGAGATACAATCATATTCGAGGCT

AACGGAAACTTGATCGCCCCAATGTACGCCTTTGCCCTCTCCCGCGGTTTCGGGAGCGGT

ATCATCACCTCAAATGCTTCTATGCATGAATGCAATACCAAATGTCAAACACCTCTGGGC

GCAATCAACTCGAGCCTGCCTTATCAGAACATTCACCCTGTCACCATTGGTGAGTGCCCC

AAGTACGTAAGATCAGCTAAGCTGCGTATGGTGACCGGGCTGAGAAACAATCCCTCCATC

CAAAGTCGCGGTTTATTCGGCGCCATTGCCGGGTTCATAGAGGGTGGGTGGACAGGAATG

ATCGATGGCTGGTATGGATATCATCATCAGAACGAACAAGGATCAGGGTATGCAGCAGAC

CAGAAGTCTACTCAAAACGCAATTAATGGCATCACCAATAAGGTTAACACTGTCATAGAA

AAGATGAACATCCAGTTCACTGCGGTGGGCAAAGAGTTTAACAAGCTCGAGAAGCGGATG

GAGAACCTCAATAAGAAAGTCGATGACGGATTCCTGGATATATGGACATATAATGCCGAG

CTGCTGGTGCTGCTGGAAAACGAAAGAACCCTCGATTTCCACGACTCTAATGTGAAGAAT

CTGTACGAGAAGGTCAAGTCCCAGCTGAAAAATAACGCCAAGGAGATAGGGAACGGCTGC

TTTGAATTCTATCACAAGTGCGACAATGAGTGCATGGAGAGCGTTCGGAACGGGACTTAC

GATTATCCGAAGTATTCAGAGGAGAGCAAGCTTAATCGTGAAAAGGTCGACGGAGTGAAA

TTAGAAAGTATGGGAATCTATCAGATTCTTGCAATCTATAGCACCGTTGCCAGCTCTCTG

GTGTTACTGGTAAGCCTCGGGGCAATATCTTTTTGGATGTGTAGCAATGGGTCTCTCCAG

TGTCGAATTTGTATT

425
ATGAAGGCCAACCTGCTCGTGCTTCTGTGTGCGCTGGCCGCCGCCGACGCAGACACTATC

TGTATCGGCTATCACGCCAATAACAGCACGGATACCGTGGATACCGTATTGGAGAAAAAT

GTCACGGTAACACACTCTGTGAATCTGCTTGAAGACTCCCATAACGGAAAACTTTGTCGG

CTCAAGGGCATTGCCCCTCTGCAACTGGGCAAGTGCAACATCGCCGGGTGGCTGCTGGGC

AATCCGGAGTGCGACCCTCTCCTGCCAGTCAGGTCCTGGTCCTATATCGTAGAAACCCCC

AATAGTGAAAACGGCATATGCTACCCAGGTGATTTCATCGATTATGAAGAGCTCAGAGAG

CAACTGAGCTCCGTCAGCAGTTTTGAGCGGTTCGAGATTTTCCCAAAGGAATCATCATGG

CCGAATCACAACACCAATGGAGTGACCGCAGCGTGTTCTCATGAGGGGAAGAGCTCGTTC

TATCGGAACCTGCTTTGGTTGACGGAGAAGGAGGGGTCATACCCCAAACTTAAGAACTCA

TACGTGAATAAAAAGGGCAAGGAGGTCCTCGTGCTGTGGGGGATTCACCACCCCCCCAAT

TCCAAGGAGCAGCAGAATCTGTACCAAAACGAGAATGCTTATGTGAGTGTGGTGACGTCT

AATTATAATAGACGGTTTACACCTGAGATCGCAGAAAGACCCAAAGTGCGCGACCAGGCT

GGGAGGATGAATTACTATTGGACTCTGTTAAAGCCCGGCGATACCATCATTTTCGAGGCA

AATGGGAATCTTATCGCTCCAATGTACGCCTTCGCCCTGTCACGGGGGTTCGGGAGCGGG

ATTATCACATCAAATGCCAGCATGCATGAATGCAACACTAAGTGCCAGACCCCACTGGGC

GCCATCAATTCCAGCCECCCTTACCAGAACATACACCCTGTTACAATAGGAGAGTGCCCC

AAGTACGTCCGATCCGCTAAACTGCGGATGGTTACAGGCCTACGTAATAATCCTAGCATT

CAGTCACGGGGACTGTTTGGCGCAATAGCCGGGTTCATCGAGGGCGGGTGGACCGGAATG

ATTGATGGGTGGTACGGATACCACCATCAGAATGAGCAGGGATCTGGGTACGCCGCCGAC

CAGAAGAGCACACAGAATGCCATTAATGGCATAACCAACAAAGTGAACACCGTGATCGAG

AAGATGAACATTCAATTTACGGCTGTAGGTAAGGAATTCAACAAACTGGAGAAACGGATG

GAGAATTTGAACAAGAAGGTCGATGATGGGTTCCTCGATATTTGGACCTACAACGCTGAG

CTTTTGGTGCTGCTGGAGAACGAGAGGACACTTGATTTTCATGATTCGAATGTGAAAAAC

TTGTACGAAAAGGTCAAGTCACAGCTGAAGAACAACGCTAAAGAGATTGGAAATGGATGC

TTCGAGTTTTATCACAAATGCGACAATGAATGTATGGAGAGTGTGCGGAACGGAACATAC

GATTACCCCAAATATTCCGAGGAGTCTAAGCTTAACCGTGAGAAGGTCGATGGCGTTAAG

TTAGAGTCCATGGGAATCTACCAGATCCTGGCTATATATAGCACCGTCGCAAGCTCTCTA

GTCTTGCTCGTCTCACTGGGAGCAATCTCGTTTTGGATGTGCTCTAACGGGTCCCTACAG

TGTCGGATTTGCATC

426
ATGAAAGCTAATCTGCTGGTCCTGTTGTGTGCACTGGCGGCTGCAGATGCGGATACCATT

TGTATCGGTTATCACGCTAATAACTCTACTGACACAGTCGACACGGTGTTGGAAAAGAAC

GTCACAGTCACCCACAGCGTCAATCTGCTCGAAGATTCACACAACGGAAAGCTATGTAGG

TTAAAGGGTATTGCACCATTGCAACTGGGAAAGTGTAACATTGCTGGATGGCTGCTGGGG

AACCCCGAGTGTGATCCTTTGCTCCCTGTCAGATCCTGGTCCTACATTGTGGAAACCCCT

AACTCAGAGAACGGGATCTGCTATCCAGGAGATTTTATCGACTATGAAGAGCTGAGGGAA

CAACTATCCAGCGTCTCCAGCTTTGAGAGGTTCGAGATATTCCCTAAGGAGTCAAGCTGG

CCAAATCACAATACAAACGGTGTCACAGCCGCCTGCAGTCACGAAGGCAAGTCATCGTTC

TACCGAAATTTGTTGTGGTTGACGGAAAAAGAGGGATCATACCCAAAACTCAAGAATAGC

TATGTCAACAAGAAAGGCAAGGAAGTGCTTGTCCTCTGGGGCATACATCATCCTCCTAAC

TCTAAGGAGCAGCAAAACTTATACCAGAACGAGAACGCCTATGTGAGTGTGGTCACCAGC

AATTATAATCGCAGGTTCACGCCTGAGATTGCCGAGAGGCCAAAAGTCAGAGACCAGGCC

GGCAGGATGAATTACTATTGGACATTACTGAAACCAGGCGATACTATTATCTTCGAGGCT

AACGGAAATCTGATAGCACCAATGTACGCCTTTGCCTTGTCCCGTGGGTTCGGCTCTGGG

ATCATAACATCCAACGCAAGCATGCATGAGTGCAACACAAAGTGCCAGACACCGCTTGGA

GCCATTAATTCTTCTCTGCCATATCAGAACATTCATCCTGTAACAATCGGGGAATGCCCA

AAGTACGTTAGAAGTGCCAAGCTGCGCATGGTGACCGGCCTGAGGAATAATCCCTCTATT

CAGTCCAGAGGACTGTTCGGAGCCATCGCTGGGTTTATTGAGGGCGGCTGGACCGGAATG

ATAGATGGCTGGTACGGGTACCACCACCAGAATGAACAGGGCTCTGGCTATGCCGCGGAC

CAGAAATCTACCCAAAATGCCATCAATGGAATCACCAATAAAGTTAACACGGTGATTGAG

AAAATGAACATTCAATTTACCGCGGTAGGAAAGGAGTTTAATAAGCTTGAGAAGCGTATG

GAGAATTTGAACAAGAAGGTGGATGACGGTTTCCTCGATATTTGGACCTATAATGCCGAA

CTACTAGTTTTATTGGAGAACGAACGCACACTGGATTTCCACGACTCTAATGTTAAAAAT

CTGTACGAGAAAGTGAAGTCACAGCTAAAGAATAATGCCAAGGAAATAGGAAATGGATGC

TTTGAATTTTACCACAAATGTGACAACGAATGCATGGAATCTGTGCGGAATGGAACTTAC

GATTACCCTAAGTACTCTGAGGAGAGTAAACTGAACAGAGAGAAGGTAGACGGCGTAAAG

CTCGAATCAATGGGAATCTACCAAATTCTGGCCATCTACTCTACCGTCGCCTCCTCTCTG

GTTTTATTGGTCTCTCTTGGAGCCATTAGTTTCTGGATGTGCAGTAACGGCTCCCTGCAG

TGCAGGATTTGTATC

427
ATGAAGGCCAACCTCCTCGTGCTGCTCTGCGCCTTGGCAGCCGCAGACGCCGATACCATC

TGTATAGGGTACCACGCCAACAATTCAACAGATACCGTCGATACCGTACTGGAGAAAAAC

GTCACCGTCACGCACAGCGTTAACCTGTTGGAAGATAGTCATAATGGAAAGCTCTGTCGC

CTAAAAGGAATCGCGCCTCTGCAGCTGGGAAAGTGCAACATAGCCGGGTGGCTCCTCGGG

AACCCGGAGTGTGACCCTCTTTTGCCGGTGCGCTCATGGTCATATATTGTTGAGACCCCT

AACAGCGAAAACGGAATATGTTACCCAGGGGACTTCATCGATTATGAGGAATTACGAGAA

CAACTAAGTTCCGTCTCTTCCTTCGAGCGCTTTGAAATCTTTCCTAAAGAGAGTTCCTGG

CCCAACCACAACACTAATGGCGTGACAGCTGCTTGCAGTCATGAGGGCAAAAGTTCATTC

TATAGAAATCTTCTCTGGCTAACTGAGAAAGAAGGATCCTACCCTAAACTCAAAAATTCC

TATGTTAACAAGAAGGGCAAAGAGGTGCTCGTGCTGTGGGGGATCCACCACCCACCAAAT

TCAAAAGAGCAACAAAACCTCTACCAGAATGAAAATGCCTACGTGAGCGTTGTGACTTCA

AATTACAATAGACGGTTTACCCCAGAGATCGCAGAACGCCCTAAGGTACGTGATCAGGCT

GGGCGAATGAACTACTACTGGACACTCCTCAAACCAGGCGACACTATAATCTTCGAGGCT

AACGGCAACCTGATTGCTCCAATGTACGCGTTCGCTCTTTCACGCGGATTCGGCTCCGGC

ATCATTACTAGTAATGCATCTATGCATGAATGCAATACTAAGTGCCAGACCCCACTCGGA

GCCATAAACAGTTCTCTGCCATATCAGAACATACACCCTGTGACTATAGGAGAATGCCCA

AAATATGTTCGGTCCGCTAAGCTGCGCATGGTGACCGGACTCCGGAACAACCCATCCATA

CAATCACGGGGGCTGTTTGGCGCCATTGCCGGCTTCATCGAGGGTGGATGGACTGGTATG

ATCGATGGTTGGTATGGATACCATCATCAGAATGAACAGGGCTCCGGCTATGCCGCCGAT

CAGAAGTCCACCCAGAACGCCATTAACGGAATTACCAACAAGGTTAATACTGTGATCGAG

AAGATGAATATTCAGTTCACAGCAGTCGGGAAGGAATTCAACAAACTGGAGAAACGTATG

GAAAATCTCAACAAGAAGGTGGACGATGGGTTTTTAGACATTTGGACTTATAATGCCGAA

CTGCTGGTGCTGCTGGAAAACGAGAGAACGTTGGACTTTCACGACAGCAACGTGAAAAAC

CTGTATGAAAAAGTGAAGTCCCAGCTCAAAAACAATGCAAAGGAAATCGGCAACGGTTGC

TTTGAGTTCTACCATAAGTGCGACAACGAATGTATGGAATCTGTGCGCAATGGAACCTAC

GACTATCCTAAGTATAGCGAAGAATCTAAATTAAATAGGGAAAAGGTTGATGGAGTGAAA

CTGGAGTCTATGGGGATCTACCAGATCCTTGCTATCTACTCAACCGTCGCTAGCTCCCTC

GTACTGCTGGTCAGTTTAGGAGCGATATCTTTCTGGATGTGTTCTAATGGGTCACTGCAG

TGTAGAATTTGCATC

428
ATGAAGGCCAATCTGCTGGTGCTTCTCTGCGCCTTAGCCGCCGCCGATGCAGATACCATT

TGTATTGGATATCACGCTAACAACAGTACAGATACTGTGGACACTGTCCTGGAAAAGAAC

GTCACCGTCACGCATAGCGTAAACCTGCTCGAGGACTCACACAACGGGAAGCTCTGTCGT

CTGAAGGGCATCGCCCCCCTGCAGCTCGGCAAATGCAACATTGCGGGATGGCTTCTTGGA

AACCCCGAGTGTGATCCCTTATTACCAGTGCGCTCTTGGTCCTATATAGTAGAAACCCCA

AACAGCGAGAACGGGATTTGTTACCCCGGCGATTTCATAGACTACGAGGAGTTGCGCGAA

CAGCTGTCTAGCGTCTCCTCATTCGAACGTTTCGAGATTTTCCCAAAGGAATCCTCGTGG

CCCAATCATAATACCAATGGAGTCACTGCCGCCTGCAGCCACGAGGGAAAGTCATCTTTC

TATCGGAATCTGCTCTGGCTGACCGAAAAGGAGGGATCTTATCCTAAACTGAAAAATTCT

TACGTCAATAAGAAAGGCAAGGAAGTCTTAGTATTATGGGGAATTCATCACCCTCCCAAC

AGTAAGGAGCAGCAGAACCTGTACCAGAACGAGAACGCCTATGTTTCTGTCGTGACATCT

AACTATAACAGACGTTTCACCCCAGAAATTGCTGAAAGGCCAAAGGTCCGTGATCAGGCC

GGCAGGATGAATTACTACTGGACTCTTCTGAAGCCTGGTGACACAATCATTTTCGAAGCC

AACGGCAACCTGATTGCTCCCATGTACGCGTTCGCTCTGAGTCGCGGCTTTGGATCGGGT

ATTATTACGTCCAATGCCTCTATGCATGAATGCAATACTAAATGTCAGACCCCTCTAGGC

GCCATCAATTCTAGCCTCCCGTACCAGAACATTCATCCTGTGACTATTGGTGAATGCCCA

AAGTACGTGAGGTCCGCCAAGCTTCGCATGGTGACCGGCCTGCGTAACAACCCCTCCATC

CAATCCAGAGGTCTCTTTGGGGCAATCGCCGGTTTTATTGAGGGTGGTTGGACCGGAATG

ATCGATGGTTGGTACGGGTACCACCATCAGAATGAGCAGGGCAGTGGATATGCCGCTGAC

CAAAAATCTACACAAAACGCGATCAATGGAATCACCAATAAAGTGAACACAGTCATAGAA

AAAATGAACATCCAGTTTACTGCGGTCGGGAAGGAATTTAATAAGCTCGAGAAAAGAATG

GAAAATCTAAACAAAAAGGTCGATGACGGTTTCCTCGATATCTGGACATACAATGCCGAA

TTACTGGTCCTGCTCGAGAATGAGCGGACATTAGACTTCCACGACAGCAATGTAAAGAAC

CTTTACGAGAAGGTGAAGTCCCAGCTGAAGAACAATGCTAAAGAGATTGGGAATGGCTGT

TTTGAATTTTACCATAAATGCGACAACGAGTGTATGGAAAGCGTGCGGAACGGGACTTAC

GATTACCCAAAATATAGTGAGGAGAGCAAATTAAACCGTGAGAAGGTCGACGGGGTGAAG

TTGGAATCCATGGGCATTTACCAAATCCTCGCAATTTACTCCACCGTGGCTTCTTCATTG

GTTCTCCTGGTGTCCCTTGGGGCCATATCATTTTGGATGTGCTCTAATGGGAGTCTCCAG

TGCCGTATATGCATT

429
ATGAAGGCTAACCTACTGGTTCTGCTGTGTGCGCTTGCCGCCGCAGATGCCGACACCATC

TGCATCGGGTATCACGCAAATAACTCCACCGACACAGTAGACACAGTATTGGAAAAAAAC

GTGACCGTCACCCACTCTGTGAACCTGCTCGAAGATAGCCATAATGGCAAATTGTGTAGA

CTCAAAGGTATCGCTCCCTTGCAGCTAGGAAAGTGCAACATTGCAGGATGGCTCCTCGGC

AACCCTGAGTGTGACCCCCTCCTGCCCGTCCGATCCTGGTCCTACATCGTGGAGACTCCA

AACTCGGAGAACGGAATATGTTATCCTGGGGATTTCATTGACTATGAGGAGCTTAGGGAG

CAACTATCCAGCGTATCTAGTTTCGAACGGTTCGAGATCTTTCCAAAAGAGTCCAGTTGG

CCTAACCATAACACGAACGGTGTGACCGCTGCTTGTAGCCATGAGGGGAAATCATCTTTC

TATCGCAACTTGCTTTGGCTCACAGAGAAGGAGGGCTCCTACCCTAAGTTGAAAAACAGC

TATGTCAATAAAAAAGGCAAAGAGGETCTCGTGTTATGGGGTATTCACCACCCTCCTAAC

TCTAAAGAGCAACAAAATCTGTATCAGAACGAGAATGCGTATGTGTCAGTCGTTACATCA

AATTACAATAGGCGGTTTACACCAGAGATCGCTGAAAGACCTAAAGTTCGGGACCAGGCC

GGCCGCATGAATTACTACTGGACTCTGCTGAAGCCAGGGGATACGATTATCTTTGAAGCT

AATGGTAACCTGATTGCTCCCATGTACGCCTTTGCCTTATCAAGAGGATTTGGATCCGGC

ATAATCACATCCAATGCTAGCATGCACGAGTGCAACACCAAATGCCAGACTCCTTTGGGA

GCCATCAACTCTAGTCTGCCATATCAGAATATCCATCCTGTGACCATCGGGGAGTGCCCG

AAGTATGTGCGATCAGCCAAGCTGCGGATGGTCACCGGATTAAGAAATAACCCCTCCATT

CAGTCTCGAGGACTGTTCGGTGCTATCGCTGGTTTTATTGAAGGTGGTTGGACAGGCATG

ATCGATGGCTGGTACGGTTATCACCACCAGAACGAACAGGGGTCTGGGTACGCTGCCGAT

CAGAAGAGTACCCAGAACGCGATCAATGGCATTACCAACAAAGTGAACACAGTAATAGAA

AAGATGAACATTCAGTTCACCGCTGTTGGTAAAGAGTTCAACAAGCTGGAAAAACGGATG

GAGAATCTCAACAAAAAGGTTGATGATGGGTTCCTGGATATCTGGACCTACAACGCGGAA

CTGCTGGTACTGCTGGAAAATGAACGGACACTTGACTTTCACGACTCTAACGTGAAGAAT

CTGTACGAAAAGGTAAAATCACAGCTAAAGAACAATGCAAAGGAGATTGGGAATGGATGC

TTCGAGTTCTACCATAAGTGCGACAACGAGTGTATGGAGTCTGTGCGGAATGGCACTTAC

GATTACCCTAAGTACTCCGAGGAATCTAAACTGAATCGAGAGAAAGTGGATGGTGTAAAG

CTCGAGAGTATGGGCATTTATCAGATTCTGGCTATCTACTCGACTGTAGCCTCCTCACTG

GTGTTACTGGTGAGCCTCGGTGCAATCTCATTCTGGATGTGTAGTAACGGCTCCTTACAG

TGTCGCATTTGTATC

430
ATGAAGGCCAACTTGTTAGTCCTGCTGTGCGCTTTAGCGGCTGCCGACGCCGATACAATC

TGTATTGGCTATCACGCTAACAATAGCACTGACACAGTCGATACAGTTCTGGAGAAGAAT

GTTACAGTCACGCATAGCGTGAACTTACTGGAAGACTCTCACAATGGCAAGTTGTGTCGG

CTGAAGGGGATCGCTCCATTGCAACTCGGAAAATGCAATATAGCGGGCTGGCTGCTCGGA

AATCCAGAATGTGATCCCCTTCTGCCTGTCCGCTCCTGGTCCTACATCGTGGAGACTCCT

AATTCTGAGAACGGAATATGCTACCCTGGCGACTTCATCGACTACGAAGAACTCCGGGAA

CAGCTCTCTAGCGTGAGTTCCTTTGAGAGATTCGAAATTTTTCCAAAAGAGTCCAGCTGG

CCTAATCATAATACAAACGGCGTGACTGCTGCATGCAGCCACGAAGGGAAATCGTCTTTT

TATAGAAATCTGCTGTGGCTGACGGAGAAAGAAGGATCATACCCAAAGCTAAAGAACTCA

TATGTTAACAAGAAAGGGAAGGAGGTGCTGGTGCTGTGGGGGATACATCACCCACCCAAT

TCTAAAGAGCAGCAGAACTTGTATCAGAACGAAAATGCCTACGTGAGCGTCGTGACTTCC

AACTATAACCGAAGATTCACTCCCGAAATTGCCGAACGCCCCAAGGTCCGGGATCAGGCG

GGACGCATGAATTACTATTGGACCCTGCTGAAACCTGGAGACACTATTATCTTCGAGGCC

AACGGCAACTTGATCGCTCCCATGTATGCCTTTGCCCTGAGTCGAGGTTTTGGAAGGGGG

ATTATCACTTCCAATGCATCAATGCATGAATGCAATACAAAGTGTCAGACACCCCTTGGC

GCAATTAACTCATCTCTGCCCTACCAGAACATTCATCCAGTCACTATCGGGGAGTGCCCT

AAATATGTTAGATCTGCCAAGCTGCGGATGGTGACAGGGCTTAGAAATAACCCCAGCATT

CAGAGCCGCGGCTTGTTTGGAGCCATTGCTGGGTTTATTGAGGGAGGGTGGACCGGAATG

ATAGACGGTTGGTACGGGTACCATCATCAGAATGAGCAGGGCAGTGGGTACGCCGCTGAC

CAAAAGAGCACCCAGAACGCTATCAACGGAATTACCAATAAGGTCAATACAGTGATAGAA

AAGATGAACATTCAGTTTACTGCTGTGGGGAAGGAGTTCAATAAACTGGAAAAACGGATG

GAGAACCTCAACAAGAAAGTGGACGACGGATTTCTGGACATTTGGACCTATAACGCCGAG

TTACTGGTACTGCTTGAAAACGAAAGGACCTTAGACTTTCATGATTCTAATGTTAAAAAT

CTGTATGAAAAGGTCAAGAGCCAACTTAAGAACAACGCCAAAGAAATCGGAAACGGTTGC

TTCGAGTTTTATCATAAGTGTGACAATGAGTGCATGGAGTCTGTTCGAAATGGTACATAC

GACTATCCCAAGTATAGTGAAGAGAGCAAACTTAATCGGGAGAAGGTGGATGGCGTGAAA

CTGGAAAGCATGGGAATCTACCAGATCTTAGCCATATACAGTACAGTCGCTTCATCTCTC

GTGCTTCTCGTCAGCCTCGGAGCAATCAGCTTTTGGATGTGTAGCAACGGCAGCCTCCAA

TGCCGAATCTGCATC

431
ATGAAGGCAAACCTCCTTGTCCTCCTGTGTGCACTGGCAGCCGCCGACGCCGACACTATT

TGTATCGGGTACCATGCAAATAACTCCACCGATACCGTGGACACAGTCCTGGAAAAAAAC

GTGACAGTGACGCATTCAGTGAATCTCCTTGAAGATAGCCACAATGGAAAGTTGTGCCGG

CTGAAAGGAATCGCACCTTTACAGCTGGGAAAGTGTAACATTGCAGGGTGGCTGTTGGGG

AACCCTGAGTGTGACCCCCTCTTACCCGTCCGGTCTTGGAGTTACATAGTGGAAACACCA

AATAGTGAGAACGGCATCTGCTACCCAGGAGATTTCATCGATTATGAAGAGCTGCGTGAA

CAACTCTCTAGTGTTAGTTCTTTCGAAAGGTTCGAGATCTTTCCTAAAGAATCGTCATGG

CCCAATCACAATACAAACGGGGTCACAGCTGCTTGCTCACACGAAGGAAAGAGCAGTTTC

TATAGAAATCTGCTGTGGCTGACCGAGAAGGAGGGTTCTTACCCTAAACTTAAAAATTCT

TATGTTAACAAGAAGGGCAAAGAAGTGCTTGTCCTGTGGGGCATCCACCATCCCCCTAAC

TCTAAAGAGCAGCAGAACTTGTACCAGAATGAGAACGCCTATGTGTCAGTGGTTACCTCA

AATTATAACCGGAGATTTACGCCTGAGATCGCCGAGCGGCCCAAAGTGCGGGATCAAGCC

GGACGTATGAACTACTATTGGACACTCCTTAAGCCAGGCGATACCATTATCTTTGAGGCA

AATGGCAACCTGATCGCACCCATGTACGCGTTCGCCTTGTCTCGAGGATTCGGCAGCGGC

ATCATCACGTCCAACGCCAGTATGCATGAGTGTAATACAAAATGCCAAACTCCCCTCGGG

GCAATTAACTCGTCTCTGCCATACCAGAACATACATCCAGTGACTATTGGTGAATGTCCC

AAGTACGTCCGGTCTGCCAAGCTGCGGATGGTGACTGGCTTGCGCAATAACCCTAGCATT

CAGTCCAGAGGGCTGTTCGGCGCAATCGCCGGGTTCATCGAGGGGGGCTGGACTGGCATG

ATCGATGGCTGGTATGGATATCACCATCAGAATGAACAGGGGAGCGGTTATGCGGCCGAT

CAGAAATCGACCCAGAACGCAATCAATGGAATTACCAACAAGGTTAACACAGTCATAGAG

AAAATGAACATCCAGTTCACGGCCGTTGGGAAGGAGTTTAATAAGTTGGAAAAGCGAATG

GAAAACCTGAATAAAAAAGTCGACGACGGCTTCCTGGATATCTGGACCTATAACGCCGAG

CTACTCGTTCTGTTGGAGAACGAGAGGACACTCGACTTCCATGACAGCAATGTGAAAAAC

CTGTACGAAAAGGTGAAAAGTCAGCTCAAGAACAATGCAAAAGAGATCGGCAACGGATGT

TTCGAGTTTTACCACAAGTGCGATAATGAGTGTATGGAAAGCGTGCGCAATGGCACTTAT

GACTACCCCAAGTATTCTGAGGAGTCCAAATTGAATCGAGAAAAGGTGGATGGCGTCAAG

CTAGAATCGATGGGGATATACCAGATATTGGCCATCTACTCCACCGTGGCCTCCTCCCTC

GTCCTTCTTGTTTCGCTGGGCGCCATCTCTTTTTGGATGTGCTCAAACGGCTCGCTTCAG

TGTCGCATTTGCATC

432
ATGAAGGCAAACCTGTTAGTTCTCCTCTGCGCTTTGGCTGCGGCCGACGCCGACACAATC

TGTATCGGTTATCATGCGAACAACTCAACTGACACAGTGGATACTGTGCTGGAAAAAAAT

GTGACAGTCACCCACTCTGTGAATCTGCTAGAGGACTCACACAACGGAAAGCTGTGCAGG

CTCAAGGGCATTGCGCCACTGCAATTAGGAAAGTGTAACATCGCTGGATGGCTACTGGGA

AACCCCGAGTGTGACCCCCTGCTTCCTGTGCGTAGTTGGAGTTATATCGTCGAAACTCCA

AACAGCGAAAACGGCATTTGTTATCCCGGCGATTTCATCGATTATGAGGAATTGCGGGAG

CAACTATCTAGCGTGTCTAGTTTTGAGAGATTCGAGATCTTCCCTAAAGAGTCTTCCTGG

CCCAATCATAACACAAATGGTGTCACCGCAGCCTGCAGTCACGAGGGGAAGAGTAGCTTT

TATCGCAACCTGCTGTGGCTGACCGAAAAGGAAGGCTCCTATCCTAAACTTAAGAACAGC

TACGTGAACAAAAAGGGTAAGGAGGTCCTTGTTCTCTGGGGAATCCACCACCCCCCTAAT

AGCAAAGAGCAGCAAAACCTTTATCAGAATGAGAACGCTTATGTTTCTGTGGTGACCTCA

AACTATAATAGACGTTTCACACCTGAAATCGCCGAAAGGCCCAAGGTTCGAGATCAAGCC

GGTCGTATGAATTACTATTGGACGCTGCTAAAGCCAGGCGACACCATAATTTTCGAAGCG

AACGGTAACTTGATCGCCCCTATGTATGCATTCGCCCTGTCACGTGGCTTTGGCTCTGGT

ATTATCACCAGCAATGCCTCTATGCACGAGTGTAATACTAAATGTCAGACCCCACTCGGC

GCTATCAACTCATCCTTGCCCTACCAGAACATACATCCAGTGACAATTGGAGAATGCCCG

AAATACGTGCGTAGTGCCAAGCTGAGAATGGTGACTGGTCTCCGGAATAACCCCTCTATA

CAGTCCAGGGGCCTGTTTGGGGCTATTGCCGGTTTTATTGAGGGAGGTTGGACTGGCATG

ATCGATGGATGGTACGGCTATCACCACCAGAACGAGCAAGGCTCTGGCTATGCCGCAGAC

CAGAAATCAACACAAAACGCTATCAATGGAATAACTAACAAGGTCAACACAGTGATTGAA

AAAATGAACATCCAGTTTACGGCTGTGGGCAAGGAGTTCAACAAGCTGGAAAAGAGGATG

GAAAATCTCAACAAAAAAGTCGACGACGGCTTCTTGGACATCTGGACTTACAATGCAGAG

TTGCTTGTTCTGCTGGAAAACGAACGTACGCTGGACTTCCACGACAGTAATGTCAAGAAT

TTGTATGAAAAAGTGAAATCACAGCTGAAAAATAATGCGAAGGAGATAGGCAATGGCTGT

TTTGAGTTCTATCATAAGTGCGATAATGAGTGCATGGAGTCAGTGCGAAACGGGACCTAC

GACTACCCCAAATATAGTGAAGAGAGCAAGCTGAATAGAGAGAAAGTCGATGGCGTTAAA

CTTGAGAGCATGGGTATCTATCAAATCCTGGCTATTTACAGTACAGTGGCCTCCTCTCTA

GTGCTGCTCGTATCTCTCGGAGCGATATCCTTCTGGATGTGTTCCAATGGCTCTCTACAG

TGCCGGATATGCATA

433
ATGAAAGCTAATCTGCTTGTACTGCTGTGCGCACTGGCAGCCGCAGACGCTGACACTATC

TGTATCGGGTACCACGCCAACAATTCGACCGATACTGTGGACACAGTGTTGGAGAAGAAC

GTCACCGTAACGCACAGCGTGAACCTTTTAGAAGATAGTCATAATGGAAAGCTGTGTAGG

CTCAAGGGAATCGCTCCACTTCAGTTGGGAAAATGCAATATCGCTGGCTGGCTACTGGGC

AACCCTGAATGCGACCCCCTGCTGCCTGTGCGATCCTGGTCCTATATTGTAGAGACCCCC

AACTCAGAGAATGGCATTTGCTACCCAGGCGATTTTATTGACTACGAGGAGCTGAGAGAG

CAGTTGTCCTCCGTCTCCAGCTTTGAAAGGTTTGAGATTTTCCCAAAAGAGTCCAGCTGG

CCAAATCACAATACAAATGGTGTGACCGCCGCTTGTTCTCACGAAGGCAAAAGCTCCTTC

TATAGAAATCTTCTGTGGCTAACAGAAAAAGAAGGATCATACCCAAAGTTGAAAAACAGC

TACGTTAATAAGAAAGGCAAAGAGGTGCTGGTCCTGTGGGGTATCCACCACCCACCCAAT

TCTAAAGAACAACAAAATTTGTACCAAAATGAAAACGCCTACGTTTCTGTCGTCACTAGC

AATTATAACCGGAGGTTCACACCCGAGATCGCAGAAAGACCTAAGGTGAGAGACCAAGCC

GGCAGAATGAATTATTACTGGACTCTCCTCAAACCCGGGGACACCATCATCTTCGAAGCT

AACGGCAATCTGATTGCTCCTATGTACGCTTTTGCTCTGTCCCGGGGGTTTGGCAGCGGT

ATTATCACATCAAACGCCAGTATGCACGAGTGTAATACGAAATGCCAGACTCCTCTGGGG

GCTATCAATTCCAGTCTGCCCTATCAGAATATTCATCCTGTCACGATCGGTGAGTGCCCT

AAGTATGTGCGAAGCGCCAAACTGCGGATGGTAACGGGCCTGAGGAATAACCCCTCTATT

CAGTCTCGCGGGCTGTTTGGCGCAATCGCCGGCTTTATCGAGGGCGGTTGGACTGGCATG

ATCGACGGATGGTACGGGTACCATCACCAGAACGAACAGGGGTCCGGCTACGCCGCCGAC

CAGAAATCAACCCAGAACGCGATTAACGGGATCACCAACAAGGTGAATACTGTGATTGAG

AAGATGAATATTCAGTTTACAGCAGTGGGCAAGGAGTTTAACAAACTTGAGAAACGCATG

GAGAATCTCAACAAAAAGGTTGACGATGGATTCCTTGATATTTGGACATATAATGCCGAG

CTGCTGGTCCTTCTGGAAAATGAACGCACACTGGATTTTCACGACTCGAACGTGAAGAAT

CTGTACGAGAAGGTAAAGTCCCAATTAAAAAACAATGCTAAGGAGATAGGCAACGGCTGC

TTCGAGTTTTACCACAAGTGCGATAACGAGTGCATGGAGTCTGTGAGAAACGGTACGTAC

GATTACCCCAAATATTCCGAAGAGAGCAAGCTCAACCGCGAGAAAGTAGACGGCGTTAAA

CTGGAGAGCATGGGCATCTACCAGATCCTCGCCATTTACTCCACTGTGGCCTCGTCACTA

GTTCTCTTGGTGTCCCTGGGAGCCATCTCATTTTGGATGTGCTCCAACGGCTCACTACAG

TGCCGGATTTGTATC

434
ATGAAGGCCAACCTCCTGGTGTTACTTTGTGCCCTAGCAGCCGCAGACGCCGACACTATC

TGCATCGGATACCATGCTAATAACAGCACCGATACAGTAGATACCGTTTTGGAAAAGAAT

GTCACTGTCACCCACAGCGTTAATCTGTTGGAGGATAGCCACAACGGTAAACTGTGCAGG

CTGAAGGGAATTGCCCCCCTTCAACTGGGCAAGTGCAACATTGCAGGCTGGCTCCTCGGT

AACCCTGAGTGCGATCCTTTACTCCCTGTTAGAAGCTGGAGCTACATCGTGGAGACCCCC

AATAGTGAGAACGGAATCTGCTACCCTGGAGATTTCATCGACTATGAAGAACTTCGGGAA

CAGCTCAGTTCAGTGTCGAGCTTCGAGAGATTCGAGATCTTTCCAAAGGAGTCCAGCTGG

CCTAATCACAACACAAATGGCGTTACAGCAGCATGCTCACACGAAGGCAAGAGCAGCTTC

TACCGCAACCTGCTGTGGCTTACCGAGAAGGAGGGATCCTATCCCAAGCTCAAGAATTCT

TATGTGAATAAAAAGGGTAAGGAAGTGCTGGTCCTGTGGGGTATCCATCATCCGCCAAAT

TCTAAGGAACAGCAGAATCTGTATCAGAATGAAAATGCCTACGTGAGTGTTGTGACTTCG

AATTACAACAGGCGGTTTACCCCGGAGATTGCTGAGCGGCCCAAAGTCCGGGATCAGGCT

GGCCGCATGAATTATTATTGGACTCTGCTCAAGCCTGGCGACACCATCATTTTTGAGGCC

AATGGCAACCTTATCGCTCCCATGTACGCCTTCGCCCTCAGTAGGGGATTCGGGTCTGGT

ATCATCACTTCAAACGCCAGCATGCACGAGTGCAATACCAAGTGCCAGACACCACTCGGT

GCCATTAATAGCTCTCTTCCATATCAGAATATACATCCAGTCACGATCGGGGAATGCCCC

AAATATGTAAGAAGTGCCAAACTGCGCATGGTGACAGGCCTGCGGAACAACCCAAGCATC

CAAAGCAGAGGGCTGTTTGGCGCCATCGCGGGCTTCATTGAAGGTGGTTGGACTGGCATG

ATTGATGGCTGGTACGGATATCATCATCAGAACGAGCAGGGATCAGGGTACGCGGCCGAT

CAGAAGAGTACCCAGAATGCCATTAACGGCATCACGAATAAAGTAAATACTGTCATCGAA

AAGATGAACATCCAATTTACTGCTGTCGGGAAGGAGTTCAACAAACTGGAAAAAAGGATG

GAGAACCTGAATAAGAAAGTTGACGACGGCTTTTTAGATATTTGGACGTATAACGCAGAA

CTGCTCGTGCTCCTGGAGAACGAGAGGACCCTGGACTTTCACGACTCCAATGTGAAGAAC

CTTTATGAGAAAGTCAAATCTCAGCTCAAAAACAACGCTAAAGAAATTGGGAATGGTTGT

TTTGAGTTTTATCACAAATGCGACAACGAATGCATGGAGAGCGTCAGGAACGGGACATAC

GACTATCCAAAGTACTCAGAAGAGTCAAAACTCAACAGAGAGAAGGTTGACGGAGTCAAA

CTTGAGTCTATGGGCATATACCAGATCTTGGCGATCTATTCCACGGTGGCCTCAAGCCTT

GTTCTGTTGGTCTCATTGGGTGCCATCAGCTTTTGGATGTGTAGTAACGGCAGTCTGCAG

TGTAGAATTTGCATC

435
ATGAAAGCAAACCTGCTCGTGCTCCTGTGCGCTCTGGCAGCCGCAGATGCCGACACTATT

TGCATCGGTTACCATGCCAACAACAGCACTGATACGGTGGATACCGTACTAGAGAAGAAT

GTCACCGTAACCCACTCAGTGAACCTGCTCGAAGACTCTCACAACGGTAAGCTGTGTAGA

TTAAAGGGAATTGCCCCCTTGCAGTTAGGAAAGTGTAACATAGCAGGTTGGCTCCTTGGC

AATCCTGAGTGTGACCCCCTACTGCCAGTCCGCAGCTGGAGCTATATCGTTGAGACTCCC

AACTCTGAAAATGGAATCTGTTATCCAGGTGACTTCATCGATTATGAAGAATTACGCGAG

CAGTTGTCCAGTGTTAGCTCTTTCGAGAGATTTGAAATATTCCCAAAGGAGTCGTCCTGG

CCCAATCACAACACCAATGGAGTGACCGCTGCTTGCTCCCACGAAGGGAAGAGCTCTTTC

TATCGGAATCTGTTGTGGCTGACAGAAAAGGAGGGCAGCTATCCTAAACTAAAGAACAGC

TACGTGAACAAGAAGGGAAAGGAGGTGCTCGTGCTGTGGGGCATTCATCATCCTCCAAAT

TCCAAGGAGCAGCAGAACTTATATCAGAATGAGAATGCTTATGTCTCAGTGGTGACGTCA

AATTACAACAGGCGCTTCACACCCGAGATCGCTGAGCGGCCCAAGGTCCGCGACCAGGCT

GGTAGAATGAATTACTATTGGACCCTCCTGAAGCCCGGAGATACTATTATCTTCGAAGCA

AATGGAAATTTGATCGCACCCATGTATGCTTTCGCTCTGTCCAGGGGATTCGGTAGTGGC

ATTATCACCAGCAATGCAAGTATGCATGAGTGCAACACAAAATGTCAGACGCCGTTAGGG

GCTATTAACAGCAGCCTCCCTTATCAGAACATTCATCCGGTTACCATCGGGGAGTGCCCT

AAGTACGTGAGAAGTGCCAAACTGAGGATGGTGACAGGCCTGCGCAATAATCCCAGTATC

CAGAGCCGAGGTCTCTTTGGTGCCATTGCGGGCTTTATTGAAGGGGGCTGGACCGGCATG

ATCGACGGTTGGTACGGATACCACCACCAGAACGAACAGGGCAGTGGCTACGCCGCCGAC

CAGAAGAGTACTCAGAACGCAATCAATGGAATTACGAACAAAGTTAATACCGTAATCGAA

AAAATGAATATCCAGTTTACCGCCGTAGGCAAGGAGTTTAACAAGCTCGAAAAACGCATG

GAAAACCTGAATAAGAAAGTGGATGATGGATTCCTTGACATCTGGACCTACAACGCGGAA

CTTCTTGTCCTGCTCGAAAATGAGAGAACGCTCGACTTTCACGACAGCAATGTCAAGAAT

CTGTACGAAAAGGTAAAGTCACAGCTGAAGAACAACGCTAAGGAGATAGGCAACGGCTGC

TTCGAGTTTTACCATAAATGCGACAATGAATGCATGGAATCCGTGAGAAACGGCACTTAC

GATTACCCCAAATACAGCGAAGAATCAAAGCTAAACAGGGAGAAGGTGGACGGGGTGAAA

CTAGAAAGCATGGGCATCTATCAGATCCTCGCCATTTACTCCACAGTCGCATCTTCTTTA

GTGCTCCTTGTGTCACTGGGCGCTATCTCGTTTTGGATGTGCTCAAACGGATCTCTGCAG

TGTCGGATCTGTATT

436
ATGAAAGCAAATCTGCTAGTGCTGCTGTGCGCCCTGGCCGCCGCAGATGCAGATACTATC

TGCATTGGTTACCATGCCAACAACTCTACCGATACCGTGGATACTGTCCTCGAGAAGAAT

GTGACTGTGACTCATTCCGTGAACTTACTCGAAGACAGCCACAACGGAAAGCTGTGCCGA

TTGAAGGGCATCGCGCCACTCCAGCTGGGGAAATGCAACATCGCCGGCTGGCTTTTGGGA

AACCCCGAGTGCGATCCGCTATTGCCCGTAAGATCATGGTCCTACATCGTGGAAACACCA

AATTCAGAAAATGGCATCTGCTACCCCGGAGATTTTATCGATTACGAGGAACTGAGGGAG

CAACTGAGCAGCGTTAGTTCTTTTGAGCGATTCGAAATTTTCCCAAAGGAGTCCTCATGG

CCCAATCACAATACCAATGGCGTTACAGCCGCTTGTAGCCATGAAGGTAAGAGTTCATTT

TATCGAAATCTTCTCTGGCTGACGGAGAAGGAGGGTAGTTACCCTAAATTGAAAAATTCA

TACGTGAACAAGAAAGGAAAGGAGGTGCTGGTCCTCTGGGGGATTCACCATCCCCCCAAT

AGCAAAGAGCAACAGAATCTGTACCAGAACGAAAACGCTTATGTCTCCGTGGTCACCTCA

AATTACAATAGACGGTTTACCCCGGAGATAGCCGAGAGGCCCAAAGTCCGCGATCAGGCC

GGCCGCATGAACTACTACTGGACCCTCCTCAAGCCAGGGGATACCATCATATTCGAGGCG

AATGGGAACTTGATTGCCCCGATGTACGCATTTGCTTTGTCCAGAGGCTTTGGCTCCGGG

ATCATCACATCTAATGCCTCCATGCATGAATGCAACACAAAATGCCAGACACCCCTGGGC

GCTATTAACTCCTCTCTACCTTACCAGAACATCCACCCGGTTACTATTGGCGAGTGTCCT

AAATATGTCCGCAGCGCCAAACTGAGGATGGTGACAGGGCTGAGGAATAACCCCAGCATT

CAGTCCAGAGGCTTGTTCGGCGCTATAGCGGGGTTCATAGAAGGAGGCTGGACCGGAATG

ATCGATGGCTGGTACGGCTACCACCATCAGAACGAGCAGGGCTCCGGGTACGCCGCTGAC

CAGAAGAGTACGCAGAACGCCATTAATGGAATCACCAACAAGGTGAATACCGTAATCGAG

AAAATGAATATTCAGTTCACAGCTGTGGGGAAGGAATTCAATAAGCTGGAAAAACGCATG

GAGAACCTGAATAAAAAAGTGGATGATGGCTTCTTGGATATCTGGACCTATAATGCGGAA

CTCCTGGTCCTTTTGGAAAATGAGCGCACACTTGACTTTCATGACTCAAACGTTAAAAAC

CTGTACGAAAAAGTCAAGTCACAGCTAAAGAATAATGCAAAGGAGATTGGCAACGGGTGC

TTCGAATTTTATCATAAATGCGACAACGAATGCATGGAAAGCGTAAGGAATGGTACATAC

GATTATCCTAAGTACAGTGAGGAGTCAAAGTTGAATCGCGAAAAAGTTGACGGTGTCAAA

CTGGAATCCATGGGGATTTATCAGATTCTTGCAATTTACTCAACGGTGGCTAGTTCTCTG

GTGCTGCTGGTCTCCCTGGGCGCAATTAGTTTCTGGATGTGTAGCAACGGCTCTCTCCAG

TGCCGGATCTGTATT

437
ATGAAAGCAAATCTTCTGGTCCTGCTGTGTGCACTAGCCGCCGCCGACGCAGACACAATT

TGCATCGGATATCACGCCAACAACTCTACGGATACAGTGGACACAGTGCTGGAGAAGAAC

GTAACTGTTACACACAGCGTGAACCTGCTAGAAGATTCTCACAATGGCAAACTGTGCAGA

CTGAAAGGAATTGCACCCTTGCAGTTGGGAAAATGTAATATCGCGGGTTGGCTCCTCGGT

AATCCCGAATGCGACCCCCTACTTCCCGTCCGTTCTTGGTCTTACATAGTGGAGACACCC

AACTCGGAGAATGGGATTTGCTATCCTGGGGATTTTATTGACTACGAGGAGCTCAGGGAA

CAGTTGAGTTCTGTGTCATCATTCGAGAGGTTTGAAATCTTTCCCAAAGAGTCTTCTTGG

CCTAATCACAACACTAACGGTGTGACCGCTGCTTGTTCTCACGAAGGCAAATCATCCTTC

TACAGAAATCTGCTCTGGCTGACGGAGAAGGAAGGATCATACCCAAAGCTAAAGAATTCA

TATGTGAATAAAAAGGGGAAGGAGGTCCTCGTTCTGTGGGGTATTCACCATCCCCCTAAT

TCTAAAGAACAGCAGAACCTTTATCAGAATGAAAATGCATACGTGTCAGTGGTGACAAGC

AACTATAACAGGCGCTTTACCCCGGAAATCGCCGAACGCCCGAAGGTGAGGGACCAGGCC

GGGAGGATGAACTACTACTGGACCTTGCTGAAGCCGGGCGACACAATCATTTTTGAAGCT

AACGGGAATCTAATTGCTCCCATGTACGCCTTTGCTCTGTCTCGCGGCTTTGGCAGGGGG

ATTATCACTAGCAACGCGTCCATGCACGAGTGTAATACTAAATGCCAGACGCCACTGGGC

GCAATCAATAGCAGCCTTCCATACCAGAACATACATCCCGTCACCATAGGAGAATGTCCA

AAGTACGTCCGGTCTGCAAAACTAAGGATGGTGACCGGGCTTAGAAACAACCCAAGTATT

CAGAGCCGGGGGCTCTTTGGTGCCATCGCAGGCTTTATCGAGGGAGGGTGGACAGGCATG

ATAGACGGATGGTATGGATACCATCACCAGAATGAGCAGGGCAGCGGATACGCTGCCGAC

CAAAAAAGCACCCAAAACGCTATCAATGGCATTACTAATAAGGTGAACACTGTGATTGAG

AAGATGAACATTCAGTTCACCGCAGTCGGGAAGGAATTTAACAAGCTGGAGAAAAGGATG

GAGAACTTAAACAAGAAGGTTGATGACGGGTTTCTCGACATATGGACGTATAACGCGGAG

TTGCTGGTATTACTGGAGAATGAACGGACTCTTGACTTCCACGATTCAAATGTGAAGAAT

CTCTATGAAAAAGTCAAATCGCAGCTCAAAAATAATGCCAAGGAGATCGGCAACGGCTGT

TTCGAGTTTTATCACAAATGCGACAACGAATGTATGGAATCAGTGCGAAATGGCACATAT

GACTATCCGAAATACTCCGAGGAAAGTAAGCTGAATAGAGAAAAGGTGGACGGAGTAAAG

CTCGAGTCCATGGGGATCTACCAGATTTTGGCTATCTATTCCACAGTTGCTTCATCTCTG

GTGCTGCTGGTTTCCTTAGGCGCCATATCGTTCTGGATGTGCTCCAACGGGTCCCTGCAG

TGTCGAATCTGCATC

438
ATGAAGGCGAATCTACTTGTCCTGCTGTGCGCGCTTGCGGCTGCTGACGCCGACACGATC

TGCATAGGCTACCATGCAAATAACTCCACTGACACCGTCGACACCGTTCTTGAGAAGAAT

GTGACGGTTACTCACTCCGTGAACCTCTTAGAGGATAGTCACAATGGCAAGTTGTGCAGA

TTAAAAGGCATAGCTCCTCTTCAGCTGGGGAAATGTAATATCGCCGGGTGGCTCCTCGGG

AACCCTGAATGCGATCCTCTGCTACCTGTGAGGAGTTGGAGCTACATAGTCGAAACTCCT

AACTCGGAGAATGGAATTTGTTACCCTGGAGACTTCATTGATTACGAAGAGCTGCGGGAA

CAATTGTCCTCTGTGTCATCATTTGAGCGGTTTGAGATTTTCCCCAAAGAAAGTAGTTGG

CCAAATCATAACACTAACGGGGTCACCGCCGCATGTTCCCATGAAGGAAAGAGCTCTTTT

TATCGAAACCTCCTCTGGCTTACTGAGAAGGAAGGATCCTATCCCAAGCTCAAGAACTCC

TACGTGAATAAAAAGGGCAAAGAAGTTCTGGTGCTGTGGGGTATTCACCATCCCCCCAAC

TCAAAAGAGCAACAGAACCTCTACCAGAATGAGAATGCGTACGTGTCAGTGGTTACTAGC

AACTACAATAGGCGGTTTACACCGGAGATCGCCGAGCGTCCTAAAGTGAGAGACCAGGCT

GGAAGAATGAACTATTATTGGACGCTGCTCAAACCCGGTGACACTATCATTTTCGAGGCT

AATGGGAACTTGATTGCCCCTATGTATGCTTTCGCCTTATCACGCGGATTTGGCTCCGGG

ATCATTACCTCAAATGCCTCAATGCACGAGTGTAACACCAAGTGTCAGACACCCCTGGGC

GCGATTAACAGCAGTCTGCCGTACCAAAATATCCACCCCGTGACGATTGGGGAGTGCCCT

AAGTACGTGCGGAGTGCCAAACTGCGTATGGTGACAGGGCTGCGCAACAATCCTTCCATT

CAGTCGAGAGGCCTGTTTGGCGCCATCGCCGGGTTCATCGAAGGGGGGTGGACCGGAATG

ATTGATGGATGGTATGGGTACCATCATCAGAATGAGCAGGGGTCTGGATATGCAGCAGAC

CAGAAATCGACTCAAAATGCAATAAATGGCATAACGAATAAAGTTAATACAGTGATAGAG

AAGATGAATATCCAGTTTACTGCCGTGGGCAAGGAGTTCAATAAACTCGAGAAGCGCATG

GAGAACCTTAACAAAAAGGTGGACGATGGATTCCTGGATATCTGGACTTATAATGCCGAG

CTGCTGGTACTTCTCGAAAATGAGCGTACACTAGACTTCCATGACTCAAATGTAAAAAAT

TTATATGAGAAGGTGAAATCCCAGCTCAAGAACAATGCAAAGGAGATCGGCAATGGGTGT

TTCGAATTTTATCACAAGTGTGACAACGAGTGCATGGAATCAGTGAGAAACGGAACATAC

GACTACCCTAAATATAGTGAAGAGTCTAAGCTGAATCGTGAGAAAGTGGACGGGGTGAAA

CTCGAGTCTATGGGCATTTACCAGATTCTGGCTATTTATAGTACAGTGGCTTCAAGCTTA

GTCCTTCTAGTGAGCTTGGGTGCCATTTCATTTTGGATGTGTAGTAATGGGTCATTGCAG

TGTAGGATTTGTATC

439
ATGAAAGCAAACCTGCTGGTCTTATTGTGCGCCTTGGCAGCTGCCGATGCCGACACCATC

TGCATCGGGTACCACGCCAATAATAGTACTGACACCGTCGATACCGTGCTCGAAAAGAAC

GTAACTGTGACTCACAGTGTGAACCTGCTGGAGGATAGCCATAACGGCAAACTCTGCCGA

CTGAAAGGAATCGCTCCCTTGCAACTGGGCAAGTGCAACATAGCAGGGTGGTTACTGGGG

AACCCCGAGTGCGACCCGCTGCTCCCTGTAAGATCTTGGAGCTATATCGTGGAAACACCT

AACTCAGAAAATGGGATATGTTACCCAGGTGACTTTATCGATTACGAAGAATTGAGGGAA

CAGCTGAGCAGCGTTAGTAGCTTTGAACGATTTGAGATCTTCCCAAAGGAGTCCTCTTGG

CCTAATCACAACACAAATGGGGTGACCGCCGCTTGCTCTCATGAGGGTAAAAGTAGCTTT

TACCGGAACTTACTATGGCTGACCGAGAAAGAAGGAAGCTACCCCAAACTGAAAAATTCG

TACGTGAATAAAAAGGGGAAAGAGGTGTTAGTGCTCTGGGGGATACATCACCCTCCAAAT

TCCAAGGAGCAGCAGAATCTGTACCAAAACGAGAACGCCTACGTTTCCGTGGTGACTAGC

AATTATAACAGGCGGTTTACACCTGAAATCGCCGAACGGCCTAAAGTTCGAGATCAGGCC

GGGCGGATGAACTACTATTGGACTTTGCTCAAGCCTGGCGACACAATCATTTTTGAAGCC

AACGGGAACCTGATCGCACCGATGTATGCTTTTGCACTGAGTCGGGGGTTTGGCTCTGGC

ATTATCACCTCTAATGCGTCCATGCACGAATGTAATACCAAGTGTCAGACACCCCTGGGG

GCTATAAACTCCTCCCTCCCCTATCAGAACATCCACCCTGTGACCATCGGAGAATGTCCT

AAATATGTCCGCTCCGCCAAACTGCGGATGGTTACTGGCCTCAGAAATAATCCAAGCATT

CAGAGTCGAGGCCTCTTCGGCGCGATCGCCGGCTTCATTGAGGGTGGCTGGACCGGCATG

ATCGATGGGTGGTACGGGTATCATCATCAGAATGAACAGGGATCCGGCTACGCAGCAGAT

CAAAAAAGCACACAGAACGCGATTAATGGCATTACTAACAAGGTGAACACGGTGATCGAG

AAGATGAATATACAATTCACTGCTGTCGGGAAAGAGTTCAATAAGCTCGAAAAGAGGATG

GAGAATTTGAACAAGAAAGTGGATGATGGCTTCCTGGACATTTGGACCTACAATGCTGAA

CTCCTGGTCCTTCTGGAAAACGAAAGAACCCTAGATTTCCATGACTCTAACGTGAAGAAC

CTTTACGAAAAGGTGAAGAGCCAGTTGAAAAACAACGCAAAGGAAATTGGAAATGGGTGC

TTCGAGTTTTATCATAAGTGCGACAACGAGTGCATGGAAAGTGTCCGTAATGGCACTTAC

GATTACCCCAAATATTCTGAAGAATCCAAGCTGAACAGGGAGAAAGTCGATGGGGTTAAA

TTAGAATCCATGGGCATCTATCAGATACTGGCCATTTATTCCACTGTGGCGAGCTCCTTA

GTGCTCTTGGTCTCTTTAGGTGCCATCTCCTTTTGGATGTGCAGTAACGGGTCCCTCCAA

TGCAGGATTTGTATC

440
ATGAAGGCCAACCTCCTCGTTCTGCTGTGTGCGCTGGCAGCGGCAGATGCCGATACCATT

TGTATCGGTTACCATGCCAACAATTCCACCGACACCGTCGACACTGTTCTTGAAAAGAAT

GTAACTGTCACCCATTCTGTCAACTTGCTTGAAGATAGTCACAACGGCAAACTGTGTCGG

CTTAAAGGCATAGCCCCGCTGCAACTGGGCAAATGTAACATCGCCGGATGGCTGCTGGGA

AATCCAGAATGCGACCCCCTGTTGCCTGTGCGGTCTTGGAGTTACATAGTAGAAACCCCC

AATTCCGAAAATGGGATTTGTTATCCTGGCGACTTCATCGATTATGAGGAGTTGAGAGAG

CAATTGAGTAGCGTTTCTTCATTTGAGCGCTTCGAAATATTCCCGAAAGAGAGTTCATGG

CCTAACCACAACACAAATGGAGTGACAGCTGCCTGTTCCCACGAAGGAAAAAGCTCCTTT

TACCGTAACCTGCTATGGCTGACTGAAAAGGAGGGGTCCTACCCCAAACTTAAGAACTCT

TATGTCAACAAGAAGGGGAAAGAGGTACTGGTTCTGTGGGGAATTCATCATCCCCCGAAT

TCAAAAGAGCAGCAAAATCTGTACCAAAATGAAAACGCGTACGTCTCCGTTGTGACATCT

AACTACAATAGGCGGTTCACGCCCGAGATCGCTGAACGGCCGAAAGTCCGGGACCAAGCT

GGCAGAATGAACTATTACTGGACACTGCTCAAACCCGGCGACACCATTATTTTCGAGGCA

AATGGGAACCTGATTGCACCAATGTACGCCTTCGCTCTGTCCAGGGGCTTTGGTAGCGGA

ATTATCACCTCGAATGCTTCAATGCATGAGTGCAACACCAAGTGCCAGACACCTTTGGGC

GCCATCAATAGTAGCCTTCCTTACCAGAACATTCACCCTGTCACCATTGGTGAATGTCCT

AAGTACGTGCGAAGCGCCAAACTGCGGATGGTTACTGGCCTGCGAAATAATCCCTCCATC

CAGTCTCGCGGTCTGTTCGGAGCCATTGCAGGGTTCATCGAGGGAGGCTGGACCGGGATG

ATTGACGGCTGGTATGGGTACCACCATCAGAACGAGCAAGGATCCGGGTATGCCGCCGAC

CAGAAGAGCACCCAGAACGCTATCAATGGGATTACAAATAAAGTCAACACCGTCATCGAG

AAGATGAACATCCAATTCACTGCGGTTGGCAAGGAGTTCAACAAACTCGAGAAAAGAATG

GAAAACTTGAATAAGAAGGTAGACGACGGGTTTCTGGATATCTGGACTTATAACGCCGAA

TTATTGGTGCTGCTGGAGAATGAACGGACTTTAGATTTCCACGACTCCAATGTGAAGAAT

CTATACGAGAAAGTGAAGTCTCAGTTGAAGAACAACGCCAAGGAGATAGGAAATGGCTGT

TTCGAGTTTTATCACAAGTGCGATAATGAGTGCATGGAAAGCGTGCGCAACGGGACATAT

GATTACCCGAAGTACTCCGAGGAAAGCAAACTAAATCGCGAAAAGGTAGATGGCGTGAAG

CTGGAATCGATGGGAATCTACCAGATCCTAGCTATTTACTCTACTGTTGCCAGCTCTCTG

GTGCTTCTGGTATCTCTGGGGGCCATTAGTTTCTGGATGTGCAGTAACGGCTCATTACAG

TGTAGGATATGCATT

441
ATGAAAGCAAACTTGCTGGTTCTGTTGTGCGCTCTCGCGGCCGCTGACGCGGACACTATC

TGCATCGGGTACCACGCGAATAATTCGACTGACACAGTTGACACTGTGCTCGAAAAGAAT

GTGACCGTCACGCACTCCGTCAATCTCCTGGAGGACTCACACAATGGCAAACTTTGTCGT

TTGAAGGGCATCGCACCCCTCCAACTCGGGAAATGCAACATTGCAGGTTGGCTTTTAGGT

AATCCTGAGTGTGATCCCCTGCTGCCTGTGCGCAGCTGGAGCTATATTGTCGAGACACCC

AACTCCGAAAATGGAATCTGTTACCCAGGAGACTTCATTGACTATGAAGAATTAAGAGAG

CAATTAAGCTCCGTGAGCTCCTTTGAGAGGTTTGAGATCTTCCCGAAGGAAAGCTCCTGG

CCTAACCATAACACCAATGGAGTGACTGCCGCCTGCAGCCACGAAGGAAAGTCTTCCTTC

TATAGAAACCTACTGTGGTTGACAGAGAAGGAAGGCTCCTATCCTAAATTGAAGAACTCA

TATGTCAACAAGAAGGGGAAAGAGGTCCTCGTGCTGTGGGGAATCCATCATCCTCCTAAC

TCTAAGGAGCAACAAAATTTATACCAGAACGAAAATGCATACGTTTCTGTGGTTACATCA

AACTATAATAGGCGCTTCACACCTGAGATTGCTGAACGTCCCAAAGTGAGGGATCAAGCG

GGGCGTATGAACTACTACTGGACACTGTTAAAACCGGGGGATACCATCATCTTTGAGGCG

AACGGCAATCTTATTGCACCTATGTATGCTTTTGCCCTCTCGCGCGGTTTCGGCAGTGGA

ATAATAACATCAAATGCCAGTATGCACGAGTGCAATACGAAGTGCCAGACTCCCTTAGGC

GCTATAAATAGTTCCTTACCTTACCAGAATATTCACCCAGTGACCATCGGCGAATGCCCA

AAGTACGTCAGGTCTGCGAAACTGAGAATGGTCACAGGGTTGAGAAATAATCCATCTATC

CAGTCACGAGGCCTGTTTGGCGCGATCGCGGGCTTTATTGAAGGAGGGTGGACGGGTATG

ATTGACGGATGGTACGGTTACCATCATCAAAATGAACAAGGTTCAGGGTATGCCGCGGAC

CAGAAGAGCACCCAGAATGCAATCAATGGCATTACCAACAAGGTGAACACGGTGATCGAG

AAGATGAATATTCAGTTTACCGCTGTGGGCAAGGAGTTTAATAAGCTCGAGAAACGCATG

GAAAATCTGAACAAAAAAGTAGACGATGGATTCCTCGACATATGGACGTACAATGCCGAG

CTTCTCGTCCTCTTAGAGAACGAGCGGACCCTGGATTTCCACGATTCAAACGTCAAAAAC

CTGTATGAGAAAGTCAAGAGCCAGCTTAAGAATAACGCCAAGGAAATCGGGAACGGCTGC

TTCGAGTTCTATCATAAATGCGACAATGAGTGTATGGAATCTGTACGCAATGGAACATAC

GACTACCCTAAGTACTCCGAAGAAAGCAAACTGAATAGGGAGAAGGTAGACGGAGTGAAA

TTGGAGAGCATGGGCATATACCAGATCCTGGCCATTTACTCAACCGTCGCCTCATCCTTG

GTGTTGCTGGTGTCCTTGGGTGCTATTTCTTTTTGGATGTGCAGCAATGGCAGTCTCCAG

TGCAGGATTTGTATC

442
ATGAAGGCTAACCTGCTGGTGCTCCTCTGCGCTCTGGCAGCTGCAGACGCTGATACCATT

TGCATTGGCTACCATGCCAATAACAGCACCGATACAGTCGATACAGTTCTGGAGAAGAAC

GTGACAGTGACTCACAGCGTTAATCTGTTGGAGGACAGCCATAATGGGAAGCTGTGTCGC

CTGAAGGGAATTGCTCCATTACAGCTGGGGAAATGTAACATCGCTGGATGGCTGTTGGGA

AACCCAGAGTGTGATCCCCTACTTCCTGTACGGAGTTGGAGTTATATCGTGGAGACACCC

AATAGTGAGAACGGTATCTGTTATCCTGGAGATTTTATAGACTATGAAGAGTTAAGGGAG

CAGCTGAGCTCCGTCAGTTCATTCGAACGCTTCGAAATTTTCCCTAAGGAGTCTTCCTGG

CCCAACCACAATACCAACGGGGTCACCGCTGCTTGTAGTCATGAAGGAAAATCTAGCTTC

TACCGAAACCTGCTCTGGCTAACTGAGAAAGAAGGATCATACCCGAAGCTGAAGAATAGC

TACGTGAACAAGAAGGGGAAGGAAGTGCTGGTTCTGTGGGGCATTCACCACCCCCCTAAC

AGTAAGGAACAGCAGAACCTCTATCAGAATGAGAACGCATACGTGAGTGTCGTTACAAGC

AACTACAATCGCCGGTTTACTCCAGAGATCGCGGAAAGACCCAAAGTCAGGGACCAGGCT

GGTAGGATGAATTACTATTGGACCCTTCTCAAACCTGGGGACACTATCATATTCGAGGCC

AATGGCAACCTGATTGCCCCTATGTACGCCTTTGCTCTGAGCCGCGGATTCGGCTCCGGC

ATAATCACGTCTAATGCTTCCATGCACGAGTGTAACACAAAATGTCAGACGCCCTTGGGC

GCTATCAATTCTAGTCTGCCTTATCAGAACATACATCCAGTCACTATCGGAGAGTGCCCA

AAGTACGTTCGCTCTGCAAAGCTCCGGATGGTTACAGGTCTAAGAAATAATCCTAGTATT

CAGAGCAGGGGCCTGTTTGGAGCCATAGCTGGATTTATAGAGGGCGGATGGACTGGGATG

ATAGATGGGTGGTATGGCTACCATCACCAGAATGAACAGGGGAGCGGATACGCTGCCGAC

CAAAAATCTACTCAGAACGCAATTAATGGTATCACAAACAAAGTGAACACAGTGATCGAA

AAGATGAACATTCAGTTCACTGCTGTGGGGAAAGAGTTCAACAAGCTGGAGAAACGAATG

GAAAATCTGAATAAAAAGGTGGACGACGGATTCCTTGACATTTGGACTTACAACGCCGAA

TTACTTGTCCTCTTGGAAAACGAACGGACCCTGGATTTTCATGACTCCAATGTTAAGAAC

CTGTATGAGAAGGTGAAGAGCCAGCTGAAAAATAACGCAAAGGAAATCGGGAACGGATGT

TTTGAGTTTTACCACAAGTGCGATAATGAATGTATGGAGAGTGTTCGGAATGGGACATAC

GACTACCCTAAGTATTCTGAGGAGTCTAAGCTCAACCGGGAGAAGGTGGATGGTGTTAAG

TTAGAGAGTATGGGAATTTACCAGATTCTGGCCATATACTCTACAGTAGCATCTTCTCTG

GTGTTATTGGTCAGTCTCGGTGCTATTTCTTTTTGGATGTGCTCAAACGGCTCACTGCAG

TGCCGCATCTGTATC

443
ATGAAAGCAAACCTGCTGGTCCTCTTGTGCGCGCTGGCAGCCGCCGATGCTGACACCATA

TGTATTGGCTATCACGCTAACAATTCTACGGACACTGTGGATACGGTGCTGGAGAAAAAC

GTAACCGTCACACACAGCGTGAATCTGCTGGAGGATTCGCATAATGGTAAACTTTGCAGA

CTGAAGGGGATAGCCCCGCTCCAGTTGGGTAAGTGTAATATCGCCGGATGGTTGCTTGGG

AACCCCGAGTGTGATCCTCTGTTGCCGGTGCGCAGTTGGTCGTACATCGTGGAAACCCCG

AATAGTGAGAATGGCATTTGTTATCCAGGGGACTTCATCGATTACGAAGAGCTCAGGGAG

CAGCTCAGCTCTGTAAGTAGCTTCGAACGGTTCGAGATCTTCCCCAAAGAAAGCTCCTGG

CCCAATCACAACACTAACGGGGTGACAGCGGCCTGCAGCCACGAGGGCAAAAGTTCTTTC

TATCGCAACCTACTGTGGCTCACCGAGAAGGAGGGAAGTTACCCTAAGCTGAAGAACAGC

TATGTCAACAAGAAAGGCAAGGAGGTCCTTGTGTTATGGGGCATTCACCACCCTCCCAAT

AGCAAAGAGCAGCAAAACCTTTATCAAAATGAGAACGCCTACGTGAGCGTGGTGACCTCT

AACTACAACAGAAGGTTTACACCAGAGATCGCCGAAAGGCCTAAAGTTAGGGACCAGGCC

GGACGGATGAATTACTATTGGACGTTATTAAAGCCTGGGGATACCATTATCTTTGAGGCC

AATGGCAACTTGATCGCCCCTATGTACGCCTTTGCTCTCTCGCGCGGATTTGGTTCCGGA

ATCATTACCAGCAATGCTTCAATGCATGAGTGCAATACAAAGTGTCAGACCCCACTGGGC

GCTATTAACTCGTCTTTACCGTATCAAAATATACATCCCGTGACTATTGGTGAGTGCCCT

AAATATGTTCGCTCTGCTAAGCTCAGGATGGTTACTGGACTGCGGAACAATCCGTCGATT

CAGTCCAGGGGACTCTTCGGCGCAATTGCGGGTTTCATCGAGGGTGGCTGGACGGGCATG

ATCGACGGCTGGTACGGTTACCACCATCAGAACGAACAGGGATCCGGCTACGCAGCCGAT

CAAAAGTCTACGCAGAACGCTATTAATGGAATCACCAACAAGGTGAATACAGTTATCGAA

AAGATGAATATACAGTTTACTGCCGTGGGGAAAGAATTCAACAAACTGGAGAAGAGAATG

GAGAATCTTAACAAGAAGGTCGACGATGGCTTCCTTGATATCTGGACGTACAATGCCGAG

CTGCTGGTCCTCCTCGAGAATGAACGAACTCTGGACTTCCACGACTCCAATGTAAAGAAT

CTCTATGAAAAGGTGAAATCCCAGCTGAAAAATAACGCCAAGGAGATAGGAAATGGCTGC

TTCGAATTTTACCACAAATGTGACAATGAATGCATGGAGTCCGTGAGAAATGGAACCTAC

GACTATCCCAAATATTCAGAAGAGTCAAAGCTAAATCGCGAAAAAGTTGACGGAGTCAAG

CTCGAGTCTATGGGCATATATCAGATTCTGGCCATCTACTCCACCGTGGCCTCTTCCCTT

GTCCTTCTAGTGTCCTTGGGTGCAATTTCTTTTTGGATGTGCAGCAACGGGTCCCTGCAA

TGCAGGATTTGTATA

444
ATGAAGGCCAACCTTCTCGTCTTACTATGTGCACTTGCCGCAGCAGATGCCGATACTATC

TGCATCGGCTATCATGCCAATAACAGCACAGACACCGTGGATACGGTGCTGGAGAAGAAC

GTTACAGTGACCCACTCCGTTAATCTGCTTGAAGATAGTCATAACGGCAAGCTGTGTCGC

TTGAAAGGGATCGCCCCTCTCCAGCTGGGTAAGTGCAACATTGCTGGGTGGCTCCTTGGC

AACCCTGAGTGTGACCCACTACTTCCTGTGAGAAGTTGGAGCTATATCGTAGAGACACCA

AATTCTGAAAACGGAATCTGTTATCCCGGAGACTTCATCGACTACGAGGAACTGCGCGAA

CAACTGTCTTCCGTCTCTTCCTTTGAGAGATTTGAGATCTTTCCCAAAGAAAGTAGTTGG

CCAAACCATAATACTAACGGCGTGACAGCAGCCTGTAGTCACGAAGGCAAGTCCAGTTTT

TACCGCAACCTGCTCTGGCTGACAGAAAAGGAGGGGAGTTATCCAAAGCTGAAAAACTCT

TACGTCAACAAGAAAGGGAAAGAGGTCCTGGTTCTTTGGGGCATTCATCATCCCCCAAAT

TCAAAGGAACAGCAGAATCTTTACCAGAACGAAAATGCTTACGTGAGTGTGGTCACCAGT

AACTACAACAGGAGGTTCACACCAGAGATAGCAGAACGGCCAAAAGTAAGAGATCAGGCT

GGTAGGATGAACTATTACTGGACACTGCTCAAGCCGGGTGACACCATAATCTTTGAGGCT

AATGGCAACCTTATTGCTCCCATGTACGCTTTCGCTCTTAGCAGAGGGTTTGGCAGCGGC

ATTATCACATCAAATGCAAGCATGCACGAGTGCAACACCAAGTGTCAAACACCCCTCGGC

GCAATAAATAGCAGCTTGCCATATCAGAATATACACCCCGTGACAATCGGCGAGTGTCCT

AAATACGTACGCTCTGCAAAACTCCGCATGGTGACCGGCCTCCGTAACAACCCCAGCATC

CAGAGTCGGGGGCTCTTTGGCGCCATCGCCGGGTTTATTGAAGGGGGGTGGACAGGGATG

ATTGATGGTTGGTATGGATATCACCACCAGAACGAACAAGGATCAGGTTACGCGGGGGAC

CAGAAGAGCACCCAAAACGCTATAAACGGCATAACCAACAAGGTAAACACCGTTATTGAA

AAGATGAATATTCAGTTTACCGCAGTCGGTAAAGAGTTTAATAAGCTCGAGAAGAGGATG

GAAAATCTGAACAAGAAGGTTGATGATGGGTTTTTAGATATTTGGACCTACAATGCGGAG

CTGCTCGTCCTGTTAGAAAATGAGAGGACACTGGACTTCCACGATAGTAATGTGAAGAAC

CTCTATGAGAAGGTGAAAAGTCAGCTCAAGAATAACGCTAAAGAGATTGGGAATGGTTGT

TTTGAATTTTATCACAAATGCGACAATGAATGTATGGAGAGTGTAAGGAACGGTACGTAC

GACTACCCAAAATATTCAGAAGAGTCTAAACTCAATAGAGAGAAGGTTGACGGAGTGAAA

CTGGAGTCCATGGGCATTTACCAGATCCTGGCAATCTACTCTACTGTTGCTAGCTCGTTG

GTGTTGCTCGTCAGTCTGGGAGCTATCTCCTTCTGGATGTGTAGTAATGGGAGCCTGCAG

TGCCGGATCTGTATT

445
ATGAAGGCTAATCTACTGGTTCTTCTGTGCGCGCTCGCCGCAGCAGATGCTGATACTATC

TGCATCGGGTATCATGCTAATAACAGCACCGACACCGTCGATACGGTACTAGAGAAAAAC

GTTACTGTGACTCACTCCGTGAACCTGCTGGAAGACTCACATAACGGCAAACTGTGTCGC

CTGAAGGGGATTGCCCCCCTGCAGCTGGGGAAGTGTAATATAGCGGGATGGCTGTTGGGG

AATCCTGAGTGTGATCCACTTCTCCCCGTGAGATCCTGGAGTTACATTGTGGAGACTCCA

AATTCGGAGAACGGGATCTGCTATCCAGGAGACTTCATCGACTACGAAGAATTGCGAGAG

CAACTGTCTAGCGTGTCCTCCTTTGAAAGATTCGAGATTTTTCCAAAGGAGTCCAGTTGG

CCTAACCATAACACTAACGGCGTGACTGCCGCTTGTTCTCACGAGGGCAAGTCTTCTTTT

TATAGAAACCTTCTCTGGCTCACCGAAAAAGAAGGTTCCTATCCCAAACTCAAAAACTCC

TACGTGAATAAGAAAGGCAAAGAAGTCCTGGTGTTGTGGGGTATACACCATCCGCCTAAC

TCCAAGGAACAGCAGAATCTCTACCAGAACGAGAATGCATACGTGTCAGTTGTCACCTCC

AACTACAACCGGCGGTTCACCCCTGAGATCGCCGAAAGGCCAAAAGTGCGTGACCAGGCC

GGACGCATGAACTACTACTGGACTCTCTTGAAGCCAGGAGACACCATTATCTTCGAAGCC

AATGGCAACCTGATTGCCCCCATGTACGCTTTCGCACTCAGCAGAGGTTTCGGGTCCGGC

ATAATTACTAGCAACGCCAGCATGCACGAATGCAACACTAAATGTCAGACCCCACTCGGA

GCCATCAACTCCAGTCTGCCCTACCAGAATATTCACCCTGTCACCATCGGCGAATGCCCC

AAGTACGTGAGGAGTGCTAAACTTCGAATGGTGACCGGCCTGCGGAACAATCCGAGCATT

CAGTCCCGGGGATTGTTTGGAGCCATCGCTGGATTTATAGAGGGGGGCTGGACCGGCATG

ATCGACGGCTGGTATGGCTATCATCATCAAAATGAACAGGGCAGCGGCTATGCAGCTGAC

CAAAAGTCAACCCAGAACGCTATTAACGGAATCACAAACAAGGTGAATACCGTGATAGAA

AAGATGAATATTCAGTTCACGGCTGTGGGAAAGGAATTCAACAAGTTAGAGAAGAGGATG

GAAAATCTGAATAAGAAGGTGGACGACGGGTTCTTGGATATCTGGACATACAACGCTGAG

CTCTTGGTGCTGCTCGAAAATGAACGGACTCTTGACTTTCACGACTCAAACGTAAAAAAT

CTCTATGAAAAGGTGAAATCTCAGTTGAAGAATAACGCAAAGGAGATTGGCAATGGGTGC

TTCGAATTCTATCACAAGTGTGATAACGAGTGTATGGAGTCAGTCCGGAATGGGACTTAC

GACTATCCCAAGTATAGTGAAGAATCTAAGCTCAATCGCGAAAAGGTGGACGGGGTGAAG

TTGGAATCAATGGGTATTTATCAGATCCTCGCAATTTACTCTACCGTGGCCTCCTCATTG

GTTTTGCTGGTGTCCCTTGGAGCTATAAGCTTCTGGATGTGCAGTAATGGGTCACTACAG

TGCCGTATTTGCATT

446
ATGAAGGCCAACTTGCTGGTGCTTCTTTGCGCCCTCGCAGCAGCTGACGCCGATACCATC

TGTATAGGCTATCACGCAAACAATAGCACCGATACTGTGGATACCGTGCTTGAGAAGAAC

GTTACAGTGACACATTCAGTGAACCTACTCGAGGACTCCCACAATGGAAAGCTGTGTAGG

CTGAAAGGCATTGCACCACTGCAGCTCGGGAAATGTAATATAGCAGGGTGGCTCCTCGGC

AATCCCGAGTGCGATCCCCTGCTGCCCGTCAGGTCATGGAGCTACATTGTAGAAACCCCG

AACTCTGAGAATGGCATTTGTTATCCCGGAGATTTCATCGACTACGAAGAACTGCGAGAG

CAACTCTCATCCGTGTCTTCATTTGAAAGGTTCGAGATCTTCCCCAAGGAGTCTAGCTGG

CCTAATCACAACACAAACGGCGTGACTGCCGCCTGTTCACACGAGGGTAAGAGTTCATTT

TACAGGAACCTCCTGTGGCTGACTGAGAAGGAAGGCAGCTATCCAAAGTTGAAGAATTCG

TACGTGAACAAGAAGGGGAAAGAAGTTCTGGTACTCTGGGGGATCCACCACCCGCCTAAT

TCCAAAGAACAGCAGAATCTATACCAGAACGAAAATGCTTACGTCAGCGTTGTGACATCC

AATTACAACAGAAGATTTACCCCAGAGATAGCCGAGCGACCCAAGGTGAGGGACCAGGCG

GGACGAATGAATTATTACTGGACCCTGTTGAAGCCAGGAGACACCATCATTTTTGAAGCC

AACGGAAATCTTATCGCGCCGATGTACGCGTTCGCACTGTCACGAGGATTTGGCTCGGGG

ATTATTACCTCAAATGCTAGCATGCACGAATGCAACACTAAGTGTCAGACTCCGCTGGGA

GCTATCAATTCATCTCTCCCATATCAGAATATTCATCCCGTGACCATAGGCGAGTGCCCC

AAATACGTCCGGTCGGCAAAATTGCGGATGGTTACTGGTCTGAGAAATAATCCATCCATA

CAGTCTCGCGGTTTATTTGGGGCGATTGCAGGCTTTATTGAGGGGGGATGGACGGGCATG

ATCGATGGTTGGTACGGATATCACCACCAAAACGAGCAAGGGAGTGGTTATGCCGCCGAT

CAGAAGTCGACACAAAACGCAATAAATGGTATAACAAATAAAGTTAACACCGTAATCGAG

AAGATGAACATCCAGTTTACAGCCGTGGGGAAGGAATTCAACAAGCTGGAAAAGCGCATG

GAGAACCTGAACAAAAAGGTGGATGACGGCTTCCTGGACATTTGGACCTACAACGCAGAG

TTGTTAGTGCTGCTGGAGAATGAGCGAACACTGGATTTTCATGACTCCAATGTGAAGAAT

CTCTACGAGAAGGTGAAGTCACAGCTCAAGAACAATGCTAAAGAGATTGGGAACGGGTGC

TTCGAATTTTACCATAAATGCGACAACGAGTGTATGGAGTCCGTCCGTAATGGCACTTAT

GACTACCCTAAATACTCTGAAGAGTCCAAACTCAATCGGGAGAAAGTGGACGGTGTGAAG

CTGGAGTCAATGGGGATATACCAGATCTTAGCAATTTACAGCACCGTCGCCTCCTCATTG

GTGCTTCTGGTCTCTCTCGGAGCAATTAGTTTTTGGATGTGTTCCAATGGGTCTCTCCAG

TGCCGGATATGCATT

447
ATGAAAGCCAACCTTCTAGTGTTACTTTGCGCTCTCGCCGCTGCCGATGCCGATACAATC

TGTATCGGTTATCACGCGAATAATTCCACCGACACTGTCGATACAGTGTTGGAAAAGAAT

GTCACAGTCACACATTCCGTCAATTTGTTGGAGGACAGCCATAACGGAAAGTTGTGTAGA

TTGAAAGGGATTGCCCCACTGCAGCTGGGTAAGTGTAATATTGCTGGTTGGCTACTGGGC

AACCCAGAATGTGACCCCCTTCTACCCGTCAGGAGTTGGAGCTACATTGTGGAGACCCCT

AACAGCGAGAATGGCATTTGCTACCCAGGCGACTTTATCGATTACGAAGAACTGCGGGAA

CAGTTGAGCTCTGTTAGTAGCTTCGAGAGATTCGAGATATTCCCAAAGGAGTCAAGCTGG

CCCAATCACAACACCAATGGGGTTACAGCAGCTTGTAGCCATGAAGGCAAAAGCAGCTTC

TATCGAAATCTACTCTGGCTCACCGAAAAGGAAGGATCCTACCCGAAACTCAAAAACAGC

TACGTCAACAAGAAGGGAAAAGAGGTGCTGGTGCTGTGGGGAATCCATCATCCTCCCAAC

AGCAAAGAGCAACAGAATTTGTATCAAAACGAAAACGCTTACGTGAGCGTGGTAACCTCA

AACTATAACAGACGGTTTACACCAGAAATCGCAGAGAGGCCAAAAGTGGGGGACCAAGCC

GGTAGAATGAACTATTACTGGACCCTCTTGAAACCTGGAGACACCATAATATTCGAGGCC

AACGGAAATCTGATCGCCCCAATGTATGCCTTCGCTCTCTCTAGGGGCTTCGGCAGCGGG

ATAATTACCTCCAACGCCAGCATGCATGAGTGCAATACCAAGTGTCAAACTCCCCTGGGC

GCAATTAACAGCTCCCTGCCTTACCAAAACATTCACCCAGTCACCATCGGAGAGTGCCCC

AAATACGTTAGATCTGCAAAGCTGCGGATGGTGACAGGTCTACGCAACAACCCCTCAATC

CAGTCACGGGGGCTTTTCGGTGCCATTGCCGGGTTTATTGAAGGTGGCTGGACCGGCATG

ATAGATGGGTGGTATGGCTACCACCATCAGAATGAACAGGGAAGTGGGTATGCAGGGGAC

CAGAAAAGCACGCAGAACGCAATAAACGGGATCACGAATAAAGTGAACACCGTCATTGAA

AAGATGAACATCCAGTTTACCGCGGTTGGAAAAGAATTTAACAAGCTCGAAAAAAGAATG

GAAAATCTGAACAAGAAGGTCGACGACGGATTCCTTGATATTTGGACTTACAATGCTGAG

CTTCTTGTACTGTTAGAAAACGAGCGAACCTTGGATTTCCACGATTCAAACGTCAAAAAC

TTGTACGAGAAAGTGAAGAGCCAACTCAAGAACAACGCCAAGGAAATTGGGAATGGTTGC

TTTGAATTTTACCATAAGTGCGACAATGAATGCATGGAGTCGGTACGAAACGGGACTTAT

GATTATCCAAAGTATAGCGAAGAGAGTAAACTCAACCGGGAGAAAGTCGATGGGGTGAAA

CTGGAGTCAATGGGAATTTATCAAATTCTGGCTATCTATTCTACAGTGGCCTCTTCTCTC

GTCTTGCTAGTGAGCCTCGGAGCAATCTCTTTTTGGATGTGCAGCAATGGCTCCCTGCAA

TGCCGCATCTGCATA

448
ATGAAGGCTAACCTCCTGGTGTTGTTGTGTGCCCTGGCTGCAGCTGACGCCGATACTATT

TGCATAGGCTATCATGCTAATAATAGTACAGATACGGTTGACACCGTTCTCGAAAAGAAC

GTGACGGTGACACATAGCGTTAATCTGCTAGAAGACTCCCACAATGGGAAGCTGTGCCGG

CTGAAGGGGATCGCACCACTCCAGCTAGGTAAGTGCAATATCGCCGGGTGGCTGTTAGGA

AATCCGGAGTGCGACCCTCTTCTCCCCGTGAGGTCTTGGTCCTACATCGTGGAAACTCCA

AACAGTGAAAACGGAATCTGCTATCCTGGCGATTTTATAGACTATGAAGAGCTGCGTGAG

CAACTGAGCAGCGTATCCAGCTTCGAAAGATTCGAGATTTTCCCTAAGGAATCGTCATGG

CCGAATCACAACACTAATGGCGTCACTGCTGCATGCAGCCATGAGGGCAAAAGCAGCTTC

TATAGAAATCTCCTGTGGCTTACCGAGAAAGAGGGTAGCTATCCTAAGCTCAAGAATAGC

TATGTCAATAAGAAAGGCAAGGAGGTGCTGGTGTTGTGGGGAATCCATCACCCACCTAAC

TCCAAAGAGCAGCAGAACCTGTATCAAAACGAGAACGCCTACGTGTCTGTAGTGACGAGC

AACTACAACAGGCGTTTCACACCTGAGATCGCGGAGCGCCCCAAGGTTCGCGACCAAGCG

GGGCGCATGAATTACTATTGGACTCTTTTAAAGCCGGGAGATACGATCATCTTTGAGGCT

AACGGCAACTTAATCGCCCCTATGTACGCCTTTGCGTTGTCGCGGGGATTCGGATCCGGT

ATAATAACAAGCAACGCAAGTATGCACGAATGTAATACTAAATGTCAAACCCCTTTAGGG

GCCATTAACAGCAGCCTTCCGTACCAGAACATTCATCCCGTCACCATCGGCGAATGCCCA

AAATATGTGCGGTCCGCGAAACTCAGAATGGTAACAGGCCTGCGGAATAATCCTAGTATA

CAGTCCAGAGGACTTTTTGGGGCGATAGCTGGATTCATTGAAGGCGGATGGACTGGGATG

ATTGACGGATGGTACGGCTACCACCATCAGAACGAACAGGGCAGTGGGTACGCTGCTGAT

CAAAAATCCACACAAAATGCCATTAATGGAATTACAAACAAAGTTAATACAGTCATCGAG

AAAATGAATATTCAGTTCACAGCTGTGGGCAAAGAGTTTAACAAACTGGAGAAACGAATG

GAGAACCTGAACAAAAAGGTTGATGATGGCTTTCTGGACATCTGGACATATAATGCTGAG

CTGTTGGTCCTACTGGAGAATGAGAGGACCTTGGACTTCCACGACTCCAATGTTAAGAAC

CTATATGAGAAGGTTAAGTCGCAATTGAAAAACAATGCAAAGGAAATCGGGAACGGGTGC

TTTGAATTCTATCATAAATGTGATAATGAGTGCATGGAAAGCGTGCGTAATGGGACTTAC

GATTATCCTAAGTATAGTGAGGAATCTAAGTTGAACAGAGAGAAAGTGGATGGAGTCAAG

TTAGAAAGTATGGGTATCTACCAAATTCTTGCTATATATAGCACAGTGGCTTCCAGCCTC

GTCTTGCTTGTCTCTCTCGGGGCTATCAGCTTTTGGATGTGCTCAAACGGCAGCCTCCAG

TGTCGGATATGTATC

449
ATGAAGGCTAACCTGCTGGTGCTGTTGTGTGCACTCGCAGCCGCGGACGCCGACACTATC

TGCATAGGCTATCACGCTAATAACTCAACGGATACGGTGGATACCGTTCTGGAGAAGAAT

GTAACCGTCACACACAGCGTCAATCTGCTCGAGGATAGCCACAACGGCAAACTATGCCGC

CTGAAGGGGATAGCTCCCCTCCAGCTGGGAAAGTGTAACATTGCCGGATGGCTCCTGGGA

AATCCAGAGTGCGATCCCCTGTTACCTGTCAGATCATGGTCTTACATCGTGGAGACCCCT

AACTCCGAGAATGGGATCTGCTACCCCGGAGACTTTATTGACTACGAGGAGCTGAGAGAG

CAATTGTCTTCAGTGAGTTCTTTTGAGAGGTTTGAAATCTTCCCGAAGGAGAGTTCATGG

CCAAATCACAATACGAATGGAGTTACCGCAGCTTGCTCTCATGAGGGCAAGAGCAGTTTC

TACAGGAACCTACTGTGGCTGACCGAGAAGGAAGGTAGCTACCCGAAGCTGAAGAATTCA

TACGTCAATAAAAAGGGCAAGGAAGTGTTAGTGCTCTGGGGCATCCATCACCCCCCCAAC

TCCAAAGAGCAGCAGAACCTTTATCAGAATGAAAACGCTTATGTTTCAGTGGTGACCTCT

AATTATAACCGACGTTTTACTCCAGAGATCGCTGAAAGACCCAAGGTCCGTGACCAAGCA

GGGCGGATGAACTATTACTGGACCCTGCTAAAGCCTGGCGATACTATAATTTTCGAAGCT

AACGGCAACCTTATTGCTCCCATGTATGCATTCGCCCTGAGTCGTGGATTTGGCAGCGGT

ATTATCACCTCTAATGCATCGATGCATGAATGTAATACAAAATGCCAGACTCCATTGGGC

GCTATTAACTCAAGCCTTCCTTATCAAAATATCCACCCTGTAACTATCGGGGAGTGTCCC

AAATATGTGCGCTCAGCCAAGCTCCGCATGGTAACTGGACTCCGCAACAATCCATCAATA

CAGAGCAGAGGACTGTTCGGGGCGATAGCCGGGTTCATCGAAGGAGGCTGGACCGGCATG

ATCGACGGGTGGTACGGTTACCATCACCAAAACGAGCAGGGCAGCGGCTACGCTGCCGAT

CAAAAGTCCACACAAAATGCCATAAACGGAATAACCAATAAGGTCAACACTGTGATCGAA

AAGATGAATATTCAGTTCACTGCTGTCGGTAAAGAATTCAATAAGCTGGAAAAGCGCATG

GAGAACCTTAACAAAAAGGTGGACGACGGCTTTTTAGACATCTGGACCTACAATGCCGAA

CTGCTAGTGCTACTTGAAAACGAAAGGACCTTGGATTTTCACGACAGTAATGTTAAAAAT

CTCTACGAGAAAGTAAAGTCTCAGTTGAAGAACAATGCTAAGGAGATCGGCAATGGATGC

TTTGAGTTCTATCACAAGTGCGATAACGAATGCATGGAAAGTGTGCGCAACGGAACCTAT

GACTACCCCAAGTATTCCGAAGAGAGCAAGCTTAACAGAGAGAAGGTCGACGGAGTGAAG

CTGGAAAGTATGGGGATCTACCAAATACTGGCAATATACAGCACAGTTGCAAGCAGTCTC

GTGTTACTCGTCTCCCTTGGAGCAATCTCTTTCTGGATGTGTTCTAACGGCAGCCTGCAG

TGCAGAATTTGTATC

450
ATGAAGGCAAACTTGCTCGTGCTGTTGTGCGCATTAGCCGCCGCCGATGCCGACACAATC

TGCATCGGCTATCACGCTAACAACTCCACTGACACTGTGGATACCGTACTTGAAAAAAAT

GTGACCGTCACACACTCGGTTAATCTCTTAGAGGACTCGCACAATGGCAAACTGTGTCGT

CTGAAAGGGATCGCTCCACTTCAACTCGGGAAGTGTAATATTGCCGGGTGGCTGCTGGGC

AACCCCGAGTGCGACCCTCTTCTGCCTGTACGGTCGTGGTCTTATATAGTGGAAACACCC

AATAGTGAGAACGGCATATGCTATCCCGGAGACTTCATTGATTATGAAGAACTTAGGGAA

CAGCTAAGCTCCGTGTCAAGCTTTGAAAGGTTTGAAATATTCCCCAAGGAGAGCTCCTGG

CCTAATCACAATACCAACGGTGTGACCGCCGCCTGTTCGCACGAGGGCAAGAGCTCATTT

TACAGGAATCTACTGTGGCTCACCGAGAAGGAAGGTTCGTACCCTAAGCTCAAGAATAGC

TACGTGAATAAAAAGGGCAAAGAGGTACTGGTGCTGTGGGGGATTCACCACCCCCCTAAT

TCGAAGGAGCAGCAAAACTTGTACCAGAATGAGAATGCCTACGTCTCTGTTGTCACTAGT

AATTACAACCGTAGATTCACGCCTGAAATTGCTGAGCGACCAAAAGTTCGAGATCAGGCT

GGCAGGATGAATTATTATTGGACCCTCCTGAAGCCCGGAGATACCATTATCTTCGAGGCT

AATGGTAACCTGATCGCTCCTATGTACGCCTTCGCTTTGAGTCGAGGCTTCGGCAGCGGG

ATAATTACGTCTAACGCTTCTATGCACGAGTGCAATACAAAGTGTCAGACTCCCCTTGGG

GCAATCAATTCAAGCCTTCCCTATCAGAATATCCACCCTGTTACTATAGGGGAGTGTCCG

AAATACGETAGGTCGGCAAAGCTGAGGATGGTCACTGGCCTGCGAAATAACCCGTCCATT

CAGTCCAGGGGGCTTTTCGGTGCTATCGCTGGATTTATTGAAGGTGGTTGGACTGGCATG

ATCGACGGATGGTACGGGTATCACCACCAGAACGAACAGGGATCTGGGTACGCTGCCGAT

CAAAAATCGACCCAGAACGCCATAAACGGCATTACAAATAAGGTGAATACCGTCATCGAA

AAAATGAATATTCAATTCACCGCCGTAGGCAAAGAGTTTAATAAACTTGAGAAAAGGATG

GAGAACCTCAATAAAAAAGTCGACGATGGGTTTCTGGATATCTGGACCTATAACGCTGAG

CTTCTTGTGCTGCTCGAAAATGAACGCACACTGGATTTCCACGATTCCAACGTGAAAAAT

TTGTACGAAAAGGTGAAGTCACAACTGAAGAATAACGCAAAGGAAATCGGGAATGGCTGT

TTTGAATTCTATCACAAGTGTGACAACGAATGCATGGAGAGTGTCCGAAACGGAACCTAC

GATTATCCAAAGTACTCGGAAGAATCTAAGCTGAATCGGGAGAAGGTGGACGGGGTCAAG

CTGGAGTCAATGGGTATTTATCAGATCCTAGCGATTTACTCAACCGTGGCATCGAGCCTG

GTCCTACTTGTTAGTCTTGGGGCAATAAGCTTCTGGATGTGCAGCAACGGCAGCTTGCAG

TGCAGAATATGTATA

451
ATGAAGGCTAACCTGCTCGTTCTCTTATGTGCACTGGCCGCCGCAGACGCGGATACTATT

TGTATAGGCTACCACGCGAATAACTCTACTGATACGGTGGACACAGTTCTCGAGAAAAAC

GTGACAGTGACTCACTCCGTGAATCTGCTGGAGGATTCACACAACGGCAAACTGTGTCGA

CTGAAAGGAATCGCACCGTTGCAACTTGGTAAGTGCAATATTGCCGGATGGCTCCTGGGA

AACCCCGAATGCGATCCTTTGCTTCCCGTGCGGAGTTGGTCCTACATCGTGGAGACCCCT

AACTCTGAGAACGGAATCTGTTATCCCGGGGATTTCATTGATTATGAAGAGCTCAGAGAA

CAATTGAGTTCTGTTTCTAGCTTTGAGAGATTCGAGATTTTCCCTAAGGAGTCGTCCTGG

CCAAATCACAACACTAACGGAGTAACCGCCGCCTGTTCTCACGAGGGCAAGTCAAGCTTT

TACAGGAATCTCCTGTGGTTAACAGAAAAGGAAGGGAGTTACCCAAAACTAAAAAACTCG

TACGTGAACAAGAAAGGCAAGGAGGTCCTGGTGCTGTGGGGAATTCATCACCCCCCGAAT

TCCAAGGAACAACAGAATCTGTATCAAAACGAAAACGCTTATGTGTCCGTCGTGACATCG

AACTACAATAGAAGATTTACCCCCGAGATTGCAGAGCGCCCTAAAGTCAGGGATCAGGCT

GGGAGAATGAACTATTATTGGACACTGCTAAAGCCCGGCGATACAATTATCTTTGAGGCC

AATGGCAATCTGATTGCTCCCATGTATGCATTTGCCCTGAGCAGAGGGTTTGGCAGTGGA

ATCATTACCAGCAATGCTAGCATGCATGAATGTAATACAAAGTGTCAGACACCATTAGGA

GCCATAAACAGTTCACTCCCTTATCAGAACATCCATCCCGTGACAATCGGAGAGTGTCCT

AAATACGTCAGAAGTGCAAAATTGAGAATGGTTACCGGCTTGAGGAATAATCCATCTATT

CAATCCCGCGGGCTCTTTGGAGCCATCGCTGGCTTTATTGAAGGAGGATGGACCGGAATG

ATTGATGGATGGTATGGTTACCACCATCAGAATGAGCAGGGCTCCGGCTACGCCGCCGAC

CAGAAGTCTACCCAAAACGCCATAAACGGAATCACCAATAAGGTGAACACTGTCATTGAA

AAGATGAATATACAATTCACTGCCGTCGGGAAGGAGTTTAACAAACTCGAAAAGCGGATG

GAGAATTTGAATAAAAAGGTCGACGACGGCTTCCTGGATATCTGGACATACAATGCCGAG

CTCCTGGTCCTGTTGGAGAATGAACGCACACTCGATTTTCACGACAGCAATGTGAAGAAT

CTTTACGAAAAGGTTAAAAGTCAGTTGAAAAACAACGCTAAAGAAATAGGTAATGGGTGT

TTCGAGTTTTACCACAAGTGCGACAATGAGTGCATGGAATCTGTCAGAAATGGGACCTAC

GACTACCCTAAGTACTCCGAAGAGTCTAAGCTGAATAGGGAGAAGGTGGATGGGGTGAAG

CTGGAATCCATGGGCATCTACCAGATCCTCGCTATCTACAGCACAGTGGCCTCTAGCTTG

GTGCTTTTGGTGTCACTTGGGGGGATTTCGTTCTGGATGTGCTCCAACGGAAGCCTGCAA

TGCCGAATCTGTATC

452
ATGAAGGCTAACCTTCTTGTGCTTCTCTGTGCACTTGCTGCCGCAGATGCTGATACAATA

TGCATCGGTTACCACGCTAATAATTCTACCGATACGGTTGACACGGTTCTTGAAAAGAAC

GTCACAGTGACTCACAGCGTCAACCTCCTGGAGGACTCTCATAACGGAAAATTGTGCCGC

CTCAAAGGCATTGCCCCATTGCAATTAGGCAAGTGTAATATTGCAGGTTGGCTCCTGGGT

AACCCGGAATGCGACCCTCTGTTGCCTGTCAGGTCTTGGAGTTATATAGTCGAAACCCCA

AATTCCGAAAATGGAATATGTTACCCTGGCGACTTTATCGACTACGAAGAACTGAGGGAG

CAGCTTAGTTCCGTCAGTTCTTTCGAACGTTTCGAAATCTTCCCCAAGGAATCTAGTTGG

CCCAACCATAACACCAACGGTGTGACGGCGGCATGCAGTCACGAGGGCAAGTCCAGCTTC

TATAGAAACTTGCTGTGGTTAACCGAGAAAGAGGGAAGTTACCCTAAGCTGAAGAACAGC

TACGTAAACAAAAAAGGCAAAGAAGTCCTGGTTCTCTGGGGCATTCACCACCCACCCAAT

TCCAAGGAACAGCAAAATCTCTATCAAAATGAAAATGCTTATGTCTCTGTTGTGACCTCG

AACTATAATCGGCGTTTTACCCCTGAGATCGCCGAGAGGCCTAAGGTCAGGGACCAAGCT

GGCCGAATGAATTATTACTGGACCCTACTGAAGCCTGGCGATACCATAATCTTCGAGGCT

AATGGAAATCTGATTGCGCCAATGTATGCTTTTGCACTGAGCCGCGGGTTTGGGAGCGGA

ATTATCACCTCTAACGCATCTATGCACGAGTGTAACACAAAGTGTCAGACCCCGCTGGGG

GCTATTAACTCCAGTTTGCCATACCAAAATATTCATCCGGTCACAATCGGTGAATGCCCC

AAGTATGTTAGAAGCGCTAAGTTAAGAATGGTGACCGGGCTGCGTAACAACCCTAGTATC

CAGTCACGCGGCCTCTTTGGGGCTATTGCCGGGTTCATCGAGGGAGGTTGGACTGGGATG

ATCGACGGATGGTATGGGTACCACCATCAAAACGAGCAGGGATCAGGCTACGCCGCAGAC

CAGAAGAGCACTCAGAACGCCATCAACGGGATCACTAATAAAGTTAATACCGTGATTGAA

AAAATGAACATACAATTTACTGCAGTGGGCAAGGAGTTCAACAAACTAGAGAAACGCATG

GAGAACTTGAACAAAAAAGTTGACGACGGATTTCTGGACATCTGGACATATAATGCAGAG

CTGCTGGTCCTGCTAGAGAACGAACGGACCCTAGACTTCCATGACTCAAACGTCAAGAAT

CTGTACGAGAAGGTGAAATCTCAGCTCAAAAATAATGCCAAAGAGATCGGCAATGGATGC

TTTGAATTCTATCACAAGTGTGACAATGAGTGCATGGAGAGCGTGCGAAATGGAACTTAC

GACTACCCAAAGTACAGCGAGGAGAGTAAGCTTAACAGGGAGAAGGTGGACGGCGTGAAG

CTCGAAAGCATGGGGATATACCAGATCCTCGCCATATACTCTACTGTGGCGTCGTCTCTC

GTGCTTTTGGTATCACTCGGCGCTATCAGCTTCTGGATGTGTTCCAATGGCAGCTTGCAG

TGCCGGATATGCATT

453
ATGAAAGCCAATCTCTTAGTGCTACTGTGCGCCCTTGCCGCCGCAGACGCAGATACGATT

TGCATTGGGTATCACGCAAACAATTCCACCGACACAGTGGATACCGTGCTCGAAAAGAAC

GTAACTGTGACTCACTCTGTGAATTTACTCGAGGACAGTCACAACGGGAAGCTCTGCAGA

CTTAAGGGGATCGCACCCTTGCAACTCGGAAAGTGTAACATTGCCGGGTGGCTTCTCGGC

AACCCCGAGTGTGACCCTCTTCTTCCAGTTCGGAGCTGGAGTTATATAGTGGAAACGCCA

AATTCCGAGAACGGCATATGTTACCCAGGAGACTTTATCGATTATGAAGAACTCCGCGAA

CAGCTCAGCAGCGTGAGTTCTTTCGAACGTTTCGAGATCTTCCCAAAAGAGTCCAGTTGG

CCAAATCATAACACCAATGGCGTAACAGCAGCGTGCAGCCACGAGGGAAAATCTAGCTTT

TACAGGAACCTACTTTGGCTCACAGAAAAGGAGGGATCCTATCCTAAACTGAAGAATTCA

TACGTCAATAAAAAAGGTAAAGAGGTGTTGGTGCTGTGGGGGATTCATCACCCACCAAAC

TCCAAAGAACAGCAGAACCTGTACCAAAACGAGAACGCCTACGTCTCCGTGGTGACGAGC

AACTATAACCGACGCTTTACCCCCGAAATCGCGGAGCGTCCAAAGGTGCGGGACCAGGCA

GGGCGTATGAACTATTATTGGACACTTCTAAAACCCGGTGACACCATTATCTTTGAAGCG

AACGGCAACTTGATTGCGCCAATGTATGCTTTCGCTCTGAGTCGGGGATTTGGATCGGGG

ATTATTACCTCCAACGCGTCTATGCATGAATGTAACACCAAATGTCAAACCCCTCTTGGG

GCCATCAACAGCTCCCTGCCATATCAGAACATTCACCCAGTCACCATCGGAGAATGCCCC

AAGTATGTCCGCAGTGCTAAGCTCCGCATGGTAACCGGCCTGAGAAACAATCCCAGTATT

CAGTCTAGGGGCCTCTTCGGCGCTATTGCAGGATTCATTGAGGGCGGATGGACAGGCATG

ATCGATGGCTGGTACGGTTATCATCACCAGAACGAGCAAGGATCCGGCTACGCTGCGGAC

CAGAAGAGCACCCAGAACGCTATTAACGGCATTACGAATAAGGTGAACACTGTCATCGAG

AAGATGAACATTCAGTTTACCGCGGTTGGGAAGGAGTTCAACAAACTTGAAAAACGAATG

GAGAATCTAAACAAAAAAGTCGACGATGGATTCCTGGATATCTGGACCTACAACGCTGAG

CTGCTGGTGCTGCTGGAAAATGAGCGGACATTGGACTTCCACGATTCCAACGTGAAGAAT

CTTTACGAGAAAGTTAAATCACAGTTGAAGAATAATGCCAAAGAGATTGGGAACGGCTGT

TTTGAATTCTACCACAAATGCGATAACGAATGTATGGAATCTGTACGGAATGGTACGTAT

GACTATCCAAAATACTCCGAAGAGTCCAAGCTGAACCGAGAAAAAGTGGACGGGGTCAAA

CTGGAAAGCATGGGGATATACCAGATCCTGGCCATATATAGCACTGTGGCTTCTTCTTTG

GTTCTCCTTGTGTCACTCGGGGCCATAAGCTTCTGGATGTGTTCAAACGGAAGCTTGCAG

TGCAGAATTTGCATC

454
ATGAAGGCCAACTTACTGGTGTTGCTATGCGCTCTGGCCGCCGCTGACGCCGATACCATC

TGTATTGGATACCACGCCAACAACAGCACCGACACTGTGGACACAGTGCTTGAGAAGAAT

GTCACCGTCACACATAGTGTAAACTTGCTCGAAGATAGTCACAACGGGAAGCTGTGCCGC

CTTAAAGGTATTGCACCACTGCAGTTAGGCAAGTGCAATATTGCCGGGTGGCTGCTTGGG

AACCCCGAGTGTGATCCTCTATTGCCAGTTCGGTCGTGGAGCTATATCGTGGAGACACCG

AACAGCGAAAACGGCATCTGTTATCCTGGAGATTTTATCGACTATGAGGAACTCAGGGAA

CAGCTCTCGTCTGTGTCTAGCTTCGAACGCTTTGAAATTTTCCCAAAAGAGAGTTCCTGG

CCAAATCATAACACTAACGGTGTGACTGCCGCTTGCTCCCATGAAGGCAAATCAAGCTTT

TATAGGAATCTGTTGTGGTTGACTGAAAAAGAAGGCTCCTACCCGAAACTCAAGAACAGC

TATGTGAACAAGAAAGGTAAGGAAGTGCTGGTGCTGTGGGGCATCCATCATCCTCCTAAC

TCAAAGGAGCAGCAAAATCTTTACCAGAATGAAAACGCATACGTGTCCGTTGTAACCTCT

AATTATAACCGCCGGTTCACCCCAGAAATCGCCGAGCGTCCAAAGGTTAGAGATCAAGCA

GGGCGCATGAATTATTACTGGACACTGCTCAAGCCCGGCGATACCATCATCTTTGAGGCT

AACGGCAACCTCATTGCTCCGATGTATGCGTTCGCTCTGAGTCGCGGCTTTGGCTCAGGC

ATTATTACTTCCAATGCCTCTATGCACGAGTGCAACACTAAATGCCAGACGCCCCTGGGT

GCAATCAACTCTAGCCTCCCATATCAGAACATACATCCCGTGACCATCGGCGAATGCCCT

AAATACGTCCGGTCCGCAAAGCTGCGAATGGTGACGGGCCTGAGAAATAACCCCTCAATA

CAGTCGCGAGGGCTGTTCGGCGCCATTGCCGGGTTTATTGAGGGGGGATGGACTGGGATG

ATAGATGGTTGGTATGGGTATCATCATCAGAACGAGCAAGGGTCTGGGTATGCCGCTGAC

CAAAAAAGCACCCAGAACGCCATAAACGGGATTACCAATAAGGTTAACACAGTTATTGAG

AAGATGAATATTCAGTTTACCGCTGTCGGGAAAGAATTCAATAAATTGGAAAAAAGGATG

GAGAACCTGAACAAAAAGGTGGACGATGGGTTTCTCGATATCTGGACATATAACGCTGAG

CTTCTCGTACTGCTGGAAAATGAAAGGACGCTCGATTTCCATGATTCCAATGTCAAGAAT

CTCTACGAGAAGGTCAAGTCTCAGCTGAAGAACAATGCCAAAGAGATCGGGAATGGATGT

TTTGAGTTCTATCACAAGTGCGATAACGAATGCATGGAGTCCGTCAGGAACGGCACCTAT

GATTACCCTAAGTACAGTGAAGAAAGCAAACTTAATAGGGAAAAGGTGGATGGTGTGAAG

CTGGAGTCAATGGGCATTTACCAGATTCTGGCCATTTACAGTACAGTAGCCTCTAGTCTG

GTGCTGCTTGTCAGCCTTGGCGCCATCTCCTTTTGGATGTGTAGCAACGGATCACTGCAG

TGCAGGATCTGCATT

455
ATGAAAGCAAACTTGCTTGTGCTGTTATGCGCTCTGGCAGCTGCGGACGCCGATACTATC

TGCATCGGTTACCACGCTAACAATTCAACAGATACCGTTGATACTGTGCTGGAGAAGAAC

GTGACCGTCACCCACAGTGTGAACCTCTTGGAAGACAGCCACAACGGAAAACTGTGCCGC

CTGAAGGGCATCGCGCCGTTACAGCTGGGAAAGTGCAATATCGCCGGATGGCTTTTGGGT

AATCCAGAATGTGATCCATTGCTCCCCGTGAGAAGCTGGAGCTATATTGTTGAAACCCCT

AACTCAGAGAATGGGATCTGCTACCCCGGGGACTTCATTGACTACGAGGAACTGCGCGAG

CAGTTGTCATCCGTCAGTTCATTCGAGCGGTTTGAAATATTTCCCAAGGAGTCAAGTTGG

CCAAACCACAACACGAACGGAGTAACAGCGGCTTGTAGCCATGAAGGTAAAAGCTCTTTT

TACAGGAATCTGCTGTGGTTGACTGAGAAGGAGGGCTCCTACCCCAAACTGAAAAACAGC

TACGTGAACAAAAAGGGCAAGGAGGTCCTGGTGCTCTGGGGAATTCACCATCCGCCCAAT

TCCAAAGAGCAGCAGAATTTATACCAAAATGAGAACGCCTACGTTTCTGTCGTCACGTCA

AATTATAACCGACGCTTTACACCTGAAATAGCTGAGAGACCCAAGGTGAGAGATCAGGCT

GGGAGGATGAATTACTATTGGACTCTGCTAAAACCTGGAGACACTATAATCTTCGAAGCC

AACGGGAACCTGATTGCCCCTATGTACGCATTTGCTTTATCCCGAGGGTTTGGAAGCGGG

ATCATTACTTCAAATGCTTCTATGCACGAGTGCAATACCAAATGCCAGACACCTTTAGGC

GCTATCAATTCATCTCTGCCTTATCAGAACATTCACCCAGTGACAATAGGAGAGTGTCCT

AAGTATGTCCGCTCCGCGAAGCTTCGTATGGTCACAGGCCTCAGGAATAACCCAAGTATC

CAGTCGAGAGGCCTTTTTGGTGCCATCGCTGGCTTTATCGAAGGAGGGTGGACCGGCATG

ATTGATGGGTGGTATGGATACCATCATCAGAACGAGCAAGGCTCAGGTTACGCCGCGGAC

CAGAAGTCCACGCAAAATGCCATTAACGGCATCACGAACAAAGTCAACACCGTTATCGAG

AAGATGAATATACAGTTCACAGCCGTAGGCAAAGAATTTAATAAACTCGAAAAGCGGATG

GAGAATTTAAACAAAAAAGTCGATGATGGATTTCTCGATATCTGGACTTATAACGCCGAA

CTTCTAGTGCTGCTTGAGAACGAGAGAACGCTTGATTTTCACGACAGTAACGTTAAAAAC

CTGTACGAAAAGGTAAAGTCCCAACTGAAAAACAATGCCAAAGAAATTGGAAACGGTTGC

TTTGAATTTTACCACAAGTGCGATAATGAGTGCATGGAAAGTGTAAGAAATGGCACGTAT

GACTATCCCAAATACTCCGAAGAAAGCAAGCTCAATCGTGAGAAGGTGGATGGTGTGAAG

CTGGAATCGATGGGGATTTATCAGATCCTAGCTATCTATTCAACAGTCGCCTCTAGTCTT

GTTCTTCTTGTATCTCTTGGAGCCATCTCATTTTGGATGTGTTCAAACGGATCCCTGCAG

TGTCGGATCTGTATC

456
ATGAAGGCTAACCTGCTGGTTCTACTCTGCGCACTCGCAGCTGCGGACGCCGACACAATT

TGTATTGGATATCACGCTAACAATAGCACCGATACCGTAGACACCGTACTGGAAAAGAAT

GTGACGGTCACACACTCAGTAAATCTCCTGGAAGACAGCCATAATGGCAAGCTGTGTAGA

TTAAAAGGGATTGCTCCTCTCCAGTTGGGCAAATGTAACATCGCCGGTTGGCTGCTGGGG

AACCCCGAGTGCGACCCATTGCTGCCCGTAAGGAGCTGGTCCTATATAGTTGAGACACCC

AATTCTGAGAATGGCATCTGCTACCCCGGAGATTTTATCGATTATGAGGAGTTGCGTGAG

CAGCTCTCTAGCGTGAGCTCGTTTGAAAGATTTGAAATTTTTCCGAAAGAATCTAGTTGG

CCCAACCACAATACGAACGGAGTGACTGCCGCCTGCTCCCACGAGGGAAAATCCTCATTT

TACAGGAACTTACTCTGGCTTACTGAGAAGGAAGGTAGCTACCCAAAGCTCAAGAACAGC

TACGTCAACAAGAAGGGCAAGGAAGTCCTGGTCCTGTGGGGAATCCATCATCCGCCAAAC

TCCAAGGAGCAACAGAATCTATATCAGAATGAGAATGCCTACGTTTCAGTGGTTACGTCT

AATTATAACCGCAGGTTTACCCCCGAGATCGCTGAGCGCCCCAAAGTTAGAGACCAGGCA

GGGCGCATGAACTACTATTGGACCCTCCTGAAACCTGGCGACACAATTATCTTCGAGGCA

AACGGTAATCTCATCGCGCCTATGTACGCTTTTGCCCTTAGCCGGGGTTTTGGATCAGGC

ATCATAACTTCTAACGCCTCTATGCACGAATGTAACACCAAGTGTCAGACCCCCCTAGGA

GCTATCAACAGCTCGCTTCCTTACCAGAACATTCATCCCGTGACCATAGGTGAGTGTCCA

AAATACGTCAGGAGTGCAAAACTAAGGATGGTTACCGGACTCCGGAATAACCCTTCGATT

CAGTCGCGCGGGCTCTTTGGAGCAATCGCCGGGTTCATCGAAGGCGGGTGGACCGGGATG

ATTGACGGTTGGTACGGCTACCATCACCAAAACGAACAAGGCTCAGGTTATGCAGCTGAC

CAGAAGTCCACTCAGAATGCCATAAATGGCATTACCAACAAAGTTAATACAGTCATTGAG

AAGATGAATATACAGTTCACCGCGGTGGGCAAAGAGTTCAACAAACTGGAGAAACGTATG

GAAAACTTGAACAAAAAAGTGGACGATGGGTTCTTGGACATCTGGACGTATAATGCCGAG

TTATTAGTGCTGCTGGAAAATGAAAGAACGTTAGACTTCCACGACTCTAATGTTAAAAAT

TTGTACGAAAAGGTCAAATCCCAACTGAAAAATAACGCCAAGGAAATAGGCAATGGCTGT

TTTGAATTCTATCATAAGTGCGATAACGAGTGTATGGAGAGTGTTCGCAATGGTACATAC

GACTACCCTAAATACTCCGAGGAAAGTAAGCTGAACAGGGAAAAGGTCGATGGAGTCAAG

CTGGAATCCATGGGGATTTATCAGATCCTGGCCATTTATAGCACTGTAGCCTCCTCCCTG

GTGCTGCTGGTATCACTCGGCGCAATAAGCTTCTGGATGTGTTCTAACGGGAGCCTGCAA

TGCAGAATATGCATT

457
ATGAAAGCAAACCTCCTCGTGTTGCTCTGTGCCCTGGCTGCAGCCGACGCCGACACCATA

TGTATCGGGTACCACGCCAATAACTCCACTGATACCGTCGATACCGTCCTTGAGAAAAAT

GTGACAGTCACACACAGCGTTAATTTATTGGAGGACAGCCACAACGGCAAGCTCTGTAGG

CTGAAAGGGATCGCCCCCTTACAGCTGGGGAAATGTAATATCGCTGGATGGCTGCTGGGA

AACCCCGAGTGCGACCCCTTGCTGCCTGTGAGGTCTTGGAGCTACATTGTTGAGACCCCT

AACAGCGAGAACGGCATTTGTTACCCTGGCGACTTCATTGACTACGAGGAGCTGAGGGAA

CAATTGTCATCTGTCAGCTCATTTGAGCGATTCGAGATCTTTCCCAAGGAATCGTCATGG

CCAAATCACAACACAAACGGGGTGACCGCGGCTTGCTCACATGAAGGAAAGAGCTCCTTT

TACCGAAATCTTCTGTGGCTGACGGAGAAGGAAGGATCATACCCAAAATTGAAAAACTCC

TATGTGAACAAGAAAGGTAAAGAGGTCCTTGTTTTATGGGGCATTCACCACCCACCTAAC

TCAAAAGAACAGCAAAACCTGTACCAGAACGAGAATGCATACGTTTCAGTAGTCACCTCT

AACTATAATAGGAGATTCACCCCCGAAATCGCCGAGAGGCCAAAGGTACGGGATCAGGCT

GGCAGGATGAATTACTATTGGACCCTACTTAAACCTGGAGACACGATCATCTTCGAGGCA

AATGGAAACCTCATCGCCCCTATGTATGCCTTTGCCCTTAGCCGAGGGTTTGGATCAGGG

ATAATAACCTCTAACGCCAGTATGCACGAATGCAATACGAAGTGTCAAACCCCTCTGGGA

GCAATAAATTCTTCCCTTCCTTATCAGAACATTCACCCCGTCACAATTGGAGAGTGCCCC

AAATACGTCAGGTCCGCCAAACTGAGAATGGTTACCGGCTTGCGGAATAATCCGAGCATT

CAGAGCCGCGGATTATTTGGTGCTATTGCTGGCTTTATCGAAGGAGGGTGGACCGGAATG

ATCGACGGGTGGTACGGCTACCATCATCAGAACGAGCAGGGTAGCGGTTACGCTGCCGAT

CAGAAATCCACTCAGAATGCCATCAATGGCATTACTAACAAAGTAAATACTGTGATTGAA

AAGATGAACATCCAGTTTACCGCAGTAGGAAAAGAGTTCAACAAATTGGAGAAAAGGATG

GAAAACCTCAACAAAAAAGTCGACGATGGATTCCTTGATATTTGGACATACAACGCTGAG

CTGCTAGTGCTGCTGGAGAACGAGCGAACACTCGATTTCCATGATAGCAACGTCAAAAAC

CTGTACGAGAAGGTCAAAAGCCAGCTGAAAAATAACGCTAAGGAGATTGGGAATGGCTGT

TTCGAATTCTACCACAAATGTGATAATGAATGCATGGAGAGTGTGCGGAATGGGACATAC

GACTACCCAAAATATTCTGAAGAGAGTAAACTTAATCGAGAGAAAGTGGATGGTGTTAAA

CTTGAGTCTATGGGCATTTACCAGATCCTGGCAATTTACAGTACCGTCGCTTCTTCTTTG

GTCCTACTAGTGAGCCTCGGAGCAATCAGCTTCTGGATGTGTAGTAACGGGAGCCTTCAG

TGTCGAATTTGCATC

458
ATGAAAGCTAATCTGCTCGTACTGCTCTGCGCTCTGGCTGCCGCTGATGCCGACACCATC

TGTATTGGATATCACGCAAACAATTCTACTGATACCGTGGACACCGTGCTCGAGAAAAAC

GTGACCGTGACGCATTCCGTTAATCTGCTGGAAGATTCACACAACGGAAAGCTGTGTAGA

CTGAAGGGAATCGCCCCACTGCAATTGGGTAAATGTAACATTGCAGGATGGCTTCTGGGT

AATCCTGAATGCGATCCACTGCTCCCTGTTAGATCATGGTCATATATCGTCGAAACACCG

AATTCTGAAAATGGTATTTGCTACCCTGGCGATTTCATCGACTACGAAGAGCTGAGAGAG

CAGCTATCTAGCGTGAGTAGCTTCGAACGCTTCGAAATTTTTCCCAAAGAGAGCTCTTGG

CCGAACCACAATACCAATGGCGTGACCGCCGCATGCAGCCATGAGGGCAAATCTTCTTTC

TACAGAAATCTACTTTGGCTGACCGAAAAAGAGGGAAGTTACCCAAAGCTGAAAAATTCC

TATGTCAACAAAAAAGGGAAGGAGGTACTTGTGTTATGGGGAATTCACCACCCCCCTAAC

TCCAAGGAGCAGCAGAACCTGTATCAGAATGAGAACGCGTATGTTTCAGTGGTCACCAGC

AACTATAATCGTCGGTTCACCCCTGAGATCGCCGAACGGCCCAAGGTGAGAGATCAGGCT

GGAAGAATGAATTACTATTGGACCTTGCTGAAGCCTGGGGATACCATCATCTTTGAAGCT

AATGGAAACCTGATCGCGCCTATGTACGCATTCGCCCTATCCCGTGGCTTCGGTTCCGGC

ATTATCACCTCAAATGCCTCAATGCACGAGTGCAACACTAAATGTCAGACCCCGCTGGGT

GCCATCAACTCCAGCCTTCCCTACCAAAACATACATCCAGTGACGATTGGCGAGTGCCCA

AAGTACGTCCGCTCTGCCAAGCTACGCATGGTCACGGGCCTGCGAAATAACCCCTCTATA

CAATCCCGTGGGCTGTTTGGCGCGATTGCCGGGTTCATCGAGGGAGGATGGACAGGTATG

ATCGATGGCTGGTACGGATACCATCATCAGAACGAACAGGGCTCCGGCTACGCTGCGGAC

CAGAAGTCTACGCAAAACGCAATTAATGGAATCACAAACAAGGTGAACACTGTGATCGAG

AAAATGAATATTCAGTTTACCGCCGTCGGTAAAGAATTCAATAAGCTCGAGAAGAGAATG

GAGAACTTGAACAAAAAAGTGGATGATGGGTTTCTCGATATTTGGACATATAACGCGGAA

CTCCTGGTGCTGCTCGAGAATGAGCGCACCCTGGATTTTCACGACTCTAACGTCAAGAAT

TTATACGAGAAAGTAAAATCCCAGCTGAAGAACAATGCTAAAGAAATTGGCAACGGATGT

TTCGAGTTTTATCATAAATGCGATAATGAGTGCATGGAGAGCGTGCGCAATGGAACATAC

GACTACCCTAAATACAGCGAGGAATCTAAGCTGAATAGAGAGAAGGTAGACGGAGTCAAG

CTGGAATCTATGGGAATATATCAAATTTTAGCTATTTACTCCACAGTTGCTTCATCCCTG

GTCTTACTGGTTTCCCTCGGCGCGATCTCGTTTTGGATGTGCAGTAATGGCTCCCTTCAG

TGTCGAATCTGCATC

459
ATGAAAGCTAATCTGTTGGTGCTGCTCTGCGCTTTGGCCGCTGCCGATGCAGATACCATC

TGTATCGGCTATCACGCGAACAATTCCACAGATACAGTGGACACCGTCCTGGAGAAAAAT

GTGACCGTGACCCACTCTGTCAACCTGCTCGAAGACAGCCATAACGGCAAACTGTGTAGA

CTGAAGGGCATTGCACCTTTACAGCTGGGCAAGTGCAATATAGCTGGATGGCTCCTCGGC

AATCCCGAATGCGACCCTCTACTGCCCGTGAGAAGCTGGTCATATATCGTTGAAACCCCG

AATTCCGAGAATGGAATCTGCTATCCCGGAGATTTCATCGACTATGAAGAGCTCAGGGAA

CAGCTGTCCTCTGTATCCTCCTTTGAACGTTTTGAGATTTTCCCAAAGGAGTCATCTTGG

CCTAACCACAACACGAACGGGGTAACCGCAGCCTGCAGTCACGAAGGTAAGAGCAGCTTT

TACAGGAATCTGCTGTGGCTAACCGAGAAAGAGGGCAGTTATCCTAAACTGAAAAATTCA

TATGTGAACAAGAAAGGAAAGGAAGTGCTGGTGCTTTGGGGAATCCACCATCCGCCCAAC

AGCAAGGAGCAGCAGAACCTATACCAGAACGAAAACGCTTATGTGTCAGTGGTGACTAGC

AACTACAACCGACGTTTTACCCCCGAGATTGCCGAGCGACCCAAGGTGAGAGACCAGGCC

GGTCGCATGAACTACTACTGGACACTCCTTAAGCCAGGCGATACAATCATATTTGAAGCT

AACGGGAACCTCATTGCTCCTATGTACGCTTTCGCGCTGTCTAGGGGTTTCGGCTCCGGA

ATAATTACAAGCAATGCTTCCATGCACGAGTGCAATACCAAGTGTCAGACTCCCCTGGGG

GCCATTAACAGCAGTCTGCCATACCAAAATATTCATCCAGTAACAATCGGCGAGTGTCCA

AAGTACGTGCGATCTGCCAAGTTACGAATGGTGACCGGCCTGCGCAATAACCCCTCAATT

CAGTCTAGGGGCTTATTCGGGGCTATCGCCGGCTTCATTGAGGGAGGATGGACAGGAATG

ATCGATGGATGGTACGGCTACCATCACCAGAATGAGCAAGGCAGCGGTTACGCTGCCGAC

CAGAAATCGACACAGAATGCTATCAATGGAATCACTAACAAAGTCAACACGGTGATTGAA

AAGATGAATATCCAATTCACTGCAGTGGGCAAGGAATTCAACAAATTAGAGAAGCGGATG

GAGAACCTGAATAAAAAAGTTGATGACGGTTTCCTGGATATCTGGACATACAATGCAGAA

CTTCTCGTCCTGCTCGAGAACGAGCGAACTCTCGATTTTCACGATTCTAATGTCAAAAAT

CTGTATGAAAAGGTGAAGTCCCAGCTGAAGAACAACGCAAAGGAAATCGGGAATGGATGC

TTCGAGTTTTACCATAAATGTGATAACGAGTGCATGGAAAGCGTCCGAAATGGCACTTAT

GACTATCCAAAATACTCAGAGGAGAGTAAACTTAACCGCGAGAAGGTTGATGGCGTTAAA

CTGGAATCCATGGGCATTTACCAGATCTTGGCTATCTATAGCACGGTGGCTTCTTCGCTG

GTGCTCTTGGTCAGTCTCGGTGCCATCTCATTCTGGATGTGTTCGAACGGATCTCTTCAA

TGCCGAATCTGTATA

460
ATGAAAGCCAACCTTCTAGTTTTACTATGTGCTCTCGCTGCTGCTGACGCCGACACTATT

TGTATTGGATATCACGCAAATAATTCCACAGATACTGTCGACACCGTTTTGGAAAAGAAC

GTGACTGTCACTCACTCAGTCAACCTGCTCGAAGATTCTCACAATGGCAAATTATGCCGC

CTCAAGGGAATCGCTCCGCTCCAATTGGGAAAATGTAACATCGCAGGATGGCTCCTCGGC

AATCCTGAATGCGACCCTCTCCTGCCCGTCCGCTCTTGGTCATACATAGTGGAAACTCCC

AACAGTGAAAATGGAATATGTTACCCCGGTGACTTCATCGACTATGAGGAATTGCGCGAG

CAACTGTCCTCAGTTTCCTCGTTCGAAAGATTTGAGATCTTCCCCAAGGAGTCCTCCTGG

CCCAATCACAATACGAATGGCGTTACGGCAGCCTGCTCTCATGAGGGGAAATCCTCATTC

TACCGCAACCTGCTCTGGCTGACAGAGAAGGAGGGGTCCTACCCTAAGCTCAAAAATTCC

TATGTGAATAAAAAGGGCAAAGAAGTACTGGTCCTGTGGGGCATTCACCATCCCCCAAAT

AGTAAAGAACAACAGAACCTCTACCAGAATGAGAACGCTTACGTGAGTGTGGTCACTAGC

AACTACAACAGGAGATTCACACCCGAGATAGCGGAACGACCCAAGGTCCGCGATCAGGCT

GGTCGCATGAATTACTACTGGACCTTGCTGAAGCCCGGAGATACGATTATTTTTGAGGCC

AATGGCAATCTTATCGCCCCAATGTACGCCTTTGCACTCAGCCGTGGGTTCGGAAGTGGA

ATCATAACTTCAAATGCCTCCATGCATGAGTGCAATACAAAATGTCAGACCCCTCTCGGA

GCCATCAACTCATCACTGCCATACCAGAATATTCACCCTGTTACAATTGGAGAGTGTCCA

AAATACGTCAGAAGTGCAAAACTGCGCATGGTTACCGGACTACGTAACAACCCGTCCATC

CAGTCAAGAGGGCTGTTTGGAGCCATCGCAGGATTTATAGAGGGAGGCTGGACCGGGATG

ATTGATGGCTGGTACGGCTACCATCACCAAAATGAGCAGGGAAGTGGGTATGCTGCCGAC

CAGAAATCCACCCAAAACGCGATCAATGGTATCACCAACAAAGTCAATACCGTGATCGAA

AAAATGAACATACAGTTTACAGCAGTGGGAAAGGAATTCAATAAACTTGAGAAACGCATG

GAGAATCTGAATAAAAAGGTCGACGATGGCTTCCTAGATATTTGGACCTACAATGCAGAA

TTACTGGTATTGTTGGAGAATGAGCGGACCCTCGACTTCCATGATTCGAACGTTAAAAAC

CTCTACGAGAAGGTAAAGTCGCAACTGAAAAACAACGCTAAGGAGATCGGGAACGGCTGC

TTCGAATTTTATCACAAATGCGACAACGAATGCATGGAATCAGTGCGAAATGGCACCTAT

GATTATCCAAAGTATTCGGAGGAGTCAAAGCTGAATAGAGAGAAGGTGGATGGTGTGAAG

TTGGAGAGTATGGGGATTTACCAGATCTTAGCAATCTATTCCACGGTTGCTAGTTCCCTC

GTGTTACTTGTGAGCCTGGGTGCGATCAGTTTCTGGATGTGCAGTAACGGTTCACTGCAA

TGCAGAATCTGCATC

461
ATGAAAGCTAATCTCCTGGTTTTGTTGTGTGCACTGGCCGCTGCCGACGCCGACACAATC

TGCATAGGATACCATGCTAACAACAGTACAGATACAGTTGACACCGTGCTGGAAAAGAAT

GTTACTGTAACCCATAGCGTTAACTTGCTAGAGGACTCTCATAATGGAAAGCTCTGTAGG

CTTAAAGGGATCGCCCCCTTACAATTGGGCAAGTGCAATATCGCCGGATGGCTGCTCGGG

AACCCTGAGTGTGATCCATTGCTGCCAGTTCGTTCCTGGTCTTACATAGTTGAAACGCCA

AACTCCGAGAACGGGATCTGTTACCCAGGTGACTTCATTGATTACGAAGAACTGAGAGAA

CAGCTAAGTTCTGTGTCTAGCTTCGAGAGATTCGAGATCTTTCCCAAAGAGTCAAGTTGG

CCTAACCACAATACCAACGGGGTTACCGCGGCTTGCTCCCACGAAGGTAAAAGCTCATTC

TACCGGAACCTTTTGTGGCTCACTGAGAAAGAGGGTAGCTACCCAAAGCTCAAGAACTCC

TACGTGAATAAGAAGGGGAAGGAGGTGCTCGTTTTATGGGGTATCCACCACCCCCCTAAT

AGTAAGGAACAGCAAAATCTCTATCAGAACGAAAACGCATATGTCTCGGTGGTGACCTCA

AACTATAATCGGAGATTCACTCCAGAGATCGCCGAGAGACCCAAAGTCCGGGACCAGGCA

GGAAGGATGAACTATTATTGGACTTTACTGAAGCCCGGGGATACTATTATTTTTGAAGCC

AATGGCAATCTTATTGCCCCCATGTACGCTTTCGCCCTGAGTCGCGGCTTCGGGAGTGGC

ATTATTACTTCCAATGCCTCGATGCATGAGTGCAATACGAAGTGTCAGACCCCATTAGGA

GCTATCAATAGCAGCCTGCCATATCAGAACATCCACCCGGTGACTATTGGAGAGTGTCCA

AAGTACGETAGGTCCGCCAAGTTACGGATGGTAACAGGCCTCCGCAATAATCCTTCTATC

CAAAGTCGGGGGCTGTTTGGAGCAATCGCCGGCTTCATCGAGGGAGGTTGGACTGGGATG

ATTGACGGATGGTATGGGTACCATCATCAGAATGAGCAAGGCAGTGGCTACGCAGCCGAC

CAGAAGTCAACCCAAAACGCCATCAATGGAATCACGAATAAAGTGAACACAGTGATCGAG

AAGATGAACATTCAGTTCACTGCAGTGGGGAAGGAATTTAACAAGTTGGAGAAGAGAATG

GAGAACCTGAACAAGAAGGTAGACGATGGATTCCTAGACATATGGACATATAATGCCGAG

CTGTTGGTCCTCCTCGAAAACGAAAGAACACTGGACTTTCATGACAGTAACGTGAAGAAT

TTGTATGAGAAAGTTAAGTCTCAACTGAAAAACAACGCCAAAGAAATAGGGAACGGTTGT

TTCGAGTTCTATCATAAGTGCGATAACGAGTGCATGGAGTCTGTGCGGAATGGCACGTAC

GATTATCCAAAATACTCCGAGGAGTCCAAACTTAACAGAGAGAAAGTGGATGGCGTGAAA

CTTGAAAGCATGGGCATTTACCAAATCCTCGCCATTTACAGCACAGTCGCTTCTAGTCTA

GTACTGCTTGTATCACTCGGCGCCATATCATTCTGGATGTGTAGTAATGGCAGCCTGCAG

TGCCGAATTTGCATT

462
ATGAAAGCCAACCTGCTCGTACTCCTGTGTGCCCTGGCTGCCGCTGACGCCGATACTATT

TGCATAGGGTATCACGCCAATAATTCAACTGACACCGTCGATACCGTTCTTGAGAAGAAC

GTGACCGTCACACATTCAGTTAACCTTCTTGAGGACTCTCATAATGGTAAATTGTGTCGC

CTCAAGGGTATCGCACCGCTACAACTAGGCAAGTTGTAATATAGCAGGGGGTTGTTGGGA

AACCCTGAGTGTGACCCGCTGCTGCCCGTTCGCAGTTGGTCTTACATCGTCGAGACACCA

AACTCTGAGAACGGGATTTGCTATCCAGGGGATTTTATCGACTATGAAGAGCTTCGCGAG

CAGTTGAGCAGTGTTTCCTCTTTTGAGCGTTTTGAAATTTTCCCGAAAGAGAGTAGCTGG

CCTAACCATAACACAAACGGGGTCACCGCAGCTTGCTCTCATGAGGGGAAGTCAAGCTTC

TATCGGAATCTGCTGTGGCTGACGGAAAAAGAAGGCTCGTACCCAAAGCTAAAAAATTCA

TACGTGAACAAGAAGGGGAAAGAGGTCCTGGTCCTGTGGGGGATCCACCATCCACCTAAT

AGTAAAGAGCAGCAAAATTTGTACCAAAACGAGAATGCGTACGTGAGCGTAGTGACATCA

AACTACAACCGCCGCTTCACTCCTGAGATTGCTGAACGGCCCAAGGTGCGTGATCAGGCC

GGCAGGATGAACTATTATTGGACTTTGCTAAAACCTGGGGATACTATAATTTTTGAGGCG

AATGGCAATCTAATCGCACCGATGTATGCCTTCGCCTTGAGCCGGGGCTTCGGCAGTGGG

ATTATTACCAGTAACGCCTCCATGCACGAATGTAACACAAAGTGTCAGACTCCATTAGGG

GCAATCAACTCGTCACTTCCGTATCAAAATATTCACCCTGTGACCATCGGCGAGTGTCCA

AAATACGTTAGAAGTGCCAAGCTGAGAATGGTGACGGGTCTCCGGAACAATCCCTCAATC

CAATCAAGGGGGTTATTTGGCGCTATTGCTGGTTTCATTGAGGGGGGATGGACCGGAATG

ATCGACGGCTGGTACGGATATCATCATCAGAACGAACAGGGGTCCGGCTATGCTGCCGAC

CAGAAGTCCACTCAGAACGCGATCAATGGGATCACCAACAAGGTCAACACCGTCATCGAA

AAGATGAATATTCAGTTTACAGCCGTCGGAAAGGAATTCAATAAGTTGGAGAAACGCATG

GAAAACTTAAACAAGAAAGTGGACGACGGATTCTTAGACATATGGACTTATAACGCAGAG

CTGCTTGTACTCCTGGAGAATGAGCGAACCTTGGATTTTCATGATTCAAACGTTAAGAAC

TTATATGAGAAGGTGAAGTCTCAACTCAAAAACAATGCCAAAGAAATCGGGAATGGGTGC

TTCGAATTCTATCATAAATGTGATAACGAGTGTATGGAGAGCGTGCGGAATGGAACTTAT

GACTACCCCAAATACAGCGAAGAAAGCAAGTTGAACAGAGAGAAGGTGGATGGCGTGAAG

CTGGAAAGCATGGGGATTTACCAGATTCTTGCAATCTATTCTACTGTTGCATCCAGTCTA

GTTCTGCTCGTCTCTCTGGGGGCAATCAGCTTTTGGATGTGCTCTAATGGTTCCCTGCAG

TGCCGTATCTGCATA

463
ATGAAAGCAAACCTTCTGGTACTGCTCTGCGCCTTAGCCGCCGCTGATGCGGACACGATT

TGTATTGGCTATCACGCCAATAATTCAACAGATACTGTCGACACAGTCTTGGAGAAAAAT

GTGACTGTAACCCATTCTGTCAATCTGCTCGAGGATTCACACAATGGAAAACTGTGTCGG

CTTAAAGGAATCGCTCCTCTGCAGTTGGGCAAGTGTAATATAGCTGGCTGGCTGTTAGGA

AACCCAGAATGCGATCCTCTCTTACCTGTGCGATCCTGGTCTTACATCGTTGAGACACCG

AACAGCGAGAATGGTATATGCTACCCGGGTGACTTTATCGATTATGAAGAATTGAGAGAA

CAGCTGTCAAGCGTCAGCTCTTTCGAACGATTCGAGATCTTTCCCAAAGAGTCAAGCTGG

CCTAACCACAATACAAATGGAGTGACAGCTGCGTGTTCCCATGAAGGCAAGAGTTCTTTC

TACCGAAACCTGCTTTGGCTGACCGAGAAGGAGGGATCATACCCTAAGTTAAAAAATTCA

TACGTCAACAAGAAGGGAAAAGAGGTACTAGTTCTTTGGGGTATTCACCACCCACCCAAC

TCCAAAGAGCAGCAGAATCTGTATCAAAATGAAAACGCGTACGTCTCCGTGGTGACCTCG

AACTACAATCGACGATTCACTCCCGAAATCGCTGAGAGGCCCAAAGTCCGGGATCAGGCC

GGACGCATGAATTATTACTGGACTCTACTAAAGCCAGGTGATACAATTATCTTCGAAGCC

AATGGCAATCTTATCGCTCCCATGTACGCATTCGCTCTGAGCCGTGGTTTTGGGTCTGGA

ATCATCACCTCCAACGCTTCTATGCATGAATGTAATACAAAATGCCAGACTCCGTTAGGG

GCAATCAACAGTTCACTGCCATACCAAAACATCCACCCCGTGACTATTGGGGAGTGCCCA

AAGTATGTCCGGAGCGCCAAACTCCGGATGGTCACCGGCCTACGCAATAACCCCAGTATC

CAGTCTAGGGGATTGTTCGGTGCTATCGCAGGTTTTATTGAGGGCGGCTGGACAGGAATG

ATCGACGGATGGTATGGGTATCATCACCAGAATGAACAAGGCTCCGGGTATGCGGCTGAC

CAAAAATCCACGCAGAACGCAATCAACGGAATCACCAATAAAGTGAATACTGTGATAGAA

AAGATGAACATTCAGTTCACGGCTGTAGGCAAGGAGTTCAATAAGCTGGAGAAGAGAATG

GAGAACCTAAATAAGAAGGTCGATGACGGCTTCCTTGACATCTGGACTTACAATGCAGAA

CTGCTGGTACTGCTTGAGAACGAACGCACCCTGGATTTCCACGACTCTAATGTGAAGAAC

CTATACGAAAAAGTGAAGTCCCAGCTGAAAAACAATGCTAAAGAGATAGGCAACGGCTGC

TTCGAATTCTATCATAAATGCGACAACGAGTGCATGGAGTCAGTCCGAAATGGTACGTAC

GATTACCCAAAATATTCTGAAGAGTCCAAGCTAAATAGAGAAAAGGTGGACGGCGTAAAA

CTCGAGTCCATGGGCATCTACCAGATTCTGGCCATCTACAGTACGGTGGCTTCATCGCTT

GTACTCCTGGTGAGCCTAGGGGCCATCTCTTTTTGGATGTGTTCTAACGGTTCCCTGCAG

TGCCGCATTTGTATT

464
ATGAAAGCTAACCTGCTGGTACTCTTATGCGCTCTGGCCGCTGCAGACGCCGATACCATC

TGTATCGGGTATCATGCCAACAATAGCACCGACACCGTGGATACAGTCCTAGAAAAGAAT

GTGACCGTCACTCACTCAGTGAACCTATTAGAAGATTCCCACAACGGCAAGTTGTGTCGC

CTCAAAGGCATCGCCCCACTGCAACTTGGGAAATGCAACATAGCCGGGTGGCTGCTGGGC

AACCCAGAGTGCGATCCCCTGTTGCCAGTGCGCAGTTGGTCATATATCGTGGAGACTCCA

AATTCAGAAAATGGGATTTGCTATCCAGGGGACTTCATCGACTACGAAGAACTGCGCGAA

CAGCTGTCCAGCGTGAGTTCCTTCGAACGATTTGAAATTTTCCCAAAGGAGAGCAGCTGG

CCTAACCACAACACGAACGGAGTGACTGCCGCTTGCAGCCACGAGGGAAAGAGCTCTTTC

TACCGCAACCTTCTGTGGTTGACAGAGAAGGAAGGGAGCTACCCCAAACTGAAGAACTCC

TACGTTAATAAGAAAGGTAAGGAAGTGCTAGTGCTCTGGGGTATCCATCATCCACCAAAT

AGCAAAGAGCAACAGAATCTGTATCAGAACGAGAACGCTTACGTGTCAGTTGTCACTTCC

AACTATAACCGCCGGTTCACTCCAGAGATCGCTGAGCGCCCCAAGGTGCGCGATCAGGCT

GGCCGCATGAACTATTACTGGACCTTGCTGAAGCCAGGGGACACAATTATCTTTGAGGCC

AATGGAAATCTCATCGCACCGATGTACGCCTTTGCCCTTTCCCGGGGCTTCGGGTCTGGC

ATCATTACCTCGAATGCTTCGATGCACGAGTGCAACACCAAGTGCCAAACTCCCTTGGGA

GCTATTAATTCTTCACTCCCATACCAGAATATTCACCCAGTTACAATCGGCGAGTGTCCA

AAGTACGTGCGTTCCGCAAAACTGCGGATGGTTACAGGTCTGCGAAACAATCCAAGTATA

CAGAGTAGAGGACTTTTTGGAGCTATTGCCGGATTCATAGAAGGGGGCTGGACCGGAATG

ATTGACGGTTGGTACGGCTACCACCATCAAAACGAACAGGGGTCCGGATACGCCGCAGAC

CAAAAAAGTACCCAAAATGCTATTAATGGCATAACCAATAAAGTCAACACGGTCATTGAA

AAGATGAACATCCAGTTCACTGCTGTGGGAAAGGAGTTCAATAAGCTGGAGAAACGAATG

GAGAACCTCAACAAAAAAGTAGATGACGGCTTTTTGGACATCTGGACCTACAATGCAGAG

CTTCTGGTGCTATTAGAGAACGAACGTACATTAGACTTTCACGACTCCAACGTCAAAAAC

CTGTATGAGAAGGTGAAATCCCAGCTTAAGAATAACGCAAAGGAAATCGGGAACGGCTGC

TTTGAATTCTATCACAAGTGTGACAATGAGTGTATGGAGAGCGTGCGCAATGGGACCTAC

GACTATCCTAAGTACTCAGAAGAGTCTAAACTGAACCGTGAAAAGGTCGACGGCGTTAAG

CTGGAGTCTATGGGGATCTATCAGATCCTTGCAATTTATTCCACCGTGGCGTCTTCCTTG

GTTTTGCTAGTGAGTTTAGGTGCTATCAGTTTCTGGATGTGCTCCAATGGCTCCCTGCAA

TGTAGGATCTGCATT

465
ATGAAGGCCAACCTCCTGGTCTTGCTGTGCGCCCTGGCTGCTGCCGATGCAGATACCATT

TGCATCGGCTATCACGCCAACAATTCTACAGATACCGTGGATACAGTACTCGAAAAAAAT

GTTACTGTGACGCACTCAGTCAACCTGTTGGAAGACTCGCACAATGGCAAACTGTGCAGG

CTGAAAGGCATTGCCCCCCTACAGCTGGGGAAGTGCAACATTGCAGGCTGGCTGTTGGGA

AACCCTGAATGTGATCCATTGCTCCCAGTGCGGTCCTGGTCTTACATCGTGGAGACACCA

AACAGCGAGAATGGGATGTGTTACCCTGGCGATTTTATAGACTACGAGGAGCTCAGGGAG

CAGCTCAGCTCTGTGTCGTCTTTCGAGCGCTTTGAGATTTTTCCTAAGGAGTCCTCCTGG

CCAAACCACAACACGAATGGAGTGACAGCCGCCTGTAGCCACGAGGGCAAGTCCTCATTC

TATAGAAACTTGCTTTGGCTAACTGAAAAGGAGGGCAGCTACCCTAAACTGAAAAATAGC

TATGTGAACAAAAAAGGCAAAGAAGTGCTCGTCCTGTGGGGGATCCATCATCCTCCTAAC

TCAAAGGAGCAGCAGAACCTGTATCAGAATGAAAACGCTTACGTGTCTGTCGTGACTTCA

AATTATAACCGGAGGTTCACTCCCGAAATTGCCGAGAGACCAAAGGTCAGGGACCAGGCA

GGCCGCATGAATTACTATTGGACACTTCTGAAACCAGGCGACACAATTATTTTCGAGGCA

AACGGGAACCTTATAGCCCCAATGTACGCCTTCGCACTATCAAGAGGCTTCGGTTCCGGC

ATCATTACAAGCAACGCGAGCATGCATGAATGCAACACCAAGTGCCAAACCCCACTGGGT

GCAATTAATAGTTCCCTGCCATATCAGAATATCCACCCGGTGACAATTGGAGAGTGCCCT

AAGTACGTGAGGAGCGCTAAGTTAAGAATGGTGACGGGACTGAGAAACAACCCTTCCATT

CAGTCCCGAGGACTTTTTGGAGCAATCGCCGGCTTTATTGAGGGGGGCTGGACGGGGATG

ATTGATGGCTGGTATGGGTATCACCACCAGAATGAACAGGGAAGTGGGTACGCTGCTGAT

CAGAAGTCAACTCAGAATGCCATCAACGGGATAACAAATAAGGTAAATACTGTGATTGAA

AAAATGAATATCCAGTTCACTGCCGTTGGGAAGGAGTTTAACAAGCTTGAGAAAAGGATG

GAAAACCTGAATAAGAAGGTAGATGACGGATTCCTCGATATATGGACCTACAACGCTGAG

CTGCTGGTTTTGCTAGAGAACGAAAGAACTTTGGATTTTCATGATTCTAACGTGAAGAAC

TTGTACGAAAAAGTGAAAAGTCAGCTTAAAAACAACGCAAAGGAGATTGGGAATGGCTGC

TTTGAGTTTTATCACAAGTGCGACAATGAATGTATGGAGAGCGTGAGGAACGGCACGTAT

GACTACCCCAAGTACAGTGAGGAATCCAAGCTGAACCGAGAAAAGGTCGACGGCGTGAAG

CTGGAGTCTATGGGAATCTATCAGATTCTCGCAATTTACTCAACTGTCGCATCATCCCTA

GTGCTCCTGGTGAGCCTGGGAGCCATTTCTTTCTGGATGTGTAGCAATGGTAGTTTACAA

TGCAGAATCTGTATT

466
ATGAAGGCAAATCTGCTGGTCTTACTGTGCGCTCTGGCCGCTGCTGATGCTGATACAATC

TGTATTGGCTACCACGCCAATAACTCCACTGATACAGTGGATACTGTGCTGGAAAAAAAT

GTTACAGTCACACATTCAGTGAACCTCCTAGAAGACAGCCATAACGGAAAACTCTGCCGG

CTGAAAGGTATCGCACCTTTGCAGCTAGGAAAGTGCAATATTGCGGGCTGGCTGCTTGGT

AATCCCGAGTGCGACCCACTCTTACCAGTGAGAAGTTGGAGCTATATCGTAGAGACCCCC

AACTCTGAGAATGGAATCTGTTATCCAGGCGACTTTATTGATTACGAGGAACTGCGCGAG

CAACTCTCTTCTGTGTCTTCATTCGAGAGGTTTGAAATCTTCCCTAAGGAGTCGTCTTGG

CCTAATCACAATACCAACGGGGTGACCGCCGCTTGCAGCCACGAGGGGAAGAGTTCTTTT

TACCGAAATCTTCTGTGGCTAACAGAAAAGGAAGGATCATACCCAAAATTAAAGAATAGC

TATGTAAACAAGAAGGGTAAGGAGGTTCTTGTCTTATGGGGCATACATCATCCCCCCAAC

TCTAAGGAACAACAGAATCTATATCAGAACGAGAATGCTTACGTGAGTGTGGTGACCAGT

AATTATAATAGAAGATTCACTCCTGAGATTGCCGAAAGGCCTAAAGTGCGCGACCAAGCG

GGACGGATGAACTACTACTGGACCTTGCTCAAGCCGGGTGACACAATTATTTTTGAAGCA

AATGGTAATCTCATTGCACCAATGTATGCGTTTGCCCTGAGTCGTGGATTTGGCAGCGGA

ATAATAACTTCAAACGCCAGCATGCACGAATGCAATACTAAATGTCAGACCCCACTGGGG

GCAATCAACTCCTCACTGCCATATCAGAACATCCACCCCGTGACCATTGGTGAGTGCCCT

AAGTATGTTAGATCAGCGAAGCTTCGGATGGTAACAGGACTTAGAAATAATCCGAGCATT

CAAAGCCGCGGGCTGTTTGGAGCCATTGCAGGGTTTATCGAAGGGGGTTGGACCGGCATG

ATTGATGGCTGGTATGGATACCACCATCAGAACGAACAAGGCAGCGGGTATGCAGCTGAC

CAAAAGTCTACCCAGAACGCCATCAATGGAATCACGAACAAGGTTAATACAGTGATTGAG

AAGATGAATATTCAGTTTACAGCCGTTGGCAAGGAGTTCAACAAGCTGGAGAAGCGAATG

GAGAACTTAAATAAAAAGGTCGACGACGGCTTCCTGGACATTTGGACATACAACGCTGAA

CTGTTGGTGCTTCTCGAGAATGAACGAACTTTAGATTTTCACGATAGCAACGTTAAAAAC

TTATATGAGAAAGTGAAGTCTCAGCTCAAGAATAATGCCAAGGAGATAGGTAATGGTTGC

TTCGAATTCTATCACAAGTGTGACAACGAATGCATGGAGAGTGTTAGAAACGGTACATAC

GATTATCCCAAGTATAGTGAGGAGTCCAAACTCAATAGGGAAAAGGTGGACGGGGTGAAG

CTCGAGAGCATGGGCATTTATCAGATCCTTGCAATATACTCAACCGTAGCATCTTCTCTC

GTTCTTCTGGTGTCCCTGGGCGCTATTTCTTTTTGGATGTGCAGTAATGGCAGCCTTCAA

TGTAGAATTTGCATC

467
ATGAAGGCCAATCTCCTGGTGCTTCTATGTGCACTGGCCGCGGCCGATGCCGACACCATT

TGCATTGGCTATCACGCCAATAATTCCACTGACACAGTTGATACCGTGCTCGAAAAAAAC

GTAACCGTGACCCATTCCGTTAACCTGCTTGAGGATTCTCACAACGGGAAACTCTGCAGA

CTGAAGGGCATCGCCCCCCTGCAGCTGGGAAAATGCAATATTGCCGGCTGGCTCTTAGGT

AACCCAGAATGTGATCCATTACTGCCGGTCAGAAGCTGGAGCTACATCGTGGAAACCCCC

AACTCTGAGAATGGAATCTGTTATCCCGGAGATTTTATTGATTACGAGGAGCTCCGCGAA

CAGCTATCCTCTGTATCTTCTTTTGAGAGATTCGAGATTTTCCCCAAGGAGAGCAGCTGG

CCAAACCACAACACTAATGGTGTCACCGCCGCCTGCTCCCATGAAGGAAAGTCCAGCTTT

TATCGGAACTTACTGTGGCTGACAGAGAAGGAGGGCTCTTACCCCAAGCTGAAGAACAGC

TATGTCAATAAAAAGGGCAAGGAAGTCCTAGTGTTGTGGGGGATCCACCATCCACCTAAC

AGCAAAGAGCAGCAGAACCTCTACCAGAATGAGAATGCGTACGTTTCTGTGGTGACTTCA

AACTATAACCGCCGATTCACACCCGAGATCGCAGAGAGACCTAAAGTCAGGGACCAAGCG

GGGAGAATGAACTACTACTGGACCCTCTTGAAGCCCGGCGATACCATTATTTTTGAGGCT

AACGGCAACCTGATCGCCCCCATGTATGCATTCGCTCTGAGCCGTGGCTTCGGATCTGGT

ATTATAACCTCAAACGCAAGCATGCATGAATGTAACACCAAATGCCAGACCCCCCTGGGG

GCCATCAACAGCAGTCTGCCATACCAGAACATCCACCCTGTCACCATTGGTGAATGCCCC

AAGTATGTCCGATCAGCGAAACTGCGGATGGTCACGGGGCTGCGAAACAATCCTTCAATC

CAGAGCCGAGGACTTTTTGGAGCTATCGCCGGATTCATTGAAGGCGGCTGGACAGGGATG

ATCGACGGTTGGTACGGGTATCACCACCAGAACGAGCAAGGCAGTGGCTACGCAGCTGAC

CAGAAATCCACCCAAAACGCCATTAACGGGATCACTAACAAAGTGAACACGGTCATCGAG

AAGATGAATATTCAATTCACTGCCGTTGGCAAAGAGTTTAATAAGTTGGAAAAGCGCATG

GAGAATCTAAACAAAAAGGTTGACGATGGTTTCTTGGATATCTGGACATATAATGCCGAG

CTGTTAGTCCTGTTAGAAAACGAGAGAACCCTTGATTTTCATGATAGCAACGTCAAAAAC

TTATACGAGAAGGTGAAAAGCCAGCTTAAAAATAATGCCAAAGAGATAGGAAATGGCTGT

TTTGAGTTCTATCATAAGTGCGATAACGAGTGCATGGAGTCCGTTCGGAATGGTACCTAC

GATTACCCGAAGTACTCTGAGGAGAGCAAGTTGAATCGGGAGAAAGTTGATGGCGTCAAG

CTCGAATCCATGGGTATCTACCAGATATTAGCTATTTACTCCACAGTCGCATCTAGCCTG

GTCCTGCTGGTTTCGCTGGGCGCCATATCTTTTTGGATGTGTTCTAATGGCAGCTTACAA

TGCAGGATTTGTATC

468
ATGAAAGCCAACCTCCTCGTGTTGCTGTGCGCTTTGGCCGCTGCCGACGCCGACACCATC

TGTATAGGCTATCATGCGAATAATAGCACCGACACAGTAGATACCGTTCTGGAGAAGAAC

GTGACCGTGACTCACAGCGTGAATCTGTTGGAGGACTCCCATAATGGGAAGCTGTGTAGA

TTGAAAGGTATTGCACCGCTACAACTCGGGAAGTGCAATATCGCCGGGTGGCTGCTTGGT

AACCCCGAGTGTGACCCACTGCTGCCAGTTCGTTCTTGGAGTTACATCGTGGAGACTCCT

AATAGCGAGAATGGTATCTGCTACCCTGGGGACTTCATCGATTATGAGGAGCTCAGAGAG

CAGTTGAGTTCCGTGTCATCATTTGAGCGGTTTGAGATTTTTCCAAAGGAAAGTTCGTGG

CCGAACCATAACACTAACGGAGTCACCGCCGCCTGTAGTCACGAGGGCAAATCTTCTTTT

TACCGGAATTTGCTGTGGCTTACAGAAAAAGAGGGCTCCTATCCGAAGCTGAAGAACTCT

TATGTGAATAAAAAAGGAAAGGAAGTCCTAGTGCTGTGGGGAATCCATCATCCTCCAAAT

AGTAAGGAGCAGCAGAACCTATATCAGAACGAGAACGCATACGTGTCCGTGGTCACGTCA

AACTACAACCGGAGGTTCACTCCCGAGATCGCCGAAAGGCCTAAGGTTCGGGATCAGGCT

GGGCGCATGAACTACTACTGGACTTTACTGAAACCAGGAGACACCATTATCTTCGAGGCT

AACGGCAATCTCATAGCTCCGATGTACGCCTTTGCCTTGAGTCGCGGATTCGGAAGTGGT

ATCATTACTAGCAATGCCTCAATGCATGAGTGTAACACAAAATGCCAGACCCCCTTGGGA

GCAATTAACTCATCTCTACCATATCAGAACATCCACCCTGTCACTATAGGGGAGTGTCCC

AAGTATGTCAGATCCGCCAAGTTGCGGATGGTAACCGGGCTGCGGAATAACCCCTCCATC

CAGTCCCGTGGCCTTTTTGGCGCCATTGCGGGATTTATTGAGGGAGGCTGGACGGGCATG

ATTGATGGCTGGTATGGTTATCACCACCAGAATGAACAGGGGTCTGGTTATGCTGCCGAC

CAGAAGAGTACCCAAAACGCCATCAATGGAATTACAAACAAGGTGAATACAGTGATCGAA

AAAATGAACATCCAGTTTACTGCAGTTGGTAAAGAATTCAACAAACTAGAAAAGCGGATG

GAGAACCTCAACAAGAAGGTCGATGACGGCTTTCTGGACATCTGGACATACAACGCCGAA

CTTCTAGTGCTTCTGGAGAATGAGCGCACACTGGATTTTCACGACTCAAATGTTAAGAAC

CTCTACGAAAAGGTGAAGTCCCAGCTCAAAAACAACGCCAAGGAGATTGGCAATGGCTGT

TTTGAATTTTACCACAAATGCGACAATGAATGTATGGAGTCCGTCCGGAATGGCACCTAT

GACTATCCAAAGTATTCTGAGGAATCCAAGCTGAATCGGGAAAAAGTGGATGGTGTGAAA

CTTGAGTCAATGGGAATTTATCAGATCCTGGCCATTTACAGTACGGTGGCCTCCTCACTG

GTGCTACTGGTAAGTCTGGGAGCAATTTCATTCTGGATGTGCTCCAATGGTTCACTGCAG

TGCAGAATCTGCATA

469
ATGAAGGCTAACCTGCTGGTACTTCTGTGTGCGCTCGCGGCAGCTGATGCCGACACGATC

TGTATTGGATATCATGCGAACAATAGCACAGACACCGTGGATACAGTTCTGGAAAAGAAC

GTGACTGTCACGCACTCCGTCAACTTACTAGAGGACTCTCACAACGGGAAGCTCTGCAGA

CTGAAGGGAATTGCACCCTTGCAGCTGGGTAAGTGTAACATCGCTGGATGGCTACTTGGT

AACCCCGAGTGTGACCCTCTCCTGCCCGTGCGGTCCTGGAGCTACATAGTTGAGACACCA

AACTCTGAGAACGGGATCTGCTATCCTGGGGACTTCATTGACTACGAGGAGCTGCGGGAG

CAGCTCTCCTCCGTCTCGTCTTTCGAAAGGTTCGAGATTTTCCCAAAAGAATCAAGTTGG

CCCAACCACAACACAAATGGTGTTACCGCCGCCTGTAGCCATGAAGGGAAATCAAGCTTC

TACCGTAATCTGCTTTGGCTTACCGAAAAAGAAGGAAGCTACCCTAAGTTAAAAAACTCT

TATGTCAACAAAAAAGGGAAAGAAGTTTTGGTGCTGTGGGGCATCCACCACCCTCCTAAT

TCGAAAGAACAGCAGAACTTGTATCAGAACGAAAATGCCTACGTGTCCGTGGTGACCAGT

AACTACAACCGACGGTTCACCCCGGAGATAGCAGAGAGGCCAAAAGTCAGAGATCAGGCT

GGCAGAATGAACTATTACTGGACCCTCCTAAAACCCGGAGACACTATTATATTTGAGGCA

AATGGTAATCTGATCGCTCCAATGTATGCTTTCGCCCTCTCCCGCGGATTCGGGTCAGGG

ATAATCACCTCTAACGCTTCTATGCACGAATGTAACACCAAGTGCCAAACTCCCCTTGGA

GCCATCAACAGTTCTCTACCATACCAGAATATCCATCCAGTGACGATCGGCGAATGCCCT

AAATACGTCAGAAGTGCTAAGCTAAGAATGGTTACTGGGCTGAGAAATAATCCGTCCATT

CAGAGCAGGGGGCTGTTTGGAGCGATCGCTGGATTTATTGAAGGAGGTTGGACCGGGATG

ATCGATGGCTGGTACGGTTATCACCATCAAAATGAGCAGGGAAGCGGATACGCCGCAGAC

CAGAAAAGCACACAGAACGCTATTAACGGAATCACTAATAAGGTGAATACTGTCATCGAG

AAAATGAACATTCAGTTCACAGCAGTGGGCAAAGAGTTTAACAAGCTTGAAAAGAGGATG

GAGAATCTCAACAAGAAGGTGGATGACGGCTTCCTCGACATCTGGACTTATAACGCCGAG

CTCCTCGTCCTGCTCGAAAATGAAAGGACTTTGGACTTCCACGATTCAAACGTGAAGAAT

TTGTACGAAAAGGTGAAGTCCCAGCTGAAAAACAACGCTAAGGAGATAGGGAATGGCTGT

TTCGAATTCTACCACAAGTGCGACAATGAGTGCATGGAGAGTGTTAGAAATGGGACGTAT

GACTATCCTAAGTATTCGGAGGAATCAAAGTTGAATCGAGAGAAGGTGGACGGTGTGAAG

TTAGAGTCGATGGGCATCTACCAGATTCTGGCTATCTATTCCACCGTGGCTAGCAGCTTG

GTCCTCCTCGTATCATTGGGCGCAATTAGCTTCTGGATGTGCTCCAACGGTTCCCTTCAG

TGCAGAATCTGTATC

470
ATGAAAGCAAATCTGCTGGTGCTGTTGTGCGCGCTGGCGGCTGCTGACGCAGACACCATT

TGCATCGGCTACCACGCCAACAACAGTACTGATACTGTGGACACAGTTTTAGAAAAGAAT

GTGACCGTAACACATAGCGTAAACTTGCTGGAAGACAGTCACAATGGAAAACTCTGCCGG

CTGAAGGGAATCGCCCCTCTACAGCTCGGCAAATGCAATATCGCCGGGTGGCTATTGGGG

AATCCAGAGTGCGACCCACTTCTGCCTGTGCGCAGTTGGTCATATATCGTGGAAACACCA

AACTCCGAAAACGGCATTTGCTATCCTGGAGACTTTATTGACTACGAAGAGCTAAGAGAG

CAGCTGAGCTCCGTGTCCAGTTTTGAGCGATTTGAGATCTTCCCAAAGGAGAGCTCTTGG

CCAAATCACAATACCAACGGAGTGACCGCGGCTTGTTCTCACGAGGGTAAATCCTCCTTT

TATAGGAACCTGCTGTGGCTGACCGAGAAAGAGGGATCTTACCCAAAACTTAAGAACAGC

TATGTTAACAAGAAGGGAAAAGAAGTGCTTGTGCTGTGGGGTATTCACCACCCTCCTAAT

TCCAAGGAGCAGCAGAATCTGTATCAGAATGAGAATGCCTACGTCAGCGTGGTCACCTCA

AATTATAACAGACGGTTCACCCCAGAGATTGCGGAGCGTCCCAAGGTAAGGGACCAAGCC

GGACGCATGAACTATTATTGGACTCTGCTGAAACCTGGTGATACTATCATCTTTGAGGCC

AATGGCAATCTTATCGCCCCTATGTATGCATTTGCCCTATCTCGCGGATTTGGGAGCGGC

ATCATCACAAGTAATGCCAGCATGCACGAATGTAATACCAAATGCCAGACACCTCTGGGC

GCTATCAACAGCAGCCTGCCTTATCAGAATATACACCCTGTCACCATCGGGGAATGCCCT

AAATATGTTCGCAGTGCCAAACTTCGTATGGTGACTGGGCTGCGCAACAACCCATCAATT

CAGAGCAGGGGCCTGTTCGGAGCGATTGCCGGGTTTATCGAGGGAGGGTGGACGGGCATG

ATAGATGGCTGGTACGGATACCACCATCAAAATGAACAGGGCAGTGGCTACGCAGCGGAC

CAGAAATCCACCCAGAATGCTATAAACGGTATCACAAATAAGGTGAATACAGTCATCGAA

AAGATGAATATTCAGTTCACTGCGGTCGGTAAGGAGTTCAACAAACTGGAGAAGAGGATG

GAAAATCTTAACAAAAAAGTGGACGACGGCTTCCTGGATATATGGACGTATAATGCAGAA

CTGTTAGTGTTACTCGAGAATGAGAGGACTCTCGACTTCCATGATTCCAACGTGAAGAAT

CTCTATGAGAAGGTGAAATCCCAACTGAAGAACAACGCCAAAGAGATAGGGAATGGATGC

TTCGAATTCTACCATAAGTGTGATAACGAGTGTATGGAGTCTGTGCGGAATGGCACTTAC

GACTATCCGAAATACAGTGAGGAGTCAAAGTTGAACCGGGAGAAGGTCGATGGCGTCAAG

CTGGAGAGTATGGGAATCTATCAGATCCTCGCAATTTACTCAACCGTGGCTAGCTCCCTG

GTACTCCTGGTCTCACTTGGAGCCATCTCCTTCTGGATGTGCAGCAACGGCAGCCTTCAG

TGCAGAATCTGCATT

471
ATGAAGGCCAATCTTTTAGTGCTGTTGTGTGCACTGGCGGCAGCTGATGCTGACACCATC

TGCATCGGATACCACGCCAATAACAGCACTGACACAGTTGACACTGTTCTGGAAAAAAAC

GTGACGGTGACCCACTCCGTCAATCTTCTGGAGGACTCCCACAACGGGAAGCTGTGTAGG

TTGAAGGGTATCGCCCCGTTGCAGCTGGGCAAATGCAACATCGCGGGTTGGCTGCTTGGC

AATCCTGAGTGCGATCCACTGCTACCCGTACGGTCTTGGTCATATATCGTTGAGACCCCA

AATAGCGAGAATGGCATCTGTTATCCTGGCGATTTCATCGACTACGAAGAGCTGCGAGAA

CAACTGAGTTCGGTGTCTAGTTTCGAGAGGTTTGAGATCTTCCCAAAAGAAAGTTCCTGG

CCTAACCACAATACCAACGGGGTAACGGCCGCTTGTAGCCACGAGGGCAAATCAAGCTTT

TACAGAAATCTGCTGTGGCTCACAGAAAAAGAAGGGAGCTATCCTAAATTAAAGAATTCA

TACGTGAACAAAAAAGGAAAGGAAGTACTCGTCCTGTGGGGAATTCACCACCCTCCAAAT

TCTAAAGAACAACAGAACTTGTACCAGAATGAAAACGCCTATGTATCCGTGGTTACCTCA

AACTACAATCGGCGGTTCACCCCCGAAATAGCTGAGAGACCGAAGGTTCGGGACCAAGCG

GGAAGAATGAACTATTACTGGACTCTCCTTAAGCCCGGTGATACTATCATCTTTGAAGCC

AACGGAAACCTTATCGCCCCAATGTATGCCTTCGCGTTATCCCGCGGGTTTGGAAGCGGT

ATTATTACTTCAAACGCGAGCATGCACGAATGTAATACTAAATGTCAGACACCCCTTGGC

GCCATCAATAGCAGTCTGCCATACCAAAATATTCACCCCGTGACAATTGGCGAGTGTCCA

AAATATGTTAGAAGCGCCAAACTCAGAATGGTTACTGGCTTGCGGAATAACCCGTCCATT

CAGTCCAGAGGGTTATTTGGGGCAATCGCCGGCTTTATAGAAGGGGGCTGGACTGGAATG

ATCGACGGTTGGTACGGATATCATCACCAGAATGAACAGGGATCAGGATATGCCGCGGAC

CAAAAGTCTACCCAGAACGCCATCAACGGCATCACTAATAAGGTCAACACTGTGATTGAG

AAGATGAATATTCAGTTCACCGCAGTCGGCAAGGAATTCAACAAACTCGAGAAACGCATG

GAAAACCTTAACAAAAAGGTGGACGATGGGTTTCTGGACATTTGGACCTACAATGCCGAG

CTGCTAGTGCTGCTGGAAAACGAGCGGACTCTTGATTTCCATGACTCTAATGTAAAAAAC

CTTTACGAAAAAGTTAAATCACAACTTAAAAATAATGCCAAAGAAATAGGGAACGGATGT

TTCGAGTTCTACCACAAATGTGATAACGAATGCATGGAGAGTGTTCGCAACGGAACATAT

GACTATCCTAAGTACAGCGAAGAGTCAAAACTAAATCGGGAGAAAGTCGACGGCGTGAAA

CTCGAATCCATGGGGATTTACCAGATCCTCGCAATCTATTCTACCGTGGCTAGCTCGCTG

GTGCTGCTTGTTAGTCTGGGAGCTATCTCCTTTTGGATGTGTAGCAATGGAAGCCTGCAG

TGTAGAATTTGCATA

472
ATGAAGGCCAACCTGCTGGTCCTGCTGTGTGCACTCGCCGCCGCCGATGCCGACACTATT

TGTATTGGCTACCACGCTAACAACTCCACAGATACAGTCGATACTGTGCTGGAAAAGAAT

GTTACCGTCACCCATAGCGTGAACTTGCTCGAGGATTCTCATAATGGGAAACTCTGTCGG

TTAAAGGGGATTGCACCTCTCCAACTGGGCAAGTGTAACATCGCGGGTTGGCTGCTTGGA

AACCCTGAGTGCGATCCTCTACTTCCGGTCAGGTCGTGGAGTTACATTGTCGAGACCCCT

AACTCAGAAAACGGTATCTGTTATCCGGGTGATTTTATCGATTACGAAGAGCTCAGAGAA

CAGCTGTCCAGCGTGTCTTCATTCGAGCGATTCGAAATTTTCCCGAAGGAATCATCTTGG

CCAAATCATAATACTAACGGGGTGACGGCCGCATGTTCACATGAGGGCAAATCCAGCTTC

TACCGAAACCTTTTGTGGTTGACGGAGAAGGAGGGCTCTTATCCCAAGCTGAAAAACAGC

TATGTGAACAAGAAGGGGAAGGAGGTGCTCGTTCTGTGGGGGATCCATCACCCTCCTAAC

AGCAAAGAGCAGCAAAACCTGTATCAGAATGAAAACGCCTATGTGTCCGTGGTGACGAGC

AACTACAACCGGCGCTTTACCCCCGAAATTGCTGAACGGCCGAAGGTGAGGGATCAAGCC

GGCCGGATGAATTATTACTGGACGCTGCTGAAACCTGGTGATACCATCATCTTTGAAGCT

AACGGAAACTTGATCGCTCCAATGTATGCATTCGCCCTGTCACGGGGATTCGGCAGCGGT

ATAATCACCAGTAATGCCTCAATGCACGAATGCAATACCAAGTGCCAAACGCCCCTTGGT

GCCATCAACTCATCTCTGCCCTATCAGAATATCCATCCTGTAACCATCGGAGAGTGTCCC

AAGTATGTCAGATCAGCAAAACTGCGGATGGTCACAGGTCTCCGAAATAATCCCTCAATC

CAGTCTCGCGGCCTGTTCGGCGCTATCGCCGGCTTTATTGAGGGGGGTTGGACCGGGATG

ATCGACGGCTGGTATGGATACCATCATCAGAACGAGCAGGGGAGCGGCTACGCGGCTGAC

CAGAAGTCAACCCAGAATGCTATCAATGGTATCACTAATAAGGTGAATACGGTGATTGAA

AAAATGAACATACAGTTCACCGCAGTGGGTAAAGAGTTCAATAAGCTGGAGAAGCGGATG

GAGAATCTGAACAAAAAGGTCGATGATGGCTTCTTGGACATCTGGACCTATAACGCCGAG

CTTCTTGTGCTGCTCGAGAACGAGAGAACACTGGACTTCCATGACTCTAACGTGAAGAAC

CTCTACGAGAAGGTGAAATCTCAGTTGAAGAACAACGCTAAGGAGATCGGCAATGGCTGC

TTCGAATTCTACCACAAGTGCGATAACGAATGCATGGAATCTGTTCGAAATGGAACTTAC

GATTACCCTAAATACAGCGAGGAAAGTAAGTTAAACAGAGAGAAAGTAGACGGGGTTAAG

CTCGAAAGCATGGGGATCTATCAGATCCTAGCCATCTACTCGACTGTCGCGTCAAGTTTG

GTGCTGCTGGTGTCTCTTGGAGCCATATCGTTTTGGATGTGCTCTAACGGCTCCCTGCAG

TGCAGAATCTGCATA

473
ATGAAGGCCAACTTGCTAGTGCTGCTGTGCGCGCTTGCAGCTGCGGATGCGGATACGATA

TGCATAGGATATCACGCCAATAATTCGACGGATACCGTGGACACAGTGCTGGAAAAGAAT

GTAACGGTCACACACAGCGTGAACCTGCTTGAAGATTCACACAACGGCAAACTGTGCAGG

CTCAAAGGAATCGCACCATTACAGCTGGGGAAATGCAACATTGCGGGGTGGCTGCTAGGA

AACCCAGAGTGCGATCCCCTGCTGCCCGTGCGGTCTTGGTCCTACATTGTAGAGACTCCG

AACTCGGAGAACGGTATTTGCTACCCTGGAGATTTCATTGACTATGAAGAACTCAGGGAG

CAACTGTCCTCAGTTTCGAGCTTTGAAAGGTTCGAGATCTTTCCTAAGGAGTCCAGCTGG

CCTAACCACAATACAAACGGGGTGACCGCGGCCTGTTCACATGAGGGTAAATCTTCATTC

TACCGCAACCTCCTGTGGTTAACCGAAAAAGAAGGAAGCTATCCTAAGCTGAAGAATTCT

TACGTGAATAAAAAGGGTAAGGAAGTTCTGGTGCTGTGGGGCATCCACCACCCACCTAAT

AGTAAGGAACAGCAGAACCTATACCAGAACGAAAATGCGTACGTGAGCGTGGTAACTTCA

AACTATAATCGGAGGTTCACACCCGAAATCGCGGAGCGGCCCAAGGTGCGGGACCAGGCT

GGGCGCATGAATTATTACTGGACACTGTTGAAACCTGGAGACACTATAATCTTCGAGGCG

AACGGAAACTTAATCGCTCCCATGTACGCATTCGCCCTGTCCCGTGGCTTTGGCAGCGGT

ATCATCACATCCAACGCCTCTATGCACGAATGCAATACGAAGTGCCAAACCCCTCTCGGA

GCCATTAATAGCTCCCTCCCATATCAGAACATTCACCCAGTGACCATAGGAGAGTGTCCT

AAGTACGTTCGGAGCGCAAAACTCCGCATGGTGACGGGGTTGCGAAACAACCCTTCCATC

CAGTCGAGGGGCCTTTTCGGGGCGATCGCTGGCTTCATCGAGGGAGGGTGGACCGGGATG

ATTGACGGCTGGTACGGGTATCACCACCAGAACGAGCAGGGTAGCGGCTACGCCGCAGAC

CAGAAATCTACGCAGAATGCCATTAATGGGATTACAAACAAGGTTAATACCGTGATCGAG

AAAATGAACATTCAGTTCACAGCCGTCGGCAAAGAATTTAACAAATTAGAGAAGCGGATG

GAGAATCTGAATAAAAAAGTGGACGATGGATTCCTGGATATCTGGACGTATAATGCCGAG

TTGCTCGTCCTTCTGGAAAACGAGAGAACCCTGGACTTTCACGATTCAAATGTAAAGAAC

CTTTACGAAAAGGTGAAGTCTCAACTGAAAAACAACGCCAAGGAGATAGGGAATGGCTGC

TTTGAATTCTACCATAAATGCGACAATGAATGTATGGAGTCTGTTAGGAATGGTACTTAC

GACTACCCGAAGTATTCCGAAGAGAGCAAGCTGAATAGGGAGAAGGTGGATGGAGTGAAA

CTGGAATCTATGGGGATTTATCAGATCCTAGCTATTTATTCTACAGTAGCCAGCTCCCTC

GTCCTTCTGGTCTCCCTGGGCGCAATTTCATTTTGGATGTGCAGCAACGGGTCCTTACAA

TGCCGCATCTGTATT

474
ATGAAGGCTAACCTGCTTGTGTTATTGTGCGCCCTGGCGGCAGCAGACGCAGATACCATA

TGTATCGGGTATCACGCTAATAATAGCACTGACACCGTTGACACCGTCCTGGAAAAAAAC

GTGACCGTGACTCATTCAGTTAATCTTTTGGAGGACAGCCATAATGGCAAGCTTTGTAGA

CTCAAGGGCATCGCACCTTTACAGTTGGGTAAGTGCAACATCGCAGGATGGCTCCTTGGC

AACCCTGAATGTGACCCGCTGCTCCCAGTCCGGAGTTGGTCATATATCGTAGAAACTCCC

AATAGCGAAAACGGCATTTGCTACCCAGGCGACTTTATAGATTACGAAGAGCTCCGGGAG

CAGCTATCAAGTGTCTCGTCGTTTGAGCGTTTTGAGATTTTTCCGAAAGAATCCAGTTGG

CCAAATCACAACACAAACGGTGTAACAGCGGCTTGTTCACACGAGGGTAAAAGTTCTTTC

TACAGAAATTTATTGTGGCTTACAGAGAAAGAAGGCTCTTACCCAAAGCTGAAGAATTCT

TATGTGAACAAGAAGGGTAAGGAGGTGTTAGTACTGTGGGGAATACATCACCCTCCTAAT

AGCAAGGAGCAGCAGAACTTGTATCAGAACGAAAACGCATATGTGTCTGTGGTGACATCC

AATTATAATAGGCGTTTTACTCCCGAAATTGCAGAGCGACCTAAAGTGCGTGACCAGGCA

GGTAGAATGAATTACTACTGGACCCTGTTGAAGCCCGGTGACACCATCATTTTCGAAGCA

AATGGTAACCTGATCGCACCAATGTACGCATTTGCACTGTCCCGCGGATTTGGCTCCGGA

ATCATTACCAGTAATGCCTCTATGCATGAATGTAACACCAAATGCCAGACCCCCCTGGGC

GCCATTAACTCCAGCCTGCCTTATCAGAATATACATCCTGTGACAATAGGTGAGTGCCCC

AAGTACGTGAGATCTGCAAAACTAAGAATGGTCACCGGACTCAGGAACAATCCCTCCATC

CAGAGTAGGGGTCTGTTCGGAGCCATAGCAGGGTTCATTGAAGGTGGATGGACAGGGATG

ATCGATGGATGGTACGGCTACCACCACCAGAATGAGCAGGGCTCTGGCTACGCCGCTGAC

CAGAAATCTACACAGAACGCCATTAATGGCATCACTAACAAAGTGAATACCGTCATTGAG

AAGATGAATATTCAGTTCACTGCCGTTGGCAAGGAATTTAACAAACTGGAGAAGCGGATG

GAGAATCTAAATAAGAAAGTAGACGACGGGTTTCTCGATATTTGGACATATAACGCTGAG

CTTCTAGTCCTACTCGAGAACGAGAGGACCCTCGACTTCCATGATAGCAACGTGAAGAAC

CTATACGAGAAGGTCAAGTCTCAACTGAAGAACAACGCTAAGGAGATCGGAAATGGATGT

TTCGAGTTTTATCACAAGTGTGATAACGAGTGTATGGAGTCTGTAAGGAACGGTACCTAT

GACTACCCAAAATACAGCGAGGAATCAAAGCTCAATCGTGAGAAAGTCGATGGAGTTAAG

CTGGAATCTATGGGGATTTATCAGATCTTAGCTATCTATTCAACCGTTGCTTCCAGCTTA

GTCCTCCTCGTGTCACTGGGGGCTATAAGTTTTTGGATGTGCAGTAATGGCAGTTTGCAG

TGTAGGATCTGCATC

475
ATGAAGGCTAATTTATTGGTGCTGTTGTGTGCACTGGCTGCCGCAGACGCCGACACCATC

TGCATTGGATATCATGCCAACAATTCAACTGATACGGTCGATACGGTGCTTGAGAAAAAT

GTGACAGTTACACACTCTGTGAACCTTCTGGAAGACTCTCATAACGGCAAACTTTGTCGG

TTGAAGGGTATCGCCCCACTGCAGCTTGGTAAGTGCAACATCGCCGGTTGGCTCCTCGGA

AATCCAGAGTGTGATCCACTGTTACCTGTGCGTAGTTGGAGTTACATCGTGGAGACTCCT

AATAGTGAAAACGGCATATGCTATCCAGGCGATTTCATCGATTATGAAGAACTGCGTGAG

CAGCTGTCCAGCGTGTCCTCATTCGAGCGCTTTGAGATCTTCCCGAAAGAGTCCAGTTGG

CCAAACCACAATACCAATGGGGTCACTGCCGCCTGTAGTCATGAGGGTAAAAGCTCCTTC

TATCGGAATCTTCTCTGGCTGACCGAAAAAGAAGGGTCCTACCCCAAACTTAAGAATTCG

TACGTCAACAAGAAGGGCAAAGAAGTACTTGTGCTGTGGGGTATCCACCACCCTCCCAAC

TCTAAGGAGCAGCAGAATCTGTACCAGAATGAGAACGCTTACGTCAGCGTGGTGACCTCA

AATTATAACCGAAGGTTCACTCCCGAGATAGCCGAGCGGCCTAAGGTCAGAGACCAAGCG

GGTAGAATGAATTACTACTGGACACTACTAAAGCCCGGCGACACCATCATCTTTGAGGCA

AATGGAAATCTGATCGCCCCCATGTATGCATTTGCACTGAGCCGGGGGTTCGGATCTGGA

ATCATAACTTCAAACGCCAGTATGCATGAATGCAATACAAAGTGTCAGACTCCCTTGGGT

GCCATCAATTCCAGCCTGCCTTATCAGAATATCCACCCTGTGACAATTGGAGAGTGCCCA

AAATACGTTCGTTCAGCTAAACTGAGAATGGTCACCGGCCTCCGGAACAATCCTAGTATA

CAGTCACGCGGCCTTTTCGGCGCCATTGCCGGATTTATTGAAGGAGGCTGGACAGGCATG

ATAGACGGATGGTACGGATATCACCACCAGAACGAACAAGGGTCTGGCTATGCCGCAGAC

CAGAAATCCACCCAGAACGCTATCAATGGTATCACGAATAAAGTCAATACCGTCATCGAG

AAGATGAATATCCAGTTTACAGCTGTGGGAAAAGAGTTCAATAAGCTTGAAAAGAGGATG

GAGAACCTGAATAAAAAAGTTGATGACGGATTTCTCGACATCTGGACGTATAACGCTGAA

CTGCTTGTGCTGCTCGAAAACGAGAGGACATTGGATTTTCACGACTCCAATGTTAAGAAT

CTGTACGAGAAGGTGAAATCTCAGCTCAAGAATAATGCTAAGGAAATAGGCAACGGATGT

TTCGAATTTTATCATAAGTGCGACAATGAATGCATGGAATCAGTGCGCAACGGGACCTAT

GACTACCCCAAGTACAGCGAGGAGTCCAAGCTGAATAGAGAAAAGGTGGACGGCGTCAAA

CTGGAAAGTATGGGCATTTACCAAATTCTCGCCATCTACTCTACCGTTGCCAGCAGTCTC

GTGCTGTTAGTATCACTCGGTGCCATCTCTTTTTGGATGTGTAGTAATGGAAGCCTGCAG

TGCCGGATCTGTATC

476
ATGAAGGCCAACCTGCTCGTGTTGCTGTGTGCACTAGCTGCCGCCGACGCAGACACCATC

TGTATCGGCTACCATGCCAACAACAGCACCGACACAGTGGATACGGTGCTCGAGAAGAAC

GTGACTGTCACCCATAGTGTGAATCTCCTAGAGGATTCTCATAATGGGAAGCTATGCCGA

CTCAAGGGGATTGCACCTCTGCAACTGGGTAAGTGCAATATCGCCGGTTGGCTTCTTGGG

AACCCCGAATGTGATCCCCTGCTCCCCGTGCGATCTTGGTCATATATCGTTGAAACACCC

AATAGCGAAAATGGCATATGCTACCCTGGAGATTTCATTGACTATGAGGAACTCCGAGAA

CAGCTGTCAAGCGTGTCTAGTTTCGAACGGTTTGAAATATTCCCTAAGGAGAGTTCCTGG

CCCAACCATAACACAAACGGAGTGACCGCAGCCTGCTCTCATGAGGGGAAGTCCTCATTT

TATCGCAATCTCCTGTGGCTCACTGAAAAGGAGGGAAGTTACCCAAAATTGAAAAACTCA

TACGTGAATAAGAAAGGCAAGGAGGTCCTCGTGCTGTGGGGGATTCATCACCCCCCTAAC

TCAAAAGAACAGCAGAACCTGTATCAGAACGAAAACGCCTACGTGAGTGTGGTGACCTCT

AACTATAACCGGAGGTTCACGCCAGAGATTGCTGAAAGACCTAAAGTCAGGGACCAAGCC

GGCAGAATGAATTACTATTGGACCCTGTTGAAGCCCGGCGATACCATTATATTCGAGGCA

AACGGCAACCTGATTGCCCCCATGTACGCGTTCGCCCTGAGTCGAGGCTTCGGCAGTGGG

ATTATTACCTCTAACGCCTCGATGCATGAGTGCAACACAAAATGTCAAACTCCACTTGGG

GCCATCAACTCGTCTCTTCCTTACCAAAATATCCACCCGGTTACAATTGGGGAATGTCCC

AAATACGTGCGGTCCGCAAAGCTTCGCATGGTCACGGGCCTGAGGAACAACCCCTCTATTC

CAGTCTCGCGGTCTATTTGGCGCTATTGCTGGCTTTATCGAGGGGGGGTGGACAGGGATG

ATTGATGGCTGGTACGGGTACCATCACCAAAATGAACAGGGGTCCGGCTATGCTGCTGAC

CAAAAATCTACTCAAAACGCCATTAATGGAATCACAAATAAAGTGAATACGGTCATAGAA

AAGATGAACATTCAATTTACAGCCGTGGGTAAGGAGTTCAACAAACTGGAGAAGCGAATG

GAGAACTTAAACAAAAAGGTAGATGATGGTTTCCTCGATATCTGGACATATAATGCTGAG

TTGTTGGTGCTCTTGGAGAATGAGCGGACCTTAGATTTCCACGACAGCAATGTTAAAAAC

CTCTATGAAAAGGTGAAAAGTCAACTGAAGAACAATGCGAAAGAGATCGGTAACGGGTGC

TTCGAGTTCTACCACAAATGCGACAACGAGTGTATGGAGAGTGTAAGGAATGGTACATAT

GATTATCCTAAATACTCTGAAGAGTCGAAGCTGAACAGAGAGAAAGTCGACGGCGTAAAG

CTGGAGAGTATGGGTATCTACCAAATCTTGGCCATTCTATCTACCGTGGCGTCATCACTA

GTTCTTCTGGTGTCCTTGGGGGCCATATCATTCTGGATGTGTTCAAACGGGTCCCTCCAG

TGCCGCATCTGCATC

477
ATGAAGGCAAACCTGTTGGTATTGTTGTGTGCCCTGGCAGCTGCGGATGCAGACACTATT

TGCATCGGCTATCATGCAAATAATTCCACGGACACAGTTGACACCGTTCTGGAGAAAAAT

GTGACGGTCACTCATTCTGTGAACCTGCTGGAAGACTCTCATAACGGAAAGCTGTGCCGG

TTGAAGGGAATTGCACCACTACAACTGGGAAAATGCAACATCGCCGGCTGGTTGCTAGGT

AACCCTGAGTGCGATCCACTCCTTCCAGTGAGATCCTGGTCCTACATCGTCGAGACCCCA

AACTCAGAGAACGGGATCTGTTATCCAGGAGATTTCATTGACTATGAAGAGTTACGTGAA

CAGCTCTCTTCCGTGTCGTCATTCGAACGGTTTGAAATCTTCCCCAAAGAGTCATCCTGG

CCAAATCATAACACTAACGGCGTGACTGCAGCTTGTTCCCACGAAGGGAAATCATCTTTC

TACAGAAATCTGCTGTGGCTCACCGAAAAAGAGGGGAGTTATCCCAAGCTGAAAAACTCC

TACGTTAATAAAAAGGGAAAAGAAGTGCTTGTCTTATGGGGTATCCATCACCCCCCAAAT

TCTAAAGAACAGCAGAACCTGTACCAGAACGAGAACGCGTATGTGTCAGTGGTGACCTCT

AACTATAATCGCAGATTTACACCAGAGATCGCAGAGCGCCCTAAAGTACGGGACCAGGCC

GGTCGGATGAACTACTATTGGACCCTACTGAAACCAGGCGATACCATCATCTTCGAGGCT

AATGGGAACTTAATTGCCCCCATGTACGCTTTCGCACTTAGCCGTGGCTTTGGCAGGGGG

ATTATCACGTCTAATGCTTCCATGCACGAGTGTAATACGAAGTGTCAGACACCTCTTGGT

GCCATTAACTCAAGTCTTCCCTATCAGAACATCCACCCGGTGACCATCGGCGAGTGTCCC

AAGTACGTTCGAAGCGCCAAACTGCGGATGGTCACAGGTCTAAGGAATAACCCCTCCATC

CAGAGCCGCGGCTTGTTTGGTGCGATTGCCGGGTTTATCGAGGGAGGGTGGACTGGCATG

ATAGACGGATGGTACGGATACCACCACCAAAATGAACAAGGCTCCGGATACGCCGCCGAC

CAAAAATCCACGCAGAACGCCATAAACGGAATTACAAACAAGGTAAACACAGTCATAGAA

AAAATGAATATTCAGTTTACAGCCGTCGGGAAAGAATTTAACAAGCTGGAAAAGAGAATG

GAAAACCTGAATAAGAAGGTCGACGATGGTTTTCTCGATATATGGACTTACAATGCTGAA

CTTCTGGTCCTTCTGGAAAACGAACGAACCTTGGATTTCCATGACTCTAATGTGAAGAAC

TTGTACGAAAAGGTGAAATCACAGTTAAAGAACAACGCCAAAGAAATAGGAAACGGGTGC

TTCGAATTTTACCATAAATGTGATAACGAGTGTATGGAGAGCGTTCGTAATGGTACGTAC

GACTATCCTAAATATAGTGAAGAGAGCAAACTCAACCGTGAAAAAGTAGACGGCGTGAAA

CTGGAATCCATGGGGATCTACCAAATCCTGGCCATCTACTCGACGGTGGCAAGTTCTCTC

GTGCTTCTTGTAAGCCTGGGTGCTATCTCTTTTTGGATGTGTAGTAACGGATCCCTGCAG

TGTCGAATTTGCATT

478
ATGAAAGCAAATCTTTTAGTTCTTCTGTGTGCGTTGGCTGCAGCCGACGCAGACACTATC

TGCATTGGCTACCATGCTAATAATAGCACTGACACTGTAGATACAGTGTTGGAAAAGAAC

GTTACAGTGACTCACTCTGTCAATCTGCTGGAGGATTCCCATAACGGCAAATTGTGCCGT

CTAAAGGGCATTGCGCCACTCCAGCTGGGAAAGTGCAATATCGCAGGCTGGCTCCTGGGC

AACCCAGAATGCGACCCGCTGCTGCCTGTTCGCTCATGGTCATACATCGTCGAAACCCCT

AACAGTGAGAACGGGATTTGCTATCCCGGGGATTTCATCGATTACGAAGAATTACGCGAG

CAACTGAGTTCCGTGTCGTCTTTTGAGAGGTTTGAGATCTTCCCGAAGGAATCTTCATGG

CCCAACCATAACACCAATGGTGTGACTGCTGCCTGTTCACACGAGGGCAAAAGCTCTTTC

TACCGAAATCTACTGTGGCTCACAGAGAAAGAGGGATCGTACCCCAAGCTGAAAAATTCC

TATGTGAACAAGAAAGGCAAAGAGGTGCTGGTGCTTTGGGGAATTCATCACCCACCCAAT

TCTAAGGAGCAGCAGAATCTGTATCAGAACGAAAATGCCTATGTTTCCGTGGTAACATCT

AATTATAATAGGCGATTCACACCTGAGATTGCAGAGCGGCCGAAAGTCCGAGACCAGGCA

GGCCGCATGAACTATTACTGGACGCTTCTCAAACCAGGCGACACCATCATCTTCGAGGCC

AATGGGAACTTGATCGCACCAATGTACGCGTTTGCCTTGAGTCGGGGCTTTGGGAGCGGT

ATTATCACCTCGAACGCCTCTATGCATGAATGTAATACGAAGTGTCAGACCCCTCTGGGG

GCAATAAATAGCTCACTGCCCTATCAGAACATCCACCCCGTGACCATCGGTGAGTGTCCC

AAATACGTCAGGTCAGCTAAACTCCGTATGGTGACCGGCCTAAGGAATAATCCGTCCATT

CAGTCCAGAGGTCTGTTCGGTGCAATCGCCGGGTTCATTGAGGGAGGATGGACGGGTATG

ATCGACGGCTGGTATGGCTATCACCACCAGAACGAACAGGGTAGTGGCTACGCCGCTGAT

CAAAAGTCCACTCAAAATGCTATCAACGGAATCACGAACAAAGTGAACACAGTGATAGAG

AAGATGAACATTCAGTTCACCGCTGTGGGTAAAGAGTTTAATAAGCTGGAGAAAAGGATG

GAAAATCTCAATAAGAAAGTTGACGATGGATTCCTTGACATTTGGACTTACAATGCCGAG

CTGCTGGTGCTTCTGGAGAATGAGAGGACCTTAGACTTTCACGACAGCAACGTTAAAAAT

CTCTATGAGAAAGTGAAATCACAGCTGAAGAATAATGCAAAAGAGATTGGGAATGGGTGC

TTCGAGTTTTATCACAAATGCGATAACGAATGTATGGAGTCCGTGAGAAATGGAACGTAC

GACTATCCTAAGTATAGCGAGGAAAGCAAACTCAACAGGGAAAAGGTGGACGGTGTTAAA

CTCGAATCCATGGGGATTTATCAGATATTAGCGATCTATTCGACCGTGGCATCATCTCTC

GTTCTTCTTGTGTCTTTGGGCGCCATCAGCTTTTGGATGTGTTCAAATGGCTCTCTGCAG

TGTCGCATCTGTATT

479
ATGAAAGCCAATCTACTGGTCCTCCTCTGCGCCTTGGCTGCCGCAGATGCTGACACGATC

TGTATTGGCTACCATGCGAACAATAGCACGGATACAGTGGACACCGTTCTGGAGAAAAAT

GTCACCGTGACACATAGCGTAAACCTGCTCGAAGATTCCCACAACGGTAAGCTCTGTAGA

CTCAAAGGTATTGCTCCCCTGCAGTTGGGCAAATGTAATATAGCCGGCTGGCTTCTCGGC

AATCCCGAATGCGATCCCCTGTTGCCCGTGCGGTCTTGGTCTTATATCGTCGAAACCCCA

AATTCAGAAAACGGAATTTGTTATCCTGGCGACTTCATCGATTACGAAGAGTTGAGGGAG

CAGCTTTCAAGCGTTAGCAGTTTCGAGAGATTTGAGATATTTCCAAAGGAAAGTTCCTGG

CCCAATCATAACACCAACGGCGTGACCGCCGCTTGCTCTCACGAAGGCAAAAGTAGTTTC

TATCGAAATCTGCTCTGGCTGACGGAGAAGGAAGGAAGTTACCCCAAGCTGAAAAACTCC

TACGTCAACAAGAAGGGCAAAGAAGTGCTCGTACTGTGGGGCATCCATCACCCTCCCAAT

TCCAAAGAGCAGCAGAACCTGTATCAGAATGAGAACGCTTATGTATCCGTTGTGACTTCA

AACTATAATCGCCGGTTCACTCCTGAGATCGCAGAGCGGCCCAAAGTGAGAGACCAGGCC

GGGAGGATGAATTATTATTGGACACTCCTCAAGCCAGGCGACACAATTATTTTTGAGGCT

AACGGGAACTTGATCGCTCCCATGTATGCGTTCGCCTTGTCAAGAGGATTCGGATCCGGG

ATTATCACCTCTAATGCTTCGATGCACGAATGTAACACAAAGTGTCAAACTCCACTGGGA

GCCATAAATTCGTCCTTGCCATATCAGAATATTCACCCTGTTACAATTGGCGAGTGTCCC

AAGTATGTCCGCTCTGCCAAGTTACGGATGGTGACCGGGTTGCGCAACAACCCAAGTATA

CAGTCACGCGGACTGTTCGGAGCTATCGCGGGATTCATTGAGGGAGGCTGGACAGGGATG

ATCGATGGGTGGTACGGGTATCATCACCAGAACGAACAGGGATCGGGATATGCCGCGGAC

CAAAAGTCAACACAAAACGCCATCAACGGTATTACCAATAAGGTCAACACAGTGATCGAA

AAGATGAATATCCAGTTCACTGCTGTGGGCAAGGAGTTTAATAAACTGGAGAAGCGCATG

GAGAACCTGAACAAGAAGGTTGACGACGGGTTCCTGGACATATGGACGTACAATGCCGAG

CTGCTTGTCCTCCTGGAGAATGAGAGAACCCTGGATTTTCACGATTCTAATGTGAAGAAT

CTGTATGAAAAAGTGAAGTCCCAACTCAAAAACAACGCAAAAGAGATCGGCAACGGATGC

TTTGAATTCTATCATAAGTGCGATAATGAATGTATGGAAAGTGTGAGGAATGGGACTTAC

GATTACCCGAAATATTCCGAAGAGAGCAAACTGAATCGCGAGAAAGTTGACGGTGTAAAG

CTGGAGTCTATGGGAATTTACCAAATTCTGGCCATTTATTCTACCGTGGCATCAAGCCTG

GTTCTGCTGGTGTCCCTTGGCGCCATTTCATTCTGGATGTGTTCCAATGGCAGCCTCCAG

TGCCGGATATGTATC

480
ATGAAGGCTAACCTTTTGGTCCTTTTGTGCGCGCTTGCCGCGGCGGATGCAGACACCATT

TGCATAGGATACCACGCCAATAATAGCACAGACACAGTGGATACAGTCCTTGAGAAAAAT

GTCACTGTAACTCATAGTGTTAACTTGCTAGAAGACTCTCATAATGGTAAATTATGTCGG

CTTAAGGGAATCGCGCCACTCCAATTGGGCAAATGCAACATTGCTGGCTGGTTGTTAGGT

AATCCCGAGTGCGATCCCCTGCTCCCTGTCCGGTCTTGGTCTTACATCGTTGAAACACCC

AACAGTGAGAATGGCATCTGTTACCCCGGAGACTTCATCGACTACGAAGAGCTGCGAGAG

CAGCTTTCTTCCGTCTCCTCCTTTGAACGATTCGAAATCTTCCCCAAAGAGAGCTCATGG

CCGAACCATAACACTAATGGAGTTACAGCCGCCTGCTCCCATGAGGGGAAAAGCAGTTTT

TATAGGAACCTGCTGTGGCTGACAGAAAAGGAGGGCAGCTACCCCAAGCTGAAGAATTCT

TACGTGAACAAGAAGGGCAAAGAAGTATTGGTGCTGTGGGGCATTCATCATCCTCCGAAC

TCCAAGGAGCAGCAGAACCTTTACCAGAACGAGAACGCCTACGTATCAGTTGTTACTAGC

AACTATAACAGACGATTCACTCCTGAAATCGCCGAGCGGCCTAAGGTTCGGGATCAGGCT

GGGAGAATGAACTATTACTGGACCCTGTTGAAGCCTGGAGACACTATTATCTTTGAGGCA

AATGGAAACCTGATCGCACCTATGTATGCTTTCGCACTCAGCCGGGGCTTTGGCTCCGGG

ATCATCACTAGTAATGCTAGCATGCATGAGTGTAACACGAAATGTCAGACCCCACTGGGT

GCTATAAACAGTTCCCTGCCTTATCAGAACATCCACCCTGTGACTATTGGAGAGTGTCCC

AAGTACGTCAGGAGCGCAAAGCTCCGGATGGTCACAGGGCTGAGGAATAACCCAAGCATT

CAGAGCCGGGGTCTATTTGGGGCCATCGCCGGATTCATCGAGGGAGGCTGGACTGGCATG

ATCGATGGCTGGTATGGCTATCATCACCAAAATGAACAGGGATCCGGCTACGCCGCAGAC

CAGAAATCTACACAGAATGCAATCAACGGAATCACAAATAAAGTGAATACCGTCATCGAG

AAGATGAACATACAATTTACCGCTGTGGGTAAAGAGTTTAATAAACTAGAGAAACGGATG

GAAAATCTTAATAAAAAGGTGGACGACGGGTTCCTCGATATTTGGACATATAATGCCGAG

CTATTGGTGCTCCTGGAAAATGAAAGAACGCTTGATTTTCACGACTCTAACGTGAAAAAT

CTGTACGAAAAGGTTAAGAGTCAGCTAAAGAACAATGCCAAAGAAATCGGAAATGGTTGC

TTCGAGTTCTACCACAAATGTGATAATGAATGCATGGAATCAGTCCGAAACGGTACCTAC

GATTATCCTAAATATTCTGAAGAATCAAAGCTAAACCGAGAGAAGGTCGATGGCGTCAAG

CTTGAGAGCATGGGTATCTACCAGATACTGGCCATCTATAGTACTGTGGCATCTTCCCTG

GTGCTTCTCGTGTCCCTGGGGGCGATCTCCTTTTGGATGTGTTCAAACGGATCCCTGCAG

TGTCGGATATGCATC

481
ATGAAGGCCAACCTGCTGGTTCTGCTTTGCGCTCTCGCCGCCGCCGATGCTGATACTATT

TGCATAGGTTATCATGCTAACAACTCCACTGATACTGTTGATACAGTTCTCGAAAAAAAC

GTAACGGTCACTCACTCTGTAAACCTATTGGAAGACAGCCACAATGGGAAGTTGTGTAGG

CTTAAAGGCATCGCTCCACTGCAGCTGGGCAAATGTAACATCGCAGGCTGGCTCCTGGGC

AACCCGGAGTGTGATCCTTTACTGCCCGTCCGCTCCTGGTCTTACATTGTTGAGACACCC

AACAGTGAAAACGGTATCTGTTATCCCGGCGATTTTATTGACTACGAGGAGTTGCGGGAA

CAACTGTCTTCTGTGAGCAGTTTCGAGCGCTTCGAGATTTTTCCTAAGGAGTCTTCTTGG

CCCAACCATAACACAAACGGGGTGACCGCTGCCTGCTCACACGAGGGCAAGAGTAGCTTC

TATAGAAATCTTCTCTGGCTTACTGAAAAAGAGGGATCTTATCCAAAGTTGAAAAACAGT

TATGTGAACAAGAAGGGAAAAGAAGTGCTGGTCCTTTGGGGGATCCATCACCCACCCAAC

TCCAAGGAGCAGCAGAACCTGTACCAAAACGAGAACGCATATGTTAGCGTCGTGACCAGC

AACTACAATCGCAGGTTCACTCCCGAGATCGCCGAGAGGCCTAAAGTTCGCGACCAGGCT

GGACGGATGAACTACTATTGGACACTATTAAAGCCAGGCGATACCATAATATTTGAAGCA

AATGGGAACTTAATTGCACCGATGTACGCCTTCGCACTGTCCCGGGGGTTCGGAAGCGGG

ATTATTACCTCTAACGCCTCCATGCATGAGTGCAACACCAAGTGTCAAACACCCCTGGGA

GCTATTAACTCTAGCTTGCCCTATCAGAACATCCACCCAGTCACTATCGGCGAGTGTCCT

AAGTACGTTAGATCAGCCAAGCTGCGCATGGTTACGGGGCTTCGGAACAACCCCTCAATC

CAATCTCGGGGGCTTTTCGGTGCAATCGCCGGCTTTATAGAAGGCGGTTGGACCGGAATG

ATTGATGGCTGGTATGGCTACCACCACCAAAACGAACAGGGAAGCGGGTATGCTGCAGAC

CAGAAGAGCACACAGAATGCTATCAATGGGATCACCAACAAAGTAAACACGGTGATTGAG

AAAATGAATATTCAGTTCACAGCGGTGGGCAAGGAGTTCAACAAACTGGAGAAGCGTATG

GAAAATCTGAATAAAAAAGTTGACGACGGTTTCCTAGACATCTGGACATATAACGCCGAG

TTGTTGGTGCTCCTCGAAAACGAGCGCACACTCGACTTCCACGATTCTAACGTTAAGAAT

CTTTACGAAAAAGTTAAATCGCAGCTGAAAAACAACGCGAAGGAGATCGGTAACGGCTGT

TTCGAGTTTTATCATAAGTGTGATAATGAATGCATGGAATCCGTGCGGAACGGTACCTAC

GATTATCCTAAATATTCAGAGGAGAGTAAACTCAATCGCGAGAAGGTCGATGGAGTCAAG

CTTGAGAGTATGGGAATTTATCAGATTCTGGCAATCTATAGCACCGTCGCATCCAGTCTC

GTCCTCCTTGTTTCACTGGGAGCTATTTCATTCTGGATGTGCTCTAACGGGTCGCTGCAG

TGCAGAATCTGCATT

482
ATGAAGGCAAATCTTCTGGTACTTCTCTGCGCCCTCGCTGCAGCCGACGCAGATACCATT

TGTATCGGCTACCACGCGAATAACTCAACGGATACCGTGGACACCGTGTTGGAGAAGAAC

GTTACCGTCACACATAGTGTGAATCTGCTTGAAGATTCACATAACGGAAAACTTTGTAGG

CTCAAAGGCATCGCGCCACTGCAGCTGGGGAAATGCAATATTGCAGGTTGGTTACTGGGT

AACCCAGAATGCGATCCTCTGTTACCTGTGCGTAGTTGGAGCTATATCGTTGAGACCCCA

AATTCGGAGAATGGGATCTGCTATCCAGGGGACTTCATTGACTATGAAGAGCTGCGAGAA

CAGCTCAGCAGCGTATCTAGCTTCGAGAGATTTGAAATTTTCCCGAAGGAATCCAGCTGG

CCAAACCACAATACCAATGGCGTTACGGCCGCCTGTAGCCACGAAGGTAAGTCTAGCTTC

TACAGAAACCTGCTGTGGCTGACAGAAAAGGAGGGGTCTTACCCGAAGTTGAAGAATAGC

TACGTCAATAAGAAAGGAAAAGAGGTCCTTGTCCTCTGGGGCATCCACCACCCTCCAAAC

TCGAAGGAACAGCAGAACCTTTATCAGAACGAGAACGCTTATGTCTCCGTGGTGACATCC

AATTATAACAGGCGTTTCACACCAGAGATAGCCGAAAGGCCCAAGGTCCGCGACCAAGCT

GGTAGGATGAATTACTATTGGACACTCCTCAAACCAGGAGACACAATTATTTTTGAAGCA

AATGGGAACCTGATTGCCCCCATGTATGCCTTTGCGCTAAGCCGCGGTTTCGGAAGCGGC

ATTATCACGAGTAATGCATCAATGCACGAGTGTAACACCAAATGTCAAACCCCCTTGGGC

GCAATTAACTCTTCCCTCCCTTACCAGAACATCCACCCCGTCACCATCGGTGAGTGCCCT

AAATACGTACGGTCTGCTAAGTTGCGGATGGTCACCGGCCTGCGAAATAACCCTAGCATT

CAGTCCAGAGGGTTATTTGGCGCGATCGCAGGATTCATCGAGGGAGGGTGGACCGGCATG

ATAGACGGGTGGTATGGATACCATCATCAGAACGAGCAAGGCAGCGGCTACGCTGCTGAC

CAAAAGAGCACGCAGAACGCGATCAATGGAATCACGAATAAGGTTAACACGGTCATCGAA

AAGATGAACATACAGTTCACAGCTGTGGGCAAGGAGTTCAACAAGCTTGAAAAAAGAATG

GAGAACTTGAACAAAAAAGTAGACGACGGCTTTCTCGATATTTGGACTTACAACGCCGAA

TTGCTAGTCTTGTTGGAGAATGAACGCACCTTGGACTTCCACGACTCCAACGTCAAGAAT

TTATACGAAAAGGTCAAAAGCCAGCTTAAGAATAACGCCAAGGAGATCGGCAATGGCTGT

TTCGAATTTTACCATAAATGCGATAATGAATGTATGGAAAGTGTTAGGAACGGCACATAC

GACTACCCTAAATACTCCGAAGAGAGCAAACTCAATCGGGAGAAGGTTGATGGAGTGAAG

TTAGAGAGCATGGGAATTTACCAAATACTCGCCATCTATAGCACCGTTGCCTCAAGCCTG

GTCCTCCTAGTGTCCCTGGGCGCCATTAGTTTCTGGATGTGTTCCAATGGGTCTTTGCAA

TGTCGCATCTGTATA

483
ATGAAAGCTAACCTGCTGGTCCTCCTATGTGCTCTCGCTGCCGCAGATGCCGATACCATA

TGCATTGGATATCACGCGAACAACAGCACCGATACGGTGGATACAGTGCTGGAAAAAAAC

GTGACTGTGACACATTCTGTCAATCTCCTGGAAGACTCCCACAATGGCAAGCTGTGTCGT

TTGAAGGGGATCGCCCCCCTGCAGCTCGGAAAGTGCAACATAGCAGGGTGGCTGCTCGGG

AATCCAGAGTGCGATCCGCTGCTCCCGGTACGGAGCTGGTCTTACATTGTTGAGACACCT

AACAGCGAGAATGGCATTTGTTATCCTGGAGACTTCATCGACTACGAGGAACTCCGGGAA

CAGCTTAGCTCCGTAAGCAGCTTCGAAAGATTTGAGATTTTCCCTAAGGAGTCATCCTGG

CCCAACCATAATACAAACGGAGTGACCGCTGCCTGTTCTCATGAAGGGAAAAGTTCCTTT

TACAGAAATCTCCTGTGGCTGACTGAGAAAGAAGGAAGCTATCCTAAGCTGAAGAATTCT

TACGTTAATAAGAAAGGAAAAGAAGTGCTGGTCCTCTGGGGGATACATCACCCCCCAAAT

AGCAAGGAGCAACAGAATTTATATCAGAATGAGAACGCATACGTCTCGGTTGTGACTTCG

AACTACAACAGGCGGTTTACACCCGAGATCGCAGAGCGCCCCAAGGTTAGAGACCAGGCT

GGGAGGATGAATTACTATTGGACGCTTCTCAAGCCAGGGGATACCATTATTTTTGAGGCT

AATGGCAATCTGATTGCCCCTATGTACGCCTTCGCTCTGTCAAGGGGATTTGGAAGCGGC

ATCATCACCTCCAACGCTTCCATGCATGAGTGCAACACCAAGTGTCAGACACCCTTAGGC

GCAATCAACAGCAGTCTGCCCTATCAAAACATTCATCCCGTGACAATCGGCGAGTGTCCG

AAATACGTTCGATCCGCGAAGTTAAGGATGGTTACGGGCCTACGTAATAACCCTTCAATC

CAGTCTCGTGGCCTCTTCGGTGCTATCGCTGGTTTCATCGAAGGAGGCTGGACAGGAATG

ATCGACGGATGGTATGGATATCACCATCAGAATGAGCAGGGCAGTGGGTATGCCGCAGAC

CAGAAATCCACCCAGAATGCCATAAATGGAATCACCAACAAGGTGAACACAGTTATCGAA

AAGATGAACATCCAGTTCACCGCCGTGGGAAAGGAGTTTAACAAACTTGAGAAGAGAATG

GAGAATCTTAATAAAAAGGTAGATGATGGGTTCCTTGATATCTGGACATATAACGCCGAG

CTTCTAGTGCTCCTGGAGAACGAGAGGACTCTGGACTTTCACGACTCCAACGTCAAAAAC

CTATACGAAAAGGTCAAGAGTCAACTGAAAAATAACGCAAAAGAGATAGGTAACGGATGT

TTTGAGTTCTACCACAAATGCGATAACGAGTGCATGGAATCCGTGAGGAATGGTACCTAT

GACTATCCAAAATATTCTGAGGAGTCCAAGCTCAACCGAGAAAAGGTGGACGGCGTAAAG

CTCGAAAGCATGGGGATTTATCAGATACTTGCAATTTATTCCACTGTGGCTTCTTCCCTG

GTGCTTTTGGTCAGCTTAGGGGCTATCAGCTTCTGGATGTGTTCCAACGGCTCCCTTCAG

TGTAGAATTTGCATC

484
ATGAAGGCAAACTTGTTGGTGCTACTCTGCGCATTAGCAGCTGCTGACGCAGATACAATT

TGTATCGGGTACCACGCCAATAACTCTACAGATACAGTAGATACCGTCCTTGAAAAAAAT

GTCACCGTGACCCATAGTGTAAACCTCCTAGAAGATAGCCATAACGGCAAACTGTGTCGG

CTTAAGGGCATCGCGCCTCTACAGCTGGGCAAGTGTAACATTGCTGGCTGGCTCCTTGGC

AATCCTGAGTGCGACCCCTTGCTGCCAGTGAGGTCCTGGAGCTACATCGTGGAAACTCCC

AATTCTGAGAATGGAATATGTTATCCGGGGGATTTCATCGACTACGAAGAGCTGCGCGAA

CAACTCTCATCAGTCAGCTCCTTTGAAAGATTCGAAATCTTCCCCAAGGAATCTAGCTGG

CCAAACCATAACACTAATGGAGTAACAGCTGCATGTTCCCACGAGGGCAAGAGCTCTTTT

TACAGGAACCTCCTATGGCTGACGGAGAAAGAAGGGTCCTACCCCAAGCTGAAAAATAGC

TACGTTAACAAGAAAGGAAAAGAGGTGTTGGTTCTGTGGGGAATTCATCATCCTCCCAAC

AGTAAGGAGCAGCAGAATCTCTATCAAAATGAAAACGCTTACGTCAGTGTGGTGACGTCT

AATTACAACAGGAGATTTACACCAGAGATTGCCGAGCGGCCGAAAGTGAGAGATCAGGCA

GGCAGGATGAATTATTACTGGACACTTCTGAAACCTGGAGACACAATCATTTTCGAAGCT

AATGGAAACCTCATCGCACCGATGTACGCATTCGCCTTGTCCCGGGGATTCGGCTCCGGC

ATCATCACCTCCAACGCTTCAATGCATGAATGTAATACTAAATGCCAGACGCCGCTTGGC

GCTATTAACTCATCCTTGCCTTATCAGAATATTCATCCCGTTACCATTGGAGAGTGTCCC

AAATACGTGCGTTCAGCCAAACTGCGGATGGTCACTGGCCTGCGAAATAACCCTTCAATT

CAATCTCGCGGACTGTTCGGAGCTATCGCCGGCTTCATAGAAGGGGGCTGGACCGGCATG

ATTGACGGATGGTACGGTTACCATCACCAAAACGAGCAGGGTTCCGGCTATGCCGCCGAC

CAGAAATCAACCCAGAACGCCATAAATGGTATTACCAACAAGGTTAATACGGTCATCGAG

AAAATGAACATCCAGTTCACAGCAGTGGGAAAAGAATTTAATAAGCTCGAGAAAAGAATG

GAAAACCTGAACAAAAAAGTGGACGATGGTTTCCTCGACATATGGACCTATAATGCTGAG

CTACTCGTCCTTCTGGAAAATGAGCGAACGCTTGACTTCCACGATTCGAATGTGAAAAAC

CTATACGAAAAAGTGAAGTCCCAGCTCAAGAACAATGCGAAGGAGATCGGGAACGGCTGC

TTTGAGTTTTACCACAAATGTGATAACGAATGCATGGAGTCTGTGCGAAATGGGACATAC

GACTATCCTAAGTATTCAGAAGAGTCAAAACTCAACCGGGAAAAGGTTGACGGAGTTAAG

CTTGAGTCAATGGGAATTTACCAAATCCTGGCAATCTACTCTACTGTTGCCTCTTCACTC

GTCCTCTTAGTTTCACTAGGGGCTATCAGTTTCTGGATGTGTTCTAATGGTAGCCTGCAG

TGTCGAATTTGTATA

485
ATGAAAGCTAATCTCTTAGTTCTGCTCTGCGCCTTAGCGGCTGCAGATGCCGACACCATA

TGCATTGGCTACCACGCTAATAACTCCACCGATACAGTGGACACCGTGCTGGAAAAGAAC

GTCACTGTGACCCACTCAGTGAACCTGTTGGAGGATTCACACAACGGCAAGTTATGCAGA

CTCAAGGGAATTGCACCACTGCAGCTGGGTAAGTGTAATATCGCTGGCTGGCTTCTCGGA

AATCCCGAGTGCGACCCTCTGTTACCTGTCAGGAGCTGGAGTTATATCGTGGAAACTCCT

AATAGTGAAAATGGAATATGCTATCCCGGCGACTTCATCGACTACGAGGAGCTAAGGGAA

CAGCTGTCAAGCGTCTCCTCCTTCGAAAGATTCGAGATCTTCCCGAAGGAGAGTTCGTGG

CCAAACCATAACACTAACGGGGTCACCGCGGCCTGTTCTCACGAGGGGAAGTCATCCTTC

TACCGAAACCTTCTGTGGCTGACGGAGAAAGAAGGCAGCTATCCCAAACTGAAGAATAGT

TACGTGAATAAGAAGGGAAAGGAGGTACTGGTCCTCTGGGGCATCCATCATCCCCCCAAC

AGTAAGGAGCAGCAGAATCTTTACCAGAACGAGAACGCTTATGTGAGCGTCGTAACCTCA

AACTACAACCGCAGGTTCACTCCTGAAATTGCCGAACGGCCGAAAGTGAGGGACCAAGCC

GGCCGCATGAACTACTATTGGACGCTTCTCAAGCCCGGTGATACTATTATTTTCGAGGCA

AACGGCAACTTAATCGCTCCTATGTACGCATTTGCACTGAGTCGGGGTTTTGGTTCGGGC

ATCATCACCTCAAATGCTTCCATGCACGAATGCAATACAAAATGCCAGACCCCACTTGGA

GCCATCAACTCCTCACTGCCTTATCAGAATATCCACCCAGTCACTATCGGGGAATGCCCG

AAATATGTCAGAAGCGCTAAGCTTCGGATGGTGACCGGTCTGCGCAATAATCCGTCTATA

CAATCCAGGGGACTGTTTGGCGCGATAGCCGGATTTATTGAGGGGGGATGGACTGGCATG

ATCGATGGGTGGTACGGGTACCATCACCAGAATGAACAGGGTTCCGGCTACGCCGCAGAT

CAAAAGTCCACCCAGAACGCTATTAACGGAATCACCAACAAGGTCAATACTGTCATTGAG

AAAATGAATATCCAGTTCACTGCCGTGGGCAAGGAGTTCAATAAGCTAGAGAAGCGTATG

GAAAACCTTAACAAGAAGGTGGACGATGGATTTTTGGATATTTGGACCTATAATGCTGAG

TTGTTGGTCCTCCTGGAGAATGAAAGAACTCTGGACTTCCATGATAGCAATGTGAAAAAC

CTCTACGAAAAAGTCAAATCACAGCTTAAGAACAACGCCAAAGAAATTGGGAATGGATGC

TTTGAGTTTTACCATAAATGCGACAACGAGTGTATGGAGTCTGTCAGAAACGGCACATAC

GATTACCCCAAGTATTCCGAAGAATCAAAACTGAATCGGGAAAAGGTTGATGGAGTGAAA

TTAGAAAGCATGGGAATCTATCAAATTCTTGCAATTTATAGCACCGTTGCTAGCTCACTG

GTCCTGCTCGTTAGTTTGGGCGCCATTAGCTTCTGGATGTGTAGCAATGGGTCTCTCCAA

TGCAGAATTTGCATT

486
ATGAAAGCGAATCTGCTGGTCCTGCTGTGCGCCCTGGCGGCTGCTGACGCGGATACTATT

TGCATCGGCTATCACGCTAATAACTCGACAGACACCGTGGATACAGTCTTGGAGAAAAAT

GTGACTGTAACCCACTCGGTTAACCTTCTCGAGGACTCGCATAACGGGAAACTGTGTAGG

CTGAAGGGAATCGCACCACTCCAGCTGGGCAAGTGCAATATAGCTGGCTGGCTGCTCGGG

AATCCTGAGTGCGACCCTCTCCTGCCCGTCCGGTCCTGGAGCTATATAGTGGAAACACCT

AACAGCGAGAATGGTATCTGCTATCCGGGGGATTTTATCGACTATGAGGAACTACGAGAA

CAGCTCTCCTCCGTTAGCAGCTTCGAGCGATTTGAAATCTTTCCTAAGGAGAGCAGTTGG

CCTAACCACAACACTAATGGGGTGACAGCCGCCTGTAGCCATGAGGGAAAGTCTTCTTTT

TATAGAAACTTGCTGTGGTTGACTGAGAAAGAGGGGAGCTACCCGAAACTAAAGAACTCC

TACGTGAACAAGAAAGGCAAAGAGGTTTTGGTTCTGTGGGGCATCCACCATCCTCCCAAT

AGCAAGGAACAGCAGAATCTCTATCAGAACGAAAACGCCTACGTGTCAGTGGTGACCAGT

AATTATAATCGACGCTTTACCCCCGAAATTGCAGAGCGGCCGAAAGTCCGCGACCAGGCC

GGACGCATGAATTACTATTGGACCCTGCTAAAGCCCGGGGACACTATCATATTTGAAGCC

AACGGGAACCTGATTGCACCCATGTATGCGTTTGCTCTGTCACGCGGGTTTGGTAGCGGG

ATTATCACTTCCAACGCTTCAATGCATGAATGTAACACTAAGTGTCAGACCCCACTGGGC

GCCATTAACAGCTCGCTGCCATACCAGAATATACACCCAGTTACTATTGGTGAATGTCCT

AAGTATGTACGGTCCGCCAAGCTGCGGATGGTTACTGGCCTCAGGAACAATCCTTCAATT

CAGTCTAGGGGGCTGTTCGGAGCCATAGCTGGCTTTATTGAGGGAGGCTGGACAGGCATG

ATTGACGGCTGGTACGGCTACCACCATCAGAACGAGCAAGGCTCCGGCTACGCCGCGGAC

CAGAAGTCAACTCAAAATGCGATAAACGGAATCACCAACAAGGTGAACACCGTCATAGAA

AAAATGAATATACAATTCACAGCCGTGGGAAAGGAGTTCAATAAGCTCGAGAAGCGTATG

GAGAATCTCAATAAAAAAGTGGATGATGGGTTCCTCGATATCTGGACCTATAACGCTGAA

CTCTTAGTCCTCCTCGAAAACGAGCGAACGCTCGACTTCCATGATTCTAATGTAAAAAAT

CTTTACGAAAAGGTTAAGTCACAGCTGAAGAACAACGCCAAGGAGATAGGAAACGGCTGT

TTCGAGTTTTATCATAAGTGTGACAACGAGTGTATGGAATCTGTCCGCAATGGCACTTAT

GATTACCCCAAGTACTCCGAGGAAAGTAAACTTAATAGAGAAAAAGTTGATGGCGTTAAG

CTGGAGTCAATGGGGATTTATCAGATCCTAGCTATATATTCTACTGTGGCTTCTAGTCTC

GTTTTGCTGGTGAGCCTGGGAGCCATAAGCTTTTGGATGTGTAGCAATGGGTCCCTCCAG

TGTCGAATCTGTATC

487
ATGAAAGCCAACTTGCTGGTGTTGCTCTGCGCCCTTGCCGCCGCCGACGCAGATACCATT

TGTATTGGCTACCATGCCAATAATTCTACGGACACTGTGGATACCGTCTTGGAGAAAAAT

GTAACTGTAACTCACTCCGTTAATCTTCTCGAAGATTCACACAATGGCAAGCTGTGCCGC

CTTAAAGGCATTGCCCCCTTGCAGCTGGGCAAGTGTAATATTGCTGGATGGCTCCTCGGC

AATCCTGAGTGTGACCCCCTCCTGCCCGTTAGGTCGTGGAGCTACATTGTGGAGACCCCA

AATTCGGAAAATGGGATATGTTACCCAGGCGACTTTATCGACTATGAGGAACTACGTGAG

CAGCTGAGTTCTGTTTCCAGTTTTGAAAGATTTGAGATCTTTCCAAAGGAGAGCTCTTGG

CCGAACCATAACACCAATGGGGTCACCGCCGCTTGCAGTCATGAAGGAAAATCAAGCTTC

TACCGAAACTTGCTGTGGCTCACGGAAAAGGAGGGCTCCTACCCCAAGTTGAAGAACTCC

TATGTGAACAAAAAGGGCAAAGAGGTTCTCGTGCTCTGGGGAATTCACCACCCTCCCAAC

AGCAAGGAGCAGCAGAACTTGTATCAGAACGAAAATGCTTACGTTAGCGTGGTGACTTCC

AATTATAATCGACGCTTTACACCGGAGATTGCTGAACGCCCGAAAGTTCGGGATCAAGCC

GGCCGGATGAACTATTATTGGACCCTCCTGAAACCCGGTGATACTATTATTTTTGAGGCA

AACGGAAACCTGATTGCTCCCATGTACGCCTTCGCCCTGTCCCGGGGGTTTGGCAGCGGA

ATTATAACTAGCAACGCTAGCATGCACGAGTGTAATACTAAGTGTCAGACCCCTCTGGGG

GCAATAAACTCCAGCTTACCTTATCAGAACATCCACCCTGTTACCATAGGCGAGTGCCCG

AAGTACGTTAGGTCAGCTAAGCTAAGAATGGTCACTGGTTTGAGGAATAACCCCAGCATT

CAGAGTAGGGGGCTGTTTGGGGCAATTGCAGGTTTTATCGAGGGCGGTTGGACTGGTATG

ATCGACGGCTGGTATGGATATCATCATCAGAATGAGCAGGGGTCTGGGTATGCTGCGGAC

CAGAAGTCCACGCAAAATGCCATAAACGGAATCACGAATAAGGTTAATACCGTCATCGAA

AAAATGAACATTCAGTTTACTGCGGTGGGTAAGGAATTCAATAAACTCGAAAAGAGAATG

GAGAACTTAAATAAGAAAGTCGACGACGGATTTTTGGATATCTGGACCTATAACGCCGAA

CTCCTCGTTCTGTTGGAGAACGAGCGCACCCTCGACTTCCACGATAGTAACGTGAAAAAT

CTGTATGAGAAGGTGAAGTCCCAGCTCAAGAACAATGCCAAGGAAATCGGAAACGGATGT

TTTGAGTTCTACCACAAGTGCGACAATGAATGCATGGAGAGTGTGCGCAATGGGACGTAC

GACTACCCTAAATATAGTGAAGAGTCTAAGCTCAACCGGGAGAAGGTGGACGGAGTGAAG

CTGGAGAGTATGGGAATTTACCAGATACTGGCTATCTACAGTACAGTTGCCAGCTCCCTC

GTTCTTCTGGTGTCTCTGGGGGCCATCTCTTTCTGGATGTGTTCCAATGGCAGCCTCCAA

TGCCGGATCTGCATT

488
ATGAAAGCAAATCTTCTGGTGTTACTATGCGCATTAGCTGCCGCTGACGCCGACACCATT

TGCATTGGCTATCACGCCAATAATAGCACTGACACTGTCGACACAGTTCTTGAAAAGAAC

GTGACTGTTACCCACTCCGTGAATCTACTCGAGGATTCTCATAACGGAAAGCTCTGTCGC

CTTAAGGGTATTGCCCCTCTCCAGCTTGGAAAATGCAACATTGCTGGCTGGCTGCTTGGA

AACCCTGAATGTGACCCACTCCTGCCCGTCCGGAGCTGGAGTTACATAGTGGAGACTCCA

AATAGCGAGAACGGTATATGTTACCCAGGTGATTTCATTGACTATGAGGAGTTGAGAGAG

CAGTTGAGCTCCGTTTCGTCTTTTGAAAGGTTCGAGATCTTCCCAAAAGAGTCAAGCTGG

CCTAACCATAACACCAATGGTGTTACGGCCGCATGTAGCCATGAGGGCAAGTCGTCCTTT

TATCGAAATCTCCTATGGCTCACAGAGAAGGAAGGATCTTACCCAAAGCTCAAGAACTCG

TACGTAAACAAGAAGGGGAAGGAAGTCCTTGTTCTGTGGGGTATACATCACCCACCAAAT

TCCAAGGAACAGCAGAATTTATATCAGAACGAAAACGCATATGTTTCTGTCGTTACATCC

AACTATAACCGGAGATTCACCCCAGAGATCGCCGAAAGACCGAAGGTGGGGGACCAGGCA

GGGCGAATGAACTATTACTGGACATTGCTCAAGCCCGGAGACACCATAATTTTCGAGGCT

AATGGCAACCTCATTGCCCCGATGTACGCATTCGCTCTTTCTCGGGGATTTGGCAGTGGG

ATTATCACCTCGAACGCCTCCATGCATGAATGTAATACTAAATGTCAAACACCACTGGGA

GCCATTAACAGTAGCCTGCCCTATCAAAATATCCACCCGGTCACTATTGGGGAGTGCCCA

AAGTATGTGCGGTCTGCAAAGTTGAGAATGGTTACCGGGCTGCGCAACAATCCAAGTATT

CAGAGTAGGGGGCTATTTGGTGCAATAGCAGGCTTTATCGAAGGGGGCTGGACTGGAATG

ATAGATGGCTGGTATGGATATCACCACCAGAACGAGCAGGGTAGCGGCTACGCCGCCGAT

CAGAAGAGCACTCAGAATGCTATCAACGGAATCACAAATAAAGTTAATACCGTAATAGAA

AAGATGAATATCCAGTTCACAGCTGTGGGTAAAGAGTTCAACAAGCTGGAAAAACGGATG

GAAAACCTGAATAAAAAGGTGGATGATGGTTTCCTCGATATATGGACTTATAACGCTGAG

CTTCTGGTTCTGCTGGAAAATGAACGCACACTGGACTTCCACGATAGTAATGTAAAAAAT

CTGTATGAAAAGGTTAAATCACAACTGAAAAATAATGCTAAGGAAATTGGGAACGGGTGT

TTCGAATTCTATCACAAGTGCGATAATGAGTGTATGGAGTCAGTTCGGAACGGGACCTAC

GATTATCCTAAGTATTCAGAAGAGTCTAAACTGAACCGCGAAAAAGTGGATGGAGTCAAA

CTGGAGTCGATGGGCATCTATCAGATCCTCGCCATTTATAGCACCGTGGCATCGTCCCTG

GTGCTTTTGGTTAGCCTGGGCGCCATTAGTTTCTGGATGTGTAGTAACGGGTCTCTGCAG

TGTAGGATTTGTATT

489
ATGAAGGCAAATCTGCTCGTGTTACTCTGCGCTTTGGCCGCCGCTGACGCCGACACTATT

TGCATCGGTTACCACGCCAACAACAGCACCGATACAGTGGACACGGTATTGGAAAAAAAC

GTAACTGTGACACATTCAGTAAACCTGCTCGAGGACAGCCACAACGGTAAGCTGTGCCGG

TTGAAAGGTATCGCACCACTGCAGCTTGGAAAATGTAATATCGCCGGGTGGCTGCTGGGC

AATCCTGAGTGTGATCCTCTGCTCCCTGTACGGAGTTGGTCGTATATTGTGGAAACCCCT

AACAGCGAAAACGGGATTTGTTATCCTGGCGACTTTATCGACTATGAGGAGCTCCGGGAG

CAGCTGTCCAGCGTAAGTTCATTCGAGAGGTTCGAGATTTTCCCCAAAGAGAGTTCCTGG

CCTAACCACAACACAAACGGTGTGACAGCTGCCTGCAGCCACGAGGGGAAGTCCTCATTC

TATAGGAATTTGCTCTGGCTGACCGAAAAGGAAGGTTCGTACCCGAAGCTTAAAAATTCT

TACGTTAACAAAAAGGGGAAGGAGGTACTCGTTCTGTGGGGGATCCATCATCCCCCAAAT

TCTAAGGAACAGCAGAACCTATACCAGAATGAAAACGCATATGTCAGCGTGGTCACATCT

AACTACAACAGACGCTTCACACCCGAAATCGCTGAGCGCCCCAAGGTACGAGATCAGGCT

GGCAGGATGAACTACTATTGGACTTTACTGAAGCCGGGCGATACAATAATTTTCGAGGCT

AACGGAAATCTGATCGCCCCAATGTATGCCTTTGCTCTTTCCCGCGGCTTTGGTTCAGGG

ATTATTACTTCTAACGCTTCGATGCACGAGTGTAATACCAAATGCCAGACCCCGCTGGGC

GCCATTAATAGCTCATTGCCTTATCAGAATATCCATCCCGTTACCATTGGCGAATGTCCC

AAGTATGTGAGGAGCGCAAAACTTCGGATGGTAACAGGTCTAAGGAATAACCCTAGCATT

CAGTCACGGGGGCTGTTTGGGGCAATAGCAGGCTTTATTGAGGGCGGATGGACAGGCATG

ATCGATGGCTGGTATGGTTACCACCATCAGAACGAGCAGGGCTCTGGATATGCAGCCGAC

CAGAAGAGTACACAAAATGCAATCAATGGCATTACTAACAAAGTGAACACGGTCATTGAA

AAAATGAATATCCAGTTCACAGCCGTGGGAAAGGAGTTTAACAAGCTGGAAAAACGGATG

GAAAATCTAAATAAGAAAGTCGACGACGGTTTTTTGGATATCTGGACCTACAACGCTGAA

CTACTGGTTCTTCTGGAGAACGAAAGAACCCTGGACTTTCACGACTCTAATGTGAAGAAT

CTGTACGAAAAAGTGAAGTCTCAGTTGAAGAACAACGCTAAAGAGATTGGGAATGGCTGT

TTCGAATTCTACCACAAATGCGATAATGAGTGCATGGAGTCTGTCAGGAATGGTACTTAC

GACTATCCCAAGTATTCTGAGGAGAGTAAGCTCAACAGGGAAAAAGTCGACGGAGTCAAA

CTGGAGTCGATGGGCATATACCAGATTCTAGCCATCTACTCCACCGTGGCCAGTAGTTTA

GTCTTGCTCGTAAGCCTTGGCGCTATCTCCTTCTGGATGTGCTCCAATGGATCCCTGCAG

TGTAGAATCTGTATC

490
ATGAAGGCGAATCTACTGGTTTTATTGTGCGCCCTCGCTGCTGCCGACGCCGATACCATC

TGCATCGGATACCATGCCAATAACTCCACAGATACCGTGGACACTGTGCTGGAAAAGAAT

GTTACAGTGACACATTCAGTGAACCTGCTGGAAGATAGTCATAATGGCAAACTGTGTAGA

CTAAAGGGCATCGCCCCCCTGCAACTTGGTAAGTGTAACATCGCTGGTTGGCTTCTGGGG

AACCCCGAATGCGATCCACTGCTGCCTGTCCGCAGTTGGTCCTATATTGTCGAAACCCCC

AACTCTGAAAACGGGATTTGTTATCCAGGAGACTTCATTGACTATGAAGAATTGCGGGAA

CAGCTTTCAAGTGTGAGCTCTTTCGAACGGTTTGAAATCTTTCCGAAGGAGTCCTCGTGG

CCAAATCATAACACTAATGGCGTGACAGCGGCATGTAGTCACGAAGGAAAATCTTCCTTT

TATAGAAACCTCCTGTGGCTGACAGAGAAGGAAGGCAGTTATCCCAAACTGAAGAACAGT

TACGTCAATAAAAAGGGGAAAGAAGTACTGGTACTTTGGGGAATCCACCATCCCCCCAAC

AGCAAGGAGCAGCAGAATCTTTATCAAAATGAGAACGCCTACGTCAGCGTGGTGACCTCG

AATTACAACAGGCGGTTCACACCAGAAATCGCGGAAAGGCCGAAGGTGGGGGATCAGGCC

GGCAGGATGAACTACTATTGGACTCTCCTAAAACCAGGCGACACTATTATATTTGAAGCC

AACGGCAACCTTATCGCTCCAATGTACGCCTTCGCTTTGAGCCGTGGGTTTGGCTCCGGA

ATTATAACATCAAATGCAAGTATGCACGAGTGCAACACAAAGTGCCAGACACCACTCGGA

GCAATCAACAGCTCCTTGCCATACCAAAACATTCATCCTGTTACCATCGGCGAATGCCCG

AAGTATGTGAGGAGCGCAAAACTGAGGATGGTGACGGGCTTGCGGAACAACCCTTCTATC

CAGTCCCGGGGCCTGTTTGGAGCGATCGCAGGATTCATTGAAGGGGGATGGACGGGGATG

ATCGATGGATGGTACGGATATCATCACCAAAATGAACAAGGGTCAGGTTATGCTGCTGAT

CAAAAGTCAACACAGAATGCAATCAACGGCATAACCAATAAAGTTAACACAGTGATTGAA

AAAATGAATATTCAGTTTACCGCCGTGGGAAAAGAGTTCAATAAACTGGAGAAGAGGATG

GAGAATTTGAACAAGAAGGTAGATGACGGCTTTCTCGACATTTGGACTTATAATGCAGAG

CTATTAGTGCTCCTCGAGAATGAGAGAACTCTTGACTTTCACGACAGTAACGTAAAAAAC

CTCTATGAAAAGGTCAAATCACAGCTTAAGAATAATGCAAAAGAGATCGGAAACGGATGC

TTCGAATTTTACCACAAATGCGACAACGAATGTATGGAATCCGTGAGGAACGGTACCTAC

GATTACCCCAAGTACAGCGAGGAAAGCAAGCTGAATCGAGAAAAAGTTGACGGTGTGAAG

CTGGAGTCCATGGGCATCTACCAGATTCTTGCTATCTATTCTACAGTAGCTTCCTCCCTT

GTACTTCTGGTGTCCCTGGGTGCCATTTCATTCTGGATGTGCAGCAACGGTTCCTTGCAG

TGTCGGATCTGCATA

491
ATGAAAGCTAATCTTCTCGTGTTGCTGTGCGCCTTAGCGGCCGCAGACGCGGACACAATC

TGTATTGGGTACCATGCCAATAATTCCACTGACACCGTAGACACTGTACTGGAAAAGAAT

GTGACGGTAACCCACTCCGTTAATCTGCTGGAGGACTCTCACAACGGCAAACTCTGTCGG

CTGAAAGGTATTGCACCACTTCAGCTGGGGAAGTGTAACATTGCCGGATGGCTACTAGGC

AACCCTGAATGTGACCCCCTGCTGCCAGTGCGAAGCTGGAGTTACATTGTGGAAACTCCC

AATAGTGAAAACGGTATCTGCTACCCTGGCGATTTCATTGATTATGAAGAGCTGAGGGAA

CAGCTTTCTAGTGTGTCGTCCTTCGAGAGGTTTGAGATCTTCCCCAAGGAGAGCTCATGG

CCAAACCACAATACAAACGGGGTCACTGCGGCATGTAGCCATGAGGGCAAGTCATCCTTC

TATCGAAACCTCCTGTGGCTGACCGAAAAGGAAGGTAGCTACCCCAAACTTAAAAACAGT

TATGTGAACAAAAAGGGCAAGGAAGTCTTAGTGCTTTGGGGCATCCACCACCCCCCAAAT

AGCAAAGAGCAACAGAATTTGTACCAGAACGAAAATGCTTATGTGTCTGTAGTAACCTCT

AACTATAACAGGCGTTTCACTCCCGAGATTGCCGAGCGACCGAAAGTTAGAGACCAGGCC

GGACGCATGAATTACTACTGGACCCTGTTGAAACCTGGAGATACGATAATCTTTGAGGCC

AACGGAAACCTGATAGCTCCTATGTATGCGTTCGCACTCAGTCGCGGGTTCGGGTCCGGG

ATAATCACCAGTAACGCGTCCATGCACGAGTGTAATACGAAGTGCCAGACCCCACTAGGA

GCGATTAACTCGTCTCTGCCATATCAGAATATCCATCCTGTGACAATCGGAGAGTGTCCT

AAATACGTCCGCTCAGCCAAACTGCGAATGGTGACGGGCCTTCGCAACAATCCCAGTATC

CAGTCTCGGGGACTCTTTGGAGCCATCGCCGGTTTTATCGAAGGCGGATGGACTGGGATG

ATCGATGGCTGGTACGGCTACCACCACCAAAATGAGCAAGGCTCCGGGTACGCTGCCGAC

CAGAAGTCAACTCAGAATGCAATTAACGGGATCACCAACAAGGTTAACACCGTAATCGAA

AAGATGAACATCCAGTTCACGGCCGTGGGGAAGGAGTTTAATAAACTTGAGAAACGGATG

GAGAACCTCAACAAAAAGGTGGACGACGGCTTTCTGGACATCTGGACCTATAATGCTGAG

CTTTTGGTGCTGCTGGAAAACGAGCGCACACTGGATTTCCACGATAGTAATGTGAAGAAC

CTGTACGAAAAGGTTAAGTCCCAACTCAAAAATAACGCGAAAGAAATCGGCAATGGGTGC

TTTGAATTTTATCACAAGTGTGACAACGAATGCATGGAATCTGTGCGGAATGGGACCTAC

GATTACCCAAAATATAGCGAAGAATCCAAGCTGAACAGAGAGAAGGTGGACGGCGTGAAA

CTCGAAAGTATGGGTATCTACCAAATCCTAGCCATCTACTCTACCGTTGCCAGTAGTCTA

GTGTTGCTGGTGTCGTTAGGTGCCATCTCTTTTTGGATGTGTAGCAATGGCTCTCTGCAA

TGTCGGATCTGTATC

492
ATGAAGGCCAACCTGCTTGTGCTGCTTTGCGCACTAGCCGCTGCAGACGCCGACACAATT

TGTATTGGATACCATGCTAATAACTCGACCGACACAGTTGACACAGTCCTTGAGAAGAAC

GTGACAGTTACTCACTCCGTGAACCTGCTCGAGGACTCGCATAATGGCAAACTCTGCCGT

CTGAAGGGTATCGCCCCCCTCCAACTGGGGAAATGCAATATAGCCGGCTGGCTGCTGGGA

AATCCAGAGTGCGATCCACTGTTGCCTGTGCGCAGTTGGAGTTATATCGTGGAGACACCC

AACTCAGAGAACGGTATCTGCTACCCTGGGGACTTCATAGATTATGAAGAGCTGCGCGAG

CAGCTATCTTCCGTTAGCTCTTTCGAACGCTTTGAAATCTTTCCTAAAGAAAGCAGCTGG

CCAAATCATAACACAAACGGAGTGACAGCTGCCTGCAGTCACGAGGGTAAAAGTTCTTTT

TATAGAAATCTCCTGTGGTTGACGGAGAAAGAGGGCAGCTATCCAAAGCTCAAGAATAGC

TACGTCAATAAAAAAGGTAAGGAGGTGCTAGTCTTATGGGGAATCCATCACCCACCCAAT

TCCAAGGAACAGCAGAACCTCTATCAGAACGAGAACGCCTATGTGTCCGTAGTGACTAGC

AACTATAATCGTAGATTCACACCTGAGATTGCAGAGAGACCCAAGGTTAGAGACCAAGCC

GGCCGCATGAATTATTACTGGACACTGCTTAAACCCGGGGATACTATCATCTTCGAAGCG

AATGGAAACCTGATCGCTCCAATGTATGCTTTTGCTCTGTCCAGGGGTTTTGGCTCGGGG

ATTATCACAAGCAACGCATCTATGCACGAGTGTAATACCAAGTGTCAGACCCCCCTTGGC

GCTATCAACTCTAGTCTACCGTACCAGAACATCCACCCTGTTACCATTGGTGAATGCCCG

AAATACGTGCGGAGTGCCAAGCTGAGAATGGTGACCGGCCTGAGGAACAATCCTTCCATC

CAGTCCCGGGGACTTTTCGGAGCTATCGCTGGCTTCATTGAAGGTGGGTGGACCGGCATG

ATCGACGGGTGGTATGGATATCACCATCAGAACGAGCAAGGAAGCGGGTATGCTGCAGAC

CAGAAGTCCACACAGAACGCAATAAACGGCATCACTAACAAAGTGAACACCGTGATTGAA

AAAATGAATATACAGTTTACCGCCGTAGGGAAGGAATTTAATAAACTGGAAAAGCGCATG

GAAAATTTGAACAAAAAAGTCGACGATGGTTTTTTAGACATTTGGACCTATAATGCGGAA

CTGCTAGTACTGCTCGAGAACGAACGGACCCTCGACTTTCACGATTCAAACGTCAAAAAT

CTATACGAGAAGGTGAAGTCGCAGCTGAAGAATAATGCCAAAGAAATCGGCAACGGATGT

TTCGAATTCTACCACAAATGCGACAATGAATGTATGGAATCTGTTAGAAACGGCACGTAT

GATTACCCCAAGTACAGCGAAGAATCTAAACTCAACCGGGAGAAAGTCGACGGAGTTAAG

CTTGAGTCCATGGGAATCTATCAGATCTTGGCGATCTATTCCACCGTGGCAAGTTCCCTC

GTATTGCTGGTGTCCCTTGGAGCAATTTCATTCTGGATGTGCAGTAACGGCAGCCTTCAA

TGCCGCATCTGTATA

493
ATGAAGGCAAACCTTCTTGTCCTGCTGTGCGCACTCGCCGCAGCCGACGCCGACACAATC

TGCATTGGGTATCACGCTAATAATTCAACTGACACTGTGGATACCGTACTGGAAAAGAAT

GTTACTGTGACTCATAGTGTAAATCTGCTCGAGGACAGTCACAATGGAAAACTTTGCCGG

TTAAAGGGCATCGCACCCCTGCAGCTGGGTAAGTGCAACATCGCGGGATGGCTGCTGGGC

AACCCCGAGTGTGATCCCCTGCTTCCAGTGCGGTCTTGGTCTTACATTGTCGAAACACCC

AACTCTGAAAACGGAATTTGTTACCCTGGCGACTTCATCGACTACGAAGAGCTTAGAGAG

CAGCTATCGAGCGTGAGTTCTTTTGAAAGATTTGAGATCTTCCCAAAGGAAAGCTCTTGG

CCCAACCATAATACTAATGGCGTCACAGCCGCCTGCTCACATGAAGGGAAGTCTTCTTTC

TACAGGAATCTGTTGTGGTTGACGGAGAAGGAGGGAAGTTATCCAAAGCTTAAAAATTCC

TACGTGAACAAGAAGGGTAAAGAGGTCCTGGTGCTCTGGGGCATCCACCATCCTCCGAAC

TCCAAAGAACAGCAGAATCTGTATCAGAACGAAAATGCATATGTCAGTGTGGTGACAAGT

AATTATAACCGCCGCTTTACCCCCGAGATCGCCGAACGCCCGAAGGTACGGGACCAAGCG

GGTCGGATGAACTACTATTGGACCCTGCTAAAGCCTGGGGACACTATCATCTTCGAGGCC

AACGGTAACCTGATCGCTCCCATGTATGCGTTTGCCCTGAGCAGAGGATTCGGCTCTGGA

ATCATAACGAGCAACGCCTCAATGCATGAATGCAACACTAAGTGTCAAACTCCCTTGGGC

GCAATAAACTCATCCTTGCCATATCAGAACATCCACCCAGTCACCATCGGGGAGTGCCCT

AAATATGTGCGTTCAGCCAAGTTACGCATGGTAACGGGACTCCGGAATAACCCCAGCATT

CAATCTCGAGGGCTTTTTGGAGCTATCGCAGGATTCATTGAAGGGGGCTGGACTGGGATG

ATCGATGGATGGTATGGGTACCATCATCAGAACGAGCAGGGCTCCGGCTACGCAGCCGAT

CAGAAGAGCACTCAGAACGCCATCAATGGCATCACAAACAAAGTCAACACTGTGATTGAA

AAAATGAATATACAGTTTACCGCAGTGGGTAAGGAATTCAACAAGCTGGAGAAACGGATG

GAAAATCTAAACAAGAAAGTGGATGATGGCTTTCTCGACATCTGGACCTACAACGCCGAA

CTGCTGGTCCTGCTGGAAAATGAGCGCACACTGGATTTCCACGACTCGAACGTCAAGAAT

CTATACGAGAAAGTGAAATCCCAGCTCAAGAATAATGCCAAGGAGATCGGCAACGGATGC

TTCGAATTTTACCATAAATGCGACAACGAGTGTATGGAGTCCGTCCGAAACGGGACATAC

GACTATCCCAAGTATTCAGAAGAGTCAAAGCTTAACCGCGAAAAGGTGGATGGCGTTAAG

CTGGAATCTATGGGTATTTACCAGATACTGGCCATTTATAGCACTGTGGCTAGCTCATTA

GTGCTGCTGGTGTCGCTGGGAGCGATTTCCTTTTGGATGTGTAGCAACGGGAGTTTACAG

TGCCGGATTTGCATC

494
ATGAAGGCTAACCTCCTGGTGCTGCTGTGTGCCCTGGCTGCAGCGGACGCCGACACGATC

TGTATCGGATACCATGCTAATAATTCTACCGACACTGTAGACACCGTGCTGGAAAAGAAT

GTTACAGTGACCCATAGTGTTAATCTCCTCGAAGATTCACACAACGGCAAGCTCTGCCGT

CTCAAAGGAATAGCACCTCTTCAGCTGGGCAAGTGTAACATCGCCGGGTGGCTTCTGGGC

AACCCCGAATGTGATCCCCTTCTGCCAGTCCGCTCATGGTCCTATATTGTGGAAACCCCT

AATTCCGAGAACGGAATTTGTTATCCCGGAGACTTTATTGATTATGAGGAACTTAGAGAA

CAACTGTCTTCGGTCTCGTCCTTTGAGAGGTTCGAGATTTTCCCTAAGGAGAGCTCCTGG

CCCAATCACAACACTAACGGTGTGACCGCCGCCTGCTCGCATGAGGGGAAGTCCTCTTTC

TACCGCAACCTCCTGTGGCTGACAGAGAAGGAGGGGTCCTATCCCAAACTAAAAAACTCA

TACGTGAACAAAAAGGGAAAAGAGGTCTTGGTTCTCTGGGGCATCCATCACCCACCAAAC

AGTAAGGAGCAGCAAAATCTGTACCAGAATGAAAACGCATATGTTAGCGTAGTGACCTCT

AACTATAACAGGCGGTTTACTCCAGAGATTGCCGAGCGGCCCAAAGTGCGAGACCAGGCA

GGAAGGATGAACTATTATTGGACTTTGTTAAAACCCGGAGACACAATTATCTTCGAGGCA

AACGGGAACTTGATCGCACCCATGTACGCCTTCGCACTGAGCAGGGGTTTCGGCTCCGGC

ATCATCACTTCTAATGCCTCTATGCACGAGTGTAATACGAAGTGTCAGACCCCATTGGGA

GCCATCAACTCCAGTCTGCCCTATCAGAACATCCATCCGGTGACTATAGGCGAATGCCCC

AAGTACGTCAGGTCCGCTAAGCTCCGCATGGTCACCGGACTTAGGAACAACCCGAGTATT

CAGAGCCGAGGCCTGTTCGGAGCCATCGCAGGGTTCATAGAGGGAGGGTGGACCGGGATG

ATAGATGGATGGTATGGCTACCATCATCAAAACGAACAGGGCAGCGGATATGCAGCTGAT

CAGAAGTCCACCCAGAACGCCATAAACGGAATCACCAACAAAGTGAACACCGTCATAGAA

AAAATGAACATACAGTTCACCGCCGTGGGCAAAGAATTCAATAAACTTGAAAAACGGATG

GAAAATTTGAATAAGAAGGTGGATGACGGCTTCCTGGATATCTGGACTTACAATGCGGAG

CTGCTCGTGCTTCTGGAGAACGAGAGAACGCTCGACTTCCACGATTCTAACGTTAAGAAC

CTGTATGAGAAAGTTAAAAGTCAGCTCAAAAATAACGCGAAGGAAATCGGGAACGGCTGC

TTTGAATTTTACCATAAATGCGATAATGAGTGCATGGAATCCGTGCGAAACGGCACGTAC

GACTATCCAAAGTATTCAGAGGAATCAAAATTGAACAGAGAAAAGGTCGATGGTGTGAAA

CTGGAGAGTATGGGGATATATCAAATCCTTGCGATCTACTCTACTGTGGCTTCTTCCCTG

GTCCTGCTGGTGTCCTTGGGGGCAATTTCATTTTGGATGTGTTCTAATGGGAGTTTACAG

TGCAGGATCTGCATA

495
ATGAAAGCCAATCTTCTGGTTCTGCTCTGCGCTCTAGCTGCTGCCGATGCTGACACTATT

TGTATAGGCTACCACGCAAATAATTCGACGGATACTGTCGACACGGTCCTGGAAAAAAAT

GTCACAGTGACTCATTCAGTTAATCTCTTGGAGGATTCTCACAATGGAAAGTTGTGTAGA

CTGAAGGGCATTGCTCCATTGCAGCTTGGGAAGTGTAATATCGCGGGCTGGTTACTGGGC

AACCCTGAATGCGACCCCCTCTTGCCTGTCCGGTCCTGGTCTTATATCGTGGAGACACCA

AATTCTGAGAATGGAATCTGCTATCCGGGTGACTTTATCGATTACGAGGAGCTTCGGGAG

CAGCTGTCTTCAGTGTCCAGTTTTGAAAGATTTGAGATATTTCCTAAGGAGAGCTCCTGG

CCAAATCATAATACCAATGGCGTGACAGCCGCATGTTCACACGAAGGAAAAAGCTCCTTC

TATCGGAACCTGCTCTGGCTTACAGAAAAGGAAGGCTCTTACCCCAAACTCAAGAACAGT

TACGTGAATAAGAAAGGTAAAGAGGTTCTAGTACTCTGGGGCATCCACCACCCGCCAAAC

AGCAAGGAGCAACAGAACCTCTATCAGAACGAGAATGCCTACGTGTCCGTGGTCACATCA

AACTATAACCGCAGGTTTACACCAGAAATTGCAGAGCGGCCTAAAGTCCGTGATCAGGCA

GGCAGGATGAACTATTACTGGACTTTGCTGAAGCCGGGAGACACCATTATCTTCGAGGCG

AATGGGAACCTCATTGCCCCAATGTACGCCTTCGCGCTCTCTCGCGGCTTTGGCTCAGGA

ATTATCACGTCAAATGCTTCTATGCACGAGTGTAATACAAAATGTCAGACCCCTCTGGGC

GCCATAAACTCTTCCCTGCCTTATCAAAATATTCACCCAGTGACTATTGGGGAGTGCCCC

AAATACGTTAGAAGCGCTAAACTGCGTATGGTAACGGGTTTGCGGAACAACCCAAGTATC

CAGAGCCGCGGCCTGTTTGGCGCCATTGCTGGTTTTATTGAGGGGGGTTGGACAGGAATG

ATCGATGGATGGTACGGCTACCACCATCAGAATGAACAGGGGAGTGGGTACGCCGCCGAC

CAAAAGTCCACACAGAATGCGATCAACGGGATCACTAACAAGGTGAACACCGTGATTGAG

AAGATGAACATACAGTTTACCGCAGTCGGAAAGGAATTCAACAAACTTGAAAAACGCATG

GAGAATCTGAATAAAAAAGTGGACGACGGATTTTTAGATATATGGACCTATAATGCCGAA

TTGCTGGTGCTCTTAGAAAACGAACGAACGCTGGACTTCCACGATTCTAACGTTAAAAAC

CTTTATGAGAAGGTTAAGAGCCAGTTGAAGAACAACGCGAAGGAAATCGGAAACGGATGC

TTCGAATTTTACCACAAGTGTGACAACGAGTGTATGGAATCTGTTAGAAATGGCACCTAC

GATTATCCAAAGTACTCAGAAGAAAGCAAACTTAACAGGGAAAAGGTGGATGGTGTGAAA

CTGGAGTCCATGGGTATCTACCAGATACTTGCAATCTACTCTACGGTTGCTTCAAGCTTG

GTGCTGCTTGTGAGCTTGGGAGCCATCTCATTTTGGATGTGTTCAAATGGCAGCTTACAG

TGTAGGATCTGCATA

TABLE 17

Codon Optimized Sequences Encoding H7 Hemagglutinin

SEQ

ID

NO.
Nucleic Acid Sequence

496
ATGAATACACAGATCCTTGTATTTGCCCTGATCGCAATCATTCCTACTAATGCTGACAAG

ATTTGCCTCGGCCACCATGCGGTTAGTAATGGGACCAAAGTGAACACACTGACGGAGAGA

GGAGTAGAGGTAGTTAACGCCACCGAGACTGTGGAGAGAACTAACATCCCACGGATTTGT

TCCAAGGGTAAACGTACTGTGGATCTGGGGCAGTGCGGCTTGTTGGGTACCATCACTGGA

CCGCCACAGTGCGACCAGTTTCTGGAGTTTTCCGCCGACCTGATTATAGAACGCCGAGAA

GGCAGCGATGTCTGTTACCCCGGTAAATTCGTGAATGAAGAAGCCCTCCGCCAAATCCTG

CGTGAGAGTGGGGGCATTGACAAAGAGGCGATGGGCTTTACATACAGCGGGATACGCACC

AACGGCGCGACGTCAGCCTGCCGCAGGAGTGGAAGTTCTTTCTATGCCGAGATGAAGTGG

CTGTTGTCTAATACTGATAATGCAGCCTTCCCCCAGATGACAAAGTCGTACAAGAACACC

AGAAAGTCACCCGCACTCATTGTGTGGGGTATTCACCATTCTGTCTCTACTGCTGAGCAG

ACGAAACTGTATGGTTCTGGGAACAAGCTCGTGACCGTGGGGTCCAGCAACTATCAGCAG

AGCTTTGTGCCCTCCCCAGGAGAGAGGCCACAGGTGAATGGGTTGTCAGGCCGTATCGAT

TTCCACTGGCTTATGTTGAATCCAAACGACACAGTGACATTTTCTTTCAACGGCGCCTTC

ATTGCACCAGACAGAGCTAGCTTTCTGCGAGGGAAGAGTATGGGTATCCAGTCTGGTGTG

CAGGTCGACGCTAACTGTGAGGGGGATTGCTACCATAGCGGGGGAACAATTATTTCAAAC

CTGCCCTTCCAGAATATTGACAGCAGGGCAGTGGGAAAGTGCCCCCGCTATGTGAAACAG

AGATCTTTGTTGCTGGCCACCGGCATGAAGAACGTTCCCGAAATTCCTAAGGGCCGGGGG

CTTTTTGGGGCGATAGCCGGGTTCATTGAAAACGGGGTGGAGGGGCTAATCGATGGTTGG

TACGGTTTTAGGCATCAAAACGCCCAGGGCGAAGGCACTGCGGCCGACTACAAATCCACA

CAGAGCGCCATCGACCAAATCACTGGGAAACTTAACCGACTTATTGAGAAAACAAATCAA

CAGTTTGAGCTGATTGATAACGAATTTAATGAGGTAGAGAAGCAGATCGGCAATGTAATA

AACTGGACAAGGGACAGCATTACTGAAGTCTGGAGCTACAACGCCGAGTTGCTCGTCGCG

ATGGAGAATCAGCATACCATCGATTTAGCCGACTCAGAGATGGATAAGCTGTATGAACGC

GTAAAGAGGCAGCTGCGCGAGAACGCTGAAGAGGACGGGACTGGCTGCTTCGAAATTTTC

CACAAATGCGATGATGATTGTATGGCTTCCATCCGGAACAATACCTACGACCATTCTAAG

TACCGTGAAGAGGCCATGCAGAATAGGATCCAGATTGACCCAGTGAAGCTGAGCTCGGGT

TATAAAGACGTGATTTTGTGGTTCAGTTTTGGCGCCTCTTGTTTTATCCTTCTGGCAATT

GTTATGGGGTTGGTTTTCATCTGCGTCAAGAACGGCAACATGCGCTGTACTATTTGTATC

497
ATGAATACCCAGATTCTCGTCTTCGCACTGATAGCTATAATTCCAACCAATGCCGACAAG

ATATGCTTGGGACACCATGCGGTGTCTAACGGCACAAAGGTGAATACTCTGACAGAGAGA

GGAGTGGAGGTGGTTAACGCTACAGAGACTGTGGAAAGGACGAATATACCAAGGATATGC

TCCAAGGGCAAGAAGACCGTCGACCTCGGCCAGTGTGGCCTGCTTGGCACTATCACAGGT

CCCCCTCAATGCGATCAATTTCTGGAATTCTCTGCTGATCTGATAATCGAGCGCCGCGAG

GGGTCTGACGTATGCTATCCCGGGAAATTCGTGAATGAGGAGGCTCTGAGACAGATATTG

CGGGAGTCGGGGGGCATCGATAAAGAAGCTATGGGATTCACTTACTCGGGGATCAGAACA

AACGGAGCTACATCTGCGTGTCGGCGGTCTGGCAGCTCGTTTTATGCCGAGATGAAGTGG

CTGCTCTCCAATACAGACAATGCCGCATTCCCACAAATGACGAAAAGCTATAAAAATACT

CGCAAGTCACCCGCACTAATCGTGTGGGGCATCCACCACAGCGTGTCCACCGCAGAGCAG

ACCAAATTGTATGGTAGCGGCAATAAGCTGGTTACAGTGGGATCCTCCAACTACCAACAG

TCCTTCGTCCCAAGCCCAGGGGCCCGACCGCAAGTTAACGGTCAGTCCGGACGCATTGAT

TTTCACTGGCTGATGCTTAACCCAAACGACACAGTTACCTTTTCGTTTAACGGCGCTTTC

ATTGCCCCAGATCGGGCCTCTTTTCTGCGGGGTAAGAGCATGGGAATCCAGTCGGGGGTA

CAGGTCGACGCGAATTGTGAAGGCGATTGTTACCATTCTGGGGGCACTATTATATCAAAT

CTTCCATTCCAGAATATTGACTCGCGCGCTGTGGGCAAATGCCCCAGGTACGTTAAGCAG

CGATCACTGCTCCTCGCCACAGGTATGAAAAATGTTCCAGAGATTCCCAAGGGCAGGGGG

CTGTTCGGTGCAATCGCCGGCTTTATAGAAAATGGGTGGGAGGGACTCATCGATGGTTGG

TACGGTTTTAGGCATCAAAACGCCCAGGGGGAGGGGACGGCTGCCGATTACAAGTCTACC

CAGTCAGCTATAGACCAGATCACTGGGAAACTAAACAGGCTGATCGAGAAAACCAACCAG

CAGTTCGAACTGATTGACAACGAGTTCAACGAGGTTGAAAAGCAGATTGGTAACGTGATT

AACTGGACCAGAGACTCTATCACCGAGGTCTGGAGCTACAATGCAGAACTACTTGTGGCT

ATGGAAAACCAGCATACAATTGATCTTGCTGACTCTGAGATGGACAAGCTTTATGAGAGG

GTGAAGAGACAGCTTCGGGAGAACGCTGAGGAGGATGGAACCGGTTGTTTCGAGATCTTT

CACAAATGCGATGACGATTGCATGGCTAGCATTAGGAATAACACCTATGACCACTCTAAA

TACAGAGAGGAGGCTATGCAGAATCGCATCCAGATCGACCCAGTGAAGCTGTCCTCTGGA

TACAAGGACGTAATCCTGTGGTTCTCATTTGGGGCTTCGTGCTTCATCTTGCTGGCGATT

GTTATGGGCTTAGTGTTTATCTGCGTTAAAAACGGGAACATGCGGTGTACAATCTGTATC

498
ATGAACACACAGATTCTGGTCTTTGCCTTGATCGCAATAATTCCAACTAATGCCGACAAA

ATTTGTTTAGGTCATCACGCCGTTTCAAATGGAACTAAGGTCAACACCCTGACCGAGAGG

GGCGTCGAGGTCGTGAATGCCACAGAAACTGTGGAGAGAACCAACATCCCTCGCATCTGT

AGCAAGGGCAAGAAGACTGTCGATCTTGGACAGTGCGGTCTCCTGGGAACGATTACAGGC

CCCCCACAGTGCGACCAATTCCTAGAATTCTCTGCCGACTTAATCATCGAAAGGCGTGAG

GGATCTGACGTGTGCTATCCGGGAAAGTTCGTGAATGAGGAGGCCCTACGGCAGATTCTG

CGGAAATCCGGAGGTATAGACAAAGAGGCAATGGGCTTCACCTACAGTGGGATACGCACA

AATGGGGCCACATCCACTTGTCGGAGAAGCGGCTCTTCCTTTTATGCCGAGATGAAGTGG

CTCTTATCCAACACAGACAATGCCGCCTTCCCTCAGATGACGAAGAGCTACAAAAACACC

AGGAAGTCTCCAGCAATCATTGTTTGGGGCATCCACCATAGCGTCTCCACCGCTGAGCAA

ACCAAATTATATGGGTCCGGGAATAAATTGGTCACAGTCGGTAGCTCCAACTACCAGCAG

TCATTTGTCCCCTCACCGGGGGCTCGCCCACAAGTAAATGGTTTGTCTGGCAGAATCGAC

TTTCATTGGCTCATGCTCAATCCAAACGACACGGTGACTTTCAGCTTTAACGGGGCATTT

ATTGCCCCCGACCGAGCATGTTTTCTTAGAGGCAAAAGCATGGGGATTCAGAGCGGAGTC

CAGGTCGACGCGGATTGCGAGGGTGACTGCTACCACTCAGGGGGTACCATTATCTCCAAC

CTTCCTTTTCAGAATATCGATTCGAGAGCTGTGGGCAAGTGCCCTCGGTATGTTAAACAG

CGATCCCTCCTTCTGGCCACTGGTATGAAGAACGTGCCTGAGATACCCAAAGGGAGGGGC

CTGTTTGGGGCTATCGCTGGATTTATTGAGAATGGTTGGGAGGGCCTTATCGACGGCTGG

TACGGCTTTAGGCACCAGAACGCGCAGGGCGAAGGCACAGCTGCCGACTACAAAAGCACC

CAGAGCGCGATTGACCAGATCACCGGCAAATTGAACAGGCTTATCGAAAAAACGAACCAA

CAGTTTGAGCTAATTGACAATGAGTTTAACGAGGTCGAGAGGCAGATTGGGAACGTCATC

AACTGGACAAGAGACAGCATTACCGAGGTGTGGTCTTACAATGCAGAGTTGCTAGTGGCC

ATGGAAAACCAACATACGATCGACCTCGCGGATTCTGAGATGGATAAGCTCTATGAAAGG

GTGAAAAGGCAGCTGCGGGAAAATGCTGAGGAAGACGGAACAGGATGTTTTGAAATCTTC

CACAAATGTGATGATGACTGTATGGCCTCTATAAGGAACAACACCTATGATCATTCCAAG

TATCGAGAAGAGGCCATGCAGAACCGTATCCAGATTGACCCTGTAAAACTCAGTTCAGGG

TACAAGGATGTGATCCTGTGGTTCAGCTTTGGCGCAAGCTGTTTCATTCTTCTCGCGATT

GTGATGGGGCTAGTGTTCATTTGTGTGAAAAATGGAAATATGAGATGTACCATTTGTATC

499
ATGAACACCCAGATTCTGGTCTTCGCTCTGATTGCTATTATCCCAACCAATGCAGACAAG

ATCTGTCTGGGGCACCATGCTGTGTCGAACGGCACGAAAGTGAACACACTGACCGAAAGA

GGAGTCGAGGTGGTGAACGCGACCGAGACAGTGGAGCGGACAAACATCCCACGTATCTGC

TCCAAGGGCAAGCGTACAGTGGACTTGGGGCAATGTGGCCTCCTTGGAACGATCACAGGA

CCACCGCAGTGCGACCAGTTTCTGGAGTTTTCTGCCGATTTAATCATCGAAAGGCGGGAG

GGTTCCGACGTTTGTTACCCGGGGAAGTTCGTTAACGAGGAAGCCCTGAGACAGATCCTA

CGTGAGAGCGGCGGTATCGACAAGGAGGCTATGGGCTTTACATATAGCGGAATTAGAACA

AACGGCGCTACCAGCGCCTGCCGCCGCAGCGGTTCATCTTTTTATGCCGAAATGAAGTGG

CTGCTCTCCAACACCGACAACGCCGCTTTTCCACAGATGACGAAATCCTATAAGAATACC

AGGAAAAGTCCAGCTCTGATTGTGTGGGGGATACACCACTCTGTGTCAACAGCGGAACAG

ACAAAGCTCTATGGAAGCGGAAACAAACTCGTAACGGTCGGCAGTTCCAACTATCAGCAA

TCCTTTGTGCCAAGTCCAGGCGCGCGTCCTCAGGTGAACGGCCTAAGTGGGAGAATCGAT

TTCCATTGGTTAATGCTTAATCCAAATGACACCGTGACCTTTAGCTTTAACGGCGCCTTT

ATTGCTCCCGACCGAGCTTCTTTCCTTAGAGGTAAGTCAATGGGTATCCAGAGCGGCGTG

CAGGTTGACGCAAACTGTGAAGGCGATTGTTACCACTCCGGAGGCACTATCATTAGCAAC

TTGCCATTTCAGAACATAGATTCACGCGCTGTGGGAAAGTGCCCTAGGTACGTGAAGCAG

AGGTCCCTGTTGCTCGCTACGGGCATGAAGAACGTGCCAGAGATTCCCAAAGGCAGAGGG

TTGTTCGGTGCCATTGCTGGTTTCATTGAGAATGGTTGGGAGGGCCTGATCGACGGGTGG

TACGGTTTCCGTCACCAGAATGCTCAAGGGGAGGGTACAGCAGCCGACTATAAATCCACC

CAGAGCGCAATCGATCAAATTACCGGCAAGCTAAATAGGCTGATTGAAAAAACTAATCAG

CAGTTCGAGCTCATAGACAATGAGTTCAACGAAGTGGAAAAGCAGATTGGCAACGTCATC

AATTGGACCAGAGATTCCATCACCGAGGTGTGGTCTTATAATGCCGAGCTGTTGGTTGCC

ATGGAAAATCAGCATACAATAGACCTGGCCGACTCCGAAATGGATAAACTGTACGAGAGG

GTTAAACGCCAACTGCGTGAGAATGCAGAGGAAGACGGAACAGGTTGTTTCGAGATCTTT

CACAAATGCGACGACGACTGCATGGCCTCCATAAGGAATAATACATATGATCATAGCAAA

TACAGGGAGGAGGCAATGCAAAACCGGATTCAGATTGATCCTGTGAAGCTGAGCAGCGGC

TACAAGGACGTTATTCTTTGGTTCAGTTTCGGTGCATCATGCTTCATACTCCTGGCAATA

GTGATGGGTCTGGTGTTCATCTGCGTGAAAAACGGAAATATGAGGTGCACCATATGCATC

500
ATGAATACCCAAATACTCGTCTTTGCTCTCATCGCTATCATTCCTACGAATGCCGACAAA

ATATGCCTAGGACATCACGCCGTGAGCAATGGGACAAAGGTGAATACCTTAACCGAAAGA

GGCGTGGAGGTCGTGAACGCCACAGAGACTGTGGAGCGCACCAATATACCTAGAATCTGC

TCAAAGGGCAAGAAAACAGTGGACCTAGGACAGTGTGGGCTTCTGGGGACGATCACTGGG

CCACCACAGTGCGACCAGTTCCTGGAGTTCAGCGCGGACCTGATCATCGAACGCCGAGAG

GGCTCTGATGTGTGCTACCCTGGCAAGTTTGTGAACGAGGAGGCTCTTAGGCAGATTCTC

AGGGAATCCGGCGGAATTGACAAGGAAGCTATGGGCTTCACTTATAGTGGAATCCGCACC

AATGGGGCAACGTCCGCTTGTAGGAGATCCGGGAGCAGTTTTTATGCAGAAATGAAATGG

CTGCTTAGTAACACGGACAACGCCGCTTTTCCGCAGATGACTAAGTCCTACAAGAACACC

CGCAAATCACCAGCTCTGATTGTGTGGGGGATTCACCATTCCGTGAGCACAGCCGAGCAG

ACAAAGTTGTATGGCTCTGGAAATAAACTCGTGACTGTGGGCAGTTCGAACTACCAGCAG

TCTTTTGTGCCTTCTCCCGGAGCCCGTCCCCAGGTCAACGGGCAGTCCGGAAGAATTGAT

TTCCACTGGTTGATGCTCAACCCGAATGATACAGTGACTTTTAGCTTCAACGGCGCTTTT

ATTGCCCCTGATCGTGCCAGCTTCCTTAGGGGCAAATCCATGGGGATTCAGTCAGGAGTT

CAGGTAGATGCCAATTGTGAGGGAGATTGTTACCACTCAGGGGGTACGATCATCAGCAAC

TTGCCATTTCAGAACATCGACAGTCGGGCAGTGGGCAAATGCCCACGTTACGTGAAGCAA

CGGAGTCTCCTGTTAGCCACAGGGATGAAAAATGTTCCAGAGATCCCTAAGGGCCGGGGA

CTGTTCGGGGCCATTGCCGGATTTATCGAGAATGGATGGGAGGGACTTATTGATGGTTGG

TACGGCTTTCGGCATCAGAATGCCCAAGGGGAGGGCACAGCTGCCGACTATAAATCAACC

CAGTCTGCAATAGATCAAATCACCGGTAAGCTGAATCGCCTTATCGAAAAAACGAACCAA

CAATTCGAGCTGATCGATAACGAATTCAATGAAGTGGAGAAACAGATTGGGAATGTTATT

AACTGGACAAGAGACAGCATAACCGAAGTCTGGTCCTATAATGCCGAGTTACTTGTGGCC

ATGGAAAACCAGCATACGATTGACTTAGCCGACTCCGAGATGGACAAGTTGTATGAGCGG

GTGAAGAGACAGTTACGGGAGAACGCCGAAGAGGACGGGACTGGTTGTTTTGAAATCTTC

CATAAGTGTGACGACGACTGCATGGCCAGTATTCGCAATAACACCTACGACCATAGCAAG

TACAGGGAAGAAGCCATGCAGAATCGTATTCAGATCGATCCTGTCAAACTTAGTAGTGGG

TACAAGGACGTTATCCTGTGGTTTTCTTTTGGGGCCTCCTGTTTCATTCTTCTGGCTATT

GTAATGGGACTGGTTTTCATATGTGTGAAAAATGGTAACATGCGGTGCACTATATGTATC

501
ATGAATACTCAGATTCTAGTGTTCGCTTTGATAGCTATAATCCCAACCAACGCCGACAAA

ATATGCCTGGGGCACCACGCAGTATCCAACGGGACCAAGGTCAATACCCTGACCGAACGG

GGTGTGGAAGTCGTGAACGCCACAGAGACCGTTGAGAGAACAAACATCCCTAGAATTTGT

AGCAAAGGGAAGAGGACTGTCGACTTGGGGCAGTGCGGGTTACTGGGAACAATCACTGGC

CCACCCCAGTGTGACCAGTTCCTCGAGTTCTCTGCTGATCTTATCATTGAGAGAAGAGAG

GGCAGTGACGTGTGTTATCCTGGAAAATTCGTAAACGAGGAGGCGCTTAGGCAGATTCTG

CGCGAATCAGGAGGTATCGATAAAGAGGCAATGGGGTTTACTTACAGCGGTATCCGAACC

AACGGCGCTACATCTGCATGCCGCAGGTCTGGCTCATCTTTCTATGCAGAGATGAAGTGG

TTGCTCTCTAACACCGATAATGCGGCATTTCCTCAGATGACCAAGAGCTACAAGAACACC

AGAAAATCCCCCGCGTTGATCGTGTGGGGCATCCACCATTCAGTGTCCACCGCTGAGCAG

ACAAAACTCTACGGATCTGGGAACAAGTTGGTGACTGTGGGGTCCTCTAACTACCAGCAA

TCGTTTGTGCCATCCCCAGGGGCTAGACCCCAGGTCAACGGTCTCTCTGGCCGGATCGAC

TTCCACTGGCTTATGCTTAACCCAAACGATACCGTCACCTTTAGCTTTAATGGTGCTTTC

ATTGCCCCCGACCGGGCAAGCTTCTTACGAGGCAAGAGTATGGGAATACAGAGTGGGGTT

CAAGTGGATGCCAACTGCGAGGGCGACTGTTACCACAGCGGCGGCACCATAATTTCAAAT

CTGCCGTTCCAGAATATAGACTCTCGAGCTGTTGGGAAGTGCCCCCGATACGTAAAGCAG

CGCTCTCTGTTACTGGCCACCGGCATGAAAAATGTTCCTGAGATACCGAAGGGACGTGGC

CTCTTCGGGGCCATCGCCGGGTTCATCGAGAACGGCTGGGAAGGACTGATCGATGGATGG

TACGGATTCAGGCATCAGAATGCTCAGGGAGAAGGGACGGCTGCAGATTATAAGTCTACA

CAGTCCGCCATCGATCAGATCACCGGTAAGCTTAATAGAATCATAGAGAAGACGAACCAG

CAGTTCGAGCTGATCGATAACGAGTTTAATGAGGTCGAAAAGCAGATTGGCAACGTGATA

AATTGGACAAGAGACAGTATTACTGAAGTGTGGTCCTACAACGCCGAGCTTTTGGTGGCC

ATGGAAAACCAACACACCATCGACTTAGCAGATTCCGAGATGGATAAACTTTACGAGCGA

GTAAAAAGACAGCTCAGGGAGAATGCTGAAGAAGACGGCACAGGATGTTTCGAGATTTTC

CACAAGTGTGATGACGATTGCATGGCATCAATTCGCAACAACACTTACGATCATAGCAAG

TATCGCGAGGAGGCCATGCAGAACCGCATCCAAATTGATCCTGTCAAGCTAAGTTCCGGG

TATAAAGACGTGATTTTGTGGTTTTCTTTTGGCGCTAGCTGCTTTATTCTACTGGCTATT

GTCATGGGCTTGGTTTTCATCTGCGTGAAAAATGGCAATATGCGCTGCACTATATGTATC

502
ATGAATACACAAATTCTGGTCTTCGCCTTGATTGCCATTATACCAACTAATGCCGATAAG

ATTTGCCTCGGGCACCATGCCGTCTCCAATGGCACAAAAGTCAACACACTGACTGAACGA

GGGGTCGAGGTGGTCAACGCCACTGAAACCGTGGAAAGGACCAACATCCCCCGCATTTGC

AGCAAGGGTAAAAAAACGGTAGACCTGGGACAGTGTGGGCTGCTAGGTACTATTACCGGC

CCCCCACAATGTGACCAATTCTTAGAGTTCTCCGCTGACTTGATAATTGAACGGAGAGAG

GGTTCTGACGTGTGCTACCCTGGGAAGTTTGTAAATGAAGAAGCCCTTCGACAGATTCTC

AGGGAGTCCGGGGGTATTGATAAGGAGGCCATGGGATTTACGTACAGCGGAATTCGGACT

AATGGGGCCACTTCGGCCTGCCGGCGCTCTGGTTCCTCCTTTTATGCAGAGATGAAATGG

CTCCTATCCAACACGGATAACGCCGCCTTCCCACAGATGACAAAATCCTACAAGAACACT

CGGAAGAGCCCAGCGCTGATTGTGTGGGGTATTCACCATAGCGTGTCCACTGCCGAGCAG

ACGAAGCTGTACGGAAGTGGCAACAAATTGGTCACTGTAGGCTCATCTAATTACCAGCAG

AGCTTTGTTCCTTCCCCTGGGGCAAGGCCACAAGTGAATGGCCAAAGTGGTAGAATCGAT

TTCCACTGGCTCATGTTGAATCCTAATGACACGGTAACTTTCAGTTTCAACGGCGCTTTC

ATTGCACCCGACCGGGCTTCATTTCTCCGGGGGAAGTCCATGGGGATCCAGTCAGGAGTC

CAGGTCGATGCTAATTGTGAAGGCGATTGTTACCACTCCGGTGGGACCATCATTAGCAAT

CTGCCATTTCAGAACATCGATTCCAGAGCAGTCGGCAAGTGCCCTAGATATGTGAAGCAG

AGGAGCCTGCTGCTAGCTACGGGTATGAAAAATGTGCCAGAGATCCCAAAGGGGGGGGGT

CTTTTCGGTGCCATAGCTGGATTTATCGAGAATGGCTGGGAGGGTCTGATCGACGGATGG

TACGGGTTCAGGCATCAGAATGCCCAGGGGGAGGGCACTGCCGCCGACTATAAGTCTACA

CAAAGCGCTATTGACCAAATTACCGGTAAGCTGAACAGACTGATCGAGAAGACAAACCAG

CAGTTCGAGCTCATCGATAATGAATTCAACGAGGTAGAAAAGCAAATCGGCAACGTGATT

AACTGGACCAGGGATTCTATCACTGAGGTGTGGTCATACAACGCGGAGCTGCTCGTTGCC

ATGGAAAATCAGCACACTATTGACCTGGCCGACAGCGAAATGGACAAGCTGTACGAAAGA

GTGAAACGACAGCTGCGGGAGAACGCCGAAGAGGACGGGACTGGTTGTTTCGAAATCTTC

CATAAGTGCGATGACGACTGTATGGCTTCAATCAGGAACAACACATACGACCACTCTAAG

TACAGAGAGGAGGCTATGCAGAATCGTATCCAGATTGACCCTGTAAAACTCTCCTCTGGG

TACAAAGACGTGATCCTGTGGTTTTCGTTCGGCGCATCCTGCTTCATCCTGCTCGCGATC

GTCATGGGATTAGTGTTCATTTGCGTCAAAAATGGCAATATGAGGTGTACCATTTGCATC

503
ATGAATACTCAGATCCTAGTGTTTGCTCTCATTGCTATAATCCCCACAAATGCTGACAAG

ATCTGCTTGGGCCATCACGCCGTGAGTAACGGCACTAAGGTGAATACGCTGACGGAACGG

GGTGTAGAAGTTGTAAACGCCACCGAAACAGTCGAAAGGACAAACATCCCGCGCATCTGC

AGTAAAGGTAAAAAGACCGTTGACCTCGGCCAATGCGGACTGCTGGGGACTATCACCGGA

CCCCCCCAATGTGATCAATTTCTGGAGTTCAGTGCGGACTTGATAATCGAAAGACGGGAA

GGTTCCGATGTGTGCTATCCAGGCAAGTTCGTTAATGAGGAAGCACTCCGGCAAATTCTT

CGGGAAAGCGGGGGCATAGACAAGGAAGCCATGGGCTTTACTTACAGCGGAATCCGCACA

AACGGAGCAACATCCGCTTGCAGGAGAAGTGGTAGTTCTTTTTATGCCGAGATGAAATGG

TTGCTGAGCAATACCGACAACGCAGCCTTTCCACAGATGACCAAGAGCTACAAAAATACA

AGAAAGTCCCCAGCTCTGATTGTGTGGGGAATACACCATAGCGTTAGCACAGCCGAACAA

ACAAAGCTGTACGGTTCAGGAAATAAACTTGTGACGGTAGGATCCAGCAATTATCAGCAA

TCTTTCGTGCCATCACCAGGCGCTCGGCCTCAGGTCAACGGGCAGTCGGGCCGTATAGAT

TTTCATTGGCTGATGCTGAATCCTAATGATACTGTGACCTTTAGCTTTAACGGGGGGTTC

ATAGCCCCCGATCGGGCATCTTTTCTCAGGGGTAAAAGCATGGGTATTCAGAGTGGAGTG

CAGGTTGACGCCAATTGCGAGGGAGATTGCTATCATTCCGGGGGGACCATTATTTCCAAC

CTCCCCTTCCAGAACATCGACAGCCGAGCTGTCGGCAAATGCCCCAGGTATGTGAAACAA

CGCAGCCTGTTGTTAGCAACAGGGATGAAGAATGTTCCTGAAATTCCAAAAGGGCGAGGT

CTGTTCGGCGCTATCGCAGGGTTCATTGAGAACGGTTGGGAGGGCCTGATCGATGGCTGG

TATGGCTTTAGGCACCAAAACGCACAGGGCGAAGGGACTGCCGCAGACTACAAATCTACA

CAGTCAGCGATTGATCAAATCACTGGCAAACTGAACCGCCTCATTGAGAAGACCAACCAG

CAGTTCGAACTGATAGACAATGAGTTCAATGAGGTTGAAAAGCAGATAGGTAATGTGATA

AATTGGACCAGAGATAGTATAACTGAAGTCTGGTCCTATAACGCCGAGTTACTTGTCGCT

ATGGAGAACCAGCACACAATTGACCTGGCGGACAGCGAGATGGATAAGCTGTACGAACGC

GTAAAAAGACAACTGCGCGAGAATGCGGAGGAGGACGGCACCGGGTGTTTCGAGATCTTT

CACAAGTGTGATGATGATTGTATGGCCTCCATTAGAAACAACACCTATGATCACTCCAAA

TACCGGGAGGAAGCAATGCAGAACCGCATACAGATTGACCCCGTCAAGTTGAGTTCCGGG

TATAAAGACGTGATACTCTGGTTCAGTTTTGGTGCCTCTTGCTTTATCCTGCTTGCCATC

GTGATGGGACTGGTGTTTATTTGCGTTAAAAACGGGAATATGCGTTGTACGATTTGTATA

504
ATGAATACCCAGATTCTTGTGTTCGCCCTCATTGCCATCATCCCCACCAATGCCGACAAG

ATTTGCTTGGGACATCACGCTGTGAGTAATGGCACAAAAGTAAATACGTTAACCGAACGC

GGGGTTGAAGTGGTGAATGCTACAGAGACGGTAGAGCGCACAAACATCCCGAGAATTTGC

TCCAAAGGCAAAAAGACTGTTGACCTTGGCCAGTGCGGGCTGCTGGGTACGATTACTGGG

CCACCTCAGTGCGATCAGTTCCTAGAATTTTCAGCAGATTTAATCATCGAAAGACGTGAA

GGATCAGATGTGTGTTATCCCGGAAAGTTCGTGAATGAGGAGGCTTTGAGACAGATCTTG

CGTGAATCTGGGGGCATAGATAAGGAAGCCATGGGGTTTACTTATTCTGGAATCCGCACT

AATGGGGCCACCAGCGCATGTAGGCGCTCCGGATCCTCATTCTATGCCGAGATGAAGTGG

CTTCTCAGTAACACAGATAATGCCGCCTTCCCCCAAATGACAAAGAGCTACAAGAATACA

CGGAAAAGCCCCGCCCTGATCGTATGGGGGATTCATCATTCTGTTAGCACTGCCGAGCAA

ACCAAACTGTACGGCTCAGGAAATAAGCTCGTGACGGTAGGGTCATCAAACTACCAGCAG

AGCTTCGTACCTTCCCCCGGCGCTAGACCTCAGGTCAACGGTCAGTCCGGACGAATTGAT

TTCCACTGGTTAATGCTCAACCCAAATGACACCGTCACATTCAGTTTTAACGGTGCCTTT

ATTGCTCCTGACAGAGCCTCTTTTCTGAGGGGCAAGTCCATGGGCATCCAGAGCGGGGTA

CAGGTCGACGCCAATTGCGAGGGCGACTGCTACCATTCAGGGGGGACGATCATTAGTAAC

TTACCCTTTCAAAACATTGATTCACGGGCCGTAGGCAAGTGTCCGAGATACGTCAAGCAG

CGGAGCTTGCTGTTGGCAACTGGCATGAAAAACGTTCCCGAAATCCCTAAGGGCCGAGGT

CTTTTTGGGGCAATTGCGGGCTTCATAGAGAATGGTTGGGAGGGACTGATCGATGGGTGG

TATGGCTTCAGACATCAGAACGCACAGGGTGAGGGTACCGCTGCTGACTATAAGAGCACC

CAGAGCGCAATAGATCAGATCACTGGCAAGCTTAACCGACTTATCGAAAAGACCAACCAG

CAGTTTGAATTGATTGACAACGAATTTAACGAAGTTGAGAAGCAAATTGGGAACGTTATT

AATTGGACAAGGGATTCCATCACAGAGGTTTGGAGTTACAATGCGGAGTTATTAGTGGCA

ATGGAGAACCAACATACTATTGACCTTGCGGATAGCGAGATGGACAAGCTGTACGAGAGG

GTCAAGCGCCAGTTACGGGAAAACGCGGAAGAGGATGGAACTGGATGTTTCGAGATCTTC

CACAAATGCGATGACGATTGCATGGCGTCGATCCGAAACAATACCTACGATCACAGTAAA

TACAGGGAAGAGGCAATGCAGAACCGAATTCAGATTGATCCCGTGAAGCTCAGCTCAGGG

TACAAGGACGTGATTCTGTGGTTTTCATTTGGAGCTAGCTGCTTTATACTGCTGGCTATT

GTTATGGGCTTGGTATTCATCTGTGTGAAGAATGGTAACATGAGGTGTACAATTTGCATT

505
ATGAATACTCAGATCCTGGTGTTTGCTCTGATAGCTATCATCCCCACCAACGCCGATAAG

ATTTGCCTGGGCCACCACGCAGTGAGTAACGGGACAAAAGTCAACACTCTAACTGAGCGC

GGCGTTGAAGTTGTAAATGCCACTGAAACTGTTGAGAGAACTAATATACCCCGCATTTGC

TCAAAAGGCAAGAGGACTGTGGATCTCGGCCAGTGTGGGCTTCTGGGGACCATAACTGGT

CCGCCCCAATGTGACCAGTTCTTGGAGTTTTCCGCAGACCTAATTATCGAGCGTCGCGAA

GGCTCCGATGTGTGCTACCCCGGCAAGTTTGTCAATGAAGAAGCCCTGAGGCAGATTCTG

CGAGAAAGCGGGGGTATAGACAAAGAAGCTATGGGCTTTACTTATAGCGGAATTCGTACA

AACGGCGCTACATCCGCCTGTCGACGGTCTGGTTCTAGCTTCTATGCTGAGATGAAATGG

TTGCTTAGCAACACAGACAATGCCGCTTTCCCCCAGATGACTAAAAGTTATAAAAATACC

CGGAAGAGCCCCGCACTTATCGTATGGGGGATCCATCACAGTGTGTCGACTGCCGAACAG

ACCAAGCTCTACGGGAGCGGCTCCAAGCTGGTGACAGTGGGGTCTTCTAATTACCAACAA

TCCTTTGTCCCTTCCCCTGGCGCCCGCCCCCAAGTGAATGGGCTAAGCGGAAGGATTGAC

TTTCATTGGCTGATGCTGAATCCCAACGATACAGTGACGTTCAGCTTTAACGGGGCGTTT

ATTGCCCCTGACCGTGCAAGTTTTCTCCGCGGGAAATCCATGGGCATCCAAAGCGGCGTC

CAAGTGGATGCAAACTGCGAAGGAGACTGCTATCACTCTGGAGGAACTATTATTTCTAAC

CTGCCTTTCCAGAACATCGACTCAAGGGCCGTGGGGAAATGCCCGCGCTATGTTAAACAG

AGAAGCCTGTTGCTTGCCACAGGTATGAAGAACGTGCCCGAGATCCCTAAGGGCAGAGGG

CTGTTCGGCGCAATCGCAGGGTTCATTGAAAACGGATGGGAGGGCCTCATCGACGGATGG

TACGGTTTTCGGCACCAAAACGCACAGGGGGAGGGCACAGCGGCGGATTATAAGAGCACT

CAGAGTGCCATAGATCAGATTACGGGGAAGCTCAATAGACTTATAGAGAAGACCAATCAG

CAATTCGAGCTGATCGATAACGAGTTCAATGAGGTAGAAAAGCAGATTGGGAATGTCATC

AACTGGACAAGAGATAGTATAACAGAGGTGTGGAGCTACAACGCCGAGTTACTTGTGGCC

ATGGAAAACCAGCACACAATCGACCTGGCTGATAGCGAAATGGACAAGCTGTATGAAAGA

GTCAAGAGACAGCTTCGAGAAAACGCAGAGGAGGACGGAACCGGCTGCTTCGAGATTTTT

CACAAATGTGACGATGATTGCATGGCGTCAATCCGGAACAACACCTATGACCACTCTAAG

TATCGAGAGGAGGCGATGCAGAACCGGATACAGATCGATCCTGTTAAGCTTTCATCAGGT

TACAAGGACGTAATCCTGTGGTTCTCGTTCGGCGCATCCTGCTTTATCCTTCTGGCAATT

GTGATGGGGCTCGTATTCATCTGCGTGAAAAATGGCAATATGAGATGTACTATTTGCATT

506
ATGAATACACAGATCCTTGTGTTCGCACTGATCGCGATTATCCCCACCAACGCAGACAAG

ATCTGTTTAGGCCACCATGCTGTGAGCAATGGGACAAAAGTCAACACGCTGACAGAGCGG

GGAGTGGAGGTGGTAAACGCTACTGAAACGGTCGAGAGAACTAACATTCCTAGAATTTGT

TCAAAAGGGAAAAGGACCGTGGATCTGGGCCAGTGTGGGCTGCTGGGAACAATCACTGGG

CCACCACAATGCGATCAGTTTTTAGAGTTCTCGGCCGACCTAATCATAGAGCGCAGAGAG

GGCTCCGATGTATGCTATCCCGGGAAGTTTGTGAATGAAGAAGCTTTAAGGCAGATTCTT

AGAGAATCCGGTGGGATTGACAAGGAGGCAATGGGGTTTACATACTCCGGTATTAGAACA

AACGGGGCCACCTCCGCGTGCAGGAGAAGCGGCTCCTCTTTTTATGCTGAGATGAAATGG

CTGCTGTCAAACACCGACAACGCCGCATTTCCCCAAATCACCAAGTCCTACAAGAATACA

AGAAAGTCTCCAGCCCTGATTGTTTGGGGGATACACCACTCAGTGTCCACCGCTGAACAG

ACCAAGTTGTATGGTAGCGGAAACAAGCTGGTGACCGTCGGGTCCTCAAATTATCAGCAG

TCATTTGTCCCATCTCCGGGCGCTAGGCCTCAGGTGAATGGGCTGAGTGGACGCATTGAC

TTCCACTGGCTTATGCTGAATCCTAATGACACAGTTACATTTAGTTTCAACGGGGCATTT

ATTGCGCCAGATAGAGCCAGTTTCTTGCGCGGCAAATCTATGGGAATCCAGAGCGGCGTT

CAAGTGGACGCCAACTGTGAGGGGGACTGCTACCACAGCGGCGGGACAATTATCAGCAAC

CTGCCATTCCAGAATATTGATTCACGGGCTGTGGGAAAGTGTCCTAGGTACGTCAAACAG

CGGTCTCTGCTGTTAGCAACCGGAATGAAGAATGTACCCGAGATCCCTAAAGGCCGAGGG

TTGTTCGGCGCAATTGGGGGCTTCATTGAGAATGGTTGGGAGGGTCTCATCGATGGTTGG

TACGGCTTCAGACACCAGAATGCCCAAGGCGAAGGAACTGCAGCCGACTATAAGTCAACT

CAAAGCGCAATCGACCAGATCACAGGGAAACTGAATCGCTTGATCGAAAAGACCAACCAG

CAATTCGAGCTGATCGACAATGAGTTTAACGAGGTCGAGAAGCAGATCGGAAATGTGATT

AATTGGACTCGAGACTCAATTACCGAGGTTTGGAGTTACAATGCCGAACTGCTGGTGGCC

ATGGAGAATCAACATACCATAGATCTCGCCGATAGCGAGATGGATAAACTGTATGAACGA

GTTAAGCGACAACTGAGAGAAAACGCCGAAGAAGACGGAACCGGGTGCTTTGAAATCTTC

CACAAATGCGATGATGATTGTATGGCTTCAATTCGCAACAACACCTACGATCACAGCAAG

TACCGAGAAGAGGCCATGCAAAACCGGATTCAAATCGATCCAGTGAAGCTGAGTTCTGGA

TATAAGGATGTGATTCTGTGGTTTTCATTTGGGGCTAGCTGTTTCATTCTTCTTGCCATC

GTGATGGGTCTCGTGTTTATTTGTGTCAAGAATGGGAACATGCGCTGCACGATATGCATC

507
ATGAACACCCAAATTCTAGTTTTCGCCCTTATCGCCATCATACCGACAAACGCAGACAAA

ATATGTCTCGGACACCACGCGGTGAGTAATGGCACCAAGGTGAACACTCTTACCGAGCGA

GGGGTGGAGGTGGTGAATGCAACAGAAACCGTGGAGCGCACCAACATCCCCCGGATTTGT

TCAAAGGGAAAAAAGACAGTCGACCTGGGGCAGTGTGGGCTCCTGGGCACTATCACTGGG

CCCCCGCAGTGCGACCAATTCCTGGAGTTTAGCGCAGACCTGATCATCGAAAGAAGGGAG

GGGTCAGACGTGTGTTACCCGGGAAAGTTCGTGAACGAAGAGGCACTTCGCCAGATATTA

AGAGAGAGCGGCGGGATTGATAAAGAAGCTATGGGCTTCACCTATTCTGGCATTAGGACC

AATGGCGCCACAAGTGCCTGTAGGAGATCAGGCTCGAGCTTCTACGCTGAGATGAAATGG

CTCCTGTCGAACACAGACAACGCCGCTTTTCCTCAGATGACGAAATCCTATAAAAACACG

CGGAAGTCTCCTGCGCTCATTGTGTGGGGAATTCATCACAGTGTGTCTACCGCTGAGCAG

ACAAAGCTTTACGGTTCCGGAAATAAATTAGTGACAGTTGGCTCTAGTAACTATCAGCAA

AGTTTCGTACCATCCCCGGGAGCGAGACCGCAGGTAAATGGACAGTCCGGGCGGATAGAT

TTCCATTGGCTCATGCTGAATCCTAATGACACCGTCACATTCAGCTTTAACGGGGCATTC

ATCGCACCCGATCGAGCTAGTTTTCTTCGCGGCAAGTCTATGGGAATTCAATCTGGCGTA

CAGGTGGATGCCAATTGCGAGGGTGATTGCTACCACTCTGGGGGTACCATCATCTCGAAC

CTCCCTTTTCAAAACATCGATAGCAGAGCCGTGGGCAAGTGCCCTCGATATGTTAAGCAG

AGAAGCCTGCTGCTCGCAACCGGCATGAAGAACGTGCCTGAGATTCCTAAGGGCCGCGGC

TTATTCGGCGCCATTGCTGGCTTCATCGAAAATGGCTGGGAAGGTTTAATCGATGGATGG

TATGGGTTCCGCCATCAGAACGCTCAAGGTGAGGGCACTGCCGCCGATTACAAAAGCACC

CAGAGTGCAATCGACCAGATTACTGGTAAGCTTAATCGACTAATTGAGAAAACCAACCAG

CAGTTCGAACTGATTGATAACGAGTTTAATGAAGTCGAGAAGCAGATTGGAAACGTTATC

AATTGGACCCGAGACAGTATAACTGAGGTGTGGAGCTACAACGCCGAGCTCCTCGTGGCT

ATGGAGAACCAACATACAATCGATCTTGCAGATTCTGAAATGGATAAGCTATACGAAAGA

GTAAAGCGACAGCTCCGGGAAAACGCAGAGGAAGACGGAACTGGATGTTTCGAGATTTTT

CACAAGTGCGACGACGATTGCATGGCAAGCATTAGAAATAACACATACGACCACTCAAAG

TACCGCGAGGAGGCGATGCAGAATAGGATACAGATCGACCCTGTAAAGCTGAGCTCTGGG

TACAAGGACGTGATCTTGTGGTTTTCTTTCGGCGCATCATGCTTCATCTTGCTGGCAATC

GTGATGGGCCTGGTCTTTATTTGCGTAAAGAACGGCAATATGCGCTGTACAATCTGTATC

508
ATGAATACTCAGATACTGGTGTTCGCACTCATCGCAATTATACCCACTAATGCCGATAAG

ATTTGTTTAGGACATCACGCCGTCAGTAACGGAACTAAGGTTAACACACTAACAGAGCGA

GGCGTCGAAGTGGTTAATGCAACTGAGACGGTCGAGCGCACAAACATCCCTCGTATTTGC

AGCAAAGGAAAGAAAACCGTCGATCTGGGACAGTGCGGACTCCTGGGGACCATAACCGGC

CCTCCCCAGTGCGATCAGTTTCTGGAGTTCTCAGCAGATCTTATAATCGAGCGACGGGAA

GGTTCCGACGTATGTTATCCCGGTAAATTCGTCAACGAAGAAGCCCTGAGACAGATCCTG

CGGGAGAGTGGAGGAATTGACAAGGAGGCCATGGGATTTACCTACAGCGGCATTAGAACG

AATGGGGCCACATCTGCCTGCCGACGCAGCGGCAGCTCATTCTACGCCGAGATGAAATGG

TTACTGTCCAATACCGACAACGCCGCGTTCCCGCAGATGACCAAATCTTACAAGAACACT

CGAAAATCCCCCGCACTTATTGTGTGGGGCATCCACCATAGTGTGTCAACCGCTGAGCAG

ACTAAACTCTACGGTTCTGGTAACAAACTCGTGACTGTGGGAAGCTCAAACTACCAGCAA

AGCTTTGTGCCCTCTCCCGGGGCCAGGCCACAGGTGAACGGACAGTCCGGACGCATAGAC

TTCCACTGGCTGATGCTAAATCCGAACGACACCGTCACCTTCAGTTTTAATGGGGCTTTC

ATCGCCCCTGACAGAGCTAGCTTCCTGCGCGGTAAGAGCATGGGTATTCAGAGCGGGGTG

CAGGTCGACGCCAACTGCGAAGGTGATTGCTATCATTCAGGGGGCACAATTATCTCCAAC

CTCCCATTTCAGAACATCGATAGCCGCGCAGTCGGTAAGTGTCCACGATACGTTAAACAA

AGGTCACTGCTCCTTGCCACTGGCATGAAAAACGTCCCGGAGATCCCGAAGGGCCGCGGA

CTCTTTGGGGCCATCGCTGGGTTCATTGAAAATGGTTGGGAGGGGCTCATTGACGGATGG

TATGGCTTTAGGCACCAGAACGCCCAAGGAGAGGGGACCGCAGCCGATTATAAGAGCACA

CAGTCTGCCATTGACCAGATAACCGGTAAACTTAACCGGTTAATCGAAAAAACTAACCAG

CAGTTCGAATTAATCGACAACGAATTTAATGAAGTCGAGAAACAGATCGGCAACGTCATC

AACTGGACCCGAGATAGCATAACTGAAGTGTGGTCCTACAACGCCGAGCTGCTCGTGGCT

ATGGAGAATCAGCATACCATCGACTTGGCCGACAGTGAAATGGATAAGCTGTACGAGAGA

GTTAAGCGCCAGCTGAGAGAGAACGCAGAAGAGGACGGGACCGGCTGCTTTGAGATTTTC

CATAAGTGCGATGACGACTGTATGGCAAGCATTCGCAATAATACTTACGATCACTCCAAA

TATAGGGAGGAGGCCATGCAAAACCGCATTCAGATTGATCCGGTGAAGTTGTCAAGTGGA

TATAAGGATGTGATTCTCTGGTTCTCCTTCGGGGCCTCCTGTTTTATTCTTCTCGCAATC

GTTATGGGCTTGGTCTTCATCTGCGTAAAAAATGGGAATATGAGATGTACTATCTGTATC

509
ATGAACACACAAATTCTTGTATTTGCCCTTATAGCAATCATTCCAACCAACGCAGACAAG

ATATGCCTGGGGCACCACGCCGTCTCTAACGGTACAAAGGTAAACACACTAACCGAACGC

GGTGTCGAGGTAGTGAATGCAACTGAGACCGTGGAGCGGACCAACATACCAAGAATCTGC

TCCAAAGGGAAGAGAACGGTGGATCTAGGACAGTGCGGGCTGCTCGGGACTATCACTGGA

CCACCTCAGTGTGATCAATTTTTAGAGTTCTCGGCAGACTTAATCATCGAACGGCGGGAA

GGATCTGATGTTTGCTACCCTGGCAAGTTTGTTAATGAAGAGGCGCTGCGACAGATTTTG

CGCGAATCCGGTGGTATCGATAAAGAAGCAATGGGCTTCACTTATAGTGGCATTCGGACC

AATGGAGCCACAAGCGCATGCCGAAGGAGCGGGTCCAGCTTTTACGCTGAAATGAAATGG

CTCTTGAGTAATACAGATAACGCCGCCTTTCCTCAAATGACAAAAAGCTATAAGAATACG

CGAAAAAGCCCTGCTCTAATCGTCTGGGGTATCCACCACTCTGTGTCTACAGCCGAACAA

ACCAAGCTGTATGGCAGCGGCTCAAAGCTGGTAACAGTGGGATCAAGCAATTACCAGCAG

AGTTTTGTGCCTAGCCCTGGAGCTAGACCGCAGGTGAACGGCCTTTCAGGTCGGATAGAC

TTTCACTGGCTTATGTTAAATCCAAATGACACGGTGACCTTCTCTTTCAACGGGGCATTT

ATCGCACCAGATAGGGCATCTTTTCTGCGGGGGAAGAGTATGGGCATCCAATCCGGAGTG

CAGGTTGATGCAAATTGCGAGGGGGATTGTTATCACTCCGGCGGTACAATAATTAGTAAC

CTCCCATTTCAGAATATTGATAGTCGTGCCGTCGGAAAATGTCCTCGCTATGTCAAGCAG

AGATCGCTGTTACTTGCCACCGGCATGAAAAATGTGCCCGAAATCCCAAAGGGCCGAGGT

CTGTTCGGGGCTATCGCAGGCTTCATTGAAAATGGATGGGAAGGCCTGATCGACGGGTGG

TACGGCTTCCGTCATCAGAACGCACAGGGGGAAGGGACTGCAGCGGATTATAAGTCCACC

CAAAGCGCTATTGACCAGATCACCGGCAAGCTCAATCGGCTCATAGAAAAAACTAATCAA

CAGTTTGAGTTGATAGATAATGAGTTTAACGAGGTCGAGAAGCAGATTGGGAATGTGATC

AATTGGACCAGAGACTCAATAACTGAGGTGTGGTCATACAATGCGGAGTTGTTGGTCGCT

ATGGAAAATCAACACACAATCGACCTGGCTGACTCAGAAATGGATAAGCTGTACGAGCGG

GTCAAGAGACAGCTGCGCGAGAATGCCGAGGAAGATGGAACAGGTTGCTTTGAAATTTTC

CATAAATGCGATGATGACTGTATGGCAAGTATTCGGAACAATACTTACGATCACAGTAAG

TATAGAGAAGAAGCAATGCAAAACAGAATTCAGATTGATCCGGTGAAGCTGAGCTCAGGA

TACAAAGATGTTATCCTATGGTTTTCTTTTGGGGCCTCATGCTTTATCTTATTGGCCATA

GTTATGGGGCTAGTATTTATCTGCGTAAAATCAAGGAATATGAGGTGCACCATCTGCATT

510
ATGAATACACAGATCTTGGTTTTTGCCCTCATCGCCATTATCCCCACAAATGCCGACAAA

ATTTGCTTGGGCCACCACGCCGTGTCCAATGGTACAAAAGTCAATACACTGACCGAGAGG

GGAGTGGAGGTGGTGAATGCCACAGAAACCGTTGAAAGAACGAATATTCCTAGAATTTGT

TCTAAAGGGAAAAGAACCGTTGATCTCGGGCAATGCGGTCTGTTAGGCACAATCACAGGC

CCTCCCCAGTGTGATCAATTTCTTGAGTTCAGTGCGGATCTTATCATTGAGAGACGGGAA

GGGTCTGATGTCTGTTACCCCGGCAAGTTTGTGAACGAGGAAGCCCTGCGCCAGATCCTC

AGAGAATCTGGGGGTATCGATAAGGAAGCTATGGGGTTTACTTATTCCGGGATCAGGACT

AATGGGGCCACCAGCGCCTGCCGGCGGTCCGGCAGCTCATTCTACGCCGAGATGAAGTGG

CTGCTGTCCAATACCGACAATGCGGCCTTTCCGCAGATGACCAAGAGCTATAAAAACACG

CGCAAATCACCCGCTTTAATCGTCTGGGGGATACATCATTCAGTGAGCACTGCCGAGCAA

ACCAAGCTGTATGGGAGCGGCAGTAAATTGGTTACTGTAGGTAGCTCTAACTACCAGCAG

TCTTTCGTCCCAAGCCCAGGAGCCCGTCCGCAGGTGAATGGACTCAGTGGAAGGATTGAT

TTTCATTGGCTAATGCTCAACCCGAACGATACTGTGACGTTTTCATTTAATGGCGCATTT

ATCGCGCCCGATCGAGCCAGCTTCCTCCGGGGTAAGAGTATGGGGATCCAATCAGGAGTG

CAGGTCGATGCTAACTGCGAGGGAGACTGTTACCATTCCGGCGGCACTATTATCAGCAAT

CTGCCCTTCCAGAATATCGACTCCAGAGCCGTGGGAAAGTGTCCAAGGTACGTGAAACAG

AGGAGCTTACTGCTTGCCACAGGGATGAAGAATGTCCCCGAGATTCCCAAAGGAAGGGGG

CTGTTCGGAGCCATCGCAGGGTTCATTGAGAACGGGTGGGAAGGCTTAATCGATGGCTGG

TACGGCTTCAGACACCAAAATGCACAGGGCGAAGGAACCGCCGCCGATTACAAGTCAACG

CAATCCGCTATAGATCAGATAACCGGAAAGCTGAACAGACTCATCGAAAAAACAAACCAA

CAGTTCGAACTTATAGACAACGAATTCAACGAGGTGGAAAAACAGATCGGGAACGTTATC

AATTGGACACGAGACTCAATCACAGAGGTATGGTCCTACAACGCTGAACTCCTGGTTGCG

ATGGAGAATCAGCACACCATTGACTTAGCCGACTCTGAGATGGATAAACTGTACGAGAGA

GTGAAAAGGCAGCTCCGAGAGAACGCAGAAGAGGATGGTACAGGATGCTTCGAAATCTTT

CACAAATGCGACGATGATTGTATGGCCAGCATCAGAAATAATACATATGACCATTCCAAA

TATCGGGAAGAAGCAATGCAAAACCGGATCCAGATCGATCCTGTTAAACTCAGCAGCGGT

TACAAGGACGTGATTCTGTGGTTCTCCTTCGGCGCATCATGTTTTATTCTTCTTGCTATT

GTGATGGGACTAGTATTTATATGCGTGAAGAATGGCAACATGAGATGTACCATTTGCATC

511
ATGAATACCCAAATCCTTGTATTCGCTCTGATCGCAATCATTCCAACCAATGCTGATAAA

ATCTGCTTAGGACACCACGCTGTGAGCAATGGTACAAAGGTCAATACACTGACAGAGCGG

GGCGTAGAAGTGGTCAACGCCACCGAGACGGTGGAAAGGACCAATATCCCTAGGATTTGC

TCGAAGGGCAAGAGAACAGTAGACCTGGGGCAATGTGGATTGTTGGGGACTATTACGGGA

CCGCCCCAGTGTGATCAGTTTCTGGAGTTCAGCGCTGATCTCATCATCGAGCGCCGAGAG

GGATCCGACGTGTGCTACCCAGGAAAATTCGTTAACGAGGAAGCATTAAGACAGATTTTA

CGTGAATCGGGTGGCATTGATAAAGAAGCCATGGGGTTTACTTACAGTGGAATTAGAACC

AATGGAGCCACCTCGGCTTGCCGGAGATCTGGGTCTAGCTTTTACGCAGAAATGAAGTGG

CTGCTGTCTAACACGGATAATGCCGCGTTCCCGCAGATGACCAAAAGTTATAAAAATACC

AGAAAGAGCCCTGCATTAATTGTCTGGGGCATTCACCACTCTGTTTCCACGGCCGAACAG

ACAAAATTGTATGGAAGCGGAAACAAGCTGGTCACAGTCGGATCTAGCAACTACCAGCAG

AGCTTTGTGCCCAGTCCAGGGGCCCGCCCTCAGGTCAATGGGCTTTCTGGGAGAATTGAT

TTTCACTGGCTGATGTTGAACCCCAACGACACTGTGACCTTTAGCTTCAATGGCGCGTTT

ATTGCGCCCGACAGAGCCTCCTTTTTACGGGGGAAAAGCATGGGAATACAATCTGGTGTG

CAGGTGGATGCAAATTGCGAAGGAGACTGCTATCACTCCGGGGGTACCATTATTAGCAAT

CTCCCATTCCAGAACATCGACTCCAGAGCCGTTGGTAAATGCCCCAGGTATGTCAAGCAG

CGTAGTCTCTTGTTGGCCACAGGAATGAAAAACGTGCCTGAGATCCCCAAAGGGCGCGGC

CTATTTGGGGCAATTGCCGGCTTTATCGAGAACGGATGGGAGGGCCTGATCGACGGTTGG

TATGGCTTTCGCCATCAGAATGCTCAGGGGGAAGGCACAGCTGCAGACTACAAGAGCACC

CAGAGCGCCATCGATCAAATCACCGGCAAGCTCAACCGGATCATCGAGAAGACAAATCAG

CAATTTGAATTAATCGACAACGAGTTCAATGAGGTAGAAAAGCAGATAGGAAACGTGATC

AACTGGACCAGGGATAGCATTACTGAAGTCTGGTCATACAATGCCGAACTCCTGGTGGCA

ATGGAGAACCAGCACACTATTGATCTTGCCGACTCTGAGATGGACAAACTGTACGAGCGC

GTGAAGCGACAGCTGAGGGAAAACGCTGAGGAAGACGGTACTGGCTGCTTTGAAATCTTC

CACAAATGCGACGACGATTGCATGGCATCCATACGGAACAACACTTATGATCACTCAAAG

TATCGGGAGGAAGCAATGCAGAATAGAATTCAAATCGATCCCGTTAAACTGAGCTCCGGC

TACAAGGATGTGATTCTCTGGTTTAGCTTCGGAGCATCATGCTTTATCCTCCTAGCAATT

GTAATGGGTCTGGTGTTCATATGCGTAAAGAATGGCAATATGCGCTGTACTATCTGTATT

512
ATGAACACGCAAATTCTAGTGTTTGCTCTAATTGCCATCATACCCACAAACGCCGATAAA

ATCTGCCTTGGGCATCACGCAGTAAGTAACGGTACCAAGGTGAACACGCTCACAGAGCGC

GGGGTCGAGGTCGTGAATGCCACCGAAACAGTGGAACGCACTAACATCCCTCGAATCTGT

TCAAAAGGTAAGCGGACTGTGGATCTGGGACAGTGTGGCCTGCTTGGTACGATCACCGGT

CCTCCCCAATGCGATCAGTTCCTGGAGTTCTCAGCAGACTTAATCATCGAGCGCAGAGAG

GGTAGCGATGTCTGTTACCCCGGAAAGTTTGTGAAGGAAGAAGCCCTTCGCCAGATTCTC

AGAGAGTCAGGAGGCATTGATAAGGAAGCCATGGGGTTTACCTACAGCGGTATCCGTACC

AACGGAGCCACCTCTGCCTGCCGACGCTCAGGTTCTAGCTTCTACGCTGAAATGAAATGG

TTACTGAGCAATACCGATAACGCCGCATTCCCCCAGATGACAAAAAGCTACAAGAATACC

CGCAAAAGCCCTGCCCTTATAGTTTGGGGGATACATCACTCCGTGTCCACCGCAGAACAG

ACCAAGCTGTACGGCAGCGGCAACAAATTGGTGACCGTGGGGAGTAGTAATTATCAACAG

AGCTTTGTGCCCTCGCCTGGGGCCAGACCTCAGGTCAATGGACTTAGTGGAAGGATTGAT

TTCCACTGGCTTATGCTCAATCCTAATGATACCGTCACATTCAGCTTCAACGGGGCGTTC

ATCGCACCCGATCGCGCAAGCTTCCTGCGTGGGAAGAGTATGGGCATCCAATCTGGGGTT

CAAGTGGATGCAAATTGTGAGGGCGATTGTTACCACAGCGGCGGGACGATCATCTCCAAC

CTCCCCTTCCAGAATATTGATTCTCGTGCCGTTGGGAAATGTCCTAGATATGTGAAGCAG

CGTTCCCTCCTGCTGGCTACAGGCATGAAGAACGTTCCGGAAATCCCCAAGGGCAGAGGA

CTGTTTGGCGCCATTGCAGGATTTATTGAGAATGGATGGGAGGGCCTCATCGATGGTTGG

TACGGATTCAGACACCAGAACGCTCAGGGGGAAGGAACAGCCGCCGATTATAAGTCTACC

CAGTCGGCTATCGACCAAATCACCGGAAAACTGAACAGGCTGATAGAGAAAACTAACCAG

CAGTTCGAGTTGATCGACAACGAGTTCAACGAAGTGGAGAAACAGATCGGCAACGTCATT

AACTGGACACGCGACTCAATTACAGAGGTGTGGTCCTACAACGCTGAGCTGCTGGTAGCA

ATGGAGAACCAGCATACCATCGACCTGGCTGATTCTGAAATGGATAAGCTGTATGAACGG

GTCAAGCGTCAACTGCGCGAAAACGCCGAAGAGGATGGAACAGGCTGCTTCGAAATTTTT

CATAAATGCGATGACGACTGCATGGCAAGCATCCGGAACAACACATACGATCACTCAAAA

TACCGCGAGGAGGCTATGCAGAATCGCATTCAGATTGATCCTGTGAAGTTATCCTCCGGC

TACAAAGATGTCATCCTCTGGTTCAGTTTCGGCGCGTCTTGCTTCATCCTCCTAGCAATC

GTGATGGGTCTCGTTTTCATCTGTGTGAAGAACGGGAATATGAGATGCACTATTTGCATA

513
ATGAATACCCAGATCCTTGTGTTTGCTCTGATCGCCATCATTCCCACAAACGCCGACAAA

ATTTGCCTCGGTCACCATGCTGTGTCAAACGGTACTAAAGTCAACACATTGACAGAGAGG

GGCGTGGAGGTGGTGAATGCAACCGAGACCGTTGAGCGAACAAATATCCCTCGCATCTGC

TCCAAGGGCAAGAAAACTGTGGATTTGGGCCAATGTGGGCTTTTGGGAACCATTACTGGG

CCTCCTCAGTGTGATCAGTTCCTCGAGTTCTCTGCCGACCTGATTATTGAACGCCGAGAA

GGTAGCGATGTCTGTTACCCAGGCAAATTCGTCAACGAAGAGGCACTTCGCCAGATACTG

AGAGAGAGTGGAGGCATTGATAAAGAAGCTATGGGGTTTACCTATTCTGGGATAAGGACC

AACGGGGCCACCAGTGCTTGTAGACGTAGTGGCAGCAGCTTCTACGCGGAAATGAAATGG

CTCCTGTCAAATACAGACAATGCTGCTTTTCCTCAGATGACTAAATCGTACAAAAACACG

CGGAAGAGCCCCGCCTTAATCGTGTGGGGAATCCACCACTCCGTGTCCACAGCGGAACAG

ACCAAACTTTACGGCTCCGGGAATAAGCTAGTGACCGTGGGCAGCTCCAACTATCAACAA

AGTTTCGTCCCTTCCCCCGGTGCGAGACCGCAGGTCAACGGACAGTCAGGGAGGATCGAT

TTCCACTGGCTGATGTTAAACCCTAATGACACTGTGACTTTCTCCTTCAATGGAGCGTTC

ATTGCACCGGATCGAGCGTCTTTTCTCCGGGGAAAGTCTATGGGTATCCAGTCTGGCGTG

CAGGTGGATGCCAATTGCGAGGGAGATTGCTACCACTCCGGGGGCACTATCATCTCGAAT

CTCCCCTTCCAGAACATCGACAGCCGGGCCGTGGGTAAATGCCCACGGTATGTCAAGCAA

AGATCCTTACTGCTCGCCACAGGGATGAAGAACGTGCCTGAGATCCCTAAGGGCCGGGGG

CTGTTTGGAGCCATCGCTGGGTTCATTGAAAACGGTTGGGAAGGCCTCATTGACGGATGG

TATGGCTTCAGGCACCAGAACGCTCAGGGGGAGGGGACCGCCGCCGACTACAAGAGTACG

CAATCTGCTATAGATCAGATCACTGGTAAACTCAACCGCTTGATCGAGAAAACCAATCAG

CAGTTCGAGCTTATTGACAACGAGTTTAACGAGGTAGAGAAGCAGATTGGAAATGTCATC

AATTGGACTAGAGACTCTATCACAGAGGTGTGGAGCTATAATGCCGAATTGTTGGTGGCA

ATGGAAAACCAGCACACCATCGACCTGGCCGACAGCGAAATGGACAAGTTGTATGAACGC

GTTAAACGTCAGTTGAGGGAGAACGCCGAGGAGGACGGGACGGGTTGCTTTGAAATCTTT

CATAAGTGCGATGACGACTGTATGGCTTCTATCCGCAATAACACTTATGACCACAGTAAG

TACCGGGAAGAAGCTATGCAAAACAGAATACAGATCGACCCAGTTAAATTATCAAGTGGC

TATAAAGATGTGATCCTCTGGTTCAGCTTTGGAGCCTCCTGTTTCATTTTATTGGCCATA

GTCATGGGCCTCGTATTTATCTGCGTGAAAAATGGCAACATGCGCTGCACCATCTGCATT

514
ATGAACACTCAGATCCTAGTGTTTGCTCTGATAGCGATCATACCCACCAATGCAGACAAA

ATCTGTCTGGGCCATCATGCAGTCTCTAATGGAACCAAAGTGAACACCCTAACTGAGAGG

GGCGTCGAGGTGGTGAATGCGACCGAAACTGTTGAAAGGACCAATATTCCCAGAATCTGC

TCAAAGGGAAAAAAAACGGTGGACCTGGGGCAGTGTGGATTACTAGGCACGATCACCGGG

CCTCCTCAGTGTGATCAATTTCTGGAGTTCAGCGCAGATCTTATTATTGAGAGAAGAGAG

GGCTCTGACGTGTGCTACCCAGGCAAGTTCGTGAACGAGGAGGCTCTGCGGCAGATCCTA

CGTGAGAGCGGAGGCATAGACAAGGAGGCAATGGGATTTACCTATAGCGGGATACGGACA

AATGGCGCAACGTCCGCATGTCGCCGGAGTGGGTCTTCCTTTTACGCGGAGATGAAGTGG

CTGCTGAGCAACACCGACAATGCCGCGTTTCCTCAGATGACAAAATCATATAAGAACACC

CGAAAGTCCCCAGCACTCATTGTTTGGGGGATCCACCACAGTGTAAGCACCGCCGAGCAG

ACTAAACTATACGGCAGCGGAAATAAACTTGTCACCGTCGGCTCCTCCAATTACCAACAG

TCCTTCGTCCCTTCACCGGGTGCCAGGCCCCAGGTGAACGGACAATCCGGGCGTATTGAC

TTTCACTGGCTGATGTTGAATCCAAACGACACCGTGACGTTTTCGTTCAACGGCGCATTT

ATTGCCCCCGATCGGGCGAGCTTCCTGCGGGGAAAATCCATGGGCATCCAGAGTGGGGTC

CAAGTGGACGCAAACTGTGAGGGCGACTGCTACCACTCCGGTGGAACAATCATTAGCAAT

CTTCCCTTTCAGAACATTGACTCTCGGGCCGTAGGCAAGTGTCCGCGCTACGTGAAACAG

CGCTCTCTGCTATTGGCTACAGGCATGAAGAATGTACCAGAGATACCTAAGGGACGAGGC

CTCTTTGGGGCCATCGCCGGCTTCATCGAGAATGGGTGGGAAGGCCTGATTGACGGTTGG

TATGGCTTTCGCCACCAGAATGCACAGGGTGAGGGAACGGCAGCCGATTACAAGTCCACG

CAGAGTGCCATCGATCAGATTACCGGTAAATTAAACCGGCTCATTGAGAAAACTAACCAG

CAGTTCGAACTGATCGATAATGAGTTTAATGAGGTGGAGAAGCAAATTGGCAACGTGATT

AATTGGACCAGGGACAGTATAACGGAAGTGTGGTCCTATAATGCAGAATTGCTGGTGGCC

ATGGAAAACCAGCACACGATCGATCTAGCTGATTCTGAGATGGACAAACTGTATGAGCGT

GTTAAGCGACAGCTTCGCGAAAATGCAGAGGAAGATGGCACAGGCTGCTTTGAGATATTC

CACAAATGCGACGATGACTGTATGGCTTCAATACGTAATAATACATACGACCACTCAAAA

TACCGTGAAGAGGCCATGCAAAATCGCATCCAGATCGATCCTGTGAAACTATCATCAGGC

TATAAAGACGTAATTCTTTGGTTTTCTTTCGGCGCAAGTTGCTTCATTCTTCTCGCCATT

GTGATGGGACTTGTCTTCATATGTGTGAAAAACGGAAATATGCGCTGCACCATCTGTATC

515
ATGAACACTCAAATTCTAGTCTTCGCCCTGATCGCAATCATCCCTACTAATGCCGACAAG

ATCTGTCTGGGACACCACGCAGTTTCAAACGGGACAAAGGTGAACACCCTGACCGAGCGG

GGGGTAGAAGTGGTTAACGCAACTGAGACCGTGGAACGTACCAATATACCCAGGATATGT

AGCAAGGGTAAAAAGACTGTCGATCTCGGTCAGTGTGGACTCCTGGGAACCATCACCGGA

CCTCCCCAGTGTGATCAGTTCCTGGAGTTCAGCGCAGATTTAATCATCGAACGTCGCGAA

GGATCCGACGTCTGCTATCCGGGTAAGTTTGTAAACGAGGAGGCTCTGAGACAAATCCTC

AGAGAAAGTGGGGGCATAGACAAGGAGGCAATGGGGTTCACTTATTCTGGGATTAGGACA

AATGGCGCCACTAGCGCTTGCCGCCGAAGTGGCAGTTCCTTCTACGCCGAGATGAAGTGG

TTGCTTAGCAATACTGATAATGCTGCTTTCCCCCAGATGACGAAGTCTTACAAAAATACT

CGTAAGAGCCCCGCGCTGATCGTGTGGGGGATCCACCACAGTGTGAGCACTGCCGAGCAA

ACCAAGCTGTATGGGTCTGGGAATAAATTAGTGACCGTGGGCTCTAGTAACTACCAGCAG

TCATTCGTTCCAAGTCCCGGCGCACGGCCTCAGGTTAATGGCCAGTCTGGCCGGATTGAC

TTTCATTGGCTCATGCTGAATCCCAATGACACGGTGACATTCTCCTTTAACGGAGCATTT

ATCGCACCAGACAGGGCTTCCTTCCTTCGCGGAAAATCCATGGGAATTCAGAGCGGGGTC

CAGGTCGATGCTAATTGTGAAGGGGATTGTTACCACTCTGGAGGCACAATTATTAGCAAT

CTGCCCTTCCAAAACATCGACTCCCGTGCTGTGGGCAAATGTCCACGCTACGTCAAGCAG

AGATCATTACTTCTTGCTACAGGTATGAAAAACGTGCCGGAAATCCCTAAGGGGAGAGGA

CTTTTCGGTGCCATAGCTGGATTCATAGAGAACGGATGGGAAGGGCTCATTGACGGCTGG

TATGGCTTCAGACATCAGAACGCTCAGGGAGAGGGAACTGCTGCTGACTACAAGAGTACC

CAGTCAGCTATCGACCAGATTACTGGGAAATTGAACCGCCTGATTGAAAAGACTAACCAG

CAGTTCGAGCTCATCGACAATGAATTCAATGAAGTGGAGAAGCAGATCGGTAATGTCATC

AATTGGACTCGGGATTCAATTACAGAGGTGTGGTCTTACAATGCAGAGCTGCTGGTTGCC

ATGGAAAACCAGCATACCATTGACCTGGCAGACAGTGAAATGGATAAACTGTACGAGAGG

GTTAAACGGCAATTGCGCGAAAATGCCGAGGAAGACGGGACAGGATGTTTTGAGATCTTT

CATAAATGCGATGACGACTGTATGGCTTCGATTCGAAACAATACTTACGACCACTCAAAG

TATAGAGAAGAAGCAATGCAGAACCGGATTCAAATCGACCCTGTTAAGCTGTCATCCGGC

TATAAGGATGTAATTCTCTGGTTCAGCTTTGGTGCATCATGTTTTATACTCCTCGCCATC

GTGATGGGCCTTGTATTCATCTGCGTCAAGAACGGGAATATGAGATGCACCATTTGTATT

516
ATGAACACACAGATCCTCGTTTTTGCCTTGATCGCAATCATCCCAACAAACGCAGACAAA

ATCTGTCTGGGTCACCACGCCGTCAGTAACGGGACTAAGGTGAACACCCTCACGGAGGGG

GGAGTCGAGGTCGTGAATGCTACTGAGACCGTGGAGCGTACCAACATCCCCAGGATTTGC

AGCAAAGGAAAGCGGACCGTAGACCTCGGGCAATGTGGGCTGTTAGGCACAATCACTGGC

CCTCCCCAGTGTGACCAGTTTCTTGAGTTCTCTGCTGACTTAATCATCGAGCGTCGAGAA

GGGTCAGATGTCTGCTATCCTGGCAAATTTGTGAATGAGGAAGCACTTCGGCAGATTTTG

AGAGAATCGGGCGGCATCGATAAGGAGGCTATGGGCTTCACCTACTCTGGGATTAGGACC

AATGGGGCCACCAGTGCCTGTAGGCGCTCAGGCAGTTCCTTTTACGCTGAGATGAAGTGG

CTACTGAGTAATACGGATAACGCCGCCTTCCCTCAGATGACTAAGAGCTACAAGAACACC

AGAAAATCTCCTGCCTTGATAGTGTGGGGAATACACCACAGCGTATCCACCGCAGAACAA

ACCAAGTTGTATGGGAGCGGAAACAAGTTGGTCACCGTTGGATCATCGAATTACCAGCAG

AGCTTTGTGCCTTCTCCCGGCGCTCGGCCCCAGGTGAACGGGCTGAGTGGTCGTATCGAC

TTCCATTGGCTTATGCTTAACCCGAATGACACCGTAACGTTCAGCTTCAATGGCGCTTTT

ATTGCACCCGACCGCGCGTCATTCCTACGCGGAAAGTCCATGGGGATCCAGTCTGGTGTG

CAGGTGGACGCCAATTGTGAGGGCGATTGCTATCACTCCGGAGGGACAATTATCTCGAAT

CTCCCGTTCCAGAACATTGACAGCCGGGCTGTCGGGAAGTGCCCGCGCTATGTGAAACAG

AGGTCCCTCCTTCTTGCAACTGGCATGAAAAACGTTCCCGAGATCCCAAAGGGCCGTGGA

CTGTTTGGAGCCATCGCTGGCTTCATAGAGAACGGCTGGGAGGGCCTGATTAATGGTTGG

TACGGCTTTAGACACCAAAATGCCCAGGGAGAAGGCACCGCCGCAGACTACAAATCGACT

CAGTCCGCAATTGATCAGATTACCGGGAAACTCAACCGGCTCATCGAAAAGACTAACCAG

CAGTTTGAATTGATTGACAACGAGTTCAATGAGGTGGAGAAGCAGATCGGGAATGTCATC

AACTGGACACGGGACTCAATAACCGAAGTGTGGTCATACAATGCGGAGCTGCTTGTCGCC

ATGGAAAATCAGCACACAATCGACCTAGCAGACTCTGAAATGGACAAGCTGTATGAGAGA

GTGAAGCGACAATTACGTGAAAATGCGGAGGAGGACGGAACTGGCTGCTTCGAGATCTTC

CACAAGTGTGATGACGATTGCATGGCCTCTATCCGCAACAACACTTACGATCATAGCAAA

TACAGGGAGGAAGCCATGCAGAACCGGATCCAGATTGATCCTGTGAAGCTGTCTAGTGGC

TATAAAGACGTAATCCTCTGGTTCAGCTTCGGCGCAAGCTGCTTCATCCTTCTCGCCATA

GTGATGGGCTTAGTGTTTATATGCGTGAAGAACGGGAACATGCGCTGTACCATTTGTATC

517
ATGAATACTCAAATCCTCGTCTTTGCACTCATAGCAATTATCCCTACCAACGCTGATAAG

ATTTGTTTGGGGCATCACGCCGTCTCCAACGGGACTAAGGTAAATACATTGACGGAAAGA

GGGGTGGAAGTTGTGAATGCCACTGAGACTGTGGAGCGGACCAACATCCCCCGTATATGT

TCAAAAGGAAAACGCACAGTCGACTTGGGTCAGTGCGGACTCCTGGGGACTATTACCGGG

CCACCTCAGTGCGACCAATTTCTGGAATTCAGCGCGGACCTGATCATTGAGCGCCGAGAG

GGAAGTGACGTATGCTACCCTGGGAAGTTTGTTAATGAGGAAGCACTAAGGCAAATACTG

CGGGAATCGGGCGGAATTGATAAGGAAGCTATGGGCTTCACGTACAGCGGAATTAGAACC

AACGGGGCTACGAGTGCGTGTAGACGGTCCGGTAGTTCCTTTTACGCCGAAATGAAATGG

CTCCTAAGCAATACGGACAACGCCGCATTTCCTCAGATCACAAAATCATACAAGAACACT

AGGAAGAGTCCCGCCCTTATTGTGTGGGGAATTCATCACAGTGTGAGTACTGCCGAACAG

ACTAAGCTCTATGGCTCAGGAAATAAGCTCGTCACCGTTGGGTCCAGTAACTATCAGCAG

TCTTTTGTCCCGTCACCTGGGGCCAGACCTCAAGTCAACGGCTTGAGTGGACGTATCGAT

TTTCATTGGCTGATGCTGAACCCAAATGACACTGTCACTTTTAGCTTCAATGGGGCTTTT

ATCGCTCCAGATCGGGCATCCTTCCTGCGTGGGAAATCCATGGGAATTCAATCAGGTGTC

CAGGTGGATGCTAATTGCGAGGGGGACTGCTATCACTCAGGGGGGACTATTATATCCAAT

CTGCCCTTTCAGAACATCGATTCCAGGGCGGTGGGCAAATGTCCTAGATATGTAAAACAG

AGGTCTCTGCTTCTGGCGACAGGCATGAAGAATGTTCCTGAAATCCCCAAGGGCAGGGGC

CTGTTCGGGGCCATTGCAGGCTTTATCGAGAACGGCTGGGAGGGGCTAATCGACGGCTGG

TACGGCTTTCGACATCAGAACGCTCAGGGTGAAGGCACGGCTGCCGATTATAAGTCGACG

CAGTCAGCCATTGATCAAATCACTGGCAAACTTAATCGCCTCATAGAGAAGACCAATCAG

CAGTTTGAACTCATCGATAACGAGTTCAACGAGGTGGAAAAACAAATTGGTAACGTCATC

AATTGGACCAGGGACAGTATTACAGAGGTTTGGTCCTACAACGCCGAATTGTTGGTGGCA

ATGGAAAATCAGCATACTATCGACCTGGCTGACAGCGAAATGGACAAGCTCTATGAACGG

GTAAAGAGGCAGTTACGGGAGAACGCTGAGGAGGACGGCACTGGGTGTTTCGAGATCTTT

CATAAATGCGATGATGACTGCATGGCTTCTATCCGTAATAACACGTATGATCACTCCAAG

TATCGGGAAGAGGCCATGCAGAACCGGATCCAAATCGATCCCGTAAAGTTGTCATCCGGC

TACAAAGACGTAATTTTGTGGTTTTCTTTCGGAGCTTCCTGTTTCATACTGCTAGCTATC

GTAATGGGGTTGGTGTTCATCTGCGTGAAGAATGGAAACATGAGGTGTACCATCTGTATC

518
ATGAACACCCAGATCCTCGTCTTCGCTCTAATCGCCATAATCCCCACTAATGCCGACAAA

ATTTGTCTCGGACACCACGCCGTTAGCAACGGGACAAAAGTTAACACACTTACTGAGAGA

GGGGTCGAGGTTGTAAATGCTACAGAAACCGTGGAGAGGACTAATATTCCAAGAATTTGT

TCAAAGGGAAAAAAGACAGTGGATCTTGGCCAGTGCGGGCTGCTGGGGACAATCACAGGA

CCACCCCAGTGCGACCAATTTCTGGAATTCTCTGCAGACCTGATTATTGAACGCCGTGAG

GGGAGTGACGTTTGCTATCCCGGGAAGTTTGTTAACGAAGAGGCTCTTAGACAAATCCTC

CGCGAATCTGGGGGGATCGATAAAGAGGCCATGGGGTTTACCTACTCCGGCATTAGGACT

AATGGAGCTACCTCCGCCTGTAGGAGGTCTGGAAGCTCATTTTACGCAGAAATGAAATGG

TTGCTCAGCAACACCGACAATGCAGCGTTTCCGCAAATGACCAAGAGTTACAAGAACACC

CGAAAGTCTCCTGCGTTGATTGTGTGGGGCATTCACCATTCAGTTTCCACTGCAGAGCAG

ACAAAACTGTACGGTTCAGGAAACAAGCTGGTAACCGTGGGATCTTCCAACTATCAGCAG

AGCTTCGTGCCCTCGCCCGGAGCCCGCCCTCAGGTGAACGGACAGAGTGGAAGGATCGAC

TTCCACTGGCTGATGTTGAATCCCAACGATACCGTGACTTTCTCTTTCAACGGTGCATTT

ATAGCCCCTGACCGCGCTTCCTTTCTCCGAGGAAAAAGCATGGGCATCCAGTCTGGAGTG

CAGGTTGACGCAAATTGCGAAGGCGACTGTTACCATAGTGGCGGCACAATAATTTCTAAC

CTTCCCTTTCAAAATATTGACAGCCGCGCAGTAGGTAAGTGTCCTAGATACGTGAAGCAG

AGGAGCCTACTGCTCGCCACTGGCATGAAAAATGTGCCGGAGATCCCTAAGGGCAGAGGG

CTGTTCGGCGCCATCGCCGGCTTCATCGAAAATGGATGGGAGGGGTTGATAGACGGTTGG

TACGGCTTCCGGCATCAGAACGCCCAGGGTGAGGGGACCGCCGCTGATTATAAAAGTACC

CAGTCTGCTATCGATCAGATCACCGGGAAGCTCAACCGTCTTATTGAGAAGACCAATCAG

CAATTCGAACTCATCGACAACGAGTTTAACGAGGTTGAAAAGCAAATTGGAAATGTGATT

AATTGGACACGGGATTCAATAACCGAAGTCTGGTCGTACAACGCAGAGCTACTTGTGGCA

ATGGAGAACCAGCACACCATAGACCTTGCCGACTCCGAAATGGATAAGTTGTATGAAAGA

GTGAAACGCCAGCTGCGGGAGAATGCCGAGGAAGATGGGACAGGATGTTTTGAGATCTTT

CACAAGTGCGACGATGATTGCATGGCCTCCATTCGAAACAATACTTATGACCATAGCAAA

TACAGAGAGGAGGCCATGCAGAACCGGATTCAAATCGATCCTGTTAAGTTATCTTCAGGT

TACAAGGATGTCATCCTTTGGTTCTCGTTTGGAGCCAGCTGCTTCATATTGCTGGCTATC

GTGATGGGTCTGGTGTTTATCTGCGTTAAGAACGGCAATATGAGATGTACGATCTGTATT

519
ATGAACACTCAGATTCTGGTCTTTGCCCTGATTGCTATCATCCCAACCAACGCAGACAAG

ATCTGTCTGGGACACCATGCCGTATCTAACGGAACCAAGGTTAACACGTTGACCGAGCGC

GGCGTTGAAGTCGTCAATGCCACTGAGACCGTGGAGCGAACAAACATTCCCAGAATCTGT

AGCAAGGGCAAACGGACTGTGGACCTGGGCCAGTGTGGGTTGTTGGGAACAATCACAGGA

CCTCCACAGTGTGATCAGTTCCTGGAGTTTAGTGCAGACCTTATCATCGAACGCAGAGAA

GGTTCCGACGTCTGTTACCCTGGGAAATTTGTAAATGAGGAGGCCTTGAGACAGATCCTT

AGGGAATCTGGAGGAATCGACAAGGAGGCCATGGGCTTTACCTATAGCGGAATAAGGACC

AATGGCGCCACTTCCGCCTGTAGGAGAAGCGGTTCATCATTCTATGCAGAGATGAAGTGG

TTGTTAAGTAACACGGATAATGCTGCGTTTCCACAGATGACCAAGTCCTACAAGAATACC

CGAAAATCCCCCGCACTCATTGTCTGGGGAATACACCACAGCGTCTCAACAGCTGAGCAA

ACAAAACTCTATGGATCCGGGAATAAGCTCGTGACCGTAGGCTCATCAAACTACCAGCAG

TCGTTCGTGCCATCTCCAGGGGCCCGGCCTCAGGTCAACGGTCTGTCAGGACGCATTGAT

TTTCACTGGCTGATGCTTAATCCCAACGATACCGTCACATTCTCCTTCAATGGGGCGTTT

ATTGCGCCTGACAGAGCTAGCTTTTTGCGAGGTAAGTCTATGGGCATACAGTCTGGGGTG

CAAGTGGACGCGAATTGCGAGGGGGACTGCTATCATTCCGGAGGCACCATCATCTCCAAC

CTCCCATTTCAAAATATCGACAGTAGGGCGGTGGGGAAGTGCCCCCGTTACGTAAAACAG

CGCTCCCTCCTGCTGGCCACAGGGATGAAGAATGTTCCAGAAATACCAAAAGGAAGGGGT

CTGTTTGGTGCCATCGCAGGCTTCATCGAAAACGGATGGGAGGGGCTGATTGATGGTTGG

TACGGATTTAGACACCAGAATGCCCAGGGCGAAGGAACTGCCGCTGATTATAAGAGCACA

CAGTCAGCTATAGACCAGATCACTGGGAAGCTAAACAGAATCATTGAAAAGACGAACCAG

CAGTTCGAACTAATCGACAATGAGTTCAACGAGGTGGAAAAGCAGATTGGGAACGTGATA

AATTGGACACGCGACTCCATAACGGAAGTGTGGAGCTACAATGCGGAGCTGCTGGTGGCT

ATGGAGAATCAGCACACCATCGACCTTGCGGATAGTGAAATGGATAAACTCTACGAGCGT

GTTAAGCGGCAATTGCGGGAGAACGCCGAGGAGGATGGGACCGGGTGCTTCGAGATTTTC

CACAAATGTGATGATGACTGTATGGCCTCCATACGCAATAATACCTACGACCATAGCAAA

TATCGGGAGGAAGCCATGCAGAACCGAATCCAAATAGACCCAGTGAAGCTGAGTTCCGGC

TATAAAGATGTGATTCTCTGGTTTAGCTTTGGAGCAAGCTGTTTTATCCTGTTAGCGATT

GTGATGGGTTTAGTGTTCATTTGTGTGAAAAACGGTAACATGCGATGCACCATTTGTATC

520
ATGAATACCCAGATCCTTGTCTTTGCCCTGATAGCCATTATTCCCACCAACGCAGATAAA

ATTTGCCTCGGGCACCACGCTGTGAGCAACGGCACAAAGGTGAATACTCTGACAGAACGG

GGTGTAGAGGTGGTTAATGCAACAGAGACAGTGGAGCGCACAAACATCCCCAGAATCTGC

TCTAAGGGCAAGCGGACTGTGGATTTAGGGCAATGTGGACTGCTAGGTACTATCACCGGG

CCTCCACAGTGTGACCAGTTTTTGGAGTTCTCTGCCGATCTTATCATCGAGCGTCGAGAG

GGGAGTGATGTGTGCTACCCAGGCAAATTTGTGAACGAGGAAGCCCTTCGGCAGATCCTG

AGAGAGTCCGGCGGCATCGACAAAGAGGCCATGGGTTTTACCTATTCAGGAATCCGAACC

AACGGAGCCACCTCCGCCTGTAGGCGGAGTGGGTCTAGCTTTTATGCAGAAATGAAATGG

TTGCTGTCCAACACCGATAATGCAGCTTTCCCACAGATAACAAAGTCTTACAAAAATACG

CGCAAGTCCCCAGCGCTAATTGTGTGGGGCATTCATCACAGCGTGTCTACTGCGGAGCAG

ACCAAGCTGTACGGGAGCGGGAATAAATTGGTCACAGTCGGGAGCTCGAACTACCAGCAA

AGCTTCGTTCCTAGCCCCGGGGCAAGGCCTCAGGTGAACGGACTGAGCGGCAGAATTGAC

TTCCACTGGTTGATGCTTAATCCTAACGATACAGTGACCTTTAGCTTCAATGGAGCGTTC

ATTGCCCCTGATCGCGCCTCCTTTCTCCGGGGGAAAAGTATGGGGATTCAATCCGGGGTG

CAGGTTGACGCTAATTGTGAGGGTGATTGCTACCACTCCGGGGGCACCATTATAAGCAAT

TTACCGTTTCAGAATATTGACTCTCGAGCCGTGGGGAAATGTCCCCGGTACGTCAAGCAA

AGGTCTTTGCTGCTGGCTACCGGCATGAAAAACGTACCCGAGATCCCAAAAGGACGCGGC

CTCTTCGGTGCAATCGCCGGCTTTATAGAGAATGGATGGGAAGGGCTTATTGACGGGTGG

TATGGGTTCCGCCATCAGAATGCGCAAGGCGAAGGAACTGCCGCCGATTACAAGAGTACA

CAGTCCGCCATCGATCAAATTACTGGCAAACTAAATAGACTCATCGAGAAGACAAACCAG

CAGTTTGAACTCATTGACAACGAATTCAACGAGGTAGAGAAACAGATTGGCAACGTCATC

AATTGGACACGGGACAGTATCACAGAAGTCTGGTCCTACAACGCAGAGCTTCTCGTTGCT

ATGGAAAATCAGCACACCATTGACCTGGCTGACTCCGAGATGGACAAGTTGTATGAGCGT

GTGAAAAGGCAGTTGCGTGAAAACGCCGAGGAAGACGGCACAGGTTGTTTTGAGATCTTT

CACAAATGCGACGACGATTGTATGGCAAGCATAAGAAACAATACTTATGACCACAGTAAA

TATCGAGAGGAAGCCATGCAGAACAGAATCCAAATCGACCCTGTGAAACTAAGCTCAGGC

TACAAGGACGTGATCCTCTGGTTCTCCTTTGGTGCTTCCTGCTTTATTCTCCTTGCCATC

GTCATGGGCCTCGTGTTCATCTGCGTTAAGAACGGTAATATGCGGTGTACTATTTGTATC

521
ATGAATACCCAGATTCTCGTTTTTGCCCTAATAGCTATCATTCCTACAAATGCCGATAAA

ATTTGCTTGGGCCATCATGCCGTGAGCAACGGGACTAAGGTTAACACCCTGACTGAGCGG

GGCGTAGAGGTGGTTAACGCCACAGAGACAGTGGAACGGACGAACATTCCAAGAATTTGT

TCAAAGGGCAAGAAAACGGTGGACCTCGGGCAATGTGGTCTGCTAGGCACTATAACAGGA

CCTCCTCAGTGCGATCAGTTTCTGGAATTCAGTGCAGATCTGATCATCGAGCGTCGAGAG

GGATCAGATGTCTGTTATCCTGGGAAGTTCGTCAATGAGGAGGCACTGAGACAGATACTC

AGAGAGAGCGGAGGCATTGATAAGGAAGCTATGGGTTTTACCTATTCTGGTATTAGAACT

AACGGAGCCACAAGTGCCTGTCGTCGGTCGGGCTCTTCGTTTTACGCTGAGATGAAGTGG

CTGCTGAGTAATACTGACAATGCAGCGTTCCCCCAGATGACTAAGAGTTATAAAAACACC

CGTAAAAGCCCAGCACTGATCGTGTGGGGAATTCATCATTCAGTCTCTACAGCCGAGCAG

ACCAAGCTCTACGGGTCTGGCAACAAGCTCGTTACAGTAGGATCTAGCAACTATCAACAG

AGCTTTGTACCATCCCCTGGAGCTCGTCCACAAGTGAACGGTCAGTCGGGCCGTATCGAC

TTTCACTGGCTGATGCTGAATCCTAATGACACGGTGACTTTCAGTTTCAATGGAGCCTTC

ATCGCACCAGACCGCGCAAGCTTTCTACGCGGGAAGAGTATGGGGATTCAGTCCGGCGTT

CAAGTGGACGCCAATTGCGAAGGGGACTGTTACCATAGGGGGGGCACCATCATTAGTAAC

CTCCCATTTCAAAACATCGATTCTCGCGCCGTGGGGAAATGTCCTAGATACGTGAAACAG

CGCAGCCTGCTCCTCGCAACTGGCATGAAGAATGTTCCAGAGATTCCGAAGGGGCGGGGT

CTCTTTGGCGCCATCGCCGGGTTCATCGAAAACGGGTGGGAGGGACTGATCGATGGCTGG

TATGGCTTCCGACATCAAAACGCACAGGGTGAGGGCACAGCTGCCGATTATAAATCCACG

CAGAGCGCAATCGATCAGATCACCGGCAAACTGAACAGGCTGATCGAGAAAACTAATCAG

CAGTTCGAGCTTATCGATAATGAATTCAATGAAGTGGAGAAGCAGATTGGGAATGTGATT

AATTGGACTCGGGACTCTATTACTGAAGTGTGGAGTTACAACGCCGAGCTCTTGGTTGCT

ATGGAGAATCAGCATACAATTGACTTGGCAGATTCCGAGATGGATAAGCTCTACGAGCGT

GTCAAGCGGCAACTGAGAGAGAACGCCGAAGAGGATGGGACGGGGTGCTTCGAGATTTTC

CATAAGTGCGACGATGATTGTATGGCCAGTATCAGAAATAATACATATGACCATAGCAAA

TACAGAGAGGAAGCAATGCAGAACCGGATCCAGATTGATCCGGTGAAGCTCTCTAGCGGA

TATAAGGATGTTATCCTGTGGTTTTCTTTTGGAGCCTCCTGTTTCATTCTGCTGGCCATT

GTAATGGGACTAGTCTTCATATGTGTAAAAAACGGCAATATGAGGTGCACTATTTGTATT

522
ATGAACACACAGATCCTGGTATTCGCGCTCATCGCAATTATACCAACAAATGCCGATAAG

ATATGCTTGGGACATCACGCCGTATCCAACGGTACCAAAGTGAATACACTGACCGAACGT

GGCGTAGAGGTGGTGAACGCCACTGAGACGGTTGAGCGCACCAACATCCCCCGCATCTGC

TCCAAGGGAAAACGCACCGTCGACCTGGGACAGTGTGGGCTGCTCGGCACAATCACGGGT

CCTCCTCAGTGTGACCAATTCTTGGAGTTCAGCGCAGATCTAATTATAGAGAGGCGGGAG

GGAAGCGATGTGTGCTATCCTGGCAAATTTGTCAACGAGGAAGCCCTTCGCCAGATTCTT

CGGGAGTCCGGCGGAATCGATAAAGAGGCTATGGGGTTTACATATAGTGGAATCCGCACC

AATGGCGCCACGTCGGCCTGTAGGAGGAGCGGATCCAGTTTCTATGCCGAGATGAAATGG

CTCCTCAGTAATACTGATAATGCTGCGTTCCCCCAGATAACCAAATCGTACAAAAATACA

CGGAAGTCTCCCGCGCTGATTGTATGGGGCATACACCACTCCGTATCGACTGCCGAACAG

ACTAAGCTCTACGGCTCTGGGAACAAGTTAGTGACCGTCGGCTCGAGCAATTACCAGCAG

AGTTTTGTCCCATCACCAGGGGCAAGACCTCAGGTGAACGGGCTTTCAGGGAGGATTGAC

TTCCACTGGCTGATGCTGAACCCAAATGACACTGTCACCTTTTCGTTCAACGGGGCATTT

ATCGCCCCAGACAGGGCCTCATTCCTTAGAGGCAAATCTATGGGCATTCAAAGCGGGGTT

CAGGTGGACGCGAACTGTGAGGGCGACTGTTATCATAGCGGTGGCACTATTATCTCCAAC

CTGCCCTTTCAGAATATAGACAGTAGAGCCGTGGGTAAGTGCCCACGGTATGTGAAGCAA

AGGTCCCTGCTCCTCGCTACGGGGATGAAGAATGTGCCAGAGATTCCTAAGGGTCGCGGC

CTGTTCGGAGCAATAGCGGGTTTTATAGAAAATGGTTGGGAAGGATTAATAGATGGGTGG

TACGGGTTTAGGCACCAGAATGCTCAGGGAGAGGGTACGGCAGCTGATTATAAGTCTACA

CAATCTGCCATCGACCAGATCACCGGAAAGCTCAACAGACTTATCGAAAAAACTAACCAG

CAGTTCGAATTGATCGACAATGAATTTAATGAAGTGGAGAAGCAGATAGGTAACGTGATT

AACTGGACTCGGGACTCAATCACTGAAGTTTGGAGTTACAACGCAGAGCTCCTGGTCGCC

ATGGAGAACCAGCATACCATAGATCTCGCTGACAGTGAGATGGACAAACTGTACGAAAGA

GTGAAGCGTCAGCTCAGAGAGAATGCGGAGGAAGATGGGACCGGATGCTTCGAAATTTTT

CACAAGTGTGACGACGACTGTATGGCCAGCATAAGGAATAACACTTATGATCATTCTAAG

TATCGTGAGGAGGCAATGCAGAACAGGATTCAAATTGATCCGGTTAAGCTTTCTTCAGGA

TACAAGGACGTCATTCTGTGGTTCTCCTTCGGGGCATCTTGCTTTATTTTACTTGCAATC

GTGATGGGGTTAGTCTTTATCTGCGTGAAAAATGGGAACATGAGGTGTACTATCTGCATC

523
ATGAATACACAGATCCTGGTCTTTGCTCTGATCGCAATTATTCCTACGAATGCAGACAAG

ATTTGCCTTGGACACCACGCCGTATCTAACGGCACCAAAGTCAATACCCTGACCGAGCGG

GGCGTTGAAGTTGTTAATGCCACCGAAACAGTAGAACGCACTAATATACCACGCATTTGC

TCGAAAGGGAAAAAGACCGTTGACCTCGGCCAGTGCGGCCTGCTTGGCACAATCACAGGA

CCACCACAGTGTGACCAATTTCTCGAATTTTCCGCTGATCTGATAATAGAGAGGCGGGAA

GGGAGCGACGTGTGTTATCCAGGGAAGTTCGTTAACGAGGAAGCACTTAGGCAAATACTG

CGGGAAAGCGGTGGCATCGATAAAGAGGCCATGGGCTTTACCTACAGTGGTATTAGGACA

AACGGCGCGACATCCGCGTGTAGGAGAAGCGGCTCATCCTTCTACGCTGAAATGAAGTGG

CTGTTAAGTAATACCGATAATGCGGCTTTCCCGCAAATGACTAAGAGTTACAAAAACACT

AGAAAGTCTCCAGCTCTGATTGTTTGGGGGATTCATCATTCTGTGAGTACAGCCGAACAG

ACCAAGTTGTACGGCTCCGGAAACAAGCTGGTGACTGTAGGCTCTTCTAATTATCAACAG

TCTTTTGTACCTAGTCCGGGTGCCCGCCCACAGGTAAACGGGCAGTCAGGCAGAATCGAT

TTCCACTGGCTCATGCTGAATCCAAACGATACCGTCACCTTCAGTTTCAATGGAGCATTT

ATAGCACCGGACCGCGCGTCATTCCTACGGGGTAAATCCATGGGCATTCAGAGCGGGGTT

CAAGTAGATGCCAACTGTGAGGGCGACTGCTATCACTCTGGCGGTACGATCATAAGCAAC

CTTCCGTTTCAAAATATCGACAGCCGTGCTGTTGGCAAATGCCCCCGTTACGTGAAGCAG

AGAAGCCTTCTGTTGGCTACTGGAATGAAGAATGTGCCCGAGATTCCTAAGGGAAGAGGC

CTCTTCGGAGCGATCGCTGGATTTATAGAAAATGGCTGGGAAGGACTAATCGACGGCTGG

TATGGGTTTAGACACCAGAACGCACAGGGGGAGGGCACTGCTGCGGATTATAAGTCGACA

CAGTCCGCGATCGACCAGATCACCGGTAAACTCAATCGGCTCATTGAGAAGACAAACCAA

CAGTTCGAGTTGATCGATAATGAATTTAATGAAGTGGAAAAGCAGATAGGAAATGTGATC

AACTGGACACGGGACAGCATTACCGAAGTATGGAGTTACAATGCAGAGCTGCTGGTTGCT

ATGGAGAACCAGCACACGATTGATTTGGCCGATTCGGAAATGGACAAGCTTTACGAGCGG

GTGAAAAGGCAACTCCGCGAAAATGCTGAAGAGGATGGGACTGGCTGTTTCGAGATTTTT

CACAAGTGCGACGACGATTGCATGGCCAGCATAAGGAATAATACATATGACCACTCCAAA

TACAGGGAAGAAGCAATGCAGAACAGAATCCAGATCGACCCTGTGAAGTTGAGTAGTGGA

TACAAGGATGTCATCCTGTGGTTTTCTTTTGGCGCCTCATGCTTCATTCTGCTGGCAATT

GTAATGGGCCTGGTGTTCATTTGTGTGAAAAACGGAAATATGAGGTGTACAATCTGTATC

524
ATGAACACGCAAATTTTGGTCTTCGCATTGATTGCAATTATTCCTACGAACGCAGACAAG

ATCTGTCTAGGACACCACGCTGTGTCAAACGGAACAAAAGTGAACACGCTGACCGAGCGG

GGGGTCGAAGTGGTGAATGCAACTGAAACTGTAGAACGAACTAACATCCCAAGAATTTGT

AGCAAAGGAAAGAAGACAGTTGACCTGGGTCAGTGCGGACTGCTCGGTACCATCACCGGT

CCGCCGCAGTGCGACCAATTTTTAGAGTTCTCTGCAGACTTAATCATCGAGCGCAGAGAG

GGCTCAGATGTCTGCTACCCCGGTAAGTTCGTGAACGAGGAGGCGCTTCGTCAGATTCTG

CGAAAGAGTGGCGGGATCGACAAGGAGGCTATGGGCTTCACTTACTCAGGCATTCGTACG

AATGGCGCCACATCCACCTGCAGGCGGAGCGGGTCTAGTTTTTACGCCGAGATGAAGTGG

TTGTTATCGAACACCGACAATGCGGCCTTCCCCCAGATGACAAAATCATACAAAAATACG

CGCAAGTCACCCGCTATAATTGTGTGGGGCATTCACCACAGCGTCTCTACGGCCGAACAG

ACGAAATTATACGGGTCTGGGAACAAACTGGTGACAGTCGGCAGCAGTAACTACCAGCAA

TCTTTCGTGCCATCGCCAGGAGCCCGCCCGCAGGTCAATGGGTTATCTGGACGGATAGAC

TTCCATTGGCTGATGCTTAACCCAAACGACACTGTTACCTTTAGCTTCAATGGGGCTTTT

ATCGCGCCTGATAGAGCTTGCTTCCTGAGAGGAAAGTCAATGGGAATCCAGTCAGGTGTG

CAGGTGGACGCGGATTGTGAAGGTGATTGCTACCACAGTGGGGGGACAATCATTAGTAAT

CTGCCATTCCAGAATATTGATTCACGTGCAGTAGGAAAATGTCCACGATATGTTAAGCAA

AGGTCGTTGCTACTCGCTACTGGTATGAAAAACGTACCAGAAATACCTAAGGGAAGGGGA

CTATTTGGTGCAATTGCAGGGTTCATCGAGAACGGCTGGGAGGGCCTCATAGACGGATGG

TATGGTTTCCGGCACCAGAACGCACAGGGCGAAGGCACAGCAGCCGATTACAAGTCCACA

CAGAGCGCAATCGACCAGATCACAGGCAAACTCAATAGGCTCATAGAAAAGACCAATCAG

CAGTTTGAGCTCATTGACAACGAATTCAATGAAGTGGAGCGGCAGATAGGAAACGTGATA

AATTGGACCCGGGATAGCATTACGGAGGTCTGGTCCTATAACGCGGAGCTGCTGGTGGCC

ATGGAGAATCAGCACACCATTGACCTGGCCGATAGCGAAATGGATAAGCTGTATGAGCGC

GTGAAGAGGCAGCTGCGGGAGAACGCTGAAGAGGACGGCACGGGCTGTTTTGAGATTTTC

CACAAGTGTGATGACGACTGCATGGCCTCCATCCGAAACAACACCTATGACCATTCCAAA

TACCGGGAAGAGGCAATGCAAAATAGAATACAGATCGATCCTGTGAAGCTGTCCAGCGGC

TATAAAGACGTTATTCTGTGGTTCTCTTTCGGGGCATCCTGTTTTATACTCTTAGCTATC

GTTATGGGCCTGGTCTTTATTTGCGTGAAGAACGGCAACATGCGGTGCACGATTTGCATC

525
ATGAACACCCAGATCCTGGTTTTCGCTTTAATCGCGATTATACCCACAAACGCTGATAAG

ATCTGCCTTGGGCATCATGCCGTGAGTAATGGTACAAAGGTCAATACACTCACTGAGAGA

GGCGTCGAGGTCGTGAATGCTACTGAAACCGTCGAGAGAACAAATATACCCAGGATTTGC

AGTAAAGGCAAGAAAACAGTAGATCTCGGTCAGTGCGGGTTGCTCGGGACCATCACTGGG

CCACCTCAGTGCGACCAATTCTTGGAGTTTTCCGCCGACCTCATTATTGAGCGCCGGGAA

GGCAGTGACGTCTGTTACCCCGGGAAATTCGTTAATGAGGAGGCCCTGAGACAGATCCTC

CGGGAGAGCGGGGGAATTGACAAGGAGGCCATGGGGTTCACCTATTCTGGAATTAGGACT

AACGGCGCCACATCCGCGTGTCGCCGGTCTGGGTCATCTTTCTACGCCGAGATGAAATGG

TTGCTCAGCAATACCGATAACGCCGCCTTTCCTCAGATGACCAAGTCATACAAAAACACA

CGAAAGTCACCCGCACTGATAGTGTGGGGCATACACCACAGCGTTTCAACTGCCGAACAG

ACAAAATTGTACGGATCTGGCAATAAGCTGGTCACCGTGGGCTCCAGTAACTACCAGCAA

AGCTTCGTCCCCTCCCCCGGTGCTAGGCCACAAGTCAATGGCCAGTCCGGTAGAATCGAC

TTCCATTGGCTAATGCTAAACCCCAATGACACTGTGACATTTTCTTTTAACGGAGCATTC

ATCGCCCCGGATAGGGCCAGCTTTCTCAGGGGCAAATCAATGGGGATTCAGAGTGGGGTG

CAAGTTGATGCTAATTGTGAGGGTGATTGCTATCATTCAGGGGGAACCATTATCAGCAAT

TTGCCCTTCCAGAACATAGACTCACGCGCCGTCGGTAAGTGCCCTCGCTATGTCAAGCAA

AGGTCCCTGCTGCTGGCCACTGGAATGAAGAACGTGCCCGAGATCCCAAAGGGCAGGGGC

TTATTCGGGGCCATTGCAGGTTTCATCGAAAACGGCTGGGAAGGACTAATAGATGGGTGG

TACGGCTTTCGTCACCAGAACGCACAAGGGGAGGGGACAGCTGCTGATTATAAAAGTACT

CAGAGCGCTATCGACCAGATTACAGGTAAGCTGAATCGGTTAATCGAGAAGACCAACCAG

CAGTTCGAACTTATTGACAATGAGTTCAATGAGGTGGAGAAGCAGATTGGCAATGTGATT

AATTGGACGCGGGATAGTATTACCGAGGTCTGGTCCTATAACGCCGAGTTGCTAGTGGCA

ATGGAAAACCAGCACACGATAGATCTTGCAGACAGCGAAATGGATAAGTTGTACGAAAGG

GTGAAACGGCAACTAAGGGAAAACGCTGAGGAAGATGGGACAGGATGCTTCGAGATCTTC

CACAAATGTGACGATGACTGTATGGCCAGTATTAGAAATAACACATATGACCATTCCAAA

TATCGGGAAGAGGCTATGCAAAATCGCATCCAGATTGATCCCGTAAAACTCTCCTCGGGA

TACAAAGACGTGATCCTGTGGTTCTCCTTCGGAGCCTCTTGTTTCATCCTACTCGCCATC

GTTATGGGGTTAGTGTTCATCTGTGTGAAGAATGGCAATATGAGGTGTACAATCTGCATT

526
ATGAATACCCAGATCCTTGTTTTCGCCCTCATCGCCATAATTCCCACCAACGCAGATAAA

ATCTGTCTCGGCCACCACGCAGTGAGCAATGGCACTAAGGTCAATACCCTCACTGAACGA

GGTGTCGAGGTTGTCAACGCCACTGAAACGGTAGAGAGAACGAACATCCCCCGCATATGC

AGTAAAGGCAAGAAAACTGTGGATCTCGGACAGTGCGGCCTGCTGGGCACCATTACCGGC

CCGCCCCAGTGCGATCAATTCCTGGAATTTTCTGCAGACCTCATCATCGAACGTCGGGAA

GGGAGTGACGTGTGTTACCCCGGGAAATTCGTAAATGAGGAGGCTCTTCGCCAGATTCTG

AGGGAAAGTGGGGGTATTGATAAGGAAGCAATGGGCTTTACCTATTCCGGAATTAGAACC

AATGGCGCCACCTCCGCATGTAGACGGTCTGGTTCATCATTCTACGCTGAGATGAAGTGG

CTGCTGTCCAACACTGACAACGCTGCATTTCCTCAGATGACTAAAAGTTACAAAAACACT

CGCAAATCCCCTGCCCTTATTGTTTGGGGCATTCATCATAGTGTAAGTACAGCCGAACAA

ACCAAACTGTATGGCTCAGGGAATAAATTAGTTACCGTGGGTTCATCCAACTACCAGCAG

TCTTTCGTCCCTTCTCCAGGCGCTCGCCCACAAGTTAATGGGCAATCTGGGCGAATCGAT

TTCCACTGGTTGATGCTGAACCCCAACGACACCGTTACCTTCAGTTTTAACGGCGCATTT

ATTGCCCCCGACCGCGCAAGTTTTCTGAGGGGCAAATCAATGGGGATCCAATCTGGCGTC

CAGGTGGATGCCAACTGCGAAGGCGACTGTTATCATTCCGGTGGAACAATAATCTCTAAT

TTGCCGTTTCAGAACATTGATTCAAGAGCCGTGGGCAAGTGCCCACGGTACGTAAAACAG

CGCTCCTTACTCCTTGCTACAGGGATGAAGAACGTGCCGGAGATCCCTAAAGGCCGAGGA

CTCTTTGGTGCTATTGCAGGGTTTATAGAAAATGGCTGGGAGGGACTGATTGATGGGTGG

TACGGATTCCGACACCAGAATGCCCAAGGCGAGGGTACCGCTGCAGACTACAAAAGTACC

CAGAGTGCTATCGACCAGATCACCGGGAAGTTAAATCGTTTGATAGAAAAAACAAATCAA

CAATTCGAGCTGATTGACAATGAGTTCAACGAGGTGGAGAAACAAATAGGAAACGTAATC

AATTGGACTCGTGACAGTATAACCGAAGTCTGGAGCTACAATGCGGAGCTACTCGTCGCT

ATGGAAAATCAGCATACAATCGATCTGGCGGACAGCGAGATGGATAAGCTGTACGAACGC

GTGAAGAGACAACTGAGAGAAAACGCCGAGGAAGATGGCACAGGCTGCTTCGAGATTTTC

CATAAGTGCGATGACGATTGCATGGCGAGTATTAGGAATAACACATATGATCACTCAAAG

TATCGCGAGGAGGCGATGCAAAACAGGATCCAGATTGACCCCGTGAAATTGTCTTCTGGC

TACAAGGACGTGATACTCTGGTTTTCCTTCGGGGCCTCCTGTTTCATTCTGCTGGCGATT

GTGATGGGGCTGGTGTTTATATGTGTGAAAAATGGGAATATGAGATGTACTATTTGCATT

527
ATGAACACCCAGATCCTTGTGTTCGCACTGATAGCGATTATACCAACCAACGCCGACAAG

ATCTGCTTAGGGCACCACGCTGTAAGTAATGGTACTAAGGTGAATACGCTGACTGAAAGA

GGTGTGGAAGTGGTGAACGCCACAGAAACCGTAGAAAGGACCAACATCCCCAGAATCTGC

AGCAAGGGGAAGCGGACCGTAGACCTGGGACAATGTGGACTTCTGGGAACAATTACTGGC

CCTCCACAGTGCGACCAGTTCTTGGAGTTTAGCGCCGACCTCATTATCGAGCGACGGGAA

GGCAGCGATGTATGTTATCCAGGCAAATTTGTGAACGAAGAAGCTCTCAGGCAGATTCTG

CGGGAATCCGGCGGCATTGATAAAGAGGCTATGGGCTTTACCTACAGGGGGATCCGTACA

AACGGGGCAACCTCTGCCTGTCGGAGATCTGGCTCAAGCTTTTATGCCGAGATGAAATGG

CTCCTGTCTAATACTGACAATGCTGCTTTCCCACAGATGACGAAGTCCTATAAAAACACC

CGGAAGTCCCCCGCCTTAATTGTATGGGGCATCCATCATTCCGTTAGCACAGCCGAACAG

ACCAAGCTTTATGGATCTGGAAACAAGCTGGTGACCGTGGGCTCAAGTAACTATCAACAG

TCATTCGTGCCTTCACCTGGAGCCCGCCCGCAGGTCAATGGCCTTAGCGGACGGATTGAC

TTTCATTGGCTTATGCTGAATCCCAATGATACAGTGACGTTCAGCTTCAACGGCGCCTTC

ATAGCCCCCGACCGTGCCAGTTTTCTTCGGGGAAAGAGCATGGGGATCCAAAGTGGCGTG

CAGGTGGACGCCAATTGCGAAGGCGATTGCTATCATTCAGGCGGAACAATTATCAGTAAC

CTGCCGTTTCAGAATATTGACAGTCGAGCAGTTGGGAAGTGTCCAAGGTACGTGAAACAG

CGCAGCCTCCTTTTAGCCACAGGCATGAAGAATGTCCCAGAGATTCCGAAGGGCCGTGGG

CTGTTTGGTGCTATTGCAGGTTTTATCGAAAATGGCTGGGAAGGACTTATTGACGGCTGG

TATGGGTTTAGGCATCAGAATGCCCAGGGTGAAGGCACTGCCGCCGACTATAAGAGCACG

CAAAGCGCGATCGATCAGATTACTGGCAAGTTAAATAGACTGATCGAAAAAACCAACCAA

CAGTTTGAGTTGATTGATAACGAGTTTAATGAGGTCGAAAAGCAGATTGGGAACGTGATA

AACTGGACCCGGGACAGCATAACCGAAGTATGGAGCTACAATGCAGAGCTGCTTGTGGCT

ATGGAGAATCAGCACACAATCGATCTGGCAGACAGTGAGATGGACAAACTCTACGAGAGG

GTCAAGCGGCAGCTCCGGGAAAATGCCGAGGAAGATGGTACCGGATGCTTTGAGATTTTC

CATAAGTGTGACGATGATTGTATGGCCTCCATTCGCAATAACACCTATGATCACTCAAAG

TATAGGGAGGAGGCAATGCAAAATCGCATCCAGATCGACCCCGTGAAGCTTAGCTCCGGA

TATAAGGACGTGATCTTGTGGTTCTCTTTTGGTGCCTCCTGCTTCATCCTTCTGGCCATT

GTGATGGGATTGGTATTTATTTGCGTGAAGAATGGCAATATGCGATGCACAATTTGCATC

528
ATGAATACACAGATACTGGTGTTTGCGCTGATTGCCATTATTCCAACAAATGCTGATAAA

ATCTGCCTGGGGCATCACGCAGTTTCAAATGGCACCAAAGTGAACACACTTACCGAGCGA

GGCGTGGAGGTGGTGAATGCCACTGAAACAGTGGAGCGTACCAATATCCCTCGTATCTGT

AGCAAGGGTAAACGGACTGTCGATCTGGGCCAGTGTGGTTTACTGGGGACAATTACAGGC

CCCCCTCAGTGTGATCAGTTCTTAGAGTTTTCAGCTGATCTGATCATAGAACGGAGAGAA

GGCAGCGACGTGTGTTACCCTGGCAAGTTCGTGAATGAGGAGGCCCTGCGCCAAATCCTG

AGAGAGTCTGGGGGGATAGATAAAGAAGCGATGGGGTTCACTTATTCTGGCATCCGAACC

AATGGCGCTACGAGCGCATGCCGCAGATCTGGCTCTAGCTTTTACGCTGAGATGAAATGG

CTCCTCTCTAATACGGACAATGCTGCATTTCCCCAGATGACCAAATCTTACAAGAATACC

CGTAAGTCCCCAGCTCTCATCGTGTGGGGAATCCACCACTCTGTGAGTACTGCCGAGCAG

ACAAAGCTCTACGGCTCTGGAAATAAGTTGGTGACCGTAGGTTCATCCAATTATCAACAG

TCATTCGTGCCTAGTCCCGGTGCTCGGCCCCAAGTGAACGGCCTCTCCGGGAGGATTGAC

TTCCATTGGCTGATGCTGAACCCTAACGATACAGTGACATTTTCATTTAACGGCGCGTTT

ATAGCTCCTGACCGAGCTTCCTTTCTCCGAGGTAAGAGCATGGGCATCCAGAGTGGGGTA

CAAGTCGATGCGAATTGCGAGGGCGATTGTTACCACAGTGGTGGCACTATCATTTCCAAC

CTTCCTTTTCAGAACATTGACTCACGGGCGGTCGGCAAATGTCCTCGCTACGTGAAGCAA

AGGTCCCTTCTGCTGGCCACAGGGATGAAAAACGTGCCTGAGATCCCCAAGGGGGGGGGT

CTCTTTGGGGCCATCGCAGGATTTATAGAAAATGGGTGGGAGGGACTCATTAATGGCTGG

TACGGATTTAGACACCAGAACGCCCAAGGGGAGGGCACTGCCGCCGATTATAAATCCACT

CAGAGCGCTATCGATCAAATAACAGGTAAACTGAATCGGTTAATTGAGAAAACCAATCAA

CAGTTTGAACTGATAGATAACGAGTTTAATGAAGTGGAGAAGCAGATTGGAAACGTGATC

AACTGGACCAGAGACTCCATTACTGAGGTTTGGTCGTATAACGCGGAGCTGCTCGTCGCT

ATGGAGAATCAACATACCATCGACCTGGCTGATAGTGAGATGGACAAGCTGTACGAGCGC

GTTAAAAGACAGCTGCGTGAGAACGCTGAAGAGGATGGTACAGGATGTTTTGAGATCTTT

CACAAGTGTGATGACGACTGCATGGCTAGTATCCGAAACAATACATACGACCACAGCAAA

TATAGAGAAGAGGCCATGCAAAATCGTATACAAATTGATCCCGTGAAACTATCCTCCGGC

TACAAGGATGTGATCTTGTGGTTTTCCTTTGGCGCATCTTGCTTCATCCTGCTGGCAATT

GTAATGGGATTGGTCTTTATCTGCGTGAAGAACGGCAATATGCGGTGTACTATCTGCATC

529
ATGAACACTCAGATCCTCGTGTTTGCCTTGATCGCCATCATACCAACGAATGCAGATAAG

ATCTGCCTGGGACACCATGCTGTATCAAATGGCACTAAGGTGAACACCCTGACTGAGCGG

GGCGTTGAAGTGGTGAACGCCACTGAAACGGTGGAAAGGACCAATATCCCCAGAATTTGC

TCAAAGGGCAAAAAAACTGTTGACCTCGGCCAGTGCGGCCTCTTAGGGACGATAACCGGT

CCCCCTCAGTGTGATCAGTTCCTGGAGTTCTCAGCCGATCTGATCATTGAAAGAAGAGAA

GGCTCGGACGTGTGTTATCCGGGCAAGTTCGTGAACGAAGAAGCCCTGCGCCAGATCCTC

CGCGAAAGCGGGGGCATCGACAAGGAAGCCATGGGTTTCACCTACTCTGGAATTCGCACC

AACGGGGCCACTTCCGCATGCCGACGGTCCGGTTCGAGCTTTTACGCTGAGATGAAGTGG

CTTTTATCAAACACAGATAACGCGGCTTTCCCGCAGATGACCAAGTCCTATAAGAACACA

AGAAAGTCTCCGGCCCTGATTGTCTGGGGGATCCACCATAGTGTTTCTACTGCGGAGCAG

ACAAAACTTTATGGTAGCGGGAACAAACTGGTCACCGTCGGCTCCTCCAATTACCAGCAG

AGTTTTGTTCCCTCCCCCGGGGCACGACCCCAAGTCAATGGGCAAAGTGGCAGGATAGAT

TTCCACTGGTTGATGCTCAACCCCAATGACACCGTGACATTTAGCTTTAACGGAGCTTTT

ATCGCACCAGACCGGGCATCATTCCTGCGTGGCAAGAGTATGGGTATTCAAAGTGGGGTT

CAGGTAGACGCAAACTGCGAGGGCGACTGTTATCACAGTGGGGGGACCATTATCAGCAAC

CTACCGTTTCAGAATATCGATAGTAGGGCAGTGGGGAAATGCCCTCGATATGTGAAGCAA

CGGTCCCTGCTCCTGGCTACGGGAATGAAAAACGTCCCAGAGATTCCCAAGGGCCGGGGC

CTTTTCGGCGCGATTGCTGGCTTTATTGAGAATGGGTGGGAGGGATTAATCGACGGGTGG

TATGGCTTTAGGCACCAGAACGCTCAGGGCGAAGGTACGGCCGCAGATTACAAGTCCACC

CAGTCCGCCATCGACCAGATTACAGGCAAGCTCAACCGTTTAATTGAGAAAACCAATCAG

CAGTTCGAGCTCATCGATAACGAGTTCAATGAGGTGGAGAAACAGATTGGCAACGTGATA

AACTGGACTAGGGACTCAATCACAGAGGTCTGGAGCTATAATGCCGAGCTGCTAGTTGCC

ATGGAAAACCAGCATACAATCGATCTTGCCGACTCCGAAATGGACAAACTATATGAGAGA

GTCAAACGTCAGCTAAGAGAGAATGCAGAAGAGGATGGCACGGGTTGCTTCGAAATTTTC

CACAAGTGTGACGACGACTGCATGGCCAGCATTAGAAACAACACATACGATCATAGCAAG

TATAGGGAGGAGGCGATGCAGAACAGGATTCAGATTGATCCCGTCAAGCTCTCTTCTGGC

TATAAGGATGTCATTCTGTGGTTTTCTTTCGGCGCCTCATGTTTCATCCTGCTTGCAATC

GTGATGGGATTAGTTTTCATTTGTGTAAAGAACGGCAATATGCGGTGTACAATCTGCATC

530
ATGAATACTCAAATCCTGGTCTTCGCCCTTATTGCGATCATACCTACCAACGCCGATAAG

ATCTGCTTGGGGCACCATGCCGTCTCAAACGGCACCAAGGTCAACACTCTTACAGAACGG

GGTGTAGAAGTGGTTAATGCCACTGAGACTGTCGAACGAACAAACATCCCTCGAATCTGC

AGCAAAGGGAAACGGACTGTCGATCTTGGCCAGTGTGGGCTCCTGGGTACCATAACGGGG

CCTCCCCAGTGCGACCAATTCTTAGAGTTCTCGGCCGATTTAATAATAGAACGCAGAGAG

GGATCAGACGTATGTTACCCGGGCAAATTCGTCAATGAGGAGGCACTCCGGCAGATCCTG

AGGGAGAGCGGCGGAATTGACAAAGAGGCCATGGGATTCACTTATAGTGGGATTCGTACC

AATGGCGCTACAAGTGCCTGCCGTAGATCCGGGTCGAGTTTTTATGCCGAAATGAAGTGG

CTACTGTCCAATACAGATAACGCTGCGTTCCCTCAGATGACTAAGTCTTACAAGAATACC

AGGAAAAGCCCTGCCCTTATTGTGTGGGGAATTCACCATTCGGTGAGCACCGCGGAACAA

ACAAAACTGTACGGCAGTGGGAACAAGCTCGTGACGGTAGGGTCCTCTAACTACCAACAA

AGTTTCGTCCCATCCCCAGGAGCTAGACCTCAGGTGAACGGGTTAAGCGGGCGAATTGAT

TTCCATTGGCTGATGCTGAACCCCAACGACACAGTGACATTTAGCTTCAATGGCGCCTTC

ATAGCTCCAGACAGAGCTTCCTTTCTGAGAGGCAAAAGTATGGGAATTCAGTCTGGAGTC

CAAGTGGATGCCAACTGCGAGGGGGACTGTTATCATTCTGGCGGGACCATTATCTCTAAC

CTACCATTCCAGAATATAGACAGTAGGGCCGTAGGGAAGTGTCCCCGCTATGTAAAGCAG

CGGAGTCTGCTGCTGGCAACAGGTATGAAGAACGTGCCCGAAATCCCCAAGGGCCGCGGA

CTCTTTGGGGCTATCGCTGGGTTCATTGAGAACGGATGGGAAGGCCTCATCGATGGGTGG

TATGGTTTTCGTCACCAGAACGCTCAGGGGGAAGGCACCGCCGCTGACTATAAATCTACT

CAATCGGCCATCGACCAGATTACAGGGAAGCTGAATCGTCTAATCGAGAAAACCAATCAG

CAATTCGAGCTTATTGACAATGAGTTCAATGAAGTGGAGAAACAGATTGGAAATGTTATA

AACTGGACCCGGGACAGCATAACTGAGGTGTGGAGTTACAACGCGGAGCTCCTCGTTGCC

ATGGAGAACCAGCACACCATAGATCTGGCCGATAGCGAAATGGACAAGCTGTACGAGCGG

GTTAAGCGTCAACTGCGAGAGAATGCCGAAGAAGATGGCACCGGATGCTTTGAAATATTC

CACAAATGCGATGATGACTGTATGGCTTCTATACGTAATAACACTTACGATCATAGCAAG

TACCGAGAGGAGGCTATGCAAAACAGGATACAGATCGACCCCGTGAAACTTTCATCAGGC

TATAAGGACGTTATACTGTGGTTCTCGTTCGGGGCAAGTTGCTTCATTCTGCTCGCCATT

GTCATGGGCCTGGTTTTTATCTGTGTGAAGAACGGCAATATGCGGTGTACCATTTGCATC

531
ATGAATACCCAGATCTTGGTTTTCGCACTGATCGCAATTATCCCAACAAACGCAGACAAA

ATTTGTCTTGGTCATCATGCCGTTTCCAACGGGACTAAAGTTAACACCCTCACGGAACGC

GGAGTAGAGGTGGTCAACGCTACAGAAACCGTGGAGCGTACGAACATCCCTCGCATATGT

TCCAAAGGAAAGAAGACTGTCGATCTGGGACAGTGCGGCCTATTAGGGACCATCACCGGC

CCTCCTCAGTGCGATCAATTCCTTGAGTTTTCCGCGGATCTCATAATAGAGCGCAGGGAG

GGTTCCGACGTCTGTTACCCTGGCAAGTTTGTGAATGAGGAAGCCTTACGGCAAATCTTG

AGGAAGTCTGGCGGTATTGACAAGGAAGCGATGGGTTTTACTTATTCCGGCATCAGGACA

AATGGGGCTACTTCTACTTGTCGGAGGAGTGGAAGCAGCTTCTATGCCGAGATGAAGTGG

CTTCTGAGCAACACTGACAATGCCGCCTTTCCCCAGATGACAAAATCATACAAAAACACA

CGCAAATCGCCCGCAATCATTGTCTGGGGCATTCATCATTCTGTCTCAACCGCCGAGCAG

ACTAAACTCTATGGCTCAGGAAATAAATTAGTGACCGTGGGATCCAGCAATTACCAGCAA

AGTTTCGTGCCTTCCCCAGGCGCAAGACCGCAGGTTAACGGCCTCTCTGGACGCATCGAC

TTTCATTGGCTCATGCTTAACCCCAATGATACAGTGACATTCTCCTTCAATGGAGCTTTT

ATCGCTCCGGACCGTGCTTGTTTCCTTCGAGGCAAGTCCATGGGAATTCAAAGTGGCGTT

CAGGTTGACGCCGACTGCGAAGGTGACTGCTATCATAGCGGAGGCACTATCATCAGCAAT

CTTCCATTCCAGAACATTGACTCGCGAGCCGTGGGAAAGTGCCCAAGGTATGTCAAGCAG

AGGAGCCTGCTGCTGGCTACCGGCATGAAAAACGTCCCCGAAATTCCAAAAGGCCGTGGT

TTGTTTGGCGCCATTGCCGGTTTTATCGAGAACGGATGGGAGGGACTGATTGACGGCTGG

TACGGCTTCAGACACCAGAACGCGCAGGGAGAAGGGACGGCGGCCGATTATAAGAGCACT

CAGAGCGCTATCGATCAGATTACCGGTAAATTGAATAGACTGATCGAAAAGACCAACCAG

CAATTTGAACTCATTGACAATGAGTTCAACGAGGTGGAACGGCAGATAGGAAATGTCATT

AACTGGACACGAGATTCTATTACTGAGGTGTGGAGTTACAACGCGGAGCTCCTAGTCGCC

ATGGAGAACCAGCATACAATCGACCTGGCCGACAGCGAAATGGACAAGCTGTATGAAAGA

GTAAAGAGGCAGCTGCGGGAGAACGCCGAGGAGGATGGAACCGGTTGTTTTGAGATCTTT

CACAAATGCGACGATGACTGCATGGCAAGCATCCGGAACAACACTTATGACCACAGCAAG

TATAGGGAGGAGGCCATGCAGAATAGAATCCAGATCGACCCAGTCAAGTTAAGCAGTGGC

TACAAAGATGTTATCCTCTGGTTCTCTTTTGGAGCCTCATGTTTCATTCTTCTAGCAATC

GTGATGGGTCTCGTCTTTATTTGTGTCAAAAATGGAAATATGCGCTGTACCATTTGTATT

532
ATGAACACTCAGATCCTTGTCTTTGCGCTAATTGCAATTATTCCAACGAATGCAGACAAA

ATCTGCCTGGGCCATCACGCTGTTTCCAACGGAACAAAGGTGAACACACTCACGGAAAGG

GGCGTCGAAGTGGTGAATGCCACGGAGACTGTTGAGAGGACCAACATCCCCAGGATCTGT

AGCAAAGGAAAGCGGACAGTTGACCTGGGCCAGTGTGGCCTTCTTGGTACCATCACCGGA

CCTCCCCAATGCGACCAGTTTCTGGAGTTTAGCGCAGACCTTATCATCGAGCGGCGCGAG

GGGAGCGACGTCTGTTACCCGGGCAAGTTCGTAAATGAAGAGGCGCTAAGGCAGATCCTT

AGGGAATCCGGGGGTATAGACAAAGAGGCAATGGGCTTTACCTACAGCGGAATCCGGACT

AATGGCGCCACCTCCGCTTGTAGGCGTTCAGGATCTAGTTTCTACGCTGAGATGAAGTGG

TTGTTGAGTAATACCGATAATGCGGCCTTCCCTCAGATGACCAAATCCTATAAAAATACA

AGAAAAAGCCCAGCCCTGATCGTATGGGGGATCCACCATTCTGTATCTACCGCAGAACAG

ACTAAGCTCTACGGGTCTGGGTCCAAATTGGTAACTGTAGGGAGCTCTAATTATCAACAG

AGCTTTGTTCCGAGTCCTGGCGCCAGGCCCCAGGTGAACGGTCTGTCCGGGAGAATTGAT

TTTCACTGGCTCATGCTCAATCCTAATGATACGGTTACCTTCAGCTTTAATGGAGCGTTC

ATCGCACCCGATAGGGCTTCATTTTTACGTGGCAAGTCCATGGGAATCCAGTCAGGAGTC

CAGGTCGACGCTAATTGCGAGGGTGATTGCTACCACAGCGGAGGAACTATCATTTCGAAC

CTCCCCTTTCAGAATATTGATTCTAGGGCCGTCGGTAAATGTCCAAGATATGTGAAGCAA

AGGTCTTTGCTACTCGCCACTGGAATGAAAAACGTGCCTGAAATCCCTAAAGGCCGGGGC

CTGTTTGGCGCAATCGCTGGATTTATCGAGAATGGTTGGGAGGGACTGATTGACGGCTGG

TATGGATTCCGGCACCAAAACGCTCAGGGGGAAGGCACTGCTGCCGATTACAAGTCCACT

CAATCCGCGATTGACCAAATAACCGGTAAGCTGAATAGGCTGATCGAGAAGACAAATCAG

CAGTTTGAGCTCATCGATAACGAGTTTAATGAAGTAGAAAAGCAGATTGGGAACGTTATT

AATTGGACAAGAGATAGTATAACCGAGGTGTGGAGCTATAATGCGGAGCTCCTGGTGGCC

ATGGAAAATCAGCATACAATAGACCTCGCCGATAGCGAAATGGATAAATTATACGAGAGA

GTGAAGCGGCAGCTGAGGGAAAACGCTGAGGAGGACGGAACTGGCTGTTTTGAGATCTTT

CATAAGTGCGATGATGACTGTATGGCCAGCATTCGGAACAACACCTACGATCATTCTAAG

TATAGGGAGGAGGCAATGCAGAACCGAATCCAAATAGATCCTGTTAAGCTGTCTAGCGGA

TATAAAGACGTGATACTTTGGTTCAGCTTCGGGGCCAGCTGTTTCATTCTGCTTGCTATC

GTCATGGGACTTGTATTTATCTGCGTGAAGTCCAGAAACATGAGGTGCACTATATGTATC

533
ATGAACACTCAAATCCTGGTGTTCGCGCTGATCGCCATCATACCTACCAATGCTGACAAA

ATCTGCTTGGGCCACCACGCCGTTAGCAATGGAACCAAAGTGAACACGTTGACGGAAAGA

GGAGTGGAGGTGGTGAATGCCACGGAAACAGTGGAGCGGACAAACATCCCCCGGATCTGT

AGTAAAGGGAAAAAGACGGTTGATCTCGGCCAGTGCGGCCTCCTGGGGACAATAACCGGG

CCTCCTCAATGTGACCAGTTCCTGGAATTCTCAGCCGATTTAATCATAGAGCGGCGGGAG

GGGAGTGATGTGTGTTATCCAGGGAAATTCGTGAATGAAGAAGCCTTGAGACAGATCCTT

CGCGAAAGTGGAGGAATCGACAAGGAGGCCATGGGCTTTACTTATAGTGGAATCAGAACC

AACGGCGCCACGTCCGCATGCCGACGCAGCGGTTCTAGCTTCTATGCCGAAATGAAGTGG

CTGCTCTCCAATACCGATAATGCAGCCTTCCCCCAAATGACGAAATCTTACAAGAATACC

CGCAAAAGTCCTGCTTTGATTGTCTGGGGCATCCACCACAGCGTCTCTACTGCCGAACAA

ACAAAGTTATACGGATCAGGCAACAAACTGGTCACCGTAGGTTCCAGCAACTACCAACAG

TCATTTGTCCCGAGCCCTGGAGCCCGCCCACAGGTGAAGGGGCAGTCCGGCCGAATTGAC

TTTCACTGGCTGATGCTCAACCCGAACGATACTGTGACCTTCAGCTTCAATGGCGCGTTC

ATTGCACCTGACCGTGCATCATTCTTGAGGGGCAAAAGCATGGGGATCCAGTCTGGAGTC

CAGGTCGACGCAAATTGCGAAGGAGATTGTTATCACAGCGGGGGCACGATTATCTCAAAT

CTCCCCTTTCAAAATATAGATAGCCGAGCAGTTGGCAAATGCCCTCGCTACGTGAAACAA

AGGAGCCTGCTCCTGGCTACCGGGATGAAGAACGTACCTGAAATCCCCAAGGGACGCGGA

CTTTTCGGCGCTATTGCTGGGTTCATAGAAAACGGCTGGGAAGGGTTGATCGACGGCTGG

TATGGCTTCAGACACCAGAATGCTCAGGGAGAAGGCACAGCAGCCGACTACAAATCAACC

CAGTCTGCCATCGATCAGATTACAGGAAAGCTGAATCGGCTCATCGAGAAAACTAACCAG

CAGTTCGAACTCATCGACAATGAGTTTAACGAGGTCGAAAAACAGATTGGTAATGTGATC

AACTGGACTAGGGACTCCATTACAGAGGTTTGGTCCTATAATGCCGAGCTTTTGGTTGCC

ATGGAAAACCAACATACCATCGACCTGGCCGATAGCGAGATGGACAAGTTGTACGAGAGG

GTAAAAAGGCAGCTCAGAGAAAACGCCGAGGAAGATGGAACCGGTTGTTTCGAAATTTTT

CATAAGTGCGATGACGACTGTATGGCTTCAATTCGAAACAATACTTACGATCACAGCAAG

TACCGCGAAGAGGCCATGCAGAATAGGATTCAGATTGATCCTGTTAAGTTGTCATCCGGC

TATAAGGATGTAATCTTATGGTTTAGTTTCGGCGCTAGCTGCTTCATACTGCTGGCAATC

GTGATGGGGCTGGTATTTATATGCGTCAAAAATGGGAATATGCGCTGTACCATCTGCATC

534
ATGAATACTCAAATCTTGGTCTTTGCACTGATCGCCATTATTCCTACTAACGCCGATAAA

ATTTGCTTGGGTCATCACGCCGTGTCAAATGGCACTAAAGTTAATACCTTAACAGAGCGC

GGAGTAGAGGTGGTGAATGCAACGGAGACTGTTGAGCGGACCAATATACCCCGCATTTGT

AGTAAAGGCAAGAAAACAGTGGACCTGGGCCAATGCGGGTTGCTTGGGACGATCACCGGC

CCCCCGCAGTGCGATCAGTTCTTAGAATTCTCCGCTGACCTAATCATCGAAAGACGGGAG

GGCAGCGATGTGTGTTATCCTGGCAAATTCGTCAACGAGGAAGCCCTCAGGCAGATTCTT

CGCAAGTCAGGGGGTATTGATAAGGAGGCGATGGGATTCACATACTCCGGAATTCGAACA

AACGGCGCTACAAGTACTTGTAGGAGGAGCGGGAGTTCATTCTACGCAGAGATGAAGTGG

CTGCTCAGCAACACCGACAACGCAGCGTTCCCACAGATGACCAAAAGCTATAAAAATACC

CGAAAGAGTCCCGCAATCATCGTATGGGGAATTCATCACAGTGTCTCTACCGCTGAGCAG

ACCAAGTTGTATGGCTCCGGCAACAAGCTCGTTACCGTTGGCAGCTCAAATTACCAACAG

TCCTTCGTCCCCTCCCCAGGGGCAAGGCCCCAAGTCAACGGCCTGTCCGGCAGAATTGAC

TTCCACTGGCTCATGCTAAACCCCAATGATACGGTCACCTTCAGTTTTAATGGGGCATTC

ATCGCACCCGACAGAGCCTGTTTTCTGCGAGGTAAATCAATGGGTATACAATCCGGGGTC

CAGGTCGACGCTGACTGCGAGGGCGACTGCTATCATTCGGGAGGCACCATTATTTCCAAC

CTGCCTTTCCAGAACATTGATTCCAGAGCCGTGGGCAAGTGTCCTCGGTACGTGAAACAA

CGATCTCTGCTTCTGGCTACCGGAATGAAGAACGTGCCCGAGATCCCCAAGGGACGAGGC

CTGTTCGGGGCCATTGCCGGATTTATTGAGAATGGCTGGGAGGGTCTCATCGATGGATGG

TACGGCTTCAGGCACCAGAACGCACAAGGTGAAGGCACAGCTGCTGATTACAAATCCACC

CAGAGTGCAATTGACCAGATCACCGGAAAACTCAATAGACTGATTGAAAAAACCAACCAA

CAGTTTGAATTGATTGATAATGAGTTTAACGAAGTCGAACGGCAGATTGGTAATGTGATC

AATTGGACCCGGGATTCCATTACAGAGGTTTGGTCCTACAACGCCGAGCTGCTCGTCGCA

ATGGAAAATCAGCACACCATAGATCTGGCCGACTCCGAGATGGACAAGCTTTACGAAAGG

GTGAAGAGACAGCTCAGGGAGAACGCCGAAGAGGACGGAACAGGGTGTTTCGAAATCTTC

CATAAGTGCGACGATGATTGTATGGCTTCTATCCGGAACAACACCTATGATCACTCCAAA

TATAGAGAGGAAGCAATGCAGAACAGGATTCAAATCGACCCTGTCAAACTCTCAAGTGGG

TACAAGGACGTAATCCTATGGTTCAGCTTTGGCGCCAGCTGTTTTATTCTGCTGGCAATC

GTGATGGGTTTGGTGTTTATCTGCGTCAAGAATGGCAACATGAGGTGTACCATTTGCATC

535
ATGAATACACAGATCCTGGTCTTCGCCCTTATCGCTATCATCCCCACAAACGCCGACAAG

ATATGCCTGGGCCACCACGCCGTTAGCAACGGCACCAAAGTAAACACTCTCACTGAAAGG

GGTGTGGAAGTTGTGAACGCAACAGAAACCGTAGAACGCACGAACATTCCAAGAATTTGC

TCAAAGGGGAAACGTACAGTCGATCTAGGACAGTGCGGCCTGCTCGGCACCATAACCGGG

CCCCCCCAATGCGATCAATTTCTGGAGTTCTCTGCCGATCTTATCATCGAGCGTCGGGAA

GGGAGCGATGTGTGCTACCCCGGCAAATTTGTGAACGAGGAGGCCCTCAGACAGATCTTA

AGAGAGTCTGGAGGGATTGACAAAGAGGCCATGGGGTTCACATACTCCGGCATACGTACG

AATGGGGCCACGAGTGCTTGTCGGAGGAGCGGTTCAAGTTTCTACGCGGAGATGAAATGG

CTGCTGAGCAATACCGATAACGCCGCCTTCCCCCAGATGACCAAAAGTTATAAAAATACA

AGGAAATCACCCGCCCTTATCGTTTGGGGAATTCATCACTCCGTCAGTACCGCCGAACAG

ACTAAGCTCTATGGATCGGGTTCAAAGCTAGTGACCGTGGGCTCAAGCAATTACCAGCAA

TCCTTTGTACCAAGCCCTGGGGCCCGTCCCCAAGTGAACGGATTAAGCGGTAGGATTGAC

TTCCATTGGTTGATGCTCAATCCGAATGATACGGTGACCTTCAGTTTCAACGGGGGGTTC

ATAGCTCCTGATCGCGCGAGCTTCCTCCGGGGAAAATCGATGGGAATTCAGTCAGGCGTT

CAGGTGGACGCCAATTGTGAAGGAGACTGCTACCATAGCGGAGGGACTATAATTTCCAAT

CTGCCTTTTCAGAACATTGACTCCCGCGCTGTGGGGAAGTGTCCCCGGTACGTGAAGCAA

CGCTCCCTGCTTCTCGCCACAGGCATGAAGAACGTACCTGAGATTCCTAAGGGCCGGGGG

CTTTTCGGCGCGATTGCTGGATTCATCGAAAACGGCTGGGAAGGTTTAATAGATGGCTGG

TATGGCTTCAGGCACCAGAATGCACAGGGCGAGGGGACCGCGGCCGACTATAAGTCTACC

CAAAGTGCTATTGATCAGATAACCGGAAAGCTTAACCGCCTGATCGAGAAAACCAATCAA

CAGTTTGAACTTATCGACAACGAATTCAACGAGGTTGAGAAGCAGATTGGGAACGTCATT

AATTGGACCCGAGATTCGATCACAGAGGTGTGGAGCTACAACGCCGAGCTGCTGGTCGCG

ATGGAAAATCAGCATACAATCGACTTGGCCGATAGTGAGATGGACAAACTATACGAGAGA

GTGAAACGGCAGCTGAGGGAGAACGCCGAAGAGGACGGCACCGGGTGCTTTGAGATTTTT

CACAAGTGCGATGACGATTGTATGGCTTCCATCAGGAATAATACTTACGACCACAGTAAG

TATCGCGAAGAGGCTATGCAAAACCGCATTCAGATCGACCCCGTCAAACTCTCATCGGGC

TATAAAGATGTGATACTCTGGTTTTCTTTTGGTGCATCATGCTTCATTCTTTTGGCAATA

GTGATGGGGCTGGTGTTCATCTGCGTAAAGAACGGTAACATGAGATGCACTATCTGTATT

536
ATGAATACACAGATCTTAGTGTTTGCTTTAATAGCTATTATTCCAACCAATGCCGATAAA

ATCTGTCTGGGACACCACGCCGTGAGCAATGGGACGAAAGTGAACACTCTTACCGAACGA

GGAGTCGAGGTTGTCAATGCTACGGAAACTGTGGAAAGGACCAACATCCCAAGGATCTGC

AGCAAAGGCAAAAAAACTGTAGATCTGGGGCAGTGTGGACTGCTGGGGACCATTACCGGA

CCCCCCCAGTGCGACCAGTTCTTGGAGTTTTCCGCCGATCTGATTATTGAGCGGCGCGAG

GGGTCTGATGTGTGCTATCCTGGTAAATTTGTCAACGAAGAGGCGCTGCGACAAATTCTC

CGCAAAAGTGGGGGAATCGACAAGGAAGCCATGGGCTTCACATACTCTGGCATTCGAACA

AATGGGGCCACTTCCACATGCAGGCGGTCTGGGTCTTCATTTTATGCCGAGATGAAGTGG

CTTCTTTCTAATACTGACAACGCCGCCTTCCCCCAAATGACCAAGTCCTACAAAAACACC

CGGAAGTCCCCAGCCATTATCGTCTGGGGAATCCATCACAGCGTTTCTACAGCCGAACAG

ACCAAGCTCTACGGATCAGGAAACAAACTGGTTACAGTGGGTAGCAGCAACTATCAGCAG

TCGTTCGTTCCTTCTCCTGGGGCGCGGCCGCAAGTAAACGGGCTCAGTGGGCGTATCGAT

TTCCACTGGCTGATGCTGAACCCAAACGACACAGTCACCTTCAGCTTTAATGGAGCCTTC

ATCGCCCCTGATAGGGCCTGCTTTCTGCGGGGAAAATCCATGGGCATCCAAAGCGGAGTG

CAGGTCGACGCCGATTGCGAAGGGGACTGCTACCATTCTGGTGGGACCATCATCTCCAAC

CTCCCATTTCAGAACATTGACTCCCGGGCGGTCGGAAAATGCCCACGTTACGTGAAGCAG

CGCAGTCTCTTACTCGCCACTGGGATGAAGAACGTGCCCGAAATTCCAAAGGGGCGTGGT

CTGTTTGGGGCGATTGCCGGCTTCATTGAGAACGGCTGGGAGGGGCTTATCGACGGCTGG

TACGGATTCCGTCACCAGAATGCCCAGGGTGAGGGCACCGCAGCAGACTATAAAAGCACA

CAGAGCGCCATTGACCAAATCACTGGGAAGCTGAATCGCCTGATTGAGAAAACTAACCAG

CAGTTTGAACTCATAGATAATGAATTTAACGAAGTCGAAAGGCAGATTGGCAACGTAATT

AATTGGACTCGCGACTCAATCACTGAGGTCTGGAGTTACAATGCAGAACTGCTTGTCGCT

ATGGAGAACCAGCATACCATTGACCTGGCTGATAGCGAGATGGATAAACTGTACGAAAGG

GTGAAGCGACAGCTCCGCGAGAACGCAGAGGAGGACGGGACCGGCTGTTTCGAGATCTTT

CACAAGTGTGACGACGACTGTATGGCTTCGATTCGGAACAACACCTATGACCACTCCAAA

TATAGGGAAGAGGCTATGCAGAATAGGATCCAAATCGATCCTGTGAAGCTGAGCTCCGGC

TACAAAGACGTAATCCTGTGGTTCTCTTTTGGCGCCTCGTGTTTTATCCTACTCGCCATC

GTCATGGGTTTAGTTTTTATCTGCGTAAAAAATGGAAATATGAGATGTACTATCTGCATC

537
ATGAACACGCAGATCCTTGTCTTCGCCCTGATTGCCATTATACCCACTAACGCCGATAAA

ATTTGCTTGGGCCACCACGCCGTGTCCAATGGAACAAAAGTGAATACTTTGACCGAGAGG

GGTGTCGAAGTCGTCAACGCCACCGAGACTGTCGAACGGACAAATATACCGCGTATCTGT

TCTAAAGGGAAGCGAACCGTGGACCTGGGTCAATGCGGACTGCTGGGGACTATTACAGGG

CCCCCTCAGTGCGATCAGTTTCTGGAATTTAGCGCTGACCTCATTATTGAAAGGAGGGAG

GGATCAGATGTGTGTTACCCAGGTAAGTTTGTCAATGAGGAAGCCCTCCGACAGATTCTC

AGGGAATCTGGAGGCATTGATAAAGAGGCTATGGGGTTCACCTATTCAGGCATCAGGACC

AATGGGGCTACCAGCGCTTGCCGCCGGAGCGGATCATCTTTTTATGCCGAGATGAAATGG

CTACTGTCAAACACCGACAACGCCGCATTCCCACAGATGACCAAGAGTTACAAGAATACA

CGCAAGTCACCCGCCCTCATCGTCTGGGGCATCCATCATTCCGTGAGCACAGCCGAGCAG

ACGAAGCTCTACGGATCGGGCAGCAAGCTCGTAACCGTCGGGAGCTCTAACTATCAGCAA

TCTTTTGTGCCCTCCCCCGGAGCCCGGCCACAGGTCAATGGACTATCCGGGCGCATCGAT

TTCCACTGGCTGATGTTGAACCCGAACGACACCGTGACATTTTCATTCAATGGGGCATTC

ATCGCGCCAGACCGCGCGTCCTTTCTGAGGGGAAAGTCCATGGGTATCCAGTCTGGTGTA

CAGGTGGATGCCAACTGTGAGGGTGACTGCTACCATAGTGGAGGAACAATTATCTCCAAC

TTGCCATTCCAAAACATCGACAGTAGAGCTGTTGGTAAATGTCCCAGGTACGTGAAGCAA

AGGTCATTGCTGCTGGCCACTGGGATGAAGAATGTGCCCGAAATTCCAAAAGGAAGGGGG

CTTTTCGGGGCAATCGCCGGCTTCATTGAGAATGGCTGGGAAGGCCTCATCGACGGGTGG

TACGGGTTTAGGCATCAAAACGCGCAGGGGGAGGGGACAGCTGCTGATTACAAGAGTACA

CAGAGCGCAATCGACCAGATCACCGGGAAACTAAATCGCCTCATCGAGAAGACTAATCAG

CAGTTCGAACTGATCGACAACGAGTTCAACGAGGTCGAAAAACAGATTGGTAACGTCATT

AACTGGACCAGAGATTCCATAACCGAAGTCTGGTCCTATAACGCAGAACTGCTGGTAGCC

ATGGAGAACCAGCACACTATCGACCTGGCAGACTCGGAAATGGATAAACTGTACGAGAGG

GTGAAGCGGCAGCTCCGGGAGAACGCTGAAGAAGATGGTACCGGCTGTTTCGAAATTTTT

CACAAATGTGACGATGATTGTATGGCCTCTATACGCAACAATACCTACGATCACTCCAAA

TACAGGGAGGAGGCTATGCAGAATCGTATCCAGATCGATCCGGTAAAACTGAGTAGCGGA

TATAAGGATGTGATCCTGTGGTTCAGCTTCGGGGCTAGTTGCTTTATTCTGTTGGCAATT

GTGATGGGCCTGGTGTTCATTTGCGTCAAAAATGGCAACATGCGCTGCACCATTTGTATC

538
ATGAACACCCAAATATTAGTGTTCGCATTGATTGCGATTATCCCAACCAACGCAGATAAG

ATCTGCTTGGGACATCACGCTGTCAGCAACGGGACCAAGGTGAACACGTTGACAGAGAGG

GGCGTAGAAGTGGTCAACGCCACTGAGACAGTGGAACGCACCAACATACCGCGGATCTGC

TCCAAGGGAAAGCGCACGGTGGATCTTGGCCAGTGCGGCCTGCTGGGTACGATAACTGGA

CCTCCCCAGTGCGACCAGTTCCTGGAGTTCTCCGCCGACCTCATCATCGAAAGGAGAGAA

GGTAGCGATGTCTGCTACCCAGGGAAATTCGTTAACGAAGAGGCCCTTAGACAAATCCTG

AGAGAATCTGGCGGGATCGATAAGGAGGCAATGGGATTTACTTACTCAGGAATTAGGACT

AACGGGGCTACCTCTGCGTGCCGACGGTCCGGTTCGAGCTTCTATGCCGAGATGAAATGG

CTTTTGAGCAACACCGATAATGCTGCTTTTCCCCAGATGACTAAGTCCTATAAGAATACC

AGAAAAAGCCCCGCCTTAATTGTGTGGGGCATCCACCACTCAGTGAGTACAGCCGAACAA

ACGAAACTGTACGGCTCTGGTTCCAAGTTGGTCACAGTCGGATCCTCAAATTATCAGCAG

AGCTTCGTACCCTCTCCGGGTGCGAGACCACAGGTGAACGGCCTGAGTGGTCGGATTGAC

TTCCACTGGCTCATGCTGAACCCCAACGATACCGTAACTTTCTCTTTCAACGGAGCCTTT

ATAGCTCCTGATAGAGCTTCTTTTCTGCGTGGGAAGTCCATGGGGATCCAGAGCGGCGTG

CAGGTGGACGCGAACTGTGAGGGTGACTGCTATCACTCAGGAGGAACAATTATCTCGAAT

CTTCCTTTTCAAAACATCGACTCCCGAGCCGTCGGAAAATGCCCTCGCTATGTGAAACAG

CGGAGCTTGTTGCTCGCCACGGGGATGAAGAACGTCCCTGAAATACCGAAGGGGGGGGGC

CTGTTTGGAGCAATCGCAGGATTTATCGAGAACGGGTGGGAAGGGCTTATTGATGGGTGG

TATGGCTTCCGCCACCAAAACGCTCAAGGCGAGGGGACTGCTGCTGATTATAAATCGACA

CAGTCTGCTATTGACCAGATTACAGGAAAGCTCAACCGATTGATAGAAAAGACTAACCAG

CAGTTTGAGCTGATCGATAATGAATTTAACGAGGTGGAGAAGCAGATCGGGAATGTGATC

AACTGGACCAGAGATTCCATCACTGAAGTTTGGAGTTACAACGCCGAGCTCCTGGTGGCT

ATGGAAAATCAGCATACCATCGACCTCGCTGACAGTGAGATGGACAAGCTCTATGAAAGA

GTTAAGCGACAGCTGCGAGAGAATGCCGAGGAGGATGGTACAGGCTGCTTTGAGATTTTC

CACAAGTGTGATGATGACTGTATGGCCTCAATACGGAATAATACATATGATCACTCCAAG

TATCGGGAGGAAGCCATGCAGAACCGTATCCAGATCGACCCTGTGAAACTGAGCTCTGGA

TACAAGGATGTCATACTCTGGTTCTCATTCGGTGCTTCTTGTTTTATTCTGCTGGCCATT

GTGATGGGCCTCGTGTTTATATGCGTAAAGTCCCGCAACATGAGATGCACCATCTGTATC

539
ATGAATACTCAGATACTGGTATTCGCTCTCATTGCTATTATTCCTACGAACGCAGATAAG

ATTTGCCTAGGCCATCATGCTGTCTCTAACGGCACTAAGGTCAACACCCTGACCGAGCGC

GGAGTGGAGGTAGTTAACGCAACTGAAACAGTCGAACGCACCAATATTCCCAGAATCTGC

TCGAAGGGAAAGAAGACCGTCGATCTGGGGCAATGTGGGCTTCTCGGCACCATCACGGGC

CCTCCACAGTGTGACCAGTTTCTGGAATTTTCCGCCGACCTGATCATAGAGCGCCGGGAA

GGATCCGATGTGTGTTATCCCGGGAAGTTCGTGAACGAGGAAGCACTGCGACAGATCCTG

AGGGAGTCCGGCGGGATTGACAAGGAGGCCATGGGCTTCACTTATAGCGGTATACGTACC

AACGGTGCAACCAGTGCTTGCAGGCGATCCGGGTCCTCCTTCTACGCTGAGATGAAGTGG

CTCCTCTCCAATACAGACAACGCCGCCTTTCCACAGATGACTAAAAGTTATAAGAACACA

CGCAAGTCCCCCGCGCTGATCGTGTGGGGGATTCATCATAGCGTGAGCACCGCGGAGCAG

ACAAAACTCTACGGAAGCGGTAACAAGCTGGTAACAGTGGGATCTTCTAACTACCAACAG

AGTTTCGTGCCTTCCCCAGGTGCGCGCCCCCAGGTAAACGGACAGAGTGGGAGAATCGAC

TTCCACTGGCTGATGCTGAATCCCAACGATACTGTCACCTTTAGTTTTAATGGTGCATTT

ATCGCCCCTGATAGAGCATCCTTCTTACGGGGGAAGAGTATGGGGATTCAGTCAGGCGTG

CAGGTTGACGCTAACTGCGAGGGCGATTGTTACCACTCGGGGGGGACTATAATCTCGAAC

CTTCCCTTTCAAAACATAGATAGCCGGGCCGTGGGCAAATGTCCGAGATACGTGAAACAG

AGGAGTCTGTTGCTGGCTACGGGCATGAAGAACGTGCCAGAAATTCCTAAGGGCCGCGGT

CTGTTCGGAGCAATCGCAGGGTTCATCGAGAATGGCTGGGAAGGGCTGATCGATGGTTGG

TATGGATTCAGACACCAGAACGCGCAGGGGGAGGGAACAGCCGCTGACTATAAATCCACA

CAGAGCGCTATAGATCAAATCACAGGGAAACTTAACAGGCTGATCGAGAAAACAAACCAG

CAGTTTGAGTTGATTGATAATGAGTTCAACGAGGTGGAGAAGCAAATCGGCAACGTCATC

AATTGGACTCGCGATTCTATCACTGAGGTATGGAGCTACAATGCAGAGCTGCTCGTAGCG

ATGGAGAATCAGCATACAATTGATCTGGCCGACTCCGAAATGGACAAGCTGTATGAGCGC

GTAAAGAGACAACTTAGAGAAAATGCCGAGGAAGATGGCACTGGCTGCTTCGAAATCTTT

CATAAATGCGATGATGACTGTATGGCATCTATCAGAAACAACACTTATGACCACTCCAAG

TATAGGGAAGAAGCTATGCAGAATAGAATCCAGATCGATCCCGTAAAACTTAGTTCCGGG

TACAAGGACGTTATTCTTTGGTTTTCTTTCGGCGCAAGCTGTTTCATCCTTCTTGCAATC

GTAATGGGTCTCGTCTTCATCTGCGTTAAAAATGGCAACATGCGTTGCACAATTTGCATT

540
ATGAATACCCAGATCCTGGTCTTTGCGCTGATCGCTATTATCCCAACTAACGCCGATAAA

ATCTGCCTGGGCCACCACGCTGTCAGCAATGGCACAAAGGTAAATACCCTAACAGAGCGG

GGGGTGGAAGTCGTTAATGCTACTGAGACCGTGGAACGAACAAATATTCCTAGGATCTGT

TCCAAGGGCAAGCGCACTGTGGACTTGGGTCAGTGCGGCTTACTTGGTACAATCACTGGG

CCGCCACAGTGCGACCAGTTTCTCGAGTTCTCGGCCGATCTGATCATAGAAAGAAGGGAG

GGCAGCGACGTGTGCTACCCCGGCAAGTTTGTTAACGAGGAGGCACTGCGGCAGATCCTG

AGAGAAAGCGGAGGCATCGACAAAGAGGCAATGGGGTTCACCTACTCTGGCATTAGGACT

AACGGTGCAACTTCTGCCTGCCGGAGAAGCGGTTCTTCCTTCTACGCCGAAATGAAGTGG

CTGCTGTCCAATACTGACAACGCTGCCTTTCCTCAGATGACAAAGAGTTACAAAAACACA

CGGAAAAGCCCAGCTCTGATCGTGTGGGGCATCCACCATAGTGTAAGCACAGCTGAACAG

ACGAAGCTGTACGGGTCTGGCAATAAACTTGTCACAGTTGGATCGTCCAATTACCAACAG

AGCTTCGTCCCCAGTCCAGGTGAGAGACCTCAGGTTAACGGCCTCTCGGGGAGAATCGAC

TTCCACTGGCTGATGCTTAACCCCAACGACACAGTAACCTTCTCCTTTAACGGCGCCTTT

ATTGCTCCTGATAGGGCCTCCTTTTTGAGAGGAAAAAGTATGGGCATCCAAAGCGGGGTG

CAGGTGGACGCCAACTGTGAAGGCGACTGCTACCACTCGGGGGGCACCATAATATCCAAC

CTACCTTTTCAGAATATTGACTCTCGGGCCGTGGGGAAGTGTCCTCGTTACGTGAAGCAG

CGAAGCCTCCTACTCGCAACCGGCATGAAGAACGTCCCAGAGATCCCAAAGGGTCGGGGC

CTGTTCGGTGCCATTGCCGGGTTTATAGAAAACGGGTGGGAAGGCCTGATCGATGGCTGG

TATGGCTTCCGCCATCAGAACGCACAGGGTGAGGGCACAGCAGCAGACTATAAAAGCACT

CAATCGGCCATCGACCAGATCACGGGGAAGTTAAATAGGCTGATTGAAAAGACAAACCAA

CAATTCGAACTTATTGATAACGAGTTTAACGAAGTGGAGAAGCAGATAGGAAACGTTATC

AATTGGACGCGAGATTCCATAACAGAAGTTTGGTCATATAATGCCGAGCTCCTAGTCGCC

ATGGAAAATCAGCACACTATTGATCTGGCTGATTCCGAGATGGATAAATTATATGAGAGA

GTGAAGCGCCAGCTTAGGGAAAACGCCGAAGAGGACGGAACTGGGTGTTTCGAGATCTTT

CATAAATGCGATGATGACTGCATGGCCTCTATTCGGAATAACACATACGATCACTCCAAG

TATCGGGAGGAGGCGATGCAGAACAGAATTCAGATTGATCCAGTGAAGCTGTCCAGCGGA

TACAAAGACGTGATACTATGGTTCAGCTTTGGTGCTAGTTGCTTTATCCTGTTGGCGATC

GTCATGGGCCTGGTATTCATTTGCGTGAAGAATGGTAACATGCGCTGCACCATATGTATT

541
ATGAACACACAGATACTGGTGTTCGCACTGATAGCCATAATACCTACCAATGCTGATAAA

ATTTGTCTTGGTCACCATGCCGTCAGCAATGGAACAAAAGTCAATACTCTGACAGAGAGG

GGAGTCGAAGTGGTGAACGCAACAGAGACGGTAGAACGGACAAACATTCCAAGAATCTGT

TCCAAAGGTAAGAGGACGGTCGATCTCGGACAGTGCGGCCTATTAGGAACTATTACTGGT

CCTCCGCAGTGCGACCAGTTTCTGGAATTTAGCGCAGACTTGATTATAGAGCGGCGAGAA

GGGTCCGATGTATGCTATCCCGGCAAATTCGTGAATGAGGAGGCCCTGCGACAGATTTTG

AGAGAAAGCGGGGGGATTGATAAAGAAGCGATGGGGTTTACATATTCAGGCATCAGGACC

AATGGCGCTACCTCAGCTTGCCGAAGAAGTGGTAGCTCTTTTTATGCCGAAATGAAGTGG

CTTCTTTCAAACACTGATAACGCAGCCTTCCCACAGATGACCAAGAGCTACAAGAATACT

CGTAAATCACCAGCCCTAATTGTGTGGGGTATCCACCATTCAGTCTCTACCGCAGAACAA

ACAAAACTGTACGGCAGCGGGAACAAGCTAGTGACCGTTGGATCCAGCAATTACCAGCAA

AGCTTTGTCCCTTCCCCCGGCGCACGTCCACAGGTAAACGGCTTGAGCGGGAGAATTGAT

TTCCACTGGCTAATGCTAAATCCCAACGATACCGTTACTTTTAGCTTCAATGGGGCTTTC

ATTGCCCCAGATAGAGCCTCTTTCCTGAGAGGTAAAAGTATGGGCATCCAATCCGGGGTG

CAGGTGGATGCGAATTGTGAAGGCGATTGTTACCACAGGGGGGGGACCATTATTTCCAAC

TTACCCTTCCAAAACATCGATTCGCGAGCAGTGGGCAAATGTCCCCGGTATGTCAAGCAG

AGGTCGCTGTTGCTGGCCACCGGCATGAAAAATGTCCCTGAGATTCCAAAAGGTCGCGGT

TTGTTTGGCGCTATTGCGGGATTTATCGAGAACGGCTGGGAGGGGCTGATTGACGGGTGG

TACGGGTTCAGACACCAGAACGCTCAGGGCGAGGGAACCGCTGCGGATTATAAAAGCACG

CAGTCGGCCATAGACCAGATCACAGGCAAGCTCAATAGGCTCATCGAGAAGACGAATCAG

CAATTCGAATTGATAGATAACGAATTCAACGAGGTGGAGAAACAGATTGGGAATGTGATC

AATTGGACAAGGGATTCAATTACGGAAGTGTGGTCCTATAACGCCGAGCTGCTCGTGGCC

ATGGAGAATCAGCATACAATCGATCTGGCCGACAGTGAGATGGATAAACTCTACGAACGT

GTGAAGCGGCAGCTACGCGAGAACGCCGAGGAAGATGGGACAGGCTGTTTTGAGATCTTC

CACAAGTGCGACGACGACTGTATGGCGTCAATCCGCAATAACACATACGACCACAGCAAG

TACCGAGAGGAAGCCATGCAAAACAGGATCCAAATCGATCCTGTAAAGCTTTCCTCTGGG

TATAAAGACGTCATTCTTTGGTTCTCTTTTGGAGCCAGTTGCTTCATCCTTCTAGCCATT

GTGATGGGGCTGGTATTCATCTGCGTGAAAAATGGGAATATGCGATGTACCATATGCATT

542
ATGAATACCCAGATCCTCGTTTTTGCTCTGATCGCAATTATTCCCACTAATGCAGACAAA

ATCTGTCTCGGTCATCATGCTGTGTCTAATGGAACGAAGGTCAATACCCTGACCGAACGC

GGTGTCGAAGTGGTCAATGCGACAGAAACTGTAGAACGAACCAATATCCCTAGGATTTGT

TCCAAGGGGAAGAAGACTGTTGACTTGGGGCAATGCGGGCTCCTAGGCACCATTACGGGC

CCCCCCCAATGTGACCAGTTCCTAGAGTTTAGCGCAGATCTGATCATCGAAAGAAGGGAA

GGCTCCGATGTGTGCTATCCCGGGAAGTTCGTGAATGAAGAGGCGCTGAGGCAGATTCTC

AGAGAGAGCGGCGGTATTGAGAAAGAAGCTATGGGATTTACATATAGCGGGATTCGCGCA

AACGGCGCAACTAGTGCGTGTCGACGCAGCGGTTCTTCTTTCTATGCCGAGATGAAGTGG

TTACTAAGCAACACCGATAACGCCGCGTTCCCCCAGATGACCAAGTCTTATAAGAACACA

CGCAAATCCCCCGCGCTCATTGTGTGGGGAATTCACCACAGCGTCTCTACTGCAGAGCAG

ACAAAACTGTACGGTTCAGGGAATAAGCTCGTAACTGTAGGGTCAAGTAACTACCAGCAG

TCCTTTGTCCCTTCTCCAGGGGCTCGGCCTCAGGTCAATGGGCTGAGCGGCCGGATCGAT

TTCCACTGGCTGATGCTGAATCCCAACGACACCGTGACTTTCTCTTTCAACGGGGCCTTT

ATCGCCCCAGATCGGGCCAGCTTTCTGAGAGGGAAGTCAATGGGAATCCAGTCTGGAGTC

CAGGTGGATGCGAACTGTGAAGGGGATTGCTACCACAGCGGCGGGACTATCATCTCCAAC

CTTCCATTCCAAAACATTGACTCTCGCGCCGTTGGCAAGTGTCCACGATACGTCAAGCAG

AGGTCTCTGCTCCTGGCTACCGGAATGAAGAATGTGCCCGAGATACCCAAAGGCCGTGGC

CTGTTCGGCGCGATAGCTGGCTTTATTGAAAACGGATGGGAGGGATTGATAGACGGCTGG

TACGGCTTTCGCCATCAGAACGCGCAGGGCGAAGGAACCGCCGCCGATTATAAATCAACA

CAGTCAGCTATCGACCAGATAACCGGCAAGCTGAACCGATTAATTGAAAAAACAAACCAG

CAGTTTGAACTGATCGATAATGAATTCAACGAAGTGGAAAAACAGATTGGGAATGTTATA

AATTGGACTCGGGACTCCATCACTGAAGTTTGGTCTTACAATGCCGAATTACTGGTTGCC

ATGGAAAATCAACACACTATCGATCTCGCGGACAGCGAAATGGACAAGCTTTACGAACGC

GTTAAACGGCAGCTTCGTGAGAATGCGGAAGAGGATGGAACGGGCTGCTTCGAGATCTTC

CATAAATGCGACGACGATTGTATGGCCTCAATTAGGAATAACACCTACGATCACAGCAAG

TACCGGGAGGAGGCCATGCAGAACCGCATTCAAATTGATCCCGTCAAACTCTCGAGCGGG

TATAAAGATGTGATCTTGTGGTTCTCTTTTGGTGCTTCCTGCTTTATCCTACTGGCCATT

GTCATGGGACTGGTGTTCATCTGCGTCAAAAACGGGAACATGCGCTGTACCATCTGTATT

543
ATGAACACCCAGATCCTTGTCTTTGCTCTGATTGCTATCATCCCTACAAATGCGGACAAG

ATTTGTCTGGGTCATCATGCAGTATCCAACGGAACCAAAGTCAACACCCTAACCGAACGC

GGCGTAGAAGTGGTCAACGCCACCGAGACCGTGGAACGCACAAATATTCCTAGGATCTGC

TCAAAAGGTAAAAAGACAGTGGATTTGGGCCAGTGTGGTCTGCTGGGGACTATAACTGGC

CCCCCCCAATGCGATCAGTTCCTTGAATTTAGCGCCGATCTCATTATAGAACGGCGGGAG

GGCAGCGATGTTTGCTATCCAGGAAAGTTTGTCAATGAAGAAGCACTAAGGCAGATTCTG

AGAGAATCTGGAGGAATCGACAAGGAGGCCATGGGATTCACGTACTCCGGCATTCGCACA

AATGGGGCCACCTCAGCTTGTAGGCGCAGTGGCAGCAGCTTTTACGCGGAGATGAAGTGG

TTGCTTTCCAATACAGATAACGCTGCATTCCCCCAGATGACAAAAAGCTACAAGAATACA

CGAAAATCCCCCGCTCTGATAGTGTGGGGGATCCACCATAGTGTGTCAACCGCCGAGCAA

ACGAAGTTGTATGGCTCCGGAAACAAATTGGTGACTGTCGGTTCATCCAACTACCAGCAG

TCTTTTGTGCCTTCTCCCGGGGCCCGACCTCAGGTAAATGGTCAGAGCGGTCGGATCGAC

TTCCACTGGCTCATGCTGAATCCCAACGACACAGTTACTTTTTCATTCAATGGGGCATTC

ATTGCGCCAGACAGGGCCTCCTTTCTAAGGGGTAAGTCGATGGGAATACAGTCTGGCGTG

CAAGTAGATGCAAATTGCGAAGGGGACTGCTATCACTCTGGGGGCACGATCATCAGTAAC

CTGCCTTTTCAGAACATCGACAGCCGAGCAGTAGGAAAATGCCCACGCTACGTGAAGCAG

CGCTCACTGCTCTTAGCCACCGGGATGAAGAACGTCCCAGAAATTCCTAAAGGAAGGGGG

CTGTTCGGCGCAATTGCTGGGTTTATTGAGAATGGATGGGAGGGTCTGATCGATGGCTGG

TACGGTTTCAGACACCAGAACGCCCAAGGCGAAGGCACAGCCGCTGACTATAAGAGTACT

CAAAGTGCAATTGACCAGATTACCGGCAAGTTGAATCGTCTGATTGAAAAGACAAATCAG

CAGTTCGAACTGATAGATAATGAGTTTAATGAGGTTGAGAAACAGATAGGCAACGTGATT

AACTGGACCAGGGACTCAATCACAGAAGTGTGGAGCTACAACGCGGAATTACTAGTGGCA

ATGGAAAATCAGCATACTATCGACCTTGCAGATTCTGAAATGGACAAACTGTATGAAAGA

GTGAAACGCCAGCTCCGTGAAAATGCCGAAGAGGACGGGACCGGTTGTTTTGAGATTTTC

CATAAGTGTGACGACGATTGTATGGCAAGCATCCGTAATAATACATACGATCATTCGAAG

TATCGCGAGGAGGCAATGCAGAACAGGATACAAATCGATCCTGTAAAACTGAGTAGTGGG

TATAAAGATGTGATTTTGTGGTTCTCATTTGGCGCCTCTTGTTTCATCCTCCTCGCTATC

GTGATGGGACTGGTGTTTATCTGCGTGAAGAATGGTAACATGCGGTGCACTATATGCATC

544
ATGAATACCCAGATCCTAGTGTTTGCCCTTATTGCCATCATACCGACAAACGCCGACAAG

ATATGCCTAGGACATCACGCTGTCTCAAACGGTACCAAGGTTAACACGTTGACGGAGCGA

GGAGTTGAGGTGGTGAACGCTACTGAGACCGTGGAACGCACTAACATTCCCCGCATTTGT

AGTAAAGGCAAGAGAACTGTCGACCTGGGACAGTGCGGCCTCTTAGGGACCATCACAGGA

CCCCCGCAGTGTGACCAGTTCCTCGAATTTTCTGCTGACCTGATCATTGAGCGGAGAGAG

GGGAGCGATGTGTGCTACCCCGGAAAATTCGTAAATGAAGAAGCACTGCGACAGATTCTG

CGGGAGAGTGGCGGAATTGATAAGGAAGCTATGGGGTTTACATACAGGGGGATCAGGACT

AACGGAGCGACCAGCGCTTGCAGGCGGTCAGGAAGTTCTTTCTATGCAGAAATGAAGTGG

CTGCTGTCCAACACGGACAATGCTGCTTTCCCCCAGATGACTAAATCCTACAAAAATACT

CGAAAATCTCCCGCCCTTATTGTTTGGGGGATCCATCACAGCGTGTCGACCGCCGAACAG

ACAAAGCTCTATGGAAGCGGTAACAAGCTTGTGACCGTTGGATCTTCCAATTATCAGCAG

TCCTTTGTCCCCTCTCCTGGTGCCAGACCCCAGGTTAATGGCCTAAGCGGGCGCATCGAC

TTTCATTGGCTCATGCTGAACCCTAATGATACCGTTACGTTTAGTTTTAATGGCGCCTTC

ATTGCCCCTGACAGAGCATCTTTCCTGCGAGGGAAGTCAATGGGCATCCAGAGCGGTGTA

CAGGTGGACGCCAATTGTGAGGGCGATTGTTATCACTCCGGGGGAACAATTATTAGTAAT

CTGCCCTTCCAGAATATAGATTCGAGGGCGGTAGGTAAGTGTCCTCGCTACGTTAAACAA

CGCTCTCTTCTTTTGGCCACTGGGATGAAGAACGTACCTGAAATACCTAAGGGTCGCGGG

CTCTTTGGCGCGATCGCAGGCTTCATTGAAAACGGCTGGGAGGGTTTAATCAACGGGTGG

TACGGTTTCCGACACCAGAACGCTCAGGGGGAAGGTACCGCTGCAGATTACAAGTCCACT

CAATCAGCTATTGATCAGATCACGGGCAAGCTGAACAGGCTCATCGAAAAGACCAATCAG

CAATTCGAACTCATCGATAACGAGTTCAACGAGGTGGAGAAGCAAATTGGAAATGTAATA

AATTGGACGCGCGATTCTATTACAGAAGTGTGGTCCTACAACGCGGAACTCTTAGTGGCA

ATGGAGAACCAGCATACTATTGACCTGGCTGACTCAGAAATGGATAAGCTGTACGAAAGG

GTGAAAAGACAGTTGAGGGAAAATGCTGAGGAAGATGGGACGGGATGCTTTGAGATTTTC

CATAAGTGCGATGATGACTGCATGGCAAGCATCCGTAACAACACATATGACCATTCTAAG

TACCGGGAGGAAGCCATGCAAAATCGCATACAGATCGACCCTGTGAAGCTCAGTTCTGGC

TACAAAGATGTGATCCTGTGGTTTTCGTTCGGAGCCAGCTGCTTTATCCTACTTGCAATA

GTCATGGGTCTTGTGTTCATATGCGTAAAGAATGGCAACATGAGGTGTACCATCTGTATC

545
ATGAACACCCAGATTCTGGTGTTTGCCCTGATTGCTATAATTCCAACCAATGCGGACAAA

ATCTGCCTGGGCCACCACGCCGTGTCGAACGGCACGAAAGTGAATACCTTAACGGAAAGA

GGCGTTGAAGTTGTGAATGCAACAGAAACTGTAGAAAGAACTAATATTCCTAGAATCTGT

TCTAAGGGGAAAAAAACGGTGGACTTAGGCCAGTGTGGTCTGCTAGGGACTATCACCGGC

CCCCCTCAATGTGACCAGTTCCTGGAGTTCAGCGCCGACCTCATTATAGAAAGAAGAGAA

GGATCAGACGTGTGCTACCCTGGCAAATTCGTAAACGAGGAGGCCCTCCGGCAGATCCTC

CGCGAATCCGGTGGAATCGACAAGGAAGCCATGGGATTTACCTATTCTGGTATTCGGACC

AACGGCGCCACGAGTGCTTGTCGGCGGTCAGGGTCTTCCTTTTACGCAGAGATGAAGTGG

CTCCTGTCCAATACTGACAATGCCGCATTCCCTCAAATGACTAAGTCCTATAAAAATACC

AGAAAATCTCCTGCACTTATCGTGTGGGGCATTCATCACTCTGTCAGTACTGCCGAGCAG

ACCAAGCTATACGGGAGCGGTAACAAGCTTGTGACAGTAGGGTCATCCAACTATCAGCAA

AGCTTTGTACCGTCCCCTGGGGCACGTCCCCAGGTGAACGGCCAGTCCGGGGGGATCGAC

TTCCACTGGTTGATGCTGAATCCTAACGATACCGTGACCTTCTCTTTCAACGGGGCATTT

ATCGCACCAGACAGGGCTTCCTTTCTGCGCGGAAAGTCCATGGGCATCCAGTCCGGCGTG

CAGGTCGATGCAAACTGCGAGGGTGATTGCTACCATTCTGGGGGGACAATAATCTCTAAT

CTGCCTTTTCAGAACATTGACAGTCGAGCGGTGGGCAAGTGTCCCAGGTACGTGAAACAA

CGCTCCCTTCTGTTGGCAACAGGGATGAAGAACGTGCCTGAGATCCCGAAAGGCCGTGGA

TTATTTGGCGCTATTGCTGGCTTCATTGAGAATGGATGGGAGGGCTTAATCGACGGTTGG

TACGGCTTCCGGCATCAGAATGCACAGGGCGAAGGAACAGCTGCCGACTATAAATCCACC

CAGTCCGCAATCGATCAGATAACCGGCAAGCTGAACCGGCTCATTGAGAAAACAAATCAG

CAGTTCGAGCTCATAGACAATGAGTTTAACGAGGTAGAGAAACAGATTGGTAATGTCATT

AACTGGACACGGGATAGCATCACGGAAGTTTGGAGCTATAATGCTGAGCTCTTGGTCGCT

ATGGAGAACCAGCATACGATTGACTTGGCAGACTCTGAGATGGATAAGCTTTATGAGCGC

GTGAAGAGGCAACTTAGAGAGAACGCTGAGGAGGACGGTACTGGGTGCTTCGAGATATTC

CATAAGTGCGACGATGACTGCATGGCCAGCATTAGAAACAACACATATGATCACTCCAAG

TATCGTGAAGAAGCCATGCAGAATCGGATTCAGATTGATCCAGTGAAGCTGTCCTCCGGC

TACAAGGATGTGATCCTGTGGTTCTCGTTCGGTGCTAGCTGCTTCATATTGTTAGCTATC

GTTATGGGCCTCGTGTTCATCTGCGTGAAGAACGGTAACATGCGTTGCACTATCTGCATA

546
ATGAACACTCAAATTCTGGTGTTCGCACTCATTGCCATCATACCAACTAACGCTGACAAG

ATATGCTTGGGCCATCACGCCGTGAGCAATGGGACAAAGGTAAACACCCTCACAGAAAGA

GGCGTCGAAGTGGTTAATGCTACAGAGACAGTCGAGAGGACAAACATCCCCCGTATTTGT

TCCAAGGGTAAGAAAACTGTTGATCTGGGCCAGTGTGGGTTGTTAGGAACCATCACCGGA

CCCCCGCAATGTGATCAATTCCTGGAATTTTCTGCGGATCTGATTATTGAGAGGCGCGAA

GGCAGCGATGTGTGTTATCCCGGAAAGTTTGTTAACGAAGAAGCACTGCGGCAGATTCTG

CGAGAATCCGGTGGCATCGACAAAGAGGCTATGGGCTTTACTTATTCCGGCATCAGGACG

AATGGAGCCACCTCTGCCTGCCGCCGGTCAGGGAGTTCCTTCTATGCAGAGATGAAGTGG

CTGCTCTCCAATACAGATAATGCCGCATTCCCTCAGATGACGAAATCTTATAAAAACACA

CGGAAGAGTCCCGCACTGATCGTCTGGGGAATTCACCACTCCGTGAGCACTGCAGAGCAA

ACCAAGCTGTACGGGTCAGGGAACAAGTTAGTGACAGTCGGAAGCTCTAATTATCAACAG

TCGTTCGTGCCAAGTCCTGGGGCCCGACCGCAGGTGAATGGTCAGTCAGGGCGTATCGAT

TTCCACTGGTTAATGCTGAATCCAAACGACACCGTGACCTTCTCCTTTAATGGCGCCTTT

ATTGCACCCGATAGAGCTTCCTTTTTAAGAGGAAAATCCATGGGAATTCAAAGTGGTGTG

CAGGTAGATGCGAATTGCGAGGGAGATTGTTATCACTCCGGTGGGACCATTATCTCCAAC

CTCCCTTTCCAGAACATCGACTCGCGAGCTGTGGGCAAGTGCCCAAGATACGTTAAGCAG

AGATCGCTTCTGTTGGCCACCGGAATGAAGAACGTTCCTGAAATTCCTAAGGGCCGCGGA

TTATTCGGCGCCATTGCAGGCTTTATAGAAAACGGTTGGGAGGGCCTTATCGATGGATGG

TATGGCTTCAGACACCAGAATGCACAAGGGGAGGGGACTGCCGCCGACTATAAGTCGACC

CAGAGCGCAATTGATCAGATTACTGGGAAGCTTAATAGACTCATCGAGAAAACAAACCAA

CAGTTCGAACTCATTGACAACGAGTTTAATGAGGTTGAGAAGCAGATCGGTAATGTCATC

AACTGGACAAGAGACAGCATCACTGAGGTGTGGTCCTATAATGCTGAGCTGCTGGTAGCT

ATGGAGAACCAACACACAATTGATCTCGCCGACTCAGAGATGGACAAGTTGTACGAGCGC

GTCAAGAGGCAATTAAGAGAAAACGCCGAGGAGGATGGGACCGGCTGTTTTGAGATCTTC

CATAAATGCGATGATGACTGTATGGCTAGCATCCGAAACAACACTTATGACCACTCCAAA

TATCGGGAAGAAGCAATGCAGAATCGAATTCAAATTGACCCAGTTAAACTCAGTTCCGGA

TATAAGGACGTTATCCTCTGGTTCAGCTTCGGAGCATCTTGCTTTATACTGCTGGCAATC

GTTATGGGACTCGTGTTCATCTGTGTCAAGAACGGTAACATGAGATGTACTATCTGCATT

547
ATGAACACACAAATCTTGGTCTTTGCTCTCATTGCAATAATACCGACAAATGCCGATAAA

ATCTGTCTAGGACACCACGCTGTATCCAATGGAACAAAGGTCAATACCTTGACAGAGCGC

GGCGTAGAGGTGGTAAATGCCACAGAGACAGTCGAGCGAACAAATATTCCCCGCATATGT

TCCAAAGGTAAAAAGACCGTTGACCTCGGGCAGTGCGGATTACTGGGAACAATCACGGGC

CCCCCACAGTGTGACCAATTTCTGGAGTTCAGTGCCGATTTAATCATAGAGCGCAGGGAA

GGTTCCGACGTCTGTTATCCTGGCAAGTTTGTAAACGAGGAGGCCTTACGGCAAATACTG

AGGGAGTCAGGCGGCATCGAGAAGGAAGCCATGGGCTTCACCTATTCCGGAATTCGGGCG

AACGGCGCAACCTCGGCCTGCCGACGGAGCGGAAGCTCATTTTACGCCGAGATGAAGTGG

CTGCTTTCCAACACTGACAACGCAGCTTTCCCTCAAATGACAAAGTCGTATAAGAACACA

AGAAAATCTCCTGCCCTCATTGTTTGGGGCATACACCATTCCGTGTCAACAGCAGAACAG

ACAAAACTCTACGGCTCGGGTAACAAGCTCGTGACAGTCGGTTCCAGTAATTACCAGCAG

TCCTTTGTACCTTCCCCCGGTGCACGGCCCCAGGTGAACGGCCTCTCTGGCAGGATTGAT

TTCCACTGGCTGATGCTGAATCCTAACGATACAGTCACTTTTAGCTTTAATGGAGCTTTC

ATTGCACCCGACCGCGCCAGCTTTTTGAGGGGAAAATCCATGGGGATCCAATCCGGAGTG

CAGGTGGATGCTAACTGCGAAGGCGATTGTTATCATAGTGGGGGGACCATAATCAGTAAC

CTCCCTTTTCAGAATATCGACTCCCGCGCAGTAGGAAAATGCCCTAGGTACGTGAAACAG

CGCTCCTTACTGCTCGCCACGGGCATGAAGAATGTTCCTGAGATACCAAAAGGGGGGGGC

CTGTTTGGGGCTATTGCGGGATTCATTGAAAACGGGTGGGAGGGGTTGATCGATGGCTGG

TACGGGTTCAGGCACCAGAATGCCCAGGGTGAAGGAACAGCAGCCGACTACAAGTCTACG

CAGTCTGCTATCGATCAGATTACCGGCAAGCTAAACCGCTTAATTGAAAAAACCAACCAA

CAGTTCGAACTGATCGACAATGAGTTTAACGAAGTGGAAAAGCAGATAGGGAACGTGATT

AATTGGACCAGAGACAGTATTACCGAGGTGTGGTCGTATAATGCCGAACTGTTGGTAGCT

ATGGAGAACCAGCACACGATAGATCTGGCAGACAGTGAAATGGATAAGCTGTATGAGAGA

GTAAAGCGGCAACTCCGGGAAAATGCAGAAGAGGATGGCACAGGATGCTTCGAGATATTC

CATAAGTGTGATGACGATTGTATGGCCAGCATCAGAAACAATACCTACGACCACTCAAAA

TACCGCGAAGAGGCCATGCAGAATAGGATTCAAATTGACCCAGTGAAGCTCTCCTCGGGA

TACAAAGATGTGATCTTGTGGTTCAGCTTCGGCGCCTCCTGTTTTATCCTCCTGGCGATA

GTGATGGGACTCGTCTTTATTTGCGTTAAGAACGGGAACATGAGGTGCACCATATGCATC

548
ATGAACACCCAGATCCTAGTGTTTGCACTTATCGCCATCATCCCGACTAATGCGGACAAG

ATCTGCCTGGGCCATCACGCTGTGTCTAATGGAACCAAGGTGAATACGCTGACGGAACGA

GGAGTGGAGGTGGTAAATGCTACGGAAACAGTCGAGAGAACCAACATCCCACGGATCTGC

TCTAAGGGAAAAAAGACCGTTGATCTGGGCCAATGCGGTCTACTCGGTACCATTACCGGA

CCACCACAATGCGACCAGTTTCTCGAATTCAGCGCCGACTTGATCATAGAAAGGCGCGAG

GGATCGGATGTGTGCTACCCTGGCAAATTCGTGAATGAGGAGGCCCTCCGCCAGATCCTT

AGAGAATCAGGTGGCATCGATAAGGAAGCTATGGGCTTCACATACTCGGGCATAAGAACA

AATGGCGCTACCAGCGCCTGTCGACGCTCGGGCAGCTCCTTTTATGCCGAGATGAAGTGG

TTGCTCAGTAACACAGATAACGCAGCCTTCCCACAGATGACAAAGTCTTACAAGAATACC

CGTAAAAGCCCAGCCCTTATTGTGTGGGGAATACACCATAGCGTGAGCACGGCAGAGCAG

ACGAAACTGTATGGTAGCGGGAACAAACTCGTTACGGTCGGGAGCTCAAACTACCAGCAG

TCTTTTGTACCTTCACCCGGCGCTCGCCCACAGGTTAACGGTCAGTCGGGGAGAATCGAT

TTCCACTGGCTGATGCTGAACCCAAATGACACCGTCACCTTCTCCTTCAACGGAGCCTTC

ATTGCCCCAGATCGCGCCTCTTTTCTTAGAGGCAAGTCCATGGGCATCCAATCAGGCGTC

CAGGTCGATGCCAATTGTGAAGGCGACTGTTATCATTCCGGAGGCACAATTATAAGCAAC

CTGCCCTTCCAGAACATCGACAGTCGAGCTGTCGGTAAGTGCCCTCGTTACGTGAAGCAG

CGGAGTCTCCTCTTAGCTACAGGAATGAAAAATGTCCCAGAGATCCCTAAAGGACGCGGT

CTCTTTGGGGCCATAGCTGGATTCATCGAAAACGGCTGGGAAGGCCTGATCGACGGCTGG

TACGGCTTCAGACACCAGAATGCACAAGGGGAAGGAACCGCTGCTGATTATAAGAGTACC

CAGTCAGCTATCGACCAAATAACCGGTAAGCTTAACCGACTGATTGAGAAAACAAACCAG

CAATTTGAGCTCATTGATAATGAGTTTAATGAGGTGGAAAAGCAGATTGGCAATGTCATT

AACTGGACCCGCGACTCGATTACAGAAGTGTGGTCTTATAACGCGGAGTTACTTGTCGCC

ATGGAAAATCAGCACACCATCGACTTGGCCGACTCTGAAATGGACAAACTGTACGAGCGA

GTCAAGCGACAACTGAGGGAGAACGCCGAGGAAGACGGGACCGGTTGTTTTGAGATATTT

CACAAATGCGACGATGACTGCATGGCCTCGATCAGGAACAATACTTACGACCACTCCAAG

TACAGGGAAGAAGCGATGCAAAACAGGATACAGATAGATCCTGTTAAGCTCTCCAGTGGG

TATAAAGACGTGATCCTGTGGTTCAGCTTCGGAGCATCCTGTTTTATCCTTTTGGCCATC

GTAATGGGATTAGTCTTCATCTGCGTGAAGAATGGGAACATGCGGTGCACCATCTGTATA

549
ATGAATACCCAGATATTGGTATTTGCCCTGATAGCGATCATTCCAACTAACGCAGATAAG

ATATGCCTCGGCCACCACGCTGTGTCGAATGGGACTAAGGTGAATACCCTGACTGAAAGA

GGTGTCGAGGTGGTCAACGCTACCGAAACAGTGGAAAGGACCAACATACCGAGAATCTGC

AGCAAAGGTAAAAAGACTGTAGACCTCGGCCAGTGCGGCCTTCTGGGGACCATTACTGGA

CCTCCCCAATGCGATCAGTTCCTGGAGTTCTCTGCCGACCTCATCATTGAGCGGAGAGAG

GGAAGCGATGTGTGCTACCCCGGCAAATTTGTGAATGAGGAGGCTCTGAGACAGATTTTG

AGGGAGAGTGGCGGGATCGAAAAGGAGGCAATGGGGTTTACCTACTCAGGAATCAGGGCC

AACGGAGCAACCTCTGCATGCAGAAGGTCCGGGTCCTCCTTCTACGCAGAGATGAAATGG

CTGTTAAGCAATACGGATAATGCCGCCTTCCCTCAGATGACTAAGTCCTATAAAAATACC

CGTAAGAGTCCAGCACTCATAGTCTGGGGCATTCACCATTCCGTCTCTACAGCAGAGCAG

ACTAAACTCTATGGAAGCGGGAACAAACTCGTGACCGTCGGCTCGAGCAACTATCAACAA

TCTTTCGTTCCATCTCCCGGAGCCAGACCCCAGGTGAACGGGCTATCGGGACGGATCGAC

TTCCACTGGCTGATGTTAAACCCCAATGATACGGTCACCTTTAGCTTCAATGGTGCATTC

ATCGCTCCAGACCGGGCCTCGTTTCTCAGAGGAAAATCTATGGGAATCCAGAGTGGTGTG

CAGGTGGACGCCAACTGCGAGGGTGATTGTTATCATTCTGGGGGCACTATCATCTCAAAC

CTCCCATTCCAGAACATAGATTCAAGAGCAGTTGGAAAGTGTCCAAGATATGTGAAGCAG

CGCTCTCTGCTTTTGGCCACCGGCATGAAAAATGTTCCTGAGATACCGAAAGGACGGGGC

CTATTTGGCGCGATCGCAGGATTCATCGAAAATGGATGGGAGGGACTGATCGACGGTTGG

TATGGCTTCCGCCACCAGAATGCCCAGGGGGAAGGTACCGCAGCTGACTATAAATCAACG

CAGTCCGCCATCGATCAGATAACTGGCAAACTGAATAGGCTAATAGAAAAGACTAACCAG

CAGTTTGAGCTGATTGACAATGAATTCAACGAAGTGGAGAAGCAGATTGGCAACGTTATT

AACTGGACCCGGGACTCCATCACGGAGGTGTGGTCTTACAACGCAGAGTTACTAGTAGCA

ATGGAGAATCAGCACACTATAGACCTAGCCGATAGTGAAATGGACAAACTATATGAGAGA

GTCAAACGCCAACTGCGGGAGAACGCCGAAGAAGATGGAACAGGATGTTTCGAGATTTTC

CACAAATGTGATGATGATTGCATGGCGTCTATCCGCAATAATACTTACGATCATTCAAAG

TACCGCGAAGAGGCCATGCAGAACCGAATCCAGATTGATCCCGTGAAGCTTTCCTCCGGA

TACAAAGATGTAATCCTGTGGTTCTCATTCGGCGCTTCCTGTTTCATCTTACTGGCAATC

GTCATGGGGCTGGTTTTCATTTGCGTCAAAAACGGCAATATGAGATGTACTATTTGCATC

550
ATGAACACCCAGATCCTGGTTTTTGCCTTGATCGCAATTATTCCTACCAATGCGGACAAA

ATTTGCCTTGGGCACCACGCCGTTTCCAATGGCACAAAGGTCAACACTTTGACCGAACGG

GGAGTGGAAGTGGTGAACGCTACAGAAACCGTTGAGCGGACTAACATTCCCAGGATCTGT

AGTAAGGGCAAGCGCACCGTGGACCTGGGCCAGTGCGGATTGTTAGGCACCATCACCGGC

CCACCCCAGTGCGACCAGTTCCTGGAATTTAGTGCAGATTTAATCATAGAACGAAGAGAG

GGTTCTGATGTGTGTTACCCGGGGAAATTCGTGAACGAAGAGGCCCTCCGCCAGATTTTG

AGAGAGAGCGGAGGCATAGATAAAGAAGCAATGGGCTTTACCTATAGCGGGATCCGGACT

AATGGAGCTACCTCTGCATGTCGGCGTAGTGGAAGTTCTTTCTATGCTGAGATGAAATGG

CTCCTTTCTAACACAGACAATGCTGCATTTCCACAAATGACAAAATCCTATAAAAATACT

CGGAAATCCCCAGCCCTGATCGTTTGGGGAATCCACCATTCAGTTTCGACTGCAGAACAG

ACTAAATTGTATGGGTCCGGGTCTAAGCTGGTAACAGTTGGAAGTTCCAATTACCAGCAA

AGCTTCGTCCCCTCGCCAGGTGCACGCCCACAGGTGAAGGGGCTAAGCGGGCGTATTGAT

TTCCACTGGTTAATGCTGAATCCAAACGACACTGTCACGTTCAGCTTTAACGGAGCGTTC

ATCGCTCCTGACCGCGCCAGTTTCCTGCGAGGTAAATCAATGGGCATCCAGTCAGGTGTT

CAGGTAGATGCCAACTGTGAGGGGGATTGCTATCATTCTGGGGGGACTATTATTAGTAAC

CTGCCCTTCCAGAATATAGATTCTCGGGCCGTCGGCAAGTGTCCAAGGTACGTTAAACAG

CGCAGTCTGTTACTTGCCACTGGAATGAAGAACGTTCCCGAGATCCCAAAGGGCCGAGGT

CTGTTCGGGGCCATCGCCGGCTTTATCGAGAATGGATGGGAAGGGTTGATTGATGGATGG

TATGGTTTCCGTCACCAAAATGCCCAGGGAGAGGGGACAGCTGCTGACTATAAGTCCACC

CAGAGTGCAATAGACCAAATCACAGGGAAACTGAATAGACTTATCGAAAAGACCAACCAG

CAGTTTGAGTTGATTGATAACGAATTCAATGAAGTCGAGAAACAGATTGGGAATGTCATT

AATTGGACACGAGACTCCATCACAGAGGTGTGGTCCTACAATGCCGAATTGTTGGTGGCC

ATGGAGAATCAACATACTATCGATCTGGCAGACTCAGAAATGGACAAGCTGTATGAGCGA

GTGAAGAGGCAGCTGAGAGAGAACGCCGAAGAAGATGGAACCGGGTGCTTTGAGATTTTT

CATAAGTGTGACGACGATTGTATGGCAAGTATCCGCAATAATACCTACGACCACTCCAAG

TATAGAGAGGAAGCCATGCAGAACCGGATTCAGATTGATCCAGTGAAACTCAGTTCCGGC

TATAAAGACGTGATCCTGTGGTTTAGCTTCGGCGCCTCCTGTTTCATCCTGTTGGCCATT

GTCATGGGGCTGGTCTTTATCTGTGTCAAGTCCCGAAACATGCGATGCACAATCTGCATC

551
ATGAACACTCAAATTCTAGTGTTCGCACTGATTGCCATTATCCCAACTAACGCCGACAAA

ATCTGTTTGGGCCACCATGCTGTTAGCAACGGTACCAAAGTGAATACCCTGACCGAAAGA

GGCGTTGAAGTAGTAAACGCCACTGAAACCGTTGAGAGGACAAACATTCCACGGATTTGT

AGCAAAGGAAAGAAAACTGTCGATCTGGGGCAATGTGGACTGCTGGGCACCATCACTGGC

CCTCCCCAGTGTGACCAGTTTCTGGAGTTTTCCGCAGATTTAATCATAGAGCGCAGAGAA

GGAAGTGACGTGTGCTACCCTGGGAAATTCGTTAATGAAGAAGCCCTCCGGCAGATCCTA

AGAGAATCTGGGGGTATCGAAAAGGAGGCAATGGGATTCACGTACTCGGGGATCCGTGCT

AACGGAGCAACTTCCGCATGCCGGAGGTCAGGGTCATCTTTTTATGCTGAAATGAAATGG

TTGCTGTCAAATACCGATAACGCCGCGTTCCCGCAAATGACAAAGAGCTACAAAAATACC

CGCAAGAGTCCCGCGCTCATCGTGTGGGGCATCCATCATAGCGTGTCCACTGCTGAGCAG

ACCAAACTTTATGGTAGTGGGAACAAGCTGGTCACGGTCGGATCAAGCAATTACCAGCAG

TCCTTCGTACCAAGCCCGGGGGCCCGGCCCCAGGTGAACGGCCTGTCAGGACGCATCGAC

TTTCACTGGTTGATGTTGAACCCGAATGATACAGTGACTTTTTCATTCAACGGCGCTTTT

ATCGCACCAGACAGGGCCTCCTTTCTCCGCGGGAAGAGCATGGGCATCCAGAGTGGTGTG

CAGGTTGACGCGAATTGCGAGGGAGACTGTTATCACTCAGGCGGAACAATTATCAGCAAT

CTTCCTTTCCAAAACATTGATTCGAGAGCCGTCGGGAAGTGCCCCAGGTACGTCAAGCAG

CGAAGTCTGCTTTTAGCTACAGGAATGAAGAACGTGCCCGAGATACCCAAAGGCAGGGGA

CTGTTCGGCGCAATCGCTGGCTTTATTGAGAACGGATGGGAAGGTCTGATCGATGGCTGG

TATGGATTTAGGCACCAGAACGCTCAGGGCGAGGGCACTGCAGCCGATTATAAGAGCACG

CAGTCTGCCATAGACCAAATCACCGGGAAACTCAACAGGCTGATCGAGAAGACCAACCAG

CAATTTGAGCTCATTGACAATGAATTTAATGAAGTGGAGAAGCAGATCGGCAATGTTATT

AATTGGACACGAGACTCTATTACTGAAGTGTGGTCTTACAATGCCGAGCTGCTTGTTGCA

ATGGAGAATCAGCATACAATCGATCTGGCCGATTCAGAGATGGACAAGCTGTACGAAAGG

GTGAAACGGCAGCTACGGGAGAACGCTGAGGAGGATGGCACAGGGTGCTTTGAGATTTTC

CATAAGTGCGACGACGATTGTATGGCGAGTATACGCAATAACACCTACGATCATTCAAAG

TATCGCGAGGAAGCCATGCAGAACCGCATTCAGATCGATCCCGTGAAGTTGTCCTCTGGC

TACAAAGACGTCATTCTGTGGTTCAGCTTTGGAGCATCCTGTTTCATCCTCCTGGCAATC

GTGATGGGACTCGTGTTTATCTGCGTCAAAAACGGCAATATGAGGTGCACCATCTGTATT

552
ATGAATACACAGATCTTGGTTTTCGCTCTGATCGCCATCATACCGACCAATGCTGACAAA

ATCTGTCTGGGTCACCATGCAGTGAGCAACGGTACCAAAGTCAATACATTGACCGAGCGT

GGCGTCGAAGTTGTTAATGCCACAGAAACAGTCGAGCGAACCAATATTCCGAGAATTTGC

TCCAAGGGGAAGAAGACCGTGGACCTAGGCCAGTGTGGACTGCTGGGTACAATTACTGGG

CCACCACAGTGTGATCAGTTCCTGGAGTTCAGCGCAGATCTGATCATCGAACGGAGAGAG

GGATCAGATGTATGCTATCCTGGTAAATTCGTAAACGAAGAGGCCCTGCGACAGATTCTA

AGAAAAAGCGGAGGCATCGATAAGGAAGCTATGGGGTTCACATATTCAGGCATCAGAACT

AATGGTGCCACTTCCACTTGCCGACGAAGCGGGAGTAGCTTCTACGCAGAAATGAAATGG

CTTCTATCAAACACGGACAACGCGGCCTTTCCTCAGATGACCAAATCCTATAAGAACACC

AGAAAAAGCCCCGCAATCATCGTATGGGGAATTCATCACTCTGTGAGTACCGCCGAGCAG

ACAAAGCTTTACGGCTCCGGAAACAAGCTGGTGACCGTTGGGAGTAGCAATTACCAGCAG

TCTTTCGTACCATCCCCCGGTGCGAGACCCCAAGTTAACGGCCTTTCAGGACGCATTGAT

TTCCACTGGCTGATGTTGAATCCGAACGACACCGTGACGTTCTCCTTCAACGGGGCATTC

ATTGCACCCGATAGAGCCTGTTTCCTCAGGGGAAAATCCATGGGCATACAGAGCGGGGTG

CAGGTGGACGCCGACTGTGAGGGAGACTGCTACCACTCTGGTGGTACGATCATAAGCAAC

CTCCCATTCCAGAATATCGATTCTAGGGCGGTGGGTAAATGTCCAAGATATGTGAAGCAG

CGGTCTCTTCTGCTGGCCACCGGCATGAAAAACGTTCCTGAGATTCCCAAAGGCAGAGGG

CTGTTCGGCGCAATCGCCGGCTTTATAGAAAACGGATGGGAGGGCCTGATCGATGGGTGG

TACGGATTCAGACACCAGAATGCCCAGGGCGAAGGTACAGCTGCAGATTACAAAAGCACA

CAGTCAGCCATTGACCAAATCACAGGCAAACTGAATCGCCTCATTGAGAAAACGAATCAG

CAGTTCGAGCTCATTGATAACGAGTTCAACGAGGTCGAAAGACAAATTGGTAATGTGATC

AACTGGACGAGGGACTCAATCACTGAGGTGTGGTCTTATAATGCAGAGCTGTTGGTGGCT

ATGGAGAATCAACACACAATTGACCTGGCGGATTCTGAAATGGATAAACTGTACGAACGA

GTCAAGCGTCAGCTGAGGGAGAACGCTGAGGAAGACGGGACTGGATGCTTCGAAATTTTC

CATAAATGCGATGACGATTGCATGGCCTCTATCCGAAACAATACATACGATCATAGTAAG

TACAGAGAAGAGGCCATGCAGAACAGAATCCAGATTGACCCGGTGAAACTGTCATCGGGA

TACAAGGACGTCATCCTCTGGTTTTCTTTTGGTGCCTCTTGCTTCATATTACTGGCAATT

GTTATGGGACTGGTCTTCATATGTGTTAAGAATGGTAACATGCGGTGTACAATATGCATC

553
ATGAACACTCAAATCCTCGTTTTCGCTCTGATTGCTATTATTCCTACTAATGCCGATAAG

ATTTGTCTGGGCCACCATGCAGTTTCCAATGGAACCAAGGTTAACACCCTGACGGAGCGT

GGTGTTGAGGTGGTTAATGCAACTGAAACTGTTGAGCGTACCAATATCCCTAGAATATGC

AGTAAGGGGAAAAAAACTGTGGACCTCGGCCAATGTGGCCTGCTGGGCACCATCACAGGG

CCGCCCCAATGTGATCAATTTTTAGAATTTAGCGCAGACCTGATTATCGAGCGCCGAGAA

GGTAGCGACGTGTGCTACCCTGGCAAGTTTGTGAATGAGGAAGCCCTGAGACAAATTCTT

AGGGAGTCAGGAGGCATCGACAAGGAAGCCATGGGCTTTACCTATAGGGGGATCAGAACA

AATGGCGCAACTTCAGCCTGTAGGCGCTCGGGGTCCTCTTTCTACGCAGAGATGAAATGG

CTGCTCAGCAATACAGACAATGCTGCTTTCCCTCAGATGACCAAGTCCTACAAAAATACC

CGGAAGTCGCCCGCTTTGATCGTTTGGGGAATTCACCATTCTGTCAGCACGGCCGAGCAG

ACTAAGCTATACGGGTCCGGTAACAAACTGGTGACAGTCGGCAGCAGCAATTACCAGCAG

TCTTTCGTGCCCTCCCCAGGCGCAAGGCCCCAGGTAAATGGTCAGTCTGGACGCATAGAT

TTTCACTGGCTCATGCTCAACCCCAATGACACAGTTACCTTTTCCTTCAATGGAGCCTTT

ATCGCCCCGGATCGCGCCAGTTTTCTGCGGGGTAAATCCATGGGGATCCAGTCAGGGGTG

CAGGTCGACGCTAACTGCGAGGGAGATTGTTACCACTCAGGAGGAACCATCATCAGCAAT

TTGCCCTTCCAGAATATCGATTCTAGGGCAGTGGGCAAGTGTCCAAGGTACGTAAAGCAG

CGATCCCTCCTGCTGGCCACCGGTATGAAAAATGTGCCAGAGATCCCTAAAGGTAGGGGG

CTCTTCGGGGCTATCGCGGGCTTCATCGAGAATGGGTGGGAGGGACTCATCGATGGATGG

TACGGCTTCAGACACCAGAACGCACAAGGCGAGGGGACAGCAGCTGATTATAAATCCACC

CAGTCCGCTATCGACCAGATTACAGGGAAACTGAATCGGCTCATCGAGAAGACCAACCAG

CAGTTCGAGCTGATTGACAATGAGTTCAATGAGGTTGAAAAGCAGATTGGCAACGTCATC

AATTGGACTCGTGACAGCATCACCGAGGTTTGGTCCTACAACGCCGAGCTGCTCGTCGCC

ATGGAGAATCAACACACTATAGACTTGGCCGACTCAGAAATGGATAAGCTATATGAGAGA

GTTAAGCGACAGTTACGCGAGAACGCAGAAGAAGACGGTACCGGATGCTTTGAAATCTTT

CACAAATGCGACGACGACTGTATGGCATCAATAAGAAACAACACCTACGATCACTCAAAG

TACCGCGAGGAGGCCATGCAAAACCGGATCCAAATAGACCCCGTTAAGTTGTCCAGGGGG

TATAAGGACGTGATTTTGTGGTTCTCTTTTGGGGCCTCCTGTTTCATTCTTCTGGCTATC

GTGATGGGCCTGGTGTTCATATGTGTTAAGAATGGTAACATGAGATGTACTATCTGTATT

554
ATGAATACACAAATTCTGGTCTTCGCTCTGATCGCCATAATTCCCACCAACGCTGATAAG

ATCTGTCTGGGCCACCACGCCGTCTCCAATGGTACTAAAGTAAACACTCTCACTGAGCGC

GGCGTTGAAGTGGTCAATGCTACCGAGACTGTGGAGCGGACAAACATCCCAAGGATTTGC

TCTAAGGGAAAGAGAACTGTGGACTTGGGCCAGTGTGGATTACTGGGCACAATTACAGGC

CCTCCCCAGTGCGATCAGTTCTTGGAGTTTAGTGCCGACCTAATAATTGAACGCAGAGAG

GGATCTGACGTGTGCTATCCAGGGAAATTTGTTAATGAAGAGGCACTCCGCCAGATTCTG

CGAGAGTCCGGCGGGATCGACAAAGAGGCCATGGGATTCACGTATTCGGGCATCAGGACC

AATGGCGCGACCTCCGCGTGTCGACGGAGCGGCAGTAGCTTTTATGCTGAGATGAAGTGG

CTCCTCAGTAACACCGACAACGCTGCTTTCCCTCAGATGACCAAGTCATACAAGAATACC

CGGAAATCCCCTGCACTTATCGTGTGGGGAATCCATCATTCCGTTAGTACCGCCGAGCAA

ACTAAACTGTACGGGAGTGGCAACAAGCTTGTGACTGTGGGCTCATCGAATTATCAACAG

TCGTTCGTCCCATCACCAGGCGCTAGGCCACAGGTTAATGGACTGTCGGGGCGCATCGAT

TTTCACTGGTTAATGTTAAACCCTAATGACACCGTTACGTTTAGCTTCAATGGTGCCTTT

ATCGCCCCCGACCGGGCCAGCTTCCTCCGTGGAAAGTCCATGGGAATTCAGTCAGGCGTA

CAAGTGGATGCCAACTGTGAAGGCGATTGCTACCATTCTGGAGGAACCATTATTAGCAAC

CTGCCCTTCCAGAACATTGATAGCAGGGCAGTAGGTAAATGTCCCCGGTATGTGAAACAA

AGAAGCCTGCTGCTCGCCACTGGCATGAAAAACGTCCCTGAGATCCCGAAAGGTAGAGGC

TTGTTCGGGGCAATTGCCGGGTTCATTGAAAACGGATGGGAAGGACTGATTGACGGATGG

TATGGGTTCCGGCACCAAAATGCTCAGGGAGAAGGGACCGCAGCCGATTATAAGTCAACC

CAAAGCGCCATTGACCAGATTACCGGAAAGCTTAACCGGCTCATCGAAAAGACAAATCAG

CAGTTTGAGCTGATCGACAACGAATTTAATGAGGTGGAGAAGCAGATCGGAAACGTGATT

AATTGGACTAGGGACAGCATCACCGAGGTCTGGTCTTATAACGCCGAACTGCTGGTAGCG

ATGGAAAATCAACACACCATCGACCTGGCTGACTCAGAGATGGATAAGCTGTATGAAAGG

GTCAAACGTCAGCTTCGTGAAAATGCTGAAGAGGATGGCACAGGTTGCTTCGAAATCTTC

CATAAGTGTGATGATGATTGTATGGCTAGTATTAGGAACAACACATACGACCATTCCAAA

TATCGGGAGGAAGCTATGCAAAACCGGATCCAAATCGACCCAGTTAAACTGTCTTCCGGC

TACAAAGATGTTATTCTCTGGTTCAGTTTTGGTGCATCCTGCTTTATACTCCTTGCCATC

GTAATGGGCCTGGTGTTTATCTGCGTCAAGAACGGAAACATGCGATGCACGATCTGTATC

555
ATGAACACTCAGATCCTCGTATTCGCCTTGATCGCTATTATTCCAACTAACGCCGATAAA

ATCTGCCTTGGCCACCATGCCGTTAGCAACGGTACTAAAGTGAATACTCTTACAGAGAGG

GGCGTCGAGGTCGTAAATGCCACTGAAACAGTTGAGCGAACAAACATTCCTCGAATTTGT

TCTAAGGGAAAAAGAACAGTCGACCTCGGCCAGTGCGGATTGCTGGGAACCATTACGGGG

CCTCCCCAGTGCGATCAGTTTCTGGAGTTTTCCGCCGACCTGATCATAGAGCGGCGCGAG

GGTTCCGACGTGTGCTACCCAGGAAAATTTGTCAACGAAGAAGCACTACGACAGATCTTG

AGAGAGAGCGGAGGGATTGACAAGGAAGCAATGGGATTCACTTATAGCGGCATCAGGACT

AATGGTGCGACCTCTGCTTGCAGACGTTCCGGGTCATCCTTCTACGCAGAGATGAAGTGG

TTACTAAGCAATACCGATAACGCAGCTTTTCCCCAGATGACCAAGTCCTACAAGAATACA

CGGAAAAGCCCCGCTTTGATCGTTTGGGGTATCCATCACTCTGTGAGCACCGCAGAACAG

ACAAAGTTGTACGGATCGGGAAGTAAGCTTGTCACCGTGGGCTCGTCCAACTACCAACAG

TCTTTTGTACCTTCTCCAGGGGCTCGTCCACAAGTCAACGGCCTGTCTGGGAGAATCGAC

TTTCACTGGCTCATGTTAAATCCCAATGACACAGTCACCTTCTCCTTTAATGGCGCCTTC

ATTGCACCCGACCGTGCCTCATTCCTGAGAGGTAAGTCCATGGGAATTCAGAGCGGTGTC

CAGGTCGACGCTAACTGCGAGGGGGACTGCTATCACTCCGGGGGGACAATTATCAGTAAT

TTGCCCTTTCAGAATATTGATTCAAGAGCTGTTGGAAAGTGCCCACGCTACGTAAAGCAG

AGAAGCCTCCTATTGGCCACAGGAATGAAGAACGTGCCGGAGATCCCCAAGGGTCGCGGT

TTGTTTGGCGCCATCGCTGGCTTTATTGAAAACGGATGGGAGGGTTTGATTGATGGCTGG

TATGGGTTCAGGCATCAGAACGCCCAGGGAGAAGGTACCGCAGCAGACTACAAGAGCACA

CAGTCCGCCATTGACCAGATTACTGGTAAGCTGAACAGATTGATCGAAAAGACTAACCAG

CAGTTTGAGCTGATTGACAATGAATTCAACGAAGTGGAAAAGCAGATCGGGAATGTGATC

AATTGGACCCGGGATTCAATCACCGAGGTGTGGAGCTATAATGCCGAGCTGCTCGTAGCC

ATGGAGAATCAACATACAATAGATCTCGCTGACTCCGAAATGGATAAGCTCTACGAGCGC

GTAAAACGGCAGCTGCGCGAAAACGCTGAAGAAGATGGAACTGGATGCTTCGAGATCTTT

CATAAGTGCGACGATGATTGTATGGCCTCCATTAGAAATAATACCTATGACCATAGCAAG

TACAGGGAAGAGGCCATGCAAAATAGAATCCAGATCGATCCCGTCAAACTAAGTTCGGGG

TATAAGGATGTGATCCTATGGTTTTCCTTTGGTGCTAGCTGTTTCATTCTGTTAGCCATC

GTCATGGGGCTTGTGTTCATATGTGTGAAAAATGGTAACATGCGGTGCACAATTTGTATA

556
ATGAATACACAGATCTTAGTATTTGCGCTAATCGCTATTATCCCTACCAATGCTGATAAG

ATCTGTCTGGGCCACCACGCCGTTTCCAATGGCACTAAAGTGAACACTCTCACTGAGCGC

GGCGTCGAGGTGGTCAACGCCACCGAGACAGTTGAGAGAACAAACATACCTCGCATCTGT

AGTAAAGGCAAGAAGACTGTCGATCTGGGCCAGTGTGGGCTGCTGGGAACGATAACCGGT

CCCCCTCAGTGTGATCAGTTTCTGGAATTCTCTGCAGACCTGATTATCGAAAGACGAGAA

GGGAGCGACGTGTGTTACCCCGGAAAGTTTGTTAATGAGGAAGCACTGCGCCAGATCCTT

CGGGAATCTGGGGGCATCGATAAGGAAGCGATGGGCTTCACTTATAGTGGGATTCGCACC

AACGGGGCTACGTCCGCTTGCCGGCGGAGCGGTTCGTCTTTTTACGCGGAAATGAAGTGG

CTGCTCAGCAATACCGATAACGCCGCCTTCCCGCAGATGACAAAAAGCTATAAGAATACC

CGGAAAAGTCCGGCACTCATAGTGTGGGGGATCCACCATAGCGTTAGCACGGCGGAGCAG

ACAAAGCTCTATGGGAGTGGAAATAAGCTGGTGACCGTCGGCTCTTCAAATTACCAGCAA

TCATTTGTGCCCTCTCCCGGCGCCCGTCCTCAAGTGAACGGACAGTCAGGAAGGATTGAC

TTCCACTGGCTCATGTTGAACCCTAATGACACAGTGACATTTTCGTTTAACGGAGCATTC

ATCGCCCCTGACAGAGCTAGTTTCCTCAGAGGGAAGAGTATGGGGATCCAGAGCGGGGTA

CAGGTGGATGCAAACTGTGAGGGGGACTGCTATCATTCTGGTGGGACCATCATTTCGAAC

CTGCCATTCCAGAACATTGACTCTCGCGCTGTTGGCAAATGTCCTAGGTACGTTAAGCAA

AGATCATTGCTGCTCGCAACGGGCATGAAAAACGTGCCGGAAATCCCTAAAGGTCGGGGT

CTCTTCGGCGCCATCGCCGGATTCATTGAGAATGGCTGGGAGGGACTCATCGACGGGTGG

TATGGGTTCCGGCATCAGAACGCACAGGGCGAGGGGACTGCCGCTGACTACAAATCGACC

CAGTCCGCTATTGACCAGATCACCGGCAAACTCAACCGGCTGATCGAGAAGACTAACCAA

CAGTTTGAACTCATCGATAATGAGTTCAACGAGGTAGAAAAACAAATTGGAAACGTGATC

AATTGGACACGCGATTCTATTACTGAGGTCTGGAGTTATAACGCAGAGCTGCTGGTGGCT

ATGGAAAACCAGCACACCATTGATCTAGCTGACTCGGAAATGGATAAGCTGTACGAAAGG

GTGAAACGCCAGCTACGCGAAAATGCCGAGGAAGACGGTACAGGATGCTTCGAGATATTC

CACAAGTGCGACGACGACTGCATGGCCAGCATCCGCAATAACACATATGACCATTCTAAA

TACCGGGAGGAAGCCATGCAGAATCGAATCCAGATCGACCCTGTCAAATTAAGCAGTGGG

TACAAGGACGTGATCCTGTGGTTTAGCTTCGGAGCTAGTTGTTTTATATTACTCGCCATC

GTTATGGGATTGGTATTTATCTGCGTCAAGAATGGAAACATGCGCTGCACTATCTGCATC

557
ATGAACACCCAGATACTCGTCTTTGCCCTCATTGCCATAATCCCGACTAATGCGGATAAG

ATTTGTCTAGGGCATCACGCTGTATCAAACGGCACGAAAGTCAACACCTTGACCGAAAGG

GGCGTAGAGGTGGTAAACGCTACAGAAACAGTCGAGCGGACAAATATCCCAAGGATTTGC

AGCAAGGGTAAAAAGACTGTAGACTTAGGACAGTGCGGCTTACTCGGCACAATCACAGGC

CCCCCCCAATGTGATCAGTTCCTTGAATTCAGTGCAGATCTGATAATCGAAAGGAGGGAG

GGATCTGACGTGTGTTACCCAGGCAAATTCGTCAACGAGGAAGCACTCAGACAGATCTTA

AGAAAGTCCGGGGGGATAGACAAAGAAGCTATGGGTTTTACGTACAGTGGGATAAGAACC

AATGGCGCCACTAGCACCTGTAGGAGGAGTGGGTCGTCCTTCTATGCTGAAATGAAGTGG

CTGCTGTCCAATACTGACAATGCAGCCTTTCCTCAGATGACAAAGAGCTACAAGAATACA

AGGAAAAGCCCGGCAATTATAGTATGGGGAATCCACCATTCAGTCAGCACCGCTGAACAA

ACTAAGCTGTATGGCTCCGGCAATAAGCTCGTCACAGTGGGGAGCTCAAATTATCAGCAG

TCATTCGTGCCAAGCCCAGGGGCGCGGCCGCAAGTTAACGGCCTCTCCGGAAGAATTGAT

TTTCATTGGTTAATGCTTAATCCTAACGACACGGTTACCTTCAGCTTTAACGGCGCTTTC

ATCGCTCCCGACAGGGCTTGTTTTCTCCGCGGCAAGTCTATGGGAATCCAGTCCGGGGTG

CAGGTCGACGCGGATTGTGAAGGAGACTGCTACCACAGTGGGGGCACTATAATCTCAAAT

CTGCCATTCCAGAATATCGACAGTCGCGCCGTGGGGAAGTGTCCGAGATACGTTAAGCAA

CGATCACTGCTACTGGCCACCGGTATGAAAAATGTGCCAGAGATTCCCAAAGGGAGAGGC

CTGTTTGGTGCCATCGCCGGGTTTATCGAGAACGGGTGGGAAGGCTTGATTGACGGCTGG

TACGGATTTCGGCACCAAAACGCCCAAGGGGAAGGTACCGCTGCCGATTACAAGAGCACC

CAAAGTGCCATTGACCAGATTACGGGGAAACTGAACAGACTGATCGAGAAAACGAATCAA

CAATTCGAACTGATAGATAACGAATTTAACGAAGTCGAGCGACAGATCGGGAATGTGATC

AACTGGACTAGGGATTCTATTACCGAGGTATGGAGCTATAATGCTGAGCTTCTTGTGGCA

ATGGAAAATCAACACACAATAGATTTAGCGGATAGTGAGATGGACAAGCTCTACGAACGG

GTAAAAAGACAGTTGAGAGAGAATGCCGAGGAGGACGGGACAGGCTGTTTTGAAATCTTC

CATAAGTGTGACGATGATTGTATGGCGAGCATCCGAAACAATACTTACGATCACAGCAAA

TACCGTGAGGAGGCGATGCAGAATAGAATCCAGATAGATCCGGTTAAACTGTCCAGCGGG

TACAAGGATGTGATCCTGTGGTTCTCATTCGGCGCTTCATGTTTCATTTTGCTGGCAATT

GTGATGGGACTCGTGTTCATATGTGTGAAAAACGGCAATATGCGCTGCACTATTTGCATC

558
ATGAATACACAGATCCTAGTGTTCGCACTCATAGCTATAATCCCTACAAATGCCGACAAG

ATATGTCTTGGCCACCACGCTGTGTCAAACGGGACAAAAGTTAACACCTTGACAGAGCGG

GGCGTCGAGGTCGTTAACGCCACCGAGACTGTGGAAAGAACAAATATACCCCGGATTTGT

TCAAAAGGGAAGAGAACTGTCGACCTGGGGCAGTGCGGACTCCTGGGGACTATCACTGGA

CCTCCACAATGCGACCAGTTCCTCGAGTTCTCTGCCGATCTCATCATTGAGAGGCGAGAG

GGGTCCGATGTGTGTTACCCAGGGAAATTTGTGAATGAGGAAGCCCTTCGGCAGATACTT

CGTGAAAGCGGGGGCATCGATAAAGAGGCCATGGGTTTTACGTATTCTGGAATTCGCACC

AACGGGGCCACAAGTGCATGTCGGAGGAGCGGATCATCATTCTATGCAGAGATGAAATGG

CTGCTTTCTAACACCGATAATGCCGCTTTCCCGCAGATGACAAAAAGTTATAAAAATACC

AGGAAATCCCCCGCTCTAATTGTGTGGGGGATTCATCACAGCGTTTCCACTGCCGAACAG

ACTAAGCTGTACGGTTCGGGCAGCAAGCTGGTGACAGTGGGTTCATCAAACTACCAACAG

TCCTTCGTGCCTTCTCCAGGCGCGCGGCCGCAGGTTAACGGACTCTCTGGCAGAATCGAC

TTTCATTGGTTGATGCTGAATCCCAACGACACCGTCACCTTCTCCTTTAACGGTGCATTT

ATCGCCCCAGATCGTGCTTCATTTCTACGCGGCAAAAGCATGGGGATTCAGTCCGGCGTC

CAGGTAGATGCAAACTGTGAGGGCGACTGTTACCACTCAGGCGGAACAATTATTAGCAAC

CTGCCATTTCAGAATATTGACTCTCGCGCCGTGGGGAAATGCCCAAGATATGTCAAGCAG

CGGAGCCTGCTCCTGGCCACTGGGATGAAGAATGTGCCAGAAATACCAAAGGGTAGAGGT

CTGTTCGGCGCCATCGCTGGCTTTATAGAGAATGGATGGGAGGGACTGATCGATGGCTGG

TACGGATTCAGACATCAAAACGCCCAAGGTGAAGGAACCGCTGCCGATTACAAGTCTACC

CAAAGTGCTATAGATCAGATAACCGGCAAGCTTAATAGGCTCATTGAGAAAACAAATCAG

CAGTTCGAGCTGATCGACAACGAGTTCAACGAGGTGGAGAAGCAGATTGGAAACGTGATT

AATTGGACGCGCGATAGCATCACAGAGGTGTGGTCCTATAACGCAGAGCTGCTGGTGGCT

ATGGAGAACCAGCACACTATCGATCTGGCCGACTCCGAAATGGACAAGCTGTACGAGAGG

GTGAAGCGGCAGTTGCGAGAGAATGCCGAGGAGGACGGGACAGGCTGCTTTGAGATCTTT

CACAAGTGCGACGATGATTGTATGGCTTCAATCCGCAATAACACATACGATCATTCCAAA

TACAGGGAGGAAGCTATGCAGAACCGAATCCAGATAGATCCAGTGAAGCTCTCTAGTGGC

TACAAGGACGTGATTCTGTGGTTCAGTTTCGGTGCTAGCTGTTTTATTCTGCTTGCAATA

GTAATGGGGTTGGTGTTTATCTGTGTTAAGTCACGGAACATGCGCTGCACCATATGCATC

559
ATGAACACACAGATCCTAGTTTTCGCGCTGATCGCAATCATACCTACAAATGCTGACAAG

ATTTGCCTAGGACATCACGCCGTGTCTAATGGAACCAAAGTAAACACTCTGACTGAGCGC

GGGGTAGAGGTCGTGAATGCAACAGAAACGGTAGAGCGGACAAATATCCCTAGGATATGC

AGTAAAGGCAAGCGTACAGTAGATCTCGGCCAGTGTGGCCTACTCGGAACAATCACCGGT

CCTCCCCAGTGCGACCAGTTCCTTGAATTCAGTGCTGATCTGATCATTGAAAGGGGGGAG

GGGTCCGATGTATGTTACCCTGGGAAGTTTGTCAATGAAGAGGCACTGCGCCAAATCCTG

AGAGAGTCAGGAGGCATAGACAAAGAGGCTATGGGATTTACATACAGTGGGATAAGAACT

AACGGCGCGACCAGCGCCTGCAGGAGGTCCGGGTCGTCTTTCTATGCCGAAATGAAATGG

CTCCTTTCTAATACAGATAACGCAGCCTTTCCCCAGATCACTAAATCATACAAGAATACT

AGGAAGTCACCCGCACTCATCGTTTGGGGCATACATCACTCGGTCAGCACCGCCGAACAG

ACTAAATTATACGGTTCAGGGAACAAGCTCGTAACCGTGGGCTCGTCTAACTATCAACAG

AGTTTCGTTCCGTCCCCCGGGGCGAGACCGCAGGTGAATGGCCTCTCCGGGCGAATCGAT

TTTCATTGGCTGATGCTGAACCCCAACGATACCGTAACCTTTTCGTTCAACGGGGCTTTC

ATCGCTCCGGATAGAGCATCATTTCTGCGCGGGAAGTCCATGGGCATTCAGAGCGGTGTT

CAAGTCGACGCCAACTGTGAGGGAGACTGTTATCACAGGGGGGGGACCATCATCAGCAAC

CTCCCGTTTCAGAATATTGACTCAAGGGCGGTCGGAAAGTGTCCACGTTACGTCAAGCAG

CGGAGTCTCCTGTTAGCGACAGGCATGAAGAATGTCCCTGAAATTCCTAAAGGCCGGGGC

CTATTTGGTGCCATCGCCGGTTTCATCGAGAACGGGTGGGAAGGTCTGATCGATGGTTGG

TATGGCTTCCGCCACCAGAATGCGCAAGGGGAAGGAACCGCGGCGGACTACAAAAGTACT

CAGTCCGCAATCGATCAGATCACAGGTAAGTTGAATAGGCTTATCGAGAAGACAAACCAG

CAGTTTGAGCTTATAGACAACGAATTCAATGAGGTGGAAAAGCAAATTGGAAATGTAATC

AATTGGACCAGGGATAGCATCACCGAAGTGTGGAGCTACAATGCCGAGCTGTTGGTGGCA

ATGGAGAACCAACATACAATCGACCTAGCCGATAGTGAGATGGACAAGCTGTATGAGCGG

GTGAAGCGGCAGCTGAGGGAAAATGCGGAGGAAGACGGAACTGGGTGTTTCGAGATTTTC

CACAAGTGTGATGACGATTGTATGGCCTCAATTCGGAACAACACATACGATCATTCCAAG

TATCGAGAAGAGGCCATGCAAAACCGGATTCAGATTGACCCCGTCAAGTTATCCTCCGGG

TACAAGGACGTTATTCTCTGGTTTAGCTTTGGAGCCAGTTGCTTCATTCTGTTGGCAATT

GTGATGGGTCTTGTATTCATCTGTGTGAAAAATGGGAATATGCGCTGCACCATCTGTATC

560
ATGAACACGCAAATCTTGGTGTTCGCACTGATCGCCATTATTCCAACCAATGCTGACAAG

ATTTGCCTTGGTCACCACGCGGTTAGCAACGGGACCAAAGTGAACACCCTGACCGAGCGA

GGGGTGGAGGTAGTGAACGCAACCGAGACAGTGGAGAGAACTAATATACCCCGGATCTGT

AGCAAGGGTAAGAGAACGGTGGATCTTGGGCAGTGTGGCTTGTTGGGGACTATCACAGGC

CCTCCTCAGTGCGACCAGTTCTTGGAATTTTCTGCCGACCTTATCATTGAGCGCAGAGAG

GGGTCAGATGTCTGTTATCCTGGAAAATTTGTGAACGAAGAGGCTCTTCGGCAGATACTG

CGCGAATCAGGCGGCATTGACAAAGAAGCCATGGGGTTTACCTATAGCGGAATCAGGACT

AACGGCGCCACCTCCGCCTGCAGGAGGAGTGGGAGCAGCTTCTACGCTGAAATGAAGTGG

TTGCTCTCTAACACAGACAATGCTGCATTCCCTCAGATTACCAAGAGTTATAAGAACACA

CGCAAATCTCCCGCGCTGATCGTGTGGGGCATTCATCACAGCGTTAGCACGGCCGAGCAG

ACAAAACTGTACGGCTCGGGAAATAAACTTGTGACGGTTGGCAGCAGCAACTATCAGCAG

TCCTTCGTTCCTTCTCCAGGCGCGCGCCCCCAGGTGAATGGGTTGTCTGGGAGAATCGAC

TTTCACTGGCTAATGCTTAATCCTAACGACACGGTGACTTTCTCATTTAACGGAGCTTTC

ATCGCACCAGACCGCGCATCCTTTCTGAGAGGGAAATCGATGGGCATCCAATCCGGGGTG

CAGGTCGATGCGAACTGCGAGGGTGATTGTTATCACTCCGGGGGCACCATAATCAGCAAC

CTGCCTTTCCAGAATATCGACTCCCGGGCAGTAGGAAAGTGCCCACGATATGTGAAGCAG

AGGAGCTTGCTGCTGGCTACAGGCATGAAGAATGTCCCAGAAATCCCCAAGGGGAGAGGT

CTATTTGGGGCCATCGCTGGCTTTATAGAGAACGGGTGGGAAGGTCTGATTGACGGGTGG

TACGGCTTTAGGCACCAGAACGCCCAGGGCGAAGGAACAGCTGCCGACTATAAATCTACA

CAGAGCGCCATTGATCAGATAACTGGCAAGTTAAACCGGCTCATCGAGAAGACTAATCAG

CAATTTGAGCTTATCGATAACGAATTCAATGAAGTAGAGAAACAAATCGGGAATGTGATC

AACTGGACTCGAGATTCAATAACGGAGGTATGGTCCTACAACGCCGAACTGCTCGTTGCT

ATGGAGAACCAGCACACCATCGATCTGGCAGACAGCGAGATGGATAAGCTCTACGAGAGA

GTCAAGCGACAGTTACGTGAAAATGCCGAAGAAGATGGAACCGGTTGCTTTGAGATATTT

CATAAATGCGATGATGATTGCATGGCTTCGATTCGGAATAACACATATGACCACAGCAAG

TACAGGGAAGAAGCGATGCAAAACCGCATTCAGATCGACCCAGTCAAACTAAGCTCTGGA

TACAAAGACGTTATACTGTGGTTCTCCTTTGGAGCCAGCTGCTTCATCCTGCTCGCCATA

GTGATGGGACTGGTGTTTATCTGCGTGAAAAACGGAAACATGAGGTGTACCATTTGTATC

561
ATGAACACACAGATTCTCGTCTTCGCACTCATTGCCATCATCCCTACAAACGCGGACAAA

ATTTGCCTTGGGCACCACGCCGTGAGCAACGGCACAAAAGTCAACACATTGACAGAGCGA

GGCGTAGAGGTCGTTAATGCCACCGAAACGGTAGAAAGGACGAACATTCCTAGGATATGT

AGTAAAGGAAAGCGTACTGTAGATTTAGGACAGTGTGGCTTGCTGGGAACTATCACAGGA

CCCCCACAATGCGACCAGTTCCTAGAGTTTAGCGCCGATCTGATAATTGAACGTAGGGAG

GGAAGCGACGTATGCTACCCAGGGAAATTTGTGAAGGAGGAGGCCCTCCGACAGATTCTG

AGAGAGTCCGGGGGAATCGACAAGGAAGCCATGGGATTCACCTATTCGGGCATAAGAACC

AACGGCGCAACATCCGCTTGCCGGAGGTCCGGGAGTAGTTTTTATGCTGAGATGAAGTGG

CTGCTTTCCAACACCGATAACGCCGCCTTTCCTCAGATGACGAAATCCTATAAGAATACA

AGAAAAAGCCCGGCACTCATCGTGTGGGGCATCCATCACAGCGTCTCCACGGCAGAGCAG

ACTAAACTCTACGGATCTGGAAATAAACTGGTAACAGTGGGGTCAAGTAACTACCAACAG

TCGTTCGTGCCATCCCCTGGCGCTCGGCCTCAGGTTAACGGGCTGTCCGGTAGGATTGAT

TTCCATTGGCTGATGTTAAACCCAAACGACACCGTGACCTTCAGTTTTAACGGCGCTTTT

ATTGCTCCCGACAGGGCAAGTTTCTTGAGGGGCAAGAGCATGGGAATCCAGTCTGGTGTG

CAGGTCGATGCCAACTGTGAGGGAGATTGTTATCATAGCGGAGGTACGATTATCTCTAAT

CTACCTTTTCAAAATATCGACTCCAGGGCGGTCGGGAAATGTCCTCGCTACGTCAAGCAG

AGGTCACTGCTTCTGGCAACCGGAATGAAGAACGTGCCCGAAATCCCAAAGGGCAGAGGT

CTGTTTGGCGCTATAGCCGGGTTCATTGAGAACGGATGGGAGGGTTTAATAGACGGGTGG

TATGGATTCCGCCACCAAAATGCCCAGGGGGAAGGGACAGCTGCCGATTACAAGTCAACA

CAGAGCGCGATCGATCAGATCACAGGAAAGTTGAACAGGTTGATAGAGAAAACAAATCAA

CAGTTTGAGCTGATCGATAATGAGTTCAATGAGGTCGAGAAGCAAATTGGGAACGTAATA

AATTGGACACGAGATTCCATAACTGAAGTGTGGTCTTACAATGCTGAACTGCTCGTGGCG

ATGGAAAACCAACACACGATTGATTTGGCCGATTCCGAGATGGATAAACTGTATGAACGT

GTGAAGCGTCAACTTCGTGAAAATGCCGAAGAGGACGGTACCGGATGCTTCGAGATCTTC

CACAAGTGTGATGATGATTGCATGGCCAGTATCAGGAATAACACATATGACCATTCCAAA

TACCGCGAAGAGGCCATGCAGAATCGTATTCAGATTGACCCCGTTAAGCTGAGTTCCGGT

TACAAAGATGTCATTCTCTGGTTTTCTTTTGGCGCCTCATGTTTCATTCTGCTAGCCATT

GTGATGGGGCTTGTCTTTATCTGTGTCAAGAACGGTAACATGAGGTGTACCATCTGTATC

562
ATGAATACCCAGATTCTGGTGTTCGCGTTAATAGCCATTATCCCAACTAACGCTGATAAG

ATATGTCTGGGCCATCACGCTGTGAGCAATGGAACTAAGGTGAACACTCTGACCGAGAGG

GGTGTGGAGGTAGTGAATGCTACCGAGACAGTAGAGCGGACTAACATTCCCAGGATTTGC

TCTAAGGGCAAGCGCACCGTCGACCTGGGACAGTGCGGGTTGCTAGGTACGATAACTGGT

CCACCACAATGTGATCAATTCTTGGAATTTTCTGCTGACCTCATTATAGAGAGGAGGGAG

GGCTCCGATGTGTGCTACCCCGGGAAATTCGTCAACGAAGAAGCACTGCGTCAGATTTTG

AGAGAATCGGGGGGTATTGACAAGGAGGCCATGGGTTTTACCTACTCCGGCATTCGTACT

AACGGAGCCACCAGTGCCTGCAGGCGGAGCGGGAGTAGCTTCTACGCTGAGATGAAATGG

CTTCTAAGCAACACTGATAACGCCGCTTTCCCCCAGATGACTAAATCTTACAAAAACACA

CGGAAGAGTCCCGCTCTGATAGTATGGGGAATACACCATTCAGTCTCTACAGCCGAGCAG

ACTAAGCTTTATGGAAGCGGGAACAAACTGGTGACCGTCGGTTCATCTAATTACCAGCAG

TCTTTCGTGCCCTCTCCTGGGGCCAGGCCCCAGGTGAATGGGCTGTCTGGCCGCATTGAT

TTCCACTGGTTAATGCTGAATCCCAATGATACCGTGACCTTTTCTTTCAATGGCGCTTTC

ATTGCTCCTGATAGAGCCTCATTTCTGAGAGGGAAGTCGATGGGGATACAGTCTGGGGTC

CAGGTCGACGCTAATTGCGAAGGCGATTGCTACCACTCTGGGGGGACAATTATAAGTAAT

TTGCCGTTCCAGAATATCGATAGTAGAGCTGTGGGGAAATGCCCCCGCTACGTAAAGCAG

CGTTCCCTTTTGCTTGCCACAGGTATGAAAAACGTGCCCGAAATTCCAAAAGGAAGAGGA

CTATTTGGTGCCATTGCGGGGTTCATCGAAAACGGATGGGAGGGCCTGATCGATGGGTGG

TACGGCTTCAGACATCAAAATGCTCAGGGGGAAGGAACTGCAGCGGACTATAAATCTACC

CAGTCTGCCATCGATCAGATCACTGGCAAACTAAATCGACTTATCGAGAAAACAAACCAG

CAGTTTGAGCTTATCGATAACGAGTTCAACGAGGTAGAAAAGCAGATTGGAAACGTCATT

AACTGGACTCGGGATTCAATCACAGAAGTATGGAGTTACAACGCTGAGCTTTTAGTGGCC

ATGGAAAATCAGCATACGATTGATCTCGCCGACTCCGAGATGGATAAGCTGTACGAACGT

GTGAAGCGCCAGCTCAGAGAGAATGCAGAGGAGGACGGGACTGGCTGCTTCGAGATCTTT

CATAAATGTGACGATGACTGCATGGCAAGCATTCGAAATAACACATACGATCATAGTAAG

TATCGGGAGGAGGCTATGCAAAATCGGATTCAAATTGATCCGGTGAAGCTGTCGAGTGGC

TACAAGGATGTGATTTTATGGTTTTCATTCGGGGCCTCCTGCTTCATCCTACTGGCCATA

GTGATGGGCCTGGTGTTTATCTGCGTGAAAAATGGTAATATGCGGTGCACCATCTGCATC

563
ATGAATACTCAAATTTTAGTTTTCGCTCTTATTGCCATCATTCCAACTAACGCTGATAAA

ATCTGCCTGGGCCACCACGCCGTCAGCAATGGGACCAAGGTAAACACACTCACCGAACGC

GGCGTGGAAGTAGTGAATGCGACCGAAACTGTTGAGCGCACCAACATTCCACGAATATGT

TCCAAGGGTAAGAAAACCGTGGATCTGGGGCAATGTGGCCTTCTGGGGACGATAACAGGA

CCACCCCAGTGTGACCAGTTTCTGGAGTTTTCCGCAGACCTGATCATCGAACGTAGGGAG

GGAAGCGACGTCTGTTATCCCGGCAAGTTCGTTAATGAGGAGGCCCTTCGACAAATCCTG

CGCGAAAGCGGTGGGATAGACAAAGAAGCCATGGGCTTCACATACAGCGGGATCAGAACC

AACGGCGCCACAAGTGCCTGCAGGCGATCTGGCTCGTCCTTCTACGCGGAGATGAAGTGG

CTGCTGTCAAACACCGACAATGCCGCTTTTCCCCAGATGACAAAAAGCTACAAAAACACC

CGAAAAAGCCCTGCATTAATAGTCTGGGGCATCCACCACAGCGTGTCTACCGCCGAACAA

ACGAAGCTGTATGGTTCCGGAAACAAACTAGTGACGGTGGGCTCATCAAATTATCAGCAG

TCCTTCGTGCCTTCCCCAGGGGCCAGGCCTCAGGTGAATGGACAATCCGGGCGAATTGAT

TTTCATTGGCTCATGTTGAACCCCAACGACACTGTAACGTTTTCTTTCAACGGTGCGTTT

ATCGCTCCAGATAGGGCCTCCTTCCTCCGAGGAAAAAGTATGGGTATCCAGAGTGGCGTG

CAGGTGGATGCCAATTGCGAGGGTGACTGCTACCACTCTGGCGGTACAATTATCTCTAAT

CTGCCCTTCCAGAACATAGACAGCCGTGCGGTCGGGAAGTGCCCCCGCTACGTTAAGCAA

CGGTCTTTATTGCTTGCCACTGGTATGAAGAACGTGCCAGAGATACCAAAAGGGAGAGGG

CTCTTTGGCGCCATCGCTGGATTTATAGAGAACGGGTGGGAGGGCCTGATTGACGGGTGG

TACGGATTCCGCCATCAGAACGCCCAAGGTGAAGGCACCGCCGCCGACTACAAGAGCACC

CAGAGCGCCATTGATCAGATCACGGGAAAACTGAATAGGCTGATTGAAAAGACAAATCAG

CAGTTCGAGCTGATAGACAACGAATTTAACGAAGTAGAAAAACAAATCGGCAACGTGATC

AACTGGACAAGAGACTCCATCACTGAAGTGTGGAGCTATAATGCCGAGTTACTCGTGGCA

ATGGAGAATCAGCATACTATTGATCTGGCCGATTCGGAAATGGACAAGCTGTACGAACGC

GTCAAGCGGCAACTGCGGGAGAATGCCGAGGAGGACGGTACCGGTTGTTTCGAGATTTTT

CATAAATGTGATGACGACTGCATGGCCTCAATTAGAAACAACACATATGATCACAGCAAG

TATCGGGAAGAAGCTATGCAAAACCGGATTCAGATCGACCCAGTTAAGCTGAGTAGCGGG

TATAAGGACGTAATCCTCTGGTTTTCTTTCGGCGCCTCCTGTTTTATTTTATTAGCGATC

GTGATGGGTCTGGTGTTTATCTGCGTCAAAAATGGTAATATGAGGTGTACTATATGTATC

564
ATGAACACTCAGATTCTAGTATTTGCACTTATTGCCATCATACCAACCAACGCTGACAAG

ATCTGTCTCGGCCATCATGCGGTCAGTAACGGTACAAAGGTCAATACACTGACAGAACGT

GGGGTAGAGGTCGTAAACGCAACCGAGACCGTGGAGAGAACCAATATTCCTCGAATATGT

TCCAAAGGCAAGAGGACTGTTGATTTAGGACAGTGCGGGCTGCTGGGAACTATAACAGGG

CCCCCACAATGTGATCAATTCCTCGAGTTCTCAGCCGACCTCATTATCGAGAGACGCGAG

GGATCTGATGTGTGCTACCCTGGCAAATTCGTGAACGAGGAGGCCCTGCGCCAGATCTTG

CGGGAAAGCGGTGGAATCGATAAGGAGGCCATGGGGTTTACTTATAGCGGCATAAGGACC

AACGGCGCCACCTCTGCATGCAGGAGGAGCGGCAGTAGCTTCTACGCAGAGATGAAATGG

CTGCTGTCTAATACCGACAATGCCGCGTTCCCTCAAATGACTAAAAGCTACAAGAATACG

CGCAAGTCTCCAGCCCTGATCGTGTGGGGCATCCATCACAGTGTCTCAACTGCAGAACAG

ACCAAACTTTACGGTTCAGGCAACAAACTCGTCACCGTCGGCTCTTCTAATTATCAACAG

AGTTTCGTGCCTAGCCCAGGCGAGCGACCCCAGGTGAACGGTCTTTCCGGTCGGATCGAT

TTTCACTGGCTCATGCTCAACCCGAACGATACTGTGACTTTCAGTTTCAACGGGGCCTTC

ATTGCTCCGGATCGGGCATCATTTCTGAGGGGCAAGTCTATGGGCATCCAGTCCGGCGTG

CAGGTGGACGCTAACTGCGAAGGTGATTGTTACCACTCGGGTGGCACAATCATTTCTAAT

CTACCCTTCCAGAACATTGACTCAAGAGCTGTCGGGAAGTGTCCACGATACGTGAAGCAG

AGATCCCTGCTCCTCGCCACAGGGATGAAGAATGTCCCAGAGATTCCTAAAGGGCGCGGC

CTGTTCGGAGCTATAGCGGGGTTCATTGAGAATGGGTGGGAAGGCCTAATTGACGGTTGG

TATGGTTTTAGGCATCAGAATGCCCAGGGCGAGGGTACCGCCGCAGATTATAAAAGTACT

CAGTCTGCCATCGATCAAATCACCGGGAAGCTAAACCGGTTGATCGAAAAAACTAACCAG

CAGTTTGAGCTGATTGACAACGAATTTAACGAGGTGGAGAAACAGATCGGCAACGTAATT

AATTGGACGCGGGATAGCATCACAGAAGTCTGGAGCTATAATGCAGAGCTCCTGGTGGCG

ATGGAGAATCAGCACACTATCGACTTGGCTGATTCGGAAATGGATAAGCTGTATGAGAGG

GTGAAACGTCAGCTGCGGGAGAATGCCGAAGAAGATGGTACCGGGTGTTTCGAAATATTC

CATAAATGTGACGATGATTGTATGGCCAGCATCCGAAATAACACATATGACCATTCTAAA

TACAGAGAAGAGGCCATGCAGAATCGAATACAAATCGACCCTGTGAAACTGTCCTCCGGA

TATAAAGATGTTATCCTTTGGTTTAGCTTCGGCGCCTCTTGCTTTATACTGTTGGCAATC

GTGATGGGCTTGGTATTTATTTGTGTCAAGAATGGCAATATGCGCTGTACGATCTGCATT

565
ATGAACACCCAGATCTTGGTGTTTGCTCTTATTGCAATCATCCCTACTAACGCCGATAAA

ATCTGTCTGGGTCACCATGCCGTCAGTAATGGAACCAAGGTAAACACACTGACGGAGAGG

GGCGTGGAGGTGGTTAACGCAACCGAAACAGTTGAGCGGACGAATATCCCCCGGATATGT

AGTAAGGGAAAGAAAACTGTCGATCTGGGACAGTGCGGCCTACTAGGAACCATCACTGGG

CCTCCCCAGTGTGACCAGTTCCTGGAATTTTCTGCCGACCTGATTATCGAACGCCGTGAG

GGATCCGACGTGTGCTATCCAGGTAAATTCGTGAATGAAGAAGCACTTAGGCAGATCCTT

CGTGAATCTGGGGGCATCGATAAGGAAGCTATGGGGTTTACTTATTCCGGTATTAGGACC

AACGGGGCAACAAGCGCCTGCAGACGAAGTGGTTCGTCATTTTACGCCGAGATGAAATGG

CTGTTGTCCAACACTGACAATGCTGCTTTTCCCCAAATGACCAAAAGCTATAAAAACACT

CGGAAATCACCCGCCCTCATCGTATGGGGGATCCACCATTCTGTTTCTACTGCAGAACAG

ACAAAACTGTACGGGAGCGGCAATAAGCTGGTGACCGTGGGGTCCTCCAATTATCAACAG

TCTTTTGTCCCGTCCCCAGGAGCGAGACCACAGGTCAATGGACAGTCAGGCCGAATCGAC

TTCCACTGGCTTATGCTTAATCCAAACGACACCGTCACCTTTAGTTTCAATGGCGCCTTC

ATCGCCCCAGACAGAGCCTCATTCCTGCGCGGGAAATCGATGGGCATTCAGTCGGGAGTC

CAAGTGGACGCAAACTGCGAAGGTGACTGTTACCATAGTGGGGGCACAATCATCAGTAAC

CTGCCCTTTCAGAACATAGATTCCCGCGCCGTAGGAAAGTGTCCCCGGTATGTGAAACAG

AGATCATTGTTGCTGGCAACAGGGATGAAAAATGTACCCGAAATTCCCAAAGGGCGAGGG

CTGTTTGGAGCCATTGCCGGTTTTATCGAGAACGGGTGGGAGGGCCTGATCGATGGGTGG

TACGGTTTCAGACACCAGAACGCCCAGGGCGAAGGGACCGCTGCAGATTACAAGTCGACC

CAATCCGCGATAGATCAGATCACTGGTAAACTCAATCGACTCATTGAAAAGACAAATCAA

CAGTTCGAGCTGATTGATAACGAGTTCAACGAAGTCGAAAAGCAGATAGGGAACGTGATC

AATTGGACACGCGACTCCATCACCGAAGTGTGGAGTTACAATGCAGAGCTGTTGGTAGCG

ATGGAGAACCAGCATACTATTGACCTGGCCGATTCAGAAATGGACAAGCTGTACGAGCGC

GTCAAGCGGCAACTGCGAGAGAATGCTGAAGAGGATGGAACCGGATGCTTCGAAATCTTC

CACAAGTGCGATGACGACTGCATGGCCTCCATCAGGAACAATACATACGATCACTCAAAG

TACCGGGAGGAGGCCATGCAGAACCGTATTCAGATCGACCCCGTAAAACTGAGCTCCGGC

TACAAGGATGTAATCTTGTGGTTCAGCTTCGGCGCTTCATGCTTTATTTTACTGGCCATC

GTCATGGGACTTGTCTTTATCTGTGTTAAGAACGGGAATATGCGGTGCACCATCTGCATC

566
ATGAATACACAGATACTGGTGTTTGCCCTCATTGCAATCATTCCAACCAATGCCGACAAG

ATTTGCCTGGGCCATCACGCTGTGTCCAACGGCACCAAGGTGAACACCCTTACAGAACGC

GGGGTGGAGGTGGTCAACGCAACCGAGACCGTGGAGAGAACCAATATTCCAAGGATCTGC

TCGAAGGGAAAGAAGACCGTAGATCTGGGACAGTGTGGGCTGCTCGGCACAATAACCGGC

CCCCCGCAGTGTGATCAGTTCTTGGAGTTCAGCGCTGATCTGATTATCGAGCGGAGGGAG

GGATCCGACGTCTGTTACCCCGGGAAGTTCGTGAATGAAGAAGCTCTTAGACAGATCCTT

CGCGAATCTGGCGGAATTGACAAGGAAGCTATGGGCTTCACTTATTCTGGAATAAGAACC

AACGGCGCAACCTCCGCCTGTAGGCGCAGCGGATCCAGCTTTTATGCCGAGATGAAATGG

TTGTTGTCCAATACTGACAATGCCGCTTTCCCCCAGATGACCAAGTCCTACAAGAATACT

CGAAAAAGCCCAGCTTTGATCGTCTGGGGCATCCACCATTCTGTCTCCACCGCGGAGCAG

ACCAAGCTTTATGGCTCTGGTAACAAGCTGGTGACTGTGGGAAGCAGCAATTACCAGCAA

AGTTTCGTGCCTAGTCCCGGGGCCCGCCCACAGGTAAACGGCCAGTCAGGGAGAATAGAC

TTCCACTGGCTGATGCTGAACCCTAATGACACGGTGACATTTAGCTTTAATGGTGCTTTC

ATCGCTCCCGATCGCGCCAGTTTTCTCAGAGGGAAGTCGATGGGAATCCAATCCGGTGTC

CAAGTGGACGCCAATTGTGAGGGAGACTGCTATCATAGCGGGGGAACAATCATATCTAAT

CTTCCATTTCAGAACATTGATTCTCGAGCAGTTGGAAAGTGCCCCCGGTACGTGAAGCAA

CGAAGCCTGCTCCTTGCAACCGGCATGAAGAATGTGCCCGAGATCCCAAAGGGACGGGGC

CTATTCGGGGCCATCGCCGGGTTCATCGAGAATGGTTGGGAGGGACTAATCGATGGATGG

TATGGCTTTCGGCACCAGAACGCTCAGGGCGAAGGAACCGCAGCAGACTACAAATCAACA

CAGTCCGCCATAGACCAGATCACAGGTAAACTCAACCGCCTGATAGAGAAAACAAATCAG

CAATTTGAACTTATCGACAATGAGTTCAACGAAGTGGAGAAACAAATAGGAAACGTAATT

AACTGGACCAGGGACTCAATCACCGAAGTGTGGAGCTATAATGCCGAGCTCCTGGTGGCT

ATGGAGAATCAGCATACTATCGACTTAGCTGACAGCGAGATGGACAAGCTGTATGAACGG

GTCAAACGGCAGCTTAGGGAGAATGCTGAAGAGGATGGCACTGGCTGCTTCGAGATCTTC

CACAAATGCGATGATGACTGTATGGCCTCTATTAGGAATAATACGTACGACCATTCTAAA

TACAGGGAGGAGGCTATGCAGAACCGGATTCAGATTGATCCAGTTAAGCTGTCTAGCGGT

TATAAAGATGTGATTTTGTGGTTCTCCTTTGGCGCCAGCTGTTTCATCTTGCTAGCAATA

GTTATGGGCCTAGTGTTTATCTGCGTGAAGAACGGCAATATGAGATGTACAATCTGCATC

567
ATGAACACACAGATCCTGGTATTTGCTCTTATCGCTATCATCCCGACCAACGCCGATAAG

ATCTGTCTTGGCCACCACGCCGTTTCGAATGGCACCAAGGTGAATACTCTTACCGAACGA

GGAGTGGAAGTTGTGAACGCCACGGAAACAGTTGAACGCACCAACATCCCGAGGATCTGT

TCCAAAGGCAAGAAAACGGTTGACCTGGGCCAGTGTGGACTGTTGGGGACTATCACCGGG

CCCCCACAGTGTGATCAGTTCCTGGAGTTTTCTGCTGACCTGATTATTGAAAGACGGGAG

GGGTCAGACGTGTGTTACCCCGGCAAGTTCGTCAATGAGGAAGCTCTTCGACAGATTTTA

AGGGAATCGGGCGGAATTGACAAGGAAGCCATGGGGTTCACCTACTCTGGGATTCGTACC

AACGGTGCTACCTCCGCTTGTCGAAGGTCTGGCAGTAGCTTCTACGCGGAGATGAAATGG

CTCCTGTCAAACACAGACAATGCCGCGTTCCCTCAAATGACTAAGTCATACAAAAACACT

CGTAAGTCCCCGGCTCTCATAGTGTGGGGCATCCACCATAGTGTGAGCACAGCGGAGCAG

ACCAAATTGTACGGAAGCGGCAACAAGCTTGTGACTGTGGGTTCCTCCAACTACCAACAG

AGTTTCGTGCCAAGCCCGGGCGCTCGCCCTCAGGTCAACGGCCAGTCCGGCAGAATTGAC

TTCCACTGGCTCATGCTCAACCCAAACGACACAGTTACATTTAGTTTCAATGGAGCGTTC

ATAGCACCTGATCGCGCTTCTTTTCTGAGAGGAAAATCCATGGGGATTCAGAGTGGTGTG

CAAGTAGATGCTAACTGCGAGGGCGACTGTTACCACTCTGGCGGTACTATCATCTCCAAC

CTCCCATTTCAAAACATAGATTCTCGTGCGGTGGGCAAATGTCCGAGGTACGTGAAACAG

CGATCACTCCTGCTAGCCACCGGAATGAAAAACGTGCCCGAGATCCCGAAGGGCCGGGGC

CTGTTCGGTGCCATCGCAGGGTTTATCGAAAACGGGTGGGAAGGCCTGATCGATGGGTGG

TATGGGTTTCGGCATCAGAACGCACAGGGAGAAGGAACAGCTGCTGACTACAAAAGCACA

CAGTCTGCCATCGACCAAATTACAGGTAAACTCAATAGGCTCATTGAGAAGACCAATCAG

CAGTTCGAGCTCATTGACAATGAGTTTAACGAGGTCGAAAAGCAAATCGGGAATGTAATA

AATTGGACCCGCGACAGTATCACAGAAGTCTGGAGTTACAACGCAGAGCTGCTCGTGGCT

ATGGAGAACCAGCACACAATTGACTTGGCTGACTCCGAAATGGATAAGTTGTACGAACGA

GTAAAGCGCCAGCTGCGCGAGAACGCTGAAGAGGACGGGACGGGGTGTTTCGAAATTTTC

CACAAATGTGACGATGATTGCATGGCCTCTATCCGCAACAATACCTACGACCACAGCAAG

TACCGCGAGGAGGCCATGCAGAACCGCATCCAAATCGACCCTGTGAAGTTGTCTTCCGGA

TACAAGGATGTGATCCTGTGGTTCTCCTTTGGGGCCAGTTGCTTTATCCTTCTCGCAATT

GTGATGGGACTCGTCTTTATCTGCGTGAAAAACGGTAACATGCGCTGTACAATTTGTATA

568
ATGAACACCCAGATCCTAGTCTTTGCTCTGATTGCGATCATCCCCACCAATGCGGATAAG

ATCTGCCTCGGACACCACGCCGTCTCTAATGGCACGAAAGTCAACACCTTAACAGAAAGG

GGGGTGGAGGTGGTTAATGCCACCGAGACAGTCGAACGAACGAATATTCCCAGAATTTGT

TCTAAAGGAAAACGCACCGTGGACTTAGGGCAGTGCGGCCTCCTCGGCACTATTACCGGC

CCTCCACAGTGTGACCAGTTCTTAGAGTTCAGCGCCGACCTGATCATAGAGCGAAGGGAA

GGGTCTGACGTGTGCTATCCTGGCAAATTTGTGAATGAGGAGGCCTTGAGACAGATTCTT

AGGGAGTCGGGCGGTATAGACAAGGAAGCTATGGGCTTTACATACAGTGGGATCCGGACA

AATGGCGCGACAAGCGCATGTAGGAGAAGCGGAAGCAGCTTTTACGCTGAGATGAAGTGG

CTACTCTCCAATACCGATAATGCCGCCTTCCCACAAATGACAAAATCCTATAAGAACACC

AGGAAGTCCCCAGCCCTCATCGTCTGGGGAATTCACCACTCCGTCTCTACAGCAGAACAA

ACTAAACTCTACGGTTCCGGAAATAAGCTCGTTACTGTCGGCAGCTCCAATTACCAGCAG

TCATTCGTCCCAAGTCCCGGAGCAAGACCTCAGGTTAATGGCCTCAGCGGAAGAATCGAC

TTCCACTGGTTGATGTTAAACCCGAACGACACAGTGACATTCTCCTTTAACGGAGCCTTC

ATCGCACCGGATCGGGCCTCTTTTTTAAGGGGAAAGAGCATGGGCATTCAGTCCGGGGTG

CAGGTCGATGCTAACTGTGAAGGCGATTGTTATCATAGCGGAGGCACCATCATCTCAAAT

CTGCCTTTTCAGAACATTGACTCCAGAGCTGTAGGAAAGTGTCCTCGCTATGTGAAACAA

AGGTCTCTTCTGCTGGCAACTGGAATGAAGAATGTGCCAGAGATTCCTAAGGGTCGGGGA

CTATTTGGAGCCATAGCCGGCTTTATAGAAAATGGATGGGAGGGCCTGATAGACGGTTGG

TACGGGTTCCGCCATCAGAATGCCCAAGGTGAGGGTACGGCCGCAGACTATAAGTCTACA

CAGAGCGCCATTGATCAGATAACCGGAAAGCTGAACCGTCTGATAGAGAAAACCAACCAG

CAATTTGAACTTATTGATAACGAGTTCAACGAGGTTGAGAAGCAGATCGGCAATGTTATT

AACTGGACAAGAGATTCGATCACCGAAGTTTGGTCATACAACGCCGAACTGCTGGTAGCC

ATGGAGAACCAGCACACAATCGACCTCGCAGATAGTGAGATGGACAAACTGTACGAGCGT

GTGAAGAGACAGCTGAGAGAGAACGCGGAGGAAGACGGCACTGGCTGTTTCGAGATTTTC

CATAAGTGCGATGACGATTGCATGGCCTCCATTAGGAATAATACCTATGACCATTCCAAA

TACCGTGAAGAAGCCATGCAAAACCGGATCCAGATTGACCCCGTCAAGCTTTCGTCAGGG

TATAAAGATGTGATCCTGTGGTTCTCTTTCGGCGCCAGTTGCTTCATCCTGCTCGCAATC

GTGATGGGACTCGTGTTCATATGTGTCAAAAACGGCAACATGCGCTGTACGATCTGCATA

569
ATGAACACTCAGATCCTTGTCTTTGCCCTAATAGCAATAATTCCAACAAATGCCGATAAA

ATCTGTTTGGGTCATCACGCCGTCTCAAACGGAACAAAGGTGAACACACTGACAGAACGG

GGTGTCGAGGTGGTCAATGCCACCGAAACTGTCGAACGCACTAATATTCCCAGAATATGC

TCGAAGGGTAAGAGGACGGTAGACTTGGGCCAGTGTGGCCTGCTTGGTACCATCACTGGC

CCTCCCCAGTGTGACCAATTCCTGGAGTTTAGCGCGGACCTGATAATTGAGAGACGTGAG

GGTAGCGATGTTTGCTATCCTGGAAAGTTCGTCAATGAAGAGGCCCTGAGGCAGATCCTA

CGAGAATCCGGCGGGATCGATAAAGAAGCTATGGGATTTACCTACTCCGGGATCAGGACA

AACGGGGCAACTTCGGCATGTCGGCGGTCTGGCAGCTCATTTTATGCTGAGATGAAATGG

TTGCTCTCAAACACCGATAACGCCGCTTTCCCACAAATCACCAAGTCCTACAAGAACACA

AGGAAGTCCCCCGCTTTGATTGTCTGGGGCATCCACCACAGCGTGTCAACTGCTGAGCAG

ACCAAGTTATACGGCTCAGGCAACAAACTCGTTACCGTGGGATCTTCGAATTATCAACAG

AGTTTTGTGCCATCCCCTGGTGCTAGGCCGCAAGTTAATGGTCTTAGTGGGCGTATAGAC

TTCCACTGGCTTATGCTGAATCCGAACGATACCGTCACCTTTTCATTCAACGGTGCTTTC

ATAGCCCCCGATCGCGCCTCTTTCCTCAGGGGGAAGTCTATGGGTATTCAGTCAGGTGTG

CAGGTGGATGCGAATTGTGAGGGAGATTGTTACCACTCCGGGGGCACCATAATAAGCAAT

CTTCCCTTTCAAAATATCGACTCTCGGGGGGTCGGAAAATGTCCGCGCTATGTGAAGCAG

CGGAGTCTCCTGCTGGCAACAGGGATGAAAAATGTGCCCGAGATTCCTAAAGGAAGAGGT

TTGTTTGGTGCGATCGCTGGTTTTATCGAGAATGGGTGGGAGGGCTTAATCGACGGTTGG

TATGGGTTTAGACACCAGAACGCCCAGGGAGAGGGTACCGCAGCCGACTATAAGAGTACA

CAGAGCGCAATCGACCAGATCACAGGCAAACTCAACCGCCTAATTGAGAAAACTAACCAG

CAATTCGAGTTAATCGACAATGAGTTCAACGAGGTAGAAAAGCAAATAGGCAACGTCATT

AATTGGACCCGGGACAGTATAACAGAGGTCTGGAGCTATAATGCCGAGCTGTTGGTGGCC

ATGGAAAACCAGCACACGATCGACCTGGCAGACAGCGAAATGGACAAGCTGTACGAGAGA

GTTAAGCGCCAGTTGCGCGAGAACGCCGAGGAAGATGGCACCGGGTGCTTCGAAATCTTT

CACAAGTGCGATGACGACTGCATGGCTTCTATTCGAAATAATACTTATGATCATAGCAAG

TATAGAGAAGAAGCCATGCAGAATAGGATCCAGATCGACCCAGTAAAGTTGTCTTCTGGC

TACAAGGATGTGATACTGTGGTTCTCCTTTGGGGCTAGTTGCTTTATTTTGCTGGCTATT

GTTATGGGTCTGGTGTTCATTTGTGTGAAGAATGGGAACATGCGCTGCACGATATGTATC

570
ATGAATACCCAGATCCTGGTGTTCGCACTGATCGCCATTATACCCACCAACGCCGACAAG

ATCTGCCTTGGCCACCACGCTGTTTCTAATGGAACGAAGGTCAATACTCTGACCGAGAGG

GGGGTGGAAGTCGTGAACGCTACAGAGACTGTTGAAAGGACAAATATTCCGCGCATTTGC

AGCAAAGGGAAGCGAACCGTGGATTTGGGCCAATGTGGCCTCCTTGGCACTATTACAGGC

CCACCTCAGTGTGATCAGTTTCTGGAATTCTCCGCTGACCTCATTATAGAACGGAGAGAA

GGATCAGACGTTTGTTACCCTGGCAAATTCGTGAATGAGGAGGCCTTGAGACAGATACTC

AGGGAGTCCGGCGGCATCGACAAGGAAGCAATGGGTTTCACCTACAGCGGCATTCGCACC

AACGGCGCCACCTCCGCCTGCCGCCGCAGCGGGTCTAGCTTTTATGCCGAAATGAAATGG

CTCTTAAGTAATACAGACAACGCTGCCTTTCCCCAGATGACAAAATCATACAAGAACACA

AGAAAATCACCCGCACTTATAGTTTGGGGGATCCATCACTCCGTGTCCACCGCTGAGCAG

ACTAAGTTGTACGGGAGTGGAAACAAACTGGTTACGGTGGGTAGTTCTAACTATCAGCAG

TCCTTTGTGCCTTCGCCCGGAGCTCGCCCACAGGTTAACGGTCTGAGCGGTCGCATCGAC

TTCCACTGGCTAATGCTGAACCCTAACGATACCGTGACATTCTCTTTTAATGGAGCTTTC

ATCGCCCCCGACCGCGCTTCCTTTTTGAGGGGGAAGTCCATGGGTATCCAGAGCGGAGTG

CAGGTGGACGCCAATTGCGAGGGAGATTGTTATCATTCTGGGGGCACCATTATCTCTAAT

TTACCGTTTCAGAATATCGACTCAAGAGCAGTGGGCAAGTGCCCTCGATACGTGAAGCAG

CGCAGCCTGCTTCTTGCTACAGGAATGAAAAACGTCCCGGAGATTCCCAAGGGGGGGGGC

CTGTTCGGCGCCATCGCAGGCTTCATAGAGAACGGTTGGGAGGGACTGATTGATGGATGG

TACGGGTTCCGCCATCAGAACGCCCAGGGCGAAGGAACCGCTGCGGACTACAAGTCCACC

CAGTCCGCAATCGACCAGATAACGGGCAAGTTGAATAGGCTCATCGAAAAAACGAACCAA

CAATTCGAGCTTATTGATAACGAGTTTAACGAAGTAGAAAAGCAGATTGGGAATGTGATA

AACTGGACCAGAGATAGCATCACCGAGGTGTGGAGCTATAATGCAGAACTGCTAGTAGCT

ATGGAAAATCAGCACACAATCGACTTAGCCGATAGTGAGATGGACAAATTGTATGAGCGA

GTAAAAAGACAATTAAGAGAAAACGCAGAGGAGGATGGCACCGGTTGTTTCGAAATCTTT

CACAAATGTGATGACGACTGTATGGCCTCAATTCGGAACAACACCTACGACCACAGCAAA

TACAGAGAAGAGGCCATGCAGAATCGCATACAGATAGATCCAGTCAAACTGTCATCTGGG

TACAAGGACGTTATATTATGGTTCTCTTTCGGGGCAAGCTGCTTCATCCTTCTGGCTATC

GTGATGGGCTTGGTCTTCATCTGCGTCAAGAATGGAAACATGCGCTGCACCATCTGCATC

571
ATGAATACCCAGATCCTGGTTTTCGCCCTGATCGCTATCATTCCTACTAACGCAGATAAG

ATCTGCCTGGGGCACCATGCAGTCAGCAACGGGACCAAGGTGAACACACTGACTGAGCGT

GGAGTCGAGGTCGTCAATGCGACTGAGACAGTAGAGCGGACGAACATACCCAGAATCTGC

AGCAAAGGGAAACGGACGGTAGACCTCGGCCAGTGCGGTCTCCTGGGTACCATCACAGGT

CCACCCCAATGCGATCAGTTTCTGGAGTTCTCCGCCGACCTCATCATCGAACGGCGCGAG

GGGTCCGATGTCTGCTACCCTGGTAAATTCGTCAATGAAGAGGCTCTCCGTCAGATTCTT

CGGGAATCAGGGGGGATTGACAAGGAAGCTATGGGATTTACATACTCCGGTATACGAACC

AACGGAGCTACCAGTGCTTGCCGACGGTCAGGGTCATCATTCTACGCCGAGATGAAATGG

CTTCTCTCGAACACTGATAATGCTGCGTTTCCACAAATTACCAAAAGCTACAAAAACACC

CGGAAGTCCCCTGCACTGATCGTGTGGGGAATTCACCACAGCGTCTCTACGGCTGAACAG

ACCAAACTGTACGGATCAGGCAACAAGTTGGTGACTGTCGGGTCATCCAATTATCAGCAG

AGTTTCGTTCCCAGCCCTGGCGCAAGACCTCAGGTGAACGGCTTGTCCGGGAGGATTGAT

TTTCACTGGCTCATGCTGAATCCTAATGACACTGTTACCTTTTCTTTTAATGGGGCTTTT

ATTGCACCGGACCGAGCAAGTTTTCTACGCGGAAAGTCCATGGGGATACAGAGTGGGGTG

CAGGTGGATGCTAATTGCGAGGGCGATTGTTATCACAGGGGCGGCACCATAATATCAAAC

CTGCCCTTCCAGAACATCGACTCCAGGGCCGTGGGCAAGTGTCCAAGATACGTCAAACAA

AGATCTCTGCTGCTGGCCACTGGGATGAAAAACGTCCCAGAAATCCCAAAAGGGAGGGGG

CTCTTCGGAGCCATAGCCGGGTTTATCGAAAATGGATGGGAAGGTCTGATAGACGGGTGG

TACGGTTTCAGACATCAGAACGCACAGGGCGAGGGAACAGCCGCCGACTACAAGAGCACC

CAGAGTGCAATCGATCAGATCACTGGTAAGCTTAATAGGCTGATCGAAAAGACTAATCAA

CAATTTGAGCTGATAGACAATGAATTCAACGAAGTTGAAAAGCAGATAGGTAATGTAATC

AATTGGACCCGAGATTCAATAACTGAAGTCTGGAGCTACAATGCCGAACTGTTGGTGGCT

ATGGAGAACCAACATACGATTGACCTGGCCGACTCCGAGATGGACAAGCTGTATGAGCGG

GTAAAGAGACAGCTGAGGGAGAATGCCGAGGAAGATGGCACCGGATGTTTCGAGATTTTT

CACAAGTGTGATGACGACTGCATGGCGTCTATCCGGAATAACACCTACGACCACTCAAAA

TATCGGGAAGAAGCGATGCAGAATCGAATTCAGATCGACCCAGTCAAACTGTCGAGTGGC

TATAAAGATGTGATACTGTGGTTTAGCTTCGGGGCATCTTGTTTCATTCTGCTGGCTATT

GTGATGGGCCTCGTGTTCATTTGCGTTAAGAATGGGAATATGCGATGCACCATTTGTATC

572
ATGAATACTCAAATACTTGTCTTTGCACTAATCGCTATCATACCCACTAATGCCGATAAA

ATCTGCTTAGGACACCATGCTGTGTCCAACGGAACTAAAGTGAACACTCTGACGGAGCGA

GGCGTCGAAGTTGTCAACGCAACCGAGACTGTGGAGCGCACGAATATCCCCCGAATCTGC

TCGAAAGGAAAGAAGACTGTTGACCTTGGTCAATGCGGATTACTGGGAACCATCACAGGA

CCCCCCCAATGCGACCAGTTTCTGGAATTTAGTGCTGATCTTATAATCGAGCGCCGGGAA

GGTAGCGACGTTTGTTATCCGGGAAAGTTTGTAAACGAGGAGGCTCTGAGACAGATCCTG

CGCGAGTCAGGGGGGATCGACAAGGAGGCCATGGGCTTTACCTACTCTGGAATCAGAACA

AATGGCGCTACTTCCGCTTGTCGGCGCTCTGGAAGCAGCTTCTATGCTGAAATGAAATGG

CTGCTGTCCAACACCGACAATGCAGCCTTTCCTCAGATGACTAAATCTTACAAAAATACC

CGGAAATCCCCAGCTCTGATAGTGTGGGGTATCCATCACTCAGTCAGTACTGCTGAACAA

ACCAAGTTATATGGCTCCGGCAATAAGCTAGTAACCGTGGGAAGCTCCAACTACCAACAG

TCTTTCGTGCCCTCACCCGGCGCAAGACCCCAGGTGAACGGCCAGTCAGGTCGCATTGAT

TTCCACTGGTTGATGCTTAACCCAAATGACACCGTTACCTTTTCCTTCAATGGCGCCTTT

ATAGCGCCCGACAGAGCTTCATTCCTTAGAGGCAAGTCTATGGGTATCCAATCCGGAGTC

CAGGTAGACGCAAACTGTGAGGGAGACTGCTATCATTCCGGTGGAACCATCATATCGAAT

TTGCCTTTCCAGAACATCGATAGCCGGGCGGTCGGCAAGTGCCCTAGATACGTTAAACAA

AGGAGCCTGCTCTTAGCAACAGGTATGAAGAACGTCCCAGAGATTCCAAAGGGCCGAGGA

CTGTTCGGTGCAATAGCTGGCTTTATCGAGAATGGGTGGGAGGGGCTCATCGATGGTTGG

TATGGGTTCAGACACCAGAATGCCCAGGGCGAAGGAACCGCTGCTGACTACAAAAGCACA

CAGAGCGCTATAGATCAGATAACAGGCAAGCTTAACCGGCTGATCGAGAAAACGAATCAG

CAGTTCGAACTCATTGATAATGAGTTCAACGAAGTGGAGAAGCAGATTGGTAATGTCATC

AACTGGACTAGAGATAGTATAACAGAAGTGTGGTCTTATAACGCCGAACTCCTGGTCGCA

ATGGAAAATCAACATACCATTGACCTGGCTGATTCGGAGATGGACAAACTTTATGAGCGG

GTGAAGAGGCAGCTCCGAGAGAATGCAGAAGAGGACGGCACAGGGTGCTTTGAGATCTTC

CATAAGTGCGACGATGATTGCATGGCTTCCATCAGGAATAATACTTATGACCACTCCAAG

TACCGGGAGGAAGCCATGCAAAATCGGATCCAAATAGATCCAGTGAAGCTTTCGTCAGGA

TATAAGGACGTGATCTTGTGGTTTAGCTTCGGGGCCTCTTGTTTCATCCTCCTGGCGATT

GTCATGGGACTTGTATTCATTTGTGTGAAGAACGGAAACATGCGCTGCACCATTTGCATA

573
ATGAACACACAGATCCTTGTGTTCGCCCTTATCGCAATAATTCCCACAAACGCCGACAAA

ATATGCCTGGGTCACCACGCCGTAAGCAATGGCACCAAAGTTAACACCCTCACCGAGCGT

GGGGTGGAGGTGGTGAACGCCACCGAGACCGTTGAAAGGACAAACATTCCACGAATTTGT

AGTAAGGGCAAACGGACTGTAGATCTGGGTCAGTGTGGGCTGCTGGGCACTATCACCGGC

CCACCACAGTGCGACCAATTCCTAGAATTCTCAGCTGATTTAATCATCGAAAGGCGCGAG

GGGTCTGACGTCTGTTACCCGGGAAAATTTGTGAACGAAGAGGCCCTGCGACAGATTCTG

CGTGAGTCCGGGGGAATCGACAAAGAGGCGATGGGATTTACCTATTCAGGCATACGGACC

AATGGAGCTACTTCTGCATGCCGGAGGAGCGGCTCGTCTTTCTACGCTGAAATGAAGTGG

TTGCTGAGTAATACCGACAACGCAGCCTTCCCCCAGATGACAAAGAGCTACAAGAACACA

CGCAAGTCACCCGCACTCATAGTCTGGGGGATTCATCACTCAGTCAGTACCGCGGAGCAG

ACCAAGCTCTACGGTAGCGGCAACAAGCTGGTCACAGTTGGTTCTAGTAATTACCAGCAG

TCCTTTGTTCCCTCCCCCGGCGCCCGTCCCCAAGTCAACGGGCTCTCGGGCAGAATCGAC

TTCCACTGGCTCATGTTGAACCCCAACGATACTGTGACATTCTCTTTTAATGGTGCTTTT

ATCGCGCCGGACAGGGCCTCTTTCTTACGCGGCAAGAGCATGGGTATACAGTCTGGAGTC

CAGGTTGATGCTAATTGCGAAGGCGACTGTTATCATTCAGGAGGCACCATCATATCAAAC

CTGCCCTTCCAAAATATAGATAGTCGGGCTGTGGGTAAATGCCCTAGGTACGTCAAGCAG

AGAAGTCTTCTGCTCGCCACTGGCATGAAAAACGTACCAGAGATTCCTAAAGGAAGAGGC

CTATTTGGAGCAATTGCCGGCTTTATCGAGAATGGGTGGGAAGGCCTTATAAACGGGTGG

TATGGCTTCAGGCACCAGAACGCCCAGGGGGAGGGTACCGCCGCCGATTACAAGAGCACT

CAGAGTGCCATAGACCAGATTACTGGAAAATTAAATAGACTGATTGAGAAAACAAACCAG

CAGTTTGAACTGATTGACAATGAATTCAATGAGGTGGAGAAGCAGATTGGGAACGTGATC

AATTGGACCCGGGACTCTATTACTGAGGTATGGAGCTATAACGCTGAGCTTTTGGTGGCC

ATGGAGAACCAACATACGATTGATCTGGCAGATAGCGAAATGGATAAGCTTTATGAGCGT

GTTAAGAGGCAGCTCCGCGAAAATGCCGAAGAGGATGGTACGGGATGCTTCGAGATTTTC

CATAAATGCGACGACGATTGCATGGCTAGCATTAGGAACAACACCTATGACCACAGTAAA

TATAGAGAGGAGGCCATGCAAAATCGCATTCAGATAGACCCTGTCAAGTTGAGCTCGGGG

TATAAGGACGTCATACTTTGGTTTAGTTTTGGGGCGAGCTGTTTTATTTTGCTGGCCATA

GTTATGGGTCTGGTCTTTATTTGTGTAAAGAACGGGAATATGCGTTGCACCATTTGCATA

574
ATGAACACCCAAATATTAGTGTTCGCCCTCATAGCAATCATTCCCACAAATGCTGATAAG

ATTTGCCTTGGTCATCATGCTGTGAGTAACGGGACCAAGGTGAACACTCTTACGGAGCGC

GGGGTTGAAGTTGTTAACGCTACCGAGACCGTTGAAAGAACCAACATCCCACGAATCTGC

AGCAAGGGGAAGCGGACCGTGGACTTGGGACAGTGTGGGTTGTTGGGGACTATCACCGGG

CCCCCTCAGTGCGACCAGTTCCTCGAATTCAGCGCCGATCTGATCATAGAGCGACGGGAG

GGGAGTGACGTTTGCTACCCCGGTAAATTCGTGAAGGAAGAAGCCCTGAGACAGATTCTA

CGGGAGTCTGGCGGCATAGATAAAGAGGCTATGGGTTTCACATATAGCGGCATCCGCACA

AACGGAGCCACTTCTGCCTGCAGGAGATCTGGCTCCTCTTTTTACGCTGAAATGAAATGG

TTACTGTCCAACACCGACAATGCCGCCTTTCCCCAAATGACCAAGTCATACAAGAATACC

CGGAAATCCCCAGCTTTGATCGTTTGGGGTATCCATCACTCAGTTTCTACCGCGGAGCAG

ACTAAACTCTATGGCTCTGGAAATAAGCTGGTGACAGTGGGCTCTTCCAATTATCAGCAG

TCGTTTGTTCCGTCCCCTGGCGCTAGACCACAGGTGAACGGCCTGTCCGGGCGAATCGAT

TTCCACTGGCTGATGCTGAACCCGAACGACACCGTCACATTTAGCTTCAATGGAGCCTTC

ATTGCTCCCGATCGAGCTTCTTTCCTGCGGGGCAAATCAATGGGCATACAATCGGGTGTG

CAGGTGGACGCCAATTGTGAGGGAGACTGTTACCATTCAGGCGGCACCATTATTAGCAAT

CTACCATTCCAGAATATAGACTCCCGGGCTGTTGGCAAGTGCCCCCGGTATGTTAAACAG

CGGTCCCTGCTCCTGGCTACCGGTATGAAGAATGTTCCGGAAATCCCGAAGGGGCGCGGA

CTCTTCGGCGCTATCGCGGGTTTTATCGAGAACGGGTGGGAGGGCCTTATCGATGGGTGG

TACGGCTTCCGGCACCAGAATGCCCAGGGAGAAGGCACCGCCGCCGACTATAAGTCAACA

CAGTCCGCAATTGACCAAATCACCGGTAAGCTGAATCGCTTAATTGAGAAAACCAACCAA

CAATTCGAACTGATTGATAACGAATTCAACGAGGTCGAAAAGCAGATCGGGAATGTGATC

AACTGGACCCGCGATAGCATTACCGAGGTCTGGTCTTACAACGCAGAACTTCTCGTTGCG

ATGGAGAATCAACACACTATTGATCTGGCTGACTCCGAGATGGACAAGCTGTACGAGCGC

GTGAAGCGCCAGCTGCGGGAAAATGCAGAAGAGGATGGCACTGGCTGCTTCGAGATCTTC

CACAAGTGCGATGATGATTGCATGGCATCGATCAGGAACAATACATACGACCACTCGAAG

TACAGAGAGGAGGCTATGCAGAACCGAATACAGATAGATCCAGTTAAACTATCATCCGGG

TACAAGGACGTTATCCTGTGGTTCTCATTTGGAGCATCCTGCTTCATTCTTCTCGCAATC

GTCATGGGACTGGTTTTCATCTGTGTGAAGAACGGCAACATGCGGTGCACCATCTGCATC

575
ATGAATACCCAGATATTAGTATTTGCCCTTATAGCCATCATCCCTACTAACGCGGACAAA

ATCTGCCTGGGACACCATGCCGTTTCTAACGGTACAAAAGTCAACACCTTAACGGAACGG

GGGGTGGAAGTGGTTAATGCTACAGAGACCGTTGAACGCACCAACATCCCCCGCATTTGC

TCCAAAGGGAAGAAAACTGTGGACCTAGGTCAGTGTGGCCTGTTGGGTACTATCACCGGC

CCACCTCAATGCGACCAGTTTCTGGAGTTCAGCGCCGATCTGATCATCGAAAGAAGAGAG

GGTAGCGACGTTTGTTATCCTGGAAAGTTTGTTAATGAAGAGGCTCTGAGACAGATTTTG

CGAGAATCCGGGGGAATCGACAAGGAAGCCATGGGCTTTACATACTCTGGTATTAGGACC

AACGGTGCCACTTCTGCCTGCAGACGGAGCGGTAGTTCTTTTTACGCCGAAATGAAATGG

CTATTGTCTAATACGGATAACGCTGCATTTCCTCAGATGACGAAATCATACAAAAATACA

AGGAAAAGCCCCGCTCTGATTGTGTGGGGTATCCACCACTCCGTATCCACAGCAGAACAA

ACAAAGCTGTATGGATCTGGTAACAAGCTCGTGACGGTGGGCTCTAGCAACTATCAGCAG

AGTTTTGTGCCATCACCTGGCGCAAGACCCCAGGTCAACGGCCAGTCCGGCCGAATCGAC

TTCCACTGGCTTATGCTAAACCCCAACGACACGGTGACTTTCAGTTTTAACGGCGCCTTT

ATCGCTCCTGATCGCGCTTCTTTCCTTAGGGGTAAATCTATGGGGATACAATCAGGAGTG

CAGGTAGACGCTAACTGCGAAGGAGACTGCTATCACTCTGGAGGAACGATAATCTCCAAT

TTACCCTTCCAGAACATAGACAGTCGGGCCGTCGGGAAATGCCCCAGGTACGTGAAGCAG

CGGTCTCTTCTGCTCGCGACTGGCATGAAAAACGTTCCCGAGATACCCAAGGGAAGGGGC

CTGTTCGGCGCAATTGCTGGGTTCATTGAAAACGGCTGGGAGGGCCTTATTGATGGTTGG

TACGGATTCAGACACCAGAATGCACAGGGCGAGGGCACAGCCGCCGATTATAAGTCAACG

CAGTCAGCGATAGACCAGATAACCGGGAAATTGAACCGTCTGATTGAGAAAACAAACCAG

CAATTCGAATTGATTGATAACGAGTTTAATGAGGTGGAAAAGCAGATTGGAAACGTCATT

AACTGGACACGAGATTCAATTACAGAGGTGTGGAGCTATAACGCGGAGTTGCTGGTCGCT

ATGGAAAACCAACATACTATAGATCTTGCCGATTCCGAGATGGACAAACTCTATGAGAGA

GTCAAACGACAATTAAGGGAAAACGCCGAGGAAGATGGCACCGGATGCTTCGAAATCTTC

CATAAGTGCGATGACGACTGTATGGCATCTATTCGCAACAACACGTACGATCACTCGAAA

TATCGGGAAGAGGCCATGCAGAATAGGATCCAGATTGACCCTGTCAAATTGAGCAGCGGC

TACAAGGATGTTATTCTGTGGTTCAGTTTCGGCGCCTCCTGTTTCATCTTACTCGCTATT

GTCATGGGCTTAGTGTTCATCTGTGTCAAGAATGGCAATATGCGGTGCACTATATGCATT

576
ATGAACACTCAGATTCTGGTGTTCGCCCTAATTGCCATTATTCCCACCAATGCCGACAAA

ATTTGCCTGGGCCATCATGCCGTCTCGAACGGTACCAAAGTCAATACCCTGACAGAGCGC

GGCGTGGAGGTGGTGAATGCAACTGAGACCGTCGAGAGGACTAATATCCCCAGAATTTGC

TCAAAGGGAAAGAAAACAGTGGATCTGGGTCAGTGCGGTCTCTTAGGGACTATCACTGGT

CCTCCTCAGTGCGACCAGTTTCTGGAATTTAGTGCTGATCTGATTATCGAGCGGCGCGAA

GGGTCCGACGTTTGCTACCCCGGAAAGTTTGTTAACGAGGAAGCCTTGCGGCAAATCCTG

CGGAAGTCCGGCGGCATCGACAAGGAGGCCATGGGCTTTACATACTCTGGCATCCGCACC

AACGGAGCTACCAGCACCTGTAGGAGGTCTGGTAGTTCATTCTATGCTGAGATGAAGTGG

CTGCTCAGTAATACCGACAATGCTGCTTTTCCTCAGATGACAAAATCATACAAGAACACG

AGAAAAAGCCCAGCTATTATTGTATGGGGGATTCATCATTCTGTCAGTACCGCTGAGCAG

ACTAAGCTTTACGGTAGCGGAAATAAGCTTGTCACAGTGGGGTCCAGCAATTACCAGCAG

TCGTTTGTTCCCTCCCCAGGAGCACGCCCCCAAGTCAACGGTCTATCGGGGAGGATCGAC

TTCCATTGGCTGATGCTCAATCCTAACGACACCGTGACATTCTCTTTCAATGGCGCCTTT

ATCGCACCGGACCGTGCCTGTTTTTTACGCGGTAAGTCAATGGGGATACAATCTGGAGTC

CAGGTGGACGCCGACTGTGAAGGGGACTGCTATCATTCGGGTGGTACTATTATCAGCAAT

CTGCCCTTCCAAAACATAGACTCAAGAGCTGTTGGAAAGTGCCCGAGATACGTGAAGCAA

AGGTCACTCTTGCTTGCAACCGGGATGAAGAACGTGCCTGAGATCCCGAAGGGCCGAGGG

CTGTTTGGTGCTATAGCTGGCTTCATCGAGAATGGATGGGAGGGTTTAATTGACGGCTGG

TATGGATTTCGGCACCAGAATGCACAGGGAGAAGGGACCGCCGCCGATTACAAAAGTACG

CAGAGTGCTATCGATCAGATTACCGGTAAATTGAATAGGCTGATTGAAAAAACTAACCAG

CAGTTCGAGCTGATTGATAACGAGTTCAACGAGGTCGAGAGACAGATTGGGAACGTCATT

AATTGGACGAGAGACTCAATCACGGAGGTCTGGAGCTACAATGCTGAGCTGTTAGTAGCA

ATGGAAAATCAGCACACTATTGACCTCGCCGACTCCGAGATGGACAAACTGTACGAACGG

GTGAAGCGGCAACTTCGCGAAAACGCTGAGGAAGACGGCACGGGATGTTTCGAAATCTTC

CATAAATGCGACGATGACTGCATGGCCTCTATCCGTAATAACACATATGACCATAGTAAG

TATAGGGAGGAAGCCATGCAGAATCGAATCCAGATCGACCCCGTGAAGCTGAGCTCCGGC

TACAAAGACGTCATCCTCTGGTTTAGCTTTGGGGCGTCTTGTTTCATTCTCCTCGCGATC

GTGATGGGTCTTGTCTTCATTTGCGTGAAAAACGGGAATATGAGGTGTACCATTTGTATC

577
ATGAATACCCAAATACTTGTGTTTGCCTTGATTGCCATAATTCCTACCAATGCCGACAAA

ATCTGCCTGGGCCATCATGCCGTTAGTAATGGGACTAAGGTGAACACCCTGACAGAACGT

GGCGTGGAGGTGGTCAACGCAACAGAAACCGTCGAGAGGACCAACATTCCTCGGATATGT

TCGAAGGGAAAGAAGACGGTGGACCTGGGGCAATGCGGGCTGCTCGGCACCATTACGGGT

CCACCTCAGTGTGATCAGTTTCTCGAGTTTTCTGCAGACCTCATCATTGAACGTAGAGAG

GGCTCAGACGTGTGTTACCCAGGCAAATTTGTTAACGAGGAAGCCCTGCGCCAGATCCTG

CGAGAATCTGGCGGCATTGACAAAGAGGCTATGGGATTCACGTACTCTGGTATCCGTACC

AACGGCGCCACGTCCGCCTGTAGAAGGTCAGGCTCATCTTTTTACGCCGAGATGAAATGG

CTCCTGTCTAATACGGACAATGCCGCATTTCCTCAGATGACCAAAAGTTACAAAAACACC

CGGAAGAGTCCAGCTCTGATTGTGTGGGGCATCCATCACAGCGTGTCAACTGCGGAACAG

ACCAAGCTGTATGGGTCCGGCAATAAACTGGTGACTGTGGGTTCCAGCAATTACCAGCAA

TCCTTTGTGCCCAGCCCTGGCGCTAGACCGCAAGTGAACGGGCAGAGCGGGAGGATTGAC

TTCCACTGGCTGATGCTCAATCCCAACGATACCGTAACCTTTTCATTTAACGGCGCTTTC

ATCGCCCCCGATAGAGCTAGTTTCCTACGGGGAAAAAGCATGGGTATTCAAAGTGGTGTG

CAGGTAGACGCAAATTGTGAAGGCGACTGTTACCATTCGGGTGGGACCATTATCTCCAAC

CTGCCCTTCCAGAACATTGATTCACGCGCCGTGGGAAAGTGCCCTAGGTATGTTAAACAG

AGAAGCCTGCTGTTGGCCACAGGGATGAAGAATGTGCCAGAGATTCCAAAGGGACGGGGA

CTCTTTGGTGCGATCGCAGGCTTCATCGAGAACGGTTGGGAAGGGCTGATAGATGGATGG

TACGGTTTCCGTCACCAGAACGCCCAAGGAGAGGGGACAGCCGCGGACTACAAATCAACG

CAGTCTGCCATTGACCAAATCACTGGCAAACTGAACCGGCTTATCGAGAAAACCAACCAG

CAGTTTGAACTGATAGATAATGAATTCAACGAGGTTGAGAAGCAAATTGGGAACGTCATA

AATTGGACTAGAGACTCTATCACAGAGGTGTGGTCATATAATGCAGAGCTGTTGGTGGCA

ATGGAAAACCAGCACACTATCGACCTAGCAGATTCTGAGATGGACAAGCTATATGAACGC

GTTAAGCGGCAGCTGCGGGAAAACGCAGAAGAAGACGGTACAGGTTGTTTCGAGATATTT

CACAAATGCGACGATGATTGTATGGCATCGATCAGAAATAATACGTATGACCACTCCAAA

TACCGAGAAGAGGCTATGCAGAACCGAATCCAGATTGATCCTGTAAAGCTCAGTTCTGGC

TACAAGGACGTCATTCTCTGGTTTAGCTTTGGAGCCTCCTGTTTCATTCTTTTGGCCATC

GTTATGGGCCTCGTGTTTATTTGCGTGAAAAATGGTAATATGCGGTGTACCATATGTATC

578
ATGAATACCCAAATTCTGGTTTTTGCGCTGATCGCGATCATACCGACCAACGCGGATAAA

ATTTGTCTCGGGCATCACGCCGTGAGCAATGGGACCAAGGTAAACACACTGACGGAGCGG

GGGGTGGAGGTGGTGAACGCCACAGAGACGGTCGAGCGGACAAATATTCCTCGGATATGC

TCCAAGGGCAAGAAGACTGTTGATTTAGGCCAGTGCGGCCTCCTCGGCACCATCACCGGA

CCGCCCCAGTGCGACCAGTTCCTGGAGTTTTCCGCTGACCTGATCATCGAAAGGAGAGAG

GGAAGCGATGTGTGTTACCCTGGAAAGTTTGTTAATGAGGAGGCCCTAAGACAGATTCTG

CGGGAATCCGGCGGCATCGAGAAGGAGGCCATGGGATTTACTTACAGCGGGATTAGAGCG

AACGGAGCTACATCTGCCTGTCGCAGGAGTGGATCTTCCTTCTACGCTGAGATGAAATGG

CTGCTCTCGAATACGGACAACGCCGCGTTTCCTCAAATGACTAAATCTTACAAAAACACT

CGGAAGTCCCCCGCGCTCATTGTGTGGGGAATCCACCACAGTGTGAGTACAGCCGAGCAG

ACTAAACTGTATGGCAGTGGGAATAAGCTGGTCACAGTTGGGTCCTCCAACTACCAGCAG

AGCTTCGTTCCCAGTCCGGGCGCACGCCCGCAGGTTAATGGCCTTAGCGGTAGAATCGAT

TTCCACTGGCTGATGCTGAATCCTAACGATACTGTGACTTTCAGCTTCAATGGCGCTTTT

ATTGCACCCGACAGAGCTTCTTTTCTGCGTGGCAAATCCATGGGCATTCAGTCCGGCGTG

CAGGTGGACGCCAACTGCGAAGGCGATTGTTACCACTCTGGGGGCACCATCATCTCCAAC

CTCCCTTTTCAAAACATAGACAGTCGCGCTGTGGGAAAATGTCCAAGGTACGTTAAACAA

CGGTCTCTGCTACTGGCTACCGGCATGAAGAATGTGCCCGAAATCCCCAAGGGACGGGGC

TTATTTGGCGCGATTGCCGGATTTATTGAAAATGGCTGGGAGGGCCTCATTGACGGATGG

TACGGTTTTCGACACCAGAACGCTCAGGGTGAAGGGACCGCTGCAGACTACAAATCCACG

CAGTCCGCTATCGATCAGATTACAGGAAAGCTGAACAGACTAATCGAGAAGACTAATCAG

CAGTTCGAGCTAATCGATAATGAGTTCAACGAGGTCGAAAAGCAGATTGGGAACGTCATC

AACTGGACTCGCGATAGCATCACGGAGGTATGGTCTTATAATGCAGAGTTGCTGGTGGCC

ATGGAAAATCAGCATACAATCGACTTGGCTGACTCTGAGATGGATAAATTGTATGAGAGG

GTAAAAAGGCAGTTGAGAGAGAACGCGGAGGAAGATGGCACTGGTTGCTTCGAGATCTTT

CACAAGTGTGACGACGATTGCATGGCCAGTATTAGAAATAATACATATGACCACAGCAAG

TACAGGGAGGAGGCCATGCAGAATCGTATCCAAATCGATCCCGTGAAATTGTCAAGCGGA

TATAAAGACGTTATACTATGGTTCTCCTTTGGGGCTAGTTGTTTCATTCTCCTGGCGATC

GTCATGGGCCTGGTTTTCATCTGCGTTAAGAATGGGAATATGAGATGTACTATCTGCATC

579
ATGAATACCCAGATTCTGGTGTTCGCTCTCATTGCAATAATCCCGACTAACGCTGATAAA

ATCTGTCTTGGCCACCACGCTGTGAGTAATGGAACGAAAGTCAATACGCTCACTGAGCGG

GGAGTCGAAGTTGTTAACGCTACCGAGACCGTGGAGCGGACAAACATACCGCGGATTTGC

TCAAAGGGCAAAAAGACAGTGGATCTGGGTCAGTGCGGCCTTCTCGGCACAATCACCGGG

CCCCCACAGTGTGACCAATTTCTCGAGTTTTCAGCTGATTTGATAATTGAGCGCCGGGAG

GGCAGTGATGTATGCTATCCAGGGAAGTTCGTGAATGAAGAGGCCCTCCGCCAAATTCTC

CGGGAATCTGGCGGGATTGACAAGGAAGCCATGGGGTTCACTTACTCTGGAATTCGGACT

AATGGTGCTACCAGTGCTTGCCGTAGAAGTGGTAGCAGTTTCTATGCCGAAATGAAATGG

TTGTTAAGCAATACCGATAACGCAGCATTTCCCCAGATGACAAAGTCGTACAAAAACACC

AGGAAAAGTCCTGCTCTGATCGTGTGGGGTATCCATCACTCTGTGAGTACAGCAGAACAG

ACTAAACTGTATGGATCAGGCAATAAGTTGGTGACAGTAGGCTCTTCGAATTACCAACAG

TCATTTGTCCCCAGCCCGGGAGCCCGGCCACAGGTCAACGGCCAAAGCGGACGCATCGAT

TTCCACTGGCTTATGCTGAATCCTAATGACACCGTCACATTTTCCTTCAATGGGGCCTTT

ATTGCCCCAGATCGTGCATCCTTTCTGAGAGGGAAATCCATGGGTATACAGAGCGGGGTG

CAGGTGGACGCAAACTGTGAGGGAGATTGTTACCATTCTGGCGGTACGATCATCAGCAAC

TTGCCATTCCAGAATATAGACTCCCGGGCAGTCGGTAAGTGTCCCCGGTACGTCAAACAA

AGAAGCTTGCTGCTGGCCACCGGGATGAAAAATGTTCCCGAGATCCCCAAGGGGCGTGGC

CTCTTTGGCGCAATCGCAGGGTTTATCGAGAATGGGTGGGAAGGGCTGATCGACGGCTGG

TATGGATTCAGGCACCAAAACGCACAGGGAGAAGGGACAGCCGCCGACTACAAAAGCACA

CAGAGTGCGATCGATCAAATCACAGGTAAATTGAACCGACTGATTGAGAAGACAAACCAA

CAGTTTGAGCTCATAGATAATGAGTTCAACGAGGTGGAGAAGCAGATAGGAAATGTGATC

AACTGGACAAGGGATTCCATCACTGAAGTCTGGTCCTATAATGCCGAGCTGTTGGTTGCC

ATGGAAAACCAGCATACCATTGACCTCGCCGATTCCGAAATGGATAAGCTGTACGAAAGG

GTGAAGCGGCAGTTGCGGGAGAACGCAGAAGAAGATGGAACAGGATGCTTTGAGATATTT

CACAAATGCGATGATGATTGCATGGCCTCGATACGCAACAATACCTATGACCATAGCAAG

TACCGAGAGGAGGCGATGCAAAACAGGATCCAGATTGACCCAGTGAAGCTCAGCAGTGGG

TACAAGGATGTCATTTTGTGGTTTAGCTTTGGAGCCTCATGCTTCATACTCCTCGCCATC

GTCATGGGGTTGGTATTTATCTGCGTCAAGAACGGCAATATGAGGTGTACTATCTGCATC

580
ATGAATACTCAGATTCTGGTGTTTGCGCTTATCGCTATTATACCCACTAATGCCGACAAA

ATCTGTCTGGGCCATCACGCCGTTAGCAACGGCACCAAAGTGAACACACTCACAGAACGT

GGTGTGGAAGTCGTCAATGCCACCGAGACAGTTGAGCGCACCAATATTCCTAGAATCTGT

TCCAAAGGCAAAAAAACTGTCGATCTAGGCCAATGCGGACTGCTCGGAACTATTACTGGA

CCACCGCAGTGCGATCAGTTCCTCGAGTTCAGCGCAGACCTGATCATAGAGAGGAGAGAA

GGTAGCGACGTTTGTTACCCTGGAAAATTTGTCAACGAGGAGGCGCTTCGACAGATTCTC

AGAGAGAGTGGAGGTATAGATAAGGAGGCCATGGGTTTCACGTATTCAGGTATCAGAACG

AATGGGGCAACCAGTGCCTGTCGCCGGTCAGGCAGCAGCTTCTATGCAGAGATGAAGTGG

CTCCTGTCAAACACAGACAATGCTGCATTCCCACAGATGACCAAGAGCTACAAGAACACG

CGAAAGTCACCTGCATTAATAGTCTGGGGTATCCACCACTCTGTCTCCACTGCCGAACAG

ACCAAACTTTACGGATCTGGAAATAAGCTGGTCACTGTGGGGTCTTCTAATTATCAGCAG

AGTTTTGTACCCTCGCCCGGGGCCCGGCCCCAGGTAAACGGACAGTCCGGACGGATTGAC

TTTCACTGGCTCATGCTTAACCCAAACGACACAGTGACCTTCAGTTTTAACGGCGCTTTC

ATCGCTCCCGACAGGGCCTCATTCCTGAGGGGAAAGTCGATGGGAATCCAGAGCGGGGTT

CAGGTTGATGCAAATTGCGAAGGGGATTGTTACCATTCCGGCGGAACCATTATCTCCAAC

CTGCCATTTCAGAATATAGATAGCCGCGCCGTGGGAAAGTGCCCTAGGTACGTCAAACAG

CGGTCTCTGCTCCTGGCTACAGGCATGAAAAATGTTCCGGAAATCCCAAAGGGGGGGGGA

CTCTTCGGAGCCATCGCAGGCTTCATCGAAAACGGCTGGGAGGGGTTAATCGATGGATGG

TATGGCTTCCGCCATCAGAACGCACAGGGGGAGGGCACCGCGGCCGATTATAAGAGTACC

CAGAGCGCAATAGATCAGATAACTGGTAAGTTGAATCGGTTAATTGAAAAAACTAACCAG

CAGTTCGAACTAATCGATAATGAGTTCAATGAAGTCGAGAAACAGATAGGCAACGTTATC

AATTGGACCAGGGACAGCATAACAGAAGTGTGGTCCTATAACGCCGAACTCCTCGTTGCC

ATGGAGAACCAGCATACCATTGACCTGGCTGATTCAGAGATGGATAAACTATACGAACGG

GTCAAGCGTCAATTGAGAGAGAATGCGGAAGAGGACGGGACTGGGTGCTTCGAAATCTTC

CATAAGTGTGATGACGATTGTATGGCGTCCATTCGCAATAACACCTACGATCATTCAAAA

TACCGTGAAGAGGCGATGCAGAATAGGATTCAGATCGACCCAGTGAAGCTCAGTAGTGGA

TATAAAGACGTAATTCTCTGGTTCTCTTTCGGAGCTAGCTGCTTCATTCTTCTGGCCATC

GTGATGGGACTCGTTTTCATATGTGTTAAAAATGGCAACATGCGTTGCACAATCTGTATC

581
ATGAACACTCAGATTTTAGTTTTCGCTCTAATTGCCATTATTCCTACAAATGCTGATAAA

ATATGCCTGGGACACCATGCTGTCTCCAACGGTACCAAAGTCAATACTCTTACGGAGAGG

GGGGTGGAGGTAGTGAACGCCACCGAGACAGTCGAACGTACAAATATACCTCGGATTTGC

TCCAAGGGAAAGAAGACAGTGGATCTGGGGCAATGTGGTCTGCTGGGAACTATCACAGGC

CCACCGCAGTGCGACCAGTTTCTTGAGTTTTCAGCCGACCTGATCATCGAGCGACGCGAG

GGCAGCGACGTGTGTTACCCCGGGAAGTTCGTAAACGAGGAAGCTCTCCGCCAGATCCTG

CGCGAGAGTGGAGGTATTGATAAGGAGGCCATGGGCTTTACATATTCTGGCATCCGGACC

AATGGGGCCACAAGCGCCTGTAGGAGATCTGGATCCAGTTTTTACGCCGAAATGAAATGG

CTGCTGAGCAACACAGACAATGCCGCCTTTCCTCAGATGACAAAGAGCTACAAAAACACA

AGGAAGTCACCCGCCCTTATTGTCTGGGGTATCCATCACTCTGTCAGTACAGCTGAGCAG

ACCAAGCTGTATGGTTCTGGCAATAAATTGGTTACCGTCGGGAGCAGTAACTATCAACAA

TCATTTGTTCCAAGTCCAGGAGCCCGGCCCCAGGTCAATGGTCAAAGTGGAAGGATTGAC

TTTCACTGGTTAATGCTTAATCCCAACGATACCGTGACCTTCTCATTTAATGGGGCCTTT

ATTGCTCCGGACCGTGCCAGCTTTCTCCGCGGTAAGTCCATGGGCATCCAGTCCGGCGTA

CAAGTGGATGCCAATTGCGAAGGCGACTGTTACCACTCTGGCGGCACCATCATCTCAAAC

CTTCCGTTCCAGAACATAGATAGTCGGGCCGTGGGCAAGTGCCCTAGGTATGTGAAGCAG

CGCTCATTACTGTTGGCTACTGGCATGAAAAATGTGCCAGAGATCCCTAAAGGTCGTGGT

CTTTTTGGAGCTATCGCTGGGTTCATTGAAAATGGATGGGAGGGGCTGATCGACGGTTGG

TACGGATTCCGGCATCAGAATGCACAGGGCGAAGGCACAGCCGCTGATTACAAGAGCACC

CAGTCAGCTATTGACCAGATCACAGGGAAGCTGAACCGGCTAATCGAGAAAACAAACCAA

CAATTTGAACTTATCGATAACGAATTTAATGAGGTGGAGAAACAGATAGGCAACGTGATC

AACTGGACACGGGATAGTATCACTGAGGTGTGGAGTTACAATGCCGAACTCTTGGTGGCT

ATGGAGAATCAGCATACTATCGATCTAGCGGACTCTGAGATGGACAAACTCTATGAACGA

GTGAAGAGGCAGCTTCGCGAGAACGCTGAGGAAGATGGGACAGGGTGTTTTGAAATTTTT

CATAAGTGTGATGATGATTGCATGGCATCTATCCGGAATAACACATACGACCATTCCAAG

TACCGTGAAGAGGCTATGCAAAACCGAATTCAGATAGACCCAGTGAAGCTCTCTTCCGGA

TACAAGGATGTAATTCTGTGGTTTTCATTCGGTGCATCCTGCTTCATCCTGCTTGCAATC

GTGATGGGTTTAGTGTTCATCTGTGTGAAGAATGGGAATATGAGGTGTACAATTTGCATC

582
ATGAACACGCAGATCCTGGTGTTCGCACTGATTGCAATTATTCCCACCAATGCCGATAAG

ATCTGTTTAGGACATCACGCCGTGTCCAACGGTACGAAGGTGAACACATTGACCGAGCGG

GGAGTCGAAGTGGTAAATGCAACCGAGACTGTTGAACGCACAAATATCCCAAGAATTTGT

TCAAAGGGTAAAAAAACCGTGGACCTCGGACAGTGCGGGCTGCTTGGAACGATTACAGGA

CCTCCACAATGCGACCAGTTCCTGGAATTTTCCGCTGACCTCATCATAGAACGACGGGAA

GGGTCCGACGTGTGTTATCCGGGAAAGTTCGTTAACGAGGAGGCTCTGAGGCAGATCTTG

AGGGAGAGTGGTGGCATCGACAAGGAGGCGATGGGCTTCACATACAGTGGCATCAGAACT

AACGGAGCCACCAGCGCATGTCGACGGTCTGGTAGCAGTTTTTATGCAGAGATGAAGTGG

TTGCTGAGCAATACAGATAATGCCGCATTCCCCCAAATGACAAAGTCCTATAAGAACACG

CGGAAAAGTCCTGCCCTAATTGTGTGGGGAATCCACCACTCTGTTAGTACCGCTGAGCAG

ACCAAGTTATACGGCAGCGGGAACAAGTTGGTGACAGTTGGATCTAGTAACTACCAGCAA

AGCTTCGTTCCTAGCCCGGGGGCACGTCCCCAGGTGAACGGGCAGAGTGGCCGGATCGAT

TTTCATTGGCTGATGCTCAATCCAAACGACACTGTCACATTCAGTTTTAACGGAGCCTTT

ATCGCCCCTGATAGAGCCTCATTCCTTAGGGGAAAAAGTATGGGAATCCAGTCTGGTGTA

CAGGTGGATGCCAACTGTGAAGGTGACTGTTATCATTCAGGTGGAACCATCATATCAAAC

CTGCCCTTCCAAAATATTGACTCAAGAGCAGTGGGCAAGTGCCCCCGATATGTGAAGCAG

CGATCCCTGCTGCTCGCAACTGGCATGAAGAATGTCCCGGAAATCCCTAAGGGGCGGGGC

CTTTTCGGGGCAATCGCAGGCTTCATCGAAAATGGATGGGAGGGCCTGATCGACGGATGG

TACGGTTTCCGGCATCAGAATGCTCAGGGGGAGGGGACCGCGGCTGACTATAAGTCGACA

CAATCTGCCATAGATCAGATCACGGGAAAACTGAACAGACTGATAGAGAAGACTAATCAG

CAGTTCGAACTGATCGATAACGAGTTCAATGAGGTTGAAAAGCAAATCGGGAACGTAATC

AACTGGACACGAGACAGCATTACTGAGGTGTGGTCCTACAATGCGGAATTGCTGGTGGCT

ATGGAAAATCAACACACAATCGATCTTGCCGATTCAGAGATGGACAAGCTTTACGAGAGA

GTAAAGCGACAACTGCGCGAGAATGCTGAGGAGGACGGGACTGGGTGCTTCGAGATCTTT

CACAAGTGTGACGACGACTGCATGGCCTCTATCCGGAATAATACTTATGACCATAGCAAA

TATAGAGAGGAGGCCATGCAAAACCGGATCCAGATTGATCCAGTCAAGCTCTCCAGCGGT

TATAAGGATGTGATTTTGTGGTTCAGTTTTGGCGCTTCATGCTTCATACTCTTGGCCATC

GTGATGGGCCTGGTGTTTATTTGTGTGAAGAACGGAAACATGCGGTGTACAATTTGCATC

583
ATGAATACCCAGATCCTCGTTTTCGCTCTGATCGCAATCATTCCCACAAACGCAGATAAA

ATCTGTCTGGGGCATCACGCTGTGAGCAACGGCACAAAAGTTAACACCTTAACCGAGCGC

GGCGTGGAGGTGGTTAATGCTACCGAGACCGTCGAACGGACCAATATCCCCAGGATCTGT

AGTAAAGGCAAGAAGACAGTCGACCTGGGGCAGTGTGGGCTCCTCGGGACTATCACAGGA

CCCCCTCAGTGTGATCAGTTCCTCGAGTTCTCAGCGGACCTTATTATAGAACGCCGAGAG

GGTTCTGATGTGTGTTACCCCGGCAAATTTGTGAACGAGGAGGCTCTGAGGCAAATTCTG

CGCGAAAGCGGCGGCATTGAAAAGGAAGCTATGGGGTTTACATACTCCGGAATAAGAGCC

AATGGCGCGACTTCTGCTTGTCGAAGGTCCGGAAGCTCCTTTTATGCGGAAATGAAATGG

CTATTGAGCAATACCGACAATGCTGCCTTCCCCCAGATGACCAAGAGTTATAAAAATACC

CGAAAAAGCCCCGCGCTTATCGTTTGGGGCATCCATCATTCTGTTTCTACAGCCGAACAG

ACTAAGCTTTATGGCAGCGGGAATAAGCTCGTGACCGTCGGCTCAAGTAACTATCAGCAG

TCATTCGTGCCTTCCCCGGGGGCTAGACCTCAAGTGAATGGATTATCCGGACGAATCGAC

TTCCATTGGTTGATGTTAAACCCTAATGATACTGTGACCTTCTCCTTCAACGGGGCCTTC

ATTGCTCCAGATCGTGCTAGTTTCCTGCGGGGCAAGTCCATGGGTATTCAATCCGGAGTC

CAGGTCGACGCAAACTGTGAGGGGGATTGCTACCACTCCGGAGGCACAATTATTTCTAAT

CTGCCATTTCAGAACATTGACTCCCGCGCCGTGGGGAAATGTCCAAGGTATGTGAAACAA

CGGAGCCTACTGCTCGCCACCGGAATGAAGAACGTTCCTGAAATACCTAAAGGTCGGGGT

TTGTTTGGGGCTATAGCCGGCTTCATAGAAAACGGATGGGAAGGCCTGATCGATGGCTGG

TATGGCTTTAGGCATCAAAATGCACAGGGGGAGGGCACTGCGGCTGACTATAAGAGCACC

CAGTCAGCGATTGACCAGATTACTGGCAAGCTGAATAGACTTATAGAAAAGACAAATCAG

CAATTCGAGCTGATAGACAACGAATTCAATGAGGTGGAGAAACAAATTGGTAACGTCATT

AACTGGACTCGTGACTCTATTACGGAAGTGTGGAGTTACAATGCTGAGCTCCTCGTCGCC

ATGGAAAACCAACACACTATAGATTTGGCCGATAGCGAGATGGACAAGCTGTACGAGAGG

GTAAAACGCCAGTTGAGAGAAAACGCCGAGGAAGATGGCACCGGTTGCTTTGAGATTTTC

CACAAGTGCGATGATGACTGCATGGCAAGCATCAGAAATAACACATACGATCATAGTAAA

TACAGGGAGGAAGCCATGCAAAACCGCATTCAGATCGATCCCGTCAAGCTCTCTTCGGGG

TACAAAGATGTCATCCTTTGGTTCTCATTCGGCGCATCTTGCTTTATCCTGCTGGCTATA

GTGATGGGGCTCGTGTTTATTTGCGTCAAAAATGGAAACATGCGCTGTACCATCTGTATT

584
ATGAATACTCAGATCCTGGTGTTTGCGCTCATTGCGATCATCCCAACCAACGCCGACAAA

ATATGTCTGGGACATCACGCCGTTTCCAACGGGACGAAGGTGAACACGTTGACAGAGCGC

GGAGTGGAGGTCGTGAATGCTACTGAGACCGTGGAGAGGACTAATATCCCGAGGATCTGC

AGTAAGGGCAAGAAGACTGTCGACTTAGGACAGTGTGGCCTGTTAGGCACAATCACAGGC

CCCCCTCAATGTGACCAATTTCTGGAGTTTTCTGCCGACCTCATAATCGAGCGCAGGGAA

GGCTCCGACGTGTGCTATCCGGGAAAGTTCGTCAACGAGGAAGCCCTCAGACAGATCCTT

CGCGAATCCGGCGGCATAGATAAGGAAGCTATGGGTTTCACATATTCAGGAATCCGCACG

AATGGCGCAACTTCCGCTTGCCGGCGATCAGGATCCTCTTTCTACGCAGAGATGAAGTGG

CTGCTGAGCAATACCGACAATGCCGCCTTCCCCCAAATGACAAAGTCATACAAGAATACT

CGTAAATCACCTGCCCTGATTGTGTGGGGAATCCATCACTCAGTGTCCACAGCGGAGCAG

ACCAAGCTGTACGGAAGCGGTAACAAGCTTGTTACCGTTGGCTCTAGCAATTATCAGCAG

AGCTTTGTTCCTTCACCTGGAGCCAGACCTCAAGTAAATGGGCAAAGCGGTAGAATCGAC

TTTCACTGGCTGATGCTGAATCCCAATGACACAGTCACCTTTTCGTTTAACGGCGCGTTT

ATAGCACCCGATAGGGCCAGTTTTTTGAGAGGAAAGTCAATGGGAATCCAAAGCGGCGTG

CAAGTCGATGCCAATTGTGAGGGCGACTGTTACCATAGTGGGGGAACCATTATAAGTAAT

TTACCCTTTCAGAATATTGACTCAAGGGCTGTGGGAAAATGTCCCAGGTATGTCAAGCAG

AGAAGCCTGCTGCTGGCCACCGGTATGAAGAACGTACCCGAGATTCCAAAAGGCAGAGGA

CTGTTTGGAGCAATTGCTGGGTTCATCGAGAACGGGTGGGAGGGGCTTATTGATGGCTGG

TACGGATTTAGACATCAAAATGCACAGGGGGAAGGCACTGCCGCTGATTATAAAAGTACG

CAGTCCGCGATAGACCAGATTACCGGAAAGTTGAACCGGCTGATCGAGAAAACTAATCAG

CAGTTTGAGTTGATCGACAACGAATTTAACGAGGTGGAGAAACAAATCGGCAATGTGATT

AACTGGACTAGAGACTCCATTACCGAGGTGTGGTCATATAACGCCGAATTGCTCGTGGCC

ATGGAAAACCAGCACACCATCGATCTCGCTGATAGCGAGATGGACAAACTCTACGAAAGG

GTCAAGAGACAACTCCGAGAGAACGCCGAGGAAGACGGGACTGGGTGTTTTGAGATCTTT

CATAAATGTGATGACGACTGTATGGCTTCTATCCGGAATAACACATACGACCACTCCAAA

TATCGGGAGGAAGCTATGCAAAATCGTATTCAAATTGATCCCGTCAAGCTGAGCTCCGGG

TATAAGGACGTTATCCTCTGGTTCTCCTTTGGCGCTTCCTGTTTCATCCTTCTGGCTATT

GTCATGGGGCTCGTTTTCATATGCGTTAAGAACGGGAATATGCGGTGTACGATCTGTATA

585
ATGAACACACAGATATTGGTGTTTGCTTTGATTGCAATCATTCCTACAAACGCGGATAAA

ATCTGCCTGGGCCACCATGCTGTGAGTAACGGCACCAAAGTGAATACTTTAACTGAACGC

GGTGTCGAGGTTGTGAACGCGACTGAAACGGTGGAGCGCACGAATATTCCCCGGATCTGC

AGCAAAGGCAAAAAGACTGTCGACCTTGGTCAGTGCGGGCTACTTGGGACTATCACTGGA

CCCCCACAGTGTGATCAATTCCTGGAATTTTCAGCCGATTTGATTATTGAGCGGAGAGAG

GGATCCGACGTGTGCTATCCAGGCAAGTTTGTGAACGAGGAGGCATTGCGGCAGATTCTC

AGGGAATCTGGAGGCATTGATAAGGAAGCTATGGGTTTCACCTATAGCGGTATCCGGACC

AACGGAGCTACCAGCGCGTGCCGGAGGAGCGGTAGCTCCTTTTACGCGGAGATGAAGTGG

TTGCTCTCTAACACGGACAACGCCGCCTTCCCACAGATGACCAAGAGCTACAAGAACACC

CGCAAATCACCTGCCTTAATTGTGTGGGGCATTCATCATAGTGTCTCTACGGCCGAGCAG

ACAAAACTGTATGGATCTGGCAATAAGCTTGTCACCGTCGGCAGCTCCAATTACCAGCAG

TCTTTCGTACCCAGTCCCGGTGCAAGGCCACAGGTCAACGGACAGTCGGGGCGGATTGAC

TTCCACTGGCTGATGCTCAACCCTAATGATACTGTAACCTTCAGCTTCAATGGCGCATTC

ATAGCTCCCGATCGGGCATCATTCCTGCGAGGTAAATCTATGGGGATCCAGTCCGGCGTG

CAGGTGGATGCCAACTGCGAGGGCGATTGCTATCACAGTGGTGGGACAATCATCTCTAAT

TTACCCTTCCAGAATATTGATAGCCGAGCTGTGGGGAAATGCCCAAGGTACGTCAAGCAG

CGTTCGCTTCTGTTAGCCACTGGCATGAAAAATGTGCCAGAGATACCCAAAGGCAGGGGG

TTATTTGGAGCAATTGCCGGTTTTATTGAAAATGGCTGGGAGGGACTCATCGACGGCTGG

TATGGCTTCAGACACCAAAATGCCCAGGGTGAAGGTACCGCCGCCGACTACAAGTCCACT

CAAAGTGCAATTGACCAAATAACTGGAAAGCTGAACCGGCTGATCGAAAAGACAAATCAG

CAGTTTGAGTTAATCGATAACGAGTTCAACGAGGTCGAGAAGCAGATTGGAAATGTCATT

AACTGGACAAGGGATTCCATCACTGAGGTGTGGAGCTACAACGCCGAGCTGCTCGTCGCA

ATGGAGAACCAGCATACTATTGACCTGGCAGACTCTGAAATGGATAAATTATACGAACGC

GTGAAACGCCAGCTCAGAGAAAATGCTGAAGAGGACGGGACCGGTTGTTTTGAGATTTTT

CACAAGTGCGACGACGATTGCATGGCCTCCATTAGGAACAATACATACGACCATAGTAAG

TATCGAGAGGAAGCCATGCAGAACAGGATACAGATAGACCCTGTTAAACTGTCCTCCGGG

TACAAGGATGTGATCCTTTGGTTTTCTTTTGGGGCATCCTGCTTTATTCTGCTGGCAATC

GTCATGGGCCTTGTTTTTATCTGCGTAAAGAATGGAAATATGAGATGCACAATCTGTATC

586
ATGAACACCCAGATCCTTGTATTCGCATTAATAGCTATCATTCCAACAAACGCGGACAAA

ATTTGCCTGGGGCACCATGCAGTCTCCAACGGCACTAAGGTGAATACGCTCACCGAGCGG

GGCGTGGAGGTTGTTAATGCGACGGAGACGGTTGAGCGGACGAATATCCCCCGAATTTGT

TCGAAGGGAAAACGGACAGTGGACCTGGGTCAGTGTGGGTTGCTGGGTACCATTACAGGC

CCCCCCCAGTGTGATCAGTTTCTGGAATTTTCCGCCGACCTTATTATCGAGCGGAGGGAA

GGGTCCGATGTCTGTTACCCAGGGAAGTTCGTTAACGAGGAGGCTTTGCGCCAGATACTC

CGGGAGAGTGGTGGTATTGACAAGGAGGCCATGGGGTTCACCTACAGCGGCATCAGGACT

AATGGAGCCACCTCGGCCTGTAGAAGAAGTGGATCTTCTTTCTATGCCGAGATGAAATGG

TTGCTATCTAACACTGACAACGCCGCCTTTCCACAGATGACTAAAAGTTACAAAAATACA

CGGAAAAGCCCAGCCTTAATAGTCTGGGGCATCCATCATAGTGTGTCCACCGCCGAACAG

ACTAAACTATATGGGTCCGGAAGCAAGCTTGTGACGGTGGGCTCTTCCAACTACCAGCAG

AGTTTTGTGCCCTCCCCCGGAGCACGGCCTCAGGTCAACGGCTTGAGCGGACGGATCGAC

TTTCATTGGTTAATGCTGAATCCAAATGATACAGTAACATTTTCATTTAATGGCGCCTTC

ATTGCTCCAGACAGAGCTAGTTTCTTACGGGGCAAATCAATGGGCATCCAGAGCGGGGTT

CAGGTGGATGCCAACTGTGAAGGAGATTGTTATCACAGCGGGGGGACTATCATTTCTAAT

CTCCCATTTCAGAATATCGATTCACGGGCAGTTGGCAAGTGCCCGAGATACGTCAAGCAG

CGATCTCTCCTTCTCGCAACCGGAATGAAAAACGTCCCAGAGATTCCTAAAGGCAGGGGC

CTGTTCGGCGCCATCGCCGGATTTATTGAGAACGGGGGGAGCGGGCTGATAGATGGCTGG

TACGGCTTTCGGCATCAGAATGCACAGGGCGAGGGTACGGCTGCGGACTACAAAAGTACT

CAAAGCGCAATCGACCAGATTACAGGAAAGCTGAACCGGTTAATTGAAAAGACAAACCAG

CAATTCGAGCTCATCGACAATGAGTTTAATGAAGTGGAGAAGCAGATCGGCAATGTAATC

AACTGGACCAGAGATAGTATCACTGAAGTGTGGTCCTACAACGCCGAGCTTCTGGTGGCT

ATGGAGAACCAGCATACTATCGATCTTGCGGATAGCGAGATGGATAAGCTGTACGAGCGT

GTTAAGCGACAGCTAAGAGAGAACGCGGAGGAGGACGGTACTGGGTGTTTCGAAATTTTT

CACAAGTGCGATGACGATTGTATGGCGTCTATCCGCAATAATACTTATGATCATAGTAAG

TATCGGGAAGAAGCTATGCAGAACCGCATCCAAATCGACCCCGTGAAGCTTTCAAGCGGT

TACAAAGACGTTATCTTGTGGTTCAGCTTCGGGGCGTCTTGCTTTATCCTGCTGGCGATT

GTAATGGGCTTGGTCTTTATCTGTGTGAAGTCCAGAAATATGAGATGCACCATTTGTATC

587
ATGAATACCCAAATCCTCGTGTTCGCTTTAATCGCAATCATCCCGACCAATGCCGACAAG

ATCTGCCTGGGTCACCACGCTGTCTCCAACGGCACTAAGGTGAACACCTTAACAGAGAGA

GGCGTGGAAGTAGTTAATGCTACCGAAACCGTGGAAAGGACCAACATTCCGCGGATATGT

TCTAAGGGAAAACGCACCGTAGATCTCGGCCAGTGTGGACTGCTGGGCACAATCACCGGT

CCTCCACAATGTGATCAGTTTCTTGAGTTCTCGGCCGACCTCATCATCGAAAGGAGGGAA

GGATCTGATGTGTGTTATCCCGGGAAGTTCGTGAAAGAAGAGGCCCTGCGTCAGATATTG

CGAGAGAGTGGGGGGATAGATAAGGAAGCAATGGGCTTCACATACAGCGGCATCAGAACA

AATGGCGCGACATCCGCCTGTAGAAGGTCTGGGTCTAGCTTCTACGCAGAGATGAAATGG

CTGCTCAGTAACACGGACAATGCGGCCTTCCCCCAGATGACTAAAAGCTATAAAAATACA

AGGAAGAGCCCCGCCTTGATAGTGTGGGGAATCCATCATAGTGTGAGTACCGCTGAACAG

ACGAAGCTATACGGATCAGGCAACAAGCTGGTTACTGTCGGCAGTTCTAACTACCAGCAA

TCCTTTGTGCCTTCTCCCGGCGCCCGCCCACAAGTGAATGGACTATCTGGCAGAATTGAT

TTCCACTGGCTGATGCTGAACCCCAATGACACTGTGACTTTCAGCTTTAACGGAGCCTTT

ATCGCCCCCGATAGAGCCAGTTTCCTGAGGGGCAAATCCATGGGCATCCAGTCAGGCGTG

CAGGTCGATGCCAACTGCGAGGGAGATTGTTACCATTCGGGTGGCACCATAATTAGTAAC

TTACCATTCCAGAATATTGACAGCAGAGCCGTTGGGAAATGCCCCAGGTATGTCAAGCAG

AGGTCCCTACTACTGGCCACAGGCATGAAGAATGTTCCTGAAATTCCTAAAGGCCGTGGT

CTTTTCGGAGCAATCGCAGGATTCATCGAAAACGGCTGGGAAGGACTGATTGATGGGTGG

TATGGTTTTAGGCACCAAAATGCACAGGGCGAGGGCACAGCTGCAGATTACAAGAGCACT

CAGTCAGCTATTGATCAGATTACCGGAAAGCTTAACAGGCTCATCGAAAAGACTAATCAG

CAGTTTGAACTGATCGACAACGAATTCAACGAAGTAGAGAAACAGATTGGGAACGTGATT

AATTGGACCCGAGACTCTATCACAGAGGTGTGGAGTTACAACGCAGAGTTGCTGGTAGCA

ATGGAAAACCAGCACACAATCGATCTCGCAGACAGTGAGATGGATAAACTTTACGAAAGG

GTCAAACGTCAGTTAAGAGAGAACGCGGAAGAGGATGGCACCGGTTGCTTTGAAATTTTC

CACAAATGCGATGACGACTGCATGGCGTCTATCAGAAATAACACTTACGACCATAGTAAG

TATCGGGAGGAGGCTATGCAGAACCGAATTCAGATCGATCCAGTAAAGCTCAGCAGCGGC

TACAAGGACGTCATCCTTTGGTTCTCTTTCGGGGCCAGTTGCTTCATCCTTCTCGCTATA

GTCATGGGCCTCGTGTTTATCTGCGTAAAAAATGGGAACATGAGGTGCACCATTTGCATA

588
ATGAATACACAGATATTGGTCTTCGCTCTCATCGCTATCATTCCCACCAACGCTGACAAA

ATCTGTTTAGGCCACCATGCCGTATCCAATGGCACTAAGGTCAACACACTTACTGAGCGA

GGCGTAGAGGTCGTCAACGCTACAGAAACTGTTGAGCGAACCAACATCCCCAGGATTTGC

TCTAAGGGGAAAAAGACTGTAGACCTTGGGCAGTGTGGCCTGCTGGGGACTATCACCGGG

CCACCTCAATGTGACCAATTTCTGGAGTTCTCAGCTGATCTGATTATCGAGAGGCGCGAG

GGATCTGATGTCTGTTACCCAGGTAAGTTCGTCAATGAGGAGGCGCTCCGCCAGATCCTC

CGCGAGAGTGGCGGGATCGATAAAGAGGCCATGGGCTTCACTTACTCCGGCATCAGGACC

AATGGCGCTACATCCGCCTGTAGACGGAGCGGATCCAGCTTTTACGCCGAAATGAAGTGG

CTGCTGTCCAACACAGACAACGCTGCTTTTCCACAGATGACAAAGTCTTATAAAAATACC

CGCAAATCTCCTGCCCTGATTGTGTGGGGCATTCACCACTCAGTGTCCACTGCCGAGCAG

ACTAAGTTGTACGGAAGTGGCAACAAGCTGGTGACGGTCGGCTCTTCAAACTATCAACAG

AGCTTTGTACCTTCCCCAGGGGCCCGGCCACAGGTGAACGGGCAGTCAGGAAGGATTGAT

TTCCACTGGCTGATGCTGAATCCAAATGATACTGTCACCTTCAGCTTTAATGGAGCTTTT

ATTGCCCCGGATCGCGCATCCTTCCTGCGCGGGAAGAGTATGGGGATCCAGTCCGGGGTA

CAAGTCGACGCTAACTGCGAAGGCGATTGCTACCATAGCGGAGGAACCATCATTAGTAAC

CTCCCCTTTCAGAATATTGATTCCCGTGCCGTTGGGAAATGTCCCAGATACGTCAAGCAG

AGGTCCTTGCTGCTCGCAACCGGCATGAAGAATGTGCCAGAGATTCCAAAGGGGAGAGGT

CTTTTCGGTGCTATCGCCGGCTTTATCGAGAACGGCTGGGAAGGGCTGATCGATGGCTGG

TACGGATTCCGGCATCAAAACGCGCAGGGAGAGGGAACTGCGGCCGACTACAAGTCAACT

CAGTCTGCCATCGATCAGATTACTGGTAAGCTTAACCGTCTCATCGAGAAAACCAACCAA

CAATTTGAATTAATTGATAACGAGTTTAACGAAGTGGAGAAGCAAATTGGGAATGTCATA

AACTGGACACGGGATTCTATCACCGAGGTATGGTCTTACAACGCGGAGTTGCTGGTCGCC

ATGGAGAACCAACATACCATCGATCTGGCTGACAGTGAAATGGACAAGCTGTATGAGCGG

GTGAAACGGCAGCTCCGGGAGAATGCAGAGGAAGACGGTACTGGCTGTTTCGAGATCTTC

CATAAGTGCGACGATGACTGTATGGCCTCGATTAGGAACAACACCTATGATCACAGCAAG

TATCGCGAGGAAGCGATGCAGAACCGGATTCAGATCGACCCAGTTAAACTCTCGTCGGGC

TACAAGGATGTAATCCTGTGGTTTAGCTTCGGAGCGTCGTGTTTCATCTTGTTGGCGATA

GTAATGGGCCTTGTTTTTATCTGCGTGAAGAACGGAAATATGAGATGCACTATCTGTATT

589
ATGAACACGCAGATCCTAGTGTTCGCACTTATCGCCATCATCCCTACCAATGCTGACAAA

ATTTGCCTGGGACATCATGCGGTTTCTAATGGAACCAAGGTGAATACCCTAACAGAACGG

GGGGTGGAAGTTGTCAATGCCACAGAAACGGTTGAGCGTACTAACATTCCCCGCATTTGC

TCCAAAGGAAAAAAAACTGTGGATCTGGGCCAGTGTGGACTTCTGGGCACTATTACCGGC

CCTCCTCAGTGCGACCAGTTCCTGGAGTTCTCTGCGGACCTTATTATTGAGAGACGTGAG

GGATCTGATGTGTGTTATCCAGGGAAGTTCGTAAACGAAGAGGCTCTTAGACAAATCCTG

CGGAAGAGCGGTGGCATAGATAAAGAGGCAATGGGGTTTACATACAGCGGCATAAGGACC

AACGGCGCCACATCCACTTGCAGGCGGTCCGGGTCGTCATTTTACGCCGAGATGAAATGG

TTGTTAAGTAATACAGACAACGCAGCCTTTCCGCAGATGACTAAATCTTATAAAAACACA

CGAAAATCTCCGGCGATCATTGTATGGGGCATACACCACAGTGTTAGCACTGCCGAGCAG

ACGAAACTATATGGCTCCGGAAATAAACTGGTCACCGTAGGATCCTCCAACTACCAGCAG

AGCTTCGTGCCCTCGCCTGGCGCACGGCCACAAGTTAATGGTCTCAGCGGTCGGATTGAC

TTTCACTGGCTCATGCTTAATCCTAATGACACAGTAACCTTCTCCTTTAACGGCGCCTTC

ATAGCTCCCGACAGGGCATGTTTTCTGCGCGGGAAGAGTATGGGGATCCAGTCCGGGGTC

CAGGTAGATGCAGACTGCGAAGGGGACTGCTACCACAGTGGGGGTACCATCATTAGTAAC

CTTCCCTTTCAGAATATTGACAGCAGGGCCGTCGGGAAGTGCCCCCGCTACGTGAAGCAG

CGGTCTTTGCTCCTGGCTACCGGTATGAAGAACGTGCCCGAGATACCAAAAGGCAGGGGG

CTCTTTGGTGCCATCGCCGGCTTTATCGAAAATGGATGGGAGGGCCTCATCGACGGTTGG

TACGGTTTCAGGCACCAGAATGCCCAGGGGGAAGGAACAGCTGCAGATTACAAGTCAACC

CAGTCTGCTATTGACCAGATAACAGGGAAACTGAACCGATTAATTGAGAAAACTAATCAA

CAGTTCGAGCTGATTGATAACGAGTTTAACGAGGTGGAACGCCAAATCGGGAACGTGATT

AACTGGACAAGGGATTCAATCACAGAGGTTTGGAGTTATAATGCCGAACTGCTGGTCGCC

ATGGAGAACCAGCACACTATCGATCTAGCTGATTCTGAGATGGACAAGCTCTATGAGCGC

GTCAAGCGTCAGCTCCGCGAAAACGCTGAAGAAGATGGCACTGGCTGTTTCGAGATCTTC

CACAAGTGTGACGACGACTGCATGGCCTCCATAAGGAATAACACTTATGATCACAGCAAG

TATCGAGAGGAGGCCATGCAGAACCGCATTCAGATTGATCCCGTTAAGTTAAGTTCTGGG

TATAAAGATGTCATTCTTTGGTTCTCTTTTGGTGCTTCATGTTTTATACTGCTGGCTATC

GTCATGGGACTCGTGTTCATCTGCGTCAAAAATGGGAATATGCGGTGTACCATATGCATT

590
ATGAATACGCAGATCCTGGTGTTCGCTCTAATCGCTATTATCCCTACAAACGCAGATAAG

ATCTGTTTAGGCCACCATGCAGTTTCTAATGGCACTAAGGTCAACACTCTCACTGAACGC

GGGGTGGAGGTAGTCAACGCTACAGAGACAGTTGAACGAACAAACATCCCCAGGATTTGC

TCTAAGGGTAAAAAAACAGTGGACCTGGGACAGTGCGGACTGCTCGGGACCATTACTGGG

CCACCTCAGTGTGACCAGTTCTTGGAGTTTTCCGCCGATCTAATCATCGAAAGACGAGAA

GGATCCGATGTGTGCTATCCTGGCAAGTTTGTGAATGAGGAAGCACTGCGGCAGATCTTG

CGGGAGTCTGGCGGAATTGATAAGGAAGCAATGGGTTTTACCTACTCCGGTATTCGGACA

AATGGAGCTACATCCGCATGTCGGCGGTCCGGAAGCAGTTTCTACGCCGAGATGAAGTGG

CTATTGTCAAACACAGATAACGCTGCCTTCCCCCAGATGACTAAGAGCTATAAGAACACC

CGGAAGAGCCCTGCCCTGATCGTCTGGGGCATTCATCATTCGGTCAGTACAGCCGAACAA

ACTAAGTTGTACGGCTCCGGAAACAAGTTGGTTACAGTGGGGTCTTCCAACTACCAGCAG

AGCTTTGTACCTTCCCCCGGAGCCCGACCCCAGGTCAACGGCCAGTCTGGAAGAATTGAT

TTTCATTGGCTAATGCTGAATCCTAATGATACTGTGACATTTTCATTCAATGGAGCCTTC

ATAGCACCTGATAGGGCCTCTTTCCTGCGGGGAAAAAGCATGGGTATTCAGAGTGGCGTT

CAGGTGGATGCTAATTGCGAGGGGGACTGCTATCATAGTGGTGGGACCATTATTAGCAAC

CTCCCCTTTCAGAATATAGATAGCAGGGCTGTCGGCAAATGTCCAAGGTACGTTAAGCAG

CGGAGTCTACTGTTGGCCACCGGTATGAAAAACGTCCCCGAGATCCCTAAGGGACGCGGC

CTGTTCGGCGCCATCGCCGGATTTATCGAGAACGGGTGGGAAGGCTTGATCGATGGGTGG

TATGGATTCCGACATCAGAACGCCCAGGGCGAAGGTACTGCTGCCGACTATAAATCTACG

CAGAGCGCAATAGACCAGATTACGGGGAAACTGAACAGGCTGATCGAGAAGACCAATCAG

CAGTTTGAGCTGATTGACAATGAATTCAACGAAGTTGAGAAACAGATCGGTAACGTGATA

AATTGGACTAGAGATAGTATCACCGAGGTATGGAGCTACAACGCCGAGCTGCTTGTCGCT

ATGGAAAACCAGCACACCATCGACCTTGCTGACAGTGAGATGGATAAACTCTATGAACGA

GTGAAGAGACAGTTGCGGGAAAACGCCGAAGAGGACGGTACCGGGTGCTTTGAGATATTT

CACAAGTGCGATGATGACTGTATGGCTAGTATCCGCAATAATACATATGACCATAGTAAG

TACAGAGAAGAAGCCATGCAAAACAGAATACAAATTGACCCCGTGAAGTTAAGCTCAGGA

TACAAAGATGTCATCCTTTGGTTCTCCTTCGGCGCATCATGCTTTATACTTCTCGCAATC

GTGATGGGTCTGGTTTTTATATGCGTCAAGAACGGCAATATGCGCTGTACGATCTGTATT

591
ATGAACACCCAGATTCTGGTTTTTGCATTGATCGCCATTATTCCGACTAATGCCGACAAA

ATCTGTTTGGGACACCACGCCGTGAGCAACGGCACGAAAGTCAACACACTCACAGAACGA

GGCGTGGAAGTTGTCAACGCAACCGAGACGGTTGAGCGCACCAACATCCCAAGGATCTGC

TCTAAGGGCAAGAAGACCGTGGACCTTGGGCAGTGTGGCCTGCTGGGGACAATAACCGGT

CCACCACAATGTGATCAATTCCTGGAGTTTTCAGCCGACCTCATCATAGAACGCCGGGAA

GGTTCTGACGTGTGCTACCCGGGCAAATTTGTCAACGAGGAGGCTCTCAGGCAGATCCTG

AGGGAGTCAGGCGGAATTGACAAGGAAGCCATGGGTTTCACGTACAGCGGTATTCGGACC

AATGGGGCTACATCAGCCTGTCGCAGATCTGGAAGTTCTTTTTACGCTGAAATGAAGTGG

CTGCTGTCAAATACCGATAACGCTGCATTTCCCCAGATGACAAAAAGTTATAAGAATACC

AGGAAGTCCCCCGCCTTGATCGTGTGGGGCATACACCACTCAGTGAGTACAGCCGAGCAG

ACCAAGTTGTATGGATCGGGTAACAAACTAGTCACCGTGGGCTCCAGCAATTATCAGCAG

AGTTTTGTCCCCAGCCCCGGGGCTAGACCGCAAGTCAATGGTCAGTCCGGCCGTATCGAT

TTTCACTGGCTGATGCTAAATCCCAATGACACTGTAACCTTTTCCTTTAATGGGGCATTC

ATTGCACCCGACAGGGCATCCTTTTTGCGGGGTAAGAGTATGGGTATCCAGAGTGGCGTC

CAGGTGGATGCAAACTGCGAGGGTGACTGCTACCATTCAGGAGGCACGATTATATCAAAT

CTGCCCTTTCAGAACATTGACAGTCGCGCCGTTGGCAAATGTCCAAGGTACGTGAAGCAG

AGAAGCCTCCTGCTCGCCACTGGCATGAAAAATGTGCCCGAGATTCCCAAAGGCCGGGGT

CTTTTTGGCGCAATAGCTGGTTTTATCGAGAATGGTTGGGAAGGACTCATCGACGGCTGG

TACGGATTTCGGCACCAAAACGCCCAAGGGGAAGGAACCGCCGCAGATTACAAGAGCACG

CAGTCAGCTATCGACCAGATCACCGGCAAGCTTAATCGGCTTATTGAAAAAACCAATCAA

CAATTCGAGCTGATTGACAATGAATTTAATGAAGTGGAGAAACAAATTGGGAACGTGATC

AATTGGACCAGAGACAGCATAACTGAAGTGTGGAGTTATAACGCAGAACTGCTGGTCGCT

ATGGAAAATCAACACACTATTGATCTGGCCGATAGCGAAATGGACAAGCTATACGAAAGG

GTTAAACGGCAGCTTCGCGAGAACGCCGAGGAGGACGGCACCGGCTGCTTCGAGATTTTC

CACAAGTGTGATGACGATTGTATGGCCTCCATCAGAAACAACACCTACGACCATAGCAAG

TATAGAGAAGAAGCCATGCAGAATCGCATCCAGATCGACCCCGTTAAGCTTTCATCCGGC

TATAAGGACGTTATCTTATGGTTCTCTTTTGGAGCATCATGCTTTATCCTCCTGGCTATC

GTTATGGGCCTTGTTTTCATCTGCGTTAAAAACGGGAATATGCGCTGCACCATCTGTATT

592
ATGAATACACAGATCTTAGTGTTTGCTCTTATAGCAATCATACCCACAAACGCCGATAAG

ATCTGTCTGGGGCACCATGCCGTGAGCAACGGAACTAAGGTTAACACATTAACTGAGAGA

GGTGTGGAGGTAGTTAACGCGACCGAGACTGTAGAGCGGACTAATATCCCTCGCATTTGC

AGTAAGGGCAAAAAGACCGTTGACCTTGGTCAGTGTGGGCTGCTTGGAACCATCACCGGA

CCTCCTCAGTGTGACCAGTTCCTCGAATTTTCCGCTGACCTGATTATTGAGAGAAGGGAA

GGGAGTGACGTGTGTTATCCTGGCAAATTCGTCAATGAAGAAGCGCTACGCCAGATCCTT

AGAGAGAGTGGGGGAATCGATAAGGAGGCAATGGGCTTTACATACAGTGGCATAAGAACC

AATGGCGCGACAAGTGCCTGCCGCCGGAGCGGCTCAAGTTTCTATGCTGAGATGAAATGG

TTACTCAGTAATACTGATAATGCCGCATTTCCACAGATGACTAAATCTTATAAAAATACA

CGGAAATCACCCGCACTGATTGTATGGGGTATCCACCACAGCGTCTCCACAGCGGAGCAA

ACAAAACTGTACGGCAGTGGGAACAAATTGGTTACTGTTGGGTCCTCGAATTATCAGCAG

TCTTTCGTCCCTAGCCCTGGAGCTCGCCCCCAAGTTAACGGTCAGAGCGGCAGGATAGAT

TTCCACTGGTTAATGCTAAACCCTAATGACACCGTAACCTTTTCGTTTAATGGAGCATTC

ATTGCGCCTGACCGCGCGAGCTTCTTAAGGGGAAAGTCAATGGGAATTCAATCTGGGGTC

CAAGTCGACGCAAATTGTGAGGGCGACTGCTACCACTCAGGAGGAACTATCATCTCGAAC

CTGCCTTTTCAAAACATCGATAGCAGAGCCGTTGGCAAGTGCCCTCGCTATGTGAAACAG

CGCTCACTTCTCTTAGCGACGGGAATGAAGAACGTTCCGGAGATCCCAAAGGGTCGTGGC

TTGTTTGGCGCAATAGCAGGGTTCATAGAGAACGGATGGGAAGGTCTGATTGACGGTTGG

TATGGCTTCAGACACCAGAATGCTCAGGGAGAAGGAACCGCAGCCGATTATAAATCAACA

CAGAGCGCCATAGATCAGATCACAGGAAAGTTAAATCGCCTGATCGAGAAGACGAATCAG

CAGTTCGAGCTGATCGACAACGAGTTCAACGAAGTCGAGAAACAAATTGGCAACGTGATC

AACTGGACGAGGGATAGCATTACGGAGGTGTGGTCTTATAACGCTGAACTACTTGTGGCA

ATGGAGAACCAGCATACAATCGACCTCGCTGACTCAGAAATGGATAAGCTGTACGAGAGA

GTTAAACGGCAGTTGAGAGAAAACGCAGAGGAGGATGGCACAGGCTGCTTTGAAATTTTT

CACAAGTGCGATGATGACTGCATGGCTTCCATTCGGAACAATACGTATGACCACTCTAAA

TACAGGGAAGAGGCCATGCAGAATCGCATCCAGATCGATCCTGTAAAGTTGTCCTCAGGC

TATAAAGATGTGATCCTCTGGTTTTCCTTTGGGGCATCATGTTTCATTCTGCTCGCCATC

GTGATGGGGCTGGTGTTCATTTGTGTTAAGAACGGGAATATGCGGTGCACTATCTGTATT

593
ATGAATACGCAGATACTCGTGTTTGCCCTGATCGCCATAATCCCTACGAACGCAGATAAG

ATCTGCCTCGGACACCACGCTGTTAGCAACGGAACCAAGGTTAACACTTTGACGGAGAGG

GGAGTGGAGGTCGTTAATGCCACCGAAACCGTGGAACGTACCAACATCCCCCGGATCTGT

TCCAAAGGTAAAAAGACTGTCGATCTGGGACAGTGCGGCTTACTGGGAACTATTACTGGG

CCCCCGCAGTGTGACCAATTCCTGGAATTCTCTGCAGATCTTATTATTGAGCGGAGGGAG

GGGAGCGACGTCTGCTATCCGGGGAAGTTCGTCAACGAGGAGGCCTTGAGACAGATCCTG

AGAGAATCTGGGGGCATCGATAAAGAAGCCATGGGATTTACTTATAGCGGCATAAGAACC

AATGGCGCCACATCCGCCTGCCGTAGGAGTGGCTCAAGTTTTTATGCAGAAATGAAATGG

CTACTCAGCAATACTGACAACGCTGCCTTCCCCCAGATGACAAAGAGCTATAAGAATACC

AGGAAGTCACCAGCCCTGATCGTTTGGGGCATACACCATTCCGTATCTACCGCGGAGCAA

ACAAAGCTTTATGGCTCTGGGAATAAGCTTGTAACTGTTGGCAGTAGTAATTATCAGCAG

AGCTTTGTTCCATCCCCTGGCGCCCGGCCCCAGGTGAATGGTCAAAGCGGCAGGATAGAC

TTTCACTGGCTGATGCTCAACCCCAACGATACTGTGACATTCTCCTTTAACGGAGCCTTC

ATTGCTCCCGACCGCGCCTCTTTCCTCAGGGGCAAAAGTATGGGGATTCAGTCAGGTGTT

CAGGTGGACGCAAACTGCGAAGGCGATTGCTACCACTCGGGGGGGACAATCATATCCAAC

CTGCCCTTCCAGAACATTGACAGTCGCGCCGTGGGTAAATGCCCACGGTACGTGAAACAG

CGGTCCCTGCTACTGGCTACTGGGATGAAAAACGTCCCTGAGATTCCCAAAGGCCGGGGA

CTGTTTGGCGCTATCGCGGGGTTCATAGAGAATGGGTGGGAGGGCTTGATCGACGGGTGG

TACGGTTTTAGACATCAGAACGCGCAAGGGGAGGGGACTGCTGCAGATTACAAGTCGACA

CAGTCCGCAATCGACCAGATCACCGGTAAATTGAACCGGCTGATAGAAAAGACCAACCAG

CAGTTTGAGTTGATAGACAATGAATTCAATGAGGTCGAAAAACAGATCGGTAATGTGATT

AATTGGACTCGGGATTCAATTACGGAAGTATGGTCTTACAACGCGGAGTTGTTAGTTGCA

ATGGAAAACCAGCACACGATCGATCTTGCAGACTCTGAAATGGATAAATTATACGAGCGG

GTCAAACGCCAGCTTCGGGAAAACGCCGAAGAGGATGGTACTGGATGTTTTGAGATCTTT

CATAAATGCGACGACGATTGTATGGCCAGCATTCGGAACAATACTTACGACCATTCAAAG

TACCGGGAGGAAGCCATGCAGAATAGAATCCAGATTGATCCAGTGAAACTCAGCTCGGGA

TACAAAGATGTGATTCTGTGGTTCTCCTTCGGGGCCTCTTGCTTCATACTGCTGGCTATC

GTAATGGGGCTTGTCTTCATATGTGTGAAAAACGGGAATATGAGATGCACCATTTGTATC

594
ATGAATACTCAGATACTCGTTTTTGCTTTGATAGCCATCATTCCAACTAACGCTGACAAA

ATCTGCCTAGGACACCATGCAGTGTCAAATGGCACAAAGGTGAATACTTTGACGGAGAGG

GGCGTGGAGGTGGTGAACGCAACAGAGACAGTGGAGCGCACCAACATTCCACGCATTTGT

AGTAAAGGAAAGAAGACAGTCGACCTCGGCCAGTGCGGGCTACTGGGTACGATTACTGGA

CCCCCCCAGTGTGATCAGTTTCTTGAGTTTAGCGCGGATCTGATAATTGAGCGCCGGGAG

GGTTCCGATGTCTGTTACCCCGGAAAGTTTGTGAACGAAGAAGCCCTTAGGCAAATCCTG

CGCGAGAGCGGCGGAATTGAGAAGGAAGCTATGGGGTTCACGTATAGCGGTATTCGGGCT

AACGGAGCCACTAGTGCATGTCGCCGCAGCGGCTCCTCATTCTACGCTGAGATGAAGTGG

CTGCTGTCCAATACCGACAATGCTGCTTTTCCGCAGATGACTAAGTCATACAAAAACACT

AGAAAGTCGCCCGCTTTGATTGTTTGGGGCATCCACCACAGCGTGAGTACAGCTGAGCAG

ACAAAGCTATATGGTTCAGGGAATAAATTAGTTACCGTGGGCAGCTCTAACTACCAGCAG

TCCTTTGTGCCCTCTCCCGGCGCTCGGCCTCAGGTAAATGGGCTTAGCGGCCGGATCGAC

TTTCATTGGCTGATGCTCAACCCTAATGACACAGTGACGTTCTCTTTCAATGGCGCGTTC

ATTGCCCCCGACAGGGCTTCTTTCCTACGGGGGAAAAGCATGGGTATTCAGTCAGGTGTT

CAAGTAGACGCAAACTGTGAAGGAGACTGTTACCACAGCGGGGGCACAATCATTTCAAAT

CTTCCTTTCCAGAACATAGATAGCCGGGCAGTCGGTAAATGCCCTCGGTATGTGAAACAA

AGATCCCTGTTGCTAGCAACAGGCATGAAAAACGTCCCAGAGATCCCTAAGGGACGCGGA

CTTTTCGGCGCGATCGCGGGATTTATCGAGAACGGCTGGGAAGGCCTAATCGATGGATGG

TATGGGTTTAGGCATCAGAATGCTCAGGGGGAGGGAACGGCTGCAGATTATAAATCTACT

CAGTCTGCTATCGACCAAATCACTGGGAAGCTCAATAGGCTGATTGAAAAAACAAATCAA

CAGTTCGAGCTGATAGACAATGAGTTCAACGAGGTAGAGAAGCAGATAGGTAACGTAATT

AATTGGACTCGCGACTCCATTACAGAAGTGTGGTCCTACAATGCTGAGCTGCTTGTGGCA

ATGGAAAACCAGCACACCATAGACCTGGCTGATTCAGAAATGGATAAACTGTATGAGAGG

GTGAAGAGGCAGCTCCGGGAAAACGCTGAGGAAGACGGCACAGGTTGCTTCGAAATTTTT

CATAAGTGCGATGACGACTGTATGGCTTCAATTCGAAACAATACATACGACCACTCCAAG

TATCGAGAGGAAGCCATGCAGAATCGTATCCAAATTGATCCCGTTAAACTATCATCCGGA

TATAAAGACGTCATCTTGTGGTTTTCCTTCGGGGCCTCTTGTTTCATCCTCCTCGCAATC

GTTATGGGATTGGTGTTTATCTGCGTGAAAAACGGCAACATGCGGTGCACAATATGCATT

595
ATGAACACCCAGATCTTGGTGTTCGCCCTCATTGCTATTATACCAACTAATGCGGACAAA

ATCTGCCTTGGACACCATGCCGTATCCAATGGAACCAAGGTCAATACACTGACGGAGAGG

GGAGTGGAAGTAGTGAACGCCACGGAAACAGTGGAAAGGACAAATATCCCTAGGATTTGC

TCCAAAGGCAAAAGAACAGTGGACCTGGGGCAATGCGGGCTTTTGGGTACTATTACAGGA

CCACCTCAGTGCGACCAATTCCTTGAGTTCAGCGCTGATCTGATTATAGAGAGGCGCGAG

GGGAGTGATGTTTGCTACCCCGGTAAGTTCGTAAATGAGGAGGCTCTGCGGCAGATCTTA

CGCGAAAGCGGGGGCATTGATAAGGAAGCTATGGGGTTTACCTACAGCGGCATTCGCACT

AATGGCGCGACATCTGCCTGTCGCCGTTCCGGGTCATCTTTCTATGCAGAGATGAAATGG

CTGCTCTCCAATACTGATAATGCTGCTTTCCCTCAAATGACAAAGTCTTACAAGAATACA

AGGAAGTCTCCCGCACTGATTGTGTGGGGCATCCACCACAGCGTCTCAACCGCTGAGCAG

ACTAAACTGTATGGTTCTGGGAACAAGCTCGTGACCGTCGGATCGTCTAATTATCAGCAG

AGCTTCGTCCCATCACCTGGCGCCAGACCCCAAGTGAACGGTCTGTCCGGCAGAATTGAT

TTCCACTGGCTGATGCTGAATCCCAATGACACGGTCACATTCTCATTTAATGGCGCATTC

ATTGCCCCGGATAGAGCTTCCTTTCTCAGGGGCAAGTCTATGGGAATTCAGAGCGGTGTC

CAGGTGGACGCGAATTGCGAAGGGGACTGCTATCACTCCGGCGGCACCATCATTTCTAAC

CTCCCTTTTCAGAATATTGACAGTCGCGCCGTCGGGAAATGCCCTCGCTACGTGAAGCAG

AGATCACTGCTCTTGGCCACAGGAATGAAGAACGTGCCCGAGATCCCGAAAGGGAGAGGG

CTCTTCGGAGCCATCGCTGGGTTCATTGAAAACGGATGGGAAGGCCTGATAGACGGCTGG

TACGGCTTCCGGCACCAAAACGCCCAGGGGGAAGGAACAGCCGCTGACTATAAATCTACA

CAGAGCGCGATAGACCAGATCACCGGCAAATTAAATCGTCTCATCGAAAAAACAAATCAG

CAGTTTGAGCTTATCGATAATGAATTCAACGAGGTTGAAAAGCAAATCGGGAATGTTATA

AATTGGACCCGAGACTCCATTACCGAGGTGTGGAGCTATAACGCCGAGCTGTTGGTGGCC

ATGGAGAACCAACATACAATTGATTTGGCCGACTCCGAGATGGACAAGCTGTATGAGCGG

GTTAAACGGCAACTGCGTGAGAATGCAGAAGAAGACGGCACTGGCTGCTTCGAAATCTTC

CACAAGTGCGATGATGATTGCATGGCTTCAATACGCAATAACACATACGATCACAGCAAA

TACAGGGAGGAAGCTATGCAGAATCGCATCCAGATTGATCCAGTGAAGCTGTCATCCGGA

TACAAAGATGTTATATTATGGTTCTCCTTTGGGGCTTCCTGTTTCATCCTGCTGGCAATC

GTGATGGGCCTAGTGTTCATATGCGTCAAGAATGGAAACATGAGATGCACCATCTGTATC

596
ATGAATACCCAGATACTTGTATTTGCCCTTATCGCCATAATCCCCACTAACGCCGACAAG

ATTTGTCTAGGGCACCATGCAGTATCTAATGGAACAAAAGTGAATACCCTCACAGAACGG

GGTGTTGAAGTGGTTAATGCCACCGAAACAGTCGAGAGAACTAACATTCCCAGGATTTGT

AGCAAGGGTAAGAAGACAGTTGACCTTGGGCAGTGTGGCTTACTTGGAACTATTACCGGC

CCACCACAGTGCGATCAGTTTCTGGAGTTCAGCGCAGATCTCATTATTGAGAGAAGAGAA

GGAAGCGACGTGTGCTACCCTGGCAAGTTCGTGAATGAGGAGGCCCTTCGGCAGATCCTT

AGGGAGTCCGGAGGCATTGATAAGGAGGCTATGGGTTTTACCTATTCTGGCATTCGTACC

AACGGGGCCACAAGTGCTTGTCGCCGCTCCGGTTCTTCCTTTTACGCTGAGATGAAATGG

TTGCTCAGCAACACTGACAATGCTGCTTTCCCACAGATGACAAAATCCTACAAAAATACC

AGAAAATCGCCCGCCTTGATTGTGTGGGGGATCCACCATAGTGTGTCTACCGCTGAGCAG

ACCAAGCTGTATGGTTCCGGGAATAAGCTCGTGACCGTAGGTTCTTCCAATTATCAGCAG

AGTTTCGTGCCTTCCCCCGGCGCCAGACCTCAGGTGAATGGCCAGAGCGGGAGAATAGAC

TTCCATTGGCTCATGCTGAACCCTAACGATACAGTGACCTTCAGTTTCAACGGCGCCTTC

ATCGCTCCAGACCGCGCCTCATTCCTTCGCGGCAAAAGCATGGGGATCCAGTCCGGGGTT

CAAGTAGACGCCAACTGCGAGGGTGACTGCTATCACTCCGGAGGGACGATAATCAGCAAT

CTTCCCTTCCAGAACATCGATAGCCGCGCCGTCGGTAAGTGCCCACGCTACGTTAAACAG

CGCAGCCTGCTCTTGGCTACCGGCATGAAGAACGTCCCCGAAATCCCTAAGGGCCGGGGC

CTGTTCGGGGCCATTGCGGGTTTTATTGAGAATGGCTGGGAGGGGCTGATAGACGGGTGG

TACGGATTTAGACACCAGAATGCTCAGGGGGAAGGGACCGCTGCCGATTATAAGAGCACC

CAGTCTGCTATTGACCAGATTACGGGTAAGCTGAACAGACTTATTGAAAAAACCAACCAG

CAGTTTGAGCTTATCGACAATGAATTCAACGAAGTGGAGAAGCAGATCGGGAATGTCATC

AACTGGACAAGAGATAGCATCACAGAGGTCTGGTCATATAACGCCGAACTGTTGGTGGCC

ATGGAAAATCAACACACTATAGATCTAGCCGACTCTGAAATGGATAAGTTGTACGAGCGG

GTAAAACGGCAGCTGCGGGAAAACGCTGAGGAAGATGGCACCGGATGCTTCGAGATTTTT

CATAAATGCGATGACGACTGTATGGCCTCTATCAGGAATAATACATACGATCATAGTAAG

TACCGGGAAGAAGCCATGCAGAACAGGATCCAGATAGATCCCGTTAAGCTGTCTAGGGGG

TACAAGGATGTCATCTTATGGTTCAGCTTCGGCGCCAGCTGCTTCATCCTATTGGCCATT

GTCATGGGACTAGTCTTTATCTGCGTGAAAAACGGTAATATGCGGTGTACTATCTGTATC

597
ATGAATACCCAGATCCTGGTTTTCGCGCTGATCGCAATCATACCTACTAACGCAGATAAG

ATTTGCTTGGGACATCATGCCGTGTCCAACGGCACAAAAGTCAATACCCTCACAGAGAGG

GGCGTTGAGGTGGTGAATGCTACCGAGACTGTGGAGAGGACCAATATTCCGAGAATTTGC

TCAAAAGGAAAGCGTACAGTCGACCTGGGGCAATGTGGCCTACTCGGCACCATTACAGGG

CCCCCCCAGTGTGACCAGTTTCTCGAATTTTCTGCTGACCTCATCATCGAGAGACGCGAG

GGGTCCGACGTGTGTTACCCTGGCAAATTCGTTAATGAAGAAGCCCTAAGACAAATTCTA

CGCGAGAGCGGAGGTATTGACAAAGAGGCTATGGGATTCACTTATTCTGGTATCCGCACC

AACGGCGCTACCTCCGCCTGCCGGCGCTCCGGATCCAGCTTTTATGCTGAGATGAAATGG

TTGCTGTCCAACACCGACAATGCTGCATTTCCTCAGATGACCAAATCTTATAAAAACACA

AGAAAGAGTCCTGCGTTGATTGTGTGGGGAATACACCACTCAGTAAGCACTGCCGAACAG

ACGAAGCTGTATGGTTCCGGAAACAAGCTCGTTACAGTGGGCAGTTCAAATTACCAGCAG

AGCTTTGTTCCTTCCCCAGGGGAACGACCCCAAGTTAATGGACTGTCCGGGAGAATTGAT

TTCCATTGGCTGATGCTGAACCCCAACGACACTGTGACGTTCTCCTTTAATGGGGCATTT

ATCGCCCCGGATAGAGCTTCTTTTCTGAGAGGCAAGTCAATGGGGATCCAGTCAGGGGTG

CAAGTCGATGCCAACTGCGAAGGAGATTGTTATCACTCAGGAGGCACGATTATTAGCAAT

CTGCCCTTCCAGAATATTGATTCTCGCGCCGTGGGCAAATGTCCTCGATACGTGAAGCAG

AGATCCCTGCTGCTGGCTACCGGCATGAAAAATGTACCAGAGATTCCAAAGGGGAGAGGA

CTGTTCGGTGCCATCGCCGGTTTCATAGAAAATGGGTGGGAGGGCCTGATTGATGGCTGG

TACGGTTTTAGGCACCAGAATGCTCAGGGAGAAGGGACCGCCGCAGATTATAAAAGCACT

CAGTCTGCAATCGATCAGATAACAGGTAAACTGAACCGCCTGATTGAGAAGACAAACCAG

CAGTTTGAACTGATCGATAATGAGTTTAATGAAGTGGAGAAGCAGATTGGCAACGTTATC

AACTGGACACGGGACTCCATCACCGAAGTGTGGAGCTACAACGCTGAGCTGCTGGTAGCC

ATGGAAAATCAGCACACAATCGATCTGGCTGACTCAGAAATGGACAAGCTCTATGAGAGG

GTCAAAAGGCAACTAAGAGAAAATGCCGAGGAAGATGGGACCGGCTGTTTCGAGATATTT

CACAAATGCGACGATGACTGCATGGCTAGCATTAGGAATAATACCTACGATCATAGCAAA

TATCGGGAAGAAGCTATGCAGAACCGCATCCAAATAGATCCCGTCAAGTTGAGCTCTGGG

TACAAGGATGTGATTCTGTGGTTCTCTTTCGGCGCCTCTTGCTTTATTCTGCTGGCAATC

GTGATGGGTCTGGTGTTTATTTGTGTCAAAAACGGTAACATGCGCTGCACTATCTGCATA

598
ATGAATACACAGATTCTAGTGTTTGCCTTGATAGCTATAATCCCAACCAACGCGGACAAG

ATCTGTCTCGGACACCATGCCGTGTCAAATGGTACTAAGGTGAATACACTGACCGAAAGA

GGAGTGGAGGTCGTGAATGCGACAGAAACGGTTGAGCGAACCAACATTCCTAGGATCTGT

AGTAAGGGAAAGCGAACTGTCGATCTGGGCCAGTGTGGACTCCTCGGGACCATTACAGGG

CCTCCTCAGTGTGATCAGTTTTTGGAATTTTCCGCAGACTTGATAATCGAGAGGCGGGAA

GGGTCTGACGTGTGCTACCCAGGCAAATTTGTAAATGAAGAGGCCCTAAGGCAGATCCTG

AGGGAGAGTGGTGGAATCGATAAAGAAGCCATGGGATTTACATATTCAGGCATCAGGACC

AACGGCGCAACATCAGCCTGCCGAAGATCGGGATCTTCATTCTACGCCGAGATGAAATGG

TTGCTATCCAACACTGACAATGCCGCATTCCCCCAGATGACTAAAAGCTACAAAAACACC

CGGAAGTCCCCAGCTCTCATCGTCTGGGGGATCCATCACAGTGTGTCCACCGCCGAGCAG

ACCAAGCTGTATGGATCCGGCAGTAAACTGGTTACTGTGGGGTCATCTAATTACCAACAG

AGTTTTGTGCCATCGCCTGGCGCCAGACCTCAAGTGAATGGACTGTCCGGTAGAATTGAT

TTTCACTGGCTCATGCTGAACCCTAATGACACGGTTACCTTTTCTTTCAACGGAGCATTT

ATAGCTCCGGATCGCGCCAGTTTTCTACGGGGGAAAAGCATGGGAATCCAGTCGGGTGTG

CAGGTAGATGCTAACTGCGAAGGTGATTGCTACCACTCCGGTGGTACAATCATCAGCAAT

CTGCCGTTCCAGAACATAGATAGTCGTGCAGTGGGTAAGTGCCCTAGGTACGTGAAACAA

AGATCTCTGCTGCTTGCAACCGGTATGAAGAACGTGCCTGAGATTCCGAAAGGGCGCGGC

TTATTCGGAGCTATAGCTGGATTCATCGAGAATGGATGGGAGGGCCTGATTGATGGTTGG

TACGGGTTTCGACATCAGAACGCCCAGGGAGAGGGTACCGCTGCTGACTACAAGAGCACC

CAATCCGCTATCGACCAGATAACTGGCAAGCTGAATAGACTGATTGAAAAGACAAATCAG

CAATTTGAATTGATCGACAACGAATTCAACGAAGTGGAAAAGCAGATTGGTAACGTGATC

AACTGGACCAGAGACTCTATCACAGAGGTATGGTCTTACAATGCCGAGCTCCTGGTTGCC

ATGGAAAACCAACATACCATTGACTTGGCCGACAGCGAAATGGATAAACTATACGAGCGG

GTCAAACGACAGCTGCGCGAGAATGCCGAGGAGGATGGAACTGGCTGCTTCGAAATCTTC

CACAAGTGTGACGACGATTGTATGGCCAGCATCCGGAACAATACATATGATCATTCAAAA

TATCGCGAGGAGGCTATGCAGAATAGAATTCAGATTGACCCCGTGAAGCTGAGCAGCGGG

TACAAGGACGTCATTCTGTGGTTCAGTTTCGGAGCCTCTTGTTTTATCCTCCTCGCGATC

GTGATGGGATTAGTGTTTATTTGTGTGAAGAACGGCAATATGAGGTGTACGATTTGTATC

599
ATGAACACGCAGATCTTGGTGTTCGCACTAATCGCGATAATCCCCACTAATGCAGACAAA

ATTTGTTTAGGCCATCATGCTGTATCCAATGGCACAAAAGTCAACACCCTGACGGAAAGA

GGTGTGGAAGTCGTCAACGCTACCGAGACTGTGGAACGGACGAATATCCCAAGGATCTGT

TCAAAGGGGAAGCGAACGGTCGACCTGGGACAGTGCGGCCTGCTGGGGACCATCACAGGA

CCGCCACAGTGCGACCAGTTTCTGGAGTTTTCTGCGGACTTGATTATCGAAAGACGGGAG

GGAAGTGACGTATGCTATCCCGGCAAATTCGTGAATGAAGAGGCCTTGCGCCAGATATTA

CGCGAGTCCGGAGGGATCGACAAGGAAGCTATGGGGTTCACATACTCCGGCATCAGAACC

AACGGCGCCACATCCGCATGCCGGCGCAGTGGATCCAGCTTCTACGCAGAAATGAAATGG

CTCCTCAGCAATACGGATAACGCCGCCTTCCCACAAATGACCAAGTCATACAAAAATACC

AGAAAGAGCCCAGCCTTGATAGTGTGGGGAATCCACCACTCTGTGTCTACCGCCGAACAG

ACTAAGCTGTATGGATCTGGCTCGAAATTAGTCACCGTCGGCTCCTCCAACTATCAGCAA

TCATTCGTGCCAAGCCCCGGAGCCCGCCCACAGGTTAATGGACTGTCAGGAAGGATTGAC

TTCCACTGGCTGATGCTGAATCCTAATGATACTGTGACTTTCTCATTTAATGGCGCTTTT

ATTGCCCCTGACAGAGCCAGCTTCCTTCGAGGGAAGTCCATGGGAATCCAGTCTGGCGTG

CAAGTAGACGCAAACTGTGAAGGGGATTGCTATCATAGTGGTGGGACAATCATTTCAAAT

CTGCCCTTCCAGAATATCGATAGTAGAGCAGTAGGAAAATGTCCCAGGTACGTGAAACAG

AGATCACTGTTATTGGCTACAGGAATGAAAAATGTCCCAGAAATCCCGAAGGGGAGAGGC

CTCTTTGGGGCCATAGCAGGCTTTATTGAGAATGGGTGGGAAGGCCTAATCGATGGATGG

TACGGGTTCCGCCATCAGAATGCGCAGGGCGAGGGGACTGCAGCCGACTACAAAAGCACG

CAATCCGCTATCGACCAGATTACTGGAAAGCTCAACCGATTAATTGAAAAGACTAATCAG

CAGTTCGAACTGATCGATAACGAGTTCAACGAGGTCGAAAAGCAGATCGGGAATGTGATC

AACTGGACCAGGGATTCCATAACCGAGGTTTGGAGCTATAATGCAGAGTTGCTTGTAGCA

ATGGAGAACCAACATACCATAGACCTGGCCGATTCGGAAATGGACAAGCTGTATGAGCGA

GTGAAACGGCAGCTGCGGGAGAATGCAGAAGAAGACGGCACAGGTTGTTTTGAAATTTTT

CACAAATGCGATGACGATTGCATGGCATCGATCAGAAATAACACCTATGATCATTCAAAG

TATCGCGAGGAGGCCATGCAGAATAGGATCCAAATCGACCCTGTCAAACTCTCTAGTGGC

TACAAGGATGTCATCCTCTGGTTCTCCTTTGGTGCCTCTTGCTTCATTTTGCTCGCCATT

GTAATGGGATTGGTGTTCATTTGTGTTAAATCCAGAAATATGCGTTGTACCATTTGTATC

600
ATGAACACCCAGATTCTGGTCTTCGCTCTGATCGCCATTATACCAACAAATGCGGATAAA

ATTTGCCTGGGACACCATGCTGTAAGCAACGGCACGAAGGTGAACACACTCACCGAAAGG

GGAGTCGAAGTAGTCAATGCCACAGAGACCGTTGAACGTACGAACATCCCTAGAATTTGT

AGCAAAGGGAAACGGACTGTCGATTTGGGACAATGTGGACTGCTTGGGACTATCACAGGG

CCCCCTCAGTGCGATCAGTTCCTGGAATTCTCGGCCGATCTGATCATTGAACGGAGAGAA

GGAAGCGACGTGTGCTACCCAGGTAAATTCGTGAACGAAGAGGCACTGCGCCAAATTCTT

CGGGAGTCCGGGGGGATCGACAAGGAGGCAATGGGATTTACGTATTCTGGCATTAGGACC

AACGGGGCTACATCTGCCTGCCGGCGAAGTGGATCCTCCTTCTATGCAGAAATGAAGTGG

CTCCTTTCAAACACAGACAATGCCGCCTTTCCACAGATGACCAAGAGTTATAAGAATACC

AGGAAAAGTCCTGCCTTGATTGTGTGGGGGATTCACCACTCCGTGAGCACTGCCGAGCAG

ACCAAGCTTTACGGGAGCGGCAATAAGCTGGTGACAGTGGGCTCTTCCAATTATCAACAA

TCCTTCGTGCCTAGCCCTGGGGAAAGACCCCAGGTGAATGGACTGTCCGGCCGGATCGAC

TTTCACTGGCTCATGCTGAATCCCAACGACACTGTAACCTTTAGCTTTAACGGCGCCTTC

ATCGCTCCCGATAGGGCGTCTTTCCTACGGGGGAAAAGTATGGGAATTCAATCAGGCGTC

CAGGTAGACGCCAACTGCGAGGGTGACTGTTACCACAGCGGAGGTACAATAATTTCCAAC

CTGCCTTTCCAAAACATAGATTCCCGCGCAGTGGGGAAATGCCCCAGGTACGTGAAGCAG

CGAAGTCTCCTCCTTGCCACAGGAATGAAGAACGTGCCTGAGATTCCAAAAGGGCGGGGG

TTGTTCGGGGCCATCGCTGGATTTATCGAAAACGGGTGGGAAGGCCTTATCGACGGCTGG

TACGGTTTTAGGCACCAGAACGCACAGGGTGAGGGGACTGCGGCCGACTACAAGTCGACA

CAAAGCGCTATAGACCAGATCACCGGGAAACTTAATCGGCTGATCGAAAAGACTAACCAG

CAGTTTGAATTAATCGACAACGAATTTAATGAGGTGGAGAAGCAGATCGGAAACGTGATT

AATTGGACCAGGGATTCCATCACGGAAGTTTGGTCCTATAACGCGGAGTTGCTTGTTGCC

ATGGAAAACCAGCACACCATTGACCTCGCTGACTCTGAGATGGACAAACTATATGAGAGA

GTCAAAAGACAGCTGCGCGAAAATGCAGAGGAGGATGGCACGGGTTGTTTCGAAATCTTT

CACAAATGTGATGACGATTGTATGGCCAGTATACGGAATAACACCTATGACCACTCAAAG

TACCGAGAAGAAGCCATGCAGAATCGCATCCAGATCGATCCTGTTAAGCTGTCCTCAGGA

TATAAAGACGTCATCCTGTGGTTCTCTTTTGGCGCAAGCTGCTTTATCCTTTTAGCGATC

GTGATGGGCCTGGTTTTTATATGTGTCAAGAATGGAAATATGCGGTGTACAATTTGCATC

601
ATGAACACTCAGATCTTAGTGTTTGCACTGATTGCCATAATCCCAACAAACGCCGATAAA

ATCTGCCTGGGCCATCACGCGGTGTCGAATGGCACAAAGGTCAACACACTGACCGAAAGA

GGCGTAGAGGTCGTGAACGCGACGGAGACCGTGGAGCGCACTAACATTCCTCGCATCTGT

TCAAAAGGTAAGAAAACAGTGGATTTGGGACAGTGTGGCCTTCTCGGTACCATTACCGGC

CCTCCCCAGTGCGACCAGTTCCTCGAATTTTCTGCTGATTTAATTATTGAACGGCGGGAG

GGGTCAGACGTGTGTTATCCCGGCAAGTTTGTGAACGAAGAAGCTCTTAGACAGATCCTC

CGGGAGAGCGGGGGGATTGACAAGGAAGCAATGGGCTTTACATACTCAGGTATTCGAACA

AATGGAGCCACTAGCGCCTGCCGACGATCCGGGTCATCTTTCTACGCAGAGATGAAATGG

CTGCTCAGCAACACTGATAATGCTGCCTTTCCACAGATGACAAAATCCTATAAAAACACC

AGAAAATCCCCTGCGTTAATTGTCTGGGGCATCCACCATTCGGTTTCTACAGCAGAGCAG

ACCAAGCTGTACGGCAGCGGAAATAAACTCGTGACTGTAGGATCGAGTAATTATCAGCAA

AGCTTTGTTCCATCACCAGGGGCCCGTCCACAGGTCAATGGACAGAGTGGAAGGATCGAT

TTCCATTGGCTAATGCTGAACCCAAACGATACTGTGACCTTTTCTTTCAACGGGGCCTTC

ATTGCTCCTGATCGGGCATCATTTTTGCGTGGGAAGTCAATGGGTATACAATCAGGGGTG

CAAGTGGACGCTAATTGCGAAGGTGACTGTTACCATTCTGGAGGCACCATTATCTCTAAC

TTGCCTTTCCAAAACATTGACAGCAGAGCCGTGGGTAAGTGCCCTCGATACGTGAAGCAG

CGGTCGCTTCTCCTTGCCACGGGCATGAAGAACGTGCCTGAAATCCCTAAAGGTCGTGGT

CTATTCGGAGCAATTGCCGGTTTCATCGAGAATGGGTGGGAAGGCCTTATCGATGGTTGG

TACGGGTTTCGGCACCAGAATGCCCAGGGCGAGGGCACAGCTGCTGACTACAAGTCGACC

CAGAGCGCTATCGACCAGATCACAGGCAAGCTCAACAGGCTGATCGAAAAGACTAACCAG

CAATTCGAATTGATCGATAACGAGTTTAATGAGGTGGAAAAGCAGATTGGGAATGTTATC

AACTGGACCCGCGATTCCATTACTGAGGTATGGTCCTACAACGCTGAGCTCTTAGTCGCT

ATGGAGAACCAGCACACCATAGATCTGGCTGATTCAGAGATGGATAAGCTCTATGAACGG

GTTAAAAGGCAGCTTCGGGAGAACGCCGAGGAAGACGGAACTGGTTGCTTCGAGATCTTT

CACAAATGTGACGATGACTGCATGGCTTCCATTAGAAATAACACGTATGACCATAGCAAG

TATAGAGAGGAAGCAATGCAAAACCGGATCCAGATCGACCCAGTCAAATTGAGCTCGGGA

TACAAGGACGTTATCCTGTGGTTCTCATTTGGCGCCTCCTGTTTCATATTGTTGGCTATT

GTGATGGGTCTGGTGTTCATCTGTGTCAAGAATGGGAACATGAGGTGCACCATTTGTATA

602
ATGAACACACAGATTCTCGTGTTTGCGCTAATTGCAATCATACCCACTAATGCAGACAAA

ATCTGTCTGGGACACCACGCGGTTAGCAATGGCACGAAGGTGAATACCCTGACAGAGAGA

GGAGTGGAGGTTGTTAACGCGACCGAAACTGTTGAAAGGACTAATATCCCTCGTATCTGT

TCAAAGGGAAAAAAGACCGTAGACCTGGGCCAGTGTGGACTGCTCGGCACGATCACAGGG

CCACCTCAGTGTGACCAATTTCTGGAGTTCAGTGCTGACCTGATTATCGAAAGAAGAGAG

GGATCAGACGTATGTTATCCCGGAAAGTTCGTGAATGAGGAAGCCCTTCGACAGATCTTA

AGAGAATCAGGCGGGATCGATAAGGAAGCAATGGGCTTCACCTACTCTGGCATTCGGACC

AATGGCGCAACTTCTGCATGCCGCAGATCCGGCTCTAGTTTTTACGCGGAGATGAAGTGG

CTCCTCTCCAATACAGACAATGCAGCATTCCCACAAATGACCAAGTCTTATAAAAACACC

CGCAAGTCCCCCGCTCTCATCGTTTGGGGTATCCACCATAGTGTGTCCACAGCCGAGCAA

ACAAAGCTATACGGAAGTGGCAACAAGCTGGTCACAGTGGGCAGTAGTAATTATCAGCAG

AGCTTCGTGCCTAGCCCCGGGGCCAGGCCACAGGTTAACGGCCAGTCAGGGCGCATCGAC

TTTCACTGGCTTATGCTGAACCCGAACGACACTGTCACATTCTCATTCAACGGCGCCTTC

ATAGCACCCGATAGGGCCTCATTTTTAAGGGGGAAGTCTATGGGAATTCAGTCCGGAGTG

CAGGTCGACGCCAACTGTGAGGGCGACTGCTACCATAGTGGAGGAACCATCATAAGTAAT

CTGCCATTTCAAAACATCGATTCACGCGCGGTGGGAAAATGCCCCAGGTATGTCAAGCAG

CGGAGCCTTTTGCTTGCTACCGGGATGAAGAATGTGCCCGAGATTCCCAAGGGGAGAGGT

TTATTCGGGGCTATAGCCGGGTTTATTGAAAACGGTTGGGAGGGGCTAATAGACGGATGG

TACGGCTTCAGGCACCAGAATGCTCAAGGGGAAGGGACTGCCGCTGATTATAAGAGCACG

CAGTCAGCTATCGACCAGATCACTGGGAAATTGAATCGTTTAATCGAGAAAACCAATCAG

CAGTTCGAACTGATTGATAACGAGTTCAACGAGGTCGAGAAACAAATAGGAAACGTTATA

AACTGGACACGAGATTCCATAACCGAGGTGTGGTCCTATAATGCTGAACTACTCGTAGCC

ATGGAGAACCAGCATACCATTGATCTGGCCGACTCTGAGATGGACAAGCTATATGAACGG

GTGAAAAGACAGTTGCGCGAAAACGCGGAAGAAGACGGGACAGGTTGCTTTGAAATTTTT

CACAAATGCGATGACGACTGCATGGCTAGTATACGGAACAACACATACGATCACTCTAAG

TATCGCGAGGAGGCAATGCAGAATCGCATCCAGATCGATCCCGTCAAACTGTCTTCCGGA

TATAAAGATGTCATACTGTGGTTCTCTTTCGGCGCAAGCTGTTTCATTCTCCTAGCCATC

GTCATGGGTCTGGTTTTCATATGTGTGAAGAACGGGAACATGCGGTGCACCATATGTATA

603
ATGAATACGCAGATCCTGGTGTTTGCTTTAATAGCCATCATCCCTACTAACGCAGACAAA

ATTTGTCTCGGGCACCACGCCGTGTCTAATGGAACAAAGGTCAACACTCTGACAGAACGC

GGAGTTGAAGTAGTGAATGCCACTGAAACTGTGGAGAGGACCAATATCCCTCGCATTTGT

TCTAAGGGAAAGAAGACCGTCGACCTCGGTCAGTGCGGCCTATTGGGAACCATCACTGGC

CCTCCTCAGTGTGACCAGTTTCTGGAGTTTAGTGCCGATTTGATCATCGAAAGAAGAGAG

GGAAGCGACGTTTGTTATCCCGGAAAGTTTGTCAACGAGGAGGCTCTCCGCCAAATTCTC

AGGGAATCTGGAGGTATCGACAAGGAAGCAATGGGCTTCACTTATTCAGGCATTCGCACA

AACGGGGCCACCTCTGCATGCCGCCGCAGCGGCTCTAGCTTTTACGCCGAAATGAAATGG

CTGCTCTCCAATACTGACAACGCTGCCTTTCCCCAAATGACCAAGTCCTATAAAAACACG

CGCAAAAGTCCGGCCCTCATTGTGTGGGGGATTCACCACTCCGTCTCCACAGCCGAGCAG

ACTAAGCTGTACGGTAGTGGTAATAAGTTGGTCACCGTGGGGTCAAGTAATTATCAGCAA

AGCTTCGTCCCTAGCCCCGGGGCCAGACCCCAGGTGAACGGACAAAGCGGAAGGATCGAT

TTTCACTGGCTGATGCTTAACCCTAATGACACCGTTACATTCAGTTTTAATGGTGCGTTT

ATCGCCCCCGATCGGGCCTCCTTTCTTAGAGGCAAAAGTATGGGTATCCAGAGTGGAGTA

CAGGTCGATGCCAATTGCGAAGGCGACTGCTATCACTCTGGGGGAACAATTATCTCCAAT

TTACCGTTCCAGAACATCGACTCTAGGGCAGTCGGCAAATGCCCTAGATATGTAAAGCAG

AGGTCTCTGCTGCTCGCCACGGGAATGAAAAACGTCCCAGAGATCCCAAAAGGCAGAGGA

CTGTTCGGAGCCATAGCTGGCTTTATCGAGAACGGCTGGGAGGGACTGATCGATGGATGG

TATGGTTTCCGGCACCAGAATGCACAAGGTGAGGGAACTGCCGCAGATTATAAGTCCACC

CAAAGTGCCATCGATCAGATTACAGGCAAGTTAAACAGACTTATTGAAAAAACAAATCAA

CAGTTTGAGCTTATTGACAACGAGTTCAATGAAGTTGAGAAGCAAATCGGTAACGTTATC

AATTGGACTCGCGACTCCATCACCGAGGTGTGGTCTTACAACGCGGAACTACTTGTAGCG

ATGGAAAATCAGCATACCATCGACTTGGCCGACTCGGAGATGGATAAGTTGTACGAGAGA

GTGAAACGGCAGCTCAGGGAAAACGCGGAGGAGGACGGAACAGGTTGTTTCGAAATATTT

CACAAGTGCGATGATGACTGTATGGCTAGCATTCGGAACAACACTTACGATCACTCCAAG

TACCGTGAAGAGGCTATGCAGAACAGGATTCAGATCGATCCGGTGAAACTCTCAAGCGGA

TACAAGGACGTTATACTTTGGTTCAGCTTCGGAGCTTCTTGCTTTATTCTTTTGGCTATC

GTTATGGGACTAGTGTTTATATGTGTGAAAAACGGCAACATGCGCTGTACGATATGCATA

604
ATGAACACACAGATCCTTGTGTTTGCACTGATTGCCATCATTCCCACCAATGCCGACAAA

ATCTGCTTAGGTCACCACGCTGTTAGCAACGGAACGAAGGTCAACACCCTGACCGAACGA

GGCGTCGAAGTAGTTAATGCTACCGAAACTGTGGAGAGGACCAACATACCCAGGATCTGC

AGTAAGGGTAAGAAGACAGTCGATCTAGGCCAGTGCGGACTACTCGGCACAATTACCGGA

CCTCCCCAGTGCGACCAGTTTCTTGAGTTCAGTGCTGATCTTATTATAGAACGACGAGAA

GGGAGTGATGTGTGCTATCCCGGCAAGTTTGTGAACGAAGAGGCGCTGCGACAAATCTTG

AGGGAGTCAGGCGGGATTGACAAGGAAGCAATGGGGTTTACATATTCAGGTATTCGTACT

AATGGAGCAACATCTGCCTGCCGGCGCAGTGGCTCCAGCTTTTACGCGGAAATGAAATGG

CTGTTAAGTAACACCGACAATGCAGCATTTCCCCAAATGACAAAGAGTTATAAGAATACA

CGAAAGTCACCCGCACTGATTGTATGGGGCATCCACCATTCGGTGTCGACCGCTGAACAG

ACAAAATTGTACGGCTCAGGCAACAAACTGGTGACTGTTGGTTCTTCTAACTACCAGCAG

AGCTTTGTCCCGTCACCCGGAGCCCGACCACAGGTGAATGGACAGTCCGGACGGATTGAC

TTTCACTGGCTTATGCTCAATCCCAATGATACTGTGACATTTAGTTTCAACGGGGCCTTT

ATAGCTCCCGATCGGGCTTCTTTTCTTCGAGGAAAATCAATGGGCATTCAATCCGGAGTT

CAGGTGGACGCCAATTGTGAAGGAGACTGTTACCATTCCGGAGGTACAATTATTTCCAAC

CTGCCTTTCCAAAATATCGATAGTCGAGCCGTGGGAAAGTGTCCCAGATATGTAAAACAG

AGAAGTCTATTGCTGGCTACAGGGATGAAAAATGTGCCCGAAATACCCAAGGGACGGGGA

TTGTTTGGTGCCATAGCTGGGTTTATCGAGAATGGGTGGGAAGGCCTTATCGACGGCTGG

TATGGCTTTCGGCACCAAAACGCGCAGGGTGAGGGGACCGCGGCAGACTACAAGTCTACT

CAGAGCGCAATTGATCAGATTACCGGCAAACTGAACCGACTAATAGAAAAAACAAACCAG

CAGTTTGAGCTCATTGATAATGAATTCAACGAAGTGGAGAAGCAGATTGGGAACGTGATC

AATTGGACGCGCGATTCCATCACTGAGGTGTGGAGTTACAATGCCGAACTCCTGGTGGCC

ATGGAAAACCAGCACACAATTGACCTCGCTGACTCTGAGATGGACAAGTTGTATGAGCGC

GTGAAGCGGCAGCTTAGAGAGAACGCCGAGGAAGACGGGACAGGGTGTTTTGAGATCTTC

CATAAGTGCGATGACGACTGCATGGCATCCATCCGTAACAACACATATGATCACTCAAAG

TATAGGGAGGAAGCCATGCAGAACAGGATTCAGATCGACCCTGTGAAACTCTCATCAGGG

TACAAAGATGTAATCTTGTGGTTTTCGTTTGGAGCTTCGTGCTTCATTCTGCTAGCGATT

GTCATGGGCCTTGTGTTTATCTGCGTCAAGAACGGCAACATGAGGTGTACTATCTGTATA

605
ATGAATACCCAGATTCTGGTGTTTGCGCTGATTGCCATAATCCCCACTAACGCTGATAAG

ATCTGCCTGGGGCACCATGCAGTGTCTAATGGCACTAAGGTCAATACGCTCACGGAGAGA

GGCGTGGAAGTGGTTAATGCTACCGAAACTGTGGAACGGACTAACATTCCAAGAATCTGT

TCAAAGGGTAAGAAAACTGTGGACCTCGGCCAATGTGGCTTGCTGGGCACCATCACTGGG

CCACCACAGTGTGATCAGTTTCTCGAGTTCTCTGCCGATTTAATCATCGAGCGCCGGGAA

GGATCAGATGTGTGCTACCCGGGTAAATTCGTGAATGAGGAAGCACTGAGACAGATTCTG

CGTGAATCAGGAGGGATTGATAAGGAGGCTATGGGGTTTACATACTCTGGCATCAGAACA

AATGGGGCCACCAGCGCGTGCCGGCGCTCTGGGAGTTCTTTCTACGCTGAAATGAAATGG

CTGCTTTCTAACACGGACAATGCCGCTTTCCCCCAGATGACAAAAAGCTACAAGAACACT

CGCAAGAGCCCTGCACTCATAGTGTGGGGCATCCACCACTCCGTCTCTACTGCAGAGCAG

ACCAAGCTGTACGGCAGCGGGAACAAGCTTGTAACCGTTGGATCTTCAAACTACCAACAA

TCATTCGTTCCCTCTCCTGGAGCCCGGCCCCAAGTTAATGGGCAGTCCGGGAGAATCGAC

TTCCATTGGCTGATGCTAAATCCCAATGATACAGTTACCTTTAGCTTTAACGGCGCCTTC

ATCGCTCCGGATAGAGCGAGCTTCCTTCGCGGTAAGTCTATGGGAATCCAGTCCGGGGTG

CAAGTCGACGCAAACTGCGAGGGAGACTGTTACCATTCCGGGGGTACTATCATTTCAAAT

TTACCCTTTCAGAACATTGATAGCCGCGCCGTAGGCAAATGTCCTAGGTATGTGAAACAG

AGAAGCCTGCTCCTGGCAACCGGAATGAAGAACGTGCCTGAGATCCCTAAGGGTAGAGGA

CTTTTCGGAGCTATCGCCGGGTTCATCGAGAACGGTTGGGAGGGACTCATTGATGGGTGG

TATGGTTTCCGCCACCAGAACGCCCAAGGGGAAGGCACTGCTGCTGACTATAAATCAACG

CAGTCCGCCATAGACCAGATTACAGGTAAATTAAATAGACTGATTGAGAAAACAAACCAG

CAATTCGAGCTAATCGACAATGAGTTTAATGAGGTCGAGAAGCAGATCGGTAACGTCATA

AATTGGACACGGGATAGTATCACCGAAGTGTGGAGCTACAATGCTGAGCTCCTAGTTGCC

ATGGAGAATCAACATACGATCGACCTGGCGGATTCTGAAATGGACAAGTTATACGAAAGA

GTGAAGCGACAGCTAAGAGAGAATGCAGAGGAAGACGGCACTGGCTGCTTCGAAATATTT

CACAAGTGTGATGATGACTGTATGGCAAGCATCAGGAATAACACCTACGACCACAGTAAG

TATAGAGAGGAGGCAATGCAGAACAGGATACAGATCGATCCCGTCAAACTTTCCAGTGGC

TATAAGGACGTTATCCTTTGGTTCTCGTTTGGGGCGAGCTGCTTCATCTTGCTGGCGATC

GTGATGGGCCTCGTGTTTATTTGCGTGAAAAACGGAAACATGAGGTGTACAATTTGTATT

606
ATGAATACACAAATTCTGGTCTTCGCACTGATCGCCATAATCCCCACTAACGCAGACAAG

ATCTGTCTCGGTCACCACGCCGTTTCGAATGGTACTAAGGTAAATACGCTGACAGAGAGG

GGGGTGGAAGTCGTGAACGCCACTGAGACCGTCGAAAGGACAAACATTCCCCGCATCTGT

TCGAAGGGAAAGAAGACCGTCGATCTTGGGCAGTGCGGTCTCTTGGGTACGATCACAGGG

CCTCCTCAGTGCGATCAATTCCTGGAGTTTTCAGCCGACCTGATAATCGAAAGAAGGGAG

GGAAGCGATGTGTGTTACCCCGGGAAGTTCGTGAATGAGGAAGCCCTGCGACAGATCCTA

AGGGAGAGCGGGGGAATCGATAAAGAGGCAATGGGGTTCACCTATAGTGGAATCAGAACT

AACGGCGCCACTTCCGCCTGCCGGAGATCGGGTAGCTCTTTCTATGCTGAAATGAAATGG

CTGCTCAGTAATACAGACAACGCGGCGTTCCCACAGATGACCAAGTCCTATAAGAATACC

CGGAAATCTCCTGCGCTTATTGTGTGGGGCATCCACCACTCTGTGTCCACCGCTGAGCAG

ACAAAACTTTACGGATCAGGAAATAAGCTCGTCACCGTGGGAAGCTCCAATTATCAGCAA

TCCTTCGTGCCATCCCCCGGAGCAAGACCACAGGTGAATGGACAGTCCGGGAGGATCGAT

TTCCACTGGTTGATGCTGAACCCCAATGATACTGTCACGTTCAGCTTCAACGGTGCTTTT

ATTGCTCCCGATAGGGCCAGCTTTCTGAGAGGCAAGTCCATGGGCATCCAGAGCGGGGTC

CAAGTGGACGCTAATTGCGAGGGTGATTGCTACCACTCTGGAGGCACCATCATCAGCAAC

CTGCCTTTCCAGAATATAGATTCCCGGGCGGTGGGGAAGTGCCCAAGATACGTCAAGCAA

CGGAGCCTCCTCCTTGCGACTGGAATGAAAAACGTGCCAGAGATTCCAAAGGGGAGGGGC

CTGTTTGGAGCGATTGCCGGATTCATCGAGAATGGCTGGGAAGGGCTCATTGACGGATGG

TATGGCTTTCGCCATCAGAACGCCCAGGGAGAGGGGACCGCGGCCGACTACAAGTCCACC

CAAAGCGCCATTGACCAAATCACAGGAAAGCTGAATCGCCTAATCGAAAAGACTAATCAG

CAGTTCGAGCTGATAGATAATGAGTTCAACGAGGTCGAGAAACAAATCGGAAATGTCATC

AATTGGACCCGCGACTCTATAACAGAAGTTTGGTCCTATAACGCGGAGCTGCTAGTCGCC

ATGGAAAACCAGCACACTATTGACCTTGCCGATAGCGAAATGGACAAGCTGTATGAAAGG

GTGAAAAGACAGCTGCGCGAGAATGCAGAAGAGGACGGTACCGGCTGTTTCGAGATTTTC

CATAAGTGTGACGACGACTGCATGGCATCGATTCGAAACAACACATACGACCACTCTAAG

TATAGAGAGGAGGCCATGCAGAACAGAATCCAGATCGATCCTGTGAAGCTGTCATCCGGG

TACAAGGATGTCATTCTTTGGTTCTCATTCGGTGCGTCTTGTTTCATCCEGCTCGCCATA

GTCATGGGGCTGGTCTTCATTTGCGTGAAAAACGGGAACATGCGGTGTACAATTTGCATC

607
ATGAATACCCAGATACTCGTGTTTGCCCTTATCGCTATAATCCCCACGAATGCAGACAAA

ATCTGCCTTGGGCATCACGCCGTGAGTAATGGCACCAAAGTGAACACATTGACCGAGCGG

GGGGTGGAGGTAGTCAATGCCACCGAAACAGTGGAACGCACCAACATTCCTCGGATCTGT

AGCAAAGGAAAGAAAACAGTCGATCTGGGCCAGTGTGGCCTGTTAGGAACCATCACTGGA

CCGCCTCAATGCGATCAGTTTCTCGAATTCAGCGCGGATCTCATTATTGAAAGAAGAGAG

GGTTCTGACGTGTGTTACCCCGGCAAGTTTGTGAACGAAGAAGCACTCCGCCAGATACTT

AGGGAGTCCGGCGGGATCGACAAAGAGGCTATGGGGTTTACTTATAGTGGAATCCGCACG

AACGGGGCCACGTCCGCCTGCAGACGGAGCGGCTCCTCATTTTACGCGGAGATGAAGTGG

CTGCTCAGCAACACAGACAATGCCGCCTTTCCCCAGATGACAAAGTCTTACAAGAACACC

AGAAAGTCGCCAGCCCTCATAGTCTGGGGGATACATCACAGCGTTTCCACCGCCGAGCAG

ACTAAGCTGTATGGCAGCGGAAATAAACTGGTGACTGTGGGCTCCAGCAATTACCAGCAA

AGCTTTGTACCCAGCCCCGGAGCAAGGCCCCAAGTGAATGGCCAGTCTGGTAGAATCGAT

TTCCATTGGCTTATGTTGAACCCTAACGACACGGTTACATTCAGTTTCAATGGGGCATTT

ATCGCCCCCGACCGTGCCTCTTTCTTGAGGGGTAAATCTATGGGCATCCAGTCAGGTGTG

CAGGTGGATGCTAATTGCGAAGGCGACTGCTATCACAGTGGCGGTACTATCATATCCAAT

CTGCCTTTTCAAAACATCGATTCCCGTGCGGTGGGGAAGTGTCCTCGATACGTGAAACAG

CGCTCATTGCTGTTGGCCACCGGAATGAAAAACGTGCCAGAGATCCCAAAGGGCAGAGGT

CTGTTCGGAGCTATTGCTGGCTTTATCGAAAACGGCTGGGAAGGGCTGATTGACGGCTGG

TATGGATTTAGGCACCAAAATGCTCAAGGCGAGGGCACAGCCGCCGACTATAAAAGCACT

CAAAGTGCGATAGACCAGATCACAGGCAAGCTGAACCGCCTGATTGAGAAAACAAACCAG

CAGTTCGAACTCATTGACAACGAATTCAACGAAGTGGAGAAACAGATCGGAAATGTTATC

AATTGGACAAGAGACAGTATTACAGAGGTGTGGTCCTATAACGCCGAGCTCCTGGTCGCT

ATGGAGAATCAGCATACCATCGACCTGGGGGATTCAGAGATGGACAAACTTTATGAGAGA

GTTAAAAGACAACTGCGTGAGAATGCTGAAGAAGATGGAACTGGATGCTTCGAAATTTTT

CATAAGTGTGATGATGACTGTATGGCGTCAATCCGGAATAACACCTACGATCACTCCAAA

TATAGAGAAGAGGCAATGCAGAATCGTATTCAGATAGACCCTGTGAAATTGTCCAGTGGA

TACAAGGACGTAATTTTGTGGTTCAGCTTCGGGGCTTCCTGTTTCATCCTCCTCGCCATC

GTGATGGGTCTCGTTTTCATATGCGTGAAGAACGGGAATATGAGGTGCACGATATGTATC

608
ATGAACACCCAGATTCTGGTGTTCGCTCTCATCGCAATCATACCCACCAATGCTGACAAA

ATCTGTTTGGGGCATCATGCCGTCAGCAACGGCACTAAGGTCAATACTCTTACAGAACGC

GGGGTTGAGGTTGTCAATGCAACTGAAACCGTGGAAAGAACGAATATCCCACGTATTTGC

AGTAAGGGCAAGAAAACCGTGGACCTCGGGCAATGCGGGCTGCTTGGAACGATTACCGGC

CCACCCCAATGCGATCAGTTCCTCGAGTTTTCTGCAGATTTGATTATTGAGCGAAGGGAG

GGCTCCGACGTCTGTTATCCTGGAAAGTTTGTGAATGAGGAGGCACTGCGCCAGATACTC

CGTGAAAGCGGCGGGATTGATAAGGAGGCCATGGGCTTTACTTACTCGGGAATACGCACA

AATGGAGCCACTAGCGCCTGCCGGAGGTCTGGATCAAGCTTCTACGCAGAAATGAAGTGG

TTACTAAGCAACACAGATAACGCAGCTTTCCCACAGATGACAAAAAGCTATAAGAATACT

CGCAAGTCCCCTGCCCTGATAGTATGGGGCATCCACCACTCTGTCTCTACCGCCGAACAG

ACTAAGCTGTATGGAAGCGGGAATAAACTGGTTACAGTGGGAAGCAGTAACTATCAGCAG

AGTTTTGTCCCATCCCCAGGCGCTAGGCCACAAGTCAACGGACAGAGGGGGAGAATAGAT

TTTCATTGGCTCATGTTAAATCCTAACGACACAGTGACTTTCTCGTTTAATGGCGCTTTT

ATCGCCCCTGATAGGGCCTCTTTTTTAAGAGGCAAGAGCATGGGAATCCAGTCTGGAGTG

CAGGTCGATGCTAATTGCGAAGGCGACTGCTACCACAGCGGAGGAACAATCATCTCTAAT

TTGCCCTTCCAGAATATTGATAGTCGCGCAGTGGGCAAATGCCCCCGGTACGTAAAGCAG

CGCTCACTCCTGCTGGCAACAGGGATGAAAAATGTCCCTGAGATCCCAAAGGGCAGAGGA

CTGTTTGGTGCCATTGCCGGATTCATCGAGAACGGATGGGAGGGGCTGATCGACGGATGG

TATGGATTCCGGCATCAGAACGCCCAGGGCGAAGGGACAGCCGCTGATTATAAGTCCACC

CAATCAGCCATTGATCAGATTACCGGCAAACTAAATCGCTTGATTGAGAAAACAAATCAG

CAATTCGAATTGATTGACAATGAGTTTAATGAGGTTGAGAAACAGATCGGAAACGTGATT

AATTGGACACGGGATTCTATAACCGAGGTCTGGTCATACAATGCTGAACTTCTGGTCGCG

ATGGAGAACCAGCACACAATTGACCTGGCCGATAGTGAAATGGATAAGTTATACGAACGG

GTCAAACGGCAGCTGAGGGAGAACGCCGAAGAAGACGGTACCGGTTGTTTCGAAATCTTC

CATAAGTGTGATGACGACTGCATGGCCTCAATTCGGAACAACACCTACGATCACAGCAAG

TATAGAGAAGAGGCTATGCAAAACCGCATACAGATCGACCCAGTAAAATTAAGTAGTGGC

TACAAAGATGTGATTCTTTGGTTCTCCTTTGGAGCCAGCTGCTTTATTCTGCTGGCAATA

GTTATGGGCCTCGTCTTTATCTGTGTCAAGAATGGAAACATGAGGTGTACTATTTGCATA

609
ATGAACACGCAGATCCTTGTATTTGCGCTCATAGCAATAATCCCTACGAATGCAGATAAG

ATTTGCCTGGGACACCATGCTGTCTCTAACGGAACCAAGGTCAATACACTGACTGAACGT

GGCGTTGAGGTGGTGAATGCAACTGAGACCGTTGAGCGAACCAACATCCCCCGCATTTGC

TCTAAGGGAAAGAAGACAGTCGATCTCGGACAGTGTGGCCTGCTCGGCACAATTACGGGG

CCCCCTCAGTGCGATCAGTTCTTGGAATTCTCTGCCGACCTCATCATCGAGCGCCGGGAA

GGCTCTGACGTTTGTTATCCTGGCAAATTCGTGAACGAGGAGGCATTGAGGCAAATCTTG

AGAGAATCTGGAGGTATAGATAAGGAAGCCATGGGCTTTACGTACTCTGGGATTAGGACC

AATGGTGCAACTTCTGCGTGCCGTAGGAGCGGAAGTTCTTTCTACGCTGAGATGAAATGG

CTGCTGTCGAATACTGATAATGCCGCTTTTCCCCAGATGACCAAGTCTTACAAGAATACC

AGGAAGTCTCCTGCCCTGATTGTGTGGGGTATCCACCACAGCGTGTCCACAGCCGAACAA

ACCAAACTTTATGGCTCAGGTAATAAGCTCGTCACTGTCGGTAGCTCTAATTATCAGCAG

TCTTTTGTCCCTAGCCCCGGGGCTAGGCCACAGGTCAACGGCCAGAGCGGACGGATTGAC

TTCCACTGGCTGATGCTGAACCCGAACGACACAGTAACGTTTAGCTTCAATGGCGCCTTT

ATTGCCCCGGACCGAGCTTCATTCCTGCGGGGTAAGAGTATGGGGATCCAATCAGGTGTT

CAGGTGGACGCCAATTGCGAAGGCGATTGCTATCATTCCGGGGGTACCATTATCTCCAAC

CTCCCATTTCAAAATATTGATAGCAGGGCCGTGGGCAAATGTCCCAGGTATGTTAAGCAG

CGTTCTCTGTTACTGGCCACTGGCATGAAGAATGTCCCTGAAATCCCAAAGGGCAGAGGA

CTGTTCGGCGCGATCGCGGGATTTATCGAAAACGGATGGGAGGGCTTGATCGATGGCTGG

TATGGGTTTCGACATCAGAACGCCCAAGGGGAGGGAACCGCCGCTGATTATAAAAGCACC

CAGAGTGCCATTGATCAGATCACGGGCAAACTGAACCGGCTCATTGAGAAAACAAACCAG

CAGTTCGAACTCATCGATAACGAGTTTAATGAGGTGGAGAAACAAATCGGCAACGTTATT

AACTGGACTAGGGATTCTATCACGGAGGTCTGGTCCTACAACGCAGAACTGCTGGTGGCA

ATGGAAAATCAACATACTATTGATCTGGCCGATTCCGAAATGGACAAGCTTTACGAGAGG

GTCAAGAGACAGCTGAGAGAGAACGCTGAAGAGGATGGGACCGGATGCTTCGAAATCTTT

CATAAGTGTGATGATGATTGCATGGCCAGTATCCGTAATAATACATATGATCATTCTAAA

TACCGCGAAGAGGCGATGCAGAATCGAATCCAAATTGACCCAGTTAAACTGTCTAGTGGC

TACAAAGACGTCATCCTGTGGTTTTCGTTCGGAGCTTCTTGCTTCATTCTGTTGGCAATA

GTGATGGGCCTCGTATTTATATGTGTGAAAAACGGGAATATGAGATGCACAATTTGTATT

610
ATGAATACCCAGATCCTGGTGTTCGCCCTTATTGCCATCATTCCGACCAACGCTGACAAA

ATCTGTCTCGGACACCACGCTGTCTCCAATGGGACAAAGGTGAATACCTTGACCGAGCGA

GGGGTCGAGGTCGTCAACGCGACAGAAACAGTGGAGAGGACCAACATTCCCCGGATATGC

TCAAAGGGCAAAAGAACGGTGGATCTGGGGCAATGCGGGCTGCTGGGCACTATAACCGGA

CCCCCCCAATGTGACCAGTTTCTTGAATTTTCTGCCGATCTGATAATCGAACGCCGGGAA

GGATCCGACGTGTGCTATCCTGGAAAGTTTGTGAATGAGGAAGCCCTCCGGCAGATTCTG

AGGGAATCCGGAGGGATAGATAAGGAAGCAATGGGGTTCACTTATAGCGGTATCCGCACA

AATGGGGCGACTAGTGCATGTCGTCGAAGTGGAAGCAGTTTCTATGCCGAGATGAAATGG

CTGCTAAGCAATACAGACAACGCCGCATTCCCACAGATGACCAAGTCCTATAAAAATACA

AGAAAGAGTCCCGCGCTTATCGTGTGGGGCATACATCACTCCGTCAGCACCGCCGAACAG

ACCAAGCTCTATGGCTCAGGCAACAAGTTGGTGACAGTCGGCAGTAGCAATTACCAGCAG

TCCTTCGTGCCTAGCCCAGGCGAAAGGCCTCAGGTGAATGGTTTGAGCGGCCGAATAGAC

TTCCATTGGTTAATGCTCAATCCTAACGATACAGTCACGTTCAGTTTCAATGGTGCCTTT

ATAGCGCCTGATCGCGCATCATTCCTGCGTGGAAAATCTATGGGCATTCAGAGCGGAGTC

CAGGTCGACGCCAACTGCGAAGGCGACTGTTATCACTCCGGGGGCACCATTATTTCCAAT

TTGCCCTTCCAGAACATTGATAGCAGAGCAGTTGGCAAGTGCCCGCGCTACGTAAAACAA

AGGTCTCTGCTTTTGGCTACAGGTATGAAAAATGTCCCAGAAATTCCCAAGGGCCGCGGA

TTGTTCGGGGCGATCGCTGGTTTTATTGAGAACGGTTGGGAAGGCCTCATCGATGGGTGG

TATGGTTTTCGGCATCAGAACGCCCAGGGCGAAGGCACTGCCGCGGATTATAAGTCCACC

CAGTCAGCGATCGATCAGATCACAGGAAAGCTGAACCGACTTATCGAAAAAACAAACCAG

CAGTTTGAACTAATTGACAATGAATTCAACGAGGTGGAGAAACAGATTGGCAATGTGATT

AACTGGACCCGTGATAGCATCACAGAGGTCTGGAGCTATAATGCAGAACTGTTGGTTGCT

ATGGAGAATCAGCACACCATCGACCTGGCCGACTCTGAAATGGACAAACTGTACGAGCGA

GTGAAACGGCAGCTGCGTGAGAACGCTGAGGAAGACGGCACCGGTTGTTTCGAAATCTTC

CATAAATGCGACGACGACTGTATGGCTTCTATTAGAAACAATACCTACGATCACTCCAAG

TACCGGGAGGAAGCAATGCAGAATCGAATCCAGATCGACCCAGTTAAGTTGTCCAGCGGA

TACAAGGACGTGATTCTATGGTTTAGTTTTGGAGCCTCCTGCTTCATTCTTCTGGCCATT

GTGATGGGTTTGGTTTTTATCTGTGTAAAAAATGGAAATATGCGCTGTACTATTTGTATT

611
ATGAACACTCAGATTCTTGTGTTCGCTCTGATCGCAATTATACCCACAAACGCGGATAAA

ATCTGCCTTGGACATCACGCAGTGTCGAACGGAACTAAGGTGAACACTCTCACCGAGCGG

GGCGTCGAAGTAGTCAATGCTACAGAGACCGTCGAACGCACTAATATTCCACGTATCTGC

TCCAAGGGGAAAAGGACCGTCGACCTGGGACAATGTGGCTTGCTAGGGACTATTACCGGC

CCACCGCAGTGTGATCAATTCCTCGAGTTCTCAGCCGACCTGATCATCGAGCGACGCGAG

GGCAGCGATGTCTGTTACCCCGGGAAATTTGTTAATGAGGAAGCATTAAGGCAGATCCTG

CGCGAGTCTGGCGGGATCGACAAGGAGGCCATGGGCTTTACATATTCCGGGATCCGGACA

AACGGCGCCACAAGTGCCTGTCGACGGTCAGGATCATCATTCTATGCCGAGATGAAATGG

CTTCTCAGCAATACCGATAACGCTGCATTTCCACAGATGACAAAGTCGTATAAAAACACA

AGAAAGTCACCCGCTCTGATTGTTTGGGGAATTCACCACAGTGTCTCAACCGCAGAACAG

ACCAAGTTGTACGGGAGTGGAAACAAGTTGGTAACCGTGGGATCTTCAAACTATCAGCAG

AGCTTCGTGCCAAGCCCCGGGGAACGCCCCCAAGTGAATGGACTGTCTGGACGGATTGAC

TTCCACTGGCTGATGCTGAACCCCAACGACACAGTGACATTCAGTTTTAATGGAGCATTT

ATCGCCCCGGACAGAGCAAGCTTTCTCAGGGGTAAGAGTATGGGAATTCAGAGTGGTGTA

CAGGTTGACGCTAACTGCGAAGGTGACTGTTATCATTCTGGTGGGACTATCATCTCCAAC

CTGCCTTTCCAGAACATTGACTCCAGAGCAGTCGGCAAGTGCCCCAGGTACGTGAAGCAA

AGGTCTTTGCTGCTCGCAACCGGCATGAAGAACGTGCCTGAAATACCTAAGGGCCGTGGC

TTGTTTGGCGCAATCGCGGGATTTATCGAAAATGGGTGGGAGGGGTTGATTGACGGTTGG

TACGGCTTCCGTCATCAGAATGCCCAAGGGGAGGGCACCGCCGCAGACTATAAAAGCACC

CAAAGTGCAATCGATCAGATCACCGGCAAATTGAACCGGCTGATTGAGAAAACGAATCAG

CAGTTCGAACTGATCGACAACGAATTTAACGAGGTCGAAAAGCAGATTGGAAATGTGATC

AACTGGACCCGGGATTCCATCACCGAAGTCTGGTCATATAACGCGGAACTGCTTGTAGCA

ATGGAGAATCAACACACTATCGATCTGGCGGACAGTGAGATGGATAAGCTCTACGAGAGG

GTTAAGAGACAACTGCGCGAGAATGCTGAGGAAGATGGTACCGGGTGTTTCGAGATTTTT

CACAAATGTGATGATGACTGCATGGCTAGTATTCGCAACAACACATATGATCACTCCAAA

TACCGCGAAGAGGCTATGCAGAACCGCATCCAAATAGATCCCGTAAAGCTTAGCTCGGGT

TACAAAGATGTAATCTTATGGTTTAGTTTCGGAGCGAGCTGTTTTATTCTACTCGCCATT

GTGATGGGGCTTGTCTTCATATGTGTGAAGAATGGAAATATGCGCTGCACAATCTGTATA

612
ATGAATACCCAGATTCTTGTCTTCGCACTCATAGCTATTATTCCTACGAACGCGGACAAG

ATTTGTCTGGGGCATCACGCCGTCTCCAATGGGACAAAAGTGAACACCCTGACTGAACGA

GGGGTTGAAGTGGTCAATGCAACTGAAACAGTGGAACGGACAAACATTCCAAGAATCTGT

TCCAAAGGAAAGCGAACAGTGGACCTGGGACAGTGCGGCCTGCTGGGTACCATTACTGGC

CCCCCACAGTGCGACCAGTTCCTGGAATTTAGCGCAGATCTTATCATCGAGCGGGGGGAA

GGAAGTGACGTGTGTTATCCCGGGAAGTTTGTAAACGAGGAGGCCCTCCGGCAGATCCTT

CGTGAGAGCGGCGGGATTGATAAAGAGGCTATGGGCTTTACCTATTCCGGAATAAGAACC

AACGGGGCCACTTCTGCGTGTCGTAGGAGCGGCAGCAGCTTCTACGCCGAAATGAAGTGG

CTGTTGTCTAACACCGATAATGCCGCCTTCCCTCAGATGACCAAGTCCTATAAGAACACC

CGGAAATCCCCTGCCCTGATTGTTTGGGGGATTCACCATTCCGTATCTACCGCCGAACAG

ACCAAGTTGTACGGTTCCGGAAACAAGCTCGTCACAGTTGGCTCCTCCAATTACCAGCAG

AGTTTCGTACCTTCTCCCGGCGCAAGACCACAGGTCAACGGACTAAGCGGGCGGATTGAC

TTTCACTGGCTCATGTTGAATCCAAATGACACTGTAACCTTTAGTTTCAACGGTGCCTTT

ATAGCACCAGATCGGGCCAGCTTTCTGCGTGGAAAGTCTATGGGCATTCAAAGTGGTGTG

CAAGTGGATGCTAACTGTGAGGGAGATTGCTACCATTCAGGTGGGACAATCATTAGCAAT

CTTCCGTTTCAGAATATTGATTCACGGGCTGTGGGCAAGTGCCCCCGTTACGTGAAGCAG

AGAAGCCTGCTTCTTGCCACGGGAATGAAGAATGTTCCCGAAATACCAAAGGGTAGGGGT

CTCTTCGGAGCAATAGCCGGATTTATCGAGAATGGCTGGGAGGGGCTTATCGATGGTTGG

TACGGCTTTCGCCATCAGAACGCTCAGGGAGAGGGGACCGCAGCAGACTACAAATCCACC

CAGTCTGCTATCGACCAGATCACTGGCAAGCTGAATCGGATAATCGAGAAGACTAACCAG

CAGTTTGAGCTGATCGACAATGAGTTTAACGAAGTGGAGAAACAGATTGGCAATGTGATC

AATTGGACAAGAGATTCCATTACGGAAGTTTGGTCATATAATGCCGAGCTCCTGGTTGCA

ATGGAGAACCAACATACAATCGACCTGGCGGACAGTGAGATGGACAAGCTGTACGAGCGT

GTGAAGCGCCAACTCCGGGAAAATGCTGAGGAAGACGGCACGGGCTGCTTTGAAATCTTC

CACAAGTGTGACGACGACTGCATGGCAAGCATAAGGAACAACACCTATGATCATTCTAAG

TACAGAGAGGAGGCGATGCAGAATCGCATCCAGATTGACCCAGTTAAGCTTTCCAGGGGG

TACAAAGACGTCATCTTGTGGTTTTCCTTTGGTGCCTCTTGTTTCATTTTGCTCGCTATC

GTAATGGGACTGGTATTCATCTGCGTGAAAAATGGAAATATGAGATGCACCATCTGCATT

613
ATGAACACACAAATTCTGGTGTTCGCTCTCATCGCAATAATTCCTACCAACGCCGATAAG

ATTTGCCTGGGGCACCATGCGGTCAGTAACGGAACCAAAGTCAATACACTCACAGAAAGA

GGCGTTGAGGTGGTGAATGCCACAGAAACTGTTGAACGTACAAATATTCCGCGAATCTGT

TCTAAAGGCAAGAAAACCGTTGATCTGGGTCAATGCGGCCTTCTGGGAACCATTACAGGG

CCACCTCAGTGCGACCAGTTTCTCGAATTTTCTGCTGATCTCATTATCGAGAGGCGGGAA

GGCAGTGACGTTTGCTACCCTGGTAAGTTCGTAAATGAGGAGGCCCTCAGGCAGATCCTG

AGGAAGTCCGGCGGTATTGATAAGGAAGCCATGGGCTTCACTTATTCTGGGATCAGGACC

AACGGGGCCACTTCAACATGTAGAAGGTCCGGAAGCTCTTTCTATGCAGAGATGAAATGG

CTCCTGAGCAACACAGACAACGCCGCCTTTCCACAGATGACCAAGAGCTATAAGAATACT

CGCAAATCTCCAGCCATCATAGTGTGGGGTATCCACCACAGCGTGTCCACGGCCGAGCAG

ACAAAGCTGTATGGGAGCGGCAACAAGCTGGTGACTGTCGGTAGCTCGAATTACCAGCAG

TCTTTCGTGCCTAGCCCCGGGGCCCGGCCGCAGGTCAATGGGCTTTCCGGGCGAATCGAC

TTTCACTGGTTGATGTTAAACCCAAACGACACGGTGACATTCAGCTTTAACGGCGCCTTT

ATTGCACCTGACCGCGCATGTTTCCTGAGGGGCAAGTCTATGGGTATCCAGTCTGGTGTA

CAAGTCGACGCCGACTGTGAAGGAGACTGCTACCATTCCGGGGGGACAATAATCTCAAAC

CTACCCTTCCAGAACATCGACAGTAGGGCGGTGGGCAAGTGTCCTAGGTACGTGAAACAG

CGGAGCCTGCTGTTGGCCACAGGCATGAAGAATGTCCCCGAAATTCCAAAGGGGGGGGGT

CTCTTTGGAGCAATTGCAGGATTCATTGAGAATGGTTGGGAAGGTCTCATCGATGGATGG

TACGGGTTCCGCCATCAGAACGCCCAGGGTGAGGGGACCGCAGCCGACTATAAGAGTACC

CAGTCAGCGATCGACCAAATCACCGGCAAGCTAAATCGGCTGATTGAGAAGACAAACCAA

CAGTTTGAATTAATTGACAACGAGTTTAATGAGGTGGAAAGACAGATCGGCAACGTGATC

AACTGGACACGCGATTCCATCACAGAAGTCTGGTCTTATAATGCAGAGCTGCTAGTGGCC

ATGGAGAATCAGCACACCATTGATCTAGCCGACTCTGAAATGGACAAGTTGTATGAACGG

GTAAAACGTCAGTTACGAGAAAATGCCGAGGAAGATGGCACAGGGTGTTTCGAGATTTTT

CACAAATGTGACGACGATTGTATGGCAAGTATTCGTAACAACACATACGACCACAGCAAA

TACAGAGAGGAGGCCATGCAGAACCGCATCCAGATAGACCCAGTTAAACTGAGCTCCGGG

TACAAGGATGTGATCCTCTGGTTTAGTTTCGGCGCAAGTTGTTTCATCCTACTCGCGATA

GTTATGGGCCTGGTATTCATTTGCGTCAAGAACGGGAACATGAGGTGTACCATCTGCATT

614
ATGAATACCCAGATTCTCGTGTTTGCTTTGATTGCTATCATCCCCACGAATGCTGATAAA

ATTTGCCTAGGCCATCATGCTGTGTCTAACGGGACCAAGGTGAACACCCTCACTGAGAGA

GGCGTGGAGGTCGTGAACGCGACCGAGACTGTTGAGCGCACAAACATTCCCAGGATTTGT

AGCAAAGGAAAAAGAACCGTTGATCTCGGCCAATGCGGCCTCCTGGGTACCATCACGGGG

CCTCCACAGTGTGACCAGTTCTTGGAATTCAGTGCAGACCTTATCATCGAGCGCAGGGAG

GGCTCTGATGTATGCTACCCTGGAAAATTCGTGAACGAGGAGGCTTTGAGACAAATCCTG

AGGGAGTCTGGAGGCATCGATAAGGAGGCCATGGGCTTTACATACAGCGGCATTCGCACT

AACGGAGCCACTTCCGCATGCAGGCGGTCCGGCAGCTCATTCTACGCTGAAATGAAGTGG

CTCCTGAGTAATACGGATAACGCCGCCTTTCCGCAGATGACCAAAAGTTATAAGAATACA

AGGAAATCACCTGCTCTCATTGTCTGGGGTATCCACCACTCGGTGAGCACCGCTGAGCAG

ACCAAACTGTACGGGTCAGGCAATAAACTTGTGACCGTGGGCTCAAGCAATTACCAGCAG

TCCTTTGTGCCTTCACCCGGCGAAAGACCTCAAGTCAACGGACTGTCTGGTCGGATCGAC

TTTCACTGGCTGATGTTAAACCCAAATGATACAGTGACATTCTCCTTCAACGGAGCATTC

ATAGCCCCCGATAGGGCCAGCTTCCTCCGGGGGAAATCCATGGGAATTCAGTCAGGCGTC

CAGGTTGACGCTAACTGCGAGGGTGACTGTTATCATTCCGGAGGTACTATAATAAGCAAT

CTTCCATTCCAGAATATAGATTCACGAGCGGTCGGCAAGTGTCCGCGGTACGTTAAACAG

CGTAGCTTACTGCTCGCAACCGGGATGAAAAACGTTCCAGAAATTCCTAAGGGCAGAGGG

CTGTTTGGGGCCATCGCCGGCTTCATCGAGAACGGTTGGGAAGGGCTCATCGATGGCTGG

TACGGTTTTAGACACCAGAATGCCCAGGGCGAGGGGACCGCAGCAGATTACAAGAGCACA

CAGTCAGCCATAGATCAAATTACTGGGAAGCTCAATCGGTTGATAGAAAAGACTAACCAG

CAGTTCGAATTGATCGATAATGAATTTAACGAGGTCGAGAAACAAATCGGCAATGTTATT

AATTGGACTAGAGACTCCATCACAGAAGTGTGGTCCTACAATGCCGAACTGCTGGTGGCT

ATGGAGAACCAGCACACAATCGACCTTGCAGACAGTGAGATGGATAAACTGTATGAGAGA

GTGAAAAGGCAGCTCCGCGAGAACGCTGAGGAAGATGGAACCGGCTGTTTTGAAATTTTC

CATAAGTGCGACGATGATTGCATGGCTTCTATCCGGAATAATACTTACGACCACAGTAAG

TACCGAGAAGAAGCCATGCAGAATCGAATTCAGATAGACCCCGTCAAGCTGAGCTCCGGC

TATAAAGATGTGATTCTGTGGTTCAGCTTTGGGGCCTCTTGTTTCATTCTTTTGGCCATC

GTGATGGGCCTTGTGTTCATTTGTGTAAAAAATGGCAATATGAGGTGCACAATATGTATT

615
ATGAATACCCAGATACTGGTGTTCGCCCTGATTGCAATCATCCCAACTAACGCTGATAAG

ATTTGTCTCGGTCACCACGCTGTGAGTAACGGAACTAAAGTTAACACACTGACAGAGAGG

GGAGTGGAGGTTGTTAACGCGACAGAGACAGTGGAGCGCACTAATATACCACGGATATGT

AGTAAGGGAAAAAGAACTGTGGACTTGGGTCAATGCGGACTGTTGGGGACGATAACTGGC

CCCCCTCAGTGTGATCAGTTTCTGGAGTTCTCAGCCGATCTGATCATCGAGAGGCGAGAG

GGGAGTGATGTGTGTTATCCTGGTAAGTTTGTGAATGAGGAGGCTCTCAGGCAAATCCTC

AGGGAATCTGGAGGGATCGATAAGGAGGCTATGGGCTTCACTTACTCTGGAATAAGAACT

AACGGCGCCACTAGCGCCTGTAGGCGATCCGGAAGTTCGTTCTACGCTGAAATGAAGTGG

TTGCTCAGCAACACTGACAACGCAGCATTTCCCCAAATGACCAAAAGCTATAAGAATACT

CGCAAGTCTCCCGCCCTGATAGTGTGGGGGATTCACCATAGTGTCTCTACAGCCGAGCAG

ACTAAATTATACGGCAGTGGCAACAAGCTGGTGACGGTGGGGAGTTCAAATTACCAGCAG

AGCTTCGTGCCCAGTCCGGGAGCTCGCCCTCAAGTTAATGGTCTTTCCGGCAGAATTGAT

TTTCACTGGCTGATGCTTAACCCTAACGACACCGTGACCTTTTCCTTCAACGGCGCTTTC

ATTGCCCCGGACCGAGCTAGTTTCCTTAGGGGGAAGTCTATGGGCATACAGTCTGGTGTG

CAAGTTGATGCGAATTGCGAGGGGGATTGTTACCACTCTGGAGGTACAATCATCAGTAAT

TTACCCTTCCAGAACATTGATAGTAGAGCCGTTGGGAAGTGTCCACGGTATGTTAAACAG

CGCAGCCTGCTTCTGGCCACAGGGATGAAGAATGTCCCCGAAATCCCCAAAGGCAGAGGA

TTGTTCGGCGCAATCGCGGGGTTTATTGAAAACGGTTGGGAAGGCCTCATTGACGGCTGG

TACGGGTTCCGGCACCAGAATGCTCAAGGAGAGGGCACCGCCGCCGATTATAAGTCTACC

CAGAGCGCCATCGACCAGATCACAGGCAAATTGAACCGAATTATCGAGAAGACCAACCAA

CAGTTCGAGCTTATCGACAACGAATTTAATGAAGTAGAAAAGCAGATCGGAAACGTTATT

AACTGGACTCGGGACAGTATTACTGAAGTGTGGTCCTATAATGCTGAGCTGTTGGTGGCA

ATGGAGAACCAGCACACCATTGACCTGGCCGACAGCGAGATGGACAAGCTTTACGAAAGA

GTGAAGCGACAGCTTCGGGAAAACGCCGAGGAAGATGGAACCGGCTGTTTTGAAATCTTC

CATAAGTGCGATGATGACTGTATGGCCAGTATACGCAACAACACTTATGACCATTCAAAA

TACCGCGAAGAAGCCATGCAGAATCGGATCCAGATCGACCCTGTGAAGCTGTCGAGCGGG

TATAAGGACGTGATACTGTGGTTCAGCTTCGGAGCCAGCTGCTTCATTCTGCTGGCTATT

GTCATGGGCCTGGTGTTCATTTGCGTCAAAAATGGTAATATGAGGTGTACGATCTGCATC

616
ATGAACACTCAGATCCTCGTGTTTGCCTTGATCGCAATAATCCCCACCAATGCCGATAAG

ATATGTCTCGGACACCACGCTGTGTCCAACGGGACCAAGGTTAATACTCTGACAGAGCGG

GGCGTTGAAGTGGTGAATGCCACCGAAACCGTGGAACGGACAAATATTCCACGAATTTGC

AGCAAGGGAAAGAAGACCGTGGACCTTGGTCAGTGTGGGCTGCTGGGGACTATCACCGGG

CCTCCCCAATGCGACCAGTTCCTCGAGTTCTCTGCAGATCTGATTATTGAGCGGCGCGAG

GGTAGTGATGTGTGCTACCCTGGCAAATTCGTGAATGAGGAGGCACTGAGACAGATCCTG

AGAGAGAGTGGCGGAATCGATAAAGAAGCAATGGGGTTTACCTATTCCGGGATACGGACT

AACGGGGCAACATCGGCTTGCAGGCGAAGTGGCTCATCTTTCTACGCCGAAATGAAGTGG

CTCCTGAGCAACACCGATAATGCCGCTTTCCCACAGATGACTAAGTCCTATAAGAACACC

CGGAAGAGCCCGGCCTTGATTGTCTGGGGGATCCACCATTCTGTCAGTACAGCTGAACAA

ACTAAGTTGTACGGTTCCGGAAACAAGCTGGTGACCGTGGGATCTAGCAATTATCAGCAG

TCATTCGTGCCTTCACCTGGCGCACGACCACAGGTCAATGGACAGAGTGGTAGAATCGAC

TTTCACTGGCTGATGCTTAATCCGAATGACACCGTGACCTTCTCCTTCAACGGAGCCTTT

ATTGCCCCTGACCGAGCTAGCTTTCTCAGGGGAAAGTCTATGGGCATACAGAGCGGCGTG

CAGGTCGACGCAAATTGTGAAGGGGACTGTTACCACTCAGGCGGGACCATTATAAGTAAT

CTGCCTTTTCAGAACATTGACAGCAGAGCGGTGGGCAAATGTCCGCGTTACGTGAAGCAG

AGATCACTGCTCTTGGCCACCGGCATGAAGAATGTCCCTGAGATCCCGAAAGGCAGGGGT

CTGTTTGGGGCTATTGCGGGCTTCATTGAAAACGGCTGGGAAGGTCTCATCGATGGTTGG

TACGGATTCCGGCACCAGAATGCTCAGGGGGAGGGCACCGCCGCCGATTATAAGAGTACC

CAGTCTGCCATCGACCAAATCACCGGCAAGCTTAACCGTCTTATCGAGAAAACAAATCAG

CAGTTCGAGCTGATCGATAACGAATTTAATGAGGTAGAGAAACAGATTGGTAATGTGATT

AACTGGACACGCGACTCCATTACCGAGGTGTGGTCGTATAATGCAGAATTACTGGTGGCC

ATGGAGAATCAACACACCATTGATCTGGCCGATAGCGAGATGGACAAGCTGTATGAGAGA

GTGAAGAGACAACTGAGGGAAAACGCGGAGGAGGATGGAACAGGATGTTTCGAGATCTTC

CACAAGTGTGACGACGATTGCATGGCGAGTATCCGGAACAACACCTACGATCATTCAAAA

TATCGAGAGGAAGCTATGCAAAACCGAATTCAGATCGATCCAGTAAAATTATCTTCAGGG

TATAAGGATGTCATACTATGGTTCAGCTTCGGGGCGTCGTGCTTCATCTTGCTGGCTATC

GTCATGGGGCTCGTCTTTATTTGTGTGAAAAATGGAAATATGCGGTGCACGATCTGCATT

617
ATGAACACGCAAATCCTGGTATTTGCGCTGATCGCTATCATTCCCACTAATGCTGACAAA

ATCTGTCTGGGCCATCACGCTGTGTCAAACGGAACCAAGGTGAATACGCTGACCGAACGC

GGCGTCGAGGTGGTCAATGCCACGGAAACAGTCGAAAGAACAAACATTCCCAGAATCTGC

TCAAAGGGTAAAAAGACGGTAGATCTCGGGCAGTGTGGGCTTCTTGGAACAATCACTGGC

CCACCACAATGCGATCAATTTCTCGAATTCAGCGCCGACCTGATCATCGAGAGGAGGGAA

GGTAGTGATGTGTGCTACCCCGGGAAGTTTGTGAATGAGGAGGCATTGCGCCAAATACTG

AGAGAGAGCGGAGGGATTGACAAGGAGGCCATGGGATTCACCTACAGCGGGATCAGAACT

AATGGAGCCACGAGCGCTTGCAGGAGGAGTGGAAGCAGCTTTTATGCTGAAATGAAGTGG

CTACTGTCCAATACGGATAACGCTGCGTTCCCACAAATGACAAAGTCGTACAAGAATACG

CGAAAGAGCCCAGCCCTCATTGTCTGGGGTATCCATCACAGCGTGAGTACCGCAGAACAA

ACCAAACTTTACGGGTCAGGTAACAAACTGGTAACCGTTGGAAGCTCCAATTATCAGCAA

TCGTTCGTTCCTTCACCTGGGGCTCGCCCACAAGTCAATGGACAGAGCGGCAGAATTGAC

TTCCATTGGCTCATGCTCAATCCAAACGATACAGTCACCTTTTCATTTAACGGAGCTTTC

ATCGCTCCTGATCGGGCTAGCTTTCTAAGGGGCAAGTCTATGGGTATTCAGTCCGGCGTA

CAAGTCGACGCCAACTGTGAGGGGGACTGCTACCATAGCGGAGGCACTATCATATCAAAT

CTCCCCTTCCAGAATATCGACTCCAGGGCTGTTGGTAAGTGCCCAAGATACGTGAAGCAG

AGATCCCTCCTTCTGGCTACAGGCATGAAAAATGTGCCAGAAATTCCAAAGGGACGGGGC

CTATTTGGAGCTATTGCAGGCTTCATCGAGAACGGATGGGAAGGACTGATCGATGGGTGG

TACGGATTTAGGCACCAGAACGCCCAGGGAGAGGGAACAGCTGCTGACTACAAATCTACC

CAGTCTGCAATTGATCAGATCACCGGTAAACTGAATAGACTGATTGAGAAAACTAACCAG

CAGTTCGAGCTAATTGATAATGAGTTCAATGAAGTGGAGAAGCAGATCGGCAACGTGATT

AACTGGACCAGAGATTCAATCACGGAGGTCTGGTCTTACAACGCCGAGTTGCTGGTGGCT

ATGGAAAACCAGCACACCATAGACCTGGCCGACTCTGAAATGGACAAATTGTACGAGAGG

GTAAAAAGGCAGCTCCGAGAAAACGCCGAGGAGGACGGTACTGGCTGCTTTGAGATATTT

CACAAGTGCGACGATGATTGCATGGCCTCCATTCGAAACAACACGTACGACCACAGTAAA

TACAGGGAGGAAGCCATGCAGAACCGCATCCAGATTGACCCTGTCAAGCTGAGTAGTGGC

TACAAGGACGTTATCCTCTGGTTTAGTTTTGGAGCATCATGTTTTATACTGTTGGCAATA

GTCATGGGGCTTGTCTTCATCTGCGTGAAAAATGGCAACATGCGTTGTACAATCTGCATT

618
ATGAATACCCAAATTCTGGTGTTCGCTCTAATTGCCATCATACCAACAAACGCAGACAAG

ATTTGTCTGGGCCACCACGCCGTGTCAAACGGAACGAAAGTGAACACTCTGACTGAGCGT

GGCGTGGAGGTAGTGAACGCTACCGAAACTGTGGAGCGGACTAATATCCCAAGGATCTGT

AGCAAGGGAAAAAAGACAGTGGACCTGGGTCAGTGCGGATTGCTAGGAACCATAACCGGT

CCACCTCAGTGCGATCAGTTTTTGGAGTTTAGCGCCGATCTCATCATCGAAAGAAGGGAG

GGTTCTGATGTTTGTTACCCAGGAAAATTTGTTAACGAAGAAGCCCTTCGCCAGATCCTT

AGAGAATCAGGCGGCATCGATAAAGAGGCAATGGGGTTCACCTATTCAGGAATACGCACA

AATGGCGCCACGAGCGCGTGCAGGCGCAGCGGGAGTTCATTTTATGCTGAAATGAAATGG

CTCCTCTCAAACACTGATAACGCTGCATTTCCACAAATGACGAAAAGTTATAAGAATACG

AGAAAGTCTCCAGCCCTCATTGTCTGGGGCATTCATCACTCAGTGTCGACTGCCGAGCAA

ACCAAGCTGTACGGCAGCGGTAACAAATTGGTAACTGTCGGCAGTAGTAACTACCAGCAA

AGTTTTGTGCCTAGCCCCGGCGCTCGGCCACAAGTGAACGGACAGAGCGGGCGCATCGAT

TTTCACTGGCTGATGCTAAATCCAAATGACACAGTCACCTTTTCGTTTAACGGGGCCTTC

ATCGCCCCTGACCGGGCTTCTTTCCTGAGAGGAAAAAGCATGGGAATCCAGTCCGGAGTC

CAGGTTGACGCCAACTGCGAAGGAGACTGTTATCATTCCGGGGGCACTATTATAAGCAAT

CTGCCTTTTCAGAACATAGATAGTCGCGCCGTAGGCAAGTGTCCCCGCTACGTCAAACAG

AGAAGCCTTCTGCTGGCTACCGGTATGAAGAACGTCCCCGAAATCCCTAAAGGCCGAGGA

CTATTCGGCGCTATCGCCGGCTTCATTGAAAATGGCTGGGAGGGCTTGATAGATGGGTGG

TATGGCTTTCGCCATCAGAATGCACAGGGTGAAGGGACTGCAGCCGATTATAAATCTACT

CAGTCCGCCATCGATCAGATTACCGGGAAGCTCAATAGACTCATTGAGAAGACAAATCAA

CAGTTCGAACTGATCGATAACGAGTTCAACGAGGTAGAGAAACAGATCGGGAATGTCATT

AACTGGACCCGAGATTCTATCACAGAAGTTTGGTCTTACAACGCGGAGCTGCTGGTCGCA

ATGGAAAATCAGCATACCATCGATCTGGCCGATTCAGAAATGGACAAGCTTTATGAGAGA

GTGAAGCGCCAGTTGCGCGAGAATGCGGAAGAGGACGGCACCGGATGCTTCGAGATTTTT

CACAAATGTGATGATGATTGTATGGCTTCGATTCGGAATAACACCTACGATCACTCCAAA

TATCGCGAAGAGGCTATGCAGAACAGAATACAAATCGATCCCGTCAAACTTAGCAGCGGC

TACAAAGACGTCATTCTGTGGTTTTCCTTCGGGGCATCCTGTTTTATACTGCTGGCCATA

GTGATGGGTCTGGTGTTTATATGTGTAAAGAACGGCAACATGCGCTGTACCATTTGCATC

619
ATGAACACCCAGATCCTCGTGTTCGCCTTAATCGCTATCATTCCAACCAATGCAGACAAG

ATATGTCTGGGTCATCATGCCGTTAGCAATGGCACCAAGGTCAACACCCTGACCGAGCGC

GGAGTCGAGGTTGTTAATGCAACCGAAACTGTGGAGCGGACAAATATTCCCCGGATCTGC

AGCAAGGGGAAGAGGACAGTCGATCTGGGCCAATGCGGACTGCTGGGCACAATCACCGGA

CCCCCTCAGTGCGATCAATTTCTGGAGTTCAGCGCCGACCTGATCATCGAGAGAAGGGAG

GGGAGTGACGTATGTTACCCAGGGAAGTTTGTGAACGAGGAGGCCCTGAGACAGATTCTG

AGAGAAAGCGGCGGCATCGATAAAGAGGCCATGGGATTTACCTATAGCGGCATTCGCACC

AATGGAGCCACTTCAGCTTGTAGGAGATCCGGGAGTAGCTTTTACGCTGAGATGAAATGG

CTGCTTTCCAATACTGATAATGCCGCTTTCCCACAGATGACTAAGTCTTATAAGAATACT

CGCAAGAGTCCTGCCCTGATAGTCTGGGGCATCCATCATTCCGTCTCAACCGCTGAACAG

ACCAAACTCTACGGGTCTGGGAACAAGTTGGTGACCGTGGGCTCCTCGAATTATCAACAA

TCATTCGTGCCGTCCCCCGGCGCTCGGCCGCAGGTTAACGGTCTTTCAGGCCGCATCGAC

TTCCACTGGCTAATGTTGAACCCAAACGATACTGTTACTTTTAGCTTTAACGGCGCATTT

ATTGCCCCCGACCGGGCCTCCTTCCTGCGAGGCAAGTCCATGGGTATCCAGTCTGGAGTC

CAAGTGGATGCTAACTGTGAAGGCGACTGTTACCATAGTGGAGGGACAATTATTAGTAAC

CTGCCCTTCCAGAACATTGACAGTAGGGCCGTGGGCAAATGCCCACGGTACGTGAAGCAG

CGGTCCCTGCTGCTGGCAACTGGAATGAAGAACGTGCCAGAGATCCCTAAAGGGGGGGGC

CTCTTCGGCGCTATCGCCGGGTTTATAGAGAATGGTTGGGAAGGGCTGATCGATGGATGG

TATGGGTTCCGCCACCAGAATGCTCAGGGTGAGGGGACAGCTGCTGACTACAAGTCTACA

CAGAGTGCTATTGACCAGATCACCGGAAAACTTAACAGGATCATCGAGAAAACGAATCAG

CAATTTGAGCTCATTGATAACGAGTTCAATGAAGTCGAGAAGCAAATCGGGAACGTGATA

AATTGGACACGCGACTCCATCACTGAGGTCTGGAGCTATAACGCCGAGCTTCTGGTGGCA

ATGGAGAATCAGCATACTATCGATCTCGCGGATTCCGAAATGGATAAGCTCTACGAGAGA

GTTAAGAGGCAGCTCCGCGAGAATGCCGAGGAAGATGGGACCGGATGCTTCGAGATATTC

CATAAGTGCGACGACGACTGCATGGCGTCAATAAGGAATAATACTTATGATCATTCTAAG

TACAGGGAGGAGGCCATGCAGAATCGCATTCAGATTGATCCTGTTAAACTAAGCTCAGGC

TATAAGGACGTAATATTATGGTTTTCTTTTGGCGCTTCCTGTTTTATCCTCCTGGCTATA

GTTATGGGGCTGGTGTTTATTTGTGTTAAAAATGGAAATATGAGATGCACAATTTGCATC

620
ATGAATACCCAAATTCTGGTCTTCGCTCTGATAGCTATAATCCCAACGAATGCCGATAAG

ATATGTCTGGGTCATCACGCTGTCTCCAATGGGACCAAAGTGAACACATTGACTGAACGC

GGCGTGGAGGTGGTTAACGCCACTGAGACCGTAGAGCGGACTAATATACCCCGGATCTGC

AGTAAGGGAAAAAAGACAGTCGACTTGGGTCAGTGCGGCCTGCTAGGGACCATCACAGGG

CCTCCTCAATGTGACCAGTTCCTGGAGTTCAGCGCAGACCTTATAATCGAAAGAAGAGAG

GGGTCGGACGTCTGTTACCCCGGCAAGTTTGTGAACGAGGAAGCACTGAGGCAGATCCTG

AGAGAATCCGGCGGAATTGATAAGGAAGCCATGGGTTTCACCTACAGTGGCATACGCACC

AATGGAGCAACATCCGCTTGTAGACGGAGCGGTTCTTCCTTTTACGCCGAGATGAAGTGG

CTGCTGTCCAACACGGATAATGCAGCCTTCCCTCAAATGACTAAGAGTTATAAGAATACG

AGAAAGTCCCCCGCCTTGATTGTGTGGGGGATCCACCATAGCGTTAGCACAGCCGAACAG

ACTAAGCTTTACGGTTCAGGCAACAAGCTCGTAACCGTGGGATCCTCCAATTATCAGCAA

TCCTTCGTGCCTTCTCCTGGCGCCCGCCCTCAGGTTAACGGTCAAAGCGGTCGCATAGAT

TTTCATTGGCTCATGCTGAACCCGAATGATACAGTCACGTTTTCTTTCAATGGGGCATTT

ATCGCACCAGACCGGGCCTCCTTTCTTCGCGGGAAGTCTATGGGAATACAATCCGGCGTA

CAGGTTGATGCTAACTGCGAGGGCGACTGTTATCATTCAGGGGGTACCATAATCTCCAAC

TTGCCTTTCCAAAATATTGATTCCCGGGCTGTCGGAAAGTGCCCGAGATATGTGAAGCAA

CGCAGTTTACTCCTGGCCACGGGAATGAAAAACGTTCCCGAAATCCCTAAGGGAAGGGGA

CTATTTGGTGCTATTGCAGGGTTTATTGAGAATGGCTGGGAGGGCTTAATCGACGGCTGG

TATGGCTTCCGCCACCAAAACGCACAGGGGGAGGGGACAGCAGCAGACTATAAAAGCACG

CAGAGCGCAATCGACCAAATTACCGGCAAGTTGAATAGGCTCATTGAAAAAACAAACCAG

CAATTTGAGCTCATCGACAACGAGTTCAATGAAGTTGAGAAACAGATAGGAAATGTGATC

AATTGGACTCGCGACAGCATTACCGAGGTATGGTCATACAACGCAGAGCTCTTAGTGGCG

ATGGAGAACCAGCACACCATCGATCTAGCCGACAGTGAGATGGACAAGCTGTACGAACGA

GTCAAGAGACAGTTACGAGAGAATGCCGAGGAGGACGGAACCGGCTGCTTTGAGATTTTC

CACAAGTGTGACGATGACTGTATGGCTAGCATTCGCAATAATACCTATGACCACAGTAAA

TACCGGGAGGAGGCTATGCAGAATCGTATTCAGATCGATCCTGTGAAGCTGTCTAGTGGA

TACAAGGACGTAATCCTGTGGTTTTCTTTCGGTGCTTCTTGTTTCATCCTGTTAGCAATA

GTAATGGGTCTGGTATTTATCTGCGTTAAGAACGGAAATATGCGGTGTACTATTTGCATC

621
ATGAACACACAGATACTGGTCTTTGCTCTTATCGCTATCATTCCCACCAATGCCGATAAA

ATCTGCTTGGGGCACCACGCCGTGTCCAACGGGACGAAAGTTAATACACTCACTGAGCGA

GGCGTGGAGGTCGTCAACGCCACAGAGACGGTGGAGCGCACCAACATCCCGAGGATCTGC

AGCAAGGGCAAACGAACCGTCGATCTTGGGCAGTGCGGGCTGTTGGGCACCATTACGGGA

CCTCCCCAGTGTGATCAGTTCTTGGAGTTTTCTGCTGACCTCATCATTGAGAGAAGGGAA

GGCAGCGACGTGTGCTATCCCGGCAAGTTCGTGAAAGAAGAGGCCCTGCGGCAGATACTG

CGGGAGTCAGGCGGTATTGATAAAGAAGCGATGGGCTTCACGTACAGCGGTATCAGGACT

AACGGCGCTACCAGCGCTTGCCGACGGAGCGGTAGCTCTTTCTACGCCGAGATGAAATGG

TTACTTTCTAACACCGATAACGCTGCGTTTCCACAGATGACGAAATCCTACAAGAATACT

AGAAAAAGTCCAGCCCTGATCGTTTGGGGAATTCACCACTCTGTCTCCACAGCTGAACAG

ACCAAGTTGTATGGCTCCGGCAACAAGCTGGTTACAGTAGGCTCCAGCAATTACCAGCAG

TCTTTTGTCCCCTCCCCTGGAGCTCGTCCACAGGTCAATGGACTGTCAGGCCGAATCGAC

TTCCACTGGCTGATGTTGAATCCAAACGATACAGTGACTTTCTCATTTAATGGCGCTTTT

ATTGCCCCAGATCGGGCCAGTTTCCTCAGAGGTAAGTCCATGGGAATCCAGTCGGGGGTC

CAAGTCGATGCCAACTGCGAAGGCGACTGTTACCACAGCGGCGGTACCATTATCTCCAAC

CTGCCCTTCCAAAACATCGACTCTCGGGCAGTTGGAAAATGTCCAAGGTACGTCAAGCAG

AGATCCCTGCTGCTGGCCACAGGCATGAAGAACGTGCCCGAGATTCCCAAAGGACGGGGC

CTATTCGGAGCGATCGCAGGATTCATTGAGAACGGATGGGAGGGCTTGATTGATGGCTGG

TACGGCTTTAGACACCAAAATGCTCAGGGGGAGGGCACTGCCGCCGACTACAAATCTACT

CAGTCGGCGATTGACCAGATTACTGGAAAGTTGAACCGGCTCATTGAAAAAACCAACCAG

CAGTTCGAATTGATTGATAATGAGTTCAATGAAGTGGAAAAACAGATCGGGAATGTGATT

AACTGGACCAGAGACTCCATCACAGAGGTTTGGAGCTACAACGCGGAATTACTAGTTGCC

ATGGAAAATCAGCACACCATTGACCTCGCTGACAGTGAGATGGATAAACTGTACGAGCGC

GTGAAAAGACAGCTACGCGAGAATGCGGAAGAAGACGGCACAGGATGCTTTGAGATCTTT

CACAAGTGCGACGATGATTGCATGGCTTCGATTCGGAATAATACCTACGATCACTCCAAA

TATAGAGAGGAGGCTATGCAAAATCGAATTCAGATCGACCCCGTCAAGTTGTCCTCCGGC

TACAAGGACGTTATCTTGTGGTTCTCCTTTGGCGCATCATGCTTCATTTTGCTGGCCATA

GTCATGGGCCTGGTATTCATTTGTGTCAAGAATGGAAATATGAGGTGCACCATATGCATC

622
ATGAATACCCAGATTCTTGTGTTCGCTCTGATCGCGATTATTCCTACCAACGCTGATAAA

ATCTGCCTCGGACATCACGCTGTTAGCAACGGAACCAAGGTGAACACACTGACAGAGCGC

GGGGTCGAAGTTGTCAACGCTACTGAGACGGTGGAACGGACCAACATACCACGGATCTGC

TCTAAGGGCAAGCGAACTGTGGATCTCGGGCAGTGTGGCTTGCTGGGAACGATTACGGGC

CCTCCTCAGTGTGATCAGTTTCTCGAGTTCTCTGCAGATCTGATAATCGAGAGAAGGGAA

GGATCAGATGTCTGCTACCCTGGGAAATTCGTGAAAGAAGAAGCACTGAGACAAATCTTA

CGCGAGTCAGGGGGCATAGATAAGGAAGCCATGGGCTTCACATACTCTGGGATCCGTACC

AACGGCGCCACGTCAGCTTGTCGTAGGTCTGGCTCTTCTTTCTATGCCGAGATGAAATGG

CTCCTGTCGAATACTGACAATGCTGCGTTCCCCCAGATGACTAAGAGCTACAAAAATACA

AGAAAGTCTCCCGCGCTGATAGTTTGGGGGATTCACCACTCTGTCTCCACTGCCGAACAG

ACAAAGTTATACGGCAGCGGTAACAAGCTAGTGACAGTTGGGAGCTCAAACTATCAACAA

TCATTTGTACCATCCCCCGGTGCCAGGCCACAGGTAAACGGCCTTTCCGGACGTATCGAC

TTTCACTGGCTGATGCTGAATCCCAATGATACCGTAACTTTTTCCTTCAACGGGGCTTTT

ATTGCCCCAGATAGGGCATCCTTTCTGCGAGGTAAGAGTATGGGCATACAGAGCGGCGTG

CAAGTGGACGCTAATTGTGAGGGGGACTGCTACCATTCCGGGGGAACCATCATCTCGAAT

TTACCGTTTCAGAACATCGATTCACGCGCTGTTGGGAAGTGTCCTAGGTATGTAAAACAG

CGATCCCTTCTTCTGGCCACAGGCATGAAGAACGTACCAGAGATACCTAAAGGACGGGGA

CTGTTCGGGGCCATTGCAGGGTTCATCGAAAACGGCTGGGAAGGCCTGATCGACGGCTGG

TATGGCTTTCGGCATCAGAACGCCCAGGGAGAGGGTACTGCAGCCGATTATAAGAGTACA

CAGTCTGCAATCGACCAAATTACAGGAAAGCTGAATAGACTCATAGAGAAGACAAATCAG

CAGTTTGAACTCATTGACAATGAGTTCAATGAAGTGGAAAAGCAAATCGGGAACGTGATT

AATTGGACCAGGGATAGCATAACAGAAGTCTGGTCCTATAACGCTGAACTACTTGTTGCA

ATGGAGAACCAGCACACTATCGATCTGGCAGACTCTGAAATGGACAAACTGTATGAGAGG

GTTAAACGCCAACTGAGAGAGAATGCTGAGGAAGACGGTACTGGCTGTTTTGAGATTTTC

CACAAATGTGACGACGATTGTATGGCGTCCATCAGGAACAACACCTATGACCATTCTAAA

TATAGAGAGGAAGCCATGCAGAATCGGATACAGATTGATCCTGTGAAACTTAGCTCTGGA

TATAAGGACGTGATCCTGTGGTTTTCATTTGGAGCGTCATGCTTTATCCTGCTGGCCATC

GTGATGGGATTGGTCTTCATATGTGTCAAGAATGGCAATATGCGGTGTACCATATGTATT

623
ATGAATACACAGATACTCGTGTTTGCCCTCATTGCCATCATCCCTACCAATGCAGATAAG

ATCTGCCTCGGCCACCATGCTGTTAGCAACGGAACCAAGGTTAACACCCTCACTGAACGA

GGAGTGGAGGTCGTTAACGCCACAGAAACCGTGGAACGGACGAACATCCCCCGCATCTGC

AGCAAAGGCAAGCGCACCGTGGATCTGGGGCAGTGCGGCCTGCTGGGCACGATTACAGGG

CCCCCCCAATGCGACCAGTTTTTGGAGTTCAGCGCAGACCTGATCATTGAAAGGCGTGAG

GGGAGTGACGTGTGTTATCCCGGTAAATTTGTGAACGAAGAGGCCCTCAGACAGATCCTG

CGGGAGTCTGGTGGGATCGATAAAGAGGCAATGGGCTTCACTTATTCTGGAATCCGGACC

AACGGGGCCACCTCTGCGTGCAGGCGTTCCGGCAGCTCATTCTATGCAGAGATGAAATGG

CTACTTAGTAACACGGACAACGCAGCTTTCCCCCAGATGACTAAAAGTTACAAGAACACT

CGAAAGAGTCCAGCACTCATTGTGTGGGGGATTCATCATTCCGTGTCTACCGCCGAGCAG

ACTAAACTATACGGTAGTGGGAATAAACTAGTAACCGTCGGCTCTTCTAACTACCAGCAG

TCTTTTGTGCCCTCTCCAGGTGAACGCCCCCAGGTCAACGGGCTGTCTGGTCGCATCGAC

TTTCATTGGCTGATGCTCAACCCTAATGACACAGTCACGTTCAGTTTCAATGGTGCTTTC

ATTGCACCCGATAGGGCCTCATTTCTTCGGGGCAAGTCCATGGGCATCCAAAGTGGAGTT

CAGGTGGACGCCAATTGCGAAGGTGACTGCTATCACAGTGGGGGCACAATCATTTCTAAC

CTGCCGTTTCAGAATATTGACTCCCGTGCTGTAGGGAAGTGTCCCCGATACGTGAAGCAG

CGGTCCTTGCTTCTGGCAACCGGTATGAAGAATGTCCCTGAGATTCCTAAAGGCCGGGGG

CTGTTCGGAGCTATTGCAGGGTTCATCGAAAACGGCTGGGAGGGGCTCATCGATGGTTGG

TACGGATTCAGACATCAAAATGCACAAGGGGAAGGAACCGCAGCCGACTATAAGAGCACA

CAAAGCGCTATCGATCAGATCACCGGGAAATTAAACCGCCTGATTGAGAAAACCAATCAG

CAGTTCGAGCTTATTGACAACGAATTCAATGAGGTGGAAAAACAGATAGGGAATGTGATC

AACTGGACCAGAGATTCTATCACCGAGGTTTGGTCTTATAACGCGGAACTGCTGGTTGCT

ATGGAGAATCAGCATACCATCGACCTGGCTGACAGCGAGATGGATAAGTTATACGAGCGT

GTCAAACGACAGCTGAGGGAGAATGCGGAGGAGGATGGAACCGGGTGTTTCGAGATCTTC

CATAAATGTGACGATGACTGCATGGCCAGTATTCGGAACAATACATATGACCATTCCAAA

TACCGCGAAGAGGCAATGCAGAATCGAATACAGATAGATCCTGTGAAACTGAGCAGCGGG

TATAAAGACGTCATCTTGTGGTTTAGTTTTGGGGCATCCTGCTTTATTCTGCTCGCCATA

GTGATGGGGTTAGTGTTTATATGTGTTAAAAACGGAAATATGCGGTGTACAATTTGTATC

624
ATGAATACCCAGATTCTTGTGTTTGCCCTGATCGCTATAATACCTACTAATGCAGATAAG

ATCTGTTTAGGACATCACGCCGTCTCCAATGGAACTAAGGTAAACACGCTGACCGAGCGG

GGCGTCGAGGTGGTGAACGCAACCGAAACTGTTGAGCGCACCAATATTCCCCGGATATGC

TCAAAGGGGAAGCGAACCGTTGACCTAGGCCAATGCGGCTTGCTGGGGACAATTACCGGA

CCACCCCAATGTGACCAGTTTCTGGAATTTTCAGCCGACCTAATCATCGAGCGACGCGAG

GGCAGCGACGTGTGTTATCCCGGTAAGTTTGTCAATGAGGAAGCCCTGAGGCAGATACTT

AGAGAATCGGGCGGGATCGACAAGGAGGCCATGGGGTTCACATATAGTGGTATCCGCACT

AATGGAGCTACATCCGCCTGTCGGAGGAGCGGGAGCTCCTTCTACGCTGAAATGAAGTGG

CTCCTCAGTAACACGGATAACGCTGCTTTCCCCCAGATGACTAAAAGCTATAAAAACACT

AGAAAGAGCCCAGCACTCATTGTGTGGGGTATTCACCACTCAGTGTCTACGGCCGAACAA

ACAAAATTATATGGATCCGGGAACAAGCTGGTAACCGTCGGAAGTAGCAATTATCAGCAG

TCCTTTGTGCCAAGCCCGGGAGCCCGGCCCCAGGTGAACGGCCTATCTGGGGGGATCGAT

TTTCATTGGCTTATGCTCAACCCTAACGACACCGTTACCTTTAGCTTCAACGGGGCTTTC

ATTGCACCCGACCGTGCATCATTCCTGCGTGGGAAGAGCATGGGGATACAGAGCGGCGTA

CAGGTGGACGCGAACTGCGAAGGCGACTGTTACCATTCAGGCGGCACCATTATTTCCAAT

TTGCCGTTTCAGAACATCGACTCACGCGCCGTAGGAAAATGTCCCCGGTACGTCAAACAG

CGCAGCCTCCTACTAGCCACCGGGATGAAAAACGTGCCCGAGATCCCCAAGGGACGGGGA

CTATTCGGAGCGATAGCCGGGTTCATTGAGAATGGATGGGAGGGTCTGATCGATGGCTGG

TACGGGTTCCGGCATCAAAACGCACAGGGCGAGGGGACTGCAGCCGATTACAAATCTACC

CAATCGGCAATCGACCAGATTACAGGCAAACTGAATAGGATCATAGAGAAAACCAATCAG

CAGTTCGAACTGATTGACAATGAGTTTAATGAAGTAGAGAAGCAGATTGGGAATGTGATA

AATTGGACTCGAGACAGCATTACCGAAGTCTGGTCTTACAATGCCGAGTTACTCGTCGCT

ATGGAGAACCAGCACACCATTGACCTGGCCGACTCAGAGATGGACAAACTCTATGAGCGC

GTAAAGAGACAATTGAGGGAAAACGCGGAGGAAGACGGAACAGGCTGTTTCGAAATATTT

CACAAGTGCGACGACGACTGTATGGCATCCATCCGGAATAATACCTATGATCACAGCAAG

TACAGGGAGGAGGCTATGCAAAATCGGATCCAGATTGATCCTGTAAAACTGAGCTCGGGA

TACAAGGATGTTATCCTGTGGTTTAGTTTCGGCGCCAGCTGCTTTATTCTCCTTGCCATC

GTCATGGGCCTGGTCTTCATCTGCGTCAAAAATGGAAATATGAGATGCACAATTTGCATT

625
ATGAACACTCAAATTCTCGTGTTTGCTCTAATTGCCATCATCCCGACAAATGCAGATAAG

ATTTGCCTGGGTCACCATGCGGTGTCTAATGGAACAAAGGTTAATACCCTGACCGAAAGG

GGCGTGGAGGTCGTGAATGCCACCGAGACGGTGGAAAGAACCAACATTCCAAGAATTTGC

TCCAAAGGAAAGAAAACCGTCGACCTGGGTCAGTGCGGATTGCTGGGAACAATCACCGGG

CCACCCCAGTGCGACCAGTTCCTGGAATTCAGCGCCGACCTCATTATTGAGCGCAGAGAA

GGTTCTGACGTGTGTTATCCAGGGAAGTTCGTGAACGAGGAGGCACTGCGGCAAATCCTG

CGTGAAAGCGGCGGCATTGACAAGGAGGCGATGGGCTTTACATACTCCGGGATCCGTACA

AACGGGGCCACTAGTGCGTGCAGAAGATCTGGAAGCAGCTTTTATGCTGAAATGAAATGG

TTGCTCTCCAACACGGACAACGCTGCCTTCCCCCAGATGACAAAGAGCTACAAAAATACT

CGAAAAAGCCCCGCCCTAATAGTGTGGGGCATCCACCATTCTGTGAGCACCGCCGAACAG

ACCAAGCTGTATGGCAGCGGTAACAAATTGGTTACCGTAGGCTCTTCTAACTATCAGCAG

AGCTTCGTCCCATCGCCTGGTGCCAGGCCCCAGGTCAACGGCCAAAGCGGTCGGATTGAT

TTTCACTGGTTAATGCTTAATCCAAATGATACAGTGACCTTTAGTTTTAACGGAGCTTTC

ATCGCCCCCGATCGGGCGAGCTTTCTCCGGGGGAAATCCATGGGAATCCAGTCTGGGGTG

CAGGTGGACGCTAATTGCGAGGGCGACTGCTACCACTCCGGGGGGACCATCATAAGTAAC

CTCCCTTTCCAAAACATCGATTCACGAGCTGTGGGAAAATGCCCCCGTTACGTAAAACAG

CGTTCTCTCTTATTGGCCACAGGTATGAAAAATGTGCCAGAAATTCCTAAGGGCCGGGGG

CTCTTCGGCGCCATAGCCGGATTCATTGAGAATGGGTGGGAAGGTCTGATCGACGGGTGG

TACGGTTTCCGACACCAGAACGCACAGGGAGAGGGTACGGCTGCAGATTACAAGTCTACT

CAGTCAGCTATTGACCAGATCACCGGCAAGCTGAATAGGCTTATCGAGAAAACAAACCAA

CAGTTTGAACTGATCGACAATGAGTTTAACGAGGTCGAGAAGCAGATCGGCAACGTTATT

AACTGGACTAGAGACTCCATCACCGAAGTGTGGAGCTACAATGCCGAGCTGCTAGTGGCT

ATGGAGAATCAACATACCATTGATCTGGCCGATAGTGAGATGGACAAGCTGTATGAACGA

GTCAAGCGACAACTACGCGAAAATGCGGAAGAAGATGGGACAGGATGTTTTGAGATTTTC

CACAAATGCGATGACGATTGTATGGCCAGCATCCGGAACAACACATACGATCATAGCAAA

TACAGAGAGGAGGCCATGCAAAATCGCATTCAAATAGACCCTGTCAAGCTTAGCTCCGGG

TATAAAGACGTGATTCTATGGTTCTCGTTTGGGGCCTCATGTTTCATTCTGCTGGCCATC

GTCATGGGCCTCGTGTTTATTTGCGTAAAGAATGGCAACATGCGCTGTACCATCTGTATT

626
ATGAACACTCAGATTCTGGTGTTTGCTCTGATCGCGATTATCCCCACTAATGCCGACAAG

ATATGTCTCGGTCATCATGCGGTTTCTAACGGGACGAAGGTGAACACATTGACAGAGCGA

GGGGTGGAGGTGGTTAATGCGACTGAGACTGTAGAAAGGACCAATATTCCGCGTATTTGT

AGCAAGGGTAAGAAAACTGTTGACTTGGGACAATGTGGTCTGCTCGGAACCATTACTGGC

CCCCCTCAGTGTGATCAATTCCTGGAGTTCAGCGCCGATCTGATTATAGAGCGAAGAGAG

GGTAGCGATGTTTGCTATCCCGGGAAATTTGTAAACGAGGAGGCCCTCCGCCAAATCCTA

CGAGAGTCAGGTGGGATTGACAAGGAGGCTATGGGGTTCACCTATAGTGGAATCCGGACC

AATGGGGCAACTTCTGCCTGTCGGAGATCTGGCTCGAGCTTCTACGCGGAGATGAAGTGG

TTGCTGAGTAACACTGATAACGCTGCGTTTCCCCAAATGACCAAGTCGTATAAAAATACA

AGAAAGAGTCCTGCTCTGATCGTGTGGGGAATCCATCACTCTGTAAGCACGGCCGAGCAA

ACTAAACTTTATGGATCGGGCAATAAACTTGTCACAGTGGGCAGCAGCAACTACCAGCAA

TCATTTGTGCCTTCTCCGGGCGCGAGACCACAGGTCAATGGCCAGTCTGGGAGGATCGAT

TTTCACTGGCTCATGCTAAATCCCAACGACACAGTGACCTTTAGCTTTAATGGCGCATTT

ATTGCACCTGATAGAGCGTCATTCCTTAGGGGAAAAAGCATGGGGATACAATCAGGGGTC

CAGGTCGACGCTAATTGCGAGGGCGACTGCTACCACTCAGGGGGTACCATCATATCTAAT

CTTCCATTCCAGAACATCGACTCGCGAGCCGTTGGAAAGTGCCCCAGGTACGTGAAGCAG

CGGAGTCTGCTCCTGGCAACTGGCATGAAGAACGTGCCTGAGATCCCCAAAGGCCGTGGC

TTATTTGGAGCTATCGCAGGGTTTATCGAGAATGGCTGGGAGGGATTGATCGATGGTTGG

TATGGCTTTCGGCACCAAAATGCCCAGGGAGAGGGAACCGCCGCCGATTATAAGTCAACT

CAGAGTGCGATAGATCAGATTACAGGTAAGCTAAATAGACTGATTGAGAAGACTAACCAA

CAGTTCGAGCTTATCGACAACGAATTTAATGAAGTGGAAAAGCAAATAGGAAACGTTATC

AACTGGACACGCGATAGCATCACAGAAGTTTGGTCTTACAACGCCGAGCTCTTGGTGGCT

ATGGAGAATCAACATACAATCGACCTGGCAGATAGCGAAATGGATAAGTTATACGAACGG

GTCAAGCGACAGCTGAGGGAGAACGCTGAAGAGGATGGAACTGGCTGTTTTGAGATCTTC

CACAAGTGCGATGATGACTGTATGGCAAGCATACGAAACAACACTTACGATCATTCAAAG

TACCGGGAGGAGGCCATGCAAAACAGGATTCAGATTGATCCAGTGAAGTTGTCCTCTGGC

TACAAGGATGTGATACTGTGGTTTTCCTTCGGAGCAAGCTGCTTTATCTTACTGGCAATT

GTGATGGGACTCGTGTTTATATGCGTGAAAAATGGAAATATGCGCTGTACAATCTGCATC

627
ATGAACACGCAGATACTTGTGTTTGCCCTTATTGCCATTATTCCCACTAACGCGGACAAA

ATATGCCTGGGCCATCACGCTGTCTCCAATGGGACGAAAGTGAACACATTGACCGAGCGA

GGCGTGGAAGTGGTAAATGCGACCGAAACCGTAGAGAGAACCAACATTCCTAGAATTTGC

TCCAAGGGCAAACGGACAGTAGATCTGGGGCAGTGCGGACTGTTGGGTACAATTACAGGA

CCTCCCCAGTGCGATCAGTTCCTGGAGTTTTCCGCTGATCTGATTATAGAAAGGCGAGAG

GGTTCCGACGTGTGCTACCCTGGTAAGTTTGTTAAAGAGGAAGCTCTCCGTCAGATTCTC

CGAGAGTCTGGCGGGATCGATAAAGAGGCGATGGGGTTTACCTACTCTGGAATAAGGACC

AACGGAGCAACCTCCGCCTGCAGGAGATCAGGGTCGTCCTTCTATGCTGAAATGAAATGG

TTGCTGTCTAATACCGACAATGCAGCCTTCCCCCAGATGACCAAAAGCTACAAGAATACA

CGCAAATCTCCCGCCCTGATTGTGTGGGGCATACACCATAGTGTGAGTACTGCAGAACAG

ACCAAGCTTTACGGATCCGGCAATAAGCTGGTGACTGTAGGCTCTAGCAACTACCAACAG

AGCTTTGTACCATCCCCCGGTGCACGCCCTCAGGTGAACGGACTCTCGGGGCGGATAGAT

TTCCACTGGTTGATGTTGAATCCCAACGACACCGTGACGTTCAGTTTCAACGGTGCTTTC

ATCGCGCCTGATAGGGCCTCTTTCTTAAGAGGGAAATCAATGGGCATCCAGAGCGGGGTT

CAGGTAGACGCTAACTGTGAGGGTGACTGCTATCATAGCGGCGGCACTATTATATCTAAC

CTGCCCTTCCAGAATATCGACTCCCGGGCCGTGGGAAAATGCCCAAGGTATGTGAAACAG

AGGTCACTGCTACTGGCGACCGGGATGAAGAACGTTCCAGAAATACCTAAAGGTCGTGGG

CTGTTCGGCGCAATTGCCGGTTTCATTGAAAACGGCTGGGAGGGCCTGATCGACGGATGG

TATGGGTTCAGACACCAGAACGCCCAGGGAGAGGGCACAGCTGCCGACTATAAGTCCACA

CAAAGCGCCATTGATCAGATCACAGGCAAGCTTAACAGACTGATCGAGAAGACAAACCAG

CAATTTGAGTTGATAGACAACGAGTTCAACGAAGTGGAGAAGCAAATCGGGAACGTCATT

AATTGGACCCGGGATTCTATCACCGAAGTATGGTCATACAACGCCGAGCTGCTCGTGGCT

ATGGAGAATCAGCATACCATTGATCTTGCCGATTCCGAGATGGACAAGCTGTATGAAAGA

GTCAAACGACAGTTGCGAGAAAACGCTGAAGAGGACGGAACAGGATGCTTTGAAATCTTT

CACAAATGTGACGACGACTGTATGGCAAGCATTCGGAACAATACCTATGATCACTCAAAG

TACCGAGAGGAGGCCATGCAGAATAGGATTCAGATCGACCCAGTCAAGCTCTCCTCCGGG

TACAAAGATGTAATCCTGTGGTTTTCGTTCGGCGCCAGTTGTTTCATCTTACTGGCCATA

GTCATGGGCCTGGTCTTTATCTGCGTTAAGAACGGCAACATGCGCTGCACTATTTGCATC

628
ATGAACACCCAGATACTTGTTTTTGCCCTGATTGCCATCATCCCAACCAACGCCGACAAG

ATCTGCTTGGGGCACCATGCTGTTAGCAACGGAACAAAAGTGAACACCCTGACCGAAAGA

GGCGTCGAGGTAGTAAACGCCACTGAAACGGTCGAGCGAACCAATATACCTAGGATATGT

TCAAAGGGAAAAAGGACGGTTGATTTAGGTCAGTGTGGACTTCTGGGGACAATCACCGGA

CCACCCCAATGTGACCAGTTCCTTGAGTTCAGCGCGGACCTGATTATTGAGAGACGTGAA

GGATCTGACGTCTGCTACCCAGGAAAGTTTGTGAATGAGGAAGCACTCCGCCAGATTCTC

AGGGAATCCGGCGGCATTGATAAAGAGGCAATGGGATTTACCTACTCCGGCATTCGGACT

AACGGTGCTACATCTGCATGTAGACGGTCCGGCTCTTCATTCTATGCAGAGATGAAATGG

CTGCTTTCAAATACTGATAACGCCGCCTTTCCTCAGATGACCAAATCCTACAAGAACACC

CGGAAATCCCCCGCCCTCATTGTTTGGGGGATCCACCACTCAGTGTCAACCGCCGAGCAG

ACCAAGCTCTACGGAAGTGGAAATAAGTTGGTAACTGTGGGAAGCTCTAACTACCAGCAA

AGCTTTGTGCCAAGTCCTGGAGAGAGGCCCCAGGTGAACGGACTTAGCGGTAGGATCGAT

TTTCATTGGCTTATGCTCAACCCCAACGATACGGTCACCTTTTCATTCAATGGGGCCTTT

ATTGCACCGGATAGAGCCAGCTTTCTGAGAGGGAAGTCTATGGGCATCCAGTCGGGCGTA

CAGGTGGATGCAAACTGTGAGGGGGATTGCTATCATAGTGGAGGCACCATCATAAGTAAT

CTGCCCTTCCAGAATATCGATAGCCGGGCCGTGGGCAAATGTCCAAGGTATGTGAAACAG

AGGTCACTGCTGCTCGCTACAGGCATGAAAAACGTGCCTGAAATACCCAAAGGACGGGGG

CTTTTCGGCGCCATCGCCGGCTTCATTGAGAACGGATGGGAAGGTTTGATCGATGGATGG

TATGGATTTAGGCACCAAAACGCCCAGGGGGAAGGCACCGCCGCGGACTACAAGAGTACT

CAGTCTGCAATCGACCAAATCACTGGCAAACTGAATCGGCTGATTGAGAAGACCAATCAG

CAATTCGAACTCATTGACAACGAGTTTAATGAAGTGGAGAAACAGATCGGTAACGTGATA

AATTGGACCAGAGACTCGATCACGGAAGTATGGAGCTACAATGCTGAACTGTTGGTCGCT

ATGGAGAATCAACACACTATCGACCTGGCCGACAGCGAGATGGATAAACTCTATGAAAGA

GTGAAACGGCAGCTCAGAGAGAACGCAGAGGAGGACGGAACCGGCTGCTTTGAAATATTC

CATAAATGCGACGACGATTGCATGGCCAGCATCAGGAACAATACCTATGATCATAGCAAG

TACCGGGAGGAAGCCATGCAGAATAGAATTCAGATCGACCCAGTGAAACTGTCTAGCGGA

TATAAGGACGTGATTCTGTGGTTCTCATTCGGCGCCTCATGCTTCATTCTATTGGCGATT

GTGATGGGACTTGTGTTCATCTGCGTCAAAAATGGCAATATGCGGTGCACGATATGTATC

629
ATGAACACCCAAATTCTGGTCTTTGCTCTGATCGCAATTATCCCAACCAATGCTGACAAA

ATTTGCCTCGGACATCATGCGGTATCCAACGGCACAAAGGTAAACACTCTCACTGAACGC

GGAGTTGAGGTGGTAAATGCCACGGAAACAGTTGAGAGGACTAATATACCTAGAATTTGT

AGCAAAGGAAAAAAAACGGTGGACCTCGGGCAGTGTGGCCTGCTTGGAACAATTACAGGC

CCGCCCCAGTGCGACCAGTTCCTAGAATTCTCCGCCGATCTGATCATCGAACGCCGCGAA

GGAAGCGATGTGTGTTATCCAGGCAAGTTTGTGAATGAGGAGGCCCTGAGACAAATCCTG

CGGGAGAGCGGCGGAATTGATAAAGAGGCAATGGGATTCACTTACAGTGGGATCCGGACA

AACGGGGCCACGTCGGCCTGCAGACGTAGCGGGAGTTCCTTCTATGCCGAAATGAAGTGG

CTGCTGTCCAACACTGACAACGCGGCCTTTCCACAAATGACTAAATCTTATAAAAACACA

CGGAAGTCACCAGCTCTCATCGTGTGGGGTATCCACCATTCGGTCTCTACAGCTGAGCAA

ACTAAGCTTTACGGAAGTGGCAACAAACTGGTGACAGTGGGCAGCTCTAACTACCAGCAG

TCATTTGTCCCGTCTCCCGGGGCCAGACCACAGGTTAATGGGCAGTCAGGCCGGATCGAT

TTTCATTGGTTGATGTTAAACCCAAACGACACAGTCACATTTAGTTTTAATGGGGCATTT

ATAGCCCCTGATAGAGCTAGTTTCTTGAGGGGAAAGAGTATGGGGATCCAGTCAGGTGTA

CAGGTCGACGCCAACTGCGAGGGTGACTGTTACCATTCCGGGGGTACCATCATTAGTAAC

CTGCCTTTCCAGAACATCGACAGTAGAGCAGTGGGTAAATGCCCAAGGTACGTGAAACAA

CGCAGCTTACTGCTGGCTACAGGAATGAAAAACGTGCCCGAGATTCCAAAAGGGAGGGGT

TTGTTCGGTGCTATTGCCGGTTTTATTGAAAACGGATGGGAGGGTCTCATCGATGGATGG

TATGGGTTTAGGCACCAGAATGCACAAGGGGAAGGAACTGCCGCCGATTATAAATCCACC

CAGTCCGCTATTGACCAGATTACCGGTAAACTGAATCGTTTGATTGAGAAAACAAACCAG

CAGTTTGAACTAATCGACAACGAATTCAATGAAGTGGAGAAGCAGATTGGTAACGTCATT

AACTGGACCCGTGACAGTATCACTGAAGTTTGGTCTTATAATGCCGAACTCCTAGTAGCG

ATGGAGAACCAGCACACCATAGACCTCGCCGATAGTGAAATGGACAAACTGTATGAGAGA

GTGAAGCGGCAGTTACGCGAAAACGCTGAGGAGGACGGGACTGGCTGCTTCGAGATTTTT

CACAAGTGCGACGACGACTGCATGGCATCAATCCGCAACAATACATACGATCATTCCAAG

TATCGTGAAGAAGCCATGCAGAACCGGATCCAAATAGACCCTGTCAAACTTAGCAGCGGG

TATAAAGATGTTATTCTGTGGTTTAGCTTTGGAGCCAGTTGTTTCATACTGCTGGCCATT

GTTATGGGCCTCGTCTTCATCTGCGTGAAAAACGGGAACATGCGATGTACGATCTGCATT

630
ATGAACACTCAAATTTTAGTCTTCGCCCTCATTGCGATAATCCCTACTAACGCAGACAAG

ATCTGTCTGGGACACCACGCCGTGTCTAATGGCACCAAAGTGAACACATTGACGGAGAGA

GGAGTAGAGGTGGTGAACGCCACCGAGACCGTCGAGAGAACCAATATACCTAGGATCTGC

AGCAAGGGAAAGAAGACTGTCGATCTGGGCCAATGCGGGTTGCTCGGGACTATTACTGGA

CCTCCGCAATGTGACCAGTTCCTTGAATTCTCTGCTGACCTGATAATCGAACGACGAGAG

GGATCCGATGTTTGCTATCCAGGGAAGTTTGTGAATGAGGAGGCTCTCAGACAAATCCTG

CGGGAGTCCGGCGGCATCGACAAAGAAGCCATGGGTTTCACCTATAGTGGAATTCGGACC

AATGGCGCAACCAGCGCATGCCGGCGTAGTGGAAGCTCCTTTTATGCCGAGATGAAGTGG

TTACTTTCCAATACCGATAACGCAGCATTCCCTCAGATGACCAAAAGTTACAAGAACACT

CGTAAATCTCCTGCTCTTATTGTATGGGGGATACACCACAGTGTGAGCACCGCCGAGCAA

ACTAAGCTTTACGGATCAGGGAATAAGCTTGTAACAGTGGGAAGCTCTAACTACCAACAG

TCCTTTGTTCCATCTCCCGGGGCGAGACCTCAAGTAAACGGGCAATCTGGTAGGATAGAC

TTTCATTGGCTGATGCTGAATCCGAATGATACAGTTACCTTCTCCTTTAATGGAGCCTTT

ATCGCCCCCGACAGAGCGAGTTTTCTGAGGGGGAAGTCTATGGGGATCCAGTCCGGCGTT

CAGGTAGACGCGAATTGCGAAGGGGATTGCTATCACAGCGGGGGTACAATTATCTCTAAC

CTCCCTTTCCAGAATATCGACTCCCGAGCCGTTGGGAAGTGCCCTCGGTATGTTAAGCAA

CGGAGCCTGCTGCTGGCTACCGGGATGAAAAACGTGCCTGAGATTCCTAAAGGCCGGGGC

CTATTTGGGGCCATCGCTGGTTTTATAGAGAACGGCTGGGAAGGTCTGATCGATGGCTGG

TATGGTTTTAGACATCAGAATGCCCAGGGTGAAGGGACCGCCGCCGACTACAAGAGTACC

CAATCTGCCATCGACCAGATCACCGGGAAGCTGAACCGTCTCATCGAGAAGACGAACCAG

CAGTTCGAACTGATTGATAATGAGTTCAATGAAGTGGAGAAGCAGATCGGTAACGTTATC

AACTGGACGCGCGACAGCATAACCGAGGTGTGGAGTTATAACGCTGAACTCTTGGTTGCC

ATGGAGAACCAGCATACCATCGATCTCGCCGATAGTGAGATGGATAAGCTGTATGAACGG

GTGAAAAGGCAACTGCGCGAGAACGCCGAGGAAGACGGCACCGGCTGCTTTGAAATCTTT

CACAAATGCGATGATGATTGTATGGCATCTATCAGGAACAATACCTACGATCACAGCAAA

TACCGCGAGGAAGCCATGCAGAATAGAATCCAGATAGATCCCGTGAAGCTGTCCAGCGGG

TATAAGGACGTCATCTTGTGGTTCAGTTTTGGGGCTTCGTGTTTTATTCTGTTGGCTATC

GTCATGGGCCTCGTGTTCATCTGCGTCAAGAACGGGAACATGCGCTGCACCATCTGCATA

631
ATGAACACTCAAATTTTAGTCTTTGCATTAATTGCCATTATCCCAACCAACGCAGACAAA

ATCTGCCTGGGACATCACGCCGTGTCAAACGGCACCAAAGTGAACACGCTGACCGAACGT

GGGGTCGAAGTGGTGAATGCCACAGAGACTGTCGAGCGCACAAATATCCCGCGCATTTGT

TCCAAGGGTAAGCGGACGGTGGACTTAGGTCAGTGTGGACTTCTAGGTACTATTACCGGA

CCTCCACAGTGTGACCAGTTCCTGGAGTTCTCTGCCGATCTCATCATTGAGCGTCGCGAA

GGAAGTGATGTCTGTTACCCAGGAAAATTCGTGAATGAAGAAGCCCTCCGGCAAATTCTG

CGCGAGTCCGGGGGCATCGACAAGGAGGCGATGGGCTTCACCTATAGTGGCATCCGAACA

AACGGCGCCACCTCCGCATGCCGGAGGAGTGGCAGCTCCTTCTACGCCGAGATGAAGTGG

CTCTTATCCAACACAGACAATGCCGCTTTCCCGCAGATGACAAAGAGTTACAAAAACACG

CGGAAAAGTCCCGCTTTGATTGTGTGGGGTATCCACCACTCTGTCTCTACAGCGGAGCAG

ACAAAGTTATACGGGTCTGGCAGTAAACTGGTTACAGTGGGCTCAAGCAACTACCAACAG

TCTTTCGTCCCCTCCCCTGGCGCAAGACCCCAGGTAAATGGCCTCTCTGGAAGGATTGAC

TTCCACTGGCTGATGCTCAACCCAAATGATACCGTGACATTTAGCTTCAACGGTGCATTT

ATCGCCCCAGACAGAGCTAGTTTCCTTCGGGGCAAATCAATGGGGATTCAGAGCGGAGTG

CAGGTGGATGCTAATTGTGAAGGCGATTGCTACCACTCCGGCGGTACTATTATCTCAAAC

CTGCCTTTTCAGAATATCGATAGTAGAGCCGTGGGCAAGTGCCCGCGTTATGTGAAACAG

CGCTCTCTTTTGCTCGCTACAGGAATGAAAAACGTACCAGAGATCCCCAAGGGGCGTGGC

CTATTTGGAGCTATCGCTGGTTTTATTGAAAACGGGTGGGAGGGCCTGATAGACGGTTGG

TATGGCTTCAGACACCAGAATGCTCAGGGAGAGGGCACCGCCGCCGACTATAAATCAACA

CAGAGTGCGATCGACCAGATTACCGGAAAACTGAATCGCCTCATAGAGAAGACAAACCAA

CAGTTCGAGCTCATCGACAACGAATTTAACGAGGTAGAAAAACAGATCGGTAACGTTATC

AACTGGACACGGGACAGCATCACGGAGGTGTGGTCTTACAATGCCGAGCTTTTGGTGGCT

ATGGAGAACCAGCACACAATCGACCTCGCCGATAGTGAAATGGATAAACTTTATGAGAGG

GTAAAGCGTCAGCTGCGAGAGAATGCTGAAGAAGATGGGACAGGTTGCTTTGAGATCTTC

CACAAGTGCGATGACGATTGCATGGCCTCTATTAGAAATAACACTTACGATCATAGCAAA

TATAGAGAGGAAGCTATGCAGAATAGGATCCAGATAGATCCCGTAAAGCTGTCCTCTGGA

TATAAGGACGTGATCCTCTGGTTCAGTTTTGGGGCATCATGTTTTATTCTGCTCGCAATC

GTTATGGGTTTAGTTTTCATTTGTGTCAAATCACGGAATATGAGATGTACAATCTGTATT

632
ATGAATACACAGATCCTGGTGTTCGCACTGATCGCTATCATCCCCACAAACGCTGACAAA

ATCTGTCTGGGGCACCACGCGGTGAGTAACGGCACTAAGGTGAATACACTGACCGAACGC

GGGGTAGAGGTGGTGAATGCTACAGAGACCGTTGAGCGCACTAACATCCCCAGAATATGT

AGTAAAGGTAAGAAAACCGTCGACCTGGGCCAGTGTGGCCTGCTGGGCACAATTACCGGT

CCACCCCAATGCGATCAGTTCTTAGAGTTCTCAGCAGATCTAATTATCGAGCGCCGCGAG

GGGAGCGACGTCTGCTACCCTGGGAAATTTGTCAACGAAGAGGCCCTTCGGCAAATCCTT

CGAGAGAGTGGCGGCATTGACAAGGAGGCAATGGGGTTTACTTATAGCGGAATCCGGACC

AATGGAGCAACCTCTGCATGCAGGAGAAGCGGCAGTTCCTTCTATGCCGAAATGAAATGG

CTGCTGAGCAATACAGATAACGCTGCCTTCCCACAGATGACCAAGAGTTACAAGAATACT

AGGAAGTCCCCAGCCCTGATTGTTTGGGGAATTCACCACTCCGTTAGTACCGCCGAGCAA

ACTAAACTGTACGGATCTGGAAACAAATTAGTTACAGTCGGAAGTTCTAACTACCAACAG

TCATTTGTTCCATCTCCTGGTGCTAGGCCGCAGGTCAATGGCCAATCCGGCCGAATAGAC

TTTCACTGGCTTATGCTTAATCCGAACGACACAGTGACCTTTAGCTTCAATGGCGCCTTC

ATTGCCCCTGACAGAGCAAGCTTCCTGAGAGGCAAGAGCATGGGGATTCAGAGCGGTGTC

CAGGTGGACGCTAACTGTGAGGGTGACTGCTATCACTCCGGTGGCACTATAATCTCTAAC

CTACCCTTTCAGAATATCGACAGTCGGGCTGTGGGCAAGTGCCCCCGGTATGTTAAACAG

CGTAGCCTTTTGCTGGCTACTGGGATGAAAAACGTGCCCGAGATACCCAAGGGGCGCGGA

CTCTTCGGGGCCATCGCGGGCTTCATCGAGAATGGTTGGGAAGGTCTCATCGATGGCTGG

TACGGATTCAGGCATCAGAACGCACAGGGTGAGGGGACAGCGGCTGACTACAAGTCGACC

CAGAGTGCTATCGATCAGATAACTGGCAAGCTCAACCGGCTCATAGAGAAAACGAACCAG

CAATTCGAGCTGATTGACAACGAATTCAACGAGGTTGAGAAGCAGATTGGCAATGTGATC

AACTGGACGAGAGACAGCATTACCGAGGTGTGGAGTTACAACGCCGAGCTACTGGTAGCA

ATGGAGAATCAACATACCATTGATTTGGCGGATTCTGAGATGGACAAGTTGTACGAGAGG

GTCAAGCGGCAGCTGCGCGAAAACGCAGAAGAGGACGGCACTGGCTGCTTCGAGATTTTT

CACAAATGTGATGACGATTGCATGGCGTCTATCAGGAATAACACATATGACCACAGCAAA

TACCGGGAGGAAGCGATGCAGAACCGGATCCAAATTGATCCAGTCAAGCTGTCAAGGGGC

TACAAGGATGTGATCTTATGGTTCAGTTTCGGAGCAAGTTGCTTTATTCTCCTTGCTATC

GTTATGGGACTTGTCTTCATCTGTGTTAAAAACGGTAATATGCGGTGTACCATTTGTATT

633
ATGAACACCCAGATCCTGGTATTTGCTCTGATTGCCATCATTCCTACCAATGCCGACAAA

ATCTGTCTGGGCCACCACGCAGTTTCGAATGGCACTAAAGTGAATACCCTGACCGAGCGC

GGCGTCGAGGTCGTGAATGCCACAGAGACCGTCGAACGCACAAATATACCTCGGATTTGC

AGCAAGGGAAAGCGGACAGTGGACCTCGGGCAGTGCGGACTGCTCGGGACTATAACTGGA

CCGCCTCAGTGCGATCAATTTTTGGAGTTTTCCGCTGATTTGATCATCGAGAGAAGAGAA

GGAAGCGACGTCTGCTATCCAGGAAAGTTCGTGAACGAGGAGGCCCTGAGGCAAATCTTG

AGGGAGAGTGGTGGCATCGACAAAGAGGCTATGGGTTTCACCTACTCAGGTATACGCACC

AACGGCGCAACAAGTGCTTGTCGGCGGTCAGGATCTTCCTTCTACGCCGAGATGAAATGG

TTGCTAAGTAATACAGACAATGCTGCGTTCCCTCAGATGACAAAGTCCTATAAGAATACA

CGGAAGTCACCTGCCCTGATCGTGTGGGGCATTCACCACAGCGTTAGCACAGCTGAGCAG

ACCAAGTTATATGGCAGTGGTAACAAACTCGTAACGGTGGGGAGTTCCAATTACCAACAG

AGCTTCGTGCCGTCTCCTGGAGCTCGTCCACAGGTCAACGGACTGAGTGGGCGCATTGAC

TTCCATTGGCTTATGTTAAACCCTAATGACACCGTGACGTTTAGCTTCAACGGCGCTTTT

ATCGCCCCTGACCGGGCCTCATTTCTGAGGGGAAAGAGCATGGGGATCCAGTCCGGAGTG

CAGGTGGATGCTAATTGCGAAGGGGACTGCTATCACAGCGGAGGCACCATCATTTCGAAT

CTCCCATTCCAGAACATCGACTCTAGGGCTGTGGGCAAGTGCCCTCGATATGTGAAACAG

CGGAGCTTGCTGCTTGCTACCGGGATGAAGAACGTGCCGGAGATCCCCAAGGGCCGTGGC

TTATTTGGCGCTATCGCGGGTTTCATCGAAAATGGTTGGGAGGGCCTAATAAACGGCTGG

TACGGTTTCCGCCACCAGAACGCGCAGGGCGAGGGGACCGCCGCCGATTACAAATCCACA

CAGAGCGCAATCGATCAAATAACTGGAAAGCTGAATCGCTTGATCGAAAAGACCAATCAG

CAGTTTGAGCTAATCGATAACGAATTTAATGAAGTGGAAAAGCAAATCGGAAACGTGATC

AATTGGACCAGAGACTCGATAACAGAGGTGTGGAGTTACAATGCAGAGCTGCTGGTAGCC

ATGGAAAATCAGCACACGATTGACCTGGCAGATTCAGAGATGGATAAGCTGTACGAGAGG

GTGAAGAGGCAGCTCCGTGAGAATGCTGAAGAGGATGGAACCGGGTGTTTCGAGATTTTT

CACAAATGCGACGACGATTGTATGGCCTCCATCAGGAATAACACATACGACCATAGCAAA

TACAGAGAGGAGGCAATGCAAAATCGGATTCAAATTGATCCCGTGAAACTTTCTAGCGGG

TACAAGGATGTTATCTTGTGGTTCAGTTTCGGCGCCTCCTGTTTTATTCTGCTGGCAATT

GTGATGGGTCTGGTGTTTATTTGTGTAAAGAACGGGAATATGAGGTGCACAATTTGCATC

634
ATGAACACTCAGATACTGGTTTTCGCTTTGATCGCTATCATACCCACAAATGCCGACAAG

ATATGCTTGGGTCATCACGCCGTGTCCAACGGCACTAAAGTGAACACATTGACCGAGAGA

GGAGTAGAAGTGGTCAATGCTACAGAGACCGTGGAACGCACTAATATCCCGCGGATATGT

AGTAAGGGCAAAAAAACCGTGGACCTCGGCCAGTGTGGCCTGCTGGGCACCATTACCGGC

CCGCCACAATGTGATCAGTTCTTGGAATTCTCTGCAGACCTTATCATAGAGCGCCGGGAA

GGATCTGACGTGTGTTATCCAGGCAAGTTCGTTAACGAGGAGGCCCTTAGGCAGATTTTG

CGTGAGAGCGGAGGCATCGATAAAGAAGCTATGGGGTTTACATATAGCGGTATTCGAACA

AACGGAGCCACCTCTGCATGCAGGCGGTCCGGGTCATCATTCTACGCGGAGATGAAGTGG

CTGCTCTCAAATACGGACAATGCGGCATTTCCCCAGATGACAAAAAGTTACAAAAACACA

AGGAAATCCCCAGCCCTGATCGTGTGGGGAATTCACCACAGTGTTAGCACCGCTGAGCAG

ACCAAACTCTATGGCTCTGGCAACAAATTAGTTACCGTCGGATCAAGTAATTACCAGCAG

TCTTTTGTCCCGAGCCCAGGGGCTAGACCTCAGGTGAATGGACAGTCCGGAAGGATCGAC

TTCCACTGGCTGATGCTTAATCCAAACGATACAGTTACTTTCTCATTCAATGGCGCCTTC

ATCGCTCCCGATAGAGCTTCTTTCTTGCGAGGCAAATCAATGGGCATCCAGAGCGGGGTG

CAGGTCGATGCAAATTGTGAGGGTGATTGCTATCATTCAGGCGGTACCATCATATCCAAT

CTCCCTTTCCAAAACATTGATTCCCGGGCAGTGGGAAAATGTCCCCGCTATGTGAAACAG

AGGTCACTTCTATTAGCCACAGGGATGAAAAATGTGCCAGAGATTCCCAAAGGAAGGGGC

CTCTTTGGCGCAATCGCAGGTTTCATCGAGAATGGTTGGGAGGGTCTGATCGACGGCTGG

TACGGCTTCAGGCACCAGAACGCTCAGGGGGAGGGCACCGCAGCCGATTATAAAAGCACC

CAAAGTGCTATTGATCAGATCACAGGCAAACTGAACCGGCTTATAGAGAAGACAAATCAG

CAGTTTGAGTTAATAGACAACGAATTCAACGAGGTGGAGAAACAGATTGGAAACGTTATA

AACTGGACTCGGGACTCTATTACCGAGGTTTGGTCTTACAACGCCGAACTCCTAGTGGCC

ATGGAGAATCAGCATACCATCGATCTCGCTGATTCTGAAATGGACAAGCTGTACGAGAGG

GTTAAACGGCAGCTGCGAGAGAATGCAGAGGAAGACGGAACAGGCTGCTTCGAGATCTTC

CACAAATGCGATGACGATTGTATGGCTTCCATCCGCAATAACACCTACGACCACAGCAAG

TATCGGGAAGAAGCCATGCAGAACCGCATTCAAATTGACCCGGTAAAACTTTCCAGCGGA

TACAAGGACGTCATCCTGTGGTTTAGTTTCGGTGCGAGCTGCTTCATCTTACTAGCTATC

GTGATGGGCCTCGTGTTCATCTGCGTTAAAAACGGCAACATGCGTTGTACCATATGTATT

635
ATGAACACACAGATCCTCGTTTTCGCTCTGATAGCAATTATCCCAACAAACGCAGACAAA

ATCTGTCTGGGGCACCATGCCGTGAGTAACGGCACTAAGGTCAATACACTGACAGAGCGC

GGCGTGGAGGTTGTCAATGCTACAGAAACTGTTGAGAGAACGAACATACCTCGGATTTGC

AGCAAGGGCAAAAAGACCGTCGACCTGGGCCAGTGTGGCTTGCTCGGAACCATCACCGGC

CCACCCCAATGCGACCAGTTCCTTGAATTCAGTGCGGACCTCATCATCGAAAGGAGAGAA

GGAAGTGATGTGTGCTATCCCGGGAAGTTCGTGAACGAAGAGGCCCTGAGGCAGATTCTT

CGGGAGTCTGGTGGTATCGAAAAGGAGGCCATGGGATTCACCTACAGCGGCATTCGCGCC

AACGGTGCAACTTCTGCATGTCGCCGCTCTGGGTCTTCTTTTTACGCCGAAATGAAGTGG

CTGCTTTCTAATACAGATAATGCGGCATTCCCACAAATGACCAAGTCATATAAAAACACG

AGAAAGAGTCCCGCCCTTATAGTGTGGGGGATTCACCACTCCGTCTCCACAGCTGAACAG

ACAAAATTATACGGCAGTGGGAATAAGCTTGTTACTGTCGGCTCCAGCAATTATCAGCAA

AGCTTCGTGCCATCCCCAGGGGCCAGACCACAGGTAAACGGGCTCAGCGGACGCATCGAT

TTTCATTGGTTGATGCTAAACCCAAACGACACCGTAACATTTAGTTTCAACGGTGCCTTC

ATAGCGCCCGATCGGGCATCGTTCCTGCGGGGAAAATCCATGGGCATTCAAAGCGGCGTG

CAGGTGGACGCGAATTGCGAAGGTGACTGTTATCATAGCGGCGGGACCATTATAAGCAAT

CTGCCTTTTCAGAACATCGACTCACGGGCCGTGGGCAAATGCCCTCGTTACGTGAAACAA

CGAAGCCTGCTGCTGGCGACCGGAATGAAAAATGTCCCGGAAATACCTAAAGGAAGGGGG

CTCTTCGGGGCTATAGCCGGTTTTATCGAGAACGGCTGGGAGGGCCTGATCGATGGATGG

TACGGGTTCAGGCACCAGAACGCCCAAGGGGAAGGCACGGCCGCGGACTATAAGTCAACT

CAGTCTGCCATTGACCAGATTACTGGGAAGCTCAATCGCCTGATCGAAAAGACCAACCAG

CAATTTGAGTTGATCGACAATGAGTTTAATGAAGTGGAAAAACAGATCGGGAATGTGATC

AACTGGACCAGGGACTCTATTACCGAGGTTTGGTCCTACAACGCAGAGTTACTCGTAGCC

ATGGAAAACCAACACACCATTGACCTCGCCGATAGTGAGATGGATAAACTGTATGAACGC

GTCAAGCGGCAGTTGCGAGAAAATGCAGAAGAGGATGGCACAGGGTGTTTTGAGATTTTC

CATAAGTGCGACGATGACTGTATGGCCTCCATCCGCAATAACACCTACGATCACTCAAAG

TACCGGGAAGAGGCCATGCAGAATCGAATTCAGATTGACCCAGTTAAACTATCTTCAGGG

TACAAAGATGTGATTCTATGGTTTAGTTTTGGTGCATCGTGCTTTATCCTCCTGGCTATC

GTTATGGGCCTCGTCTTTATCTGTGTCAAGAACGGGAATATGAGATGTACTATTTGCATC

636
ATGAACACCCAGATTCTAGTATTCGCCCTGATTGCAATAATCCCAACAAATGCAGATAAA

ATCTGTCTGGGACACCACGCGGTCTCAAACGGGACTAAGGTTAATACCCTCACGGAAAGA

GGAGTGGAGGTGGTGAACGCTACGGAGACCGTCGAGCGTACAAACATACCCCGGATCTGC

TCAAAAGGCAAGAGGACCGTGGATTTAGGACAGTGCGGATTGTTGGGAACAATCACCGGC

CCTCCTCAGTGTGACCAATTTCTCGAGTTTAGTGCCGATCTGATTATCGAACGGCGCGAG

GGATCAGACGTGTGCTACCCGGGGAAATTCGTAAACGAGGAGGCTCTGCGCCAGATTCTC

CGGGAGTCCGGGGGGATTGATAAGGAGGCCATGGGGTTCACATATTCTGGCATTCGGACC

AATGGCGCCACTTCTGCCTGCAGACGCTCCGGCTCGAGCTTTTATGCCGAAATGAAATGG

CTCCTTAGCAACACCGATAATGCCGCATTCCCCCAAATGACCAAAAGTTACAAGAATACA

CGTAAGTCGCCTGCACTTATCGTGTGGGGCATACACCACTCAGTGAGCACAGCTGAGCAA

ACCAAGTTATATGGTTCGGGGAGTAAGCTGGTGACCGTAGGGTCTTCAAATTATCAGCAG

AGTTTCGTCCCTAGTCCAGGCGCCAGGCCTCAGGTTAACGGTCTGTCTGGACGCATCGAT

TTTCATTGGTTGATGCTTAATCCGAACGATACAGTGACTTTCTCTTTTAATGGCGCCTTC

ATCGCCCCCGATCGCGCTAGCTTCCTCCGGGGTAAAAGCATGGGTATCCAGAGCGGCGTG

CAGGTTGACGCCAACTGCGAGGGAGACTGCTATCACAGCGGGGGTACCATCATCTCCAAC

CTTCCCTTTCAGAACATAGACTCTCGGGCTGTCGGAAAATGTCCTCGATACGTGAAGCAG

AGATCACTGCTGCTTGCTACTGGAATGAAGAACGTCCCCGAGATACCGAAAGGGAGAGGT

CTCTTTGGTGCTATAGCAGGGTTTATTGAAAACGGGTGGGAAGGCTTGATCGACGGTTGG

TATGGCTTCAGACATCAGAATGCTCAGGGCGAGGGCACAGCAGCAGATTATAAGTCGACA

CAGAGTGCAATCGATCAGATTACTGGCAAACTGAATAGGCTTATTGAGAAGACCAATCAG

CAATTTGAGCTTATCGACAACGAGTTTAACGAAGTTGAAAAGCAAATTGGGAACGTCATC

AACTGGACCCGGGACTCAATCACCGAAGTATGGAGCTATAATGCCGAGTTGCTGGTTGCA

ATGGAGAACCAGCACACTATCGATCTTGCGGATTCCGAAATGGATAAACTTTACGAAAGA

GTGAAGAGACAGCTCAGAGAAAACGCCGAGGAGGACGGTACGGGTTGTTTTGAGATATTC

CACAAGTGCGATGATGATTGCATGGCTAGCATCAGGAACAACACCTATGATCACAGCAAA

TACCGTGAGGAGGCAATGCAGAACAGGATTCAGATTGACCCTGTGAAACTGTCTAGCGGC

TACAAGGACGTGATCTTGTGGTTTTCTTTCGGTGCCAGTTGTTTTATCTTACTCGCCATT

GTCATGGGGCTCGTTTTCATTTGTGTAAAAAATGGAAACATGAGGTGTACGATTTGTATA

637
ATGAACACACAAATTCTCGTGTTTGCCCTAATCGCCATTATCCCGACAAACGCAGATAAG

ATCTGTCTGGGGCACCACGCAGTCAGCAATGGCACCAAAGTGAATACTCTTACCGAGAGA

GGAGTGGAAGTCGTGAATGCCACGGAGACCGTCGAGAGGACTAATATCCCAAGGATTTGT

AGCAAAGGTAAGAAAACGGTTGACCTGGGCCAATGCGGCCTGCTGGGCACAATCACAGGT

CCGCCCCAGTGCGATCAGTTCCTGGAGTTCTCAGCGGATCTGATAATTGAGCGGCGAGAG

GGGTCAGATGTATGTTACCCAGGTAAATTCGTCAACGAGGAGGCACTGCGGCAGATCCTG

CGAGAAAGTGGAGGGATAGAAAAGGAAGCAATGGGTTTTACCTACTCCGGAATCCGAGCC

AATGGGGCCACTTCCGCGTGTAGGAGAAGCGGAAGTTCTTTCTACGCTGAAATGAAGTGG

CTCCTGAGTAACACAGATAACGCGGCTTTCCCTCAAATGACCAAGTCATACAAGAATACG

CGCAAGTCACCAGCCCTCATTGTGTGGGGAATCCATCATTCCGTCTCGACTGCGGAACAG

ACAAAACTCTACGGATCCGGAAACAAACTGGTGACCGTAGGTTCCAGTAATTACCAGCAA

AGTTTTGTGCCCTCACCCGGAGCCAGGCCTCAGGTCAATGGGTTAAGTGGGCGCATTGAC

TTCCACTGGTTGATGCTGAATCCCAACGACACAGTGACTTTCTCTTTCAACGGGGCTTTC

ATAGCTCCCGATCGGGCCTCTTTCCTGCGGGGTAAGTCTATGGGTATTCAAAGCGGCGTC

CAGGTGGATGCTAATTGTGAAGGGGACTGTTACCACTCGGGAGGCACAATCATTAGTAAC

CTGCCTTTCCAGAATATTGACTCGAGGGCAGTAGGCAAGTGTCCCCGCTATGTGAAGCAA

AGGTCACTCCTTTTGGCAACCGGGATGAAGAATGTGCCCGAGATACCAAAGGGTAGAGGG

CTATTTGGCGCAATTGCAGGATTTATCGAGAATGGTTGGGAGGGCCTGATTGACGGCTGG

TACGGGTTTCGGCATCAGAATGCCCAGGGGGAAGGGACTGCCGCAGACTACAAAAGCACA

CAGTCGGCTATTGATCAGATAACGGGAAAACTGAACAGGTTGATTGAGAAGACCAACCAA

CAATTCGAACTTATAGACAACGAGTTCAACGAGGTCGAGAAGCAAATCGGCAACGTGATC

AATTGGACCCGGGACTCGATCACCGAGGTGTGGTCATATAACGCTGAGCTGTTAGTAGCT

ATGGAGAATCAGCACACGATCGACCTTGCAGATAGCGAGATGGATAAACTGTATGAACGG

GTCAAGCGGCAGCTGAGAGAAAATGCCGAAGAGGACGGTACGGGCTGCTTTGAAATTTTT

CATAAGTGCGACGATGACTGCATGGCCAGTATTAGAAACAACACCTACGACCATTCCAAA

TATCGGGAAGAAGCGATGCAGAACAGAATTCAGATAGATCCAGTTAAGCTGTCCTCTGGA

TATAAGGATGTGATACTGTGGTTTTCTTTTGGCGCCAGTTGCTTTATATTGCTCGCAATT

GTGATGGGGCTGGTGTTCATTTGCGTCAAAAACGGGAACATGAGGTGCACCATTTGCATT

638
ATGAATACACAGATTCTGGTATTTGCTCTGATCGCGATTATTCCGACGAATGCAGATAAG

ATCTGTTTAGGCCACCACGCTGTTAGCAATGGGACGAAAGTGAATACTCTAACAGAACGT

GGGGTGGAAGTCGTCAATGCTACGGAGACTGTCGAGCGCACCAATATTCCAAGGATCTGT

TCCAAGGGTAAGAAGACTGTGGACCTCGGGCAATGCGGTCTCCTAGGCACCATTACCGGT

CCTCCTCAGTGCGATCAGTTTCTGGAATTCTCTGCAGATCTTATTATAGAGCGGCGCGAG

GGCAGTGATGTGTGCTACCCAGGTAAGTTCGTCAATGAAGAGGCTCTGCGTCAAATTTTG

AGAGAGTCAGGCGGCATTGATAAGGAGGCCATGGGCTTTACCTACAGCGGAATCCGCACC

AACGGAGCAACCAGCGCCTGTCGGAGAAGCGGTAGCAGTTTCTACGCCGAAATGAAATGG

CTACTTTCTAATACCGATAATGCTGCGTTTCCACAGATGACAAAGAGTTACAAGAACACC

CGTAAGAGTCCTGCCCTCATCGTGTGGGGGATCCATCACAGTGTGTCAACCGCAGAGCAA

ACCAAATTGTATGGTTCCGGAAACAAACTGGTTACCGTGGGCTCTAGCAATTACCAGCAG

AGTTTCGTTCCGTCCCCCGGCGCTAGACCCCAAGTCAATGGTCAGAGCGGAAGAATCGAT

TTCCACTGGCTGATGCTGAATCCCAATGACACTGTGACTTTCTCCTTTAATGGGGCCTTC

ATTGCTCCCGACCGCGCTTCATTCTTGCGCGGCAAATCCATGGGAATACAGAGCGGTGTG

CAGGTGGATGCCAATTGCGAAGGTGATTGTTATCACAGTGGAGGAACTATTATCTCTAAT

CTGCCGTTTCAGAACATTGACAGCAGAGCCGTTGGCAAGTGTCCACGATACGTCAAACAG

CGGTCCCTCCTGTTGGCCACAGGCATGAAGAACGTGCCTGAGATCCCTAAGGGGCGCGGA

CTGTTTGGAGCCATCGCGGGATTTATTGAGAACGGATGGGAAGGCTTGATAGATGGCTGG

TATGGCTTTAGGCACCAGAATGCACAGGGGGAGGGCACCGCCGCTGATTACAAGAGCACG

CAGTCTGCGATCGACCAAATAACCGGTAAGTTAAATCGCCTGATCGAGAAAACCAATCAG

CAGTTCGAGCTGATCGACAACGAGTTTAATGAAGTCGAAAAACAGATCGGCAACGTGATC

AATTGGACCAGGGACAGTATCACAGAGGTATGGAGCTACAATGCCGAGCTGCTGGTGGCC

ATGGAGAATCAGCATACAATTGACCTAGCTGATAGTGAGATGGACAAACTGTATGAGAGG

GTCAAGAGACAATTGCGGGAAAACGCGGAGGAAGATGGGACAGGCTGCTTCGAGATCTTC

CATAAGTGCGACGACGACTGTATGGCCAGTATCAGAAATAACACGTACGACCACTCGAAG

TATAGGGAGGAGGCAATGCAGAACAGAATTCAGATCGACCCTGTGAAGCTTAGTAGTGGA

TACAAGGACGTGATTCTCTGGTTCTCTTTCGGGGCCTCATGTTTCATTTTGCTCGCTATA

GTTATGGGCCTAGTGTTCATCTGCGTGAAGAATGGGAATATGCGGTGCACGATTTGCATC

639
ATGAATACTCAGATCTTAGTGTTCGCATTGATCGCCATCATCCCAACCAACGCCGATAAA

ATTTGCCTTGGACATCATGCTGTGAGCAACGGCACAAAGGTCAATACACTTACAGAAAGA

GGGGTGGAAGTGGTGAACGCCACAGAAACCGTGGAACGGACGAACATTCCCCGAATTTGT

TCTAAGGGAAAGAGAACAGTAGACCTCGGACAGTGTGGCCTCCTGGGCACCATAACCGGC

CCTCCACAGTGTGACCAGTTTCTGGAATTCAGCGCGGATCTGATTATTGAGAGGCGGGAG

GGCTCCGATGTCTGCTACCCTGGCAAGTTTGTGAACGAGGAGGCCCTGAGGCAGATCCTA

CGGGAGTCCGGAGGGATCGATAAAGAGGCAATGGGTTTTACCTACAGCGGCATCCGGACC

AATGGAGCCACTTCTGCATGCCGGCGCTCCGGGAGTTCATTTTATGCTGAGATGAAATGG

TTACTTTCTAACACCGATAACGCAGCCTTCCCACAGATCACCAAGAGCTATAAAAATACG

CGAAAATCTCCAGCCCTCATAGTCTGGGGTATCCATCACTCTGTTAGCACAGCGGAGCAG

ACCAAGTTATACGGGTCAGGAAATAAACTTGTGACAGTGGGCTCCTCTAACTATCAGCAG

TCTTTTGTGCCCAGCCCTGGGGCCAGGCCCCAAGTCAATGGCCTTTCTGGTAGGATTGAT

TTCCACTGGTTGATGTTGAACCCCAATGATACCGTCACATTCAGCTTTAATGGTGCTTTT

ATCGCCCCTGACCGAGCTAGTTTCCTAAGAGGAAAATCTATGGGTATCCAGTCTGGCGTT

CAGGTGGACGCCAATTGTGAGGGCGACTGTTATCATTCCGGGGGAACCATCATCTCTAAC

CTTCCCTTCCAAAATATCGACTCCAGGGCAGTTGGCAAATGTCCACGGTATGTGAAGCAG

AGATCACTCCTGTTAGCGACTGGGATGAAAAACGTGCCAGAAATCCCTAAAGGTCGTGGA

TTGTTCGGAGCGATCGCGGGATTTATCGAAAACGGGTGGGAGGGTCTTATAGACGGCTGG

TATGGGTTTAGACACCAGAACGCACAGGGTGAGGGCACCGCGGCAGACTACAAATCTACA

CAATCTGCAATAGATCAGATCACCGGCAAGCTGAACCGACTTATTGAAAAGACCAATCAG

CAGTTTGAGTTAATCGATAACGAATTCAACGAGGTGGAGAAGCAAATAGGGAATGTTATT

AACTGGACACGGGACTCAATCACAGAAGTATGGTCGTATAATGCAGAGCTGCTAGTCGCA

ATGGAGAATCAGCATACGATTGACCTCGCCGACAGTGAGATGGACAAGTTGTATGAAAGG

GTCAAAAGACAGCTCCGGGAAAATGCCGAGGAAGACGGCACAGGCTGTTTTGAAATATTC

CATAAGTGCGACGATGACTGCATGGCAAGTATTAGGAACAACACGTATGACCATTCAAAG

TACAGGGAGGAGGCCATGCAGAACCGCATCCAGATTGATCCAGTTAAGCTTAGCAGTGGC

TATAAGGATGTCATCCTGTGGTTTAGTTTTGGCGCCTCCTGTTTTATCCTGCTGGCCATC

GTTATGGGGCTTGTGTTCATATGCGTGAAGAATGGCAATATGCGCTGCACCATTTGTATT

640
ATGAATACACAAATTCTGGTATTCGCCCTCATAGCTATAATTCCCACCAACGCCGATAAG

ATTTGTTTAGGTCACCACGCCGTGTCAAACGGGACAAAGGTTAATACACTTACAGAGCGG

GGCGTGGAAGTCGTGAACGCTACTGAGACAGTCGAAAGGACTAACATCCCCAGAATTTGT

AGCAAAGGAAAAAAGACCGTGGATTTGGGGCAGTGTGGCTTACTAGGGACAATCACCGGT

CCACCCCAGTGTGACCAGTTCCTCGAGTTCTCAGCGGACCTAATTATCGAGCGTCGAGAG

GGCAGCGATGTGTGCTATCCCGGGAAATTCGTGAATGAGGAGGCCTTACGGCAGATCTTG

CGTGAAAGTGGGGGCATAGATAAAGAGGCGATGGGGTTCACGTATTCTGGCATTCGCACC

AACGGAGCTACCTCAGCCTGTCGTCGTTCAGGATCCAGCTTCTACGCAGAAATGAAGTGG

TTACTCTCTAACACAGATAACGCAGCCTTCCCGCAAATGACGAAGAGCTACAAAAACACT

CGCAAATCCCCCGCCCTCATCGTCTGGGGTATTCACCACAGCGTTAGCACCGCTGAACAG

ACTAAATTATACGGCAGCGGAAATAAGCTTGTCACCGTCGGGAGCTCCAACTATCAGCAG

AGCTTTGTCCCATCTCCTGGGGCCCGGCCCCAGGTGAACGGACAGTCCGGGCGCATTGAT

TTCCACTGGTTGATGCTGAACCCAAACGACACTGTTACGTTCAGCTTTAACGGCGCCTTC

ATTGCACCTGACCGAGCTAGCTTTTTGCGGGGCAAATCGATGGGAATACAGTCAGGGGTC

CAGGTAGACGCCAACTGCGAAGGCGATTGCTACCATTCCGGCGGGACAATCATCTCCAAC

CTGCCCTTCCAGAACATTGACAGCCGGGCAGTCGGGAAGTGTCCCAGATATGTGAAACAA

CGCTCTCTGCTGCTTGCGACCGGCATGAAAAACGTTCCAGAAATCCCGAAGGGGCGAGGT

TTGTTTGGCGCTATAGCTGGGTTCATTGAGAACGGCTGGGAAGGCCTCATCGACGGCTGG

TATGGATTTAGGCATCAAAATGCACAGGGCGAAGGTACCGCTGCCGACTATAAGTCAACT

CAGAGCGCAATAGACCAAATTACCGGAAAGCTCAATCGCCTGATTGAGAAAACCAATCAG

CAGTTTGAACTGATAGACAACGAATTTAATGAAGTGGAGAAGCAGATCGGGAATGTGATC

AACTGGACTCGTGACAGTATTACTGAGGTATGGAGTTATAACGCTGAACTTCTGGTGGCT

ATGGAGAACCAACACACTATTGATCTCGCCGACTCCGAGATGGATAAACTCTACGAAAGA

GTTAAAAGACAGCTTAGGGAAAACGCCGAGGAGGATGGTACTGGATGTTTCGAGATCTTT

CATAAATGCGATGACGACTGCATGGCTAGCATCCGGAATAACACCTACGATCATTCTAAG

TATCGTGAAGAAGCCATGCAAAATCGTATTCAGATTGATCCGGTAAAATTGAGCTCAGGC

TATAAGGACGTCATACTGTGGTTCTCCTTCGGCGCTTCCTGCTTTATCTTATTAGCAATT

GTGATGGGATTAGTTTTCATCTGCGTGAAAAACGGAAACATGCGCTGTACCATTTGCATA

641
ATGAACACTCAAATTTTAGTGTTCGCCTTGATAGCAATCATCCCCACAAATGCGGATAAA

ATCTGTCTCGGCCATCATGCCGTGTCTAATGGTACCAAAGTAAATACCCTTACCGAGCGT

GGGGTTGAGGTCGTTAATGCCACCGAGACTGTGGAGAGAACCAATATCCCCCGCATCTGT

TCCAAGGGAAAAAAGACCGTTGACCTCGGTCAGTGTGGTCTGCTTGGTACAATAACCGGA

CCGCCCCAGTGCGACCAATTCCTGGAATTCAGTGCGGATCTCATAATCGAAAGGCGAGAA

GGCTCCGATGTTTGTTACCCCGGAAAGTTCGTCAACGAGGAGGCCCTGCGACAGATATTG

CGGGAAAGCGGAGGCATCGATAAGGAGGCTATGGGCTTCACATATAGTGGAATCCGCACG

AATGGGGCCACCTCAGCCTGTCGGCGCAGCGGGTCTAGTTTTTATGCTGAAATGAAGTGG

CTTCTTTCGAATACTGACAATGCTGCCTTCCCCCAGATGACCAAGAGTTATAAAAATACC

AGAAAGAGCCCTGCCCTGATAGTCTGGGGAATCCATCACAGCGTAAGCACTGCCGAACAG

ACTAAGCTCTATGGCAGCGGGAATAAGCTCGTGACCGTGGGCAGTTCCAATTACCAGCAG

AGCTTTGTGCCATCCCCGGGGGCCCGTCCACAGGTTAACGGGCAATCTGGCCGAATTGAT

TTTCATTGGCTGATGCTGAATCCAAACGATACTGTGACTTTCTCTTTTAACGGAGCCTTC

ATTGCACCCGATCGGGCAAGCTTCCTGCGGGGAAAATCTATGGGAATTCAGAGTGGGGTG

CAGGTGGACGCAAACTGTGAAGGCGATTGCTACCACTCTGGCGGGACAATCATTAGCAAT

CTGCCTTTCCAGAACATAGACAGCCGCGCAGTTGGAAAATGCCCGCGTTATGTCAAGCAA

AGGAGTTTACTGCTCGCTACAGGCATGAAGAATGTTCCGGAGATCCCGAAGGGAAGAGGT

TTGTTCGGCGCCATAGCAGGATTCATTGAAAATGGCTGGGAAGGGTTAATCGACGGGTGG

TATGGTTTTCGACACCAGAACGCACAAGGGGAGGGGACAGCAGCAGATTACAAGAGCACA

CAGTCAGCAATTGACCAGATTACTGGAAAGCTAAACCGGCTCATCGAGAAGACCAACCAG

CAGTTCGAATTGATTGACAACGAATTTAATGAGGTGGAAAAACAGATCGGTAACGTCATA

AACTGGACTAGAGATTCCATTACTGAGGTCTGGTCATATAATGCCGAACTGCTCGTGGCG

ATGGAGAATCAGCATACCATAGATCTCGCCGACTCCGAGATGGACAAACTTTATGAACGG

GTGAAGCGCCAGCTGCGGGAAAATGCCGAAGAGGACGGTACAGGGTGTTTCGAGATTTTC

CATAAATGTGATGACGACTGCATGGCAAGCATACGCAATAACACATATGATCACTCTAAG

TATAGGGAAGAGGCCATGCAGAACCGAATTCAAATCGACCCAGTAAAGCTTTCTAGCGGC

TATAAAGATGTGATTCTGTGGTTTAGCTTCGGGGCCTCTTGTTTTATCCTGTTAGCCATC

GTCATGGGGCTAGTTTTCATCTGCGTGAAAAATGGCAACATGCGTTGCACTATATGCATC

642
ATGAATACGCAGATCCTCGTGTTCGCACTGATAGCGATCATCCCGACAAATGCTGACAAA

ATCTGTTTGGGCCATCATGCCGTTAGCAATGGTACCAAAGTGAACACTCTCACTGAGCGC

GGCGTGGAAGTGGTGAACGCCACTGAAACAGTAGAAAGAACAAACATTCCCAGAATCTGC

AGTAAGGGTAAGAAAACTGTCGACTTGGGCCAGTGTGGCCTATTAGGAACAATCACCGGA

CCTCCCCAATGCGATCAGTTCCTAGAATTTAGCGCTGATCTGATAATTGAAAGAAGAGAA

GGTTCGGATGTCTGTTACCCGGGTAAATTCGTGAACGAAGAAGCCTTAAGACAGATTCTC

AGAGAAAGTGGCGGAATTGATAAAGAAGCCATGGGGTTCACTTATTCTGGCATACGGACA

AATGGGGCCACTAGCGCATGTAGACGATCAGGCAGCTCTTTCTACGCCGAGATGAAGTGG

CTGTTATCCAACACAGACAATGCAGCCTTTCCTCAGATGACCAAATCCTACAAAAATACA

AGGAAGAGCCCCGCACTAATCGTATGGGGCATCCATCACTCTGTGTCGACGGCAGAACAA

ACCAAGCTCTATGGTAGTGGGAACAAGTTGGTGACGGTGGGGTCCTCTAATTACCAGCAG

TCGTTCGTGCCCTCTCCAGGTGCCCGGCCCCAGGTGAATGGTCAGTCCGGCCGAATCGAC

TTTCACTGGCTTATGCTGAATCCCAATGATACCGTAACATTTAGCTTTAATGGAGCTTTC

ATTGCTCCTGACCGTGCCAGCTTCTTGAGAGGAAAATCTATGGGCATACAGTCTGGTGTC

CAGGTGGATGCTAACTGCGAAGGTGACTGTTACCACTCAGGAGGTACTATAATTAGCAAT

CTCCCCTTCCAGAACATCGACAGCCGCGCTGTAGGAAAGTGCCCTCGCTACGTGAAGCAA

CGATCATTACTGCTGGCCACTGGCATGAAGAACGTACCCGAGATCCCAAAGGGAAGGGGT

TTGTTTGGCGCCATTGCGGGCTTTATTGAGAACGGATGGGAGGGTCTGATCGATGGATGG

TATGGATTCCGTCATCAGAATGCCCAGGGCGAGGGGACCGCTGCTGATTACAAATCCACA

CAATCTGCAATAGATCAAATCACAGGAAAACTGAACCGGCTTATTGAAAAAACCAATCAG

CAGTTCGAGTTGATCGACAATGAGTTCAATGAAGTGGAAAAGCAGATCGGCAACGTCATC

AACTGGACTCGGGACTCTATCACAGAGGTCTGGTCCTACAATGCAGAGTTACTAGTTGCC

ATGGAGAACCAGCACACGATTGATTTGGCCGATAGCGAGATGGATAAACTCTACGAGCGT

GTGAAGAGGCAGCTGCGCGAAAATGCCGAAGAGGATGGAACAGGTTGCTTCGAGATCTTC

CACAAATGCGATGACGACTGCATGGCCTCCATCAGGAATAATACTTATGATCACAGCAAG

TACCGGGAGGAAGCCATGCAAAACAGAATTCAGATTGATCCCGTAAAGTTAAGCTCCGGC

TACAAAGATGTGATTCTGTGGTTCTCTTTCGGAGCTTCATGCTTCATCCTCCTCGCTATA

GTGATGGGTCTCGTATTCATTTGCGTTAAGAACGGCAATATGAGATGCACAATCTGTATT

643
ATGAATACTCAAATCCTGGTGTTCGCACTCATTGCCATCATACCAACCAACGCAGACAAG

ATATGCTTGGGCCATCACGCCGTGTCTAATGGTACGAAAGTGAATACTCTGACTGAGCGC

GGGGTCGAAGTAGTAAACGCGACTGAAACAGTGGAACGAACTAATATTCCCAGAATTTGC

AGTAAAGGGAAAAAGACCGTCGATCTCGGCCAATGCGGACTGCTGGGGACAATCACAGGG

CCACCGCAATGCGATCAGTTCCTGGAGTTTAGCGCGGATCTCATCATCGAGCGAAGAGAA

GGGTCCGACGTCTGTTACCCGGGTAAATTTGTGAATGAAGAGGCCCTGCGTCAGATTCTG

CGGGAAAGCGGCGGAATTGACAAGGAGGCAATGGGGTTCACGTACAGTGGTATCAGAACC

AACGGAGCTACAAGCGCATGCAGACGGTCCGGGTCCTCGTTTTACGCGGAGATGAAGTGG

CTGTTATCCAACACTGACAACGCTGCTTTCCCACAGATGACCAAAAGCTATAAGAACACA

AGAAAAAGTCCAGCCCTGATTGTGTGGGGGATCCACCATTCGGTATCAACTGCTGAGCAA

ACAAAGTTATATGGAAGTGGAAACAAGCTTGTCACCGTAGGTTCATCCAACTATCAACAG

AGTTTCGTGCCCTCCCCCGGAGCCCGCCCCCAGGTGAATGGACAGTCGGGAAGAATAGAC

TTTCATTGGTTGATGCTGAATCCCAATGACACCGTGACCTTCAGCTTTAATGGGGCCTTC

ATTGCCCCGGACAGGGCTAGCTTTCTCCGAGGAAAGAGCATGGGCATTCAATCTGGAGTT

CAAGTGGATGCCAACTGTGAGGGCGATTGCTACCATAGCGGAGGGACAATCATCAGCAAC

CTCCCCTTCCAAAACATTGATAGTCGTGCTGTAGGAAAATGCCCTCGGTACGTTAAACAA

AGATCGCTGCTACTGGCTACAGGAATGAAGAACGTGCCCGAGATCCCAAAAGGACGAGGC

CTATTTGGGGCCATCGCGGGTTTTATCGAAAATGGATGGGAGGGCCTCATCGACGGGTGG

TATGGCTTTCGTCATCAGAATGCTCAAGGCGAAGGAACAGCCGCTGATTACAAATCAACC

CAATCTGCCATCGACCAGATCACCGGAAAGCTCAACCGCCTGATTGAAAAGACTAATCAG

CAGTTCGAGCTGATCGACAATGAGTTCAATGAAGTGGAAAAGCAGATTGGTAACGTGATT

AACTGGACTAGAGATTCCATTACCGAAGTGTGGTCTTATAACGCCGAGCTACTGGTCGCC

ATGGAGAACCAGCATACCATTGATTTAGCTGATTCTGAGATGGACAAGCTGTACGAAAGG

GTGAAACGGCAGCTCCGAGAAAATGCCGAAGAAGACGGAACCGGGTGTTTCGAGATCTTC

CACAAGTGCGACGACGATTGCATGGCTAGCATTAGAAACAACACTTATGACCACAGCAAG

TATCGCGAAGAGGCGATGCAGAATCGAATCCAGATCGATCCTGTCAAGCTGAGCAGGGGG

TACAAGGACGTGATCTTATGGTTTTCCTTCGGGGCTAGCTGTTTTATCCTGCTGGCTATC

GTGATGGGTCTGGTTTTTATATGTGTTAAAAACGGCAACATGCGGTGCACAATCTGCATT

644
ATGAATACCCAGATTTTAGTGTTTGCACTTATCGCTATCATACCAACTAATGCTGACAAG

ATCTGCCTGGGCCACCATGCAGTGAGCAACGGGACCAAAGTGAACACCCTAACCGAGCGG

GGCGTGGAGGTGGTAAATGCCACTGAAACCGTCGAAAGGACGAACATTCCGCGGATTTGC

AGTAAAGGCAAACGAACCGTGGACCTGGGCCAGTGTGGCCTCCTGGGGACCATCACGGGA

CCACCCCAATGTGACCAGTTCCTGGAGTTCTCCGCTGACCTTATCATCGAAAGGCGAGAA

GGGTCTGATGTCTGTTACCCTGGAAAATTCGTAAACGAGGAGGCTCTCCGACAAATTCTG

CGGGAATCCGGCGGCATCGACAAGGAGGCGATGGGTTTTACCTATTCCGGGATACGCACT

AACGGAGCTACATCAGCATGTAGGCGCTCTGGGTCTAGTTTCTATGCCGAAATGAAATGG

TTGCTGTCAAACACTGACAACGCTGCTTTCCCTCAGATGACTAAGTCCTATAAGAATACC

CGGAAGTCCCCAGCACTAATAGTCTGGGGGATTCACCACTCCGTATCTACTGCGGAGCAG

ACGAAACTTTACGGGAGCGGGAACAAACTGGTCACTGTTGGGTCATCAAATTATCAGCAA

TCATTCGTACCCTCTCCCGGCGCTCGGCCCCAGGTCAATGGCCTGTCCGGCAGAATTGAC

TTCCACTGGCTTATGCTAAATCCTAACGACACCGTGACCTTCTCCTTCAACGGCGCCTTC

ATCGCGCCTGACCGAGCTAGCTTTCTGCGTGGGAAAAGTATGGGAATTCAGAGCGGTGTG

CAGGTGGATGCAAATTGTGAAGGCGACTGCTATCATAGCGGGGGTACCATTATCTCTAAT

CTGCCTTTCCAGAACATCGACAGTAGAGCCGTGGGCAAATGCCCCAGATATGTGAAACAA

CGTAGCCTTCTGCTGGCAACAGGAATGAAAAATGTGCCCGAGATTCCCAAAGGGCGTGGG

CTGTTTGGGGCCATCGCCGGCTTCATCGAAAACGGTTGGGAGGGATTAATCGACGGGTGG

TATGGCTTCAGGCACCAAAACGCTCAAGGGGAGGGCACGGCGGCGGATTACAAATCTACC

CAGTCCGCCATTGATCAAATTACTGGCAAATTAAACAGAATCATCGAAAAGACTAACCAG

CAGTTCGAACTGATTGATAATGAGTTCAACGAGGTTGAGAAGCAAATCGGTAACGTTATC

AACTGGACGCGTGACAGTATCACCGAGGTCTGGTCATATAATGCTGAGCTGCTCGTGGCT

ATGGAAAACCAGCACACTATCGATCTGGCGGACTCCGAGATGGACAAGTTGTATGAACGG

GTGAAAAGACAGCTTCGGGAGAACGCCGAGGAGGACGGGACCGGATGCTTCGAGATCTTT

CACAAGTGCGATGATGATTGCATGGCTTCAATTCGCAATAATACATATGACCATTCTAAG

TACAGGGAGGAGGCTATGCAGAACCGGATCCAGATAGATCCCGTCAAACTTAGTAGCGGG

TACAAGGATGTCATCCTGTGGTTTTCCTTCGGGGCCTCATGCTTTATTCTTCTGGCCATC

GTGATGGGACTCGTGTTCATCTGCGTTAAGAATGGCAACATGCGATGTACAATCTGCATC

645
ATGAACACCCAGATTCTCGTGTTCGCTTTGATCGCGATTATACCTACTAACGCAGATAAA

ATATGTCTGGGTCATCACGCTGTCAGTAACGGGACAAAGGTGAACACGTTGACCGAGAGG

GGCGTCGAGGTGGTTAACGCCACTGAAACAGTGGAACGGACCAATATACCAAGGATCTGT

AGCAAGGGTAAGAAGACTGTCGACCTCGGTCAGTGTGGGTTGCTTGGGACCATCACCGGG

CCTCCACAGTGTGATCAGTTTCTGGAGTTCTCGGCTGACCTGATAATCGAGAGACGGGAG

GGCAGTGACGTGTGCTACCCAGGGAAGTTTGTGAACGAAGAAGCATTGCGACAGATTCTT

CGGGAATCAGGTGGAATCGACAAGGAGGCCATGGGATTTACATACTCTGGGATCAGGACC

AACGGTGCTACCTCCGCTTGTAGGAGAAGTGGATCAAGCTTTTATGCTGAAATGAAATGG

CTTCTGTCCAATACGGACAACGCAGCTTTCCCTCAGATGACAAAGTCCTACAAAAACACA

AGAAAGTCACCCGCTCTGATTGTTTGGGGAATCCACCACTCAGTGTCCACGGCGGAGCAG

ACGAAACTCTATGGCTCTGGGAATAAGCTGGTGACAGTCGGGAGCTCAAATTATCAGCAA

TCCTTCGTTCCATCCCCCGGCGCCCGACCTCAGGTCAACGGCCAATCGGGCAGGATTGAC

TTCCATTGGCTAATGCTCAATCCCAATGACACCGTCACATTCTCTTTTAATGGTGCCTTC

ATCGCCCCAGATCGAGCCTCTTTTCTCAGAGGTAAGTCGATGGGAATACAGTCAGGGGTT

CAGGTGGACGCTAATTGCGAAGGGGACTGCTATCATTCTGGGGGCACAATTATTTCAAAT

CTGCCATTCCAGAACATTGACTCTCGAGCCGTCGGAAAATGCCCTCGATATGTAAAGCAG

CGAAGTCTGCTGCTGGCAACCGGCATGAAAAACGTACCCGAGATCCCAAAGGGCAGAGGG

CTTTTCGGTGCGATCGCCGGGTTTATCGAAAATGGCTGGGAGGGCCTGATCGATGGGTGG

TACGGTTTTCGGCACCAGAACGCTCAGGGTGAGGGCACTGCAGCGGATTATAAGAGTACC

CAGTCAGCCATTGACCAGATCACAGGTAAGTTGAACCGCCTCATTGAAAAGACCAACCAG

CAGTTTGAGCTGATCGATAATGAGTTTAATGAGGTGGAGAAGCAGATCGGGAATGTTATT

AATTGGACGCGCGATTCAATCACAGAGGTATGGTCATACAACGCTGAGCTGCTGGTGGCA

ATGGAGAATCAACACACGATCGACCTCGCTGACTCAGAAATGGATAAACTGTACGAAAGG

GTCAAAAGGCAGCTGCGCGAGAACGCCGAAGAAGACGGAACTGGTTGTTTCGAAATTTTC

CACAAGTGTGACGACGACTGTATGGCATCCATCAGAAACAACACATACGACCATAGCAAA

TACCGGGAGGAGGCAATGCAGAATCGAATCCAGATTGATCCCGTGAAGTTGTCTAGCGGA

TACAAAGATGTGATCTTATGGTTTTCATTCGGGGCTAGCTGTTTCATCCTCCTGGCCATA

GTTATGGGGCTCGTTTTCATCTGCGTAAAGAATGGGAATATGAGATGTACTATCTGCATT

646
ATGAATACGCAGATTCTGGTGTTCGCTCTCATCGCTATTATTCCTACCAATGCCGATAAG

ATCTGTCTGGGGCACCACGCCGTCAGCAACGGCACTAAAGTGAACACCTTGACAGAAAGG

GGGGTGGAAGTGGTGAACGCAACGGAAACAGTGGAGAGGACAAACATACCGCGGATTTGC

TCGAAAGGAAAACGGACTGTAGACCTGGGCCAATGCGGCCTGCTCGGAACCATCACCGGG

CCACCCCAATGTGACCAGTTCCTAGAATTTTCCGCCGACCTTATAATTGAGCGGAGGGAG

GGATCCGATGTGTGTTATCCTGGCAAGTTCGTGAACGAGGAGGCCCTGCGGCAGATATTG

CGTGAATCTGGGGGCATCGACAAGGAGGCGATGGGATTCACATACTCCGGCATCCGCACC

AACGGCGCGACCAGCGCATGCCGTCGCTCCGGGTCCTCATTCTACGCTGAAATGAAATGG

CTCCTCTCAAATACTGATAATGCTGCTTTTCCTCAAATGACCAAAAGTTACAAAAACACC

AGGAAAAGCCCAGCTCTGATTGTCTGGGGCATTCACCATTCCGTATCTACGGCAGAACAG

ACTAAACTATATGGCAGTGGCAGCAAGCTCGTGACCGTCGGCTCCTCCAACTATCAGCAA

TCTTTCGTTCCATCACCAGGCGCCCGGCCCCAGGTCAATGGGCTCTCCGGCCGTATCGAT

TTCCACTGGCTGATGCTCAATCCTAACGACACCGTTACCTTTTCTTTTAACGGCGCCTTT

ATTGCTCCAGACAGAGCGTCTTTCCTGCGGGGTAAAAGCATGGGCATTCAGTCTGGTGTC

CAAGTGGACGCAAACTGTGAAGGGGATTGCTATCATAGTGGCGGCACTATCATTAGTAAC

CTGCCTTTCCAGAACATTGATTCGCGGGCAGTTGGCAAATGCCCCAGGTATGTCAAACAG

AGATCACTCTTGTTAGCTACCGGAATGAAGAACGTACCGGAGATTCCTAAGGGTAGGGGA

CTGTTCGGGGCTATTGCCGGGTTCATCGAGAATGGGTGGGAAGGTCTCATCGACGGGTGG

TATGGCTTTCGTCATCAGAACGCCCAGGGCGAAGGTACAGCAGCCGATTATAAGTCTACC

CAGTCCGCTATCGACCAAATAACCGGGAAGTTGAACCGGTTAATCGAGAAAACCAACCAA

CAGTTCGAATTGATCGACAATGAATTTAATGAGGTGGAAAAACAAATAGGGAACGTGATA

AACTGGACAAGGGACTCCATTACAGAAGTCTGGAGCTATAACGCCGAACTGCTGGTAGCT

ATGGAGAATCAGCATACCATTGACCTGGCAGACAGTGAGATGGACAAACTTTACGAACGG

GTTAAAAGACAGTTGCGAGAGAATGCCGAAGAAGATGGAACTGGCTGCTTTGAGATTTTT

CACAAATGCGATGATGACTGTATGGCCAGCATTAGAAACAACACATACGACCACAGTAAG

TACAGGGAAGAAGCCATGCAAAACCGGATCCAGATTGACCCCGTCAAGCTGAGCTCGGGT

TATAAGGATGTAATCTTATGGTTCAGTTTTGGCGCCTCCTGCTTCATTCTTCTAGCAATC

GTGATGGGATTGGTCTTCATTTGCGTGAAAAATGGCAATATGAGGTGCACCATCTGCATT

647
ATGAATACACAGATCCTAGTCTTCGCCTTAATTGCAATAATACCTACCAACGCAGACAAA

ATTTGTCTTGGGCACCACGCCGTGTCCAACGGGACCAAAGTTAATACCCTCACCGAACGT

GGGGTGGAGGTGGTAAACGCTACGGAGACAGTAGAAAGGACCAACATACCTCGCATCTGT

TCCAAAGGGAAAAGAACCGTCGACCTGGGGCAGTGCGGGCTGCTAGGAACTATTACTGGC

CCACCACAGTGCGATCAGTTTCTGGAATTTAGTGCTGATCTGATCATCGAAAGGCGTGAG

GGTAGCGATGTCTGTTATCCCGGGAAGTTCGTGAATGAAGAGGCGCTGAGACAAATTCTG

AGAGAAAGCGGGGGGATCGATAAGGAAGCAATGGGGTTTACTTATTCTGGCATTAGAACC

AATGGGGCCACATCCGCCTGCCGCAGGTCTGGAAGCTCCTTTTATGCTGAAATGAAATGG

CTGCTGAGTAATACTGACAACGCCGCTTTTCCTCAGATGACAAAATCTTATAAAAACACG

AGAAAATCTCCTGCCCTGATTGTGTGGGGCATTCACCATTCGGTTTCAACAGCGGAGCAA

ACTAAACTATATGGAAGCGGCAGCAAGCTGGTCACAGTGGGAAGCTCTAACTACCAACAG

TCTTTTGTTCCCAGTCCCGGCGCCCGACCTCAGGTCAACGGACTGAGTGGCAGAATTGAT

TTCCACTGGCTGATGCTTAATCCGAACGATACCGTCACCTTTTCTTTCAATGGTGCTTTT

ATTGCCCCTGACAGGGCAAGCTTCTTGCGCGGGAAGTCTATGGGAATCCAATCCGGCGTA

CAAGTGGACGCAAACTGTGAAGGGGACTGTTATCACTCCGGAGGCACAATTATTAGTAAC

TTGCCTTTCCAGAATATCGATTCCAGAGCCGTGGGTAAATGCCCTCGATACGTAAAACAG

CGCTCTCTGCTTCTGGCTACCGGAATGAAGAATGTGCCTGAGATCCCTAAGGGCAGAGGC

CTGTTCGGGGCCATCGCTGGTTTTATTGAGAATGGGTGGGAAGGCTTAATAGACGGGTGG

TACGGTTTTCGTCACCAAAATGCACAGGGCGAAGGCACAGCAGCCGACTACAAAAGTACG

CAAAGCGCCATAGATCAGATAACAGGAAAACTTAATCGCCTGATCGAAAAAACGAACCAA

CAGTTCGAACTGATTGACAATGAATTTAACGAAGTCGAAAAGCAGATAGGCAATGTCATC

AATTGGACGAGAGACAGTATTACAGAAGTTTGGAGCTATAATGCAGAGCTGTTAGTGGCG

ATGGAAAATCAGCACACCATTGATTTGGCGGACAGCGAAATGGACAAGCTGTACGAACGA

GTGAAGCGACAGCTACGCGAGAATGCAGAAGAAGATGGGACTGGCTGCTTCGAAATCTTT

CACAAGTGCGACGACGATTGCATGGCCAGCATTCGCAATAACACATACGATCACTCCAAG

TATCGAGAGGAGGCGATGCAAAACCGAATCCAAATTGACCCTGTGAAATTATCTAGTGGG

TATAAAGACGTGATACTGTGGTTTTCATTCGGAGCTTCATGTTTCATTCTGTTGGCAATT

GTCATGGGACTGGTGTTTATATGTGTAAAAAGCAGAAATATGCGATGCACCATTTGCATC

648
ATGAATACCCAGATCCTGGTATTCGCATTAATTGCTATCATTCCTACAAATGCTGACAAA

ATCTGTCTCGGCCATCACGCCGTGAGTAATGGAACTAAAGTGAATACTCTCACTGAGCGC

GGGGTAGAGGTAGTGAATGCCACTGAGACCGTCGAGCGAACTAACATCCCCCGCATCTGT

AGCAAAGGCAAGAAGACGGTGGACTTAGGACAGTGTGGCCTCCTGGGGACCATCACAGGA

CCTCCTCAGTGCGACCAGTTTCTGGAATTTAGTGCTGACCTTATCATTGAACGGCGCGAG

GGCAGCGATGTCTGCTACCCTGGCAAGTTTGTCAATGAGGAAGCCTTACGACAGATCCTC

AGAGAATCAGGGGGGATTGACAAGGAGGCAATGGGGTTCACCTATAGCGGAATCCGGACT

AATGGCGCAACAAGTGCATGTAGACGGAGTGGGAGTAGTTTTTACGCCGAAATGAAGTGG

CTGTTAAGCAACACGGACAACGCTGCTTTTCCACAGATGACTAAGTCTTACAAAAACACC

AGGAAGTCACCTGCTCTGATCGTGTGGGGAATTCACCATAGCGTGAGCACAGCTGAGCAG

ACCAAGCTTTACGGAAGTGGCAACAAACTCGTGACAGTGGGCAGCTCCAACTACCAGCAG

TCTTTCGTGCCCTCCCCCGGCGCAAGACCTCAGGTCAACGGGCAGTCGGGGCGTATTGAC

TTCCACTGGCTCATGCTGAACCCCAATGATACTGTGACCTTTTCGTTCAATGGGGCGTTT

ATCGCCCCTGATCGGGCAAGCTTCCTGAGGGGTAAATCAATGGGAATACAGTCCGGCGTC

CAGGTGGATGCCAACTGTGAAGGCGACTGCTATCATTCCGGGGGTACCATTATCAGCAAC

CTTCCCTTTCAGAACATTGATTCTCGGGCTGTGGGAAAATGTCCCAGGTACGTCAAGCAG

CGGTCACTCCTGCTGGCAACTGGGATGAAGAACGTCCCTGAAATCCCGAAAGGGCGTGGG

CTGTTTGGTGCTATCGCTGGATTCATCGAAAACGGCTGGGAAGGGCTTATTGATGGTTGG

TACGGGTTTCGCCACCAGAACGCGCAGGGCGAGGGCACCGCTGCAGACTATAAATCTACT

CAGTCTGCAATTGACCAGATCACCGGCAAACTGAACCGCCTGATTGAGAAGACCAACCAA

CAGTTTGAGCTCATAGATAACGAATTTAACGAGGTGGAAAAGCAAATCGGAAACGTTATC

AACTGGACTAGGGACTCTATCACTGAAGTGTGGTCCTACAATGCAGAGCTGCTCGTTGCC

ATGGAAAACCAGCACACCATTGACCTAGCTGACTCCGAGATGGATAAACTGTATGAGCGG

GTAAAACGGCAGCTGAGAGAGAACGCCGAAGAGGACGGGACAGGATGTTTTGAGATATTT

CACAAATGCGACGACGACTGTATGGCAAGCATCCGGAACAACACCTACGATCATTCTAAA

TATCGGGAGGAAGCCATGCAGAATCGCATTCAGATTGATCCCGTCAAACTGAGTTCTGGC

TATAAGGACGTAATTCTGTGGTTCTCCTTCGGAGCTAGTTGCTTCATTCTGCTTGCAATA

GTAATGGGACTCGTTTTTATTTGTGTCAAGAACGGCAACATGAGGTGTACCATTTGCATA

649
ATGAATACACAGATTCTGGTCTTTGCTCTCATCGCTATAATCCCGACCAACGCTGACAAA

ATCTGTCTGGGTCACCACGCCGTATCTAATGGAACTAAGGTGAATACATTGACCGAGCGC

GGCGTTGAGGTCGTTAATGCTACAGAAACTGTTGAGCGGACAAATATCCCCCGGATATGC

TCAAAGGGAAAAAAGACTGTCGACTTAGGACAATGCGGGTTACTAGGCACAATAACAGGG

CCGCCCCAGTGCGACCAGTTTCTCGAGTTCAGTGCCGATCTGATTATCGAACGCCGGGAG

GGAAGCGACGTCTGTTATCCCGGCAAATTCGTGAATGAAGAGGCCCTCCGCCAGATCCTG

AGAGAATCCGGAGGCATCGACAAGGAGGCCATGGGATTCACTTACTCTGGAATCAGGACC

AACGGGGCTACCTCCGCGTGCCGACGGTCCGGGTCCTCTTTCTACGCAGAGATGAAGTGG

CTACTATCTAATACCGATAACGCAGCTTTCCCCCAAATGACAAAATCATATAAGAATACA

AGGAAATCTCCGGCATTGATCGTCTGGGGCATTCATCACTCTGTCAGTACCGCTGAACAA

ACAAAGCTGTATGGCAGCGGGAACAAGCTGGTTACAGTGGGGTCTAGTAACTATCAACAG

TCCTTCGTGCCATCTCCGGGAGCGCGGCCACAGGTGAATGGGCAGTCTGGCCGGATTGAC

TTTCACTGGTTAATGTTAAATCCAAACGACACGGTGACTTTTTCATTTAACGGTGCCTTT

ATTGCTCCTGACAGAGCCTCATTTCTCAGAGGCAAATCAATGGGTATCCAATCAGGCGTG

CAGGTGGACGCTAACTGCGAGGGCGATTGCTACCACTCTGGGGGCACAATCATATCCAAC

CTGCCCTTCCAGAATATTGACTCAAGAGCCGTCGGGAAATGTCCACGGTACGTGAAACAG

AGGAGTCTACTGCTAGCTACAGGAATGAAGAATGTGCCCGAGATTCCGAAAGGGAGAGGG

TTGTTTGGAGCCATCGCAGGATTCATTGAAAATGGATGGGAAGGTCTCATAGATGGTTGG

TATGGCTTTCGACACCAAAACGCGCAGGGCGAGGGGACTGCAGCTGACTACAAAAGTACG

CAATCTGCCATTGATCAGATTACAGGAAAGCTCAACCGACTGATCGAAAAAACAAATCAG

CAGTTTGAGCTCATAGACAATGAGTTCAATGAAGTGGAAAAGCAGATCGGCAACGTTATC

AACTGGACGCGCGACTCAATCACAGAAGTGTGGTCTTACAATGCAGAATTGCTTGTCGCC

ATGGAGAATCAGCACACTATCGACCTGGCCGACAGCGAAATGGATAAGCTCTACGAGAGG

GTCAAGCGCCAACTTCGAGAGAATGCTGAGGAGGACGGAACCGGTTGCTTTGAGATATTT

CACAAGTGTGATGACGATTGCATGGCATCAATCAGAAATAATACTTACGACCATTCGAAA

TACAGGGAAGAGGCAATGCAGAACAGAATTCAGATCGACCCTGTGAAGCTTTCTAGTGGG

TATAAAGACGTGATCCTCTGGTTCAGTTTTGGAGCATCTTGTTTCATTCTGCTAGCCATT

GTTATGGGACTTGTCTTCATTTGCGTGAAGAACGGGAATATGCGTTGTACGATCTGCATT

650
ATGAACACTCAGATACTCGTCTTCGCCCTCATAGCCATCATTCCCACGAATGCCGACAAA

ATCTGTCTGGGTCACCACGCGGTAAGTAACGGGACTAAGGTCAACACACTGACAGAAAGA

GGCGTCGAAGTCGTGAACGCCACAGAGACGGTGGAGAGGACAAACATACCCAGAATTTGC

TCGAAGGGCAAGAAGACCGTAGATCTGGGCCAGTGCGGGCTGTTGGGCACCATCACAGGC

CCCCCCCAGTGCGATCAGTTCCTGGAATTCTCTGCCGACCTTATCATTGAAAGGAGAGAG

GGGAGCGATGTTTGTTACCCCGGGAAGTTCGTTAACGAGGAGGCCCTTAGACAGATCCTT

CGGGAATCCGGTGGGATTGACAAGGAAGCCATGGGATTCACCTACTCTGGTATACGGACT

AACGGAGCCACCTCAGCCTGCAGAAGAAGCGGTAGTTCTTTTTATGCCGAAATGAAATGG

CTGTTGTCAAACACCGACAATGCTGCCTTCCCACAGATGACCAAATCATACAAGAATACC

CGCAAGTCTCCCGCCCTGATTGTGTGGGGCATCCATCACTCGGTGTCCACCGCCGAACAG

ACTAAGCTCTACGGCTCAGGGAATAAGCTGGTGACTGTTGGCAGCTCAAACTACCAGCAG

TCCTTCGTGCCTAGCCCTGGTGCCCGTCCCCAGGTGAACGGCCAGAGCGGTCGGATTGAC

TTCCATTGGCTTATGTTGAACCCAAACGATACCGTGACCTTCTCCTTCAATGGTGCCTTT

ATAGCACCCGATCGGGCGTCCTTTCTGCGCGGTAAATCTATGGGGATTCAAAGCGGCGTC

CAGGTGGATGCTAATTGTGAAGGAGATTGCTATCACAGCGGGGGAACTATAATTTCTAAC

CTGCCATTTCAAAATATTGATAGCCGGGCAGTGGGAAAGTGTCCTCGCTATGTTAAACAA

AGATCTCTTTTGCTGGCTACCGGAATGAAGAACGTGCCAGAGATCCCCAAAGGAAGGGGA

CTGTTCGGAGCAATCGCCGGGTTTATTGAAAATGGATGGGAGGGCCTCATTGACGGTTGG

TACGGGTTCCGCCACCAGAACGCTCAAGGAGAGGGGACGGCAGCGGATTATAAGAGCACT

CAGTCCGCAATCGACCAGATCACAGGAAAGCTGAATCGCCTCATTGAGAAAACAAACCAG

CAGTTCGAGTTGATTGATAACGAATTCAACGAGGTGGAAAAACAGATCGGCAATGTGATA

AACTGGACCCGCGACTCCATTACTGAGGTCTGGTCTTACAACGCAGAACTGCTTGTCGCA

ATGGAGAATCAACACACCATAGATCTCGCTGATTCTGAAATGGATAAGCTGTACGAAAGG

GTGAAAAGACAGCTGAGAGAGAATGCTGAAGAAGATGGCACCGGTTGCTTCGAGATCTTT

CACAAATGTGACGATGACTGCATGGCCTCCATTAGGAATAACACATATGATCATTCCAAG

TACAGGGAAGAGGCCATGCAGAACCGGATTCAGATTGATCCGGTTAAGCTGAGTTCCGGG

TACAAAGATGTGATACTATGGTTTTCTTTCGGCGCGAGTTGCTTCATTTTGCTTGCCATA

GTGATGGGTTTAGTTTTCATCTGCGTGAAGAACGGAAACATGCGCTGCACTATTTGCATA

651
ATGAATACCCAGATTCTTGTTTTTGCTCTTATAGCCATAATACCCACGAACGCAGACAAA

ATCTGCTTGGGCCACCACGCAGTATCTAACGGCACCAAGGTGAATACTCTCACCGAACGT

GGGGTGGAGGTCGTGAATGCTACAGAAACAGTGGAGCGCACAAACATTCCTCGTATTTGT

TCAAAAGGGAAGAAGACAGTGGATCTGGGCCAGTGCGGCCTATTAGGAACAATCACAGGG

CCCCCTCAATGTGACCAGTTTCTGGAGTTTTCCGCGGACCTCATTATCGAGCGACGGGAA

GGGAGCGACGTATGCTACCCGGGAAAATTCGTCAATGAGGAGGCCCTGCGTCAGATTCTT

AGGGAGTCAGGCGGCATCGACAAGGAAGCTATGGGATTTACATATTCTGGAATTCGCACT

AACGGCGCCACCTCCGCTTGTCGACGGAGCGGATCGTCCTTCTATGCCGAAATGAAGTGG

CTGCTGTCGAATACGGACAACGCTGCTTTTCCACAAATGACTAAGAGCTATAAGAATACC

AGAAAGTCTCCTGCGTTAATTGTATGGGGAATACATCATAGTGTGTCTACCGCCGAGCAG

ACAAAACTGTACGGTTCCGGCAATAAGCTAGTCACTGTGGGCTCTTCCAATTACCAGCAG

TCGTTTGTCCCCTCGCCAGGGGCCCGCCCGCAAGTAAATGGACAATCTGGGCGTATCGAT

TTCCATTGGCTTATGCTGAACCCTAATGACACCGTGACATTTTCATTCAATGGGGCTTTC

ATTGCCCCCGACAGGGCTAGCTTCCTTCGCGGCAAGAGCATGGGGATACAATCCGGGGTT

CAAGTGGATGCCAACTGCGAGGGCGACTGTTACCACTCAGGCGGAACCATCATTTCAAAT

CTGCCCTTTCAGAACATTGACAGCCGCGCCGTGGGCAAGTGTCCACGATATGTGAAGCAG

AGATCACTGCTCCTTGCAACCGGTATGAAAAATGTTCCTGAGATACCGAAGGGCCGGGGG

CTCTTCGGTGCTATCGCTGGATTCATTGAAAACGGGTGGGAAGGACTGATCGACGGTTGG

TATGGATTTAGGCACCAGAACGCACAGGGCGAAGGGACCGCCGCTGATTATAAAAGCACG

CAGAGCGCTATAGATCAGATCACCGGAAAGCTGAACCGCCTGATCGAGAAAACGAACCAA

CAGTTCGAACTGATTGATAACGAGTTTAACGAAGTGGAAAAACAGATTGGTAACGTGATC

AACTGGACTAGAGACTCCATCACCGAAGTGTGGTCATATAACGCAGAGTTACTCGTCGCG

ATGGAAAACCAACACACCATCGACCTGGCAGACAGTGAGATGGATAAACTCTACGAACGG

GTCAAGAGACAACTACGTGAGAATGCCGAGGAAGATGGCACAGGTTGTTTTGAAATTTTT

CACAAGTGTGACGACGACTGCATGGCATCAATAAGAAACAATACTTACGACCATAGTAAG

TACCGGGAGGAAGCTATGCAGAATAGAATCCAAATAGATCCAGTGAAATTGAGTAGCGGA

TATAAGGATGTGATTCTATGGTTTAGCTTCGGCGCTAGTTGTTTTATCCTTTTGGCTATA

GTGATGGGGCTCGTTTTTATCTGCGTGAAGAACGGAAACATGAGATGTACGATCTGCATT

652
ATGAATACCCAAATTCTCGTTTTTGCCCTCATCGCCATTATCCCTACTAACGCCGATAAG

ATCTGTCTGGGGCATCATGCCGTCTCCAACGGGACCAAGGTAAACACTCTGACCGAGCGC

GGTGTCGAAGTAGTCAATGCTACAGAGACAGTTGAACGCACTAATATTCCCAGGATCTGT

AGTAAAGGAAAGCGTACCGTGGACCTAGGACAATGTGGCTTGCTCGGCACTATCACCGGC

CCTCCACAGTGCGACCAATTTCTGGAATTCTCCGCTGATCTGATTATCGAGAGAAGAGAA

GGCAGTGACGTGTGCTACCCGGGAAAGTTTGTCAACGAAGAGGCCTTAAGGCAGATCCTG

CGCGAGAGCGGGGGTATAGATAAAGAAGCCATGGGCTTCACTTACAGTGGAATTAGGACA

AACGGCGCCACGTCGGCCTGCAGAAGGTCTGGGTCCTCATTCTACGCCGAGATGAAGTGG

CTTCTGTCGAATACCGACAATGCAGCATTTCCACAAATGACTAAATCCTATAAGAACACC

CGGAAGTCACCAGCCCTCATAGTGTGGGGGATCCATCACTCCGTGAGCACTGCAGAGCAA

ACAAAGCTGTATGGGTCCGGGAATAAACTGGTAACCGTTGGCAGTAGCAATTATCAGCAG

TCATTTGTTCCCTCCCCAGGTGCCCGGCCTCAGGTGAATGGTCTGTCTGGTCGCATCGAC

TTTCACTGGCTGATGCTGAATCCAAATGATACAGTCACATTTTCGTTTAATGGAGCCTTC

ATCGCGCCCGACAGGGCTAGCTTCCTACGCGGCAAGAGCATGGGCATTCAGAGCGGCGTC

CAGGTTGACGCCAATTGCGAGGGAGATTGTTATCATAGCGGAGGCACAATCATCTCAAAC

CTCCCCTTTCAGAATATAGACTCCAGAGCCGTTGGGAAGTGCCCTAGATACGTGAAACAG

CGATCCCTGCTCCTAGCTACAGGAATGAAGAATGTGCCAGAAATCCCCAAGGGTCGGGGG

CTCTTTGGAGCCATCGCCGGTTTTATCGAAAATGGTTGGGAAGGCCTCATTAATGGCTGG

TACGGCTTTCGACACCAGAATGCCCAGGGTGAAGGAACAGCGGCAGACTATAAGTCCACA

CAGAGTGCTATAGACCAGATCACCGGCAAGCTTAACAGACTGATTGAAAAGACCAATCAG

CAGTTCGAGTTGATCGACAACGAATTCAACGAGGTTGAGAAACAAATAGGAAACGTGATA

AATTGGACCCGCGATTCTATAACAGAAGTGTGGTCATATAATGCGGAACTGCTCGTGGCA

ATGGAGAACCAACATACAATAGACCTTGCAGACTCCGAAATGGATAAGCTGTACGAGCGC

GTCAAGCGACAGCTCAGAGAAAATGCAGAGGAGGATGGAACAGGCTGTTTTGAAATTTTC

CACAAGTGTGACGACGATTGCATGGCCTCCATCAGAAATAACACATATGACCATTCAAAG

TATCGCGAAGAAGCTATGCAGAATCGAATCCAAATAGATCCTGTGAAGTTGTCGTCCGGC

TACAAAGATGTTATCCTGTGGTTCAGTTTCGGGGCCTCATGCTTCATCCTGCTGGCCATA

GTGATGGGTCTCGTGTTCATCTGCGTGAAGAACGGCAACATGCGCTGCACTATCTGCATT

653
ATGAATACCCAGATTTTGGTGTTCGCACTTATCGCAATAATCCCGACTAACGCTGATAAA

ATTTGTTTAGGACATCATGCCGTTTCTAACGGAACTAAGGTGAACACACTTACCGAGAGA

GGTGTGGAAGTGGTGAACGCTACCGAAACTGTGGAGCGGACTAACATCCCCCGGATATGC

TCAAAGGGCAAGAGAACTGTGGATTTAGGTCAATGTGGTCTACTGGGCACAATTACCGGC

CCACCCCAATGCGACCAGTTCCTGGAGTTTAGCGCCGACCTGATTATTGAGAGACGTGAG

GGCTCAGACGTATGTTATCCTGGGAAATTTGTCAACGAAGAAGCCTTGCGGCAGATCCTA

CGTGAGAGCGGGGGCATTGACAAAGAGGCCATGGGGTTTACATACTCAGGCATCCGAACT

AACGGGGCAACAAGTGCATGTAGACGATCTGGGTCTAGCTTCTATGCCGAGATGAAATGG

CTCCTCTCGAACACCGATAACGCCGCTTTTCCGCAGATGACTAAATCTTATAAGAATACA

AGGAAGTCCCCCGCTTTAATTGTCTGGGGCATCCACCACTCTGTGAGCACCGCCGAACAG

ACAAAATTGTACGGCTCGGGGTCCAAGCTTGTCACTGTGGGCTCATCCAATTACCAGCAA

AGCTTTGTGCCCTCCCCCGGGGCAAGACCTCAGGTGAACGGGTTGAGCGGAAGGATTGAT

TTCCATTGGCTGATGTTGAACCCTAACGACACAGTCACCTTCTCGTTTAACGGGGCCTTC

ATTGCCCCAGATAGGGCCTCTTTTCTGCGCGGAAAGTCGATGGGGATCCAGTCAGGGGTG

CAGGTGGACGCCAACTGTGAAGGCGACTGTTATCACAGCGGAGGAACGATAATTTCCAAT

CTACCCTTTCAGAATATAGATTCAAGAGCCGTTGGGAAATGTCCCAGGTACGTCAAGCAG

AGGTCGCTCCTCTTGGCTACCGGCATGAAGAATGTTCCTGAAATCCCGAAGGGCAGAGGA

CTCTTTGGCGCCATAGCCGGCTTTATTGAAAATGGATGGGAAGGATTAATTGACGGCTGG

TACGGCTTCCGGCATCAGAATGCACAGGGCGAGGGCACGGCGGCTGACTACAAGTCTACT

CAGAGTGCCATAGACCAGATTACCGGGAAGTTAAATCGTCTGATCGAGAAGACCAACCAA

CAGTTTGAACTCATTGACAATGAGTTCAACGAAGTGGAGAAACAGATCGGCAACGTAATC

AATTGGACTCGCGATTCCATTACCGAGGTGTGGTCTTATAACGCAGAACTCTTGGTGGCC

ATGGAAAACCAACACACGATTGATCTCGCAGACAGCGAGATGGACAAGTTGTATGAGAGA

GTTAAGCGCCAGCTCAGGGAGAATGCCGAAGAGGACGGAACCGGTTGCTTTGAGATCTTT

CACAAATGTGATGATGACTGCATGGCGAGCATTCGTAATAATACTTATGACCATAGTAAA

TACCGGGAGGAAGCCATGCAGAATCGCATCCAAATTGACCCCGTAAAGCTAAGTTCAGGT

TATAAGGATGTTATTCTTTGGTTTTCATTCGGAGCTTCATGCTTCATCCTTCTTGCAATT

GTAATGGGACTGGTTTTCATTTGTGTAAAGAACGGAAATATGCGATGTACGATTTGTATT

654
ATGAATACTCAAATCCTTGTCTTTGCGCTGATCGCTATCATTCCAACAAATGCAGATAAA

ATCTGTCTAGGACATCATGCTGTGTCAAACGGTACTAAAGTGAATACACTGACGGAGAGG

GGAGTCGAGGTGGTGAACGCAACAGAGACAGTGGAACGCACAAATATCCCCCGCATCTGT

TCTAAGGGGAAAAAAACCGTGGACTTGGGGCAGTGCGGTTTACTGGGGACCATTACTGGT

CCGCCCCAGTGCGACCAGTTCCTAGAGTTTTCCGCAGACCTGATTATAGAGAGACGCGAA

GGAAGCGACGTATGTTACCCCGGGAAGTTTGTCAATGAAGAAGCCCTCAGACAGATTCTT

CGGGAGTCCGGAGGCATCGATAAAGAGGCTATGGGCTTCACCTACTCCGGCATTCGTACA

AATGGTGCTACGTCTGCCTGTCGACGCAGTGGGTCATCCTTTTACGCCGAAATGAAGTGG

CTATTGAGCAATACCGACAACGCAGCTTTCCCTCAGATGACTAAGAGCTATAAAAACACC

CGCAAGAGCCCAGCTCTGATCGTATGGGGAATTCACCACTCAGTTTCGACTGCAGAGCAG

ACTAAACTGTATGGCTCCGGGAATAAGCTGGTTACCGTGGGTAGCTCTAACTACCAGCAG

TCATTCGTTCCTTCACCCGGCGCACGCCCCCAAGTGAATGGGCAATCTGGGCGCATAGAC

TTCCACTGGCTTATGCTAAACCCAAACGACACTGTGACCTTTTCATTCAACGGCGCATTC

ATTGCACCTGACCGCGCGTCATTTCTCCGGGGCAAGAGCATGGGGATCCAGAGCGGCGTA

CAGGTGGACGCGAATTGCGAGGGGGATTGCTACCATTCAGGAGGAACCATTATTTCTAAC

CTCCCGTTCCAAAATATAGACTCTCGTGCTGTGGGAAAGTGCCCGAGATACGTCAAACAG

CGTTCTCTACTCCTGGCTACGGGGATGAAGAACGTGCCCGAGATTCCGAAAGGGCGCGGA

CTGTTTGGCGCCATCGCGGGATTTATTGAGAACGGCTGGGAGGGGCTTATTGATGGTTGG

TATGGCTTCCGGCACCAGAACGCTCAGGGGGAGGGGACTGCAGCTGATTACAAGTCAACA

CAATCAGCAATCGATCAGATTACCGGAAAGCTGAACAGACTCATCGAGAAGACGAATCAA

CAGTTTGAATTGATCGATAACGAATTCAACGAAGTCGAGAAACAAATCGGAAACGTCATT

AACTGGACTAGAGATTCCATCACCGAGGTGTGGTCTTATAACGCCGAGCTCCTGGTGGCG

ATGGAGAACCAGCACACAATTGATCTCGCTGACAGCGAGATGGACAAGTTGTACGAGAGG

GTAAAACGACAGCTCCGGGAAAATGCCGAGGAAGATGGGACAGGGTGCTTCGAGATCTTT

CACAAGTGTGACGACGACTGTATGGCCTCAATTCGAAATAACACCTATGATCACTCGAAA

TACCGCGAGGAAGCTATGCAGAACAGAATCCAGATTGACCCTGTGAAGCTGAGCAGTGGG

TATAAAGACGTCATCTTATGGTTCAGCTTCGGGGCTTCTTGCTTCATACTGCTTGCCATC

GTTATGGGCCTGGTGTTTATCTGTGTCAAGAATGGTAACATGAGGTGCACTATCTGTATA

655
ATGAACACCCAAATTCTTGTATTTGCTCTGATCGCCATTATTCCAACCAATGCCGACAAG

ATCTGTTTGGGGCACCATGCCGTTTCTAATGGCACAAAAGTCAATACATTAACTGAGCGC

GGCGTAGAAGTCGTGAACGCTACCGAAACAGTTGAGAGAACCAACATCCCTCGAATATGT

TCCAAGGGGAAGAAAACAGTGGATCTCGGGCAGTGCGGCTTGCTGGGAACAATAACTGGC

CCGCCTCAGTGTGATCAGTTCCTGGAATTTAGTGCTGACCTGATAATCGAGCGAAGAGAG

GGGAGCGATGTGTGTTATCCCGGGAAATTTGTAAACGAGGAGGCCCTGCGGCAGATACTT

AGAGAGAGTGGGGGAATCGACAAAGAAGCGATGGGGTTTACCTACTCTGGAATCAGAACT

AACGGGGCTACAAGCGCCTGCCGGCGCAGCGGATCGTCCTTCTACGCAGAGATGAAGTGG

CTGCTCAGCAACACTGACAATGCCGCTTTTCCTCAAATGACCAAGTCTTACAAGAACACC

CGTAAAAGTCCCGCGCTCATAGTATGGGGTATCCACCATTCTGTCTCAACAGCAGAACAG

ACCAAACTGTACGGCAGCGGCAACAAACTGGTGACAGTGGGATCTAGCAATTACCAGCAG

AGTTTTGTCCCATCCCCTGGCGCGCGGCCCCAGGTGAATGGGCAAAGTGGACGGATAGAC

TTCCACTGGTTGATGCTGAACCCAAATGATACCGTGACATTTTCTTTCAACGGTGCATTT

ATAGCCCCTGACCGTGCAAGCTTCTTGAGAGGTAAGAGCATGGGAATTCAGTCAGGTGTT

CAGGTGGATGCCAATTGCGAGGGCGATTGCTACCACAGCGGCGGCACTATTATTTCTAAT

CTTCCTTTCCAGAATATAGACTCCCGTGCTGTGGGTAAATGCCCTAGGTACGTAAAGCAA

AGGAGCTTACTGTTGGCAACAGGCATGAAGAATGTGCCAGAAATTCCCAAGGGGGGGGGC

CTGTTTGGCGCCATTGCAGGCTTTATTGAGAATGGCTGGGAGGGCCTAATTGATGGTTGG

TACGGCTTCAGGCACCAGAACGCACAGGGGGAAGGCACAGCTGCGGATTACAAAAGTACC

CAGAGCGCCATAGATCAAATAACCGGCAAGTTAAACCGATTGATTGAGAAAACAAACCAG

CAATTTGAGCTGATAGACAATGAATTCAACGAAGTCGAAAAGCAGATTGGCAACGTGATC

AATTGGACCCGGGATAGCATTACTGAGGTATGGAGCTATAATGCAGAGTTGCTGGTGGCC

ATGGAAAACCAGCATACCATCGATCTGGCCGACTCAGAAATGGATAAGCTCTACGAGCGG

GTGAAGAGGCAGCTGAGAGAAAATGCCGAAGAAGACGGAACCGGCTGCTTTGAGATTTTT

CACAAGTGCGACGATGATTGCATGGCCAGTATTAGAAACAACACCTATGATCACTCCAAG

TACCGCGAAGAAGCCATGCAGAACCGCATCCAAATCGATCCGGTCAAACTCTCCTCTGGC

TATAAGGATGTAATCCTGTGGTTCTCTTTTGGAGCGTCCTGCTTCATATTATTGGCTATT

GTGATGGGCTTGGTGTTTATCTGTGTTAAGAACGGAAACATGCGGTGTACAATCTGCATT

656
ATGAATACACAGATACTCGTGTTCGCCCTTATTGCTATCATCCCTACAAATGCTGACAAG

ATATGTCTGGGCCACCACGCCGTGAGCAATGGCACCAAGGTTAATACCCTAACCGAACGG

GGAGTTGAGGTGGTTAACGCTACCGAGACCGTAGAGCGCACTAATATTCCACGCATTTGC

TCGAAAGGCAAGAAAACAGTGGACTTAGGCCAATGTGGACTCCTCGGAACAATAACCGGC

CCACCACAGTGCGATCAGTTCCTCGAGTTTTCAGCCGACCTAATTATTGAGCGACGGGAA

GGTAGCGATGTGTGTTATCCAGGGAAGTTCGTCAATGAAGAGGCCTTGCGGCAGATACTG

CGCGAAAGTGGGGGCATAGACAAGGAGGCTATGGGGTTTACATACAGTGGAATTCGCACC

AATGGGGCCACTAGCGCCTGTAGGAGATCAGGCTCCTCTTTCTACGCTGAGATGAAATGG

TTACTGTCAAATACTGATAACGCCGCCTTTCCTCAGATGACAAAATCCTATAAGAACACT

AGGAAGTCACCTGCTCTAATCGTTTGGGGAATCCATCACTCCGTGAGCACCGCTGAGCAG

ACCAAGCTTTATGGCTCAGGAAACAAGCTCGTGACGGTGGGCTCCAGTAACTATCAACAA

AGCTTCGTGCCTTCTCCAGGAGCAAGGCCCCAGGTGAATGGACAGTCCGGGAGAATCGAC

TTTCACTGGCTCATGCTGAATCCAAACGATACCGTTACCTTTTCATTCAATGGGGCCTTC

ATCGCCCCAGACAGGGCCAGCTTCCTCCGCGGCAAAAGCATGGGCATACAAAGCGGCGTG

CAGGTGGATGCTAATTGCGAGGGTGACTGCTATCATTCAGGCGGCACCATAATCAGTAAC

CTGCCCTTTCAAAATATAGATTCGCGGGCAGTAGGTAAATGCCCTCGTTATGTGAAACAG

CGGTCCTTGCTGCTTGCGACTGGAATGAAAAACGTGCCCGAGATTCCCAAGGGCCGTGGA

TTATTTGGCGCTATCGCCGGGTTCATCGAGAACGGCTGGGAGGGTCTCATTGATGGATGG

TACGGTTTCAGACACCAGAACGCCCAGGGGGAGGGGACCGCAGCCGACTACAAATCAACC

CAGTCCGCCATTGATCAGATCACAGGGAAGCTAAATCGCCTGATTGAGAAGACAAATCAG

CAGTTCGAGCTGATCGACAACGAATTCAATGAGGTAGAGAAACAGATTGGGAACGTTATT

AATTGGACCAGAGATTCCATAACAGAGGTATGGTCTTATAACGCAGAACTGCTCGTTGCG

ATGGAGAACCAGCATACAATCGACCTGGCAGACAGTGAAATGGACAAGCTCTATGAGAGG

GTCAAGAGGCAATTGAGAGAGAATGCCGAAGAAGACGGGACCGGTTGCTTCGAGATCTTC

CACAAATGTGATGATGACTGCATGGCAAGCATTAGAAACAACACCTACGATCACTCCAAA

TACCGAGAGGAGGCTATGCAAAATCGGATACAGATCGATCCTGTCAAGCTGTCTTCTGGT

TACAAAGATGTTATTCTGTGGTTCAGTTTTGGGGCCTCATGTTTCATCTTACTGGCAATC

GTGATGGGACTCGTTTTCATCTGTGTTAAAAATGGCAACATGAGGTGTACCATTTGTATC

657
ATGAACACACAAATTTTAGTGTTTGCTCTGATTGCCATTATCCCCACCAACGCTGATAAG

ATTTGTCTGGGGCACCACGCAGTGTCTAATGGCACCAAAGTCAACACACTTACAGAGAGA

GGAGTGGAGGTGGTTAACGCCACTGAAACCGTCGAGAGAACCAATATTCCTCGGATCTGC

TCCAAGGGCAAGAAAACAGTTGATCTAGGACAGTGTGGGTTGCTAGGGACAATCACCGGA

CCACCTCAGTGTGATCAGTTCTTAGAGTTCTCCGCTGATCTAATTATTGAGCGAAGAGAA

GGGTCCGATGTGTGCTACCCCGGTAAATTTGTCAATGAAGAAGCCTTGAGGCAGATTCTG

AGAGAAAGCGGCGGCATCGATAAGGAGGCAATGGGTTTCACTTACTCTGGAATCCGGACC

AACGGAGCCACTAGCGCTTGTCGAAGGAGTGGATCGTCCTTCTACGCCGAGATGAAATGG

CTCTTGTCAAATACAGATAATGCCGCATTTCCCCAGATGACTAAGAGCTACAAGAATACA

CGTAAGAGCCCGGCTCTGATCGTCTGGGGTATTCATCATAGTGTGTCTACTGCAGAGCAG

ACCAAACTATACGGTAGTGGCAACAAACTTGTCACCGTCGGCAGTTCTAATTACCAGCAA

TCCTTTGTCCCTTCCCCCGGCGCTCGGCCTCAGGTGAATGGACAGAGCGGCAGGATTGAC

TTCCACTGGCTTATGCTGAACCCTAATGATACTGTTACCTTCTCGTTTAATGGGGCGTTT

ATTGCTCCCGATAGGGCCAGTTTTCTTCGGGGCAAGTCCATGGGGATCCAGTCAGGTGTG

CAGGTCGATGCTAATTGTGAGGGCGACTGCTATCATTCTGGCGGCACGATCATCTCAAAC

TTGCCCTTCCAAAATATAGATAGCCGAGCAGTGGGAAAATGCCCTCGTTACGTCAAGCAG

AGGAGCCTCCTGTTAGCCACCGGGATGAAAAATGTTCCAGAAATACCCAAGGGGAGGGGC

TTATTTGGCGCTATTGCAGGATTTATCGAGAACGGTTGGGAGGGACTCATTGACGGATGG

TATGGCTTCCGCCACCAGAACGCCCAGGGGGAGGGTACCGCAGCTGATTACAAGTCCACA

CAGAGTGCCATAGATCAAATCACCGGTAAGCTGAATAGGCTGATCGAAAAAACCAATCAG

CAGTTTGAGCTCATCGATAATGAGTTCAACGAGGTGGAGAAACAGATTGGTAATGTCATC

AACTGGACAAGGGACTCGATTACCGAAGTGTGGAGCTATAACGCAGAGCTCTTGGTTGCC

ATGGAGAATCAGCACACCATCGATTTAGCAGATAGCGAAATGGACAAACTATACGAAAGG

GTGAAACGGCAACTTAGGGAGAACGCCGAAGAGGATGGGACCGGGTGCTTCGAAATTTTT

CACAAGTGTGATGACGACTGCATGGCCTCTATCCGGAATAATACCTACGATCACAGCAAA

TACAGGGAGGAAGCCATGCAGAACCGCATCCAGATCGATCCAGTCAAGCTGTCTTCTGGC

TATAAGGACGTGATCCTGTGGTTCTCTTTCGGCGCTAGTTGTTTTATCCTGCTGGCCATC

GTGATGGGCCTTGTTTTCATCTGTGTGAAAAACGGGAATATGAGGTGCACAATCTGCATT

658
ATGAACACACAGATCCTCGTCTTTGCACTCATCGCAATCATCCCCACCAACGCTGATAAA

ATTTGTCTCGGACATCATGCCGTGAGCAATGGGACCAAAGTTAACACCCTAACGGAGAGA

GGTGTCGAGGTGGTGAACGCGACAGAAACCGTAGAACGAACCAATATTCCAAGGATCTGC

AGTAAGGGAAAAAGGACCGTGGATTTGGGGCAGTGTGGATTGCTGGGGACTATCACAGGA

CCACCACAGTGCGACCAATTCCTTGAATTTTCCGCGGATCTGATTATTGAGAGGAGGGAG

GGATCTGACGTCTGTTACCCAGGCAAGTTCGTTAATGAGGAAGCGCTGAGACAGATTCTG

CGAGAGAGCGGAGGCATAGACAAAGAGGCTATGGGTTTTACCTATTCTGGGATACGCACA

AACGGAGCTACAAGCGCATGCCGGAGAAGTGGAAGCTCATTTTATGCGGAAATGAAATGG

CTCCTCTCCAACACCGACAATGCAGCATTCCCTCAGATGACCAAATCATATAAAAACACC

AGAAAAAGTCCGGCTCTCATAGTGTGGGGTATACATCATTCCGTCTCGACCGCAGAGCAA

ACTAAGCTCTACGGCTCTGGAAACAAACTCGTGACTGTCGGCAGTTCTAATTACCAGCAG

TCTTTTGTACCTAGCCCCGGGGCTAGGCCACAGGTGAATGGCTTATCTGGGCGCATAGAC

TTCCACTGGCTTATGCTGAACCCAAACGATACAGTGACCTTCTCCTTTAACGGCGCCTTC

ATTGCCCCCGACAGAGCTAGTTTCCTGCGCGGAAAATCAATGGGAATCCAGAGTGGGGTG

CAGGTGGATGCAAACTGCGAAGGCGACTGCTATCACTCAGGCGGCACAATAATTAGTAAC

CTACCATTCCAGAACATTGATTCACGCGCCGTCGGGAAGTGTCCGAGATACGTGAAACAG

CGGTCTCTCCTGTTAGCAACAGGCATGAAGAATGTGCCTGAGATTCCCAAAGGCCGGGGG

CTCTTCGGAGCCATTGCTGGTTTCATCGAGAACGGGTGGGAGGGTCTGATCGATGGCTGG

TATGGTTTCCGGCATCAGAACGCGCAGGGGGAGGGCACAGCCGCAGATTACAAGAGTACT

CAGAGTGCCATCGATCAGATTACAGGGAAGCTGAATAGAATAATCGAAAAAACTAATCAG

CAGTTTGAACTGATAGACAACGAATTCAACGAGGTCGAGAAGCAGATCGGGAATGTGATC

AACTGGACCCGCGACTCAATCACAGAGGTTTGGAGTTATAATGCCGAGCTCCTCGTTGCC

ATGGAGAATCAACATACAATTGACCTTGCTGACTCTGAGATGGATAAACTGTATGAACGA

GTTAAGCGACAGTTGAGGGAGAATGCGGAAGAAGACGGGACCGGCTGCTTCGAAATATTC

CATAAGTGCGACGATGACTGTATGGCATCAATCAGGAACAACACCTATGACCACTCCAAG

TATCGAGAGGAAGCGATGCAGAACAGGATCCAGATCGATCCAGTCAAGTTGTCCTCTGGC

TATAAGGACGTGATTCTGTGGTTTTCTTTCGGCGCAAGCTGTTTCATTTTATTAGCTATC

GTCATGGGTCTAGTGTTCATCTGTGTTAAAAATGGCAATATGCGATGTACAATCTGTATT

659
ATGAACACCCAAATCCTTGTTTTCGCTCTGATTGCAATTATCCCAACGAATGCTGACAAA

ATTTGCCTGGGCCACCACGCTGTGTCCAACGGAACTAAGGTAAATACTCTGACTGAACGC

GGCGTGGAGGTGGTGAACGCCACCGAAACAGTGGAGAGAACTAATATTCCCCGCATCTGT

TCTAAGGGCAAAAAGACAGTGGATCTCGGTCAGTGCGGGCTGTTGGGAACAATTACCGGA

CCTCCCCAATGCGATCAGTTCCTAGAGTTTTCCGCCGACCTGATAATCGAAAGACGTGAA

GGCTCTGACGTGTGTTACCCCGGAAAGTTTGTGAATGAAGAAGCACTGCGGCAGATCTTA

CGCGAGAGTGGCGGCATTGACAAGGAGGCAATGGGATTTACCTACTCCGGAATCAGGACA

AATGGCGCAACCAGTGCTTGTAGGCGCTCCGGAAGCTCCTTTTATGCCGAGATGAAATGG

CTTCTGTCCAACACGGACAACGCCGCTTTCCCTCAAATGACCAAATCCTACAAAAATACC

CGTAAGTCACCGGCGCTGATTGTATGGGGGATACACCACAGTGTTTCTACCGCCGAACAA

ACCAAGCTGTACGGCAGCGGAAATAAACTGGTAACTGTCGGATCATCCAATTACCAGCAG

TCCTTCGTCCCTAGCCCTGGGGCGCGCCCGCAGGTCAATGGGCAGTCTGGAAGAATTGAC

TTTCATTGGCTGATGTTAAATCCAAACGACACAGTTACATTCAGTTTCAACGGGGCCTTT

ATTGCACCCGATAGAGCATCCTTTCTGCGAGGCAAAAGTATGGGGATTCAATCTGGGGTG

CAGGTTGATGCGAATTGCGAGGGAGATTGCTATCACTCTGGCGGAACCATCATCAGCAAC

CTCCCATTCCAAAATATTGACTCACGCGCTGTGGGAAAGTGCCCTAGGTATGTGAAGCAG

CGGTCCTTGCTTTTAGCTACCGGAATGAAAAACGTGCCAGAAATCCCTAAGGGGCGCGGA

TTATTCGGCGCCATTGCTGGCTTCATTGAGAATGGATGGGAGGGCCTAATCGACGGTTGG

TATGGTTTTCGTCATCAGAACGCACAAGGGGAAGGGACTGCTGCCGACTACAAGTCTACC

CAGTCCGCTATAGACCAGATTACCGGTAAGCTAAATCGGCTTATAGAGAAGACTAACCAA

CAGTTCGAGCTGATCGACAACGAATTTAACGAAGTGGAGAAGCAGATTGGGAACGTCATC

AACTGGACGCGAGACTCTATTACTGAAGTCTGGTCTTACAATGCTGAGTTGCTCGTGGCT

ATGGAAAACCAGCATACTATAGACCTGGCCGACTCAGAGATGGATAAGTTATATGAACGC

GTGAAGCGGCAGCTCCGAGAAAATGCCGAAGAGGACGGAACAGGGTGTTTTGAGATCTTC

CACAAATGTGACGATGACTGCATGGCATCTATACGGAACAATACCTATGACCATTCCAAG

TACCGTGAGGAAGCCATGCAAAATAGAATACAAATCGATCCAGTCAAACTCTCTAGCGGC

TACAAGGACGTTATCTTGTGGTTCTCCTTCGGAGCGAGCTGTTTTATTTTGCTCGCGATT

GTGATGGGATTGGTGTTTATTTGCGTTAAAAACGGAAACATGCGGTGCACCATCTGTATC

660
ATGAATACCCAGATCCTGGTCTTCGCTCTGATCGCAATCATTCCTACCAACGCTGACAAA

ATTTGCCTGGGCCACCACGCAGTTAGTAATGGAACAAAAGTGAATACTCTTACAGAGCGG

GGTGTCGAGGTAGTAAACGCTACGGAAACCGTAGAGCGCACAAATATCCCCAGAATGTGT

AGCAAAGGTAAAAGGACAGTAGACTTGGGCCAGTGTGGACTGCTCGGAACAATTACAGGC

CCCCCTCAGTGTGATCAGTTCCTGGAATTCTCAGCCGACCTTATCATCGAACGAAGGGAG

GGGAGCGATGTCTGCTACCCAGGCAAGTTTGTGAATGAAGAGGCCCTTCGTCAAATACTC

CGAGAATCGGGGGGAATCGATAAAGAAGCAATGGGATTTACCTATAGCGGAATCAGAACT

AACGGCGCAACTTCCGCCTGCAGGCGGTCTGGCAGCTCCTTTTATGCCGAGATGAAGTGG

CTATTGAGCAATACTGACAACGCAGCCTTCCCTCAAATGACCAAGTCATACAAAAATACA

CGCAAGTCTCCAGCTCTGATCGTGTGGGGCATTCACCATAGCGTCAGCACAGCCGAGCAA

ACAAAGCTCTACGGCAGCGGCAACAAACTCGTGACCGTCGGCAGTTCTAACTACCAGCAG

TCCTTTGTGCCCAGCCCAGGGGCCCGTCCACAGGTTAACGGACTGTCTGGCCGGATCGAT

TTCCACTGGCTGATGTTAAATCCCAACGACACAGTCACGTTTAGCTTTAACGGAGCCTTT

ATCGCCCCCGACAGGGCTAGCTTTCTTAGGGGCAAGAGCATGGGAATTCAATCAGGGGTT

CAAGTGGACGCAAACTGCGAGGGCGATTGCTATCACTCCGGTGGAACTATTATAAGTAAT

CTACCATTCCAAAACATCGATTCAAGGGCGGTGGGTAAGTGTCCTCGCTACGTTAAGCAG

CGCAGCCTGCTACTCGCGACGGGAATGAAAAATGTCCCGGAGATACCTAAAGGCAGAGGC

CTCTTCGGCGCCATCGCAGGTTTCATCGAAAACGGCTGGGAAGGTCTGATCGACGGTTGG

TATGGATTCCGTCACCAAAACGCACAGGGAGAGGGTACAGCCGCAGACTATAAGTCTACC

CAGTCAGCTATCGACCAAATTACTGGAAAACTGAATCGTATCATTGAAAAGACCAATCAA

CAATTCGAGCTGATCGACAACGAGTTTAATGAAGTTGAGAAACAGATCGGAAATGTGATT

AACTGGACACGTGACAGCATTACTGAGGTCTGGAGCTACAACGCGGAACTTCTCGTAGCG

ATGGAGAACCAGCACACTATTGACCTGGCTGATAGTGAAATGGATAAACTATATGAAAGG

GTCAAAAGACAACTGCGGGAAAATGCCGAGGAAGATGGTACTGGATGTTTTGAAATCTTT

CACAAGTGCGATGACGACTGTATGGCTAGCATCAGGAACAATACATACGACCATTCGAAG

TATCGCGAAGAGGCCATGCAGAACCGAATACAGATTGATCCGGTTAAGCTGTCTTCTGGA

TATAAAGACGTCATCCTGTGGTTTAGTTTCGGGGCGAGTTGTTTCATTCTACTGGCTATT

GTCATGGGCCTGGTTTTTATCTGCGTGAAAAATGGCAACATGCGGTGCACGATCTGCATC

661
ATGAACACACAGATCTTGGTGTTCGCCCTCATCGCGATAATACCCACTAATGCCGACAAA

ATTTGTTTGGGTCATCACGCCGTGAGCAATGGCACTAAGGTGAACACGCTTACAGAACGG

GGCGTAGAAGTTGTGAACGCCACAGAGACAGTGGAGAGGACAAATATCCCGCGGATCTGC

TCAAAGGGGAAAAAAACCGTTGACCTGGGACAGTGCGGCCTGCTGGGGACAATAACAGGC

CCCCCCCAGTGTGACCAATTTCTGGAGTTCTCTGCCGACCTGATTATCGAAAGACGGGAG

GGCAGTGATGTCTGCTACCCCGGCAAGTTCGTAAATGAAGAGGCTCTGCGGCAGATCCTA

CGGGAGTCCGGAGGAATCGATAAGGAGGCAATGGGGTTTACGTATAGCGGCATTAGAACC

AACGGAGCAACCAGTGCTTGCAGGAGGAGCGGCAGCTCATTCTACGCGGAAATGAAGTGG

CTGCTGTCAAATACAGATAACGCCGCTTTCCCACAGATGACTAAATCCTATAAGAACACC

CGCAAGAGTCCTGCTCTCATCGTTTGGGGTATCCACCACTCTGTGTCAACTGCCGAGCAG

ACCAAACTTTACGGATCTGGGAATAAGCTTGTGACAGTTGGGAGCAGCAACTATCAGCAG

TCATTTGTGCCCTCTCCGGGTGCCAGGCCACAGGTTAATGGACAGTCGGGGCGTATCGAC

TTCCATTGGCTTATGCTCAATCCTAATGACACTGTTACCTTTTCTTTCAACGGCGCGTTC

ATTGCCCCCGACAGAGCGAGCTTTCTTAGGGGGAAATCGATGGGTATTCAGAGCGGGGTC

CAGGTCGATGCGAACTGCGAGGGCGATTGCTACCACTCAGGGGGAACAATTATCTCTAAT

TTACCCTTTCAGAACATCGACTCAAGGGCAGTGGGGAAGTGTCCGCGATACGTTAAACAA

CGGAGTTTGCTCCTGGCCACAGGCATGAAAAACGTCCCAGAAATCCCCAAAGGCAGAGGG

TTGTTTGGGGCGATCGCCGGCTTTATCGAGAACGGATGGGAAGGCTTAATTGACGGCTGG

TACGGCTTCCGCCACCAGAACGCTCAGGGGGAAGGTACCGCCGCTGATTATAAAAGTACG

CAAAGCGCTATTGATCAGATTACGGGCAAATTGAATCGGCTGATTGAGAAAACAAATCAG

CAGTTTGAACTGATCGACAACGAGTTTAATGAGGTGGAGAAGCAGATAGGAAATGTAATT

AACTGGACTCGGGATTCGATCACGGAGGTTTGGTCCTATAACGCAGAGCTACTGGTCGCC

ATGGAGAATCAGCACACTATTGACCTGGCAGATTCTGAGATGGACAAGCTGTACGAGAGG

GTAAAAAGACAACTGCGGGAGAACGCTGAAGAGGATGGAACAGGGTGTTTTGAGATCTTT

CACAAGTGCGACGATGATTGCATGGCATCTATCCGCAACAATACTTACGACCACTCTAAG

TACAGAGAAGAGGCGATGCAGAATCGAATTCAGATTGACCCGGTGAAGCTGAGCAGTGGA

TATAAAGATGTAATCCTCTGGTTTAGCTTCGGAGCCTCATGTTTTATCCTCCTTGCTATC

GTTATGGGCCTCGTCTTTATATGTGTCAAAAACGGCAATATGCGCTGCACAATCTGCATT

662
ATGAATACCCAAATTTTGGTTTTTGCTCTGATTGCCATTATTCCCACTAATGCCGACAAG

ATCTGCCTCGGCCATCATGCCGTGTCTAATGGCACAAAGGTGAATACCTTGACAGAAAGG

GGTGTGGAAGTAGTGAATGCCACAGAAACTGTAGAGCGGACCAATATTCCCAGGATTTGC

TCTAAGGGAAAGAAGACCGTTGATCTGGGCCAATGCGGCTTGCTGGGCACCATCACTGGG

CCACCACAGTGCGACCAGTTCCTGGAATTTAGCGCCGATCTGATAATAGAGAGACGGGAA

GGTAGCGACGTCTGCTATCCTGGGAAATTCGTCAACGAGGAAGCTCTGCGGCAGATCCTA

CGGGAGAGTGGCGGGATAGACAAGGAGGCAATGGGCTTTACGTACTCAGGAATTCGAACC

AATGGGGCGACGTCCGCCTGCCGGAGATCGGGCTCTTCTTTTTACGCAGAAATGAAGTGG

CTGCTGTCGAATACAGATAATGCGGCTTTCCCCCAGATGACCAAGTCATATAAAAATACG

AGAAAATCGCCCGCACTTATTGTGTGGGGCATCCACCACTCCGTGTCAACTGCCGAGCAA

ACCAAGCTATATGGCAGCGGCAATAAGCTGGTGACAGTAGGAAGTTCTAATTACCAGCAG

TCTTTCGTGCCGAGCCCTGGAGCCAGACCACAGGTGAATGGCCAGTCGGGCAGGATAGAT

TTCCACTGGTTAATGCTTAACCCAAACGACACGGTGACCTTCAGTTTCAACGGTGCCTTC

ATCGCCCCCGATCGCGCCTCCTTTTTGCGCGGCAAGTCTATGGGTATTCAGAGTGGAGTG

CAGGTGGACGCAAACTGCGAAGGGGATTGTTATCACAGGGGGGGGACCATAATCAGCAAT

CTCCCGTTTCAAAATATCGATTCTCGGGCAGTCGGTAAATGTCCCAGGTACGTTAAGCAA

CGGAGCCTGCTGCTCGCTACAGGCATGAAGAATGTGCCCGAGATCCCCAAGGGAAGAGGC

CTGTTCGGGGCCATCGCTGGTTTCATCGAGAACGGATGGGAGGGATTAATCGACGGGTGG

TACGGTTTCCGACACCAGAACGCACAGGGTGAGGGCACTGCCGCTGATTACAAATCAACC

CAGTCTGCAATCGACCAGATCACTGGGAAATTGAACCGATTGATCGAAAAGACGAACCAG

CAGTTCGAACTCATTGACAACGAGTTTAATGAAGTCGAGAAGCAGATTGGAAATGTGATC

AACTGGACAAGGGATTCTATCACAGAGGTCTGGTCATACAACGCTGAACTCCTTGTGGCC

ATGGAGAACCAGCACACCATCGATCTGGCTGATTCAGAAATGGATAAACTATATGAAAGG

GTGAAGCGGCAACTTAGGGAAAATGCTGAGGAGGACGGCACGGGATGCTTTGAAATCTTC

CACAAGTGTGATGATGACTGTATGGCGTCCATCCGGAACAATACATATGACCATTCAAAA

TATAGAGAAGAGGCAATGCAGAACAGGATACAGATTGACCCTGTCAAGTTGAGTTCTGGC

TACAAGGACGTGATTCTGTGGTTCAGCTTCGGAGCCAGTTGTTTCATCCTCCTGGCCATC

GTGATGGGCCTAGTGTTCATCTGCGTGAAAAATGGCAATATGCGCTGCACAATATGTATA

663
ATGAATACCCAAATCCTCGTTTTCGCACTGATTGCTATTATACCCACCAACGCTGACAAG

ATTTGTCTGGGTCACCACGCAGTTTCTAACGGCACAAAGGTGAATACTCTCACAGAGCGC

GGGGTTGAGGTCGTCAACGCTACTGAGACCGTCGAACGAACCAATATCCCCAGGATCTGT

AGCAAGGGAAAGAAAACAGTCGATTTAGGCCAGTGTGGCCTCTTAGGCACCATCACAGGC

CCACCCCAATGCGACCAGTTCCTGGAGTTCTCCGCAGATTTAATCATTGAGCGGCGAGAG

GGGAGTGATGTTTGCTACCCAGGTAAGTTCGTCAATGAAGAAGCCTTGCGCCAGATCCTG

CGGGAAAGCGGCGGCATTGACAAAGAGGCTATGGGATTTACTTATTCTGGCATACGAACT

AACGGGGCAACGTCTGCTTGTCGACGCTCAGGCTCATCCTTCTACGCAGAAATGAAATGG

TTGCTCAGTAATACAGATAATGCCGCATTTCCCCAAATGACCAAGAGCTACAAGAATACA

CGGAAGAGCCCAGCCCTGATTGTGTGGGGTATCCACCATTCTGTAAGTACAGCAGAGCAG

ACAAAACTGTATGGGTCTGGCAACAAACTGGTGACGGTGGGCAGTAGCAACTACCAACAG

AGTTTCGTGCCGTCACCTGGGGCAAGACCCCAGGTTAACGGGCAGTCCGGCCGCATAGAC

TTTCACTGGCTCATGCTGAATCCGAACGATACAGTGACTTTTTCATTCAATGGTGCATTT

ATCGCCCCCGATCGCGCTTCGTTCCTCCGCGGCAAATCTATGGGAATTCAATCCGGGGTA

CAGGTCGACGCCAACTGCGAGGGCGACTGTTACCATTCCGGCGGGACTATTATAAGTAAT

CTACCTTTTCAGAACATAGATTCCAGAGCCGTGGGAAAATGCCCTCGCTACGTGAAACAG

AGGTCCCTGCTTCTGGCTACTGGAATGAAGAATGTTCCAGAGATACCTAAGGGACGGGGC

CTTTTCGGGGCAATCGCCGGATTCATCGAAAATGGGTGGGAAGGGCTGATCGATGGCTGG

TACGGCTTTCGCCATCAGAACGCACAGGGAGAGGGTACAGCGGCTGATTACAAATCGACT

CAAAGTGCTATAGATCAGATTACCGGCAAACTGAACAGGCTGATCGAGAAAACGAATCAA

CAGTTCGAACTGATTGATAACGAGTTTAACGAGGTGGAAAAACAAATCGGAAACGTTATC

AATTGGACGAGGGACAGCATTACCGAAGTGTGGTCGTATAATGCAGAGCTGTTAGTCGCC

ATGGAGAATCAACACACCATCGATCTTGCCGACAGCGAGATGGACAAGCTTTATGAGCGC

GTGAAGAGACAACTGCGAGAAAATGCCGAGGAAGATGGAACCGGATGTTTTGAGATATTC

CACAAGTGCGACGATGATTGTATGGCGAGCATCCGCAACAATACCTATGATCACTCCAAA

TACAGGGAAGAGGCTATGCAAAATAGAATCCAAATTGATCCCGTCAAACTGTCAAGTGGG

TACAAGGATGTGATATTATGGTTTTCCTTTGGCGCCTCATGCTTTATACTGCTGGCTATC

GTGATGGGCTTGGTCTTTATTTGCGTGAAGAATGGCAACATGCGGTGTACAATATGTATT

664
ATGAATACACAAATTCTGGTGTTCGCACTCATTGCTATCATACCCACTAATGCCGATAAG

ATCTGTCTGGGCCACCACGCTGTTAGCAACGGGACCAAAGTTAACACCCTTACCGAGAGG

GGCGTGGAGGTGGTCAACGCAACCGAAACCGTCGAACGGACAAACATCCCGAGGATCTGC

AGTAAAGGAAAGAGAACAGTCGACCTCGGGCAATGTGGACTGCTGGGGACTATTACAGGG

CCCCCCCAATGTGATCAGTTCCTGGAGTTTTCTGCGGATTTAATCATTGAGAGGGGGGAG

GGGAGTGATGTTTGTTACCCAGGTAAGTTTGTTAATGAAGAAGCGCTGCGCCAGATACTT

AGAGAGAGTGGGGGAATCGACAAGGAGGCTATGGGTTTTACCTACAGCGGCATCAGAACA

AATGGCGCCACCAGCGCATGCCGCAGGAGCGGTTCCTCATTCTACGCCGAAATGAAGTGG

CTCCTATCCAATACAGATAACGCCGCCTTCCCCCAGATGACAAAGTCCTACAAAAACACC

CGGAAGAGCCCTGCCCTAATTGTGTGGGGTATCCACCACTCCGTGTCTACGGCCGAGCAG

ACCAAGCTGTACGGAAGCGGCAACAAACTAGTGACCGTAGGATCTAGTAACTATCAGCAG

AGTTTCGTACCTTCACCAGGAGCGCGGCCTCAGGTTAATGGTCTGAGCGGGAGGATCGAT

TTCCATTGGCTTATGCTGAACCCCAATGACACTGTTACGTTTTCTTTCAACGGAGCATTC

ATCGCTCCAGACCGCGCGAGCTTTCTCCGAGGAAAATCAATGGGGATACAGTCTGGGGTC

CAAGTGGACGCTAACTGTGAGGGGGACTGTTATCACTCAGGTGGAACCATTATTTCTAAC

TTGCCATTCCAGAACATAGATTCGCGAGCCGTGGGCAAATGTCCCCGTTACGTGAAACAG

CGTTCCCTCCTGCTAGCCACCGGGATGAAGAACGTACCCGAAATTCCTAAAGGGAGAGGC

CTCTTTGGCGCTATTGCGGGGTTTATTGAAAACGGATGGGAGGGCCTAATTGACGGCTGG

TATGGGTTCAGACATCAGAATGCACAGGGTGAGGGGACAGCTGCTGACTACAAGTCCACG

CAGTCTGCAATAGATCAAATAACCGGCAAACTCAACCGCTTAATCGAGAAAACGAACCAG

CAGTTCGAGCTTATAGACAATGAGTTCAATGAGGTTGAAAAACAGATCGGCAACGTGATT

AATTGGACTCGGGACTCTATCACCGAGGTCTGGAGCTATAACGCAGAGTTGCTGGTCGCC

ATGGAGAATCAGCACACAATAGATCTTGCTGACTCGGAAATGGACAAACTTTACGAAAGG

GTCAAGCGGCAGCTGAGGGAGAACGCTGAAGAAGATGGGACGGGGTGCTTCGAAATTTTT

CATAAGTGCGATGATGATTGTATGGCGTCCATTAGAAATAACACCTACGACCATAGTAAA

TACCGGGAGGAAGCCATGCAGAACAGGATCCAGATCGACCCAGTAAAACTGTCAAGTGGG

TATAAGGATGTTATATTGTGGTTCTCGTTCGGCGCCAGTTGCTTCATCCTCCTCGCTATT

GTCATGGGCCTTGTGTTTATTTGCGTGAAGAATGGAAATATGCGCTGCACCATTTGCATT

665
ATGAATACCCAGATACTGGTGTTTGCCTTAATAGCAATTATCCCAACAAATGCCGACAAG

ATCTGCCTTGGACACCACGCCGTGTCCAATGGTACTAAAGTGAACACCTTGACCGAGCGG

GGGGTGGAGGTGGTAAATGCCACGGAGACTGTCGAACGTACAAATATCCCCCGCATCTGT

TCTAAAGGCAAAAAAACTGTCGACTTGGGCCAGTGCGGACTACTGGGGACGATTACTGGT

CCGCCTCAGTGCGACCAATTCCTCGAATTTAGTGCAGATCTCATTATTGAAAGACGAGAG

GGGAGTGACGTTTGCTATCCAGGCAAGTTCGTTAACGAGGAAGCCCTTAGGCAAATTTTG

AGGGAGTCGGGGGGAATTGATAAAGAAGCAATGGGATTTACTTACAGCGGCATTCGGACC

AACGGTGCTACCTCAGCATGCAGGCGCTCTGGCTCCTCCTTCTACGCTGAGATGAAATGG

CTACTGTCCAACACCGACAATGCAGCATTTCCTCAAATGACTAAGAGCTATAAGAACACA

AGAAAATCCCCCGCCCTCATAGTCTGGGGGATCCACCACTCAGTGTCCACCGCAGAGCAG

ACGAAATTATATGGATCCGGAAATAAACTGGTGACAGTGGGGAGTAGTAACTACCAACAG

AGTTTTGTTCCCAGCCCAGGCGCCAGACCTCAGGTAAATGGACAGTCCGGAAGGATCGAT

TTTCATTGGCTCATGCTAAACCCCAACGATACCGTCACATTCTCATTCAACGGAGCATTT

ATAGCTCCCGACCGGGCTTCATTCCTTCGGGGTAAATCAATGGGCATTCAGTCTGGGGTA

CAAGTGGACGCCAATTGTGAGGGCGACTGCTATCACTCTGGCGGAACAATCATATCTAAT

CTCCCATTCCAGAACATCGATTCCCGCGCAGTCGGCAAGTGTCCAAGGTACGTGAAACAG

CGCTCCCTGTTGTTGGCAACTGGAATGAAAAATGTACCAGAGATTCCTAAGGGACGTGGA

CTGTTCGGAGCTATTGCAGGGTTCATCGAAAATGGGTGGGAGGGCCTAATCGACGGTTGG

TATGGGTTCAGACATCAGAACGCCCAGGGGGAGGGTACTGCCGCCGATTACAAGTCCACC

CAGTCCGCAATTGACCAGATCACGGGTAAATTAAACAGACTCATTGAAAAAACTAATCAG

CAGTTCGAGCTTATTGATAATGAATTTAATGAAGTGGAAAAGCAGATAGGGAATGTGATT

AACTGGACCCGCGACTCTATCACAGAAGTCTGGTCATACAATGCTGAACTGCTTGTCGCC

ATGGAAAATCAGCATACCATAGACCTTGCAGATTCAGAAATGGACAAGCTGTACGAAAGA

GTCAAAAGACAGCTGAGGGAGAATGCCGAGGAGGATGGTACAGGGTGCTTCGAAATCTTC

CACAAGTGCGACGATGACTGTATGGCGAGCATCCGCAATAATACGTATGACCATTCTAAA

TACAGAGAAGAGGCGATGCAGAATCGGATCCAAATCGACCCGGTAAAGCTCAGTTCGGGC

TACAAAGACGTAATACTATGGTTCTCCTTTGGAGCTTCGTGCTTCATTCTCCTAGCTATC

GTCATGGGGTTAGTCTTCATCTGCGTGAAGAATGGTAATATGCGCTGTACAATTTGTATA

666
ATGAACACACAGATCCTAGTGTTTGCCCTCATCGCCATTATTCCAACAAACGCTGATAAG

ATTTGCCTAGGACATCACGCAGTGTCCAACGGAACTAAGGTGAACACCTTAACTGAGAGG

GGAGTAGAGGTGGTGAATGCCACAGAGACTGTTGAAAGAACCAATATTCCCCGTATCTGC

TCAAAGGGGAAGAGAACGGTAGACCTGGGGCAGTGTGGCTTGCTGGGCACCATCACCGGC

CCACCCCAGTGCGATCAGTTTTTGGAATTCTCTGCCGATTTAATAATAGAACGCAGAGAA

GGTTCCGACGTGTGCTACCCTGGAAAATTCGTCAATGAGGAAGCACTGAGGCAGATCTTA

CGCGAGTCCGGAGGCATCGACAAAGAGGCAATGGGATTCACTTACTCCGGAATCCGGACT

AACGGGGCGACGAGCGCCTGCAGGCGTAGCGGCTCCTCTTTTTACGCGGAAATGAAGTGG

CTTCTATCCAACACTGACAATGCCGCTTTTCCACAAATGACCAAGTCTTATAAAAACACA

CGCAAGTCGCCCGCCTTAATAGTGTGGGGCATTCATCATTCCGTGTCAACAGCAGAGCAG

ACTAAGTTGTATGGCAGTGGTTCTAAGTTGGTGACAGTAGGATCCTCCAACTACCAGCAA

AGTTTCGTGCCTAGCCCAGGCGCACGTCCCCAGGTGAACGGCCTTTCAGGGAGGATCGAT

TTCCATTGGCTGATGCTCAACCCCAACGACACTGTTACTTTCTCCTTCAACGGAGCATTT

ATCGCACCAGATCGGGCCTCCTTCTTGCGGGGAAAATCTATGGGAATCCAGAGCGGAGTG

CAGGTGGATGCCAATTGTGAAGGGGATTGCTACCACTCTGGGGGAACAATTATCTCCAAT

TTGCCCTTCCAGAATATCGATTCCCGAGCTGTCGGAAAATGTCCGAGGTATGTCAAGCAG

CGTAGTCTGCTCCTTGCCACGGGCATGAAGAACGTCCCAGAGATTCCCAAGGGCCGGGGC

TTATTCGGGGCTATCGCCGGGTTCATCGAGAACGGATGGGAGGGGCTAATAGACGGCTGG

TATGGCTTCAGGCATCAGAATGCACAAGGTGAAGGAACGGCGGCTGATTATAAATCCACC

CAGAGTGCCATCGATCAGATTACAGGTAAGCTTAACCGGCTAATCGAAAAGACGAATCAG

CAGTTTGAACTCATCGATAACGAGTTCAATGAGGTGGAGAAGCAGATCGGAAATGTCATC

AACTGGACTCGAGACTCGATCACTGAGGTGTGGTCCTACAATGCTGAGCTTCTGGTCGCT

ATGGAAAATCAACACACCATCGATCTGGCAGACTCAGAAATGGACAAGTTGTACGAGCGG

GTGAAGAGACAACTAAGGGAAAACGCCGAGGAAGATGGCACTGGATGCTTTGAAATCTTT

CACAAGTGCGACGATGACTGCATGGCTTCAATCAGAAATAACACCTACGATCACAGCAAG

TACAGAGAAGAAGCAATGCAGAACCGTATTCAAATCGACCCCGTCAAGCTGTCCAGCGGA

TACAAGGATGTGATCCTGTGGTTCTCCTTCGGGGCAAGCTGTTTCATCCTGCTGGCTATA

GTGATGGGCCTGGTCTTCATTTGTGTCAAGTCCAGGAATATGCGGTGTACTATCTGTATT

667
ATGAACACCCAGATACTGGTCTTTGCTCTCATAGCGATCATACCAACCAACGCTGACAAA

ATCTGTCTGGGGCACCACGCGGTGTCTAACGGCACTAAGGTAAACACCCTCACTGAACGC

GGTGTGGAGGTGGTGAACGCCACCGAGACCGTTGAGCGTACAAATATACCCAGGATCTGT

TCCAAGGGTAAAAGGACCGTCGACCTTGGCCAGTGTGGCCTGCTGGGCACCATTACGGGC

CCTCCCCAATGCGATCAATTTCTTGAGTTCAGCGCCGATTTGATCATAGAGCGACGTGAG

GGGTCAGACGTGTGTTACCCTGGGAAATTTGTGAAGGAAGAAGCACTGCGACAGATCCTT

CGAGAGTCTGGAGGGATTGATAAGGAAGCTATGGGCTTCACCTATAGCGGAATCAGGACT

AACGGCGCTACTAGTGCGTGCAGACGATCTGGAAGCAGTTTTTACGCCGAAATGAAGTGG

CTGCTGTCTAATACTGATAATGCCGCCTTCCCACAAATGACCAAGTCCTACAAGAACACA

CGGAAGTCCCCAGCTCTGATCGTGTGGGGCATCCATCACTCGGTCTCCACAGCCGAGCAA

ACAAAGCTTTACGGGTCAGGAAACAAATTGGTAACCGTGGGCTCTAGTAACTATCAACAG

AGCTTCGTCCCGTCCCCCGGTGCACGCCCACAGGTGAACGGTTTAAGTGGGCGCATCGAC

TTCCATTGGCTCATGCTGAACCCTAATGACACAGTGACCTTTTCCTTTAACGGGGCATTC

ATCGCCCCTGATAGGGCATCCTTCCTCCGGGGCAAGAGTATGGGGATACAATCGGGGGTG

CAAGTCGACGCAAATTGCGAGGGTGATTGTTACCACTCTGGGGGTACCATCATTTCCAAC

CTGCCCTTTCAGAACATAGATTCGAGGGCTGTCGGGAAGTGCCCTCGATATGTGAAGCAG

CGGAGTCTCCTGCTGGCAACAGGCATGAAGAACGTCCCCGAGATCCCCAAAGGACGAGGA

CTCTTCGGCGCAATCGCCGGTTTTATAGAGAACGGATGGGAAGGCCTGATCGACGGTTGG

TATGGCTTTCGTCACCAGAACGCGCAGGGTGAGGGCACTGCCGCCGACTATAAGAGCACA

CAGTCCGCCATCGACCAAATTACTGGAAAGCTTAATAGACTAATCGAAAAAACAAACCAA

CAGTTTGAGCTGATTGACAATGAGTTTAATGAGGTGGAGAAGCAGATAGGTAATGTGATA

AATTGGACCCGGGATTCTATTACCGAAGTGTGGTCATACAATGCGGAACTGCTGGTAGCA

ATGGAAAATCAGCACACAATCGATCTGGCCGATAGTGAGATGGACAAGTTGTACGAGAGG

GTTAAGAGGCAGCTTCGGGAAAATGCAGAAGAGGATGGTACCGGGTGTTTTGAAATCTTC

CACAAGTGCGATGACGACTGCATGGCTTCTATCAGAAACAATACATACGACCACAGCAAA

TATCGGGAGGAAGCCATGCAGAACCGAATCCAGATCGATCCCGTCAAGCTTAGCTCGGGC

TATAAAGATGTCATTCTGTGGTTTTCCTTTGGAGCCTCCTGTTTCATCCTCCTAGCCATT

GTGATGGGTCTTGTGTTTATCTGCGTGAAGAACGGCAATATGAGGTGCACTATCTGCATT

668
ATGAATACCCAAATTCTTGTGTTCGCCCTGATCGCTATTATCCCGACGAACGCCGATAAG

ATCTGCCTAGGACACCACGCTGTGAGTAATGGAACCAAGGTGAACACACTGACTGAGAGG

GGCGTGGAGGTGGTGAACGCGACAGAGACCGTGGAACGAACAAATATTCCGAGGATCTGT

TCAAAGGGGAAGAGAACCGTGGATCTGGGCCAGTGCGGACTGCTAGGCACTATTACCGGC

CCACCACAGTGTGACCAGTTCCTGGAGTTTAGTGCCGACCTGATTATTGAAAGGCGCGAG

GGAAGTGACGTTTGTTACCCCGGGAAATTCGTAAATGAGGAGGCCCTCAGACAAATACTA

AGAGAGTCCGGCGGAATTGACAAAGAGGCGATGGGCTTTACATACAGCGGTATAAGAACG

AACGGGGCGACCTCCGCATGTAGGCGTAGTGGCTCAAGTTTCTATGCCGAGATGAAGTGG

CTGCTGAGCAATACAGACAATGCCGCCTTTCCCCAGATGACCAAGTCTTACAAGAATACG

AGAAAAAGTCCAGCACTCATTGTGTGGGGTATCCATCATTCTGTGAGCACAGCAGAACAA

ACAAAGCTGTACGGCTCAGGAAACAAGCTCGTGACTGTGGGCAGCTCTAACTACCAGCAA

TCATTCGTCCCCTCCCCGGGAGCCAGACCACAGGTTAACGGACTGAGTGGGCGAATTGAT

TTCCACTGGCTTATGTTAAACCCCAATGATACTGTGACATTTTCTTTCAACGGCGCGTTT

ATCGCTCCAGATCGTGCCAGTTTTCTGAGGGGGAAGTCCATGGGCATCCAGTCCGGAGTG

CAGGTTGACGCCAATTGTGAAGGGGACTGTTACCATTCTGGTGGGACTATTATTTCGAAC

CTACCCTTCCAGAATATTGACAGCCGGGCCGTTGGTAAATGCCCTCGGTACGTTAAACAA

AGAAGCCTCCTGCTGGCGACCGGAATGAAGAATGTGCCTGAAATTCCGAAAGGACGCGGA

CTGTTCGGCGCTATCGCAGGGTTTATAGAAAACGGTTGGGAGGGCTTAATTAACGGTTGG

TATGGCTTTCGGCACCAGAACGCCCAGGGCGAGGGGACCGCCGCCGACTATAAAAGCACA

CAGTCTGCGATTGATCAGATTACCGGGAAGCTCAACAGGCTCATAGAGAAAACAAACCAA

CAGTTTGAACTGATTGACAATGAATTTAACGAGGTAGAAAAACAGATTGGCAATGTTATC

AACTGGACCAGGGATTCAATTACAGAGGTGTGGTCTTATAATGCCGAGCTATTGGTGGCC

ATGGAAAACCAACATACAATCGACCTCGCCGATTCAGAGATGGACAAGCTGTATGAGAGG

GTCAAAAGACAGTTGCGCGAGAATGCCGAGGAGGACGGGACTGGCTGCTTCGAGATCTTT

CACAAATGCGATGACGACTGTATGGCTAGTATCCGCAACAACACGTATGATCACTCTAAG

TACCGCGAGGAAGCCATGCAGAATCGGATCCAAATTGATCCAGTTAAACTGTCTAGCGGC

TACAAGGATGTGATTCTGTGGTTTTCTTTCGGAGCATCCTGCTTCATCTTGTTAGCCATT

GTGATGGGCCTGGTTTTTATCTGCGTGAAGAACGGCAATATGCGGTGTACTATCTGCATC

669
ATGAATACGCAGATTCTGGTGTTTGCCTTAATAGCTATTATCCCCACTAATGCCGACAAG

ATCTGTTTAGGGCACCACGCTGTATCAAATGGCACCAAAGTCAATACGCTCACCGAACGG

GGGGTGGAAGTTGTGAACGCGACTGAAACTGTCGAAAGAACCAATATTCCGCGAATTTGC

AGTAAGGGAAAGAAGACTGTGGACCTGGGCCAATGTGGCTTGTTGGGCACCATTACCGGT

CCACCGCAGTGCGATCAATTTCTTGAATTCTCTGCAGACCTGATAATCGAACGCCGCGAG

GGCTCTGACGTGTGTTATCCTGGGAAATTTGTTAATGAGGAAGCCCTCAGGCAGATACTC

AGGGAATCTGGCGGTATTGATAAGGAGGCCATGGGGTTCACGTACTCTGGTATACGCACC

AATGGTGCCACATCCGCATGCAGGAGAAGCGGCTCCTCGTTCTATGCAGAAATGAAGTGG

TTGCTGTCGAACACAGACAACGCCGCCTTTCCACAGATGACAAAGAGTTACAAGAACACA

AGGAAGTCACCTGCCCTGATCGTTTGGGGTATTCATCATTCTGTCTCCACAGCTGAGCAG

ACCAAACTGTACGGGTCAGGAAACAAGCTGGTGACTGTGGGTTCCTCGAATTATCAGCAG

AGCTTTGTTCCGTCCCCAGGTGCGAGGCCCCAGGTGAACGGCCAATCCGGGCGCATCGAC

TTTCACTGGCTGATGCTTAACCCAAACGATACTGTGACCTTCTCCTTTAACGGAGCGTTT

ATCGCTCCAGACAGGGCCTCGTTTCTGAGAGGGAAAAGCATGGGAATCCAGTCAGGGGTG

CAGGTGGATGCTAATTGTGAAGGTGACTGTTACCACTCAGGAGGCACAATCATTAGCAAC

CTGCCCTTTCAGAACATTGACTCCAGGGCAGTGGGCAAATGTCCACGGTATGTGAAGCAG

AGAAGCCTCCTCCTGGCCACAGGCATGAAGAACGTGCCAGAGATTCCCAAGGGTAGGGGC

CTGTTCGGTGCTATAGCCGGATTTATTGAGAATGGATGGGAAGGGCTGATCGACGGTTGG

TACGGCTTTAGACACCAGAACGCTCAGGGAGAGGGAACTGCCGCAGACTATAAAAGTACT

CAAAGCGCGATCGACCAGATAACAGGTAAGCTCAACCGTCTCATTGAGAAAACAAACCAG

CAGTTCGAACTCATCGATAACGAGTTTAACGAAGTCGAGAAACAAATTGGAAACGTCATT

AACTGGACTAGAGATTCAATCACTGAGGTGTGGAGCTACAACGCTGAGCTGCTTGTGGCT

ATGGAGAATCAGCATACCATAGATCTGGCTGACTCTGAAATGGATAAACTCTATGAACGA

GTCAAGAGACAGCTCAGGGAGAATGCTGAAGAGGATGGCACAGGATGTTTCGAAATCTTC

CACAAGTGTGACGACGACTGCATGGCAAGCATTAGGAATAACACATATGATCATTCTAAA

TATAGGGAAGAGGCAATGCAGAATCGGATCCAAATTGATCCAGTCAAGTTATCTTCCGGG

TATAAAGACGTGATCCTTTGGTTCAGCTTTGGCGCTTCATGTTTCATCTTGCTTGCCATC

GTCATGGGACTCGTCTTTATCTGCGTCAAAAATGGTAACATGAGATGCACAATTTGTATC

670
ATGAATACCCAGATTTTAGTGTTTGCCCTGATTGCCATAATCCCAACTAACGCCGATAAG

ATTTGCTTGGGCCACCACGCTGTGAGCAACGGCACCAAAGTCAACACCCTGACCGAACGC

GGCGTGGAGGTCGTCAATGCCACCGAAACCGTGGAGCGAACCAACATTCCACGCATCTGT

TCCAAGGGAAAAAGAACGGTTGATCTCGGCCAGTGTGGCCTGCTCGGGACAATCACCGGG

CCGCCGCAGTGCGACCAGTTCCTGGAGTTTAGCGCCGACCTAATCATCGAACGCCGGGAG

GGTTCTGATGTGTGCTACCCTGGCAAATTTGTGAATGAGGAGGCGCTTAGGCAGATTCTC

AGGGAGTCCGGTGGAATTGACAAGGAAGCCATGGGTTTCACATACAGCGGTATTAGGACT

AATGGCGCAACATCAGCTTGTCGAAGATCTGGTTCTAGCTTTTACGCAGAGATGAAATGG

CTTCTATCCAATACTGATAATGCAGCTTTTCCCCAAATTACAAAGTCATATAAAAACACC

CGCAAATCGCCCGCTCTCATAGTGTGGGGAATTCACCATTCCGTTAGTACCGCTGAACAG

ACCAAATTGTATGGGAGCGGTAACAAGCTGGTCACCGTTGGGTCCTCCAATTATCAGCAG

TCGTTCGTGCCGAGTCCTGGAGCCCGCCCCCAGGTCAACGGCCTTTCTGGCCGGATTGAC

TTTCATTGGCTGATGTTGAACCCTAACGACACAGTTACATTCTCATTTAATGGAGCCTTC

ATCGCTCCGGATCGAGCCAGCTTCCTCCGTGGTAAGAGTATGGGGATCCAAAGCGGTGTT

CAGGTCGATGCCAACTGCGAGGGCGATTGTTATCATTCAGGGGGTACTATAATCAGCAAC

CTGCCCTTTCAAAACATAGACAGCAGGGCAGTCGGAAAATGTCCTCGATATGTCAAACAA

CGGTCTCTGTTGCTGGCTACAGGGATGAAGAACGTGCCGGAGATCCCCAAAGGACGTGGA

TTATTTGGGGCCATAGCCGGGTTTATTGAGAATGGATGGGAGGGCCTGATTGATGGATGG

TACGGTTTTCGCCATCAGAATGCACAGGGAGAAGGAACAGCTGCCGACTACAAGTCAACG

CAGAGTGCTATTGACCAGATAACTGGCAAGTTAAACCGGCTGATCGAAAAGACTAATCAA

CAATTTGAGTTGATCGACAATGAGTTTAATGAAGTTGAGAAACAGATCGGCAACGTCATC

AACTGGACGCGCGATAGCATTACAGAAGTCTGGTCTTATAACGCCGAGTTGCTTGTAGCA

ATGGAGAACCAGCATACCATTGATCTCGCGGACAGTGAAATGGACAAGCTCTACGAGCGC

GTAAAGCGACAGCTAAGAGAAAATGCAGAAGAAGATGGGACGGGATGTTTCGAAATCTTC

CACAAATGCGATGACGATTGCATGGCCAGCATACGGAATAATACCTACGATCATTCCAAG

TATCGGGAAGAGGCCATGCAGAACCGCATTCAGATTGATCCCGTGAAACTTTCAAGTGGC

TACAAGGACGTCATCCTGTGGTTCTCTTTCGGGGCAAGTTGTTTTATTCTGCTCGCTATT

GTCATGGGTCTGGTCTTTATCTGTGTCAAAAATGGCAACATGCGGTGCACAATCTGTATT

671
ATGAACACACAGATTCTAGTGTTTGCACTGATTGCTATCATTCCTACAAATGCAGACAAG

ATTTGTCTGGGCCATCACGCCGTCTCGAATGGTACAAAAGTGAATACCCTGACTGAAAGA

GGGGTCGAAGTGGTTAACGCAACAGAGACCGTAGAGAGAACGAATATTCCAAGAATCTGC

TCTAAGGGCAAAAAAACAGTGGATCTGGGTCAGTGTGGACTGTTAGGGACAATCACAGGT

CCACCACAATGCGACCAGTTCCTTGAATTCTCGGCGGATCTTATCATCGAGCGCCGAGAA

GGTTCCGACGTGTGTTACCCAGGAAAATTCGTCAATGAGGAGGCTTTGAGACAGATCTTG

CGCGAAAGCGGTGGCATCGACAAAGAGGCTATGGGATTCACTTACTCTGGAATACGAACT

AACGGTGCCACGTCCGCTTGCCGCAGGAGTGGATCTAGCTTCTATGCAGAGATGAAGTGG

CTATTGAGCAACACTGATAATGCTGCCTTCCCTCAGATGACAAAGAGCTATAAAAACACT

AGAAAGAGCCCAGCATTGATCGTTTGGGGCATTCACCACAGTGTATCCACAGCAGAGCAG

ACCAAACTGTATGGGAGTGGAAACAAGCTTGTTACTGTAGGGTCCAGCAACTATCAACAG

AGCTTTGTTCCGTCACCAGGTGCTCGGCCCCAGGTTAATGGGCAAAGTGGGGGGATCGAC

TTCCACTGGCTGATGCTCAATCCTAATGACACGGTCACATTTTCCTTTAACGGGGCCTTC

ATTGCTCCGGATCGCGCCAGCTTTCTGCGTGGAAAGAGTATGGGTATTCAAAGTGGCGTT

CAGGTCGACGCCAACTGCGAGGGCGACTGCTATCATAGCGGTGGAACAATCATCTCTAAC

CTGCCTTTCCAGAACATCGATAGCAGAGCCGTTGGCAAGTGTCCCAGGTACGTGAAGCAG

CGATCACTGTTGTTGGCTACGGGCATGAAAAACGTCCCAGAGATTCCAAAAGGGAGGGGA

CTATTCGGCGCCATTGCTGGGTTCATTGAAAATGGCTGGGAGGGTCTGATTGATGGATGG

TACGGGTTTAGGCACCAAAACGCCCAAGGCGAAGGGACAGCAGCTGACTATAAATCCACT

CAATCTGCTATCGACCAGATCACTGGAAAACTCAACAGACTTATTGAGAAGACTAATCAG

CAGTTTGAGCTCATCGACAACGAGTTTAATGAAGTGGAGAAGCAGATTGGGAACGTTATC

AACTGGACGAGGGACTCAATCACGGAAGTATGGTCCTACAATGCCGAATTGCTGGTGGCC

ATGGAGAACCAGCACACCATTGACCTGGCGGACTCCGAAATGGATAAACTCTACGAACGA

GTGAAGAGGCAACTCCGAGAAAATGCTGAGGAAGATGGGACCGGTTGTTTCGAGATCTTT

CATAAGTGTGACGATGACTGCATGGCTTCTATTAGAAACAATACTTACGATCACTCAAAA

TATAGAGAAGAGGCAATGCAGAACCGCATTCAGATCGACCCGGTGAAGCTGAGCAGTGGT

TATAAGGATGTCATTTTATGGTTTAGTTTTGGAGCATCTTGTTTTATTTTGCTCGCTATC

GTAATGGGCCTCGTGTTTATCTGCGTGAAAAATGGTAACATGCGGTGCACGATATGCATT

672
ATGAATACGCAGATTTTGGTTTTCGCCTTGATTGCCATTATTCCTACAAACGCCGACAAG

ATCTGCCTGGGACATCACGCCGTGAGTAATGGAACCAAGGTGAATACACTGACCGAGAGG

GGCGTAGAAGTTGTAAATGCTACTGAGACAGTGGAGCGAACAAATATTCCCAGAATTTGC

TCCAAGGGCAAGAAGACTGTCGACCTTGGCCAATGTGGGCTGCTCGGCACGATCACGGGG

CCACCCCAATGTGATCAGTTTCTGGAGTTTTCTGCCGACCTCATTATAGAACGCCGGGAG

GGGAGCGACGTATGCTACCCCGGTAAGTTCGTAAACGAAGAAGCCCTCAGACAGATTTTG

AGGGAGTCCGGAGGCATCGATAAGGAGGCAATGGGCTTCACCTACAGCGGCATCAGAACA

AACGGTGCCACAAGTGCATGTAGGCGCTCTGGCTCATCATTCTATGCAGAGATGAAGTGG

CTGCTTTCCAATACTGATAATGCGGCCTTTCCTCAGATGACTAAATCATATAAGAACACC

AGAAAATCTCCCGCCTTGATCGTCTGGGGGATCCATCACAGCGTCTCTACCGCTGAGCAG

ACCAAACTCTACGGTTCAGGGAACAAATTAGTGACCGTTGGCAGCTCCAACTACCAGCAA

TCATTTGTGCCTTCCCCAGGTGCCAGGCCGCAAGTAAACGGTCAGTCAGGACGAATTGAT

TTCCACTGGCTAATGCTGAACCCGAATGACACAGTCACCTTCAGCTTTAACGGGGCTTTC

ATCGCACCCGACCGCGCCAGTTTCTTACGGGGAAAATCAATGGGAATACAATCCGGCGTT

CAAGTGGACGCGAATTGCGAGGGAGATTGTTACCATAGTGGTGGTACAATTATCTCCAAT

CTTCCCTTTCAGAATATCGACAGTAGGGCAGTGGGAAAATGTCCCCGATACGTCAAACAG

CGGAGCCTGCTCCTCGCCACCGGGATGAAGAACGTCCCCGAGATTCCAAAAGGTAGGGGT

TTGTTCGGAGCTATCGCAGGGTTCATCGAAAACGGCTGGGAAGGCCTGATAGACGGTTGG

TATGGATTCCGACACCAAAACGCTCAAGGCGAGGGCACTGCAGCAGATTACAAATCTACA

CAAAGCGCTATCGACCAGATTACCGGAAAACTTAACCGTCTAATCGAAAAGACCAATCAG

CAGTTCGAGCTCATCGATAACGAATTCAATGAGGTGGAGAAACAGATCGGAAACGTAATC

AATTGGACACGAGATTCCATCACTGAGGTTTGGTCTTATAACGCCGAACTCTTAGTGGCT

ATGGAGAATCAGCACACCATCGACCTGGCTGATTCCGAGATGGACAAGCTGTACGAAAGA

GTGAAGAGACAGCTTCGCGAAAACGCAGAGGAGGATGGGACCGGATGTTTCGAAATCTTC

CACAAATGTGATGATGATTGCATGGCCAGCATCCGGAACAACACATATGATCATTCGAAA

TATCGCGAGGAGGCTATGCAAAATCGGATCCAGATCGATCCCGTCAAGCTAAGCTCTGGG

TACAAGGACGTGATTTTATGGTTTTCCTTCGGCGCTTCATGTTTCATCCTTCTGGCCATC

GTGATGGGCCTAGTGTTTATCTGCGTCAAGAATGGAAACATGAGATGTACGATCTGCATC

673
ATGAACACTCAGATTCTGGTATTTGCGCTAATCGCAATCATTCCCACCAACGCAGACAAG

ATTTGTCTGGGACATCATGCCGTGAGCAACGGCACAAAAGTGAACACTCTGACTGAAAGG

GGAGTGGAGGTTGTAAATGCGACCGAAACTGTGGAAAGAACCAATATACCCCGAATCTGT

AGCAAGGGTAAAAAGACCGTAGACTTAGGACAGTGTGGTCTCTTGGGGACAATCACAGGC

CCCCCTCAATGTGACCAGTTCTTAGAGTTTAGCGCAGATTTGATTATCGAGCGAAGGGAG

GGAAGTGACGTTTGTTACCCTGGGAAGTTCGTGAATGAAGAAGCTCTCCGTCAGATCTTG

AGGGAGTCCGGAGGCATAGACAAAGAGGCCATGGGGTTCACTTACTCCGGGATTCGCACA

AATGGAGCTACAAGTGCCTGTAGAAGGTCAGGCAGTTCTTTCTATGCTGAGATGAAATGG

CTCTTATCAAACACAGACAACGCTGCCTTCCCACAGATGACAAAATCCTACAAAAACACT

CGCAAATCCCCAGCCCTTATCGTGTGGGGGATCCATCACTCCGTGTCCACTGCGGAACAG

ACTAAGCTGTATGGATCCGGGAACAAACTGGTAACTGTAGGGAGTAGCAACTACCAGCAG

TCCTTCGTCCCATCTCCTGGGGCACGCCCCCAGGTAAACGGACAGTCTGGAAGAATTGAT

TTCCACTGGTTGATGCTGAACCCAAATGATACTGTGACCTTCTCTTTCAATGGCGCTTTC

ATCGCGCCCGATCGCGCTAGCTTCCTAAGGGGAAAATCCATGGGGATTCAGTCTGGCGTC

CAGGTCGATGCAAATTGCGAAGGCGACTGTTACCATTCTGGAGGGACCATTATCAGTAAC

CTGCCATTCCAGAATATTGACTCGAGGGCAGTGGGTAAGTGCCCCAGGTACGTGAAACAA

AGATCACTGCTTCTGGCTACAGGAATGAAGAACGTACCTGAGATCCCTAAAGGGGGGGGA

TTATTCGGAGCCATCGCAGGCTTCATAGAGAACGGGTGGGAGGGCCTGATTGATGGGTGG

TACGGATTCAGGCACCAAAATGCCCAGGGAGAAGGGACCGCTGCGGATTACAAGAGTACC

CAGTCCGCTATAGACCAGATCACAGGCAAACTTAATAGGCTGATTGAAAAGACCAATCAG

CAGTTTGAACTCATCGATAACGAATTTAACGAGGTGGAAAAGCAGATTGGGAACGTGATT

AACTGGACAAGGGATTCTATTACCGAGGTGTGGAGCTACAATGCCGAGCTGTTGGTTGCG

ATGGAGAATCAGCACACTATCGATCTAGCAGACTCCGAAATGGACAAGTTGTATGAAAGA

GTGAAGCGCCAATTAAGGGAAAACGCAGAGGAGGATGGGACCGGATGTTTTGAGATCTTC

CATAAATGCGATGACGACTGCATGGCCAGCATTAGAAATAATACCTACGACCATAGTAAG

TATAGGGAGGAGGCGATGCAAAACAGAATTCAAATAGACCCAGTGAAACTGAGTTCTGGG

TACAAAGACGTTATTCTCTGGTTTTCATTCGGCGCCAGCTGCTTTATACTGCTGGCTATC

GTCATGGGCTTGGTCTTCATCTGCGTGAAAAACGGGAATATGCGATGCACAATTTGTATT

674
ATGAATACCCAGATCCTGGTGTTCGCTCTCATCGCCATCATACCAACAAACGCTGACAAG

ATCTGCCTAGGTCACCACGCTGTGTCTAATGGAACCAAAGTGAATACACTGACCGAGCGC

GGTGTGGAGGTGGTGAACGCTACAGAGACCGTGGAACGCACTAATATCCCTCGAATATGT

TCTAAGGGCAAGAAAACTGTAGATCTGGGGCAGTGCGGCCTTCTGGGAACTATCACGGGC

CCTCCACAGTGCGATCAATTTTTGGAGTTTTCTGCCGACCTCATCATCGAACGCCGTGAG

GGATCGGACGTGTGTTATCCAGGAAAGTTTGTGAATGAGGAAGCGCTCCGGCAGATCTTA

AGAGAAAGCGGTGGTATTGACAAAGAAGCAATGGGCTTCACCTATTCAGGAATTAGGACC

AACGGAGCAACCAGTGCGTGTAGACGAAGCGGGTCTTCATTCTACGCCGAAATGAAGTGG

CTGCTTTCTAACACCGATAACGCAGCATTCCCACAAATGACCAAGAGCTACAAGAATACA

AGAAAATCCCCTGCATTAATTGTATGGGGAATCCATCACTCCGTCTCAACAGCAGAACAG

ACAAAACTTTATGGCAGTGGCAACAAACTCGTCACCGTTGGTAGCTCCAACTACCAGCAG

TCTTTCGTGCCAAGTCCCGGGGCCCGACCGCAAGTGAACGGGCAGTCTGGCAGAATCGAC

TTTCACTGGCTCATGCTGAATCCAAACGACACAGTTACCTTCAGCTTCAATGGGGCATTC

ATTGCCCCAGACAGAGCCAGCTTTCTTCGAGGCAAGAGCATGGGCATCCAGAGCGGGGTA

CAGGTCGACGCAAACTGTGAAGGAGATTGCTACCACTCCGGGGGGACGATCATTTCGAAT

CTGCCATTCCAGAATATCGACTCTAGGGCTGTGGGGAAATGTCCTAGGTATGTGAAACAG

CGGAGCCTCCTTCTGGCAACAGGAATGAAAAACGTACCTGAGATCCCTAAGGGGCGAGGA

TTGTTTGGTGCCATCGCGGGATTCATTGAAAATGGCTGGGAGGGATTGATTGACGGCTGG

TACGGATTCCGGCATCAAAACGCGCAAGGGGAGGGTACGGCGGCAGATTACAAAAGCACT

CAGTCCGCGATCGACCAGATCACCGGCAAACTCAATAGACTTATCGAGAAGACTAACCAA

CAGTTCGAGCTCATCGACAATGAGTTTAATGAAGTAGAGAAACAGATCGGCAATGTCATA

AACTGGACCAGGGACAGCATCACCGAAGTGTGGTCCTATAACGCCGAGCTCCTGGTGGCC

ATGGAGAATCAGCACACTATAGACTTAGCTGACTCTGAGATGGACAAGCTCTATGAGAGA

GTTAAACGGCAGCTCAGAGAAAACGCAGAAGAAGATGGCACCGGGTGCTTCGAGATCTTT

CATAAATGTGATGACGACTGCATGGCCTCGATACGTAACAATACATATGATCATAGTAAG

TATCGGGAGGAAGCAATGCAGAACAGGATTCAGATCGACCCCGTTAAATTGTCCAGCGGC

TATAAGGACGTAATTCTGTGGTTCTCGTTTGGCGCCTCCTGTTTCATTTTGTTGGCCATT

GTGATGGGTCTCGTCTTCATTTGCGTAAAAAATGGCAATATGCGGTGCACTATTTGTATC

675
ATGAATACTCAGATCCTAGTTTTTGCTCTGATTGCCATAATTCCGACGAATGCGGACAAG

ATTTGCCTGGGACACCACGCTGTCAGTAACGGTACCAAAGTAAATACCCTGACGGAGCGA

GGTGTCGAGGTGGTGAATGCCACCGAAACTGTGGAGAGAACCAACATCCCTCGGATCTGT

AGCAAGGGCAAGAAAACTGTGGACCTCGGTCAGTGTGGGTTGCTCGGGACCATTACAGGC

CCCCCACAGTGCGATCAATTTCTGGAGTTCTCTGCCGACTTAATTATTGAAAGACGGGAG

GGTAGCGACGTTTGTTATCCCGGCAAATTCGTAAATGAGGAGGCCTTGCGCCAGATTTTG

CGCGAGTCCGGCGGCATTGATAAAGAGGCTATGGGATTCACTTATTCTGGCATTAGGACA

AACGGCGCGACCAGTGCATGTCGCCGATCCGGCTCCTCCTTTTACGCTGAGATGAAATGG

CTGTTGTCGAACACTGACAACGCTGCATTTCCACAGATGACAAAGTCCTATAAGAACACC

AGGAAGAGTCCGGCCCTGATCGTGTGGGGAATACATCACTCTGTGTCCACCGCCGAACAG

ACCAAGCTGTACGGAAGTGGCAATAAGCTGGTTACTGTCGGGAGCAGCAATTACCAGCAG

AGTTTTGTGCCGTCACCCGGGGCCCGGCCTCAGGTGAATGGTCAGTCCGGTAGAATAGAC

TTCCACTGGCTTATGCTAAACCCAAATGACACCGTTACCTTCTCATTTAACGGTGCCTTT

ATTGCCCCCGACCGGGCTTCATTCCTGCGCGGGAAATCCATGGGCATCCAATCTGGGGTG

CAGGTTGACGCTAATTGTGAGGGAGACTGTTATCATAGCGGAGGCACCATAATCTCCAAT

CTGCCCTTCCAGAACATTGACAGCAGAGCAGTAGGCAAATGCCCCAGGTATGTCAAGCAA

CGAAGCCTTCTTCTCGCTACCGGTATGAAGAATGTGCCCGAAATACCAAAGGGACGGGGG

CTCTTTGGCGCGATAGCCGGGTTCATCGAGAATGGATGGGAGGGACTCATTGACGGTTGG

TATGGGTTCCGCCATCAGAACGCGCAGGGGGAAGGCACAGCAGCCGACTATAAGTCCACA

CAGAGTGCAATTGACCAAATTACCGGCAAATTAAACAGACTCATTGAGAAGACTAACCAG

CAGTTTGAGTTAATTGATAATGAGTTTAACGAAGTGGAGAAACAAATTGGAAACGTGATC

AACTGGACACGAGATAGCATTACGGAGGTATGGTCATATAACGCCGAGCTGCTCGTTGCG

ATGGAGAATCAACACACAATTGATTTAGCAGACTCCGAAATGGACAAACTTTACGAACGG

GTGAAACGCCAGCTGCGCGAAAACGCTGAAGAAGATGGGACAGGTTGCTTTGAAATTTTT

CACAAGTGCGATGATGACTGCATGGCCTCAATCCGTAATAATACATACGATCACAGCAAG

TATAGGGAAGAAGCCATGCAGAATAGGATTCAAATAGACCCGGTGAAATTATCTTCTGGC

TATAAAGATGTTATTCTGTGGTTCTCCTTCGGCGCGTCATGTTTCATTTTATTGGCCATT

GTGATGGGCCTGGTTTTCATATGCGTGAAGAACGGAAATATGAGATGCACCATCTGTATT

676
ATGAACACACAAATCCTGGTGTTTGCCTTAATAGCTATTATCCCAACCAACGCAGACAAG

ATCTGTCTTGGACACCATGCTGTAAGCAATGGAACCAAAGTGAACACATTGACCGAGCGT

GGGGTCGAAGTGGTTAACGCCACCGAGACAGTGGAGAGGACTAATATCCCCAGAATTTGT

AGTAAAGGGAAGAGGACAGTTGACTTAGGACAATGCGGACTGTTGGGTACCATTACAGGT

CCACCCCAGTGTGATCAGTTTCTGGAATTCAGCGCTGATTTGATCATCGAGCGGAGAGAA

GGCAGTGATGTCTGTTACCCTGGGAAATTCGTCAACGAAGAGGCATTGCGCCAGATTTTG

AGGGAATCCGGCGGAATCGACAAAGAAGCCATGGGGTTCACATACTCAGGGATCCGGACG

AATGGCGCAACGAGCGCTTGTAGGAGGTCCGGGAGTTCTTTCTATGCGGAGATGAAATGG

CTATTGAGCAACACAGATAATGCCGCTTTCCCTCAAATGACCAAGTCATACAAAAATACA

AGGAAGAGCCCAGCCCTTATCGTGTGGGGTATCCATCACAGTGTGTCTACCGCAGAACAG

ACAAAACTCTACGGCAGCGGGAACAAACTTGTGACCGTCGGCTCTTCAAACTATCAACAG

AGTTTCGTTCCGTCTCCAGGCGCAAGGCCACAGGTGAATGGATTAAGTGGGCGGATCGAT

TTTCATTGGCTTATGCTCAACCCTAATGATACAGTCACATTCTCTTTTAATGGAGCTTTC

ATTGCCCCAGACAGGGCGTCCTTCCTGCGAGGCAAATCTATGGGTATACAAAGCGGCGTC

CAGGTAGACGCAAATTGTGAGGGTGATTGCTACCACAGCGGGGGAACCATTATCAGCAAC

TTGCCATTCCAAAACATCGATTCCCGTGCTGTGGGCAAGTGTCCAAGATATGTGAAACAG

AGGAGTCTGTTGTTGGCGACGGGAATGAAAAACGTTCCCGAGATTCCAAAGGGCCGGGGA

CTTTTTGGGGCCATCGCCGGATTCATAGAGAACGGCTGGGAAGGACTCATTAATGGATGG

TATGGGTTCCGGCATCAGAACGCTCAGGGGGAGGGCACCGCTGCTGACTACAAGAGTACC

CAGTCTGCCATCGATCAGATTACCGGTAAGTTGAATAGGCTGATCGAGAAAACTAACCAG

CAGTTTGAGCTCATTGATAATGAATTCAACGAGGTAGAAAAACAGATAGGCAACGTGATT

AACTGGACCCGTGACTCCATAACGGAGGTATGGAGTTATAATGCAGAACTCCTCGTGGCT

ATGGAAAATCAGCACACAATTGATTTAGCTGACTCAGAAATGGATAAGCTGTACGAGCGG

GTCAAACGCCAACTGCGCGAGAATGCAGAAGAAGACGGGACCGGGTGTTTCGAAATCTTT

CATAAATGCGACGATGACTGTATGGCCAGCATCCGTAACAACACTTACGACCACAGCAAG

TATCGGGAGGAAGCTATGCAAAATAGGATCCAGATCGACCCTGTCAAATTATCCAGTGGG

TACAAAGATGTCATCCTGTGGTTTTCCTTTGGCGCGTCATGCTTTATTTTGTTGGCTATC

GTGATGGGCCTCGTTTTTATCTGTGTGAAGAATGGAAACATGCGATGCACCATCTGTATT

677
ATGAACACTCAGATTCTGGTGTTCGCACTAATCGCAATCATACCTACTAATGCCGACAAA

ATTTGCCTCGGCCACCATGCCGTGTCAAATGGCACAAAAGTGAATACCCTGACGGAGCGC

GGCGTCGAGGTTGTCAATGCCACAGAGACAGTGGAACGGACCAACATTCCACGTATTTGT

TCAAAAGGCAAGCGTACCGTTGACCTGGGTCAGTGCGGACTTCTCGGGACAATCACTGGA

CCACCACAGTGCGATCAGTTCTTGGAGTTTTCAGCAGACCTTATCATCGAGAGGGGGGAA

GGTAGCGACGTTTGCTACCCCGGCAAATTTGTTAATGAAGAAGCCTTAAGGCAGATCCTA

CGAGAATCAGGGGGCATTGACAAAGAAGCGATGGGATTCACTTACAGTGGAATTAGAACA

AACGGTGCCACGTCTGCTTGCAGACGCTCGGGCTCTAGCTTTTATGCTGAAATGAAATGG

TTGCTGAGCAATACCGATAATGCTGCCTTCCCACAGATGACAAAAAGTTACAAGAATACT

AGAAAGTCACCCGCACTGATCGTCTGGGGGATTCACCATTCAGTCAGCACCGCCGAGCAG

ACCAAACTTTATGGTAGCGGTAACAAGTTAGTGACAGTTGGAAGCTCCAATTATCAACAG

TCATTTGTGCCATCTCCCGGGGCTCGACCCCAAGTGAACGGGTTAAGTGGTCGGATCGAC

TTCCACTGGTTGATGCTCAACCCTAACGACACAGTCACATTCTCCTTCAACGGCGCATTC

ATAGCCCCCGACCGGGCAAGCTTCCTAAGGGGAAAGAGTATGGGAATCCAGTCTGGGGTG

CAAGTTGATGCCAACTGCGAAGGGGATTGCTATCATTCCGGCGGGACAATTATAAGCAAC

CTGCCATTCCAGAACATCGATTCACGGGCAGTCGGGAAGTGCCCCAGGTATGTGAAGCAG

CGGTCACTGCTGTTGGCTACTGGCATGAAAAACGTGCCGGAGATCCCAAAAGGCCGTGGG

CTCTTCGGGGCTATCGCCGGGTTTATCGAGAACGGCTGGGAGGGCCTGATTAATGGGTGG

TATGGCTTTAGGCATCAGAACGCGCAAGGAGAGGGAACCGCGGCCGACTATAAGAGCACA

CAGTCTGCGATCGATCAAATAACCGGTAAGCTCAATCGGCTGATTGAAAAAACCAACCAG

CAGTTTGAGCTAATCGACAATGAATTCAACGAGGTGGAAAAGCAGATTGGTAACGTCATT

AATTGGACAAGAGACAGTATTACTGAGGTGTGGAGTTATAACGCTGAACTGCTGGTTGCC

ATGGAGAATCAGCACACTATTGACCTGGCAGATTCTGAGATGGATAAGCTCTATGAGAGA

GTGAAACGGCAGCTGAGAGAGAATGCTGAAGAGGATGGAACCGGGTGCTTCGAAATTTTT

CATAAGTGTGATGACGATTGTATGGCCTCGATTAGAAATAATACATACGATCACTCCAAG

TACCGAGAGGAGGCCATGCAGAACAGGATCCAAATTGACCCGGTTAAGCTGAGTAGTGGC

TACAAGGATGTTATATTATGGTTTAGCTTCGGAGCCTCCTGCTTCATACTGCTGGCTATT

GTGATGGGGTTAGTCTTTATCTGCGTGAAAAATGGGAACATGAGATGTACAATCTGTATA

678
ATGAACACGCAGATCCTAGTCTTTGCCCTTATTGCCATAATCCCTACCAACGCCGATAAG

ATCTGCCTCGGTCACCACGCCGTTTCCAATGGCACAAAGGTGAATACTTTGACAGAACGG

GGGGTTGAGGTGGTCAATGCTACCGAAACCGTAGAGCGAACAAATATCCCGAGAATATGT

TCCAAAGGCAAGAAGACCGTGGACCTCGGACAGTGTGGATTACTCGGGACAATCACAGGT

CCCCCACAGTGCGATCAGTTCTTGGAATTCTCTGCCGACCTCATTATCGAACGGAGAGAA

GGATCGGATGTGTGTTATCCTGGCAAGTTCGTCAATGAGGAAGCTCTTAGACAGATCTTA

CGCGAGAGTGGTGGCATCGACAAGGAAGCAATGGGTTTCACATATAGCGGAATTCGGACT

AATGGAGCAACTTCAGCTTGTAGGAGAAGCGGCTCATCTTTTTATGCCGAAATGAAGTGG

CTGTTATCTAACACCGATAACGCTGCCTTCCCACAGATGACGAAATCATACAAGAACACT

AGGAAGAGCCCAGCTCTGATTGTGTGGGGTATTCATCATAGTGTCTCCACGGCGGAACAG

ACTAAGCTGTATGGGTCCGGCAATAAACTTGTCACCGTAGGCAGCAGCAACTACCAGCAG

AGCTTCGTGCCTAGCCCAGGAGCTAGGCCCCAGGTGAATGGACAGTCTGGGCGAATAGAC

TTCCACTGGCTTATGCTCAATCCGAATGACACAGTGACATTCAGCTTCAATGGGGCTTTT

ATTGCTCCAGACAGAGCCAGCTTCCTGAGAGGCAAATCAATGGGGATCCAAAGCGGAGTA

CAGGTTGACGCCAACTGTGAAGGCGATTGCTACCACTCAGGGGGCACAATTATCTCTAAC

CTGCCATTCCAGAATATTGATTCGAGAGCTGTGGGGAAGTGTCCTAGGTATGTAAAACAG

CGGAGCCTGCTCCTCGCTACAGGGATGAAGAATGTCCCGGAAATCCCAAAAGGACGGGGC

CTGTTTGGCGCAATTGCCGGCTTCATAGAGAATGGGTGGGAGGGACTGATCGATGGATGG

TACGGGTTTCGCCACCAGAACGCCCAGGGAGAAGGGACAGCCGCTGATTACAAATCCACA

CAAAGCGCAATCGACCAGATCACAGGTAAACTGAATAGGCTCATCGAGAAGACCAATCAG

CAATTCGAACTTATCGACAATGAGTTTAATGAGGTGGAGAAACAAATCGGAAATGTGATC

AATTGGACGCGAGATTCTATTACTGAGGTGTGGTCATACAATGCCGAACTCCTTGTGGCT

ATGGAAAATCAGCACACCATAGACCTGGCCGACTCCGAGATGGATAAGCTATACGAGCGC

GTCAAGCGCCAGCTGAGGGAAAATGCTGAGGAAGACGGAACGGGTTGCTTCGAAATTTTT

CACAAGTGCGACGATGACTGCATGGCCTCTATTAGAAATAATACATACGACCACTCTAAG

TATAGGGAAGAGGCCATGCAGAATCGCATACAGATCGATCCTGTGAAACTCTCCAGCGGG

TATAAGGATGTCATTCTGTGGTTCAGTTTCGGCGCTAGCTGTTTTATACTTTTGGCTATT

GTTATGGGTCTAGTGTTTATTTGCGTGAAAAACGGCAATATGCGGTGCACAATATGCATT

679
ATGAATACCCAGATCCTTGTCTTCGCATTAATAGCAATCATTCCAACCAATGCTGACAAG

ATCTGTCTGGGTCACCATGCAGTTTCCAATGGCACAAAAGTTAATACACTGACAGAACGC

GGGGTGGAAGTAGTCAACGCCACCGAAACCGTAGAGAGGACCAATATCCCCAGGATCTGC

TCAAAGGGAAAGCGTACAGTGGACCTGGGACAGTGTGGGCTGCTCGGCACAATTACAGGA

CCACCACAGTGTGACCAGTTCCTGGAGTTTAGCGCTGACTTAATAATCGAGAGAAGAGAG

GGAAGCGACGTCTGTTATCCTGGCAAGTTTGTCAAGGAGGAGGCTCTTAGGCAGATCTTG

AGAGAGTCGGGCGGCATAGATAAAGAGGCAATGGGATTCACCTATTCAGGGATTAGGACC

AATGGTGCCACAAGTGCCTGCAGAAGATCAGGCTCTAGTTTTTACGCTGAGATGAAGTGG

CTTCTGTCGAACACAGATAACGCCGCGTTCCCTCAGATGACTAAGTCATACAAAAATACA

CGCAAAAGTCCTGCCTTAATCGTGTGGGGGATACATCATAGTGTATCCACCGCCGAGCAG

ACTAAGCTCTACGGTAGCGGTAATAAGCTGGTCACTGTGGGCAGTTCCAACTACCAGCAG

AGTTTTGTTCCCAGCCCCGGTGCTCGTCCCCAAGTGAACGGACTTAGCGGTAGGATTGAC

TTTCATTGGCTGATGTTGAATCCTAATGACACGGTCACTTTTAGTTTCAACGGCGCTTTC

ATCGCTCCCGATAGAGCTTCCTTCTTGCGCGGAAAGAGTATGGGGATACAGTCAGGCGTG

CAGGTCGACGCGAATTGTGAAGGGGATTGCTACCATAGTGGAGGCACTATTATCTCAAAC

CTCCCTTTCCAGAACATCGACAGTAGGGCCGTGGGAAAATGCCCTAGGTACGTTAAGCAG

AGATCCCTATTGCTGGCCACGGGTATGAAGAATGTCCCCGAAATTCCAAAAGGAAGAGGA

CTGTTCGGCGCCATCGCTGGCTTTATCGAGAACGGGTGGGAGGGGCTCATCGACGGGTGG

TACGGGTTCAGACACCAGAATGCCCAAGGGGAGGGCACCGCCGCTGACTACAAATCTACG

CAAAGTGCCATTGACCAGATTACCGGAAAGCTCAACCGGCTGATTGAGAAGACCAACCAG

CAATTTGAGCTAATTGACAATGAATTTAACGAGGTCGAGAAGCAAATTGGGAACGTCATA

AACTGGACTAGGGATTCAATTACCGAAGTCTGGAGCTATAACGCAGAACTATTGGTCGCT

ATGGAGAACCAGCACACAATCGATCTCGCTGATTCTGAGATGGATAAGCTGTATGAGAGG

GTGAAGAGACAGTTGAGGGAGAATGCTGAGGAGGATGGTACCGGCTGTTTTGAAATCTTT

CATAAGTGTGACGATGACTGTATGGCTTCAATCCGGAACAATACGTACGATCACAGTAAA

TATAGGGAAGAAGCTATGCAGAACAGAATTCAGATTGATCCTGTGAAACTAAGCAGTGGT

TATAAAGATGTGATCCTCTGGTTCAGTTTCGGCGCCAGCTGTTTCATCCTGCTCGCCATC

GTAATGGGACTGGTCTTCATATGCGTGAAGAATGGAAACATGCGTTGCACCATCTGTATT

680
ATGAATACACAGATTCTGGTGTTCGCTTTGATAGCGATCATTCCAACAAATGCAGACAAG

ATCTGCCTCGGTCATCACGCGGTTTCAAATGGCACCAAAGTGAACACTCTCACCGAACGG

GGGGTCGAGGTAGTTAACGCGACCGAGACTGTGGAGCGTACTAATATCCCCAGGATCTGT

TCAAAGGGAAAGAGAACTGTGGACCTTGGGCAGTGTGGTCTGCTGGGCACCATCACTGGC

CCCCCCCAGTGTGACCAGTTCCTGGAGTTCTCAGCCGACCTTATAATTGAGCGACGCGAA

GGATCTGATGTATGCTACCCAGGCAAGTTTGTGAAAGAGGAGGCGTTACGCCAGATTCTG

AGAGAGTCTGGTGGGATCGACAAAGAAGCGATGGGTTTCACATACAGCGGGATCCGGACC

AACGGTGCCACCTCGGCATGTCGTCGTAGCGGCTCATCCTTCTACGCCGAGATGAAATGG

CTGCTGTCAAACACCGACAACGCCGCTTTCCCGCAGATGACTAAGAGCTACAAAAACACC

AGAAAGTCACCCGCCCTGATTGTGTGGGGAATTCATCACTCTGTGTCTACCGCCGAACAG

ACCAAATTGTATGGTTCGGGGAATAAGCTGGTTACGGTAGGATCGTCAAATTACCAACAA

AGCTTTGTGCCCTCTCCAGGAGCCAGACCTCAGGTAAACGGCCTCTCAGGAAGGATTGAC

TTCCACTGGCTGATGCTGAATCCCAATGATACCGTAACATTCTCATTTAATGGCGCGTTC

ATCGCACCGGATAGGGCATCCTTCTTAAGGGGGAAGAGTATGGGCATCCAGTCCGGGGTT

CAAGTGGATGCCAATTGCGAAGGCGATTGTTACCACTCCGGAGGAACGATTATTAGCAAT

CTGCCCTTCCAAAACATCGACTCTAGGGCCGTGGGCAAATGCCCTAGATATGTGAAGCAG

AGGTCCCTGCTCCTAGCGACTGGCATGAAGAATGTGCCCGAGATACCAAAAGGGAGAGGA

CTATTCGGTGCCATCGCCGGGTTCATTGAAAACGGATGGGAAGGCCTCATCGATGGGTGG

TACGGATTTCGGCACCAGAATGCGCAAGGGGAAGGTACTGCTGCTGATTATAAGAGCACT

CAGAGCGCTATTGATCAGATTACCGGTAAATTGAACCGTCTCATTGAAAAGACGAACCAG

CAGTTCGAGCTGATCGATAATGAGTTTAATGAAGTGGAAAAGCAAATCGGGAACGTGATC

AACTGGACAAGAGACTCAATCACTGAAGTCTGGTCCTACAATGCCGAGCTTTTGGTTGCC

ATGGAGAACCAGCATACGATCGACCTTGCCGATAGCGAGATGGACAAACTATACGAGCGA

GTCAAGAGGCAACTCAGAGAAAATGCAGAAGAGGATGGAACCGGCTGTTTCGAGATCTTT

CATAAGTGCGACGACGATTGCATGGCTTCCATTAGAAATAACACCTACGACCACTCTAAG

TATAGAGAGGAGGCTATGCAAAATCGCATCCAGATTGATCCGGTGAAACTCTCCTCGGGG

TACAAAGATGTGATCCTGTGGTTCTCCTTTGGCGCAAGCTGTTTCATTTTATTAGCTATT

GTGATGGGGCTCGTCTTTATCTGCGTGAAGAATGGCAACATGCGGTGTACCATCTGTATA

681
ATGAACACTCAGATACTCGTCTTTGCGCTCATCGCTATTATTCCTACCAACGCGGATAAA

ATTTGCCTCGGGCACCACGCAGTGTCCAACGGAACTAAAGTGAACACGCTGACTGAACGT

GGTGTGGAAGTGGTGAACGCAACAGAAACAGTGGAAAGGACTAATATTCCGCGTATATGC

AGTAAGGGTAAGAAGACGGTCGACCTGGGGCAGTGCGGGCTTCTCGGTACCATCACGGGT

CCTCCTCAGTGTGATCAGTTCCTTGAGTTTTCAGCCGACCTCATCATTGAACGTCGTGAG

GGAAGTGATGTTTGTTATCCCGGGAAGTTCGTGAACGAAGAGGCATTGAGACAGATTCTG

CGGGAGTCTGGGGGAATCGATAAGGAGGCCATGGGTTTCACATACTCCGGTATCAGGACT

AACGGCGCAACCTCCGCCTGCCGGCGAAGCGGCAGCTCTTTCTACGCTGAAATGAAGTGG

CTGTTGTCTAACACCGATAACGCCGCTTTCCCTCAGATGACCAAATCCTATAAGAATACG

AGAAAGTCTCCTGCTCTCATCGTATGGGGGATCCACCATAGTGTGTCTACCGCCGAGCAG

ACCAAACTGTACGGCTCAGGCAACAAATTGGTGACTGTAGGGAGCAGTAATTATCAGCAA

AGCTTCGTTCCTTCCCCTGGAGCCAGACCTCAGGTGAATGGACAGTCAGGGCGGATCGAT

TTCCATTGGCTGATGCTGAACCCAAACGATACAGTGACATTCTCATTCAATGGCGCGTTC

ATAGCCCCAGATCGCGCCTCTTTCCTGCGCGGGAAATCAATGGGCATTCAATCTGGGGTA

CAGGTGGACGCTAACTGTGAGGGGGACTGCTATCATTCCGGGGGCACAATTATTAGTAAC

CTCCCTTTCCAGAACATTGATTCCAGAGCCGTGGGTAAGTGCCCGCGGTACGTGAAGCAG

AGGTCACTGCTGCTAGCCACCGGAATGAAAAATGTGCCTGAAATCCCAAAAGGACGGGGC

TTATTCGGCGCTATTGCTGGCTTCATCGAAAATGGGTGGGAGGGGTTGATCGACGGTTGG

TACGGGTTCCGCCACCAGAACGCTCAGGGCGAAGGAACCGCCGCTGACTATAAGTCCACC

CAGTCTGCCATCGACCAGATCACAGGAAAACTGAATAGGCTGATAGAAAAAACCAATCAG

CAGTTCGAACTGATTGACAACGAGTTCAACGAGGTCGAGAAACAGATCGGAAATGTTATT

AATTGGACCCGAGATAGCATCACTGAAGTCTGGTCCTATAACGCTGAGCTTCTAGTAGCG

ATGGAAAATCAGCACACGATCGACCTGGCAGATAGCGAAATGGACAAACTCTACGAGAGA

GTGAAGCGCCAGCTTCGAGAAAACGCCGAAGAAGATGGAACTGGGTGCTTTGAAATTTTC

CACAAGTGTGATGACGATTGCATGGCCTCTATCCGCAATAATACCTACGATCACAGTAAA

TATCGCGAAGAAGCGATGCAAAATCGTATCCAGATCGATCCTGTAAAGCTCAGCTCCGGA

TACAAAGACGTGATTCTCTGGTTCAGTTTTGGCGCCAGCTGTTTTATCCTGCTCGCCATA

GTCATGGGTTTGGTATTTATCTGCGTCAAGAACGGGAACATGCGTTGCACAATCTGCATA

682
ATGAATACTCAAATCCTGGTATTCGCCCTAATTGCAATCATTCCAACCAACGCTGACAAG

ATCTGTTTAGGCCACCACGCCGTTTCGAACGGTACAAAGGTGAATACCCTGACAGAGAGG

GGCGTGGAAGTGGTGAACGCGACAGAGACCGTGGAACGGACCAATATCCCCCGCATTTGC

TCCAAGGGAAAAAAAACTGTAGACCTCGGACAGTGCGGCCTGCTCGGAACGATCACCGGA

CCCCCTCAGTGCGACCAATTTCTGGAATTTAGTGCAGATCTCATTATTGAGAGGCGGGAA

GGAAGTGACGTTTGCTATCCCGGCAAATTTGTGAATGAAGAGGCCCTTCGCCAGATCCTC

AGAGAAAGCGGGGGCATAGACAAAGAGGCCATGGGCTTTACCTATTCTGGCATTCGAACC

AACGGCGCTACCAGTGCTTGCAGACGGAGCGGCTCGTCCTTCTACGCAGAGATGAAGTGG

CTTTTGTCCAATACCGACAACGCTGCTTTCCCTCAGATGACCAAGTCTTACAAGAACACC

CGAAAGTCTCCAGCGCTGATTGTGTGGGGGATTCATCACTCAGTGAGTACAGCAGAGCAG

ACTAAGCTGTATGGATCCGGCAATAAACTCGTGACTGTAGGTTCCTCAAATTATCAACAG

AGCTTTGTCCCCTCTCCAGGAGCCAGGCCCCAGGTGAACGGACAATCTGGGCGTATAGAT

TTTCACTGGCTGATGTTAAATCCAAACGACACCGTAACCTTCTCGTTTAATGGAGCCTTT

ATCGCTCCTGACAGAGCGAGCTTTTTAAGAGGAAAAAGTATGGGAATACAGTCCGGAGTT

CAGGTGGATGCCAACTGTGAGGGTGATTGCTACCACAGTGGCGGTACAATTATCAGTAAT

CTACCCTTCCAAAATATCGATTCTCGGGCAGTGGGCAAGTGTCCCCGCTATGTCAAGCAG

CGGAGCCTTCTCTTGGCAACAGGTATGAAAAACGTGCCTGAAATCCCTAAAGGAAGGGGC

CTGTTCGGTGCCATTGCAGGATTTATCGAGAATGGGTGGGAAGGGCTTATTGACGGGTGG

TATGGATTCCGGCACCAGAATGCCCAGGGGGAAGGCACCGCCGCTGACTACAAATCTACA

CAGAGTGCCATTGATCAGATCACGGGCAAACTCAACAGACTTATCGAGAAGACAAATCAG

CAATTTGAGCTGATAGACAATGAGTTCAATGAAGTGGAAAAACAGATCGGGAATGTGATT

AACTGGACCAGAGATTCCATCACAGAGGTCTGGTCCTATAACGCCGAACTGCTCGTTGCC

ATGGAAAACCAGCATACCATCGATCTTGCCGATTCCGAGATGGACAAGCTCTATGAACGC

GTCAAGCGACAGCTCAGAGAAAATGCAGAGGAGGATGGGACAGGATGTTTTGAAATTTTC

CACAAGTGCGATGACGACTGTATGGCATCCATTCGCAACAACACATACGATCACAGCAAG

TATAGAGAGGAGGCCATGCAGAACAGAATACAGATCGATCCAGTTAAACTGAGTTCTGGC

TATAAGGATGTGATTCTCTGGTTCTCTTTCGGAGCCAGCTGCTTTATCCTGCTGGCTATC

GTCATGGGCCTGGTGTTCATCTGCGTCAAGAATGGAAACATGCGGTGCACGATTTGCATT

683
ATGAATACTCAGATCCTTGTGTTCGCCTTAATCGCCATCATCCCTACTAACGCCGACAAG

ATCTGCCTGGGCCACCACGCTGTTTCCAATGGCACGAAGGTCAACACTCTCACCGAAAGA

GGGGTTGAGGTGGTGAACGCCACCGAAACAGTAGAGAGAACGAACATCCCCCGTATTTGC

TCCAAGGGGAAACGCACTGTGGATTTAGGACAGTGCGGCCTGCTGGGGACAATTACCGGA

CCTCCTCAGTGCGACCAATTCCTGGAATTTTCAGCTGACCTCATCATAGAGCGGCGAGAG

GGGTCCGATGTATGCTACCCTGGAAAGTTTGTGAATGAAGAGGCCCTTCGGCAGATCCTG

CGCGAGAGCGGGGGGATTGATAAGGAAGCCATGGGTTTTACCTATTCCGGAATTAGAACG

AACGGCGCTACATCAGCTTGCCGCCGTTCAGGTTCCAGCTTCTATGCCGAGATGAAGTGG

CTACTTTCCAATACCGACAATGCGGCATTCCCTCAGATGACTAAGTCTTACAAGAATACT

CGGAAGTCACCAGCCCTTATCGTCTGGGGCATTCACCACAGCGTGTCAACCGCGGAGCAA

ACCAAACTATATGGGTCGGGGTCTAAACTCGTAACCGTGGGTTCGAGCAATTACCAGCAG

AGCTTCGTTCCCAGTCCTGGCGCTCGACCTCAGGTGAATGGGCTGAGTGGGAGGATAGAC

TTTCATTGGTTAATGTTAAATCCTAACGATACTGTCACCTTCTCCTTCAATGGTGCTTTC

ATTGCACCAGACCGTGCTAGCTTCCTCCGCGGGAAATCGATGGGCATACAGTCCGGAGTG

CAAGTCGACGCTAACTGTGAAGGCGATTGTTACCATTCAGGCGGCACCATAATCAGCAAT

CTGCCTTTTCAGAACATTGATAGTCGTGCTGTGGGAAAGTGTCCTAGATACGTGAAGCAG

AGGAGTCTTCTTTTGGCCACTGGCATGAAAAACGTACCAGAGATCCCCAAAGGACGGGGC

CTGTTTGGCGCTATCGCGGGCTTTATAGAAAATGGCTGGGAGGGATTAATCGACGGCTGG

TACGGTTTTAGGCACCAGAATGCCCAAGGCGAAGGTACAGCAGCCGATTACAAAAGTACA

CAGTCCGCCATCGATCAGATTACCGGGAAACTCAATCGTCTCATTGAGAAGACAAACCAA

CAGTTTGAGCTTATAGACAACGAATTTAATGAAGTGGAGAAACAGATTGGAAACGTAATC

AACTGGACACGGGACTCCATAACTGAGGTCTGGAGCTACAATGCTGAACTCTTGGTGGCC

ATGGAGAACCAGCATACCATTGACTTGGCAGACTCTGAGATGGATAAGCTGTACGAAAGG

GTGAAACGGCAGCTTCGTGAAAATGCCGAGGAGGATGGCACCGGATGTTTTGAGATATTC

CACAAGTGTGATGACGACTGCATGGCGAGCATTCGTAACAATACTTACGATCACTCAAAG

TACCGGGAGGAAGCCATGCAGAATAGAATCCAGATCGATCCTGTGAAGCTGTCCTCGGGC

TACAAGGACGTCATCCTGTGGTTCTCCTTTGGCGCTAGCTGTTTCATTCTGTTGGCGATC

GTTATGGGTCTCGTCTTTATTTGCGTTAAGAACGGCAACATGCGTTGCACAATTTGCATT

684
ATGAATACTCAAATTCTCGTCTTTGCCCTGATTGCTATCATTCCCACCAATGCAGACAAG

ATTTGCCTCGGTCACCACGCCGTATCAAACGGCACAAAAGTGAACACACTGACCGAAAGA

GGTGTCGAGGTCGTTAATGCCACTGAGACCGTTGAGCGGACTAACATCCCTAGAATCTGC

AGCAAGGGGAAGAAAACTGTGGATCTTGGGCAGTGCGGACTGCTGGGAACAATAACCGGG

CCTCCCCAATGCGACCAATTCCTGGAGTTTTCCGCTGATCTCATTATTGAGCGCAGAGAA

GGGAGCGATGTATGCTACCCCGGAAAGTTTGTCAACGAGGAAGCTTTGCGCCAGATTCTG

AGGGAATCTGGCGGCATCGACAAAGAGGCTATGGGATTCACATACAGTGGTATAAGGACT

AATGGAGCAACCAGCGCTTGTCGGCGGTCGGGGAGCTCCTTTTATGCTGAAATGAAATGG

CTGCTTTCTAACACTGATAACGCTGCCTTCCCCCAGATGACTAAATCGTACAAGAACACA

CGAAAATCGCCGGCACTGATCGTGTGGGGAATACACCATTCAGTGTCCACTGCCGAACAG

ACCAAACTGTATGGCAGCGGCAACAAGCTCGTGACCGTTGGTTCCTCGAACTATCAGCAA

AGCTTCGTGCCTTCGCCAGGTGCTCGCCCTCAGGTCAATGGACAGTCCGGAAGGATTGAC

TTTCACTGGCTTATGTTGAACCCGAACGATACTGTTACATTTAGTTTTAACGGCGCCTTT

ATTGCACCCGACAGGGCCTCATTTTTGCGAGGCAAGTCGATGGGCATACAATCTGGCGTG

CAGGTAGATGCAAACTGTGAAGGCGATTGCTATCACTCCGGAGGCACAATTATTAGTAAT

CTACCCTTCCAGAATATCGACTCTCGGGCGGTCGGCAAATGTCCCCGATACGTAAAGCAA

CGCTCCCTGTTGCTGGCCACTGGTATGAAGAACGTCCCTGAAATCCCCAAAGGCCGGGGA

TTGTTCGGCGCCATAGCAGGATTCATCGAGAACGGCTGGGAAGGTCTCATAGATGGTTGG

TATGGTTTCCGTCACCAGAACGCCCAGGGGGAAGGCACCGCAGCGGATTACAAGTCGACG

CAGTCTGCAATCGACCAGATCACCGGTAAACTGAACCGCCTGATTGAGAAAACAAACCAA

CAATTCGAATTAATTGACAATGAGTTTAATGAGGTAGAGAAACAGATTGGCAACGTGATT

AACTGGACAAGGGATTCAATTACCGAAGTTTGGAGCTACAACGCCGAGTTGCTGGTCGCT

ATGGAAAACCAGCACACAATCGACCTGGCCGACTCCGAGATGGACAAGTTATATGAACGG

GTGAAACGGCAGCTGCGGGAGAATGCCGAGGAGGATGGTACAGGGTGTTTTGAAATCTTT

CACAAATGTGATGATGATTGCATGGCGTCAATACGCAACAACACATATGACCACTCAAAA

TATCGAGAAGAAGCCATGCAGAACAGAATACAGATTGACCCCGTGAAGCTTTCAAGTGGC

TATAAAGATGTCATTCTGTGGTTCTCCTTCGGGGCATCCTGCTTTATCCTGCTCGCCATC

GTTATGGGGCTTGTGTTCATTTGTGTCAAGAATGGAAACATGAGGTGCACCATCTGCATC

685
ATGAATACCCAGATCCTGGTTTTTGCCCTGATCGCTATCATACCAACAAACGCTGACAAG

ATCTGTCTTGGCCACCACGCTGTCTCTAATGGGACCAAAGTCAATACCCTGACCGAAAGG

GGAGTGGAGGTAGTCAACGCTACTGAGACAGTCGAAAGAACTAATATTCCTAGAATTTGC

AGTAAGGGCAAGAAAACCGTGGATCTGGGGCAGTGTGGCCTGCTGGGCACCATAACCGGG

CCTCCTCAGTGCGATCAGTTCCTGGAGTTTTCCGCCGATCTGATCATTGAACGCAGGGAA

GGCAGCGACGTATGCTACCCAGGGAAGTTTGTTAATGAGGAAGCACTCCGCCAGATTCTC

CGAGAGTCTGGGGGTATTGATAAGGAGGCAATGGGTTTTACATACAGCGGCATTAGGACT

AATGGGGCTACTTCAGCTTGCCGAAGGAGCGGATCTTCCTTTTACGCTGAGATGAAATGG

CTCCTGAGCAATACCGACAATGCCGCCTTTCCTCAGATGACGAAATCTTATAAGAACACA

AGAAAGTCCCCAGCACTGATCGTGTGGGGGATTCACCACTCAGTCTCCACAGCCGAGCAG

ACCAAGCTGTACGGCTCAGGCAATAAACTCGTGACGGTTGGCAGCTCCAATTACCAGCAG

TCCTTTGTCCCTAGTCCTGGAGCCCGGCCTCAGGTGAATGGGCAGTCCGGTCGAATAGAC

TTTCACTGGCTCATGTTAAACCCCAATGACACAGTGACCTTCAGCTTCAATGGGGCTTTC

ATCGCCCCCGACCGTGCCAGCTTTCTGCGGGGGAAAAGCATGGGGATACAGTCTGGGGTT

CAGGTGGATGCCAATTGTGAAGGGGACTGTTACCACTCTGGGGGCACCATCATCAGTAAT

TTACCATTCCAGAATATTGACTCGAGAGCCGTAGGAAAGTGCCCCAGGTACGTGAAGCAG

AGATCTCTGCTGCTTGCGACGGGTATGAAAAATGTCCCAGAGATCCCGAAAGGCCGGGGA

CTTTTTGGAGCAATCGCCGGCTTCATCGAGAATGGCTGGGAAGGGCTGATCGACGGCTGG

TACGGCTTTCGCCACCAGAACGCCCAGGGCGAGGGTACAGCGGCAGACTATAAGTCCACT

CAGAGTGCCATCGATCAGATCACAGGTAAGCTCAATCGTCTCATTGAGAAGACCAATCAG

CAGTTCGAGCTCATCGACAACGAATTCAACGAGGTTGAGAAACAGATCGGCAACGTGATC

AACTGGACAAGGGACAGTATCACCGAGGTGTGGAGCTACAACGCTGAGCTGCTGGTGGCT

ATGGAAAACCAGCACACCATCGATCTGGCAGATTCCGAAATGGATAAGCTTTATGAGCGG

GTGAAGCGTCAACTGAGAGAGAACGCCGAGGAGGATGGAACTGGCTGCTTCGAAATCTTT

CATAAATGTGATGACGACTGCATGGCCTCAATCCGGAATAACACTTATGACCACAGCAAA

TACAGAGAAGAGGCGATGCAGAATCGAATCCAGATAGACCCCGTCAAGCTTTCATCGGGT

TATAAGGACGTTATCCTATGGTTTTCTTTTGGCGCCAGCTGCTTTATCCTCCTCGCGATT

GTCATGGGACTTGTGTTCATTTGCGTGAAAAACGGCAATATGCGCTGTACAATTTGTATC

686
ATGAACACACAGATTCTGGTTTTCGCCTTGATTGCCATTATTCCTACTAATGCAGACAAG

ATCTGTTTGGGCCATCACGCCGTAAGTAACGGTACGAAGGTCAACACCTTGACAGAGCGC

GGGGTTGAGGTTGTCAATGCAACAGAAACCGTCGAACGGACAAACATCCCAAGGATCTGC

TCAAAAGGCAAGAAAACCGTCGACCTGGGGCAATGTGGCCTTCTCGGAACTATAACCGGA

CCCCCACAATGCGATCAATTTCTGGAGTTCAGCGCTGACCTAATAATAGAGAGACGGGAG

GGGTCAGATGTGTGTTATCCGGGGAAATTCGTGAACGAAGAAGCCCTTAGGCAGATCTTA

CGGGAAAGCGGTGGCATCGACAAAGAGGCCATGGGATTTACCTACAGCGGGATCCGGACG

AACGGTGCCACTAGTGCATGTCGGAGGTCGGGAAGCTCTTTTTACGCCGAGATGAAGTGG

CTTCTGAGCAATACAGATAATGCTGCTTTCCCGCAGATGACAAAGTCTTACAAGAATACA

AGAAAATCCCCAGCTCTCATAGTCTGGGGTATCCATCATTCTGTATCCACGGCCGAGCAA

ACCAAACTTTACGGCTCTGGGAATAAACTGGTGACAGTGGGATCATCTAATTATCAGCAG

TCTTTCGTGCCATCACCAGGCGCACGACCGCAAGTTAACGGACAGTCTGGTAGAATCGAC

TTTCATTGGCTAATGCTGAACCCGAATGATACTGTGACCTTCAGTTTCAATGGGGCTTTC

ATAGCACCAGACAGGGCATCATTTCTCAGAGGAAAATCAATGGGCATTCAGTCTGGTGTG

CAGGTGGATGCAAATTGCGAGGGAGACTGCTATCACAGTGGCGGCACTATCATCTCGAAT

CTCCCGTTCCAGAATATCGATAGCCGCGCCGTGGGGAAGTGCCCTCGGTACGTTAAACAA

CGATCTCTGCTGTTAGCCACCGGCATGAAGAATGTACCCGAGATCCCTAAGGGTCGAGGC

CTCTTTGGCGCCATTGCTGGCTTTATCGAGAATGGCTGGGAAGGACTCATAGACGGCTGG

TATGGGTTCCGGCATCAGAACGCTCAGGGAGAAGGGACCGCTGCGGACTATAAGTCAACA

CAGTCCGCCATTGACCAAATCACAGGCAAGCTGAACCGGCTGATTGAAAAAACTAATCAA

CAATTCGAGCTGATAGATAACGAGTTCAACGAAGTCGAAAAGCAGATTGGCAATGTCATT

AATTGGACACGCGATAGCATCACTGAAGTGTGGAGCTACAACGCAGAGCTGCTGGTTGCC

ATGGAGAACCAGCACACCATCGATCTGGCTGACTCTGAGATGGACAAGCTGTACGAACGG

GTGAAGCGTCAGCTCCGTGAGAACGCTGAAGAAGATGGGACAGGTTGCTTCGAAATCTTT

CATAAATGCGACGACGATTGTATGGCCTCAATAAGGAACAATACATATGACCACTCTAAG

TATAGAGAGGAGGCCATGCAGAATCGTATCCAGATCGATCCAGTGAAGCTGTCTTCAGGG

TACAAAGATGTGATCCTCTGGTTTTCATTCGGTGCCAGCTGTTTTATCTTACTGGCCATC

GTCATGGGCCTCGTCTTCATTTGTGTGAAAAACGGTAACATGAGATGCACCATTTGTATT

687
ATGAATACGCAGATTTTGGTGTTCGCCCTGATCGCCATAATCCCCACTAACGCCGACAAA

ATCTGTCTGGGGCACCACGCGGTGTCTAATGGGACTAAGGTAAACACACTGACAGAGAGA

GGCGTTGAGGTTGTTAACGCCACGGAGACAGTAGAACGTACAAACATCCCCCGCATCTGC

TCCAAGGGCAAAAAGACTGTGGATCTGGGGCAGTGCGGTTTGCTCGGAACCATTACAGGC

CCCCCTCAGTGTGACCAATTTCTTGAATTCTCCGCCGACCTCATCATCGAGCGCCGGGAA

GGAAGTGATGTTTGCTATCCCGGGAAATTTGTGAATGAGGAAGCCCTGAGGCAAATTCTC

CGGGAGTCAGGGGGTATTGACAAAGAGGCTATGGGGTTTACATACTCCGGTATCCGTACC

AATGGAGCAACCTCGGCTTGCCGTAGGTCCGGCAGCTCCTTTTACGCTGAGATGAAATGG

CTGCTCTCGAACACCGACAATGCCGCATTTCCCCAGATGACTAAGTCTTACAAGAATACC

CGGAAGTCTCCGGCCCTGATTGTGTGGGGAATCCACCATTCCGTGTCCACCGCCGAACAG

ACTAAGCTTTACGGCTCGGGCAACAAACTGGTCACCGTTGGCTCTTCTAACTATCAGCAG

AGCTTTGTGCCTTCACCAGGGGCTCGACCTCAGGTGAACGGGCAGTCCGGCCGGATCGAT

TTCCACTGGCTAATGCTGAACCCAAATGATACTGTTACGTTTTCCTTCAATGGTGCTTTT

ATAGCACCTGATCGCGCTTCCTTTCTGAGGGGGAAAAGCATGGGCATACAATCTGGGGTT

CAGGTTGATGCCAACTGTGAGGGGGATTGCTATCACTCTGGTGGGACCATAATTTCCAAC

CTCCCCTTTCAGAACATCGACTCACGAGCCGTCGGTAAGTGTCCAAGATACGTGAAGCAA

CGCTCATTACTCCTGGCTACCGGAATGAAAAATGTTCCAGAGATCCCGAAGGGGAGGGGT

CTGTTCGGTGCCATTGCGGGATTTATTGAAAACGGATGGGAGGGACTAATCGACGGATGG

TATGGGTTTAGGCATCAGAACGCACAGGGCGAGGGAACCGCCGCGGACTATAAAAGCACT

CAGTCCGCCATTGATCAGATTACAGGGAAACTCAATAGACTCATTGAGAAGACGAATCAG

CAGTTCGAGCTGATCGACAACGAGTTCAATGAGGTCGAAAAACAGATCGGGAATGTGATA

AATTGGACTAGGGATTCAATAACAGAGGTCTGGAGCTACAACGCAGAGTTACTCGTTGCG

ATGGAGAACCAACATACTATTGATCTTGCAGACTCCGAGATGGATAAGCTATACGAGCGG

GTCAAGCGACAGTTAAGGGAGAATGCAGAAGAAGATGGAACTGGGTGCTTCGAAATATTT

CATAAGTGCGACGACGACTGTATGGCCTCAATCCGCAACAACACATACGACCACTCAAAG

TACAGGGAGGAAGCCATGCAGAACCGGATCCAAATTGACCCGGTGAAACTGAGCTCTGGC

TACAAGGACGTGATCCTATGGTTTTCTTTTGGGGCCAGTTGCTTCATCCTACTCGCTATA

GTCATGGGTCTGGTGTTCATTTGTGTCAAGAACGGGAACATGCGTTGTACTATCTGCATT

688
ATGAATACCCAAATCTTGGTGTTCGCGTTGATCGCAATCATCCCCACTAACGCCGACAAA

ATCTGTTTAGGGCATCACGCTGTTTCCAACGGTACGAAAGTGAATACACTGACTGAACGC

GGGGTCGAGGTCGTTAACGCTACAGAGACGGTGGAGAGAACTAATATCCCTAGGATCTGC

TCCAAGGGCAAGCGCACTGTGGACCTGGGGCAATGCGGACTGCTAGGGACAATTACTGGC

CCGCCCCAGTGCGACCAATTTTTGGAGTTTAGCGCAGACCTGATCATAGAGCGACGCGAG

GGTTCAGACGTTTGTTACCCTGGAAAGTTTGTAAATGAGGAAGCCCTTCGCCAGATCCTG

CGGGAGAGCGGCGGTATCGATAAAGAGGCTATGGGGTTTACGTACTCTGGAATCAGAACC

AATGGGGCCACCTCTGCTTGTAGAAGATCTGGATCCTCCTTTTATGCAGAAATGAAGTGG

TTGTTATCAAATACTGATAACGCGGCATTTCCACAGATGACTAAGAGCTACAAGAACACG

CGGAAGTCACCCGCTTTAATAGTCTGGGGCATCCACCACTCAGTTAGTACAGCTGAGCAG

ACTAAGCTGTATGGCAGTGGTAACAAGCTGGTCACCGTGGGTAGCTCTAATTATCAGCAA

TCTTTCGTACCATCACCCGGAGCTAGACCTCAGGTGAACGGTCTGTCAGGCCGGATCGAC

TTCCACTGGTTGATGCTCAATCCCAATGACACTGTTACATTCAGCTTTAATGGCGCCTTC

ATCGCTCCTGACCGAGCCAGCTTTCTGCGCGGCAAGTCTATGGGGATCCAATCTGGCGTG

CAGGTTGATGCGAACTGCGAAGGGGACTGCTACCACAGTGGAGGCACCATCATTTCTAAC

CTGCCATTCCAGAATATCGACAGTCGCGCCGTGGGGAAGTGTCCTCGATACGTGAAGCAG

AGGAGCCTCCTCCTAGCGACTGGAATGAAGAACGTCCCAGAAATCCCTAAGGGCCGGGGG

CTCTTTGGAGCGATTGCCGGATTTATCGAAAACGGCTGGGAAGGGCTTATTAATGGCTGG

TACGGCTTCAGGCATCAGAATGCTCAAGGCGAGGGAACTGCCGCCGACTACAAGTCCACT

CAATCCGCCATTGATCAGATAACCGGGAAACTTAACCGCCTGATCGAGAAGACAAACCAG

CAGTTTGAGCTGATAGATAATGAGTTCAATGAAGTCGAGAAACAGATAGGAAACGTCATT

AATTGGACCCGCGACTCAATTACAGAAGTCTGGAGCTATAACGCAGAGCTGTTGGTAGCG

ATGGAAAACCAACACACAATTGACCTGGCCGATTCCGAAATGGATAAGCTGTACGAGCGC

GTGAAAAGACAGTTAAGGGAAAATGCCGAGGAAGATGGTACCGGCTGTTTCGAGATCTTC

CACAAGTGCGATGATGATTGCATGGCCTCCATCCGAAATAATACTTACGATCACTCCAAG

TACAGAGAGGAGGCAATGCAAAACAGAATTCAGATCGACCCCGTTAAGTTATCAAGCGGA

TACAAGGACGTCATCCTGTGGTTCTCATTTGGCGCATCGTGTTTTATTCTGCTTGCTATT

GTGATGGGTCTCGTTTTCATTTGTGTCAAGAACGGGAATATGAGGTGTACGATCTGCATC

689
ATGAACACCCAGATTTTAGTCTTTGCACTGATTGCAATTATTCCCACTAATGCTGACAAG

ATCTGTCTGGGCCACCACGCTGTGTCAAACGGAACTAAGGTGAACACGCTGACTGAGCGA

GGTGTCGAAGTGGTGAATGCGACGGAAACCGTGGAGAGAACAAATATCCCCAGAATCTGC

AGTAAAGGAAAAAAAACTGTGGATCTGGGCCAATGCGGGCTGCTGGGTACTATCACCGGG

CCACCACAATGCGACCAGTTTCTTGAGTTCTCCGCAGATCTCATCATCGAACGCCGGGAA

GGCTCCGATGTTTGTTACCCAGGGAAGTTCGTAAATGAAGAAGCCTTAAGGCAAATCCTT

AGAGAGAGCGGAGGAATTGAGAAAGAGGCAATGGGCTTTACCTACTCAGGAATTAGAGCC

AACGGCGCTACTTCCGCTTGTCGACGAAGTGGCTCCAGTTTCTATGCCGAAATGAAGTGG

CTGTTGTCTAACACGGATAACGCAGCCTTTCCTCAGATGACTAAGTCGTACAAAAACACC

CGGAAATCTCCAGCTCTGATTGTGTGGGGAATCCACCATAGTGTGTCCACCGCCGAGCAA

ACCAAACTTTATGGGAGCGGAAACAAGTTGGTTACTGTTGGATCCTCGAACTATCAGCAG

AGCTTCGTGCCTAGCCCAGGCGCTCGTCCACAGGTGAACGGACTCTCCGGTAGAATCGAT

TTTCATTGGCTTATGCTCAATCCTAATGACACTGTGACCTTTAGCTTCAACGGCGCGTTT

ATCGCCCCTGATCGAGCCTCTTTCCTGCGCGGAAAGTCAATGGGTATCCAGTCGGGCGTT

CAGGTGGATGCAAATTGCGAGGGGGACTGCTATCACTCTGGTGGCACCATTATCTCAAAC

CTGCCATTTCAGAACATCGACTCCCGTGCGGTCGGTAAATGCCCGAGATACGTTAAGCAG

CGAAGCCTGCTACTGGCAACAGGCATGAAGAACGTGCCTGAGATACCTAAGGGACGTGGT

CTGTTTGGAGCAATTGCCGGGTTCATTGAGAATGGCTGGGAGGGGCTCATCGATGGGTGG

TATGGCTTTAGACATCAAAATGCTCAGGGAGAAGGTACTGCAGCCGATTACAAGAGTACC

CAGAGCGCCATCGATCAGATCACTGGCAAGTTAAACCGCCTTATCGAAAAGACCAACCAG

CAGTTTGAGCTTATCGACAATGAATTTAACGAAGTGGAGAAGCAAATCGGCAACGTCATC

AACTGGACTCGCGATTCTATCACCGAGGTCTGGTCATATAACGCAGAGTTACTCGTTGCG

ATGGAAAACCAGCACACTATTGACTTGGCCGACTCTGAGATGGACAAACTGTACGAAAGA

GTTAAAAGACAGCTGCGGGAAAACGCTGAGGAAGATGGGACTGGCTGTTTCGAGATCTTT

CACAAATGCGATGACGACTGCATGGCTTCGATTCGGAATAATACATACGATCACTCTAAG

TACAGAGAAGAGGCTATGCAGAACAGAATCCAAATCGATCCCGTTAAGCTGTCATCAGGC

TACAAGGACGTGATCCTGTGGTTCTCTTTCGGGGCGAGTTGCTTTATCCTTCTTGCCATC

GTGATGGGCCTTGTGTTTATTTGTGTTAAAAACGGTAACATGCGCTGTACAATCTGTATA

690
ATGAACACACAAATTCTGGTCTTCGCACTGATTGCAATCATCCCAACTAACGCTGACAAA

ATTTGTCTGGGGCACCATGCGGTCAGTAATGGCACCAAGGTCAACACTCTCACTGAACGC

GGAGTGGAAGTGGTGAACGCAACCGAGACAGTGGAGCGGACCAACATCCCCAGAATATGC

TCAAAGGGTAAAAAGACTGTGGATTTGGGACAGTGCGGTCTTCTTGGGACAATCACCGGC

CCTCCCCAGTGTGACCAGTTCCTGGAATTCTCTGCCGACCTGATTATAGAGCGGCGTGAG

GGCTCCGATGTGTGTTACCCCGGCAAGTTCGTGAACGAGGAGGCACTGCGACAGATCTTG

AGAGAAAGCGGGGGGATTGACAAAGAGGCTATGGGCTTCACTTATTCGGGCATCAGGACT

AATGGCGCAACCTCCGCTTGTAGGAGATCAGGATCCTCTTTCTACGCCGAAATGAAGTGG

CTGCTGTCGAATACAGACAATGCCGCTTTCCCCCAAATGACTAAGAGTTATAAAAACACG

CGTAAATCCCCAGCGCTGATTGTCTGGGGAATCCACCACTCGGTGAGCACTGCAGAGCAG

ACTAAACTGTACGGGAGCGGCAATAAACTTGTTACAGTGGGATCCTCGAATTACCAACAG

AGCTTCGTCCCATCACCAGGTGCTCGACCACAGGTGAACGGCCAGTCTGGGCGAATAGAT

TTTCATTGGCTCATGCTTAATCCCAATGACACTGTGACTTTTTCTTTCAATGGGGCCTTC

ATCGCGCCTGATCGGGCCAGTTTCCTGAGAGGCAAGAGTATGGGAATCCAGTCCGGCGTG

CAGGTGGACGCTAATTGTGAGGGGGATTGCTATCACTCAGGTGGCACTATAATTTCAAAT

CTTCCTTTCCAGAACATCGATTCTCGAGCCGTCGGAAAGTGCCCTAGGTACGTGAAACAA

AGGTCACTCCTTTTGGCAACCGGGATGAAGAACGTGCCAGAGATTCCCAAGGGTCGGGGG

CTCTTTGGCGCTATTGCTGGATTTATCGAGAATGGGTGGGAGGGTCTGATAGACGGTTGG

TATGGCTTCAGACACCAGAACGCCCAGGGGGAGGGCACCGCCGCCGACTATAAGAGTACC

CAGAGCGCAATTGACCAGATTACCGGAAAATTGAACCGACTGATTGAGAAGACAAATCAG

CAGTTTGAGTTGATCGACAACGAATTCAATGAGGTTGAAAAACAGATCGGGAACGTTATA

AACTGGACACGAGATAGCATAACAGAGGTCTGGAGTTACAATGCTGAACTGCTGGTTGCT

ATGGAAAACCAGCATACTATTGACCTTGCGGACAGCGAGATGGACAAACTATACGAAAGA

GTGAAGCGCCAGCTGCGTGAGAACGCCGAAGAAGACGGGACTGGATGCTTCGAGATATTC

CACAAGTGTGATGACGATTGTATGGCAAGCATACGGAACAACACATACGATCATAGCAAA

TATAGGGAGGAGGCGATGCAGAACAGAATACAGATAGACCCTGTGAAGTTATCTTCCGGT

TACAAAGACGTTATCCTCTGGTTTAGCTTCGGAGCCAGCTGCTTTATATTATTAGCCATC

GTCATGGGCCTCGTTTTCATCTGCGTGAAGAATGGAAATATGCGCTGCACCATCTGCATC

691
ATGAATACGCAGATCTTGGTATTCGCACTTATAGCCATCATCCCCACCAACGCCGATAAG

ATTTGCTTAGGCCACCATGCTGTTTCTAACGGCACAAAAGTGAACACACTTACCGAGAGA

GGGGTCGAAGTTGTGAACGCCACGGAGACAGTCGAAAGGACAAACATTCCTCGAATCTGC

AGTAAGGGCAAGAAAACAGTGGATCTCGGCCAGTGTGGGCTGCTGGGAACCATCACGGGT

CCTCCGCAGTGTGACCAGTTCCTGGAGTTCTCTGCCGATCTCATCATCGAAAGGCGGGAG

GGATCCGACGTGTGCTACCCAGGCAAATTCGTGAACGAAGAAGCGCTTCGGCAAATTCTG

CGAGAGTCAGGGGGGATAGATAAAGAGGCAATGGGGTTTACTTATTCTGGCATTAGAACC

AATGGGGCCACGAGTGCATGTAGACGGTCCGGAAGTAGCTTTTACGCAGAAATGAAGTGG

CTGTTGTCTAACACTGACAACGCTGCATTTCCACAGATGACCAAGTCTTATAAAAACACG

AGAAAATCCCCAGCCCTCATTGTGTGGGGGATCCACCATTCTGTGAGCACCGCCGAGCAA

ACGAAGCTGTATGGCAGTGGTAACAAGCTAGTCACAGTAGGATCCAGTAATTACCAGCAA

AGCTTCGTGCCCAGTCCCGGAGCTCGGCCTCAGGTCAACGGGCAATCTGGGAGAATCGAC

TTCCACTGGCTGATGCTGAACCCAAACGACACAGTGACATTTTCTTTTAATGGCGCTTTC

ATTGCCCCCGACAGGGCTAGTTTTCTGAGAGGCAAGTCCATGGGGATCCAAAGCGGAGTG

CAGGTGGACGCTAATTGCGAGGGCGATTGTTACCACAGTGGGGGGACCATTATCAGTAAT

CTGCCTTTCCAGAACATCGATAGTAGAGCCGTGGGCAAATGTCCACGTTACGTCAAGCAG

CGGAGCCTGCTCTTAGCCACGGGCATGAAGAACGTGCCTGAGATCCCAAAGGGCAGAGGG

CTGTTTGGCGCTATCGCGGGATTCATTGAAAATGGGTGGGAGGGACTAATCGACGGATGG

TACGGTTTTCGACACCAGAACGCACAGGGGGAAGGGACAGCTGCCGATTATAAGTCTACT

CAATCTGCTATCGACCAGATAACTGGGAAACTTAATCGGCTGATTGAGAAAACAAACCAG

CAGTTTGAGCTGATAGACAACGAATTCAACGAAGTGGAGAAACAGATCGGTAACGTGATA

AACTGGACTAGGGACTCTATCACCGAGGTGTGGTCCTACAACGCGGAACTCCTTGTCGCT

ATGGAGAATCAGCACACTATAGACCTGGCAGACTCTGAAATGGATAAACTGTACGAACGG

GTTAAGCGGCAATTGCGGGAGAACGCTGAGGAGGATGGCACAGGATGTTTTGAAATTTTT

CATAAATGTGACGACGATTGCATGGCTTCCATTCGCAACAATACTTATGATCATTCGAAG

TACCGGGAAGAGGCCATGCAAAACCGTATCCAGATCGATCCCGTCAAACTGTCGTCGGGG

TACAAGGACGTTATACTTTGGTTCAGCTTTGGAGCCTCTTGTTTCATCTTGCTCGCTATA

GTGATGGGCTTGGTGTTTATATGCGTAAAAAATGGCAACATGCGGTGCACAATTTGCATT

692
ATGAACACTCAGATACTCGTCTTTGCTCTCATTGCAATTATTCCTACCAATGCTGATAAG

ATTTGCTTGGGGCACCACGCAGTTTCCAATGGGACAAAGGTGAACACCCTAACTGAGCGG

GGCGTTGAAGTGGTGAACGCAACCGAGACAGTGGAAAGAACAAATATCCCCCGCATTTGC

AGTAAAGGCAAAAAAACCGTCGACTTGGGACAGTGTGGCCTGCTTGGGACTATCACCGGA

CCCCCACAGTGTGACCAATTTTTGGAGTTTTCAGCTGATCTGATTATCGAAAGACGCGAG

GGAAGCGATGTTTGCTATCCAGGAAAATTTGTGAATGAAGAAGCACTCCGACAGATCCTG

CGGGAGTCCGGCGGAATAGATAAGGAAGCAATGGGGTTCACTTACTCGGGCATCCGGACT

AACGGAGCCACTTCCGCCTGCAGAAGGTCAGGCTCGTCGTTCTATGCCGAGATGAAGTGG

CTGCTTTCAAACACTGATAATGCCGCATTCCCACAGATGACAAAGTCATACAAAAACACC

AGGAAATCACCCGCATTGATAGTGTGGGGCATCCATCATTCTGTGTCCACTGCCGAGCAG

ACTAAACTGTACGGGAGCGGGAATAAGCTTGTTACCGTCGGGTCAAGCAACTATCAGCAA

AGTTTTGTACCAAGCCCGGGCGCACGGCCCCAGGTTAATGGTCAGTCCGGTCGCATTGAT

TTCCATTGGCTAATGCTAAATCCAAATGACACTGTAACGTTCTCATTCAACGGAGCGTTC

ATCGCTCCAGACCGTGCCTCTTTTCTGCGCGGGAAAAGCATGGGGATACAGTCCGGGGTG

CAGGTAGATGCTAACTGTGAGGGAGACTGTTATCACTCTGGCGGCACGATCATCTCCAAC

CTTCCCTTTCAGAACATTGACAGCAGAGCCGTCGGGAAATGCCCCCGATATGTTAAGCAG

AGGTCACTTCTTCTCGCTACGGGTATGAAGAATGTCCCAGAAATTCCTAAAGGCCGGGGA

TTGTTTGGAGCAATCGCCGGCTTCATCGAAAACGGTTGGGAAGGCTTGATTGATGGCTGG

TACGGCTTCCGCCACCAAAATGCTCAGGGAGAAGGAACTGCAGCTGACTATAAATCAACA

CAGAGCGCCATTGACCAGATCACAGGGAAGCTGAACAGACTTATCGAGAAAACCAATCAG

CAGTTTGAGCTCATAGACAACGAATTTAACGAAGTGGAGAAACAGATTGGCAACGTTATC

AATTGGACCCGGGACTCAATCACTGAAGTCTGGTCCTACAATGCAGAGCTGCTCGTCGCT

ATGGAAAACCAGCACACTATCGATTTGGCTGACAGCGAAATGGATAAACTATATGAAAGG

GTCAAGCGTCAGCTCCGAGAAAATGCAGAAGAGGATGGAACAGGCTGTTTCGAAATCTTC

CATAAGTGTGATGACGATTGCATGGCCAGTATCAGAAACAACACTTACGATCACTCCAAA

TACAGGGAGGAGGCCATGCAGAACCGGATCCAGATTGACCCTGTAAAACTGTCGAGCGGC

TATAAAGATGTTATCCTGTGGTTCAGCTTCGGGGCCAGCTGCTTCATACTGCTTGCCATT

GTGATGGGACTGGTGTTCATTTGCGTTAAAAATGGAAACATGAGATGCACCATCTGTATC

693
ATGAACACACAAATCCTGGTGTTCGCTCTAATAGCGATCATCCCAACCAATGCCGATAAG

ATCTGTCTGGGCCACCACGCCGTATCCAATGGGACTAAGGTTAATACACTGACAGAGCGA

GGAGTCGAAGTGGTGAACGCAACCGAGACAGTCGAAAGGACGAATATTCCCAGGATCTGC

AGCAAGGGGAAGAAGACTGTTGACCTGGGACAATGTGGCCTACTGGGAACTATAACCGGC

CCTCCACAATGCGACCAATTCCTGGAGTTTTCCGCTGACCTGATTATTGAACGGCGCGAA

GGGAGCGACGTATGTTATCCCGGGAAATTCGTGAATGAGGAGGCTCTGCGCCAGATCCTG

CGCGAGAGCGGGGGAATCGATAAGGAGGCCATGGGTTTCACCTATTCCGGAATAAGGACT

AACGGCGCAACCTCAGCTTGTAGACGCAGTGGCTCTTCTTTTTATGCTGAAATGAAATGG

TTATTATCAAACACGGACAACGCCGCTTTTCCCCAGATGACCAAGAGTTATAAGAACACC

CGGAAATCACCTGCTCTGATAGTATGGGGAATTCATCACTCGGTGTCCACTGCGGAGCAA

ACCAAACTGTACGGGAGCGGCAATAAGTTGGTTACAGTAGGAAGCTCCAATTATCAGCAA

AGTTTCGTCCCCTCCCCTGGCGCCAGGCCTCAAGTGAACGGACAGTCAGGGAGAATCGAC

TTCCACTGGCTGATGCTCAATCCAAACGACACCGTAACTTTCTCATTCAATGGGGCATTT

ATCGCCCCAGACCGGGCCTCGTTCTTACGAGGTAAATCCATGGGGATTCAGAGCGGCGTC

CAAGTGGATGCCAACTGCGAAGGCGATTGCTACCACTCTGGTGGGACAATCATCTCGAAC

TTGCCGTTCCAAAACATCGATTCCCGAGCAGTGGGGAAATGCCCCAGATACGTAAAACAA

AGGTCGCTGCTCCTTGCTACCGGCATGAAAAACGTCCCTGAAATCCCAAAGGGTCGTGGT

CTGTTTGGCGCAATTGCTGGGTTTATTGAGAACGGCTGGGAAGGCCTGATAGACGGGTGG

TATGGATTTCGTCATCAGAATGCACAGGGCGAGGGGACCGCAGCCGATTACAAGAGTACC

CAGTCCGCTATTGACCAGATAACAGGGAAACTGAACCGGCTGATTGAGAAGACCAACCAG

CAGTTCGAGTTGATTGACAATGAGTTCAACGAAGTCGAGAAGCAGATCGGGAATGTAATA

AATTGGACAAGAGACAGCATTACAGAGGTGTGGAGCTACAATGCAGAGCTGTTAGTGGCC

ATGGAGAACCAACACACGATTGACCTTGCCGATTCCGAGATGGACAAGTTGTACGAGAGA

GTAAAGAGGCAGCTGAGGGAGAATGCTGAAGAAGACGGAACAGGCTGCTTTGAAATCTTC

CACAAGTGTGATGATGACTGTATGGCTTCGATACGCAATAATACATACGACCATAGCAAG

TATCGGGAGGAAGCCATGCAGAATAGAATTCAGATTGATCCCGTGAAACTAAGCTCGGGA

TACAAGGACGTGATACTATGGTTTTCATTTGGCGCCTCCTGTTTCATCCTCCTGGCTATT

GTCATGGGTTTGGTTTTTATTTGTGTTAAAAACGGCAACATGCGGTGTACTATTTGCATC

694
ATGAACACGCAGATACTGGTTTTCGCACTCATTGCAATCATCCCTACGAACGCCGACAAG

ATTTGTCTGGGCCACCACGCTGTCTCTAACGGCACCAAGGTGAACACCCTGACCGAGCGC

GGAGTGGAAGTGGTCAATGCGACAGAAACTGTGGAACGGACAAACATTCCACGGATCTGT

AGCAAAGGCAAGAAGACAGTGGATCTGGGGCAGTGCGGCCTACTGGGCACCATCACCGGA

CCTCCTCAATGCGATCAGTTTCTTGAGTTTTCCGCCGATTTGATTATAGAAAGACGGGAG

GGATCCGATGTCTGCTACCCAGGCAAGTTTGTCAACGAGGAGGCCCTAAGACAGATTCTG

CGGGAATCTGGCGGGATCGACAAGGAGGCAATGGGCTTCACCTACAGCGGGATCAGGACA

AACGGAGCCACAAGCGCTTGTAGGCGCTCTGGTTCCTCGTTTTACGCAGAAATGAAGTGG

TTACTTTCAAATACGGACAATGCGGCCTTCCCCCAGATGACCAAATCATATAAGAATACT

CGCAAGAGCCCGGCATTGATTGTCTGGGGCATCCATCATTCTGTGTCTACTGCTGAACAG

ACTAAACTGTATGGCTCTGGCAACAAGCTGGTGACTGTCGGAAGCAGTAACTACCAACAG

AGCTTCGTGCCTAGCCCAGGGGCAAGACCCCAGGTCAACGGGCAGAGGGGGCGTATTGAC

TTTCACTGGCTGATGCTGAACCCAAACGACACTGTGACATTCAGTTTCAATGGGGCCTTT

ATAGCCCCTGACAGGGCCAGCTTCTTGAGGGGCAAGTCCATGGGAATACAGTCTGGTGTC

CAGGTCGATGCCAATTGCGAGGGGGACTGTTATCATAGGGGCGGCACAATCATCTCAAAT

CTGCCTTTCCAGAATATCGATAGTCGTGCCGTGGGAAAATGCCCCCGTTATGTAAAGCAA

AGATCCTTGCTGCTAGCTACCGGGATGAAGAATGTGCCAGAAATTCCAAAGGGACGAGGC

CTGTTCGGCGCTATTGCTGGCTTCATTGAGAACGGGTGGGAAGGCCTGATAGATGGGTGG

TACGGGTTCAGGCACCAGAACGCACAGGGCGAGGGTACAGCTGCCGACTATAAATCTACG

CAGAGCGCAATTGACCAGATCACCGGGAAGCTAAACCGTCTGATTGAAAAGACCAATCAA

CAATTTGAGCTCATAGATAATGAGTTCAACGAAGTTGAAAAGCAGATTGGGAACGTCATC

AACTGGACACGGGATAGTATAACGGAAGTGTGGAGTTATAACGCCGAATTACTGGTGGCG

ATGGAAAACCAGCACACTATCGATTTGGCCGACTCCGAGATGGATAAGCTGTACGAGCGG

GTTAAACGCCAGTTAAGGGAGAATGCTGAGGAGGATGGCACAGGTTGCTTTGAGATTTTC

CATAAATGCGATGACGATTGCATGGCCTCTATTCGAAATAACACATACGACCACTCGAAG

TACCGTGAGGAGGCAATGCAAAATCGAATCCAGATTGACCCAGTGAAACTCTCCAGTGGC

TATAAGGATGTGATCTTGTGGTTCTCTTTTGGGGCCTCATGTTTTATTCTCCTTGCGATC

GTGATGGGATTGGTTTTTATCTGTGTCAAGAATGGAAACATGAGATGCACGATCTGTATC

695
ATGAATACACAGATCTTAGTTTTTGCACTAATAGCTATCATCCCCACAAACGCCGACAAA

ATTTGTCTGGGTCATCATGCTGTGTCTAACGGTACCAAGGTTAATACCCTGACCGAACGC

GGGGTTGAGGTGGTTAACGCGACTGAAACGGTGGAACGCACGAATATACCCAGGATCTGT

TCAAAAGGCAAAAAGACCGTTGATCTGGGTCAGTGCGGCCTTCTGGGGACAATCACCGGC

CCCCCCCAGTGCGACCAGTTCCTCGAGTTTAGTGCTGATTTGATCATTGAGCGAAGAGAG

GGGTCCGACGTGTGCTATCCAGGGAAGTTTGTTAATGAAGAGGCGTTGCGCCAGATCCTA

CGCGAATCCGGGGGAATCGATAAGGAAGCAATGGGCTTCACCTATTCTGGCATTAGAACC

AACGGAGCTACATCCGCCTGTAGAAGGAGTGGCTCGTCTTTCTATGCAGAGATGAAATGG

CTGCTGTCCAACACCGACAATGCCGCTTTCCCCCAGATGACTAAAAGCTACAAGAATACC

CGAAAAAGTCCAGCTCTGATCGTCTGGGGCATCCACCACTCAGTTAGTACAGCCGAACAG

ACAAAGTTGTATGGCAGTGGCAACAAACTAGTCACAGTTGGCTCGTCCAACTATCAGCAG

AGTTTTGTGCCCAGTCCCGGGGCACGTCCGCAGGTCAATGGACAGAGCGGCCGGATTGAT

TTCCATTGGCTGATGCTGAACCCTAACGATACAGTGACATTTTCCTTCAACGGCGCGTTC

ATCGCACCCGATCGCGCTTCATTCCTGAGGGGGAAGAGCATGGGGATTCAGTCGGGAGTC

CAGGTTGACGCCAACTGTGAAGGAGACTGCTACCATTCAGGGGGGACAATCATCTCCAAC

CTACCATTCCAGAACATTGATTCAAGAGCTGTTGGAAAGTGTCCAAGATATGTCAAGCAA

AGGTCTCTATTGCTAGCTACCGGTATGAAGAATGTCCCTGAAATACCGAAGGGGAGGGGT

CTGTTCGGTGCCATAGCTGGTTTTATCGAAAATGGGTGGGAGGGTCTTATCGACGGGTGG

TATGGATTTCGCCACCAGAACGCCCAGGGGGAAGGCACTGCAGCTGACTATAAGTCGACT

CAGTCTGCCATCGACCAGATCACCGGTAAATTAAATAGACTGATTGAGAAGACAAATCAG

CAATTCGAGCTCATCGATAATGAGTTCAACGAGGTCGAGAAGCAGATTGGAAATGTGATT

AACTGGACGCGCGATTCCATTACCGAGGTGTGGAGCTATAACGCGGAGTTGTTAGTGGCG

ATGGAGAATCAGCATACAATTGATCTAGCGGACAGTGAAATGGACAAGCTGTACGAGAGA

GTTAAACGACAGCTGCGCGAGAACGCCGAGGAGGATGGGACAGGGTGTTTTGAGATCTTC

CATAAGTGTGACGATGATTGTATGGCTAGCATTAGAAATAACACTTACGATCATAGCAAA

TACAGGGAGGAGGCCATGCAGAACCGAATTCAAATCGACCCCGTGAAGCTGTCTTCGGGC

TACAAAGACGTTATTCTCTGGTTTAGCTTTGGTGCGTCATGCTTCATTCTGCTGGCGATT

GTAATGGGGTTGGTTTTCATATGCGTTAAGAACGGCAACATGCGGTGCACTATTTGTATT

TABLE 18

Codon Optimized Sequences Encoding H10 Hemagglutinin

Seq

ID

No.
Nucleic Acid Sequence

696
5′^7MeGpppG_2′OMeGGAAAUAAGAGAGAAAAGAAGAGUAAGAAGAAAUAUAAGAGCCACCA

UGUACAAAAUCGUCGUCAUUAUCGCAUUGCUGGGCGCUGUCAAGGGACUCGACAAGAU

CUGUCUCGGACACCACGCGGUGGCUAACGGAACCAUCGUCAAGACCCUGACUAACGAG

CAGGAAGAAGUGACCAACGCCACCGAAACUGUGGAAUCCACCGGGAUCAACAGAUUGU

GCAUGAAGGGUCGGAAGCACAAGGAUCUGGGAAACUGCCACCCGAUUGGAAUGCUCAU

CGGCACCCCGGCAUGCGAUCUGCAUCUGACUGGGAUGUGGGAUACCCUUAUCGAGCGG

GAAAACGCGAUCGCAUACUGUUACCCCGGUGCCACCGUGAACGUGGAGGCGCUCAGAC

AGAAGAUUAUGGAGUCAGGCGGCAUCAACAAGAUUUCCACGGGCUUCACCUACGGGUC

CUCCAUUAACUCCGCCGGUACCACUCGGGCCUGCAUGCGGAACGGAGGGAACUCCUUU

UACGCCGAGCUCAAGUGGCUUGUGUCAAAAUCCAAGGGACAGAAUUUCCCCCAAACCA

CCAACACCUAUAGGAACACCGACACCGCCGAACAUCUCAUUAUGUGGGGCAUCCAUCA

CCCUUCGAGCACACAGGAGAAGAAUGACCUCUACGGCACCCAGUCGCUGAGCAUCUCC

GUGGGCUCAUCGACCUAUCGCAACAACUUCGUGCCUGUGGUCGGCGCCCGACCUCAAG

UCAACGGACAGUCCGGACGCAUUGACUUCCAUUGGACUCUGGUGCAACCGGGAGACAA

CAUCACUUUCUCCCACAACGGCGGACUGAUUGCCCCAAGCCGCGUGUCAAAGCUGAUC

GGUAGAGGGCUGGGUAUUCAGUCGGAUGCUCCCAUCGAUAACAACUGCGAAUCCAAGU

GCUUUUGGAGAGGCGGCUCCAUCAAUACUCGGCUGCCGUUUCAGAACCUGAGCCCGAG

GACCGUGGGGCAGUGCCCAAAAUACGUGAAUCGCCGGUCACUGAUGCUGGCGACCGGA

AUGAGGAACGUGCCUGAACUCAUCCAGGGACGGGGGCUGUUCGGCGCCAUCGCCGGCU

UCCUGGAAAACGGAUGGGAGGGAAUGGUGGACGGUUGGUACGGCUUCCGCCACCAAAA

CGCCCAGGGAACUGGACAGGCCGCCGACUACAAGUCCACACAGGCCGCAAUAGACCAG

AUCACUGGGAAGCUCAACCGCCUUGUGGAAAAGACUAACACUGAAUUCGAGUCGAUCG

AGUCUGAGUUCUCCGAGAUCGAACACCAGAUUGGGAACGUGAUCAACUGGACGAAGGA

CUCCAUUACCGACAUCUGGACCUACCAGGCGGAACUGCUCGUGGCGAUGGAGAACCAG

CACACUAUCGACAUGGCCGACUCCGAGAUGCUGAAUCUGUACGAACGCGUGCGGAAGC

AACUGAGACAAAACGCUGAAGAAGAUGGAAAGGGUUGUUUCGAGAUCUACCACGCCUG

CGACGACAGCUGCAUGGAAAGCAUUAGGAACAAUACCUACGACCACUCGCAGUACCGG

GAGGAGGCCCUUCUGAACCGGCUGAACAUUAACCCCGUGACCUUGAGCUCCGGCUACA

AGGACAUCAUCCUGUGGUUCUCGUUUGGAGCCAGCUGCUUCGUGCUGCUGGCCGUCGU

GAUGGGAUUGUUCUUCUUCUGCCUGAAAAACGGAAACAUGCGCUGCACCAUCUGUAUU

UGAUAAUAGGCUGGAGCCUCGGUGGCCAUGCUUCUUGCCCCUUGGGCCUCCCCCCAGC

CCCUCCUCCCCUUCCUGCACCCGUACCCCCGUGGUCUUUGAAUAAAGUCUGAGUGGGC

GGCAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAA

AAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAUCUAGCH3′

697
ATGTACAAGATCGTCGTGATTATCGCCCTTCTGGGGGCAGTCAAGGGACTAGACAAAATAT

GCCTGGGCCATCATGCAGTGGCTAACGGGACGATAGTGAAGACGCTGACCAACGAACAGGA

GGAGGTCACTAACGCCACTGAGACAGTGGAGTCGACGGGCATCAATCGTTTGTGCATGAAA

GGCCGGAAACACAAAGACTTAGGTAATTGTCATCCGATAGGGATGCTGATAGGCACCCCTG

CATGCGACCTCCATCTCACTGGGATGTGGGACACCCTGATCGAAAGGGAAAATGCAATAGC

CTATTGCTACCCCGGTGCTACCGTTAATGTCGAGGCGCTGAGACAGAAAATCATGGAATCC

GGGGGAATCAACAAGATTAGCACGGGGTTTACATATGGGAGCTCAATAAATTCCGCCGGTA

CTACCCGAGCATGCATGCGGAACGGCGGAAATAGTTTTTATGCCGAACTCAAGTGGCTTGT

CTCCAAGTCTAAGGGACAAAATTTCCCGCAGACAACAAATACGTATCGTAACACTGATACC

GCCGAGCATCTTATCATGTGGGGCATCCATCACCCTAGCTCAACGCAGGAGAAAAACGACT

TGTACGGTACTCAGTCTCTATCTATCTCCGTGGGATCTTCCACCTATAGAAACAATTTTGT

GCCCGTCGTAGGGGCCCGCCCTCAGGTGAATGGCCAGTCAGGCCGTATAGACTTCCATTGG

ACTCTCGTACAGCCCGGGGATAATATAACCTTTAGTCATAACGGAGGCCTCATTGCTCCCA

GCAGGGTTTCTAAGTTGATCGGTCGCGGGCTGGGCATTCAGTCTGATGCCCCAATTGATAA

CAACTGTGAAAGCAAGTGCTTCTGGAGGGGTGGGAGTATCAATACTAGACTCCCATTCCAG

AACTTGTCTCCGCGGACTGTAGGACAGTGCCCAAAGTATGTGAATCGTCGGTCTCTCATGC

TGGCAACCGGTATGAGAAATGTTCCTGAGCTAATACAGGGAAGAGGACTTTTTGGAGCAAT

CGCCGGATTTTTAGAAAATGGTTGGGAGGGGATGGTTGACGGATGGTACGGTTTCAGGCAC

CAGAACGCCCAGGGAACCGGCCAGGCCGCGGACTACAAAAGCACACAGGCAGCCATTGATC

AGATTACTGGCAAGCTGAACCGCTTAGTCGAGAAGACCAACACGGAATTTGAATCAATCGA

GTCAGAATTTAGCGAAATCGAACATCAGATTGGGAACGTAATTAATTGGACAAAAGATAGC

ATCACAGATATTTGGACCTACCAGGCTGAGCTACTGGTGGCTATGGAGAACCAACACACTA

TTGATATGGCCGACAGCGAAATGTTAAATTTGTATGAACGGGTACGGAAGCAGCTTAGACA

GAACGCAGAAGAAGATGGCAAGGGCTGCTTTGAAATTTACCACGCTTGCGATGACAGTTGC

ATGGAGTCTATTAGGAACAATACATATGATCACTCTCAGTACAGAGAGGAGGCCTTGCTCA

ATAGGCTGAATATCAACCCTGTCACCCTGAGCAGTGGTTATAAGGACATCATCCTGTGGTT

CAGCTTTGGCGCTTCATGTTTCGTGCTGCTGGCTGTCGTCATGGGCCTTTTCTTTTTTTGT

TTGAAGAACGGCAACATGCGTTGCACTATCTGCATC

698
ATGTACAAGATCGTGGTGATCATCGCTCTGCTCGGCGCCGTTAAGGGACTGGATAAGATTT

GTTTAGGGCACCATGCAGTGGCAAACGGGACCATTGTCAAGACACTCACCAATGAACAGGA

GGAAGTGACCAACGCGACTGAGACTGTTGAGTCCACCGGCATAAACAGGCTTTGTATGAAA

GGCAGAAAGCACAAGGATTTGGGTAATTGTCACCCAATAGGAATGCTAATTGGGACTCCTG

CCTGCGATCTCCACCTGACAGGCATGTGGGACACCCTGATTGAACGGGAGAATGCTATCGC

ATACTGCTACCCAGGTGCAACCGTAAACGTGGAGGCCCTGCGACAGAAGATAATGGAGAGC

GGAGGCATCAACAAGATCAGTACGGGATTTACCTACGGGTCTTCTATCAATTCGGCTGGCA

CAACACGTGCTTGCATGAGAAACGGAGGCAACTCCTTCTACGCTGAACTCAAATGGTTGGT

GAGTAAGAGTAAGGGTCAGAATTTCCCACAGACGACCAACACATACAGGAACACCGATACG

GCCGAACACCTCATCATGTGGGGCATACACCACCCTAGTAGTACACAAGAGAAAAACGACC

TGTATGGGACACAATCCCTTTCAATCAGTGTTGGTAGCTCGACCTACCGTAATAATTTCGT

CCCTGTGGTGGGTGCTAGACCGCAGGTCAATGGCCAGTCAGGAAGGATCGATTTCCACTGG

ACCCTCGTGCAGCCAGGTGATAACATTACTTTTTCTCATAATGGCGGACTAATTGCGCCTA

GCAGGGTGTCAAAGCTTATTGGGAGAGGCCTAGGCATACAAAGCGACGCCCCAATCGATAA

CAATTGCGAGTCGAAGTGTTTCTGGAGGGGGGGATCAATTAACACACGTCTGCCCTTCCAG

AATCTGTCACCAAGGACTGTGGGCCAGTGTCCAAAGTATGTTAATCGACGTTCACTCATGC

TTGCCACCGGCATGCGGAATGTGCCTGAACTGATTCAGGGCCGCGGACTTTTTGGCGCCAT

TGCAGGTTTCTTGGAGAACGGGTGGGAAGGTATGGTCGACGGATGGTATGGCTTCAGACAC

CAGAACGCCCAAGGAACTGGCCAGGCCGCCGATTATAAGAGCACCCAGGCTGCGATCGATC

AAATTACCGGTAAACTCAACCGGCTGGTCGAGAAGACTAATACAGAGTTTGAGTCAATAGA

ATCCGAGTTTTCCGAAATAGAACATCAGATCGGTAATGTAATCAACTGGACCAAGGACAGC

ATCACCGACATATGGACATACCAGGCCGAACTGCTCGTCGCCATGGAGAATCAACACACGA

TTGACATGGCCGATTCGGAAATGCTGAATCTGTACGAAAGGGTGCGTAAACAGTTGCGGCA

GAATGCAGAAGAAGATGGAAAAGGGTGTTTTGAAATCTACCACGCCTGCGACGATAGCTGC

ATGGAATCTATCCGGAATAACACCTATGACCATTCCCAATACCGAGAAGAGGCCCTGCTCA

ACCGCTTGAACATTAATCCCGTTACATTGTCATCCGGATACAAGGACATCATCTTGTGGTT

CTCTTTCGGGGCTTCCTGTTTTGTGCTTCTAGCAGTTGTGATGGGTCTGTTTTTCTTCTGC

TTAAAGAACGGCAATATGAGATGTACTATTTGCATC

699
ATGTACAAGGTAGTGGTAATTATCGCTCTGCTAGGTGCCGTTCGTGGCTTGGACAAGATTT

GTTTGGGGCACCATGCCGTAGCCAACGGAACAATTGTGAAGACACTGACTAACGAACAAGA

GGAAGTAACCAACGCTACAGAAACAGTCGAATCTAAAAGTTTGGGCAAGTTATGTATGAAA

GGGCGGAGTTACAACGACCTCGGAAATTGCCACCCCATCGGAATTTTAATCGGCACTCCAG

CCTGCGATCTGCACTTAACAGGAACCTGGGACACCCTCATCGAACGCGAAAATGCCGTTGC

ATACTGTTACCCAGGTGCGACTGTCAACGAGGAAGCGCTCCGCCAGAAGATCATGGAAAGC

GGGGGGATTTCAAAAATCTCTACCGGGTTTACATACGGGACTTCCATCAACAGCGCTGGCA

CCACAAAGGCCTGCATGCGCAATGGCGGTAACAGCTTCTACGCTGAGCTCAAGTGGCTGGT

CAGCAAAAACAAAGGCCAGAACTTCCCCCAAACTACTAATACCTACAGAAACACAGATACC

GCCGAGCACCTCATAATTTGGGGGATCCATCACCCATCTAGCACTCAGGAGAAAAACGATC

TCTATGGCACACAGTCTCTCAGCATTTCAGTGGGAAGCTCGACATACCAGAATAACTTTGT

TCCCGTGGTGGGCGCAAGACCACAGGTCAACGGCCAGTCCGGGAGAATTGATTTCCATTGG

ACGCTGCTGCAACCTGGAGACAACATCACCTTTTCTCATAATGGCGGCCTAATTGCGCCTT

CCAGAGTTAGCAAGCTGATCGGCCGGGGCCTAGGTATTCAGAGCGAGGCCCCAATTGACAA

CGGTTGCGAATCAAAGTGCTTCTGGAAAGGCGGATCCATTAACACGAAGTTGCCCTTCCAG

AACTTATCACCCAGAACCGTGGGGCAGTGTCCCAAATACGTGAATAAGAGGTCCCTGATGC

TCGCTACCGGTATGCGGAATGTGCCTGAGATAATGCATGGAAGAGGACTGTTTGGGGCAAT

CGCTGGGTTTATCGAAAACGGTTGGGAAGGGATGGTTGATGGATGGTACGGGTTTCGGCAT

CAGAATGCACAGGGAACTGGTCAGGCCGCCGATTACAAATCAACGCAAGCCGCCATCGACC

AGATAACTGGAAAGCTGAATAGGCTCATCGAAAAAACCAACACCGAGTTCGAATCAATTGA

GTCTGAGTTCTCTGAGATCGAGCACCAAATCGGGAATATCATCAATTGGACCAAAGATAGC

ATTACTGATATCTGGACATATCAGGCTGAGCTGCTGGTCGCCATGGAGAACCAGCATACAA

TCGACATGGCAGACTCGGAGATGCTTAACCTGTATGAGAGGGTGCGTAAACAATTGCGACA

GAATGCCGAAGAGGATGGTAAGGGTTGCTTCGAAATCTACCACGCTTGCGACGATTCTTGC

ATGGAAAGTATAAGAAATAATACCTATGATCATTCACAATACCGCGAAGAGGCTTTGCTGA

ACAGACTCAACATCAATCCGGTGAAGCTTTCCTCTGGGTACAAGGATATAATTCTGTGGTT

TTCCTTTGGAGCTTCCTGTCTCATATTATTGGCTGTTGTTATGGGCCTCGTTTTTTTTTGC

CTGAAGAACGGTAACATGCGCTGTACAATATGTATC

700
ATGTACAAAATTATCGTGATCATCGCTCTTCTGGGCGCCGTCAAAGGTCTCGATAAAATTT

GCCTTGGGCACCATGCTGTGGCAAACGGAACTATTGTAAAAACTCTTACGAATGAGCAAGA

AGAGGTGACCAATGCCACCGAAACCGTCGAGTCCACCGGGATCAATAGGTTGTGCATGAAG

GGGCGTAAACACAAGGACCTTGGCAATTGCCATCCGATCGGCATGTTGATCGGAACACCAG

CTTGTGACCTTCACTTGACCGGAACATGGGACACTCTGATCGAGCGAGAGAACGCAATTGC

ATATTGCTATCCGGGAGCAACCGTGAATGTGGAGGCCCTGCGGCAGAAGATCATGGAATCC

GGAGGTATCGACAAAATCTCTACCGGATTCACCTACGGATCTTCAATTAACTCCGCTGGCA

CTACACGCGCTTGCATGCGAAATGGCGGTAACTCATTCTACGCCGAGCTGAAGTGGCTGGT

GTCCAAGTCTAAAGGGCAGAATTTTCCGCAGACCACTAACACCTACAGAAACACTGATACC

GCCGAACATCTCATTATGTGGGGAATCCACCACCCATCAAGCACTCAAGAAAAAAACGACT

TGTATGGTACACAGTCACTAAGCATTTCCGTGGGCAGCTCTACCTACCGCAACAACTTTGT

CCCCGTGGTTGGCGCCCGACCCCAAGTAAATGGTCAGTCCGGCAGGATCGATTTTCATTGG

ACCCTGGTGCAGCCAGGGGATAACATCACTTTTAGCCATAACGGCGGCTTGATAGCGCCGT

CAAGGGTGTCCAAACTGATCGGAAGAGGGCTGGGAATTCAGAGTGACGCACCCATCGATAA

CAACTGCGAAAGCAAATGTTTCTGGGGGGGGGGTTCGATCAACACCCGATTACCTTTCCAG

AACCTCTCCCCCAGGACTGTTGGTCAGTGCCCGAAATATGTTAATCGACGCAGCTTGATGC

TCGCCACCGGGATGCGCAATGTTCCCGAGCTCATTCAGGGGCGGGGCCTCTTTGGCGCAAT

AGCTGGGTTCCTCGAGAATGGTTGGGAAGGCATGGTGGATGGATGGTACGGCTTCCGGCAT

CAAAACGCACAGGGCACAGGCCAGGCCGCAGATTACAAGTCTACACAGGCCGCCATTGATC

AGATTACAGGTAAACTGAACAGGCTAGTGGAAAAGACCAATACCGAGTTCGAATCCATCGA

ATCTGAGTTCTCAGAGATAGAGCACCAGATCGGGAACGTTATCAACTGGACCAAGGACAGC

ATTACCGACATTTGGACCTACCAGGCAGAGCTCCTGGTCGCCATGGAAAATCAGCATACCA

TCGACATGGCCGATTCAGAGATGCTTAACCTTTATGAGCGGGTGAGGAAACAGCTGAGGCA

GAATGCAGAAGAAGATGGTAAGGGTTGCTTCGAAATTTACCATGCTTGTGATGATAGTTGT

ATGGAGAGTATCCGTAACAATACTTACGATCACAGCCAGTACAGGGAAGAAGCACTCCTCA

ATCGCCTCAACATCAATCCTGTAACTCTCTCGTCTGGTTACAAAGATATCATCTTATGGTT

CTCTTTTGGGGCCTCATGTTTCGTGCTCCTGGCCGTGGTGATGGGCCTGTTCTTTTTCTGC

TTAAAGAATGGAAATATGAGGTGCACAATCTGCATT

701
ATGTACAAGATAGTCGTTATCATCGCCTTACTCGGAGCAGTTAAAGGTTTAGATAAGATCT

GCCTGGGGCACCACGCCGTCGCTAACGGCACTATTGTGAAGACGCTGACCAATGAACAAGA

GGAAGTCACTAACGCAACAGAAACCGTGGAGAGCACTGGCATCAATCGCCTCTGTATGAAA

GGGCGCAAGCATAAGGACCTCGGCAATTGCCACCCTATAGGCATGCTGATTGGAACGCCTG

CTTGTGACCTTCACCTGACAGGGATGTGGGATACCCTAATTGAACGAGAGAACGCGATCGC

ATACTGCTATCCTGGTGCCACTGTGAACGTGGAAGCCTTACGCCAAAAAATCATGGAGAGC

GGAGGGATCAATAAAATCAGTACAGGTTTCACCTACGGATCCTCCATCAACAGTGCCGGTA

CTACACGCGCCTGTATGAGAAACGGAGGCAACAGCTTCTATGCTGAGCTGAAATGGTTAGT

GAGCAAATCCAAAGGTCAGAATTTTCCCCAGACCACAAATACTTACCGAAATACGGACACC

GCCGAGCATCTGATAATGTGGGGCATCCACCATCCTAGTTCTACTCAGGAGAAAAACGACC

TTTATGGAACGCAGAGCCTGTCTATAAGCGTGGGGTCTTCAACATACAGGAATAACTTTGT

CCCTGTAGTGGGCGCCGGTCCTCAGGTGAATGGGCAAAGCGGCCGCATCGATTTTCACTGG

ACCCTGGTTCAACCTGGAGACAATATTACGTTCAGTCACAACGGCGGCCTTATTGCCCCTT

CCAGAGTCTCTAAGCTCATTGGCAGGGGACTCGGTATCCAATCCGACGCCCCTATTGACAA

CAACTGCGAGTCCAAATGCTTCTGGAGGGGAGGAAGCATCAACACCCGCCTGCCATTTCAG

AATCTTTCACCTCGAACCGTGGGCCAGTGTCCTAAATACGTCAATCGGAGAAGCTTGATGT

TGGCCACTGGGATGCGGAACGTACCCGAGCTTATCCAAGGCAGAGGCCTTTTCGGTGCCAT

CGCAGGGTTCTTGGAAAATGGCTGGGAAGGCATGGTCGATGGCTGGTATGGCTTTCGCCAT

CAAAATGCTCAGGGCACGGGCCAGGCCGCTGACTACAAAAGTACACAAGCTGCCATCGATC

AGATTACAGGCAAGCTCAATAGGTTGGTGGAGAAGACAAACACCGAGTTTGAGTCAATCGA

GAGCGAGTTTAGCGAGATAGAGCATCAGATCGGCAACGTGATTAACTGGACTAAGGACTCT

ATAACAGACATTTGGACGTACCAGGCAGAGCTCCTTGTAGCAATGGAAAATCAGCACACAA

TTGACATGGCTGACTCTGAAATGCTCAACCTGTATGAGCGGGTTCGGAAGCAGCTGAGGCA

GAATGCAGAGGAAGATGGTAAGGGCTGCTTTGAAATCTACCATGCCTGTGATGACAGTTGC

ATGGAGAGTATTCGAAATAACACATACGATCATTCGCAGTACAGAGAGGAAGCCTTGTTGA

ACCGCCTGAATATCAACCCCGTGACATTATCCTCAGGCTATAAAGACATCATCCTCTGGTT

TTCGTTTGGGGCCTCGTGCTTTGTCTTGCTGGCTGTTGTCATGGGGCTGTTTTTCTTTTGT

TTAAAGAACGGGAACATGCGATGCACAATCTGTATT

702
ATGTACAAGATTGTGCTGGTACTTGCACTTCTGGGTGCCGTTCACGGCCTCGACAAAATCT

GCCTAGGCCACCACGCTGTGCCTAACGGGACCATTGTGAAAACCCTGACTAACGAGAAGGA

GGAGGTTACCAACGCAACCGAGACTGTAGAGTCTAAGTCCTTGGATAAACTGTGCATGAAG

AACCGAAACTACAAAGACCTGGGCAATTGCCATCCTATCGGGATGGTCGTCGGAACTCCAG

CCTGCGATCTCCACCTAACTGGCACCTGGGACACCCTCATCGAGAGGGACAATTCAATTGC

ATACTGCTATCCTGGGGCTACCGTGAGTGAAGAAGCACTGCGACAAAAAATCATGGAGTCA

GGAGGGATCGACAAAATATCGACGGGATTCACATACGGCTCATCTATTAATTCAGCAGGAA

CCACGAAAGCTTGTATGCGCAACGGAGGTAACTCCTTCTATAGCGAACTCAAGTGGTTAGT

GTCTAAGAATAAGGGACAGAACTTTCCACAGACAACAAACACTTACCGGAACACAGACAGC

GTAGAACACCTCATAATATGGGGGATCCACCACCCAAGCTCCACACAGGAGAAGAACGATT

TATACGGCACTCAGTCCCTGAGCATCAGCGTCGGATCAAGCACCTACCAGAACAACTTCGT

CCCCGTGGTGGGAGCTCGCCCACAGGTGAATGGCCAGAGCGGACGCATCGATTTCCACTGG

ACTATGGTCCAGCCGGGTGACAACATCACCTTCTCTCACAATGGGGGGCTGATTGCTCCGA

ACCGAGTGTCCAAGCTGAAAGGGAGGGGGTTAGGAATCCAGAGCGGCGCCTCGGTAGACAA

CGACTGCGAGAGCAAATGTTTCTGGAAAGGTGGCTCGATTAATACCAAGCTTCCATTTCAG

AATTTATCTCCTAGAACTGTCGGCCAGTGTCCAAAATACGTCAACAAAAAGTCTCTGCTCC

TCGCAACAGGCATGCGGAATGTTCCCGAAGTTGCACAGGGCCGAGGCCTGTTTGGTGCCAT

TGCCGGGTTTATCGAGAACGGATGGGAGGGCATGGTGGATGGATGGTACGGATTCCGACAC

CAGAATGCGCAGGGGACGGGCCAAGCAGCGGATTACAAGTCCACACAAGCAGCAATTGACC

AAATCACTGGCAAGTTGAATCGCCTCATAGAGAAAACTAATACAGAGTTCGAATCTATCGA

AAGTGAGTTTTCCGAGATCGAACACCAGATCGGGAATGTGATCAACTGGACGAAGGATTCT

ATTACTGACATATGGACCTACCAGGCCGAGCTCCTGGTGGCTATGGAAAACCAACATACAA

TTGACATGGCTGACTCTGAAATGCTGAATCTGTACGAACGAGTGAGGAAGCAGCTCCGCCA

AAACGCAGAGGAAGACGGAAAGGGTTGTTTTGAGATATATCACAAGTGCGACGACAACTGC

ATGGAGTCCATCCGAAACAATACTTACGACCATACACAATACAGAGAGGAGGCCCTGCTGA

ACCGCCTGAATATCAATCCCGTGAAGCTCAGTTCCGGTTACAAGGACGTCATTTTATGGTT

CAGCTTTGGAGCGTCCTGCTTCGTGCTTCTGGCCGTCATCATGGGCCTTGTCTTCTTTTGT

CTGAAAAACGGTAATATGAGATGCACCATCTGCATT

703
ATGTATAAAATTGTCGTGATCATCGCCCTGCTCGGGGCCGTCAAGGGATTGGATAAGATAT

GTCTCGGTCATCATGCAGTGGCTAACGGCACGATCGTGAAGACCCTGACCAACGAGCAGGA

GGAAGTGACTAATGCCACCGAAACCGTTGAGTCTACTGGTATCAATAGGCTGTGCATGAAA

GGGAGAAAGCACAAGGACCTCGGCAATTGTCACCCAATCGGGATGCTCATTGGGACACCCG

CATGTGACCTCCACCTGACAGGCATGTGGGATACACTGATTGAGCGCGAAAATGCCATCGC

GTACTGCTACCCTGGCGCCACCGTGAATGTGGAAGCTCTGCGACAGAAAATAATGGAGAGT

GGGGGGATTAATAAGATCTCTACAGGGTTTACGTACGGATCAAGTATTAACTCCGCCGGGA

CTACTCGAGCATGTATGCGCAATGGCGGCAATTCCTTTTACGCCGAGCTGAAGTGGCTTGT

GTCGAAGTCAAAAGGACAGAATTTTCCCCAGACAACAAACACATATCGCAATACCGATACT

GCAGAACACTTGATTATGTGGGGGATTCACCACCCGTCATCTACTCAGGAGAAGAACGATC

TGTATGGCACTCAGAGCCTGAGTATCTCAGTAGGCAGCAGCACCTACAGAAATAACTTCGT

GCCGGTTGTCGGGGCCCGCCCACAAGTGAATGGCCAGTCAGGGCGGATCGACTTTCACTGG

ACGCTGGTTCAGCCTGGAGATAACATTACGTTTAGTCACAATGGCGGGCTCATCGCGCCAA

GTCGGGTATCCAAACTGATCGGCCGAGGACTTGGGATACAATCGGACGCCCCCATCGATAA

CAATTGCGAATCCAAATGTTTTTGGAGAGGAGGATCCATAAATACACGACTGCCCTTTCAG

AACCTGTCTCCTCGGACAGTTGGGCAGTGTCCAAAGTACGTAAACCGGAGGTCTCTCATGC

TCGCGACAGGAATGCGTAATGTGCCAGAACTGATTCAGGGCCGCGGCCTCTTCGGTGCGAT

CGCGGGGTTCCTCGAGAATGGTTGGGAAGGCATGGTGGACGGGTGGTATGGTTTTCGTCAT

CAGAACGCTCAAGGCACTGGGCAGGCCGCCGATTACAAGTCCACGCAGGCGGCAATTGACC

AAATCACCGGGAAGTTAAACCGGCTTGTCGAGAAAACCAATACCGAGTTTGAATCCATAGA

GTCCGAGTTTTCCGAGATCGAGCACCAAATCGGAAACGTTATAAATTGGACCAAGGACTCT

ATCACCGACATCTGGACCTACCAGGCCGAACTCCTGGTCGCCATGGAAAATCAGCACACAA

TAGACATGGCAGATTCAGAGATGCTGAACCTGTACGAGCGGGTGCGTAAGCAGCTCCGGCA

GAATGCGGAAGAGGACGGCAAGGGATGTTTCGAAATATACCACGCTTGTGATGATTCATGT

ATGGAGTCGATCAGGAACAATACATACGACCATTCCCAGTACAGGGAAGAGGCCCTCCTGA

ACAGGCTTAACATCAACCCCGTCACCCTGTCCAGCGGCTACAAGGATATTATCCTTTGGTT

TTCATTCGGCGCAAGCTGCTTCGTCTTACTGGCCGTGGTAATGGGACTATTCTTTTTTTGC

CTGAAAAACGGCAACATGAGGTGTACCATTTGTATT

704
ATGTACAAAATCGTGCTCGTTCTGGCCCTGCTCGGCGCCGTGCACGGCCTCGACAAGATTT

GCCTGGGACATCACGCTGTGCCCAACGGTACTATTGTCAAGACACTGACGAACGAAAAAGA

AGAGGTTACAAACGCTACCGAAACCGTTGAATCTAAGAGCTTGGATAAACTGTGCATGAAA

AATCGCAACTATAAAGACCTCGGTAATTGTCACCCTATAGGGATGGTGGTCGGCACCCCAG

CTTGCGACCTGCATTTGACAGGTACTTGGGATACTTTGATCGAACGGGATAACAGTATCGC

CTACTGTTATCCGGGAGCCACGGTGTCGGAAGAGGCTCTGCGTCAGAAAATCATGGAGAGC

GGCGGGATAGACAAGATCTCCACTGGCTTCACTTATGGCTCCAGCATTAATAGCGCAGGTA

CAACCAAGGCTTGCATGAGAAATGGGGGGAACTCCTTCTACTCAGAACTGAAATGGCTGGT

GTCCAAAAATAAGGGACAGAATTTCCCGCAGACGACAAACACCTATAGAAACACAGACTCT

GTAGAGCACCTCATTATTTGGGGTATCCATCACCCAAGCTCCACCCAGGAAAAGAATGACC

TGTACGGCACACAGTCCTTGAGCATTTCAGTGGGCAGCTCCACATATCAGAATAACTTTGT

GCCAGTCGTTGGCGCACGACCCCAGGTGAATGGGCAGTCAGGTCGCATTGACTTCCACTGG

ACTATGGTGCAGCCCGGCGATAACATTACCTTCTCCCATAACGGGGGACTGATAGCCCCCA

ATAGGGTCTCTAAGCTCAAGGGTCGGGGTTTGGGCATCCAGTCCGGAGCATCCGTCGATAA

CGACTGTGAGTCGAAATGCTTTTGGAAAGGTGGATCCATCAATACAAAGCTACCTTTCCAA

AATTTATCCCCTCGAACGGTCGGACAGTGCCCTAAATACGTAAACAAGAAGTCACTGCTCC

TCGCTACCGGCATGCGCAATGTACCTGAAGTTGCCCAAGGACGGGGGCTTTTCGGCGCAAT

CGCTGGCTTCATTGAGAATGGATGGGAGGGCATGGTTGACGGCTGGTACGGCTTTAGGCAC

CAGAATGCTCAGGGTACCGGTCAGGCAGCAGATTATAAAAGCACCCAGGCTGCCATCGATC

AGATAACCGGGAAGTTGAACAGGCTGATCGAGAAGACCAACACTGAGTTTGAGAGCATTGA

ATCGGAGTTCTCGGAAATCGAACATCAAATCGGCAATGTGATCAATTGGACTAAGGATTCT

ATCACCGACATCTGGACGTACCAGGCAGAACTGTTAGTTGCAATGGAAAATCAGCATACTA

TTGATATGGCAGACAGTGAGATGCTGAACCTGTACGAGCGTGTTAGAAAGCAGCTCAGACA

GAACGCCGAGGAGGACGGGAAAGGATGCTTTGAAATCTATCACAAATGTGATGATAATTGC

ATGGAGTCAATCAGGAATAATACATACGATCACACGCAATACAGAGAGGAGGCTCTCCTGA

ACCGCCTTAATATCAACCCCGTGAAACTCAGCTCCGGATATAAAGACGTCATCCTCTGGTT

TTCTTTTGGAGCAAGCTGCTTCGTGCTGCTCGCCGTTATCATGGGGTTGGTGTTCTTCTGC

CTGAAGAATGGTAACATGAGATGCACCATTTGTATA

705
ATGTACAAGATTGTGCTCGTTCTGGCACTATTGGGCGCAGTGCATGGTCTGGATAAAATCT

GTCTGGGTCATCACGCAGTGCCCAACGGTACTATCGTCAAAACACTAACGAACGAGAAGGA

AGAAGTAACTAATGCAACGGAGACAGTGGAGTCAAAAAGTCTGGACAAGTTATGTATGAAG

AACAGAAACTATAAGGATCTCGGTAATTGCCACCCCATCGGTATGGTGGTTGGGACCCCAG

CCTGCGACCTTCACCTGACGGGAACCTGGGACACCCTCATCGAGCGGGACAACTCCATTGC

CTATTGCTATCCTGGGGCCACCGTCTCCGAGGAGGCACTGAGGCAGAAAATTATGGAATCC

GGCGGGATTGACAAGATTTCTACCGGCTTTACCTATGGCTCCTCAATCAACAGCGCTGGGA

CAACTAAAGCCTGCATGAGGAACGGAGGAAATTCTTTTTACTCTGAGTTGAAGTGGTTGGT

GAGCAAAAATAAGGGCCAAAATTTTCCTCAGACGACCAATACCTACCGTAATACTGACTCA

GTTGAGCACCTCATCATTTGGGGAATTCATCATCCCAGCAGCACTCAGGAGAAGAATGATC

TGTACGGGACCCAATCGTTGAGTATATCCGTGGGATCTAGTACTTATCAGAACAACTTTGT

ACCTGTAGTGGGTGCCCGCCCACAGGTAAACGGACAGTCGGGGCGTATTGACTTTCATTGG

ACAATGGTGCAGCCCGGGGATAATATCACTTTTAGCCATAATGGAGGCCTGATCGCACCAA

ACCGAGTGAGCAAGCTGAAGGGTAGAGGATTGGGAATCCAGTCTGGAGCCAGCGTTGATAA

CGACTGTGAGTCTAAATGCTTCTGGAAAGGGGGTAGCATAAATACCAAGCTGCCCTTCCAA

AACCTGAGCCCTCGGACCGTGGGCCAGTGCCCAAAGTACGTGAATAAGAAAAGCCTCCTGC

TCGCTACAGGCATGAGAAATGTGCCCGAGGTTGCACAGGGCAGAGGGCTCTTCGGCGCTAT

AGCTGGATTCATTGAAAATGGCTGGGAAGGTATGGTAGATGGTTGGTACGGCTTCAGACAC

CAGAATGCTCAGGGAACCGGACAGGCTGCTGATTATAAATCTACCCAGGCTGCTATCGATC

AGATCACTGGGAAATTGAACCGGCTGATCGAAAAAACAAACACCGAATTCGAGAGTATTGA

ATCCGAGTTTAGCGAAATTGAACATCAGATCGGCAATGTGATAAACTGGACTAAGGATAGT

ATAACTGACATCTGGACATACCAAGCTGAGCTCCTGGTGGCCATGGAGAATCAACACACGA

TCGACATGGCAGACTCTGAAATGTTGAACCTGTACGAGAGGGTGCGGAAGCAGCTCAGACA

AAACGCTGAGGAGGACGGCAAAGGTTGCTTCGAAATCTACCATAAGTGCGACGATAACTGT

ATGGAGAGTATTAGAAACAATACCTACGACCACACGCAGTATAGGGAGGAGGCTCTGTTGA

ATAGGTTAAATATCAACCCTGTGAAACTATCCAGCGGCTATAAGGACGTGATTTTATGGTT

CTCGTTTGGTGCCAGCTGTTTTGTCCTACTGGCAGTGATCATGGGTCTTGTTTTTTTTTGC

CTGAAGAACGGCAACATGAGATGCACGATATGTATT

706
ATGTACAAGATCGTTGTGATTATCGCCCTGCTCGGCGCCGTCAAAGGATTAGACAAGATCT

GTCTAGGCCATCACGCCGTTGCGAACGGAACCATCGTGAAGACCCTGACAAATGAGCAGGA

AGAAGTTACCAATGCCACTGAGACCGTAGAAAGCACCGGGATCAACAGACTATGTATGAAA

GGCCGCAAGCATAAGGATCTGGGAAACTGCCATCCTATCGGAATGCTCATTGGAACTCCCG

CCTGTGACCTGCACCTGACCGGCATGTGGGACACACTGATTGAGCGGGAGAACGCCATCGC

TTACTGTTATCCTGGTGCAACTGTGAACGTCGAAGCTTTGCGGCAGAAAATAATGGAATCG

GGGGGGATTAATAAAATAAGTACCGGATTCACATATGGAAGCTCAATTAACTCCGCAGGAA

CTACAAGAGCATGTATGCGAAACGGCGGCAACTCATTCTACGCTGAACTTAAGTGGCTGGT

GTCTAAGTCAAAGGGGCAGAACTTTCCGCAAACCACTAATACATATCGCAATACAGACACA

GCCGAGCACCTCATCATGTGGGGAATTCACCACCCAAGTAGTACCCAGGAGAAGAACGACC

TGTACGGCACTCAGTCGCTTAGCATAAGTGTTGGCTCATCGACTTATCGGAATAACTTCGT

CCCAGTGGTTGGTGCTCGTCCCCAAGTGAATGGTCAGTCCGGCAGAATTGATTTTCATTGG

ACACTGGTGCAACCCGGTGACAACATCACTTTTAGCCATAATGGTGGTCTAATCGCCCCGT

CCCGGGTGTCCAAGTTAATTGGGAGAGGTCTGGGTATCCAGAGTGATGCTCCAATCGATAA

TAATTGCGAGAGTAAGTGCTTCTGGCGCGGCGGAAGTATCAACACCCGGCTCCCTTTCCAG

AATCTATCACCTAGAACTGTTGGGCAGTGCCCTAAATATGTTAATCGCCGCTCACTTATGC

TGGCAACCGGGATGCGAAACGTTCCAGAACTGATCCAAGGGGGGGGGCTTTTCGGGGCTAT

TGCCGGGTTTTTGGAGAACGGCTGGGAAGGGATGGTCGATGGTTGGTATGGCTTCCGCCAT

CAGAATGCACAGGGTACCGGCCAGGCCGCCGACTACAAGTCAACGCAGGCTGCAATTGACC

AAATCACTGGGAAACTGAACCGGCTCGTTGAAAAGACTAACACTGAGTTTGAAAGCATAGA

AAGTGAATTCAGTGAAATTGAGCATCAAATCGGCAACGTGATCAATTGGACCAAGGACTCA

ATCACGGATATCTGGACATACCAGGCCGAGCTGCTCGTTGCGATGGAGAACCAACACACCA

TCGATATGGCAGACTCTGAGATGCTAAATCTCTACGAAAGAGTGAGAAAGCAGTTGCGACA

AAATGCGGAGGAGGATGGTAAGGGTTGCTTCGAAATTTACCATGCCTGCGACGACAGTTGC

ATGGAATCCATTAGGAACAATACCTACGATCATTCGCAGTATAGGGAGGAGGCCCTCTTAA

ACCGCCTGAACATCAACCCAGTAACCTTGAGCAGCGGGTATAAAGATATAATCCTGTGGTT

TAGCTTCGGTGCCTCCTGCTTTGTTCTGCTGGCCGTAGTCATGGGTCTGTTTTTTTTCTGC

CTGAAGAATGGTAATATGCGCTGCACCATTTGCATT

707
ATGTACAAGATCATTGTAATCATCGCCTTGTTGGGAGCCGTCAAAGGGCTCGATAAAATTT

GCTTGGGCCATCATGCAGTCGCCAACGGGACAATAGTCAAGACGCTCACGAATGAACAGGA

GGAAGTGACAAACGCCACAGAAACCGTTGAAAGTACAGGGATTAATAGGCTGTGTATGAAA

GGGCGCAAACATAAGGATTTGGGCAATTGTCACCCAATAGGGATGCTTATTGGGACACCAG

CTTGTGATCTCCATCTCACTGGAACATGGGACACCCTAATCGAGCGCGAAAACGCTATTGC

ATATTGCTATCCGGGAGCGACGGTTAACGTGGAGGCACTCCGACAGAAAATCATGGAGAGC

GGGGGGATCGACAAGATTTCCACAGGCTTTACTTACGGCTCTAGTATAAATTCCGCCGGGA

CCACAAGGGCCTGTATGAGAAACGGTGGCAACAGTTTTTACGCTGAGTTAAAATGGCTCGT

TAGCAAGAGCAAGGGTCAGAACTTTCCGCAGACCACAAACACATACCGGAACACCGATACA

GCAGAGCATCTAATCATGTGGGGCATACATCATCCTTCCAGTACCCAGGAGAAGAACGATT

TATACGGGACCCAATCCCTGAGCATCAGCGTTGGGTCATCTACTTACCGCAATAATTTTGT

CCCGGTTGTGGGAGCAAGGCCCCAAGTGAATGGTCAGAGTGGCAGGATTGACTTTCACTGG

ACACTGGTGCAACCTGGTGACAACATTACCTTCAGCCATAACGGAGGACTGATCGCGCCTT

CACGGGTGAGCAAGCTTATTGGTAGAGGACTCGGGATCCAAAGTGATGCCCCAATCGACAA

TAACTGTGAGAGCAAATGCTTTTGGCGAGGGGGATCCATCAATACACGCCTCCCCTTTCAA

AACCTGAGCCCACGCACTGTGGGGCAATGCCCTAAGTACGTAAACCGCAGGTCTCTAATGC

TTGCAACCGGGATGAGAAACGTTCCAGAATTAATTCAGGGACGGGGACTGTTTGGGGCGAT

CGCCGGCTTTCTGGAAAATGGCTGGGAAGGGATGGTGGATGGCTGGTATGGCTTCCGGCAC

CAAAATGCCCAGGGCACAGGGCAGGCTGCAGATTACAAATCAACTCAGGCTGCCATCGACC

AAATCACAGGCAAGCTGAATAGGCTCGTGGAGAAAACGAACACGGAATTCGAGTCTATTGA

ATCTGAGTTCTCCGAAATCGAGCACCAGATCGGGAATGTAATTAACTGGACCAAGGACTCA

ATCACTGACATTTGGACCTATCAGGCAGAATTACTGGTAGCGATGGAGAACCAACACACAA

TTGACATGGCAGATTCTGAAATGCTCAACCTCTATGAACGAGTGAGGAAACAGCTCCGGCA

GAACGCCGAGGAGGATGGAAAGGGATGTTTCGAGATCTATCACGCATGTGACGATAGCTGT

ATGGAATCTATACGGAATAACACATACGATCATTCTCAATATCGGGAGGAGGCTCTGCTTA

ACCGACTCAACATAAACCCAGTCACTCTATCCAGTGGCTACAAGGATATTATCCTGTGGTT

TAGCTTTGGCGCCTCGTGCTTCGTGCTTCTCGCTGTTGTCATGGGCCTGTTCTTCTTCTGT

CTGAAGAACGGGAATATGCGGTGCACCATTTGCATC

708
ATGTATAAAATCGTGGTTATTATCGCATTGCTGGGTGCTGTGAAAGGCCTCGATAAAATTT

GCCTCGGGCATCACGCCGTGGCCAACGGCACAATTGTGAAGACACTGACAAACGAACAGGA

AGAAGTTACCAACGCTACTGAGACCGTGGAATCCACAGGTATTAATAGGCTTTGTATGAAG

GGTCGGAAGCACAAAGACCTGGGGAATTGCCACCCTATCGGAATGCTCATTGGAACTCCGG

CCTGTGACCTGCACCTCACAGGTATGTGGGATACTCTGATTGAGCGAGAGAACGCGATTGC

CTACTGTTACCCGGGAGCAACCGTGAACGTGGAGGCGCTCCGGCAGAAGATCATGGAGTCT

GGCGGCATTAACAAGATCAGTACCGGGTTCACATATGGAAGTTCAATCAATAGTGCCGGCA

CTACCAGGGCATGTATGCGCAACGGAGGAAATAGCTTCTACGCGGAATTGAAATGGTTAGT

CAGCAAGAGCAAGGGACAGAACTTTCCTCAGACTACGAACACTTACCGTAATACTGATACT

GCCGAACATCTAATTATGTGGGGGATCCATCACCCATCCAGCACCCAGGAAAAGAACGATT

TGTACGGCACCCAGTCTTTATCTATTTCCGTGGGGAGTTCGACATATAGAAATAACTTTGT

GCCCGTTGTCGGTGCTGGGCCCCAAGTTAACGGCCAATCGGGACGTATCGATTTCCACTGG

ACACTGGTTCAGCCAGGGGACAATATCACCTTTTCTCACAACGGAGGTCTTATAGCTCCAT

CTCGTGTGTCTAAACTCATTGGACGGGGGCTTGGGATCCAAAGCGATGCCCCCATCGACAA

TAATTGCGAAAGTAAGTGCTTCTGGCGGGGAGGTTCTATTAATACTAGGCTTCCTTTCCAG

AACCTCTCACCACGAACAGTCGGCCAATGCCCCAAGTACGTTAATCGACGTTCACTCATGC

TGGCCACGGGAATGCGCAACGTGCCCGAGCTTATCCAGGGGCGCGGATTGTTCGGCGCCAT

CGCTGGCTTCTTGGAGAACGGTTGGGAGGGTATGGTCGATGGGTGGTACGGCTTTCGCCAC

CAAAACGCTCAAGGGACAGGACAGGCCGCCGATTATAAGAGCACTCAGGCCGCCATAGATC

AGATTACGGGCAAGCTAAACAGGCTGGTCGAGAAAACCAATACGGAATTCGAGTCCATTGA

ATCAGAGTTCTCTGAGATCGAGCACCAGATCGGCAACGTAATCAACTGGACCAAAGATTCT

ATCACCGATATTTGGACATATCAGGCAGAACTACTGGTCGCCATGGAAAACCAGCATACCA

TCGATATGGCGGACAGTGAGATGCTTAATCTCTACGAAAGAGTACGAAAGCAGCTGCGACA

AAACGCCGAGGAAGACGGTAAAGGCTGCTTCGAAATTTATCACGCGTGCGACGACTCTTGT

ATGGAATCTATACGAAACAACACATACGATCACTCCCAATACCGGGAGGAGGCTCTCCTCA

ATAGACTGAATATCAACCCAGTCACTTTGAGTAGTGGGTATAAGGACATTATTCTTTGGTT

CTCCTTCGGGGCTTCTTGTTTTGTCCTTCTGGCAGTGGTTATGGGGCTCTTCTTTTTTTGC

CTCAAGAACGGCAACATGCGCTGTACTATATGTATT

709
ATGTATAAAGTCGTTGTGATCATCGCTTTGTTGGGAGCTGTCCGGGGTTTGGATAAGATCT

GCCTCGGCCATCACGCAGTAGCAAATGGAACCACTGTGAAGACCCTAACTAACGAACAAGA

GGAAGTCACAAATGCCACTGAGACTGTCGAGTCTACTAGCCTGAATAAACTGTGCATGAAG

GGGAGGAGGTACAAAGATCTTGGAAATTGCCACCCAATCGGAATGCTGATAGGCACCCCTG

TGTGTGATCTCCATCTGACCGGAACATGGGATACCCTGATTGAGAGAGAGAATGCTACTGC

ATACTGCTACCCTGGAGTCACTATCAATGAAGAGGCCCTGCGTCAAAAGATCATGGAGTCC

GGGGGTATTTCTAAGATGCGCACCGGCTTTACCTACGGACCATCTATCAATTCGGCAGGTA

CTACCCGGTCATGTATGCGCAATGGAGGCAACTCCTTCTATGCCGAACTGAAGTGGCTGGT

CTCGGGCACTAAGGGTCAGAACTTCCCGCAGACTACTAATACATACCGAAATACCGACACT

GCCGAGCACCTGATTATCTGGGGAATTCACCATCCCTCGTCCACTCAAGAGAAGAATGACC

TTTATGGCACACAGAGCCTCTCGATCAGCGTGGGCTCCTCGACTTACCAGAATAACTTTGT

CCCGGTAATTGGCGCTAGGCCTCAGGTGAACGGCCAGTCCGGCAGAATCGAGTTCCATTGG

ACTCTGGTGCGCCCAGGCGACAATATCACATTCAGCCATAATGGGGGTCTGATCGCACCTG

ACCGAGTTAGTAAACTGATTGGCAAGGGGATCGGGATCCAATCAGGGGCTGTGATCGACAA

AGACTGTGAGTCAAAGTGCTTCTGGAGGGGCGGAAGCATAATTACGGAGCTGCCTTTTCAG

AACCTGAGCCCAAGAACTGTTGGACAATGCCCTAAGTACGTTAAGAAGCGATCTCTCTTGT

TGGCCACTGGAATGAGGAACGTGCCGGAAGTGGTTCAGGGGCGCGGCCTCTTCGGGGCTAT

AGCCGGATTCATAGAAAACGGCTGGGAGGGGATGGTGGATGGCTGGTACGGCTTCAGACAC

CAAAATGCGCAGGGCATCGGCCAGGCTGCTGATTACAAGTCTACCCAAACTGCGATTGATC

AGATCACCGGAAAACTGAATCGACTGATCGAAAAAACTAACACTGAGTTCGAAAGCATCGA

AAGTGAATTTAGCGAGATTGAACATCAGATCGGCAATGTCATAAATTGGACCAAGGATTCC

ATTACAGATATTTGGACATACCAGGCCGAGCTCCTCGTGGCAATGGAAAATCAGCATACTA

TTGATATGGCCGATTCGGAAATGCTGAACCTCTACGAACGTGTCCGGAAACAGCTGCGCCA

GAACGCTGAGGAGGACGGAAAGGGATGCTTTGAGATTTACCACACCTGCGACAATTCTTGT

ATGGAGAGTATACGCAATAATACATATGACCATTCACAATACCGCGAAGAAGCCCTTCTGA

ATCGTCTCAATATCAATCCCGTCAAACTGTCCTCAGGGTATAAAGACATTATCCTATGGTT

CAGTTTTGGTGCCAGCTGCTTTGTGCTGCTGGCTGTCATCATGGGGCTGGGCTTTTTTTGT

CTAAAAAACGGAAACATGCGGTGCACGATCTGCATT

710
ATGTATAAGATCGTAGTGATCATTGCGCTGCTTGGCGCTGTCAAGGGCCTAGATAAGATAT

GTCTCGGACACCATGCTGTTGCCAATGGGACAATTGTGAAGACTCTAACTAACGAACAGGA

AGAAGTTACGAATGCTACAGAAACTGTGGAGTCCACTGGAATCAATAGACTCTGTATGAAA

GGCCGGAAACACAAGGATCTGGGCAACTGCCACCCCATTGGTATGCTTATAGGAACACCTG

CGTGCGATCTGCACCTCACTGGAATGTGGGATACCCTCATCGAGCGGGAGAACGCAATCGC

GTACTGTTACCCCGGAGCTACGGTTAACGTCGAAGCTCTTCGGCAGAAGATCATGGAATCC

GGGGGGATCAATAAGATCTCTACTGGATTCACATATGGGTCTTCAATTAACTCCGCTGGGA

CGACCCGTGCCTGCATGAGGAACGGCGGTAACTCTTTCTATGCTGAGCTGAAGTGGCTGGT

CAGTAAAAGTAAAGGACAGAACTTTCCGCAGACCACCAACACGTATCGGAACACTGATACA

GCAGAGCACCTTATCATGTGGGGAATCCACCATCCCTCTTCTACACAAGAAAAGAATGACC

TGTACGGCACTCAGAGCCTTTCAATCTCAGTGGGCAGTTCCACCTATCGAAACAACTTCGT

GCCCGTGGTTGGAGCACGCCCACAGGTGAACGGCCAATCCGGGCGCATTGATTTTCATTGG

ACCCTGGTTCAGCCAGGGGATAACATAACTTTCAGTCATAATGGTGGGCTCATCGCACCAA

GCCGTGTTTCCAAGTTAATCGGCCGGGGGCTGGGCATCCAGAGCGACGCTCCTATCGACAA

TAACTGCGAAAGTAAATGCTTCTGGCGCGGAGGTAGCATCAACACCCGACTACCCTTCCAG

AATCTTAGCCCACGAACCGTGGGACAATGCCCAAAATACGTCAACCGCAGGTCTCTTATGC

TAGCTACCGGTATGCGTAATGTCCCTGAGCTGATTCAGGGCCGCGGGCTTTTTGGGGCCAT

TGCAGGATTTCTTGAGAATGGATGGGAAGGTATGGTTGACGGATGGTATGGCTTTAGACAC

CAGAACGCGCAGGGCACTGGTCAAGCTGCAGATTACAAGTCCACACAGGCTGCTATAGACC

AGATAACAGGCAAGCTGAATAGATTAGTGGAGAAAACCAACACAGAATTCGAGAGTATTGA

GTCTGAATTTAGCGAGATTGAGCATCAGATTGGGAACGTGATCAATTGGACTAAAGACAGC

ATCACGGACATCTGGACATACCAGGCTGAACTTTTGGTGGCCATGGAGAATCAGCACACAA

TCGATATGGCAGACTCAGAGATGCTCAATTTGTATGAACGGGTGAGAAAGCAATTACGCCA

GAACGCGGAAGAGGATGGCAAAGGCTGCTTTGAGATATACCACGCATGTGACGACTCATGC

ATGGAATCCATCAGGAACAACACCTATGACCATTCCCAGTACCGGGAGGAAGCTCTGTTGA

ACCGCCTCAACATAAACCCGGTGACACTGTCTAGCGGTTATAAAGATATCATCCTTTGGTT

CTCATTCGGGGCGTCTTGTTTTGTTCTCCTTGCAGTGGTTATGGGCCTATTCTTCTTCTGC

CTGAAGAATGGAAATATGAGATGTACAATCTGTATC

711
ATGTATAAAGTTGTTGTTATCATAGCGCTGCTAGGCGCTGTCAAGGGGTTAGACAAAATTT

GTCTGGGCCATCACGCAGTGGCTAACGGCACAATAGTTAAGACATTGACCAATGAACAGGA

GGAGGTTACAAATGCAACCGAGACCGTGGAATCAACCGGCATTAATAGACTATGTATGAAG

GGCCGGAAGCATAAGGATCTGGGGAACTGCCATCCAATCGGTATGCTGATCGGCACGCCAG

CTTGCGATTTGCACCTAACGGGAACCTGGGACACTTTAATCGAGAGGGAGAATGCTATAGC

TTATTGCTACCCCGGCGCTACCGTTAATGTTGAGGCACTTCGGCAGAAGATCATGGAAAGC

GGGGGGATCGATAAAATCAGCACAGGATTCACCTACGGGAGTTCTATCAACTCTGCCGGGA

CTACACGTGCATGTATGAGAAACGGCGGTAATTCCTTCTATGCCGAGCTCAAATGGCTTGT

TTCCAAGAATAAGGGCCAGAACTTCCCACAGACCACTAATACTTACAGGAATACCGACACT

GCGGAGCACCTCATTATGTGGGGCATACATCACCCTTCTTCGATCCAAGAAAAGAATGACC

TCTATGGTACTCAGTCCCTCAGCATATCTGTGGGGAGCAGTACTTACCGGAATAATTTCGT

ACCCGTTGTGGGAGCACGCCCACAGGTGAACGGCCAGTCTGGTAGAATTGATTTCCATTGG

ACTTTGGTGCAGCCGGGGGATAACATCACCTTTTCCCATAACGGGGGACTGATCGCTCCAA

GCAGAGTTTCCAAACTTATTGGGAGAGGTTTAGGGATCCAGTCAGACGCCCCAATTGATAA

CAACTGTGAGTCGAAGTGCTTTTGGAGAGGGGGCAGCATCAATACGGGGCTGCCTTTCCAG

AACCTGTCACCCAGGACTGTCGGCCAGTGCCCAAAGTACGTGAACAGACGATCCTTGATGC

TTGCCACCGGAATGCGTAATGTGCCCGAGCTGATACAGGGCCGTGGACTTTTCGGAGCCAT

CGCGGGATTTCTGGAGAATGGTTGGGAAGGAATGGTCGACGGCTGGTATGGATTCCGCCAT

CAAAACGCCCAAGGAACAGGCCAGGCCGCTGACTATAAAAGCACGCAGGCTGCTATTGACC

AGATCACAGGTAAGCTGAACCGCCTGGTCGAAAAGACCAACACTGAATTTGAGTCCATCGA

GAGCGAGTTTAGCGAAATCGAACACCAAATCGGCAATGTAATCAACTGGACCATGGACAGC

ATAACCGATATTTGGACTTACCAGGCGGAATTACTGGTCGCCATGGAAAATCAGCACACAA

TCGATATGGCAGACAGCGAAATGTTGAACCTCTATGAGAGAGTCAGAAAACAATTGGGGCA

GAATGCTGAAGAGGATGGCAAAGGCTGCTTCGAAATCTATCACGCATGCGATGATAGTTGC

ATGGAATCAATTCGGAATAATACGTATGACCATAGCCAGTACAGGGAAGAGGCCCTTCTCA

ACCGACTTAATATCAATCCTGTGACACTTAGTTCTGGATATAAGGACATTATTCTCTGGTT

CTCTTTTGGAGCATCATGTTTTGTGCTGCTAGCCGTGGTGATGGGCCTGGTGTTCTTTTGT

CTCAAGAACGGTAACATGAGGTGTACTATATGCATC

712
ATGTATAAAATCGTGGTTATTATCGCCTTGCTAGGGGCCGTCAAAGGCCTGGACAAGATCT

GTTTGGGCCACCATGCTGTGGCAAATGGCACAATTGTTAAGACACTTACCAATGAGCAGGA

GGAAGTGACCAATGCTACCGAGACCGTCGAGTCTACCGGCATTAACAGGCTGTGTATGAAG

GGGCGGAAACACAAAGACCTGGGAAACTGCCACCCAATCGGAATGCTGATTGGGACTCCTG

CTTGCGACTTACACCTGACCGGAATGTGGGATACCCTCATAGAGAGAGAGAACGCGATAGC

CTACTGTTATCCTGGGGCGACCGTGAATGTTGAGGCCCTGAGACAGAAGATTATGGAATCT

GGGGGCATCAACAAAATTTCTACCGGATTTACATACGGCAGTTCCATCAACTCAGCCGGCA

CAACCCGCGCGTGTATGAGAAACGGGGGGAACAGCTTTTACGCCGAGCTGAAGTGGCTGGT

TTCCAAAAGCAAAGGGCAGAATTTTCCGCAGACTACGAATACCTACAGAAATACAGATACT

GCCGAACACCTCATAATGTGGGGCATCCATCATCCGTCCAGTACACAGGAGAAAAATGACT

TATATGGTACCCAGTCTTTATCAATTTCTGTAGGCTCCTCAACTTACCGTAACAATTTCGT

GCCCGTGGTCGGAGCTCGCCCGCAGGTGAACGGCCAGAGTGGGCGCATTGACTTTCATTGG

ACCCTCGTACAACCAGGCGACAACATCACTTTTTCTCATAATGGTGGTCTCATCGCCCCAA

GCCGAGTCTCTAAGCTGATTGGGGGGGGTCTTGGGATCCAATCAGATGCACCTATCGATAA

CAACTGCGAAAGTAAATGTTTTTGGCGTGGCGGTTCAATCAACACCCGGCTGCCGTTCCAG

AACCTGAGTCCAAGAACAGTTGGTCAGTGCCCCAAGTACGTAAACCGGAGGTCTTTGATGC

TGGCCACCGGAATGCGGAACGTGCCAGAACTGATCCAGGGCCGAGGCCTTTTCGGAGCCAT

TGCTGGCTTTCTCGAGAACGGTTGGGAAGGAATGGTAGATGGTTGGTACGGGTTCAGACAC

CAGAACGCCCAGGGCACCGGTCAGGCCGCTGATTATAAATCAACCCAGGCCGCTATAGACC

AAATCACCGGCAAGCTCAACAGACTCGTGGAAAAAACGAATACGGAGTTCGAGAGCATCGA

GTCAGAGTTTTCGGAAATCGAACACCAAATAGGGAATGTCATTAACTGGACTAAGGACAGC

ATCACCGACATTTGGACATATCAGGCAGAATTATTAGTGGCGATGGAGAATCAGCATACCA

TCGATATGGCAGACAGCGAAATGCTCAATCTGTACGAACGAGTACGCAAACAACTTCGCCA

AAACGCAGAGGAGGATGGGAAGGGCTGCTTCGAGATATACCATGCATGCGATGATTCTTGC

ATGGAGAGTATCCGTAACAATACATACGATCATTCCCAGTACCGAGAAGAGGCCCTGCTGA

ACCGGCTGAATATCAACCCAGTTACACTCTCATCTGGCTACAAGGATATTATCCTCTGGTT

CAGTTTTGGGGCATCTTGTTTCGTCCTGCTAGCTGTCGTCATGGGCCTGTTCTTTTTCTGT

CTCAAAAACGGCAATATGCGGTGTACCATATGCATC

713
ATGTATAAAATTGTGGTCATTATCGCCCTTCTTGGTGCCGTGAAGGGACTTGACAAAATCT

GCCTGGGCCACCACGCCGTCGCAAACGGTACTATTGTGAAAACTCTTACAAATGAGCAGGA

GGAAGTGACAAATGCTACCGAGACCGTTGAAAGCACAGGTATCAACAGACTTTGTATGAAG

GGACGCAAACACAAGGATCTCGGTAATTGTCATCCAATCGGTATGCTGATCGGCACTCCAG

CATGTGACCTCCACCTCACCGGCATGTGGGATACTCTAATTGAGAGAGAGAACGCGATCGC

TTACTGCTATCCCGGTGCGACTGTCAATGTGGAAGCCCTTCGACAGAAGATCATGGAGTCG

GGCGGCATTAACAAAATTTCTACAGGTTTCACCTATGGCAGCAGTATTAACTCTGCCGGAA

CAACAAGAGCCTGCATGAGGAACGGCGGAAACAGTTTCTACGCTGAACTTAAATGGTTGGT

CAGCAAGAGCAAAGGCCAGAATTTCCCGCAGACCACTAACACATATCGCAACACCGACACC

GCTGAGCACCTTATTATGTGGGGAATACACCACCCCTCCAGCACCCAGGAGAAGAACGACT

TGTACGGTACTCAGAGCCTCTCTATCTCCGTGGGATCCTCCACATACCGCAATAACTTTGT

CCCCGTGGTTGGTGCCCGCCCCCAGGTAAACGGACAGTCAGGCAGGATTGACTTCCACTGG

ACCCTGGTGCAACCCGGTGACAACATTACATTCAGCCATAACGGCGGCCTAATCGCTCCCT

CTCGCGTGAGTAAACTGATTGGACGGGGACTGGGGATTCAATCCGATGCTCCCATCGACAA

CAATTGCGAATCCAAGTGCTTTTGGCGAGGAGGGTCCATTAACACCAGGCTGCCGTTCCAA

AACTTGTCTCCCCGTACGGTGGGGCAGTGTCCCAAATACGTTAACCGCCGGTCCTTAATGC

TCGCTACAGGGATGAGAAATGTGCCCGAGCTGATCCAGGGTAGAGGCCTCTTCGGTGCCAT

TGCTGGATTCCTGGAGAATGGATGGGAGGGTATGGTCGACGGCTGGTACGGTTTTCGGCAT

CAAAATGCTCAGGGAACAGGACAGGCGGCCGATTATAAGAGCACCCAAGCTGCTATCGATC

AGATTACAGGAAAGCTGAATAGGCTGGTCGAGAAGACAAACACGGAGTTCGAAAGTATCGA

ATCAGAGTTTAGCGAGATTGAACATCAGATTGGCAATGTGATTAATTGGACCAAGGACTCA

ATTACCGATATCTGGACCTATCAGGCCGAGCTGCTTGTGGCCATGGAGAATCAGCATACAA

TCGATATGGCCGATTCAGAAATGCTGAACCTGTACGAGCGTGTGCGTAAACAGCTGCGCCA

GAATGCCGAGGAGGACGGAAAGGGGTGTTTTGAGATCTACCACGCGTGTGACGACTCATGT

ATGGAGAGTATCCGGAACAATACTTACGACCATTCACAGTATCGCGAAGAGGCATTATTAA

ACCGCCTTAATATCAACCCCGTGACACTCAGCAGCGGGTATAAGGACATCATTCTGTGGTT

CTCATTTGGGGCCTCCTGCTTCGTTCTGCTGGCCGTGGTGATGGGGTTATTCTTTTTTTGT

CTAAAGAACGGTAATATGAGGTGCACAATATGTATC

714
ATGTATAAGGTAGTAGTGATCATCGCCCTGCTGGGGGCCGTGAGAGGCCTTGATAAGATCT

GTTTGGGTCACCACGCCGTTGCAAACGGGACCACTGTTAAGACCCTTACCAATGAGCAGGA

GGAGGTGACGAATGCAACCGAGACCGTCGAGTCCACAAGTCTGAACAAGCTGTGTATGAAA

GGGAGGAGGTATAAAGATCTGGGGAACTGCCACCCCATCGGAATGTTGATTGGAACCCCAG

TCTGCGATCTGCACTTGACCGGCACCTGGGATACACTGATTGAGCGGGAGAACGCTACCGC

CTACTGCTATCCCGGGGTCACTATTAATGAGGAAGCCTTGAGACAGAAGATCATGGAGAGT

GGAGGGATATCCAAGATGCGGACAGGGTTCACCTACGGTCCCTCCATCAATTCCGCTGGCA

CCACCCGGTCATGCATGCGCAATGGCGGCAATTCCTTTTACGCCGAGCTGAAATGGCTGGT

TAGCGGGACTAAGGGACAGAACTTCCCACAAACCACTAACACCTATAGAAATACTGATACC

GCGGAGCATCTGATCATATGGGGAATTCATCATCCTTCATCGACCCAGGAGAAAAACGACC

TGTACGGGACTCAGTCCCTGTCCATATCCGTGGGAAGTTCCACTTATCAGAACAATTTCGT

GCCTGTTATCGGAGCCCGACCTCAGGTTAACGGACAATCGGGACGGATTGAGTTCCACTGG

ACTTTAGTGAGACCGGGCGACAACATCACCTTTTCTCATAACGGCGGCCTGATTGCCCCCG

ATAGAGTCAGCAAATTAATCGGCAAGGGAATCGGCATACAGAGCGGGGCTGTTATTGACAA

GGACTGCGAATCTAAATGCTTTTGGCGTGGTGGCTCCATTATCACTGAACTGCCCTTCCAG

AATCTCAGCCCTAGAACTGTGGGCCAGTGCCCGAAGTATGTGAAAAAGAGGTCTCTTCTTC

TTGCTACAGGTATGAGGAACGTCCCTGAGGTTGTCCAGGGGCGCGGCTTGTTCGGCGCTAT

CGCCGGGTTCATCGAAAACGGGTGGGAGGGGATGGTGGACGGCTGGTATGGCTTTCGACAC

CAGAATGCTCAAGGGATCGGGCAGGCAGCCGACTACAAATCCACCCAGACAGCTATAGACC

AGATCACGGGGAAACTTAATCGTCTGATCGAAAAGACAAATACGGAGTTTGAGTCTATCGA

GTCCGAATTCTCGGAGATTGAGCACCAGATTGGTAATGTCATCAATTGGACTAAGGACAGT

ATTACTGACATCTGGACTTATCAAGCAGAGCTGCTGGTAGCTATGGAAAACCAACATACAA

TCGATATGGCCGATAGCGAGATGCTGAACCETTACGAACGAGTAAGGAAACAGCTGAGGCA

GAACGCCGAAGAGGACGGCAAAGGTTGCTTTGAAATTTACCACACCTGTGACAATTCCTGT

ATGGAAAGCATACGAAATAATACCTATGATCACTCCCAGTACAGAGAGGAAGCGCTCCTGA

ACCGACTGAATATCAACCCCGTGAAACTGAGTTCCGGATACAAGGATATCATCCTATGGTT

CTCATTCGGCGCCAGCTGTTTCGTTCTGTTAGCGGTTATAATGGGTCTGGGGTTTTTTTGT

CTCAAAAATGGCAATATGCGTTGTACCATTTGTATA

715
ATGTACAAGGTTGTGGTCATCATCGCCCTGCTTGGTGCTGTGAAAGGGCTTGATAAGATAT

GTTTGGGCCACCATGCCGTGGCTAACGGAACCATTGTGAAGACCTTGACCAACGAGCAGGA

GGAAGTGACTAATGCCACAGAAACTGTAGAGTCTACCGGTATAAACAGGCTGTGCATGAAG

GGAAGGAAGCACAAAGATCTCGGCAATTGTCATCCCATAGGCATGCTGATCGGTACCCCCG

CCTGCGATCTGCACTTGACTGGCACCTGGGACACGCTGATCGAGAGGGAAAACGCTATAGC

CTATTGTTACCCTGGGGCTACCGTTAATGTGGAAGCGCTGCGACAAAAGATAATGGAGAGC

GGGGGCATTGATAAAATTTCAACCGGATTTACCTACGGCTCTAGTATCAACTCTGCGGGTA

CTACGCGAGCATGCATGAGAAACGGGGGGAATTCCTTTTATGCAGAGCTTAAGTGGCTGGT

TAGCAAGAACAAGGGTCAGAATTTCCCCCAAACTACTAACACTTACAGAAACACAGATACC

GCCGAACATCTGATCATGTGGGGCATTCATCACCCATCCTCTATTCAAGAGAAGAATGACC

TTTATGGCACTCAAAGCCTCTCTATCTCCGTGGGAAGCAGCACTTACCGCAATAATTTCGT

GCCCGTCGTTGGGGCACGACCGCAGGTCAATGGCCAGAGTGGCAGGATCGATTTCCATTGG

ACCTTAGTCCAGCCGGGCGATAATATTACCTTCAGCCATAACGGAGGACTTATTGCGCCGT

CCAGAGTGTCAAAACTGATCGGGAGAGGACTCGGCATCCAGAGCGATGCTCCTATTGATAA

TAATTGCGAGTCCAAGTGTTTTTGGCGTGGGGGTTCGATCAATACTAGACTACCTTTCCAG

AACTTGAGCCCACGCACTGTGGGCCAGTGCCCCAAATATGTAAATAGAAGGTCCCTTATGC

TCGCTACAGGTATGAGGAACGTCCCAGAACTCATTCAGGGCCGAGGTTTGTTTGGCGCAAT

CGCCGGATTTCTGGAGAACGGGTGGGAGGGCATGGTCGACGGCTGGTACGGATTCCGCCAC

CAGAACGCCCAAGGTACAGGTCAGGCCGCCGACTATAAGAGCACGCAGGCTGCTATAGATC

AGATTACAGGAAAGCTAAACCGACTTGTGGAGAAGACAAATACAGAGTTCGAGTCAATAGA

GAGTGAGTTCAGTGAGATAGAGCATCAGATCGGTAATGTCATTAACTGGACAATGGATAGC

ATCACCGATATTTGGACTTATCAGGCCGAATTGCTGGTGGCTATGGAAAATCAGCACACCA

TTGATATGGCAGACTCTGAGATGCTAAATCTTTACGAGCGGGTGCGAAAGCAGTTGCGGCA

GAACGCAGAAGAAGACGGAAAAGGCTGCTTCGAAATATATCACGCTTGCGACGATTCCTGT

ATGGAAAGCATCAGAAATAACACATATGACCACAGTCAGTATCGCGAGGAGGCTCTCCTGA

ACAGACTCAATATCAATCCGGTCACCCTCTCCTCAGGTTACAAGGACATTATTCTCTGGTT

TTCTTTCGGTGCGTCTTGCTTTGTGCTACTCGCTGTGGTGATGGGCTTGGTGTTCTTCTGC

CTGAAGAACGGCAATATGCGGTGCACTATCTGTATC

716
ATGTACAAAATTGTGGTCATCATCGCTTTACTAGGAGCTGTGAAAGGCTTGGATAAAATTT

GTCTGGGACATCATGCTGTCGCTAACGGGACCATAGTGAAAACACTCACGAACGAACAGGA

GGAAGTTACCAATGCCACCGAAACGGTCGAGTCAACAGGGATTAACCGGCTGTGTATGAAG

GGAAGAAAGCATAAAGATCTGGGGAACTGCCACCCTATAGGAATGTTGATAGGCACGCCTG

CTTGTGACCTGCACCTGACTGGGATGTGGGATACCCTGATCGAAAGAGAGAACGCTATAGC

CTATTGCTATCCCGGTGCAACAGTGAACGTGGAGGCATTGAGACAGAAAATAATGGAAAGT

GGAGGGATCAATAAGATCTCAACCGGTTTTACCTATGGATCTAGTATAAATAGTGCAGGGA

CCACACGTGCCTGCATGAGAAATGGGGGCAATTCTTTCTACGCGGAACTGAAGTGGCTGGT

GAGCAAATCTAAGGGGCAGAATTTTCCACAGACCACGAATACATATCGTAACACAGACACC

GCGGAGCACTTGATTATGTGGGGTATCCACCACCCCAGCAGCACGCAGGAAAAAAACGATC

TCTACGGTACTCAGAGCCTGTCTATCTCAGTAGGCTCATCAACATACCGGAATAACTTTGT

TCCAGTTGTGGGGGCCCGGCCTCAGGTGAATGGCCAGTCTGGACGCATTGATTTTCATTGG

ACGCTGGTACAGCCAGGAGACAATATCACATTTAGTCATAATGGCGGTTTGATCGCCCCGA

GTAGAGTGTCTAAGCTGATCGGCCGAGGCCTTGGCATTCAGTCCGACGCCCCCATCGACAA

TAACTGCGAAAGCAAATGCTTTTGGAGAGGAGGTTCTATTAATACACGCCTGCCATTTCAA

AACTTGAGCCCTAGAACTGTGGGTCAGTGTCCCAAGTACGTGAATCGCCGCTCCCTGATGT

TAGCCACCGGGATGAGGAATGTGCCTGAGCTGATCCAGGGCAGGGGCCTATTTGGAGCCAT

CGCTGGTTTCTTGGAGAATGGTTGGGAGGGTATGGTAGATGGATGGTATGGGTTTCGGCAT

CAGAATGCGCAAGGCACTGGCCAGGCCGCGGATTACAAAAGCACTCAGGCTGCCATTGACC

AGATAACCGGAAAACTCAACAGACTGGTTGAGAAGACCAACACTGAATTTGAGAGCATTGA

GTCAGAGTTTAGCGAAATAGAACACCAGATCGGGAACGTTATTAACTGGACAAAGGACTCC

ATTACGGACATATGGACATATCAGGCAGAGCTGCTAGTGGCAATGGAGAACCAACACACTA

TTGACATGGCCGACTCTGAGATGCTGAACCTCTATGAGCGCGTCAGAAAGCAGCTAAGGCA

GAATGCAGAAGAGGATGGTAAAGGGTGTTTTGAAATCTATCATGCATGCGACGATTCATGC

ATGGAAAGCATCAGGAACAATACTTATGACCATTCCCAATACCGAGAGGAAGCCCTGCTGA

ACAGACTGAATATTAACCCAGTGACCCTATCCAGTGGCTATAAGGATATCATCCTGTGGTT

CAGCTTTGGCGCTAGCTGTTTCGTGTTACTCGCGGTCGTCATGGGACTGTTTTTTTTTTGT

TTGAAGAACGGGAATATGAGATGCACAATCTGTATT

717
ATGTATAAAATCGTAGTGATTATTGCGTTGCTTGGCGCTGTGAAAGGGCTAGATAAGATCT

GCCTGGGCCACCACGCCGTAGCTAACGGAACCATCGTCAAAACTTTGACTAACGAGCAGGA

AGAGGTCACCAATGCTACTGAGACAGTCGAGTCTACAGGCATAAATAGACTCTGTATGAAG

GGTAGAAAGCACAAGGATCTTGGGAATTGCCACCCCATTGGTATGCTGATTGGGACACCCG

CCTGCGACCTGCACCTCACAGGGATGTGGGACACCTTAATTGAGCGAGAGAATGCAATCGC

CTACTGTTACCCCGGGGCTACTGTTAACGTCGAAGCTCTGCGCCAGAAAATCATGGAGAGC

GGGGGGATCAACAAGATCTCCACCGGCTTCACCTATGGCTCATCTATCAATTCTGCAGGCA

CTACCAGAGCGTGCATGAGAAATGGAGGAAATTCCTTCTATGCGGAATTGAAATGGCTTGT

GTCAAAATCTAAAGGGCAAAATTTTCCGCAGACCACCAACACCTACAGGAACACCGATACT

GCAGAGCATCTGATTATGTGGGGGATTCACCACCCTTCATCCACTCAGGAAAAGAACGATC

TCTATGGGACACAATCATTGTCCATTAGCGTGGGCTCTTCCACTTACAGAAACAACTTCGT

GCCTGTCGTTGGGGCGCGACCGCAAGTTAATGGGCAATCCGGGCGAATTGATTTCCACTGG

ACGCTGGTTCAACCTGGAGACAATATCACTTTCTCACATAATGGAGGGTTAATTGCTCCCT

CCCGCGTCTCCAAACTGATTGGAAGAGGCCTGGGCATTCAGTCCGATGCCCCAATCGACAA

CAATTGCGAATCCAAGTGTTTCTGGCGCGGGGGCTCAATCAATACCCGCCTGCCCTTCCAA

AACCTGAGTCCCCGCACAGTGGGCCAATGCCCTAAATATGTCAACCGTCGATCCCTCATGC

TTGCCACAGGCATGAGGAACGTCCCAGAGCTGATCCAGGGCCGCGGACTCTTTGGAGCTAT

CGCAGGCTTTCTTGAAAACGGGTGGGAGGGCATGGTCGATGGTTGGTATGGATTTCGGCAT

CAGAATGCACAAGGTACTGGACAGGCCGCTGATTACAAGTCAACCCAGGCGGCCATTGACC

AGATAACCGGGAAGCTCAACCGGTTGGTCGAGAAGACTAATACTGAGTTTGAATCCATCGA

AAGTGAGTTCTCTGAGATAGAACATCAGATTGGTAATGTCATAAATTGGACTAAAGATAGC

ATAACGGACATTTGGACCTATCAGGCAGAATTACTGGTGGCAATGGAAAATCAACACACCA

TCGACATGGCCGATTCTGAAATGCTCAACCTATACGAAAGAGTCAGAAAGCAGCTCAGACA

GAACGCCGAGGAAGACGGCAAAGGGTGCTTTGAAATTTACCATGCTTGTGACGATTCTTGT

ATGGAGAGTATACGCAATAACACTTATGACCATTCACAGTACCGAGAGGAGGCACTCCTGA

ATCGACTGAACATCAACCCCGTCACACTGTCCTCAGGCTACAAGGATATTATCCTTTGGTT

TAGTTTTGGTGCGTCGTGCTTCGTCCTCCTGGCCGTCGTGATGGGGTTATTCTTTTTTTGC

TTGAAAAATGGAAATATGCGTTGCACCATCTGTATC

718
ATGTATAAGATAGTCGTCATAATCGCTCTGCTCGGCGCAGTGAAAGGGCTGGATAAAATTT

GTCTGGGTCACCACGCCGTAGCGAATGGCACCATCGTGAAGACACTGACTAACGAGCAAGA

GGAGGTGACTAATGCCACAGAAACCGTCGAGTCTACAGGAATTAACCGCCTCTGCATGAAA

GGCAGGAAACACAAAGATCTCGGCAACTGTCACCCGATCGGAATGCTCATAGGGACTCCAG

CCTGTGATCTCCACCTTACCGGAATGTGGGATACTCTCATAGAGAGGGAGAATGCCATCGC

TTATTGTTACCCCGGCGCGACAGTTAACGTGGAAGCTCTCAGACAGAAGATCATGGAAAGT

GGGGGCATTAACAAGATATCCACCGGATTCACTTACGGTTCATCCATTAATTCTGCGGGAA

CCACTCGGGCCTGTATGCGGAACGGTGGCAATTCTTTCTATGCCGAGCTGAAGTGGCTGGT

CTCCAAGTCCAAGGGCCAGAATTTCCCACAGACTACCAACACATATAGAAACACTGACACT

GCCGAGCATCTGATCATGTGGGGGATCCATCACCCAAGTTCAACTCAGGAGAAGAATGACC

TCTACGGTACCCAGAGCTTATCTATTAGTGTTGGCTCCTCTACTTACCGCAATAATTTTGT

GCCAGTAGTCGGTGCTCGCCCTCAGGTGAATGGGCAGTCCGGCAGGATCGACTTCCACTGG

ACTCTAGTCCAACCCGGGGATAACATCACATTCAGTCATAACGGGGGATTGATCGCTCCAA

GTAGAGTTTCAAAACTCATAGGTAGGGGCCTCGGGATTCAGTCGGACGCTCCTATCGACAA

CAATTGCGAGTCTAAGTGTTTCTGGCGAGGGGGAAGCATAAATACCCGACTCCCCTTCCAG

AATCTCAGCCCAAGGACTGTGGGTCAGTGCCCAAAATACGTTAACCGCCGGAGCCTAATGC

TGGCGACTGGCATGAGAAACGTCCCCGAACTGATTCAAGGTCGCGGACTCTTCGGGGCAAT

CGCGGGATTTCTGGAAAACGGCTGGGAGGGAATGGTGGACGGCTGGTACGGCTTCCGACAC

CAGAACGCTCAAGGGACAGGCCAAGCGGCTGACTACAAGTCCACCCAGGCCGCGATTGACC

AAATCACAGGGAAATTGAATAGGCTGGTAGAAAAGACGAATACAGAGTTCGAATCCATAGA

GAGTGAATTTTCCGAGATCGAACACCAAATAGGAAATGTCATCAATTGGACGAAGGACAGC

ATTACGGACATCTGGACATACCAGGCAGAGCTCCTCGTGGCGATGGAAAATCAGCACACAA

TCGACATGGCTGACTCAGAGATGCTCAATCTGTACGAGCGGGTCCGCAAACAGTTGAGGCA

GAATGCTGAAGAAGACGGTAAAGGGTGTTTTGAAATCTATCATGCCTGCGACGATTCATGC

ATGGAATCTATTAGAAACAATACGTACGATCACTCCCAGTATAGGGAGGAAGCTCTGCTGA

ATAGACTGAACATAAACCCCGTCACCCTGTCTTCCGGTTACAAGGACATCATACTTTGGTT

CTCGTTCGGTGCAAGCTGCTTCGTTCTGCTCGCTGTTGTCATGGGCCTGTTCTTCTTCTGT

TTGAAAAACGGCAATATGCGATGCACCATTTGTATT

719
ATGTATAAAATTGTCGTAATCATTGCCCTGCTGGGAGCGGTTAAGGGGCTTGATAAGATAT

GCTTGGGGCATCACGCCGTAGCTAATGGTACAATCGTCAAAACACTAACTAATGAACAGGA

GGAAGTAACAAACGCAACTGAAACTGTTGAGTCTACGGGAATCAACAGGCTCTGTATGAAA

GGCCGAAAGCACAAAGACTTGGGTAATTGTCACCCGATCGGGATGCTCATCGGGACACCTG

CATGCGACCTCCACCTCACCGGCATGTGGGATACACTTATTGAACGGGAGAACGCGATCGC

CTACTGCTACCCTGGGGCAACGGTGAATGTAGAAGCTCTCCGGCAGAAGATCATGGAAAGC

GGCGGAATTAATAAAATTAGTACCGGATTTACCTACGGGTCATCCATAAACAGCGCCGGGA

CCACACGCGCCTGCATGAGGAACGGCGGCAACAGCTTTTATGCCGAGCTCAAGTGGCTTGT

CTCCAAATCCAAAGGACAGAACTTTCCTCAGACAACGAACACATATCGTAATACTGATACC

GCAGAACATCTGATCATGTGGGGAATCCACCACCCCAGTAGCACCCAAGAGAAGAACGATC

TATACGGAACTCAGTCTCTTTCCATCAGCGTTGGGTCCTCTACTTACAGGAACAATTTTGT

ACCGGTCGTGGGAGCCCGCCCCCAGGTGAATGGGCAGTCCGGAAGGATTGATTTTCACTGG

ACTTTAGTACAGCCTGGAGACAACATAACCTTTTCCCACAACGGAGGTCTCATAGCCCCTT

CTCGAGTGAGCAAGTTGATAGGGCGTGGGTTGGGAATCCAGTCTGACGCTCCGATCGACAA

TAATTGTGAGTCCAAGTGCTTTTGGAGGGGCGGCTCTATCAATACGAGATTGCCTTTCCAG

AACCTTAGTCCAAGAACCGTGGGGCAATGTCCAAAGTATGTCAATCGACGCTCACTAATGT

TAGCAACCGGCATGAGGAATGTTCCCGAGCTAATCCAAGGCCGGGGACTCTTTGGCGCCAT

CGCGGGCTTCTTGGAGAACGGTTGGGAAGGAATGGTCGACGGGTGGTATGGCTTCCGGCAC

CAAAACGCCCAGGGTACAGGCCAGGCAGCCGACTATAAATCCACACAGGCAGCCATCGATC

AGATCACCGGCAAGCTCAATAGGCTCGTGGAAAAAACAAACACTGAGTTCGAGTCCATTGA

ATCCGAGTTCTCGGAGATCGAGCACCAAATCGGGAACGTCATCAATTGGACTAAGGACAGT

ATTACAGATATCTGGACATATCAGGCCGAACTTTTGGTCGCTATGGAAAATCAACATACGA

TTGACATGGCAGACTCAGAGATGTTAAACCTGTATGAGAGAGTGCGCAAACAGCTGCGGCA

GAATGCCGAAGAAGATGGGAAGGGATGTTTCGAGATTTACCATGCCTGTGACGATTCCTGC

ATGGAGTCGATTCGTAATAATACTTATGATCATTCCCAATATAGAGAGGAAGCATTATTAA

ACCGGCTGAATATTAACCCCGTGACCCTGAGCTCCGGGTACAAGGACATTATTCTGTGGTT

CTCATTCGGCGCATCTTGTTTCGTCTTACTCGCAGTGGTCATGGGACTGTTTTTCTTTTGT

CTGAAGAATGGGAACATGCGCTGTACCATTTGTATC

720
ATGTACAAGATTGTCGTCATCATAGCCCTCCTAGGTGCTGTTAAAGGGCTCGATAAGATCT

GCCTTGGACATCACGCCGTGGCAAATGGAACAATAGTAAAGACACTCACAAACGAGCAGGA

AGAAGTGACGAATGCCACCGAAACCGTCGAGAGTACCGGCATCAACAGACTGTGCATGAAG

GGCAGGAAGCATAAAGACCTGGGCAACTGCCACCCTATCGGCATGCTAATCGGTACACCAG

CCTGCGATTTACACCTGACCGGAATGTGGGACACACTGATTGAACGAGAAAATGCCATTGC

TTACTGTTATCCTGGCGCTACCGTGAATGTGGAGGCTCTCAGGCAGAAAATTATGGAGAGT

GGGGGGATCAACAAGATTAGTACTGGCTTTACCTACGGCTCTAGCATCAACTCTGCTGGCA

CAACGCGCGCTTGTATGAGAAATGGCGGCAATTCATTCTACGCCGAGCTTAAGTGGCTGGT

TAGCAAGTCCAAGGGACAGAACTTTCCTCAAACGACGAATACATACCGCAACACCGATACT

GCTGAGCATCTGATCATGTGGGGCATCCATCATCCCTCCTCAACTCAGGAAAAAAATGACC

TCTACGGGACTCAGTCCCTATCAATCTCCGTTGGTAGTAGCACTTATCGGAACAACTTTGT

GCCTGTGGTGGGCGCTAGACCTCAGGTCAATGGGCAGTCTGGGCGGATCGACTTTCACTGG

ACTCTCGTACAACCTGGTGACAACATAACTTTCTCACACAATGGCGGCCTCATCGCCCCAA

GCCGAGTCAGTAAATTAATCGGCCGGGGTCTGGGCATCCAGAGCGACGCACCAATTGATAA

CAATTGTGAATCCAAATGCTTCTGGCGGGGGGGGAGCATTAACACTCGGTTACCCTTTCAG

AACTTGAGTCCTCGCACCGTGGGACAATGCCCGAAGTACGTGAACCGCCGCTCACTCATGC

TGGCAACCGGCATGCGGAACGTCCCCGAACTCATCCAGGGCAGAGGGCTCTTTGGCGCCAT

CGCTGGATTTCTGGAGAACGGATGGGAGGGCATGGTCGATGGCTGGTACGGCTTCAGGCAT

CAGAACGCCCAGGGGACCGGCCAAGCCGCTGATTACAAATCTACTCAGGCTGCCATAGACC

AAATCACAGGGAAGCTTAATCGCCTGGTGGAAAAGACCAATACAGAATTTGAAAGCATCGA

GTCTGAGTTCAGTGAAATTGAACATCAGATCGGGAACGTGATCAATTGGACCAAAGACAGC

ATTACCGATATTTGGACCTACCAGGCAGAGTTGCTCGTTGCCATGGAGAACCAGCACACTA

TTGATATGGCCGACTCCGAGATGCTGAATCTCTATGAGAGGGTTCGCAAACAACTGAGACA

AAATGCGGAAGAAGATGGAAAGGGCTGTTTTGAGATCTATCACGCCTGCGATGATAGTTGC

ATGGAAAGTATCAGAAATAACACATACGATCACTCTCAGTACCGGGAAGAGGCCCTCCTGA

ACAGGCTTAATATTAACCCCGTGACGCTTTCATCTGGCTATAAGGACATCATTTTGTGGTT

CTCATTTGGCGCCAGCTGCTTTGTGCTGCTGGCTGTAGTTATGGGCTTATTCTTCTTCTGC

CTGAAGAACGGAAACATGAGATGTACCATTTGCATT

721
ATGTATAAAATTGTGGTCATAATTGCCCTGCTTGGGGCAGTGAAGGGGTTAGACAAAATTT

GCTTGGGGCACCACGCAGTGGCCAACGGGACAATTGTCAAAACACTGACAAATGAACAGGA

GGAAGTGACAAACGCCACAGAAACCGTTGAATCAACCGGAATCAATAGACTTTGTATGAAG

GGCAGAAAGCACAAAGATTTGGGCAATTGCCATCCAATTGGAATGTTGATCGGCACCCCTG

CCTGTGACCTGCATCTGACTGGGATGTGGGACACCCTGATCGAACGGGAGAACGCAATTGC

GTACTGTTATCCCGGCGCTACAGTTAATGTGGAGGCCCTCCGACAGAAGATCATGGAGAGT

GGCGGCATTAACAAGATAAGCACCGGCTTCACCTATGGCTCCAGCATAAACTCAGCTGGCA

CTACTCGGGCATGCATGAGGAACGGCGGGAACTCCTTCTACGCTGAACTCAAGTGGCTGGT

GTCGAAATCTAAGGGACAGAACTTCCCGCAAACCACCAACACTTACCGGAATACGGACACA

GCAGAGCATCTGATCATGTGGGGCATACACCATCCATCCAGCACGCAGGAAAAAAACGACC

TGTATGGAACACAGAGCTTGTCTATCTCGGTGGGGAGCAGCACCTACAGGAACAATTTCGT

CCCTGTTGTTGGAGCCGGGCCCCAAGTTAATGGCCAGAGTGGCAGAATCGACTTTCATTGG

ACACTGGTGCAGCCTGGAGATAATATTACTTTTAGCCACAACGGTGGACTCATTGCTCCCA

GTAGGGTCTCGAAGTTGATCGGTCGTGGCCTGGGTATTCAGAGCGACGCTCCCATTGACAA

TAATTGCGAGAGCAAATGTTTCTGGCGGGGAGGTAGTATTAATACTAGGCTCCCTTTCCAG

AATCTGTCACCGCGCACCGTTGGCCAGTGTCCGAAATATGTCAACCGGCGATCCCTAATGC

TAGCCACTGGCATGCGGAACGTCCCTGAACTCATTCAAGGCAGGGGACTGTTCGGCGCTAT

CGCTGGGTTTCTGGAAAATGGATGGGAGGGCATGGTTGATGGCTGGTATGGCTTCAGGCAC

CAGAACGCTCAGGGCACCGGGCAAGCCGCCGATTATAAATCCACTCAGGCGGCCATCGATC

AAATAACTGGCAAACTAAATAGGCTGGTCGAAAAGACAAACACTGAGTTTGAGAGCATTGA

GAGCGAATTTTCTGAAATTGAGCACCAGATCGGTAACGTTATTAACTGGACCAAGGATTCA

ATTACAGATATTTGGACCTACCAGGCAGAGCTTCTGGTCGCCATGGAAAACCAGCACACAA

TTGATATGGCCGACAGCGAAATGTTGAACCETTACGAGAGAGTGCGGAAGCAGTTGAGACA

GAACGCTGAGGAGGATGGGAAAGGGTGCTTCGAGATTTACCATGCCTGCGATGATTCTTGT

ATGGAGAGCATCAGGAACAATACCTATGACCACAGCCAGTATCGCGAAGAGGCCCTGCTGA

ACAGACTGAACATCAACCCCGTGACACTCTCTTCTGGCTATAAGGATATAATCCTGTGGTT

TAGCTTCGGAGCCAGCTGCTTTGTCCTTCTAGCAGTTGTCATGGGGCTCTTCTTTTTCTGC

CTGAAGAATGGAAACATGAGATGTACAATTTGCATT

722
ATGTACAAAGTGGTGGTCATCATTGCCTTGTTGGGTGCTGTCCGGGGGTTAGACAAGATCT

GTCTGGGGCATCACGCCGTAGCCAATGGAACTACTGTCAAGACCTTAACCAACGAGCAAGA

AGAGGTCACAAATGCGACGGAGACCGTGGAAAGCACATCGCTTAATAAGCTGTGCATGAAG

GGGCGTCGCTACAAAGATCTGGGAAATTGCCATCCAATCGGCATGCTGATTGGAACTCCCG

TCTGTGATCTACACCTGACTGGAACTTGGGATACTTTGATTGAAAGAGAGAACGCTACGGC

TTACTGTTATCCAGGGGTAACCATCAATGAGGAGGCCCTGCGTCAGAAGATTATGGAGAGT

GGGGGAATCAGCAAAATGCGGACAGGATTCACCTATGGGCCGTCCATTAATTCTGCCGGTA

CCACGAGAAGCTGCATGCGGAACGGTGGAAACTCGTTTTACGCAGAACTGAAATGGTTGGT

CTCTGGCACGAAAGGACAGAACTTCCCACAGACTACAAACACCTATCGAAATACCGATACC

GCCGAGCACCTGATCATTTGGGGGATCCACCACCCTAGCAGCACCCAGGAAAAAAATGACT

TATATGGCACTCAATCCCTGAGCATCTCTGTGGGCTCCTCTACTTATCAAAACAATTTTGT

GCCTGTGATTGGAGCCAGGCCCCAGGTGAATGGACAATCCGGACGCATTGAGTTCCACTGG

ACACTTGTCAGACCCGGGGATAATATCACCTTTTCTCACAACGGCGGTCTTATAGCGCCAG

ACCGTGTTAGCAAGCTGATTGGCAAGGGGATCGGCATCCAATCAGGTGCTGTGATCGACAA

GGATTGTGAGTCTAAGTGCTTTTGGAGGCGGGGGTCCATCATTACCGAGCTGCCTTTTCAG

AACCTAAGCCCACGCACCGTCGGACAGTGCCCCAAATATGTGAAAAAAAGATCTTTACTGT

TGGCCACCGGAATGAGAAATGTGCCAGAGGTGGTCCAAGGTCGGGGCTTGTTCGGGGCGAT

TGCAGGCTTTATAGAGAACGGCTGGGAGGGCATGGTGGACGGTTGGTACGGTTTCCGGCAC

CAGAACGCACAGGGAATTGGGCAAGCCGCCGACTACAAGTCAACCCAAACAGCCATAGACC

AGATTACGGGAAAACTGAACAGATTAATCGAGAAAACTAATACAGAATTTGAGAGCATCGA

ATCTGAGTTTTCCGAAATCGAGCACCAGATAGGGAATGTCATCAATTGGACTAAGGACTCC

ATTACAGACATCTGGACTTACCAGGCCGAGTTGCTGGTCGCCATGGAGAATCAGCATACAA

TTGATATGGCTGACAGCGAAATGCTCAACCTGTACGAGCGCGTAAGGAAGCAACTGCGCCA

GAATGCTGAGGAAGACGGGAAGGGTTGCTTTGAGATTTACCACACCTGTGACAACTCATGT

ATGGAAAGCATCCGGAACAACACTTACGATCACTCTCAATATCGCGAGGAGGCCCTTCTGA

ATCGGCTGAATATAAACCCAGTTAAATTGTCTTCAGGCTATAAAGACATCATCCTGTGGTT

CTCGTTCGGGGCTAGCTGTTTCGTGCTGCTGGCCGTGATAATGGGCCTTGGATTCTTTTGT

CTCAAGAACGGCAATATGAGGTGCACCATATGTATC

723
ATGTACAAGGTCGTTGTTATCATCGCCCTGTTGGGCGCGGTGAGGGGACTCGATAAGATTT

GTCTGGGCCACCACGCCGTCGCCAACGGCACGACTGTGAAGACATTGACCAACGAGCAGGA

GGAGGTTACTAATGCCACCGAAACTGTGGAGAGTACCAGTCTGAACAAGTTGTGCATGAAG

GGCCGGCGGTATAAGGATCTGGGAAATTGCCACCCCATCGGAATGCTCATTGGTACCCCAG

TGTGTGATCTTCACCTCACAGGAACCTGGGATACCCTCATCGAGCGTGAGAACGCAACCGC

GTATTGCTATCCCGGCGTGACCATAAATGAGGAAGCCCTGAGACAGAAGATCATGGAGAGC

GGCGGCATAAGTAAGATGAGGACCGGCTTCACTTATGGCCCCTCAATTAACAGTGGGGGAA

CAACCCGGTCCTGCATGAGAAATGGCGGCAATAGTTTCTATGCTGAACTGAAGTGGCTTGT

GAGCGGAACAAAGGGACAGAATTTTCCTCAGACAACGAACACGTATCGCAACACTGATACC

GCTGAACACCTGATCATCTGGGGCATCCATCATCCCAGTTCTACTCAGGAGAAAAATGACT

TGTATGGTACCCAATCTTTGTCTATATCCGTCGGGAGTTCCACATACCAGAACAACTTCGT

CCCTGTGATTGGGGCGCGACCTCAAGTGAACGGCCAGTCGGGCCGCATAGAGTTTCACTGG

ACCTTGGTCCGACCAGGCGATAACATTACATTTTCGCACAATGGCGGCTTGATCGCCCCCG

ATCGCGTGAGCAAACTTATCGGGAAGGGGATCGGAATCCAGAGCGGCGCAGTGATAGACAA

GGACTGCGAAAGCAAATGCTTCTGGCGCGGTGGATCTATCATCACTGAATTGCCTTTCCAA

AACCTGTCCCCCCGAACAGTGGGTCAGTGCCCGAAGTATGTGAAGAAGCGCAGTTTGCTAT

TAGCGACTGGCATGCGGAACGTGCCTGAGGTGGTTCAGGGGCGCGGTCTCTTTGGCGCCAT

CGCAGGATTTATTGAGAATGGCTGGGAGGGCATGGTCGACGGCTGGTACGGATTTAGACAT

CAGAATGCTCAGGGAATTGGGCAGGCCGCCGATTACAAGAGTACCCAGACAGCAATTGACC

AGATCACAGGCAAACTTAACAGGCTTATTGAGAAAACCAACACCGAGTTCGAGTCCATCGA

GTCAGAGTTTAGCGAGATCGAACATCAAATCGGCAATGTGATTAATTGGACAAAAGATTCT

ATTACCGATATCTGGACCTACCAGGCAGAGCTGCTGGTGGCTATGGAAAACCAGCACACCA

TAGACATGGCAGACAGTGAGATGCTGAACCTATATGAGCGTGTGAGGAAACAATTGAGACA

AAATGCCGAGGAAGACGGGAAGGGATGCTTCGAAATATACCACACATGTGATAACTCCTGT

ATGGAATCAATTCGGAACAATACTTACGACCACAGCCAGTATCGCGAGGAAGCCTTACTTA

ATCGTTTAAATATTAATCCCGTTAAGCTGAGCTCCGGTTATAAAGACATCATTCTGTGGTT

CTCCTTTGGAGCCAGTTGCTTCGTTTTGCTCGCCGTTATCATGGGCCTGGGGTTTTTCTGT

CTCAAGAATGGAAATATGCGATGCACCATTTGCATC

724
ATGTATAAGATTGTCGTGATTATCGCTCTCCTTGGTGCCGTTAAGGGCCTGGACAAGATCT

GTCTTGGACACCACGCTGTGGCCAATGGCACTATTGTCAAAACCCTCACTAATGAGCAGGA

GGAGGTCACCAACGCAACGGAGACAGTAGAAAGCACCGGGATCAACCGTCTGTGCATGAAG

GGGCGGAAACATAAAGACCTCGGAAACTGCCATCCGATTGGAATGCTGATCGGGACCCCAG

CTTGCGACCTCCATCTGACAGGGATGTGGGACACGCTTATCGAACGCGAGAATGCCATTGC

CTATTGTTATCCTGGGGCTACTGTGAACGTAGAAGCCCTGCGTCAGAAGATTATGGAGTCC

GGCGGGATCAATAAAATCAGCACAGGGTTCACCTATGGCTCTTCAATCAACAGTGCCGGAA

CAACCCGCGCCTGCATGCGGAACGGCGGGAATTCCTTCTACGCCGAATTAAAGTGGTTGGT

TTCTAAAAGTAAAGGGCAAAACTTCCCTCAGACCACGAACACCTATCGTAACACAGACACC

GCCGAGCATCTCATCATGTGGGGGATCCACCATCCCAGCAGTACACAGGAAAAGAATGATC

TGTACGGCACACAGTCGCTGTCGATCTCAGTTGGGAGTAGCACTTACCGCAACAACTTTGT

GCCCGTCGTGGGGGCGAGGCCGCAGGTAAATGGGCAATCTGGACGTATAGACTTCCACTGG

ACTCTAGTGCAACCCGGCGACAACATCACATTTTCTCATAACGGGGGCCTTATAGCCCCGT

CTCGAGTGTCCAAACTGATTGGCCGCGGCCTCGGAATCCAGTCCGATGCCCCCATCGACAA

TAATTGCGAGTCTAAATGTTTTTGGCGAGGGGGGAGCATTAACACACGGCTCCCATTTCAA

AATTTGAGTCCGCGCACCGTCGGTCAGTGTCCAAAATATGTGAACAGACGCAGCTTGATGC

TCGCAACGGGCATGAGAAACGTTCCTGAATTGATCCAGGGTCGGGGACTGTTTGGGGCCAT

CGCAGGCTTTTTGGAGAACGGTTGGGAAGGAATGGTGGACGGATGGTACGGCTTTAGACAC

CAGAACGCACAGGGAACCGGTCAGGCAGCTGACTACAAGTCAACTCAGGCCGCCATTGACC

AGATCACAGGCAAGCTGAATCGACTCGTCGAGAAGACCAACACCGAATTTGAGTCTATCGA

ATCAGAGTTTTCGGAGATCGAGCACCAGATCGGCAATGTGATCAATTGGACAAAGGATTCT

ATCACCGATATCTGGACGTATCAGGCGGAATTGCTGGTAGCCATGGAGAATCAACACACAA

TAGATATGGCCGATTCTGAGATGCTTAACCTGTACGAACGGGTCCGGAAGCAACTCCGCCA

GAATGCAGAGGAGGATGGGAAGGGCTGCTTCGAGATTTACCACGCTTGTGATGACTCCTGC

ATGGAGTCAATTCGAAACAACACTTACGATCACTCACAGTACCGCGAGGAAGCACTTCTTA

ATAGGCTGAACATCAATCCTGTTACTCTCTCCAGCGGATATAAAGATATCATTCTGTGGTT

CAGCTTCGGTGCCAGCTGCTTTGTGCTACTGGCAGTGGTCATGGGGCTCTTCTTCTTCTGC

CTTAAAAATGGGAATATGCGTTGCACCATTTGCATT

725
ATGTATAAAGTGGTAGTGATCATCGCTCTGCTGGGTGCCGTGCGAGGCCTTGATAAGATCT

GTCTTGGCCACCATGCAGTGGCCAACGGGACCATAGTTAAGACATTAACCAACGAACAGGA

GGAGGTTACCAACGCTACCGAAACTGTCGAGAGCAAATCTCTGGGTAAGCTGTGTATGAAG

GGCCGTAGCTACAATGATCTTGGTAACTGTCATCCTATCGGCATACTAATTGGGACCCCAG

CCTGTGACTTGCACCTTACTGGTACTTGGGACACCTTGATAGAACGTGAAAATGCCGTGGC

TTACTGTTACCCGGGCGCCACTGTGAACGAGGAGGCCCTGCGGCAGAAAATTATGGAGTCA

GGTGGCATCTCTAAGATTTCAACAGGCTTCACCTACGGGACAAGTATTAATTCAGCTGGGA

CTACCAAAGCCTGTATGCGAAATGGGGGTAACTCTTTTTATGCCGAGCTTAAGTGGCTGGT

TTCTAAAAATAAAGGACAGAATTTTCCACAAACTACAAACACTTATCGGAACACGGACACC

GCCGAGCACCTGATTATTTGGGGAATCCACCATCCATCTAGCACTCAGGAAAAAAATGATC

TGTATGGTACTCAGAGCCTGAGCATTAGCGTAGGCAGCTCTACATATCAGAATAACTTTGT

GCCTGTTGTAGGGGCTAGGCCTCAAGTGAACGGGCAGAGCGGTAGGATTGATTTCCACTGG

ACCCTGTTGCAGCCCGGAGACAATATAACCTTCTCGCATAACGGAGGGCTGATAGCCCCGT

CCAGAGTGAGTAAGCTGATCGGTAGAGGACTGGGAATTCAGAGCGAAGCCCCAATTGATAA

CGGCTGCGAGAGTAAGTGCTTCTGGAAGGGCGGTAGCATTAACACGAAGTTGCCATTTCAG

AATCTCAGTCCACGTACGGTGGGCCAGTGTCCCAAATACGTCAACAAACGCTCTCTGATGC

TTGCTACTGGGATGAGGAATGTCCCCGAGATAATGCATGGACGCGGGTTGTTTGGCGCCAT

CGCCGGGTTTATTGAGAATGGCTGGGAGGGCATGGTAGATGGATGGTACGGTTTTCGGCAT

CAGAATGCCCAGGGGACCGGACAGGCTGCGGATTACAAGTCTACACAGGCAGCCATCGATC

AGATCACAGGCAAGTTGAACCGACTGATCGAAAAGACAAACACAGAGTTCGAATCAATTGA

GAGCGAGTTTTCCGAGATAGAGCATCAGATTGGCAACATTATTAATTGGACTAAAGATAGC

ATTACCGATATATGGACCTATCAGGCAGAACTGCTCGTCGCAATGGAGAATCAGCACACTA

TCGATATGGCCGATTCAGAGATGCTAAACCTGTACGAACGCGTTCGCAAGCAACTCAGACA

GAATGCTGAGGAGGATGGCAAGGGTTGTTTCGAGATCTACCATGCGTGCGACGATAGTTGT

ATGGAGAGCATTCGGAATAATACCTACGATCACTCCCAGTACAGGGAAGAGGCTTTGTTAA

ATAGACTGAATATAAACCCTGTCAAGCTATCATCAGGTTACAAAGACATCATTCTTTGGTT

CTCTTTTGGCGCTTCCTGTCTGATCCTTCTAGCCGTGGTGATGGGTCTGGTTTTCTTTTGC

CTCAAAAATGGAAACATGCGTTGTACGATATGTATA

726
ATGTATAAGATAGTTGTGATAATTGCGCTGTTGGGGGCCGTGAAGGGACTCGACAAAATCT

GCCTCGGCCACCATGCAGTCGCCAACGGTACTATTGTGAAAACCCTAACCAACGAACAGGA

GGAGGTTACTAATGCCACCGAGACTGTCGAATCAACCGGCATCAACCGCCTCTGTATGAAA

GGCCGCAAACACAAGGATCTGGGAAACTGCCACCCCATCGGCATGTTAATAGGCACCCCCG

CATGCGATCTGCACCTGACAGGAATGTGGGACACCTTGATCGAGCGTGAAAACGCGATCGC

TTATTGTTACCCTGGCGCGACTGTGAATGTCGAGGCTCTGAGACAGAAGATTATGGAAAGC

GGTGGCATTAATAAGATTAGTACTGGATTTACTTACGGTTCCAGCATAAATTCTGCAGGGA

CCACTCGCGCGTGCATGCGCAATGGTGGCAATAGTTTCTACGCTGAACTTAAGTGGCTTGT

ATCTAAGTCGAAGGGACAAAATTTTCCACAGACGACCAACACATATAGGAACACAGATACA

GCAGAGCACCTTATCATGTGGGGCATTCATCATCCGAGCAGTACTCAGGAGAAGAACGACC

TGTACGGGACTCAGTCTTTGAGCATTAGCGTGGGAAGCAGCACTTACCGGAACAATTTTGT

TCCTGTAGTGGGCGCTCGTCCTCAGGTCAATGGGCAGTCAGGACGGATAGACTTTCACTGG

ACACTCGTGCAGCCCGGCGATAACATTACTTTTTCACATAATGGGGGTCTGATAGCACCAA

GTCGCGTCTCTAAACTGATTGGTAGGGGCCTGGGAATTCAGTCCGACGCTCCCATCGACAA

TAATTGCGAATCCAAATGCTTTTGGGGGGGAGGGTCTATTAACACCAGGTTGCCATTTCAG

AATCTGTCCCCGCGGACAGTTGGCCAGTGCCCCAAGTATGTCAACCGCAGGTCCCTGATGC

TCGCTACAGGAATGCGCAATGTGCCAGAGTTGATCCAGGGACGGGGCTTGTTCGGTGCAAT

TGCAGGCTTTCTGGAAAACGGCTGGGAGGGGATGGTCGATGGCGGGTACGGCTTTCGCCAC

CAGAACGCCCAGGGAACAGGCCAGGCCGCCGATTACAAATCTACCCAGGCTGCCATCGATC

AAATTACAGGGAAATTAAACCGACTAGTCGAGAAGACCAACACTGAATTTGAATCCATTGA

ATCTGAGTTTTCTGAGATAGAGCACCAGATTGGAAATGTTATTAATTGGACAAAGGATAGC

ATCACAGACATATGGACATACCAAGCCGAATTGCTCGTGGCGATGGAAAACCAGCACACAA

TTGATATGGCCGACAGCGAAATGCTAAACCTTTACGAGAGAGTCCGAAAGCAGCTAAGGCA

GAATGCCGAGGAAGACGGTAAAGGCTGTTTCGAAATCTACCATGCATGCGACGATTCATGC

ATGGAAAGTATACGCAACAATACCTATGATCATTCCCAGTACCGCGAAGAGGCCTTGCTGA

ACCGACTCAACATCAACCCTGTAACCCTGAGTTCTGGGTATAAGGACATCATCCTGTGGTT

TAGTTTTGGAGCATCGTGCTTTGTGCTGCTCGCTGTGGTGATGGGATTGTTCTTCTTTTGC

TTAAAGAACGGCAACATGAGGTGCACCATCTGTATA

727
ATGTATAAGATTGTCGTCATCATCGCCCTACTGGGCGCGGTGAAAGGGCTAGATAAGATAT

GTCTCGGGCACCATGCAGTGGCTAACGGAACAATTGTTAAAACCTTAACGAATGAACAGGA

GAAGGTTACCAACGCTACTGAAACAGTTGAGTCAACTGGCCTCAACAGACTGTGCATGAAG

GGTCGCAAACACAAAGATTTAGGCAACTGCCACCCCATTGGTATGTTAATCGGAACCCCAG

CCTGTGATCTCCATCTGACCGGCACATGGGATACGATAATTGAGAGGGAGAATGCTATTGC

CTACTGTTACCCTGGCGCCACCGTCAATGAAGAGGCCCTCAGACAGAAGATCATGGAGTCC

GGGGGTATCGACAAAATTTCCACCGGTTTCACCTACGGTAGCTCCATCAATAGTGCCGGCA

CTACACGCGCATGCATGCGCAATGGGGGCAACTCATTCTACGCGGAGCTAAAGTGGCTCGT

TAGTAAGAGCAAAGGACAGAACTTCCCACAGACTACTAACACTTATAGGAACACTGATACG

GCAGAACATTTAATTATGTGGGGCATACACCATCCTAGCTCAACGCAGGAGAAGAATGACC

TATACGGTACCCAATCCCTCTCCATCAGTGTGGGGAGCTCTACTTATAGAAACAACTTCGT

GCCCGTCGTAGGCGCTCGACCTCAGGTCAATGGACAGTCTGGCAGAATCGACTTCCACTGG

ACTCTGGTACAACCTGGCGATAATATTACCTTTAGCCACAATGGCGGCTTAATAGCACCAT

CTCGTGTGAGCAAGTTGATTGGGCGAGGATTGGGCATTCAGTCGGACGCGCCCATTGATAA

CAACTGTGAATCCAAATGCTTCTGGCGTGGAGGGTCAATCAATACCCGCCTCCCCTTCCAG

AACCTGTCCCCGAGGACTGTGGGCCAATGTCCCAAATATGTGAACAAGAGGTCTCTGATGC

TGGCAACCGGGATGAGAAATGTGCCCGAACTGATCCAGGGACGCGGGCTATTCGGGGCTAT

AGCAGGTTTTCTCGAAAATGGATGGGAGGGCATGGTGGACGGGTGGTACGGCTTTCGCCAC

CAGAATGCACAGGGAACCGGCCAGGCCGCAGATTACAAATCCACCCAGGCGGCCATCGATC

AGATAACCGGCAAATTGAACAGGCTGGTTGAAAAAACAAATACAGAATTCGAATCCATTGA

GTCTGAGTTTAGCGAGATAGAGCACCAGATAGGCAATGTCATAAACTGGACCAAAGATTCC

ATTACAGATATCTGGACATATCAGGCAGAGCTGCTCGTGGCAATGGAGAATCAGCATACTA

TTGATATGGCAGACAGCGAGATGCTCAATCTGTATGAACGGGTAAGGAAACAGCTGCGTCA

GAATGCTGAGGAGGACGGTAAGGGGTGTTTTGAAATATACCACGCTTGCGATGACAGTTGC

ATGGAATCTATTCGCAACAATACGTACGACCACTCTCAGTACCGCGAGGAGGCCCTTCTTA

ACAGGCTGAACATTAATCCCGTCACACTAAGCTCCGGTTATAAGGACATCATTCTTTGGTT

TTCATTTGGCGCTAGCTGCTTCGTTCTGCTTGCCGTGGTTATGGGCCTGGTCTTTTTCTGC

CTTAAGAACGGAAATATGAGGTGTACAATCTGCATT

728
ATGTACAAGATAGTGGTCATTATTGCTCTGTTGGGAGCTGTGAAAGGGCTTGATAAGATTT

GCCTGGGCCACCACGCGGTGGCGAATGGGACGATCGTGAAAACTCTCACAAACGAGCAGGA

AGAAGTGACTAACGCTACAGAGACCGTGGAAAGCACGGGGATCAATAGGCTGTGCATGAAG

GGCCGGAAGCATAAGGATCTAGGCAACTGCCACCCAATTGGCATGCTCATCGGGACGCCCG

CATGCGATCTGCACCTGACAGGGATGTGGGACACCCTTATCGAGCGTGAGAACGCCATCGC

CTATTGCTACCCCGGGGCAACAGTGAATGTGGAAGCACTGAGGCAGAAGATCATGGAGAGC

GGGGGAATCAACAAGATATCCACAGGCTTCACATATGGATCATCAATCAACAGCGCCGGCA

CCACCCGGGCATGTATGCGGAACGGGGGCAATAGTTTCTACGCTGAGCTCAAATGGCTTGT

TAGTAAGTCTAAGGGGCAGAACTTTCCACAGACTACGAATACGTACCGCAATACGGATACT

GCAGAACACTTAATAATGTGGGGAATCCACCACCCAAGTTCCACCCAGGAGAAAAACGATT

TGTACGGAACCCAATCCCTGTCAATATCCGTGGGAAGCTCTACCTATAGGAACAATTTCGT

CCCGGTCGTGGGAGCTCGGCCACAGGTGAACGGACAGAGTGGAAGGATCGACTTCCACTGG

ACGCTCGTGCAACCAGGTGATAATATCACGTTCAGTCACAACGGCGGACTGATTGCTCCAA

GCCGCGTCAGCAAGCTGATAGGCCGGGGGCTGGGGATCCAGTCAGACGCCCCTATTGACAA

TAATTGTGAGTCCAAATGTTTCTGGAGAGGTGGCTCTATCAATACCCGCCTTCCCTTTCAG

AACTTGTCCCCACGGACAGTGGGACAGTGCCCCAAGTATGTCAATCGCAGGTCACTGATGC

TGGCAACCGGGATGAGGAACGTTCCCGAACTCATTCAAGGCCGGGGTCTATTTGGCGCAAT

CGCCGGCTTCCTGGAAAATGGCTGGGAAGGAATGGTGGACGGGTGGTATGGTTTCCGGCAC

CAGAATGCTCAGGGCACAGGCCAGGCTGCTGATTATAAGTCTACTCAGGCAGCCATTGACC

AGATCACCGGTAAGCTCAATAGATTGGTAGAAAAAACAAACACGGAGTTCGAGAGCATCGA

GTCTGAATTTTCCGAGATCGAACATCAGATCGGGAACGTCATCAATTGGACCAAGGACTCT

ATTACGGACATTTGGACTTACCAAGCTGAGCTCCTGGTGGCAATGGAGAACCAGCATACCA

TTGATATGGCCGACTCTGAGATGCTGAACTTATACGAACGGGTGCGAAAGCAACTGAGGCA

GAACGCCGAGGAGGATGGTAAGGGCTGCTTTGAGATATATCATGCCTGTGATGATTCTTGC

ATGGAGAGCATCCGTAATAATACTTACGACCATAGCCAGTATCGAGAGGAAGCGCTACTCA

ATCGATTAAATATCAACCCTGTGACCCTATCTTCGGGTTACAAGGACATAATTCTGTGGTT

CTCATTCGGCGCATCTTGTTTCGTATTGCTCGCAGTGGTGATGGGCCTTTTTTTCTTCTGT

CTGAAAAATGGTAACATGCGCTGTACTATATGCATT

729
ATGTACAAAATAGTGGTGATTATCGCCCTCCTGGGTGCTGTCAAGGGCCTGGATAAGATCT

GTCTTGGCCATCACGCTGTCGCAAATGGCACTATAGTCAAAACTCTGACAAACGAGCAGGA

GGAGGTGACCAACGCAACCGAGACGGTGGAATCTACTGGAATTAACAGGCTGTGTATGAAG

GGTAGGAAGCATAAGGATCTAGGTAATTGCCATCCCATCGGTATGCTGATCGGAACTCCCG

CGTGCGACTTACATCTCACTGGAATGTGGGACACGTTGATCGAGCGGGAGAATGCTATTGC

GTACTGCTACCCCGGCGCTACGGTGAACGTCGAGGCTTTGCGTCAGAAGATCATGGAGAGC

GGGGGTATCAACAAAATAAGTACCGGATTCACATACGGAAGCAGTATCAATTCCGCCGGAA

CAACCCGCGCATGCATGCGGAACGGTGGTAATTCCTTCTATGCTGAACTCAAGTGGCTCGT

GTCAAAGAGCAAGGGACAAAACTTTCCCCAAACGACCAATACCTATAGAAATACAGACACT

GCTGAGCATCTGATCATGTGGGGCATTCACCATCCATCATCTACTCAGGAAAAAAACGACC

TGTACGGTACCCAGAGCCTGTCTATTAGCGTCGGATCATCGACCTACAGGAATAACTTCGT

GCCAGTCGTTGGGGCCCGCCCTCAGGTGAACGGCCAGAGCGGACGGATTGATTTTCACTGG

ACCCTGGTCCAGCCAGGTGATAACATCACCTTCTCACATAACGGAGGCCTGATCGCCCCCA

GCCGAGTTAGTAAACTAATCGGAAGGGGACTTGGTATCCAGAGTGACGCACCCATCGACAA

CAACTGTGAGTCTAAGTGTTTTTGGCGAGGGGGGAGTATCAATACTAGACTGCCGTTTCAG

AATTTGAGTCCCAGAACAGTGGGCCAGTGCCCTAAGTACGTGAACCGGAGGTCTCTGATGC

TCGCAACCGGGATGCGGAATGTTCCCGAGCTGATCCAGGGACGCGGTCTCTTCGGTGCCAT

CGCTGGGTTTCTCGAAAACGGCTGGGAGGGAATGGTGGATGGTTGGTACGGCTTCAGACAT

CAAAACGCTCAAGGAACTGGCCAGGCCGCTGACTATAAGTCAACTCAGGCTGCAATCGATC

AGATCACCGGGAAACTGAATCGCCTCGTGGAGAAGACAAACACCGAGTTCGAGTCAATCGA

GTCCGAGTTCTCCGAGATCGAACACCAAATAGGCAACGTTATAAACTGGACGAAGGACTCC

ATTACGGACATCTGGACATACCAGGCCGAGCTCCTCGTTGCTATGGAGAACCAACACACAA

TCGATATGGCTGATTCCGAGATGCTCAATCTCTACGAGAGGGTGAGGAAACAGTTGAGGCA

GAATGCAGAAGAGGATGGAAAGGGATGCTTTGAAATCTACCATGCCTGCGACGACTCATGC

ATGGAGTCCATTAGAAATAACACTTATGACCATTCGCAATACAGAGAAGAAGCTCTTCTCA

ACAGGCTCAACATCAACCCGGTCACCCTTAGCTCCGGCTACAAGGACATTATCCTCTGGTT

CTCTTTCGGGGCATCATGCTTTGTTCTCCTGGCAGTGGTGATGGGTCTCTTCTTCTTCTGT

CTCAAAAACGGCAACATGAGATGTACGATTTGTATC

730
ATGTATAAGATCGTGGTGATCATAGCGCTCCTGGGCGCCGTGAAAGGACTGGATAAAATTT

GTCTGGGGCATCATGCAGTCGCCAACGGAACCATCGTAAAGACTTTGACTAATGAGCAGGA

AAAGGTTACCAATGCAACCGAAACCGTGGAGAGCACCGGTCTGAACCGCCTCTGCATGAAG

GGCCGTAAACACAAAGATCTGGGCAATTGTCATCCCATCGGAATGCTAATCGGCACTCCTG

CCTGTGACCTACACTTGACCGGGACTTGGGATACCATTATAGAGAGAGAGAATGCTATTGC

CTACTGTTACCCCGGGGCAACCGTGAACGAAGAAGCTTTGAGACAGAAAATTATGGAGAGT

GGCGGAATAGATAAGATTAGCACAGGGTTCACCTACGGAAGCTCTATTAATAGTGCGGGCA

CCACAAGGGCATGCATGCGGAACGGCGGTAACTCTTTCTATGCTGAGTTGAAGTGGCTCGT

GAGCAAGTCTAAAGGGCAGAACTTTCCACAAACCACCAACACTTACAGAAACACGGATACT

GCCGAGCACCTCATCATGTGGGGCATCCACCATCCTTCATCAACACAAGAGAAGAACGACT

TATATGGTACTCAGAGTCTGTCGATTAGCGTCGGCTCTTCAACGTACAGGAACAATTTCGT

TCCTGTAGTCGGGGCCCGGCCACAAGTAAATGGACAGAGGGGGAGGATTGATTTCCATTGG

ACGCTGGTCCAGCCCGGAGATAACATAACTTTCTCTCATAACGGAGGACTCATAGCTCCAT

CAAGGGTGAGCAAACTGATTGGCAGGGGATTGGGAATCCAGTCTGACGCTCCCATCGACAA

CAATTGTGAGAGTAAGTGCTTTTGGCGGGGCGGTTCCATCAACACACGACTGCCTTTCCAG

AATCTGAGTCCCAGAACTGTGGGGCAGTGCCCAAAGTATGTGAATAAAAGATCTTTGATGT

TAGCTACTGGAATGAGAAATGTGCCTGAGCTAATACAGGGTAGAGGTCTGTTCGGAGCAAT

AGCAGGGTTCCTGGAGAATGGGTGGGAAGGCATGGTCGACGGATGGTACGGTTTCCGGCAT

CAGAACGCACAAGGTACAGGGCAGGCGGCTGATTACAAATCTACACAAGCCGCTATTGACC

AAATCACCGGCAAATTGAACCGGCTCGTGGAGAAGACGAATACGGAGTTTGAATCTATTGA

GAGTGAGTTCAGTGAGATTGAACATCAGATTGGCAACGTTATAAATTGGACCAAGGACAGC

ATAACTGATATATGGACCTATCAAGCCGAGCTTCTCGTGGCCATGGAAAATCAGCATACTA

TCGACATGGCTGACTCTGAGATGCTCAACTTATACGAACGTGTAAGGAAGCAGCTGCGGCA

AAACGCCGAGGAAGACGGTAAGGGCTGCTTCGAGATTTATCACGCGTGCGATGACTCTTGT

ATGGAGTCCATCAGAAACAACACCTACGATCACTCACAGTATAGAGAAGAGGCTTTGTTGA

ATCGGCTCAACATCAATCCAGTTACCCTTTCAAGTGGTTACAAGGACATCATCCTATGGTT

TAGCTTCGGTGCCTCTTGTTTCGTGTTGCTGGCGGTCGTTATGGGGTTGGTCTTTTTTTGC

TTGAAAAATGGTAATATGCGGTGTACCATTTGCATC

731
ATGTACAAGATTGTGGTGATCATCGCGCTGCTTGGTGCTGTGAAGGGACTCGACAAAATAT

GCCTGGGGCATCATGCTGTCGCCAATGGGACAATTGTGAAGACATTGACGAACGAGCAGGA

GGAAGTCACTAACGCAACAGAGACAGTTGAGAGCACCGGGATTAACCGACTGTGTATGAAG

GGTCGGAAGCACAAGGACTTGGGTAACTGTCACCCGATCGGCATGTTAATCGGAACCCCTG

CCTGTGACCTGCATCTGACCGGCATGTGGGACACACTGATAGAAAGGGAAAACGCCATTGC

ATACTGCTACCCCGGGGCTACGGTAAATGTGGAGGCTCTCCGGCAGAAGATAATGGAGTCA

GGCGGCATCAACAAGATCTCTACCGGGTTCACGTACGGCTCTTCTATCAATTCAGCTGGAA

CTACCCGCGCATGCATGAGAAACGGTGGGAACTCCTTTTACGCCGAACTGAAATGGCTAGT

GTCCAAATCTAAGGGCCAGAATTTCCCACAGACCACTAATACTTACAGAAACACGGATACA

GCCGAACACTTGATAATGTGGGGGATTCATCACCCATCATCTACACAGGAAAAAAATGATT

TGTACGGTACCCAGAGCCTTAGCATTTCTGTGGGCAGCTCTACCTACAGAAATAACTTCGT

GCCAGTAGTAGGTGCTCGACCGCAGGTTAATGGCCAAAGCGGTAGAATCGATTTTCACTGG

ACATTGGTGCAGCCGGGCGACAACATAACCTTTTCCCATAATGGGGGACTTATTGCACCTT

CCAGGGTGTCCAAACTCATAGGCCGCGGCCTCGGCATTCAAAGCGATGCTCCCATTGACAA

TAATTGTGAATCAAAGTGCTTCTGGCGTGGAGGAAGTATAAACACACGGCTGCCCTTCCAG

AACTTAAGCCCAAGAACCGTGGGGCAGTGCCCTAAGTACGTTAATAGGCGGTCGCTTATGC

TTGCAACAGGTATGAGGAACGTCCCGGAGCTTATCCAAGGCAGGGGACTTTTCGGAGCTAT

CGCCGGTTTTTTAGAGAACGGATGGGAAGGAATGGTGGACGGTTGGTATGGATTCCGGCAC

CAAAATGCTCAGGGCACCGGGCAGGCGGCTGACTACAAATCTACACAGGCGGCTATCGATC

AGATTACGGGAAAGCTGAATAGGTTAGTGGAAAAAACAAACACAGAGTTTGAGAGCATCGA

AAGCGAGTTTTCTGAGATAGAGCATCAGATCGGTAATGTAATCAACTGGACCAAAGACAGC

ATCACAGACATATGGACGTACCAGGCTGAGCTTCTAGTCGCCATGGAAAACCAGCACACTA

TTGATATGGCAGATTCTGAGATGCTTAATCTGTATGAACGAGTGCGAAAACAGCTGCGCCA

GAACGCCGAAGAGGATGGGAAGGGCTGTTTCGAAATCTACCACGCCTGCGACGACTCCTGC

ATGGAAAGCATTAGAAATAATACCTACGATCATTCGCAATATCGGGAAGAGGCCCTCCTGA

ATCGCCTAAATATCAATCCTGTTACACTAAGCAGCGGCTACAAAGACATTATTTTATGGTT

CTCCTTCGGCGCCTCCTGCTTCGTACTATTAGCCGTAGTTATGGGTCTGTTCTTCTTTTGC

CTTAAGAACGGTAACATGAGATGCACAATCTGTATA

732
ATGTACAAAATTGTTGTGATCATTGCCCTCCTGGGGGCAGTGAAGGGACTGGACAAAATCT

GCCTGGGTCACCACGCCGTGGCGAACGGCACCATTGTGAAGACCCTGACCAATGAACAGGA

AGAGGTGACCAATGCTACCGAGACTGTAGAGAGTACAGGCATCAATAGGTTATGCATGAAA

GGCCGCAAACACAAGGACTTGGGAAACTGCCACCCTATAGGCATGTTGATCGGGACGCCAG

CTTGCGACTTGCACCTTACAGGAATGTGGGATACCTTGATAGAAAGGGAAAACGCTATCGC

TTACTGCTACCCGGGCGCTACCGTCAATGTGGAAGCACTGCGACAGAAAATTATGGAGAGT

GGTGGCATAAATAAAATATCAACTGGGTTCACATACGGAAGCTCAATCAATAGCGCGGGCA

CAACACGAGCCTGCATGCGTAACGGAGGAAACAGCTTTTATGCAGAGCTCAAATGGTTAGT

TTCAAAATCTAAGGGGCAGAACTTTCCTCAAACCACTAACACGTATCGGAATACCGACACA

GCAGAGCACTTAATAATGTGGGGCATACATCATCCCTCAAGCACACAGGAAAAGAACGACC

TGTACGGAACGCAGTCCTTATCAATCTCTGTGGGGTCCAGCACATACCGAAACAACTTTGT

ACCAGTCGTGGGTGCTCGCCCACAAGTGAACGGCCAGTCTGGGCGCATCGACTTTCACTGG

ACTTTGGTTCAGCCTGGTGATAATATCACCTTTAGCCATAATGGCGGACTCATAGCGCCAA

GCAGGGTGTCCAAACTTATCGGACGTGGGTTGGGTATTCAGAGCGACGCACCAATCGACAA

TAACTGCGAGTCAAAGTGTTTTTGGAGAGGGGGGTCAATCAACACCCGCCTGCCCTTCCAG

AACCTGTCTCCCCGTACGGTGGGGCAGTGTCCAAAGTACGTGAATAGGCGGAGCCTGATGC

TGGCCACAGGGATGCGCAACGTGCCTGAGCTCATTCAAGGCCGGGGCTTGTTTGGAGCCAT

CGCGGGTTTTCTCGAAAACGGGTGGGAAGGGATGGTCGATGGCTGGTACGGCTTTCGGCAC

CAGAATGCTCAGGGAACGGGGCAGGCTGCCGACTACAAGTCAACGCAGGCGGCCATCGATC

AAATCACCGGCAAGCTCAACAGGCTCGTGGAAAAAACCAATACGGAGTTCGAAAGTATCGA

AAGCGAGTTCAGCGAAATTGAGCACCAGATCGGCAATGTAATCAATTGGACTAAGGATAGC

ATCACCGATATCTGGACATACCAAGCTGAGCTGTTAGTCGCCATGGAGAATCAGCATACAA

TAGACATGGCTGATAGTGAAATGTTGAATCTGTACGAGAGGGTTAGGAAACAGCTGCGCCA

GAATGCTGAGGAAGACGGAAAGGGCTGCTTTGAAATCTATCACGCTTGCGACGATTCCTGT

ATGGAGTCCATACGAAATAATACGTACGACCATTCCCAGTACCGCGAAGAGGCTCTCCTGA

ATCGGCTGAACATCAACCCTGTGACACTTAGCTCGGGCTATAAGGACATAATTTTGTGGTT

CTCTTTTGGGGCATCATGTTTTGTCTTGCTGGCCGTCGTTATGGGGCTCTTCTTCTTCTGT

CTAAAAAATGGAAACATGCGGTGCACCATTTGTATT

733
ATGTATAAAATCGTGGTGATCATTGCTCTGTTAGGCGCCGTGAAGGGCCTGGACAAGATTT

GCCTAGGACATCATGCCGTCGCTAACGGCACTATCGTGAAGACTCTGACCAATGAGAAAGA

GGAGGTGACTAACGCAACAGAAACAGTTGAGTCAACTGGCCTGAACCGGCTCTGCATGAAA

GGGAGAAAGCATAAAGACCTAGGCAATTGCCATCCTATTGGTATGCTCATTGGCTCTCCCG

CCTGTGACCTGCATCTTACTGGAACGTGGGACACCCTGATTGAAAGAGAAAACGCCATCGC

GTATTGCTACCCGGGGGCCACCGTGAACGGAGAAGCGTTACGCCAAAAGATCATGGAGTCA

GGCGGCATCGATAAGATCAGCACTGGCTTTACCTACGAAAGTAGCATCAACAGCGCTGGAA

CCACCCGCGCCTGTATGAGAAACGGGGGTAATTCCTTCTATGCGGAGCTGAAATGGCTTGT

GTCTAAATCCAAAGGCCAGAACTTTCCACAGACAACGAACACTTATCGGAATACTGACACA

GCAGAGCATCTTATCATGTGGGGGATCCACCATCCTAGTTCCACGCAGGAGAAGAATGACC

TGTATGGGACACAAAGCCTGTCTATTAGCGTGGGATCATCAACTTACAGGAACAATTTTGT

CCCTGTGGTGGGCGCCAGGCCCCAGGTAAACGGACAGAGTGGACGCATCGACTTTCATTGG

ACTCTCGTGCAGCCTGGGGATAATATTACCTTCAGCCATAATGGTGGCCTGATAGCACCCT

CAAGAGTGTCAAAACTCATCGGTCGCGGATTGGGGATTCAATCTGACGCCCCTATAGATAA

CAATTGCGAGAGCAAGTGCTTTTGGAGAGGAGGCAGCATCAACACCCGCCTTCCCTTTCAG

AATCTGAGTCCCCGGACGGTTGGGCAGTGTCCTAAATATGTCAATAAGCGGTCACTCATGT

TGGCAACTGGCATGCGCAACGTACCTGAGCTCATGCAGGGAAGGGGCCTCTTTGGAGCTAT

TGCAGGGTTCCTGGAGAACGGCTGGGAGGGGATGGTAGACGGATGGTACGGATTCCGGCAT

CAAAATGCGCAAGGCACTGGTCAAGCTGCTGATTATAAGTCCACCCAGGCCGCTATTGATC

AGATTACCGGAAAGCTGAACCGGCTGGTGGAAAAGACCAATACAGAATTTGAGAGCATTGA

ATCGGAGTTTAGCGAAATCGAACATCAAATTGGGAACGTCATAAACTGGACAAAAGACAGC

ATCACCGATATCTGGACATACCAGGCGGAGCTGCTAGTGGCGATGGAGAATCAGCACACGA

TTGATATGGCCGACTCTGAGATGCTGAATCTGTATGAGCGGGTTAGAAAGCAGCTGAGGCA

AAACGCAGAAGAAGATGGTAAAGGATGCTTTGAGATCTATCATGCCTGCGATGACTCATGT

ATGGAATCTATCCGTAACAATACATACGATCACAGTCAGTATCGGGAGGAAGCTCTGCTGA

ATAGGCTAAACATCAATCCCGTGACCCTCTCGAGTGGCTATAAGGATATCATCTTGTGGTT

CTCTTTCGGCGCCAGCTGTTTCGTGCTACTGGCCGTCGTGATGGGGCTGGTATTCTTCTGC

CTGAAGAACGGTAATATGCGCTGCACCATATGTATT

734
ATGTACAAGATCGTGGTCATCATTGCACTGCTTGGCGCTGTGAAAGGATTAGACAAGATTT

GCCTCGGCCACCACGCCGTCGCCAATGGGACCATCGTTAAGACATTAACAAATGAACAAGA

AGAGGTAACCAACGCCACCGAGACCGTGGAGTCGACAGGCATCAACCGGTTATGCATGAAA

GGGCGGAAACACAAAGATCTGGGGAACTGCCATCCAATCGGAATGCTCATTGGCACCCCAG

CGTGCGATCTCCATCTCACTGGCATGTGGGATACATTAATTGAGAGGGAGAATGCAATCGC

ATATTGCTACCCTGGCGCCACTGTCAACGTCGAGGCCCTGCGCCAGAAAATAATGGAATCA

GGTGGCATAAACAAGATTTCCACCGGATTTACTTATGGCTCTTCCATCAACAGCGCTGGCA

CCACACGGGCTTGTATGCGAAACGGGGGCAACTCATTTTATGCAGAACTGAAGTGGCTTGT

CTCAAAAAGTAAGGGTCAGAACTTTCCACAGACAACAAATACATACAGGAATACCGACACT

GCAGAGCATCTGATCATGTGGGGCATCCACCATCCTAGTTCGACACAGGAGAAGAACGACC

TGTATGGCACCCAATCACTGAGTATCTCTGTGGGGAGTAGTACTTATCGGAACAATTTTGT

GCCAGTCGTGGGCGCAAGACCACAAGTCAATGGCCAGAGTGGCCGTATCGACTTCCATTGG

ACCCTGGTACAGCCTGGTGATAACATCACCTTTAGCCACAACGGAGGACTGATTGCACCGT

CAAGAGTTTCAAAACTGATCGGCCGAGGCCTGGGAATCCAGAGCGACGCTCCCATCGATAA

TAATTGTGAAAGTAAGTGCTTCTGGCGGGGTGGATCCATCAACACCCGTCTACCCTTTCAG

AATCTGTCACCCCGGACCGTCGGACAGTGCCCAAAATACGTGAACAGGCGCAGTTTGATGT

TAGCTACAGGGATGAGAAACGTGCCAGAACTGATTCAGGGACGCGGACTGTTCGGCGCCAT

CGCCGGCTTCCTCGAAAACGGTTGGGAGGGTATGGTGGACGGTTGGTATGGCTTCAGGCAT

CAGAACGCCCAGGGGACAGGCCAGGCCGCTGACTATAAGAGCACTCAGGCGGCTATCGACC

AGATCACTGGGAAGCTCAATCGTCTCGTCGAGAAAACGAATACCGAGTTTGAGAGCATCGA

AAGTGAATTCTCTGAGATAGAGCACCAGATCGGTAATGTGATCAATTGGACAAAGGACTCG

ATTACTGACATCTGGACGTACCAAGCCGAGCTGCTCGTCGCCATGGAAAATCAGCATACCA

TTGATATGGCTGACTCAGAGATGCTTAACTTGTACGAACGGGTCCGGAAACAACTGAGACA

GAATGCCGAAGAGGACGGGAAAGGCTGTTTTGAAATCTATCACGCCTGTGATGATTCTTGT

ATGGAAAGCATTAGAAACAATACATACGACCATTCACAGTACAGGGAGGAGGCTTTACTCA

ATCGCCTGAACATCAATCCCGTAACATTGAGCTCTGGATATAAAGACATTATCCTCTGGTT

CTCCTTTGGTGCCTCTTGTTTTGTACTCCTGGCAGTGGTTATGGGTCTCTTCTTCTTTTGT

CTAAAGAACGGTAATATGAGGTGTACCATTTGCATA

735
ATGTACAAGATCGTGGTGATTATTGCCCTGTTGGGGGCCGTGAAGGGCTTGGACAAGATAT

GCCTTGGTCACCATGCTGTGGCCAACGGCACTATCGTCAAAACACTGACAAACGAGCAGGA

AGAGGTGACCAACGCCACGGAGACTGTAGAAAGCACCGGGATTAACCGACTATGTATGAAA

GGCCGCAAACACAAGGACCTCGGGAACTGCCATCCCATCGGCATGTTAATAGGCACCCCCG

CTTGCGATCTGCACCTGACAGGGATGTGGGATACCCTAATTGAGCGCGAGAACGCAATTGC

CTATTGTTACCCAGGAGCCACAGTAAATGTAGAAGCTTTAAGGCAGAAGATTATGGAGAGT

GGAGGGATTAACAAGATCAGCACGGGCTTCACATACGGTTCCTCCATCAATTCTGCTGGAA

CCACCAGGGCATGCATGCGTAATGGGGGAAACTCATTCTACGCAGAGCTAAAGTGGCTGGT

TTCCAAGTCTAAGGGACAGAACTTCCCGCAGACAACGAATACTTATCGGAACACCGACACT

GCCGAACATTTAATCATGTGGGGGATCCACCACCCCAGTTCTACCCAGGAGAAAAATGATC

TCTACGGTACTCAGTCCCTGTCCATCTCCGTTGGTTCCTCCACCTATCGGAATAATTTTGT

CCCTGTTGTGGGAGCACGGCCACAGGTGAATGGCCAGTCCGGGAGGATAGACTTTCACTGG

ACCCTTGTTCAGCCCGGGGACAATATCACTTTCTCACATAATGGGGGCCTGATTGCTCCTT

CCAGAGTGAGTAAATTGATAGGCCGGGGGCTGGGCATCCAATCAGATGCACCCATTGATAA

CAACTGCGAGTCCAAATGCTTCTGGCGCGGAGGCAGCATCAATACCCGACTGCCCTTCCAG

AACCTGTCTCCTAGGACAGTTGGCCAGTGTCCCAAATATGTAAACCGCAGATCACTGATGC

TGGCTACCGGTATGAGAAACGTCCCAGAGCTAATTCAAGGCCGAGGACTTTTTGGCGCTAT

TGCAGGATTCCTTGAGAACGGGTGGGAGGGCATGGTCGACGGCTGGTACGGGTTCAGACAC

CAAAACGCTCAGGGAACAGGCCAAGCCGCGGACTATAAATCAACACAAGCGGCCATTGATC

AGATAACCGGCAAGCTGAATAGGCTGGTGGAAAAGACTAACACTGAGTTTGAAAGCATCGA

GTCGGAATTCTCTGAGATTGAACACCAGATTGGAAATGTAATCAACTGGACAAAGGATTCC

ATCACCGACATCTGGACTTATCAAGCAGAACTGTTAGTGGCCATGGAAAATCAGCATACCA

TCGACATGGCCGACAGCGAGATGCTGAATCTGTACGAAGGGGTTCGTAAACAGCTGAGGCA

GAACGCAGAGGAGGACGGTAAGGGATGCTTTGAAATTTATCACGCTTGTGACGATAGTTGT

ATGGAGAGCATTAGGAACAACACTTACGACCACTCTCAGTATAGGGAAGAAGCACTCCTTA

ACAGGCTGAACATCAACCCTGTGACGCTCTCTTCCGGGTATAAAGACATCATCCTGTGGTT

TTCATTTGGCGCTTCATGTTTTGTACTGCTAGCAGTGGTGATGGGTCTCTTCTTTTTTTGC

CTCAAAAACGGGAACATGAGGTGCACTATTTGCATC

736
ATGTACAAGATCGTAGTGATAATCGCTCTACTAGGAGCTGTCAAAGGTCTCGATAAGATAT

GTCTGGGGCACCATGCGGTAGCCAATGGAACGATCGTGAAAACACTTACTAACGAGCAGGA

GGAGGTCACCAACGCCACAGAAACGGTGGAATCTACGGGGATCAACCGCTTATGCATGAAG

GGGAGGAAGCATAAGGATTTGGGCAATTGCCACCCGATTGGAATGCTGATTGGGACTCCTG

CTTGCGATCTGCACTTAACCGGCATGTGGGATACGCTAATAGAGCGCGAAAACGCCATCGC

CTACTGTTATCCCGGCGCGACAGTAAACGTAGAGGCACTAAGACAGAAGATTATGGAGTCC

GGGGGAATAAACAAGATAAGCACGGGCTTTACCTATGGATCATCCATCAATTCTGCTGGAA

CAACACGCGCCTGCATGCGGAACGGAGGCAATTCTTTCTATGCAGAGCTGAAATGGCTCGT

GTCCAAAAGTAAAGGTCAGAACTTCCCGCAGACTACAAACACTTATAGGAACACTGACACA

GCTGAGCATCTAATCATGTGGGGTATTCACCACCCAAGTTCAACCCAAGAAAAAAATGATC

TCTACGGCACGCAGTCACTTTCCATCTCTGTGGGCTCTAGCACCTACAGAAACAACTTTGT

CCCAGTGGTGGGAGCTCGGCCTCAAGTGAACGGACAGTCCGGTAGGATCGATTTTCATTGG

ACCCTCGTACAGCCCGGGGATAACATCACTTTTAGTCACAATGGTGGCCTGATTGCCCCCT

CCAGGGTGTCTAAGTTGATTGGGCGCGGCCTAGGTATACAGAGTGACGCCCCCATAGATAA

TAATTGCGAGAGCAAATGTTTCTGGAGGGGCGGAAGTATCAATACTCGGCTGCCTTTTCAG

AACCTTAGCCCACGTACTGTGGGCCAGTGTCCCAAGTACGTTAATCGAAGAAGCCTGATGC

TTGCAACCGGAATGAGGAACGTGCCCGAACTGATCCAAGGTCGTGGCTTATTCGGAGCCAT

CGCCGGATTCCTGGAGAACGGATGGGAAGGGATGGTGGATGGGTGGTACGGGTTCCGACAC

CAGAACGCCCAGGGAACAGGTCAAGCCGCCGATTACAAATCAACACAAGCGGCCATCGATC

AGATTACTGGAAAACTGAACAGGTTGGTGGAGAAGACTAACACAGAGTTCGAGTCAATCGA

AAGCGAATTTAGCGAGATTGAGCACCAAATCGGGAACGTGATCAACTGGACAAAGGATTCC

ATTACCGACATATGGACCTACCAGGCTGAGCTGTTGGTGGCAATGGAAAATCAGCATACTA

TCGATATGGCCGATTCTGAGATGCTGAATCTGTACGAGCGGGTCAGAAAGCAGCTGAGACA

AAATGCTGAGGAAGACGGTAAGGGTTGTTTCGAGATCTACCATGCCTGCGACGACTCTTGC

ATGGAGAGCATCAGGAACAACACATACGATCACTCCCAGTATAGAGAAGAAGCTCTGTTGA

ATAGGCTTAACATCAACCCAGTGACGCTTAGTAGCGGTTACAAAGATATCATTCTGTGGTT

TAGTTTTGGGGCCTCATGTTTCGTGCTTTTGGCAGTAGTTATGGGGCTGTTTTTCTTCTGT

CTCAAAAATGGTAATATGCGATGCACGATTTGTATT

737
ATGTACAAAATCGTGGTCATTATCGCCCTGCTGGGCGCGGTGAAAGGCTTGGATAAAATCT

GCCTCGGGCATCACGCCGTGGTGAATGGAACGATCGTGAAGACTCTGACCAACGAACAGGA

AGAGGTTACCAACGCAACGGAAACAGTCGAATCAACCGGACTCAATCGTTTATGTATGAAG

GGCAGAAATCACAAGGACCTTGGAAACTGCCACCCAATAGGGATGCTTATAGGAACCCCAG

CTTGCGACCTGCACCTAACCGGCACCTGGGACACTCTTATTGAGAGAGAGAACGCAATTGC

TTACTGTTACCCCGGCGCAACAGTGAACGAAGAGGCCCTCAGGCAGAAGATTATGGAGTCT

GGAGGGATAAACAAGATATCGACCGGTTTCACCTATGGATCCTCTATCAATTCTGCAGGGA

CAACCCGCGCCTGTATGAGAAATGGCGGAAACTCCTTTTATGCCGAACTGAAGTGGCTTGT

TTCCAAAAGCAAAGGTCAGAACTTTCCTCAAACAACTAATACGTACAGGAACACCGATACC

GCCGAGCACCTGATCATGTGGGGAATCCATCACCCTAGCAGTACCCAAGAAAAAAACGACC

TATATGGTACCCAGTCCCTCAGCATCTCAGTGGGCTCATCAACCTATCAAAACAACTTCGT

GCCTGTTGTCGGCGCACGACCCCAGGTGAACGGTCAAAGCGGAAGGATCGATTTCCATTGG

ACCCTGGTTCAGCCCGGCGACAATATCACATTTAGTCACAATGGCGGTCTGATTGCACCTT

CCCGCGTGAGTAAACTGATCGGTCGGGGGCTTGGAATTCAAAGCGACGCCCCCATCGACAA

CAATTGTGAGAGCAAGTGTTTTTGGAGAGGCGGGTCAATAAACACCAGGCTGCCCTTTCAG

AACCTAAGTCCCAGGACTGTAGGCCAGTGTCCCAAATACGTCAATAAGCGTTCACTAATGT

TGGCCACGGGAATGAGAAACGTGCCCGAGCTGATGCAAGGCAGAGGCCTGTTCGGGGCCAT

CGCGGGGTTCATCGAGAACGGTTGGGAAGGCATGGTTGATGGTTGGTATGGATTTAGGCAC

CAGAACGCTCAGGGCACAGGACAGGCCGCTGACTATAAGAGTACTCAAGCCGCAATTGACC

AGATCACCGGGAAGTTGAACCGACTCATCGAGAAGACGAACACAGAATTCGAGAGCATAGA

GTCAGAGTTCTCGGAGATCGAACACCAAATTGGCAACGTTATCAATTGGACTAAGGACTCG

ATCACTGACATCTGGACATACCAGGCTGAGCTGTTGGTGGCCATGGAAAACCAGCACACCA

TAGACATGGCCGACAGCGAGATGCTGAATCTCTACGAAAGAGTTCGCAAACAGCTCAGGCA

GAATGCCGAAGAAGACGGTAAAGGATGCTTTGAAATCTATCACGCTTGTGACGATTCCTGC

ATGGAGAGCATCAGAAACAATACCTACGATCACAGCCAGTACCGGGAAGAAGCACTCCTGA

ATAGGCTGAACATAAATCCAGTAACTCTTTCGTCCGGATACAAAGACATAATACTCTGGTT

TTCGTTTGGTGCATCCTGCTTCGTGCTGCTCGCAGTGGTGATGGGGCTTGTCTTTTTCTGT

TTGAAGAACGGAAATATGCGGTGCACCATATGCATC

738
ATGTACAAGATCGTTGTGATAATTGCCTTGCTGGGCGCAGTCAAAGGACTCGATAAGATCT

GTCTCGGCCATCACGCCGTTGCCAATGGAACCATTGTGAAGACTCTCACTAACGAGAAAGA

GGAGGTTACAAACGCTACCGAAACTGTGGAGAGTACTGGTCTGAACCGACTGTGTATGAAG

GGCAGAAAGCATAAGGATCTGGGTAATTGTCACCCCATCGGAATGTTAATCGGTAGCCCAG

CCTGTGATTTGCACCTTACAGGGACCTGGGATACACTCATAGAGAGGGAAAACGCCATCGC

ATATTGTTATCCCGGGGCCACGGTGAACGGAGAAGCTTTACGCCAGAAGATCATGGAGTCC

GGGGGGATCGATAAGATCAGCACCGGATTCACCTACGAGAGTAGTATAAACTCAGCGGGCA

CCACCAGAGCGTGCATGCGGAATGGCGGCAATAGCTTTTATGCTGAGCTTAAGTGGTTGGT

GTCCAAATCTAAGGGACAGAATTTCCCCCAGACCACCAATACGTACCGCAATACAGACACA

GCCGAGCATTTAATCATGTGGGGAATCCACCACCCATCGTCTACCCAGGAAAAGAACGACT

TGTATGGGACTCAGAGTCTTTCCATCTCCGTCGGATCCTCAACCTACCGGAACAATTTCGT

GCCCGTGGTAGGGGCGCGTCCCCAAGTTAACGGCCAATCTGGCAGGATAGATTTCCATTGG

ACTCTGGTGCAGCCTGGCGACAACATTACCTTCTCGCATAACGGGGGACTGATCGCCCCCT

CTCGCGTTTCTAAGCTGATCGGCCGCGGTCTGGGCATCCAGTCTGACGCTCCCATTGACAA

TAACTGCGAATCAAAGTGCTTTTGGAGAGGAGGGTCTATTAATACTAGGTTGCCCTTTCAG

AATCTGTCCCCCCGAACCGTCGGGCAGTGTCCGAAATATGTCAACAAACGCTCATTAATGC

TTGCTACTGGCATGAGGAATGTCCCTGAGTTGATGCAGGGCAGGGGGCTGTTCGGCGCCAT

AGCAGGGTTTCTCGAGAACGGGTGGGAGGGCATGGTAGATGGGTGGTACGGCTTTAGGCAT

CAGAATGCTCAAGGTACCGGCCAAGCCGCCGACTACAAATCCACACAGGCCGCAATTGACC

AGATCACAGGTAAATTGAATCGGCTTGTGGAGAAGACCAATACTGAATTCGAAAGTATTGA

ATCCGAATTTTCTGAGATAGAGCACCAAATCGGTAACGTGATCAACTGGACTAAAGATTCT

ATCACCGACATTTGGACATATCAGGCGGAATTGCTGGTGGCTATGGAGAACCAGCACACGA

TTGATATGGCTGACAGCGAGATGCTGAACCTTTACGAGCGAGTGCGTAAGCAACTGAGGCA

GAACGCAGAGGAGGATGGTAAGGGGTGCTTCGAGATATATCACGCATGTGATGATTCATGC

ATGGAGTCCATTCGCAACAATACATACGATCACAGCCAGTATCGGGAGGAAGCTCTGCTAA

ACCGATTGAACATTAATCCGGTAACTTTGTCCTCCGGTTACAAGGACATTATCCTCTGGTT

CTCGTTCGGGGCAAGTTGCTTCGTTCTTTTGGCAGTCGTTATGGGTCTGGTTTTTTTTTGC

CTGAAGAACGGCAATATGCGCTGCACAATCTGCATC

739
ATGTATAAGATTATAGTAATCATAGCTCTTCTAGGCGCTGTCAAAGGACTAGACAAGATCT

GTTTAGGCCATCATGCTGTTGCAAATGGAACAATCGTGAAAACATTAACAAACGAACAGGA

AGAGGTAACAAATGCTACTGAGACAGTCGAAAGCACTGGCATCAACAGGCTGTGCATGAAG

GGGCGTAAACACAAGGACCTTGGCAACTGCCATCCCATCGGAATGCTCATCGGCACCCCCG

CATGCGATCTGCACCTAACCGGAACCTGGGACACTCTCATCGAGCGCGAAAACGCAATCGC

CTACTGCTACCCCGGCGCTACGGTGAACGTCGAGGCGTTGCGACAGAAGATTATGGAATCA

GGTGGAATCGATAAGATCTCCACTGGATTTACATACGGATCGTCTATCAACAGCGCCGGTA

CAACTCGCGCCTGTATGCGTAACGGCGGAAACTCATTTTACGCCGAATTAAAGTGGCTGGT

GAGCAAAAGTAAAGGGCAGAACTTTCCGCAAACAACAAATACCTATAGAAATACAGACACT

GCCGAGCACCTCATTATGTGGGGTATACACCACCCTAGCAGCACGCAGGAGAAAAACGACC

TCTACGGAACCCAGTCACTGAGCATCTCAGTTGGTTCCTCCACATACCGGAACAATTTCGT

GCCCGTCGTGGGCGCACGCCCTCAGGTCAATGGACAGTCTGGTCGTATAGACTTTCATTGG

ACGCTTGTGCAGCCAGGCGATAACATCACATTTAGCCATAACGGGGGGTTGATTGCTCCCT

CACGGGTGAGCAAGCTAATAGGTAGGGGCCTCGGTATCCAGTCCGATGCACCTATTGATAA

CAACTGCGAGTCTAAATGTTTTTGGCGAGGTGGGTCCATCAATACGCGGCTGCCTTTTCAG

AATCTTTCTCCTCGAACTGTCGGGCAATGCCCAAAATACGTCAACCGTCGTAGTCTTATGT

TGGCTACAGGGATGCGGAACGTACCGGAACTTATTCAGGGCAGAGGCCTGTTTGGTGCGAT

AGCCGGCTTCCTGGAAAACGGATGGGAGGGAATGGTCGATGGATGGTACGGTTTTCGACAT

CAAAATGCCCAGGGAACCGGGCAGGCAGCGGACTATAAGTCTACCCAGGCAGCCATAGACC

AGATTACAGGAAAGCTCAATAGACTCGTGGAGAAAACTAACACAGAGTTTGAATCAATCGA

GAGCGAGTTCAGCGAGATTGAACATCAAATCGGGAACGTGATCAACTGGACCAAAGATTCT

ATCACAGACATTTGGACATACCAAGCTGAACTCCTAGTTGCCATGGAAAATCAACACACTA

TCGATATGGCCGATTCAGAAATGTTGAATCTGTATGAGCGCGTGAGAAAACAACTCCGCCA

AAACGCAGAAGAGGATGGCAAGGGCTGTTTTGAGATCTACCACGCCTGTGATGACTCTTGT

ATGGAGTCCATTCGGAATAATACCTACGATCATAGCCAGTATCGGGAAGAGGCTCTGCTTA

ACCGATTGAACATTAATCCCGTGACCTTGTCAAGCGGTTACAAAGACATAATTCTATGGTT

CTCATTTGGCGCCTCCTGCTTTGTGCTGCTCGCTGTTGTCATGGGCCTCTTTTTTTTTTGT

CTGAAAAATGGAAATATGCGATGTACCATCTGCATT

740
ATGTATAAAATTGTCGTGATCATAGCTCTCCTTGGGGCTGTGAAAGGCCTGGATAAGATCT

GTCTGGGACACCACGCGGTGGCAAATGGCACTATCGTCAAAACCCTGACAAACGAGCAGGA

GGAGGTTACTAACGCCACGGAAACGGTTGAGTCCACCGGGATTAACAGACTTTGCATGAAG

GGCAGGAAACACAAGGATCTCGGTAACTGTCACCCCATTGGCATGCTGATTGGGACTCCCG

CATGTGACCTTCACTTAACCGGAATGTGGGACACTCTGATCGAGCGTGAAAACGCCATTGC

CTACTGTTATCCCGGGGCAACAGTGAACGTCGAGGCGTTGAGGCAAAAGATCATGGAAAGC

GGCGGCATCAACAAAATCAGCACTGGGTTCACATACGGATCTAGCATTAACAGCGCCGGCA

CTACACGTGCATGTATGAGGAATGGCGGCAATTCTTTTTACGCCGAACTGAAGTGGCTTGT

TTCCAAATCCAAGGGTCAGAACTTTCCACAAACCACGAATACCTATCGGAATACTGACACT

GCAGAGCATCTAATTATGTGGGGCATCCACCACCCCAGTTCAACTCAGGAGAAGAATGACT

TGTACGGGACCCAGAGCCTGAGTATTTCTGTTGGGAGTTCAACCTACAGAAATAACTTCGT

CCCTGTCGTCGGGGCTAGACCTCAAGTTAATGGTCAGTCCGGCCGTATCGACTTTCACTGG

ACTCTGGTACAGCCGGGGGATAACATTACATTCTCACACAATGGGGGTCTCATCGCACCCA

GCCGGGTGTCCAAACTCATTGGCCGAGGATTGGGGATCCAATCCGATGCCCCCATAGACAA

CAATTGCGAGTCTAAATGCTTTTGGAGGGGCGGCTCTATAAACACACGCCTGCCATTCCAG

AACCTCAGTCCCCGGACCGTCGGGCAGTGCCCAAAATATGTGAATCGAAGGAGTCTTATGC

TGGCTACTGGCATGCGTAACGTGCCTGAGCTGATACAGGGAAGGGGCCTTTTCGGGGCTAT

CGCCGGATTTTTAGAGAATGGATGGGAGGGGATGGTTGACGGGTGGTATGGATTTCGGCAC

CAGAATGCACAGGGTACAGGACAAGCCGCCGATTACAAGTCTACCCAAGCTGCAATAGATC

AGATCACCGGCAAACTCAACCGGCTTGTTGAAAAGACCAACACAGAATTCGAATCAATCGA

GAGCGAGTTCTCTGAAATAGAGCATCAGATTGGCAACGTGATCAACTGGACAAAAGACTCT

ATTACAGACATCTGGACTTACCAGGCTGAGTTGCTCGTGGCCATGGAGAACCAACATACAA

TCGATATGGCAGACTCAGAGATGCTTAACCTGTATGAACGTGTGAGGAAGCAGCTCCGCCA

GAATGCTGAAGAGGACGGAAAGGGGTGTTTTGAGATATACCATGCCTGCGACGATAGCTGC

ATGGAGTCCATCAGGAACAATACGTACGATCACTCCCAATACAGAGAGGAGGCCTTGCTGA

ATCGGCTTAATATCAACCCCGTCACGCTGAGTTCCGGATACAAGGATATTATACTATGGTT

CTCATTTGGCGCTTCATGCTTCGTGCTCCTCGCCGTGGTGATGGGCCTGTTTTTCTTTTGC

CTGAAGAACGGTAACATGAGGTGTACAATCTGCATT

741
ATGTACAAAATCGTGGTCATTATTGCCCTGCTGGGCGCCGTAAAAGGCCTCGATAAGATTT

GTCTGGGACATCACGCGGTGGCTAACGGAACAATTGTTAAAACCCTGACTAACGAGCAGGA

AGAAGTCACAAACGCTACGGAGACCGTGGAGAGTACCGGAATCAATCGCCTGTGCATGAAG

GGCCGTAAGCACAAGGACCTGGGTAACTGCCATCCAATCGGGATGCTTATCGGCACGCCTG

CTTGCGATTTGCATCTGACTGGGATGTGGGACACTCTGATCGAGCGTGAGAACGCTATAGC

TTACTGCTACCCCGGAGCCACCGTCAATGTTGAAGCACTGCGTCAGAAGATCATGGAAAGC

GGTGGCATCAACAAGATCTCTACCGGATTCACTTATGGCTCTTCCATAAACTCAGCAGGCA

CCACACGGGCATGCATGCGGAATGGCGGCAACTCTTTCTACGCCGAACTAAAATGGCTGGT

GAGTAAGAGCAAGGGGCAAAACTTTCCACAGACCACTAATACATACAGGAATACTGACACC

GCAGAGCACCTCATCATGTGGGGAATCCACCATCCTTCAAGTACCCAAGAGAAAAACGATC

TCTACGGGACACAGTCACTTAGTATATCCGTTGGCTCAAGCACTTACAGAAATAATTTTGT

GCCCGTGGTCGGCGCCCGCCCCCAGGTTAATGGACAGAGCGGACGGATTGACTTTCATTGG

ACCCTGGTCCAGCCCGGAGACAACATAACTTTTAGCCACAATGGGGGGTTGATCGCACCCA

GCAGAGTTTCCAAGCTGATAGGAAGAGGGCTGGGTATCCAATCCGATGCCCCCATCGATAA

CAATTGTGAGTCAAAATGCTTCTGGCGCGGAGGGTCAATCAACACACGCCTTCCCTTTCAA

AACCTCTCACCTCGGACCGTGGGTCAGTGTCCGAAATATGTTAATCGACGGAGCCTGATGC

TGGCCACCGGGATGCGCAACGTGCCCGAGTTGATCCAGGGTAGGGGCTTATTTGGTGCAAT

CGCCGGGTTCCTGGAGAACGGATGGGAAGGCATGGTAGACGGCTGGTATGGATTCCGCCAT

CAGAACGCCCAGGGGACAGGCCAGGCAGCCGATTATAAAAGCACCCAGGCTGCAATCGACC

AGATCACGGGAAAGCTGAACCGGCTGGTGGAGAAGACTAATACGGAATTCGAATCTATTGA

GTCTGAATTCAGTGAGATTGAGCATCAGATCGGCAACGTGATTAATTGGACTAAGGATAGC

ATCACCGACATTTGGACCTATCAGGCCGAGCTGCTGGTGGCTATGGAAAATCAGCATACAA

TCGACATGGCTGACTCTGAGATGCTGAACCTCTACGAGAGAGTCAGAAAACAGTTACGTCA

GAACGCCGAGGAGGATGGCAAGGGGTGCTTTGAGATCTATCACGCGTGCGACGATAGTTGC

ATGGAGTCAATTAGGAACAATACCTATGACCATAGTCAATACCGGGAGGAGGCCCTGTTGA

ACCGGCTGAACATCAACCCTGTGACACTGTCCTCGGGGTATAAGGACATCATCCTTTGGTT

CTCATTTGGAGCTAGCTGCTTCGTGTTATTGGCCGTTGTGATGGGCCTTTTCTTCTTCTGT

CTCAAAAATGGAAACATGCGCTGTACCATTTGTATT

742
ATGTACAAAATCGTGCTCGTTCTGGCTCTTCTTGGGGCTGTGCACGGGCTGGATAAAATTT

GCCTGGGCCACCATGCCGTCCCAAATGGCACTATTGTTAAGACTTTAACCAACGAGAAAGA

GGAAGTGACTAATGCTACCGAGACAGTGGAAAGCAAAAGCCTGGACAAGCTTTGTATGAAA

AATAGGAATTACAAGGATCTGGGCAATTGTCATCCAATTGGCATGGTCGTCGGCACTCCCG

CCTGCGATCTGCACCTTACAGGCACGTGGGATACCCTCATCGAGCGCGATAACAGCATTGC

ATATTGTTACCCAGGGGCCACGGTTAGTGAGGAAGCATTGAGACAGAAGATCATGGAGAGT

GGTGGCATCGATAAGATTTCAACAGGGTTCACCTATGGATCTTCTATCAATAGTGCAGGTA

CCACTAAGGCTTGCATGCGCAACGGCGGCAACTCATTTTACTCTGAGTTGAAGTGGCTCGT

CAGTAAAAATAAGGGCCAGAACTTTCCGCAGACAACAAATACTTACCGAAACACGGATAGT

GTGGAACACCTCATAATTTGGGGAATCCACCACCCCTCCAGCACACAGGAGAAGAACGACT

TGTATGGCACTCAAAGCCTATCAATTAGCGTGGGATCATCTACTTACCAAAACAACTTTGT

CCCAGTCGTGGGTGCCAGGCCACAAGTGAATGGCCAGAGTGGTCGGATTGATTTCCACTGG

ACGATGGTCCAACCCGGCGATAACATTACATTTTCTCATAATGGAGGCCTCATTGCTCCTA

ACAGGGTGTCTAAGCTGAAGGGCAGAGGACTCGGAATCCAATCCGGCGCCTCAGTGGATAA

TGATTGTGAGAGCAAGTGTTTTTGGAAGGGGGGTTCTATCAATACTAAGCTCCCCTTCCAG

AACCTGAGCCCACGCACCGTAGGACAATGCCCCAAATACGTGAACAAGAAGTCCCTGCTCC

TCGCAACAGGCATGCGGAACGTTCCAGAAGTGGCACAGGGCAGGGGGTTATTTGGGGCTAT

CGCTGGTTTTATTGAGAACGGATGGGAGGGGATGGTGGATGGCTGGTACGGTTTCCGCCAT

CAGAACGCCCAGGGGACTGGCCAAGCGGCAGACTACAAGTCCACACAGGCAGCCATAGATC

AGATAACTGGAAAGCTTAATAGGCTCATTGAGAAGACAAATACCGAGTTTGAAAGCATCGA

ATCCGAATTTTCCGAGATTGAGCATCAAATTGGCAACGTAATCAACTGGACAAAGGACAGC

ATTACTGACATCTGGACGTACCAGGCCGAACTGCTGGTGGCGATGGAAAACCAGCACACTA

TCGATATGGCAGATAGTGAAATGCTGAACTTATATGAGCGCGTGCGAAAGCAACTGAGGCA

AAACGCTGAAGAGGACGGCAAAGGGTGTTTCGAAATTTACCATAAGTGCGATGATAATTGT

ATGGAGAGTATCCGGAATAACACGTATGATCATACCCAGTATCGCGAAGAAGCTCTCCTTA

ACAGGCTTAATATTAATCCAGTCAAGCTAAGTTCCGGATATAAGGACGTCATTCTCTGGTT

TAGTTTTGGCGCTTCCTGCTTTGTATTGCTGGCTGTGATCATGGGCCTGGTCTTCTTCTGT

CTCAAGAACGGGAACATGCGATGCACCATATGCATC

743
ATGTATAAAATTGTGGTCATCATCGCTTTATTGGGAGCAGTTAAGGGGCTCGATAAGATCT

GTCTGGGCCACCACGCCGTTGCAAACGGGACCATTGTGAAGACTCTCACCAATGAGCAGGA

GAAAGTTACTAATGCAACAGAGACCGTCGAATCTACAGGCCTGAATCGGCTTTGTATGAAG

GGACGCAAGCATAAGGACCTGGGCAATTGCCACCCTATAGGCATGCTAATTGGGACGCCGG

CCTGCGACTTGCACCTCACAGGTACGTGGGACACTATCATCGAAAGGGAGAACGCTATCGC

CTACTGTTACCCAGGCGCTACCGTGAACGAGGAAGCGCTGAGACAGAAAATCATGGAATCC

GGTGGAATCGATAAGATATCTACTGGCTTTACTTACGGCTCATCCATTAATTCCGCTGGCA

CCACTCGCGCCTGTATGCGGAACGGCGGCAATTCCTTCTACGCTGAACTTAAATGGCTCGT

GTCCAAGAGCAAAGGCCAGAACTTTCCACAGACCACCAATACTTATAGAAATACAGACACG

GCCGAGCACCTGATCATGTGGGGGATCCATCACCCTAGTAGTACACAGGAGAAAAATGACT

TATACGGCACCCAATCCCTTAGTATATCTGTTGGGTCAAGCACGTACAGAAACAATTTCGT

GCCTGTAGTGGGCGCCAGGCCACAGGTCAACGGGCAGTCAGGCAGGATTGATTTCCATTGG

ACACTGGTGCAACCTGGTGATAATATCACTTTCTCCCACAACGGCGGTTTAATTGCTCCCA

GCAGAGTAAGTAAGCTCATCGGCCGAGGACTCGGCATTCAGAGCGACGCACCCATAGATAA

TAACTGCGAATCTAAATGTTTTTGGAGGGGGGGCTCTATCAATACACGCCTCCCTTTTCAG

AACCTGTCTCCTAGGACTGTAGGGCAGTGCCCCAAGTACGTAAACAAAAGATCGCTGATGT

TAGCCACCGGGATGCGGAACGTCCCTGAGCTCATTCAGGGAAGGGGCCTGTTCGGAGCCAT

TGCAGGGTTCTTGGAGAATGGATGGGAAGGAATGGTTGACGGGTGGTACGGGTTCCGACAT

CAGAATGCCCAAGGCACCGGACAGGCCGCTGACTACAAAAGCACCCAGGCAGCCATAGACC

AGATTACCGGCAAACTAAATCGTTTAGTGGAGAAGACCAATACCGAATTTGAATCCATAGA

GAGCGAATTCAGCGAGATAGAGCATCAAATCGGCAATGTGATTAACTGGACAAAAGATTCC

ATAACCGACATTTGGACTTATCAGGCCGAGTTGCTAGTCGCAATGGAGAATCAGCATACAA

TCGACATGGCTGACTCTGAGATGTTGAATCTGTACGAGAGGGTTCGGAAGCAGCTGCGGCA

GAACGCCGAGGAAGACGGGAAAGGGTGTTTTGAGATCTACCATGCGTGTGATGATAGCTGT

ATGGAAAGCATTCGCAATAACACCTATGACCACTCACAGTATCGGGAAGAGGCGTTGTTAA

ACAGGCTGAACATCAACCCAGTAACACTGTCTAGCGGTTATAAGGACATAATATTGTGGTT

CTCCTTTGGTGCAAGCTGCTTTGTCTTGCTGGCGGTCGTGATGGGGCTGGTGTTCTTTTGT

CTGAAAAACGGTAACATGAGGTGTACTATTTGTATC

744
ATGTATAAGATCGTTCTCGTGTTGGCTCTACTGGGTGCCGTCCATGGTTTGGACAAGATCT

GCCTGGGCCACCATGCAGTGCCAAACGGTACCATAGTGAAAACCTTGACTAATGAAAAAGA

AGAGGTGACTAATGCCACCGAGACCGTGGAGTCGAAATCCCTCGATAAACTGTGTATGAAG

AACAGGAACTACAAGGACCTGGGCAATTGCCATCCAATTGGCATGGTGGTGGGGACACCTG

CCTGCGACTTACACCTCACCGGGACATGGGACACTTTGATCGAGAGGGATAATTCAATTGC

GTACTGCTATCCCGGGGCCACTGTGAGTGAGGAGGCGCTGAGGCAAAAGATCATGGAGTCT

GGGGGCATAGACAAGATTAGCACCGGCTTCACATATGGAAGCTCCATCAACTCAGCTGGCA

CGACGAAAGCTTGCATGCGGAACGGTGGGAACTCCTTTTATTCTGAGCTGAAGTGGTTAGT

TAGCAAGAACAAAGGCCAGAACTTCCCCCAGACTACAAACACATATAGAAACACAGACTCA

GTGGAGCATTTGATCATTTGGGGGATTCACCATCCATCGTCCACACAGGAAAAGAACGACC

TGTATGGCACCCAATCGCTGAGCATCTCAGTCGGGTCCAGTACTTATCAGAATAACTTCGT

GCCCGTGGTGGGCGCTCGCCCACAGGTAAACGGGCAAAGCGGGAGAATCGACTTCCATTGG

ACTATGGTGCAGCCTGGGGATAATATTACCTTCTCCCACAATGGAGGTCTTATAGCCCCCA

ATCGAGTTAGCAAACTGAAAGGCCGAGGACTGGGTATCCAGAGCGGCGCAAGCGTGGATAA

TGATTGTGAGTCCAAATGTTTTTGGAAGGGAGGATCAATTAATACCAAATTGCCCTTCCAG

AACTTGAGCCCTCGCACTGTTGGCCAGTGTCCAAAGTACGTTAACAAGAAATCATTACTGC

TAGCCACCGGCATGCGTAACGTGCCTGAGGTCGCCCAGGGGCGCGGTCTCTTCGGAGCAAT

AGCAGGATTCATAGAGAATGGTTGGGAGGGAATGGTGGACGGCTGGTATGGATTCCGCCAT

CAGAATGCTCAAGGAACCGGCCAGGCTGCGGACTATAAAAGCACGCAAGCTGCGATAGACC

AAATTACGGGAAAGCTGAACCGCCTGATTGAAAAGACCAATACTGAGTTTGAATCTATTGA

GTCTGAGTTCTCCGAAATCGAACATCAGATTGGGAATGTTATCAACTGGACTAAAGACAGT

ATAACTGACATTTGGACGTACCAGGCGGAGCTTCTAGTGGCCATGGAAAATCAGCACACCA

TAGATATGGCAGATTCTGAAATGCTGAACCTCTACGAACGAGTGCGAAAGCAATTGCGTCA

GAACGCCGAGGAGGACGGCAAGGGATGTTTCGAGATTTACCACAAATGTGACGACAACTGC

ATGGAAAGCATTAGGAATAACACTTACGACCATACACAGTACAGGGAAGAGGCCCTGCTCA

ACCGCCTCAATATTAACCCGGTGAAACTATCTTCTGGGTACAAGGATGTTATTCTGTGGTT

TAGCTTCGGCGCCTCCTGTTTTGTACTGCTTGCCGTGATTATGGGTTTGGTTTTCTTCTGC

CTCAAGAATGGCAATATGAGATGTACAATTTGCATA

745
ATGTACAAGATCGTGGTCATCATTGCGCTCCTGGGTGCCGTGAAAGGGCTTGACAAGATCT

GCCTGGGTCACCATGCTGTCGCCAATGGGACAATAGTGAAGACTCTTACCAACGAGAAGGA

AGAAGTCACCAACGCAACAGAGACTGTCGAGAGTACCGGCTTAAACAGACTTTGTATGAAA

GGGCGCAAGCACAAGGACCTGGGGAACTGTCACCCAATTGGCATGCTGATAGGGTCTCCAG

CCTGTGATCTGCACCTAACTGGCACATGGGACACCCTGATTGAGAGAGAAAACGCCATTGC

ATACTGTTATCCAGGTGCCACCGTTAATGGGGAGGCATTGAGGCAGAAAATCATGGAGTCC

GGAGGAATAGACAAGATATCAACAGGGTTCACATATGAGAGCTCTATCAACTCGGCTGGGA

CAACCAGGGCATGTATGCGCAACGGAGGAAATTCGTTCTATGCCGAGCTGAAATGGCTTGT

TAGCAAGTCTAAGGGCCAGAATTTTCCTCAGACTACCAATACATACCGCAACACCGACACT

GCCGAGCATCTGATTATGTGGGGGATTCACCACCCCTCTAGTACTCAGGAGAAGAACGACT

TGTACGGGACACAAAGCCTGTCAATTAGTGTCGGGAGCTCTACATACCGGAATAATTTCGT

TCCTGTTGTCGGGGCGAGGCCACAGGTGAACGGCCAGAGTGGGAGGATCGACTTCCACTGG

ACTCTCGTCCAACCAGGGGACAACATCACTTTCAGCCACAACGGAGGCCTTATTGCTCCTT

CGAGAGTCAGTAAGCTGATTGGCAGGGGTTTGGGCATTCAAAGTGATGCCCCAATTGATAA

TAACTGCGAAAGCAAGTGCTTCTGGCGAGGGGGCTCTATTAATACTCGATTGCCTTTTCAG

AACCTGAGCCCGAGAACAGTTGGGCAATGTCCCAAGTACGTTAATAAGAGGTCTCTGATGC

TGGCGACAGGGATGAGAAATGTCCCTGAGCTGATGCAAGGGGGGGGACTGTTTGGCGCTAT

AGCGGGCTTCCTCGAAAACGGATGGGAGGGAATGGTTGATGGATGGTATGGGTTCCGACAC

CAGAATGCACAGGGCACCGGGCAAGCTGCTGATTACAAGTCTACTCAAGCCGCCATCGACC

AGATCACCGGCAAACTTAACCGCCTGGTCGAGAAAACAAATACAGAATTTGAATCTATTGA

ATCCGAGTTCTCTGAGATAGAACACCAAATCGGCAACGTGATTAATTGGACCAAGGATAGT

ATCACAGATATCTGGACCTATCAAGCGGAGCTGCTGGTGGCCATGGAGAACCAGCACACAA

TCGATATGGCTGACTCAGAGATGCTTAATTTGTATGAGCGGGTTCGCAAGCAGCTCCGACA

AAATGCTGAGGAGGATGGAAAGGGATGTTTTGAGATCTATCATGCCTGCGACGACTCATGC

ATGGAAAGCATTCGCAATAATACCTATGATCATTCACAGTACAGAGAAGAGGCTCTCCTGA

ACAGGCTGAACATAAACCCCGTTACACTTTCTAGCGGGTACAAAGACATTATCTTATGGTT

CAGTTTCGGAGCATCTTGCTTCGTACTACTGGCCGTTGTCATGGGCCTGGTGTTCTTCTGT

CTAAAGAATGGGAACATGCGCTGCACCATTTGCATT

746
ATGTACAAGATCGTCGTGATTATCGCCTTATTGGGAGCAGTCAAGGGGCTCGATAAGATCT

GTTTAGGGCATCATGCGGTTGCAAACGGCACTATCGTTAAGACCTTGACAAATGAACAGGA

GGAAGTGACGAATGCCACTGAAACCGTTGAGTCCACTGGGATTAATCGGCTGTGCATGAAA

GGACGAAAGCATAAGGACCTTGGAAACTGCCACCCCATTGGCATGCTGATTGGGACCCCTG

CTTGCGACCTGCATCTGACTGGAACCTGGGATACCCTTATTGAGCGAGAAAATGCCATCGC

CTATTGCTATCCAGGCGCCACAGCAAACGTCGAGGCCCTCAGACAGAAAATCATGGAGTCC

GGTGGAATTGACAAAATCTCTACCGGCTTTACCTACGGGTCTAGCATCAATTCCGCAGGGA

CTACGAGGGCATGTATGAGAAATGGCGGCAACAGCTTCTATGCCGAGCTTAAATGGCTTGT

TTCAAAATCCAAGGGACAGAACTTCCCTCAGACTACAAACACTTATCGGAATACAGATACA

GCAGAACACTTGATTATGTGGGGCATTCACCACCCAAGCAGTATCCAGGAGAAAAATGACC

TCTACGGCACGCAGTCACTGAGTATATCCGTGGGCTCTTCAACCTACAGGAACAATTTTGT

CCCCGTCGTCGGTGCGAGGCCTCAAGTGAAGGGGCAATCGGGAAGGATCGACTTCCATTGG

ACACTGGTGCAACCTGGAGATAATATCACGTTTAGCCACAACGGAGGCTTGATTGCTCCAT

CCAGAGTGAGCAAACTGATCGGCAGGGGCCTAGGGATCCAATCAGACGCACCAATCGATAA

CAACTGTGAGTCTAAGTGTTTCTGGAGAGGTGGCAGCATTAACACCCGGTTGCCCTTCCAG

AATTTGAGCCCCCGGACTGTCGGTCAGTGCCCAAAGTACGTGAATCGGCGCTCTCTTATGC

TGGCCACCGGAATGAGGAACGTCCCCGAGCTCATACAGGGCCGGGGTTTATTCGGGGCAAT

TGCTGGGTTCCTGGAGAACGGCTGGGAAGGCATGGTGGATGGCTGGTACGGATTTAGGCAC

CAGAACGCACAAGGCACTGGCCAAGCCGCGGACTACAAATCAACTCAAGCTGCCATCGATC

AGATAACCGGGAAGTTGAACAGACTGGTAGAAAAAACCAATACCGAGTTCGAGTCAATTGA

GTCCGAGTTTAGTGAGATAGAACACCAGATCGGTAACGTGATCAACTGGACAATGGATAGT

ATTACTGACATTTGGACCTATCAAGCAGAACTGCTGGTGGCGATGGAGAACCAGCACACTA

TCGACATGGCAGACAGCGAAATGCTTAACCTGTACGAACGGGTGCGGAAACAGCTAAGACA

AAACGCCGAAGAGGACGGCAAAGGTTGCTTCGAAATCTACCACGCCTGTGACGACTCTTGT

ATGGAAAGCATAAGGAACAATACCTACGATCACTCCCAGTACCGAGAGGAGGCGTTACTCA

ATAGACTGAACATCAACCCTGTGACCCTGAGCTCTGGATATAAAGACATCATTCTCTGGTT

TTCTTTTGGGGCCAGCTGCTTCGTGCTTCTCGCAGTCGTTATGGGACTCGTGTTCTTCTGC

TTGAAGAACGGTAATATGAGATGCACAATCTGCATA

747
ATGTATAAGATTGTCGTGATTATTGCCCTGTTAGGGGCCGTGAAAGGACTAGATAAAATTT

GCCTGGGCCACCATGCTGTCGCCAATGGCACGATCGTTAAAACTTTAACAAACGAGCAGGA

GGAAGTAACGAACGCAACAGAGACAGTTGAGAGTACAGGAATCAATAGACTGTGTATGAAG

GGGAGGAAACACAAGGATTTAGGAAATTGCCACCCTATCGGAATGCTCATCGGAACTCCAG

CATGTGATCTGCATCTGACAGGCATGTGGGACACACTGATCGAGCGGGAAAATGCGATTGC

CTATTGCTATCCCGGGGCTACAGTGAATGTCGAGGCTCTGCGGCAGAAGATCATGGAATCC

GGCGGCATCAATAAAATTTCTACTGGGTTCACTTACGGGAGTTCTATTAATAGTGCCGGCA

CGACCAGAGCCTGCATGCGGAACGGCGGCAACTCGTTCTATGCAGAGCTGAAATGGCTGGT

TTCAAAATCTAAAGGACAGAACTTTCCACAAACAACAAATACTTATAGGAACACCGACACC

GCCGAGCATCTGATTATGTGGGGAATCCATCACCCAAGTAGCACACAGGAAAAGAACGACC

TTTACGGCACTCAGTCACTGAGCATAAGCGTTGGGTCCTCTACTTACCGCAATAATTTCGT

GCCAGTCGTCGGCGCTAGACCACAAGTCAATGGGCAATCAGGGAGAATCGATTTTCACTGG

ACCCTTGTGCAGCCTGGTGATAATATCACTTTCAGCCACAACGGGGGCCTGATTGCTCCAA

GTAGAGTCTCCAAGCTTATTGGACGGGGACTCGGGATTCAGTCTGATGCTCCCATAGATAA

TAATTGTGAGTCGAAGTGCTTTTGGCGAGGAGGGTCCATCAACACGGGGTTGCCCTTCCAG

AACCTCTCACCTCGGACCGTGGGGCAGTGCCCCAAATACGTGAACAGGAGGAGTCTGATGC

TGGCCACCGGGATGCGCAACGTGCCCGAATTGATCCAGGGGAGAGGCCTTTTCGGCGCTAT

AGCGGGGTTTTTAGAAAACGGGTGGGAGGGCATGGTGGACGGCTGGTACGGATTTCGCCAT

CAGAATGCCCAGGGTACTGGTCAAGCCGCCGATTACAAATCTACCCAGGCTGCCATCGACC

AGATTACAGGAAAGTTGAACCGACTGGTGGAAAAGACCAACACTGAGTTTGAGAGTATTGA

AAGTGAATTCTCTGAGATCGAACACCAGATTGGGAACGTTATCAACTGGACGAAAGATTCC

ATCACAGACATCTGGACCTACCAAGCCGAACTCCTTGTGGCCATGGAGAATCAACACACGA

TCGACATGGCTGACTCAGAAATGCTGAATTTGTACGAAAGAGTGAGAAAACAGCTGAGGCA

AAATGCCGAGGAGGATGGCAAAGGCTGTTTCGAGATTTATCACGCCTGCGATGATTCCTGT

ATGGAATCAATCAGGAATAATACCTACGACCACTCTCAGTACCGCGAGGAAGCCCTATTGA

ACCGACTTAACATAAACCCTGTGACTTTGTCCAGTGGTTACAAGGATATCATTCTTTGGTT

TTCGTTCGGAGCTTCCTGCTTCGTACTCCTCGCGGTGGTAATGGGCTTATTCTTTTTTTGC

CTAAAGAACGGAAATATGAGGTGTACGATCTGCATC

748
ATGTACAAAATTGTGGTGATTATTGCTCTGCTCGGAGCCGTCAAGGGCCTGGATAAGATCT

GTCTGGGCCACCACGCCGTGGCCAACGGAACAATTGTGAAGACACTCACAAACGAGCAGGA

AGAAGTGACTAATGCCACCGAGACCGTTGAAAGTACCGGGATAAACCGCCTTTGCATGAAG

GGTCGGAAACATAAAGACCTGGGGAACTGCCACCCTATAGGTATGCTTATTGGAACACCCG

CTTGTGATCTACACCTTACTGGGATGTGGGACACCCTTATAGAGCGCGAGAACGCCATCGC

ATACTGTTATCCTGGTGCCACGGTTAACGTGGAGGCTCTTAGGCAGAAGATCATGGAGTCA

GGCGGTATTAATAAGATTTCCACAGGCTTTACTTACGGGAGCTCAATAAACAGCGCCGGGA

CCACGAGGGCCTGCATGCGGAACGGGGGGAACTCCTTTTACGCGGAATTGAAATGGCTGGT

GTCAAAGTCCAAAGGACAAAACTTCCCTCAAACCACTAATACCTACAGGAATACCGACACT

GCAGAACATCTTATCATGTGGGGCATACACCACCCGTCGTCTACACAAGAGAAGAACGATC

TTTATGGGACCCAGTCTCTGTCCATCAGCGTGGGGTCATCCACTTACCGAAATAATTTTGT

GCCTGTGGTTGGGGCTAGGCCACAGGTGAATGGGCAGTCTGGCCGTATTGATTTCCACTGG

ACACTTGTGCAGCCAGGGGATAATATAACATTCAGCCACAATGGGGGCCTAATCGCTCCAT

CCCGGGTGTCTAAGTTGATCGGTCGCGGACTTGGAATCCAATCTGACGCTCCAATCGACAA

CAATTGTGAGTCTAAATGCTTTTGGCGCGGGGGCTCTATCAACACTAGACTGCCATTCCAA

AATCTGTCTCCTCGCACCGTTGGGCAGTGTCCTAAGTATGTAAACAGACGGTCCCTGATGC

TTGCGACAGGAATGCGGAATGTACCTGAACTCATCCAGGGAAGAGGGCTGTTCGGAGCTAT

TGCCGGCTTTCTGGAGAATGGTTGGGAGGGAATGGTAGACGGCTGGTACGGCTTTCGGCAT

CAAAATGCGCAGGGAACAGGCCAGGCAGCAGACTACAAATCAACCCAGGCTGCCATTGACC

AGATTACAGGGAAGCTCAATAGACTTGTGGAGAAAACAAACACCGAGTTCGAATCCATCGA

GTCCGAGTTCAGTGAGATCGAGCACCAGATTGGGAACGTGATAAACTGGACGAAAGATTCT

ATCACCGATATTTGGACATACCAGGCTGAGCTCCTGGTCGCCATGGAGAATCAACATACAA

TTGATATGGCGGACAGCGAGATGCTGAACCTATATGAGCGCGTACGAAAGCAATTGAGACA

GAACGCCGAGGAGGACGGTAAGGGGTGCTTTGAAATATATCATGCTTGTGACGACTCATGC

ATGGAATCAATTAGAAATAATACATATGACCACTCTCAATATAGAGAGGAGGCCCTCTTGA

ATCGCTTGAACATCAATCCGGTGACTCTCTCTAGTGGGTACAAAGACATTATACTGTGGTT

CAGTTTCGGGGCCAGCTGCTTCGTGCTGCTGGCAGTAGTTATGGGGCTCTTCTTTTTTTGC

CTGAAAAATGGCAATATGCGATGTACCATTTGTATC

749
ATGTATAAAATTGTCGTGATTATTGCCTTGCTAGGCGCCGTCAAGGGCCTGGACAAAATCT

GCCTGGGACACCACGCTGTGGCGAACGGCACTATCGTTAAGACTCTGACCAATGAGCAGGA

AAAGGTCACAAACGCTACAGAAACGGTCGAATCTACAGGCCTGAACAGGCTGTGTATGAAA

GGTAGAAAGCACAAAGACCTGGGAAATTGCCACCCAATAGGGATGTTAATCGGCACCCCAG

CATGCGATTTGCACCTGACAGGTACATGGGACACCATCATCGAAAGGGAGAATGCCATTGC

TTACTGTTATCCCGGAGCCACAGTGAATGAGGAGGCCCTCAGACAAAAAATAATGGAATCC

GGCGGAATCGACAAGATAAGTACAGGATTTACCTATGGGAGCTCTATTAATTCCGCCGGCA

CTACAAGAGCTTGTATGAGGAACGGTGGAAATTCGTTTTACGCAGAGCTTAAATGGCTAGT

GAGCAAGTCCAAAGGACAGAACTTTCCTCAGACAACAAATACTTATCGGAACACCGATACG

GCTGAACACTTAATAATGTGGGGGATCCACCATCCGTCGTCAACGCAGGAGAAAAATGATC

TGTACGGTACGCAATCACTGTCCATCTCCGTAGGCAGCTCCACCTACAGAAATAATTTTGT

TCCAGTTGTCGGTGCTCGGCCACAAGTGAATGGCCAGAGCGGCCGAATCGACTTTCACTGG

ACCCTGGTGCAGCCAGGGGATAACATCACCTTCAGCCACAACGGTGGCCTTATCGCCCCCT

CTAGGGTGAGTAAGCTGATCGGGGGGGGCCTCGGAATCCAATCTGACGCACCCATTGATAA

CAACTGCGAGAGCAAGTGTTTCTGGGGGGGTGGTTCTATCAATACCCGACTCCCGTTTCAG

AATCTATCTCCTAGGACCGTCGGCCAGTGCCCAAAATATGTGAACAAGCGCAGCCTTATGC

TAGCAACTGGAATGAGGAATGTTCCCGAGCTGATTCAGGGCCGAGGTCTCTTCGGAGCTAT

TGCCGGGTTTCTCGAGAACGGATGGGAAGGCATGGTGGACGGGTGGTACGGTTTTCGGCAC

CAGAACGCCCAGGGAACCGGACAAGCAGCCGATTACAAGAGCACCCAGGCTGCTATCGATC

AGATTACCGGCAAGCTCAATCGCTTGGTGGAGAAAACCAATACTGAATTTGAGTCCATTGA

ATCAGAGTTCAGCGAGATCGAGCATCAGATCGGGAACGTCATTAATTGGACAAAGGATAGC

ATCACCGATATCTGGACATACCAGGCTGAGCTTCTGGTTGCAATGGAAAATCAGCATACTA

TCGACATGGCTGATAGCGAAATGTTGAATTTGTATGAAAGGGTGCGTAAGCAGCTGCGGCA

GAACGCCGAGGAGGACGGCAAGGGATGCTTCGAGATCTACCACGCATGTGACGACTCATGC

ATGGAGAGCATTCGGAACAACACTTATGATCACTCTCAATATCGTGAAGAGGCACTCCTAA

ACAGACTAAATATAAACCCGGTCACCCTCAGCAGCGGCTATAAGGACATCATTCTTTGGTT

CTCTTTTGGTGCAAGCTGTTTCGTCCTCCTCGCCGTGGTTATGGGCCTGGTGTTTTTTTGC

CTGAAGAATGGCAATATGCGGTGCACCATTTGCATC

750
ATGTATAAGATTGTGGTGATTATTGCGTTGCTGGGGGCTGTGAAAGGCCTGGATAAGATCT

GTCTTGGGCATCATGCCGTAGCTAACGGCACAATTGTGAAAACTCTGACAAATGAGCAGGA

GGAGGTGACAAACGCAACCGAGACCGTTGAGAGCACAGGGATTAATCGCCTGTGCATGAAG

GGGCGCAAACACAAGGACCTGGGGAACTGTCACCCTATCGGAATGCTGATCGGGACCCCAG

CCTGTGATTTACACCTAACAGGAATGTGGGACACACTCATTGAAAGAGAGAACGCGATAGC

ATACTGCTACCCCGGAGCTACTGTGAATGTGGAAGCACTGCGCCAGAAGATTATGGAATCC

GGAGGCATAAATAAGATTTCCACTGGGTTCACCTATGGCTCCTCTATCAACAGTGCAGGAA

CGACGAGAGCCTGCATGCGCAATGGGGGAAATAGTTTCTACGCCGAGCTGAAGTGGCTGGT

GTCTAAGTCAAAGGGTCAAAACTTTCCCCAAACTACCAATACGTACCGAAATACTGACACG

GCAGAACACCTAATAATGTGGGGGATTCACCATCCCAGCAGCACCCAGGAGAAGAATGATT

TGTATGGGACTCAGTCTCTGTCGATTTCCGTGGGCAGCAGCACGTACCGAAATAATTTCGT

ACCCGTGGTTGGAGCTCGACCTCAGGTGAACGGCCAGTCCGGCAGAATTGATTTTCACTGG

ACACTAGTTCAGCCAGGCGATAATATAACATTTTCGCACAACGGAGGTCTGATCGCACCTT

CACGCGTGTCCAAGCTTATCGGTCGGGGCCTGGGGATCCAGAGTGATGCTCCCATCGATAA

CAATTGCGAGTCTAAATGTTTTTGGCGAGGTGGATCCATCAATACCCGTCTGCCCTTCCAG

AACCTGTCTCCACGCACAGTCGGTCAGTGCCCCAAGTATGTGAATAGAAGGTCCCTGATGC

TCGCCACAGGAATGAGAAACGTTCCGGAACTAATTCAGGGCCGTGGACTATTCGGGGCCAT

AGCAGGGTTCCTGGAGAATGGCTGGGAGGGTATGGTTGACGGTTGGTACGGCTTTCGGCAT

CAGAACGCCCAAGGGACCGGGCAGGCCGCCGACTACAAAAGTACCCAGGCTGCAATCGACC

AGATCACGGGGAAACTGAACCGACTCGTGGAGAAGACTAACACTGAGTTTGAGTCCATCGA

GTCTGAGTTTAGCGAAATCGAGCATCAGATTGGGAACGTTATTAACTGGACAAAGGACAGC

ATCACCGATATATGGACCTACCAGGCAGAACTATTAGTGGCAATGGAGAACCAGCACACAA

TTGACATGGCGGACAGCGAGATGCTGAATCTTTATGAGCGTGTCCGGAAACAGCTGAGACA

GAACGCCGAAGAAGATGGCAAAGGCTGCTTTGAGATATACCATGCGTGCGATGATTCATGC

ATGGAGTCTATTCGCAATAATACATACGATCACAGTCAGTACAGAGAGGAAGCTCTACTGA

ATCGGCTCAACATCAATCCAGTCACCCTGTCTTCCGGCTACAAGGACATCATTCTGTGGTT

CAGCTTTGGAGCCTCCTGTTTTGTACTTCTAGCCGTTGTGATGGGCTTGTTTTTTTTCTGT

TTGAAGAACGGGAATATGAGATGTACCATCTGCATC

751
ATGTACAAGATCGTGGTAATTATCGCTCTGCTAGGAGCCGTGAAGGGGCTAGACAAGATAT

GTCTCGGGCACCACGCCGTGGTTAACGGAACCATTGTGAAGACATTGACTAACGAACAGGA

GGAGGTGACCAATGCGACGGAAACAGTTGAGTCAACAGGATTGAATAGGCTGTGTATGAAG

GGGCGTAACCACAAAGACCTGGGCAATTGCCATCCAATCGGAATGCTTATTGGAACTCCCG

CTTGCGACTTACACCTGACCGGCACATGGGATACCCTGATAGAAAGAGAAAACGCTATTGC

GTATTGCTACCCAGGAGCTACCGTAAACGAAGAGGCCCTTCGGCAGAAAATAATGGAGTCC

GGGGGAATTAACAAAATATCTACTGGCTTTACTTATGGATCGTCCATCAACAGCGCTGGAA

CTACACGCGCTTGCATGCGTAACGGAGGTAATTCATTTTATGCCGAACTGAAGTGGCTGGT

GTCAAAGTCAAAGGGACAGAACTTCCCCCAAACTACAAATACATACAGGAATACCGACACT

GCTGAACACCTGATTATGTGGGGTATTCACCACCCCTCAAGCACCCAGGAAAAGAATGACC

TGTACGGAACTCAGAGTTTGTCTATCAGCGTGGGAAGTTCAACCTACCAAAATAACTTCGT

TCCGGTGGTTGGCGCCAGGCCCCAGGTGAACGGACAGTCGGGGCGCATCGACTTTCATTGG

ACTTTAGTCCAGCCTGGCGACAATATCACATTCTCCCACAACGGAGGGCTTATCGCCCCGA

GTCGCGTGAGCAAGCTCATTGGTCGGGGGTTGGGAATTCAGAGCGATGCCCCTATTGACAA

CAACTGCGAAAGCAAGTGCTTCTGGAGAGGCGGTTCTATTAACACAAGACTCCCATTCCAA

AACCTGAGCCCACGGACAGTCGGGCAGTGCCCCAAGTACGTAAATAAAAGGTCACTCATGT

TGGCTACCGGGATGCGGAATGTCCCAGAACTGATGCAGGGAAGGGGGCTGTTCGGCGCAAT

CGCCGGCTTTATTGAGAATGGCTGGGAGGGAATGGTTGACGGATGGTATGGTTTCAGGCAC

CAGAATGCCCAGGGTACCGGTCAGGCAGCCGATTATAAATCCACCCAGGCAGCGATTGACC

AGATTACTGGAAAGTTGAACCGGCTTATTGAAAAAACCAACACTGAGTTCGAGAGCATCGA

GAGTGAGTTCAGCGAGATCGAACATCAGATCGGTAACGTGATAAACTGGACCAAGGACTCC

ATCACTGATATTTGGACCTACCAGGCTGAGTTATTGGTTGCCATGGAGAACCAGCACACCA

TCGACATGGCCGATTCTGAAATGCTGAATCTCTATGAGAGAGTTCGGAAACAGCTGAGACA

AAATGCAGAGGAGGATGGGAAGGGCTGTTTTGAGATTTACCACGCCTGTGACGACAGTTGT

ATGGAGTCTATTAGAAATAATACCTACGATCATTCTCAATATCGAGAAGAGGCCTTGTTAA

ATAGGCTGAATATTAACCCAGTCACCCTAAGCAGCGGGTACAAAGATATCATACTGTGGTT

CTCGTTTGGAGCCTCTTGCTTTGTGCTATTGGCAGTCGTGATGGGTTTGGTGTTCTTCTGC

CTCAAAAACGGGAATATGAGATGTACGATTTGCATC

752
ATGTATAAGATTGTCCTTGTGCTCGCCCTGCTCGGAGCAGTGCACGGCCTCGATAAAATCT

GTCTGGGGCACCACGCCGTGCCTAACGGCACCATCGTCAAGACTCTCACAAACGAGAAGGA

GGAAGTGACAAACGCTACTGAAACAGTAGAAAGTAAGAGCCTGGACAAACTTTGCATGAAA

AACAGGAATTATAAAGACTTGGGTAATTGTCACCCGATTGGCATGGTCGTCGGAACGCCTG

CTTGTGACCTCCATCTGACGGGAACCTGGGATACCTTGATCGAGCGGGACAACTCAATTGC

ATACTGCTATCCAGGCGCCACCGTTAGTGAGGAGGCTTTGAGACAGAAGATCATGGAGTCT

GGAGGGATTGACAAAATTTCCACCGGCTTTACATATGGTAGCTCAATCAACTCGGCTGGGA

CTACAAAAGCTTGTATGAGGAACGGTGGAAATAGCTTTTACTCGGAACTAAAATGGTTGGT

GTCTAAAAACAAGGGTCAGAACTTTCCTCAGACGACCAACACTTATCGAAATACTGACTCC

GTGGAGCACCTGATTATTTGGGGGATCCATCATCCCAGCAGCACACAAGAGAAGAATGACC

TGTATGGGACGCAGTCTCTGTCCATTAGCGTCGGCAGTTCAACTTACCAGAATAATTTCGT

GCCTGTGGTGGGAGCGCGCCCCCAAGTCAATGGGCAGAGCGGAAGGATTGATTTCCACTGG

ACTATGGTCCAGCCCGGCGATAACATTACTTTCAGCCACAACGGAGGGCTCATTGCACCAA

ACCGTGTCTCAAAACTGAAGGGCAGGGGGCTTGGTATTCAGAGCGGAGCTAGTGTGGACAA

TGACTGCGAATCTAAGTGTTTTTGGAAAGGAGGATCAATTAACACTAAGCTTCCGTTTCAA

AACCTGAGTCCACGCACAGTCGGACAGTGCCCTAAATATGTGAACAAAAAGTCGCTTCTGC

TAGCTACCGGGATGAGGAACGTGCCAGAGGTCGCCCAGGGCAGAGGTTTGTTCGGCGCGAT

CGCCGGTTTCATCGAAAACGGATGGGAGGGAATGGTGGATGGCTGGTACGGATTTCGTCAT

CAAAACGCACAGGGAACGGGTCAGGCCGCAGATTATAAATCTACTCAGGCCGCTATAGATC

AGATCACAGGCAAGCTGAATAGGTTAATAGAGAAGACGAATACCGAGTTTGAGAGCATCGA

AAGCGAGTTCAGTGAAATAGAGCATCAGATTGGCAATGTGATCAATTGGACAAAAGATTCG

ATCACTGATATTTGGACATATCAGGCAGAACTTCTTGTGGCAATGGAGAACCAGCATACGA

TTGATATGGCCGATTCGGAAATGCTGAATCTTTACGAGAGAGTCAGAAAACAGCTGCGCCA

AAATGCTGAGGAAGACGGGAAGGGGTGCTTTGAAATATACCATAAATGTGACGACAACTGC

ATGGAGTCGATCCGCAACAACACATATGACCATACCCAGTACCGTGAGGAAGCTCTGTTAA

ATAGACTTAACATCAATCCAGTTAAACTGTCCTCTGGGTATAAAGATGTGATTTTGTGGTT

CTCTTTCGGCGCTTCATGCTTTGTCCTCCTCGCCGTCATCATGGGACTGGTGTTTTTTTGC

CTCAAAAACGGGAATATGCGATGTACGATATGCATC

753
ATGTATAAAATAGTAGTGATCATCGCTCTGTTAGGAGCGGTGAAAGGGCTCGACAAGATTT

GTCTGGGCCACCACGCCGTTGCTAACGGCACCATCGTCAAGACCCTCACTAATGAACAGGA

GGAGGTCACTAACGCCACTGAGACAGTTGAATCGACCGGGATTAACCGGTTGTGTATGAAA

GGCCGGAAGCATAAAGATCTCGGGAATTGCCACCCAATAGGGATGCTTATCGGCACACCAG

CATGCGACCTCCATCTCACGGGCATGTGGGACACCCTTATCGAAAGAGAAAATGCCATTGC

CTATTGCTATCCGGGCGCAACCGTGAATGTGGAGGCCCTTCGACAAAAAATCATGGAAAGC

GGCGGCATTAACAAAATCAGCACGGGATTCACCTACGGGTCTAGTATCAATTCAGCAGGCA

CGACCAGAGCTTGTATGCGTAACGGGGGTAATTCTTTCTACGCAGAGCTGAAATGGCTCGT

GTCTAAGAGCAAAGGTCAGAATTTTCCCCAGACTACTAATACATATAGGAATACCGACACT

GCGGAGCATCTTATAATGTGGGGCATCCACCACCCATCCTCCACACAGGAAAAGAACGACC

TGTATGGTACGCAGTCACTGAGTATAAGCGTTGGGTCCAGCACTTATCGAAATAACTTTGT

GCCCGTAGTGGGAGCCCGCCCACAGGTTAACGGCCAGAGTGGCAGAATCGACTTCCATTGG

ACCCTGGTGCAGCCCGGCGACAACATCACTTTCTCACATAACGGAGGGTTAATAGCTCCAT

CCAGGGTATCCAAACTCATTGGTAGGGGGCTGGGCATCCAATCCGACGCCCCCATTGACAA

TAATTGTGAGAGCAAATGTTTCTGGAGGGGTGGAAGCATCAATACCAGACTCCCATTCCAG

AATTTATCTCCCCGCACAGTAGGGCAGTGCCCCAAATATGTTAACAGAAGATCCCTGATGC

TCGCGACAGGAATGCGGAATGTGCCCGAGCTGATCCAGGGCCGCGGGTTGTTTGGCGCCAT

AGCTGGTTTTCTCGAGAATGGTTGGGAAGGGATGGTTGACGGCTGGTATGGGTTTCGCCAT

CAGAACGCTCAGGGAACAGGACAAGCTGCCGACTACAAGAGCACTCAAGCAGCAATCGATC

AAATCACGGGGAAGCTCAACAGGCTTGTTGAAAAGACTAATACTGAGTTCGAAAGCATTGA

GTCCGAGTTTTCCGAGATTGAGCATCAGATTGGGAACGTCATCAACTGGACCAAAGACAGT

ATCACGGACATATGGACTTATCAAGCCGAACTCCTGGTGGCCATGGAAAACCAGCACACAA

TCGATATGGCTGATTCTGAGATGCTTAACCTGTACGAGCGCGTGCGGAAACAACTGCGGCA

AAACGCAGAGGAAGACGGAAAAGGATGTTTTGAAATATACCACGCATGTGATGATAGCTGC

ATGGAGAGCATTCGTAACAACACTTATGATCATTCTCAGTACCGCGAGGAAGCTCTCCTAA

ACAGACTCAACATTAATCCAGTGACCCTGAGCTCTGGATATAAAGACATTATTCTGTGGTT

TAGTTTCGGCGCCAGCTGCTTTGTGCTGCTGGCGGTGGTTATGGGACTGTTCTTCTTCTGT

TTGAAAAACGGAAATATGAGATGTACTATTTGCATC

754
ATGTATAAGATAGTAGTAATTATTGCTCTCTTGGGGGCGGTGAAAGGGCTGGATAAAATCT

GCCTGGGGCATCACGCCGTGGCCAATGGCACCATTGTAAAAACGCTTACAAATGAGCAGGA

AGAAGTGACCAACGCCACAGAAACTGTGGAGAGCACTGGCATCAACCGGCTCTGTATGAAG

GGTAGAAAGCACAAGGATCTGGGGAATTGCCACCCCATCGGCATGTTAATAGGCACTCCGG

CTTGCGATTTGCACCTTACCGGAATGTGGGACACACTAATCGAGAGGGAAAATGCCATTGC

GTACTGCTACCCAGGTGCCACCGTGAATGTCGAGGCACTGAGGCAGAAAATCATGGAATCA

GGAGGAATAAACAAGATCTCTACCGGCTTTACGTATGGCTCATCCATCAACTCTGCAGGTA

CCACTCGAGCTTGCATGCGGAACGGCGGCAATTCCTTCTACGCAGAACTAAAGTGGCTTGT

GTCCAAAAGTAAGGGTCAGAATTTCCCCCAAACTACCAATACGTACAGGAACACTGACACG

GCAGAACACCTGATCATGTGGGGCATCCATCATCCCTCCTCTACCCAGGAAAAAAATGACC

TGTACGGGACACAGAGCCTGTCCATATCTGTAGGCTCAAGTACATATCGTAACAACTTCGT

GCCCGTTGTGGGCGCACGTCCACAGGTTAACGGCCAAAGCGGACGCATTGATTTCCATTGG

ACCCTAGTCCAGCCCGGAGACAATATAACCTTCTCGCATAATGGAGGACTGATCGCTCCCT

CTCGCGTGTCTAAGCTGATCGGTCGGGGATTGGGGATTCAGAGCGACGCTCCTATTGATAA

CAACTGCGAATCCAAGTGCTTTTGGAGAGGGGGCAGCATCAATACTAGATTGCCTTTTCAG

AACCTTTCTCCCCGCACAGTGGGGCAATGCCCTAAATACGTCAATAGAAGGTCTCTTATGC

TTGCCACCGGAATGCGTAATGTACCAGAACTCATACAAGGTAGAGGGTTATTCGGCGCCAT

CGCTGGCTTTCTGGAAAATGGCTGGGAGGGGATGGTTGACGGCTGGTATGGTTTCAGACAC

CAAAATGCTCAGGGTACAGGTCAGGCCGCCGATTACAAGTCCACACAGGCAGCTATTGATC

AGATCACAGGCAAGTTGAACCGCCTCGTGGAAAAGACTAACACAGAGTTTGAGTCTATTGA

ATCCGAATTCTCTGAGATTGAACACCAAATTGGAAATGTTATCAACTGGACAAAGGACTCT

ATTACCGATATTTGGACCTATCAAGCCGAGTTGTTGGTCGCCATGGAGAATCAACATACTA

TTGACATGGCGGACTCTGAAATGCTAAATCTCTACGAGAGAGTAAGAAAGCAGCTTCGACA

GAACGCAGAGGAAGACGGAAAGGGATGTTTTGAGATCTATCATGCTTGTGACGATTCGTGC

ATGGAATCCATTCGGAATAATACATATGACCATTCTCAGTATAGAGAAGAAGCCCTGCTTA

ACCGGCTAAACATCAATCCCGTGACGCTATCATCCGGGTATAAAGATATCATCCTGTGGTT

CTCATTCGGGGCTTCGTGTTTTGTGCTCCTGGCGGTCGTGATGGGCCTGTTCTTTTTCTGT

CTTAAAAACGGGAACATGCGATGCACCATATGCATC

755
ATGTACAAGGTCGTAGTTATTATCGCGCTGCTAGGTGCAGTTCGGGGGCTCGATAAGATTT

GCCTGGGGCACCATGCGGTCGCCAACGGAACTATCGTTAAGACATTAACCAACGAACAGGA

GGAGGTGACAAATGCAACCGAGACCGTGGAATCTAAATCCCTGGGTAAGCTGTGCATGAAA

GGGAGGAGTTATAACGACCTTGGAAACTGTCACCCAATCGGCATTCTTATCGGGACCCCCG

CTTGTGATCTCCATTTAACCGGCACCTGGGATACACTCATTGAGCGCGAAAATGCTGTTGC

CTACTGTTACCCAGGAGCTACAGTAAACGAGGAAGCTCTTAGACAGAAGATAATGGAGTCC

GGAGGGATTTCCAAGATCAGCACTGGCTTCACCTATGGCACATCAATCAACAGCGCAGGGA

CGACAAAGGCCTGTATGAGGAACGGCGGCAACTCATTCTACGCCGAGCTGAAATGGCTGGT

GTCAAAGAACAAAGGCCAGAACTTCCCACAAACCACGAACACCTACAGGAACACCGATACC

GCAGAGCATCTTATAATATGGGGAATCCACCACCCCTCTTCCACCCAGGAGAAAAATGATC

TTTATGGCACTCAATCTTTATCTATATCAGTAGGGTCTTCAACTTACCAGAACAATTTCGT

GCCTGTGGTGGGAGCGCGGCCGCAAGTGAACGGTCAGAGCGGTCGTATAGACTTTCACTGG

ACCCTGCTGCAGCCAGGTGACAACATCACCTTCTCTCACAATGGTGGGCTAATTGCTCCCT

CCAGAGTCAGCAAGCTTATAGGGAGAGGCCTCGGGATACAGTCAGAAGCCCCTATCGACAA

TGGGTGCGAGTCGAAGTGTTTCTGGAAGGGTGGATCTATTAACACAAAACTTCCTTTTCAG

AACTTATCTCCGAGGACTGTGGGCCAATGCCCTAAATACGTTAACAAGCGCAGTTTAATGC

TTGCTACGGGTATGAGGAATGTCCCAGAGATCATGCACGGCCGCGGGCTCTTCGGGGCCAT

TGCCGGATTTATTGAGAACGGGTGGGAGGGCATGGTAGATGGATGGTACGGGTTCCGCCAC

CAAAACGCACAGGGAACGGGACAGGCAGCTGACTACAAATCAACACAAGCGGCTATCGACC

AGATAACAGGCAAGCTGAATAGACTGATCGAGAAAACTAATACAGAGTTCGAGAGCATAGA

GAGCGAATTTTCCGAGATCGAGCATCAGATCGGTAACATTATAAATTGGACTAAGGATAGC

ATTACTGATATTTGGACCTATCAGGCTGAGCTGCTGGTTGCCATGGAAAACCAACATACAA

TCGATATGGCCGATTCAGAAATGCTGAATCTATATGAGAGAGTGAGGAAGCAGCTGAGACA

GAACGCTGAGGAGGACGGTAAAGGCTGTTTCGAAATTTACCATGCATGCGACGACTCTTGT

ATGGAATCTATCCGCAACAACACATACGACCACTCCCAGTACAGGGAGGAAGCCCTGCTGA

ATCGACTGAACATTAATCCAGTCAAGCTTTCCTCTGGTTATAAGGACATCATCTTATGGTT

CAGCTTCGGGGCTTCGTGTCTCATTCTCTTGGCTGTGGTAATGGGCTTAGTTTTCTTTTGT

CTTAAGAACGGCAACATGAGGTGCACAATTTGCATC

756
ATGTATAAAATCGTGGTTATTATTGCACTGCTAGGGGCCGTCAAGGGCTTAGATAAGATTT

GCCTGGGCCACCACGCGGTGGCCAATGGGACCATTGTGAAAACTCTGACCAACGAGCAGGA

AGAAGTGACTAACGCCACCGAGACTGTGGAATCAACAGGAATCAATCGTCTGTGCATGAAA

GGCAGAAAGCATAAGGACCTTGGAAACTGTCATCCTATTGGGATGCTGATCGGCACCCCAG

CTTGTGATTTGCACCTCACCGGTATGTGGGATACTCTTATCGAAAGGGAAAACGCTATCGC

TTATTGTTACCCAGGAGCGACTGTCAATGTCGAGGCCCTACGCCAGAAAATAATGGAAAGT

GGAGGGATTAATAAGATAAGCACTGGTTTCACGTATGGCAGTTCGATCAATAGTGCCGGAA

CAACTCGCGCTTGCATGCGTAATGGTGGAAACTCATTTTACGCAGAGCTCAAATGGCTAGT

TTCGAAGTCCAAAGGTCAGAACTTTCCACAGACGACCAACACCTATCGCAATACCGACACT

GCAGAGCACCTGATCATGTGGGGAATTCATCACCCGTCAAGCACTCAAGAGAAGAACGATC

TTTATGGAACCCAGAGTCTCAGTATTTCCGTTGGCTCGAGTACGTACCGCAATAACTTCGT

TCCTGTCGTGGGTGCCAGGCCTCAGGTTAACGGGCAGTCCGGGCGCATCGATTTTCACTGG

ACTCTCGTTCAGCCCGGGGATAATATCACATTCAGTCACAACGGTGGGCTGATCGCGCCGT

CCAGAGTGTCAAAACTGATCGGCAGGGGCCTGGGCATTCAGAGCGACGCACCAATTGATAA

CAATTGTGAGAGCAAATGTTTCTGGCGTGGAGGCAGCATCAATACCCGACTCCCGTTTCAG

AATCTGAGCCCCAGAACTGTCGGACAATGTCCTAAATATGTGAATCGGCGCTCCCTGATGC

TCGCAACTGGCATGCGGAACGTGCCCGAGTTGATTCAAGGACGCGGGCTGTTCGGTGCCAT

CGCTGGGTTCCTGGAAAACGGCTGGGAAGGCATGGTAGATGGATGGTACGGGTTCAGGCAC

CAGAACGCCCAAGGGACAGGACAGGCCGCCGACTACAAGAGTACTCAAGCTGCTATTGACC

AAATTACCGGAAAACTGAATAGGCTGGTGGAAAAGACCAATACAGAGTTCGAGTCTATCGA

GAGCGAGTTTAGCGAGATCGAGCATCAGATTGGTAATGTGATTAACTGGACGAAAGATAGT

ATCACCGACATCTGGACATATCAAGCAGAACTTCTTGTGGCTATGGAGAATCAACATACTA

TTGACATGGCTGATAGCGAGATGTTGAATCTTTACGAGAGAGTGCGCAAACAGCTGCGGCA

GAATGCTGAGGAAGATGGCAAAGGTTGTTTCGAGATCTACCATGCCTGCGACGACAGTTGT

ATGGAGAGCATTAGGAATAACACTTACGACCACTCACAATATCGAGAAGAGGCTCTACTCA

ACAGGCTAAACATCAATCCAGTGACCCTCTCCTCCGGTTATAAGGATATCATTCTCTGGTT

CTCCTTCGGAGCTTCCTGTTTTGTCCTTCTGGCAGTGGTGATGGGATTATTTTTTTTCTGC

CTTAAGAATGGGAATATGAGATGTACAATCTGTATT

757
ATGTACAAGATCGTAGTGATTATCGCATTACTTGGCGCCGTGAAGGGACTCGATAAGATTT

GCTTGGGCCATCATGCTGTGGCCAATGGCACTATAGTGAAGACACTCACCAATGAACAGGA

AGAAGTGACCAACGCCACCGAGACCGTGGAGTCTACAGGCATCAACAGGCTCTGTATGAAG

GGCCGTAAGCACAAGGATCTTGGCAACTGCCATCCTATCGGAATGCTCATTGGAACACCAG

CTTGTGATCTCCACTTAACAGGCATGTGGGACACACTGATTGAGCGGGAGAATGCGATTGC

CTACTGTTATCCCGGGGCCACCGTGAACGTTGAGGCTCTCAGACAGAAAATCATGGAGAGC

GGCGGGATAAACAAGATAAGCACAGGCTTCACTTACGGTTCTAGCATTAATTCGGCAGGAA

CCACACGGGCCTGCATGCGCAACGGCGGCAATTCATTTTACGCCGAACTTAAGTGGCTGGT

GTCCAAGAGCAAGGGCCAGAACTTCCCCCAGACCACTAATACTTACCGCAACACCGACACA

GCAGAGCACCTTATCATGTGGGGTATACACCATCCTAGCAGTACCCAAGAAAAAAACGATC

TGTACGGAACACAAAGCCTTTCAATTTCTGTAGGAAGTTCCACATATAGGAACAACTTTGT

CCCGGTGGTGGGCGCTGGCCCTCAGGTTAATGGCCAGTCCGGGAGGATCGATTTCCATTGG

ACACTCGTGCAGCCTGGGGACAACATTACTTTCTCTCACAACGGGGGTTTAATCGCCCCCT

CAAGGGTCTCTAAGCTCATCGGGCGCGGTCTGGGAATCCAATCCGACGCTCCTATTGACAA

CAACTGCGAGTCAAAGTGCTTCTGGAGAGGTGGATCCATCAACACGCGCCTCCCATTTCAG

AACTTGTCCCCGCGTACAGTGGGCCAGTGTCCCAAGTATGTGAATCGACGGAGCTTGATGC

TGGCCACTGGGATGAGGAACGTGCCTGAACTTATCCAGGGAAGGGGCCTCTTCGGAGCCAT

CGCTGGCTTCCTGGAAAACGGCTGGGAGGGGATGGTGGACGGGTGGTACGGCTTTCGACAT

CAGAATGCCCAGGGGACTGGACAGGCAGCAGATTATAAGAGTACCCAAGCCGCCATTGACC

AGATCACAGGGAAGCTAAACAGGTTGGTCGAAAAGACTAACACAGAATTCGAATCCATCGA

GAGCGAGTTTTCCGAGATTGAGCACCAGATCGGTAACGTGATTAACTGGACGAAAGACTCA

ATAACCGATATCTGGACATATCAGGCGGAGTTGCTTGTGGCGATGGAGAACCAGCACACTA

TTGATATGGCAGACTCTGAGATGCTCAACCTGTATGAGCGGGTTCGGAAGCAGCTGCGACA

AAATGCTGAGGAAGACGGAAAGGGGTGTTTCGAAATCTATCACGCCTGTGATGACTCTTGC

ATGGAGTCGATTAGGAACAATACCTATGATCACTCTCAATATAGAGAGGAGGCTTTACTAA

ATCGGCTCAACATAAATCCAGTGACCCTGTCCAGCGGATATAAAGACATTATTCTATGGTT

CTCTTTCGGAGCGAGCTGCTTTGTGCTTCTCGCTGTGGTGATGGGTCTCTTCTTTTTTTGC

CTGAAGAATGGTAACATGCGCTGCACTATTTGTATT

758
ATGTACAAGGTGGTAGTGATTATTGCCCTGCTGGGAGCAGTTAGAGGCTTAGATAAAATTT

GCCTCGGGCATCATGCTGTTGCTAATGGTACAATTGTCAAGACCTTAACAAATGAGCAGGA

GGAGGTAACCAATGCGACCGAGACGGTGGAGTCTAAGTCTTTGGGGAAACTGTGTATGAAG

GGAAGATCATATAACGACCTAGGCAATTGCCACCCCATCGGGATTCTGATTGGGACCCCCG

CCTGTGATCTGCACCTGACAGGCACATGGGACACCCTGATCGAACGGGAAAACGCGGTGGC

CTATTGCTACCCTGGGGCGACAGTCAACGAGGAAGCTTTGAGGCAGAAAATCATGGAGAGC

GGGGGCATCTCTAAAATCTCCACCGGGTTCACGTATGGTACCTCCATTAATTCAGCCGGAA

CGACCAAGGCATGTATGCGTAATGGAGGCAACTCCTTCTACGCCGAGCTCAAGTGGCTTGT

TTCCAAAAATAAGGGGCAGAATTTCCCTCAGACAACGAACACATACCGGAATACTGACACT

GCAGAGCACCTAATCATCTGGGGAATTCACCACCCATCCAGTACGCAGGAAAAAAACGACC

TCTACGGGACTCAGTCTCTGTCAATTTCTGTGGGCTCCTCAACATACCAAAATAACTTCGT

TCCAGTGGTGGGCGCCCGGCCCCAGGTCAATGGACAGAGCGGAAGGATAGACTTCCACTGG

ACACTCCTTCAGCCGGGGGACAATATCACGTTCTCTCACAACGGGGGACTGATAGCTCCAT

CTAGGGTGAGCAAACTGATTGGACGGGGATTGGGCATACAATCAGAAGCGCCCATAGACAA

TGGATGCGAAAGCAAATGCTTTTGGAAGGGAGGTTCAATAAACACAAAACTCCCATTCCAG

AATCTGTCTCCTAGAACAGTGGGGCAGTGCCCCAAATATGTTAATAAGAGATCTCTCATGC

TTGCTACTGGCATGCGGAACGTCCCCGAAATTATGCATGGGAGGGGCCTCTTCGGGGCGAT

TGCCGGCTTCATTGAAAATGGCTGGGAAGGAATGGTCGATGGATGGTATGGCTTTCGACAT

CAGAACGCACAGGGCACTGGGCAGGCAGCAGACTACAAAAGTACTCAGGCCGCAATAGACC

AGATAACCGGAAAGCTCAATCGCCTCATCGAAAAGACAAACACTGAATTCGAAAGTATTGA

ATCCGAATTCTCTGAAATAGAGCACCAGATTGGTAATATCATCAACTGGACCAAGGATAGT

ATTACTGATATCTGGACATACCAAGCCGAACTGCTGGTAGCAATGGAGAATCAGCACACGA

TTGATATGGCAGATTCTGAAATGCTGAACCTGTATGAGCGAGTGCGCAAGCAGCTGCGCCA

AAACGCTGAAGAGGATGGGAAAGGCTGCTTCGAAATCTACCACGCTTGCGACGATTCCTGC

ATGGAGAGTATCCGGAATAACACCTACGATCATAGCCAGTACAGGGAGGAAGCCCTTCTGA

ACAGACTGAACATTAACCCAGTTAAGCTTAGTAGTGGATACAAAGACATAATCCTCTGGTT

CTCCTTTGGCGCTTCATGCTTAATTTTACTTGCCGTCGTAATGGGACTGGTGTTTTTCTGC

CTTAAGAACGGCAATATGAGGTGCACGATTTGCATC

759
ATGTACAAGATCGTGGTTATTATTGCCTTGTTGGGCGCCGTGAAGGGTCTCGATAAGATTT

GTCTGGGCCATCATGCTGTAGCCAATGGCACCATTGTGAAGACGCTCACTAACGAGCAGGA

AGAGGTTACGAACGCAACCGAGACAGTGGAGAGCACTGGGATAAACAGACTGTGCATGAAA

GGACGTAAACACAAGGACCTTGGTAATTGCCACCCTATCGGGATGCTGATTGGGACACCCG

CATGCGACTTGCATTTGACCGGAATGTGGGATACATTGATTGAGCGCGAGAACGCAATTGC

CTACTGTTACCCAGGAGCCACCGTCAATGTTGAGGCCCTGCGGCAGAAGATCATGGAGAGC

GGCGGCATTAACAAGATATCTACAGGCTTTACATATGGATCATCCATAAATTCAGCAGGAA

CTACGCGCGCATGCATGCGCAACGGCGGCAACAGCTTTTACGCTGAGCTTAAGTGGCTCGT

CAGTAAGTCAAAGGGCCAGAATTTCCCCCAAACCACCAATACATACAGAAACACCGACACG

GCAGAGCACCTGATCATGTGGGGAATCCATCACCCATCTTCCACGCAAGAGAAGAATGACC

TATACGGGACTCAGAGCCTCTCCATATCCGTCGGGTCCTCCACCTACAGGAACAACTTTGT

ACCTGTTGTAGGGGCTCGCCCCCAGGTGAATGGCCAGAGCGGACGGATCGACTTTCATTGG

ACACTTGTTCAGCCCGGCGACAACATTACTTTCTCCCACAACGGAGGTCTGATCGCCCCCA

GCAGGGTAAGTAAACTGATTGGCCGCGGCTTAGGAATACAGAGCGACGCCCCAATCGATAA

CAATTGTGAATCTAAGTGCTTTTGGAGGGGGGGCAGTATAAACACCCGGCTACCCTTTCAG

AATCTGAGTCCACGCACCGTGGGGCAGTGTCCAAAGTATGTGAACCGGAGAAGTTTAATGC

TGGCAACCGGCATGAGAAATGTCCCTGAGCTAATTCAGGGTCGCGGGCTTTTCGGCGCAAT

CGCAGGCTTTCTCGAAAACGGTTGGGAGGGCATGGTGGACGGGTGGTACGGGTTCCGGCAC

CAAAACGCCCAGGGAACTGGGCAGGCCGCCGATTACAAAAGCACTCAGGCAGCTATAGACC

AGATCACAGGCAAACTGAATCGGCTGGTGGAAAAGACAAATACAGAGTTCGAGAGCATTGA

GAGCGAGTTTAGCGAGATCGAACATCAGATCGGGAACGTTATTAACTGGACCAAGGATAGC

ATCACTGATATTTGGACCTACCAGGCTGAACTGTTGGTCGCCATGGAGAACCAGCACACAA

TCGACATGGCAGACTCGGAGATGCTTAACCTCTATGAGCGGGTGAGAAAGCAGCTCCGACA

GAACGCCGAAGAGGACGGGAAGGGGTGCTTCGAAATTTATCATGCATGTGACGATAGTTGT

ATGGAGTCAATCCGCAATAATACTTATGATCATAGCCAGTATCGTGAGGAGGCCCTGCTCA

ATCGTCTGAATATAAATCCCGTGACCCTGAGTTCGGGCTACAAAGACATAATACTCTGGTT

TTCGTTTGGCGCGAGTTGCTTCGTGCTGTTAGCTGTTGTAATGGGATTGTTCTTTTTCTGC

CTAAAAAACGGCAACATGAGGTGTACTATTTGCATC

760
ATGTACAAGATTGTCCTGGTGCTTGCTCTGCTGGGAGCCGTGCACGGCCTCGATAAAATCT

GCTTAGGCCACCACGCTGTCCCTAATGGCACCATTGTTAAGACCTTGACAAACGAAAAGGA

AGAGGTGACCAACGCCACTGAGACTGTGGAATCCAAGTCACTCGACAAATTATGTATGAAG

AACAGGAACTATAAAGATCTTGGTAACTGCCATCCAATTGGCATGGTGGTAGGAACTCCTG

CTTGCGATCTACACCTGACGGGCACATGGGACACCCTGATTGAGAGGGACAACTCTATTGC

ATACTGCTATCCAGGTGCGACCGTTTCCGAAGAAGCACTCCGGCAGAAGATTATGGAGTCC

GGCGGCATCGATAAAATCTCCACCGGCTTCACATACGGAAGTAGCATCAACTCTGCTGGGA

CGACCAAAGCGTGTATGAGGAACGGGGGGAATAGTTTCTACTCAGAACTCAAGTGGCTGGT

CAGTAAGAACAAGGGGCAGAACTTCCCTCAAACGACCAACACATACCGAAATACAGATTCT

GTGGAGCACTTAATCATCTGGGGGATTCATCATCCATCCAGCACGCAGGAGAAAAACGATC

TCTATGGTACACAGTCTCTCAGCATCAGTGTGGGAAGCAGTACGTATCAGAACAATTTTGT

CCCCGTCGTTGGCGCCCGGCCACAAGTGAACGGACAAAGTGGTCGTATTGATTTTCATTGG

ACCATGGTCCAACCTGGTGATAATATAACATTTTCACACAATGGAGGACTGATAGCTCCTA

ACAGAGTATCCAAGCTGAAGGGAAGGGGGTTGGGGATTCAGTCCGGAGCATCAGTGGACAA

TGATTGCGAGAGCAAGTGCTTCTGGAAGGGAGGTTCCATCAACACGAAGCTGCCTTTCCAG

AATCTGAGCCCACGAACAGTGGGACAGTGCCCGAAGTATGTGAATAAGAAGAGCCTTCTGC

TTGCGACTGGCATGAGGAATGTTCCTGAAGTTGCGCAGGGAAGGGGGCTATTCGGGGCAAT

CGCCGGATTCATCGAGAACGGCTGGGAGGGCATGGTGGACGGGTGGTACGGGTTCAGGCAC

CAGAACGCCCAGGGTACAGGGCAGGCCGCTGATTACAAGTCAACACAGGCGGCGATAGACC

AGATCACCGGCAAACTGAATAGGCTAATAGAGAAGACTAACACTGAATTTGAATCTATTGA

GAGCGAGTTCTCGGAAATTGAACACCAGATCGGAAATGTGATCAATTGGACCAAGGATTCC

ATTACCGATATCTGGACTTATCAGGCAGAGCTGTTAGTGGCAATGGAAAACCAGCATACCA

TAGACATGGCTGATTCTGAGATGTTGAACCTCTACGAGGGGGTACGGAAACAACTGAGACA

GAATGCAGAGGAAGACGGCAAGGGCTGTTTCGAAATCTACCACAAGTGCGACGATAATTGT

ATGGAAAGTATACGCAACAATACCTATGATCACACACAATATAGGGAAGAGGCTCTTCTGA

ACCGACTGAACATCAATCCCGTGAAACTTAGCTCAGGATACAAGGACGTGATCCTTTGGTT

TTCTTTCGGGGCTAGTTGCTTCGTGCTGCTTGCGGTTATCATGGGGCTTGTTTTCTTTTGT

CTAAAGAATGGGAATATGAGATGCACAATCTGCATC

761
ATGTACAAAATCGTGGTGATCATCGCCCTCCTGGGAGCTGTGAAGGGCCTTGACAAAATCT

GCCTCGGCCACCACGCCGTCGCCAATGGAACCATCGTGAAGACTCTGACCAATGAGCAGGA

GGAAGTTACCAATGCAACTGAGACCGTGGAAAGTACCGGGATAAATCGCCTCTGCATGAAG

GGAAGGAAACATAAAGACCTGGGGAACTGTCATCCGATTGGGATGCTGATTGGGACCCCTG

CCTGTGATTTGCACCTTACCGGCACATGGGACACACTGATCGAGCGAGAAAATGCTATCGC

ATATTGTTATCCCGGGGCAACCGCAAACGTAGAGGCCCTACGGCAGAAAATTATGGAGTCC

GGTGGCATAGACAAAATAAGCACAGGATTTACCTACGGCTCGAGCATCAACTCTGCTGGCA

CCACCAGAGCTTGCATGAGGAATGGGGGGAACTCCTTTTACGCTGAGTTGAAGTGGCTGGT

GAGCAAGAGTAAAGGGCAGAACTTTCCTCAGACGACTAATACATATAGAAACACCGACACA

GCAGAGCACCTCATAATGTGGGGAATCCATCACCCATCTTCAATTCAGGAGAAGAATGACC

TTTATGGTACTCAGAGCCTCAGTATTTCCGTGGGATCTTCTACGTACAGAAACAACTTTGT

GCCAGTTGTCGGCGCAAGACCTCAGGTCAACGGGCAGTCAGGGAGAATTGACTTTCATTGG

ACACTGGTGCAACCTGGGGATAATATCACTTTTAGCCATAATGGAGGACTGATTGCTCCCA

GTAGAGTCTCTAAACTGATTGGGAGGGGACTCGGTATCCAGTCGGATGCTCCTATCGATAA

TAACTGTGAGAGCAAGTGTTTTTGGCGAGGGGGATCTATCAATACACGGTTGCCATTTCAG

AATCTATCGCCCCGCACGGTTGGTCAGTGCCCCAAGTACGTTAATCGTCGGTCGCTGATGC

TGGCTACGGGAATGAGGAATGTTCCAGAACTGATTCAAGGACGCGGTTTGTTCGGCGCCAT

CGCAGGTTTCCTTGAAAACGGCTGGGAAGGTATGGTTGACGGTTGGTACGGATTCCGACAT

CAGAACGCCCAGGGTACGGGACAGGCGGCTGACTACAAAAGCACCCAGGCAGCAATTGATC

AGATCACGGGGAAGCTCAATAGACTGGTGGAAAAGACCAACACGGAATTTGAATCAATTGA

GTCCGAATTTTCCGAGATTGAACATCAGATCGGCAATGTCATTAATTGGACAATGGATAGC

ATCACTGACATATGGACTTATCAGGCCGAGCTGCTGGTTGCAATGGAGAATCAGCACACTA

TCGACATGGCTGATTCCGAGATGCTGAACCTTTACGAGAGAGTGCGCAAGCAGCTCCGGCA

GAACGCCGAAGAAGATGGAAAGGGGTGCTTTGAGATTTATCACGCGTGCGACGACAGTTGC

ATGGAATCCATCCGGAACAATACTTATGATCATTCTCAGTACCGCGAGGAAGCACTGCTCA

ACAGACTGAATATTAACCCAGTGACCCTAAGCTCAGGGTACAAGGACATCATTCTGTGGTT

CTCTTTCGGCGCGTCATGCTTCGTGCTGCTGGCAGTTGTGATGGGACTCGTGTTCTTTTGC

CTCAAAAATGGAAACATGAGATGTACCATTTGTATC

762
ATGTATAAAGTCGTAGTGATCATCGCACTGTTAGGAGCTGTAAAGGGACTGGACAAGATCT

GCTTAGGACACCACGCAGTGGCAAACGGGACCATAGTCAAGACATTGACTAATGAACAAGA

GGAAGTCACCAACGCGACTGAAACAGTCGAATCTACAGGAATCAACAGACTTTGTATGAAA

GGACGGAAACATAAAGATCTGGGCAACTGTCACCCCATAGGAATGCTGATTGGTACACCAG

CTTGTGACTTGCATCTGACCGGCACATGGGACACGCTGATCGAGAGAGAAAATGCCATTGC

CTACTGTTACCCTGGGGCTACAGTAAACGTCGAGGCGCTGCGTCAGAAGATCATGGAATCT

GGGGGCATCGATAAAATCAGCACGGGGTTCACATACGGATCCAGTATTAATTCTGCTGGCA

CTACCCGTGCTTGTATGCGGAACGGTGGAAACTCCTTCTATGCAGAGCTCAAATGGCTGGT

TTCTAAGAACAAGGGGCAGAATTTTCCCCAGACGACAAATACATATAGAAATACAGACACT

GCTGAGCACCTAATCATGTGGGGCATCCACCACCCAAGTAGTATCCAGGAGAAAAACGACC

TGTACGGCACACAAAGCCTGTCAATCTCAGTGGGCTCCTCAACTTACCGCAATAATTTTGT

GCCAGTTGTGGGCGCCAGGCCCCAGGTTAATGGTCAGTCTGGGCGCATCGATTTTCATTGG

ACTCTGGTGCAACCTGGCGACAATATTACATTCTCTCACAACGGAGGACTCATCGCCCCAT

CCAGAGTGTCTAAGTTGATAGGACGAGGGTTAGGCATCCAAAGCGATGCCCCCATTGACAA

TAACTGCGAATCAAAGTGCTTTTGGCGGGGAGGATCCATTAACACACGGTTGCCTTTCCAG

AATCTGTCTCCAAGGACCGTAGGGCAGTGCCCAAAATACGTGAACAGGCGGTCTCTTATGC

TGGCCACGGGGATGCGCAACGTGCCAGAGCTCATCCAGGGGCGTGGATTATTTGGAGCTAT

TGCCGGATTTCTGGAAAATGGCTGGGAGGGGATGGTTGACGGTTGGTACGGTTTCAGGCAC

CAGAACGCACAGGGCACAGGACAGGCCGCCGACTATAAAAGTACCCAGGCAGCGATTGATC

AGATAACCGGAAAGCTGAACAGGTTGGTGGAAAAAACCAATACTGAGTTCGAGTCTATCGA

GAGCGAATTCTCGGAAATCGAACACCAGATTGGAAATGTAATCAACTGGACTATGGATAGC

ATCACCGATATCTGGACCTACCAGGCTGAACTGTTGGTGGCTATGGAGAATCAACACACGA

TCGATATGGCTGACAGCGAGATGCTCAACCTGTATGAACGTGTTAGGAAACAGCTAAGGCA

AAACGCTGAAGAAGACGGAAAGGGATGTTTTGAAATATATCATGCATGCGATGACTCATGT

ATGGAGTCAATCCGGAACAATACATATGACCATTCTCAGTATAGGGAGGAGGCCCTCCTGA

ACAGACTGAATATTAATCCCGTTACCCTATCCAGCGGGTATAAGGACATCATCCTCTGGTT

CTCTTTTGGTGCCAGTTGTTTCGTTTTGCTTGCTGTTGTGATGGGACTCGTCTTTTTCTGT

CTGAAGAACGGGAACATGAGATGCACCATTTGCATC

763
ATGTACAAAATTGTCGTCATCATAGCACTTCTAGGTGCCGTGAAAGGTTTGGATAAGATCT

GTCTAGGCCATCATGCTGTCGCAAACGGCACTATCGTGAAAACTTTGACTAACGAACAAGA

GGAAGTGACTAACGCTACGGAGACAGTCGAATCGACCGGGATCAACAGACTGTGCATGAAA

GGCCGCAAACACAAAGATTTGGGGAACTGCCATCCTATAGGCATGCTGATTGGGACACCAG

CTTGCGACCTCCACCTGACGGGAATGTGGGACACCCTCATTGAGCGGGAGAATGCGATCGC

GTACTGTTACCCGGGGGCTACCGTCAATGTGGAGGCACTCAGGCAAAAGATCATGGAGTCT

GGCGGCATCAATAAGATTTCCACTGGGTTCACCTATGGATCTAGCATTAATTCTGCAGGTA

CAACTAGAGCTTGTATGAGAAATGGGGGGAATAGTTTCTACGCCGAACTTAAATGGCTGGT

GAGCAAGTCAAAGGGACAAAACTTCCCCCAGACAACGAATACTTACAGGAATACGGATACC

GCAGAGCACTTGATCATGTGGGGGATTCATCATCCATCAAGCACACAGGAAAAAAACGATT

TGTATGGGACTCAGTCACTGTCTATTAGCGTGGGATCTAGTACTTACAGAAACAACTTCGT

ACCTGTGGTGGGAGCCCGACCACAGGTGAATGGACAGAGTGGGAGGATTGACTTTCACTGG

ACCCTGGTGCAACCTGGTGATAATATTACATTTAGCCACAATGGCGGATTGATCGCACCAT

CCCGAGTCAGTAAGCTCATAGGCCGGGGACTTGGCATACAGAGCGACGCTCCTATCGATAA

CAATTGCGAGTCCAAATGCTTCTGGCGGGGAGGAAGTATAAACACACGGCTGCCATTTCAG

AACCTTTCGCCCCGCACGGTCGGCCAGTGCCCCAAATATGTGAATAGGCGTTCACTCATGC

TCGCAACAGGAATGAGAAATGTGCCTGAGCTGATTCAGGGCAGGGGGCTTTTCGGTGCTAT

AGCGGGATTTTTAGAGAACGGCTGGGAAGGGATGGTTGATGGGtGGTACGGGTTCCGGCAC

CAAAATGCGCAGGGAACAGGACAGGCTGCCGACTACAAATCTACCCAGGCTGCAATTGATC

AAATAACTGGCAAACTCAATAGGTTGGTGGAAAAGACGAACACCGAGTTCGAGTCAATCGA

ATCTGAATTCAGCGAGATTGAACACCAAATCGGAAATGTGATTAACTGGACCAAGGACTCC

ATCACCGACATCTGGACCTATCAGGCCGAACTGCTCGTCGCTATGGAGAACCAGCATACCA

TAGATATGGCCGACAGCGAGATGCTCAACCTTTACGAGCGCGTCAGGAAACAGCTTAGGCA

GAATGCTGAAGAAGACGGGAAGGGATGTTTTGAGATCTATCACGCTTGCGATGATTCCTGT

ATGGAGTCCATAAGGAACAACACCTATGACCATTCACAGTACCGTGAAGAGGCCTTGCTTA

ACCGCCTCAACATAAATCCCGTTACTCTCAGCTCAGGTTATAAGGATATCATCCTGTGGTT

TAGCTTTGGAGCCTCCTGCTTTGTGCTCCTCGCCGTCGTGATGGGCCTATTCTTTTTTTGT

CTGAAAAACGGGAATATGCGATGCACTATATGTATA

764
ATGTATAAGATCGTGGTGATCATTGCACTCCTGGGAGCCGTCAAGGGCCTGGATAAAATAT

GCCTGGGGCACCACGCCGTTGCCAACGGAACTATAGTAAAGACCCTGACCAATGAACAGGA

AGAAGTGACCAACGCAACCGAAACCGTGGAGAGTACAGGCATAAATCGCCTTTGCATGAAG

GGTCGAAAGCACAAAGACCTGGGGAATTGCCACCCCATAGGGATGCTGATCGGCACCCCGG

CTTGTGATTTGCACTTGACTGGGATGTGGGATACACTCATTGAGCGCGAAAACGCAATCGC

ATATTGCTACCCCGGGGCAACCGTGAACGTCGAGGCCCTGCGGCAGAAAATTATGGAGTCT

GGCGGAATAAATAAGATTTCAACCGGTTTTACATACGGAAGTTCTATTAATAGCGCAGGCA

CAACAAGGGCGTGTATGAGGAACGGTGGTAATAGTTTCTATGCAGAACTAAAATGGTTGGT

GTCTAAATCGAAAGGTCAAAATTTCCCCCAAACTACCAACACCTACCGCAATACTGATACT

GCCGAACACTTGATTATGTGGGGTATTCACCACCCATCCTCAACACAGGAAAAGAACGATT

TGTACGGGACACAGAGTCTGAGTATTAGTGTAGGCTCTAGCACCTACAGAAATAACTTTGT

CCCAGTGGTGGGCGCTCGGCCTCAGGTGAATGGCCAATCTGGAAGAATTGACTTCCATTGG

ACACTTGTGCAGCCAGGTGATAACATCACTTTTAGCCATAATGGTGGGCTGATTGCCCCTT

CCAGGGTGAGTAAACTTATTGGTCGCGGGCTGGGGATACAATCGGATGCCCCTATCGACAA

TAATTGCGAATCCAAGTGTTTTTGGAGGGGGGGGTCAATCAATACCAGGCTACCTTTCCAG

AATCTGAGTCCACGTACCGTCGGGCAGTGTCCTAAGTATGTCAATCGACGGTCACTGATGC

TCGCTACCGGCATGCGGAATGTCCCAGAGCTGATCCAAGGGCGTGGTCTGTTCGGCGCAAT

TGCCGGCTTCCTCGAGAATGGATGGGAGGGCATGGTAGATGGATGGTATGGTTTTAGACAC

CAAAACGCCCAAGGAACTGGGCAGGCGGCCGATTATAAATCCACTCAGGCCGCAATTGATC

AGATTACTGGCAAGCTAAACCGTTTAGTTGAGAAAACGAACACCGAATTCGAGAGCATAGA

GAGTGAATTTAGTGAGATCGAGCATCAAATTGGGAATGTGATTAACTGGACCAAAGACTCA

ATAACCGATATCTGGACCTACCAGGCAGAGTTACTGGTAGCTATGGAGAACCAGCATACCA

TCGACATGGCCGACTCTGAGATGCTCAATTTGTATGAGAGGGTCAGGAAACAACTGCGGCA

GAATGCTGAAGAAGATGGAAAAGGGTGCTTTGAAATATATCACGCATGCGACGATAGTTGC

ATGGAGTCCATACGAAACAATACCTACGATCACTCACAGTATAGAGAGGAAGCCCTCTTAA

ATAGGCTAAATATAAACCCTGTCACACTGAGCTCTGGGTACAAAGATATTATCTTATGGTT

CTCATTTGGGGCTAGTTGTTTCGTGCTCCTGGCGGTCGTGATGGGCCTGTTCTTCTTCTGT

CTAAAGAACGGTAATATGAGATGTACTATCTGCATT

765
ATGTATAAAGTGGTGGTTATTATAGCGTTGCTGGGCGCTGTTAAAGGTTTGGACAAGATCT

GCTTGGGACATCATGCTGTCGCCAACGGGACAATCGTCAAGACCCTGACAAACGAACAGGA

AGAGGTCACAAACGCGACTGAAACCGTGGAGAGCACAGGAATTAATCGGCTCTGTATGAAA

GGCCGCAAACACAAAGATCTTGGAAATTGCCACCCAATTGGGATGCTCATTGGCACACCAG

CCTGTGATCTACATCTGACCGGCACATGGGACACTCTCATCGAACGCGAGAACGCTATCGC

ATATTGTTACCCCGGGGCGACCGTGAATGTTGAGGCCCTGCGCCAGAAGATTATGGAGAGT

GGAGGCATCGATAAGATATCGACCGGCTTCACTTACGGAAGCTCCATTAACTCCGCTGGTA

CCACCCGGGCCTGCATGAGGAACGGCGGCAATTCCTTTTACGCCGAACTGAAGTGGTTAGT

GTCTAAAAATAAGGGGCAGAATTTTCCCCAAACCACAAACACATACCGAAACACCGACACG

GCCGAGCATCTGATCATGTGGGGGATTCACCATCCTTCTTCCATCCAGGAAAAGAACGATC

TGTACGGAACTCAATCTCTCTCCATCTCCGTTGGTTCCTCCACGTATAGGAACAATTTCGT

ACCCGTGGTCGGCGCCCGACCACAAGTAAACGGCCAGTCCGGCCGCATCGACTTCCACTGG

ACACTTGTGCAGCCAGGAGACAACATTACATTCTCCCATAATGGCGGGCTGATTGCACCCA

GCCGGGTCTCCAAGCTTATCGGCCGCGGCCTGGGGATCCAGTCAGACGCGCCCATCGATAA

CAACTGCGAAAGCAAGTGTTTTTGGCGGGGtGGATCTATTAACACCCGTCTGCCTTTCCAG

AATCTTAGTCCCCGGACAGTGGGGCAGTGCCCCAAGTATGTGAATCGAAGGTCTCTGATGC

TGGCCACAGGCATGAGAAATGTGCCAGAGTTGATTCAGGGCCGGGGTCTCTTTGGAGCCAT

TGCCGGTTTTCTTGAAAACGGTTGGGAGGGTATGGTCGACGGTTGGTACGGTTTCCGGCAC

CAGAACGCACAGGGCACTGGTCAGGCTGCAGATTATAAATCTACACAAGCCGCTATCGACC

AGATCACGGGCAAACTAAATAGACTGGTCGAGAAGACTAACACTGAATTTGAGAGCATTGA

GTCGGAGTTTTCCGAGATTGAACACCAGATCGGAAATGTGATTAATTGGACAATGGACTCA

ATTACTGACATCTGGACATACCAAGCCGAACTGCTGGTTGCGATGGAGAACCAGCACACCA

TCGATATGGCCGATAGCGAAATGCTAAATCTGTATGAGAGGGTAAGGAAGCAGCTGCGCCA

GAATGCCGAAGAAGACGGGAAGGGTTGTTTTGAGATCTACCATGCTTGTGACGACAGTTGC

ATGGAAAGCATTCGAAACAACACTTATGACCACTCGCAATATCGCGAAGAGGCCCTTTTGA

ATCGGCTCAACATAAACCCAGTGACACTTTCTTCCGGTTACAAGGATATTATCCTGTGGTT

CTCTTTTGGAGCATCGTGTTTTGTACTGCTCGCTGTCGTTATGGGCTTGGTCTTCTTTTGT

CTGAAAAATGGCAATATGCGGTGTACCATCTGCATT

766
ATGTATAAGATTGTGGTGATCATTGCACTGCTGGGGGCTGTGAAGGGACTCGACAAGATTT

GCCTGGGCCACCATGCCGTTGCAAACGGGACCATCGTCAAAACATTGACAAACGAGCAGGA

AGAGGTGACAAACGCCACTGAAACAGTCGAAAGTACGGGGATTAACCGGCTATGTATGAAG

GGGAGGAAACATAAAGATCTAGGCAACTGCCACCCCATAGGCATGCTTATCGGCACCCCGG

CCTGCGACCTTCACCTGACCGGAATGTGGGATACCTTGATCGAGAGGGAAAACGCCATCGC

TTATTGCTACCCAGGAGCCACGGTGAACGTAGAGGCTCTACGACAAAAGATTATGGAGAGC

GGCGGAATAAATAAAATATCCACGGGATTCACCTACGGTTCCTCGATAAATTCAGGGGGCA

CCACCAGAGCCTGCATGCGCAACGGCGGCAATTCCTTTTATGCCGAGCTTAAGTGGCTCGT

TTCCAAAAGCAAGGGGCAGAACTTTCCTCAGACCACAAACACCTATAGGAATACCGACACC

GCGGAGCACCTGATTATGTGGGGGATCCACCATCCCTCAAGTACACAGGAAAAGAACGATC

TCTATGGAACCCAGAGCCTGAGTATCAGCGTGGGGTCCAGCACATATCGCAACAACTTTGT

CCCAGTGGTCGGAGCCCGCCCACAGGTTAACGGCCAATCCGGTCGCATTGACTTTCACTGG

ACCTTGGTGCAACCAGGGGATAATATTACCTTCAGCCACAATGGTGGACTGATTGCCCCAA

GTCGTGTTTCCAAGCTGATCGGAAGAGGGTTAGGTATCCAGAGTGACGCCCCAATTGATAA

TAACTGCGAGAGCAAATGCTTCTGGCGGGGGGGATCGATTAATACGCGTCTCCCCTTTCAG

AACCTCTCCCCACGTACGGTCGGGCAGTGTCCAAAGTATGTGAACAGACGTTCACTGATGC

TGGCAACAGGGATGAGAAACGTACCCGAGCTGATCCAGGGGAGAGGGCTGTTCGGTGCCAT

TGCCGGATTTCTCGAAAATGGTTGGGAGGGAATGGTGGACGGTTGGTACGGATTCCGGCAC

CAGAACGCTCAGGGGACCGGCCAAGCAGCTGATTATAAATCTACCCAGGCCGCCATTGATC

AGATCACCGGGAAGTTGAACCGCCTCGTGGAGAAGACTAACACAGAGTTCGAGTCTATCGA

ATCAGAGTTCAGCGAGATTGAACACCAGATTGGGAACGTGATTAACTGGACCAAGGACTCC

ATCACCGACATTTGGACATATCAAGCCGAGCTGCTGGTAGCCATGGAGAACCAGCACACCA

TAGATATGGCAGATAGTGAGATGCTGAACCTCTATGAACGCGTGCGAAAGCAACTGCGACA

AAATGCTGAGGAGGATGGGAAGGGATGCTTTGAAATCTACCACGCGTGCGACGATTCTTGT

ATGGAAAGTATCCGGAATAATACTTATGATCACTCTCAGTATAGGGAGGAGGCACTACTAA

ATCGTCTGAATATCAACCCAGTGACCTTATCCTCCGGATACAAGGACATTATCCTGTGGTT

CAGTTTTGGCGCTTCCTGTTTCGTGCTCCTGGCTGTAGTGATGGGCTTATTTTTCTTCTGC

CTGAAAAACGGAAATATGCGGTGCACCATTTGCATT

767
ATGTATAAGATAGTCGTAATTATCGCACTCCTCGGGGCTGTTAAGGGCCTGGACAAAATCT

GTCTGGGTCACCATGCAGTCGCCAACGGAACAATAGTCAAGACTCTGACCAATGAACAGGA

GGAGGTTACGAATGCCACGGAAACCGTGGAAAGTACAGGGATCAACCGCCTGTGTATGAAA

GGGAGAAAGCATAAAGACTTGGGTAATTGCCATCCAATCGGGATGCTGATTGGAACACCCG

CTTGTGACCTCCATTTGACCGGTATGTGGGACACACTGATCGAAAGAGAGAATGCCATCGC

GTATTGTTACCCTGGTGCCACTGTGAACGTGGAGGCACTGCGCCAGAAGATCATGGAATCC

GGCGGAATCAATAAGATCTCCACCGGATTTACCTACGGATCCAGTATAAATTCAGCCGGGA

CGACAAGAGCATGCATGAGAAACGGCGGCAACAGTTTTTACGCCGAGCTGAAGTGGCTTGT

GTCCAAGTCTAAAGGCCAGAACTTTCCTCAGACAACCAACACCTACCGTAACACTGATACA

GCAGAGCATCTGATCATGTGGGGCATTCACCATCCATCTTCCACCCAAGAAAAGAATGATC

TGTACGGAACACAGAGCCTGTCTATTAGTGTTGGATCGTCAACCTACCGGAATAACTTTGT

TCCCGTAGTGGGCGCACGCCCCCAGGTGAATGGGCAGTCAGGTCGAATTGATTTTCACTGG

ACCCTCGTGCAGCCTGGCGACAATATTACATTCAGTCATAACGGGGGACTGATCGCCCCAA

GCCGCGTTTCTAAGCTGATTGGGAGAGGTTTGGGAATTCAGAGCGACGCACCTATCGATAA

CAATTGCGAATCAAAGTGCTTTTGGGGGGGGGGCAGCATAAATACCAGACTGCCCTTTCAG

AACCTTAGCCCTAGGACAGTCGGGCAGTGTCCCAAATACGTCAACCGCCGGAGTCTGATGC

TCGCTACAGGAATGAGAAATGTTCCAGAGCTAATCCAGGGACGAGGACTCTTCGGAGCCAT

CGCTGGATTTCTGGAGAATGGCTGGGAGGGGATGGTTGATGGGTGGTATGGCTTTAGACAT

CAGAACGCCCAGGGGACAGGTCAGGCCGCCGATTACAAGTCTACCCAGGCCGCGATTGACC

AGATCACTGGCAAATTGAATAGGCTGGTTGAGAAAACTAACACTGAATTTGAGTCAATCGA

GAGCGAGTTTTCTGAGATCGAACACCAGATCGGGAACGTGATTAATTGGACTAAAGACTCT

ATAACGGACATTTGGACCTATCAAGCCGAGTTATTAGTCGCGATGGAGAACCAGCACACAA

TAGATATGGCAGACTCTGAGATGCTGAACCTGTACGAGAGGGTGCGGAAGCAATTAAGGCA

GAATGCCGAAGAGGATGGGAAGGGATGCTTCGAAATATACCATGCCTGCGACGACTCGTGC

ATGGAGAGCATTAGAAACAATACATACGACCATAGCCAGTATCGCGAGGAAGCACTACTGA

ATCGGCTGAATATCAATCCAGTCACACTCTCTTCTGGGTACAAAGATATCATTCTGTGGTT

TAGCTTCGGCGCCTCCTGCTTCGTCCTTCTGGCCGTGGTTATGGGGCTGTTTTTTTTCTGT

CTTAAGAACGGAAATATGAGGTGTACCATCTGTATT

768
ATGTATAAGATTGTGGTGATCATTGCCCTCCTAGGCGCCGTAAAAGGGTTAGATAAAATCT

GCCTGGGACACCACGCCGTGGCCAACGGCACTATAGTCAAGACCCTCACTAACGAGCAGGA

AAAAGTGACCAATGCTACGGAAACAGTGGAATCTACAGGCCTGAATCGCCTTTGCATGAAA

GGCAGGAAACACAAAGACTTAGGGAATTGTCACCCCATTGGAATGTTAATTGGGACTCCAG

CTTGCGATCTGCACCTCACTGGTACATGGGATACAATTATTGAACGGGAGAATGCCATCGC

ATACTGCTACCCTGGGGCGACCGTCAATGAGGAAGCTCTGCGGCAGAAGATCATGGAGTCT

GGTGGCATTGATAAAATCTCCACCGGGTTCACGTATGGGTCTTCAATTAATAGCGCTGGAA

CGACTAGAGCTTGTATGCGCAATGGTGGAAATTCCTTTTACGCTGAGCTTAAATGGCTCGT

CTCGAAATCCAAGGGACAGAACTTTCCGCAAACTACAAACACTTATAGAAACACAGACACC

GCAGAACACCTCATCATGTGGGGGATTCACCACCCTTCTAGTACCCAAGAAAAGAATGACC

TCTATGGCACACAGAGCCTGTCCATCTCGGTCGGCAGCAGCACCTACCGGAACAACTTTGT

GCCCGTGGTGGGCGCGCGCCCCCAAGTTAACGGACAGTCCGGTCGGATAGATTTCCACTGG

ACACTGGTCCAGCCCGGGGATAACATAACGTTCTCTCACAACGGAGGGCTGATAGCTCCTT

CTCGAGTGTCAAAATTGATTGGAAGGGGCTTGGGGATCCAGTCCGATGCCCCAATAGACAA

TAACTGCGAGTCTAAATGTTTTTGGAGGGGCGGTTCTATAAATACCCGTCTGCCTTTTCAG

AATCTTAGCCCCAGAACAGTGGGACAGTGTCCCAAGTACGTAAATAAAAGAAGTCTGATGC

TTGCAACCGGCATGAGGAATGTCCCTGAGCTGATCCAGGGTCGTGGCTTGTTCGGTGCCAT

TGCGGGCTTCTTGGAAAATGGTTGGGAGGGAATGGTAGACGGATGGTATGGGTTCCGCCAC

CAAAATGCTCAGGGGACGGGCCAAGCTGCCGACTATAAGAGTACGCAAGCCGCTATTGACC

AGATCACTGGCAAATTGAACAGACTTGTTGAAAAAACAAATACAGAATTCGAAAGCATCGA

ATCAGAATTTAGCGAGATTGAGCACCAAATCGGCAACGTGATCAATTGGACAAAAGACTCC

ATAACCGATATTTGGACCTACCAGGCCGAGCTGCTCGTGGCTATGGAGAACCAGCACACCA

TCGACATGGCTGATAGCGAGATGCTGAATCTATATGAAAGGGTTCGGAAGCAGTTGCGTCA

GAATGCGGAGGAGGATGGGAAGGGTTGCTTTGAAATCTATCACGCCTGCGATGACAGCTGT

ATGGAGAGCATACGAAATAATACCTATGACCATTCACAGTACCGCGAGGAGGCCCTGCTCA

ATCGGCTGAACATCAATCCGGTGACACTGAGCTCTGGCTACAAGGACATCATTCTGTGGTT

CTCATTCGGGGCGAGCTGCTTTGTTTTGTTAGCCGTCGTGATGGGCCTCGTTTTCTTCTGC

CTGAAGAATGGGAATATGCGCTGTACAATCTGCATC

769
ATGTACAAGATTGTCGTGATTATCGCTTTGCTCGGCGCCGTGAAGGGACTGGATAAAATCT

GTCTGGGGCATCACGCTGTGGCTAATGGAACAATTGTGAAGACCCTCACCAATGAGCAGGA

GGAAGTGACAAACGCTACAGAGACAGTCGAGTCCACCGGAATCAACAGGCTGTGCATGAAG

GGCCGGAAACATAAGGACCTCGGGAACTGCCACCCTATTGGGATGCTGATAGGCACACCTG

CCTGTGACTTACACCTTACCGGGATGTGGGATACACTGATAGAACGGGAGAATGCCATAGC

ATACTGCTACCCAGGAGCTACGGTGAATGTGGAAGCTCTCCGCCAGAAAATTATGGAATCA

GGCGGGATTAATAAGATTTCTACGGGCTTCACTTATGGAAGTTCAATAAATTCAGCCGGAA

CAACCCGGGCTTGTATGAGAAATGGTGGAAATTCTTTCTACGCAGAACTCAAGTGGCTTGT

TAGCAAGTCCAAGGGCCAAAACTTCCCTCAGACCACTAATACTTACAGGAATACTGACACC

GCCGAACACCTTATCATGTGGGGTATCCACCATCCATCTAGCACCCAGGAGAAAAATGATC

TTTACGGTACCCAATCACTGAGCATCAGCGTGGGGAGCTCAACTTATCGCAACAATTTCGT

GCCTGTGGTGGGTGCCCGACCACAGGTTAACGGACAAAGTGGACGAATTGACTTTCATTGG

ACCCTGGTGCAGCCTGGCGACAACATCACATTCTCGCATAATGGAGGTTTGATCGCTCCCT

CCCGTGTGTCTAAGCTGATAGGGAGAGGCCTCGGTATACAGTCCGACGCTCCCATCGATAA

TAATTGTGAAAGCAAGTGCTTTTGGCGAGGTGGCAGCATTAACACGCGGTTACCCTTTCAG

AACCTCAGCCCACGCACAGTCGGCCAATGCCCTAAGTATGTAAACCGCCGGAGCTTGATGC

TGGCAACGGGCATGAGAAACGTCCCCGAGCTAATCCAGGGCAGAGGACTGTTCGGCGCCAT

TGCTGGCTTTCTTGAGAACGGATGGGAGGGAATGGTGGACGGCTGGTACGGATTCCGGCAC

CAGAACGCCCAGGGCACCGGCCAGGCCGCCGATTATAAGTCCACCCAAGCTGCCATCGACC

AGATCACCGGCAAACTGAATCGGCTTGTAGAGAAAACCAACACCGAATTCGAGTCAATCGA

GTCCGAATTTAGCGAGATCGAACACCAGATCGGCAATGTGATTAACTGGACAAAGGACAGT

ATCACTGATATCTGGACCTACCAAGCAGAATTACTGGTCGCTATGGAAAATCAGCACACCA

TTGATATGGCCGACAGCGAGATGCTCAACCTATATGAACGCGTCCGCAAGCAGCTGCGTCA

GAACGCAGAGGAAGATGGAAAAGGCTGCTTCGAGATCTACCATGCTTGCGATGACTCTTGT

ATGGAGTCCATCCGCAATAACACATACGACCACTCCCAGTACAGGGAGGAGGCGCTTTTGA

ACAGACTGAATATAAATCCTGTTACTCTTTCATCGGGGTATAAAGACATCATCCTGTGGTT

CTCCTTCGGCGCCTCCTGTTTCGTCCTGCTGGCGGTAGTTATGGGCCTATTTTTTTTTTGT

CTGAAGAATGGGAACATGCGCTGTACAATTTGTATC

770
ATGTACAAAATTGTTGTCATCATTGCTCTGCTGGGGGCTGTGAAAGGACTGGACAAAATCT

GCTTAGGCCATCACGCTGTAGCCAATGGTACCATTGTGAAGACACTGACCAATGAACAGGA

AAAAGTAACAAATGCTACCGAGACGGTCGAGTCCACAGGGCTGAACCGATTGTGCATGAAG

GGACGCAAGCACAAGGATCTGGGAAATTGCCACCCGATTGGTATGCTGATTGGGACTCCAG

CCTGCGATCTGCATCTGACCGGGACTTGGGATACTATCATAGAACGGGAGAACGCCATCGC

CTACTGCTACCCAGGTGCCACTGTAAACGAGGAAGCCTTGCGCCAGAAAATTATGGAGTCA

GGTGGGATTGACAAGATTTCCACTGGGTTCACTTATGGGAGCAGTATTAACTCAGCTGGCA

CAACCCGTGCTTGTATGCGGAACGGAGGAAACTCATTCTACGCAGAGCTGAAATGGCTGGT

TAGCAAAAGCAAGGGCCAGAATTTCCCACAGACAACCAATACATATCGGAACACTGATACC

GCAGAGCACCTGATTATGTGGGGCATTCACCACCCATCCTCCACGCAAGAGAAGAATGATC

TGTATGGAACTCAGAGCCTGTCAATCTCCGTGGGATCTAGCACATATAGAAATAATTTTGT

GCCTGTGGTCGGCGCGCGACCACAGGTTAATGGACAATCAGGACGCATTGATTTCCACTGG

ACCTTGGTTCAGCCCGGGGACAATATAACATTCAGCCACAACGGTGGCCTGATCGCCCCCT

CGCGGGTGAGTAAGCTGATTGGCAGAGGACTCGGTATTCAGAGCGATGCCCCTATTGATAA

TAACTGCGAAAGCAAATGTTTTTGGAGAGGGGGGTCGATCAACACCAGATTACCCTTTCAG

AATCTCTCTCCTAGAACCGTTGGTCAGTGCCCGAAATATGTCAACAAGCGTAGTTTGATGC

TAGCCACTGGAATGCGCAACGTACCAGAACTCATCCAGGGAAGGGGTTTGTTCGGAGCGAT

TGCAGGTTTCCTGGAAAATGGGTGGGAGGGAATGGTGGACGGGTGGTATGGGTTTCGCCAT

CAGAACGCACAGGGAACAGGTCAGGCAGCCGACTATAAGTCTACACAAGCCGCCATAGATC

AGATCACGGGAAAGCTAAACCGCTTGGTGGAGAAGACAAATACCGAGTTCGAGTCTATAGA

GAGTGAGTTTTCCGAGATAGAACATCAAATCGGTAATGTGATCAACTGGACTAAAGACTCG

ATAACAGACATCTGGACCTACCAGGCGGAACTGCTCGTCGCCATGGAGAACCAGCACACTA

TCGATATGGCTGATTCAGAAATGCTGAACCTGTATGAACGCGTACGGAAACAGCTGCGCCA

GAATGCAGAGGAGGATGGGAAAGGCTGTTTTGAAATCTACCACGCCTGCGACGATAGCTGC

ATGGAAAGCATCCGCAATAACACATATGACCACTCTCAGTATCGCGAGGAAGCTCTTCTGA

ACCGTCTCAACATCAATCCAGTGACGTTGTCATCTGGATACAAAGACATCATATTATGGTT

TTCCTTCGGCGCAAGTTGCTTCGTGCTCCTGGCAGTTGTCATGGGCCTGGTCTTCTTCTGT

CTCAAGAATGGGAATATGAGATGCACGATCTGTATC

771
ATGTACAAGATTGTTGTGATCATCGCTCTGCTCGGTGCCGTCAAAGGGTTGGATAAGATTT

GCCTCGGCCACCATGCAGTAGCCAACGGCACAATTGTGAAAACTCTCACCAACGAGCAGGA

AGAGGTCACCAATGCCACCGAAACAGTCGAGTCAACTGGCATTAATCGATTATGTATGAAA

GGAAGAAAGCATAAAGACTTGGGAAACTGTCATCCTATCGGGATGCTCATCGGAACACCAG

CATGTGACCTCCATTTAACCGGAATGTGGGACACATTAATCGAGCGTGAGAACGCAATTGC

CTATTGCTACCCTGGCGCAACAGTTAACGTCGAAGCTTTGAGACAGAAGATTATGGAGTCA

GGAGGCATCAATAAAATCTCGACCGGGTTTACCTACGGCTCCTCCATCAACTCGGCTGGCA

CAACCAGAGCCTGCATGCGTAACGGAGGCAATAGTTTCTACGCTGAGCTTAAGTGGCTGGT

AAGTAAATCAAAAGGTCAAAATTTCCCACAGACTACGAATACTTACAGAAATACAGACACA

GCCGAACACCTTATCATGTGGGGGATCCACCACCCTAGCAGTACTCAGGAAAAAAACGATC

TGTACGGCACCCAGAGCCTGTCGATCTCTGTGGGAAGTTCAACTTACCGAAATAATTTCGT

CCCTGTCGTTGGTGCAAGGCCTCAGGTCAATGGCCAGTCAGGACGCATCGATTTCCATTGG

ACTCTGGTGCAACCGGGCGACAACATTACCTTTTCACATAATGGCGGCCTTATCGCCCCCT

CCCGAGTGAGTAAGCTGATCGGTCGGGGATTGGGAATCCAGTCTGATGCACCCATTGATAA

TAACTGTGAATCTAAATGTTTCTGGAGAGGAGGTTCCATTAATACACGGCTGCCCTTTCAG

AACCTGTCCCCTCGAACCGTCGGACAGTGCCCCAAGTACGTGAACAGGAGAAGTCTCATGC

TGGCGACAGGGATGAGAAACGTTCCCGAACTGATTCAGGGACGGGGCTTATTCGGGGCTAT

TGCAGGCTTTCTGGAAAACGGCTGGGAGGGGATGGTGGACGGCTGGTACGGATTCAGGCAT

CAGAACGCACAGGGCACCGGCCAAGCAGCCGACTACAAGAGCACTCAGGCAGCCATCGACC

AGATTACAGGAAAACTTAATAGGCTTGTGGAGAAAACCAATACCGAATTCGAGTCAATTGA

ATCCGAGTTTAGCGAGATCGAACATCAAATCGGCAACGTGATTAACTGGACAAAGGACTCC

ATCACGGACATATGGACTTACCAGGCCGAACTGTTGGTGGCCATGGAAAATCAACATACAA

TTGATATGGCAGACAGTGAGATGCTGAACCTGTACGAGAGGGTCAGAAAGCAGCTACGTCA

GAACGCTGAAGAGGACGGGAAGGGCTGTTTCGAAATTTATCACGCCTGTGACGACTCCTGC

ATGGAATCTATCCGCAATAATACTTATGACCACAGTCAGTATCGCGAAGAGGCCCTCTTAA

ACAGATTAAACATCAATCCGGTGACTCTTAGCAGTGGCTACAAGGACATTATTTTATGGTT

TTCGTTCGGAGCTAGCTGTTTCGTCCTCCTCGCCGTGGTGATGGGTCTGTTCTTCTTTTGC

CTCAAGAATGGAAATATGAGATGTACAATCTGTATA

772
ATGTATAAGATAGTCGTGATCATTGCGCTTCTGGGAGCAGTAAAGGGTCTTGACAAGATTT

GTCTGGGCCACCATGCTGTGGCCAACGGGACTATTGTTAAGACTCTGACTAATGAACAGGA

AGAAGTTACAAACGCTACTGAGACGGTGGAGAGCACTGGCATAAATAGATTGTGTATGAAA

GGGAGGAAACACAAAGACTTGGGTAATTGCCACCCGATTGGGATGCTAATTGGGACTCCCG

CTTGTGACCTGCACCTTACTGGCATGTGGGATACCCTAATAGAACGTGAGAACGCCATTGC

CTATTGTTACCCAGGCGCTACTGTCAATGTGGAGGCACTTAGGCAGAAGATCATGGAAAGC

GGCGGCATCAACAAGATCTCCACCGGATTTACCTATGGTTCAAGTATCAACAGTGCCGGTA

CCACCCGCGCTTGTATGCGCAACGGAGGAAACAGTTTTTATGCTGAGCTCAAATGGCTAGT

AAGTAAGTCTAAGGGACAAAATTTCCCTCAGACCACCAACACTTATCGTAACACAGACACC

GCAGAGCATCTCATTATGTGGGGGATACACCATCCCAGCAGCACACAGGAGAAGAACGATC

TGTATGGCACCCAATCGCTCTCCATCTCAGTGGGTTCTTCTACCTATAGAAATAACTTCGT

GCCTGTCGTGGGCGCACGGCCACAGGTGAACGGGCAGAGTGGCAGAATCGATTTTCATTGG

ACGCTGGTCCAGCCCGGCGATAACATTACCTTCTCACACAATGGGGGATTGATCGCCCCTT

CTAGGGTATCAAAATTGATCGGCAGGGGACTTGGGATCCAAAGCGATGCCCCTATTGACAA

CAACTGCGAATCGAAATGCTTCTGGCGGGGGGGCAGCATTAATACACGGCTGCCCTTCCAA

AATTTATCCCCAAGAACAGTTGGCCAGTGCCCTAAATACGTCAACCGTCGCAGCCTTATGT

TAGCCACAGGAATGCGGAACGTCCCGGAGCTTATTCAGGGCAGGGGCCTGTTCGGCGCAAT

CGCGGGCTTTCTGGAAAATGGTTGGGAAGGGATGGTTGACGGCTGGTACGGGTTCAGGCAC

CAGAATGCCCAGGGAACAGGTCAGGCCGCTGACTATAAGTCAACACAAGCAGCCATCGACC

AAATTACCGGCAAGCTGAATAGACTTGTGGAAAAAACGAATACAGAATTCGAGAGTATTGA

AAGTGAATTTAGTGAGATTGAACACCAAATTGGCAATGTCATTAACTGGACGAAAGATTCA

ATCACCGACATCTGGACCTATCAGGCTGAACTCTTGGTCGCAATGGAAAACCAACATACCA

TCGACATGGCTGATTCTGAGATGCTCAACTTATACGAGCGAGTTCGAAAGCAACTGCGGCA

GAATGCCGAGGAGGATGGGAAGGGGTGTTTCGAAATTTATCATGCCTGCGACGACAGTTGT

ATGGAGAGCATCCGTAATAATACTTATGACCATAGTCAATACAGAGAGGAGGCTCTTCTGA

ACAGGCTGAACATCAACCCTGTGACCTTAAGCTCCGGATACAAGGACATTATCTTGTGGTT

CAGTTTTGGAGCCTCATGTTTCGTTCTGTTGGCAGTTGTGATGGGCCTCTTCTTCTTCTGC

CTGAAAAACGGAAACATGCGTTGCACTATATGCATC

773
ATGTACAAGATTGTGGTCATCATTGCCCTGCTTGGGGCCGTCAAGGGCCTGGACAAAATTT

GCTTGGGGCACCATGCCGTGGTTAATGGCACCATCGTCAAAACCCTTACGAACGAACAAGA

AGAGGTCACCAACGCCACTGAGACAGTTGAAAGTACAGGCCTCAATCGATTGTGCATGAAA

GGTAGGAATCACAAAGATCTGGGGAACTGTCACCCCATAGGGATGCTGATTGGCACACCAG

CCTGTGATCTGCATTTGACAGGGACCTGGGATACTCTAATTGAGAGAGAGAACGCTATTGC

CTACTGCTACCCCGGCGCCACAGTTAACGAAGAGGCTCTGCGGCAGAAAATAATGGAATCC

GGTGGTATTAACAAGATTAGTACAGGGTTTACATACGGATCGTCTATTAATTCAGCTGGTA

CAACTCGGGCTTGCATGAGGAACGGTGGCAACTCATTCTATGCAGAACTGAAGTGGTTGGT

AAGTAAGTCGAAAGGTCAAAATTTTCCCCAGACAACAAATACATATCGCAATACCGACACC

GCGGAACATTTGATCATGTGGGGCATCCACCATCCATCAAGTACACAGGAGAAGAATGACC

TTTACGGTACTCAGAGTCTGAGCATTTCAGTTGGATCCAGTACATACCAAAATAACTTCGT

TCCTGTCGTCGGAGCCCGCCCGCAGGTAAATGGTCAGTCCGGGCGCATTGACTTTCATTGG

ACCCTCGTGCAGCCCGGCGATAACATAACCTTCTCACACAATGGAGGACTGATCGCACCCA

GCAGAGTGAGCAAACTTATCGGGAGAGGTCTGGGGATCCAAAGTGACGCCCCCATTGATAA

CAACTGTGAGTCCAAATGTTTCTGGCGAGGGGGTTCAATTAACACCCGCTTGCCTTTCCAA

AACCTGAGCCCTCGGACGGTGGGCCAGTGTCCAAAGTATGTGAATAAACGGTCTCTGATGT

TAGCTACTGGCATGAGAAACGTTCCTGAGTTGATGCAGGGAAGGGGTCTCTTCGGCGCAAT

CGCTGGCTTTATTGAGAACGGGTGGGAGGGAATGGTGGACGGCTGGTATGGTTTTAGGCAT

CAGAATGCCCAGGGCACCGGACAGGCGGCTGATTATAAATCAACTCAAGCCGCCATCGACC

AAATCACCGGGAAACTAAACCGTCTGATCGAAAAAACCAATACTGAGTTCGAGTCTATCGA

GAGCGAGTTTAGTGAAATCGAACACCAGATTGGAAACGTGATCAATTGGACAAAAGATAGC

ATTACCGATATTTGGACCTACCAGGCCGAATTGCTGGTGGCGATGGAAAATCAGCACACAA

TCGACATGGCAGACTCGGAGATGTTGAATCTGTATGAGAGAGTGAGGAAGCAGCTGCGCCA

GAATGCCGAAGAGGATGGAAAGGGATGCTTCGAGATCTACCATGCATGTGACGACTCCTGT

ATGGAAAGCATCAGAAATAATACATACGATCACTCTCAATATCGAGAGGAGGCGCTTCTTA

ATCGTTTAAATATCAATCCCGTCACACTGTCCTCTGGTTATAAGGACATAATTTTGTGGTT

CTCGTTCGGTGCCAGTTGTTTCGTCCTGCTAGCGGTCGTGATGGGCCTGGTGTTTTTTTGC

CTTAAAAACGGGAACATGCGGTGCACCATCTGCATC

774
ATGTACAAGATTGTCGTCATTATCGCGCTGTTGGGGGCCGTCAAGGGACTGGATAAGATTT

GTCTGGGCCATCACGCCGTGGCCAACGGCACAATCGTCAAGACTCTGACCAACGAACAGGA

AGAGGTCACCAACGCCACAGAAACCGTGGAGAGTACGGGTATTAACCGCCTCTGCATGAAG

GGTCGGAAGCATAAGGACCTCGGTAACTGTCATCCAATCGGCATGTTGATTGGCACACCCG

CCTGCGACCTGCACCTGACTGGCATGTGGGACACACTGATTGAAAGGGAAAACGCAATCGC

GTACTGTTACCCAGGTGCAACGGTGAACGTTGAAGCACTGAGGCAGAAGATCATGGAGAGC

GGGGGCATCAACAAAATTAGCACGGGCTTCACATACGGTAGCAGTATCAACAGCGCTGGCA

CCACACGGGCCTGCATGCGGAATGGAGGGAACAGTTTCTACGCTGAACTGAAGTGGTTAGT

GAGCAAATCTAAGGGTCAGAATTTCCCCCAAACCACTAATACCTACCGCAACACTGACACC

GCCGAGCACTTAATAATGTGGGGCATCCATCATCCTTCAAGCACGCAGGAGAAGAACGACC

TGTACGGCACCCAGTCTCTGAGTATCTCGGTGGGTTCGTCCACCTATAGAAACAATTTTGT

GCCAGTGGTGGGGGCCAGGCCACAGGTCAATGGACAATCGGGACGTATCGACTTTCATTGG

ACCCTCGTGCAGCCTGGTGATAACATTACATTCAGCCATAATGGGGGCCTCATCGCCCCCA

GTAGGGTCTCCAAGCTCATTGGGAGAGGACTCGGAATCCAGAGTGATGCACCTATTGACAA

CAACTGTGAGAGCAAATGTTTTTGGAGAGGCGGGTCTATTAACACTCGATTGCCTTTCCAA

AATCTCTCACCTAGGACCGTCGGTCAGTGTCCTAAGTACGTGAATAGGAGAAGCCTCATGC

TCGCGACAGGCATGAGAAACGTGCCCGAACTGATCCAGGGCAGGGGACTCTTCGGGGCTAT

CGCAGGATTCTTAGAGAATGGGTGGGAAGGAATGGTGGATGGATGGTATGGCTTTAGGCAT

CAGAACGCTCAGGGCACTGGCCAAGCTGCGGACTACAAGAGCACTCAGGCCGCAATAGACC

AGATTACCGGCAAGTTGAATCGCCTAGTTGAAAAGACTAATACAGAGTTTGAGAGCATTGA

AAGCGAGTTTAGCGAAATTGAACATCAGATCGGCAATGTTATAAACTGGACAAAGGACTCC

ATAACTGATATATGGACTTACCAGGCAGAGCTACTAGTCGCCATGGAGAACCAGCATACTA

TCGACATGGCCGACTCAGAGATGCTGAACCTATACGAAAGAGTTCGGAAGCAGTTAAGACA

AAACGCCGAGGAGGACGGAAAGGGTTGCTTCGAAATCTACCACGCATGTGACGACTCATGC

ATGGAATCTATCAGGAATAACACATACGATCATTCACAGTATAGGGAGGAGGCTTTGCTGA

ATCGCCTCAATATCAATCCCGTCACTTTATCTAGCGGCTACAAGGACATTATCTTGTGGTT

CAGTTTTGGTGCCTCTTGCTTTGTGCTCCTGGCAGTGGTGATGGGACTCTTTTTTTTCTGT

TTGAAGAACGGTAATATGCGTTGTACAATTTGCATC

775
ATGTACAAGATTGTGGTGATCATCGCACTGCTGGGTGCTGTGAAAGGCCTGGACAAAATAT

GTTTGGGTCACCACGCCGTGGCAAATGGCACCATAGTCAAAACCCTCACCAACGAACAAGA

GGAAGTGACGAATGCGACTGAAACAGTGGAGTCGACCGGCATCAACCGTCTGTGTATGAAA

GGCAGAAAACATAAGGATCTCGGCAATTGCCATCCCATTGGAATGTTAATAGGGACGCCTG

CGTGCGATTTGCATCTGACTGGGATGTGGGATACCCTAATAGAGCGGGAGAACGCCATAGC

CTATTGCTACCCAGGAGCTACCGTCAATGTGGAAGCCCTACGGCAGAAAATTATGGAAAGC

GGTGGTATCAATAAGATTTCCACCGGATTTACATACGGGTCCTCCATCAATTCAGCCGGGA

CGACTCGTGCTTGCATGCGCAACGGAGGTAACTCGTTCTATGCCGAACTCAAATGGCTGGT

GAGCAAGTCTAAGGGACAGAATTTTCCACAAACAACCAACACCTACCGTAATACCGATACC

GCTGAACACCTTATCATGTGGGGCATTCACCACCCTTCCAGCACACAGGAGAAAAACGACT

TGTACGGCACACAGTCCCTCAGTATTTCCGTTGGTAGCTCTACTTACAGAAACAATTTTGT

TCCCGTCGTCGGTGCCCGTCCTCAAGTCAACGGACAGTCCGGCAGAATTGACTTTCATTGG

ACGTTAGTGCAGCCTGGGGACAACATTACCTTCAGCCACAATGGGGGTCTGATTGCGCCGT

CCCGCGTTAGCAAGCTGATAGGCCGAGGGCTGGGCATTCAGAGCGATGCACCCATCGACAA

TAATTGCGAATCCAAATGCTTTTGGCGGGGTGGGAGTATTAATACTCGCCTCCCCTTTCAA

AATCTCTCACCACGCACTGTTGGGCAGTGTCCCAAATACGTGAATCGGCGTAGCTTAATGC

TGGCTACAGGGATGAGGAACGTGCCCGAACTGATTCAAGGCCGTGGTCTTTTTGGAGCCAT

TGCCGGCTTTTTAGAGAATGGCTGGGAGGGCATGGTTGACGGTTGGTATGGGTTTAGGCAC

CAGAACGCCCAGGGCACTGGACAGGCAGCCGATTATAAGTCCACACAGGCCGCTATTGATC

AGATTACTGGAAAATTGAATAGACTCGTGGAGAAAACTAACACCGAGTTCGAGTCTATTGA

GTCAGAATTTTCTGAGATTGAGCACCAGATCGGTAATGTTATCAATTGGACAAAGGACAGC

ATCACTGACATTTGGACGTACCAGGCCGAGCTGCTGGTGGCAATGGAGAACCAGCACACCA

TCGACATGGCGGACTCAGAGATGCTGAACCTATATGAAAGGGTGCGTAAACAGCTTAGGCA

AAATGCTGAGGAGGACGGCAAAGGATGTTTCGAGATTTATCATGCCTGCGATGACTCCTGC

ATGGAATCAATTCGCAATAATACTTATGACCATTCACAGTATCGCGAAGAAGCGCTTCTGA

ATCGGCTAAATATTAACCCCGTAACTCTGTCTTCTGGATACAAGGATATTATCCTGTGGTT

TAGTTTTGGAGCTTCATGTTTCGTATTGTTGGCCGTGGTGATGGGGCTGTTCTTTTTCTGT

CTTAAGAACGGCAACATGAGGTGTACAATTTGCATT

776
ATGTACAAGATCGTCGTGATCATTGCCCTGCTCGGGGCCGTGAAGGGCCTTGACAAGATTT

GTCTAGGCCACCATGCAGTTGCTAACGGAACTATTGTCAAGACATTGACCAACGAACAGGA

GGAAGTGACAAATGCCACAGAGACAGTTGAGTCTACTGGGATAAACAGATTGTGTATGAAA

GGCAGGAAACACAAAGATCTCGGAAATTGTCATCCTATCGGAATGCTGATAGGAACTCCCG

CTTGCGATTTGCATTTGACAGGAATGTGGGACACACTGATCGAACGAGAAAACGCCATCGC

GTACTGCTACCCCGGTGCCACTGTGAACGTGGAGGCCCTTCGGCAAAAGATCATGGAATCA

GGAGGAATCAATAAGATCTCTACCGGGTTCACTTATGGCAGCTCTATCAACTCCGCCGGTA

CTACTAGGGCCTGCATGAGAAATGGGGGAAATAGCTTCTACGCAGAACTGAAGTGGCTGGT

GAGCAAGTCGAAGGGGCAGAACTTCCCTCAGACTACGAATACCTATCGCAATACCGATACT

GCTGAGCATTTGATTATGTGGGGCATCCATCATCCGTCGTCGACGCAAGAGAAAAATGACC

TTTATGGCACACAGTCCTTGTCTATTTCTGTAGGGTCTTCTACCTATCGCAATAACTTTGT

GCCTGTTGTCGGCGCCAGGCCACAGGTAAATGGACAGTCTGGCAGAATTGATTTCCACTGG

ACGCTCGTACAGCCTGGGGATAATATTACATTCTCACACAACGGCGGACTTATCGCCCCGA

GCCGTGTCTCAAAGCTGATTGGAAGGGGACTCGGCATTCAGTCCGATGCGCCCATTGACAA

CAATTGCGAGAGCAAGTGTTTTTGGCGCGGTGGATCCATCAATACCCGCCTTCCTTTTCAG

AATTTATCACCACGTACCGTCGGCCAGTGTCCCAAATATGTGAATCGAAGATCTCTGATGC

TGGCCACAGGCATGCGGAACGTCCCTGAGCTGATCCAGGGAAGGGGGCTTTTCGGAGCGAT

TGCCGGGTTTCTGGAAAATGGATGGGAAGGAATGGTGGACGGCTGGTACGGCTTCAGACAT

CAGAATGCCCAGGGAACCGGGCAGGCTGCGGATTACAAATCTACCCAAGCTGCTATCGACC

AGATCACAGGTAAGCTGAATCGGCTCGTGGAGAAAACTAACACTGAATTTGAGTCCATAGA

AAGCGAATTTAGTGAAATCGAACACCAAATCGGAAATGTGATTAACTGGACAAAAGATAGC

ATTACCGATATCTGGACCTACCAAGCTGAATTGCTGGTCGCCATGGAGAACCAACACACTA

TTGACATGGCAGACTCCGAAATGCTAAATTTGTACGAGCGCGTCCGCAAACAGTTGCGGCA

AAACGCAGAAGAAGATGGAAAGGGCTGCTTTGAGATCTACCACGCCTGTGACGATTCCTGC

ATGGAATCGATACGAAACAATACTTATGACCATAGCCAGTATCGTGAAGAAGCTCTGCTAA

ATCGCCTCAACATTAACCCTGTGACATTGAGCAGTGGGTACAAGGATATTATTCTCTGGTT

TTCTTTCGGTGCCTCGTGCTTTGTTCTGCTGGCGGTGGTGATGGGACTCTTCTTCTTCTGC

CTCAAAAATGGGAATATGCGGTGTACAATCTGTATC

777
ATGTACAAGATCGTCGTTATCATTGCCCTGCTGGGAGCAGTAAAAGGACTGGACAAAATTT

GCTTAGGCCATCACGCGGTGGCAAATGGGACCATCGTAAAGACACTGACCAACGAGCAGGA

GGAGGTGACAAACGCTACAGAAACAGTAGAATCGACCGGGATCAACAGGCTCTGTATGAAG

GGCCGGAAACATAAGGATCTGGGGAATTGCCATCCTATCGGAATGCTCATTGGTACGCCTG

CTTGTGACCTCCACCTCACTGGAATGTGGGACACACTCATCGAGCGCGAGAACGCAATAGC

ATATTGTTATCCGGGCGCAACTGTCAACGTTGAGGCACTGAGGCAGAAGATTATGGAGAGT

GGGGGCATCAACAAGATATCAACAGGCTTTACATATGGATCGAGCATCAATTCAGCAGGGA

CGACCCGGGCGTGCATGAGGAATGGAGGGAATAGCTTTTACGCCGAATTGAAATGGCTCGT

GTCTAAGAGCAAAGGCCAAAATTTTCCACAGACAACTAATACCTATCGCAACACCGATACG

GCCGAACATCTAATCATGTGGGGAATTCACCACCCAAGTTCGACCCAGGAAAAGAACGATC

TCTACGGCACCCAGAGTCTGAGCATCTCGGTGGGATCCTCGACGTACCGGAACAATTTCGT

GCCTGTCGTGGGAGCGCGACCGCAGGTTAATGGGCAATCCGGGAGGATCGATTTTCACTGG

ACGCTAGTCCAACCCGGGGACAACATCACTTTCAGCCACAACGGTGGACTTATTGCTCCTT

CCCGAGTCAGTAAACTCATCGGCCGGGGACTTGGGATTCAAAGCGATGCACCAATAGATAA

TAACTGTGAGTCTAAGTGCTTCTGGCGGGGAGGTAGTATTAACACACGACTCCCATTTCAG

AACCTGTCCCCAAGGACCGTGGGTCAGTGCCCTAAGTACGTGAACAGACGAAGCCTGATGT

TGGCAACCGGAATGAGAAACGTCCCCGAGCTGATCCAGGGGAGGGGACTGTTTGGGGCAAT

AGCGGGATTTCTGGAGAACGGATGGGAAGGGATGGTTGACGGATGGTACGGGTTTAGGCAC

CAGAACGCCCAAGGGACTGGACAGGCTGCAGATTATAAAAGTACACAAGCGGCCATCGATC

AGATCACCGGTAAACTGAATAGACTTGTCGAGAAAACCAATACAGAGTTCGAGTCGATAGA

ATCGGAATTCAGCGAGATCGAACACCAGATCGGCAATGTGATCAATTGGACTAAAGACAGC

ATCACCGATATCTGGACCTATCAAGCTGAGCTCCTAGTAGCTATGGAGAATCAACACACAA

TAGACATGGCTGACTCGGAAATGTTGAACCTGTATGAACGTGTCCGCAAGCAGCTGAGGCA

GAACGCCGAGGAGGACGGTAAGGGATGCTTCGAGATCTACCATGCTTGTGACGATTCTTGT

ATGGAAAGTATCAGAAACAACACCTACGACCATAGCCAGTACAGGGAAGAGGCCCTGCTGA

ATAGACTGAATATCAACCCAGTGACCCTCAGCTCTGGGTATAAAGATATCATTCTGTGGTT

CTCATTCGGTGCATCGTGCTTCGTACTGCTGGCCGTTGTCATGGGACTCTTTTTCTTTTGT

CTTAAAAATGGCAATATGCGATGCACAATTTGCATT

778
ATGTATAAAATAGTTGTCATCATCGCCCTCCTAGGTGCAGTTAAGGGGCTCGACAAAATTT

GTTTAGGCCACCACGCCGTGGCAAACGGCACCATCGTCAAGACCCTTACTAATGAACAAGA

GGAGGTGACTAATGCTACAGAGACCGTGGAGTCTACCGGCATAAATCGACTATGTATGAAA

GGCCGAAAGCACAAAGATTTGGGGAACTGTCATCCTATCGGAATGCTGATTGGAACCCCAG

CCTGCGATCTGCACCTCACCGGCATGTGGGATACCCTGATCGAACGTGAAAATGCTATCGC

ATACTGTTACCCTGGAGCCACAGTCAACGTTGAGGCATTGAGGCAAAAGATCATGGAGAGC

GGTGGAATCAATAAGATCTCAACAGGGTTTACCTACGGCAGCTCTATAAACTCCGCTGGCA

CAACAAGAGCCTGTATGCGCAATGGGGGAAATTCCTTTTATGCCGAACTGAAATGGCTTGT

ATCAAAGAGCAAGGGCCAGAACTTCCCCCAAACGACTAATACTTATCGCAACACAGATACA

GCTGAGCACCTGATAATGTGGGGTATCCACCATCCATCATCAACGCAAGAAAAGAACGATC

TGTACGGGACTCAAAGCCTGTCTATCTCCGTCGGCAGCAGCACATATAGGAATAACTTTGT

GCCCGTCGTCGGCGCTAGACCGCAGGTTAACGGACAGAGTGGCCGGATAGACTTCCACTGG

ACTCTGGTCCAGCCTGGCGATAACATCACCTTCAGCCACAATGGCGGTTTGATAGCACCCT

CTCGTGTGTCTAAGCTGATCGGAAGAGGCCTCGGGATTCAGTCCGACGCCCCGATCGACAA

TAACTGCGAGAGTAAATGTTTTTGGAGAGGAGGATCCATTAACACCCGGCTGCCGTTCCAG

AATTTGAGCCCTAGGACAGTGGGGCAGTGTCCCAAATATGTCAACCGCCGAAGTCTGATGC

TAGCGACTGGCATGAGGAACGTTCCCGAGCTCATCCAGGGACGCGGGCTGTTTGGCGCCAT

TGCCGGTTTTCTGGAAAACGGATGGGAAGGTATGGTAGATGGCTGGTATGGATTTCGCCAC

CAGAACGCGCAGGGCACTGGGCAGGCGGCGGATTACAAGTCCACACAGGCAGCGATTGATC

AGATCACCGGCAAACTGAATCGCCTGGTGGAGAAAACAAATACAGAGTTTGAGTCCATCGA

AAGCGAGTTTAGCGAAATTGAGCATCAAATTGGCAACGTCATTAATTGGACAAAAGACAGC

ATTACCGATATCTGGACATACCAGGCGGAGCTACTGGTCGCAATGGAGAACCAGCATACCA

TCGATATGGCCGACAGTGAAATGCTGAACCTCTATGAGAGAGTGCGAAAGCAGTTAAGACA

GAATGCGGAAGAGGATGGGAAAGGTTGTTTTGAGATCTATCACGCCTGTGACGACTCTTGC

ATGGAAAGCATTCGAAATAATACCTACGACCATAGTCAGTATCGAGAAGAGGCTCTGTTAA

ACCGATTAAATATTAACCCGGTAACTTTGTCGAGTGGGTACAAGGATATTATCCTTTGGTT

TTCCTTCGGGGCATCCTGTTTTGTGTTGCTGGCTGTGGTAATGGGACTGTTCTTTTTTTGC

TTAAAGAACGGTAATATGAGATGCACAATCTGTATA

779
ATGTATAAAGTAGTTGTGATCATCGCTTTACTGGGCGCAGTCAAAGGTTTGGACAAGATTT

GTCTGGGTCACCATGCCGTTGCCAATGGGACCATAGTTAAAACCTTAACAAATGAGCAGGA

AGAGGTCACAAACGCTACAGAGACTGTGGAGTCCACTGGGATAAACAGACTGTGTATGAAA

GGACGCAAGCACAAGGACCTCGGAAATTGTCACCCAATTGGAATGCTGATTGGCACTCCTG

CCTGCGATTTACATCTAACCGGCACATGGGACACCCTGATCGAGCGGGAGAACGCGATCGC

CTACTGCTACCCCGGAGCCACCGTCAACGTAGAGGCATTACGGCAGAAGATCATGGAGAGT

GGAGGCATAGATAAGATCTCCACCGGATTCACCTATGGTTCTAGCATTAACTCCGCAGGTA

CAACAAGAGCTTGCATGCGAAATGGAGGGAATAGCTTTTACGCTGAGCTCAAATGGCTTGT

GAGCAAAAACAAGGGACAGAATTTTCCCCAGACCACTAATACTTATAGAAACACTGACACC

GCTGAGCACTTAATCATGTGGGGAATCCACCACCCCTCCAGTATCCAAGAAAAGAACGACC

TGTATGGAACACAGAGCTTAAGTATCAGCGTGGGGTCATCTACCTACCGGAACAACTTCGT

TCCTGTGGTTGGGGCTAGACCACAGGTGAATGGTCAGAGCGGCAGAATCGATTTCCACTGG

ACCCTCGTCCAGCCAGGAGACAACATCACCTTCAGCCATAATGGCGGCCTGATTGCCCCTT

CTAGGGTTTCCAAATTGATTGGACGCGGCCTCGGGATTCAATCAGACGCTCCCATTGATAA

TAATTGTGAGAGCAAATGCTTCTGGAGGGGAGGATCCATTAACACCCGATTGCCATTCCAG

AATTTATCCCCACGGACCGTGGGCCAGTGCCCTAAATACGTGAATAGGCGATCCCTGATGT

TGGCAACAGGCATGAGAAACGTCCCTGAGCTGATCCAAGGGCGCGGACTATTTGGAGCAAT

AGCCGGCTTCTTAGAGAACGGATGGGAAGGAATGGTGGATGGTTGGTACGGTTTCCGACAC

CAGAACGCCCAAGGAACTGGACAGGCTGCCGATTACAAATCTACTCAGGCCGCTATAGATC

AGATTACAGGAAAACTGAATAGGCTGGTTGAGAAGACGAATACGGAATTTGAATCCATTGA

GAGTGAATTCAGTGAGATCGAACACCAGATTGGCAATGTGATTAACTGGACAATGGACTCC

ATCACTGATATTTGGACTTACCAGGCCGAGCTGCTTGTAGCGATGGAGAATCAACATACTA

TCGACATGGCAGACTCCGAGATGCTGAACCTGTATGAAAGAGTGCGCAAGCAGCTGAGACA

GAACGCCGAAGAAGACGGCAAAGGCTGTTTTGAAATTTACCATGCCTGCGACGACTCCTGT

ATGGAGTCCATTCGCAACAATACATACGATCACAGCCAGTACAGGGAGGAAGCGTTGCTGA

ACAGGTTGAACATAAATCCCGTGACACTTAGCTCTGGTTACAAGGATATTATACTCTGGTT

TTCCTTTGGAGCTTCTTGCTTCGTGCTGCTCGCAGTCGTGATGGGTCTGGTTTTTTTTTGC

CTCAAGAATGGCAACATGCGTTGCACTATATGTATC

780
ATGTACAAGATCATCGTCATCATCGCTCTCCTCGGTGCGGTGAAGGGTCTGGATAAGATTT

GCTTGGGTCACCACGCTGTTGCCAATGGCACGATTGTAAAGACCCTGACTAACGAGCAAGA

AGAAGTTACTAATGCCACAGAAACCGTGGAGTCTACCGGCATTAACAGATTATGCATGAAA

GGTCGGAAACATAAAGATTTGGGGAATTGCCACCCTATAGGGATGCTCATCGGGACTCCTG

CGTGCGACCTCCACCTTACCGGAACCTGGGACACTCTGATTGAGCGCGAAAATGCAATTGC

CTATTGTTATCCCGGGGCAACAGTGAACGTCGAGGCCTTGCGGCAGAAGATAATGGAATCC

GGCGGAATCGACAAGATTAGCACCGGCTTCACCTACGGCTCCTCTATTAATTCTGCTGGAA

CAACTAGGGCTTGCATGAGAAACGGCGGCAACTCATTCTACGCCGAGCTCAAGTGGCTTGT

GTCTAAGTCTAAAGGACAAAATTTCCCACAGACCACCAATACGTATCGCAATACAGACACT

GCGGAACATCTAATCATGTGGGGCATCCATCACCCGAGTAGTACCCAGGAAAAGAACGACC

TCTACGGCACTCAATCACTGTCCATCAGCGTTGGCTCTAGCACATACCGGAACAATTTCGT

CCCTGTGGTAGGAGCTAGACCCCAGGTTAACGGACAGTCAGGCCGTATCGACTTTCATTGG

ACCTTAGTACAACCAGGGGATAACATTACCTTTTCCCATAACGGGGGACTGATCGCCCCTA

GCCGCGTCAGTAAGCTCATCGGACGTGGACTCGGAATCCAGTCAGACGCCCCCATCGATAA

CAACTGCGAGTCAAAATGCTTTTGGCGAGGAGGATCTATCAACACTAGGCTGCCCTTTCAA

AATCTGTCCCCTCGCACAGTGGGTCAGTGTCCTAAATACGTGAACCGCAGATCACTCATGC

TCGCCACCGGAATGAGGAATGTGCCCGAACTCATCCAAGGGAGGGGCCTCTTCGGTGCCAT

CGCGGGATTCCTCGAAAATGGATGGGAGGGGATGGTGGATGGATGGTACGGCTTTCGGCAC

CAAAACGCTCAGGGCACCGGGCAGGCCGCCGATTATAAATCTACGCAGGCAGCTATAGACC

AAATAACCGGCAAATTAAATCGGCTGGTAGAAAAGACCAACACCGAATTCGAGAGCATAGA

GAGCGAATTTTCAGAAATAGAGCACCAGATTGGGAACGTAATTAACTGGACAAAGGACTCT

ATAACCGATATCTGGACATACCAGGCGGAACTCTTGGTGGCCATGGAGAATCAGCACACCA

TTGACATGGCCGATAGTGAGATGCTGAATCTCTACGAGAGGGTGCGAAAACAGCTAAGGCA

AAATGCCGAAGAGGACGGCAAGGGTTGCTTTGAGATCTACCACGCCTGCGACGACTCTTGT

ATGGAGTCCATTCGAAACAACACCTACGACCATTCTCAATACAGGGAGGAAGCTTTGCTCA

ATCGGCTCAACATCAATCCAGTCACGCTGTCTTCCGGTTATAAGGACATCATCCTCTGGTT

TAGTTTCGGAGCTTCTTGTTTTGTACTCTTAGCCGTGGTGATGGGCCTGTTCTTCTTCTGC

CTAAAAAACGGCAACATGCGGTGCACAATCTGTATT

781
ATGTACAAAATAGTGGTCATCATAGCCCTTCTGGGTGCCGTGAAGGGGCTAGACAAAATCT

GTTTGGGACATCACGCAGTAGCGAACGGCACCATCGTCAAAACGCTGACGAACGAGCAAGA

AGAGGTTACCAATGCTACAGAGACTGTGGAGTCTACTGGCATCAATAGGCTCTGCATGAAA

GGACGGAAACACAAGGACCTGGGCAATTGTCACCCTATCGGCATGTTGATCGGAACTCCCG

CCTGTGATCTGCACCTTACAGGGATGTGGGATACGCTGATCGAGCGGGAAAATGCCATAGC

TTACTGCTACCCCGGAGCGACCGTTAACGTGGAGGCCTTAAGACAGAAGATCATGGAGTCC

GGCGGGATCAATAAGATTTCCACTGGCTTTACGTACGGTTCCAGTATCAACTCCGCAGGGA

CGACGCGCGCGTGCATGAGAAACGGCGGCAACAGCTTTTACGCTGAACTCAAGTGGCTGGT

TAGCAAGTCAAAGGGCCAGAATTTCCCTCAGACCACTAACACATACAGGAATACTGACACC

GCCGAGCACCTCATCATGTGGGGAATTCACCACCCTTCCTCCACCCAGGAAAAGAACGATC

TATACGGGACCCAGTCTTTGTCCATATCTGTGGGCAGTTCAACATACCGGAACAACTTTGT

GCCTGTGGTGGGTGCTAGGCCACAGGTCAACGGGCAATCCGGTAGGATTGATTTTCACTGG

ACTCTGGTCCAGCCCGGGGACAATATAACTTTTTCGCATAATGGCGGGCTGATCGCTCCCT

CCCGGGTGTCAAAGCTGATTGGACGGGGCCTTGGTATACAGTCTGACGCGCCCATTGATAA

CAACTGCGAGTCTAAGTGTTTTTGGCGGGGAGGCAGCATCAATACTCGCCTCCCTTTTCAA

AACCTCTCCCCTAGAACAGTGGGGCAATGCCCAAAATACGTCAATAGGAGGTCCCTCATGC

TAGCAACCGGTATGCGCAACGTTCCCGAACTGATCCAGGGCCGAGGGCTGTTCGGAGCTAT

CGCAGGGTTTCTCGAAAACGGCTGGGAAGGAATGGTCGATGGCTGGTATGGGTTCAGACAT

CAGAATGCCCAGGGCACAGGACAGGCAGCAGATTACAAAAGTACTCAGGCCGCCATCGACC

AGATCACCGGCAAACTTAATAGGCTGGTGGAAAAAACCAACACCGAGTTTGAGAGTATAGA

GAGCGAGTTTTCAGAGATCGAGCATCAGATTGGGAATGTTATCAACTGGACCAAGGATTCC

ATTACTGATATTTGGACTTACCAGGCGGAACTGCTGGTTGCCATGGAGAATCAGCACACGA

TCGATATGGCCGACTCCGAAATGTTGAATTTATATGAGCGGGTGAGAAAGCAGCTCAGGCA

GAACGCAGAAGAGGACGGAAAGGGGTGCTTCGAGATCTACCATGCTTGTGACGATTCCTGT

ATGGAGTCAATTAGAAACAATACCTACGACCACTCCCAGTATAGAGAGGAGGCTCTGCTAA

ACCGCCTTAATATCAACCCGGTTACCCTGTCAAGCGGATACAAGGATATTATATTGTGGTT

TTCTTTTGGCGCATCTTGCTTCGTGTTACTCGCTGTGGTGATGGGTTTATTCTTCTTTTGT

CTGAAGAATGGGAACATGCGGTGTACCATTTGCATA

782
ATGTACAAGGTGGTGGTCATCATTGCCCTGCTGGGGGCAGTCAGGGGCTTAGATAAGATTT

GTCTTGGGCATCACGCCGTGGCCAACGGAACGACCGTGAAAACCCTCACAAATGAGCAGGA

GGAAGTTACGAATGCCACCGAGACTGTGGAGTCTACTTCTCTGAACAAACTGTGCATGAAA

GGCCGGCGTTATAAAGATCTGGGAAATTGTCATCCTATCGGCATGCTGATTGGTACTCCTG

TATGTGACCTGCACCTCACGGGCACTTGGGATACACTGATCGAGAGGGAAAATGCCACAGC

TTACTGCTACCCCGGAGTCACAATTAACGAGGAGGCACTCAGACAGAAAATCATGGAGAGC

GGTGGTATCAGCAAAATGCGCACCGGCTTTACTTATGGCCCAAGCATCAACTCTGCCGGTA

CAACACGAAGTTGCATGAGGAACGGCGGCAATAGCTTCTACGCTGAACTCAAGTGGTTAGT

CTCCGGTACGAAGGGGCAGAATTTTCCGCAGACTACAAATACATACCGAAATACAGATACA

GCTGAGCACCTGATCATCTGGGGCATCCACCACCCTAGTTCAACCCAGGAGAAAAACGATT

TGTATGGAACGCAATCTCTCTCCATTTCCGTAGGGTCCTCCACCTATCAAAACAACTTTGT

CCCGGTTATTGGGGCTAGACCTCAGGTCAATGGCCAGAGCGGTAGGATTGAGTTTCATTGG

ACTCTCGTCAGACCAGGGGACAACATCACGTTTTCCCATAATGGCGGACTCATCGCTCCAG

ACAGGGTTTCCAAGCTCATCGGAAAGGGGATTGGGATTCAGTCAGGGGCAGTAATAGATAA

GGACTGTGAGTCTAAATGTTTTTGGCGGGGAGGTTCCATAATTACCGAACTGCCATTTCAG

AATCTCTCCCCTAGAACAGTGGGGCAGTGTCCCAAATACGTTAAAAAAAGGAGTTTGCTGC

TGGCAACAGGCATGCGGAACGTCCCTGAGGTAGTACAGGGGGGGGGATTATTCGGAGCAAT

AGCCGGGTTTATCGAAAACGGGTGGGAAGGTATGGTGGATGGATGGTACGGCTTCCGTCAC

CAAAATGCTCAGGGGATCGGACAGGCCGCCGACTACAAATCTACTCAGACTGCCATAGATC

AGATTACCGGTAAACTCAACAGGCTCATCGAAAAAACAAATACTGAGTTTGAAAGCATTGA

GTCTGAGTTTTCTGAGATTGAGCATCAGATTGGCAACGTCATCAACTGGACCAAGGATTCC

ATTACAGATATCTGGACGTACCAAGCCGAGCTGCTCGTGGCAATGGAGAACCAGCATACAA

TAGACATGGCTGATTCTGAAATGCTGAATCTGTACGAACGTGTGAGAAAGCAACTGAGGCA

GAACGCTGAGGAGGACGGCAAGGGCTGTTTCGAGATCTATCATACCTGCGATAACTCATGT

ATGGAATCCATCCGGAATAATACTTATGATCACAGTCAGTATCGCGAGGAAGCCCTGCTGA

ATAGATTAAATATCAATCCTGTGAAACTGAGTTCTGGGTACAAAGATATCATCCTGTGGTT

CAGCTTTGGGGCCAGCTGTTTCGTACTGCTGGCCGTAATCATGGGGCTAGGATTCTTTTGC

CTGAAGAACGGCAATATGCGCTGCACGATTTGCATT

783
ATGTACAAAATTGTGGTGATAATTGCCCTTTTAGGCGCCGTGAAGGGCCTCGATAAAATTT

GCCTTGGCCATCATGCAGTCGCTAACGGGACTATCGTAAAGACCCTGACCAACGAACAGGA

AGAAGTTACCAATGCCACTGAAACTGTGGAGAGTACAGGCATTAACAGGCTGTGCATGAAG

GGACGCAAGCACAAGGATTTAGGGAATTGCCATCCGATCGGAATGCTGATCGGGACCCCCG

CGTGCGACCTGCACCTGACAGGAATGTGGGACACCCTTATTGAGAGAGAAAATGCTATCGC

TTATTGCTACCCTGGTGCCACTGTCAACGTGGAGGCCTTACGTCAGAAGATTATGGAATCC

GGAGGCATAAATAAGATTAGTACCGGGTTCACATATGGCTCTTCCATAAACTCTGCGGGCA

CCACTAGAGCATGTATGAGGAACGGTGGGAATAGCTTCTATGCTGAGCTCAAGTGGTTGGT

CAGCAAGTCCAAAGGTCAGAACTTTCCGCAGACAACTAATACCTACCGAAATACAGACACC

GCTGAGCACCTCATTATGTGGGGCATTCACCACCCGAGCTCAACTCAAGAGAAGAATGACT

TGTACGGAACACAATCTCTGTCCATCTCTGTGGGCAGCAGTACCTATCGGAATAATTTCGT

CCCAGTAGTGGGCGCAGGACCTCAGGTCAATGGTCAGTCCGGTCGCATCGACTTCCATTGG

ACCCTGGTGCAACCAGGCGACAACATCACCTTTTCTCACAACGGGGGGCTGATCGCACCCT

CGCGTGTGTCTAAGCTAATCGGCCGTGGCCTGGGGATCCAGTCTGATGCACCCATTGACAA

TAACTGCGAGTCTAAATGTTTCTGGAGAGGCGGATCCATTAACACGCGGCTGCCATTTCAG

AACCTGAGTCCAAGAACGGTAGGCCAGTGTCCGAAGTACGTCAATCGGAGGTCATTGATGC

TGGCAACCGGCATGAGAAATGTCCCGGAGCTGATACAGGGAAGGGGACTATTTGGAGCTAT

CGCTGGCTTCCTAGAAAATGGATGGGAGGGTATGGTCGATGGATGGTATGGGTTTCGCCAC

CAAAACGCACAGGGGACTGGGCAGGCCGCAGATTATAAGAGCACTCAAGCTGCAATCGACC

AGATCACTGGCAAACTGAATCGGCTTGTGGAGAAAACCAACACAGAATTCGAGTCAATTGA

GTCCGAGTTTAGCGAAATTGAACACCAGATCGGAAATGTTATTAACTGGACTAAGGATTCC

ATCACAGATATCTGGACCTACCAGGCAGAGCTATTGGTAGCCATGGAGAACCAACATACAA

TCGACATGGCGGATTCAGAAATGCTGAACCTGTATGAACGCGTTAGGAAGCAGCTCAGGCA

GAACGCCGAGGAGGATGGGAAAGGTTGCTTCGAGATATATCATGCCTGCGACGACAGCTGT

ATGGAGTCCATACGAAATAACACGTATGACCACAGCCAGTACCGAGAAGAGGCTCTTCTTA

ATCGGCTCAATATAAACCCAGTGACACTGTCATCCGGATACAAGGACATCATACTATGGTT

CAGCTTTGGTGCCTCTTGTTTCGTGCTACTTGCTGTGGTGATGGGCCTTTTTTTTTTCTGC

CTCAAGAACGGGAACATGAGGTGTACGATATGCATC

784
ATGTACAAGATAGTCGTGATCATTGCCCTCCTTGGTGCAGTAAAGGGATTAGACAAGATTT

GCTTGGGACACCACGCGGTTGCTAACGGAACAATAGTTAAGACACTCACTAATGAGCAAGA

GGAAGTCACAAATGCTACCGAAACCGTAGAGTCTACGGGCATCAACAGGCTTTGTATGAAA

GGCAGGAAGCACAAGGACCTTGGGAATTGTCACCCTATTGGTATGCTTATTGGCACCCCAG

CCTGCGATCTACATCTGACTGGGATGTGGGACACCCTCATCGAACGAGAGAATGCCATAGC

CTATTGCTACCCTGGCGCAACTGTGAATGTGGAAGCTTTGAGGCAGAAGATAATGGAATCC

GGCGGAATCAACAAGATATCAACAGGCTTTACTTACGGCTCGAGTATCAATTCAGCCGGCA

CAACTCGGGCCTGCATGCGGAATGGGGGAAACTCTTTCTACGCAGAACTGAAATGGCTGGT

ATCCAAGTCTAAGGGCCAGAATTTCCCGCAGACCACCAACACCTATCGCAACACTGACACA

GCAGAACATTTGATAATGTGGGGTATCCACCACCCGTCTAGTACCCAGGAGAAGAACGACT

TGTATGGCACGCAGTCATTATCTATCAGCGTGGGCTCCAGCACGTACCGGAACAACTTTGT

CCCCGTGGTTGGCGCACGACCACAAGTGAACGGACAATCCGGCCGGATCGATTTTCATTGG

ACACTCGTTCAGCCCGGCGACAATATCACCTTTTCTCACAATGGGGGCCTGATCGCGCCAA

GCCGGGTTTCCAAGCTGATCGGCAGAGGCCTCGGCATACAGAGCGATGCCCCGATCGATAA

CAATTGTGAGTCGAAATGTTTTTGGAGAGGCGGCTCTATTAACACGCGACTGCCCTTTCAG

AATCTGAGCCCGCGGACAGTGGGACAATGCCCAAAATACGTAAACAGGAGGAGTCTGATGC

TCGCGACTGGCATGAGGAACGTTCCTGAGTTGATCCAGGGCCGGGGCCTATTTGGCGCCAT

CGCAGGGTTCCTGGAGAATGGTTGGGAGGGTATGGTAGATGGATGGTACGGGTTCCGCCAC

CAGAATGCCCAGGGAACAGGCCAGGCTGCGGACTACAAATCCACTCAGGCCGCCATCGATC

AAATTACCGGAAAGCTTAACAGACTCGTCGAGAAAACGAATACAGAGTTTGAGTCAATTGA

GTCCGAGTTCAGTGAAATCGAGCACCAAATAGGAAACGTGATCAATTGGACAAAGGACAGT

ATCACCGATATCTGGACTTACCAGGCTGAACTGCTCGTAGCTATGGAGAATCAGCACACCA

TAGATATGGCAGACTCCGAGATGTTGAATTTATACGAGAGAGTCCGGAAACAGCTGCGCCA

GAACGCCGAAGAGGATGGGAAGGGCTGCTTCGAGATATACCACGCCTGTGACGACTCATGC

ATGGAGTCTATCCGAAACAATACCTACGATCATTCCCAGTATAGGGAAGAGGCCTTGCTGA

ACCGGTTGAATATTAATCCTGTCACATTGTCTAGCGGCTACAAAGACATCATCTTATGGTT

TTCGTTTGGTGCTTCATGTTTCGTGCTTCTGGCTGTGGTGATGGGACTCTTTTTCTTTTGC

CTTAAGAATGGCAATATGAGATGCACCATTTGTATT

785
ATGTATAAGATCGTGGTGATCATTGCCCTACTGGGTGCCGTGAAAGGGCTGGACAAAATTT

GCCTCGGCCACCATGCTGTCGCCAACGGCACCATCGTCAAAACGCTTACGAATGAGAAGGA

GGAAGTGACCAATGCTACCGAGACTGTGGAAAGTACAGGCCTCAACAGGCTCTGTATGAAG

GGCAGGAAACACAAAGACTTGGGTAACTGCCATCCTATAGGAATGCTCATTGGCAGCCCGG

CTTGTGACCTGCACCTTACTGGGACCTGGGATACTCTGATCGAGAGGGAGAATGCCATTGC

GTATTGTTATCCAGGAGCCACCGTAAACGGCGAGGCACTAAGGCAAAAGATTATGGAAAGC

GGGGGTATTGACAAAATTTCAACAGGGTTCACATATGAGTCTAGCATCAACTCAGCCGGCA

CAACGAGAGCATGCATGCGGAACGGGGGCAATTCCTTTTACGCTGAGTTGAAGTGGCTGGT

GTCCAAGAGCAAAGGGCAGAATTTCCCACAGACTACCAACACCTATAGAAATACGGATACA

GCAGAGCACCTGATTATGTGGGGTATCCACCACCCAAGCTCCACGCAAGAAAAGAATGATC

TGTATGGAACTCAAAGCCTCTCTATTAGTGTGGGGTCTAGCACTTACCGGAACAACTTCGT

CCCTGTGGTGGGCGCTCGCCCTCAGGTTAATGGCCAGTCCGGAAGAATTGACTTTCATTGG

ACTCTCGTCCAGCCAGGGGATAATATAACATTCTCTCACAATGGAGGACTGATTGCACCTT

CTCGGGTGAGCAAGCTGATAGGCCGCGGGCTGGGGATCCAGAGCGATGCTCCAATAGATAA

TAATTGCGAATCAAAGTGCTTTTGGAGGGGGGGATCTATTAATACGCGGCTTCCATTCCAG

AACCTCAGTCCTCGGACTGTTGGACAATGCCCCAAATATGTGAACAAGCGCAGCCTTATGC

TCGCTACCGGGATGAGGAATGTCCCTGAATTAATGCAGGGACGCGGCCTATTCGGAGCAAT

TGCCGGATTTCTCGAGAACGGTTGGGAAGGCATGGTTGACGGGTGGTATGGTTTCAGACAC

CAGAACGCCCAGGGGACAGGGCAGGCCGCCGATTATAAATCCACCCAGGCCGCCATCGACC

AGATTACCGGTAAATTAAACAGGCTAGTTGAAAAAACCAATACCGAGTTTGAATCCATAGA

ATCTGAATTCTCCGAAATTGAACACCAGATCGGTAATGTTATCAACTGGACCAAAGACAGC

ATCACCGACATATGGACTTATCAGGCTGAGCTGCTTGTCGCTATGGAGAACCAGCACACCA

TCGACATGGCCGATTCTGAAATGCTGAACCTGTACGAAAGGGTGCGGAAGCAGCTACGGCA

GAACGCTGAGGAGGACGGCAAGGGGTGCTTTGAAATCTACCACGCCTGCGATGATTCCTGT

ATGGAGTCCATCCGTAACAACACGTACGACCACTCACAGTATAGAGAGGAAGCCCTCCTAA

ACCGCCTGAATATCAACCCCGTAACCCTCTCATCTGGTTATAAAGACATCATCCTCTGGTT

TAGTTTCGGCGCCTCATGTTTCGTACTGCTCGCAGTGGTGATGGGCCTGGTATTCTTCTGT

CTAAAGAACGGGAATATGAGATGCACCATCTGCATT

786
ATGTATAAGATCGTGGTGATCATTGCACTCCTTGGGGCAGTCAAAGGCTTGGACAAAATTT

GTTTGGGACACCACGCAGTCGCTAACGGTACAATAGTCAAAACACTGACAAATGAGCAGGA

AGAAGTGACTAACGCCACAGAAACAGTGGAGTCCACAGGCATTAATCGCCTTTGTATGAAG

GGTCGCAAGCATAAGGATCTGGGGAACTGTCACCCTATAGGTATGCTGATAGGGACTCCAG

CCTGTGATTTACACCTGACAGGGATGTGGGACACGCTCATCGAGAGGGAAAACGCCATCGC

CTACTGCTATCCTGGGGCTACAGTCAACGTCGAGGCCCTACGACAAAAAATTATGGAGAGC

GGCGGGATCAATAAGATTTCCACTGGCTTTACTTATGGCTCATCTATAAACTCCGCAGGCA

CAACACGCGCCTGTATGCGCAACGGCGGAAACTCATTTTACGCGGAACTGAAGTGGCTGGT

TTCTAAAAGCAAGGGCCAGAATTTCCCACAGACTACAAATACCTATCGCAACACTGACACC

GCAGAACACTTAATAATGTGGGGGATTCACCACCCCTCGAGCACCCAAGAGAAGAACGACC

TTTATGGAACGCAGTCTCTCAGCATCAGCGTGGGATCATCCACATACCGGAACAACTTTGT

GCCTGTGGTGGGAGCTCGACCACAAGTCAACGGCCAGTCTGGTAGAATTGATTTTCACTGG

ACCCTTGTGCAACCTGGGGATAATATAACTTTCTCGCACAATGGTGGTTTAATAGCCCCAT

CTCGCGTCAGCAAACTGATCGGTAGAGGCCTCGGAATACAGTCCGATGCACCTATCGATAA

CAATTGTGAATCCAAGTGCTTCTGGAGGGGGGGATCCATTAATACTCGGCTGCCTTTCCAA

AATTTGTCACCCCGCACTGTGGGCCAGTGTCCAAAGTACGTGAACAGAAGGAGCCTGATGT

TGGCAACCGGGATGCGCAACGTTCCCGAACTCATCCAGGGGAGAGGTTTGTTTGGAGCTAT

CGCGGGCTTTCTCGAAAACGGCTGGGAGGGGATGGTGGATGGATGGTACGGCTTTCGTCAC

CAGAACGCCCAGGGAACGGGGCAAGCAGCCGATTACAAGAGCACCCAGGCCGCTATCGACC

AGATTACGGGGAAGCTGAACCGCCTAGTAGAGAAGACCAACACAGAATTCGAATCTATTGA

ATCAGAGTTTAGCGAAATAGAGCATCAGATCGGAAACGTGATCAATTGGACTAAAGATTCT

ATCACAGATATCTGGACTTACCAGGCTGAACTGCTTGTAGCAATGGAGAATCAACACACAA

TAGACATGGCCGATTCTGAGATGCTGAACCTGTACGAGCGTGTACGCAAACAGCTGAGACA

GAACGCCGAAGAGGATGGTAAAGGATGTTTCGAAATCTACCATGCTTGCGACGACTCTTGC

ATGGAAAGTATCCGGAACAATACATACGATCACTCCCAATATCGCGAGGAGGCGCTGCTGA

ACAGACTGAACATTAACCCCGTGACTCTATCCTCAGGGTACAAGGATATCATATTATGGTT

CTCTTTCGGCGCCTCCTGTTTCGTCCTGCTGGCCGTCGTAATGGGCCTTTTCTTTTTCTGT

TTGAAGAATGGAAATATGCGGTGCACCATCTGTATA

787
ATGTACAAAATCGTGGTAATTATTGCTCTTCTTGGGGCTGTTAAAGGGTTGGACAAGATTT

GTCTCGGGCATCACGCCGTGGCCAATGGAACGATTGTGAAGACACTGACCAACGAACAGGA

GGAGGTAACTAACGCCACGGAAACTGTCGAGTCCACTGGCATCAATCGGCTCTGTATGAAG

GGCCGCAAACACAAGGACTTGGGGAACTGCCACCCAATCGGCATGCTTATCGGCACACCCG

CTTGTGACTTACATCTGACTGGGATGTGGGACACGCTTATAGAACGGGAAAACGCCATTGC

CTACTGCTACCCAGGTGCAACTGTTAACGTCGAAGCTCTGCGCCAAAAGATCATGGAAAGC

GGCGGTATCAACAAAATTAGTACGGGCTTTACCTATGGCTCAAGCATTAACTCAGCTGGCA

CCACCCGTGCCTGTATGAGGAATGGAGGCAACTCCTTTTACGCTGAGCTCAAGTGGCTCGT

GTCCAAGTCCAAGGGACAGAATTTCCCCCAGACTACCAATACCTATAGAAATACTGACACC

GCTGAACACTTGATTATGTGGGGTATCCATCACCCTAGCTCCACTCAGGAAAAAAACGATC

TATACGGCACCCAGTCGTTGTCCATCTCAGTCGGCAGTTCCACTTATCGCAACAACTTTGT

GCCCGTGGTCGGAGCACGTCCTCAGGTTAATGGCCAGTCTGGCCGTATCGATTTTCACTGG

ACACTGGTACAGCCTGGCGATAATATTACTTTTAGCCACAACGGGGGCCTGATCGCCCCGA

GTCGTGTGTCCAAGCTTATCGGACGAGGTCTTGGGATTCAATCTGATGCCCCAATTGACAA

TAACTGTGAAAGCAAATGCTTTTGGCGCGGGGGATCCATTAACACGCGGCTTCCTTTCCAG

AATCTATCCCCTCGTACTGTCGGGCAATGCCCTAAGTACGTCAACCGGAGGTCCCTGATGC

TGGCCACTGGCATGCGTAACGTCCCAGAGCTCATTCAGGGCAGAGGTTTATTCGGAGCAAT

TGCAGGGTTCCTGGAGAACGGCTGGGAGGGAATGGTCGATGGCTGGTATGGTTTCCGCCAT

CAAAACGCTCAAGGCACAGGCCAGGCGGCCGATTACAAATCGACTCAGGGGGCCATTGACC

AAATCACAGGCAAACTGAATAGACTGGTGGAAAAAACAAACACCGAGTTTGAGTCTATTGA

ATCTGAGTTTAGCGAAATCGAGCACCAAATCGGCAATGTTATTAACTGGACTAAGGATTCA

ATTACGGATATTTGGACATACCAGGCGGAGTTATTAGTTGCCATGGAGAATCAGCACACTA

TTGATATGGCTGATAGTGAGATGTTAAATTTGTACGAGAGGGTTAGGAAGCAGTTGAGGCA

GAACGCGGAGGAAGACGGGAAAGGCTGCTTCGAGATTTACCACGCCTGCGACGATTCCTGC

ATGGAGAGCATCCGGAATAATACCTACGACCATTCACAGTATCGAGAAGAAGCTCTATTAA

ACCGTTTGAACATCAACCCAGTGACCTTAAGTAGCGGATACAAAGACATTATTCTATGGTT

CTCCTTCGGCGCCTCCTGTTTCGTGTTGCTCGCCGTTGTAATGGGATTGTTTTTCTTCTGT

CTGAAGAATGGAAACATGAGATGCACAATTTGTATC

788
ATGTACAAGATTGTTGTGATCATCGCCCTTCTGGGGGCCGTGAAGGGACTTGACAAAATAT

GCCTCGGTCATCACGCTGTTGTGAATGGCACAATAGTTAAAACGCTGACCAACGAGCAAGA

AGAGGTGACCAACGCAACCGAGACAGTGGAGAGTACAGGTCTGAACCGACTGTGCATGAAG

GGCCGAAACCACAAGGACCTCGGCAATTGTCACCCCATCGGAATGTTAATTGGTACCCCCG

CCTGCGATCTGCATCTGACCGGTACTTGGGATACCTTAATTGAAAGGGAAAACGCCATCGC

GTACTGTTATCCCGGAGCAACCGTGAACGAGGAAGCCCTCAGACAGAAGATCATGGAGTCG

GGAGGCATCAACAAGATCTCCACAGGCTTCACGTACGGCTCCTCTATTAATTCTGCCGGAA

CAACTCGGGCCTGTATGCGCAACGGAGGCAACTCCTTCTACGCAGAACTGAAATGGCTTGT

CAGCAAGAGCAAGGGTCAGAATTTCCCCCAAACTACCAATACTTATAGGAATACGGACACC

GCAGAACACCTGATAATGTGGGGCATTCATCATCCCTCTTCAACTCAGGAGAAAAATGATT

TGTATGGGACTCAATCCTTATCAATCTCCGTGGGTAGCAGCACCTATCAGAATAACTTTGT

TCCAGTCGTAGGGGCCCGGCCTCAGGTGAACGGGCAGTCAGGCAGAATTGATTTCCACTGG

ACCCTTGTGCAACCCGGAGACAACATTACCTTTAGTCACAATGGCGGTCTCATCGCCCCTT

CCAGAGTGTCTAAACTGATCGGTCGGGGCCTGGGCATCCAGAGCGACGCACCAATCGACAA

TAATTGCGAGAGTAAGTGCTTCTGGAGAGGTGGTAGTATCAATACTAGGCTCCCATTCCAA

AATTTATCGCCTAGGACCGTCGGACAGTGTCCCAAATATGTAAATAAAAGGTCCTTAATGC

TTGCGACGGGAATGCGTAACGTTCCTGAACTGATGCAGGGCAGAGGCCTATTTGGCGCAAT

AGCCGGTTTTATCGAGAACGGCTGGGAGGGGATGGTGGACGGTTGGTATGGATTTAGGCAC

CAAAATGCCCAGGGAACTGGGCAGGCGGCGGATTACAAGAGCACACAAGCTGCTATCGACC

AGATCACGGGCAAACTGAATCGATTGATTGAAAAGACCAACACTGAGTTTGAATCAATTGA

GAGTGAGTTTTCAGAGATTGAACACCAGATCGGGAACGTGATAAACTGGACTAAAGATTCC

ATCACTGACATCTGGACATATCAGGCGGAGCTCCTGGTGGCCATGGAGAACCAACACACCA

TCGACATGGCAGACTCTGAAATGTTAAATCTGTACGAGAGAGTCAGGAAACAGCTGCGCCA

GAATGCCGAGGAAGATGGCAAGGGTTGCTTCGAGATCTACCACGCATGTGACGACAGCTGC

ATGGAGTCAATTCGCAACAACACCTACGACCACTCCCAATACAGGGAGGAGGCACTGCTTA

ACAGGCTGAACATTAATCCGGTCACCCTCTCTAGCGGCTATAAGGATATTATTCTGTGGTT

CAGTTTTGGCGCTTCTTGTTTTGTCCTGCTGGCAGTGGTGATGGGCCTGGTCTTCTTTTGC

CTAAAAAATGGGAATATGAGGTGCACCATCTGTATT

789
ATGTATAAAATTGTGGTCATCATTGCTCTGCTGGGTGCAGTAAAGGGGCTGGACAAAATTT

GTCTGGGACACCATGCCGTTGCCAACGGAACAATCGTGAAGACGCTTACTAACGAACAGGA

AGAAGTTACCAACGCTACCGAAACCGTCGAATCCACGGGTATCAACAGGCTGTGTATGAAA

GGGAGGAAGCACAAAGATTTGGGGAACTGCCACCCAATCGGCATGTTGATTGGCACTCCCG

CCTGTGATCTGCATTTAACTGGTATGTGGGATACCCTGATCGAGCGAGAAAATGCTATTGC

ATACTGTTATCCAGGCGCGACTGTGAATGTCGAAGCTCTGCGACAGAAAATCATGGAATCC

GGCGGTATCAATAAAATTTCGACAGGCTTCACATATGGGAGTTCTATTAACTCTGCCGGGA

CCACCAGAGCCTGCATGCGCAACGGAGGAAATAGCTTCTACGCTGAGTTAAAGTGGCTAGT

CTCTAAATCTAAAGGACAAAACTTCCCACAGACCACTAACACCTACCGGAATACCGATACC

GCGGAACACTTAATTATGTGGGGGATCCACCACCCAAGCTCTACGCAGGAAAAGAACGATC

TCTACGGGACTCAGTCTTTATCAATTTCCGTGGGCTCCTCTACATACCGCAATAATTTCGT

GCCCGTGGTTGGCGCTAGGCCTCAGGTAAACGGGCAGAGTGGAAGGATAGATTTTCACTGG

ACCCTGGTTCAGCCGGGCGACAACATCACTTTCAGTCACAATGGCGGCCTTATCGCTCCCA

GCCGGGTGTCTAAATTGATCGGCAGGGGACTGGGTATCCAGTCGGACGCTCCAATTGACAA

CAATTGTGAGTCAAAGTGCTTTTGGCGAGGGGGGAGCATCAACACTCGCCTCCCTTTCCAA

AACCTGTCTCCTCGGACGGTCGGACAATGCCCTAAGTACGTAAACAGGCGGTCGCTGATGC

TGGCCACTGGGATGAGAAACGTGCCAGAACTTATTCAGGGCCGTGGCTTGTTCGGCGCAAT

CGCTGGGTTTCTTGAAAATGGCTGGGAAGGGATGGTGGATGGTTGGTATGGGTTCCGACAT

CAGAACGCTCAGGGCACTGGGCAGGCCGCTGATTATAAGTCCACCCAGGCAGCTATAGACC

AAATAACAGGGAAACTAAATCGCCTGGTCGAAAAGACAAATACAGAGTTCGAATCTATCGA

GAGCGAATTCTCAGAAATCGAGCACCAGATTGGGAATGTGATTAATTGGACCAAGGATAGT

ATCACAGATATCTGGACATACCAGGCAGAACTGTTGGTTGCCATGGAAAACCAGCACACCA

TTGATATGGCAGATTCAGAGATGCTTAACCTGTATGAGAGAGTGCGAAAGCAGCTGCGCCA

GAACGCAGAAGAGGATGGAAAGGGGTGCTTCGAAATTTACCACGCTTGCGATGATAGCTGT

ATGGAGTCAATAAGAAACAACACCTATGACCACAGCCAGTACAGGGAGGAGGCACTACTTA

ATAGGCTGAATATCAATCCAGTTACTTTGTCCAGCGGCTATAAGGACATTATACTGTGGTT

TAGCTTTGGGGCGTCCTGCTTTGTGCTCCTGGCTGTAGTGATGGGGCTATTTTTCTTCTGT

TTAAAGAACGGTAATATGCGGTGCACAATCTGTATC

790
ATGTACAAAATAGTGCTGGTGCTCGCCCTCCTCGGTGCTGTGCATGGTCTTGACAAGATAT

GTCTCGGACATCACGCCGTCCCGAACGGAACTATTGTGAAAACCCTAACCAACGAGAAGGA

AGAGGTGACTAACGCGACCGAAACTGTGGAAAGCAAGAGTCTGGATAAACTGTGTATGAAG

AATAGGAATTACAAGGACCTGGGCAATTGTCATCCTATTGGGATGGTGGTCGGTACCCCCG

CTTGTGATCTTCATCTGACCGGAACCTGGGATACCCTGATAGAGCGCGACAATTCAATTGC

GTATTGCTACCCCGGTGCCACAGTTAGCGAGGAAGCCTTGCGCCAGAAGATCATGGAGAGT

GGCGGCATAGATAAAATCAGCACCGGATTCACGTACGGGAGTAGTATCAATTCAGCCGGCA

CAACAAAAGCCTGCATGAGAAATGGCGGAAACTCCTTTTATTCTGAACTGAAATGGCTCGT

GTCCAAGAACAAGGGCCAGAACTTTCCTCAGACGACCAATACTTATCGCAACACAGATTCC

GTCGAACATTTGATCATTTGGGGCATTCACCATCCTAGCTCTACCCAGGAGAAAAACGATC

TGTACGGCACCCAAAGCCTGTCCATTAGCGTCGGGTCCAGTACATACCAGAACAACTTCGT

GCCAGTCGTCGGGGCGCGGCCGCAGGTCAACGGCCAGTCAGGGAGAATAGACTTTCATTGG

ACCATGGTGCAGCCCGGGGACAACATTACTTTTTCCCATAATGGAGGCCTGATCGCACCAA

ATCGGGTCTCTAAGCTGAAAGGGAGAGGTCTCGGGATCCAGTCCGGAGCATCTGTGGACAA

CGACTGTGAATCCAAATGCTTCTGGAAGGGTGGGTCTATCAATACCAAGCTCCCCTTTCAG

AATCTCTCGCCTAGGACCGTGGGACAGTGCCCAAAATACGTGAACAAAAAAAGTCTCCTCC

TGGCTACTGGTATGCGGAATGTCCCAGAGGTTGCACAGGGGCGAGGCCTGTTCGGTGCCAT

AGCGGGTTTTATTGAGAACGGTTGGGAGGGAATGGTGGATGGCTGGTATGGGTTTCGGCAC

CAAAATGCACAGGGCACAGGTCAGGCCGCCGATTATAAGAGCACACAGGCAGCCATTGATC

AGATTACAGGGAAGCTGAATCGACTGATAGAAAAAACAAATACCGAGTTTGAGTCCATTGA

AAGCGAATTTAGCGAGATTGAGCACCAGATAGGGAATGTCATCAATTGGACCAAAGATTCA

ATCACTGATATTTGGACTTACCAGGCTGAGCTGCTGGTTGCAATGGAAAATCAGCACACAA

TTGACATGGCCGACAGCGAGATGCTGAACCTCTACGAGAGAGTGCGTAAACAGCTGCGCCA

GAACGCAGAAGAGGATGGGAAGGGATGTTTCGAAATTTATCACAAGTGTGATGACAACTGT

ATGGAGAGCATTCGAAACAACACGTACGACCATACTCAGTATCGGGAGGAAGCCCTGTTGA

ATCGCCTCAATATTAATCCCGTGAAACTCTCATCCGGTTATAAAGACGTCATACTGTGGTT

TTCCTTCGGGGCCAGCTGCTTCGTACTGCTGGCCGTCATTATGGGCCTTGTTTTTTTCTGT

CTGAAAAATGGAAACATGAGGTGTACCATCTGTATT

791
ATGTATAAAATCGTGGTGATCATCGCACTGCTGGGTGCGGTTAAGGGGCTCGACAAGATTT

GCCTGGGACACCATGCAGTGGCAAATGGCACTATTGTCAAAACACTTACTAACGAGCAGGA

GGAAGTGACAAACGCCACGGAGACCGTTGAGAGCACGGGCATCAATCGGCTGTGCATGAAA

GGCAGGAAGCATAAGGACCTCGGCAACTGCCATCCTATTGGTATGCTGATTGGCACGCCCG

CTTGCGATCTGCATCTGACCGGAATGTGGGATACGCTTATAGAGAGAGAGAACGCGATTGC

CTACTGCTACCCCGGCGCTACAGTCAATGTCGAAGCTCTGCGCCAAAAAATTATGGAATCT

GGCGGGATTAACAAGATCTCCACTGGCTTCACGTATGGATCTTCAATAAACTCAGCCGGCA

CCACACGGGCCTGCATGCGCAATGGGGGAAACTCATTCTATGCTGAACTGAAATGGCTTGT

CTCAAAATCTAAGGGGCAGAATTTTCCTCAAACTACCAACACCTACAGGAATACGGATACC

GCTGAGCACCTGATCATGTGGGGTATCCACCACCCTTCGTCCACCCAGGAAAAAAATGACC

TATATGGTACCCAGTCACTGAGTATCAGCGTAGGCAGTTCTACATATCGTAACAACTTTGT

CCCAGTAGTCGGGGCCCGCCCTCAAGTGAACGGCCAATCTGGACGTATTGATTTCCACTGG

ACACTGGTGCAACCCGGAGACAACATCACTTTCTCCCACAACGGAGGGCTGATAGCCCCCT

CCAGGGTCTCCAAGTTGATCGGACGTGGACTTGGGATACAGTCTGATGCCCCAATTGATAA

TAACTGTGAGTCTAAATGCTTCTGGAGGGGGGGCAGTATCAATACACGCCTGCCTTTCCAG

AACCTGTCGCCACGGACAGTTGGACAGTGTCCAAAATATGTGAACCGCAGGTCGCTGATGT

TGGCAACCGGAATGAGGAATGTGCCCGAGCTGATTCAGGGTCGGGGATTATTTGGCGCCAT

CGCAGGGTTCCTGGAAAATGGATGGGAAGGCATGGTGGATGGATGGTACGGCTTTAGACAC

CAAAACGCCCAGGGAACAGGGCAAGCAGCAGACTACAAATCCACGCAAGCTGCTATAGACC

AGATTACTGGTAAGCTCAACCGTCTCGTTGAGAAAACAAATACGGAATTTGAGAGTATCGA

GTCAGAGTTTTCTGAAATCGAACATCAAATAGGGAATGTAATTAATTGGACAAAAGACTCA

ATCACTGACATATGGACCTATCAGGCTGAACTGCTAGTTGCAATGGAGAATCAACATACCA

TCGACATGGCTGACAGCGAGATGCTGAATTTGTACGAAGGGGTCAGAAAACAACTGCGGCA

GAATGCTGAGGAAGATGGAAAGGGGTGTTTCGAAATATATCACGCTTGTGATGACTCTTGC

ATGGAATCCATCCGGAATAATACCTACGATCACTCGCAGTATCGAGAGGAGGCCCTGCTGA

ATCGCTTAAACATTAATCCAGTGACACTGTCTTCCGGGTATAAAGATATCATTCTGTGGTT

TTCCTTTGGCGCATCCTGCTTCGTATTACTAGCCGTTGTCATGGGATTGTTTTTCTTTTGT

CTGAAAAACGGGAACATGCGGTGTACCATTTGTATT

792
ATGTACAAGATCGTGGTCATCATCGCTCTGTTGGGCGCCGTGAAAGGGCTTGATAAGATCT

GTCTTGGGCACCACGCCGTGGCCAACGGGACCATTGTGAAAACCCTCACGAACGAGCAGGA

GGAAGTGACAAACGCAACTGAGACCGTTGAGTCAACCGGTATTAATCGCTTGTGCATGAAA

GGACGAAAGCACAAGGACTTGGGCAACTGCCATCCAATTGGGATGCTGATCGGTACCCCAG

CATGTGATCTGCATTTAACAGGCATGTGGGATACCCTTATTGAGCGAGAAAATGCCATCGC

GTATTGCTATCCTGGAGCCACTGTGAATGTGGAGGCACTGCGTCAGAAGATTATGGAATCT

GGCGGGATCAATAAAATAAGCACCGGCTTTACATACGGCAGCTCGATTAATTCCGCTGGCA

CCACTAGAGCTTGCATGCGCAATGGGGGCAACTCATTCTATGCCGAGCTGAAGTGGTTGGT

GAGTAAGAGCAAAGGGCAGAACTTTCCTCAGACCACCAACACCTATCGAAATACGGACACA

GCTGAACACCTTATAATGTGGGGGATCCACCACCCGTCATCTACCCAGGAAAAGAACGACT

TATACGGAACACAGTCTCTGTCCATCTCGGTTGGATCCTCTACTTACCGAAATAATTTTGT

GCCCGTCGTGGGGGCCAGACCCCAGGTAAACGGACAGTCTGGCAGGATCGATTTCCATTGG

ACTCTGGTCCAGCCCGGAGATAATATCACCTTTAGTCACAACGGTGGACTGATCGCTCCCA

GTAGAGTGTCCAAGCTGATAGGCAGAGGGCTTGGAATCCAAAGCGACGCCCCAATCGATAA

TAACTGCGAAAGCAAGTGTTTCTGGCGGGGCGGATCCATCAACACCAGGCTTCCCTTCCAG

AACTTGTCCCCAAGGACTGTTGGACAGTGCCCAAAGTATGTTAATCGACGGAGTCTGATGC

TCGCTACTGGCATGAGAAACGTACCCGAGCTGATACAAGGGCGCGGGCTGTTCGGCGCAAT

AGCCGGATTCCTGGAGAACGGATGGGAGGGTATGGTGGACGGCTGGTATGGCTTTCGGCAT

CAGAATGCCCAGGGTACTGGTCAGGCAGCCGATTATAAGTCAACCCAGGCTGCCATCGATC

AGATTACAGGGAAACTGAATCGGCTGGTGGAAAAAACCAATACCGAATTTGAGTCCATTGA

ATCTGAATTCAGCGAGATCGAGCACCAGATCGGTAATGTCATAAATTGGACTAAGGATTCC

ATCACAGATATCTGGACATACCAAGCTGAGCTGCTTGTGGCCATGGAAAACCAGCATACAA

TAGACATGGCCGACAGTGAGATGCTAAATCTGTATGAGAGAGTGAGAAAACAACTAAGACA

GAATGCTGAGGAGGACGGCAAAGGTTGTTTTGAGATCTACCACGCTTGCGACGACTCGTGT

ATGGAATCCATACGCAACAATACTTACGACCACTCTCAGTACCGCGAGGAAGCTTTACTTA

ACCGCCTGAATATTAACCCTGTTACCTTATCCAGTGGGTACAAAGACATAATATTGTGGTT

CAGTTTTGGCGCGTCGTGTTTTGTTCTCCTGGCCGTTGTGATGGGCCTGTTTTTTTTCTGC

CTGAAGAACGGGAATATGCGCTGTACTATCTGCATA

793
ATGTACAAGATAATCGTCATTATCGCACTGTTGGGCGCCGTTAAAGGACTGGATAAAATCT

GCCTGGGCCATCACGCAGTCGCTAACGGTACAATCGTGAAAACTCTGACCAATGAGCAGGA

GGAAGTCACCAACGCAACCGAAACCGTAGAGTCCACCGGCATCAACCGGCTCTGTATGAAG

GGCCGCAAGCATAAAGACCTGGGTAACTGCCACCCCATAGGCATGCTTATTGGCACTCCGG

CATGCGACTTGCACCTGACGGGGACCTGGGACACATTGATTGAACGGGAAAATGCTATTGC

TTATTGCTATCCTGGAGCCACAGTGAATGTGGAGGCTCTCCGCCAAAAGATCATGGAATCT

GGGGGGATAGATAAGATTAGTACTGGGTTTACGTATGGGAGTTCTATCAACAGCGCCGGGA

CCACAAGAGCCTGTATGAGAAACGGAGGAAACAGCTTTTACGCAGAGTTGAAATGGCTTGT

TAGTAAATCTAAGGGGCAGAATTTCCCTCAGACCACGAACACTTACAGGAATACGGATACT

GCGGAGCACCTTATTATGTGGGGCATCCATCATCCCTCCTCTACTCAGGAGAAAAACGACC

TCTATGGCACTCAATCCTTGTCCATCTCCGTCGGTTCCTCAACCTATAGGAACAACTTTGT

GCCAGTTGTAGGCGCAAGGCCACAGGTTAACGGGCAGAGCGGTCGCATCGACTTCCACTGG

ACCCTGGTGCAGCCAGGCGATAACATCACCTTTTCACACAACGGCGGGCTGATCGCACCTT

CCCGAGTGTCTAAGCTGATAGGGAGGGGCCTCGGCATCCAGTCTGACGCACCAATTGACAA

TAATTGTGAGTCCAAGTGTTTTTGGCGCGGAGGTTCAATTAACACGCGCCTGCCCTTTCAG

AATCTGTCTCCCCGTACTGTGGGCCAGTGTCCAAAGTATGTTAATAGGCGGTCCCTCATGC

TGGCTACGGGAATGAGAAACGTGCCTGAGCTGATACAGGGCCGAGGACTATTCGGGGCGAT

CGCCGGCTTTTTAGAAAACGGGTGGGAGGGCATGGTCGACGGATGGTATGGCTTCAGACAC

CAGAATGCGCAGGGGACTGGCCAGGCTGCTGACTATAAGAGTACCCAGGCCGCTATAGACC

AGATCACGGGTAAGCTGAATCGTCTGGTTGAAAAGACTAATACTGAATTTGAAAGCATCGA

AAGCGAGTTTAGCGAAATTGAGCATCAGATCGGGAACGTCATTAATTGGACTAAAGACTCC

ATTACTGATATCTGGACGTACCAGGCTGAGTTGTTAGTGGCCATGGAAAATCAGCATACCA

TTGATATGGCAGATAGCGAAATGCTGAATCTGTACGAGAGAGTTCGTAAGCAGCTGCGCCA

GAACGCTGAAGAGGACGGAAAGGGATGCTTTGAGATCTACCACGCCTGCGACGACAGCTGT

ATGGAATCGATCCGGAACAACACCTATGACCACTCCCAGTATAGGGAAGAAGCCCTGTTAA

ACCGCCTGAATATTAATCCCGTCACTCTGTCATCCGGCTATAAGGACATAATTCTTTGGTT

TAGCTTCGGCGCTAGTTGCTTTGTGCTACTGGCTGTCGTGATGGGCCTCTTTTTTTTTTGC

CTTAAAAATGGCAATATGAGGTGTACAATCTGTATC

794
ATGTATAAGATCGTCGTAATCATCGCCCTGCTGGGCGCTGTTAAGGGGCTGGATAAGATCT

GCCTAGGCCACCATGCCGTAGCCAATGGTACAATCGTTAAGACATTAACCAATGAGCAGGA

GGAGGTTACAAACGCTACCGAAACCGTTGAGAGCACCGGGATTAACCGACTCTGTATGAAG

GGTAGGAAACATAAGGACCTCGGCAATTGCCATCCTATTGGCATGCTCATAGGGACCCCAG

CGTGTGACTTGCACCTCACTGGAATGTGGGACACTCTGATCGAGAGGGAAAATGCCATAGC

TTATTGTTACCCAGGAGCCACAGTGAATGTGGAAGCCCTGAGACAGAAGATCATGGAGTCC

GGCGGAATCAACAAGATCAGCACTGGTTTCACCTATGGGAGTAGCATAAACAGCGCTGGTA

CTACCCGAGCATGCATGCGGAATGGAGGCAATAGCTTTTACGCTGAACTGAAATGGCTGGT

CTCAAAATCGAAAGGGCAGAATTTTCCTCAGACGACAAATACCTATCGCAATACGGACACC

GCAGAACACCTGATTATGTGGGGTATCCACCATCCTAGCTCCACACAGGAGAAAAATGATC

TGTACGGAACCCAGTCCCTGTCTATCTCCGTGGGATCCTCCACTTACCGGAACAATTTTGT

TCCTGTCGTGGGGGCTCGGCCGCAAGTGAACGGTCAGAGCGGACGAATTGATTTCCACTGG

ACTCTGGTGCAGCCTGGGGACAATATCACGTTCTCCCATAACGGAGGACTGATCGCCCCCA

GCCGCGTGAGCAAGTTGATTGGGCGCGGCCTTGGAATTCAGTCAGATGCGCCAATAGATAA

TAATTGTGAATCTAAGTGTTTCTGGAGGGGAGGCTCCATCAATACCCGGCTCCCTTTCCAA

AATTTGTCCCCGAGAACAGTGGGTCAGTGCCCAAAATATGTGAACCGCCGATCTCTGATGC

TGGCCACCGGCATGAGGAACGTGCCTGAGCTGATTCAGGGTAGAGGCCTGTTTGGAGCCAT

CGCCGGCTTTTTAGAGAACGGCTGGGAAGGAATGGTCGACGGATGGTATGGCTTCAGGCAC

CAGAACGCCCAAGGGACTGGCCAGGCGGCTGACTACAAGTCCACTCAAGCGGCTATTGACC

AAATTACAGGAAAGCTGAATAGACTCGTTGAAAAAACTAATACAGAGTTTGAAAGTATAGA

ATCTGAGTTCTCAGAAATAGAGCATCAGATTGGAAACGTGATCAACTGGACTAAAGACTCT

ATCACCGATATTTGGACGTATCAGGCGGAGTTGCTCGTCGCGATGGAGAACCAACACACAA

TAGATATGGCTGATTCTGAGATGCTGAACTTGTACGAACGGGTGCGTAAACAACTGCGCCA

AAATGCTGAGGAGGACGGGAAGGGGTGTTTTGAGATCTACCATGCTTGCGACGATAGCTGC

ATGGAGTCAATTCGAAATAACACGTATGACCACAGCCAGTACAGGGAAGAGGCCCTGCTGA

ACAGGCTGAATATAAATCCCGTTACCCTCTCCTCTGGATACAAAGACATCATCCTCTGGTT

TTCATTCGGAGCTAGTTGCTTCGTACTACTAGCTGTTGTAATGGGCCTGTTCTTCTTCTGT

CTCAAGAATGGTAACATGCGGTGTACGATCTGCATC

795
ATGTATAAGATCGTGGTGATCATTGCCCTCTTGGGCGCCGTGAAGGGTCTGGATAAAATAT

GTCTTGGTCACCACGCTGTGGCTAATGGTACCATCGTGAAGACGCTTACCAACGAACAAGA

GGAAGTGACAAATGCTACCGAGACCGTGGAGTCTACCGGGATCAACCGACTGTGCATGAAA

GGACGAAAGCACAAAGACCTCGGCAATTGCCACCCTATTGGGATGTTGATTGGCACTCCAG

CTTGCGACCTTCACCTGACCGGAATGTGGGACACGCTCATCGAGCGCGAGAACGCCATTGC

CTACTGCTACCCCGGGGCCACCGTTAACGTGGAAGCACTTAGGCAAAAAATTATGGAATCC

GGTGGAATAAACAAGATTAGCACTGGTTTCACTTATGGGAGTAGTATTAACTCTGCCGGGA

CAACCAGGGCTTGTATGAGAAATGGCGGCAATTCATTTTACGCAGAGCTCAAGTGGCTGGT

TTCAAAAAGTAAAGGGCAGAATTTCCCGCAAACCACTAATACCTACAGGAACACAGACACG

GCCGAGCACCTGATCATGTGGGGTATTCACCACCCTAGCAGCACGCAAGAGAAAAATGACC

TTTATGGAACCCAGAGCCTCAGTATTTCAGTGGGAAGCAGCACGTACCGTAATAATTTTGT

TCCGGTAGTCGGCGCCCGACCCCAGGTGAACGGGCAGTCGGGACGAATCGACTTTCATTGG

ACGCTTGTGCAGCCTGGCGACAACATCACCTTTAGCCACAATGGCGGCCTGATTGCTCCCA

GCCGCGTCAGCAAGCTGATCGGGCGCGGACTGGGCATTCAGTCTGATGCCCCTATTGATAA

CAACTGCGAGAGCAAGTGTTTTTGGCGGGGAGGCTCCATAAATACTCGCTTACCTTTCCAG

AACCTCAGTCCAAGGACCGTAGGGCAGTGTCCTAAGTATGTTAACAGAAGGAGTCTCATGT

TAGCCACAGGAATGCGCAATGTACCAGAACTCATTCAGGGCAGGGGACTCTTTGGTGCAAT

TGCTGGGTTTCTGGAGAACGGTTGGGAAGGTATGGTCGACGGCTGGTACGGCTTTCGACAT

CAAAATGCACAGGGCACAGGCCAGGCGGCTGATTATAAATCCACTCAGGCCGCCATCGACC

AAATCACAGGAAAGCTCAACCGTCTGGTCGAGAAGACCAATACTGAGTTCGAAAGCATCGA

GTCAGAGTTTAGCGAGATTGAGCATCAGATTGGCAATGTCATCAACTGGACTAAAGATAGC

ATAACCGATATTTGGACGTACCAAGCAGAGCTACTTGTTGCTATGGAGAATCAGCATACCA

TTGATATGGCCGATAGCGAGATGCTGAATCTGTATGAGAGAGTGAGAAAGCAGTTGAGACA

AAACGCGGAGGAGGATGGGAAGGGCTGTTTCGAGATCTACCACGCCTGCGACGACTCCTGT

ATGGAGTCTATACGCAACAACACATACGACCACAGCCAGTATAGGGAGGAAGCCTTGCTGA

ATAGGCTGAATATCAATCCTGTAACGCTGTCGAGTGGGTACAAAGACATCATTTTATGGTT

CAGTTTTGGAGCCTCTTGTTTCGTTTTGCTGGCCGTCGTCATGGGACTATTTTTTTTTTGT

TTAAAGAACGGGAACATGAGATGCACTATTTGCATC

796
ATGTACAAGATTGTGTTGGTCCTAGCCCTCCTCGGCGCTGTGCATGGGCTGGATAAGATCT

GCCTTGGGCACCACGCCGTGCCTAATGGCACTATCGTGAAAACACTCACAAACGAAAAAGA

GGAAGTAACAAATGCCACCGAGACTGTGGAAAGCAAGAGCCTTGATAAACTCTGTATGAAA

AACAGAAATTATAAAGATTTAGGCAACTGTCATCCCATTGGTATGGTTGTGGGAACGCCCG

CTTGTGATCTGCATTTAACGGGTACATGGGATACCCTCATCGAGCGAGATAACTCAATCGC

CTACTGCTACCCGGGCGCCACTGTGTCAGAGGAAGCCTTGAGACAGAAGATTATGGAATCC

GGCGGTATTGACAAGATTTCTACCGGGTTTACGTATGGGTCTTCCATAAACTCCGCAGGCA

CCACAAAGGCATGCATGAGAAATGGTGGTAATTCTTTCTACTCAGAGCTTAAATGGCTGGT

GTCTAAGAACAAAGGCCAGAACTTTCCCCAGACGACCAACACATACCGTAACACGGACAGC

GTCGAGCACCTGATCATCTGGGGCATTCACCATCCTTCCTCAACTCAGGAGAAAAACGATC

TCTATGGTACCCAAAGCCTCTCTATTTCAGTCGGATCAAGCACATACCAGAACAACTTTGT

GCCCGTCGTTGGAGCCAGGCCACAGGTGAACGGCCAGAGTGGTCGAATTGATTTTCACTGG

ACAATGGTGCAACCTGGGGATAATATCACATTCAGCCATAATGGTGGTCTGATCGCCCCAA

ATAGAGTTTCAAAGCTTAAGGGCAGGGGTCTGGGGATTCAAAGCGGTGCTTCCGTCGATAA

TGACTGTGAGTCAAAATGCTTTTGGAAGGGGGGCAGCATCAATACAAAGCTACCGTTTCAG

AACCTCAGTCCCAGGACAGTTGGGCAGTGTCCTAAGTATGTGAATAAAAAATCCTTACTGT

TGGCCACTGGAATGAGAAACGTTCCAGAGGTAGCTCAGGGCCGTGGTCTCTTTGGGGCCAT

CGCCGGCTTTATTGAAAACGGGTGGGAAGGAATGGTTGATGGGTGGTATGGGTTCAGGCAT

CAGAACGCCCAGGGCACTGGACAAGCAGCTGACTATAAGAGCACACAGGCTGCTATTGACC

AGATTACTGGAAAACTGAATAGGTTGATAGAGAAGACCAACACTGAGTTCGAGTCTATCGA

GTCAGAGTTTTCAGAAATCGAGCATCAGATCGGTAACGTAATCAACTGGACCAAGGACTCA

ATAACCGACATCTGGACATATCAAGCCGAGTTGCTGGTAGCTATGGAGAATCAACATACTA

TCGACATGGCTGATTCCGAAATGCTCAACTTGTATGAGCGCGTGCGTAAGCAGTTGAGACA

GAATGCTGAGGAAGATGGCAAGGGCTGCTTCGAGATTTACCACAAGTGTGACGATAATTGT

ATGGAGAGCATTCGAAACAACACTTACGACCACACCCAATACCGCGAGGAAGCCCTGTTGA

ATCGGCTCAACATCAATCCCGTAAAGTTGTCCAGTGGTTATAAAGACGTCATCTTATGGTT

TAGTTTTGGAGCTTCTTGTTTTGTGCTCCTGGCAGTCATTATGGGACTGGTATTCTTCTGC

CTGAAAAATGGGAATATGAGATGCACTATCTGTATC

797
ATGTATAAAATTGTCGTGATTATTGCTCTGCTCGGTGCCGTTAAGGGACTCGATAAGATCT

GCTTAGGACATCACGCTGTAGTGAACGGCACAATCGTGAAAACACTCACGAACGAGCAGGA

AGAGGTCACAAACGCCACAGAAACTGTCGAGAGCACCGGTCTAAACCGACTGTGTATGAAA

GGAAGGAATCATAAGGACCTAGGCAATTGTCACCCAATCGGAATGCTTATCGGCACCCCTG

CATGCGATTTGCACCTGACAGGTACATGGGATACGCTGATCGAGCGCGAGAATGCCATCGC

CTATTGTTACCCCGGTGCAACCGTAAACGAGGAGGCCCTGAGGCAAAAGATAATGGAGTCA

GGCGGCATAAATAAGATTAGCACCGGTTTTACCTATGGGAGCAGTATAAATAGTGCCGGTA

CTACGCGCGCATGTATGCGCAATGGGGGCAACTCTTTTTACGCCGAACTCAAGTGGCTAGT

GTCAAAATCGAAGGGCCAGAACTTTCCACAGACCACTAACACTTATAGGAACACGGACACA

GCCGAACATTTAATAATGTGGGGTATCCATCACCCAAGTTCCACTCAGGAGAAAAACGATT

TATACGGAACTCAGTCGCTGTCAATCAGCGTAGGGAGCTCAACATACCAGAACAACTTTGT

TCCAGTGGTGGGCGCACGTCCCCAGGTGAACGGTCAAAGCGGCCGGATAGATTTTCACTGG

ACCCTGGTGCAGCCTGGAGATAATATTACTTTTAGTCACAACGGTGGCCTAATCGCACCCA

GTCGTGTATCGAAGCTTATCGGACGGGGCCTCGGGATACAGTCTGATGCTCCCATAGACAA

CAACTGTGAGTCTAAGTGCTTTTGGCGGGGGGGGTCTATTAACACCAGGCTCCCATTTCAG

AACCTCAGTCCTCGGACCGTGGGTCAGTGTCCGAAGTATGTTAATAAGCGTTCTCTCATGC

TCGCCACTGGAATGAGGAACGTGCCAGAGCTAATGCAGGGAAGAGGACTGTTCGGGGCCAT

AGCCGGCTTCATTGAAAATGGCTGGGAGGGTATGGTTGACGGATGGTACGGCTTCCGACAC

CAGAATGCTCAAGGCACAGGCCAGGCTGCAGATTATAAATCAACACAGGCTGCTATTGACC

AAATCACTGGCAAGCTCAATCGATTAATTGAAAAAACAAATACCGAGTTTGAAAGCATCGA

GAGTGAATTTTCCGAGATCGAACACCAAATCGGAAACGTGATCAACTGGACCAAGGACTCT

ATCACCGATATATGGACCTATCAGGCAGAACTTTTAGTTGCCATGGAGAACCAGCATACCA

TTGATATGGCCGACAGCGAAATGCTGAACTTGTATGAGCGGGTCCGGAAACAATTACGCCA

GAATGCCGAGGAAGACGGAAAAGGGTGCTTTGAGATCTATCATGCTTGCGACGACTCTTGT

ATGGAGTCAATCAGAAATAATACTTATGACCATAGTCAGTATAGGGAAGAGGCGCTGCTCA

ACAGACTAAATATCAACCCCGTTACGCTGAGCTCCGGTTATAAGGACATCATTCTTTGGTT

TTCCTTTGGCGCAAGCTGCTTTGTTCTGCTAGCTGTAGTGATGGGACTCGTCTTTTTCTGC

CTGAAGAACGGAAACATGCGCTGTACAATCTGTATT

798
ATGTATAAGATCGTTGTGATCATCGCCCTGCTGGGCGCCGTGAAAGGGCTGGACAAGATTT

GTCTGGGTCACCACGCCGTCGCCAACGGGACAATTGTTAAAACACTGACTAACGAGAAGGA

GGAGGTGACTAACGCAACCGAGACAGTTGAGTCCACAGGATTGAATCGGCTTTGTATGAAA

GGCCGGAAGCACAAAGACCTGGGAAACTGCCACCCTATAGGGATGCTGATCGGAAGTCCTG

CTTGTGATCTACACCTGACAGGTACTTGGGACACACTGATCGAGCGGGAGAATGCCATTGC

TTACTGCTACCCAGGAGCCACCGTGAATGGTGAAGCTCTGAGACAGAAGATTATGGAATCC

GGAGGCATTGATAAAATCTCTACAGGATTTACATACGAGTCCTCAATCAATTCAGCTGGCA

CAACTCGAGCATGTATGCGCAATGGCGGGAATAGTTTTTATGCCGAGCTCAAGTGGCTCGT

CTCTAAAAGCAAGGGGCAGAACTTTCCCCAGACCACGAACACCTATAGAAATACCGATACA

GCCGAGCATCTTATTATGTGGGGCATACATCATCCCTCCTCTACACAAGAGAAGAATGATC

TTTACGGAACGCAGTCCCTCTCGATCAGCGTGGGAAGCTCCACATATAGGAACAATTTTGT

TCCCGTGGTTGGCGCTCGTCCTCAGGTGAACGGACAGAGTGGCCGAATCGACTTTCACTGG

ACCCTTGTTCAGCCCGGCGACAACATAACGTTTTCGCATAATGGCGGCCTCATTGCACCTT

CCCGTGTCAGCAAACTGATTGGCCGCGGGCTGGGCATCCAATCTGACGCTCCCATCGATAA

CAACTGCGAATCAAAATGCTTCTGGAGGGGAGGGTCTATTAATACTCGGCTGCCATTCCAA

AACCTTTCCCCCCGGACAGTTGGCCAGTGTCCGAAATATGTGAACAAACGGAGTTTGATGC

TCGCTACCGGGATGCGGAACGTGCCTGAATTGATGCAGGGAAGAGGTCTTTTCGGCGCCAT

TGCCGGCTTCTTGGAAAATGGTTGGGAAGGGATGGTCGACGGATGGTATGGATTTCGGCAT

CAGAACGCTCAAGGCACTGGGCAGGCAGCTGATTATAAATCAACCCAGGCTGCCATTGACC

AGATAACTGGCAAACTCAACAGGCTGGTGGAGAAGACCAACACCGAATTCGAGAGTATTGA

GTCTGAATTCAGCGAGATCGAGCACCAGATAGGGAACGTTATTAACTGGACCAAGGATTCT

ATTACGGACATTTGGACATACCAAGCTGAGCTCTTAGTGGCCATGGAGAATCAGCATACCA

TTGACATGGCCGATTCTGAGATGCTTAATCTCTATGAGAGGGTGAGAAAGCAGCTGCGGCA

GAATGCCGAAGAAGATGGCAAGGGGTGCTTTGAGATTTACCACGCTTGCGATGATTCATGT

ATGGAATCTATTCGCAATAACACCTACGATCATTCTCAGTATCGGGAGGAAGCCCTGCTGA

ATCGCCTGAACATTAATCCCGTGACACTTTCAAGTGGTTACAAGGACATAATTCTATGGTT

CAGTTTTGGGGCTAGTTGTTTTGTGCTCCTAGCCGTTGTGATGGGTCTTGTCTTCTTTTGT

TTGAAGAACGGAAATATGCGGTGTACAATCTGTATA

799
ATGTACAAGATCGTGGTGATCATTGCGCTCCTGGGCGCCGTCAAGGGACTGGACAAGATCT

GCCTGGGCCATCACGCTGTGGCAAATGGGACAATCGTGAAAACGCTGACTAACGAGCAAGA

GGAGGTGACAAATGCGACGGAGACAGTGGAATCGACTGGGATTAACCGACTGTGTATGAAA

GGAAGAAAACATAAAGACCTCGGAAATTGCCATCCCATTGGGATGCTGATCGGAACTCCAG

CCTGTGACCTGCACCTGACAGGAATGTGGGATACCCTGATTGAGCGGGAGAATGCTATCGC

ATATTGTTACCCCGGGGCTACCGTAAACGTCGAAGCCCTTAGGCAGAAGATAATGGAAAGC

GGTGGCATCAATAAGATTTCGACAGGCTTCACTTATGGAAGTAGTATTAATAGCGCAGGAA

CCACTCGAGCCTGTATGAGAAACGGCGGTAACAGCTTTTATGCTGAGCTCAAGTGGCTTGT

CTCCAAGTCTAAGGGACAGAATTTCCCACAGACTACAAACACTTACAGGAATACCGATACA

GCTGAGCATCTAATTATGTGGGGAATACATCACCCTTCTTCCACCCAGGAAAAAAACGACC

TCTACGGCACTCAATCTCTCAGCATATCGGTGGGGAGTTCGACTTACCGAAACAACTTTGT

CCCGGTTGTCGGTGCCAGGCCCCAGGTGAACGGACAAAGCGGTCGGATCGATTTTCATTGG

ACTTTGGTCCAGCCTGGGGACAATATCACATTCTCACATAACGGCGGATTAATTGCCCCCT

CTCGCGTGTCAAAGCTCATAGGCCGGGGCCTGGGGATTCAGTCTGACGCTCCAATTGATAA

TAATTGCGAGTCAAAATGCTTCTGGCGCGGGGGGTCTATTAATACTCGATTGCCATTCCAG

AATCTCAGTCCCCGGACCGTGGGGCAGTGCCCAAAGTATGTGAACCGGCGGAGCCTGATGC

TGGCTACTGGAATGCGGAATGTGCCCGAACTTATTCAGGGCCGAGGTCTGTTCGGCGCCAT

CGCCGGGTTCCTGGAGAATGGGTGGGAGGGCATGGTCGATGGATGGTATGGATTTCGTCAC

CAGAACGCACAGGGCACAGGACAGGCTGCCGACTATAAGTCTACACAAGCGGCTATCGACC

AGATTACTGGTAAACTCAACCGGCTGGTGGAGAAGACCAACACTGAGTTCGAATCCATTGA

ATCTGAATTTTCGGAGATCGAACACCAGATTGGAAACGTGATCAACTGGACCAAGGACTCA

ATCACTGACATCTGGACTTACCAGGCCGAACTGCTTGTGGCTATGGAGAATCAGCATACTA

TCGATATGGCCGACTCCGAAATGCTCAACCTTTACGAGCGAGTGCGGAAACAATTGAGACA

AAACGCCGAAGAGGATGGGAAGGGCTGTTTTGAAATATACCACGCCTGCGATGATAGTTGT

ATGGAGTCAATCAGGAATAACACTTATGATCATAGTCAGTATAGAGAGGAAGCTCTTCTGA

ATCGACTGAACATCAACCCAGTAACACTTAGTAGTGGGTACAAAGACATCATCTTGTGGTT

CTCATTCGGAGCCTCTTGTTTTGTGCTGCTTGCCGTCGTAATGGGACTGTTTTTTTTTTGT

CTCAAGAACGGCAACATGAGGTGCACTATTTGCATT

800
ATGTACAAAATCGTGGTGATCATCGCACTGCTAGGGGCAGTGAAAGGCCTGGATAAAATCT

GCCTGGGACACCACGCAGTAGCCAACGGTACCATTGTGAAAACACTGACAAACGAACAGGA

GGAGGTCACAAATGCTACAGAGACCGTGGAGTCTACAGGTATTAATCGGCTGTGCATGAAG

GGAAGAAAGCACAAGGATCTGGGGAACTGCCACCCCATTGGAATGCTCATCGGGACACCTG

CATGCGATCTGCACCTCACTGGCATGTGGGACACATTGATCGAAAGAGAAAATGCCATTGC

ATATTGCTATCCTGGAGCAACGGTCAATGTGGAAGCACTGAGGCAAAAGATCATGGAGTCC

GGAGGCATCAACAAAATCTCAACCGGTTTCACATACGGAAGCAGTATTAACTCTGCCGGCA

CAACCCGTGCTTGCATGCGAAATGGAGGGAACTCTTTCTACGCGGAACTCAAATGGTTGGT

GTCTAAGTCGAAAGGACAGAACTTTCCGCAAACTACAAATACTTACAGGAATACTGACACT

GCAGAACATCTGATCATGTGGGGCATCCACCACCCCTCTTCAACACAGGAAAAGAATGACC

TGTACGGGACCCAGAGTCTGTCAATCTCCGTGGGCTCCTCAACTTATCGTAACAACTTTGT

CCCTGTTGTGGGAGCACGACCTCAAGTGAACGGACAGAGCGGGAGAATCGATTTTCACTGG

ACCCTCGTGCAGCCTGGAGATAACATCACATTTAGCCATAACGGAGGGTTGATCGCTCCGT

CCCGTGTGTCTAAACTTATCGGACGGGGCCTGGGTATCCAGAGTGATGCACCAATCGATAA

CAACTGTGAGAGCAAGTGTTTCTGGCGTGGTGGTTCTATAAACACACGACTGCCCTTCCAG

AACCTGTCGCCTAGAACCGTGGGACAGTGTCCTAAATACGTCAACCGAAGAAGCCTAATGC

TGGCCACAGGAATGCGCAACGTGCCCGAGCTAATTCAGGGCAGGGGCCTCTTCGGCGCAAT

CGCAGGCTTTCTGGAGAATGGGTGGGAGGGGATGGTGGATGGTTGGTACGGGTTCCGACAT

CAGAACGCCCAGGGGACGGGGCAGGCAGCCGACTACAAATCCACTCAGGCCGCAATAGACC

AGATTACCGGGAAACTGAATAGACTGGTGGAGAAAACAAATACTGAGTTCGAGAGTATTGA

ATCAGAGTTCTCCGAAATCGAGCATCAGATCGGCAACGTGATTAACTGGACTAAGGACTCT

ATCACAGATATATGGACATATCAGGCCGAGCTGCTGGTGGCCATGGAGAACCAGCACACCA

TCGACATGGCCGACTCAGAAATGTTAAACCTCTATGAGCGGGTTCGTAAGCAGTTACGCCA

AAACGCCGAAGAGGATGGCAAGGGGTGCTTCGAAATTTATCACGCTTGTGATGATTCCTGT

ATGGAGTCCATTCGGAACAACACCTACGACCACAGCCAGTACCGCGAGGAGGCCCTTCTGA

ATCGTCTGAACATAAACCCGGTCACCCTCAGTTCAGGATACAAGGACATAATTCTTTGGTT

CTCCTTTGGCGCCTCATGCTTCGTGCTCCTGGCCGTGGTGATGGGGCTCTTTTTCTTCTGC

TTGAAGAACGGGAACATGCGGTGTACTATCTGCATT

801
ATGTACAAAGTGGTGGTGATCATCGCCTTACTCGGGGCAGTGCGAGGGCTGGATAAGATTT

GCCTGGGTCACCACGCTGTGGCAAACGGGACAACAGTGAAAACTCTCACAAATGAACAGGA

GGAAGTCACCAACGCAACAGAGACCGTCGAAAGTACCTCACTCAATAAGTTGTGTATGAAA

GGTCGCCGGTACAAGGACCTCGGGAACTGCCACCCAATTGGAATGCTGATTGGTAGGCCCG

TGTGTGACCTGCACCTGACCGGGACGTGGGACACCCTGATCGAGCGCGAGAATGCAACTGC

TTACTGCTACCCCGGCGTGACCATTAACGAAGAAGCGCTGCGCCAGAAAATCATGGAATCA

GGGGGGATTAGCAAAATGAGGACAGGGTTCACATATGGTCCTAGCATCAATAGCGCCGGAA

CGACACGGAGCTGCATGCGCAACGGAGGCAACTCATTTTATGCCGAACTTAAGTGGCTGGT

GTCTGGGACAAAGGGGCAGAACTTCCCACAGACTACTAATACATATCGAAATACCGACACT

GCCGAGCACCTTATCATCTGGGGAATCCACCATCCTAGCTCAACTCAGGAAAAGAATGACC

TCTACGGTACTCAGTCTCTGTCCATTAGCGTGGGATCCAGCACCTACCAAAACAATTTTGT

TCCTGTTATCGGGGCAAGACCCCAAGTGAATGGCCAATCTGGGAGAATCGAATTCCACTGG

ACACTGGTCAGACCAGGCGACAACATAACTTTTTCACACAATGGAGGACTTATCGCCCCAG

ACAGGGTGTCAAAGCTGATCGGAAAGGGCATCGGAATTCAGAGTGGTGCGGTGATTGATAA

GGATTGTGAAAGCAAGTGCTTTTGGCGCGGGGGCTCCATTATCACCGAGCTCCCTTTTCAA

AACCTTAGCCCCCGGACAGTCGGCCAATGCCCAAAATATGTCAAAAAGCGCTCACTGCTCC

TTGCCACGGGGATGCGGAACGTGCCGGAAGTGGTGCAAGGTCGAGGCCTCTTTGGCGCGAT

CGCCGGATTCATCGAGAATGGTTGGGAAGGCATGGTGGACGGGTGGTACGGGTTTAGACAC

CAGAATGCGCAGGGCATTGGGCAGGCTGCTGACTACAAATCAACTCAGACTGCGATTGATC

AGATCACGGGAAAACTGAACCGTCTCATCGAAAAAACAAACACTGAGTTCGAATCCATCGA

GTCGGAATTTAGTGAAATCGAACACCAGATCGGCAACGTCATTAATTGGACGAAGGACTCT

ATTACAGATATCTGGACCTATCAGGCTGAGCTCTTGGTAGCAATGGAAAACCAACACACTA

TCGATATGGCCGATAGCGAGATGCTGAACCTGTATGAAAGGGTTAGAAAGCAGCTGAGACA

GAACGCTGAAGAAGACGGTAAGGGCTGCTTTGAGATCTATCATACATGCGACAATTCATGT

ATGGAGTCCATACGGAATAATACATATGACCATTCGCAGTACCGAGAGGAGGCCTTACTGA

ACAGACTGAACATCAATCCTGTTAAGCTGTCAAGCGGTTACAAGGACATAATTCTCTGGTT

CTCCTTTGGTGCCTCCTGTTTCGTACTTCTCGCCGTCATCATGGGGTTGGGCTTCTTTTGC

CTGAAAAATGGCAACATGAGATGCACTATATGCATT

802
ATGTATAAGATAGTGGTAATAATTGCCCTCTTGGGGGCAGTGAAAGGACTCGATAAGATAT

GCCTGGGACACCATGCCGTGGCTAACGGCACAATTGTGAAAACGCTAACAAACGAGCAGGA

GGAAGTTACCAACGCTACCGAAACCGTTGAGAGTACCGGCATTAATAGACTTTGTATGAAG

GGCCGAAAACACAAAGATCTCGGGAACTGTCATCCGATCGGCATGTTGATTGGAACACCTG

CATGTGATCTCCATTTAACAGGCATGTGGGATACATTGATTGAGCGGGAGAACGCTATAGC

CTATTGCTATCCCGGAGCCACAGTGAATGTTGAGGCGCTTCGTCAGAAAATCATGGAGAGC

GGAGGCATCAACAAGATCTCCACCGGGTTTACCTATGGCTCGTCTATAAACTCAGCTGGTA

CAACCAGGGCTTGCATGAGAAATGGGGGAAATTCCTTTTATGCAGAGCTGAAGTGGCTGGT

GTCAAAGAGCAAAGGACAGAATTTCCCGCAGACCACAAACACCTATCGTAATACCGACACC

GCCGAGCACCTTATTATGTGGGGCATACACCATCCAAGCTCAACCCAGGAGAAGAACGATC

TGTACGGCACGCAGAGTCTGAGCATCTCAGTCGGCTCTTCCACTTATAGGAACAACTTCGT

TCCAGTTGTCGGGGCGCGCCCTCAAGTCAACGGACAATCTGGCAGGATCGACTTCCACTGG

ACTCTTGTACAACCCGGCGATAACATCACCTTCTCCCATAACGGGGGTCTTATCGCCCCAT

CCCGGGTGAGCAAGCTCATTGGTCGCGGACTGGGGATTCAGAGCGATGCGCCTATTGACAA

TAACTGCGAGAGTAAATGCTTTTGGAGGGGCGGTAGCATCAACACCCGGTTGCCTTTCCAA

AACCTTTCCCCTAGAACAGTTGGCCAGTGTCCGAAGTATGTAAACAGGCGAAGTCTCATGC

TCGCGACAGGCATGCGGAATGTTCCCGAGCTGATTCAGGGCAGGGGACTGTTTGGAGCTAT

CGCGGGATTTCTGGAAAACGGTTGGGAAGGGATGGTGGACGGATGGTATGGATTCCGCCAC

CAGAATGCACAAGGAACGGGCCAGGCCGCCGACTACAAGTCCACTCAGGCCGCTATTGATC

AGATTACCGGCAAGCTCAATCGCCTGGTGGAGAAGACTAATACCGAGTTCGAGAGCATCGA

GTCCGAATTCTCGGAAATTGAGCATCAGATCGGCAATGTCATAAATTGGACCAAAGACTCA

ATCACAGATATATGGACTTATCAGGCTGAGTTGCTTGTGGCTATGGAAAACCAGCACACAA

TCGATATGGCTGATTCCGAGATGCTTAATCTGTATGAACGCGTAAGGAAGCAGTTACGGCA

AAATGCAGAAGAAGATGGCAAGGGCTGTTTTGAGATCTATCATGCCTGCGATGACAGTTGC

ATGGAGTCAATTAGGAATAATACGTATGATCACTCTCAGTATCGTGAGGAAGCTCTGCTGA

ACCGTCTGAACATCAATCCTGTGACCTTATCGTCCGGATATAAGGATATCATTCTATGGTT

CAGCTTTGGCGCTAGCTGCTTTGTCTTACTCGCTGTGGTCATGGGCCTGTTTTTTTTCTGC

TTAAAGAACGGGAACATGCGTTGTACAATCTGCATT

803
ATGTATAAAATCGTCGTTATAATCGCGTTATTGGGAGCAGTGAAGGGCTTAGACAAGATTT

GTCTGGGACATCATGCAGTGGTGAACGGAACCATCGTGAAGACACTAACAAATGAACAGGA

GGAAGTCACCAACGCAACCGAAACTGTGGAATCTACAGGTCTAAACAGGTTGTGTATGAAA

GGCAGGAATCATAAAGACCTCGGCAACTGCCATCCAATTGGTATGCTTATTGGAACGCCCG

CATGTGACCTGCATCTCACAGGTACATGGGACACACTCATTGAGCGCGAAAATGCTATCGC

CTACTGCTATCCTGGCGCTACCGTCAATGAGGAGGCACTGAGACAGAAGATCATGGAGAGC

GGCGGAATAAACAAAATTTCTACAGGCTTCACCTATGGGAGCAGCATCAATTCTGCCGGCA

CAACAAGGGCCTGTATGCGTAACGGGGGAAACTCCTTTTACGCCGAGCTGAAATGGTTGGT

GTCCAAGAGCAAGGGGCAGAACTTTCCCCAGACCACAAATACATATAGGAATACGGATACT

GCCGAGCACCTCATCATGTGGGGCATCCATCACCCAAGCTCCACCCAGGAGAAGAATGACC

TCTACGGGACCCAGTCCCTTAGCATTTCTGTGGGCAGTAGCACTTATCAAAATAACTTCGT

CCCCGTCGTAGGGGCGAGACCACAGGTTAACGGACAAAGCGGCAGAATTGACTTCCACTGG

ACACTCGTTCAGCCAGGTGATAATATTACTTTTAGCCATAATGGGGGACTGATAGCACCCA

GCAGAGTGAGTAAGTTGATAGGCAGGGGGCTTGGTATTCAGTCAGATGCGCCCATTGATAA

CAACTGTGAGAGTAAGTGCTTCTGGAGAGGGGGCTCCATTAATACCCGCTTGCCATTTCAA

AACCTGTCCCCCAGGACTGTAGGGCAGTGCCCTAAGTACGTGAACAAACGGTCCTTAATGC

TGGCCACTGGTATGCGCAATGTGCCAGAGCTCATGCAGGGCAGAGGGCTCTTTGGAGCCAT

AGCAGGGTTTATTGAAAATGGGTGGGAGGGCATGGTGGACGGATGGTACGGATTTAGACAC

CAAAACGCGCAGGGCACTGGACAGGCGGCCGACTATAAGTCCACCCAGGCCGCGATCGATC

AGATCACCGGAAAGTTGAACCGCTTAATAGAGAAGACAAACACCGAGTTCGAAAGCATAGA

GTCCGAATTTTCCGAAATCGAACACCAGATCGGCAACGTGATCAACTGGACGAAGGATTCG

ATTACCGACATTTGGACTTATCAGGCTGAACTACTCGTGGCTATGGAGAACCAACATACTA

TCGATATGGCAGATTCTGAAATGCTTAACCTCTATGAAGGGGTTAGGAAACAGCTGAGGCA

GAACGCAGAAGAAGACGGCAAGGGGTGCTTCGAAATTTATCATGCATGTGACGATAGTTGC

ATGGAAAGCATTAGAAACAACACCTATGACCATTCTCAGTATCGGGAGGAGGCACTCCTGA

ATCGTCTGAATATCAACCCAGTCACACTGAGTTCAGGGTATAAAGACATAATTCTCTGGTT

CTCATTCGGAGCCTCCTGTTTTGTGCTACTCGCAGTTGTGATGGGACTGGTCTTTTTTTGC

CTGAAAAATGGCAATATGAGATGTACAATTTGCATC

804
ATGTATAAAATTGTGGTCATAATTGCACTGCTCGGCGCAGTAAAGGGGCTCGATAAGATTT

GCCTGGGCCACCACGCCGTCGCTAACGGGACGATTGTCAAGACCCTGACTAACGAACAAGA

GGAGGTGACTAATGCTACCGAAACCGTCGAATCCACCGGCATTAACAGACTCTGTATGAAA

GGCAGAAAACATAAGGATCTGGGAAATTGCCACCCAATCGGAATGCTGATCGGGACACCCG

CCTGCGACCTGCACCTGACTGGGACTTGGGATACACTTATCGAAAGGGAGAATGCCATTGC

TTATTGTTACCCCGGCGCAACAGCGAATGTTGAAGCCCTGCGGCAAAAAATTATGGAATCC

GGTGGCATTGACAAGATCAGCACCGGGTTCACCTACGGCTCATCTATTAACAGTGCTGGGA

CCACCAGAGCTTGCATGCGGAACGGTGGCAACAGTTTCTACGCTGAACTCAAGTGGTTAGT

CTCAAAGTCTAAAGGACAGAACTTCCCCCAGACTACTAATACGTATAGGAACACTGATACT

GCTGAACATCTGATTATGTGGGGCATTCACCATCCAAGCTCAATTCAGGAGAAAAACGACC

TGTATGGCACCCAGTCGCTGTCTATCAGCGTGGGTTCCAGCACCTACCGGAACAATTTTGT

ACCGGTGGTTGGCGCGCGTCCTCAGGTCAATGGTCAATCTGGGCGGATTGACTTCCACTGG

ACTCTGGTTCAACCCGGCGACAACATAACTTTCTCTCACAATGGTGGATTGATCGCTCCTT

CCCGCGTTTCAAAACTGATAGGCCGCGGCTTAGGAATTCAGAGCGACGCCCCGATAGACAA

TAATTGCGAGTCCAAGTGCTTCTGGAGGGGAGGAAGCATTAACACGCGGTTGCCTTTCCAG

AACCTGTCCCCAAGGACAGTGGGACAATGCCCAAAATATGTCAATAGAAGAAGTCTCATGC

TGGCGACTGGTATGCGCAACGTGCCTGAGCTTATCCAGGGCCGCGGATTGTTCGGGGCAAT

CGCCGGCTTCCTGGAAAATGGGTGGGAAGGAATGGTGGATGGTTGGTACGGTTTTCGACAT

CAGAATGCCCAGGGTACTGGCCAGGCTGCAGACTATAAAAGCACTCAGGCTGCCATTGACC

AGATCACGGGTAAACTGAATAGGCTGGTGGAGAAGACGAACACAGAGTTCGAGTCTATTGA

ATCTGAGTTTTCTGAGATAGAGCACCAGATCGGAAACGTCATCAACTGGACCATGGATTCC

ATAACTGACATCTGGACTTACCAGGCGGAACTGCTGGTTGCAATGGAGAATCAGCACACTA

TTGACATGGCCGATTCCGAGATGCTCAATCTTTACGAGGGGGTCCGTAAACAGCTAAGGCA

GAATGCCGAGGAAGATGGGAAGGGTTGCTTCGAAATATATCATGCATGTGATGATTCTTGT

ATGGAGTCGATTCGTAATAACACCTACGATCACAGTCAATACAGAGAAGAAGCTCTTCTTA

ATCGGCTAAACATTAACCCAGTCACATTGAGCTCAGGATACAAGGACATCATCCTGTGGTT

CTCATTCGGGGCTTCCTGTTTTGTCCTGCTGGCCGTGGTCATGGGGCTGGTTTTTTTTTGC

CTGAAGAACGGCAATATGAGATGCACAATTTGCATC

805
ATGTATAAGGTGGTTGTGATTATTGCGCTGCTCGGGGCCGTTCGAGGCCTGGATAAAATCT

GTCTGGGCCATCACGCTGTCGCCAATGGCACGACTGTGAAAACTTTAACAAATGAGCAGGA

AGAGGTGACAAATGCCACTGAAACCGTCGAGAGTACATCACTGAATAAACTGTGCATGAAG

GGACGCCGCTATAAGGACCTGGGTAATTGCCATCCAATTGGTATGTTGATCGGGACCCCTG

TGTGCGACTTACACCTAACTGGCACTTGGGACACACTGATCGAGAGGGAGAATGCCACCGC

CTATTGTTACCCTGGTGTGACCATTAACGAAGAGGCTCTCAGACAAAAGATTATGGAGTCT

GGAGGAATCTCTAAGATGCGTACTGGGTTTACCTATGGGCCAAGCATCAACTCGGCTGGCA

CTACTCGCTCCTGTATGAGAAATGGAGGAAACTCCTTTTATGCTGAGTTGAAGTGGCTCGT

TTCCGGCACCAAGGGGCAAAACTTTCCACAGACGACCAATACTTATAGGAATACGGACACC

GCTGAACACCTGATTATTTGGGGAATCCATCACCCCAGCTCTACGCAGGAGAAGAACGACC

TTTACGGTACCCAGAGTCTTTCGATTAGCGTGGGCAGCAGCACATACCAGAATAATTTCGT

GCCCGTAATAGGTGCACGGCCTCAGGTGAATGGACAGTCGGGCCGGATAGAATTCCACTGG

ACGCTCGTTAGGCCCGGAGACAACATAACTTTTTCTCATAATGGCGGACTTATCGCTCCAG

ATCGGGTCAGCAAGCTTATAGGGAAGGGGATCGGCATCCAGTCCGGTGCTGTCATCGATAA

GGACTGTGAATCCAAGTGTTTCTGGCGTGGCGGTTCAATTATCACCGAACTACCTTTTCAA

AACTTGTCACCAAGAACCGTGGGACAGTGTCCAAAGTATGTCAAAAAAAGATCCTTGTTAC

TGGCTACCGGGATGAGGAATGTGCCTGAAGTCGTTCAGGGCCGCGGGCTGTTCGGAGCCAT

CGCGGGATTTATCGAAAACGGGTGGGAGGGGATGGTGGACGGTTGGTACGGATTCAGGCAT

CAGAATGCTCAGGGGATTGGGCAGGCTGCCGACTACAAGTCTACCCAGACGGCTATTGACC

AGATCACCGGCAAGTTGAATCGCCTGATAGAAAAAACTAATACGGAATTCGAAAGCATCGA

ATCCGAGTTCTCAGAAATCGAGCACCAGATAGGTAATGTAATCAATTGGACAAAGGACTCT

ATCACCGATATCTGGACCTATCAGGCAGAATTGCTGGTGGCAATGGAGAACCAGCACACAA

TCGATATGGCTGATTCAGAAATGCTGAATTTGTACGAGAGGGTCCGGAAGCAGCTCCGACA

GAACGCAGAAGAAGATGGGAAGGGTTGTTTCGAGATATATCATACCTGCGACAACTCGTGT

ATGGAATCAATACGCAATAATACATACGATCACAGTCAGTATCGTGAGGAGGCTCTCCTGA

ACAGGCTGAATATTAATCCTGTGAAACTGAGCTCCGGGTACAAGGATATTATTCTGTGGTT

CAGTTTTGGCGCTTCATGTTTCGTGTTGCTGGCAGTTATTATGGGGCTTGGTTTCTTCTGC

CTGAAGAATGGGAACATGCGCTGCACGATTTGCATA

806
ATGTATAAGGTGGTCGTAATCATCGCCCTTCTGGGTGCTGTCCGGGGCTTGGACAAAATTT

GTCTCGGGCATCACGCAGTGGCTAACGGCACAATAGTGAAGACCCTCACTAACGAACAGGA

GGAAGTGACAAACGCGACAGAAACAGTTGAGAGTAAATCCCTCGGCAAGCTGTGCATGAAA

GGGAGGAGTTATAATGACCTCGGCAATTGTCATCCGATAGGTATTCTGATCGGCACTCCTG

CGTGCGACCTGCACCTGACCGGGACCTGGGATACCCTCATCGAGAGGGAGAACGCCGTGGC

CTACTGCTACCCAGGCGCCACAGTAAATGAGGAAGCGCTGCGGCAGAAAATTATGGAATCT

GGAGGAATTAGCAAGATTTCTACTGGCTTCACCTATGGGACAAGCATCAACAGCGCCGGTA

CCACGAAGGCCTGTATGAGAAACGGTGGGAATTCTTTTTACGCAGAGCTCAAATGGCTGGT

GAGCAAAAACAAGGGGCAAAATTTCCCCCAGACCACAAACACATATAGGAATACAGACACA

GCTGAGCATTTAATTATTTGGGGCATCCATCACCCCTCCAGCACACAAGAAAAGAATGACC

TGTACGGTACCCAGTCTCTCTCTATTAGCGTTGGCTCTTCTACATACCAGAATAACTTTGT

TCCAGTCGTCGGAGCACGGCCACAGGTTAACGGGCAGAGTGGACGTATCGATTTCCACTGG

ACTCTTCTACAGCCTGGCGACAATATTACTTTTAGTCACAACGGCGGCCTTATAGCCCCGT

CCAGAGTCTCCAAGCTGATCGGCAGAGGGCTGGGCATTCAGTCCGAGGCTCCAATTGATAA

TGGCTGCGAAAGCAAATGCTTTTGGAAAGGCGGGAGTATCAACACAAAACTGCCCTTTCAG

AATCTGAGCCCTCGAACTGTGGGTCAGTGCCCAAAATACGTTAATAAGCGGAGTCTGATGT

TAGCTACTGGCATGCGGAACGTTCCAGAAATCATGCACGGCCGCGGACTCTTTGGAGCTAT

CGCCGGGTTTATAGAAAATGGCTGGGAAGGCATGGTTGACGGCTGGTACGGATTCAGGCAC

CAAAACGCCCAGGGAACCGGACAGGCCGCCGATTACAAAAGCACGCAAGCAGCTATTGATC

AGATCACTGGAAAACTCAATCGACTGATCGAAAAGACTAACACAGAATTTGAATCCATTGA

GTCCGAATTTAGTGAGATCGAGCACCAAATCGGCAACATCATTAACTGGACGAAGGACAGC

ATAACAGACATATGGACATATCAGGCAGAGCTCCTGGTCGCAATGGAAAACCAGCATACCA

TAGATATGGCTGATTCTGAGATGCTCAATCTGTATGAACGAGTCAGAAAGCAATTAAGACA

AAACGCTGAGGAGGATGGTAAGGGATGCTTCGAGATTTACCATGCTTGCGACGATTCCTGC

ATGGAAAGCATCCGTAATAACACCTACGACCACAGCCAATACCGTGAAGAAGCCCTCCTAA

ATCGATTGAACATTAATCCTGTGAAATTGAGTTCCGGCTACAAGGACATCATCCTGTGGTT

CTCATTTGGCGCATCATGCTTGATTCTTTTGGCCGTGGTGATGGGCCTGGTTTTCTTCTGT

CTGAAAAATGGCAACATGAGATGTACTATCTGCATT

807
ATGTACAAGATCGTGGTTATAATTGCCCTCCTGGGCGCCGTTAAGGGCCTTGATAAGATAT

GTCTGGGGCACCATGCCGTGGCTAATGGGACCATAGTGAAAACCCTGACTAATGAGCAGGA

GGAGGTCACTAACGCCACCGAGACTGTGGAATCCACCGGCATCAACAGGCTGTGTATGAAG

GGGCGCAAACACAAGGACCTAGGGAATTGCCACCCCATCGGTATGCTTATCGGCACGCCAG

CCTGTGACCTTCACCTGACTGGGATGTGGGACACTCTGATTGAAAGAGAAAACGCTATAGC

GTACTGCTACCCCGGCGCAACTGTGAACGTAGAAGCGTTGCGGCAGAAGATCATGGAGTCT

GGGGGAATCAATAAGATCTCAACAGGGTTTACATACGGCTCATCTATCAATTCCGCGGGCA

CGACCAGGGCGTGCATGAGGAACGGCGGGAACTCTTTTTACGCCGAGCTTAAATGGTTAGT

ATCTAAGAGCAAGGGGCAGAACTTTCCACAAACGACCAACACATACCGCAACACCGATACC

GCAGAACACCTCATCATGTGGGGAATCCACCATCCCAGTTCCACTCAAGAAAAAAACGATC

TATACGGCACTCAGTCCCTCTCAATCTCCGTGGGAAGTAGCACATATCGGAACAACTTCGT

GCCCGTGGTTGGGGCCCGCCCCCAGGTCAATGGCCAGTCAGGAAGAATTGACTTCCATTGG

ACACTTGTGCAGCCAGGCGACAATATCACATTTTCCCACAACGGCGGATTGATCGCCCCCT

CCAGAGTTAGCAAGCTGATCGGGAGAGGCCTGGGTATCCAGAGTGACGCGCCAATCGATAA

CAACTGCGAGAGCAAGTGCTTTTGGCGCGGAGGCTCAATTAACACACGGCTACCTTTCCAA

AACCTCAGTCCGCGTACAGTTGGCCAGTGCCCCAAGTATGTGAACCGGAGATCTTTGATGC

TCGCTACCGGCATGCGAAATGTCCCGGAGCTGATTCAAGGCCGCGGGCTCTTTGGAGCGAT

TGCGGGGTTTCTGGAGAACGGATGGGAAGGAATGGTGGATGGTTGGTACGGATTTCGGCAT

CAAAATGCACAGGGGACTGGCCAAGCCGCAGACTATAAGAGCACCCAGGCTGCGATCGACC

AGATCACCGGAAAGCTCAACCGCCTGGTGGAGAAGACCAATACGGAATTTGAATCAATCGA

AAGCGAGTTTAGTGAAATAGAACACCAGATTGGTAATGTGATTAATTGGACAAAAGACAGC

ATTACTGATATTTGGACATATCAGGCTGAGTTACTGGTAGCTATGGAGAATCAGCACACCA

TTGATATGGCCGACTCCGAAATGCTGAATCTGTACGAACGGGTTCGGAAACAGCTCAGGCA

GAACGCCGAAGAAGACGGTAAGGGATGCTTCGAAATCTACCACGCCTGCGATGATAGTTGC

ATGGAGTCTATACGGAACAACACCTATGACCATTCTCAGTATAGAGAAGAGGCCCTACTGA

ACCGTTTGAACATTAATCCAGTGACCCTGTCCTCCGGTTACAAGGACATAATCCTGTGGTT

CTCGTTTGGTGCTAGCTGCTTTGTGCTGCTGGCGGTGGTAATGGGACTGTTTTTCTTTTGC

CTGAAAAATGGCAATATGAGATGCACCATTTGCATC

808
ATGTACAAGATTGTGGTGATTATAGCCCTTCTGGGGGCTGTCAAGGGACTGGACAAAATCT

GCCTGGGACATCATGCTGTGGCAAACGGAACTATTGTGAAGACTTTGACTAACGAACAGGA

GGAGGTGACCAACGCCACCGAAACCGTGGAATCCACAGGCATCAACCGGCTCTGCATGAAA

GGAAGAAAGCACAAGGACCTGGGCAATTGTCATCCAATCGGAATGCTTATCGGGACTCCGG

CCTGTGATTTGCATCTGACCGGCATGTGGGATACGTTAATCGAACGAGAGAACGCCATTGC

CTATTGCTACCCTGGCGCGACCGTGAATGTCGAGGCCTTGAGGCAGAAGATCATGGAGAGC

GGCGGAATCAACAAAATAAGCACTGGTTTCACCTACGGTAGTAGCATAAATTCCGCTGGGA

CCACGCGGGCCTGCATGCGGAACGGCGGCAATTCCTTTTACGCAGAGCTTAAATGGTTAGT

GAGCAAAAGCAAGGGACAGAATTTCCCCCAGACCACAAACACATATCGTAACACCGACACC

GCGGAACATCTGATTATGTGGGGCATACATCACCCCTCTTCCACGCAAGAAAAGAATGACC

TGTACGGAACACAATCCTTATCCATTAGCGTAGGAAGCAGCACTTATCGGAACAACTTTGT

GCCCGTGGTGGGAGCTCGGCCTCAGGTAAACGGCCAGTCCGGTCGGATAGATTTCCATTGG

ACTTTGGTTCAGCCGGGGGATAACATTACATTTTCCCATAACGGCGGCCTCATTGCTCCCT

CGCGGGTCTCTAAACTTATTGGGGGGGGCCTGGGGATCCAGTCAGATGCCCCTATCGATAA

TAATTGCGAATCCAAATGTTTTTGGAGAGGAGGCAGTATTAACACCCGGCTGCCTTTCCAG

AATCTCAGCCCCCGTACAGTCGGACAGTGTCCCAAATATGTGAATAGACGCTCGCTAATGC

TGGCCACCGGCATGCGGAACGTTCCTGAGCTGATCCAGGGACGGGGGCTCTTTGGTGCAAT

TGCTGGATTTCTGGAAAATGGCTGGGAAGGCATGGTGGATGGCTGGTACGGCTTTAGGCAC

CAGAATGCCCAAGGCACGGGGCAGGCAGCCGACTACAAATCCACACAAGCCGCCATTGACC

AAATCACCGGGAAATTAAATAGGCTTGTGGAGAAAACCAATACCGAATTCGAAAGCATCGA

GAGCGAATTTTCAGAGATCGAGCACCAGATCGGGAATGTGATAAATTGGACCAAAGATTCC

ATTACCGATATTTGGACTTACCAAGCTGAGCTGCTCGTGGCCATGGAAAACCAGCACACAA

TCGATATGGCCGACTCTGAAATGTTGAACTTGTATGAAAGAGTGCGAAAACAGTTGCGTCA

AAACGCCGAGGAAGACGGGAAAGGTTGTTTCGAAATCTATCACGCGTGCGATGACAGCTGT

ATGGAAAGTATTAGGAACAATACATATGACCACTCACAGTATCGCGAGGAGGCACTGTTGA

ATCGCCTAAACATCAACCCCGTTACATTGTCTTCTGGTTACAAAGACATTATCTTATGGTT

TTCGTTTGGAGCCTCGTGTTTCGTGCTCCTAGCGGTAGTGATGGGGCTCTTCTTCTTCTGT

CTGAAGAACGGGAACATGCGCTGCACTATCTGTATC

809
ATGTACAAGATCGTAGTCATCATCGCCCTGCTGGGGGCCGTCAAAGGACTGGACAAGATTT

GCCTGGGCCATCATGCAGTCGCAAATGGCACTATCGTGAAGACTCTGACAAACGAACAGGA

AGAGGTGACAAATGCCACTGAAACAGTCGAGTCTACTGGGATCAACAGACTTTGCATGAAG

GGCCGCAAGCACAAGGACCTGGGTAATTGCCACCCCATTGGAATGCTTATTGGCACACCCG

CTTGCGACETACACCTAACCGGTATGTGGGATACTCTGATCGAAAGGGAAAACGCCATTGC

ATACTGCTACCCCGGCGCTACAGTGAACGTCGAGGCTCTGCGCCAGAAAATTATGGAGTCT

GGTGGAATCAATAAGATCTCAACTGGCTTCACCTATGGGAGTTCCATCAACAGCGCTGGGA

CTACGCGTGCGTGCATGCGTAACGGCGGAAACAGCTTTTACGCAGAGCTGAAATGGCTCGT

CAGCAAGTCCAAGGGTCAGAATTTCCCACAGACTACGAATACCTACCGAAATACTGACACT

GCGGAGCATCTCATCATGTGGGGAATCCACCATCCAAGCAGCACCCAGGAAAAGAACGATC

TGTACGGCACTCAGTCCCTAAGCATCTCCGTCGGCAGCAGTACTTATCGCAATAACTTTGT

CCCCGTGGTAGGAGCCCGTCCTCAGGTGAACGGACAGAGCGGACGTATCGACTTTCATTGG

ACACTCGTGCAACCCGGGGACAATATAACGTTCAGCCATAACGGAGGTTTAATAGCGCCTA

GCCGTGTGTCCAAACTCATCGGCCGTGGCCTGGGGATCCAATCCGATGCACCAATCGACAA

TAACTGCGAGTCTAAGTGCTTCTGGCGGGGAGGCTCAATTAATACCCGCCTACCCTTCCAG

AATCTGTCACCCAGGACCGTGGGCCAGTGTCCTAAGTACGTCAACAGGCGATCTCTCATGT

TGGCCACTGGCATGCGAAACGTGCCTGAGCTGATCCAAGGTAGAGGGCTGTTCGGAGCAAT

CGCCGGATTCCTGGAGAACGGCTGGGAGGGAATGGTGGACGGATGGTATGGTTTCAGGCAC

CAAAACGCTCAAGGAACTGGCCAGGCAGCTGACTATAAGTCCACTCAGGCTGCAATCGATC

AAATCACCGGCAAGCTGAACAGGCTCGTTGAGAAAACGAACACGGAATTTGAGTCCATCGA

ATCTGAATTTTCCGAGATCGAACATCAGATAGGCAACGTTATCAACTGGACGAAGGACTCT

ATCACTGACATTTGGACGTATCAGGCGGAGCTCTTAGTGGCCATGGAAAACCAGCACACTA

TCGACATGGCCGACAGTGAAATGCTGAACCTCTACGAAAGAGTTCGCAAGCAGCTCCGGCA

GAATGCAGAAGAGGATGGAAAAGGCTGTTTTGAAATCTACCACGCATGTGACGACTCATGC

ATGGAGTCTATACGAAATAATACTTACGACCATTCGCAATATCGCGAGGAGGCTCTGCTAA

ATAGGTTGAACATCAATCCCGTCACACTGTCCAGTGGCTACAAGGATATCATTCTGTGGTT

CTCATTTGGAGCCTCCTGCTTCGTTCTGCTGGCCGTGGTTATGGGATTATTCTTCTTTTGC

CTCAAGAACGGAAATATGCGCTGCACAATCTGCATC

810
ATGTACAAGATTGTGGTGATTATCGCATTGCTGGGCGCCGTGAAGGGGCTGGATAAAATAT

GTCTGGGGCACCATGCCGTAGCAAACGGTACGATAGTTAAGACTCTTACCAACGAACAGGA

AGAGGTGACGAACGCGACAGAGACCGTTGAGAGTACAGGTATTAATCGACTCTGTATGAAG

GGCCGCAAGCACAAGGACCTGGGCAATTGCCACCCCATCGGGATGCTGATCGGCACTCCTG

CGTGTGATCTGCACTTGACCGGCACTTGGGACACTTTGATTGAGAGAGAAAACGCGATTGC

TTATTGCTACCCTGGAGCAACCGCCAATGTTGAAGCCCTGAGGCAGAAGATTATGGAGTCG

GGAGGTATTGATAAGATCTCCACTGGATTCACTTACGGCTCATCTATAAATAGCGCCGGGA

CTACCCGCGCTTGCATGAGGAACGGGGGGAACAGCTTCTATGCCGAGCTCAAATGGCTTGT

GTCTAAGTCGAAAGGTCAAAACTTCCCACAGACAACTAACACATACCGCAACACCGACACT

GCAGAGCACTTGATTATGTGGGGCATCCATCATCCGTCTAGCATCCAGGAGAAGAATGATC

TCTATGGGACCCAGAGCCTCAGCATTTCAGTCGGAAGTTCCACCTACAGGAATAATTTCGT

GCCTGTGGTGGGCGCACGGCCTCAAGTGAACGGCCAGTCCGGAAGAATAGACTTTCACTGG

ACTCTGGTGCAGCCGGGGGATAACATTACATTCTCGCACAACGGTGGGCTTATAGCCCCCA

GCAGAGTAAGTAAACTTATCGGTCGGGGTTTGGGCATTCAGTCGGATGCCCCTATCGATAA

TAATTGTGAATCTAAATGTTTTTGGAGGGGGGGGAGCATCAACACCAGGCTGCCTTTCCAG

AATCTGTCCCCCCGAACTGTGGGACAGTGCCCCAAGTATGTTAACAGACGGTCCCTTATGC

TGGCCACTGGCATGCGCAACGTCCCCGAACTCATTCAGGGGCGCGGTCTGTTTGGTGCAAT

TGCCGGGTTTCTGGAGAACGGCTGGGAAGGGATGGTAGACGGTTGGTATGGCTTCCGGCAC

CAAAACGCCCAGGGAACTGGCCAAGCTGCCGACTACAAATCTACCCAGGCTGCCATAGATC

AGATCACTGGCAAACTCAATCGCCTGGTGGAAAAAACCAACACAGAGTTTGAGAGCATCGA

GTCCGAATTCTCCGAAATCGAACACCAGATCGGTAATGTGATTAACTGGACCATGGATAGT

ATCACCGACATATGGACATATCAGGCTGAACTCCTGGTGGCCATGGAGAACCAACATACTA

TTGATATGGCCGACTCAGAAATGTTAAATCTGTATGAGCGTGTGAGAAAACAGCTCAGGCA

GAACGCTGAGGAAGACGGAAAGGGCTGCTTCGAAATCTACCACGCATGCGATGACTCTTGC

ATGGAATCAATCCGGAACAACACATATGACCACAGCCAGTACCGGGAGGAGGCCCTTTTGA

ATAGGCTGAATATCAATCCCGTCACGCTTTCTTCCGGTTACAAAGATATAATTCTGTGGTT

CTCATTCGGGGCAAGCTGCTTTGTGCTTCTCGCTGTCGTGATGGGCCTCGTTTTCTTTTGC

TTGAAGAATGGAAATATGCGGTGCACGATCTGTATC

811
ATGTACAAGATCATCGTTATAATCGCACTCCTGGGCGCCGTCAAAGGCCTGGACAAGATTT

GCCTAGGGCATCACGCCGTAGCCAATGGAACCATTGTCAAGACCCTGACCAACGAGCAGGA

AGAGGTGACAAACGCCACAGAGACAGTAGAGTCCACCGGAATCAATCGCTTGTGCATGAAA

GGACGGAAGCATAAAGACTTAGGAAATTGTCATCCAATCGGCATGCTGATTGGGACACCCG

CCTGTGACTTGCATTTGACAGGGACCTGGGACACCCTTATCGAGCGTGAGAATGCCATCGC

GTACTGCTACCCCGGGGCTACGGTGAACGTCGAGGCTTTAAGACAGAAGATCATGGAGTCC

GGCGGAATCGATAAGATTTCTACCGGTTTCACTTACGGGAGTTCTATCAACTCTGCAGGAA

CCACTCGGGCCTGCATGAGGAATGGAGGCAACTCATTCTACGCAGAATTGAAATGGCTGGT

AAGCAAGAGCAAGGGCCAAAATTTCCCCCAGACCACGAATACCTATAGGAATACTGACACT

GCGGAGCATCTGATTATGTGGGGCATCCACCACCCGAGCTCAACTCAAGAGAAAAATGATC

TTTACGGAACCCAGAGCCTGTCAATTTCCGTGGGGAGCAGTACTTATCGCAATAATTTCGT

ACCTGTCGTAGGTGCCAGACCGCAGGTCAATGGACAGAGCGGCCGTATCGACTTCCACTGG

ACACTGGTGCAGCCAGGGGATAACATCACTTTTTCCCACAACGGCGGCCTGATCGCTCCCA

GCAGGGTGTCGAAGCTGATCGGTCGGGGGCTGGGGATACAGTCAGACGCACCCATTGATAA

CAATTGCGAGAGCAAATGTTTCTGGCGTGGTGGAAGCATAAACACAAGACTTCCGTTTCAG

AACCTTAGTCCACGCACTGTCGGCCAGTGCCCAAAATACGTAAACCGACGTTCCCTGATGC

TCGCTACGGGGATGCGAAACGTACCAGAGTTAATCCAGGGCCGCGGGCTGTTCGGAGCTAT

TGCCGGCTTCCTCGAAAACGGGTGGGAAGGCATGGTAGACGGGTGGTACGGGTTTAGGCAT

CAAAACGCCCAGGGCACAGGCCAGGCGGCCGACTATAAAAGCACCCAGGCTGCAATTGACC

AGATTACCGGGAAACTGAACAGACTTGTAGAAAAAACCAATACAGAATTTGAGTCTATCGA

ATCAGAGTTCTCTGAGATAGAGCATCAGATCGGTAACGTGATCAATTGGACTAAAGATTCA

ATAACTGACATATGGACTTACCAGGCCGAACTTCTGGTGGCTATGGAAAACCAGCATACAA

TTGACATGGCCGACTCCGAGATGTTGAACCTTTACGAGCGCGTGCGTAAACAGCTGAGGCA

AAATGCTGAAGAAGACGGAAAAGGCTGCTTCGAGATATATCACGCTTGTGACGATTCATGT

ATGGAATCCATACGGAATAATACTTACGACCATTCGCAATATAGGGAGGAGGCCTTGTTGA

ACCGGCTGAATATCAATCCAGTGACCCTTAGCTCCGGCTATAAAGATATTATTTTGTGGTT

CTCTTTTGGAGCTTCCTGCTTTGTCCTATTAGCTGTGGTCATGGGCCTCTTTTTTTTCTGC

CTTAAAAATGGGAATATGCGGTGCACTATCTGTATC

812
ATGTATAAGATCGTGGTGATAATCGCCCTGCTGGGGGCTGTTAAAGGTCTCGACAAAATCT

GCTTAGGGCATCACGCCGTGGCCAATGGCACCATAGTTAAGACCCTGACCAATGAACAGGA

AGAGGTTACCAACGCAACGGAGACCGTCGAATCTACCGGCATCAACCGATTATGCATGAAG

GGTCGCAAGCACAAAGATCTCGGAAACTGCCACCCCATTGGCATGCTCATCGGGACCCCTG

CTTGCGACCTGCATTTAACAGGTATGTGGGACACGCTGATTGAAAGAGAGAACGCGATCGC

CTACTGTTACCCAGGCGCTACAGTGAACGTGGAGGCTCTGCGACAGAAAATTATGGAGTCG

GGCGGCATCAATAAAATCAGCACGGGTTTCACTTATGGCAGTTCAATCAACTCCGCCGGTA

CTACCAGGGCCTGTATGCGGAATGGGGGCAACTCTTTTTATGCCGAGCTGAAGTGGCTGGT

CTCCAAGAGTAAGGGCCAGAATTTCCCACAGACCACAAACACTTACAGGAACACGGACACC

GCCGAGCATCTGATTATGTGGGGCATTCACCACCCATCTAGTACCCAGGAGAAGAACGACT

TGTACGGCACACAGTCTCTGTCAATTAGTGTTGGGTCTTCCACATATCGTAATAATTTTGT

ACCGGTCGTGGGCGCGGGGCCCCAAGTGAACGGTCAAAGCGGTAGGATTGATTTTCATTGG

ACCCTCGTGCAACCAGGAGATAATATCACTTTTTCGCACAATGGCGGTCTCATAGCCCCGA

GCCGGGTCAGCAAGCTAATCGGACGGGGGCTCGGGATCCAGTCCGATGCTCCCATCGATAA

TAACTGTGAATCTAAGTGTTTTTGGCGGGGCGGATCCATAAACACCAGGCTTCCCTTCCAG

AACTTGTCCCCAAGGACGGTAGGCCAATGCCCAAAGTACGTTAACCGCCGCTCACTCATGT

TGGCCACTGGGATGAGAAACGTCCCGGAACTGATTCAGGGCCGGGGCCTGTTTGGCGCAAT

CGCTGGGTTCTTAGAGAACGGCTGGGAGGGCATGGTGGACGGATGGTACGGGTTCCGCCAT

CAGAACGCTCAAGGCACTGGGCAGGCTGCAGATTACAAGAGTACCCAGGCTGCCATTGATC

AGATTACCGGAAAACTGAATAGGCTGGTCGAAAAGACAAACACTGAGTTCGAAAGCATCGA

GAGCGAATTTTCTGAGATCGAGCACCAGATCGGGAATGTGATTAACTGGACTAAAGATAGC

ATAACGGATATTTGGACATATCAAGCAGAGTTGTTGGTGGCCATGGAGAATCAGCATACAA

TCGACATGGCCGATAGTGAAATGCTGAATCTTTATGAAAGGGTACGGAAGCAGCTGCGCCA

AAACGCCGAGGAAGATGGGAAGGGGTGTTTTGAAATCTATCATGCCTGTGACGATTCCTGC

ATGGAATCTATTCGTAATAATACTTACGACCATAGCCAATATCGAGAGGAGGCATTGTTGA

ACAGGCTAAACATCAATCCGGTGACACTCAGTTCCGGATATAAAGATATAATCCTCTGGTT

CTCTTTTGGCGCTTCTTGTTTCGTGCTGCTTGCTGTCGTAATGGGACTGTTCTTTTTTTGT

CTCAAAAACGGCAACATGAGATGCACCATTTGCATA

813
ATGTATAAAATCGTTGTGATCATTGCCCTGCTGGGCGCCGTAAAGGGCCTGGACAAAATAT

GCCTGGGGCACCATGCAGTAGTGAATGGCACAATTGTCAAGACACTCACTAACGAACAGGA

AGAAGTCACCAATGCCACGGAGACGGTGGAGAGTACCGGTCTGAACCGTCTGTGCATGAAG

GGCCGCAACCATAAAGACTTGGGTAACTGTCATCCTATAGGTATGCTAATCGGTACTCCGG

CCTGCGATCTGCACCTCACCGGTACCTGGGACACCCTGATCGAGCGTGAGAACGCGATCGC

CTATTGCTATCCAGGCGCTACTGTAAATGAGGAAGCCCTGAGACAGAAGATCATGGAGTCC

GGAGGGATCAATAAGATCTCTACTGGATTCACCTATGGCAGCAGTATTAACTCCGCCGGAA

CTACGCGGGCCTGCATGAGAAATGGCGGGAATAGCTTCTACGCTGAACTGAAATGGCTCGT

TTCGAAGTCAAAAGGACAGAACTTCCCTCAGACAACGAACACATACCGCAACACCGACACC

GCGGAGCATCTAATCATGTGGGGTATCCATCACCCCAGCTCTACACAGGAAAAAAATGATC

TTTATGGAACCCAGTCTTTGTCCATTTCTGTGGGCAGCTCCACCTACCAGAACAATTTCGT

CCCAGTCGTGGGCGCGCGGCCACAGGTGAACGGACAGTCGGGGCGCATTGACTTTCACTGG

ACCCTGGTGCAGCCCGGTGACAATATCACTTTTTCTCACAACGGCGGACTTATTGCTCCCT

CCCGGGTGAGCAAACTGATCGGGGGGGGGCTGGGGATCCAGTCCGATGCACCTATCGATAA

CAATTGCGAGAGTAAATGCTTCTGGCGTGGGGGATCAATAAATACCAGGCTCCCATTCCAA

AATCTTTCACCCCGTACAGTTGGACAGTGCCCCAAATACGTGAACAAGCGCTCTCTTATGC

TGGCAACAGGAATGAGAAACGTTCCAGAGCTAATGCAGGGTCGAGGGCTTTTCGGAGCTAT

TGCTGGATTTATCGAAAATGGCTGGGAGGGAATGGTCGATGGATGGTATGGATTCCGACAC

CAGAACGCTCAGGGGACCGGCCAGGCCGCGGACTACAAGAGCACACAGGCTGCAATTGATC

AGATCACAGGGAAGTTAAATAGGCTCATCGAAAAGACGAACACCGAGTTCGAGTCAATCGA

GTCCGAATTCTCTGAGATCGAACACCAAATTGGCAATGTCATCAATTGGACAAAGGATAGT

ATCACCGATATTTGGACGTACCAAGCAGAGCTTCTGGTTGCCATGGAGAACCAACACACCA

TCGATATGGCCGACAGCGAGATGCTTAATCTGTACGAGCGCGTGCGAAAGCAACTTAGGCA

AAACGCCGAAGAAGATGGTAAGGGCTGCTTTGAGATTTATCACGCTTGCGATGACTCCTGC

ATGGAGTCTATTAGAAATAATACCTACGATCATTCTCAGTATAGAGAGGAGGCCCTGCTGA

ACCGGTTGAACATTAACCCAGTTACACTGAGCTCCGGATACAAAGATATTATTCTGTGGTT

TTCCTTTGGCGCGTCCTGCTTTGTGCTGTTAGCCGTGGTGATGGGGCTGGTATTCTTCTGT

CTCAAGAACGGTAATATGCGTTGTACCATATGCATC

814
ATGTATAAGATCGTGGTCATAATTGCACTCTTGGGGGCAGTGAAAGGGCTGGATAAAATTT

GTCTGGGACACCACGCCGTTGCTAATGGCACCATCGTGAAAACCCTTACCAACGAGCAGGA

AGAGGTTACTAACGCAACCGAGACGGTCGAGTCCACTGGAATCAATCGTCTTTGCATGAAG

GGCCGTAAACATAAGGATTTAGGAAATTGTCATCCCATTGGCATGCTGATCGGAACACCTG

CCTGCGACCTGCACCTGACAGGGATGTGGGACACGCTGATCGAGAGGGAGAATGCAATTGC

GTACTGTTATCCTGGAGCTACCGTGAATGTTGAAGCACTGCGTCAAAAAATCATGGAATCC

GGCGGGATCAACAAAATTAGCACTGGGTTCACATATGGAAGCAGCATAAACTCCGCCGGCA

CTACAAGGGCCTGCATGAGAAACGGCGGCAATAGTTTCTACGCTGAACTTAAGTGGCTTGT

GTCAAAATCAAAGGGGCAAAACTTTCCTCAGACTACAAATACATATAGAAACACTGACACC

GCCGAGCACCTGATCATGTGGGGCATTCACCATCCTAGCTCTACCCAGGAGAAAAATGATT

TATACGGCACTCAGAGTCTGTCTATTTCTGTGGGGTCGTCCACATATAGAAATAATTTCGT

GCCAGTCGTGGGGGCTCGGCCGCAAGTGAATGGGCAGAGTGGTAGAATCGATTTCCACTGG

ACACTTGTGCAGCCCGGGGATAACATTACTTTCTCTCATAACGGGGGCCTGATCGCACCCT

CCAGGGTGAGTAAACTAATAGGCAGGGGTCTGGGCATTCAGTCCGACGCTCCAATCGATAA

CAACTGCGAGTCCAAGTGCTTCTGGCGCGGGGGTTCCATCAACACCCGGTTACCTTTTCAG

AACCTGTCCCCCCGCACCGTTGGCCAGTGCCCTAAATACGTAAATCGAAGATCATTAATGC

TGGCGACCGGTATGAGGAACGTACCTGAGCTGATTCAGGGGAGGGGGTTATTTGGTGCCAT

TGCCGGGTTTCTCGAAAACGGGTGGGAGGGAATGGTTGATGGCTGGTACGGGTTCAGGCAC

CAGAATGCCCAGGGCACAGGACAGGCTGCCGATTACAAGAGCACTCAGGCCGCTATTGACC

AGATCACCGGCAAGCTGAATCGGCTGGTAGAGAAAACCAATACGGAGTTTGAGTCCATTGA

GTCCGAGTTCTCAGAGATCGAGCACCAGATTGGCAATGTCATCAATTGGACCAAGGATTCA

ATTACGGATATATGGACATACCAGGCTGAGCTGCTTGTAGCAATGGAGAACCAACATACCA

TAGACATGGCTGATTCTGAGATGCTGAACCTCTACGAAAGGGTCAGAAAACAACTCAGACA

AAACGCAGAAGAAGACGGGAAAGGGTGTTTCGAAATTTACCATGCTTGTGATGACTCCTGC

ATGGAGAGCATCAGAAACAACACTTATGACCACAGCCAGTACCGTGAAGAGGCATTGTTGA

ACCGACTCAACATCAACCCTGTTACGCTGTCATCTGGGTATAAAGACATTATTCTATGGTT

CTCTTTTGGCGCTTCATGTTTTGTTCTGTTGGCGGTAGTGATGGGTCTGTTCTTTTTCTGT

TTAAAAAATGGCAATATGAGGTGCACCATCTGCATA

815
ATGTACAAGATCGTGGTTATTATCGCTCTTCTGGGTGCCGTTAAAGGGCTGGACAAAATTT

GTCTGGGGCATCACGCCGTGGCGAATGGTACTATCGTCAAGACATTGACCAACGAGCAGGA

GGAGGTTACAAATGCAACCGAGACCGTTGAGAGTACTGGAATCAACCGGCTGTGCATGAAG

GGAAGAAAGCACAAGGATCTGGGGAATTGTCACCCTATCGGAATGTTAATTGGTACACCTG

CTTGTGACCTGCACCTGACAGGCATGTGGGACACCCTGATCGAACGGGAGAACGCCATTGC

CTATTGTTATCCAGGGGCCACTGTTAATGTCGAGGCACTCAGGCAGAAGATTATGGAATCC

GGTGGAATTAATAAAATTAGCACAGGGTTTACTTACGGTTCCTCAATAAATTCAGCCGGCA

CTACACGGGCGTGTATGAGGAATGGAGGAAACTCCTTCTATGCCGAACTGAAATGGCTCGT

CAGCAAATCCAAGGGTCAAAATTTTCCTCAAACAACTAACACCTATAGAAATACCGATACC

GCAGAGCACCTCATAATGTGGGGGATACACCATCCGAGCTCCACACAAGAAAAAAACGACC

TGTATGGCACTCAAAGTCTTAGCATTTCCGTCGGAAGTTCTACATACCGGAATAACTTTGT

GCCGGTGGTAGGTGCCCGACCCCAAGTCAACGGCCAGAGTGGCCGCATCGATTTCCATTGG

ACACTGGTGCAGCCAGGAGATAACATTACCTTTTCTCACAATGGCGGCTTGATCGCTCCTT

CGAGGGTGAGCAAGCTGATTGGCCGGGGTCTGGGCATTCAATCCGACGCGCCTATCGACAA

TAATTGTGAGTCTAAATGCTTTTGGAGAGGAGGGTCAATCAACACAAGACTACCCTTCCAG

AATCTTTCCCCCCGAACAGTGGGACAGTGCCCCAAATATGTGAATCGGCGCTCTCTTATGC

TGGCCACTGGGATGAGAAACGTGCCTGAGTTAATACAGGGCCGGGGACTTTTCGGAGCAAT

CGCCGGATTCCTAGAGAACGGTTGGGAGGGGATGGTCGACGGATGGTACGGGTTCAGACAC

CAAAATGCTCAGGGGACAGGGCAGGCAGCAGACTATAAATCAACGCAGGCCGCTATCGACC

AGATCACCGGTAAACTGAACCGGCTTGTCGAAAAGACCAACACTGAGTTCGAGAGTATTGA

ATCCGAGTTTAGCGAGATCGAACACCAGATAGGCAATGTTATCAATTGGACAAAGGATTCA

ATCACGGACATATGGACATACCAAGCAGAACTGCTGGTAGCTATGGAAAATCAACATACAA

TCGATATGGCCGACTCAGAGATGCTCAACCTCTACGAAAGAGTAAGGAAACAACTCAGACA

AAATGCCGAAGAGGACGGCAAGGGTTGCTTTGAAATATATCATGCGTGCGACGACAGCTGC

ATGGAGAGCATACGGAACAATACGTACGACCATTCCCAGTATCGCGAAGAAGCCTTACTGA

ACCGCTTGAACATTAACCCCGTGACCCTTTCCTCCGGATATAAAGATATCATTCTCTGGTT

CAGTTTTGGAGCCTCATGCTTTGTCCTTTTGGCTGTGGTAATGGGATTATTTTTCTTCTGT

CTCAAGAATGGTAACATGCGATGTACAATTTGCATC

816
ATGTACAAGATCGTGGTGATCATAGCACTGCTGGGCGCCGTGAAAGGCTTAGACAAAATCT

GCTTAGGGCATCATGCCGTCGCTAATGGGACTATAGTCAAGACATTGACCAACGAGCAAGA

AGAGGTGACAAACGCAACTGAAACTGTTGAAAGTACCGGGATAAACCGGTTGTGCATGAAA

GGGCGAAAGCACAAGGACCTTGGCAACTGTCATCCCATCGGCATGCTTATAGGAACACCTG

CTTGCGATCTCCATCTGACTGGCATGTGGGACACCCTGATAGAACGAGAAAATGCCATTGC

CTACTGTTACCCAGGCGCCACCGTTAATGTTGAGGCCCTCAGACAGAAGATAATGGAATCT

GGAGGCATCAACAAAATCTCTACGGGCTTTACCTACGGTTCTAGCATTAACTCTGCCGGGA

CTACCCGAGCTTGTATGCGCAACGGGGGCAACTCTTTCTACGCCGAACTTAAGTGGCTGGT

GAGCAAGAGCAAGGGACAGAATTTCCCTCAAACTACTAACACTTATAGGAACACAGACACC

GCCGAACATCTAATAATGTGGGGAATACACCATCCCTCATCCACACAGGAAAAAAACGACC

TTTATGGGACCCAGTCTCTGAGCATTTCAGTCGGCTCATCCACTTATCGTAACAACTTTGT

GCCCGTGGTTGGGGCTCGGCCCCAGGTGAATGGCCAGTCTGGGCGTATTGATTTCCACTGG

ACCCTAGTGCAACCCGGAGACAACATCACCTTTAGTCATAATGGTGGCCTTATAGCCCCTA

GCAGGGTGTCAAAACTTATTGGGAGAGGCCTCGGGATTCAGAGTGACGCACCCATCGACAA

CAACTGCGAGAGTAAGTGTTTTTGGAGAGGGGGTTCGATCAACACCCGCCTCCCCTTCCAG

AACCTATCGCCACGCACTGTTGGTCAGTGCCCAAAATACGTCAACAGGAGGTCACTTATGC

TGGCTACAGGGATGCGGAACGTGCCGGAGCTGATACAGGGACGCGGTCTGTTCGGAGCCAT

TGCCGGATTCTTGGAGAATGGCTGGGAGGGGATGGTGGACGGCTGGTACGGCTTCCGACAC

CAGAATGCCCAGGGTACAGGTCAGGCAGCGGACTATAAGAGTACTCAAGCCGCTATCGATC

AAATCACTGGGAAGCTCAACCGACTGGTCGAGAAGACAAACACAGAATTCGAGTCTATCGA

GTCAGAATTCTCTGAAATCGAGCACCAGATTGGTAACGTAATCAATTGGACCAAGGATAGT

ATTACCGACATCTGGACATACCAAGCAGAACTGCTCGTGGCAATGGAAAATCAGCACACAA

TAGACATGGCCGATAGTGAGATGCTCAACCTGTACGAACGCGTTCGAAAACAGCTGAGACA

GAACGCTGAAGAAGACGGGAAAGGGTGCTTCGAGATCTATCACGCCTGCGACGATTCATGC

ATGGAGAGCATTAGAAACAATACCTACGACCACAGCCAGTATAGGGAGGAGGCTCTGCTAA

ACAGGCTCAACATTAATCCCGTAACACTCTCAAGCGGATATAAAGACATAATTCTGTGGTT

TTCCTTCGGAGCTTCCTGCTTCGTCCTGCTGGCGGTAGTCATGGGGTTATTCTTTTTTTGT

CTGAAGAACGGGAATATGCGATGTACAATATGCATT

817
ATGTACAAGGTTGTGGTTATTATAGCACTCCTCGGGGCTGTGCGCGGACTGGATAAGATCT

GCCTGGGACATCATGCCGTGGCAAATGGTACCACTGTAAAAACTCTCACCAATGAGCAGGA

AGAGGTGACCAACGCCACTGAGACAGTGGAATCTACAAGCCTGAACAAGCTGTGTATGAAG

GGCAGACGATATAAGGATCTGGGTAATTGCCATCCCATCGGCATGTTGATCGGAACACCAG

TTTGCGATCTGCATCTAACTGGAACCTGGGACACGCTTATCGAGCGGGAAAACGCCACCGC

GTACTGCTACCCAGGAGTCACCATCAACGAAGAAGCACTGAGACAGAAGATCATGGAGAGT

GGGGGGATCTCCAAGATGCGCACCGGGTTCACTTATGGGCCCAGCATTAACAGCGCTGGGA

CAACCAGATCCTGCATGAGGAATGGAGGGAACTCTTTTTATGCCGAATTAAAATGGCTGGT

TTCAGGAACAAAAGGACAAAATTTCCCGCAGACCACCAATACATATAGAAACACCGATACA

GCAGAACACTTAATCATCTGGGGGATCCATCACCCTTCATCTACGCAGGAAAAGAATGATC

TGTATGGTACCCAGTCTTTGAGTATTAGTGTAGGCTCTTCCACGTACCAGAATAACTTTGT

CCCTGTTATAGGTGCTCGACCTCAGGTCAATGGGCAGTCTGGGCGTATCGAGTTCCATTGG

ACCCTCGTACGACCCGGCGACAACATCACATTTAGCCACAACGGCGGATTGATAGCCCCCG

ACAGAGTGTCCAAGTTAATCGGCAAAGGAATTGGTATCCAGTCCGGCGCCGTGATCGATAA

GGATTGTGAGTCAAAATGCTTCTGGAGAGGCGGCAGCATCATAACAGAGCTTCCGTTTCAA

AACCTGAGTCCCCGCACCGTTGGGCAATGTCCTAAGTACGTGAAAAAACGAAGCCTCCTGC

TGGCAACCGGCATGCGGAATGTTCCCGAGGTGGTCCAGGGAAGAGGCCTGTTTGGCGCGAT

TGCTGGGTTCATCGAGAATGGCTGGGAAGGCATGGTTGACGGATGGTATGGGTTCAGGCAT

CAGAACGCGCAGGGCATCGGGCAGGCTGCTGACTACAAGAGCACTCAGACCGCCATCGATC

AGATCACAGGGAAGCTAAATCGGCTGATTGAAAAGACTAACACGGAGTTTGAGAGCATTGA

AAGCGAATTTAGTGAAATCGAACACCAGATAGGAAACGTTATTAACTGGACAAAGGATAGT

ATTACCGACATATGGACGTATCAAGCAGAGCTGCTGGTCGCCATGGAGAACCAGCATACTA

TAGATATGGCAGACAGCGAAATGCTCAATTTGTACGAGAGGGTAAGAAAACAACTGAGACA

AAATGCTGAAGAGGATGGCAAAGGCTGCTTTGAAATATACCACACCTGTGACAATTCCTGT

ATGGAGTCCATTCGGAACAATACGTATGATCATTCCCAGTATCGCGAGGAAGCCCTACTCA

ACCGCCTCAATATCAACCCCGTTAAGCTATCATCAGGCTACAAGGACATTATCCTGTGGTT

CAGCTTCGGAGCCTCCTGTTTCGTGCTACTTGCTGTGATCATGGGTTTGGGGTTCTTTTGC

CTGAAAAATGGAAATATGAGATGCACAATTTGTATT

818
ATGTATAAGATAGTCGTGATAATCGCCCTTTTGGGAGCGGTGAAGGGACTGGACAAGATTT

GTCTCGGCCATCATGCAGTCGCCAACGGTACAATTGTTAAAACCCTCACCAACGAACAAGA

AAAAGTGACAAATGCCACAGAAACTGTGGAGAGCACCGGCCTTAACCGGTTGTGCATGAAG

GGGCGAAAGCATAAGGACTTGGGTAATTGTCATCCAATTGGGATGCTGATTGGGACTCCCG

CCTGCGATCTGCACCTGACCGGCACATGGGATACCATTATCGAGAGGGAGAACGCGATCGC

TTACTGCTATCCTGGGGCTACAGTCAATGAGGAGGCCCTAAGGCAGAAAATAATGGAGTCA

GGGGGAATCGATAAAATTTCTACAGGCTTCACTTACGGATCTTCTATTAACAGCGCAGGCA

CCACGCGCGCCTGCATGAGAAATGGCGGGAATAGTTTTTATGCCGAGCTGAAATGGCTGGT

GTCCAAGAGCAAGGGACAGAACTTTCCGCAAACCACTAATACATACCGTAATACTGACACA

GCAGAACATCTGATTATGTGGGGAATCCACCACCCCTCCAGCACTCAAGAGAAAAATGATC

TTTACGGAACACAGTCCCTCAGCATAAGCGTGGGTTCGAGTACATATAGGAACAATTTCGT

GCCAGTGGTAGGCGCGCGACCGCAGGTCAATGGACAGTCAGGAAGGATCGACTTCCATTGG

ACTCTAGTGCAACCTGGGGATAATATTACCTTTAGCCATAATGGAGGTCTGATAGCCCCAT

CTCGCGTCTCCAAGCTGATTGGGCGCGGTCTGGGGATTCAGAGTGACGCTCCTATTGATAA

CAACTGCGAGAGTAAATGTTTCTGGCGCGGCGGCTCGATTAACACCCGTCTTCCCTTTCAG

AACCTGAGTCCCCGGACAGTAGGACAGTGCCCTAAATACGTGAACAAAAGAAGTCTTATGC

TCGCCACTGGGATGCGAAACGTTCCGGAACTGATCCAGGGTCGCGGCCTGTTCGGCGCAAT

TGCTGGTTTCCTCGAAAATGGATGGGAAGGTATGGTGGATGGGTGGTACGGGTTCAGACAT

CAAAACGCTCAGGGCACGGGCCAGGCTGCCGACTACAAGAGCACACAGGCTGCCATCGACC

AGATTACTGGGAAACTCAATAGACTCGTGGAAAAAACTAATACGGAATTCGAAAGCATCGA

ATCTGAGTTCAGTGAGATCGAACATCAGATCGGAAACGTGATCAACTGGACAAAGGATTCG

ATTACTGATATTTGGACGTACCAGGCAGAGTTGTTGGTCGCCATGGAGAATCAACACACAA

TCGATATGGCCGACTCAGAGATGTTGAATCTTTACGAGAGGGTGCGAAAGCAGCTGAGGCA

GAATGCCGAGGAAGATGGAAAGGGGTGTTTTGAGATCTACCACGCCTGCGACGATTCTTGC

ATGGAATCCATCCGCAATAATACATACGATCACTCACAGTATAGGGAGGAGGCCCTACTCA

ACAGACTGAACATCAATCCCGTGACACTTTCAAGTGGTTACAAGGATATCATACTTTGGTT

CAGCTTCGGCGCCAGTTGCTTTGTTCTGCTTGCCGTTGTGATGGGCCTGGTGTTCTTTTGC

CTGAAGAATGGTAACATGAGATGTACCATCTGCATT

819
ATGTATAAAATTGTCGTTATCATTGCCTTGCTCGGCGCTGTGAAGGGGCTGGATAAAATTT

GTCTGGGACATCACGCCGTGGCGAACGGGACTATCGTCAAGACGCTTACTAACGAACAGGA

AGAGGTGACTAACGCGACGGAAACCGTGGAGTCAACTGGGATTAATCGCTTGTGCATGAAG

GGCAGAAAGCACAAGGACTTAGGCAACTGTCATCCTATCGGCATGCTGATCGGTACCCCAG

CCTGCGACCTTCACTTGACTGGCACCTGGGATACCCTGATCGAAAGAGAGAACGCAATAGC

ATACTGTTATCCAGGCGCCACAGCCAACGTAGAGGCCCTGAGACAGAAGATCATGGAATCT

GGAGGTATCGATAAAATTAGCACCGGATTTACATATGGATCAAGTATAAACTCGGCAGGAA

CGACGCGGGCGTGCATGCGAAATGGCGGAAATTCCTTCTACGCCGAATTGAAATGGCTAGT

GTCCAAAAGCAAAGGCCAAAACTTTCCACAGACTACTAACACCTACAGAAATACTGACACC

GCTGAACATTTGATTATGTGGGGGATCCACCACCCAAGTAGCATTCAGGAGAAGAACGATC

TGTATGGCACTCAGTCACTAAGTATTTCCGTGGGCAGCTCTACCTACCGCAATAACTTCGT

GCCGGTTGTGGGCGCCAGACCTCAGGTGAACGGACAAAGTGGTCGCATTGATTTCCACTGG

ACACTTGTGCAACCTGGGGACAATATCACTTTCAGCCACAACGGGGGGCTGATCGCCCCAT

CAAGAGTGAGCAAATTGATAGGGAGAGGCTTGGGAATCCAGTCAGATGCACCTATCGATAA

TAATTGTGAAAGCAAATGCTTTTGGCGTGGGGGATCCATAAACACTCGACTGCCATTCCAG

AATTTGTCCCCCCGCACCGTTGGCCAGTGTCCCAAGTACGTTAATCGCAGAAGTCTGATGC

TGGCCACCGGCATGAGAAACGTGCCCGAACTGATACAGGGACGCGGGCTCTTTGGAGCAAT

TGCCGGCTTTCTGGAGAACGGATGGGAGGGAATGGTGGACGGATGGTACGGCTTTCGGCAC

CAGAATGCCCAGGGGACAGGACAAGCCGCCGATTATAAGTCAACACAGGCCGCAATCGACC

AGATTACCGGCAAGCTCAACAGGCTCGTGGAAAAGACAAACACTGAGTTTGAGTCAATCGA

GTCAGAATTTTCCGAGATCGAGCATCAAATCGGCAACGTGATCAATTGGACTATGGATTCT

ATCACCGACATTTGGACTTACCAGGCAGAGCTCCTGGTGGCAATGGAGAACCAACACACTA

TCGACATGGCAGATTCAGAGATGCTCAACCTCTATGAAAGGGTACGAAAACAGCTTCGGCA

GAACGCCGAGGAGGACGGTAAGGGGTGTTTTGAAATCTATCATGCGTGCGACGATAGCTGT

ATGGAAAGTATCCGGAATAATACATACGATCACTCCCAGTACCGCGAAGAGGCTCTCTTGA

ACCGGCTTAACATCAACCCGGTAACTCTCAGTAGCGGGTACAAGGACATCATTCTGTGGTT

TTCTTTTGGTGCCTCCTGTTTTGTGCTGCTGGCCGTGGTGATGGGACTCGTGTTTTTTTGC

CTCAAGAACGGGAATATGCGGTGCACAATATGCATT

820
ATGTATAAGATTGTGGTGATTATTGCTCTCTTGGGGGCAGTCAAAGGACTTGATAAGATTT

GTCTGGGCCACCATGCTGTCGCAAATGGGACAATCGTCAAGACCCTTACCAACGAGCAAGA

AAAGGTAACCAACGCAACCGAGACTGTTGAGAGTACAGGGCTGAATAGACTCTGTATGAAG

GGCCGCAAACATAAGGACCTAGGTAACTGTCATCCAATAGGGATGCTGATTGGAACACCGG

CATGTGACTTACACCTCACAGGTACATGGGATACTATTATAGAGAGAGAAAATGCCATTGC

CTACTGTTATCCTGGGGCTACCGTTAACGAGGAAGCCTTACGTCAGAAAATTATGGAATCC

GGGGGCATTGATAAAATATCCACTGGATTTACTTATGGAAGCTCAATCAACTCCGGGGGCA

CTACTCGAGCATGTATGCGCAACGGAGGTAACTCCTTCTACGCCGAACTGAAGTGGCTCGT

TTCAAAATCCAAAGGACAGAACTTTCCGCAGACCACTAATACCTACCGCAATACAGACACA

GCAGAACATCTGATCATGTGGGGCATTCATCACCCCAGCTCTACTCAAGAAAAGAATGACC

TGTACGGGACTCAAAGTCTGTCCATTTCTGTTGGGTCTAGTACCTACCGGAATAACTTTGT

CCCCGTTGTTGGAGCACGCCCTCAGGTTAACGGTCAGAGTGGAAGGATCGACTTTCACTGG

ACCCTCGTCCAGCCTGGCGACAATATCACATTTAGTCACAACGGGGGCCTAATCGCTCCCT

CTCGGGTGAGCAAGCTGATAGGTCGGGGCTTGGGTATACAGTCTGACGCCCCAATCGATAA

CAACTGTGAAAGCAAGTGCTTCTGGCGGGGTGGCTCTATCAACACCCGACTGCCATTTCAA

AATCTCAGTCCAAGGACAGTGGGGCAATGCCCAAAATACGTCAACAAAAGGTCACTCATGC

TCGCCACAGGAATGCGCAATGTGCCTGAACTGATTCAAGGACGAGGACTGTTTGGCGCTAT

TGCCGGGTTTTTAGAGAATGGCTGGGAAGGCATGGTAGACGGGTGGTACGGGTTCCGGCAT

CAGAATGCCCAAGGGACGGGTCAGGCCGCTGACTATAAGTCCACTCAGGCCGCAATAGATC

AGATCACCGGAAAGTTGAACAGACTAGTGGAGAAGACAAACACTGAGTTCGAGTCCATTGA

GAGCGAATTCAGCGAGATAGAACACCAAATCGGCAATGTGATTAACTGGACCAAAGACAGT

ATTACTGATATCTGGACTTATCAAGCCGAACTGTTGGTGGCAATGGAGAACCAACACACGA

TCGACATGGCAGACAGTGAGATGCTCAATCTGTACGAGAGGGTGCGTAAACAGCTGAGGCA

GAACGCCGAAGAAGACGGAAAGGGGTGTTTCGAGATATACCACGCCTGTGATGACTCCTGT

ATGGAAAGCATCAGGAACAACACTTATGACCATAGTCAATATAGGGAAGAAGCACTGCTCA

ACCGCCTGAACATCAATCCTGTAACACTTTCATCAGGATATAAGGACATCATCCTCTGGTT

TAGTTTCGGAGCTTCATGCTTTGTGCTGCTCGCGGTAGTCATGGGGCTGGTCTTCTTTTGT

TTGAAGAACGGTAACATGAGATGCACCATTTGTATC

821
ATGTACAAAATCGTCGTCATCATCGCCTTACTGGGAGCCGTCAAAGGACTTGATAAAATTT

GTCTTGGTCACCACGCTGTTGCCAATGGAACAATCGTGAAGACACTTACCAATGAGCAGGA

GGAGGTGACTAATGCAACAGAGACAGTGGAGTCCACTGGAATAAATCGGCTGTGCATGAAG

GGCAGAAAACACAAGGATTTGGGCAACTGCCACCCTATTGGAATGCTCATAGGCACCCCTG

CGTGTGACCTTCATCTGACTGGCACTTGGGACACTCTCATCGAACGCGAGAACGCCATCGC

CTACTGCTATCCTGGAGCCACCGCCAACGTGGAGGCTCTACGGCAGAAGATTATGGAGAGC

GGAGGGATTGACAAGATCTCCACGGGTTTCACTTACGGCAGCTCCATCAACAGTGCCGGTA

CAACTCGGGCGTGCATGAGAAACGGGGGCAACAGCTTTTATGCCGAGCTGAAGTGGCTGGT

GAGTAAGTCAAAAGGGCAGAACTTTCCACAGACAACAAATACGTACAGAAATACAGATACA

GCCGAGCACCTGATCATGTGGGGGATTCATCATCCAAGTTCTATCCAGGAGAAAAACGACT

TGTATGGGACTCAGAGTCTCAGTATCAGCGTAGGTTCCTCTACCTACAGGAACAACTTCGT

GCCCGTCGTCGGGGCCCGTCCCCAAGTCAACGGCCAGAGTGGACGGATTGATTTTCACTGG

ACTCTTGTGCAGCCCGGCGACAACATTACCTTCAGTCACAACGGAGGGCTGATTGCACCTT

CCAGAGTCTCGAAGCTGATCGGACGTGGATTGGGGATTCAGTCGGACGCTCCTATCGACAA

TAATTGCGAGAGCAAATGTTTCTGGCGCGGGGGTTCTATTAACACCAGGCTCCCCTTTCAA

AATTTGAGCCCGCGAACCGTCGGCCAATGTCCCAAGTATGTCAACCGGAGAAGCCTGATGT

TGGCTACAGGAATGCGCAATGTGCCGGAGCTCATCCAGGGCCGTGGCTTGTTCGGTGCAAT

TGCCGGATTCCTAGAAAATGGATGGGAGGGAATGGTTGATGGGTGGTACGGCTTCCGCCAC

CAAAACGCTCAGGGCACTGGACAGGCCGCGGACTATAAGTCTACTCAGGCGGCTATCGATC

AGATCACTGGGAAACTGAATAGGCTTGTGGAAAAAACCAATACGGAGTTCGAAAGTATCGA

GTCAGAGTTTAGCGAAATCGAGCATCAGATTGGTAACGTGATCAACTGGACCATGGATAGC

ATTACCGACATCTGGACCTACCAGGCCGAATTGCTGGTGGCCATGGAGAATCAGCACACAA

TTGACATGGCAGACTCTGAAATGCTTAACCTATATGAGCGCGTACGGAAACAGCTCAGACA

GAACGCGGAGGAAGATGGAAAGGGCTGCTTCGAAATTTATCACGCTTGCGACGACTCCTGT

ATGGAGTCTATCAGAAACAATACGTATGATCATTCGCAATACCGGGAGGAAGCACTCCTGA

ATAGACTCAACATCAACCCCGTTACACTGAGCTCAGGGTACAAAGACATTATTCTCTGGTT

TTCCTTCGGAGCTTCTTGCTTCGTACTGTTAGCTGTCGTCATGGGGCTAGTTTTTTTTTGT

CTTAAAAACGGCAACATGAGATGCACCATCTGTATA

822
ATGTATAAAATCGTGGTAATCATTGCACTGCTGGGAGCAGTCAAAGGGCTCGATAAAATAT

GCCTTGGCCACCACGCCGTAGCAAATGGTACAATCGTGAAGACCCTCACGAACGAACAGGA

GGAAGTCACCAACGCTACAGAAACTGTCGAAAGTACCGGGATCAACCGGCTCTGTATGAAG

GGCAGGAAGCATAAAGACTTAGGTAACTGCCATCCTATCGGCATGCTGATTGGCACACCTG

CCTGCGACTTGCACTTAACGGGAATGTGGGACACATTGATTGAGAGAGAGAATGCTATTGC

TTACTGTTACCCAGGAGCGACTGTGAACGTGGAGGCACTACGGCAAAAAATAATGGAGTCC

GGGGGAATCAATAAGATCTCGACAGGATTTACCTATGGGAGCTCAATCAATTCTGCGGGAA

CAACCCGGGCCTGCATGCGCAATGGGGGGAATAGCTTCTATGCCGAACTCAAGTGGCTCGT

TAGCAAGAGCAAAGGGCAGAATTTCCCGCAAACTACTAACACATACAGGAACACAGACACA

GCAGAGCATTTGATTATGTGGGGGATTCACCACCCCTCTAGTACGCAGGAAAAGAACGATC

TTTACGGGACCCAGTCCCTTTCTATCAGCGTAGGAAGCAGCACTTACAGGAATAATTTTGT

CCCTGTGGTTGGCGCGGGCCCTCAGGTTAATGGGCAATCTGGCCGCATTGATTTTCATTGG

ACCCTCGTACAGCCTGGCGACAATATAACATTCTCACATAATGGCGGCCTGATCGCACCTT

CCCGGGTATCTAAATTGATAGGTAGAGGCCTGGGGATTCAAAGCGATGCTCCAATAGATAA

TAACTGTGAATCAAAGTGCTTTTGGGGGGGAGGGTCAATTAATACGCGGCTACCCTTTCAG

AATCTTAGCCCACGCACCGTTGGCCAATGTCCAAAGTACGTGAATCGTAGATCACTGATGC

TGGCTACAGGGATGCGGAATGTGCCAGAACTCATTCAGGGCCGTGGGCTATTCGGCGCTAT

CGCCGGGTTTCTGGAAAACGGCTGGGAGGGGATGGTCGATGGCTGGTACGGCTTCCGGCAC

CAGAACGCTCAGGGTACAGGGCAGGCGGCTGATTATAAAAGCACACAGGCTGCAATCGACC

AAATTACTGGAAAACTAAATAGGCTAGTGGAAAAAACCAACACCGAATTCGAAAGTATTGA

AAGTGAGTTCAGTGAAATTGAGCACCAGATTGGAAACGTGATCAACTGGACTAAGGACAGT

ATCACCGATATTTGGACATATCAGGCAGAACTTCTCGTGGCCATGGAAAACCAGCATACTA

TTGACATGGCTGACAGTGAAATGTTAAATCTCTATGAGCGCGTACGCAAACAATTGCGGCA

GAATGCCGAGGAAGATGGGAAGGGCTGCTTCGAAATCTATCACGCTTGCGACGATTCCTGC

ATGGAGTCCATCAGGAACAATACATACGATCACAGCCAGTATCGCGAAGAAGCCCTGCTTA

ATAGACTAAATATTAATCCCGTCACCCTGTCCTCAGGCTATAAGGACATCATCCTTTGGTT

TTCATTTGGCGCAAGTTGCTTCGTCTTGCTCGCAGTCGTCATGGGGCTGTTTTTTTTCTGT

CTCAAAAACGGAAACATGAGGTGTACCATTTGCATT

823
ATGTACAAAATTGTGGTTATCATCGCTTTGCTTGGCGCTGTGAAGGGGCTGGATAAGATCT

GTCTCGGGCATCACGCTGTCGCCAATGGCACAATTGTCAAGACATTGACGAACGAGCAGGA

GGAAGTGACAAATGCCACTGAAACAGTGGAATCCACTGGGATCAACCGATTGTGCATGAAA

GGTAGGAAGCATAAGGATCTCGGTAACTGTCATCCAATCGGCATGTTGATTGGAACCCCGG

CCTGTGATCTTCACCTCACTGGTATGTGGGACACACTGATTGAAAGAGAAAACGCTATTGC

CTACTGTTACCCAGGTGCAACGGTTAATGTCGAGGCACTGAGACAGAAAATTATGGAAAGC

GGAGGCATCAACAAGATATCAACCGGGTTTACCTATGGCTCATCGATTAATAGCGCAGGCA

CCACTCGCGCGTGTATGCGAAATGGAGGAAATTCATTTTATGCCGAGTTAAAATGGCTGGT

TAGTAAGAGCAAGGGTCAGAACTTCCCTCAGACCACAAATACGTATCGCAATACGGACACT

GCAGAACACCTTATCATGTGGGGTATTCACCACCCTAGCAGTACTCAAGAAAAAAATGACC

TGTATGGTACCCAGAGTCTGAGTATAAGCGTGGGTTCCAGTACTTACCGGAACAACTTCGT

TCCAGTTGTGGGGGCCCGCCCACAGGTTAACGGGCAATCGGGGCGCATCGATTTTCACTGG

ACCTTGGTGCAACCTGGAGACAATATTACTTTCAGTCACAACGGCGGATTGATAGCTCCAT

CCCGTGTCAGTAAATTGATTGGGCGCGGACTGGGAATCCAGTCTGACGCACCCATAGATAA

CAACTGTGAGTCTAAGTGTTTCTGGAGGGGCGGTTCCATTAATACTCGGCTGCCATTTCAG

AATCTTAGCCCGCGCACTGTGGGTCAATGTCCCAAGTACGTGAACAGGCGTTCTCTAATGC

TTGCCACCGGGATGAGAAACGTTCCTGAACTGATACAAGGTAGGGGACTGTTCGGTGCAAT

CGCTGGCTTTTTGGAGAATGGCTGGGAGGGAATGGTGGACGGCTGGTATGGATTCCGCCAT

CAGAACGCCCAGGGAACCGGACAGGCTGCCGACTATAAGTCCACGCAGGCCGCGATTGACC

AAATTACCGGAAAACTCAATCGCCTAGTCGAGAAAACAAACACCGAATTCGAGAGTATCGA

GTCCGAATTTTCTGAGATCGAGCACCAAATCGGCAACGTAATCAATTGGACGAAGGATTCC

ATTACTGACATCTGGACCTACCAAGCCGAATTGTTGGTCGCAATGGAGAACCAGCACACCA

TAGACATGGCTGACAGCGAAATGCTGAACCTGTACGAGCGGGTTCGGAAACAGCTGCGCCA

GAACGCAGAGGAGGATGGCAAAGGCTGCTTCGAAATCTATCACGCCTGCGACGATAGCTGC

ATGGAATCAATAAGGAATAACACTTATGATCACAGCCAGTATCGGGAAGAGGCCCTGCTGA

ATCGGCTCAACATCAATCCCGTGACTCTCTCTTCCGGCTATAAAGACATTATCTTGTGGTT

CTCTTTCGGCGCGTCATGCTTCGTGCTGCTGGCAGTGGTAATGGGACTCTTCTTTTTTTGC

CTGAAAAACGGGAACATGCGCTGCACAATCTGCATC

824
ATGTATAAGATTGTGGTGATTATTGCCCTGCTCGGCGCCGTGAAGGGGTTGGACAAGATTT

GTCTTGGTCACCACGCCGTGGCTAACGGGACCATAGTCAAGACTCTGACCAATGAACAGGA

AGAGGTAACAAACGCAACCGAAACAGTCGAGTCTACAGGAATCAATCGGTTATGTATGAAA

GGCCGAAAACATAAAGACCTCGGCAATTGTCACCCCATAGGGATGCTGATCGGGACTCCAG

CTTGCGACCTGCATTTAACAGGCATGTGGGACACTCTCATCGAGAGAGAGAACGCGATCGC

ATACTGCTACCCAGGAGCTACCGTGAATGTAGAGGCATTGAGACAGAAAATCATGGAAAGT

GGCGGAATAAATAAGATTTCTACAGGGTTTACGTACGGCAGCTCCATTAACAGTGCCGGAA

CAACCCGAGCATGTATGAGAAATGGAGGTAATAGCTTTTACGCCGAACTGAAGTGGCTTGT

GTCCAAAAGTAAGGGGCAAAATTTTCCTCAGACAACGAACACCTACCGGAACACCGACACA

GCTGAGCACCTGATTATGTGGGGGATACATCATCCTAGCAGCACGCAGGAGAAGAATGATC

TATACGGGACCCAATCTCTCAGCATCTCAGTGGGCTCCTCAACTTACCGCAACAACTTCGT

GCCTGTCGTCGGCGCCCGCCCTCAGGTCAACGGTCAGTCTGGCCGAATCGACTTTCACTGG

ACACTGGTGCAGCCTGGAGACAACATCACTTTCTCCCATAACGGGGGACTTATCGCACCGA

GCAGAGTGAGCAAGCTGATTGGAAGAGGACTCGGAATACAATCCGATGCCCCGATAGATAA

TAATTGTGAGAGCAAGTGTTTCTGGCGCGGCGGATCCATCAATACACGCTTACCGTTTCAG

AACTTGAGCCCACGGACTGTTGGGCAGTGCCCAAAGTACGTGAACCGCCGCAGTTTAATGC

TTGCTACCGGTATGAGAAATGTACCTGAACTCATTCAAGGCAGGGGCCTGTTTGGCGCAAT

CGCTGGCTTTCTCGAAAATGGATGGGAAGGCATGGTAGACGGTTGGTACGGATTCAGACAC

CAGAATGCCCAGGGCACGGGTCAAGCAGCCGATTATAAAAGCACACAAGCAGCAATTGATC

AGATTACAGGTAAGCTCAACCGTCTCGTGGAAAAAACTAACACCGAGTTCGAATCCATTGA

GAGTGAGTTCAGTGAGATAGAGCACCAGATCGGAAATGTGATTAACTGGACAAAAGATAGC

ATTACAGATATCTGGACGTACCAGGCTGAGCTCTTGGTGGCGATGGAAAATCAGCATACCA

TTGACATGGCCGACTCAGAGATGCTTAACCTGTATGAGAGAGTGCGCAAACAGCTTAGACA

GAACGCCGAAGAGGATGGCAAGGGATGTTTCGAGATCTACCACGCTTGTGATGACAGCTGT

ATGGAGAGTATTAGAAACAACACGTATGACCATTCCCAGTACCGAGAGGAGGCTTTGCTTA

ATCGTTTGAATATTAACCCCGTCACGCTCAGCAGCGGGTACAAAGATATCATACTCTGGTT

CTCTTTCGGAGCATCATGCTTCGTACTTTTGGCTGTGGTGATGGGGCTGTTTTTCTTCTGC

TTGAAAAACGGCAACATGAGGTGCACTATCTGTATC

825
ATGTACAAAATCGTTGTGATCATTGCTCTGTTGGGCGCGGTAAAGGGCCTAGATAAGATTT

GTCTGGGCCATCACGCCGTTGCCAACGGCACTATAGTTAAAACGCTGACAAATGAACAGGA

AAAGGTAACTAACGCCACCGAGACTGTGGAGTCCACTGGTCTGAACCGACTCTGCATGAAA

GGGCGAAAACATAAAGACCTGGGCAACTGTCACCCAATTGGGATGCTGATCGGGACACCTG

CCTGCGATCTCCACCTGACCGGTACATGGGACACAATCATTGAAAGGGAAAACGCCATCGC

CTACTGTTATCCAGGCGCTACAGTCAACGAGGAAGCATTGCGGCAGAAAATTATGGAGTCT

GGCGGAATCGATAAGATATCCACTGGCTTCACCTACGGATCGTCTATTAACTCTGCGGGTA

CGACACGCGCCTGTATGAGGAACGGCGGAAATAGCTTTTACGCTGAACTAAAGTGGTTAGT

TTCTAAGAGCAAGGGCCAGAATTTCCCACAGACCACAAATACATACAGGAATACAGATACC

GCTGAGCATCTAATCATGTGGGGAATACACCACCCCTCGTCAACTCAGGAGAAGAATGATC

TGTATGGCACACAGTCTCTGTCAATTTCCGTGGGCTCAAGCACATATAGGAACAACTTCGT

GCCTGTTGTTGGCGCCAGACCCCAAGTCAATGGCCAGTCTGGAAGGATTGACTTCCATTGG

ACCCTGGTCCAACCCGGGGATAATATCACCTTTTCCCATAATGGAGGGCTGATCGCGCCTA

GTCGCGTCAGTAAACTCATCGGGAGAGGGCTGGGAATTCAATCAGATGCCCCCATTGATAA

CAACTGTGAAAGTAAATGCTTTTGGCGGGGGGGTTCCATCAATACACGCCTGCCATTTCAG

AATCTGAGCCCCAGGACGGTTGGTCAGTGCCCCAAGTACGTGAACAAGAGAAGCCTGATGC

TGGCAACTGGGATGCGCAATGTTCCTGAACTGATTCAGGGACGCGGGTTATTTGGAGCTAT

TGCCGGTTTTCTCGAGAATGGCTGGGAGGGAATGGTCGATGGGTGGTACGGATTTAGACAC

CAAAACGCTCAGGGAACAGGCCAGGCGGCTGATTACAAAAGCACCCAGGCCGCTATTGATC

AGATCACTGGAAAACTGAACCGCCTTGTCGAGAAAACAAACACCGAATTTGAGAGCATAGA

GTCCGAATTCTCAGAGATTGAACATCAAATTGGCAACGTGATAAATTGGACTAAAGACTCC

ATTACCGACATCTGGACCTACCAGGCCGAGCTCTTGGTTGCTATGGAAAATCAGCATACTA

TCGACATGGCCGACTCTGAAATGCTTAATCTGTACGAACGCGTGAGAAAACAGTTACGCCA

GAACGCGGAGGAAGATGGCAAAGGGTGCTTCGAGATCTACCATGCATGCGATGACAGCTGT

ATGGAAAGCATCCGTAATAATACCTATGATCACTCTCAGTATAGGGAAGAGGCCCTGTTGA

ATAGATTAAACATTAACCCAGTGACACTGAGCAGCGGCTATAAGGACATTATTTTATGGTT

TTCCTTTGGAGCAAGTTGTTTTGTGCTGCTGGCGGTGGTGATGGGGCTCGTGTTCTTTTGC

CTGAAGAATGGTAACATGCGCTGTACTATCTGTATT

826
ATGTACAAGATAGTCGTGATAATTGCACTCCTCGGCGCAGTTAAGGGCTTGGATAAGATCT

GCCTGGGACACCACGCCGTCGCGAACGGCACTATTGTCAAGACTTTAACGAACGAGCAAGA

AGAGGTAACAAATGCAACAGAAACTGTTGAGAGCACGGGCATCAATCGGCTGTGCATGAAG

GGTAGGAAGCATAAGGACCTGGGAAACTGTCACCCCATCGGCATGCTGATCGGGACCCCCG

CATGTGATTTACACCTTACAGGAATGTGGGATACTCTGATCGAAAGAGAGAATGCCATTGC

TTACTGTTACCCTGGGGCCACGGTGAACGTGGAGGCCCTTAGGCAGAAAATCATGGAAAGT

GGAGGGATCAACAAGATTTCCACCGGTTTCACGTATGGCTCTTCTATTAATTCCGCTGGAA

CCACTAGGGCCTGTATGCGAAATGGAGGCAACTCCTTCTACGCTGAATTGAAGTGGCTGGT

AAGCAAGTCCAAAGGGCAGAATTTCCCACAGACAACAAACACGTACAGAAACACGGACACC

GCTGAGCACCTCATCATGTGGGGCATCCACCACCCTAGCTCTACCCAGGAAAAAAATGATT

TATACGGAACGCAGTCTCTTTCAATCTCCGTCGGCTCAAGCACTTATAGAAATAATTTTGT

GCCCGTCGTGGGGGCCCGGCCCCAGGTAAACGGCCAATCAGGGAGGATCGACTTTCATTGG

ACCCTGGTTCAGCCCGGGGATAACATAACCTTTAGCCATAACGGAGGTCTTATAGCGCCGA

GTCGAGTGTCAAAGCTGATCGGGCGCGGTTTGGGCATCCAGTCTGATGCCCCCATCGACAA

CAACTGCGAGAGCAAATGCTTTTGGAGGGGAGGGTCCATTAATACCCGTCTGCCATTCCAG

AATCTCTCTCCCCGGACCGTCGGCCAGTGCCCCAAATACGTGAATCGTCGTTCTCTCATGC

TCGCCACCGGAATGCGCAACGTGCCTGAGTTGATCCAAGGTCGGGGACTGTTCGGGGCCAT

TGCCGGCTTTCTGGAGAACGGGTGGGAGGGGATGGTGGATGGCTGGTACGGCTTTAGGCAC

CAGAACGCTCAGGGAACTGGGCAGGCGGCCGACTACAAGTCAACCCAGGCCGCAATAGATC

AAATTACAGGCAAGCTGAACCGACTGGTCGAAAAAACCAACACAGAATTCGAGTCCATAGA

ATCCGAATTTTCTGAAATAGAACACCAGATTGGGAACGTTATCAATTGGACTAAAGATTCC

ATCACCGATATCTGGACATATCAGGCCGAACTGCTTGTGGCCATGGAAAACCAGCATACCA

TCGATATGGCTGACTCCGAAATGTTGAATTTGTATGAAAGGGTACGCAAGCAGCTGAGGCA

GAACGCTGAGGAGGACGGTAAGGGATGTTTTGAGATCTACCATGCATGCGATGACAGCTGT

ATGGAGTCAATACGCAACAACACTTATGACCACTCCCAATATCGGGAGGAAGCACTTCTCA

ATCGCTTGAATATTAATCCCGTCACTCTGTCTAGTGGTTATAAGGACATTATTTTGTGGTT

CAGCTTTGGAGCCTCCTGTTTCGTTCTACTGGCCGTTGTGATGGGACTATTCTTTTTCTGC

CTCAAAAACGGCAACATGCGGTGCACCATCTGTATT

827
ATGTACAAAATAATTGTTATCATAGCCCTCCTGGGTGCCGTCAAAGGGCTGGATAAAATAT

GCTTAGGGCACCACGCGGTTGCTAACGGCACCATCGTCAAAACCCTCACAAACGAACAGGA

GGAAGTCACCAACGCAACAGAAACAGTCGAATCAACGGGCATCAATAGACTGTGTATGAAA

GGGCGCAAGCACAAGGACTTGGGAAACTGCCACCCGATTGGTATGCTAATTGGAACCCCAG

CCTGTGACCTACACCTGACCGGGACTTGGGATACTCTTATTGAGCGCGAAAACGCTATTGC

GTATTGTTACCCTGGGGCTACCGTCAACGTTGAGGCACTGAGACAGAAAATAATGGAATCA

GGTGGCATAGACAAAATTTCTACCGGCTTCACCTACGGGAGCAGCATAAACTCCGCTGGCA

CTACACGCGCCTGTATGAGGAATGGCGGCAACTCCTTCTACGCCGAGCTGAAGTGGCTGGT

TAGTAAGTCCAAGGGACAGAACTTCCCACAGACCACCAACACTTACCGCAACACCGATACA

GCCGAGCACCTGATTATGTGGGGAATACACCACCCAAGCTCTACCCAGGAAAAAAACGACT

TGTACGGCACTCAAAGTCTGTCCATCTCCGTTGGGTCGTCCACTTACCGCAATAATTTCGT

CCCCGTGGTTGGAGCCCGCCCTCAGGTGAACGGCCAAAGCGGGCGCATCGATTTCCATTGG

ACCCTCGTTCAGCCTGGCGACAACATTACCTTTAGTCACAATGGCGGTCTGATTGCCCCTT

CACGCGTGTCCAAGTTGATTGGACGGGGATTGGGCATCCAGTCGGACGCACCCATCGATAA

CAATTGTGAGAGTAAATGTTTCTGGCGGGGTGGCTCCATTAATACCCGACTGCCATTCCAA

AACCTCTCTCCTCGTACGGTGGGTCAGTGTCCCAAGTATGTGAACAGAAGATCTCTGATGT

TAGCAACCGGTATGAGAAACGTCCCGGAGCTGATCCAGGGCAGAGGCCTGTTCGGAGCCAT

TGCGGGGTTTCTTGAAAACGGATGGGAGGGCATGGTGGACGGATGGTATGGGTTTCGACAT

CAAAATGCCCAGGGGACCGGGCAGGCAGCTGACTACAAATCTACCCAGGCGGCAATAGATC

AGATCACTGGAAAGTTAAACAGACTCGTGGAGAAAACTAACACTGAGTTCGAATCTATCGA

GTCAGAGTTTTCAGAAATTGAACATCAGATCGGAAACGTTATCAATTGGACGAAAGATAGT

ATCACAGACATTTGGACCTATCAAGCTGAATTGCTTGTGGCCATGGAAAACCAACATACCA

TCGACATGGCTGACTCGGAAATGTTGAATTTGTACGAGCGGGTGAGGAAGCAACTGAGGCA

AAATGCCGAGGAGGACGGCAAAGGCTGCTTTGAGATCTACCACGCATGCGATGACTCTTGT

ATGGAAAGTATTCGGAATAATACTTATGACCATTCCCAGTATCGTGAGGAAGCACTGCTCA

ACCGCCTAAATATTAATCCCGTGACCCTGTCATCAGGGTATAAGGACATTATCCTTTGGTT

TTCCTTCGGCGCTAGCTGTTTCGTGCTGCTAGCGGTAGTGATGGGCCTTTTCTTCTTTTGT

TTGAAGAATGGCAATATGCGATGCACAATCTGCATA

828
ATGTATAAGATCGTGGTCATCATAGCCCTGCTCGGAGCCGTTAAGGGTCTTGACAAGATTT

GTCTTGGTCATCATGCTGTTGCTAACGGAACCATCGTGAAAACTCTGACAAACGAGCAGGA

GGAAGTGACAAACGCCACGGAGACAGTGGAATCTACTGGAATCAACCGCTTATGCATGAAA

GGCAGGAAACACAAAGACCTGGGGAATTGCCACCCAATTGGAATGCTGATCGGCACACCTG

CCTGCGACCTGCATCTCACAGGGATGTGGGATACACTGATCGAAAGAGAGAATGCTATCGC

ATACTGCTACCCAGGGGCTACTGTCAATGTGGAGGCCCTTCGACAGAAGATTATGGAATCC

GGAGGTATCAACAAAATTAGCACTGGCTTCACCTACGGGTCTTCCATCAATTCTGCCGGCA

CGACCAGAGCATGTATGAGAAATGGGGGCAACAGTTTTTACGCCGAGTTGAAGTGGCTGGT

GAGTAAGAGCAAAGGACAGAACTTCCCGCAGACCACCAACACATACAGGAATACGGATACC

GCCGAGCACTTAATCATGTGGGGAATTCACCACCCCAGTTCGACACAGGAGAAGAACGATC

TCTATGGCACTCAGTCTCTGTCTATTTCTGTGGGATCATCAACATATCGCAATAACTTTGT

ACCTGTTGTGGGGGCTAGGCCTCAGGTGAACGGCCAATCCGGACGAATCGACTTCCACTGG

ACTCTGGTTCAACCAGGTGATAATATTACTTTCTCACACAACGGCGGACTGATTGCACCTA

GCCGAGTGAGTAAGCTCATTGGTAGAGGACTGGGGATTCAGTCCGATGCCCCTATAGACAA

TAACTGCGAAAGCAAATGCTTCTGGCGCGGCGGAAGCATAAATACAAGATTGCCATTTCAG

AACCTGAGTCCTCGGACCGTTGGACAGTGTCCTAAATACGTGAACAGAAGAAGCCTGATGC

TTGCCACTGGCATGCGGAATGTGCCCGAGCTCATTCAGGGACGGGGCCTATTCGGCGCAAT

CGCCGGATTTCTGGAGAATGGTTGGGAAGGGATGGTCGATGGCTGGTACGGCTTTAGACAC

CAGAATGCACAGGGGACAGGGCAGGCGGCCGATTACAAATCCACTCAGGCTGCTATCGACC

AGATCACCGGCAAGTTAAATAGGTTGGTCGAGAAGACGAACACCGAATTCGAATCTATCGA

GTCAGAGTTTAGCGAGATTGAGCATCAGATAGGTAATGTGATTAACTGGACTAAGGACAGC

ATCACTGATATCTGGACTTACCAGGCAGAGCTCCTGGTTGCCATGGAGAACCAGCACACAA

TAGACATGGCCGACAGTGAAATGCTAAACCTGTACGAACGCGTGCGCAAGCAGCTCCGGCA

GAACGCAGAAGAAGATGGCAAGGGGTGTTTTGAGATATATCATGCATGCGATGACTCCTGT

ATGGAGAGTATCCGTAACAACACTTACGATCACTCCCAGTACCGTGAGGAGGCTCTGCTGA

ACAGACTGAACATCAACCCCGTAACTTTAAGTAGTGGATATAAGGATATCATTCTTTGGTT

TAGCTTCGGAGCAAGCTGTTTCGTCCTTCTCGCAGTGGTTATGGGCCTGTTCTTTTTTTGC

CTAAAGAATGGGAATATGCGGTGCACAATATGTATT

829
ATGTATAAGATCGTGGTGATTATTGCCCTGCTGGGCGCTGTGAAGGGCTTAGACAAGATTT

GCTTAGGTCACCATGCAGTGGCAAATGGAACAATTGTCAAGACATTGACCAATGAACAGGA

GGAGGTAACCAACGCTACAGAAACCGTTGAGTCCACCGGTATTAACCGGCTTTGCATGAAG

GGTCGCAAGCACAAGGATCTGGGCAATTGCCACCCCATCGGTATGCTCATTGGAACTCCCG

CATGTGATCTGCATCTGACAGGGATGTGGGATACGTTGATAGAGCGTGAGAACGCCATCGC

CTACTGTTACCCAGGTGCCACAGTGAACGTGGAAGCCCTGCGTCAAAAGATCATGGAATCC

GGAGGGATCAATAAAATTAGTACAGGCTTCACGTATGGCTCTTCCATCAACTCTGCTGGGA

CTACTCGTGCGTGCATGCGGAATGGAGGCAATTCATTTTACGCGGAACTAAAATGGCTTGT

GAGCAAAAGCAAAGGACAAAACTTCCCGCAGACGACCAACACGTATCGGAACACCGACACC

GCCGAACATCTAATCATGTGGGGCATCCATCATCCCTCATCCACCCAGGAAAAAAATGACT

TATACGGAACACAGTCATTGAGCATTTCCGTAGGATCAAGTACATACCGAAATAATTTCGT

GCCTGTGGTGGGTGCGGGCCCCCAAGTTAATGGCCAATCAGGCCGTATTGACTTTCATTGG

ACCCTCGTTCAGCCTGGCGACAACATCACCTTCTCCCATAACGGGGGACTCATCGCCCCAT

CAAGAGTGTCGAAGCTGATCGGCCGAGGACTCGGGATACAGTCTGACGCCCCCATCGACAA

TAATTGTGAATCCAAGTGCTTTTGGAGAGGAGGGTCAATCAACACCCGCCTACCTTTTCAG

AATCTTTCACCCAGGACCGTTGGGCAGTGTCCCAAATACGTGAACCGGAGATCTCTCATGC

TTGCAACCGGGATGAGAAACGTGCCAGAGCTCATCCAGGGGCGCGGCCTATTTGGGGCCAT

AGCCGGTTTTCTGGAGAACGGATGGGAGGGAATGGTTGATGGCTGGTACGGCTTCAGGCAC

CAGAACGCACAGGGCACCGGGCAAGCCGCAGACTACAAATCAACTCAGGCGGCTATCGATC

AGATCACAGGTAAATTAAACCGACTCGTCGAAAAGACAAATACCGAGTTTGAGTCTATCGA

ATCCGAGTTTTCTGAAATTGAGCATCAAATCGGCAACGTGATTAACTGGACTAAGGACTCC

ATCACCGATATTTGGACTTATCAAGCAGAACTACTGGTCGCCATGGAAAATCAACATACTA

TCGATATGGCAGATAGCGAAATGCTTAACCTCTACGAAAGAGTGCGAAAGCAGCTACGCCA

AAATGCCGAGGAAGACGGGAAGGGCTGCTTCGAGATTTACCATGCGTGTGATGATTCCTGC

ATGGAAAGTATTAGGAACAATACTTATGATCACAGCCAGTATCGTGAGGAAGCTCTGCTTA

ACAGACTTAACATCAATCCAGTGACACTCAGCAGTGGGTACAAAGACATCATCCTCTGGTT

CAGCTTTGGAGCTTCTTGCTTCGTTTTGCTTGCTGTAGTCATGGGACTGTTTTTTTTTTGT

CTGAAGAACGGTAATATGCGATGCACTATTTGTATA

830
ATGTATAAGATCGTGGTCATCATCGCTTTGCTGGGGGCTGTTAAGGGGCTCGACAAGATTT

GTTTGGGCCACCACGCCGTGGCCAACGGGACCATTGTGAAGACGCTGACAAATGAACAAGA

AGAAGTCACAAATGCCACAGAGACTGTTGAATCCACTGGCATTAATAGACTCTGCATGAAA

GGCAGGAAACACAAAGATCTGGGCAACTGTCACCCTATCGGAATGCTGATTGGCACTCCCG

CTTGTGATCTCCATCTTACAGGTATGTGGGATACCCTTATTGAGCGAGAAAATGCCATCGC

CTACTGTTATCCAGGTGCTACTGTGAACGTGGAGGCCTTGAGGCAGAAGATTATGGAGTCA

GGAGGCATCAATAAGATTTCCACCGGGTTTACATACGGCTCATCCATCAACTCCGCCGGCA

CGACTCGAGCTTGCATGAGAAACGGTGGCAACTCCTTTTATGCGGAGCTAAAGTGGCTGGT

CAGCAAGTCAAAAGGTCAGAACTTCCCCCAGACTACGAACACCTATCGGAATACAGACACC

GCTGAGCATTTGATCATGTGGGGAATCCACCATCCTAGCTCCACCCAGGAGAAGAATGACC

TGTATGGAACACAATCTCTTTCTATCTCCGTGGGCTCTTCTACCTACCGTAACAATTTCGT

TCCCGTTGTGGGGGCTCGGCCTCAGGTGAATGGTCAATCCGGAAGAATCGACTTTCACTGG

ACATTAGTACAGCCCGGCGACAACATTACATTTAGTCATAATGGGGGGCTGATCGCGCCTA

GTCGGGTCTCAAAGTTGATCGGGAGAGGCCTCGGAATCCAGAGCGATGCACCTATCGATAA

CAACTGTGAAAGCAAGTGCTTCTGGCGCGGCGGTTCTATTAATACCAGATTGCCCTTCCAG

AACCTGTCTCCCCGAACAGTCGGGCAGTGCCCCAAATACGTGAACAGGAGATCTCTGATGC

TGGCCACAGGGATGCGCAACGTGCCAGAGCTGATCCAGGGAAGGGGTCTCTTCGGGGCCAT

TGCCGGCTTTCTGGAAAATGGCTGGGAAGGGATGGTGGACGGGTGGTATGGCTTCAGGCAC

CAAAACGCGCAAGGCACTGGCCAGGCGGCGGATTACAAGAGCACGCAAGCTGCTATAGACC

AGATCACGGGGAAGCTGAACAGACTCGTGGAAAAGACTAATACTGAATTTGAATCGATCGA

GTCTGAGTTCTCCGAAATCGAGCATCAGATCGGGAATGTCATAAATTGGACCAAGGATTCC

ATTACAGATATTTGGACCTATCAGGCCGAACTGCTGGTGGCCATGGAGAATCAGCACACTA

TTGATATGGCCGACAGTGAGATGCTGAACCTGTATGAGCGTGTTAGGAAGCAACTTCGACA

GAACGCAGAAGAAGATGGTAAGGGATGTTTCGAGATTTACCATGCCTGTGACGACAGTTGT

ATGGAGAGCATTAGGAATAACACTTATGACCATAGCCAATACCGGGAAGAAGCTTTGTTAA

ATCGCCTGAATATCAATCCCGTCACGTTATCGTCGGGGTATAAGGATATTATTCTGTGGTT

CAGCTTCGGAGCGTCCTGCTTTGTTCTGTTGGCCGTGGTAATGGGGCTGTTTTTCTTTTGT

CTTAAGAACGGGAACATGCGCTGCACAATCTGCATC

831
ATGTACAAGATTGTGGTTATCATCGCACTGTTAGGAGCCGTGAAGGGGTTGGACAAGATCT

GTCTGGGGCATCATGCCGTTGCTAATGGAACAATCGTGAAGACGCTCACCAATGAACAAGA

AGAAGTCACAAACGCCACCGAAACCGTGGAGAGCACCGGAATTAACAGACTTTGTATGAAG

GGACGCAAACACAAGGATCTGGGGAACTGCCACCCAATCGGCATGCTGATAGGAACCCCTG

CCTGTGATCTGCACTTAACTGGCATGTGGGACACACTTATAGAGCGCGAGAACGCGATCGC

GTACTGCTACCCCGGAGCAACCGTTAACGTCGAAGCTTTGAGGCAGAAAATTATGGAAAGC

GGCGGCATAAATAAAATTTCTACTGGCTTTACGTACGGCAGCTCTATAAACAGTGCTGGCA

CCACTCGTGCCTGTATGCGGAACGGCGGCAATTCCTTTTACGCCGAATTAAAATGGCTTGT

TAGCAAGTCAAAGGGCCAGAACTTTCCGCAGACGACTAATACATACCGAAACACCGACACC

GCTGAACATCTGATTATGTGGGGTATACATCATCCAAGTTCCACCCAAGAAAAAAATGACT

TGTATGGGACCCAGAGCCTAAGCATCTCCGTGGGGAGTTCTACTTACCGAAACAACTTCGT

ACCTGTGGTGGGGGCCCGACCACAGGTAAATGGACAGTCGGGCCGGATTGATTTCCACTGG

ACCTTGGTGCAGCCGGGAGATAACATAACATTCTCTCATAACGGAGGTCTCATAGCCCCAA

GTCGTGTGTCAAAGCTCATCGGTAGAGGCCTGGGCATTCAGTCAGACGCACCCATTGATAA

TAACTGTGAGTCTAAATGCTTTTGGCGCGGGGGGAGTATCAATACTAGACTGCCTTTTCAG

AACCTCAGCCCAAGGACCGTGGGGCAGTGTCCCAAGTATGTAAATCGGCGAAGCTTAATGC

TGGCTACTGGTATGCGGAATGTGCCTGAACTCATTCAGGGACGGGGCCTCTTCGGAGCAAT

AGCTGGTTTCCTGGAGAACGGCTGGGAAGGCATGGTGGATGGTTGGTACGGTTTTAGACAC

CAAAATGCCCAGGGAACGGGACAGGCTGCCGACTATAAGTCAACTCAAGCCGCGATCGACC

AGATCACTGGTAAATTAAACCGACTCGTCGAAAAGACAAACACGGAGTTCGAGTCTATCGA

AAGTGAGTTCTCAGAGATTGAACACCAAATCGGGAATGTGATTAACTGGACAAAGGACTCG

ATAACCGATATCTGGACCTACCAGGCAGAACTTCTGGTGGCCATGGAAAACCAGCACACTA

TTGACATGGCCGACTCAGAGATGCTGAATCTGTACGAGAGAGTGAGGAAGCAGCTCCGCCA

GAATGCGGAGGAGGATGGTAAAGGCTGCTTCGAAATCTACCACGCTTGCGATGACTCCTGC

ATGGAATCAATCCGAAATAATACATATGACCACTCACAGTACAGAGAAGAAGCCCTTCTGA

ACCGCCTGAACATCAACCCCGTGACGCTGAGTTCAGGATATAAGGATATCATTCTCTGGTT

CTCCTTTGGGGCGAGTTGCTTCGTGCTGCTTGCGGTAGTCATGGGACTCTTTTTTTTTTGT

CTTAAGAACGGTAATATGCGGTGCACTATTTGTATC

832
ATGTACAAGATCGTGGTAATTATCGCCCTGCTCGGAGCTGTGAAAGGATTAGACAAAATTT

GCCTCGGCCACCATGCTGTAGCTAATGGTACAATAGTCAAAACCCTAACTAATGAACAGGA

AGAGGTGACTAATGCAACGGAAACTGTCGAGAGTACCGGCATTAACCGCCTGTGTATGAAA

GGGAGAAAGCACAAGGACTTAGGCAATTGTCATCCAATCGGGATGCTAATTGGCACTCCAG

CCTGTGATCTGCATCTGACCGGAATGTGGGACACCTTAATTGAGAGGGAAAACGCCATAGC

CTATTGCTATCCTGGGGCAACTGTTAATGTGGAAGCTCTCCGGCAAAAAATCATGGAATCT

GGAGGCATTAATAAGATCTCCACGGGCTTCACATATGGGTCCTCTATCAATTCCGCCGGGA

CCACGCGCGCATGCATGAGAAACGGAGGGAATTCTTTCTACGCGGAACTTAAGTGGCTGGT

CAGTAAGTCTAAAGGGCAGAATTTTCCTCAGACCACTAATACCTACAGAAATACGGATACA

GCTGAGCACCTCATTATGTGGGGAATACACCACCCTTCAAGCACACAGGAAAAAAACGATC

TCTACGGGACCCAGAGCCTGTCCATTAGTGTCGGATCTAGCACATACCGGAACAATTTCGT

ACCCGTTGTGGGAGCACGCCCACAGGTGAATGGGCAGTCAGGCAGAATCGATTTCCATTGG

ACTCTCGTGCAGCCCGGCGATAATATAACCTTCAGTCATAATGGCGGATTGATCGCCCCCT

CGCGTGTTTCAAAATTAATCGGGAGGGGGCTCGGGATACAAAGCGACGCTCCTATCGACAA

CAACTGTGAGTCCAAGTGTTTTTGGCGCGGGGGGAGCATTAATACCCGTCTCCCGTTCCAG

AACCTGTCTCCCCGGACAGTAGGACAGTGTCCGAAGTATGTCAATCGTAGAAGTCTTATGC

TGGCGACGGGAATGCGGAACGTGCCCGAGCTGATTCAAGGCCGGGGTCTGTTCGGAGCAAT

AGCTGGTTTCCTGGAGAATGGTTGGGAGGGCATGGTTGACGGCTGGTATGGGTTCAGACAT

CAGAACGCACAGGGAACCGGCCAGGCTGCTGACTATAAATCCACTCAGGCAGCCATAGATC

AGATCACCGGGAAGCTAAACCGGCTGGTTGAGAAAACTAATACGGAGTTCGAGTCTATCGA

GTCCGAGTTTAGCGAAATAGAGCATCAGATAGGGAACGTGATAAATTGGACGAAAGACTCT

ATTACCGACATCTGGACCTACCAGGCGGAACTGCTGGTGGCTATGGAGAATCAGCACACCA

TCGACATGGCTGATAGCGAAATGTTGAATCTGTACGAGCGGGTCAGAAAACAGTTAAGACA

GAACGCAGAGGAAGATGGAAAGGGCTGCTTCGAAATATATCACGCATGTGATGATTCCTGC

ATGGAGTCTATTAGAAACAACACTTATGACCATTCGCAGTACCGCGAAGAAGCGCTGCTAA

ACAGACTCAACATCAATCCTGTGACCTTGAGTAGCGGATACAAGGACATTATACTGTGGTT

CTCCTTTGGTGCCTCCTGTTTTGTCTTGCTTGCCGTAGTTATGGGCCTGTTCTTTTTCTGC

TTGAAGAACGGGAACATGCGCTGCACAATTTGTATC

833
ATGTATAAAGTGGTGGTGATTATCGCTTTACTGGGAGCTGTAAAGGGGCTGGATAAGATTT

GTCTGGGACATCACGCAGTCGCGAACGGCACCATTGTGAAAACACTTACTAATGAACAGGA

GGAGGTGACCAACGCCACCGAAACCGTCGAGTCAACAGGTATAAACAGATTGTGCATGAAG

GGCCGAAAGCACAAGGACCTGGGAAATTGTCATCCAATTGGAATGTTGATCGGCACTCCAG

CCTGCGATCTTCATCTTACCGGAACATGGGACACGCTTATTGAACGGGAAAATGCGATCGC

ATATTGCTACCCCGGGGCCACAGTGAATGTGGAGGCACTGAGACAGAAAATCATGGAAAGT

GGCGGGATCGACAAGATTAGTACTGGCTTTACATACGGGAGCAGCATCAACTCCGCCGGGA

CCACCCGAGCCTGCATGAGGAACGGGGGCAACAGTTTTTATGCTGAGCTGAAGTGGCTCGT

GTCAAAAAATAAGGGCCAGAATTTCCCTCAAACAACGAATACATATCGCAACACAGATACA

GCGGAACACTTAATCATGTGGGGCATTCACCACCCTAGCTCCATTCAAGAAAAGAACGATC

TCTACGGAACACAATCGTTGAGCATCTCAGTGGGGTCTTCCACCTATAGAAACAACTTTGT

ACCTGTGGTCGGCGCAAGACCTCAAGTCAATGGACAAAGCGGCAGAATCGACTTCCACTGG

ACTCTGGTGCAGCCAGGCGATAATATAACCTTCTCTCACAACGGGGGCTTGATCGCTCCCA

GCCGGGTATCTAAGTTAATCGGCCGTGGTCTCGGAATCCAGAGCGATGCACCGATTGACAA

TAACTGTGAAAGTAAATGTTTCTGGCGTGGGGGCTCTATAAACACTAGACTCCCCTTCCAG

AACTTGAGTCCTAGAACAGTGGGGCAGTGCCCGAAATACGTCAACCGGAGATCGTTGATGC

TCGCAACTGGCATGAGGAACGTCCCCGAGTTAATACAGGGACGGGGACTATTCGGCGCCAT

AGCCGGGTTCCTCGAGAACGGATGGGAGGGTATGGTTGATGGTTGGTACGGCTTTCGACAT

CAAAACGCACAAGGTACAGGGCAGGCTGCCGATTACAAGAGCACTCAGGCCGCCATCGACC

AGATCACTGGGAAACTCAACAGGTTAGTGGAGAAAACCAATACCGAATTTGAATCCATCGA

GAGCGAATTCTCAGAGATTGAGCATCAGATAGGAAATGTGATAAACTGGACCATGGATAGT

ATTACAGACATTTGGACGTACCAAGCAGAGCTGCTTGTCGCGATGGAGAATCAACACACCA

TCGACATGGCGGACTCCGAAATGCTGAATCTGTATGAGAGGGTTCGGAAACAGCTTAGACA

AAATGCAGAGGAGGATGGCAAGGGCTGCTTTGAGATCTACCACGCATGTGATGACTCCTGT

ATGGAATCCATCCGGAACAACACGTATGACCACTCTCAGTACAGAGAAGAGGCTCTCCTGA

ATCGCCTTAATATTAACCCTGTGACACTGTCCTCCGGCTATAAGGATATCATCCTGTGGTT

TAGCTTTGGAGCAAGCTGCTTCGTGTTGCTGGCCGTAGTTATGGGCCTGGTCTTCTTCTGT

CTTAAGAACGGAAACATGCGGTGCACAATCTGTATT

834
ATGTATAAGGTCGTCGTTATTATAGCGCTGCTTGGAGCTGTCAAAGGTTTGGATAAAATCT

GTCTGGGCCATCACGCAGTCGCCAACGGTACCATTGTGAAAACGCTCACAAACGAACAGGA

AGAGGTCACGAACGCCACAGAGACTGTGGAGTCTACAGGGATTAACCGCCTGTGCATGAAA

GGCCGGAAACATAAGGACCTTGGCAACTGCCATCCAATCGGCATGCTGATTGGCACTCCGG

CCTGTGATCTGCATTTGACCGGCACATGGGATACCCTGATCGAAAGGGAGAATGCCATCGC

TTACTGTTATCCCGGCGCAACTGTGAATGTGGAGGCACTGAGACAGAAGATCATGGAGTCT

GGGGGGATCGATAAAATTAGTACCGGGTTTACTTACGGCAGTTCGATTAATAGCGCGGGAA

CAACGAGGGCGTGTATGAGGAATGGAGGAAACTCCTTCTATGCCGAGCTCAAGTGGCTGGT

GAGCAAGAACAAGGGGCAAAACTTTCCCCAAACAACTAACACATACCGGAATACAGATACT

GCTGAACATCTGATAATGTGGGGAATCCACCATCCTTCTTCAATTCAGGAGAAAAACGATC

TTTACGGAACTCAAAGTTTAAGCATAAGTGTGGGGTCATCTACGTATAGAAACAACTTTGT

GCCCGTGGTTGGCGCAAGGCCGCAGGTGAATGGTCAATCTGGGAGGATAGATTTCCACTGG

ACATTGGTGCAGCCGGGTGATAATATCACCTTTTCCCATAATGGGGGATTGATTGCCCCCT

CCCGGGTGTCGAAACTTATTGGCCGCGGGCTAGGTATTCAGAGTGACGCCCCCATTGATAA

TAATTGTGAGTCTAAATGTTTTTGGGGGGGTGGCAGCATTAATACACGTCTGCCATTCCAG

AACCTGTCCCCCAGGACTGTCGGGCAATGCCCCAAATACGTGAATAGACGGTCTCTGATGC

TGGCCACTGGGATGCGCAATGTACCCGAGCTTATCCAGGGACGGGGCCTTTTTGGGGCCAT

CGCCGGTTTCCTGGAGAACGGGTGGGAAGGCATGGTTGATGGCTGGTATGGGTTTAGACAC

CAGAATGCTCAAGGGACTGGGCAGGCGGCCGATTATAAGAGTACACAGGCGGCCATCGACC

AGATCACAGGCAAGCTCAACCGTCTGGTGGAGAAAACAAATACAGAATTCGAAAGCATAGA

GAGTGAATTTTCTGAGATTGAGCACCAGATTGGTAATGTCATCAATTGGACAATGGATTCC

ATCACTGACATCTGGACATACCAAGCCGAGCTATTGGTGGCGATGGAGAATCAGCATACAA

TAGATATGGCCGACTCTGAAATGCTGAACTTATATGAGAGAGTGCGTAAACAGTTGAGGCA

GAATGCTGAAGAAGACGGTAAGGGATGTTTTGAGATATATCATGCCTGTGATGACAGTTGC

ATGGAATCCATCAGAAATAACACTTACGACCACAGCCAGTACAGAGAGGAAGCCCTACTGA

ACAGGCTCAATATCAATCCAGTGACTCTATCCAGCGGCTACAAGGACATTATCTTATGGTT

TTCTTTTGGTGCTTCATGTTTTGTGCTCCTCGCCGTGGTCATGGGGCTCGTCTTCTTCTGT

TTAAAGAATGGGAATATGCGGTGCACAATATGTATC

835
ATGTACAAAATAGTAGTAATCATTGCTTTGCTTGGCGCGGTGAAAGGCTTGGATAAGATTT

GCCTGGGACACCATGCTGTCGCGAATGGAACCATAGTTAAGACTTTGACTAATGAGCAAGA

GGAGGTGACCAACGCCACCGAAACGGTGGAGTCCACAGGCATCAACAGGCTCTGTATGAAA

GGACGGAAGCATAAGGACCTGGGGAACTGTCATCCAATTGGAATGCTGATCGGGACGCCCG

CGTGTGACCTCCATCTGACAGGGATGTGGGATACTCTTATTGAGAGAGAGAACGCTATCGC

CTACTGTTATCCTGGTGCTACAGTGAACGTGGAAGCCCTCAGGCAGAAGATTATGGAGAGC

GGTGGGATCAACAAGATTAGTACAGGGTTTACCTATGGGTCATCCATAAACAGTGCGGGCA

CTACCCGAGCGTGCATGCGCAATGGGGGCAATTCGTTCTATGCCGAACTGAAGTGGTTAGT

CTCTAAGTCTAAAGGTCAGAATTTTCCTCAGACAACTAACACATACCGGAATACCGATACC

GCTGAACACCTGATCATGTGGGGAATACATCACCCTAGTAGTACACAAGAGAAAAATGACC

TATATGGGACACAGAGCCTGTCAATTAGCGTGGGTAGTTCCACATATAGAAACAACTTTGT

TCCTGTCGTGGGTGCCCGGCCTCAGGTAAATGGGCAGAGCGGACGGATAGATTTTCATTGG

ACTTTGGTCCAGCCCGGGGATAACATTACCTTCTCTCATAACGGGGGGCTGATCGCTCCAA

GCCGGGTGTCTAAGCTCATAGGCAGAGGCCTGGGTATCCAATCGGACGCCCCCATCGATAA

CAACTGTGAAAGTAAATGCTTTTGGAGGGGCGGCAGTATTAATACGCGGCTACCGTTTCAG

AATCTGTCTCCACGCACAGTAGGGCAGTGTCCAAAGTACGTCAACCGCAGATCCCTCATGC

TGGCCACGGGGATGAGGAACGTGCCCGAGCTGATCCAGGGGAGGGGCCTATTTGGGGCTAT

CGCCGGCTTCCTGGAGAATGGTTGGGAGGGAATGGTCGATGGCTGGTACGGCTTTCGCCAT

CAGAACGCCCAAGGAACTGGACAAGCTGCCGACTACAAAAGCACGCAAGCCGCCATCGATC

AAATTACCGGAAAGCTGAATCGGCTAGTGGAGAAGACCAACACCGAATTTGAGTCTATAGA

GTCAGAGTTTAGCGAAATCGAGCATCAGATTGGCAACGTCATTAATTGGACCAAGGACAGC

ATAACCGACATATGGACATACCAAGCCGAACTCCTGGTAGCTATGGAAAATCAGCATACCA

TCGATATGGCAGATTCCGAAATGCTGAACCTGTATGAAAGAGTGAGGAAGCAACTGCGTCA

GAATGCCGAGGAAGACGGCAAGGGGTGCTTTGAGATCTACCACGCATGTGATGATTCTTGC

ATGGAGAGCATCAGGAATAATACATACGACCACAGCCAGTACCGGGAAGAAGCCCTATTGA

ACAGGCTTAACATCAATCCCGTCACTCTATCCAGCGGCTATAAAGATATAATCTTATGGTT

TTCCTTTGGCGCGTCTTGCTTTGTGCTCCTGGCGGTGGTGATGGGCTTATTCTTCTTTTGT

CTCAAGAATGGCAACATGAGGTGCACAATCTGCATT

836
ATGTACAAGATAGTGGTCATCATCGCACTCCTGGGCGCCGTGAAGGGCCTGGATAAAATTT

GCCTGGGGCACCATGCCGTCGTGAACGGCACGATCGTCAAGACTCTCACTAATGAGCAGGA

GGAAGTCACTAATGCTACGGAGACAGTTGAGTCGACCGGATTGAATAGATTGTGCATGAAG

GGACGTAACCACAAGGACCTCGGGAACTGCCACCCAATTGGCATGTTGATCGGAACACCCG

CCTGCGATCTCCATCTGACCGGTACGTGGGATACACTTATCGAGAGGGAAAACGCAATCGC

CTATTGCTATCCCGGTGCAACCGTTAACGAAGAAGCTCTGAGGCAGAAAATCATGGAGTCT

GGTGGGATTAACAAGATTAGTACAGGGTTTACATACGGAAGCTCCATCAACAGTGCAGGCA

CTACCCGTGCCTGCATGAGAAACGGAGGCAACTCTTTTTACGCTGAACTTAAATGGTTAGT

AAGCAAGAGTAAAGGCCAGAATTTTCCACAGACGACAAACACATACAGAAACACCGACACA

GCCGAACACCTGATCATGTGGGGCATCCACCACCCATCCAGCACCCAGGAGAAGAACGATC

TATATGGAACTCAGAGCCTGTCTATTAGCGTAGGCAGTTCAACCTACCAGAATAACTTCGT

GCCAGTGGTGGGAGCTCGGCCTCAGGTTAATGGACAGAGCGGCAGAATCGACTTCCACTGG

ACTCTCGTGCAACCCGGCGATAACATCACTTTTTCGCATAATGGAGGCTTAATCGCACCCT

CCCGAGTCAGCAAGCTCATCGGAAGGGGATTAGGCATACAGAGTGATGCACCCATCGATAA

CAACTGCGAAAGTAAGTGCTTCTGGCGAGGGGGTTCCATTAATACTAGATTACCATTTCAA

AATCTGAGTCCAAGAACCGTTGGTCAGTGCCCGAAGTATGTCAATAAGCGTTCTCTGATGT

TGGCAACTGGGATGAGGAATGTGCCAGAACTGATGCAAGGGCGAGGCCTCTTTGGTGCAAT

CGCTGGCTTTATAGAGAACGGGTGGGAAGGGATGGTGGATGGCTGGTATGGGTTCCGCCAT

CAGAATGCACAAGGCACCGGTCAGGCCGCCGACTACAAGTCAACCCAGGCGGCTATCGATC

AAATCACGGGGAAACTGAACAGGTTAATCGAAAAAACAAACACAGAGTTCGAGTCAATCGA

GTCTGAGTTTTCTGAAATTGAGCACCAAATCGGGAATGTGATTAACTGGACAAAAGACTCT

ATCACAGACATCTGGACCTACCAGGCCGAACTCCTGGTGGCCATGGAGAATCAACACACCA

TTGACATGGCGGACTCCGAAATGCTGAATCTGTATGAGAGGGTTAGGAAACAACTTAGGCA

GAATGCTGAGGAAGACGGCAAAGGCTGTTTTGAAATTTACCACGCCTGTGATGATAGTTGT

ATGGAGAGCATTCGGAACAATACCTACGATCACTCTCAATATCGCGAGGAAGCTCTGCTTA

ACAGGCTTAACATTAACCCCGTGACGCTGTCAAGTGGCTACAAAGACATTATTCTCTGGTT

CTCCTTCGGTGCATCATGCTTTGTTCTGCTGGCTGTTGTCATGGGCTTAGTGTTCTTCTGC

CTCAAGAACGGTAATATGAGATGTACCATCTGCATT

837
ATGTATAAGGTGGTGGTGATCATCGCCCTCTTGGGTGCTGTTAGAGGGCTGGATAAAATCT

GTCTAGGACATCATGCCGTGGCAAACGGTACTATCGTAAAAACTCTGACAAATGAGCAGGA

GGAGGTGACCAACGCTACTGAGACCGTCGAGTCAAAGAGCCTGGGAAAGTTGTGCATGAAA

GGGAGGTCATATAATGACCTGGGGAACTGTCACCCTATAGGTATACTTATTGGCACCCCTG

CCTGCGATCTCCATCTCACTGGGACATGGGACACCCTGATTGAACGGGAGAACGCTGTTGC

TTATTGCTACCCCGGTGCTACAGTTAATGAGGAGGCGTTGCGTCAGAAGATAATGGAAAGC

GGGGGAATCTCGAAGATTAGCACTGGCTTTACCTACGGGACCAGTATTAATAGCGCGGGAA

CCACAAAAGCCTGCATGAGAAACGGAGGCAACAGCTTTTACGCCGAATTGAAATGGTTAGT

GTCAAAGAACAAAGGACAGAACTTCCCTCAGACCACAAACACGTACAGAAACACCGATACT

GCTGAGCACTTGATTATCTGGGGCATTCATCACCCATCTAGCACACAAGAGAAAAATGATC

TGTATGGAACCCAGTCACTGAGCATCTCAGTCGGCAGTTCCACTTACCAAAATAATTTTGT

TCCTGTGGTGGGAGCACGCCCACAGGTGAATGGACAGTCTGGAAGGATTGATTTTCACTGG

ACCCTGTTGCAGCCAGGAGACAATATAACCTTCAGTCATAACGGGGGCCTCATCGCGCCGT

CTCGGGTGTCAAAGTTGATTGGAAGAGGACTCGGGATTCAATCCGAAGCCCCCATCGATAA

TGGCTGTGAATCTAAATGCTTTTGGAAAGGTGGTTCGATCAATACAAAGCTGCCCTTCCAA

AACCTTTCCCCGCGGACAGTTGGACAATGCCCCAAGTACGTGAACAAGCGCAGTCTGATGC

TCGCCACCGGGATGAGAAACGTGCCGGAGATTATGCATGGCAGGGGCCTGTTCGGAGCTAT

CGCTGGATTCATTGAAAACGGGTGGGAGGGCATGGTTGACGGCTGGTATGGATTCAGGCAT

CAGAACGCACAGGGGACAGGCCAGGCAGCTGACTATAAGAGTACCCAGGCCGCTATCGACC

AAATAACAGGTAAGCTTAACCGTCTTATCGAAAAAACTAACACAGAGTTCGAATCAATCGA

AAGCGAATTCAGTGAGATTGAACACCAGATTGGTAACATAATTAATTGGACAAAAGACTCT

ATCACAGATATTTGGACCTACCAGGCAGAACTGCTCGTGGCCATGGAAAACCAGCACACTA

TCGATATGGCAGATTCCGAAATGTTAAACCTGTATGAGCGAGTGCGAAAACAACTGCGCCA

AAATGCAGAGGAAGACGGGAAAGGCTGTTTTGAAATTTACCATGCGTGCGACGATTCTTGT

ATGGAATCCATCAGAAACAACACATATGATCACTCTCAGTATAGAGAAGAGGCTCTTCTGA

ATCGCTTGAATATAAACCCTGTGAAGTTAAGTTCAGGGTATAAAGATATCATCCTTTGGTT

CTCTTTCGGGGCTTCTTGTCTGATCTTGCTTGCTGTGGTCATGGGTCTCGTGTTTTTTTGT

CTGAAAAACGGCAACATGCGATGTACAATTTGTATT

838
ATGTACAAGATTGTAGTCATCATCGCCCTACTGGGTGCAGTCAAGGGACTGGACAAAATAT

GCCTGGGCCATCATGCAGTGGCCAACGGGACCATTGTTAAGACACTTACAAATGAGAAAGA

AGAGGTTACTAATGCCACCGAAACTGTGGAGTCCACCGGCCTAAACCGACTCTGCATGAAG

GGAAGGAAACACAAAGATCTGGGAAACTGCCACCCCATAGGGATGCTCATCGGCTCTCCCG

CATGTGACCTGCATCTGACAGGAACCTGGGATACCCTGATCGAGAGAGAAAACGCGATCGC

CTATTGTTACCCCGGCGCGACAGTGAATGGTGAGGCTCTGCGCCAAAAAATAATGGAATCA

GGAGGAATAGACAAAATTTCAACAGGATTTACATACGAATCCTCCATTAATAGCGCCGGCA

CAACTAGAGCTTGTATGCGGAATGGGGGCAATTCCTTTTACGCGGAGCTGAAATGGTTGGT

ATCTAAAAGCAAAGGACAGAACTTCCCTCAGACTACCAACACCTATCGAAATACAGACACA

GCCGAGCACTTAATTATGTGGGGGATACATCACCCCTCTTCTACACAGGAGAAAAATGACT

TATACGGAACCCAATCCTTAAGCATTAGTGTGGGCAGCAGCACATATCGAAACAATTTTGT

ACCAGTGGTAGGAGCTCGCCCTCAGGTGAATGGACAGAGCGGCCGGATTGATTTCCACTGG

ACACTGGTTCAGCCTGGCGACAATATCACATTCAGCCATAACGGTGGTTTGATTGCTCCTT

CCAGAGTCAGTAAATTGATCGGGAGAGGACTGGGGATTCAGTCAGACGCCCCCATTGATAA

TAACTGTGAAAGCAAGTGCTTTTGGAGAGGTGGATCCATCAACACACGTCTGCCCTTCCAG

AACCTGAGTCCCCGGACAGTCGGTCAGTGTCCGAAGTACGTCAACAAACGGAGTTTAATGC

TCGCGACTGGGATGAGGAACGTGCCTGAACTTATGCAAGGCCGGGGCTTATTCGGGGCCAT

TGCGGGCTTTCTGGAAAACGGGTGGGAAGGGATGGTTGATGGGTGGTACGGGTTCAGACAC

CAGAATGCTCAGGGCACCGGACAAGCCGCAGATTATAAGTCAACCCAGGCCGCAATAGATC

AGATTACCGGCAAACTGAACAGGCTCGTCGAGAAAACCAATACTGAGTTTGAATCTATTGA

AAGCGAGTTTTCAGAGATTGAACATCAAATCGGCAATGTGATTAATTGGACCAAAGATTCG

ATTACAGATATATGGACCTACCAGGCTGAACTTCTTGTCGCCATGGAAAACCAGCATACGA

TCGATATGGCCGACAGCGAAATGTTAAACCTATACGAGCGGGTGAGGAAGCAGCTGAGGCA

GAACGCAGAAGAGGACGGGAAAGGCTGTTTTGAAATATACCACGCCTGTGATGATTCTTGC

ATGGAGTCGATCCGTAACAACACATACGACCATTCTCAATATCGAGAGGAAGCATTATTGA

ACAGGTTAAACATCAATCCCGTTACTCTCTCCAGCGGATATAAAGACATTATCCTTTGGTT

TTCATTCGGAGCATCCTGTTTTGTCTTACTAGCCGTCGTAATGGGTTTAGTCTTCTTTTGC

CTTAAGAACGGGAATATGAGGTGTACCATATGTATT

839
ATGTATAAAATCGTGGTGATCATCGCTCTTCTTGGCGCTGTGAAGGGGCTCGACAAGATCT

GCTTAGGTCATCACGCAGTGGCTAATGGTACGATCGTGAAGACACTGACGAATGAACAGGA

AGAAGTCACAAATGCCACGGAGACCGTTGAGAGCACTGGCATCAATAGACTGTGCATGAAA

GGACGCAAGCACAAGGACCTGGGCAATTGCCATCCTATCGGCATGCTGATTGGAACGCCGG

CGTGTGACCTGCATTTGACCGGGATGTGGGATACCCTAATCGAGAGGGAGAACGCAATTGC

CTATTGTTACCCCGGCGCAACCGTGAATGTGGAAGCCCTGCGACAAAAGATCATGGAGAGT

GGTGGCATTAATAAGATTTCTACCGGGTTCACTTATGGCAGTAGCATCAACTCTGCCGGCA

CAACCAGGGCTTGTATGAGGAATGGAGGCAACAGCTTTTATGCTGAACTTAAATGGCTCGT

CAGCAAGTCTAAAGGTCAGAACTTCCCTCAGACCACAAATACATACAGAAATACTGACACA

GCCGAGCACCTCATCATGTGGGGCATCCATCATCCATCTTCCACCCAAGAGAAAAACGACC

TCTACGGGACACAGAGCCTGTCTATAAGCGTGGGCTCTAGCACTTATAGAAATAATTTCGT

TCCAGTGGTGGGCGCACGTCCCCAAGTTAACGGCCAGAGCGGAAGGATCGATTTCCATTGG

ACTCTGGTGCAGCCTGGGGACAACATTACATTTTCCCACAATGGAGGTCTTATTGCACCCT

CACGGGTATCCAAGTTAATCGGCCGCGGACTTGGCATCCAATCAGATGCACCCATCGACAA

CAATTGTGAGAGTAAGTGCTTCTGGCGTGGTGGGAGCATCAACACGAGATTACCTTTCCAG

AATCTGAGCCCGAGAACAGTAGGGCAATGTCCAAAGTATGTGAACAGGCGCAGCCTCATGC

TCGCGACCGGAATGAGAAATGTTCCCGAACTGATACAAGGAAGGGGTTTGTTCGGCGCCAT

CGCAGGATTTCTGGAAAACGGGTGGGAGGGAATGGTGGACGGTTGGTACGGCTTCCGTCAC

CAGAACGCCCAGGGCACGGGTCAGGCCGCAGACTATAAAAGTACCCAGGCGGCCATTGATC

AGATAACAGGCAAGCTCAACCGGCTGGTAGAAAAAACCAATACAGAGTTTGAGAGCATAGA

GTCCGAGTTTAGCGAGATAGAACATCAAATAGGAAATGTCATCAACTGGACCAAGGACAGC

ATCACGGATATTTGGACTTACCAGGCCGAATTACTGGTTGCTATGGAGAACCAGCACACTA

TTGATATGGCAGATTCTGAAATGTTAAACTTATATGAACGCGTGAGAAAGCAGTTGAGGCA

GAATGCTGAGGAGGACGGGAAGGGCTGCTTTGAAATATACCATGCCTGCGACGATAGCTGT

ATGGAGAGCATCAGGAACAATACATACGATCACAGTCAATACCGCGAGGAGGCTTTACTCA

ACCGGCTCAACATAAACCCCGTCACTCTCTCTTCGGGCTACAAGGATATTATTCTGTGGTT

TTCATTCGGCGCTTCCTGCTTCGTTCTCCTAGCCGTAGTAATGGGCCTCTTCTTCTTCTGC

CTGAAAAACGGCAACATGCGGTGTACTATCTGCATT

840
ATGTACAAGATTGTGGTCATCATCGCCCTGCTGGGCGCCGTCAAGGGGCTCGATAAGATTT

GCCTAGGTCACCACGCCGTCGCCAATGGCACGATTGTTAAAACACTGACCAATGAACAGGA

GGAAGTGACTAACGCTACGGAAACAGTGGAATCTACAGGGATTAACAGACTTTGCATGAAG

GGGCGCAAGCATAAGGACCTTGGAAATTGCCACCCAATCGGAATGCTTATCGGAACACCTG

CTTGTGACCTTCATCTGACCGGCATGTGGGACACCCTGATAGAGAGGGAGAACGCCATCGC

CTACTGCTATCCTGGAGCCACCGTCAATGTCGAAGCCTTAAGACAGAAAATAATGGAAAGT

GGGGGTATAAACAAAATCAGCACTGGCTTCACTTATGGTTCTTCTATCAATAGCGCAGGGA

CAACCAGAGCCTGCATGCGCAATGGGGGCAATAGCTTTTATGCCGAACTGAAGTGGCTGGT

CTCTAAATCTAAGGGTCAAAATTTTCCTCAGACAACCAACACATACCGCAATACGGACACC

GCGGAGCATCTCATTATGTGGGGGATTCACCACCCTTCAAGCACCCAGGAGAAGAATGACC

TCTATGGGACACAGAGCCTGTCAATCTCAGTGGGATCTAGCACTTATCGTAACAATTTCGT

TCCAGTAGTTGGTGCACGCCCCCAGGTTAATGGGCAGAGTGGGCGAATTGATTTCCACTGG

ACGCTCGTGCAGCCCGGCGATAATATCACATTCAGTCACAATGGGGGGCTAATCGCCCCGT

CCAGAGTTTCTAAGCTGATCGGCAGAGGATTAGGAATTCAATCCGACGCACCCATTGACAA

CAATTGTGAATCAAAATGCTTCTGGCGCGGAGGGTCGATAAACACACGACTTCCTTTTCAA

AACTTATCCCCAAGAACCGTGGGACAGTGCCCCAAGTACGTCAATAGAAGATCACTGATGC

TGGCCACCGGTATGAGGAATGTGCCCGAACTAATCCAGGGCCGCGGGTTGTTCGGCGCTAT

TGCAGGCTTTTTAGAAAACGGCTGGGAAGGGATGGTCGACGGATGGTACGGGTTCAGGCAT

CAGAATGCGCAGGGCACTGGGCAGGCCGCGGATTATAAGAGTACCCAGGCGGCCATAGATC

AAATAACCGGCAAGCTCAACAGGCTGGTCGAGAAGACAAACACAGAGTTTGAGTCAATAGA

GTCCGAATTCTCCGAAATCGAACACCAAATAGGCAATGTGATAAACTGGACCAAGGACTCC

ATCACCGATATCTGGACTTATCAGGCTGAACTGTTAGTGGCGATGGAAAACCAGCACACAA

TCGATATGGCAGACTCAGAGATGCTTAATCTGTATGAACGAGTTAGAAAGCAGCTCCGGCA

GAATGCCGAGGAAGACGGAAAGGGCTGCTTCGAGATCTACCACGCGTGCGATGATTCCTGT

ATGGAGTCTATTCGCAATAACACGTATGATCATTCACAGTATAGAGAAGAGGCCCTCCTAA

ACAGGCTCAACATCAACCCTGTGACGCTGTCGAGCGGCTATAAGGATATTATACTGTGGTT

TAGTTTCGGCGCCAGTTGCTTTGTCCTTCTTGCCGTGGTAATGGGATTATTCTTCTTCTGT

CTGAAAAACGGAAACATGAGATGCACAATATGTATC

841
ATGTATAAAATTGTAGTCATTATTGCCTTGTTAGGTGCAGTGAAGGGCTTAGACAAAATAT

GCCTAGGTCATCACGCCGTCGCTAATGGTACAATAGTCAAGACCCTCACCAATGAACAGGA

GGAGGTCACGAACGCAACAGAGACCGTGGAGTCCACAGGAATAAACCGACTGTGTATGAAG

GGCAGAAAACATAAAGACTTGGGCAACTGTCACCCTATAGGCATGTTGATTGGCACACCAG

CTTGTGATCTCCACCTAACCGGGATGTGGGACACCCTCATAGAACGCGAGAACGCTATCGC

CTATTGTTATCCCGGGGCCACGGTTAATGTGGAAGCTCTGCGACAGAAGATCATGGAGAGC

GGGGGGATTAATAAGATAAGCACTGGTTTCACCTACGGCTCAAGTATCAATTCAGCTGGCA

CCACCCGAGCATGTATGAGGAATGGCGGAAATAGCTTTTATGCAGAACTGAAGTGGTTAGT

CAGTAAAAGTAAAGGTCAGAACTTTCCACAGACCACCAACACATATCGCAATACTGATACA

GCTGAGCACTTAATCATGTGGGGAATTCACCATCCCAGTTCCACACAAGAAAAAAATGATT

TATACGGCACTCAGTCCCTTTCAATCAGCGTGGGGTCCTCTACCTACAGGAATAACTTTGT

CCCCGTGGTTGGCGCCAGACCCCAGGTAAACGGTCAGTCTGGACGGATCGATTTCCACTGG

ACACTGGTGCAGCCAGGTGACAATATTACCTTCAGCCACAATGGGGGCCTGATCGCCCCCT

CAAGAGTGTCCAAGCTGATCGGAAGAGGGTTGGGGATCCAGTCCGATGCCCCAATCGACAA

TAACTGCGAATCCAAATGTTTCTGGCGCGGAGGCTCAATAAATACCAGACTCCCTTTCCAG

AACCTTTCACCAAGAACAGTCGGACAATGCCCTAAGTATGTCAATCGCCGATCGCTAATGC

TTGCGACAGGGATGAGAAATGTGCCAGAGCTGATTCAAGGGCGCGGGCTGTTCGGCGCTAT

CGCCGGCTTTTTAGAGAATGGTTGGGAAGGGATGGTGGATGGCTGGTATGGATTTAGGCAC

CAGAACGCTCAGGGGACAGGGCAGGCTGCCGACTATAAGAGCACACAGGCAGCCATTGACC

AAATCACTGGGAAATTGAACCGTCTTGTGGAAAAAACTAACACCGAGTTCGAGTCCATTGA

GTCCGAGTTCTCGGAGATAGAACACCAAATCGGGAACGTCATCAATTGGACAAAAGATTCC

ATCACCGATATCTGGACTTACCAGGCTGAGTTGCTGGTCGCTATGGAGAACCAGCACACGA

TCGACATGGCAGACTCTGAGATGTTGAACCTGTATGAGAGAGTGCGAAAACAGCTCAGACA

GAACGCTGAAGAAGACGGAAAGGGGTGCTTCGAGATCTATCATGCCTGTGACGATAGCTGT

ATGGAGAGCATAAGAAACAATACGTATGATCACTCTCAGTACAGAGAAGAGGCCCTGCTAA

ATCGGTTAAACATTAATCCAGTGACCCTGAGCAGCGGCTACAAGGACATCATCCTATGGTT

TTCTTTCGGTGCCTCGTGCTTCGTCTTACTCGCTGTCGTCATGGGTCTGTTCTTCTTTTGC

CTGAAGAACGGCAATATGCGGTGTACAATCTGTATT

842
ATGTATAAAGTGGTCGTGATTATTGCTCTGTTAGGCGCCGTGCGCGGCTTGGATAAGATCT

GCCTAGGCCATCACGCCGTCGCTAACGGCACTACCGTAAAGACCCTGACCAACGAGCAGGA

AGAAGTCACAAATGCTACCGAGACCGTTGAGAGCACTTCGTTGAACAAGTTATGCATGAAG

GGCAGACGCTACAAGGATCTGGGTAATTGCCACCCCATAGGGATGCTCATTGGAACGCCCG

TCTGTGACTTGCATTTGACCGGCACATGGGATACCCTCATCGAGCGGGAAAACGCCACAGC

ATACTGCTATCCTGGGGTGACTATCAACGAGGAAGCATTGAGGCAAAAGATCATGGAATCA

GGCGGGATCAGTAAGATGAGAACCGGGTTCACCTACGGGCCTTCCATCAACTCCGCCGGCA

CCACCCGCAGTTGTATGAGAAACGGCGGCAATTCTTTTTATGCTGAGCTGAAGTGGTTGGT

CTCTGGGACCAAGGGCCAAAATTTTCCTCAAACAACGAATACCTACCGGAATACTGACACG

GCTGAACATCTGATCATCTGGGGGATTCACCACCCCTCATCCACCCAAGAGAAGAATGATC

TGTATGGAACGCAGAGCCTGTCTATTTCGGTTGGAAGCAGTACATACCAGAATAACTTCGT

GCCCGTTATTGGGGCCCGTCCCCAGGTCAACGGTCAGTCGGGCCGGATTGAGTTCCATTGG

ACCCTGGTCCGCCCTGGTGACAACATTACTTTTTCGCATAACGGTGGGCTAATCGCACCTG

ATCGAGTGTCCAAGCTGATCGGCAAAGGAATTGGTATACAGTCTGGTGCGGTAATCGATAA

GGACTGTGAAAGCAAATGCTTCTGGAGAGGCGGCAGTATCATCACCGAACTCCCCTTTCAG

AATCTCTCTCCACGTACAGTGGGCCAGTGTCCAAAGTATGTTAAAAAGCGGTCTCTGTTAC

TAGCCACGGGGATGAGGAATGTTCCCGAGGTGGTACAAGGACGGGGCCTCTTCGGGGCGAT

CGCCGGCTTCATTGAAAACGGCTGGGAGGGTATGGTTGACGGATGGTACGGATTCCGCCAC

CAAAACGCCCAGGGAATCGGCCAGGCTGCCGACTACAAATCCACTCAGACCGCCATCGACC

AAATTACGGGTAAACTGAACCGCCTAATCGAGAAGACAAATACTGAATTTGAGAGCATTGA

GAGTGAGTTCAGCGAAATCGAGCACCAGATCGGAAATGTGATTAATTGGACAAAGGATAGT

ATTACCGACATCTGGACCTACCAGGCGGAGCTCCTTGTGGCTATGGAAAACCAACACACCA

TTGACATGGCCGACAGTGAAATGCTGAATCTCTACGAGCGCGTGAGAAAGCAGCTCCGGCA

GAACGCCGAGGAGGACGGCAAAGGATGCTTCGAAATATATCACACATGTGACAACTCATGC

ATGGAAAGTATTAGGAACAACACCTACGACCATTCCCAATACAGAGAGGAGGCCCTACTTA

ACCGCCTTAACATCAATCCCGTGAAACTCTCCTCCGGTTATAAAGATATCATTTTATGGTT

CAGCTTCGGGGCGAGTTGCTTTGTGCTGCTGGCTGTGATTATGGGCCTGGGATTCTTTTGC

CTAAAAAACGGAAACATGCGATGCACTATCTGTATC

843
ATGTATAAAATTATTGTGATCATTGCACTGCTGGGGGCCGTTAAGGGTCTGGACAAAATTT

GTCTAGGACACCACGCTGTGGCAAACGGTACTATCGTGAAAACATTGACCAACGAACAGGA

GGAGGTTACCAACGCCACCGAGACAGTCGAAAGTACCGGAATTAATCGCCTCTGCATGAAA

GGCCGAAAGCATAAGGACCTGGGGAATTGCCATCCCATCGGAATGCTGATCGGCACCCCAG

CCTGTGACTTGCATCTTACAGGAACCTGGGACACACTAATCGAAAGGGAAAACGCCATTGC

TTACTGTTACCCGGGCGCTACAGTTAACGTGGAGGCCCTTAGGCAGAAAATCATGGAGTCC

GGCGGGATCGACAAGATCAGTACCGGCTTCACCTATGGGTCAAGCATCAATTCTGCGGGCA

CTACGAGGGCATGCATGAGGAACGGAGGCAACTCATTCTATGCGGAATTGAAGTGGCTGGT

CTCCAAGTCCAAAGGGCAGAACTTCCCTCAAACTACTAACACCTACCGGAATACAGACACA

GCGGAACACCTCATTATGTGGGGCATCCACCACCCTTCTAGTACTCAAGAGAAGAATGATC

TCTACGGCACTCAGTCCCTGAGTATTAGTGTCGGCTCAAGCACCTATAGAAACAATTTCGT

GCCCGTTGTGGGGGCCCGCCCTCAGGTTAATGGTCAATCAGGGCGAATTGATTTTCACTGG

ACCCTGGTCCAGCCCGGGGACAACATAACATTCAGCCATAATGGGGGTCTGATTGCCCCCA

GCCGGGTGAGCAAGTTGATAGGGAGGGGACTTGGCATCCAGAGTGACGCCCCTATTGACAA

CAACTGCGAAAGCAAATGCTTTTGGCGGGGTGGCTCAATAAACACAAGGCTACCCTTCCAA

AATTTGAGTCCAAGGACCGTGGGTCAATGCCCTAAATACGTCAATCGCCGCTCCTTGATGC

TCGCCACTGGGATGCGCAACGTGCCTGAGCTTATTCAGGGTCGGGGTCTGTTCGGGGCTAT

CGCCGGGTTCCTTGAAAATGGCTGGGAGGGTATGGTAGACGGCTGGTACGGATTTAGACAC

CAGAACGCCCAGGGAACGGGCCAGGCGGCAGACTACAAGTCTACCCAAGCTGCAATCGATC

AGATCACTGGCAAGTTAAACAGACTGGTGGAAAAGACAAATACCGAATTTGAAAGCATTGA

ATCGGAATTCTCAGAGATCGAGCACCAGATTGGAAATGTGATTAATTGGACGAAAGACAGT

ATTACCGACATCTGGACTTATCAGGCAGAACTGCTGGTTGCCATGGAAAACCAGCATACCA

TAGATATGGCAGATTCTGAAATGCTCAATCTTTACGAGCGCGTACGGAAACAGTTAAGACA

GAACGCAGAGGAGGACGGGAAAGGTTGCTTTGAAATATACCACGCATGTGACGATTCTTGC

ATGGAAAGTATCCGCAATAATACGTATGATCACAGTCAATACCGAGAAGAGGCTCTCTTGA

ATCGTTTGAATATCAATCCAGTGACCCTGTCCTCCGGATATAAGGATATAATTCTGTGGTT

CAGTTTTGGGGCAAGTTGCTTCGTCCTCCTCGCTGTCGTTATGGGACTGTTTTTTTTTTGT

CTAAAGAACGGAAACATGCGCTGCACTATATGCATT

844
ATGTATAAAATAGTTGTCATCATTGCACTCTTGGGCGCCGTGAAAGGACTGGATAAAATAT

GTCTCGGCCACCATGCAGTTGCAAACGGGACAATTGTGAAAACATTGACCAACGAGCAGGA

GGAGGTGACCAATGCTACAGAGACGGTGGAATCTACTGGCATCAACCGATTGTGCATGAAA

GGTAGGAAACACAAGGATTTGGGTAATTGCCATCCGATTGGGATGCTTATCGGAACCCCAG

CTTGCGATCTGCATTTGACCGGAATGTGGGACACCCTGATTGAGAGGGAAAACGCCATCGC

CTACTGCTATCCTGGCGCAACAGTTAACGTGGAGGCACTTCGCCAGAAGATCATGGAAAGC

GGGGGGATAAACAAGATCTCTACAGGTTTCACCTATGGTTCTTCCATTAACAGCGCCGGTA

CCACACGAGCTTGTATGCGAAATGGGGGCAACTCCTTCTACGCTGAATTAAAATGGCTGGT

GTCGAAGTCCAAAGGGCAGAACTTCCCTCAGACAACAAACACCTACCGGAACACAGACACC

GCGGAGCACCTGATCATGTGGGGTATACACCACCCCAGCTCTACCCAGGAAAAGAATGATC

TCTATGGAACCCAGTCATTAAGTATCAGCGTCGGTTCCTCTACATATCGTAATAATTTCGT

GCCTGTGGTTGGCGCCAGGCCACAAGTGAATGGGCAGTCCGGCAGAATTGACTTTCATTGG

ACTCTGGTGCAGCCAGGCGACAATATCACATTCTCTCACAACGGGGGACTTATCGCCCCCT

CCAGGGTGTCAAAACTCATCGGCCGGGGGCTGGGAATCCAAAGCGATGCTCCCATCGACAA

CAATTGCGAATCAAAATGTTTCTGGCGAGGGGGTTCCATAAATACCAGACTGCCATTCCAG

AACCTGTCCCCAAGAACAGTGGGCCAATGTCCCAAGTATGTGAACAGAAGGTCTTTGATGC

TCGCAACTGGGATGCGAAATGTTCCAGAGCTGATTCAGGGTCGAGGACTTTTTGGAGCCAT

CGCTGGCTTCTTAGAGAACGGCTGGGAAGGAATGGTGGACGGCTGGTATGGCTTTAGACAC

CAGAACGCCCAGGGTACGGGACAGGCTGCAGATTACAAATCTACACAGGCCGCAATCGACC

AGATCACAGGCAAGCTCAATCGGCTTGTGGAGAAGACAAACACAGAGTTTGAGAGCATTGA

ATCGGAATTTAGTGAGATTGAGCACCAGATTGGCAATGTGATTAATTGGACTAAAGACTCT

ATTACGGATATCTGGACGTATCAGGCAGAGCTGTTGGTGGCAATGGAAAATCAACACACTA

TCGACATGGCCGATAGTGAGATGCTCAATCTATATGAGAGGGTTCGCAAGCAGCTGCGTCA

AAATGCCGAGGAGGATGGCAAGGGATGTTTCGAGATTTATCACGCCTGCGATGATTCGTGC

ATGGAGAGCATTCGCAATAACACGTACGATCACTCTCAGTACAGGGAGGAGGCACTTTTAA

ACCGTCTCAACATCAACCCTGTGACCCTGAGCTCTGGCTACAAAGACATCATTTTGTGGTT

CTCCTTTGGAGCCAGCTGCTTCGTGCTCCTCGCCGTGGTCATGGGCTTGTTTTTCTTCTGT

CTGAAGAATGGAAATATGCGATGCACCATCTGTATT

845
ATGTACAAGGTGGTAGTTATAATCGCACTTCTGGGAGCAGTGAGAGGTCTCGACAAGATTT

GCCTCGGGCACCACGCTGTGGCTAATGGCACAATTGTGAAGACCTTGACAAATGAGCAGGA

AGAAGTGACAAATGCGACTGAGACTGTCGAGTCCAAGTCTCTGGGCAAGTTGTGCATGAAG

GGCAGATCCTACAACGACTTAGGGAACTGTCATCCGATAGGGATCTTAATCGGGACCCCAG

CCTGCGATCTCCACCTGACTGGCACCTGGGATACCTTAATCGAGAGGGAAAACGCAGTGGC

CTACTGCTATCCCGGTGCTACCGTGAATGAGGAGGCTCTGAGGCAGAAGATCATGGAGTCA

GGGGGAATTTCGAAAATAAGCACCGGGTTCACTTACGGTACCAGCATCAATTCTGCTGGAA

CAACTAAGGCATGTATGCGTAATGGCGGAAACTCATTTTACGCAGAGCTCAAGTGGCTAGT

GAGCAAGAATAAAGGGCAGAACTTTCCGCAGACCACTAACACTTACAGAAACACAGATACC

GCTGAACATTTGATTATCTGGGGCATTCACCACCCGTCGTCAACACAGGAGAAGAATGATC

TGTATGGTACACAGTCACTGTCAATTTCTGTCGGATCTTCCACCTACCAGAATAATTTCGT

TCCAGTGGTTGGTGCTAGGCCCCAGGTTAACGGACAATCCGGTCGCATTGACTTCCATTGG

ACCCTGCTGCAGCCAGGCGATAACATTACGTTCTCGCATAACGGCGGCCTAATCGCACCTA

GCAGAGTGTCAAAGTTGATTGGGAGGGGCCTTGGCATCCAGAGCGAGGCCCCCATCGACAA

TGGCTGCGAGTCCAAATGCTTCTGGAAAGGGGGGTCAATCAACACCAAGCTGCCCTTTCAG

AACCTCAGCCCCCGAACCGTCGGGCAGTGCCCTAAATACGTGAATAAGCGCAGTCTGATGT

TAGCTACAGGGATGCGGAATGTACCCGAAATCATGCACGGGCGAGGTCTGTTCGGGGCAAT

TGCAGGCTTCATTGAAAATGGGTGGGAAGGCATGGTCGATGGGTGGTATGGGTTTAGACAC

CAAAACGCACAAGGAACAGGCCAGGCAGCGGACTATAAGAGCACCCAGGCAGCTATTGACC

AGATTACCGGCAAGCTGAACAGGCTTATAGAGAAGACTAACACAGAATTCGAGTCCATTGA

GTCAGAGTTCAGCGAGATTGAGCACCAGATCGGAAACATCATTAACTGGACTAAGGACTCA

ATTACAGATATATGGACGTATCAGGCCGAACTGTTGGTGGCAATGGAGAATCAGCATACCA

TTGATATGGCAGATAGTGAGATGCTGAATCTTTACGAACGCGTTCGCAAACAGTTGCGGCA

GAATGCCGAAGAAGACGGCAAGGGTTGCTTTGAGATATACCACGCTTGTGACGATTCCTGC

ATGGAGTCTATCAGAAACAACACGTACGATCACAGTCAGTATCGCGAGGAGGCATTACTCA

ATCGACTAAATATCAACCCGGTGAAACTGTCTAGCGGATACAAAGACATCATCCTTTGGTT

TTCCTTTGGCGCAAGTTGTTTGATTCTGTTGGCCGTGGTTATGGGTTTAGTCTTTTTTTGT

CTCAAAAACGGTAATATGCGCTGTACGATCTGCATT

846
ATGTACAAGATCGTGGTCATCATCGCCTTGTTGGGGGCAGTGAAAGGATTGGATAAAATTT

GCCTGGGACACCACGCCGTCGCCAATGGAACCATAGTCAAGACGCTGACAAACGAGCAGGA

GGAAGTAACCAATGCGACTGAAACCGTGGAATCAACCGGAATCAATCGACTGTGTATGAAA

GGCAGGAAGCATAAAGACCTGGGCAACTGTCACCCGATCGGGATGTTAATCGGGACACCCG

CTTGTGACTTGCACCTGACCGGCATGTGGGACACTCTGATTGAGCGAGAGAATGCAATCGC

CTATTGTTACCCCGGAGCCACTGTTAACGTTGAGGCCCTCAGACAGAAGATTATGGAGTCT

GGCGGGATCAACAAGATCTCCACAGGGTTTACTTACGGAAGCAGCATCAACTCTGCCGGCA

CTACTCGCGCTTGCATGCGTAACGGGGGTAACAGCTTCTATGCTGAACTCAAATGGCTGGT

GTCTAAAAGTAAGGGCCAGAACTTTCCGCAGACGACTAATACATATAGAAATACCGATACA

GCCGAGCACCTGATTATGTGGGGGATACACCACCCCAGTTCCACCCAGGAAAAGAACGACC

TATATGGAACCCAGTCCCTCTCTATTAGCGTCGGCTCTTCAACTTATCGTAATAATTTTGT

GCCGGTCGTCGGAGCAAGACCTCAGGTCAACGGGCAGTCCGGTCGAATAGATTTTCACTGG

ACCCTAGTTCAGCCAGGAGATAATATCACATTCAGCCACAACGGAGGGTTGATAGCTCCAT

CACGAGTGTCCAAGCTGATCGGCAGGGGGCTCGGCATCCAGTCCGACGCCCCAATTGATAA

CAACTGTGAATCCAAGTGCTTCTGGAGAGGAGGCTCTATCAATACCCGATTGCCGTTCCAA

AATCTATCCCCTAGAACAGTCGGGCAGTGCCCTAAATACGTGAATAGAAGAAGCTTAATGT

TGGCAACAGGAATGAGGAACGTGCCGGAACTCATCCAGGGGCGCGGCTTATTCGGCGCTAT

CGCAGGTTTTCTTGAGAATGGATGGGAGGGCATGGTTGATGGTTGGTACGGATTCAGACAC

CAAAACGCTCAAGGCACCGGCCAAGCTGCCGATTATAAAAGCACTCAAGCTGCTATCGACC

AGATTACCGGAAAACTTAATAGGCTGGTTGAGAAAACGAACACCGAATTCGAGAGCATCGA

GAGCGAATTTAGTGAGATCGAGCATCAAATAGGCAACGTGATCAATTGGACGAAAGATTCT

ATCACCGATATTTGGACTTATCAAGCCGAACTTCTAGTGGCAATGGAGAACCAGCACACAA

TCGACATGGCAGATTCGGAAATGCTGAATTTATACGAGAGGGTGCGTAAACAGTTAAGGCA

AAACGCCGAAGAGGACGGTAAAGGTTGCTTTGAAATTTATCACGCGTGCGATGATTCCTGT

ATGGAGAGTATTCGGAATAATACATATGATCACTCCCAATATCGCGAAGAGGCATTGTTAA

ACCGGCTGAATATAAATCCAGTAACCCTGTCCTCCGGGTACAAAGACATAATCCTGTGGTT

CTCCTTCGGGGCTAGTTGTTTTGTTCTGCTGGCTGTGGTTATGGGATTATTCTTTTTTTGT

CTGAAAAACGGGAATATGCGCTGTACAATATGCATA

847
ATGTACAAAATTGTAGTGATTATCGCTCTTCTAGGCGCCGTAAAGGGGCTTGACAAGATCT

GTCTAGGACACCACGCCGTGGCCAATGGAACCATTGTAAAAACACTGACGAACGAGCAGGA

GGAGGTGACAAACGCCACTGAAACAGTTGAGAGCACCGGGATTAACCGTCTCTGTATGAAG

GGTAGGAAACACAAAGATCTCGGGAATTGTCATCCAATTGGAATGCTGATAGGCACTCCCG

CCTGTGACCTTCACTTAACTGGCATGTGGGACACACTGATCGAGAGGGAGAATGCAATTGC

GTATTGTTACCCGGGCGCCACTGTTAATGTGGAGGCGCTGAGGCAGAAAATAATGGAGTCC

GGCGGAATAAATAAAATCTCTACGGGGTTCACCTACGGATCCTCCATCAACTCTGCAGGCA

CAACAAGAGCCTGCATGAGAAACGGGGGCAACAGTTTTTACGCCGAGCTGAAATGGTTAGT

CAGTAAATCTAAAGGGCAAAATTTCCCTCAGACGACCAACACCTACCGGAACACCGATACC

GCTGAGCATCTCATCATGTGGGGTATCCATCACCCTTCCAGCACTCAGGAGAAAAACGACC

TGTACGGTACTCAATCCCTCTCTATCTCAGTCGGAAGCTCCACATACCGCAATAATTTCGT

GCCTGTGGTCGGGGCCCGCCCGCAGGTTAACGGACAGTCAGGACGGATTGACTTCCACTGG

ACTCTGGTGCAGCCCGGTGACAACATTACGTTTAGCCATAACGGTGGTCTCATTGCCCCGT

CGCGTGTATCCAAGCTGATTGGCCGGGGGTTAGGGATTCAAAGTGACGCACCCATCGACAA

CAATTGCGAATCGAAGTGTTTTTGGAGAGGCGGCAGTATTAATACCCGGTTGCCATTCCAA

AACCTCTCCCCAAGAACAGTTGGCCAGTGTCCAAAATATGTCAACCGGCGGTCCCTTATGC

TCGCCACCGGCATGCGAAACGTACCCGAACTGATCCAAGGCCGCGGTCTGTTTGGAGCTAT

CGCAGGCTTCCTGGAGAACGGGTGGGAGGGCATGGTCGACGGATGGTATGGTTTTAGGCAC

CAGAATGCACAAGGGACGGGTCAAGCCGCCGATTACAAGAGCACACAGGCGGCCATCGACC

AAATCACTGGGAAACTGAATAGACTGGTGGAGAAGACCAACACTGAGTTCGAAAGCATCGA

ATCAGAATTTAGCGAAATAGAACACCAGATCGGCAATGTGATTAACTGGACAAAGGATAGC

ATAACAGACATCTGGACATATCAGGCTGAACTGCTTGTCGCGATGGAGAACCAGCACACCA

TAGATATGGCAGATAGTGAAATGCTCAATTTATACGAGGGGGTGAGAAAACAGCTTAGACA

GAACGCTGAAGAGGACGGCAAGGGGTGCTTTGAGATATACCACGCCTGCGACGACAGCTGC

ATGGAAAGTATCAGGAACAATACATATGACCACTCACAGTATCGCGAAGAGGCACTTCTCA

ATAGACTAAACATCAATCCCGTGACACTGAGTAGTGGATATAAAGATATTATATTATGGTT

CTCTTTTGGGGCGTCATGTTTCGTGCTTCTGGCCGTGGTGATGGGTCTCTTCTTCTTCTGT

CTTAAAAATGGCAATATGCGGTGCACCATTTGCATA

848
ATGTACAAAATCGTACTGGTGCTGGCATTGCTCGGGGCAGTGCACGGCCTGGACAAGATAT

GCCTGGGACACCACGCTGTGCCTAACGGTACCATTGTGAAGACTCTGACGAATGAGAAGGA

AGAGGTGACGAACGCAACGGAGACGGTCGAGTCCAAGAGCCTCGATAAGCTGTGTATGAAG

AACAGGAACTACAAGGACCTCGGGAATTGTCATCCAATTGGCATGGTGGTGGGCACTCCCG

CCTGCGACCTCCATCTGACTGGTACATGGGATACCCTAATAGAGCGGGACAATAGTATCGC

CTACTGTTATCCCGGCGCCACCGTGTCAGAGGAGGCCCTGCGACAGAAAATAATGGAGTCC

GGCGGCATTGATAAGATTTCCACTGGGTTTACATACGGTAGCTCCATTAATTCTGCGGGAA

CTACCAAGGCTTGTATGAGAAATGGCGGTAACTCTTTCTATAGCGAGTTAAAATGGCTGGT

GAGCAAGAATAAGGGCCAAAATTTCCCCCAGACTACGAACACCTACAGAAACACCGACAGT

GTTGAGCACCTGATTATATGGGGGATACATCATCCCAGTTCTACTCAGGAGAAAAACGATT

TATACGGCACTCAAAGTCTGAGTATCTCTGTGGGGTCTAGCACATACCAGAACAACTTCGT

CCCAGTGGTTGGGGCAAGGCCGCAGGTGAATGGACAATCAGGGAGAATCGATTTCCACTGG

ACAATGGTACAGCCTGGGGATAATATCACCTTTTCTCATAACGGCGGACTTATAGCCCCCA

ACCGCGTGAGCAAGCTAAAGGGAAGAGGCCTAGGAATTCAAAGCGGTGCTTCGGTGGACAA

TGACTGCGAGAGCAAGTGCTTCTGGAAAGGTGGCTCCATCAATACTAAGTTGCCTTTTCAG

AACTTGAGCCCGAGAACCGTTGGCCAGTGCCCTAAATATGTGAACAAAAAGTCACTCCTGC

TCGCCACAGGGATGAGGAATGTCCCCGAAGTGGCTCAGGGTCGCGGGCTCTTCGGAGCCAT

CGCCGGATTCATCGAGAACGGCTGGGAAGGGATGGTAGACGGCTGGTATGGCTTTAGGCAT

CAAAACGCCCAGGGGACAGGGCAAGCCGCTGACTATAAGAGTACCCAGGCAGCCATCGACC

AGATCACTGGGAAATTAAATCGGCTGATTGAAAAGACGAACACCGAATTTGAAAGCATCGA

GTCAGAGTTCTCCGAGATAGAGCATCAAATTGGGAACGTGATTAACTGGACGAAGGATAGC

ATCACCGATATTTGGACATACCAGGCGGAGCTGCTGGTGGCCATGGAGAATCAACATACAA

TCGACATGGCCGACTCTGAGATGTTGAATCTCTACGAAAGGGTGAGAAAGCAGTTAAGGCA

GAATGCCGAGGAGGATGGGAAAGGATGCTTCGAGATCTATCACAAATGCGATGACAATTGT

ATGGAATCTATTCGTAACAATACTTACGACCACACTCAGTATCGTGAGGAAGCGCTGTTGA

ATCGGCTCAATATCAATCCAGTGAAGCTGTCATCTGGCTACAAAGATGTGATATTATGGTT

TTCTTTTGGGGCATCTTGCTTCGTGCTGCTGGCTGTCATTATGGGACTTGTATTTTTTTGT

TTGAAGAATGGAAACATGCGCTGCACAATCTGCATC

849
ATGTATAAGATAGTGGTCATAATTGCCCTGCTGGGGGCGGTGAAGGGCCTGGACAAGATTT

GTCTGGGTCATCATGCTGTGGCAAACGGTACGATCGTTAAGACCCTGACGAATGAACAAGA

GGAGGTGACTAACGCTACCGAAACCGTGGAGTCCACCGGCATAAACCGCCTTTGCATGAAG

GGGAGGAAGCACAAGGACCTCGGTAACTGTCACCCAATCGGCATGTTAATTGGCACACCAG

CTTGTGATCTGCACCTGACCGGAATGTGGGATACACTCATTGAAAGAGAAAACGCTATCGC

GTATTGCTACCCTGGAGCAACTGTTAATGTCGAGGCTTTGCGCCAAAAAATAATGGAAAGT

GGCGGTATCAATAAAATCTCAACAGGGTTTACCTACGGGAGCAGTATCAACTCAGCCGGAA

CAACCCGGGCCTGCATGCGCAATGGCGGCAACTCTTTTTACGCTGAACTGAAATGGTTGGT

GTCAAAATCAAAGGGTCAAAACTTTCCTCAAACTACAAATACATATCGGAACACCGATACA

GCTGAGCACTTAATAATGTGGGGGATCCACCACCCTTCTTCAACTCAGGAAAAGAATGATC

TGTATGGCACTCAGTCACTCTCCATTAGCGTAGGGTCATCTACCTATAGAAATAATTTCGT

ACCAGTGGTAGGTGCAAGGCCCCAGGTGAACGGCCAGAGTGGCAGAATAGACTTCCACTGG

ACTCTTGTTCAGCCAGGGGATAACATTACATTCTCGCACAACGGCGGCCTGATAGCCCCAT

CTAGGGTGTCTAAGCTAATTGGCAGAGGTCTGGGCATCCAATCCGACGCACCAATTGACAA

CAATTGCGAAAGTAAGTGTTTCTGGAGAGGAGGGTCAATTAATACAAGATTGCCGTTTCAA

AATCTGTCCCCGAGAACAGTGGGACAGTGCCCAAAATATGTAAATAGACGGTCACTGATGT

TAGCTACCGGCATGCGAAACGTCCCCGAGCTGATTCAGGGTAGAGGCCTGTTCGGAGCTAT

TGCAGGGTTTTTGGAAAATGGGTGGGAGGGCATGGTGGACGGATGGTACGGGTTCCGACAC

CAGAATGCCCAGGGAACCGGCCAGGCGGCTGACTACAAGTCTACACAGGCAGCAATTGACC

AAATCACCGGAAAGTTGAACCGCCTTGTAGAGAAAACAAACACGGAATTTGAATCAATTGA

ATCAGAGTTTTCCGAGATAGAGCACCAGATCGGGAATGTCATAAATTGGACAAAGGATTCT

ATTACGGATATTTGGACCTACCAAGCAGAACTGCTTGTGGCTATGGAAAATCAGCACACCA

TAGATATGGCCGACAGTGAGATGCTGAACCTGTACGAGCGGGTAAGAAAGCAGTTGCGCCA

GAACGCAGAGGAAGACGGGAAAGGCTGCTTCGAAATCTATCACGCCTGTGACGACTCATGC

ATGGAAAGTATCAGGAATAATACATACGATCATTCCCAATACCGTGAGGAAGCACTACTCA

ACCGGCTGAATATCAACCCCGTTACACTCTCCTCAGGTTATAAAGACATAATCCTGTGGTT

CTCCTTCGGCGCTAGCTGCTTTGTCCTGTTGGCCGTAGTAATGGGGCTGTTCTTCTTTTGC

CTTAAAAACGGGAACATGCGATGTACTATCTGCATT

850
ATGTACAAGGTCGTAGTGATTATCGCCCTCCTTGGCGCCGTTAAAGGCCTAGACAAGATCT

GTCTGGGACATCACGCCGTCGCTAATGGCACAATAGTGAAAACGCTCACTAATGAGCAGGA

GGAAGTAACCAACGCCACAGAAACGGTCGAATCCACCGGCATAAATCGGCTTTGCATGAAG

GGGCGTAAACATAAGGACCTGGGGAACTGTCACCCAATAGGGATGCTGATCGGAACACCTG

CTTGTGACCTCCACCTGACAGGCACCTGGGATACGTTGATCGAGCGGGAGAACGCTATCGC

ATACTGCTACCCCGGCGCTACCGTCAATGTGGAAGCACTGCGTCAGAAGATAATGGAATCA

GGAGGCATTGATAAGATCTCAACAGGGTTTACCTACGGCTCTAGTATCAATAGCGCAGGTA

CCACCAGGGCATGCATGCGCAATGGTGGCAACAGTTTCTACGCAGAGCTGAAGTGGCTGGT

GTCTAAAAATAAAGGCCAGAACTTCCCTCAGACCACAAACACTTACCGCAATACAGATACT

GCAGAGCATCTGATTATGTGGGGGATCCACCACCCTTCCTCCATTCAAGAGAAGAACGACC

TGTACGGCACTCAGAGCTTATCAATATCGGTGGGTTCCTCCACTTACCGTAACAATTTCGT

CCCCGTAGTCGGGGCTAGGCCTCAGGTGAATGGTCAGTCAGGGAGGATAGACTTTCACTGG

ACGCTGGTTCAGCCAGGCGACAATATAACCTTCTCACACAACGGGGGTCTGATTGCTCCTT

CTAGGGTGTCAAAGCTGATCGGGAGAGGACTGGGTATACAAAGCGATGCCCCCATCGATAA

TAACTGTGAAAGTAAGTGTTTTTGGCGCGGAGGGAGCATTAACACGCGGCTGCCTTTTCAG

AACCTGTCCCCCCGGACTGTGGGCCAGTGTCCCAAGTACGTGAACCGCAGGTCACTCATGC

TAGCCACGGGTATGAGAAATGTGCCAGAGTTAATTCAGGGCCGCGGTCTGTTTGGGGCTAT

TGCAGGTTTTCTGGAGAACGGGTGGGAGGGCATGGTGGACGGTTGGTACGGCTTTAGGCAT

CAGAACGCACAGGGTACTGGACAGGCAGCCGATTACAAGAGCACTCAGGCAGCGATAGACC

AGATAACTGGCAAGCTCAACCGTTTAGTGGAGAAGACCAACACCGAATTTGAAAGTATTGA

GTCCGAGTTCTCAGAGATTGAGCATCAGATCGGCAATGTCATTAATTGGACAATGGATTCG

ATCACCGATATATGGACCTATCAGGCCGAGTTGCTGGTCGCCATGGAAAATCAACACACTA

TAGATATGGCAGATTCCGAAATGCTGAATCTCTATGAGAGGGTGAGAAAACAACTGAGGCA

AAATGCGGAGGAAGACGGGAAAGGTTGCTTCGAAATTTACCATGCTTGCGATGATAGTTGC

ATGGAGTCCATCCGGAATAACACGTATGATCACAGCCAATACCGGGAAGAAGCCCTGCTTA

ACCGGCTTAACATAAATCCTGTGACTCTCTCATCAGGATATAAGGATATCATCCTCTGGTT

CTCTTTCGGGGCCAGCTGCTTTGTTTTGTTAGCCGTGGTGATGGGACTCGTGTTCTTCTGC

TTAAAAAACGGCAATATGCGTTGCACCATCTGCATC

851
ATGTATAAGATCGTCGTTATTATTGCCCTGCTTGGTGCTGTCAAGGGGTTGGACAAAATTT

GCTTGGGCCACCACGCAGTGGCTAACGGCACTATAGTCAAAACCCTGACGAACGAGCAGGA

GGAGGTGACAAACGCCACTGAGACCGTGGAATCTACGGGAATCAACAGGCTCTGCATGAAG

GGGCGCAAACACAAAGACCTCGGGAACTGCCACCCTATCGGGATGCTCATAGGTACTCCAG

CGTGTGACCTGCACTTAACAGGCACTTGGGATACCCTTATTGAACGGGAAAATGCTATCGC

TTACTGCTACCCGGGCGCGACCGCCAACGTGGAAGCATTACGCCAAAAGATAATGGAATCA

GGCGGCATAGATAAAATCTCCACCGGATTTACATACGGGTCTAGCATAAATTCTGCCGGCA

CCACTAGAGCCTGTATGAGAAACGGCGGAAATTCATTCTACGCTGAGCTGAAATGGCTGGT

CTCAAAGTCTAAGGGGCAGAATTTCCCCCAGACCACGAATACGTACCGGAACACAGATACC

GCCGAGCATCTGATCATGTGGGGAATCCATCACCCCAGTTCAATCCAGGAGAAGAATGACT

TATACGGTACACAATCCCTGTCCATATCAGTAGGTAGCTCTACATATCGGAACAATTTCGT

GCCTGTCGTCGGGGCTAGGCCTCAGGTAAACGGCCAGTCCGGTAGAATCGATTTTCACTGG

ACCCTCGTCCAGCCTGGGGACAATATAACGTTTAGTCACAACGGAGGTCTCATCGCCCCCA

GCCGGGTATCTAAGCTTATTGGCAGGGGCCTGGGTATTCAGAGCGACGCCCCAATTGACAA

TAATTGCGAAAGCAAGTGCTTCTGGAGGGGTGGAAGTATTAACACAAGACTGCCTTTCCAA

AACCTGAGCCCTAGAACTGTGGGACAGTGCCCAAAATACGTCAACAGGAGATCACTTATGC

TGGCGACAGGAATGCGCAATGTACCTGAACTTATTCAAGGGCGAGGACTGTTTGGTGCCAT

AGCTGGGTTCCTGGAAAACGGTTGGGAGGGAATGGTGGACGGCTGGTACGGGTTTAGACAC

CAAAACGCACAAGGAACCGGCCAGGCTGCCGATTATAAGTCCACACAAGCAGCCATCGATC

AAATTACCGGTAAGCTGAATCGGTTAGTTGAAAAAACCAATACCGAGTTTGAATCCATCGA

GAGTGAGTTCTCAGAGATCGAGCACCAGATAGGCAATGTGATCAACTGGACAATGGATTCA

ATTACCGATATCTGGACCTACCAGGCTGAGCTGCTGGTGGCCATGGAAAATCAGCATACAA

TTGATATGGCCGACAGTGAGATGCTGAACTTGTATGAAAGAGTTAGAAAACAGCTGAGGCA

AAATGCCGAAGAGGATGGCAAGGGATGTTTTGAAATCTATCATGCGTGTGATGATAGCTGT

ATGGAATCCATCAGGAACAATACATACGATCACTCACAGTATAGAGAAGAAGCACTCCTGA

ACAGATTAAATATCAATCCAGTGACCTTATCATCTGGCTACAAGGATATAATTCTTTGGTT

TTCGTTTGGGGCTTCCTGCTTCGTGTTGCTGGCCGTGGTCATGGGTCTAGTGTTTTTTTGC

TTGAAAAACGGAAATATGCGGTGTACCATCTGTATC

852
ATGTACAAGATTGTGGTTATAATTGCGCTTCTGGGAGCTGTGAAGGGATTGGACAAGATCT

GCCTTGGGCACCATGCCGTTGCAAATGGTACCATTGTGAAGACGCTGACCAATGAGCAGGA

AGAGGTGACCAATGCTACAGAGACAGTGGAGTCCACTGGCATCAACCGACTCTGTATGAAA

GGTAGAAAACACAAAGATCTCGGCAATTGCCATCCTATAGGTATGCTGATTGGTACGCCTG

CCTGTGACCTCCATCTGACTGGCATGTGGGACACGCTGATCGAAAGGGAGAATGCCATTGC

GTACTGTTATCCTGGCGCTACGGTGAACGTGGAAGCCTTACGGCAGAAGATCATGGAATCC

GGCGGGATCAATAAGATTAGCACCGGATTCACTTACGGATCTTCTATCAACAGCGCTGGCA

CCACTAGGGCATGCATGAGAAACGGGGGGAATAGTTTTTACGCTGAGCTTAAGTGGTTGGT

TTCTAAGAGTAAGGGACAGAACTTCCCTCAGACCACTAATACCTACAGGAACACCGACACC

GCAGAGCATTTAATCATGTGGGGAATCCACCATCCATCCTCCACTCAGGAAAAGAATGACT

TATACGGAACACAGAGCCTTTCCATATCTGTCGGTTCCTCCACATATAGAAATAATTTTGT

GCCCGTGGTCGGTGCACGACCTCAGGTGAATGGCCAGTCAGGAAGAATCGATTTTCACTGG

ACCCTGGTACAGCCTGGCGACAATATCACCTTCAGCCATAACGGCGGTCTGATCGCCCCTA

GTCGGGTGAGTAAATTGATAGGTCGGGGACTGGGAATCCAGAGTGATGCTCCTATTGATAA

TAATTGCGAGTCAAAATGTTTTTGGCGCGGCGGCTCTATTAACACCAGATTACCTTTCCAG

AACCTGAGCCCTCGGACTGTTGGACAGTGTCCTAAATATGTGAATCGCAGGTCTCTGATGC

TGGCTACAGGCATGAGGAACGTGCCTGAGCTCATCCAGGGAAGGGGGCTGTTCGGGGCCAT

CGCTGGATTCCTGGAAAACGGATGGGAGGGAATGGTCGATGGTTGGTACGGTTTTCGGCAT

CAGAATGCTCAAGGGACGGGCCAGGCGGCTGATTATAAGTCAACGCAGGCGGCCATAGACC

AGATCACCGGAAAGCTCAACCGCCTGGTGGAGAAGACAAATACAGAGTTTGAGTCTATAGA

GTCCGAGTTTTCCGAAATCGAACACCAGATCGGGAATGTGATAAACTGGACCAAAGATTCT

ATCACTGACATTTGGACTTACCAGGCAGAACTATTGGTGGCCATGGAAAATCAGCACACCA

TCGACATGGCCGACTCTGAAATGCTGAACTTGTATGAGAGAGTGCGCAAGCAGCTGCGACA

AAATGCCGAAGAAGACGGAAAGGGCTGTTTTGAAATCTATCATGCTTGTGATGACTCTTGC

ATGGAATCTATTAGGAACAATACCTATGATCATTCTCAGTACCGGGAAGAAGCATTGCTGA

ACCGCTTGAATATAAACCCAGTGACGCTGTCATCTGGTTATAAAGACATTATCCTGTGGTT

TAGCTTTGGTGCCTCATGCTTTGTACTCCTAGCCGTAGTCATGGGCCTGTTTTTCTTCTGC

CTGAAGAACGGGAACATGCGATGCACTATTTGCATC

853
ATGTACAAGATCGTGGTGATCATAGCCTTACTGGGGGCCGTAAAAGGTCTGGATAAGATTT

GTCTGGGCCACCACGCTGTCGCCAATGGTACCATTGTGAAGACACTAACCAACGAGCAGGA

GGAGGTCACAAACGCTACCGAGACGGTTGAATCTACTGGTATAAACCGCCTTTGCATGAAG

GGACGCAAACATAAGGATCTGGGGAACTGTCACCCCATTGGTATGCTGATCGGAACCCCTG

CATGTGACCTACACCTGACCGGAATGTGGGATACCTTAATAGAGCGAGAGAACGCGATCGC

CTACTGTTATCCGGGGGCTACGGTGAACGTTGAGGCTCTGAGGCAGAAGATAATGGAAAGT

GGGGGCATCAACAAGATTAGTACCGGATTCACTTATGGTAGTAGCATTAATAGTGCTGGGA

CTACCAGAGCATGTATGAGAAATGGGGGGAACAGCTTCTATGCCGAGCTGAAGTGGCTAGT

GAGCAAGAGCAAGGGCCAAAACTTTCCCCAAACGACCAACACATACCGCAATACCGATACA

GCAGAGCATCTCATAATGTGGGGAATCCACCACCCTAGTTCAACCCAGGAGAAGAACGATC

TTTATGGAACTCAGTCCCTGTCTATCAGCGTGGGGAGTTCTACATATCGCAATAACTTTGT

GCCAGTCGTGGGGGCCCGACCACAGGTAAACGGTCAGTCTGGTCGAATTGACTTTCATTGG

ACCTTGGTCCAGCCGGGCGATAATATCACATTTTCCCATAATGGAGGCCTGATAGCCCCTT

CCAGAGTTAGCAAATTGATAGGCCGAGGACTCGGGATCCAGAGCGATGCACCCATCGACAA

CAACTGCGAGAGCAAATGCTTCTGGCGGGGCGGAAGCATTAACACTAGATTACCCTTCCAG

AACCTTAGTCCTCGCACCGTGGGCCAGTGCCCTAAATATGTGAACCGGCGCTCACTGATGC

TGGCCACAGGCATGAGGAATGTCCCCGAGCTGATCCAGGGCAGAGGACTCTTCGGTGCTAT

CGCAGGATTTCTTGAGAACGGATGGGAAGGAATGGTAGACGGATGGTACGGGTTCCGACAT

CAGAACGCTCAGGGCACTGGCCAAGCAGCCGACTACAAATCCACACAGGCGGCCATCGATC

AGATAACAGGCAAACTGAATCGGCTAGTAGAGAAGACCAACACCGAATTCGAATCAATCGA

GTCTGAATTCAGCGAGATAGAGCACCAAATCGGGAATGTGATTAACTGGACAAAGGATTCC

ATAACCGACATTTGGACCTACCAAGCCGAACTGCTGGTCGCGATGGAAAACCAACATACCA

TCGACATGGCAGACTCCGAAATGCTGAATCTGTACGAACGTGTGCGGAAACAGCTGAGACA

GAATGCTGAAGAAGACGGGAAAGGCTGTTTTGAAATCTACCACGCCTGCGACGACTCATGC

ATGGAAAGCATCAGGAATAACACTTATGACCATTCCCAGTACCGGGAAGAAGCACTCCTGA

ACCGGTTGAACATTAATCCGGTTACCTTGAGCTCTGGATATAAAGACATCATCCTATGGTT

CAGCTTCGGCGCATCCTGCTTTGTTCTGCTTGCAGTGGTCATGGGGCTGTTCTTTTTTTGC

CTGAAGAATGGCAACATGAGATGTACCATTTGCATC

854
ATGTATAAGATAGTAGTCATCATAGCTCTCTTGGGCGCCGTGAAAGGGCTGGACAAGATCT

GTCTGGGTCATCATGCCGTGGCCAACGGAACAATCGTGAAAACCTTGACTAATGAGCAGGA

GGAGGTGACCAATGCGACCGAGACCGTTGAAAGTACGGGCATTAATAGGCTCTGTATGAAG

GGTAGGAAACATAAGGACCTTGGGAACTGTCACCCCATTGGAATGCTGATTGGGACTCCTG

CATGTGACTTACACTTAACAGGCATGTGGGACACTCTGATTGAGAGGGAGAACGCCATTGC

CTATTGTTATCCCGGCGCCACCGTGAACGTGGAGGCACTGCGGCAGAAGATAATGGAAAGC

GGAGGGATTAATAAAATCAGCACCGGATTCACTTATGGTAGTTCTATTAATTCCGCCGGGA

CAACAAGGGCATGTATGAGGAACGGAGGTAATTCCTTCTACGCGGAGCTGAAGTGGCTGGT

CTCTAAGTCCAAGGGGCAGAACTTTCCCCAGACTACAAACACCTACCGAAATACAGATACC

GCTGAGCACCTGATCATGTGGGGAATTCATCACCCTTCATCAACACAAGAGAAGAACGACC

TGTACGGCACACAGTCACTGTCAATCTCAGTAGGGAGCTCGACATATAGAAATAATTTCGT

CCCGGTGGTGGGCGCTCGGCCGCAGGTTAATGGCCAGAGTGGTAGAATCGACTTTCACTGG

ACGCTGGTCCAGCCAGGCGATAATATCACGTTCTCACACAATGGAGGCCTGATAGCCCCAA

GCCGCGTGTCCAAGCTGATAGGGCGAGGACTTGGTATCCAGAGTGATGCCCCCATCGATAA

CAACTGCGAATCCAAGTGTTTCTGGCGTGGCGGCTCAATTAACACCCGGCTTCCATTCCAG

AACCTTAGCCCCCGCACTGTCGGACAATGCCCAAAGTATGTCAACAGGCGGAGCCTGATGC

TGGCCACCGGCATGAGAAATGTGCCTGAGCTCATTCAGGGGCGGGGCCTTTTTGGGGCAAT

CGCTGGCTTTCTCGAGAATGGTTGGGAGGGAATGGTTGACGGCTGGTATGGCTTTAGACAT

CAGAATGCCCAGGGAACGGGCCAGGCTGCTGACTACAAGTCCACCCAGGCCGCCATCGACC

AAATTACCGGGAAGCTGAATAGACTCGTCGAAAAGACCAACACTGAATTTGAGAGTATCGA

GTCTGAGTTTTCCGAGATCGAACATCAAATCGGAAACGTTATCAACTGGACTAAGGACTCA

ATCACCGACATTTGGACATATCAAGCGGAGCTCCTGGTGGCCATGGAAAATCAGCACACGA

TCGACATGGCCGACAGTGAGATGCTGAATCTGTATGAGCGAGTCCGTAAGCAGCTTAGGCA

GAACGCTGAGGAGGATGGAAAAGGATGTTTCGAGATATATCACGCCTGTGATGACTCCTGT

ATGGAATCCATCAGGAACAACACATACGATCATAGTCAGTACAGGGAAGAAGCCTTGCTAA

ATAGGTTGAACATCAACCCTGTCACTCTGAGTTCTGGATACAAGGACATCATATTATGGTT

TTCCTTTGGCGCCTCCTGCTTCGTCCTGCTAGCAGTGGTGATGGGCCTGTTTTTTTTTTGC

CTTAAAAATGGCAATATGCGGTGCACCATTTGCATA

855
ATGTATAAGATCGTTGTCATCATTGCTCTCCTCGGAGCCGTGAAAGGGCTCGATAAGATCT

GTTTAGGACACCATGCCGTGGCAAACGGTACTATAGTCAAGACCCTAACAAATGAGAAAGA

GGAGGTGACGAATGCCACAGAAACAGTAGAATCTACAGGACTGAACCGGCTGTGCATGAAG

GGCCGCAAACACAAGGATTTAGGTAATTGTCACCCAATAGGCATGTTGATTGGAAGTCCGG

CATGTGACCTGCACTTGACGGGCACATGGGATACCCTGATAGAAAGGGAGAACGCTATCGC

CTACTGCTATCCGGGAGCCACGGTCAACGGGGAAGCGCTGCGGCAGAAGATTATGGAGTCG

GGCGGTATAGATAAGATATCCACAGGCTTTACCTATGAATCCTCTATTAACTCAGCTGGTA

CAACTCGCGCTTGCATGAGGAACGGGGGGAACAGTTTCTACGCCGAACTCAAGTGGCTTGT

TTCTAAGTCTAAGGGCCAGAATTTCCCACAGACTACCAATACCTATAGAAACACCGACACG

GCTGAGCACCTTATTATGTGGGGTATTCACCACCCCTCAAGCACTCAGGAGAAGAACGACC

TCTATGGTACCCAGTCCCTTTCCATCTCCGTTGGTAGTTCTACCTACCGCAACAATTTTGT

TCCCGTGGTCGGTGCAAGACCACAGGTTAACGGCCAGAGTGGGCGCATCGATTTCCACTGG

ACGTTGGTCCAGCCTGGGGATAACATCACCTTTTCCCACAACGGGGGATTAATCGCACCCT

CTCGGGTCTCTAAGCTGATCGGACGAGGACTGGGAATCCAAAGTGACGCACCAATAGATAA

TAATTGCGAGAGCAAATGCTTCTGGCGCGGTGGGTCAATCAATACACGGCTGCCGTTTCAG

AATCTATCACCAAGGACTGTGGGACAGTGCCCCAAATATGTAAATAAGCGGTCCCTGATGC

TCGCCACTGGTATGCGGAACGTGCCTGAGCTAATGCAAGGAAGGGGCCTGTTTGGGGCCAT

TGCCGGCTTTCTCGAAAACGGGTGGGAGGGCATGGTGGACGGATGGTACGGTTTCCGGCAC

CAGAATGCTCAAGGCACCGGTCAGGCTGCCGATTATAAAAGCACCCAAGCCGCTATCGATC

AGATCACTGGCAAGTTAAACAGGCTGGTAGAAAAAACTAATACTGAATTCGAGTCCATTGA

GTCCGAGTTCTCTGAGATTGAGCATCAGATCGGGAATGTTATTAACTGGACGAAAGACAGT

ATTACGGATATCTGGACATATCAAGCCGAGCTCCTGGTCGCTATGGAAAACCAACACACTA

TCGACATGGCCGACAGCGAAATGTTGAATCTTTATGAAAGAGTGAGGAAGCAGCTGCGTCA

GAACGCAGAGGAGGATGGGAAAGGATGTTTTGAGATCTACCACGCCTGTGACGATTCCTGC

ATGGAGAGTATTAGAAACAACACATACGACCACAGCCAGTACCGGGAAGAGGCCCTATTGA

ACAGGCTTAATATTAATCCAGTAACCCTGTCGAGTGGGTATAAAGATATTATACTGTGGTT

CTCCTTTGGCGCTTCTTGCTTTGTGCTGCTCGCGGTAGTTATGGGTTTGGTGTTTTTTTGC

CTCAAGAACGGAAATATGCGTTGCACCATCTGTATC

856
ATGTATAAGATCGTGGTCATCATCGCCCTGCTTGGAGCTGTAAAAGGTCTCGACAAGATTT

GTCTTGGACATCATGCTGTGGCAAATGGCACCATTGTAAAGACCCTGACTAATGAGCAAGA

AGAAGTAACCAACGCAACTGAGACCGTAGAGTCAACCGGCATTAATCGGCTCTGCATGAAG

GGAAGGAAGCACAAAGATCTCGGCAATTGTCACCCAATAGGCATGTTGATTGGAACCCCTG

CTTGTGACCTGCATCTCACGGGGATGTGGGATACTTTGATTGAAAGGGAAAACGCAATTGC

GTATTGTTACCCGGGAGCCACCGTGAACGTCGAGGCCCTCCGACAAAAGATCATGGAATCA

GGAGGGATCAACAAAATAAGCACTGGGTTTACCTATGGAAGTTCGATCAACTCAGCCGGGA

CAACGCGCGCTTGCATGAGGAATGGCGGAAATTCCTTCTACGCTGAACTCAAATGGCTCGT

GTCGAAATCAAAGGGTCAGAACTTCCCACAGACTACTAATACCTACAGAAATACTGACACA

GCGGAGCATTTGATCATGTGGGGCATACACCACCCTTCTTCCACACAGGAGAAGAATGACC

TTTACGGCACGCAGAGTCTGTCCATCAGCGTAGGAAGCTCAACCTACAGAAATAATTTCGT

TCCCGTGGTGGGGGCTCGACCACAGGTTAACGGGCAGTCCGGTCGTATTGATTTTCATTGG

ACATTGGTGCAGCCCGGCGATAACATTACTTTTAGCCACAACGGAGGCCTAATTGCCCCTA

GCAGAGTCTCCAAACTGATCGGGAGGGGACTGGGGATACAGTCAGATGCCCCTATCGACAA

CAATTGTGAGAGCAAGTGTTTCTGGCGAGGCGGAAGCATTAACACCCGGTTACCCTTTCAG

AACCTATCTCCAAGAACTGTGGGTCAGTGCCCAAAATACGTGAACAGACGGTCTCTGATGT

TGGCTACTGGTATGCGCAACGTTCCGGAACTAATTCAAGGCAGAGGACTGTTCGGCGCCAT

CGCAGGGTTCCTCGAGAACGGGTGGGAGGGGATGGTCGATGGGTGGTACGGCTTTAGGCAT

CAGAACGCTCAGGGGACTGGTCAGGCCGCCGATTACAAAAGCACGCAAGCTGCTATAGATC

AGATCACAGGGAAACTGAATCGCCTCGTTGAGAAAACTAACACCGAATTTGAATCAATAGA

ATCCGAATTCAGTGAAATCGAGCACCAGATAGGGAACGTAATCAACTGGACCAAAGACAGT

ATTACAGACATCTGGACATACCAGGCGGAACTTTTAGTCGCTATGGAGAATCAGCACACAA

TAGACATGGCCGACAGCGAAATGTTGAACCTGTACGAACGAGTAAGGAAGCAGCTGAGGCA

AAACGCAGAAGAGGACGGAAAGGGCTGCTTTGAGATATACCACGCATGTGATGATAGCTGT

ATGGAGTCAATTCGGAACAATACATATGATCACTCTCAATACCGTGAGGAAGCTCTGCTCA

ATCGTCTGAATATTAACCCAGTGACTCTTTCCAGTGGGTACAAAGACATCATTCTTTGGTT

TTCCTTCGGAGCTTCCTGCTTTGTGCTGCTGGCAGTCGTTATGGGATTGTTCTTTTTCTGC

CTGAAGAACGGGAACATGCGCTGTACTATATGTATC

857
ATGTACAAGGTAGTGGTAATAATTGCTCTGCTGGGAGCCGTGAGAGGTCTGGATAAAATCT

GTTTGGGTCACCACGCCGTCGCCAACGGGACGATCGTCAAAACACTAACAAATGAGCAAGA

AGAAGTGACCAACGCAACAGAGACAGTGGAGAGTAAGAGCCTGGGAAAGCTTTGCATGAAG

GGCCGCTCATATAACGACCTGGGCAACTGTCACCCCATCGGTATTCTGATTGGGACTCCAG

CTTGCGACTTGCATCTGACCGGCACCTGGGACACACTCATCGAGAGAGAAAACGCAGTGGC

TTACTGCTACCCTGGCGCTACCGTCAATGAAGAAGCCCTGCGACAGAAGATTATGGAGAGC

GGTGGGATCAGCAAAATCTCCACCGGTTTCACCTATGGAACCTCCATTAACAGCGCAGGCA

CAACAAAAGCTTGCATGAGGAATGGGGGCAACTCGTTCTATGCTGAACTGAAATGGCTGGT

GTCCAAAAATAAGGGTCAGAATTTCCCTCAGACTACCAACACTTACAGGAACACGGATACA

GCAGAGCACCTGATTATATGGGGGATTCACCACCCTTCGTCTACCCAAGAGAAAAATGACC

TGTACGGAACTCAGAGCCTTTCAATATCCGTGGGGTCCAGTACATATCAAAATAATTTTGT

CCCCGTGGTTGGCGCCCGTCCACAGGTTAACGGTCAGTCAGGGCGGATCGATTTTCATTGG

ACCTTACTTCAGCCCGGAGACAATATCACTTTTTCTCACAACGGAGGACTCATCGCCCCCT

CCCGTGTGTCCAAGCTCATAGGACGGGGCCTGGGTATCCAGAGCGAGGCCCCCATCGATAA

CGGCTGCGAGAGCAAATGTTTTTGGAAGGGAGGGAGTATAAACACTAAGCTCCCATTCCAA

AATTTAAGTCCACGTACTGTGGGCCAGTGTCCCAAGTATGTGAACAAAAGAAGCTTGATGC

TGGCAACTGGGATGCGGAACGTGCCTGAGATCATGCACGGTCGGGGCCTGTTTGGCGCTAT

CGCAGGGTTTATTGAAAATGGCTGGGAGGGCATGGTTGATGGGTGGTACGGGTTTAGGCAT

CAGAATGCCCAGGGCACTGGTCAGGCGGCCGATTACAAGAGTACTCAGGCTGCCATCGACC

AGATCACCGGCAAGCTGAACCGGTTGATCGAAAAGACAAACACTGAATTCGAGAGTATCGA

AAGCGAATTTTCTGAGATCGAGCACCAAATCGGGAATATAATTAATTGGACAAAGGACTCG

ATCACTGACATATGGACATACCAAGCCGAGCTGCTGGTGGCCATGGAAAACCAGCATACCA

TAGACATGGCCGATTCAGAAATGCTTAATCTTTACGAGCGTGTTAGGAAGCAACTGAGGCA

GAATGCCGAAGAGGACGGTAAGGGGTGCTTTGAGATTTATCACGCATGTGACGACAGCTGT

ATGGAGTCCATTAGAAATAATACCTACGATCACAGTCAGTATAGAGAAGAGGCATTGCTTA

ATAGGCTGAACATAAATCCCGTCAAGCTGTCTTCGGGGTACAAGGACATTATCCTGTGGTT

CAGCTTTGGCGCATCGTGTCTGATATTACTGGCCGTCGTGATGGGATTAGTGTTTTTCTGC

TTAAAGAACGGTAACATGCGCTGTACTATCTGTATC

858
ATGTACAAGATCGTGGTCATTATCGCTCTGTTAGGGGCAGTAAAAGGCCTGGACAAAATCT

GCCTTGGCCATCATGCTGTGGCTAATGGTACAATTGTCAAAACCCTCACAAATGAACAGGA

GGAGGTGACAAACGCCACAGAAACTGTGGAGAGTACAGGGATCAACCGTCTCTGCATGAAG

GGAAGAAAGCATAAAGACCTTGGAAACTGTCATCCCATAGGCATGCTGATCGGCACTCCCG

CCTGTGACCTGCACCTGACCGGTATGTGGGACACCCTGATCGAAAGGGAGAATGCCATTGC

CTACTGTTATCCTGGCGCAACAGTGAACGTAGAAGCCTTAAGACAGAAGATCATGGAATCC

GGAGGCATAAACAAAATTAGTACTGGATTCACCTACGGGAGCTCCATTAACTCTGCAGGCA

CCACTCGGGCATGCATGCGCAACGGCGGTAACAGCTTCTATGCCGAGCTGAAGTGGTTAGT

GTCCAAGTCGAAAGGCCAGAACTTTCCCCAGACGACAAACACATATCGGAACACCGATACT

GCAGAACACCTGATCATGTGGGGGATTCACCACCCCAGTTCCACCCAGGAGAAGAACGATC

TGTACGGTACTCAGAGCCTGTCCATAAGTGTTGGATCCTCTACATATCGGAATAATTTCGT

GCCCGTGGTGGGCGCAAGACCACAGGTGAACGGCCAGTCTGGGAGAATTGACTTTCATTGG

ACTCTGGTGCAACCAGGGGACAATATTACCTTCTCACATAATGGCGGCCTGATCGCACCTA

GCAGGGTGTCCAAGCTGATAGGACGCGGACTCGGAATTCAGTCGGATGCACCTATCGATAA

TAACTGCGAGTCTAAGTGTTTTTGGAGAGGCGGTTCAATCAATACTAGGCTTCCTTTTCAG

AACCTGAGCCCCAGAACAGTGGGGCAATGCCCTAAATATGTGAATAGGCGGTCTCTGATGC

TGGCCACTGGGATGAGAAATGTGCCAGAGCTGATTCAGGGTAGAGGCCTGTTCGGCGCAAT

CGCAGGGTTCCTCGAAAACGGCTGGGAAGGTATGGTGGACGGATGGTACGGGTTCCGACAC

CAAAACGCCCAGGGGACGGGCCAGGCCGCCGATTACAAATCAACTCAAGCCGCGATAGATC

AGATAACCGGAAAGCTGAACAGACTCGTCGAGAAGACCAATACCGAGTTTGAGTCCATCGA

AAGCGAGTTCTCAGAGATTGAGCATCAGATAGGGAACGTAATTAACTGGACGAAAGATAGC

ATCACGGACATCTGGACATATCAGGCGGAACTACTGGTGGCAATGGAAAATCAGCATACCA

TCGACATGGCCGACAGTGAGATGTTAAATCTCTATGAGCGGGTGCGGAAACAGCTGAGGCA

AAACGCTGAAGAAGACGGAAAAGGGTGCTTTGAGATCTACCATGCCTGCGACGATAGCTGC

ATGGAGTCAATTCGGAACAATACTTATGACCACTCCCAGTATCGGGAGGAGGCCCTGCTCA

ATCGACTGAACATAAACCCAGTGACTCTGAGTTCCGGATACAAAGATATTATTCTTTGGTT

CAGCTTCGGAGCTTCTTGTTTTGTCCTCCTAGCAGTGGTAATGGGCCTCTTTTTCTTTTGC

CTGAAGAACGGAAACATGAGGTGCACAATTTGTATT

859
ATGTACAAAATAGTGGTGATAATCGCCCTTCTCGGCGCAGTGAAAGGGCTCGACAAGATAT

GTCTGGGACATCACGCTGTGGCTAATGGCACTATCGTGAAGACGCTCACAAATGAACAGGA

GGAGGTTACAAATGCCACTGAGACAGTTGAAAGCACAGGAATCAATAGATTGTGTATGAAA

GGCAGAAAGCATAAGGACTTGGGGAACTGTCACCCTATTGGCATGCTTATCGGCACCCCTG

CTTGTGATCTACATTTGACAGGCATGTGGGACACCCTTATTGAGCGCGAAAACGCAATCGC

GTACTGTTATCCTGGTGCTACTGTGAACGTAGAAGCTCTGAGGCAGAAGATAATGGAATCT

GGCGGGATAAATAAAATCTCAACCGGCTTCACATACGGGAGTAGCATTAATAGCGCCGGTA

CTACCCGGGCCTGTATGAGGAATGGAGGAAACTCTTTTTACGCAGAGCTCAAGTGGCTAGT

ATCTAAGTCCAAGGGACAGAATTTTCCCCAGACTACTAATACTTACCGCAATACGGATACC

GCAGAACACTTAATTATGTGGGGCATACATCACCCATCCTCTACCCAAGAAAAGAACGACC

TTTACGGCACACAGTCCTTGAGTATATCTGTGGGGAGTAGCACCTATAGGAACAATTTCGT

TCCGGTCGTGGGCGCTCGCCCCCAGGTGAACGGCCAATCAGGACGGATCGACTTCCACTGG

ACCCTGGTCCAGCCCGGCGATAACATCACATTTTCCCATAACGGAGGACTTATAGCACCCT

CCCGGGTGTCTAAACTTATTGGACGGGGGCTGGGAATCCAGTCCGACGCCCCCATCGATAA

CAACTGTGAGTCTAAATGTTTTTGGCGCGGCGGATCTATCAACACCAGGCTTCCCTTCCAG

AATCTGTCCCCCCGGACAGTGGGCCAGTGCCCAAAGTACGTTAACAGAAGGTCTTTAATGC

TCGCCACCGGCATGCGAAACGTGCCTGAACTGATCCAGGGAAGAGGACTTTTCGGAGCCAT

CGCCGGCTTTTTAGAGAACGGATGGGAAGGGATGGTAGACGGGTGGTATGGATTCAGGCAC

CAAAACGCTCAGGGGACCGGGCAAGCAGCAGACTACAAAAGTACACAAGCCGCTATCGACC

AAATCACGGGTAAACTGAACCGGCTTGTGGAAAAGACAAACACCGAATTTGAATCGATAGA

GAGCGAATTCAGCGAGATCGAGCACCAAATAGGAAATGTGATCAACTGGACAAAGGATTCG

ATCACAGACATCTGGACGTACCAAGCCGAGCTCCTCGTAGCAATGGAGAACCAGCATACCA

TCGACATGGCCGATTCCGAGATGCTTAATCTTTATGAACGGGTCCGCAAACAGCTGCGCCA

AAATGCCGAAGAAGATGGTAAAGGATGTTTTGAAATCTATCATGCTTGTGATGATTCCTGT

ATGGAGTCAATCCGGAATAATACATACGACCACAGCCAGTACCGGGAAGAAGCCCTGCTGA

ATCGCTTAAATATCAACCCCGTTACCCTTTCCTCTGGATATAAGGATATTATCCTGTGGTT

TTCATTTGGGGCATCCTGTTTCGTCCTTCTGGCAGTGGTCATGGGACTTTTTTTTTTCTGT

CTGAAGAACGGAAACATGCGGTGTACGATCTGTATA

860
ATGTATAAAGTCGTGGTTATCATCGCCCTTCTGGGAGCCGTCAGAGGCCTGGACAAGATAT

GTTTGGGGCATCATGCGGTAGCTAATGGAACCACTGTCAAAACACTTACTAATGAACAGGA

AGAGGTTACGAACGCCACCGAAACAGTGGAATCTACCAGCCTGAATAAATTATGCATGAAG

GGACGACGCTACAAGGATCTGGGGAATTGCCACCCCATCGGAATGCTGATTGGAACACCAG

TCTGTGACCTCCACCTTACAGGGACGTGGGATACCTTGATTGAGCGGGAGAATGCAACAGC

TTACTGTTATCCCGGAGTAACTATTAATGAGGAGGCTCTCCGTCAAAAGATAATGGAGTCA

GGAGGTATTAGTAAAATGCGCACTGGCTTTACATACGGGCCCTCTATAAACAGCGCAGGAA

CCACTCGTTCATGTATGCGCAATGGGGGCAACTCGTTCTACGCCGAGCTGAAGTGGCTGGT

GAGTGGCACCAAAGGTCAGAATTTTCCCCAGACTACAAACACCTACCGGAACACAGACACT

GCCGAGCATCTGATCATCTGGGGGATACATCACCCTTCCTCTACTCAAGAAAAGAACGATC

TGTATGGCACACAAAGCCTGTCTATATCCGTGGGTTCTTCTACCTATCAAAACAACTTTGT

TCCAGTTATAGGCGCCCGGCCCCAGGTGAACGGGCAGTCAGGCCGCATCGAGTTTCACTGG

ACTCTGGTCCGGCCCGGAGATAATATTACATTCAGTCATAACGGCGGTTTGATCGCCCCAG

ACCGAGTGAGCAAGCTCATCGGGAAGGGGATTGGCATACAATCCGGTGCTGTGATTGACAA

GGATTGCGAGAGTAAGTGCTTTTGGCGAGGCGGATCTATTATTACCGAGCTGCCATTTCAG

AACCTTTCTCCTCGAACCGTTGGGCAGTGCCCCAAATATGTGAAAAAGAGGTCACTGCTCC

TCGCCACTGGCATGCGAAATGTTCCTGAGGTGGTGCAGGGCCGTGGGTTGTTCGGTGCCAT

CGCAGGGTTCATCGAGAATGGATGGGAAGGTATGGTCGACGGATGGTACGGATTCCGCCAT

CAGAATGCACAGGGTATCGGACAGGCCGCCGATTATAAGAGCACCCAGACGGCTATAGACC

AAATCACCGGCAAGCTTAACCGGCTCATAGAAAAGACCAACACAGAATTTGAGTCCATCGA

GTCAGAATTCAGCGAAATTGAACATCAGATTGGCAACGTCATCAATTGGACCAAGGACTCC

ATCACTGATATCTGGACATACCAGGCAGAACTTTTGGTTGCTATGGAGAACCAACACACCA

TAGATATGGCCGATTCCGAGATGTTGAATCTGTACGAGAGGGTCCGTAAGCAGCTGAGGCA

GAACGCTGAGGAGGACGGGAAGGGGTGCTTTGAGATCTACCACACCTGTGACAATAGCTGC

ATGGAGTCGATCCGGAATAACACTTATGACCATAGTCAATACAGAGAGGAAGCCCTGCTCA

ATCGTTTAAATATTAATCCAGTAAAGTTATCTTCAGGGTACAAGGATATTATTCTCTGGTT

CTCTTTTGGGGCTAGCTGTTTTGTGCTCCTGGCCGTTATAATGGGACTCGGGTTCTTCTGC

CTAAAAAATGGCAACATGCGCTGTACCATTTGCATT

861
ATGTACAAGATTATCGTGATCATCGCACTGCTGGGCGCCGTTAAAGGGCTGGACAAAATAT

GCTTGGGACACCACGCCGTAGCTAATGGAACAATCGTCAAAACCCTGACTAATGAGCAAGA

GGAGGTCACAAATGCAACGGAAACAGTCGAATCCACTGGCATTAATAGGTTGTGCATGAAG

GGCCGAAAGCACAAAGATCTCGGAAATTGTCATCCCATCGGGATGCTGATTGGCACCCCTG

CCTGTGATTTGCACTTAACAGGGACTTGGGACACTCTGATAGAGCGTGAAAACGCAATTGC

ATATTGCTACCCAGGGGCAACGGTCAACGTGGAGGCTCTCCGACAGAAAATTATGGAAAGC

GGAGGGATCGATAAGATTTCGACAGGCTTCACGTACGGCTCCTCAATCAACTCTGCCGGTA

CGACGCGCGCGTGTATGCGGAATGGAGGGAACAGCTTTTACGCAGAACTGAAGTGGCTCGT

AAGCAAAAGTAAAGGGCAAAATTTCCCTCAGACTACAAATACCTACCGCAACACAGACACA

GCGGAGCACCTGATTATGTGGGGAATTCACCATCCCTCAAGTACCCAGGAGAAGAACGACT

TATATGGCACGCAGAGTCTTTCCATTTCTGTGGGGTCTAGCACCTATAGGAACAATTTCGT

CCCAGTTGTCGGCGCTAGGCCTCAGGTGAATGGACAAAGCGGCCGCATAGATTTCCACTGG

ACCCTGGTCCAGCCCGGCGATAATATCACATTTTCTCACAACGGAGGACTGATTGCTCCTA

GCAGAGTATCAAAACTGATTGGGAGAGGCCTTGGCATTCAGTCTGACGCCCCCATTGACAA

TAATTGTGAGTCTAAGTGTTTTTGGGGGGGAGGAAGCATCAATACCAGACTTCCCTTTCAA

AACCTGAGTCCGCGAACTGTCGGACAGTGCCCCAAATACGTTAATAGGCGCTCCCTAATGC

TTGCTACAGGTATGAGGAATGTACCAGAGTTAATTCAGGGGCGCGGCCTTTTTGGCGCCAT

CGCCGGCTTCCTGGAGAACGGCTGGGAGGGCATGGTGGATGGGTGGTATGGCTTCCGCCAT

CAGAACGCACAGGGGACGGGCCAGGCTGCAGATTATAAGTCAACCCAGGCTGCAATAGACC

AAATTACTGGGAAGCTGAATAGGCTAGTGGAGAAGACCAACACTGAGTTTGAATCAATTGA

GAGCGAATTTAGTGAGATCGAGCACCAGATCGGTAACGTGATTAACTGGACGAAAGATTCA

ATTACTGACATTTGGACATATCAGGCTGAGTTGCTGGTGGCGATGGAGAACCAGCACACCA

TAGATATGGCGGATAGCGAGATGCTTAATCTGTACGAACGGGTGCGCAAGCAGCTCCGCCA

GAACGCTGAAGAAGATGGCAAGGGGTGCTTTGAGATTTACCACGCTTGCGATGATTCATGC

ATGGAGTCCATTCGGAATAATACATACGACCACAGTCAGTACAGGGAAGAAGCCCTACTGA

ACCGGTTGAACATTAACCCTGTGACCCTCAGTTCAGGGTACAAAGACATAATACTTTGGTT

CTCCTTCGGGGCCTCATGTTTCGTGCTGCTGGCAGTCGTTATGGGCCTATTCTTCTTCTGC

TTGAAGAATGGAAATATGCGTTGCACCATCTGCATC

862
ATGTACAAAATCGTCGTCATCATTGCACTTCTGGGAGCCGTGAAGGGGCTGGATAAGATCT

GCCTCGGCCATCATGCCGTCGTGAACGGTACCATAGTGAAGACATTGACGAACGAGCAAGA

GGAAGTCACGAACGCCACCGAGACGGTGGAATCCACGGGACTGAATCGTTTGTGCATGAAA

GGCAGGAACCATAAGGATCTGGGAAATTGCCATCCCATAGGCATGCTTATTGGCACGCCAG

CCTGTGACCTACACTTAACCGGCACTTGGGACACTTTGATCGAGCGCGAGAATGCCATCGC

CTACTGTTATCCAGGAGCCACCGTAAACGAAGAGGCTCTGAGACAGAAGATCATGGAGAGT

GGCGGTATAAACAAAATCAGCACCGGCTTCACCTACGGGAGCTCTATCAACTCAGCCGGTA

CTACTAGAGCTTGCATGCGCAACGGCGGAAACTCCTTCTACGCAGAACTTAAGTGGCTCGT

CAGCAAGAGCAAGGGCCAGAACTTTCCTCAGACAACCAACACCTACCGGAATACCGATACT

GCCGAGCACTTGATAATGTGGGGCATCCACCACCCTTCCTCTACTCAGGAAAAGAACGATC

TGTATGGTACCCAGTCTCTGTCCATATCAGTGGGTTCTTCAACATACCAGAACAATTTCGT

CCCTGTGGTAGGAGCAAGGCCCCAGGTAAATGGCCAGAGCGGCCGCATCGACTTTCATTGG

ACTCTGGTGCAGCCAGGGGACAATATTACCTTCAGTCACAACGGCGGCCTGATCGCACCAT

CCAGAGTGTCTAAACTGATAGGCCGAGGATTGGGAATTCAGTCAGACGCACCCATAGATAA

CAATTGCGAATCGAAGTGTTTCTGGCGCGGCGGCTCAATAAACACCCGACTTCCATTCCAA

AACCTCTCTCCCAGAACTGTGGGGCAGTGCCCCAAATACGTGAATAAGAGGTCGCTCATGT

TAGCCACTGGTATGCGAAACGTCCCGGAACTGATGCAGGGACGAGGCCTTTTTGGGGCTAT

AGCAGGCTTCATCGAGAATGGATGGGAAGGCATGGTTGATGGGTGGTATGGCTTCCGCCAT

CAGAATGCTCAGGGGACAGGGCAAGCGGCCGATTACAAATCAACCCAGGCCGCTATAGATC

AAATCACTGGCAAGCTGAATCGCCTCATCGAAAAAACAAATACGGAGTTCGAGTCCATTGA

AAGCGAGTTTTCCGAGATTGAACACCAAATTGGCAACGTCATAAACTGGACTAAGGACTCT

ATTACCGACATATGGACTTACCAGGCAGAGCTTCTGGTCGCTATGGAGAACCAGCACACCA

TCGATATGGCCGATTCCGAAATGTTAAACCTCTACGAAAGAGTGCGCAAGCAGCTCAGACA

GAACGCCGAAGAAGATGGCAAAGGGTGCTTTGAAATCTACCATGCCTGCGACGATAGTTGT

ATGGAGTCGATCCGCAATAACACTTACGATCACAGTCAATATCGGGAGGAGGCACTGTTAA

ACAGGCTGAACATTAACCCGGTAACCCTCTCTAGTGGTTACAAAGACATCATACTTTGGTT

TTCGTTTGGGGCATCTTGTTTTGTGCTCTTGGCCGTAGTGATGGGACTTGTTTTCTTTTGT

CTCAAGAACGGCAATATGCGGTGTACTATTTGCATC

863
ATGTATAAAATCGTCGTGATCATCGCCCTGETAGGTGCGGTCAAGGGCTTGGACAAGATTT

GTCTGGGACATCACGCAGTCGCCAACGGAACCATCGTTAAAACGCTGACTAACGAGCAGGA

AAAAGTTACTAATGCCACAGAGACCGTTGAGTCAACCGGCCTCAATAGGCTTTGCATGAAA

GGACGGAAGCATAAAGACCTGGGCAACTGCCATCCTATTGGGATGTTAATCGGTACCCCCG

CATGCGACCTGCATCTGACTGGAACCTGGGACACCATTATTGAGCGCGAAAATGCCATCGC

ATATTGTTACCCCGGAGCTACTGTGAATGAAGAGGCCCTGAGGCAGAAGATCATGGAGTCC

GGTGGAATTGACAAGATCTCCACTGGATTTACCTACGGGAGTTCTATCAATAGTGCAGGTA

CCACAAGAGCCTGTATGAGAAATGGGGGCAACAGCTTTTACGCCGAATTAAAATGGCTGGT

GAGCAAGAGTAAGGGACAAAATTTTCCTCAGACTACAAACACCTACAGAAATACAGATACG

GCTGAGCACCTTATCATGTGGGGCATCCACCATCCGTCATCCACCCAAGAGAAGAATGATC

TTTACGGAACCCAGAGCTTGAGCATCTCCGTGGGTTCATCCACCTACCGGAACAACTTCGT

GCCAGTGGTGGGGGCTAGGCCACAGGTGAACGGCCAGTCAGGCCGCATCGACTTCCACTGG

ACACTCGTGCAGCCTGGAGATAACATCACTTTCTCCCACAATGGAGGACTGATAGCCCCAT

CTCGCGTTAGCAAGCTGATTGGCCGGGGTCTCGGAATTCAATCTGACGCCCCCATAGACAA

TAACTGTGAAAGCAAGTGCTTCTGGCGTGGGGGGTCCATTAATACCCGTCTACCTTTTCAG

AATCTGTCCCCCCGCACCGTCGGACAATGCCCTAAGTACGTGAATAAAAGGTCCCTTATGC

TAGCTACGGGGATGCGGAATGTTCCGGAGCTAATCCAGGGGCGCGGGCTGTTCGGAGCCAT

CGCAGGTTTTCTCGAGAATGGCTGGGAGGGAATGGTGGACGGTTGGTACGGATTCCGCCAC

CAGAATGCCCAAGGCACAGGACAGGCAGCTGACTACAAATCAACGCAAGCTGCCATCGACC

AGATAACAGGAAAACTGAACAGACTCGTCGAGAAGACCAATACAGAGTTCGAATCCATCGA

GTCTGAATTTAGCGAAATCGAGCACCAGATCGGAAACGTTATCAACTGGACAAAAGACTCC

ATCACCGATATCTGGACTTACCAGGCTGAACTTCTTGTTGCCATGGAGAATCAGCATACTA

TTGATATGGCCGACTCAGAGATGCTCAACCTCTATGAACGGGTCCGGAAACAATTACGACA

GAACGCGGAGGAGGACGGCAAAGGTTGCTTTGAGATATATCACGCGTGCGACGATTCGTGC

ATGGAATCTATCCGCAATAATACTTACGACCACTCTCAGTACCGGGAGGAAGCACTCCTGA

ATCGGTTGAACATCAACCCCGTGACACTTTCTTCCGGCTATAAGGATATAATCCTGTGGTT

TTCCTTTGGAGCATCCTGTTTTGTACTCCTCGCCGTAGTGATGGGGCTGGTCTTTTTCTGC

CTTAAGAACGGGAACATGAGGTGTACTATATGTATT

864
ATGTACAAGGTGGTGGTCATAATCGCCTTGCTAGGCGCCGTGAGAGGGCTCGACAAAATTT

GCTTGGGGCATCATGCAGTCGCTAATGGAACCATCGTGAAAACACTCACCAACGAGCAAGA

AGAGGTTACTAACGCCACCGAGACCGTAGAGAGTAAATCCCTGGGGAAGCTGTGTATGAAG

GGCCGGTCTTATAATGATCTGGGCAATTGCCATCCCATCGGAATTCTGATCGGGACCCCTG

CATGTGATCTGCATCTAACTGGGACGTGGGATACTCTGATCGAGCGCGAGAACGCAGTTGC

TTACTGTTATCCGGGCGCCACCGTGAACGAGGAGGCACTCCGACAGAAAATTATGGAATCG

GGTGGAATTAGCAAGATATCTACTGGGTTCACCTATGGCACTAGCATCAACTCCGCTGGGA

CAACCAAAGCGTGTATGAGAAACGGGGGGAATTCTTTCTACGCCGAACTGAAATGGCTGGT

GTCCAAAAATAAAGGGCAGAATTTTCCTCAGACCACCAACACATACCGGAACACCGACACC

GCCGAGCACCTGATCATCTGGGGCATTCATCACCCGAGCTCGACTCAAGAGAAGAACGATC

TCTACGGGACTCAGTCGCTGAGTATCAGCGTGGGAAGCAGTACTTACCAGAACAATTTTGT

ACCCGTGGTGGGAGCCCGGCCTCAAGTCAACGGCCAGTCCGGCAGGATTGACTTCCACTGG

ACCTTACTGCAGCCAGGGGACAACATCACCTTTTCACACAATGGTGGACTCATCGCACCCT

CCAGAGTTAGCAAACTGATTGGAAGAGGGCTTGGTATTCAGTCGGAAGCCCCTATTGATAA

TGGTTGTGAGAGTAAGTGCTTCTGGAAAGGAGGCAGCATAAATACCAAACTCCCCTTCCAG

AACCTCTCTCCCAGAACCGTCGGCCAGTGCCCTAAGTACGTGAATAAACGCTCGTTGATGC

TCGCGACAGGAATGAGGAACGTGCCTGAAATTATGCATGGTCGCGGACTGTTCGGAGCTAT

CGCCGGGTTCATCGAGAATGGCTGGGAAGGGATGGTGGACGGTTGGTACGGGTTTCGACAC

CAGAACGCACAGGGCACTGGCCAGGCAGCAGATTATAAGTCCACTCAGGCCGCAATCGACC

AGATTACCGGCAAATTAAATAGATTGATCGAGAAAACGAATACTGAGTTCGAGAGCATCGA

ATCGGAGTTCTCTGAAATCGAGCATCAGATTGGAAACATTATAAATTGGACCAAGGACAGC

ATTACAGATATTTGGACGTATCAGGCAGAGCTGCTGGTGGCCATGGAAAACCAGCATACGA

TCGACATGGCCGATTCCGAAATGCTCAACCTGTATGAAAGGGTGAGGAAACAGCTGAGACA

AAACGCAGAAGAAGACGGCAAAGGTTGCTTCGAAATTTACCACGCTTGCGACGATTCATGC

ATGGAGAGCATTCGGAATAATACCTATGATCATAGCCAGTACAGAGAGGAGGCCCTGCTAA

ATAGACTGAATATAAATCCCGTAAAACTGAGCTCTGGCTATAAGGACATTATTCTGTGGTT

TAGTTTCGGAGCATCCTGCCTCATCCTCCTGGCAGTGGTCATGGGCCTCGTGTTCTTTTGT

CTGAAGAACGGAAATATGCGATGTACTATTTGTATC

865
ATGTACAAAATAGTCGTGATCATCGCACTGCTGGGGGCCGTGAAAGGTCTCGATAAGATTT

GCCTTGGACACCATGCCGTGGCTAACGGGACTATTGTGAAGACACTTACCAATGAGCAGGA

GGAAGTTACCAACGCTACAGAAACTGTCGAGTCGACTGGTATTAATAGGCTGTGTATGAAG

GGACGTAAGCATAAAGACCTCGGGAATTGCCACCCTATAGGCATGCTGATAGGCACCCCAG

CATGTGACCTGCACCTCACAGGCATGTGGGACACATTAATCGAAAGGGAGAATGCCATAGC

CTATTGCTACCCAGGTGCAACAGTTAATGTTGAAGCATTGCGGCAGAAAATCATGGAGTCC

GGCGGCATTAACAAGATCTCTACGGGATTTACGTACGGCTCAAGCATTAATAGTGCCGGGA

CTACTCGAGCATGCATGAGGAATGGAGGGAACAGTTTCTACGCCGAGCTGAAGTGGCTCGT

GTCTAAAAGTAAAGGGCAGAACTTCCCTCAGACCACTAATACCTACAGAAACACAGACACC

GCAGAACACTTAATAATGTGGGGCATACATCACCCCAGCAGCACTCAGGAGAAAAACGACC

TGTACGGTACCCAGTCCCTGTCCATTTCCGTGGGAAGTTCTACGTATCGGAATAACTTCGT

CCCGGTGGTGGGAGCCAGGCCGCAGGTTAACGGACAAAGCGGGCGAATTGATTTCCACTGG

ACACTGGTGCAGCCTGGCGACAATATAACTTTCTCCCATAATGGCGGACTGATCGCTCCAT

CCCGGGTCAGCAAGCTAATCGGTAGAGGGCTGGGGATCCAATCAGACGCACCTATTGATAA

CAACTGCGAGAGTAAGTGCTTCTGGCGAGGCGGTAGCATAAACACACGTTTGCCATTTCAG

AATCTTAGTCCTCGTACTGTGGGCCAATGTCCAAAGTATGTCAACAGGCGCAGTTTAATGT

TAGCTACTGGAATGCGCAACGTACCTGAGCTCATTCAAGGTCGAGGCCTGTTCGGAGCCAT

TGCTGGGTTCCTTGAGAATGGGTGGGAGGGCATGGTCGACGGATGGTACGGATTCCGCCAC

CAGAACGCCCAGGGCACAGGCCAGGCAGCCGATTATAAAAGTACCCAGGCTGCCATCGACC

AGATCACTGGGAAACTCAACCGTCTGGTCGAAAAGACTAACACCGAATTTGAGTCTATTGA

ATCAGAATTCAGCGAAATTGAGCACCAGATCGGCAATGTGATCAATTGGACGAAAGACTCT

ATTACCGACATTTGGACCTACCAGGCCGAGTTACTGGTGGCCATGGAGAACCAGCACACCA

TCGACATGGCCGATAGTGAAATGCTTAACCTCTACGAAAGAGTCCGAAAACAACTCCGCCA

GAACGCGGAGGAGGATGGAAAGGGCTGCTTCGAAATCTATCATGCCTGCGACGACTCCTGT

ATGGAAAGCATTCGCAACAACACCTACGACCACAGTCAGTACAGGGAGGAGGCGCTGCTTA

ATAGGCTGAACATCAATCCGGTAACACTGTCATCGGGATACAAGGACATCATACTCTGGTT

CTCATTCGGCGCGTCCTGTTTCGTACTGCTCGCAGTCGTAATGGGGCTCTTCTTCTTCTGC

TTAAAGAACGGCAACATGCGCTGCACTATCTGCATT

866
ATGTATAAAATTGTGGTCATAATTGCACTGCTCGGCGCAGTCAAGGGTCTGGATAAGATTT

GCCTTGGTCACCATGCCGTAGCCAACGGAACCATTGTGAAGACCCTTACAAATGAACAAGA

AGAAGTGACTAATGCAACTGAGACCGTGGAATCTACAGGTATCAATCGCCTGTGTATGAAG

GGGCGAAAACATAAAGATCTCGGCAATTGTCACCCCATTGGGATGCTGATTGGCACCCCGG

CATGTGACCTACATTTGACCGGAATGTGGGATACACTAATCGAACGGGAGAATGCTATTGC

GTACTGTTACCCTGGCGCTACCGTCAATGTGGAGGCCCTGCGCCAAAAAATCATGGAATCT

GGGGGAATCAATAAGATCTCCACTGGCTTCACTTATGGATCCAGCATTAACAGCGCTGGCA

CAACTCGCGCCTGTATGCGCAATGGGGGCAATTCCTTCTATGCAGAGCTTAAGTGGTTAGT

GAGCAAGTCGAAAGGCCAAAACTTCCCTCAAACAACCAATACATATAGGAACACCGATACC

GCTGAACATCTCATTATGTGGGGAATACATCATCCCAGCTCCACACAAGAGAAGAATGATT

TGTACGGGACCCAATCCTTGTCTATTAGCGTAGGCTCCTCCACATACCGGAACAACTTCGT

CCCAGTCGTGGGGGCACGGCCTCAGGTTAACGGACAGTCCGGCCGTATTGACTTCCACTGG

ACTCTGGTGCAACCAGGGGACAACATCACTTTCTCTCATAACGGGGGTCTGATCGCACCTA

GTAGGGTGTCCAAACTTATAGGAAGGGGTCTCGGCATCCAAAGCGACGCCCCCATCGATAA

TAATTGCGAAAGCAAGTGTTTTTGGAGGGGAGGGAGCATCAATACTCGGTTACCATTTCAG

AATTTAAGTCCAAGAACAGTAGGACAATGCCCTAAGTATGTTAATAGACGTTCCCTCATGT

TAGCAACTGGAATGAGGAACGTTCCGGAGCTGATTCAGGGAAGAGGACTCTTCGGGGCAAT

CGCCGGTTTTTTGGAGAACGGATGGGAGGGCATGGTGGATGGTTGGTACGGATTCCGCCAT

CAGAACGCCCAGGGCACCGGGCAAGCTGCAGACTATAAATCAACACAAGCAGCAATTGATC

AAATCACCGGCAAGTTGAACAGGCTGGTCGAGAAAACCAACACTGAATTCGAGTCCATCGA

GAGCGAGTTCTCTGAAATAGAGCATCAGATTGGAAACGTTATCAACTGGACCAAGGATAGT

ATCACGGACATTTGGACTTATCAAGCCGAGCTGCTGGTCGCCATGGAGAATCAACATACTA

TCGACATGGCGGATAGTGAAATGCTCAACCTGTACGAGCGCGTGCGCAAGCAACTGCGCCA

GAACGCTGAAGAGGACGGTAAAGGTTGCTTTGAAATTTATCACGCTTGTGATGACTCCTGC

ATGGAGTCGATCCGCAATAATACGTACGATCACAGCCAGTACCGGGAGGAGGCTTTGCTGA

ACCGGCTGAACATCAACCCTGTAACCTTGTCTTCTGGCTACAAGGATATTATACTCTGGTT

CAGCTTCGGCGCCAGCTGCTTCGTCCTGCTGGCCGTGGTTATGGGACTCTTCTTTTTCTGT

CTGAAAAATGGTAATATGCGGTGCACAATTTGTATC

867
ATGTACAAGATTGTGGTAATCATCGCTTTACTTGGGGCAGTGAAAGGATTGGACAAGATTT

GTTTGGGGCACCATGCAGTGGCCAACGGCACCATTGTTAAAACACTGACAAATGAGCAGGA

AGAGGTTACCAATGCAACGGAAACCGTGGAATCTACTGGAATCAACAGACTGTGCATGAAG

GGCCGCAAGCATAAAGACTTGGGGAATTGCCACCCAATTGGAATGCTTATTGGAACACCAG

CTTGCGATTTACATCTGACTGGCATGTGGGACACCCTCATCGAGCGGGAAAATGCTATCGC

TTATTGCTACCCGGGGGCCACAGTGAATGTGGAAGCACTACGGCAAAAAATCATGGAATCA

GGCGGAATCAACAAAATCTCAACCGGCTTCACCTATGGGTCATCCATCAATAGTGCTGGCA

CCACACGCGCCTGCATGCGAAATGGTGGAAACTCATTCTATGCGGAACTGAAATGGCTAGT

GTCAAAAAGCAAAGGGCAGAATTTTCCACAGACTACGAACACTTATAGAAATACTGACACA

GCTGAGCATCTTATTATGTGGGGCATCCATCATCCAAGCAGTACACAGGAAAAGAATGACC

TATACGGTACACAGTCCCTGTCTATTTCCGTGGGATCCTCCACATACAGAAACAACTTTGT

CCCTGTGGTGGGAGCAAGGCCTCAGGTCAACGGACAGTCTGGCCGCATCGATTTCCATTGG

ACCCTGGTTCAACCGGGCGATAACATCACCTTCAGCCACAATGGAGGCCTGATCGCCCCTA

GCAGGGTGTCAAAGCTTATAGGCAGGGGTCTTGGGATCCAATCCGACGCCCCCATAGACAA

TAACTGCGAGTCGAAATGTTTCTGGCGGGGTGGTTCCATTAATACTCGTCTCCCCTTCCAG

AATCTTTCTCCCAGAACTGTTGGGCAATGCCCCAAGTACGTAAATCGTAGAAGTCTTATGC

TCGCAACCGGTATGCGCAACGTGCCTGAGCTCATTCAGGGCCGGGGCCTCTTTGGGGCTAT

TGCCGGCTTCCTTGAAAACGGCTGGGAGGGTATGGTGGATGGCTGGTACGGATTCCGCCAC

CAGAATGCCCAAGGCACAGGTCAGGCTGCCGACTATAAGTCAACGCAGGCTGCCATCGATC

AGATCACAGGCAAGTTGAACAGGCTAGTGGAGAAGACCAACACAGAGTTTGAGAGTATTGA

GAGCGAGTTTTCCGAAATCGAACACCAGATAGGCAACGTTATCAACTGGACAAAGGACAGT

ATTACAGACATTTGGACATATCAGGCTGAACTGTTGGTGGCCATGGAGAACCAGCACACTA

TCGATATGGCAGACTCCGAGATGCTGAATTTGTACGAAAGGGTCCGGAAGCAGCTCCGCCA

GAACGCCGAAGAGGATGGGAAAGGCTGCTTTGAAATTTACCACGCTTGCGACGACTCCTGT

ATGGAATCCATTCGAAATAATACATATGATCACAGCCAGTACCGGGAAGAAGCTTTACTTA

ATCGATTGAATATCAATCCAGTTACCCTTTCCTCCGGCTACAAGGACATCATTCTGTGGTT

CTCCTTCGGTGCCTCGTGCTTCGTCCTGCTTGCAGTTGTTATGGGGCTGTTTTTTTTCTGT

CTGAAGAACGGGAATATGCGGTGCACTATTTGCATC

868
ATGTATAAAATCGTGGTTATCATCGCCCTGTTGGGCGCAGTCAAAGGCTTAGACAAAATTT

GCCTGGGCCACCATGCCGTGGCCAATGGCACAATTGTAAAAACTTTGACTAATGAGCAGGA

GGAAGTCACTAACGCCACGGAAACCGTGGAGTCCACTGGAATCAACCGCCTGTGCATGAAG

GGACGGAAGCATAAGGACCTCGGTAATTGTCATCCGATAGGTATGCTCATCGGCACCCCCG

CTTGCGACTTACATTTGACAGGAATGTGGGACACTCTGATTGAGAGGGAGAACGCCATTGC

CTACTGTTACCCCGGCGCAACAGTCAATGTGGAGGCGCTGCGTCAAAAGATAATGGAGAGT

GGAGGCATCAACAAAATTTCAACAGGGTTCACATACGGGAGCTCAATTAACTCTGCGGGCA

CGACCAGGGCTTGCATGAGAAACGGCGGTAATTCCTTTTATGCGGAGTTGAAATGGCTGGT

CTCCAAGTCCAAGGGTCAGAATTTCCCACAAACCACAAATACTTACCGAAATACGGACACT

GCCGAGCATCTGATAATGTGGGGAATACACCATCCTAGTTCTACGCAAGAGAAAAATGACC

TCTATGGGACGCAATCCTTGAGTATCAGCGTTGGCTCCTCAACCTACCGGAACAACTTCGT

CCCAGTTGTAGGAGCTCGACCTCAGGTGAATGGACAGTCAGGTCGTATCGATTTTCATTGG

ACCCTCGTGCAACCTGGGGACAACATAACCTTCTCCCACAACGGGGGGCTGATAGCACCCA

GTCGTGTCTCCAAATTGATCGGGAGGGGGCTGGGCATCCAATCAGATGCACCAATTGATAA

TAATTGTGAGAGCAAGTGCTTCTGGCGTGGGGGTAGCATCAACACTCGCCTCCCCTTTCAG

AACTTGTCACCCCGGACCGTCGGTCAGTGTCCCAAGTATGTTAATCGGCGTTCATTAATGC

TGGCAACCGGTATGCGCAACGTCCCCGAGCTAATCCAAGGAAGAGGGCTTTTTGGGGCTAT

AGCAGGATTTTTAGAGAACGGTTGGGAGGGCATGGTGGACGGATGGTACGGCTTTCGGCAC

CAGAATGCGCAGGGGACAGGGCAAGCTGCCGATTATAAGTCCACTCAAGCTGCTATTGATC

AGATTACAGGCAAGCTTAATCGCCTGGTCGAGAAGACTAACACAGAGTTCGAGAGCATTGA

GTCAGAATTCTCTGAAATTGAGCACCAAATCGGGAATGTAATAAATTGGACAAAGGACAGT

ATTACCGACATCTGGACTTATCAAGCCGAGCTCCTGGTTGCTATGGAGAATCAGCACACAA

TCGACATGGCCGATAGCGAGATGCTAAACCTGTACGAAAGGGTGCGCAAGCAGCTGAGGCA

AAACGCTGAGGAAGATGGCAAGGGCTGTTTCGAGATTTATCACGCGTGTGATGATTCATGC

ATGGAATCAATTAGGAACAACACTTACGATCATTCTCAGTACCGGGAGGAGGCACTCCTGA

ACAGGCTCAACATAAACCCTGTCACCCTGTCTTCAGGCTATAAGGACATTATACTATGGTT

TTCTTTTGGCGCCTCCTGTTTTGTGCTCCTCGCCGTTGTAATGGGCCTTTTTTTTTTTTGC

CTGAAGAACGGTAATATGCGGTGTACTATTTGCATT

869
ATGTACAAGATTGTAGTGATTATCGCACTGCTAGGCGCGGTGAAGGGTCTCGACAAGATTT

GCCTGGGCCATCACGCGGTGGCCAACGGGACTATCGTGAAGACTCTGACCAATGAACAAGA

GGAAGTTACTAACGCCACCGAAACTGTGGAGTCCACAGGCATCAATCGCTTGTGTATGAAG

GGAAGGAAGCATAAAGACCTGGGTAATTGTCACCCCATAGGGATGCTTATCGGTACACCAG

CTTGTGATCTGCATTTAACGGGGATGTGGGACACACTTATAGAACGTGAGAATGCCATTGC

CTATTGTTACCCCGGAGCTACCGTAAACGTGGAGGCCCTGCGCCAGAAGATCATGGAGTCA

GGGGGCATCAATAAGATCAGTACCGGCTTTACCTATGGTAGCTCTATCAACTCCGCCGGCA

CTACCAGGGCCTGTATGAGGAATGGGGGAAACAGCTTCTATGCTGAGCTGAAGTGGCTAGT

TAGCAAGAGCAAGGGCCAGAACTTCCCTCAAACTACAAATACGTATCGGAACACCGACACA

GCGGAGCACCTGATAATGTGGGGAATCCACCACCCATCGTCCACCCAAGAAAAGAACGATC

TGTACGGTACTCAGTCCCTGAGTATTTCCGTGGGCTCCAGTACGTACCGAAATAATTTCGT

CCCAGTGGTCGGGGCAAGGCCGCAAGTGAATGGCCAGTCAGGACGGATAGACTTTCATTGG

ACACTGGTGCAACCCGGCGATAACATCACCTTCAGCCATAACGGGGGGCTGATCGCCCCGA

GCCGAGTTAGCAAACTTATCGGCCGGGGCCTGGGCATCCAGAGTGATGCACCCATCGACAA

TAATTGCGAGAGCAAATGTTTTTGGAGGGGTGGATCGATAAACACACGCCTCCCGTTCCAA

AATCTCAGTCCTAGAACAGTGGGGCAGTGTCCTAAGTATGTGAATCGCCGGAGCCTTATGT

TGGCCACTGGGATGCGAAATGTGCCCGAACTAATTCAAGGGCGAGGACTGTTCGGCGCCAT

TGCCGGCTTCCTGGAGAATGGCTGGGAAGGCATGGTTGATGGTTGGTATGGCTTTCGCCAT

CAGAATGCACAGGGGACAGGCCAGGCCGCGGATTACAAATCGACCCAAGCTGCAATTGATC

AGATCACAGGGAAACTGAATCGACTTGTGGAGAAAACTAATACCGAATTTGAATCTATCGA

GTCCGAATTTAGCGAAATCGAGCACCAGATCGGTAACGTGATCAATTGGACTAAGGACTCC

ATTACAGACATATGGACATATCAGGCCGAGTTGTTGGTGGCAATGGAGAACCAGCATACTA

TCGACATGGCCGATTCTGAGATGCTAAATCTGTATGAACGCGTCCGGAAACAGCTCAGACA

GAATGCTGAGGAAGATGGGAAGGGATGCTTCGAAATATACCACGCCTGCGACGACAGCTGT

ATGGAGTCAATTCGCAACAACACTTACGATCACTCCCAATACCGGGAGGAGGCCCTTCTTA

ACAGACTCAACATTAATCCTGTGACTCTGTCATCCGGATACAAAGACATAATACTCTGGTT

TAGCTTTGGCGCAAGTTGTTTTGTGCTGCTCGCAGTGGTGATGGGGTTGTTTTTTTTCTGC

CTGAAAAATGGTAATATGCGATGCACTATCTGCATC

870
ATGTACAAAATTGTGGTGATAATTGCATTGCTCGGAGCAGTCAAAGGGCTGGACAAAATAT

GTTTGGGGCACCACGCCGTGGTTAATGGTACCATCGTTAAGACTCTGACCAACGAACAGGA

AGAGGTGACCAATGCTACCGAGACCGTGGAAAGCACTGGGTTGAACAGGCTGTGCATGAAA

GGAAGGAATCACAAGGACCTGGGAAACTGTCATCCAATCGGAATGCTCATTGGGACTCCCG

CATGTGATCTGCATCTGACGGGCACCTGGGATACCTTGATAGAGAGGGAGAACGCCATAGC

ATACTGTTATCCCGGAGCCACCGTGAACGAGGAGGCACTGAGGCAGAAAATTATGGAATCT

GGAGGGATCAATAAAATTAGCACAGGGTTTACCTATGGCTCAAGTATCAATAGCGCCGGGA

CTACACGGGCCTGCATGCGAAATGGAGGGAACTCCTTCTACGCTGAACTAAAGTGGCTGGT

CAGTAAGTCCAAAGGGCAGAATTTCCCGCAGACAACCAACACTTACCGCAATACCGATACG

GCTGAACACTTAATCATGTGGGGCATCCATCATCCCTCTAGCACACAAGAGAAAAACGACC

TGTATGGAACACAAAGCCTCAGCATCTCCGTGGGTTCATCTACATATCAGAACAACTTCGT

GCCCGTCGTTGGCGCCCGACCTCAGGTGAATGGTCAATCGGGCCGGATTGACTTTCACTGG

ACCCTCGTCCAGCCAGGTGATAACATCACCTTCAGCCACAACGGCGGACTCATCGCCCCAT

CTCGTGTGTCCAAGCTCATTGGCAGAGGGCTTGGCATCCAGTCTGATGCACCCATCGATAA

CAATTGCGAGAGCAAGTGTTTCTGGCGCGGTGGATCAATAAATACGCGGCTCCCCTTTCAG

AATCTTTCTCCCAGAACCGTAGGCCAGTGTCCAAAGTATGTAAACAAAAGATCATTGATGC

TGGCCACAGGAATGAGGAATGTGCCTGAGCTGATGCAGGGCAGAGGCCTGTTCGGTGCGAT

CGCCGGCTTCATCGAAAATGGCTGGGAGGGGATGGTGGACGGATGGTATGGCTTCCGCCAC

CAGAACGCTCAGGGGACCGGACAAGCTGCGGATTATAAGAGCACTCAGGCGGCAATCGACC

AGATCACCGGAAAACTCAACCGTCTCATCGAGAAGACAAACACCGAATTTGAGTCTATAGA

ATCTGAGTTCAGTGAAATCGAACACCAAATCGGCAACGTCATAAATTGGACTAAGGACTCC

ATCACCGATATCTGGACCTATCAAGCCGAGCTGCTGGTTGCCATGGAGAATCAGCACACGA

TCGACATGGCTGATTCTGAAATGCTGAACCTCTATGAAAGAGTTCGGAAACAGCTCAGACA

AAACGCCGAAGAGGACGGCAAAGGATGTTTTGAGATCTATCATGCCTGCGATGATAGTTGT

ATGGAGAGCATCAGGAATAATACATACGACCACTCCCAGTATCGCGAGGAAGCACTGCTCA

ATCGGTTAAATATAAATCCAGTGACGCTTAGTAGTGGGTATAAGGACATAATCCTCTGGTT

CTCTTTCGGCGCCAGCTGTTTCGTTCTGCTGGCCGTGGTCATGGGACTTGTGTTCTTTTGT

CTTAAAAATGGGAACATGAGATGCACAATATGTATT

871
ATGTATAAAATAGTGGTGATAATCGCGCTACTGGGCGCAGTGAAGGGGCTCGATAAGATTT

GCTTGGGTCATCATGCTGTTGCAAACGGCACCATCGTTAAAACACTGACCAACGAGCAGGA

GGAGGTAACGAACGCCACGGAGACGGTGGAGTCTACCGGGATCAACCGTCTGTGTATGAAG

GGTCGCAAGCATAAGGATTTAGGAAATTGTCATCCTATCGGAATGCTTATAGGTACCCCGG

CCTGCGATCTCCATCTGACAGGCATGTGGGATACTCTCATCGAAAGAGAGAATGCCATCGC

GTATTGTTACCCTGGGGCCACAGTAAATGTCGAAGCATTGAGACAGAAAATCATGGAGTCC

GGAGGCATTAATAAGATTTCCACCGGCTTCACCTACGGATCTTCCATCAATTCCGCAGGCA

CAACCAGAGCCTGCATGCGGAATGGAGGGAATTCCTTTTACGCCGAATTGAAATGGCTTGT

GTCAAAGTCAAAGGGACAGAACTTTCCCCAAACTACGAACACATATAGAAATACAGATACC

GCAGAACACTTAATTATGTGGGGCATCCACCACCCGTCAAGTACTCAGGAGAAGAATGACC

TTTACGGCACCCAGTCTCTTTCAATCTCAGTCGGGAGCTCCACATATAGAAACAACTTTGT

ACCTGTGGTCGGTGCAGGACCGCAGGTGAATGGCCAATCAGGAAGGATCGATTTTCACTGG

ACACTGGTCCAGCCTGGTGACAACATCACGTTCTCACACAATGGGGGCCTAATAGCCCCCT

CCCGCGTGAGCAAGCTAATTGGCCGCGGATTGGGTATCCAGAGCGACGCCCCTATAGACAA

TAACTGTGAGAGCAAGTGCTTCTGGCGCGGAGGGTCAATTAACACCCGGCTCCCCTTCCAG

AACCTGTCCCCCCGGACGGTGGGCCAGTGCCCAAAATACGTCAATCGGCGCTCCCTGATGT

TGGCCACAGGCATGCGGAATGTTCCTGAACTGATACAGGGTCGGGGGTTGTTCGGAGCAAT

TGCCGGGTTTCTTGAAAACGGCTGGGAAGGTATGGTGGATGGTTGGTACGGGTTCAGGCAC

CAGAACGCTCAGGGTACCGGCCAGGCGGCTGACTACAAATCAACCCAGGCAGCAATCGACC

AGATTACAGGAAAGCTGAATCGCCTTGTGGAGAAAACCAATACCGAATTTGAGTCCATCGA

GTCTGAGTTCAGCGAGATAGAGCATCAGATTGGCAACGTCATCAACTGGACGAAGGACTCC

ATTACTGATATATGGACTTATCAGGCTGAACTGCTGGTAGCCATGGAGAACCAGCACACAA

TTGACATGGCTGACTCCGAGATGCTGAATCTATACGAGCGCGTGAGGAAGCAGCTCAGACA

GAACGCTGAGGAGGACGGTAAGGGTTGCTTCGAGATTTACCACGCCTGTGATGACTCCTGT

ATGGAGTCAATCAGGAACAATACCTATGACCACTCTCAATATCGGGAGGAAGCGCTTCTCA

ACCGTCTTAACATTAATCCCGTGACACTGTCTTCAGGTTACAAGGATATCATCCTGTGGTT

CAGCTTTGGCGCCAGCTGTTTCGTGCTACTAGCAGTGGTGATGGGCCTGTTTTTTTTCTGC

CTGAAAAATGGGAACATGAGGTGCACGATTTGCATC

872
ATGTATAAAATCGTTGTAATTATTGCACTGCTTGGCGCCGTGAAGGGACTCGACAAGATCT

GCCTGGGCCACCACGCTGTAGCCAACGGCACCATTGTGAAGACCCTGACAAATGAGCAGGA

GGAGGTTACCAATGCCACTGAGACCGTGGAATCCACAGGCATTAACCGCCTGTGTATGAAG

GGAAGGAAGCACAAGGACCTTGGCAATTGTCACCCAATCGGCATGCTCATCGGCACACCAG

CATGCGACTTGCACCTGACCGGAATGTGGGACACGCTCATAGAAAGAGAGAATGCCATTGC

CTATTGCTACCCAGGAGCCACCGTTAACGTGGAGGCACTGAGGCAGAAGATCATGGAGAGC

GGAGGCATCAATAAAATTAGTACGGGGTTTACATATGGCTCCTCTATAAATTCCGCCGGCA

CCACCCGGGCCTGCATGCGGAATGGCGGAAATAGTTTCTACGCTGAGTTGAAATGGCTGGT

GAGCAAGAGTAAGGGGCAGAACTTTCCGCAAACTACCAATACGTATAGGAACACTGACACC

GCCGAGCACCTAATCATGTGGGGCATACATCATCCCAGCTCCACGCAGGAGAAGAACGACC

TGTATGGAACTCAAAGCCTATCTATCTCCGTGGGATCCAGTACATACCGGAATAACTTTGT

GCCAGTAGTGGGCGCCAGACCGCAGGTGAACGGGCAATCCGGCAGGATCGACTTCCACTGG

ACACTGGTGCAACCAGGCGACAACATTACTTTCAGCCACAATGGTGGTTTAATAGCCCCCT

CAAGGGTTTCCAAATTGATTGGGCGGGGGCTTGGTATTCAATCTGACGCTCCAATAGATAA

CAATTGTGAAAGTAAGTGTTTCTGGCGCGGCGGCTCTATTAATACTCGCCTTCCATTCCAA

AATCTCTCACCACGTACCGTTGGCCAATGTCCCAAATATGTGAACCGTAGGTCCTTGATGC

TCGCAACGGGAATGAGGAACGTTCCGGAGCTGATCCAGGGCCGAGGACTCTTTGGTGCTAT

TGCCGGATTTCTGGAGAACGGGTGGGAGGGCATGGTGGATGGATGGTACGGCTTCCGACAT

CAGAATGCACAAGGCACCGGGCAGGCCGCCGATTACAAGTCCACGCAAGCTGCCATTGACC

AGATTACGGGGAAGTTGAACCGGCTCGTCGAGAAGACCAATACTGAATTCGAATCCATTGA

GAGCGAATTTTCTGAAATTGAACATCAGATTGGTAACGTCATCAATTGGACTAAGGACTCA

ATAACAGACATCTGGACTTATCAGGCTGAACTCCTCGTCGCGATGGAAAATCAGCACACCA

TCGATATGGCCGACTCTGAGATGCTGAACTTGTACGAGCGGGTGAGAAAACAGCTTCGACA

GAATGCCGAGGAAGATGGCAAGGGCTGCTTCGAGATCTATCACGCTTGCGATGACTCATGC

ATGGAGTCTATCCGGAACAACACTTATGACCACTCCCAATACCGCGAGGAGGCCCTGCTGA

ATAGGCTGAACATCAACCCAGTGACCTTGAGCTCAGGCTATAAGGACATAATCCTGTGGTT

TAGCTTTGGGGCCTCGTGCTTTGTCCTGCTGGCCGTAGTTATGGGGCTTTTCTTCTTTTGT

CTTAAGAATGGGAATATGAGGTGTACAATCTGTATC

873
ATGTACAAGATCGTGGTTATCATCGCACTCCTCGGGGCTGTGAAGGGTCTCGACAAAATCT

GCCTTGGTCATCACGCAGTTGCCAACGGAACTATTGTTAAGACCTTGACTAATGAGCAGGA

GGAGGTGACAAACGCCACAGAAACCGTGGAAAGTACGGGGATCAACCGTTTATGCATGAAG

GGAAGGAAACACAAAGATCTCGGTAACTGCCATCCGATCGGTATGCTCATTGGCACTCCAG

CTTGCGACTTGCACTTGACCGGTATGTGGGACACATTAATTGAACGCGAGAACGCCATCGC

CTATTGCTACCCCGGAGCCACTGTGAACGTGGAAGCACTCCGACAGAAAATAATGGAAAGT

GGGGGGATAAATAAGATCTCAACCGGATTTACATACGGTTCCTCAATTAATAGCGCCGGGA

CCACTAGAGCATGCATGCGAAATGGAGGTAATTCTTTTTACGCTGAGCTTAAATGGCTGGT

GTCTAAAAGCAAGGGCCAGAATTTTCCACAGACGACGAACACTTATAGGAATACAGACACA

GCCGAACACCTGATCATGTGGGGAATCCACCACCCATCTAGCACACAGGAGAAAAACGACC

TATATGGTACCCAAAGCCTGTCAATTAGCGTCGGCAGTAGTACATACCGCAATAATTTCGT

TCCCGTTGTCGGAGCCAGGCCGCAAGTGAACGGGCAAAGTGGCAGAATTGATTTCCACTGG

ACACTGGTCCAGCCCGGGGATAACATTACATTCAGCCACAACGGGGGGCTTATCGCCCCCT

CCCGTGTGAGTAAGCTGATCGGCCGGGGCTTAGGTATCCAGTCCGATGCTCCCATCGACAA

CAATTGTGAATCGAAGTGCTTTTGGCGGGGGGGCTCCATCAATACCCGGCTGCCTTTCCAG

AACCTGAGCCCCAGGACCGTTGGACAGTGTCCCAAATACGTTAACCGGCGGAGTCTGATGC

TTGCAACCGGGATGCGCAATGTGCCCGAACTGATCCAGGGGCGAGGACTGTTCGGGGCCAT

CGCCGGATTCCTGGAGAATGGCTGGGAGGGTATGGTGGACGGCTGGTACGGCTTTAGGCAC

CAAAATGCTCAAGGAACAGGGCAGGCTGCTGACTACAAATCAACCCAGGCCGCTATTGATC

AAATTACTGGAAAGCTGAATAGATTGGTGGAGAAAACTAATACTGAATTCGAGTCCATCGA

AAGTGAGTTCAGCGAGATCGAGCACCAGATTGGTAACGTTATTAACTGGACCAAAGACAGC

ATCACCGACATTTGGACCTACCAGGCCGAGCTTCTAGTAGCCATGGAAAATCAACACACGA

TCGATATGGCTGATTCAGAGATGCTGAATCTGTATGAGCGGGTCCGGAAACAGCTGAGACA

GAATGCAGAGGAAGACGGTAAGGGGTGTTTTGAGATTTACCATGCCTGCGATGATTCTTGC

ATGGAATCTATCAGGAACAACACCTATGACCACTCCCAATATCGCGAGGAGGCCCTGCTGA

ACAGGTTAAACATCAACCCCGTCACCCTGTCTTCAGGATATAAAGACATCATCTTATGGTT

CTCCTTCGGAGCGTCCTGTTTTGTGCTGTTGGCAGTGGTCATGGGGCTTTTCTTTTTCTGT

CTAAAAAACGGTAACATGCGGTGCACCATATGCATC

874
ATGTATAAAATTGTAGTTATTATCGCCCTGTTGGGCGCTGTGAAGGGCTTGGACAAGATCT

GCCTGGGACACCATGCAGTCGCAAATGGAACAATTGTCAAGACACTGACTAATGAGCAGGA

AGAGGTTACCAACGCCACAGAGACCGTAGAGTCCACCGGGATTAATCGGCTATGCATGAAA

GGAAGAAAGCACAAAGATCTCGGGAACTGTCATCCAATTGGTATGCTGATCGGAACCCCCG

CCTGTGATCTCCATCTTACTGGCACTTGGGACACCTTGATTGAGAGGGAAAACGCCATTGC

TTATTGTTACCCAGGAGCTACCGCCAACGTCGAGGCCCTAAGGCAGAAGATCATGGAGTCT

GGAGGAATTGATAAGATCTCAACGGGGTTTACATACGGGTCTAGTATCAATAGCGCAGGCA

CTACCCGCGCTTGTATGAGGAACGGCGGCAACTCGTTTTACGCCGAGTTGAAATGGCTGGT

CAGTAAATCAAAGGGGCAGAATTTTCCACAGACCACAAACACTTATAGGAATACCGATACA

GCTGAACACCTCATCATGTGGGGCATCCATCACCCCAGCTCCATTCAAGAGAAGAACGACT

TGTATGGCACACAGTCATTGAGCATCAGTGTGGGCAGCAGCACATACAGAAACAACTTCGT

GCCCGTGGTTGGGGCAAGACCTCAGGTAAACGGCCAGTCCGGTAGGATTGACTTCCATTGG

ACGCTCGTGCAACCGGGAGATAACATCACCTTCAGCCACAATGGGGGACTCATCGCACCCT

CTCGAGTTAGCAAACTGATCGGGCGAGGCTTAGGCATACAATCCGACGCGCCTATCGATAA

CAATTGCGAATCCAAATGTTTCTGGCGCGGCGGTAGCATTAATACTCGTCTGCCATTCCAG

AACCTTAGCCCCAGGACAGTGGGACAGTGTCCAAAATACGTGAATCGCAGAAGTCTCATGC

TGGCTACCGGCATGAGGAACGTGCCAGAGCTTATACAGGGGGGGGGCTTGTTCGGAGCGAT

CGCTGGCTTCTTGGAGAATGGCTGGGAGGGCATGGTCGACGGATGGTATGGTTTTCGACAT

CAAAACGCCCAGGGCACGGGGCAGGCCGCCGATTACAAGTCCACTCAGGCAGCAATCGACC

AGATCACCGGTAAGCTTAATAGACTGGTCGAGAAGACAAATACCGAGTTCGAATCTATTGA

ATCCGAGTTCAGCGAAATCGAACACCAAATAGGGAACGTCATCAACTGGACCATGGACAGC

ATCACCGATATATGGACATATCAGGCTGAGTTGCTTGTGGCCATGGAAAATCAGCACACAA

TCGATATGGCTGATTCCGAAATGCTGAACCTGTACGAACGGGTAAGGAAGCAGCTGCGGCA

GAACGCAGAAGAGGATGGGAAGGGCTGCTTCGAAATTTACCACGCTTGTGATGACTCTTGT

ATGGAGTCTATTCGCAACAACACCTACGACCATTCTCAGTATCGTGAGGAGGCCCTTCTCA

ATCGTCTGAACATCAATCCGGTGACCCTATCTTCAGGATATAAGGATATTATACTCTGGTT

CTCCTTCGGGGCAAGCTGCTTCGTCTTGCTGGCCGTCGTCATGGGGCTGGTTTTCTTCTGT

TTAAAAAATGGAAATATGAGGTGCACCATTTGTATC

875
ATGTACAAGATTGTAGTTATTATCGCTTTACTGGGAGCGGTCAAAGGTCTGGACAAGATAT

GCCTTGGACACCACGCAGTGGCTAACGGCACAATCGTCAAAACTCTGACAAACGAGCAGGA

GGAGGTCACTAATGCGACCGAAACGGTGGAGAGCACCGGAATTAATCGACTATGTATGAAG

GGCAGGAAGCACAAGGATCTCGGGAACTGCCATCCCATCGGCATGCTGATAGGCACGCCAG

CCTGCGATCTTCATCTGACCGGAATGTGGGATACCCTGATCGAGAGAGAAAACGCCATTGC

ATACTGTTACCCGGGAGCAACCGTCAATGTGGAGGCGCTGAGACAGAAAATTATGGAAAGC

GGAGGGATCAATAAAATCAGTACCGGGTTTACTTATGGCTCATCAATCAATTCAGCAGGCA

CTACTAGAGCTTGCATGAGGAATGGAGGGAATAGTTTCTACGCGGAGTTGAAATGGCTCGT

GAGTAAATCTAAGGGGCAGAATTTTCCCCAGACTACAAATACGTATAGAAACACCGATACT

GCCGAGCACTTAATCATGTGGGGCATCCATCATCCAAGCAGTACCCAGGAGAAAAACGACC

TCTATGGGACTCAGTCCTTGAGCATTAGCGTCGGATCTTCCACATACAGAAACAATTTCGT

TCCAGTCGTCGGAGCTCGACCTCAGGTTAACGGGCAATCCGGGCGAATAGACTTTCATTGG

ACTCTGGTGCAGCCCGGGGACAACATAACCTTCAGTCACAATGGAGGGCTGATAGCCCCCA

GTCGCGTGAGTAAATTGATTGGCAGGGGCCTAGGAATCCAATCTGACGCACCCATCGACAA

CAACTGCGAGAGCAAATGCTTTTGGCGCGGTGGGTCAATAAACACTCGCCTCCCTTTTCAG

AATTTGTCACCTCGGACAGTGGGACAGTGCCCTAAGTATGTGAATCGCCGATCCCTGATGC

TAGCCACCGGCATGCGCAATGTGCCCGAGCTGATTCAGGGAAGGGGCCTGTTCGGCGCCAT

CGCCGGCTTCTTGGAAAATGGCTGGGAGGGGATGGTTGACGGCTGGTATGGCTTCCGGCAT

CAGAACGCACAGGGCACCGGCCAGGCGGCCGACTATAAGTCCACACAAGCAGCCATCGATC

AAATCACGGGAAAGCTCAATAGGCTGGTCGAGAAAACAAACACAGAATTCGAAAGTATCGA

ATCAGAGTTCTCCGAGATAGAGCACCAGATCGGAAATGTGATCAATTGGACAAAGGACAGC

ATCACTGACATATGGACGTACCAGGCAGAGCTGCTTGTCGCCATGGAGAACCAGCATACGA

TTGATATGGCAGACTCTGAAATGCTGAACCTCTACGAGAGAGTACGGAAGCAACTACGTCA

GAATGCAGAGGAGGATGGGAAAGGATGCTTTGAAATCTATCATGCATGTGACGATTCTTGC

ATGGAGTCAATACGCAACAATACGTACGACCACAGCCAGTATCGGGAGGAAGCGCTGCTTA

ACAGACTGAATATAAATCCGGTGACACTGTCATCTGGCTACAAGGACATCATCTTATGGTT

TTCGTTTGGTGCGAGTTGTTTTGTCTTACTAGCCGTCGTTATGGGTTTATTCTTTTTTTGT

TTGAAGAATGGGAACATGAGGTGTACAATTTGCATT

876
ATGTACAAGATCGTGGTCATAATCGCCCTTCTCGGTGCTGTTAAGGGACTAGATAAGATAT

GCCTGGGCCACCATGCCGTAGCTAACGGTACAATAGTGAAGACATTAACTAATGAGCAAGA

AGAGGTGACGAACGCTACTGAGACTGTTGAGAGCACAGGCATTAACCGGCTGTGTATGAAG

GGCCGCAAGCACAAGGATCTGGGAAATTGCCACCCAATTGGCATGCTGATCGGAACACCAG

CGTGCGATTTGCACCTAACCGGTATGTGGGATACTCTGATTGAGCGTGAAAATGCTATTGC

CTACTGTTATCCCGGCGCTACAGTCAACGTGGAAGCGCTGCGCCAGAAGATCATGGAATCT

GGAGGAATTAATAAGATCTCAACTGGTTTCACCTACGGTAGCTCGATTAACAGCGCAGGAA

CAACTCGTGCCTGCATGAGAAATGGAGGCAATAGCTTTTATGCTGAACTGAAATGGCTCGT

GTCTAAGTCAAAGGGCCAGAATTTCCCTCAAACAACTAACACCTACAGGAATACTGACACT

GCGGAACATCTGATCATGTGGGGCATTCACCACCCCTCTTCAACACAGGAGAAAAACGATC

TCTACGGCACTCAGTCGCTGTCCATCTCTGTGGGGAGCTCTACCTATCGTAACAATTTCGT

CCCGGTTGTTGGCGCCCGGCCACAAGTGAACGGGCAGAGCGGCCGGATCGACTTCCACTGG

ACCCTCGTACAGCCTGGGGACAACATCACCTTCTCACACAACGGAGGGCTAATCGCCCCCT

CAAGGGTCAGCAAGTTGATAGGCAGGGGCTTGGGAATTCAGTCGGATGCCCCAATTGATAA

CAACTGCGAGAGCAAATGCTTTTGGCGCGGAGGATCCATCAATACAAGGCTCCCCTTCCAA

AACCTCAGCCCCAGAACCGTTGGGCAGTGTCCTAAATATGTGAACAGGAGATCTCTGATGC

TGGCCACTGGAATGAGAAATGTGCCTGAGCTGATCCAGGGCCGAGGACTGTTTGGAGCGAT

CGCCGGATTTCTTGAAAACGGCTGGGAAGGCATGGTGGATGGCTGGTACGGATTTAGACAT

CAGAATGCCCAAGGGACCGGCCAAGCTGCAGACTACAAAAGTACCCAGGCCGCGATAGATC

AGATTACGGGAAAGCTGAACCGTCTGGTGGAAAAAACTAATACGGAGTTTGAGTCCATAGA

GAGTGAGTTTTCTGAAATTGAACACCAGATTGGGAACGTGATCAACTGGACCAAGGACTCA

ATCACTGATATATGGACCTACCAGGCCGAGCTCCTAGTGGCAATGGAAAACCAGCACACAA

TAGACATGGCCGACAGCGAAATGTTGAATCTCTACGAAAGAGTGAGGAAGCAGCTTCGGCA

GAATGCTGAGGAGGACGGAAAGGGATGTTTCGAGATCTACCACGCCTGTGACGATAGTTGC

ATGGAAAGCATCCGTAACAATACCTACGATCACAGTCAATATAGGGAAGAAGCATTGCTGA

ATAGGTTGAATATAAATCCCGTTACTCTTTCCTCGGGGTATAAGGATATTATCCTTTGGTT

TTCATTTGGTGCCTCGTGTTTCGTCCTGCTGGCAGTGGTGATGGGCCTCTTTTTCTTCTGT

TTGAAGAACGGGAATATGCGCTGTACCATCTGCATA

877
ATGTACAAAGTAGTCGTAATCATCGCCCTTTTGGGAGCCGTCAAGGGCCTGGACAAGATAT

GCCTGGGACATCACGCTGTCGCCAACGGGACGATTGTCAAAACACTGACAAACGAGCAGGA

AGAGGTTACCAACGCGACTGAGACTGTTGAGTCAACAGGTATAAACCGACTGTGTATGAAA

GGACGGAAACACAAAGATCTGGGGAATTGCCACCCCATCGGGATGCTGATCGGTACCCCTG

CATGCGACCTGCACCTCACTGGTACTTGGGATACTCTCATAGAACGGGAGAACGCAATCGC

ATACTGCTATCCTGGAGCCACCGTTAATGTTGAGGCCTTGAGACAAAAAATTATGGAGAGT

GGGGGAATCGACAAAATCTCCACCGGCTTTACCTATGGCAGCTCCATCAATTCAGCCGGTA

CCACGCGTGCCTGTATGCGCAACGGAGGTAATTCATTCTACGCCGAGCTAAAATGGCTGGT

GTCCAAAAATAAAGGGCAAAACTTCCCGCAAACAACAAACACTTACAGAAACACAGACACT

GCAGAACATCTGATAATGTGGGGAATCCACCATCCGTCATCTATACAGGAGAAAAACGATC

TGTATGGCACTCAGTCACTCAGTATCTCCGTCGGCTCATCAACGTACAGGAATAATTTTGT

GCCCGTCGTCGGCGCACGTCCACAAGTCAACGGTCAGTCCGGGAGAATCGACTTTCATTGG

ACGCTTGTTCAACCGGGCGATAACATTACATTTTCACATAACGGAGGGCTCATCGCTCCAA

GTAGAGTCTCTAAACTGATCGGACGTGGCCTGGGAATTCAGTCAGATGCGCCCATCGACAA

CAATTGCGAGTCGAAGTGCTTCTGGCGGGGGGGGTCCATAAATACCCGCCTCCCCTTTCAA

AACCTCTCACCCCGTACCGTGGGCCAGTGCCCTAAATATGTGAATCGGCGATCCCTGATGC

TGGCAACTGGAATGCGCAACGTACCAGAGCTGATTCAGGGCAGAGGACTCTTCGGGGCCAT

TGCAGGGTTCCTGGAAAATGGTTGGGAAGGAATGGTTGACGGATGGTATGGCTTCCGCCAC

CAGAATGCACAAGGGACAGGTCAGGCTGCAGATTATAAGTCCACGCAGGCCGCTATTGATC

AGATTACGGGAAAACTCAACAGACTGGTGGAAAAAACCAACACTGAGTTTGAGAGCATTGA

GTCCGAGTTTTCCGAGATTGAACATCAAATCGGTAATGTTATCAATTGGACTATGGATAGT

ATTACGGATATTTGGACTTACCAGGCCGAATTGTTAGTGGCTATGGAAAACCAACACACTA

TTGACATGGCAGACTCAGAGATGCTCAATCTTTATGAGCGCGTGAGGAAGCAGCTCAGACA

GAACGCGGAAGAAGACGGCAAGGGGTGCTTTGAGATTTACCACGCCTGCGACGACTCCTGC

ATGGAAAGCATCCGCAACAACACCTACGACCACAGCCAATATCGCGAGGAGGCCCTCCTTA

ATCGGTTGAACATCAATCCCGTAACACTGTCCTCCGGGTACAAAGACATCATCCTGTGGTT

CAGTTTTGGCGCGAGCTGTTTCGTCTTGTTGGCTGTGGTGATGGGCCTCGTATTTTTTTGC

CTTAAAAACGGGAACATGCGGTGTACAATCTGTATT

878
ATGTACAAAATAATTGTGATCATTGCCCTCCTGGGGGCTGTGAAGGGCCTTGACAAGATCT

GCCTAGGACACCATGCAGTTGCAAACGGAACAATTGTGAAGACCCTAACCAACGAACAAGA

GGAGGTGACAAACGCAACTGAGACCGTGGAGTCAACCGGCATAAATAGGCTTTGCATGAAG

GGAAGGAAACACAAAGATCTCGGCAACTGTCATCCAATCGGCATGCTTATCGGGACGCCTG

CATGTGATCTGCACCTAACTGGCACCTGGGACACACTGATTGAAAGGGAGAATGCTATCGC

TTACTGTTACCCTGGTGCTACTGTGAACGTTGAGGCTTTGCGGCAGAAAATCATGGAGTCA

GGGGGCATTGACAAAATCTCGACAGGCTTTACCTACGGCTCAAGCATTAACTCCGCTGGGA

CCACTAGAGCATGTATGAGAAATGGAGGTAACTCATTCTATGCCGAGCTCAAATGGCTCGT

GTCAAAAAGCAAGGGGCAGAACTTCCCGCAGACGACCAATACTTATCGGAATACAGACACT

GCCGAACATCTTATTATGTGGGGAATTCATCATCCATCCTCAACTCAGGAAAAAAACGACT

TGTACGGGACTCAATCCCTCTCCATTTCCGTGGGCAGTAGCACATATAGGAATAATTTCGT

TCCTGTCGTTGGGGCGAGGCCACAAGTGAATGGCCAGAGCGGCCGAATCGATTTTCATTGG

ACCCTTGTACAACCAGGGGACAATATCACTTTCTCACACAACGGAGGGTTGATTGCCCCAT

CCCGCGTTAGTAAGCTTATCGGCCGCGGCCTGGGTATACAGTCCGATGCACCCATCGATAA

TAATTGTGAGTCTAAGTGTTTTTGGCGAGGTGGCTCCATCAATACGCGGCTACCTTTTCAG

AACCTGTCGCCTCGCACCGTAGGGCAGTGTCCAAAGTATGTCAATAGACGGTCTTTGATGT

TGGCCACCGGAATGAGAAACGTTCCAGAGCTGATTCAGGGGCGCGGGCTGTTCGGCGCCAT

CGCCGGCTTCCTTGAGAATGGGTGGGAGGGCATGGTTGATGGATGGTACGGGTTTCGGCAC

CAGAACGCCCAGGGGACCGGCCAAGCCGCAGATTACAAGAGCACCCAGGCTGCCATCGACC

AGATTACCGGCAAGCTCAATAGGCTCGTGGAAAAAACTAACACCGAGTTTGAGTCTATCGA

ATCGGAGTTTAGCGAGATAGAGCATCAGATTGGAAATGTCATAAATTGGACAAAAGACAGT

ATCACAGATATCTGGACATACCAGGCTGAGCTGCTGGTCGCTATGGAAAATCAGCACACTA

TTGATATGGCCGATTCAGAAATGTTGAACCTGTATGAGCGGGTGCGTAAGCAGCTCCGACA

GAATGCTGAGGAAGATGGGAAGGGCTGCTTCGAGATATACCACGCTTGTGATGACTCTTGC

ATGGAGAGCATCCGGAACAACACGTATGACCATAGTCAGTATCGGGAAGAGGCACTGCTCA

ACAGGCTGAATATCAATCCCGTGACGCTCTCATCTGGATACAAGGACATCATCCTGTGGTT

CAGCTTTGGGGCATCTTGTTTCGTACTTCTGGCTGTCGTCATGGGCCTGTTTTTCTTCTGC

TTAAAGAACGGAAATATGAGATGTACCATATGCATA

879
ATGTATAAAGTGGTAGTCATCATCGCGTTACTGGGGGCAGTGCGAGGCCTTGATAAAATTT

GTCTGGGACATCATGCCGTCGCCAACGGCACCATCGTCAAGACACTAACTAACGAGCAGGA

GGAGGTCACCAATGCCACCGAGACCGTCGAAAGTAAATCGTTGGGAAAGCTATGCATGAAG

GGGAGGTCCTACAACGACCTGGGTAATTGCCATCCTATTGGGATCCTCATCGGTACCCCCG

CATGTGACCTGCACCTGACAGGCACATGGGATACTCTGATTGAAAGAGAGAACGCTGTAGC

GTACTGCTACCCCGGCGCAACTGTCAACGAAGAAGCGCTGAGACAGAAGATCATGGAATCC

GGGGGCATTTCAAAGATCTCTACCGGTTTCACGTATGGAACCAGTATCAACAGCGCAGGCA

CAACAAAGGCCTGCATGCGCAATGGCGGCAATTCCTTCTACGCCGAGCTTAAATGGCTCGT

CAGTAAGAATAAAGGCCAGAATTTTCCCCAGACCACCAACACTTACCGGAACACTGACACG

GCCGAGCATCTCATTATTTGGGGGATTCATCATCCAAGCTCGACTCAAGAAAAGAATGATC

TGTATGGCACTCAGTCTCTGTCTATCTCAGTTGGCAGCTCCACGTACCAGAATAATTTCGT

GCCTGTCGTTGGGGCTAGACCCCAAGTGAATGGACAATCAGGTAGGATAGATTTTCACTGG

ACCTTATTACAGCCTGGAGATAACATAACATTCAGTCACAATGGAGGATTAATAGCTCCAT

CCCGCGTGTCTAAACTGATCGGCAGAGGCTTGGGCATCCAGTCTGAAGCCCCTATTGACAA

TGGTTGCGAGAGCAAATGCTTTTGGAAAGGCGGAAGCATTAACACAAAGTTGCCTTTCCAG

AACCTGTCTCCCCGCACTGTGGGCCAGTGTCCCAAGTACGTCAATAAACGATCTCTGATGC

TGGCTACCGGTATGCGCAATGTTCCCGAAATCATGCATGGGAGAGGGCTGTTCGGGGCTAT

AGCAGGATTTATCGAAAATGGATGGGAAGGGATGGTGGATGGATGGTACGGTTTCAGACAC

CAAAATGCCCAGGGGACGGGGCAGGCTGCTGATTACAAAAGTACGCAGGCCGCCATTGATC

AGATTACCGGCAAGCTTAATCGGCTGATTGAAAAAACGAACACCGAGTTTGAGAGCATCGA

GTCCGAGTTTAGCGAGATTGAGCATCAAATTGGCAACATCATCAACTGGACAAAAGACAGC

ATCACTGATATCTGGACTTACCAAGCTGAACTGCTCGTGGCCATGGAGAATCAGCACACCA

TTGACATGGCAGATTCCGAGATGCTAAACCTGTACGAACGCGTCCGCAAGCAGCTCCGGCA

GAACGCAGAGGAAGATGGAAAGGGGTGCTTCGAGATTTACCACGCTTGCGATGACAGCTGT

ATGGAATCCATTCGAAACAATACATACGATCACTCACAGTATCGCGAGGAGGCTCTGCTCA

ACCGTTTGAATATTAATCCAGTGAAGCTATCTAGCGGCTATAAGGACATAATCCTGTGGTT

CAGCTTCGGCGCCTCTTGCCTAATCTTACTCGCCGTCGTGATGGGACTGGTGTTTTTTTGT

CTCAAGAACGGCAACATGAGGTGCACCATATGCATC

880
ATGTATAAGATCGTGGTCATAATCGCCCTGCTGGGCGCCGTCAAAGGGCTGGACAAAATAT

GCCTCGGACACCATGCTGTCGCCAATGGGACGATTGTCAAAACGCTCACCAACGAACAGGA

GGAAGTTACTAACGCCACAGAAACGGTAGAATCCACAGGGATCAATCGATTGTGTATGAAG

GGTCGTAAGCACAAAGACTTGGGAAACTGTCACCCCATCGGCATGCTGATCGGCACGCCTG

CCTGCGATCTACATCTGACAGGCATGTGGGACACACTAATAGAGAGGGAAAACGCAATCGC

CTACTGTTACCCCGGTGCCACAGTAAACGTGGAAGCTCTGCGGCAGAAGATAATGGAGTCT

GGAGGAATCAATAAAATCAGCACCGGTTTCACATATGGCTCCAGTATCAACTCCGCAGGCA

CTACCAGGGCTTGCATGCGCAATGGGGGAAATTCTTTCTACGCGGAGCTAAAATGGTTAGT

CTCTAAGTCCAAAGGACAGAACTTTCCACAGACAACAAACACCTACAGGAATACAGATACC

GCTGAGCACCTGATCATGTGGGGTATTCATCATCCCAGTTCTACTCAGGAAAAGAACGATC

TGTATGGGACACAGTCGCTGAGTATATCTGTCGGTAGTAGTACATACCGTAATAATTTCGT

GCCCGTTGTAGGCGCTAGACCTCAGGTGAATGGGCAATCCGGCCGGATTGATTTCCACTGG

ACTCTCGTGCAGCCTGGGGATAATATCACGTTTAGCCACAATGGAGGTCTAATCGCCCCCT

CCCGGGTTTCTAAACTGATTGGCCGGGGACTGGGAATCCAATCTGACGCCCCAATAGACAA

CAACTGCGAATCCAAGTGTTTCTGGCGGGGCGGCTCCATAAATACGCGACTTCCCTTCCAG

AACTTAAGTCCCCGGACTGTGGGTCAGTGTCCAAAATACGTGAATCGCCGGAGTCTTATGC

TCGCCACAGGCATGCGTAACGTCCCGGAACTTATACAGGGCCGGGGACTGTTTGGAGCTAT

CGCAGGATTCCTGGAGAACGGATGGGAGGGAATGGTGGACGGATGGTATGGTTTCCGGCAC

CAAAACGCTCAAGGAACGGGCCAGGCAGCAGATTATAAGTCAACACAGGCCGCGATCGACC

AAATTACTGGCAAACTCAATAGGCTGGTCGAGAAAACCAACACTGAGTTTGAGAGCATTGA

ATCCGAATTCAGCGAAATCGAACACCAGATCGGCAACGTGATAAATTGGACGAAAGATTCC

ATTACCGACATTTGGACATACCAGGCCGAGTTGCTGGTCGCTATGGAAAATCAGCATACGA

TTGATATGGCCGATAGTGAGATGCTTAACCTGTATGAACGCGTACGCAAACAGCTGCGCCA

AAATGCTGAAGAGGACGGTAAAGGCTGCTTTGAGATTTATCACGCTTGCGACGATTCATGC

ATGGAAAGTATCAGAAACAATACATATGACCACAGCCAGTACAGGGAGGAAGCGCTGCTCA

ATCGACTAAACATCAATCCTGTGACCCTGTCGAGTGGCTATAAAGACATAATTCTATGGTT

TTCATTCGGAGCATCTTGCTTCGTCCTGCTCGCAGTTGTGATGGGACTCTTCTTCTTTTGT

CTGAAAAATGGTAATATGCGGTGTACCATCTGCATT

881
ATGTACAAGATCGTGGTGATCATTGCTCTGCTTGGAGCCGTCAAGGGCCTGGATAAGATTT

GCCTGGGACATCACGCTGTCGCAAATGGCACCATCGTCAAGACTTTAACAAACGAGCAGGA

AGAGGTGACTAATGCCACTGAGACAGTAGAGAGCACTGGGATAAATAGGTTGTGCATGAAG

GGGAGAAAGCACAAGGACCTCGGAAACTGCCACCCAATTGGTATGCTAATCGGCACTCCAG

CTTGCGACTTGCATCTGACTGGCATGTGGGATACGCTGATAGAACGTGAGAATGCCATCGC

CTACTGTTATCCTGGGGCTACTGTGAACGTCGAGGCTTTAAGACAAAAGATCATGGAAAGT

GGCGGCATCAACAAGATAAGTACCGGGTTTACCTATGGGAGTAGTATTAATTCAGCAGGCA

CAACTCGGGCCTGCATGCGGAATGGGGGGAACAGCTTCTACGCCGAGCTAAAGTGGCTTGT

GAGCAAGTCCAAAGGGCAGAATTTCCCGCAGACCACCAATACTTACCGCAACACCGATACT

GCAGAACACTTAATAATGTGGGGCATCCACCATCCTAGTAGCACGCAAGAGAAGAATGACT

TGTACGGTACCCAGTCGCTAAGTATCAGCGTGGGCAGTTCGACATATAGAAATAACTTTGT

CCCTGTTGTGGGCGCGCGCCCTCAGGTAAATGGACAGTCTGGTCGGATCGACTTTCATTGG

ACCCTGGTGCAGCCAGGGGACAACATTACCTTTTCACATAATGGCGGTCTCATCGCACCCA

GTCGGGTCTCAAAGCTGATCGGGGGGGGGCTGGGCATTCAGTCAGACGCTCCCATAGATAA

TAATTGCGAGTCCAAGTGTTTCTGGAGAGGGGGCTCCATCAATACTAGGCTGCCTTTTCAG

AACCTCTCGCCCCGGACTGTGGGGCAGTGCCCCAAATACGTAAACCGAAGATCCCTAATGC

TGGCTACTGGGATGCGGAACGTACCTGAACTGATCCAGGGACGTGGGCTATTCGGAGCCAT

AGCTGGATTTCTGGAAAATGGCTGGGAGGGAATGGTTGATGGGTGGTACGGGTTTCGGCAC

CAGAATGCCCAGGGCACTGGGCAGGCTGCCGACTACAAATCAACTCAGGCCGCTATTGATC

AAATTACAGGTAAGCTCAACCGTCTAGTTGAGAAAACAAATACTGAGTTCGAAAGCATTGA

GTCTGAGTTTTCCGAGATTGAGCATCAGATCGGCAACGTTATTAATTGGACAAAGGACAGC

ATCACTGACATTTGGACATACCAGGCTGAACTTCTGGTTGCAATGGAAAATCAGCACACTA

TCGACATGGCTGATTCCGAGATGCTAAATCTCTACGAACGGGTCAGAAAGCAACTGCGGCA

GAATGCCGAGGAAGATGGAAAAGGCTGTTTCGAAATTTACCATGCTTGCGACGACTCCTGT

ATGGAGTCGATCAGGAACAACACCTACGATCACAGTCAGTATCGTGAGGAGGCACTTTTGA

ACCGTCTGAACATCAACCCCGTGACCCTTTCCTCCGGGTATAAAGATATCATCCTCTGGTT

CTCCTTCGGAGCATCTTGCTTCGTTCTCCTGGCCGTAGTGATGGGCCTGTTTTTTTTCTGC

CTGAAGAATGGGAACATGAGATGCACCATCTGCATT

882
ATGTATAAAATCGTTGTTATTATCGCCTTATTGGGCGCTGTGAAAGGGCTGGATAAAATCT

GCTTAGGGCATCATGCCGTTGCTAATGGAACGATTGTCAAAACCCTGACAAATGAGCAGGA

AGAGGTTACAAACGCTACTGAGACAGTGGAAAGCACCGGGATAAACCGGTTATGTATGAAA

GGTCGGAAGCACAAAGACCTAGGAAACTGCCACCCAATCGGCATGCTGATTGGTACCCCAG

CATGTGATCTGCACCTAACAGGAACCTGGGACACACTCATCGAGCGGGAAAACGCCATTGC

CTATTGTTATCCTGGCGCCACGGCAAACGTGGAGGCGCTGCGCCAGAAGATTATGGAGTCC

GGAGGTATCGACAAAATCTCTACCGGCTTTACGTACGGGAGTTCAATTAATTCAGCCGGAA

CAACCAGGGCCTGTATGCGCAATGGGGGGAATTCATTTTATGCCGAATTGAAGTGGCTCGT

CTCCAAGAGCAAAGGACAGAACTTTCCTCAGACAACGAATACTTACAGAAACACCGATACC

GCTGAGCACTTAATTATGTGGGGAATCCACCATCCTAGTTCAATCCAGGAAAAAAACGATC

TGTACGGGACACAGAGTCTCTCTATATCTGTTGGATCTTCCACCTATAGGAACAATTTTGT

TCCCGTGGTGGGCGCCAGGCCACAGGTGAATGGCCAGTCCGGGAGAATAGATTTTCACTGG

ACCCTTGTCCAGCCTGGGGATAACATTACTTTCAGCCACAACGGAGGCCTCATCGCGCCAA

GTAGGGTTTCCAAATTGATAGGGAGAGGCCTGGGGATTCAGTCCGACGCCCCCATAGATAA

TAATTGCGAATCAAAGTGTTTTTGGAGGGGGGGGTCCATCAACACAAGACTCCCCTTTCAG

AATCTGTCACCCCGAACCGTTGGCCAGTGTCCGAAATATGTGAACCGGAGGTCCTTAATGC

TGGCCACTGGAATGCGGAATGTGCCAGAGCTTATCCAAGGAAGGGGACTGTTTGGAGCAAT

CGCCGGCTTCCTAGAAAATGGCTGGGAGGGTATGGTGGACGGCTGGTATGGGTTTAGACAT

CAGAATGCCCAAGGAACCGGTCAGGCTGCGGACTATAAGTCCACCCAGGCCGCTATCGACC

AGATCACAGGTAAGCTCAACAGGCTGGTCGAGAAAACAAATACAGAGTTCGAGTCCATAGA

GTCCGAGTTCAGCGAAATAGAACACCAGATTGGAAATGTGATTAACTGGACGATGGATTCC

ATCACAGACATCTGGACCTACCAGGCAGAGTTACTGGTAGCTATGGAAAATCAGCATACAA

TCGACATGGCCGACTCTGAAATGCTAAATCTTTACGAGAGAGTTCGTAAACAGCTTCGCCA

GAACGCCGAGGAAGATGGGAAAGGGTGCTTTGAAATATATCACGCCTGTGATGATAGCTGT

ATGGAATCAATTAGAAATAACACATATGACCATTCTCAGTACAGAGAAGAGGCTCTGCTCA

ATAGGCTCAATATCAATCCAGTGACCCTATCCTCAGGATACAAGGACATCATACTCTGGTT

CAGTTTTGGCGCCTCTTGTTTCGTTCTGTTGGCCGTCGTCATGGGCCTCGTGTTTTTTTGT

TTAAAGAACGGCAATATGCGATGCACTATTTGCATC

883
ATGTATAAGATTGTAGTGATCATTGCTCTGCTCGGGGCCGTGAAGGGCCTGGATAAGATCT

GCCTGGGTCACCATGCCGTCGCAAACGGCACGATTGTGAAAACACTGACGAATGAGCAGGA

GGAGGTTACTAACGCTACAGAGACGGTCGAGTCAACTGGAATTAACCGGCTTTGCATGAAA

GGACGAAAACACAAAGATCTTGGGAACTGCCACCCAATTGGGATGCTGATTGGAACCCCAG

CCTGTGATCTGCACTTGACAGGCATGTGGGACACTCTGATCGAGAGGGAGAACGCAATAGC

CTATTGCTACCCTGGCGCAACCGTGAACGTGGAGGCCTTGCGCCAGAAGATAATGGAGTCT

GGGGGTATCAACAAGATCAGTACAGGTTTCACTTACGGCAGTTCTATTAACTCTGCCGGAA

CCACAAGAGCATGCATGCGTAACGGAGGCAATTCCTTCTATGCCGAACTTAAATGGCTTGT

CTCCAAGTCTAAGGGGCAGAACTTCCCCCAGACAACGAACACTTACCGCAATACGGACACA

GCAGAACACTTAATCATGTGGGGGATCCATCATCCCAGCAGTACACAGGAGAAAAATGACT

TATACGGAACTCAGAGCTTAAGTATCTCCGTGGGCAGTAGTACTTACAGAAACAATTTCGT

CCCTGTCGTAGGCGCTAGGCCTCAGGTGAATGGCCAGTCTGGACGCATCGACTTCCACTGG

ACTCTGGTTCAACCAGGGGACAACATCACTTTCTCGCACAACGGAGGGTTGATCGCACCCA

GTCGGGTGAGTAAACTTATCGGGAGAGGCCTCGGAATACAATCCGATGCTCCCATCGATAA

TAATTGCGAGAGCAAATGTTTTTGGCGCGGAGGGAGCATTAATACACGCCTGCCTTTTCAG

AACTTGTCACCACGAACCGTGGGCCAATGCCCCAAGTACGTCAACAGAAGATCATTGATGC

TGGCTACTGGCATGAGGAATGTGCCTGAATTAATTCAAGGAAGAGGACTGTTCGGCGCCAT

CGCAGGTTTTCTTGAGAATGGGTGGGAGGGGATGGTGGATGGTTGGTATGGCTTTCGCCAC

CAGAATGCGCAGGGCACAGGGCAGGCTGCTGATTACAAGTCAACCCAGGCAGCCATCGACC

AGATTACTGGCAAGCTGAATAGGCTCGTTGAAAAAACCAACACAGAGTTCGAGTCAATTGA

GAGCGAGTTTTCTGAAATAGAGCATCAGATAGGCAACGTGATAAATTGGACCAAAGACAGT

ATCACAGACATTTGGACTTATCAAGCAGAGTTGTTGGTAGCCATGGAGAATCAACACACGA

TCGACATGGCCGATAGCGAAATGCTAAACCTGTATGAGCGCGTTCGGAAGCAGCTGCGCCA

GAACGCAGAGGAGGACGGGAAGGGCTGTTTCGAAATTTATCACGCTTGTGACGACAGTTGC

ATGGAATCCATCCGCAACAATACGTATGATCACTCCCAGTATAGAGAAGAGGCCCTCTTGA

ATAGACTGAACATCAACCCAGTGACTCTGAGCTCAGGTTACAAGGACATTATTCTCTGGTT

TTCTTTCGGAGCTTCCTGCTTTGTCCTCCTCGCTGTCGTAATGGGACTCTTTTTCTTTTGC

CTGAAGAACGGGAATATGAGATGCACCATTTGCATC

884
ATGTATAAGATTGTCGTTATCATTGCACTGCTTGGTGCAGTTAAAGGGCTGGATAAGATTT

GTCTAGGGCACCATGCCGTGGCCAACGGGACCATAGTGAAAACACTGACCAATGAACAGGA

GGAAGTCACCAATGCTACTGAAACTGTTGAATCCACCGGCATTAACCGGCTGTGTATGAAG

GGCCGCAAACACAAGGACCTGGGCAATTGTCACCCCATCGGCATGTTGATTGGCACCCCTG

CATGTGACTTGCACCTCACTGGCATGTGGGACACACTGATCGAACGAGAGAATGCAATTGC

CTACTGCTACCCTGGTGCCACAGTGAACGTGGAGGCTCTTCGACAAAAGATCATGGAAAGC

GGGGGCATCAATAAGATTTCTACAGGGTTCACATACGGTTCATCTATTAACAGTGCAGGAA

CGACCCGGGCCTGCATGCGGAACGGCGGCAATTCATTCTACGCCGAATTGAAGTGGTTGGT

GTCGAAGAGTAAGGGCCAGAATTTCCCGCAGACAACAAACACATATCGCAATACGGATACG

GCCGAACACTTAATCATGTGGGGAATCCATCACCCTTCTTCTACCCAAGAAAAGAACGATC

TATACGGCACCCAGTCCCTGTCAATTTCAGTGGGTTCTTCGACATACAGGAACAATTTCGT

CCCTGTTGTCGGCGCACGGCCCCAGGTAAATGGGCAGAGTGGGAGAATCGACTTCCACTGG

ACTCTGGTGCAGCCTGGGGATAACATTACGTTCAGTCACAATGGCGGCCTCATAGCCCCAT

CACGGGTGAGCAAACTAATAGGACGAGGCCTGGGAATACAGTCCGACGCCCCAATCGATAA

CAACTGCGAGTCAAAATGTTTCTGGCGAGGAGGCAGCATCAATACAAGACTCCCTTTTCAG

AATCTTAGTCCAAGGACAGTCGGACAGTGCCCAAAATACGTGAATAGACGCAGCTTGATGT

TGGCAACGGGGATGCGCAATGTTCCTGAGCTCATACAGGGTAGAGGCCTATTTGGGGCCAT

CGCAGGCTTCCTGGAAAACGGATGGGAGGGCATGGTGGACGGATGGTACGGATTTCGTCAC

CAGAATGCTCAAGGCACAGGTCAGGCTGCCGACTACAAATCTACCCAGGCCGCCATCGACC

AGATTACCGGAAAACTGAACAGGTTGGTGGAAAAAACGAATACAGAATTCGAGAGTATTGA

GAGTGAGTTCTCCGAGATCGAGCACCAAATCGGCAATGTGATTAATTGGACAAAAGACTCC

ATTACCGACATCTGGACTTACCAGGCTGAGTTGCTCGTGGCGATGGAAAACCAGCATACCA

TTGATATGGCCGATAGTGAAATGCTGAATCTGTACGAACGCGTCAGAAAACAGCTACGACA

GAACGCGGAGGAGGATGGGAAGGGCTGCTTCGAAATCTACCACGCTTGCGATGATTCCTGC

ATGGAGTCCATTCGGAATAACACGTACGACCATAGCCAATACAGGGAGGAGGCGCTCCTAA

ATAGGTTGAACATAAATCCAGTTACCCTTTCTTCCGGTTACAAGGATATTATCCTGTGGTT

CTCCTTTGGCGCCTCTTGTTTCGTCCTTCTCGCCGTGGTGATGGGATTATTTTTCTTCTGC

CTCAAGAATGGAAATATGCGGTGTACGATCTGTATT

885
ATGTACAAAGTGGTGGTGATAATTGCTCTCCTCGGCGCCGTGAAAGGCCTCGACAAGATAT

GTCTGGGCCATCATGCAGTCGCCAACGGGACCATCGTCAAGACCCTCACCAATGAACAGGA

GGAGGTTACCAACGCCACTGAAACAGTTGAGTCTACTGGAATCAATCGACTGTGTATGAAG

GGGAGAAAACACAAGGACCTCGGTAACTGTCATCCTATTGGGATGCTTATTGGAACACCAG

CCTGTGATTTACATCTGACGGGCACCTGGGACACCCTGATCGAAAGAGAGAACGCAATTGC

ATATTGCTACCCTGGCGCTACAGTTAATGTTGAAGCTCTGAGGCAAAAAATCATGGAGTCC

GGGGGAATCGACAAGATTTCAACCGGCTTCACGTACGGCAGTTCTATCAACAGCGCAGGTA

CCACAAGGGCCTGTATGAGGAACGGCGGAAATAGCTTTTACGCCGAACTGAAATGGCTGGT

GTCAAAGAACAAAGGACAGAACTTCCCTCAGACCACAAACACATACCGGAATACAGACACC

GCAGAGCACCTTATAATGTGGGGCATCCATCATCCCTCCTCTATTCAGGAGAAGAATGATC

TGTACGGTACACAGTCACTCTCCATCTCTGTAGGCAGCTCCACATATCGTAATAACTTTGT

CCCAGTTGTGGGAGCCCGACCACAGGTGAACGGCCAATCAGGACGAATTGATTTTCACTGG

ACCCTCGTGCAGCCTGGCGACAACATAACATTCAGCCATAATGGAGGACTCATCGCCCCGT

CCCGCGTGTCTAAATTAATCGGTCGGGGGCTGGGGATCCAGTCCGATGCGCCCATAGATAA

CAACTGCGAGTCTAAATGCTTCTGGCGGGGGGGGTCCATTAACACTCGACTGCCCTTCCAA

AATCTCAGCCCACGCACAGTAGGCCAGTGTCCAAAATATGTCAATAGACGTTCTCTAATGC

TCGCCACCGGAATGAGAAATGTGCCTGAGCTGATTCAGGGAAGGGGATTGTTTGGAGCTAT

AGCCGGATTCTTGGAGAATGGTTGGGAAGGCATGGTCGACGGATGGTATGGATTCAGACAC

CAGAACGCTCAAGGCACGGGCCAAGCAGCCGACTACAAATCCACCCAAGCAGCCATTGATC

AGATTACAGGGAAGCTGAACAGGCTGGTGGAGAAGACAAACACAGAATTCGAAAGTATTGA

GAGCGAATTTTCCGAGATCGAGCACCAGATCGGTAATGTGATCAATTGGACCATGGACAGC

ATAACGGACATCTGGACCTATCAGGCCGAACTCCTGGTCGCAATGGAAAATCAGCATACTA

TCGACATGGCCGATAGTGAGATGTTGAACCTGTATGAGAGGGTTCGTAAGCAGCTCCGTCA

GAACGCAGAGGAGGATGGTAAAGGATGTTTTGAGATCTATCACGCATGCGATGACAGTTGC

ATGGAATCTATTCGTAACAATACGTACGATCATAGCCAATACCGCGAAGAAGCATTGCTGA

ACCGGCTGAATATTAACCCCGTGACATTATCCTCCGGGTACAAGGACATAATTCTGTGGTT

CTCCTTCGGGGCCAGCTGCTTCGTGCTGCTCGCTGTGGTCATGGGCCTGGTCTTCTTCTGC

CTGAAAAATGGCAACATGCGATGCACAATATGCATC

886
ATGTACAAAATCGTCGTGATCATAGCACTGCTGGGAGCCGTAAAGGGTCTCGATAAGATCT

GCCTAGGGCACCACGCAGTAGCCAATGGAACCATAGTAAAAACACTCACGAATGAGCAGGA

GGAAGTTACCAACGCCACTGAAACCGTCGAATCTACCGGGATCAACAGATTGTGCATGAAA

GGGCGCAAACACAAGGATCTGGGGAACTGTCACCCAATCGGAATGCTAATTGGAACACCAG

CCTGTGATCTCCATTTGACAGGAATGTGGGATACACTGATAGAGCGTGAAAACGCCATAGC

GTACTGTTACCCCGGCGCCACAGTGAACGTGGAAGCGTTACGACAAAAGATAATGGAATCA

GGAGGCATTAATAAGATAAGTACTGGCTTTACCTACGGGTCTTCAATCAACTCTGCCGGGA

CAACTAGAGCCTGTATGAGAAACGGTGGTAATTCGTTCTACGCTGAGCTGAAGTGGCTGGT

GTCCAAGAGCAAAGGGCAGAATTTCCCACAGACTACAAACACCTACAGAAACACCGATACA

GCCGAACACCTCATCATGTGGGGAATTCATCACCCAAGCAGCACGCAGGAGAAGAACGATT

TATATGGGACACAAAGCTTGTCAATTTCCGTGGGCAGTAGCACATACAGAAATAACTTCGT

GCCAGTGGTAGGGGGGGGTCCCCAGGTGAATGGACAGTCCGGCCGCATTGATTTCCATTGG

ACCCTCGTGCAGCCGGGAGACAACATCACATTCAGCCACAATGGTGGACTAATCGCCCCAT

CCCGCGTCTCCAAACTGATCGGGAGAGGACTGGGTATTCAGTCTGACGCGCCCATTGATAA

TAACTGCGAGTCAAAATGTTTCTGGCGAGGGGGGAGCATCAATACACGATTGCCTTTTCAG

AACTTGTCCCCTCGGACTGTCGGCCAGTGCCCTAAGTATGTGAATAGGAGATCCCTGATGC

TTGCCACCGGAATGAGAAACGTTCCTGAGCTGATTCAGGGTCGCGGTCTATTTGGCGCAAT

CGCCGGCTTTCTCGAAAACGGCTGGGAGGGCATGGTAGATGGTTGGTACGGTTTCCGGCAT

CAGAACGCCCAGGGAACTGGACAAGCCGCTGATTACAAGTCAACACAGGCAGCAATCGACC

AAATTACTGGCAAACTGAACCGGCTTGTCGAGAAAACCAATACTGAATTTGAGTCAATTGA

ATCCGAATTTAGTGAAATTGAACACCAGATCGGCAATGTGATTAATTGGACTAAGGACTCT

ATTACCGATATTTGGACTTATCAGGCTGAGCTACTTGTGGCCATGGAGAACCAGCACACAA

TCGACATGGCTGATAGTGAGATGCTGAACCTTTACGAGCGAGTCAGGAAACAGCTGAGACA

GAACGCCGAGGAGGATGGAAAAGGCTGTTTCGAAATCTATCATGCTTGCGACGATTCATGC

ATGGAGTCAATCAGAAATAACACCTACGACCACAGTCAGTATCGCGAGGAAGCTTTACTCA

ACAGACTCAATATCAATCCTGTAACATTGTCTTCCGGCTACAAAGACATCATCCTGTGGTT

CTCATTTGGAGCCAGCTGCTTTGTCTTGTTGGCTGTGGTGATGGGACTGTTCTTTTTTTGC

CTCAAAAATGGCAATATGAGATGTACCATTTGTATC

887
ATGTATAAGATCGTGGTGATCATTGCTCTCCTGGGCGCAGTAAAGGGTCTTGACAAGATAT

GTCTTGGACACCATGCAGTGGCAAACGGCACAATTGTTAAAACACTCACCAACGAGCAGGA

GGAAGTGACCAATGCCACTGAAACAGTAGAGTCCACGGGGATCAATAGGCTCTGCATGAAA

GGGAGGAAGCACAAAGATCTGGGTAATTGCCATCCAATCGGAATGCTCATAGGAACACCAG

CCTGCGACCTTCATCTGACCGGTATGTGGGATACATTGATCGAACGCGAGAACGCGATAGC

TTACTGCTATCCCGGCGCCACAGTGAATGTGGAGGCCCTCCGACAGAAGATTATGGAGTCG

GGCGGTATTAACAAAATATCCACTGGTTTTACTTACGGATCTTCGATCAATTCCGCAGGAA

CAACACGAGCCTGTATGAGGAATGGCGGGAACTCTTTCTATGCTGAGCTTAAGTGGCTCGT

TTCTAAGTCTAAGGGCCAGAATTTCCCTCAGACGACTAATACCTACAGGAACACGGATACA

GCAGAGCACCTGATTATGTGGGGTATCCATCATCCATCTAGCACCCAAGAGAAAAATGATC

TGTATGGGACCCAGTCACTTTCCATTAGCGTGGGCTCTAGTACATACAGGAATAACTTTGT

ACCTGTGGTGGGGGCTAGACCGCAAGTGAATGGCCAGAGCGGCCGGATTGACTTCCACTGG

ACTTTAGTCCAGCCTGGAGATAACATTACATTTTCACACAACGGCGGGCTGATTGCGCCTA

GTAGGGTGAGCAAACTTATTGGACGAGGATTAGGAATCCAGAGCGATGCCCCCATCGACAA

CAACTGCGAAAGCAAATGCTTTTGGAGGGGCGGTTCAATCAACACCCGTCTCCCTTTCCAG

AATCTGTCCCCCCGTACCGTGGGGCAGTGTCCAAAGTATGTTAATAGAAGGTCACTGATGC

TAGCCACTGGCATGCGGAATGTGCCCGAGCTGATCCAGGGCCGTGGGCTGTTCGGTGCTAT

TGCAGGATTTCTGGAAAATGGCTGGGAAGGCATGGTAGATGGTTGGTACGGTTTTCGGCAC

CAGAACGCCCAGGGGACCGGACAGGCGGCCGACTACAAATCCACTCAAGCCGCTATCGATC

AGATTACGGGAAAGCTAAATAGACTGGTCGAAAAAACCAACACAGAGTTCGAATCCATAGA

GTCCGAGTTCTCTGAGATCGAGCACCAGATCGGGAATGTGATCAACTGGACTAAGGATAGC

ATTACTGATATTTGGACCTACCAGGCAGAGCTGCTGGTCGCCATGGAAAACCAACACACAA

TCGATATGGCGGATAGTGAGATGCTGAACCTGTATGAAAGAGTGAGGAAACAGCTGAGACA

GAACGCAGAGGAGGACGGAAAAGGGTGCTTCGAGATTTACCACGCTTGCGATGACAGTTGC

ATGGAAAGCATACGCAATAACACTTACGACCATAGTCAATACCGGGAGGAGGCTCTCCTGA

ATAGGCTCAACATCAATCCTGTGACCCTGAGTTCAGGTTACAAAGATATCATCTTGTGGTT

TTCATTTGGGGCGAGCTGCTTTGTGCTGCTGGCCGTCGTGATGGGCCTGTTCTTTTTTTGC

CTGAAGAATGGCAATATGCGATGTACCATATGCATC

888
ATGTATAAAATAGTGGTGATCATAGCACTCTTGGGAGCCGTAAAGGGACTGGATAAGATCT

GCCTGGGGCATCATGCCGTTGCCAACGGCACAATCGTGAAGACCCTTACTAATGAACAAGA

AGAAGTGACCAACGCTACTGAGACCGTTGAATCCACCGGCATTAACCGCCTCTGCATGAAG

GGGCGGAAGCACAAAGATCTCGGCAACTGCCACCCAATCGGGATGCTGATTGGGACCCCCG

CGTGCGATTTACATCTGACAGGTATGTGGGATACATTAATTGAAAGGGAGAACGCGATTGC

GTACTGCTACCCTGGGGCTACCGTGAATGTCGAAGCACTCCGACAGAAGATCATGGAATCT

GGGGGGATCAACAAGATCTCGACCGGTTTTACCTATGGGAGTTCTATTAACTCTGCTGGCA

CAACACGGGCATGTATGCGCAATGGGGGGAATAGTTTCTATGCTGAGCTCAAATGGCTTGT

ATCCAAATCCAAAGGGCAGAATTTCCCCCAGACTACAAATACCTACAGAAACACGGATACC

GCTGAGCACCTAATAATGTGGGGAATTCACCATCCTTCCTCAACCCAAGAGAAGAATGATC

TTTACGGGACCCAGAGTCTCAGCATTAGCGTCGGATCGTCGACTTACCGCAACAATTTCGT

CCCAGTGGTCGGAGCCAGGCCACAGGTCAACGGCCAGTCTGGCAGGATAGACTTCCACTGG

ACCCTGGTTCAGCCTGGAGATAACATTACATTTAGTCATAACGGCGGCCTGATTGCTCCCA

GTCGCGTGTCTAAACTAATCGGACGTGGTCTGGGCATCCAATCCGATGCGCCGATCGACAA

TAACTGCGAAAGCAAGTGCTTTTGGAGGGGAGGATCCATCAATACACGACTTCCCTTCCAG

AACCTATCACCAAGAACCGTAGGCCAGTGCCCGAAATACGTGAATCGACGGAGTCTGATGC

TGGCCACCGGCATGAGAAATGTGCCTGAGCTGATTCAGGGACGAGGACTGTTTGGCGCAAT

CGCTGGCTTCCTGGAAAACGGGTGGGAAGGAATGGTCGATGGCTGGTACGGATTTCGGCAT

CAGAACGCCCAAGGCACTGGCCAAGCCGCCGACTACAAGAGTACACAGGCCGCAATCGACC

AGATCACAGGTAAGTTGAATCGATTGGTGGAGAAGACCAACACTGAGTTCGAATCTATTGA

GAGCGAATTCAGTGAAATCGAGCATCAGATCGGAAATGTGATAAATTGGACCAAGGACTCA

ATTACCGACATCTGGACATACCAAGCAGAGCTTCTGGTTGCGATGGAAAACCAACACACAA

TTGATATGGCAGATTCCGAGATGCTGAACCTCTATGAGCGCGTCAGGAAGCAATTGAGGCA

GAATGCAGAGGAAGATGGAAAAGGGTGTTTCGAAATCTATCACGCCTGCGACGACAGTTGC

ATGGAATCGATCCGCAACAATACTTATGACCACTCACAGTATAGAGAGGAGGCTTTGCTGA

ACCGGTTAAATATCAATCCTGTCACGTTGAGTAGCGGCTACAAGGATATCATCCTATGGTT

TTCCTTCGGGGCGTCTTGTTTTGTGCTGTTAGCAGTGGTGATGGGACTTTTCTTCTTCTGT

CTTAAAAACGGAAACATGAGATGTACCATCTGCATA

889
ATGTATAAGATCGTGGTTATCATTGCCCTCCTGGGCGCAGTCAAAGGCTTGGACAAAATCT

GTCTCGGACATCACGCCGTTGCTAACGGCACCATTGTTAAGACCCTTACCAACGAGCAGGA

AGAAGTGACAAATGCAACAGAAACGGTCGAGTCCACAGGCATCAACCGGCTCTGTATGAAA

GGTCGGAAGCACAAGGATCTTGGGAATTGTCACCCAATAGGTATGCTGATTGGCACTCCTG

CCTGCGATCTTCATCTAACTGGGATGTGGGACACCCTTATCGAACGAGAAAATGCCATTGC

ATACTGTTACCCTGGTGCTACTGTCAACGTGGAAGCCCTCAGGCAGAAAATAATGGAGTCG

GGTGGGATAAATAAGATAAGCACCGGGTTCACTTACGGCAGCTCCATTAATTCCGCCGGAA

CTACGCGCGCCTGTATGAGAAATGGCGGTAACTCCTTCTACGCGGAGCTGAAGTGGCTGGT

CTCGAAGTCTAAAGGCCAGAACTTCCCCCAAACAACAAACACCTACAGGAACACTGACACC

GCTGAACACCTCATCATGTGGGGCATTCACCACCCCTCCAGCACCCAGGAAAAAAACGACT

TATACGGCACACAGAGCCTTAGTATAAGCGTGGGAAGCTCAACTTATCGCAACAATTTTGT

TCCAGTGGTGGGCGCAAGACCGCAGGTGAACGGGCAAAGTGGTCGAATTGACTTTCACTGG

ACACTCGTGCAACCAGGCGACAATATCACCTTTTCACATAACGGAGGACTCATTGCCCCGT

CCCGCGTCAGTAAGTTAATTGGGGGGGGCCTCGGCATTCAGTCAGACGCCCCTATCGATAA

CAACTGTGAATCTAAGTGCTTTTGGAGAGGAGGGTCTATAAACACGAGACTCCCCTTCCAG

AACTTATCGCCTCGCACTGTGGGTCAGTGTCCTAAGTACGTTAACAGACGTTCCCTGATGC

TGGCAACGGGAATGAGAAACGTTCCAGAACTGATCCAGGGGCGCGGGTTATTTGGGGCTAT

CGCTGGTTTCCTGGAGAATGGCTGGGAGGGAATGGTTGACGGGTGGTATGGGTTTCGTCAC

CAAAACGCCCAGGGGACGGGGCAGGCCGCAGATTACAAGTCTACTCAGGCGGCCATAGACC

AGATTACAGGCAAGCTGAATAGACTGGTCGAGAAGACGAACACGGAGTTTGAGTCTATTGA

GTCCGAGTTCAGCGAGATTGAACATCAGATAGGTAATGTTATCAATTGGACAAAGGATAGC

ATAACCGATATTTGGACATACCAGGCAGAGTTACTGGTTGCAATGGAAAATCAACACACTA

TTGACATGGCTGACTCAGAGATGCTCAACTTATACGAACGAGTGAGGAAGCAACTACGACA

GAACGCCGAAGAGGACGGAAAGGGTTGCTTTGAGATCTACCACGCCTGCGACGATAGCTGC

ATGGAGAGCATCAGGAATAATACTTACGATCACTCACAGTACAGGGAGGAAGCCCTCTTGA

ACCGTCTGAACATAAATCCTGTCACACTTAGCTCCGGCTACAAAGATATCATCTTGTGGTT

TTCATTTGGCGCGTCATGTTTTGTGCTCCTAGCTGTGGTCATGGGCTTATTCTTTTTCTGC

CTGAAAAATGGCAATATGAGGTGCACAATTTGTATC

890
ATGTACAAGATAGTGGTAATTATCGCGCTGTTGGGCGCAGTGAAAGGACTGGACAAGATCT

GCCTGGGTCACCACGCCGTGGCCAATGGAACGATTGTGAAAACCTTGACAAACGAACAGGA

GGAAGTGACCAACGCAACGGAGACTGTGGAATCAACTGGTATCAATCGGCTATGCATGAAA

GGCAGAAAACACAAAGATTTGGGCAATTGCCATCCCATCGGTATGCTCATTGGAACACCCG

CTTGCGACCTCCACCTGACTGGGACGTGGGATACTTTGATCGAGAGGGAGAATGCTATTGC

CTACTGTTACCCTGGCGCAACAGCTAATGTGGAGGCCCTCCGGCAGAAGATCATGGAGAGC

GGTGGAATCGATAAGATTTCAACTGGCTTCACATACGGCTCCTCGATCAATTCTGCCGGCA

CTACTCGGGCTTGCATGAGAAACGGAGGAAATAGTTTCTATGCTGAGCTGAAGTGGCTTGT

GAGTAAATCTAAAGGCCAGAACTTTCCCCAGACAACCAACACATACCGGAATACCGACACC

GCAGAACATCTGATTATGTGGGGGATACATCACCCATCTAGCATTCAGGAGAAAAACGACC

TGTATGGCACTCAGTCCCTGAGCATTTCCGTAGGCTCTAGTACCTACCGGAACAATTTCGT

ACCCGTCGTAGGCGCCCGCCCCCAAGTGAACGGCCAGTCCGGTCGAATTGACTTCCACTGG

ACACTAGTGCAGCCTGGGGACAATATCACATTTAGTCATAACGGCGGACTGATCGCCCCAT

CGAGAGTGTCTAAACTGATCGGACGCGGGCTGGGTATTCAATCAGATGCCCCCATCGACAA

CAACTGCGAAAGCAAATGCTTCTGGCGCGGCGGGAGTATAAACACCCGGCTTCCATTTCAG

AACCTCTCTCCTCGGACCGTCGGACAGTGCCCGAAATATGTGAACCGCAGGTCACTGATGT

TGGCAACTGGAATGAGGAATGTCCCCGAATTAATACAGGGCCGGGGCTTATTCGGAGCCAT

CGCAGGCTTCCTGGAGAACGGTTGGGAAGGCATGGTGGATGGATGGTATGGATTTAGACAT

CAAAATGCACAGGGAACAGGCCAGGCTGCCGACTACAAATCTACCCAGGCCGCGATAGATC

AAATTACAGGAAAGTTGAACAGGCTGGTGGAAAAGACTAATACCGAATTTGAATCAATCGA

GTCCGAATTCTCCGAAATCGAACACCAGATCGGGAATGTCATTAACTGGACTATGGATTCT

ATAACCGATATCTGGACATACCAGGCAGAACTGCTAGTAGCCATGGAAAATCAACACACGA

TCGACATGGCTGACTCAGAGATGCTGAACCTCTACGAGCGGGTCAGAAAACAGCTCCGACA

GAATGCAGAGGAAGACGGAAAAGGCTGTTTTGAGATTTACCACGCTTGCGACGACTCTTGT

ATGGAGTCCATACGGAATAATACGTACGATCACTCACAGTATAGGGAGGAGGCCCTACTGA

ATAGACTGAACATCAACCCCGTCACGCTGTCTAGTGGCTATAAAGACATCATTTTGTGGTT

TTCTTTCGGAGCAAGTTGCTTCGTGCTCCTCGCCGTGGTGATGGGACTCGTGTTCTTCTGC

TTGAAAAATGGGAATATGCGATGTACCATTTGCATC

891
ATGTATAAAATTGTCGTGATAATCGCTCTGCTTGGCGCTGTGAAGGGCTTAGATAAGATAT

GCCTCGGACACCATGCAGTTGCCAATGGCACGATAGTGAAAACATTGACCAACGAGAAAGA

AGAGGTGACCAACGCTACCGAGACTGTGGAATCCACCGGTCTGAATAGACTCTGCATGAAG

GGGCGGAAGCATAAGGACTTGGGCAATTGTCACCCAATTGGGATGCTCATCGGATCGCCCG

CATGTGACCTGCATCTCACTGGGACCTGGGACACATTGATTGAACGAGAGAACGCTATTGC

GTACTGCTACCCGGGAGCCACTGTTAATGGTGAAGCACTTCGCCAGAAGATCATGGAGTCC

GGAGGCATCGACAAGATCAGCACTGGATTCACCTATGAAAGTTCCATAAACTCCGCAGGCA

CTACAAGAGCTTGCATGAGGAACGGCGGGAATTCATTCTACGCTGAGCTCAAGTGGCTGGT

GAGCAAATCTAAGGGACAGAATTTTCCACAGACAACCAACACGTATCGAAACACCGATACT

GCAGAGCACCTTATTATGTGGGGCATTCACCATCCATCCAGCACGCAGGAGAAAAACGATC

TGTACGGTACCCAGTCTCTGTCTATCTCCGTGGGATCTTCCACCTATAGAAACAATTTCGT

ACCCGTAGTGGGGGCCAGGCCGCAAGTCAATGGCCAATCTGGCCGCATCGACTTCCACTGG

ACCTTGGTACAGCCTGGCGACAATATCACATTCTCACACAACGGCGGCTTGATTGCTCCGA

GCCGGGTGTCTAAGTTGATCGGAAGAGGGCTCGGCATCCAGTCTGATGCCCCTATCGATAA

CAACTGTGAAAGTAAGTGCTTCTGGCGGGGCGGAAGTATTAATACCAGGCTGCCATTCCAG

AATCTTTCCCCCCGCACCGTCGGTCAATGTCCCAAATACGTGAACAAGCGAAGCCTGATGT

TGGCCACTGGGATGCGAAATGTTCCTGAGCTGATGCAGGGACGAGGACTGTTCGGAGCCAT

TGCTGGGTTCCTCGAGAACGGCTGGGAGGGCATGGTTGACGGTTGGTACGGATTCAGACAC

CAAAACGCGCAGGGCACGGGTCAAGCCGCCGATTACAAATCTACACAGGCGGCGATTGACC

AGATTACAGGTAAGCTGAATAGACTCGTGGAGAAAACAAACACCGAATTCGAGTCAATAGA

GTCCGAGTTCTCTGAGATAGAACACCAGATCGGCAATGTAATCAACTGGACGAAAGACTCT

ATTACAGACATTTGGACCTACCAGGCGGAACTCCTGGTGGCTATGGAGAACCAGCATACTA

TTGATATGGCTGACTCTGAGATGCTGAATCTGTACGAGCGCGTCCGGAAGCAACTGCGTCA

GAATGCAGAGGAAGACGGAAAGGGGTGCTTTGAGATTTATCACGCCTGCGATGATAGCTGT

ATGGAGTCAATCCGAAACAACACTTATGATCATAGCCAGTACCGTGAGGAGGCACTACTGA

ACAGGCTGAACATTAATCCCGTCACCCTGAGCAGTGGCTACAAAGACATCATCTTGTGGTT

CTCTTTCGGCGCCTCATGCTTTGTCTTGCTTGCCGTAGTCATGGGTTTAGTGTTTTTTTGT

CTCAAAAACGGTAATATGCGGTGTACAATTTGCATC

892
ATGTACAAAATCGTGGTAATAATCGCGCTTCTGGGCGCAGTGAAGGGCCTGGACAAAATCT

GCCTGGGACATCACGCTGTGGCAAATGGGACCATCGTGAAAACCCTCACCAATGAGAAAGA

GGAAGTGACCAACGCCACGGAAACAGTAGAAAGCACAGGATTAAACCGGCTTTGCATGAAA

GGCCGCAAGCACAAAGACCTGGGCAATTGCCATCCCATCGGGATGCTGATCGGATCACCCG

CCTGTGATCTCCATCTAACCGGCACCTGGGACACTCTGATCGAAAGGGAGAACGCGATCGC

TTACTGCTACCCAGGCGCTACCGTTAATGGCGAGGCTTTGCGCCAGAAGATCATGGAGTCA

GGAGGGATCGACAAGATTAGTACAGGCTTCACCTATGAGAGCTCGATCAATTCCGCAGGAA

CAACCCGGGCCTGCATGAGAAACGGCGGCAATTCCTTTTACGCCGAACTTAAGTGGCTGGT

GAGTAAAAGCAAGGGACAAAACTTCCCACAGACCACCAACACCTACCGTAATACCGATACC

GCTGAGCATTTGATCATGTGGGGAATTCATCATCCCAGCTCCACACAGGAGAAGAATGATC

TTTACGGGACACAGTCACTCAGCATTTCCGTCGGTTCGAGCACTTACCGGAATAATTTTGT

CCCTGTGGTCGGCGCCCGCCCTCAGGTCAACGGGCAGAGCGGCAGGATCGACTTCCATTGG

ACACTAGTTCAGCCTGGCGACAATATTACCTTTAGCCACAACGGCGGTCTGATCGCTCCTT

CGCGTGTCTCAAAACTGATCGGTCGGGGGTTAGGCATTCAAAGCGATGCCCCCATTGACAA

CAATTGTGAATCAAAATGTTTCTGGCGCGGTGGCTCCATTAACACCAGACTGCCTTTCCAG

AATCTTAGCCCAAGAACAGTCGGCCAGTGCCCCAAGTATGTGAATAAAAGGTCTCTGATGC

TGGCTACCGGCATGCGTAATGTCCCAGAGCTTATGCAAGGCAGAGGACTGTTCGGCGCAAT

CGCGGGTTTTCTTGAGAACGGATGGGAGGGTATGGTTGACGGATGGTACGGTTTCCGGCAC

CAGAACGCCCAGGGAACTGGCCAGGCCGCAGACTACAAGTCCACACAGGCGGCAATTGACC

AGATCACTGGCAAACTTAACCGTCTAGTGGAAAAAACCAACACTGAATTCGAGAGTATCGA

GAGTGAGTTCTCCGAGATTGAGCATCAGATAGGGAACGTGATCAATTGGACAAAGGACTCT

ATTACAGACATTTGGACTTATCAGGCCGAGCTGCTGGTGGCCATGGAGAATCAGCACACAA

TCGACATGGCCGACTCTGAGATGCTCAATCTTTATGAACGGGTGCGCAAACAGCTGCGACA

GAATGCAGAGGAGGATGGGAAGGGGTGCTTCGAAATCTATCACGCATGCGACGATTCATGT

ATGGAGTCCATCCGGAATAATACATACGATCATAGTCAGTATCGCGAGGAAGCCTTATTGA

ACAGGCTGAACATTAATCCAGTCACTCTCAGCTCAGGGTACAAGGACATCATTTTGTGGTT

CTCATTTGGAGCATCGTGCTTCGTGCTCCTTGCGGTTGTCATGGGTCTGGTCTTTTTTTGC

CTGAAGAATGGAAACATGAGATGCACCATATGTATC

893
ATGTACAAGATCGTGGTTATTATCGCCCTCCTGGGTGCTGTGAAAGGACTGGATAAGATCT

GTCTGGGACACCATGCTGTGGCAAACGGCACTATTGTTAAAACTCTGACTAACGAGCAAGA

AGAAGTTACTAATGCTACTGAGACGGTCGAAAGTACTGGAATCAATCGGCTTTGCATGAAG

GGCCGGAAGCACAAAGACCTTGGGAATTGCCATCCTATTGGGATGCTGATCGGTACCCCCG

CATGTGACCTCCATCTGACTGGGATGTGGGACACGCTCATCGAGAGGGAGAATGCCATCGC

TTACTGTTATCCCGGAGCCACAGTTAATGTCGAAGCCTTACGACAAAAAATCATGGAGTCA

GGTGGTATCAACAAGATCAGCACCGGTTTCACATACGGCTCCTCCATCAACTCAGCAGGTA

CTACACGCGCATGCATGCGGAACGGCGGAAACAGTTTCTACGCCGAGCTGAAGTGGCTTGT

TAGCAAATCAAAAGGTCAGAATTTCCCTCAGACTACAAACACATACCGTAACACCGATACC

GCAGAACATCTCATCATGTGGGGTATTCATCACCCAAGTTCCACACAAGAAAAGAACGATC

TCTACGGGACTCAATCACTCTCCATCTCCGTCGGATCCTCTACATACCGTAACAACTTTGT

TCCTGTGGTGGGCGCAAGACCTCAGGTTAATGGGCAGTCAGGTAGAATTGACTTCCATTGG

ACACTGGTGCAACCTGGGGACAACATCACCTTCTCCCACAACGGCGGTCTGATCGCGCCCT

CAAGGGTCTCCAAGCTGATAGGTCGGGGCCTCGGCATCCAGAGCGACGCCCCGATCGATAA

CAATTGTGAAAGCAAATGCTTCTGGAGGGGGGGCTCTATCAACACACGACTGCCTTTCCAG

AATCTCTCTCCCCGAACCGTGGGACAGTGTCCTAAATACGTCAACAGGAGGAGCCTGATGC

TCGCCACAGGTATGCGTAATGTCCCAGAGCTGATTCAAGGCCGCGGGTTATTTGGCGCGAT

AGCCGGTTTTCTGGAGAACGGCTGGGAGGGAATGGTGGATGGCTGGTATGGATTCCGGCAC

CAAAATGCTCAGGGAACTGGTCAAGCAGCCGACTATAAATCCACGCAGGCCGCCATCGACC

AGATTACTGGCAAATTAAATCGCCTCGTGGAGAAGACTAACACTGAGTTCGAATCCATAGA

GTCAGAGTTTTCCGAGATCGAGCACCAGATCGGTAATGTGATTAATTGGACCAAAGATTCC

ATCACTGATATTTGGACATACCAAGCCGAGCTCTTGGTGGCTATGGAGAACCAACATACTA

TCGATATGGCCGATAGCGAAATGCTCAACCTGTACGAGAGGGTCAGGAAACAGCTTCGCCA

GAACGCAGAGGAAGACGGCAAAGGATGTTTCGAGATTTACCATGCGTGCGACGATTCTTGC

ATGGAGAGCATTCGGAACAACACGTATGATCACAGCCAGTACAGGGAAGAGGCACTTCTGA

ACCGCCTGAACATAAATCCAGTCACATTGAGCAGCGGCTACAAAGACATTATACTCTGGTT

TTCATTTGGGGCCTCTTGCTTCGTCCTGCTGGCAGTGGTGATGGGATTGTTCTTCTTTTGC

CTCAAAAACGGTAATATGCGCTGCACCATTTGCATC

894
ATGTATAAAATAGTGGTCATTATTGCTCTTCTCGGTGCAGTTAAGGGTCTGGATAAGATCT

GCTTGGGCCATCACGCTGTTGCCAATGGGACCATAGTGAAGACCTTGACAAACGAACAGGA

AGAAGTGACAAACGCCACCGAAACCGTCGAATCCACTGGCATTAACCGGCTGTGCATGAAG

GGGCGAAAACACAAAGACCTCGGTAATTGTCATCCCATAGGGATGCTGATTGGTACACCTG

CCTGTGACCTGCACCTGACCGGAATGTGGGATACGCTCATTGAACGAGAGAATGCCATCGC

CTATTGTTATCCGGGTGCAACTGTGAACGTGGAGGCCCTGCGTCAAAAGATCATGGAAAGC

GGGGGGATAAACAAAATCTCGACCGGTTTCACGTATGGTTCAAGCATTAACAGTGCCGGCA

CAACAAGGGCATGCATGCGCAATGGAGGTAACTCATTCTACGCCGAGCTCAAGTGGCTCGT

GAGCAAGTCCAAAGGACAGAACTTCCCTCAGACTACCAATACCTACCGTAATACTGACACA

GCGGAACATCTGATAATGTGGGGCATTCACCATCCTTCCTCGACCCAGGAAAAAAACGACC

TGTACGGAACCCAGTCTCTCAGCATCTCCGTCGGGAGTAGCACTTACCGCAATAACTTTGT

GCCCGTCGTGGGAGCCCGCCCCCAAGTGAATGGACAGAGGGGGAGGATTGATTTCCACTGG

ACCCTCGTGCAACCGGGGGACAATATTACTTTCAGTCATAATGGAGGACTGATCGCCCCCA

GTCGCGTGTCCAAACTGATCGGAAGGGGGCTCGGTATCCAATCCGATGCACCGATAGATAA

CAATTGCGAGTCTAAGTGTTTCTGGCGTGGAGGCAGTATTAACACTCGGTTACCTTTTCAA

AATCTTTCGCCGCGGACCGTTGGCCAGTGCCCTAAGTACGTCAATCGTAGGTCCCTCATGC

TAGCCACTGGAATGCGCAACGTCCCGGAGCTCATCCAGGGGCGTGGATTGTTTGGAGCTAT

TGCTGGCTTCCTGGAGAATGGCTGGGAGGGAATGGTCGATGGCTGGTACGGGTTTCGGCAT

CAGAACGCACAGGGCACAGGCCAGGCCGCCGACTACAAGTCTACACAGGCCGCCATTGATC

AGATCACCGGGAAGCTGAACCGGCTGGTTGAGAAGACCAATACCGAATTTGAGAGCATCGA

ATCGGAATTCTCGGAAATCGAGCACCAGATTGGTAACGTAATAAACTGGACAAAGGATTCC

ATTACGGACATTTGGACGTATCAAGCAGAACTGCTCGTGGCCATGGAGAACCAACACACGA

TTGATATGGCAGATTCAGAAATGCTAAACTTGTACGAACGGGTCAGAAAGCAGCTGCGTCA

GAATGCTGAGGAGGACGGCAAGGGATGTTTTGAGATCTACCATGCTTGCGATGATTCTTGT

ATGGAGTCCATTCGGAATAACACGTACGACCATTCACAATATCGGGAGGAAGCACTTTTAA

ACCGGCTGAATATCAATCCAGTCACACTGAGTTCAGGCTACAAGGATATCATATTATGGTT

CTCATTCGGTGCCTCATGCTTCGTCCTTTTGGCAGTGGTGATGGGTTTGTTCTTTTTTTGT

CTGAAGAATGGCAACATGAGATGTACAATATGCATC

895
ATGTACAAGATTGTGGTGATCATCGCACTCCTTGGAGCTGTGAAAGGACTGGACAAAATTT

GTCTGGGACATCACGCTGTGGCTAACGGGACCATCGTGAAAACCCTAACGAATGAGCAGGA

AGAAGTCACAAATGCGACAGAGACAGTGGAATCCACTGGTATCAATCGACTGTGTATGAAG

GGCAGAAAACACAAGGACCTGGGCAATTGTCATCCGATAGGCATGTTAATCGGGACACCAG

CCTGTGACCTGCATCTGACCGGCATGTGGGATACTCTTATTGAGCGGGAGAACGCAATAGC

TTACTGCTACCCAGGCGCTACTGTGAATGTGGAAGCTCTGCGTCAGAAAATTATGGAGAGC

GGAGGGATTAACAAAATCTCTACTGGTTTCACATACGGCAGCAGTATTAACTCAGCCGGCA

CCACCAGGGCGTGTATGCGGAATGGTGGAAACTCATTTTATGCTGAGCTTAAATGGCTTGT

CTCAAAGTCGAAAGGCCAGAACTTCCCCCAGACTACAAACACCTACAGGAATACGGATACA

GCCGAGCATCTCATTATGTGGGGAATACATCATCCCAGCAGTACCCAGGAGAAAAACGATC

TGTACGGAACCCAGAGTCTCTCAATCTCAGTGGGATCAAGCACGTACAGAAATAATTTCGT

CCCTGTGGTGGGAGCCAGACCCCAGGTAAATGGACAGTCAGGGCGCATTGACTTTCACTGG

ACTCTCGTCCAGCCAGGAGACAATATCACATTTAGTCACAATGGCGGCCTGATAGCTCCTT

CTCGAGTGAGCAAACTGATCGGACGGGGTCTCGGTATCCAGTCCGACGCCCCCATCGATAA

CAACTGCGAGTCGAAGTGCTTCTGGCGTGGCGGGTCAATTAACACAAGACTACCATTTCAG

AACCTTTCACCTAGAACCGTGGGACAGTGCCCAAAGTACGTCAATAGACGGAGCCTGATGC

TGGCCACAGGGATGAGGAACGTTCCTGAACTGATACAAGGTCGGGGGCTTTTCGGTGCCAT

CGCAGGTTTTCTCGAGAACGGCTGGGAGGGCATGGTGGATGGGTGGTATGGGTTTAGGCAC

CAAAATGCACAAGGGACCGGCCAGGCCGCCGATTATAAGTCTACGCAAGCCGCCATTGACC

AGATCACTGGGAAGCTTAATAGGTTAGTAGAGAAGACAAATACCGAATTCGAGAGTATTGA

GTCAGAATTCTCCGAGATCGAGCACCAGATAGGCAACGTCATTAATTGGACAAAGGACTCT

ATTACCGACATTTGGACGTATCAAGCCGAACTTCTGGTGGCAATGGAAAATCAGCACACAA

TCGACATGGCCGACTCGGAGATGTTGAACTTATATGAAAGGGTGCGCAAACAGCTGCGCCA

GAACGCTGAAGAAGACGGTAAGGGATGCTTTGAGATCTATCATGCCTGCGATGATTCCTGT

ATGGAGTCGATAAGAAACAATACCTATGACCATAGCCAGTACCGGGAAGAAGCCCTCCTGA

ACAGACTGAATATTAACCCCGTTACCTTGTCCTCAGGATACAAGGACATTATCCTGTGGTT

TTCTTTCGGTGCTAGCTGTTTCGTGCTGCTCGCCGTCGTAATGGGGTTGTTTTTCTTCTGC

CTCAAAAACGGTAACATGCGATGCACCATTTGCATT

896
ATGTATAAGATCGTCGTCATTATCGCTCTCCTCGGAGCCGTGAAAGGTCTTGACAAAATTT

GTCTGGGCCATCACGCAGTGGCCAATGGGACCATCGTGAAGACGCTGACGAACGAGAAAGA

AGAGGTGACAAACGCTACTGAGACGGTCGAGAGCACCGGACTCAATAGGTTGTGCATGAAA

GGACGAAAGCATAAAGATCTGGGCAACTGTCACCCCATCGGGATGCTGATTGGCTCCCCAG

CCTGCGACTTACACCTGACTGGCACCTGGGATACACTGATCGAGCGCGAGAACGCCATTGC

CTACTGTTACCCCGGCGCTACAGTGAATGGTGAGGCCCTTCGCCAAAAGATTATGGAGTCA

GGCGGAATAGATAAGATCTCTACAGGCTTCACTTATGAGAGTTCGATTAACTCGGCCGGGA

CAACTAGGGCGTGTATGCGGAATGGCGGGAATTCCTTCTATGCTGAGCTTAAGTGGTTGGT

TTCCAAGAGCAAGGGGCAGAATTTTCCTCAGACCACCAACACCTATCGAAACACAGACACC

GCTGAACACCTCATCATGTGGGGCATTCACCACCCATCTTCAACCCAGGAGAAGAACGACC

TCTACGGTACTCAAAGCCTTAGTATCAGCGTGGGGTCATCTACCTACCGGAACAATTTTGT

GCCCGTGGTGGGAGCGCGCCCTCAAGTGAACGGACAAAGTGGCAGGATCGATTTCCATTGG

ACTTTGGTCCAGCCTGGTGACAACATCACATTCAGTCACAACGGTGGCCTGATCGCACCGT

CCAGAGTTTCCAAACTGATCGGCCGGGGTCTAGGGATTCAGAGCGACGCCCCTATTGATAA

CAACTGCGAGTCAAAATGCTTCTGGAGGGGGGGCTCCATTAACACTCGACTGCCCTTTCAG

AATCTGTCACCCCGAACCGTGGGTCAGTGTCCTAAGTACGTGAACAAGAGATCACTCATGC

TTGCCACTGGGATGCGCAATGTGCCCGAGCTCATGCAGGGAAGAGGACTGTTCGGAGCGAT

TGCTGGGTTTCTGGAAAATGGGTGGGAAGGGATGGTAGATGGATGGTACGGATTTCGTCAT

CAAAACGCACAGGGCACTGGACAAGCGGCGGACTATAAGTCAACTCAGGCTGCCATAGACC

AAATAACCGGGAAACTAAACCGGCTCGTCGAGAAGACCAACACCGAATTTGAATCTATCGA

GTCGGAATTTAGCGAGATTGAGCACCAGATAGGAAATGTTATCAATTGGACCAAGGACTCC

ATTACGGATATTTGGACTTACCAGGCGGAGCTGCTGGTTGCCATGGAGAATCAGCACACTA

TTGACATGGCCGATAGTGAGATGTTGAATTTGTACGAAAGAGTGCGCAAGCAGCTGAGGCA

GAACGCTGAAGAGGACGGTAAGGGATGCTTCGAAATTTATCACGCATGCGATGATTCCTGC

ATGGAATCGATCAGAAACAATACATATGATCATTCTCAATACCGGGAGGAGGCTTTGCTCA

ACCGCCTGAATATAAATCCTGTGACTCTCAGTTCGGGCTATAAAGACATCATCCTGTGGTT

CTCTTTTGGCGCCTCCTGCTTTGTCCTGCTGGCGGTGGTGATGGGACTCGTCTTCTTCTGC

CTAAAGAATGGCAACATGCGGTGTACAATCTGTATT

An alignment of amino acid sequences of hemagglutinin proteins from influenza A H7N9 strains are shown relative to a consensus sequence in FIG. 22. An alignment of amino acid sequences of hemagglutinin proteins from influenza A H10N8 strains are shown relative to a consensus sequence in FIG. 23.

Aspects of the present disclosure provide RNA polynucleotides encoding an influenza hemagglutinin protein or a fragment thereof. The terms “hemagglutinin,” “hemagglutinin protein,” and “HA” may be used interchangeably throughout and refer to a hemagglutinin protein that may be present on the surface of an influenza virus. On the viral surface, the hemagglutinin protein is present in homotrimers, each monomer of which is comprised of two subunits, HA1 and HA2, linked by a disulfide bond. Structurally, hemagglutinin proteins are comprised of several domains: a globular head domain, a stalk domain (also referred to as a stem domain), a transmembrane domain, and a cytoplasmic domain. It is generally though that during infection of a host cell (e.g., a eukaryotic cell such as a human cell) with an influenza virus, the hemagglutinin protein recognizes and binds to sialic acid of a receptor on the surface of a host cell facilitating attachment of the virus to the host cell (Gamblin et al., 2004; Ha et al., 2000). Following endocytosis of the virus and acidification of the endosome, the hemagglutinin protein undergoes a pH-dependent conformational change that allows for the hemagglutinin protein to facilitate fusion of the viral envelope with the endosome membrane of host cell and entry of the viral nucleic acid into the host cell.

In general, influenza viruses are classified based on the amino acid sequence of the viral hemagglutinin protein and/or the amino acid sequence of the viral neuraminidase (NA). In some embodiments, the hemagglutinin is of the subtype H1, H2, H3, H4, H5, H6, H7, H8, H9, H10, H11, H12, H13, H14, H15, H16, H17, or H18. The differences in amino acid sequences between hemagglutinin proteins of different subtypes are largely found within the sequence of the head domain of the protein. The amino acid sequence of the stalk domain is considered to be more conserved between hemagglutinin subtypes compared to sequence of the head domain. Domains of the hemagglutinin protein may be predicted using conventional methods known in the art.

Many naturally occurring and experimentally derived antibodies that bind and neutralize the hemagglutinin protein are thought to bind epitopes within the head domain of hemagglutinin and prevent or reduce interaction of hemagglutinin with sialic acid on receptors of host cells, thereby preventing or reducing infection of the cell. Alternatively or in addition, neutralizing antibodies may prevent or reduce fusion of the virus membrane with the membrane of the endosome. Such antibodies may bind epitopes within the stalk domain, thereby inhibiting the conformations change of the protein.

In some embodiments, the RNA polynucleotides described herein encode a fragment of a hemagglutinin protein, such as a truncated hemagglutinin protein. In some embodiments, the fragment is a headless hemagglutinin, meaning the fragment does not comprise the head domain In some embodiments, the fragment comprises a portion of the head domain. In some embodiments, the fragment is a stalk fragment (see, e.g., Mallajosyula et al. PNAS (2014) E2514-E2523). In some embodiments, fragment does not comprise the cytoplasmic domain. In some embodiments, the fragment does not comprise the transmembrane domain. In such embodiments, the fragment may be referred to as a soluble or secreted hemagglutinin protein or fragment.

In some embodiments, the RNA polypeptide encodes a hemagglutinin protein or fragment thereof that is at least 90% (e.g., 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%) identical to a hemagglutinin protein provided by an amino acid sequence in Table 14-16. The terms “identical” or percent “identity” in the context of two or more polypeptide sequences refer to two or more sequences that are the same. The percent identity between polypeptide sequences may be performed using algorithms known in the art, such as BLAST and CLUSTAL.

The sequence of the hemagglutinin protein or fragment thereof may be obtained from any source. In some embodiments, the sequence of the hemagglutinin protein or fragment thereof is from an avian influenza strain. In some embodiments, the sequence of the hemagglutinin protein or fragment thereof is from an avian influenza strain that is capable of or at risk of infecting human subjects. In some embodiments, the sequence of the hemagglutinin protein or fragment thereof is from a porcine influenza strain. In some embodiments, the sequence of the hemagglutinin protein or fragment thereof is from a porcine influenza strain that is capable of or at risk of infecting human subjects.

In any of the embodiments described herein, the sequence of the hemagglutinin or fragment thereof may be modified or optimized (such as codon optimized) for expression in a particular cell or host organism.

Methicillin-Resistant Staphylococcus aureus (MRSA)

MRSA is the most common invasive bacterial infection with an incidence of 20-100 per 100,000 persons. It is responsible for ˜20,000 deaths in US alone

Risk factors for MRSA include healthcare exposure, antibiotic use, and HIV. It is a common complication of joint replacement surgery which then requires removal and replacement of the joint. Symptoms include pneumonia, skin and soft-tissue infections, osteomyelitis (e.g., prostheses), endocarditis, bacteremia and sepsis.

Current treatment includes intravenous anti-staphylococal antibiotics (e.g., Vancomycin, Zyvox, Cubicin), contact precautions, and managment of sepsis (Goal-directed therapy+/−ICU admission).

The MRSA HA pathogens have multiple antigens so a combinatorial approach is an important principle to combat multi-drug resistance. Cell culture limits number of antigens in traditionally-produced vaccines making the present NAV approach superior.

MRSA antigens may include but not limited to NDM1, mecA, all b-lactamases (antibiotic resistance); Protein A mutant (immune escape); SDRD/SDRE (adherence); IsdA or IsdB (Lactoferrin excape, Fe transport); TSST, a-HL, and PVL(toxins).

In one embodiment, the NAVs of the present invention may comprise a multivalent vaccine, e.g., comprising a polynucleotide which encodes at least two MRSA antigens, including but not limited to NDM-1 and SpAmut.

In one embodiment, the SpA antigen or loss of function mutant SpAKKAA of MRSA is encoded by a polynucleotide of a NAV. Kim et al. (J. Exp. Med. Vol. 207 No. 9; 1863-1870; the contents of which are herein incorporated by reference in its entirety) describes that the mutation of the staphylococcal protein A (SpA) at five Ig-binding domains resulted in variant SpAKKAA which cannot bind to Fcγ or Fab V_H3 and promote cell apoptosis. Immunization of mice with SpAKKAA raised antibodies was found to protect mice against challenge with highly virulent MRSA strains and even enabled MRSA-challenged mice to mount antibody responses to different staphylococcal antigens. Falugi et al. (mBio 4(5):e00575-13. doi:10.1128/mBio.00575-13; the contents of which are herein incorporated by reference in its entirety) found that the SpAKKAA mutant elicited B cell responses to key virulence antigens that protected animals against a lethal S. aureus challenge and the SpAKKAA mutant was able to elicit an adaptive response that protected against recurrent infection. Schineewind et al. describes a SpA antigen or loss of function mutant of SpA in International Patent Publication Nos. WO2011127032, WO2011005341, WO2012003474, WO2012034067 and WO2013025834 and US Patent Publication Nos. US20130136746, US20120114686, US20130171183 and US20130230550, the contents of each of which are herein incorporated by reference in their entirety. As a non-limiting example, the SpA mutant may comprise at least one substitution in the amino acid sequence that disrupts the Fc binding and at least one substitution in the amino acid sequence that disrupts the VH3 binding (see e.g., International Publication No. WO2011005341 and US Patent publication No. US20120114686, the contents of each of which are herein incorporated by reference in its entirety). As another non-limiting example, the SpA mutant may comprise a substitution in the D domain of a SpA sequence at positions 9, 10, 36 and 37 of the SpA sequence (see e.g., International Patent Publication Nos. WO2011127032, WO2012003474 and WO2012034067 and US Patent Publication Nos. US20130136746, US20130171183 and US20130230550, the contents of each of which are herein incorporated by reference in their entirety). The amino acids at positions 9 and 10 may be substituted for glycine and the amino acids at positions 36 and 37 may be substituted for serine (see e.g., International Patent Publication Nos. WO2011127032 and WO2012003474 and US Patent Publication Nos. US20130136746 and US20130171183, the contents of each of which are herein incorporated by reference in their entirety). As yet another non-limiting example, the SpA mutant may comprise a substitution at position 9, 10, 36 and 37 of SEQ ID NO: 2 described in International Patent Publication Nos. WO2011127032 and WO2012003474 and US Patent Publication Nos. US20130136746 and US20130171183, the contents of each of which are herein incorporated by reference in their entirety.

SpA-binding to B-cell surface V(H)3 leads to B-cell receptor crosslinking followed by B-cell apoptosis, clonal B-cell deletion and block of affinity maturation and B-cell memory. SpA-binding to Fcg at the FcR-binding site of secreted antibodies inhibits activation of effector cells critical for bacterial clearance and adaptive immunity.

SpAKKAA is a loss-of-function mutant of SpA without a functional Fcg and V(H)3 binding site.

Vaccination with SpAKKAA allows clonal B-cell expansion and sufficient time for antibody affinity maturation leading to B-cell clones with higher affinity to SpA epitopes than Fcg or V(H)3 binding of SpA. This enables antibody binding to SpA through affinity-matured CDRs with Fc portions freely available for effector cell activation and B-cell memory creation.

Thus, SpAKKAA immunization enable MRSA-challenged subjects to mount antibody responses to many different staphylococcal antigens.

In one embodiment, the NAV is a multi-valent vaccine with SpAKKAA as the center antigen. This provides a key advantage over inactivated, whole MRSA vaccines currently in clinical development.

In one embodiment, the MRSA NAVs are used to target at risk populations such as those having linezolid-resistant joint/bone infections; chronic disease; healthcare workers and to prevent outbreak of resistant strains.

MRSA toxins such as PVL, a-HL, TSST-1 may be encoded by the NAVs of the invention. Alternatively, any of the beta-lactamase genes may be targeted in a manner which reduces their ability to protect the bacteria thereby rendering it more susceptible to traditional antibiotic attack. Such targeting of the lactamase enzymes may be personalized to a particular subject where a sample is obtained and the unique lactamase sequence is determined through standard techniques in the art. Inhibitors of the unique lactamase sequence can then be designed creating a personalized medicine or vaccine.

Dengue

Dengue fever is a mosquito-borne virus and is epidemic (SE Asia) and endemic (Sub-Saharan Africa. India). As much as 40% of world's population is at risk with over 100 million infections per year according to the World Health Organization. There have been about 1-2 million clinically documented cases. The mortality rate depends on access to healthcare and can reach as high as 20%.

Symptoms include acute onset fevers with terrible joint and muscle pain for 5-7 days, followed by weeks of lethargy and fatigue. Dehydration and hemorrhage are the main drivers of mortality, hence need for access to IV fluids to avoid shock. Supportive care includes fluid resuscitation but prevention is the primary means of limiting the impact of virus (e.g., mosquito control, personal protection).

For Dengue fever, disease characteristics requires a neutralizing—but not enhancing—antibody response to the four most critical Dengue serotypes (DENV1-4). Therefore a multivalent antigen targeting key proteins/protein domains of four serotypes of Dengue virus (DENV 1-4) would have value as a vaccine.

In one embodiment, NAVs of the invention comprise one or more polynucleotides which encode the E protein domain III (DENV1-4 tandem mRNA), the E protein domain I/II hinge region (DENV1-4 individual mRNAs), the prM protein (DENV1-4 tandem or individual mRNAs) and the C protein (DENV1-4 tandem or single mRNAs).

In one embodiment, the most potent NAV vaccine is selected by measuring the antibody titer in Balb/c mice followed by tests of selected vaccines in Dengue disease models. Upon rescue in disease model, crossreactivity analysis in in-vitro viral assays to ensure activity of multi-valent vaccine against all serotypes is performed.

In some embodiments cross-neutralizing Ab-titers agains each of the four Dengue strains (DENV1-4) in a virus neutralization assay are tested either in vitro or in vivo as in (BMC Microbiol. 2014; 14: 44; and Immunology. 2012 July; 136 (3):334-43), the contents of which are incorporated herein by reference.

In some embodiments, neutralizing vs enhancing Ab-titers is evaluated and in another embodiment the RNAV are tested in humanized mouse model for Dengue disease (J Virol. 2014 February; 88(4):2205-18, then contents of which are incorporated herein by reference in their entirety).

The NAV targeting Dengue is referred to as a multi-genotype antigen NAV.

Enterotoxic E. Coli (ETEC)

ETEC is the most common cause of diarrhea in the developing world with between 300k-500k deaths per year. Transmission is via fecal-oral transmission (water, food). Symptoms include secretory diarrhea (mediated by two toxins: heat-stable and heat-labile), abdominal pain and cramping, nausea and vomiting. Generally symptoms last less than 1 week, and rarely greater than 2 weeks. The resultant dehydration is the primary cause of more serious sequelae. Currently supportive care and fluid resuscitation are the treatment where generally an uncomplicated infection resolves on its own.

Previous ETEC vaccines were based on a single antigen or had a sole focus on toxin neutralization that was not effective in providing long-lasting immunity.

According to the present invention three pathways are addressed by the selected antigens in a multivalent approach: (1) Toxins: Sta3 and eltA/eltB; (2) Adhesion proteins critical for delivery of toxins to the endothelium: EatA, etpA, and etpB; and (3) Proteins enabling colonialization: cssA.

The ETEC NAV of the present invention is designed to enable long-term protection against ETEC. And even to provide prophylactic treatment such as for travelers.

Clostridium difficile

C. difficile causes an increasingly common diarrheal illness associated with key risk factors including exposure to a healthcare setting (e.g., hospitalization, nursing home residence), and antibiotics (esp. amoxicillin, clindamycin).

Symptoms include recurrent diarrhea and Pseudomembranous colitis. Current treatment includes diagnostics with toxin and reflex antigen and/or treatment with metronidazole and vanocmycin.

The present invention provides a trivalent antigen approach to the treatment of C. difficile infection. The antigens encoded include toxin A (enterotoxin; CD Toxin A 136754); toxin b (cytotoxin; CD Toxin B 136755), and binary toxin (cdtB; CD cdtB 136757).

In some embodiments, the multivalent NAV prevents C. Difficile infection among patients: (1) receiving certain medications (antibiotics, PPIs) or (2) with healthcare exposure (hospitalized, nursing home etc) in a manner which blocks the effects of the organisms' toxin and key virulence factors.

Tuberculosis

Tuberculosis is an infectious disease caused by various strains of mycobacteria, usually Mycobacterium tuberculosis. Symptoms include a chronic cough with blood-tinged sputum, fever, night sweats, and weight loss.

The current challenges for the development of a vaccine against TB are (i) three different disease states requiring a different set of antigens: pre-infection (prophylactic vaccine), latent infection (therapeutic vaccine) and active infection (therapeutic vaccine); and (ii) different set of adjuvants critical to induce a protective while not overshooting immune response; and (iii) an unclear understanding on the necessary immune response to clear the infection.

Therefore it will be required to combine different sets of cytokines as an adjuvant with a different set of antigens dependent on the disease state. The following cytokines provide a potential adjuvant arm of the vaccine: GM-CSF, IL-17, IFNg, IL-15, IL-2, IL-21, Anti-PD1/2, lactoferrin. The following antigens represent a non-exhaustive list: Ag85A (Rv3804c). Ag85B (Rv 1886c), TB10.4 (Rv0288), ESAT6(Rv3785), Rv2660L, Rv3619, Rv1813c, Rv3620c, Rv2608, Rv1196, Rv0125, and MT401.

Middle-East Respiratory Syndrome Coronavirus (MERS-CoV)

MERS-CoV, previously known as the Novel Coronavirus or SARS-like virus, is a member of the coronavirus family. Symptoms are similar to SARS infections and include coughing, production of mucous, shortness of breath, malaise—a general feeling of being unwell, chest pain, fever, diarrhea (in some cases) and renal (kidney) failure. Human enterovirus 71 and Human enterovirus 68

Enterovirus 71 (EV-71) is one of the major causative agents for hand, foot and mouth disease (HFMD), and is sometimes associated with severe central nervous system diseases. The Enterovirus 71 (EV71) infection may be asymptomatic.

Enterovirus 68 (EV68, EV-D68) is a member of the Picornaviridae family, an enterovirus (a group of ssRNA viruses containing the polioviruses, coxsackievirus, and echoviruses). First isolated in 1962, it has been on a worldwide upswing in the last few years. It may be involved in cases of a recent outbreak of polio-like disease in California.

Antigens

Antigens of the present invention include polypeptides, peptides and/or polypeptides of interest and are encoded by the polynucleotides of the invention. Polynucleotides encoding such antigens of the invention are described in more detail below under “Design, Synthesis and Quantitation of NAV Polynucleotides”.

III. Design, Synthesis and Quantification of NAV Polynucleotides

According to the present invention, the polynucleotides encode at least one polypeptide of interest, e.g., an antigen. Antigens of the present invention may be wild type (i.e., derived from the infectious agent) or modified (e.g., engineered, designed or artificial). They may have any combination of the features described herein.

The present invention provides nucleic acid molecules, specifically polynucleotides which, in some embodiments, encode one or more peptides or polypeptides of interest. Such peptides or polypeptides, according to the invention may serve as an antigen or antigenic molecule. The term “nucleic acid,” in its broadest sense, includes any compound and/or substance that comprise a polymer of nucleotides. These polymers are often referred to as polynucleotides.

Exemplary nucleic acids or polynucleotides of the invention include, but are not limited to, ribonucleic acids (RNAs), deoxyribonucleic acids (DNAs), threose nucleic acids (TNAs), glycol nucleic acids (GNAs), peptide nucleic acids (PNAs), locked nucleic acids (LNAs, including LNA having a β-D-ribo configuration, α-LNA having an α-L-ribo configuration (a diastereomer of LNA), 2′-amino-LNA having a 2′-amino functionalization, and 2′-amino-α-LNA having a 2′-amino functionalization), ethylene nucleic acids (ENA), cyclohexenyl nucleic acids (CeNA) or hybrids or combinations thereof.

In one embodiment, linear polynucleotides encoding one or more antigens of the NAVs of the present invention which are made using only in vitro transcription (IVT) enzymatic synthesis methods are referred to as “IVT polynucleotides.”

In another embodiment, the polynucleotides of the present invention which have portions or regions which differ in size and/or chemical modification pattern, chemical modification position, chemical modification percent or chemical modification population and combinations of the foregoing are known as “chimeric polynucleotides.” A “chimera” according to the present invention is an entity having two or more incongruous or heterogeneous parts or regions. As used herein a “part” or “region” of a polynucleotide is defined as any portion of the polynucleotide which is less than the entire length of the polynucleotide.

In yet another embodiment, the polynucleotides of the present invention that are circular are known as “circular polynucleotides” or “circP.” As used herein, “circular polynucleotides” or “circP” means a single stranded circular polynucleotide which acts substantially like, and has the properties of, an RNA. The term “circular” is also meant to encompass any secondary or tertiary configuration of the circP.

In some embodiments, the polynucleotide includes from about 30 to about 100,000 nucleotides (e.g., from 30 to 50, from 30 to 100, from 30 to 250, from 30 to 500, from 30 to 1,000, from 30 to 1,500, from 30 to 3,000, from 30 to 5,000, from 30 to 7,000, from 30 to 10,000, from 30 to 25,000, from 30 to 50,000, from 30 to 70,000, from 100 to 250, from 100 to 500, from 100 to 1,000, from 100 to 1,500, from 100 to 3,000, from 100 to 5,000, from 100 to 7,000, from 100 to 10,000, from 100 to 25,000, from 100 to 50,000, from 100 to 70,000, from 100 to 100,000, from 500 to 1,000, from 500 to 1,500, from 500 to 2,000, from 500 to 3,000, from 500 to 5,000, from 500 to 7,000, from 500 to 10,000, from 500 to 25,000, from 500 to 50,000, from 500 to 70,000, from 500 to 100,000, from 1,000 to 1,500, from 1,000 to 2,000, from 1.000 to 3,000, from 1,000 to 5,000, from 1.000 to 7,000, from 1,000 to 10,000, from 1,000 to 25,000, from 1,000 to 50,000, from 1,000 to 70,000, from 1,000 to 100,000, from 1,500 to 3,000, from 1,500 to 5,000, from 1,500 to 7,000, from 1,500 to 10,000, from 1,500 to 25,000, from 1,500 to 50,000, from 1,500 to 70,000, from 1,500 to 100,000, from 2,000 to 3,000, from 2,000 to 5,000, from 2,000 to 7,000, from 2,000 to 10,000, from 2,000 to 25,000, from 2,000 to 50,000, from 2,000 to 70,000, and from 2,000 to 100,000).

In one embodiment, the polynucleotides of the present invention may encode at least one peptide or polypeptide of interest. In another embodiment, the polynucleotides of the present invention may be non-coding.

In one embodiment, the length of a region encoding at least one peptide polypeptide of interest of the polynucleotides present invention is greater than about 30 nucleotides in length (e.g., at least or greater than about 35, 40, 45, 50, 55, 60, 70, 80, 90, 100, 120, 140, 160, 180, 200, 250, 300, 350, 400, 450, 500, 600, 700, 800, 900, 1,000, 1,100, 1,200, 1,300, 1,400, 1,500, 1,600, 1,700, 1,800, 1,900, 2,000, 2,500, and 3,000, 4,000, 5,000, 6,000, 7,000, 8,000, 9,000, 10,000, 20,000, 30,000, 40,000, 50,000, 60,000, 70,000, 80,000, 90,000 or up to and including 100,000 nucleotides). As used herein, such a region may be referred to as a “coding region” or “region encoding.”

In one embodiment, the polynucleotides of the present invention is or functions as a messenger RNA (mRNA). As used herein, the term “messenger RNA” (mRNA) refers to any polynucleotide which encodes at least one peptide or polypeptide of interest and which is capable of being translated to produce the encoded peptide polypeptide of interest in vitro, in vivo, in situ or ex vivo.

In one embodiment, the polynucleotides of the present invention may be structurally modified or chemically modified. As used herein, a “structural” modification is one in which two or more linked nucleosides are inserted, deleted, duplicated, inverted or randomized in a polynucleotide without significant chemical modification to the nucleotides themselves. Because chemical bonds will necessarily be broken and reformed to effect a structural modification, structural modifications are of a chemical nature and hence are chemical modifications. However, structural modifications will result in a different sequence of nucleotides. For example, the polynucleotide “ATCG” may be chemically modified to “AT-5meC-G”. The same polynucleotide may be structurally modified from “ATCG” to “ATCCCG”. Here, the dinucleotide “CC” has been inserted, resulting in a structural modification to the polynucleotide.

In one embodiment, the polynucleotides of the present invention, such as IVT polynucleotides or circular polynucleotides, may have a uniform chemical modification of all or any of the same nucleoside type or a population of modifications produced by mere downward titration of the same starting modification in all or any of the same nucleoside type, or a measured percent of a chemical modification of all any of the same nucleoside type but with random incorporation, such as where all uridines are replaced by a uridine analog, e.g., pseudouridine. In another embodiment, the polynucleotides may have a uniform chemical modification of two, three, or four of the same nucleoside type throughout the entire polynucleotide (such as all uridines and all cytosines, etc. are modified in the same way).

When the polynucleotides of the present invention are chemically and/or structurally modified the polynucleotides may be referred to as “modified polynucleotides.”

In one embodiment, the polynucleotides of the present invention may include a sequence encoding a self-cleaving peptide. The self-cleaving peptide may be, but is not limited to, a 2A peptide. As a non-limiting example, the 2A peptide may have the protein sequence: GSGATNFSLLKQAGDVEENPGP (SEQ ID NO: 963), fragments or variants thereof. In one embodiment, the 2A peptide cleaves between the last glycine and last proline. As another non-limiting example, the polynucleotides of the present invention may include a polynucleotide sequence encoding the 2A peptide having the protein sequence GSGATNFSLLKQAGDVEENPGP (SEQ ID NO: 963) fragments or variants thereof.

One such polynucleotide sequence encoding the 2A peptide is GGAAGCGGAGCTACTAACTTCAGCCTGCTGAAGCAGGCTGGAGACGTGGA GGAGAACCCTGGACCT (SEQ ID NO: 964). The polynucleotide sequence of the 2A peptide may be modified or codon optimized by the methods described herein and/or are known in the art.

In one embodiment, this sequence may be used to separate the coding region of two or more polypeptides of interest. As a non-limiting example, the sequence encoding the 2A peptide may be between a first coding region A and a second coding region B (A-2Apep-B). The presence of the 2A peptide would result in the cleavage of one long protein into protein A, protein B and the 2A peptide. Protein A and protein B may be the same or different peptides or polypeptides of interest. In another embodiment, the 2A peptide may be used in the polynucleotides of the present invention to produce two, three, four, five, six, seven, eight, nine, ten or more proteins.

Polynucleotide Architecture

Traditionally, the basic components of an mRNA molecule include at least a coding region, a 5′UTR, a 3′UTR, a 5′ cap and a poly-A tail. The IVT polynucleotides of the present invention may function as mRNA but are distinguished from wild-type mRNA in their functional and/or structural design features which serve to overcome existing problems of effective polypeptide production using nucleic-acid based therapeutics. It is to be understood that the antigens of the NAVs of the present invention may be encoded by IVT polynucleotides, as described herein.

FIG. 1 shows a primary construct 100 of an IVT polynucleotide of the present invention. Such polynucleotides are useful in NAV compositions, RNAV compositions or mRNA vaccines. As used herein, “primary construct” refers to a polynucleotide of the present invention which encodes one or more polypeptides of interest and which retains sufficient structural and/or chemical features to allow the polypeptide of interest encoded therein to be translated.

According to FIGS. 1A and 1B, the polynucleotide 100 here contains a first region of linked nucleotides 102 that is flanked by a first flanking region 104 and a second flaking region 106. The polypeptide of interest may comprise at its 5′ terminus one or more signal sequences encoded by a signal sequence region 103. The flanking region 104 may comprise a region of linked nucleotides comprising one or more complete or incomplete 5′ UTRs sequences which may be completely codon optimized or partially codon optimized. The flanking region 104 may include at least one nucleic acid sequence including, but not limited to, miR sequences, TERZAK™ sequences and translation control sequences. The flanking region 104 may also comprise a 5′ terminal cap 108. The 5′ terminal capping region 108 may include a naturally occurring cap, a synthetic cap or an optimized cap. Non-limiting examples of optimized caps include the caps taught by Rhoads in U.S. Pat. No. 7,074,596 and International Patent Publication No. WO2008157668, WO2009149253 and WO2013103659, the contents of each of which are herein incorporated by reference in its entirety. The second flanking region 106 may comprise a region of linked nucleotides comprising one or more complete or incomplete 3′ UTRs. The second flanking region 106 may be completely codon optimized or partially codon optimized. The flanking region 106 may include at least one nucleic acid sequence including, but not limited to, miR sequences and translation control sequences. The flanking region 106 may also comprise a 3′ tailing sequence 110. The 3′ tailing sequence 110 may include a synthetic tailing region 112 and/or a chain terminating nucleoside 114. Non-liming examples of a synthetic tailing region include a polyA sequence, a polyC sequence, and/or a polyA-G quartet. Non-limiting examples of chain terminating nucleosides include 2′-O methyl, F and locked nucleic acids (LNA).

Bridging the 5′ terminus of the first region 102 and the first flanking region 104 is a first operational region 105. Traditionally this operational region comprises a Start codon. The operational region may alternatively comprise any translation initiation sequence or signal including a Start codon.

Bridging the 3′ terminus of the first region 102 and the second flanking region 106 is a second operational region 107. Traditionally this operational region comprises a Stop codon. The operational region may alternatively comprise any translation initiation sequence or signal including a Stop codon. Multiple serial stop codons may also be used in the IVT polynucleotide. In one embodiment, the operation region of the present invention may comprise two stop codons. The first stop codon may be “TGA” or “UGA” and the second stop codon may be selected from the group consisting of “TAA,” “TGA,” “TAG,” “UAA,” “UGA” or “UAG.”

The shortest length of the first region of the primary construct of the IVT polynucleotide of the present invention can be the length of a nucleic acid sequence that is sufficient to encode for a dipeptide, a tripeptide, a tetrapeptide, a pentapeptide, a hexapeptide, a heptapeptide, an octapeptide, a nonapeptide, or a decapeptide. In another embodiment, the length may be sufficient to encode a peptide of 2-30 amino acids, e.g. 5-30, 10-30, 2-25, 5-25, 10-25, or 10-20 amino acids. The length may be sufficient to encode for a peptide of at least 11, 12, 13, 14, 15, 17, 20, 25 or 30 amino acids, or a peptide that is no longer than 40 amino acids, e.g. no longer than 35, 30, 25, 20, 17, 15, 14, 13, 12, 11 or 10 amino acids. Examples of dipeptides that the polynucleotide sequences can encode or include, but are not limited to, carnosine and anserine. It is understood that the NAV, RNAV or mRNA vaccines of the invention may be translatable and include such first region of a primary construct.

The length of the first region of the primary construct of the IVT polynucleotide encoding the polypeptide of interest of the present invention is greater than about 30 nucleotides in length (e.g., at least or greater than about 35, 40, 45, 50, 55, 60, 70, 80, 90, 100, 120, 140, 160, 180, 200, 250, 300, 350, 400, 450, 500, 600, 700, 800, 900, 1,000, 1,100, 1,200, 1,300, 1,400, 1,500, 1,600, 1,700, 1,800, 1,900, 2,000, 2,500, and 3,000, 4,000, 5,000, 6,000, 7,000, 8,000, 9,000, 10,000, 20,000, 30,000, 40,000, 50,000, 60,000, 70,000, 80,000, 90,000 or up to and including 100,000 nucleotides).

In some embodiments, the IVT polynucleotide includes from about 30 to about 100,000 nucleotides (e.g., from 30 to 50, from 30 to 100, from 30 to 250, from 30 to 500, from 30 to 1,000, from 30 to 1,500, from 30 to 3,000, from 30 to 5,000, from 30 to 7,000, from 30 to 10,000, from 30 to 25,000, from 30 to 50,000, from 30 to 70,000, from 100 to 250, from 100 to 500, from 100 to 1,000, from 100 to 1,500, from 100 to 3,000, from 100 to 5,000, from 100 to 7,000, from 100 to 10,000, from 100 to 25,000, from 100 to 50,000, from 100 to 70,000, from 100 to 100,000, from 500 to 1,000, from 500 to 1,500, from 500 to 2,000, from 500 to 3,000, from 500 to 5,000, from 500 to 7,000, from 500 to 10,000, from 500 to 25,000, from 500 to 50,000, from 500 to 70,000, from 500 to 100,000, from 1,000 to 1,500, from 1,000 to 2,000, from 1,000 to 3,000, from 1,000 to 5,000, from 1,000 to 7,000, from 1,000 to 10,000, from 1,000 to 25,000, from 1,000 to 50,000, from 1,000 to 70,000, from 1,000 to 100,000, from 1,500 to 3,000, from 1,500 to 5,000, from 1,500 to 7,000, from 1,500 to 10,000, from 1,500 to 25,000, from 1,500 to 50,000, from 1,500 to 70,000, from 1,500 to 100,000, from 2,000 to 3,000, from 2,000 to 5,000, from 2,000 to 7,000, from 2,000 to 10,000, from 2,000 to 25,000, from 2,000 to 50,000, from 2,000 to 70,000, and from 2,000 to 100,000).

According to the present invention, the first and second flanking regions of the IVT polynucleotide may range independently from 15-1,000 nucleotides in length (e.g., greater than 30, 40, 45, 50, 55, 60, 70, 80, 90, 100, 120, 140, 160, 180, 200, 250, 300, 350, 400, 450, 500, 600, 700, 800, and 900 nucleotides or at least 30, 40, 45, 50, 55, 60, 70, 80, 90, 100, 120, 140, 160, 180, 200, 250, 300, 350, 400, 450, 500, 600, 700, 800, 900, and 1,000 nucleotides).

According to the present invention, the tailing sequence of the IVT polynucleotide may range from absent to 500 nucleotides in length (e.g., at least 60, 70, 80, 90, 120, 140, 160, 180, 200, 250, 300, 350, 400, 450, or 500 nucleotides). Where the tailing region is a polyA tail, the length may be determined in units of or as a function of polyA Binding Protein binding. In this embodiment, the polyA tail is long enough to bind at least 4 monomers of PolyA Binding Protein. PolyA Binding Protein monomers bind to stretches of approximately 38 nucleotides. As such, it has been observed that polyA tails of about 80 nucleotides and 160 nucleotides are functional.

According to the present invention, the capping region of the IVT polynucleotide may comprise a single cap or a series of nucleotides forming the cap. In this embodiment the capping region may be from 1 to 10. e.g. 2-9, 3-8, 4-7, 1-5, 5-10, or at least 2, or 10 or fewer nucleotides in length. In some embodiments, the cap is absent.

According to the present invention, the first and second operational regions of the IT polynucleotide may range from 3 to 40, e.g., 5-30, 10-20, 15, or at least 4, or 30 or fewer nucleotides in length and may comprise, in addition to a Start and/or Stop codon, one or more signal and/or restriction sequences.

In one embodiment, the IVT polynucleotides of the present invention may be structurally modified or chemically modified. When the IVT polynucleotides of the present invention are chemically and/or structurally modified the polynucleotides may be referred to as “modified IVT polynucleotides.”

In one embodiment, if the IVT polynucleotides of the present invention are chemically modified they may have a uniform chemical modification of all or any of the same nucleoside type or a population of modifications produced by mere downward titration of the same starting modification in all or any of the same nucleoside type, or a measured percent of a chemical modification of all any of the same nucleoside type but with random incorporation, such as where all uridines are replaced by a uridine analog, e.g., pseudouridine. In another embodiment, the IVT polynucleotides may have a uniform chemical modification of two, three, or four of the same nucleoside type throughout the entire polynucleotide (such as all uridines and all cytosines, etc. are modified in the same way).

In one embodiment, the IVT polynucleotides of the present invention may include a sequence encoding a self-cleaving peptide, described herein, such as but not limited to the 2A peptide. The polynucleotide sequence of the 2A peptide in the IVT polynucleotide may be modified or codon optimized by the methods described herein and/or are known in the art.

In one embodiment, this sequence may be used to separate the coding region of two or more polypeptides of interest in the IVT polynucleotide.

In one embodiment, the IVT polynucleotide of the present invention may be structurally and/or chemically modified. When chemically modified and/or structurally modified the IVT polynucleotide may be referred to as a “modified IVT polynucleotide.”

In one embodiment, the IVT polynucleotide may encode at least one peptide or polypeptide of interest. In another embodiment, the IVT polynucleotide may encode two or more peptides or polypeptides of interest. Non-limiting examples of peptides or polypeptides of intest include heavy and light chains of antibodies, an enzyme and its substrate, a label and its binding molecule, a second messenger and its enzyme or the components of multimeric proteins or complexes.

Chimeric Polynucleotide Architecture

The chimeric polynucleotides or RNA constructs of the present invention maintain a modular organization similar to IVT polynucleotides, but the chimeric polynucleotides comprise one or more structural and/or chemical modifications or alterations which impart useful properties to the polynucleotide. As such, the chimeric polynucleotides which are modified mRNA molecules of the present invention are termed “chimeric modified mRNA” or “chimeric mRNA.”

It is to be understood that the antigens of the NAVs of the present invention may be encoded by a chimeric polynucleotide, RNA construct, chimeric modified mRNA or chimeric mRNA.

Chimeric polynucleotides have portions or regions which differ in size and/or chemical modification pattern, chemical modification position, chemical modification percent or chemical modification population and combinations of the foregoing.

Examples of parts or regions, where the chimeric polynucleotide functions as an mRNA and encodes a polypeptide of interest include, but are not limited to, untranslated regions (UTRs, such as the 5′ UTR or 3′ UTR), coding regions, cap regions, polyA tail regions, start regions, stop regions, signal sequence regions, and combinations thereof. FIG. 2 illustrates certain embodiments of the chimeric polynucleotides of the invention which may be used as mRNA. FIG. 3 illustrates a schematic of a series of chimeric polynucleotides identifying various patterns of positional modifications and showing regions analogous to those regions of an mRNA polynucleotide. Regions or parts that join or lie between other regions may also be designed to have subregions. These are shown in the figure.

In some embodiments, the chimeric polynucleotides of the invention have a structure comprising Formula I.

5′[A_n]_x-L1-[B_o]_y-L2-[C_p]_z-L3 3′ Formula I

- wherein:
- each of A and B independently comprise a region of linked nucleosides;
- C is an optional region of linked nucleosides;
- at least one of regions A, B, or C is positionally modified, wherein said positionally modified region comprises at least two chemically modified nucleosides of one or more of the same nucleoside type of adenosine, thymidine, guanosine, cytidine, or uridine, and wherein at least two of the chemical modifications of nucleosides of the same type are different chemical modifications;
- n, o and p are independent an integer between 15-1000;
- x and y are independently 1-20:
- z is 0-5;
- L1 and L2 are independently optional linker moieties, said linker moieties being either nucleic acid based or non-nucleic acid based; and
- L3 is an optional conjugate or an optional linker moiety, said linker moiety being either nucleic acid based or non-nucleic acid based.

In some embodiments the chimeric polynucleotide of Formula I encodes one or more peptides or polypeptides of interest. Such encoded molecules may be encoded across two or more regions.

In another aspect, the invention features a chimeric polynucleotide encoding a polypeptide, wherein the polynucleotide has a sequence including Formula II:

[A_n]-L¹-[B_o] Formula II

- wherein each A and B is independently any nucleoside;
- n and o are, independently 15 to 1000; and
- L¹has the structure of Formula III:

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- wherein a, b, c, d, e, and f are each, independently, 0 or 1;
- each of R¹, R³, R⁵, and R⁷, is, independently, selected from optionally substituted C₁-C₆alkylene, optionally substituted C₁-C₆heteroalkylene, O, S, and NR⁸.
- R²and R⁶are each, independently, selected from carbonyl, thiocarbonyl, sulfonyl, or phosphoryl;
- R⁴is optionally substituted C₁-C₁₀alkylene, optionally substituted C₂-C₁₀alkenylene, optionally substituted C₂-C₁₀alkynylene, optionally substituted C₂-C₉heterocyclylene, optionally substituted C₆-C₁₂arylene, optionally substituted C₂-C₁₀₀polyethylene glycolene, or optionally substituted C₁-C₁₀heteroalkylene, or a bond linking (R¹)_n—(R²)_b—(R³)_cto (R⁵)_d—(R⁶)_e—(R⁷)_f, wherein if c, d, e, f, g, and h are 0. R⁴is not a bond; and
- R⁸is hydrogen, optionally substituted C₁-C₄₁alkyl, optionally substituted C₂-C₄alkenyl, optionally substituted C₁-C₄alkynyl, optionally substituted C₂-C₆heterocyclyl, optionally substituted C₆-C₁₂aryl, or optionally substituted C₁-C₂heteroalkyl;
- wherein L¹is attached to [A_n] and [B_o] at the sugar of one of the nucleosides (e.g., at the 3′ position of a five-membered sugar ring or 4′ position of a six membered sugar ring of a nucleoside of [A_n] and the 5′ position of a five-membered sugar ring or 6′ position of a six membered sugar ring of a nucleoside of [B_o] or at the 5′ position of a five-membered sugar ring or 6′ position of a six membered sugar ring of a nucleoside of [A_n] and the 3′ position of a five-membered sugar ring or 4′ position of a six membered sugar ring of a nucleoside of [B_o]).

In some embodiments, at least one of [A_n] and [B_o] includes the structure of Formula IV:

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- wherein each of N¹and N²is independently a nucleobase;
- each of R⁹, R¹⁰, R¹¹, R¹², R¹³, R¹⁴, R¹⁵, and R¹⁶is, independently, H, halo, hydroxy, thiol, optionally substituted C₁-C₆alkyl, optionally substituted C₁-C₆heteroalkyl, optionally substituted C₂-C₆heteroalkenyl, optionally substituted C₂-C₆heteroalkynyl, optionally substituted amino, azido, or optionally substituted C₆-C₁₀aryl;
- each of g and h is, independently, 0 or 1;
- each X¹and X⁴is, independently, O, NH, or S;
- each X²is independently O or S; and
- each X³is OH or SH, or a salt thereof.

In another aspect, the invention features a chimeric polynucleotide encoding a polypeptide, wherein the polynucleotide has a sequence including Formula II:

[A_n]-L¹-[B_o] Formula II

- wherein each A and B is independently any nucleoside;
- n and o are, independently 15 to 1000; and
- L¹is a bond or has the structure of Formula III:

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- wherein a, b, c, d, e, and f are each, independently, 0 or 1;
- each of R¹, R³, R⁵, and R⁷, is, independently, selected from optionally substituted C₁-C₆alkylene, optionally substituted C₁-C₆heteroalkylene, O, S, and NR⁸.
- R²and R⁶are each, independently, selected from carbonyl, thiocarbonyl, sulfonyl, or phosphoryl;
- R⁴is optionally substituted C₁-C₁₀alkylene, optionally substituted C₂-C₁₀alkenylene, optionally substituted C₂-C₁₀alkynylene, optionally substituted C₂-C₉heterocyclylene, optionally substituted C₆-C₁₂arylene, optionally substituted C₂-C₁₀₀polyethylene glycolene, or optionally substituted C₁-C₁₀heteroalkylene, or a bond linking (R¹)_a—(R²)_b—(R³)_cto (R⁵)_d—(R⁶)_e—(R⁷)_f, and
- R⁸is hydrogen, optionally substituted C₁-C₄alkyl, optionally substituted C₂-C₄alkenyl, optionally substituted C₂-C₄alkynyl, optionally substituted C₂-C₆heterocyclyl, optionally substituted C₆-C₁₂aryl, or optionally substituted C₁-C₇heteroalkyl;
- wherein L¹is attached to [A_n] and [B_o] at the sugar of one of the nucleosides (e.g., at the 3′ position of a five-membered sugar ring or 4′ position of a six membered sugar ring of a nucleoside of [A_n] and the 5′ position of a five-membered sugar ring or 6′ position of a six membered sugar ring of a nucleoside of [B,] or at the 5′ position of a five-membered sugar ring or 6′ position of a six membered sugar ring of a nucleoside of [A_n] and the 3′ position of a five-membered sugar ring or 4′ position of a six membered sugar ring of a nucleoside of [B_o]).
- wherein at least one of [A_n] or [B_o] includes the structure of Formula IV:

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- wherein each of N¹and N²is independently a nucleobase;
- each of R⁹, R¹⁰, R¹¹, R¹², R¹³, R¹⁴, R¹⁵, and R¹⁶is, independently, H, halo, hydroxy, thiol, optionally substituted C₁-C₆alkyl, optionally substituted C₁-C₆heteroalkyl, optionally substituted C₂-C₆heteroalkenyl, optionally substituted C₂-C₆heteroalkynyl, optionally substituted amino, azido, or optionally substituted C₆-C₁₀aryl;
- each of g and h is, independently, 0 or 1;
- each X¹and X⁴is, independently, O, NH, or S; and
- each X²is independently O or S; and
- each X³is OH or SH, or a salt thereof;
- wherein at least one of X¹, X², or X⁴is NH or S.

In some embodiments, X¹is NH. In other embodiments, X⁴is NH. In certain embodiments, X²is S.

In some embodiments, the polynucleotide includes: (a) a coding region; (b) a 5′ UTR including at least one Kozak sequence; (c) a 3′ UTR; and (d) at least one 5′ cap stucture. In other embodiments, the polynucleotide further includes (e) a poly-A tail.

In some embodiments, one of the coding region, the 5′ UTR including at least one Kozak sequence, the 3′ UTR, the 5′ cap structure, or the poly-A tail includes [A_n]-L¹-[B_o].

In other embodiments, one of the coding region, the 5′ UTR including at least one Kozak sequence, the 3′ UTR, the 5′ cap structure, or the poly-A tail includes [A_n] and another of the coding region, the 5′ UTR including at least one Kozak sequence, the 3′ UTR, the 5′ cap structure, or the poly-A tail includes [B_o].

In certain embodiments, the polynucleotide includes at least one modified nucleoside (e.g., a nucleoside of Table 2).

In some embodiments, R⁴is optionally substituted C_2-9heterocyclylene, for example, the heterocycle may have the structure:

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In certain embodiments, L¹is attached to [A_n] at the 3′ position of a five-membered sugar ring or 4′ position of a six membered sugar ring of one of the nucleosides and to [B_o] at the 5′ position of a five-membered sugar ring or 6′ position of a six membered sugar ring of one of the nucleosides.

In some embodiments, the polynucleotide is circular.

In another aspect, the invention features a method of producing a composition including a chimeric polynucleotide encoding a polypeptide, wherein the polynucleotide includes the structure of Formula V:

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This method includes reacting a compound having the structure of Formula VI:

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with a compound having the structure of Formula VII:

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- wherein each of N¹and N²is, independently, a nucleobase; each of R⁹, R¹⁰, R¹¹, R¹², R¹³, R¹⁴, R¹⁵, and R¹⁶is, independently, H, halo, hydroxy, thiol, optionally substituted C₁-C₆alkyl, optionally substituted C₁-C₆heteroalkyl, optionally substituted C₂-C₆heteroalkenyl, optionally substituted C₂-C₆heteroalkynyl, optionally substituted amino, azido, or optionally substituted C₆-C₁₀aryl;
- each of g and h is, independently, 0 or 1;
- each X¹and X⁴is, independently, O, NH, or S; and
- each X³is independently OH or SH, or a salt thereof;
- each of R¹⁷and R¹⁹is, independently, a region of linked nucleosides; and
- R¹⁸is a halogen.

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This method includes reacting a compound having the structure of Formula IX:

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with a compound having the structure of Formula X:

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- wherein each of N¹and N²is, independently, a nucleobase;
- each of R⁹, R¹⁰, R¹¹, R¹², R¹³, R¹⁴, R¹⁵, and R¹⁶is, independently. H, halo, hydroxy, thiol, optionally substituted C₁-C₆alkyl, optionally substituted C₁-C₆heteroalkyl, optionally substituted C₂-C₆heteroalkenyl, optionally substituted C₂-C₆heteroalkynyl, optionally substituted amino, azido, or optionally substituted C₆-C₁₀aryl;
- each of g and h is, independently, 0 or 1;
- each X⁴is, independently, O, NH, or S; and
- each X²is independently O or S;
- each X³is independently OH, SH, or a salt thereof;
- each of R²⁰and R²³is, independently, a region of linked nucleosides; and
- each of R²¹and R²²is, independently, optionally substituted C₁-C₆alkoxy.

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This method includes reacting a compound having the structure of Formula XII:

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with a compound having the structure of Formula XIII:

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- wherein each of N¹and N²is, independently, a nucleobase;
- each of R⁹, R¹⁰, R¹¹, R¹², R¹³, R⁴, R¹⁵, and R¹⁶is, independently, H, halo, hydroxy, thiol, optionally substituted C₁-C₆alkyl, optionally substituted C₁-C₆heteroalkyl, optionally substituted C₂-C₆heteroalkenyl, optionally substituted C₂-C₆heteroalkynyl, optionally substituted amino, azido, or optionally substituted C₆-C₁₀aryl;
- each of g and h is, independently, 0 or 1;
- each X⁴is, independently, O, NH, or S; and
- each X²is independently O or S;
- each X³is independently OH, SH, or a salt thereof;
- each of R²⁴and R²¹is, independently, a region of linked nucleosides; and
- R²⁵is optionally substituted C₁-C₆alkylene or optionally substituted C₁-C₆heteroalkylene or R²and the alkynyl group together form optionally substituted cycloalkynyl.

In another aspect, the invention features a method of producing a composition including a chimeric polynucleotide encoding a polypeptide, wherein the polynucleotide has a sequence including Formula II:

[A_n]-L¹-[B_o], Formula II

This method includes reacting a compound having the structure of Formula XIV

[A_n]—(R¹)_a—(R²)_b—(R³)_c—N₃ Formula XIV

with a compound having the structure of Formula XV:

R²⁷—(R⁵)_d—(R⁶)_e—(R⁷)_f—[B_o] Formula XV

- wherein each A and B is independently any nucleoside;
- n and o are, independently 15 to 1000; and
- L¹has the structure of Formula III:

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- wherein a, b, c, d, e, and f are each, independently, 0 or 1;
- wherein each A and B is independently any nucleoside;
- n and o are, independently 15 to 1000;
- R¹, R³, R⁵, and R⁷each, independently, is selected from optionally substituted C₁-C₆alkylene, optionally substituted C₁-C₆heteroalkylene, O, S, and NR⁸;
- R²and R⁶are each, independently, selected from carbonyl, thiocarbonyl, sulfonyl, or phosphoryl;
- R⁴is an optionally substituted triazolene; and
- R⁸is hydrogen, optionally substituted C₁-C₄alkyl, optionally substituted C₃-C₄alkenyl, optionally substituted C₂-C₄alkynyl, optionally substituted C₂-C₆heterocyclyl, optionally substituted C₆-C₁₂aryl, or optionally substituted C₁-C₇heteroalkyl; and
- R²⁷is an optionally substituted C₂-C₃alkynyl or an optionally substituted C₈-C₁₂cycloalkynyl,
- wherein L¹is attached to [A_n] and [B_o] at the sugar of one of the nucleosides.

In some embodiments, the optionally substituted triazolene has the structure:

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In one embodiment, at least one of the regions of linked nucleosides of A may comprise a sequence of linked nucleosides which can function as a 5′ untranslated region (UTR). The sequence of linked nucleosides may be a natural or synthetic 5′ UTR. As a non-limiting example, the chimeric polynucleotide may encode a polypeptide of interest and the sequence of linked nucleosides of A may encode the native 5′ UTR of a polypeptide encoded by the chimeric polynucleotide or the sequence of linked nucleosides may be a non-heterologous 5′ UTR such as, but not limited to a synthetic UTR.

In another embodiment, at least one of the regions of linked nucleosides of A may be a cap region. The cap region may be located 5′ to a region of linked nucleosides of A functioning as a 5′UTR. The cap region may comprise at least one cap such as, but not limited to, Cap0, Cap1, ARCA, inosine, N1-methyl-guanosine, 2′fluoro-guanosine, 7-deaza-guanosine, 8-oxo-guanosine, 2-amino-guanosine, LNA-guanosine, 2-azido-guanosine, Cap2 and Cap4.

In one embodiment, at least one of the regions of linked nucleosides of B may comprise at least one open reading frame of a nucleic acid sequence. The nucleic acid sequence may be codon optimized and/or comprise at least one modification.

In one embodiment, at least one of the regions of linked nucleosides of C may comprise a sequence of linked nucleosides which can function as a 3′ UTR. The sequence of linked nucleosides may be a natural or synthetic 3′ UTR. As a non-limiting example, the chimeric polynucleotide may encode a polypeptide of interest and the sequence of linked nucleosides of C may encode the native 3′ UTR of a polypeptide encoded by the chimeric polynucleotide or the sequence of linked nucleosides may be a non-heterologous 3′ UTR such as, but not limited to a synthetic UTR.

In one embodiment, at least one of the regions of linked nucleosides of A comprises a sequence of linked nucleosides which functions as a 5′ UTR and at least one of the regions of linked nucleosides of C comprises a sequence of linked nucleosides which functions as a 3′ UTR. In one embodiment, the 5′ UTR and the 3′ UTR may be from the same or different species. In another embodiment, the 5′ UTR and the 3′ UTR may encode the native untranslated regions from different proteins from the same or different species.

FIGS. 4 and 5 provide schematics of a series of chimeric polynucleotides illustrating various patterns of positional modifications based on Formula I as well as those having a blocked or structured 3′ terminus.

Chimeric polynucleotides, including the parts or regions thereof, of the present invention may be classified as hemimers, gapmers, wingmers, or blockmers.

As used herein, a “hemimer” is chimeric polynucleotide comprising a region or part which comprises half of one pattern, percent, position or population of a chemical modification(s) and half of a second pattern, percent, position or population of a chemical modification(s). Chimeric polynucleotides of the present invention may also comprise hemimer subregions. In one embodiment, a part or region is 50% of one and 50% of another.

In one embodiment the entire chimeric polynucleotide can be 50% of one and 50% of the other. Any region or part of any chimeric polynucleotide of the invention may be a hemimer. Types of hemimers include pattern hemimers, population hemimers or position hemimers. By definition, hemimers are 50:50 percent hemimers.

As used herein, a “gapmer” is a chimeric polynucleotide having at least three parts or regions with a gap between the parts or regions. The “gap” can comprise a region of linked nucleosides or a single nucleoside which differs from the chimeric nature of the two parts or regions flanking it. The two parts or regions of a gapmer may be the same or different from each other.

As used herein, a “wingmer” is a chimeric polynucleotide having at least three parts or regions with a gap between the parts or regions. Unlike a gapmer, the two flanking parts or regions surrounding the gap in a wingmer are the same in degree or kind. Such similarity may be in the length of number of units of different modifications or in the number of modifications. The wings of a wingmer may be longer or shorter than the gap. The wing parts or regions may be 20, 30, 40, 50, 60 70, 80, 90 or 95% greater or shorter in length than the region which comprises the gap.

As used herein, a “blockmer” is a patterned polynucleotide where parts or regions are of equivalent size or number and type of modifications. Regions or subregions in a blockmer may be 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105, 106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 118, 119, 120, 121, 122, 123, 124, 125, 126, 127, 128, 129, 130, 131, 132, 133, 134, 135, 136, 137, 138, 139, 140, 141, 142, 143, 144, 145, 146, 147, 148, 149, 150, 151, 152, 153, 154, 155, 156, 157, 158, 159, 160, 161, 162, 163, 164, 165, 166, 167, 168, 169, 170, 171, 172, 173, 174, 175, 176, 177, 178, 179, 180, 181, 182, 183, 184, 185, 186, 187, 188, 189, 190, 191, 192, 193, 194, 195, 196, 197, 198, 199, 200, 201, 202, 203, 204, 205, 206, 207, 208, 209, 210, 211, 212, 213, 214, 215, 216, 217, 218, 219, 220, 221, 222, 223, 224, 225, 226, 227, 228, 229, 230, 231, 232, 233, 234, 235, 236, 237, 238, 239, 240, 241, 242, 243, 244, 245, 246, 247, 248, 249, 250, 251, 252, 253, 254, 255, 256, 257, 258, 259, 260, 261, 262, 263, 264, 265, 266, 267, 268, 269, 270, 271, 272, 273, 274, 275, 276, 277, 278, 279, 280, 281, 282, 283, 284, 285, 286, 287, 288, 289, 290, 291, 292, 293, 294, 295, 296, 297, 298, 299, 300, 310, 320, 330, 340, 350, 360, 370, 380, 390, 400, 410, 420, 430, 440, 450, 460, 470, 480, 490 or 500, nucleosides long.

Chimeric polynucleotides, including the parts or regions thereof, of the present invention having a chemical modification pattern are referred to as “pattern chimeras.” Pattern chimeras may also be referred to as blockmers. Pattern chimeras are those polynucleotides having a pattern of modifications within, across or among regions or parts.

Patterns of modifications within a part or region are those which start and stop within a defined region. Patterns of modifications across a part or region are those patterns which start in on part or region and end in another adjacent part or region. Patterns of modifications among parts or regions are those which begin and end in one part or region and are repeated in a different part or region, which is not necessarily adjacent to the first region or part.

The regions or subregions of pattern chimeras or blockmers may have simple alternating patterns such as ABAB[AB]n where each “A” and each “B” represent different chemical modifications (at at least one of the base, sugar or backbone linker), different types of chemical modifications (e.g., naturally occurring and non-naturally occurring), different percentages of modifications or different populations of modifications. The pattern may repeat n number of times where n=3-300. Further, each A or B can represent from 1-2500 units (e.g., nucleosides) in the pattern. Patterns may also be alternating multiples such as AABBAABB[AABB]n (an alternating double multiple) or AAABBBAAABBB[AAABBB]n (an alternating triple multiple) pattern. The pattern may repeat n number of times where n=3-300.

Different patterns may also be mixed together to form a second order pattern. For example, a single alternating pattern may be combined with a triple alternating pattern to form a second order alternating pattern A‘B’. One example would be [ABABAB][AAABBBAAABBB][ABABAB][AAABBBAAABBB][ABABAB][AAABBBAAABBB], where [ABABAB] is A′ and [AAABBBAAABBB] is B′. In like fashion, these patterns may be repeated n number of times, where n=3-300.

Patterns may include three or more different modifications to form an ABCABC[ABC]n pattern. These three component patterns may also be multiples, such as AABBCCAABBCC[AABBCC]n and may be designed as combinations with other patterns such as ABCABCAABBCCABCABCAABBCC, and may be higher order patterns.

Regions or subregions of position, percent, and population modifications need not reflect an equal contribution from each modification type. They may form series such as “1-2-3-4”, “1-2-4-8”, where each integer represents the number of units of a particular modification type. Alternatively, they may be odd only, such as ‘1-3-3-1-3-1-5” or even only “2-4-2-4-6-4-8” or a mixuture of both odd and even number of units such as “1-3-4-2-5-7-3-3-4”.

Pattern chimeras may vary in their chemical modification by degree (such as those described above) or by kind (e.g., different modifications).

Chimeric polynucleotides, including the parts or regions thereof, of the present invention having at least one region with two or more different chemical modifications of two or more nucleoside members of the same nucleoside type (A, C, G, T, or U) are referred to as “positionally modified” chimeras. Positionally modified chimeras are also referred to herein as “selective placement” chimeras or “selective placement polynucleotides”. As the name implies, selective placement refers to the design of polynucleotides which, unlike polynucleotides in the art where the modification to any A, C, G, T or U is the same by virtue of the method of synthesis, can have different modifications to the individual As, Cs, Gs, Ts or Us in a polynucleotide or region thereof. For example, in a positionally modified chimeric polynucleotide, there may be two or more different chemical modifications to any of the nucleoside types of As, Cs, Gs, Ts, or Us. There may also be combinations of two or more to any two or more of the same nucleoside type. For example, a positionally modified or selective placement chimeric polynucleotide may comprise 3 different modifications to the population of adenines in the molecule and also have 3 different modifications to the population of cytosines in the construct-all of which may have a unique, non-random, placement.

Chimeric polynucleotides, including the parts or regions thereof, of the present invention having a chemical modification percent are referred to as “percent chimeras.” Percent chimeras may have regions or parts which comprise at least 1%, at least 2%, at least 5%, at least 8%, at least 10%, at least 20%, at least 30%, at least 40%, at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, at least 95%, or at least 99% positional, pattern or population of modifications. Alternatively, the percent chimera may be completely modified as to modification position, pattern, or population. The percent of modification of a percent chimera may be split between naturally occurring and non-naturally occurring modifications.

Chimeric polynucleotides, including the parts or regions thereof, of the present invention having a chemical modification population are referred to as “population chimeras.” A population chimera may comprise a region or part where nucleosides (their base, sugar or backbone linkage, or combination thereof) have a select population of modifications. Such modifications may be selected from functional populations such as modifications which induce, alter or modulate a phenotypic outcome. For example, a functional population may be a population or selection of chemical modifications which increase the level of a cytokine. Other functional populations may individually or collectively function to decrease the level of one or more cytokines. Use of a selection of these like-function modifications in a chimeric polynucleotide would therefore constitute a “functional population chimera.” As used herein, a “functional population chimera” may be one whose unique functional feature is defined by the population of modifications as described above or the term may apply to the overall function of the chimeric polynucleotide itself. For example, as a whole the chimeric polynucleotide may function in a different or superior way as compared to an unmodified or non-chimeric polynucleotide.

It should be noted that polynucleotides which have a uniform chemical modification of all of any of the same nucleoside type or a population of modifications produced by mere downward titration of the same starting modification in all of any of the same nucleoside type, or a measured percent of a chemical modification of all any of the same nucleoside type but with random incorporation, such as where all uridines are replaced by a uridine analog, e.g., pseudouridine, are not considered chimeric. Likewise, polynucleotides having a uniform chemical modification of two, three, or four of the same nucleoside type throughout the entire polynucleotide (such as all uridines and all cytosines, etc. are modified in the same way) are not considered chimeric polynucleotides. One example of a polynucleotide which is not chimeric is the canonical pseudouridine/5-methyl cytosine modified polynucleotide of the prior art. These uniform polynucleotides are arrived at entirely via in vitro transcription (IVT) enzymatic synthesis; and due to the limitations of the synthesizing enzymes, they contain only one kind of modification at the occurrence of each of the same nucleoside type, i.e., adenosine (A), thymidine (T), guanosine (G), cytidine (C) or uradine (U), found in the polynucleotide. Such polynucleotides may be characterized as IVT polynucleotides.

The chimeric polynucleotides of the present invention may be structurally modified or chemically modified. When the chimeric polynucleotides of the present invention are chemically and/or structurally modified the polynucleotides may be referred to as “modified chimeric polynucleotides.”

In some embodiments of the invention, the chimeric polynucleotides may encode two or more peptides or polypeptides of interest. Such peptides or polypeptides of interest include the heavy and light chains of antibodies, an enzyme and its substrate, a label and its binding molecule, a second messenger and its enzyme or the components of multimeric proteins or complexes.

The regions or parts of the chimeric polynucleotides of the present invention may be separated by a linker or spacer moiety. Such linkers or spaces may be nucleic acid based or non-nucleosidic.

In one embodiment, the chimeric polynucleotides of the present invention may include a sequence encoding a self-cleaving peptide described herein, such as, but not limited to, a 2A peptide. The polynucleotide sequence of the 2A peptide in the chimeric polynucleotide may be modified or codon optimized by the methods described herein and/or are known in the art.

Notwithstanding the foregoing, the chimeric polynucleotides of the present invention may comprise a region or part which is not positionally modified or not chimeric as defined herein.

For example, a region or part of a chimeric polynucleotide may be uniformly modified at one ore more A, T, C, G, or U but according to the invention, the polynucleotides will not be uniformly modified throughout the entire region or part.

Regions or parts of chimeric polynucleotides may be from 15-1000 nucleosides in length and a polynucleotide may have from 2-100 different regions or patterns of regions as described herein.

In one embodiment, chimeric polynucleotides encode one or more polypeptides of interest. In another embodiment, the chimeric polynucleotides are substantially non-coding. In another embodiment, the chimeric polynucleotides have both coding and non-coding regions and parts.

FIG. 2 illustrates the design of certain chimeric polynucleotides of the present invention when based on the scaffold of the polynucleotide of FIG. 1. Shown in the figure are the regions or parts of the chimeric polynucleotides where patterned regions represent those regions which are positionally modified and open regions illustrate regions which may or may not be modified but which are, when modified, uniformly modified. Chimeric polynucleotides of the present invention may be completely positionally modified or partially positionally modified. They may also have subregions which may be of any pattern or design. Shown in FIG. 2 are a chimeric subregion and a hemimer subregion.

In one embodiment, the shortest length of a region of the chimeric polynucleotide of the present invention encoding a peptide can be the length that is sufficient to encode for a dipeptide, a tripeptide, a tetrapeptide, a pentapeptide, a hexapeptide, a heptapeptide, an octapeptide, a nonapeptide, or a decapeptide. In another embodiment, the length may be sufficient to encode a peptide of 2-30 amino acids, e.g. 5-30, 10-30, 2-25, 5-25, 10-25, or 10-20 amino acids. The length may be sufficient to encode for a peptide of at least 11, 12, 13, 14, 15, 17, 20, 25 or 30 amino acids, or a peptide that is no longer than 40 amino acids, e.g. no longer than 35, 30, 25, 20, 17, 15, 14, 13, 12, 11 or 10 amino acids. Examples of dipeptides that the polynucleotide sequences can encode or include, but are not limited to, carnosine and anserine.

In one embodiment, the length of a region of the chimeric polynucleotide of the present invention encoding the peptide or polypeptide of interest is greater than about 30 nucleotides in length (e.g., at least or greater than about 35, 40, 45, 50, 55, 60, 70, 80, 90, 100, 120, 140, 160, 180, 200, 250, 300, 350, 400, 450, 500, 600, 700, 800, 900, 1,000, 1,100, 0.200, 1,300, 1,400, 1,500, 1,600, 1,700, 1.800, 1,900, 2,000, 2,500, and 3,000, 4,000, 5,000, 6,000, 7,000, 8,000, 9,000, 10,000, 20,000, 30,000, 40,000, 50,000, 60,000, 70,000, 80,000, 90,000 or up to and including 100,000 nucleotides). As used herein, such a region may be referred to as a “coding region” or “region encoding.”

In some embodiments, the chimeric polynucleotide includes from about 30 to about 100,000 nucleotides (e.g., from 30 to 50, from 30 to 100, from 30 to 250, from 30 to 500, from 30 to 1.000, from 30 to 1,500, from 30 to 3,000, from 30 to 5,000, from 30 to 7,000, from 30 to 10,000, from 30 to 25,000, from 30 to 50,000, from 30 to 70,000, from 100 to 250, from 100 to 500, from 100 to 1,000, from 100 to 1,500, from 100 to 3,000, from 100 to 5,000, from 100 to 7,000, from 100 to 10,000, from 100 to 25,000, from 100 to 50,000, from 100 to 70,000, from 100 to 100,000, from 500 to 1,000, from 500 to 1,500, from 500 to 2,000, from 500 to 3,000, from 500 to 5,000, from 500 to 7,000, from 500 to 10,000, from 500 to 25,000, from 500 to 50,000, from 500 to 70,000, from 500 to 100,000, from 1,000 to 1,500, from 1,000 to 2,000, from 1,000 to 3,000, from 1,000 to 5,000, from 1,000 to 7,000, from 1,000 to 10,000, from 1,000 to 25,000, from 1,000 to 50,000, from 1,000 to 70,000, from 1,000 to 100,000, from 1,500 to 3,000, from 1,500 to 5,000, from 1,500 to 7,000, from 1,500 to 10,000, from 1,500 to 25,000, from 1,500 to 50,000, from 1,500 to 70,000, from 1,500 to 100,000, from 2,000 to 3,000, from 2,000 to 5,000, from 2,000 to 7,000, from 2,000 to 10,000, from 2,000 to 25,000, from 2,000 to 50,000, from 2,000 to 70,000, and from 2,000 to 100,000).

According to the present invention, regions or subregions of the chimeric polynucleotides may also range independently from 15-1,000 nucleotides in length (e.g., greater than 30, 40, 45, 50, 55, 60, 70, 80, 90, 100, 110, 120, 130, 140, 150, 160, 170, 180, 190, 200, 225, 250, 275, 300, 325, 350, 375, 400, 425, 450, 475, 500, 550, 600, 650, 700, 750, 800, 850, 900 and 950 nucleotides or at least 30, 40, 45, 50, 55, 60, 70, 80, 90, 100, 110, 120, 130, 140, 150, 160, 170, 180, 190, 200, 225, 250, 275, 300, 325, 350, 375, 400, 425, 450, 475, 500, 550, 600, 650, 700, 750, 800, 850, 900, 950 and 1,000 nucleotides).

According to the present invention, regions or subregions of chimeric polynucleotides may range from absent to 500 nucleotides in length (e.g., at least 60, 70, 80, 90, 100, 110, 120, 130, 140, 150, 160, 170, 180, 190, 200, 250, 300, 350, 400, 450, or 500 nucleotides). Where the region is a polyA tail, the length may be determined in units of or as a function of polyA Binding Protein binding. In this embodiment, the polyA tail is long enough to bind at least 4 monomers of PolyA Binding Protein. PolyA Binding Protein monomers bind to stretches of approximately 38 nucleotides. As such, it has been observed that polyA tails of about 80 nucleotides to about 160 nucleotides are functional. The chimeric polynucleotides of the present invention which function as an mRNA need not comprise a polyA tail.

According to the present invention, chimeric polynucleotides which function as an mRNA may have a capping region. The capping region may comprise a single cap or a series of nucleotides forming the cap. In this embodiment the capping region may be from 1 to 10, e.g. 2-9, 3-8, 4-7, 1-5, 5-10, or at least 2, or 10 or fewer nucleotides in length. In some embodiments, the cap is absent.

The present invention contemplates chimeric polynucleotides which are circular or cyclic. As the name implies circular polynucleotides are circular in nature meaning that the termini are joined in some fashion, whether by ligation, covalent bond, common association with the same protein or other molecule or complex or by hybridization. Any of the circular polynucleotides as taught in for example U.S. Provisional Application No. 61/873,010 filed Sep. 3, 2013, (Attorney Docket number M51) the contents of which are incorporated herein by reference in their entirety, may be made chimeric according to the present invention.

Chimeric polynucleotides, formulations and compositions comprising chimeric polynucleotides, and methods of making, using and administering chimeric polynucleotides are also described in co-pending U.S. Provisional Application No. 61/873,034, filed Sep. 3, 2013, entitled Chimeric Polynucleotides, and U.S. Provisional Application No. 61/877,582, filed Sep. 13, 2013, entitled Chimeric Polynucleotides (Attorney Docket Number M57); each of which is incorporated by reference in its entirety.

Circular Polynucleotide Architecture

The present invention contemplates polynucleotides which are circular or cyclic. As the name implies circular polynucleotides are circular in nature meaning that the termini are joined in some fashion, whether by ligation, covalent bond, common association with the same protein or other molecule or complex or by hybridization. Any of the circular polynucleotides as taught in for example U.S. Provisional Application No. 61/873,010 filed Sep. 3, 2013. (Attorney Docket number M51.60) the contents of which are incorporated herein by reference in their entirety.

Circular polynucleotides of the present invention may be designed according to the circular RNA construct scaffolds shown in FIGS. 6-12. Such polynucleotides are circular polynucleotides or circular constructs.

The circular polynucleotides or circPs of the present invention which encode at least one peptide or polypeptide of interest are known as circular RNAs or circRNA. The antigens of the NAVs of the present invention may be encoded by one or more circular RNAs or circRNAs.

As used herein, “circular RNA” or “circRNA” means a circular polynucleotide that can encode at least one peptide or polypeptide of interest. The circPs of the present invention which comprise at least one sensor sequence and do not encode a peptide or polypeptide of interest are known as circular sponges or circSP. As used herein, “circular sponges,” “circular polynucleotide sponges” or “circSP” means a circular polynucleotide which comprises at least one sensor sequence and does not encode a polypeptide of interest. Such noncoding polynucleotides may be useful in the NAVs of the present invention as noncoding nucleic acids may function as an antigenic composition.

As used herein, “sensor sequence” means a receptor or pseudo-receptor for endogenous nucleic acid binding molecules. Non-limiting examples of sensor sequences include, microRNA binding sites, microRNA seed sequences, microRNA binding sites without the seed sequence, transcription factor binding sites and artificial binding sites engineered to act as pseudo-receptors and portions and fragments thereof.

The circPs of the present invention which comprise at least one sensor sequence and encode at least one peptide or polypeptide of interest are known as circular RNA sponges or circRNA-SP. As used herein, “circular RNA sponges” or “circRNA-SP” means a circular polynucleotide which comprises at least one sensor sequence and at least one region encoding at least one peptide or polypeptide of interest.

FIG. 6A shows a representative circular construct 200 of the circular polynucleotides of the present invention. As used herein, the term “circular construct” refers to a circular polynucleotide transcript which may act substantially similar to and have properties of a RNA molecule. In one embodiment the circular construct acts as an mRNA. If the circular construct encodes one or more peptides or polypeptides of interest (e.g., a circRNA or circRNA-SP) then the polynucleotide transcript retains sufficient structural and/or chemical features to allow the polypeptide of interest encoded therein to be translated. Circular constructs may be polynucleotides of the invention. When structurally or chemically modified, the construct may be referred to as a modified circP, modified circSP, modified circRNA or modified circRNA-SP.

Returning to FIG. 6A, the circular construct 200 here contains a first region of linked nucleotides 202 that is flanked by a first flanking region 204 and a second flanking region 206. As used herein, the “first region” may be referred to as a “coding region.” a “non-coding region” or “region encoding” or simply the “first region.” In one embodiment, this first region may comprise nucleotides such as, but is not limited to, encoding at least one peptide or polypeptide of interest and/or nucleotides encoding a sensor region. The peptide or polypeptide of interest may comprise at its 5′ terminus one or more signal peptide sequences encoded by a signal peptide sequence region 203. The first flanking region 204 may comprise a region of linked nucleosides or portion thereof which may act similarly to an untranslated region (UTR) in an mRNA and/or DNA sequence. The first flanking region may also comprise a region of polarity 208. The region of polarity 208 may include an IRES sequence or portion thereof. As a non-limiting example, when linearized this region may be split to have a first portion be on the 5′ terminus of the first region 202 and second portion be on the 3′ terminus of the first region 202. The second flanking region 206 may comprise a tailing sequence region 210 and may comprise a region of linked nucleotides or portion thereof 212 which may act similarly to a UTR in an mRNA and/or DNA.

Bridging the 5′ terminus of the first region 202 and the first flanking region 104 is a first operational region 205. In one embodiment, this operational region may comprise a start codon. The operational region may alternatively comprise any translation initiation sequence or signal including a start codon.

Bridging the 3′ terminus of the first region 202 and the second flanking region 106 is a second operational region 207. Traditionally this operational region comprises a stop codon. The operational region may alternatively comprise any translation initiation sequence or signal including a stop codon. According to the present invention, multiple serial stop codons may also be used. In one embodiment, the operation region of the present invention may comprise two stop codons. The first stop codon may be “TGA” or “UGA” and the second stop codon may be selected from the group consisting of “TAA,” “TGA.” “TAG,” “UAA,” “UGA” or “UAG.”

Turning to FIG. 6B, at least one non-nucleic acid moiety 201 may be used to prepare a circular construct 200 where the non-nucleic acid moiety 201 is used to bring the first flanking region 204 near the second flanking region 206. Non-limiting examples of non-nucleic acid moieties which may be used in the present invention are described herein. The circular construct 200 may comprise more than one non-nucleic acid moiety wherein the additional non-nucleic acid moeities may be heterologous or homologous to the first non-nucleic acid moiety.

Turning to FIG. 7A, the first region of linked nucleosides 202 may comprise a spacer region 214. This spacer region 214 may be used to separate the first region of linked nucleosides 202 so that the circular construct can include more than one open reading frame, non-coding region or an open reading frame and a non-coding region.

Turning to FIG. 7B, the second flanking region 206 may comprise one or more sensor regions 216 in the 3′UTR 212. These sensor sequences as discussed herein operate as pseudo-receptors (or binding sites) for ligands of the local microenvironment of the circular construct. For example, microRNA binding sites or miRNA seeds may be used as sensors such that they function as pseudoreceptors for any microRNAs present in the environment of the circular polynucleotide. As shown in FIG. 9, the one or more sensor regions 216 may be separated by a spacer region 214.

As shown in FIG. 8A, a circular construct 200, which includes one or more sensor regions 216, may also include a spacer region 214 in the first region of linked nucleosides 202. As discussed above for FIG. 7, this spacer region 214 may be used to separate the first region of linked nucleosides 202 so that the circular construct can include more than one open reading frame and/or more than one non-coding region.

Turning to FIG. 8B, a circular construct 200 may be a non-coding construct known as a circSP comprising at least one non-coding region such as, but not limited to, a sensor region 216. Each of the sensor regions 216 may include, but are not limited to, a miR sequence, a miR seed, a miR binding site and/or a miR sequence without the seed.

Turning to FIG. 9, at least one non-nucleic acid moiety 201 may be used to prepare a circular construct 200 which is a non-coding construct. The circular construct 200 which is a non-coding construct may comprise more than one non-nucleic acid moiety wherein the additional non-nucleic acid moeities may be heterologous or homologous to the first non-nucleic acid moiety.

Circular polynucleotides, formulations and compositions comprising circular polynucleotides, and methods of making, using and administering circular polynucleotides are also described in co-pending US Provisional Application No 61/873,010, filed Sep. 3, 2013, entitled Circular Polynucleotides, and U.S. Provisional Application No. 61/877,527, filed Sep. 13, 2013, entitled Circular Polynucleotides; each of which is incorporated by reference in its entirety.

Multimers of Polynucleotides

According to the present invention, multiple distinct chimeric polynucleotides and/or IVT polynucleotides may be linked together through the 3′-end using nucleotides which are modified at the 3′-terminus. Chemical conjugation may be used to control the stoichiometry of delivery into cells. For example, the glyoxylate cycle enzymes, isocitrate lyase and malate synthase, may be supplied into cells at a 1:1 ratio to alter cellular fatty acid metabolism. This ratio may be controlled by chemically linking chimeric polynucleotides and/or IVT polynucleotides using a 3′-azido terminated nucleotide on one polynucleotides species and a C₅-ethynyl or alkynyl-containing nucleotide on the opposite polynucleotide species. The modified nucleotide is added post-transcriptionally using terminal transferase (New England Biolabs, Ipswich, MA) according to the manufacturer's protocol. After the addition of the 3′-modified nucleotide, the two polynucleotides species may be combined in an aqueous solution, in the presence or absence of copper, to form a new covalent linkage via a click chemistry mechanism as described in the literature.

In another example, more than two chimeric polynucleotides and/or IVT polynucleotides may be linked together using a functionalized linker molecule. For example, a functionalized saccharide molecule may be chemically modified to contain multiple chemical reactive groups (SH—, NH₂—, N₃, etc. . . . ) to react with the cognate moiety on a 3′-functionalized mRNA molecule (i.e., a 3′-maleimide ester, 3′-NHS-ester, alkynyl). The number of reactive groups on the modified saccharide can be controlled in a stoichiometric fashion to directly control the stoichiometric ratio of conjugated chimeric polynucleotides and/or IVT polynucleotides.

In one embodiment, the chimeric polynucleotides and/or IVT polynucleotides may be linked together in a pattern. The pattern may be a simple alternating pattern such as CD[CD]A where each “C” and each “D” represent a chimeric polynucleotide, IVT polynucleotide, different chimeric polynucleotides or different IVT polynucleotides. The pattern may repeat x number of times, where x=1-300. It is to be understood that the antigens of the NAVs of the present invention may be encoded by such linked polynucleotides, as described herein. Patterns may also be alternating multiples such as CCDD[CCDD]_x(an alternating double multiple) or CCCDDD[CCCDDD]_x(an alternating triple multiple) pattern. The alternating double multiple or alternating triple multiple may repeat x number of times, where x=1-300.

Conjugates and Combinations of Polynucleotides

In order to further enhance protein production, polynucleotides of the present invention can be designed to be conjugated to other polynucleotides, dyes, intercalating agents (e.g. acridines), cross-linkers (e.g. psoralene, mitomycin C), porphyrins (TPPC4, texaphyrin, Sapphyrin), polycyclic aromatic hydrocarbons (e.g., phenazine, dihydrophenazine), artificial endonucleases (e.g. EDTA), alkylating agents, phosphate, amino, mercapto, PEG (e.g., PEG-40K), MPEG, [MPEG]₂, polyamino, alkyl, substituted alkyl, radiolabeled markers, enzymes, haptens (e.g. biotin), transport/absorption facilitators (e.g., aspirin, vitamin E, folic acid), synthetic ribonucleases, proteins, e.g., glycoproteins, or peptides, e.g., molecules having a specific affinity for a co-ligand, or antibodies e.g., an antibody, that binds to a specified cell type such as a cancer cell, endothelial cell, or bone cell, hormones and hormone receptors, non-peptidic species, such as lipids, lectins, carbohydrates, vitamins, cofactors, or a drug.

In a preferred embodiment, the polynucleotides of the present invention which encode an antigen are conjugated to one or more dendritic cell markers.

Conjugation may result in increased stability and/or half life and may be particularly useful in targeting the polynucleotides to specific sites in the cell, tissue or organism.

According to the present invention, the polynucleotides may be administered with, conjugated to or further encode one or more of RNAi agents, siRNAs, shRNAs, miRNAs, miRNA binding sites, antisense RNAs, ribozymes, catalytic DNA, tRNA, RNAs that induce triple helix formation, aptamers or vectors, and the like.

Bifunctional Polynucleotides

In one embodiment of the invention NAVs may comprise bifunctional polynucleotides (e.g., bifunctional IVT polynucleotides, bifunctional chimeric polynucleotides or bifunctional circular polynucleotides). As the name implies, bifunctional polynucleotides are those having or capable of at least two functions. These molecules may also by convention be referred to as multi-functional. It is to be understood that the NAV polynucleotides of the present invention may be conjugated to other molecules or agents, as described supra.

The multiple functionalities of bifunctional polynucleotides may be encoded by the NAV (the function may not manifest until the encoded product is translated) or may be a property of the polynucleotide itself. It may be structural or chemical. Bifunctional modified polynucleotides may comprise a function that is covalently or electrostatically associated with the polynucleotides. Further, the two functions may be provided in the context of a complex of a chimeric polynucleotide and another molecule.

Noncoding Polynucleotides

As described herein, provided are polynucleotides having sequences that are partially or substantially not translatable, e.g., having a noncoding region. As one non-limiting example, the noncoding region may be the first region of the IVT polynucleotide or the circular polynucleotide. Alternatively, the noncoding region may be a region other than the first region. As another non-limiting example, the noncoding region may be the A. B and/or C region of the chimeric polynucleotide.

Such molecules are generally not translated, but can exert an effect on the immune response or protein production by one or more of binding to and sequestering one or more translational machinery components such as a ribosomal protein or a transfer RNA (tRNA), thereby effectively reducing protein expression in the cell or modulating one or more pathways or cascades in a cell which in turn alters protein levels. The polynucleotide may contain or encode one or more long noncoding RNA (OncRNA, or lincRNA) or portion thereof, a small nucleolar RNA (sno-RNA), micro RNA (miRNA), small interfering RNA (siRNA) or Piwi-interacting RNA (piRNA). Examples of such lncRNA molecules and RNAi constructs designed to target such lncRNA any of which may be encoded in the polynucleotides are taught in International Publication, WO2012/018881 A2, the contents of which are incorporated herein by reference in their entirety.

According to the present invention, the polynucleotide may be designed to encode one or more polypeptides of interest or fragments thereof. Such polypeptide of interest may include, but is not limited to, whole polypeptides, a plurality of polypeptides or fragments of polypeptides, which independently may be encoded by one or more regions or parts or the whole of a polynucleotide. As used herein, the term “polypeptides of interest” refer to any polypeptide which is selected to be encoded within, or whose function is affected by, the polynucleotides of the present invention. Any of the peptides or polypeptides of the invention may be antigenic.

As used herein, “polypeptide” means a polymer of amino acid residues (natural or unnatural) linked together most often by peptide bonds. The term, as used herein, refers to proteins, polypeptides, and peptides of any size, structure, or function. In one embodiment, the polypeptides of interest are antigens encoded by the polynucleotides as described herein.

In some instances the polypeptide encoded is smaller than about 50 amino acids and the polypeptide is then termed a peptide. If the polypeptide is a peptide, it will be at least about 2, 3, 4, or at least 5 amino acid residues long. Thus, polypeptides include gene products, naturally occurring polypeptides, synthetic polypeptides, homologs, orthologs, paralogs, fragments and other equivalents, variants, and analogs of the foregoing. A polypeptide may be a single molecule or may be a multi-molecular complex such as a dimer, trimer or tetramer. They may also comprise single chain or multichain polypeptides such as antibodies or insulin and may be associated or linked. Most commonly disulfide linkages are found in multichain polypeptides. The term polypeptide may also apply to amino acid polymers in which one or more amino acid residues are an artificial chemical analogue of a corresponding naturally occurring amino acid.

The term “polypeptide variant” refers to molecules which differ in their amino acid sequence from a native or reference sequence. The amino acid sequence variants may possess substitutions, deletions, and/or insertions at certain positions within the amino acid sequence, as compared to a native or reference sequence. Ordinarily, variants will possess at least about 50% identity (homology) to a native or reference sequence, and preferably, they will be at least about 80%, more preferably at least about 90% identical (homologous) to a native or reference sequence.

In some embodiments “variant mimics” are provided. As used herein, the term “variant mimic” is one which contains one or more amino acids which would mimic an activated sequence. For example, glutamate may serve as a mimic for phosphoro-threonine and/or phosphoro-serine. Alternatively, variant mimics may result in deactivation or in an inactivated product containing the mimic, e.g., phenylalanine may act as an inactivating substitution for tyrosine; or alanine may act as an inactivating substitution for serine.

“Homology” as it applies to amino acid sequences is defined as the percentage of residues in the candidate amino acid sequence that are identical with the residues in the amino acid sequence of a second sequence after aligning the sequences and introducing gaps, if necessary, to achieve the maximum percent homology. Methods and computer programs for the alignment are well known in the art. It is understood that homology depends on a calculation of percent identity but may differ in value due to gaps and penalties introduced in the calculation.

By “homologs” as it applies to polypeptide sequences means the corresponding sequence of other species having substantial identity to a second sequence of a second species.

“Analogs” is meant to include polypeptide variants which differ by one or more amino acid alterations, e.g., substitutions, additions or deletions of amino acid residues that still maintain one or more of the properties of the parent or starting polypeptide.

The present invention contemplates several types of compositions which are polypeptide based including variants and derivatives. These include substitutional, insertional, deletion and covalent variants and derivatives. The term “derivative” is used synonymously with the term “variant” but generally refers to a molecule that has been modified and/or changed in any way relative to a reference molecule or starting molecule.

As such, polynucleotides encoding peptides or polypeptides containing substitutions, insertions and/or additions, deletions and covalent modifications with respect to reference sequences, in particular the polypeptide sequences disclosed herein, are included within the scope of this invention. For example, sequence tags or amino acids, such as one or more lysines, can be added to the peptide sequences of the invention (e.g., at the N-terminal or C-terminal ends). Sequence tags can be used for peptide purification or localization. Lysines can be used to increase peptide solubility or to allow for biotinylation. Alternatively, amino acid residues located at the carboxy and amino terminal regions of the amino acid sequence of a peptide or protein may optionally be deleted providing for truncated sequences. Certain amino acids (e.g., C-terminal or N-terminal residues) may alternatively be deleted depending on the use of the sequence, as for example, expression of the sequence as part of a larger sequence which is soluble, or linked to a solid support.

“Substitutional variants” when referring to polypeptides are those that have at least one amino acid residue in a native or starting sequence removed and a different amino acid inserted in its place at the same position. The substitutions may be single, where only one amino acid in the molecule has been substituted, or they may be multiple, where two or more amino acids have been substituted in the same molecule.

As used herein the term “conservative amino acid substitution” refers to the substitution of an amino acid that is normally present in the sequence with a different amino acid of similar size, charge, or polarity. Examples of conservative substitutions include the substitution of a non-polar (hydrophobic) residue such as isoleucine, valine and leucine for another non-polar residue. Likewise, examples of conservative substitutions include the substitution of one polar (hydrophilic) residue for another such as between arginine and lysine, between glutamine and asparagine, and between glycine and serine. Additionally, the substitution of a basic residue such as lysine, arginine or histidine for another, or the substitution of one acidic residue such as aspartic acid or glutamic acid for another acidic residue are additional examples of conservative substitutions. Examples of non-conservative substitutions include the substitution of a non-polar (hydrophobic) amino acid residue such as isoleucine, valine, leucine, alanine, methionine for a polar (hydrophilic) residue such as cysteine, glutamine, glutamic acid or lysine and/or a polar residue for a non-polar residue.

“Insertional variants” when referring to polypeptides are those with one or more amino acids inserted immediately adjacent to an amino acid at a particular position in a native or starting sequence. “Immediately adjacent” to an amino acid means connected to either the alpha-carboxy or alpha-amino functional group of the amino acid.

“Deletional variants” when referring to polypeptides are those with one or more amino acids in the native or starting amino acid sequence removed. Ordinarily, deletional variants will have one or more amino acids deleted in a particular region of the molecule.

“Covalent derivatives” when referring to polypeptides include modifications of a native or starting protein with an organic proteinaceous or non-proteinaceous derivatizing agent, and/or post-translational modifications. Covalent modifications are traditionally introduced by reacting targeted amino acid residues of the protein with an organic derivatizing agent that is capable of reacting with selected side-chains or terminal residues, or by harnessing mechanisms of post-translational modifications that function in selected recombinant host cells. The resultant covalent derivatives are useful in programs directed at identifying residues important for biological activity, for immunoassays, or for the preparation of anti-protein antibodies for immunoaffinity purification of the recombinant glycoprotein. Such modifications are within the ordinary skill in the art and are performed without undue experimentation.

Certain post-translational modifications are the result of the action of recombinant host cells on the expressed polypeptide. Glutaminyl and asparaginyl residues are frequently post-translationally deamidated to the corresponding glutamyl and aspartyl residues. Alternatively, these residues are deamidated under mildly acidic conditions. Either form of these residues may be present in the polypeptides produced in accordance with the present invention.

Other post-translational modifications include hydroxylation of proline and lysine, phosphorylation of hydroxyl groups of seryl or threonyl residues, methylation of the alpha-amino groups of lysine, arginine, and histidine side chains (T. E. Creighton, Proteins: Structure and Molecular Properties, W.H. Freeman & Co., San Francisco, pp. 79-86 (1983)).

“Features” when referring to polypeptides are defined as distinct amino acid sequence-based components of a molecule. Features of the polypeptides encoded by the polynucleotides of the present invention include surface manifestations, local conformational shape, folds, loops, half-loops, domains, half-domains, sites, termini or any combination thereof.

As used herein when referring to polypeptides the term “surface manifestation” refers to a polypeptide based component of a protein appearing on an outermost surface.

As used herein when referring to polypeptides the term “local conformational shape” means a polypeptide based structural manifestation of a protein which is located within a definable space of the protein.

As used herein when referring to polypeptides the term “fold” refers to the resultant conformation of an amino acid sequence upon energy minimization. A fold may occur at the secondary or tertiary level of the folding process. Examples of secondary level folds include beta sheets and alpha helices. Examples of tertiary folds include domains and regions formed due to aggregation or separation of energetic forces. Regions formed in this way include hydrophobic and hydrophilic pockets, and the like.

As used herein the term “turn” as it relates to protein conformation means a bend which alters the direction of the backbone of a peptide or polypeptide and may involve one, two, three or more amino acid residues.

As used herein when referring to polypeptides the term “loop” refers to a structural feature of a polypeptide which may serve to reverse the direction of the backbone of a peptide or polypeptide. Where the loop is found in a polypeptide and only alters the direction of the backbone, it may comprise four or more amino acid residues. Oliva et al. have identified at least 5 classes of protein loops (J. Mol Biol 266 (4): 814-830; 1997). Loops may be open or closed. Closed loops or “cyclic” loops may comprise 2, 3, 4, 5, 6, 7, 8, 9, 10 or more amino acids between the bridging moieties. Such bridging moieties may comprise a cysteine-cysteine bridge (Cys-Cys) typical in polypeptides having disulfide bridges or alternatively bridging moieties may be non-protein based such as the dibromozylyl agents used herein.

As used herein when referring to polypeptides the term “half-loop” refers to a portion of an identified loop having at least half the number of amino acid resides as the loop from which it is derived. It is understood that loops may not always contain an even number of amino acid residues. Therefore, in those cases where a loop contains or is identified to comprise an odd number of amino acids, a half-loop of the odd-numbered loop will comprise the whole number portion or next whole number portion of the loop (number of amino acids of the loop/2+/−0.5 amino acids). For example, a loop identified as a 7 amino acid loop could produce half-loops of 3 amino acids or 4 amino acids (7/2=3.5+/−0.5 being 3 or 4).

As used herein when referring to polypeptides the term “domain” refers to a motif of a polypeptide having one or more identifiable structural or functional characteristics or properties (e.g., binding capacity, serving as a site for protein-protein interactions).

As used herein when referring to polypeptides the term “half-domain” means a portion of an identified domain having at least half the number of amino acid resides as the domain from which it is derived. It is understood that domains may not always contain an even number of amino acid residues. Therefore, in those cases where a domain contains or is identified to comprise an odd number of amino acids, a half-domain of the odd-numbered domain will comprise the whole number portion or next whole number portion of the domain (number of amino acids of the domain/2+/−0.5 amino acids). For example, a domain identified as a 7 amino acid domain could produce half-domains of 3 amino acids or 4 amino acids (7/2=3.5+/−0.5 being 3 or 4). It is also understood that sub-domains may be identified within domains or half-domains, these subdomains possessing less than all of the structural or functional properties identified in the domains or half domains from which they were derived. It is also understood that the amino acids that comprise any of the domain types herein need not be contiguous along the backbone of the polypeptide (i.e., nonadjacent amino acids may fold structurally to produce a domain, half-domain or subdomain).

As used herein when referring to polypeptides the terms “site” as it pertains to amino acid based embodiments is used synonymously with “amino acid residue” and “amino acid side chain.” A site represents a position within a peptide or polypeptide that may be modified, manipulated, altered, derivatized or varied within the polypeptide based molecules of the present invention.

As used herein the terms “termini” or “terminus” when referring to polypeptides refers to an extremity of a peptide or polypeptide. Such extremity is not limited only to the first or final site of the peptide or polypeptide but may include additional amino acids in the terminal regions. The polypeptide based molecules of the present invention may be characterized as having both an N-terminus (terminated by an amino acid with a free amino group (NH2)) and a C-terminus (terminated by an amino acid with a free carboxyl group (COOH)). Proteins of the invention are in some cases made up of multiple polypeptide chains brought together by disulfide bonds or by non-covalent forces (multimers, oligomers). These sorts of proteins will have multiple N- and C-termini. Alternatively, the termini of the polypeptides may be modified such that they begin or end, as the case may be, with a non-polypeptide based moiety such as an organic conjugate.

Once any of the features have been identified or defined as a desired component of a polypeptide to be encoded by a polynucleotide of the invention, any of several manipulations and/or modifications of these features may be performed by moving, swapping, inverting, deleting, randomizing or duplicating. Furthermore, it is understood that manipulation of features may result in the same outcome as a modification to the molecules of the invention. For example, a manipulation which involved deleting a domain would result in the alteration of the length of a molecule just as modification of a nucleic acid to encode less than a full length molecule would.

Modifications and manipulations can be accomplished by methods known in the art such as, but not limited to, site directed mutagenesis or a priori incorporation during chemical synthesis. The resulting modified molecules may then be tested for activity using in vitro or in vivo assays such as those described herein or any other suitable screening assay known in the art.

According to the present invention, the polypeptides may comprise a consensus sequence which is discovered through rounds of experimentation. As used herein a “consensus” sequence is a single sequence which represents a collective population of sequences allowing for variability at one or more sites.

As recognized by those skilled in the art, protein fragments, functional protein domains, and homologous proteins are also considered to be within the scope of polypeptides of interest of this invention. For example, provided herein is any protein fragment (meaning a polypeptide sequence at least one amino acid residue shorter than a reference polypeptide sequence but otherwise identical) of a reference protein 10, 20, 30, 40, 50, 60, 70, 80, 90, 100 or greater than 100 amino acids in length. In another example, any protein that includes a stretch of about 20, about 30, about 40, about 50, or about 100 amino acids which are about 40%, about 50%, about 60%, about 70%, about 80%, about 90%, about 95%, or about 100% identical to any of the sequences described herein can be utilized in accordance with the invention. In certain embodiments, a polypeptide to be utilized in accordance with the invention includes 2, 3, 4, 5, 6, 7, 8, 9, 10, or more mutations as shown in any of the sequences provided or referenced herein.

In one embodiment, at least one polypeptide of interest may be an antigen or fragment thereof, or any component of a ribonucleic acid vaccine.

Reference molecules (polypeptides or polynucleotides) may share a certain identity with the designed molecules (polypeptides or polynucleotides). The term “identity” as known in the art, refers to a relationship between the sequences of two or more peptides, polypeptides or polynucleotides, as determined by comparing the sequences. In the art, identity also means the degree of sequence relatedness between them as determined by the number of matches between strings of two or more amino acid residues or nucleosides. Identity measures the percent of identical matches between the smaller of two or more sequences with gap alignments (if any) addressed by a particular mathematical model or computer program (i.e., “algorithms”). Identity of related peptides can be readily calculated by known methods. Such methods include, but are not limited to, those described in Computational Molecular Biology, Lesk, A. M., ed., Oxford University Press, New York, 1988; Biocomputing: Informatics and Genome Projects, Smith, D. W., ed., Academic Press, New York, 1993; Computer Analysis of Sequence Data, Part 1, Griffin, A. M., and Griffin, H. G., eds., Humana Press, New Jersey, 1994; Sequence Analysis in Molecular Biology, von Heinje, G., Academic Press, 1987; Sequence Analysis Primer, Gribskov, M. and Devereux, J., eds., M. Stockton Press, New York, 1991; and Carillo et al., SIAM J. Applied Math. 48, 1073 (1988).

In some embodiments, the encoded polypeptide variant may have the same or a similar activity as the reference polypeptide. Alternatively, the variant may have an altered activity (e.g., increased or decreased) relative to a reference polypeptide. Generally, variants of a particular polynucleotide or polypeptide of the invention will have at least about 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% but less than 100% sequence identity to that particular reference polynucleotide or polypeptide as determined by sequence alignment programs and parameters described herein and known to those skilled in the art. Such tools for alignment include those of the BLAST suite (Stephen F. Altschul, Thomas L. Madden, Alejandro A. Schaffer, Jinghui Zhang, Zheng Zhang, Webb Miller, and David J. Lipman (1997), “Gapped BLAST and PSI-BLAST: a new generation of protein database search programs”, Nucleic Acids Res. 25:3389-3402.) Other tools are described herein, specifically in the definition of “Identity.”

Default parameters in the BLAST algorithm include, for example, an expect threshold of 10, Word size of 28, Match/Mismatch Scores 1, −2, Gap costs Linear. Any filter can be applied as well as a selection for species specific repeats, e.g., Homo sapiens.

Cell-Penetrating Polypeptides

The polynucleotides disclosed herein (e.g., antigen-encoding polynucleotides featured in the NAVs of the invention), may also encode one or more cell-penetrating polypeptides. As used herein, “cell-penetrating polypeptide” or CPP refers to a polypeptide which may facilitate the cellular uptake of molecules. A cell-penetrating polypeptide of the present invention may contain one or more detectable labels. The polypeptides may be partially labeled or completely labeled throughout. The polynucleotides may encode the detectable label completely, partially or not at all. The cell-penetrating peptide may also include a signal sequence. As used herein, a “signal sequence” refers to a sequence of amino acid residues bound at the amino terminus of a nascent protein during protein translation. The signal sequence may be used to signal the secretion of the cell-penetrating polypeptide.

In one embodiment, the polynucleotides may also encode a fusion protein. The fusion protein may be created by operably linking a charged protein to a therapeutic protein. As used herein, “operably linked” refers to the therapeutic protein and the charged protein being connected in such a way to permit the expression of the complex when introduced into the cell. As used herein, “charged protein” refers to a protein that carries a positive, negative or overall neutral electrical charge. Preferably, the therapeutic protein may be covalently linked to the charged protein in the formation of the fusion protein. The ratio of surface charge to total or surface amino acids may be approximately 0.1, 0.2, 0.3, 0.4, 0.5, 0.6, 0.7, 0.8 or 0.9.

The cell-penetrating polypeptide encoded by the polynucleotides may form a complex after being translated. The complex may comprise a charged protein linked, e.g. covalently linked, to the cell-penetrating polypeptide. “Therapeutic protein” refers to a protein that, when administered to a cell has a therapeutic, diagnostic, and/or prophylactic effect and/or elicits a desired biological and/or pharmacological effect.

In one embodiment, the cell-penetrating polypeptide may comprise a first domain and a second domain. The first domain may comprise a supercharged polypeptide. The second domain may comprise a protein-binding partner. As used herein, “protein-binding partner” includes, but is not limited to, antibodies and functional fragments thereof, scaffold proteins, or peptides. The cell-penetrating polypeptide may further comprise an intracellular binding partner for the protein-binding partner. The cell-penetrating polypeptide may be capable of being secreted from a cell where the polynucleotides may be introduced. The cell-penetrating polypeptide may also be capable of penetrating the first cell.

In a further embodiment, the cell-penetrating polypeptide is capable of penetrating a second cell. The second cell may be from the same area as the first cell, or it may be from a different area. The area may include, but is not limited to, tissues and organs. The second cell may also be proximal or distal to the first cell.

In one embodiment, the polynucleotides may encode a cell-penetrating polypeptide which may comprise a protein-binding partner. The protein binding partner may include, but is not limited to, an antibody, a supercharged antibody or a functional fragment. The polynucleotides may be introduced into the cell where a cell-penetrating polypeptide comprising the protein-binding partner is introduced.

Anti-Microbial and Anti-Viral Polypeptides

The polynucleotides of the present invention (e.g., antigen-encoding polynucleotides featured in the NAVs of the invention) may be designed to encode, or be co-administered with, a polynucleotide encoding one or more antimicrobial peptides (AMP) or antiviral peptides (AVP). AMPs and AVPs have been isolated and described from a wide range of animals such as, but not limited to, microorganisms, invertebrates, plants, amphibians, birds, fish, and mammals (Wang et al., Nucleic Acids Res. 2009; 37 (Database issue):D933-7). For example, anti-microbial polypeptides are described in Antimicrobial Peptide Database (http://aps.unmc.edu/AP/main.php; Wang et al., Nucleic Acids Res. 2009; 37 (Database issue):D933-7), CAMP: Collection of Anti-Microbial Peptides (http://www.bicnirrh.res.in/antimicrobial/); Thomas et al., Nucleic Acids Res. 2010; 38 (Database issue):D774-80), U.S. Pat. Nos. 5,221,732, 5,447,914, 5,519,115, 5,607,914, 5,714,577, 5,734,015, 5,798,336, 5,821,224, 5,849,490, 5,856,127, 5,905,187, 5,994,308, 5,998,374, 6,107,460, 6,191,254, 6,211,148, 6,300,489, 6,329,504, 6,399,370, 6,476,189, 6,478,825, 6,492,328, 6,514,701, 6,573,361, 6,573,361, 6,576,755, 6,605,698, 6,624,140, 6,638,531, 6,642,203, 6,653,280, 6,696,238, 6,727,066, 6,730,659, 6,743,598, 6,743,769, 6,747,007, 6,790,833, 6,794,490, 6,818,407, 6,835,536, 6,835,713, 6,838,435, 6,872,705, 6,875,907, 6,884,776, 6,887,847, 6,906,035, 6,911,524, 6,936,432, 7,001,924, 7,071,293, 7,078,380, 7,091,185, 7,094,759, 7,166,769, 7,244,710, 7,314,858, and 7,582,301, the contents of which are incorporated by reference in their entirety.

The anti-microbial polypeptides described herein may block cell fusion and/or viral entry by one or more enveloped viruses (e.g., HIV, HCV). For example, the anti-microbial polypeptide can comprise or consist of a synthetic peptide corresponding to a region, e.g., a consecutive sequence of at least about 5, 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, or 60 amino acids of the transmembrane subunit of a viral envelope protein, e.g., HIV-1 gp120 or gp41. The amino acid and nucleotide sequences of HIV-1 gp120 or gp41 are described in, e.g., Kuiken et al., (2008). “HIV Sequence Compendium,” Los Alamos National Laboratory.

In some embodiments, the anti-microbial polypeptide may have at least about 75%, 80%, 85%, 90%, 95%, 100% sequence homology to the corresponding viral protein sequence. In some embodiments, the anti-microbial polypeptide may have at least about 75%, 80%, 85%, 90%, 95%, or 100% sequence homology to the corresponding viral protein sequence.

In other embodiments, the anti-microbial polypeptide may comprise or consist of a synthetic peptide corresponding to a region, e.g., a consecutive sequence of at least about 5, 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, or 60 amino acids of the binding domain of a capsid binding protein. In some embodiments, the anti-microbial polypeptide may have at least about 75%, 80%, 85%, 90%, 95%, or 100% sequence homology to the corresponding sequence of the capsid binding protein.

The anti-microbial polypeptides described herein may block protease dimerization and inhibit cleavage of viral proproteins (e.g., HIV Gag-pol processing) into functional proteins thereby preventing release of one or more enveloped viruses (e.g., HIV, HCV). In some embodiments, the anti-microbial polypeptide may have at least about 75%, 80%, 85%, 90%, 95%, 100% sequence homology to the corresponding viral protein sequence.

In other embodiments, the anti-microbial polypeptide can comprise or consist of a synthetic peptide corresponding to a region, e.g., a consecutive sequence of at least about 5, 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, or 60 amino acids of the binding domain of a protease binding protein. In some embodiments, the anti-microbial polypeptide may have at least about 75%, 80%, 85%, 90%, 95%, 100% sequence homology to the corresponding sequence of the protease binding protein.

The anti-microbial polypeptides described herein can include an in vitro-evolved polypeptide directed against a viral pathogen.

Anti-Microbial Polypeptides

Anti-microbial polypeptides (AMPs) are small peptides of variable length, sequence and structure with broad spectrum activity against a wide range of microorganisms including, but not limited to, bacteria, viruses, fungi, protozoa, parasites, prions, and tumor/cancer cells. (See, e.g., Zaiou, J Mol Med, 2007; 85:317; herein incorporated by reference in its entirety). It has been shown that AMPs have broad-spectrum of rapid onset of killing activities, with potentially low levels of induced resistance and concomitant broad anti-inflammatory effects.

In some embodiments, the anti-microbial polypeptide (e.g., an anti-bacterial polypeptide) may be under 10 kDa, e.g., under 8 kDa, 6 kDa, 4 kDa, 2 kDa, or 1 kDa. In some embodiments, the anti-microbial polypeptide (e.g., an anti-bacterial polypeptide) consists of from about 6 to about 100 amino acids, e.g., from about 6 to about 75 amino acids, about 6 to about 50 amino acids, about 6 to about 25 amino acids, about 25 to about 100 amino acids, about 50 to about 100 amino acids, or about 75 to about 100 amino acids. In certain embodiments, the anti-microbial polypeptide (e.g., an anti-bacterial polypeptide) may consist of from about 15 to about 45 amino acids. In some embodiments, the anti-microbial polypeptide (e.g., an anti-bacterial polypeptide) is substantially cationic.

In some embodiments, the anti-microbial polypeptide (e.g., an anti-bacterial polypeptide) may be substantially amphipathic. In certain embodiments, the anti-microbial polypeptide (e.g., an anti-bacterial polypeptide) may be substantially cationic and amphipathic. In some embodiments, the anti-microbial polypeptide (e.g., an anti-bacterial polypeptide) may be cytostatic to a Gram-positive bacterium. In some embodiments, the anti-microbial polypeptide (e.g., an anti-bacterial polypeptide) may be cytotoxic to a Gram-positive bacterium. In some embodiments, the anti-microbial polypeptide (e.g., an anti-bacterial polypeptide) may be cytostatic and cytotoxic to a Gram-positive bacterium. In some embodiments, the anti-microbial polypeptide (e.g., an anti-bacterial polypeptide) may be cytostatic to a Gram-negative bacterium. In some embodiments, the anti-microbial polypeptide (e.g., an anti-bacterial polypeptide) may be cytotoxic to a Gram-negative bacterium. In some embodiments, the anti-microbial polypeptide (e.g., an anti-bacterial polypeptide) may be cytostatic and cytotoxic to a Gram-positive bacterium. In some embodiments, the anti-microbial polypeptide may be cytostatic to a virus, fungus, protozoan, parasite, prion, or a combination thereof. In some embodiments, the anti-microbial polypeptide may be cytotoxic to a virus, fungus, protozoan, parasite, prion, or a combination thereof. In certain embodiments, the anti-microbial polypeptide may be cytostatic and cytotoxic to a virus, fungus, protozoan, parasite, prion, or a combination thereof. In some embodiments, the anti-microbial polypeptide may be cytotoxic to a tumor or cancer cell (e.g., a human tumor and/or cancer cell). In some embodiments, the anti-microbial polypeptide may be cytostatic to a tumor or cancer cell (e.g., a human tumor and/or cancer cell). In certain embodiments, the anti-microbial polypeptide may be cytotoxic and cytostatic to a tumor or cancer cell (e.g., a human tumor or cancer cell). In some embodiments, the anti-microbial polypeptide (e.g., an anti-bacterial polypeptide) may be a secreted polypeptide.

In some embodiments, the anti-microbial polypeptide comprises or consists of a defensin. Exemplary defensins include, but are not limited to, α-defensins (e.g., neutrophil defensin 1, defensin alpha 1, neutrophil defensin 3, neutrophil defensin 4, defensin 5, defensin 6), β-defensins (e.g., beta-defensin 1, beta-defensin 2, beta-defensin 103, beta-defensin 107, beta-defensin 110, beta-defensin 136), and O-defensins. In other embodiments, the anti-microbial polypeptide comprises or consists of a cathelicidin (e.g., hCAP18).

Anti-Viral Polypeptides

Anti-viral polypeptides (AVPs) are small peptides of variable length, sequence and structure with broad spectrum activity against a wide range of viruses. See, e.g., Zaiou, J Mol Med, 2007; 85:317. It has been shown that AVPs have a broad-spectrum of rapid onset of killing activities, with potentially low levels of induced resistance and concomitant broad anti-inflammatory effects. In some embodiments, the anti-viral polypeptide is under 10 kDa, e.g., under 8 kDa, 6 kDa, 4 kDa, 2 kDa, or 1 kDa. In some embodiments, the anti-viral polypeptide comprises or consists of from about 6 to about 100 amino acids, e.g., from about 6 to about 75 amino acids, about 6 to about 50 amino acids, about 6 to about 25 amino acids, about 25 to about 100 amino acids, about 50 to about 100 amino acids, or about 75 to about 100 amino acids. In certain embodiments, the anti-viral polypeptide comprises or consists of from about 15 to about 45 amino acids. In some embodiments, the anti-viral polypeptide is substantially cationic. In some embodiments, the anti-viral polypeptide is substantially amphipathic. In certain embodiments, the anti-viral polypeptide is substantially cationic and amphipathic. In some embodiments, the anti-viral polypeptide is cytostatic to a virus. In some embodiments, the anti-viral polypeptide is cytotoxic to a virus. In some embodiments, the anti-viral polypeptide is cytostatic and cytotoxic to a virus. In some embodiments, the anti-viral polypeptide is cytostatic to a bacterium, fungus, protozoan, parasite, prion, or a combination thereof. In some embodiments, the anti-viral polypeptide is cytotoxic to a bacterium, fungus, protozoan, parasite, prion or a combination thereof. In certain embodiments, the anti-viral polypeptide is cytostatic and cytotoxic to a bacterium, fungus, protozoan, parasite, prion, or a combination thereof. In some embodiments, the anti-viral polypeptide is cytotoxic to a tumor or cancer cell (e.g., a human cancer cell). In some embodiments, the anti-viral polypeptide is cytostatic to a tumor or cancer cell (e.g., a human cancer cell). In certain embodiments, the anti-viral polypeptide is cytotoxic and cytostatic to a tumor or cancer cell (e.g., a human cancer cell). In some embodiments, the anti-viral polypeptide is a secreted polypeptide.

Cytotoxic Nucleosides

In one embodiment, the polynucleotides of the present invention (e.g., antigen-encoding polynucleotides featured in the NAVs of the invention) may incorporate one or more cytotoxic nucleosides. For example, cytotoxic nucleosides may be incorporated into polynucleotides such as bifunctional modified RNAs or mRNAs. Cytotoxic nucleoside anti-cancer agents include, but are not limited to, adenosine arabinoside, cytarabine, cytosine arabinoside, 5-fluorouracil, fludarabine, floxuridine, FTORAFUR® (a combination of tegafur and uracil), tegafur ((RS)-5-fluoro-1-(tetrahydrofuran-2-yl)pyrimidine-2,4(1H,3H)-dione), and 6-mercaptopurine.

A number of cytotoxic nucleoside analogues are in clinical use, or have been the subject of clinical trials, as anticancer agents. Examples of such analogues include, but are not limited to, cytarabine, gemcitabine, troxacitabine, decitabine, tezacitabine, 2′-deoxy-2′-methylidenecytidine (DMDC), cladribine, clofarabine, 5-azacytidine, 4′-thio-aracytidine, cyclopentenylcytosine and 1-(2-C-cyano-2-deoxy-beta-D-arabino-pentofuranosyl)-cytosine. Another example of such a compound is fludarabine phosphate. These compounds may be administered systemically and may have side effects which are typical of cytotoxic agents such as, but not limited to, little or no specificity for tumor cells over proliferating normal cells.

A number of prodrugs of cytotoxic nucleoside analogues are also reported in the art. Examples include, but are not limited to, N4-behenoyl-1-beta-D-arabinofuranosylcytosine, N4-octadecyl-1-beta-D-arabinofuranosylcytosine, N4-palmitoyl-1-(2-C-cyano-2-deoxy-beta-D-arabino-pentofuranosyl) cytosine, and P-4055 (cytarabine 5′-elaidic acid ester). In general, these podrugs may be converted into the active drugs mainly in the liver and systemic circulation and display little or no selective release of active drug in the tumor tissue. For example, capecitabine, a prodrug of 5′-deoxy-5-fluorocytidine (and eventually of 5-fluorouracil), is metabolized both in the liver and in the tumor tissue. A series of capecitabine analogues containing “an easily hydrolysable radical under physiological conditions” has been claimed by Fujiu et al. (U.S. Pat. No. 4,966,891) and is herein incorporated by reference. The series described by Fujiu includes N4 alkyl and aralkyl carbamates of 5′-deoxy-5-fluorocytidine and the implication that these compounds will be activated by hydrolysis under normal physiological conditions to provide 5′-deoxy-5-fluorocytidine.

A series of cytarabine N4-carbamates has been by reported by Fadl et al (Pharmazie. 1995, 50, 382-7, herein incorporated by reference in its entirety) in which compounds were designed to convert into cytarabine in the liver and plasma. WO 2004/041203, herein incorporated by reference in its entirety, discloses prodrugs of gemcitabine, where some of the prodrugs are N4-carbamates. These compounds were designed to overcome the gastrointestinal toxicity of gemcitabine and were intended to provide gemcitabine by hydrolytic release in the liver and plasma after absorption of the intact prodrug from the gastrointestinal tract. Nomura et al (Bioorg Med. Chem. 2003, 11, 2453-61, herein incorporated by reference in its entirety) have described acetal derivatives of 1-(3-C-ethynyl-β-D-ribo-pentofaranosyl) cytosine which, on bioreduction, produced an intermediate that required further hydrolysis under acidic conditions to produce a cytotoxic nucleoside compound.

Cytotoxic nucleotides which may be chemotherapeutic also include, but are not limited to, pyrazolo [3,4-D]-pyrimidines, allopurinol, azathioprine, capecitabine, cytosine arabinoside, fluorouracil, mercaptopurine, 6-thioguanine, acyclovir, ara-adenosine, ribavirin, 7-deaza-adenosine, 7-deaza-guanosine, 6-aza-uracil, 6-aza-cytidine, thymidine ribonucleotide, 5-bromodeoxyuridine, 2-chloro-purine, and inosine, or combinations thereof.

Polynucleotides Having Untranslated Regions (UTRs)

The polynucleotides of the present invention (e.g., antigen-encoding polynucleotides featured in the NAVs of the invention) may comprise one or more regions or parts which act or function as an untranslated region. Where polynucleotides are designed to encode at least one polypeptide of interest, the polynucleotides may comprise one or more of these untranslated regions.

By definition, wild type untranslated regions (UTRs) of a gene are transcribed but not translated. In mRNA, the 5′UTR starts at the transcription start site and continues to the start codon but does not include the start codon; whereas, the 3′UTR starts immediately following the stop codon and continues until the transcriptional termination signal. There is growing body of evidence about the regulatory roles, played by the UTRs in terms of stability of the nucleic acid molecule and translation. The regulatory features of a UTR can be incorporated into the polynucleotides of the present invention to, among other things, enhance the stability of the molecule. The specific features can also be incorporated to ensure controlled down-regulation of the transcript in case they are misdirected to undesired organs sites.

Tables 19 and 20 provide a listing of exemplary UTRs which may be utilized in the polynucleotides of the present invention. Shown in Table 19 is a listing of a 5′-untranslated region of the invention. Variants of 5′ UTRs may be utilized wherein one or more nucleotides are added or removed to the termini, including A. T, C or CG.

TABLE 19

5′-Untranslated Regions

5′ UTR
Name/

SEQ ID

Identifier
Description
Sequence
NO.

5UTR-001
Upstream UTR
GGGAAATAAGAGAGAAAAGAAGAGTAAGAAG
897

AAATATAAGAGCCACC

5UTR-002
Upstream UTR
GGGAGATCAGAGAGAAAAGAAGAGTAAGAAG
898

AAATATAAGAGCCACC

5UTR-003
Upstream UTR
GGAATAAAAGTCTCAACACAACATATACAAAA
899

CAAACGAATCTCAAGCAATCAAGCATTCTACT

TCTATTGCAGCAATTTAAATCATTTCTTTTAAA

GCAAAAGCAATTTTCTGAAAATTTTCACCATTT

ACGAACGATAGCAAC

5UTR-004
Upstream UTR
GGGAGACAAGCUUGGCAUUCCGGUACUGUUG
900

GUAAAGCCACC

5UTR-005
Upstream UTR
GGGAGATCAGAGAGAAAAGAAGAGTAAGAAG
901

AAATATAAGAGCCACC

5UTR-006
Upstream UTR
GGAATAAAAGTCTCAACACAACATATACAAAA
902

CAAACGAATCTCAAGCAATCAAGCATTCTACT

TCTATTGCAGCAATTTAAATCATTTCTTTTAAA

GCAAAAGCAATTTTCTGAAAATTTTCACCATTT

ACGAACGATAGCAAC

5UTR-007
Upstream UTR
GGGAGACAAGCUUGGCAUUCCGGUACUGUUG
903

GUAAAGCCACC

5UTR-008
Upstream UTR
GGGAATTAACAGAGAAAAGAAGAGTAAGAAG
904

AAATATAAGAGCCACC

5UTR-009
Upstream UTR
GGGAAATTAGACAGAAAAGAAGAGTAAGAAG
905

AAATATAAGAGCCACC

5UTR-010
Upstream UTR
GGGAAATAAGAGAGTAAAGAACAGTAAGAAG
906

AAATATAAGAGCCACC

5UTR-011
Upstream UTR
GGGAAAAAAGAGAGAAAAGAAGACTAAGAAG
907

AAATATAAGAGCCACC

5UTR-012
Upstream UTR
GGGAAATAAGAGAGAAAAGAAGAGTAAGAAG
908

ATATATAAGAGCCACC

5UTR-013
Upstream UTR
GGGAAATAAGAGACAAAACAAGAGTAAGAAG
909

AAATATAAGAGCCACC

5UTR-014
Upstream UTR
GGGAAATTAGAGAGTAAAGAACAGTAAGTAG
910

AATTAAAAGAGCCACC

5UTR-015
Upstream UTR
GGGAAATAAGAGAGAATAGAAGAGTAAGAAG
911

AAATATAAGAGCCACC

5UTR-016
Upstream UTR
GGGAAATAAGAGAGAAAAGAAGAGTAAGAAG
912

AAAATTAAGAGCCACC

5UTR-017
Upstream UTR
GGGAAATAAGAGAGAAAAGAAGAGTAAGAAG
913

AAATTTAAGAGCCACC

Shown in Table 20 is a listing of 3′-untranslated regions of the invention. Variants of 3′ UTRs may be utilized wherein one or more nucleotides are added or removed to the termini, including A, T, C or G.

TABLE 20

3′-Untranslated Regions

3′ UTR
Name/

SEQ ID

Identifier
Description
Sequence
NO.

3UTR-001
Creatine
GCGCCTGCCCACCTGCCACCGACTGCTGGAACCCAGC
914

Kinase
CAGTGGGAGGGCCTGGCCCACCAGAGTCCTGCTCCCT

CACTCCTCGCCCCGCCCCCTGTCCCAGAGTCCCACCTG

GGGGCTCTCTCCACCCTTCTCAGAGTTCCAGTTTCAAC

CAGAGTTCCAACCAATGGGCTCCATCCTCTGGATTCTG

GCCAATGAAATATCTCCCTGGCAGGGTCCTCTTCTTTT

CCCAGAGCTCCACCCCAACCAGGAGCTCTAGTTAATG

GAGAGCTCCCAGCACACTCGGAGCTTGTGCTTTGTCTC

CACGCAAAGCGATAAATAAAAGCATTGGTGGCCTTTG

GTCTTTGAATAAAGCCTGAGTAGGAAGTCTAGA

3UTR-002
Myoglobin
GCCCCTGCCGCTCCCACCCCCACCCATCTGGGCCCCGG
915

GTTCAAGAGAGAGCGGGGTCTGATCTCGTGTAGCCAT

ATAGAGTTTGCTTCTGAGTGTCTGCTTTGTTTAGTAGA

GGTGGGCAGGAGGAGCTGAGGGGCTGGGGCTGGGGT

GTTGAAGTTGGCTTTGCATGCCCAGCGATGCGCCTCCC

TGTGGGATGTCATCACCCTGGGAACCGGGAGTGGCCC

TTGGCTCACTGTGTTCTGCATGGTTTGGATCTGAATTA

ATTGTCCTTTCTTCTAAATCCCAACCGAACTTCTTCCA

ACCTCCAAACTGGCTGTAACCCCAAATCCAAGCCATT

AACTACACCTGACAGTAGCAATTGTCTGATTAATCACT

GGCCCCTTGAAGACAGCAGAATGTCCCTTTGCAATGA

GGAGGAGATCTGGGCTGGGCGGGCCAGCTGGGGAAG

CATTTGACTATCTGGAACTTGTGTGTGCCTCCTCAGGT

ATGGCAGTGACTCACCTGGTTTTAATAAAACAACCTG

CAACATCTCATGGTCTTTGAATAAAGCCTGAGTAGGA

AGTCTAGA

3UTR-003
α-actin
ACACACTCCACCTCCAGCACGCGACTTCTCAGGACGA
916

CGAATCTTCTCAATGGGGGGGCGGCTGAGCTCCAGCC

ACCCCGCAGTCACTTTCTTTGTAACAACTTCCGTTGCT

GCCATCGTAAACTGACACAGTGTTTATAACGTGTACAT

ACATTAACTTATTACCTCATTTTGTTATTTTTCGAAACA

AAGCCCTGTGGAAGAAAATGGAAAACTTGAAGAAGC

ATTAAAGTCATTCTGTTAAGCTGCGTAAATGGTCTTTG

AATAAAGCCTGAGTAGGAAGTCTAGA

3UTR-004
Albumin
CATCACATTTAAAAGCATCTCAGCCTACCATGAGAAT
917

AAGAGAAAGAAAATGAAGATCAAAAGCTTATTCATCT

GTTTTTCTTTTTCGTTGGTGTAAAGCCAACACCCTGTCT

AAAAAACATAAATTTCTTTAATCATTTTGCCTCTTTTCT

CTGTGCTTCAATTAATAAAAAATGGAAAGAATCTAAT

AGAGTGGTACAGCACTGTTATTTTTCAAAGATGTGTTG

CTATCCTGAAAATTCTGTAGGTTCTGTGGAAGTTCCAG

TGTTCTCTCTTATTCCACTTCGGTAGAGGATTTCTAGTT

TCTTGTGGGCTAATTAAATAAATCATTAATACTCTTCT

3UTR-005
α-globin
AATGGTCTTTGAATAAAGCCTGAGTAGGAAGTCTAGA
918

GCTGCCTTCTGCGGGGCTTGCCTTCTGGCCATGCCCTT

CTTCTCTCCCTTGCACCTGTACCTCTTGGTCTTTGAATA

AAGCCTGAGTAGGAAGGCGGCCGCTCGAGCATGCATC

TAGA

3UTR-006
G-CSF
GCCAAGCCCTCCCCATCCCATGTATTTATCTCTATTTA
919

ATATTTATGTCTATTTAAGCCTCATATTTAAAGACAGG

GAAGAGCAGAACGGAGCCCCAGGCCTCTGTGTCCTTC

CCTGCATTTCTGAGTTTCATTCTCCTGCCTGTAGCAGT

GAGAAAAAGCTCCTGTCCTCCCATCCCCTGGACTGGG

AGGTAGATAGGTAAATACCAAGTATTTATTACTATGA

CTGCTCCCCAGCCCTGGCTCTGCAATGGGCACTGGGAT

GAGCCGCTGTGAGCCCCTGGTCCTGAGGGTCCCCACC

TGGGACCCTTGAGAGTATCAGGTCTCCCACGTGGGAG

ACAAGAAATCCCTGTTTAATATTTAAACAGCAGTGTTC

CCCATCTGGGTCCTTGCACCCCTCACTCTGGCCTCAGC

CGACTGCACAGCGGCCCCTGCATCCCCTTGGCTGTGA

GGCCCCTGGACAAGCAGAGGTGGCCAGAGCTGGGAG

GCATGGCCCTGGGGTCCCACGAATTTGCTGGGGAATC

TCGTTTTTCTTCTTAAGACTTTTGGGACATGGTTTGACT

CCCGAACATCACCGACGCGTCTCCTGTTTTTCTGGGTG

GCCTCGGGACACCTGCCCTGCCCCCACGAGGGTCAGG

ACTGTGACTCTTTTTAGGGCCAGGCAGGTGCCTGGAC

ATTTGCCTTGCTGGACGGGGACTGGGGATGTGGGAGG

GAGCAGACAGGAGGAATCATGTCAGGCCTGTGTGTGA

AAGGAAGCTCCACTGTCACCCTCCACCTCTTCACCCCC

CACTCACCAGTGTCCCCTCCACTGTCACATTGTAACTG

AACTTCAGGATAATAAAGTGTTTGCCTCCATGGTCTTT

GAATAAAGCCTGAGTAGGAAGGCGGCCGCTCGAGCAT

GCATCTAGA

3UTR-007
Col1a2;
ACTCAATCTAAATTAAAAAAGAAAGAAATTTGAAAAA
920

collagen,
ACTTTCTCTTTGCCATTTCTTCTTCTTCTTTTTTAACTGA

type I, alpha
AAGCTGAATCCTTCCATTTCTTCTGCACATCTACTTGC

2
TTAAATTGTGGGCAAAAGAGAAAAAGAAGGATTGATC

AGAGCATTGTGCAATACAGTTTCATTAACTCCTTCCCC

CGCTCCCCCAAAAATTTGAATTTTTTTTTCAACACTCTT

ACACCTGTTATGGAAAATGTCAACCTTTGTAAGAAAA

CCAAAATAAAAATTGAAAAATAAAAACCATAAACATT

TGCACCACTTGTGGCTTTTGAATATCTTCCACAGAGGG

AAGTTTAAAACCCAAACTTCCAAAGGTTTAAACTACC

TCAAAACACTTTCCCATGAGTGTGATCCACATTGTTAG

GTGCTGACCTAGACAGAGATGAACTGAGGTCCTTGTT

TTGTTTTGTTCATAATACAAAGGTGCTAATTAATAGTA

TTTCAGATACTTGAAGAATGTTGATGGTGCTAGAAGA

ATTTGAGAAGAAATACTCCTGTATTGAGTTGTATCGTG

TGGTGTATTTTTTAAAAAATTTGATTTAGCATTCATAT

TTTCCATCTTATTCCCAATTAAAAGTATGCAGATTATT

TGCCCAAATCTTCTTCAGATTCAGCATTTGTTCTTTGCC

AGTCTCATTTTCATCTTCTTCCATGGTTCCACAGAAGC

TTTGTTTCTTGGGCAAGCAGAAAAATTAAATTGTACCT

ATTTTGTATATGTGAGATGTTTAAATAAATTGTGAAAA

AAATGAAATAAAGCATGTTTGGTTTTCCAAAAGAACA

TAT

3UTR-008
Col6a2;
CGCCGCCGCCCGGGCCCCGCAGTCGAGGGTCGTGAGC
921

collagen,
CCACCCCGTCCATGGTGCTAAGCGGGCCCGGGTCCCA

type VI,
CACGGCCAGCACCGCTGCTCACTCGGACGACGCCCTG

alpha 2
GGCCTGCACCTCTCCAGCTCCTCCCACGGGGTCCCCGT

AGCCCCGGCCCCCGCCCAGCCCCAGGTCTCCCCAGGC

CCTCCGCAGGCTGCCCGGCCTCCCTCCCCCTGCAGCCA

TCCCAAGGCTCCTGACCTACCTGGCCCCTGAGCTCTGG

AGCAAGCCCTGACCCAATAAAGGCTTTGAACCCAT

3UTR-009
RPN1;
GGGGCTAGAGCCCTCTCCGCACAGCGTGGAGACGGGG
922

riophorin I
CAAGGAGGGGGGTTATTAGGATTGGTGGTTTTGTTTTG

CTTTGTTTAAAGCCGTGGGAAAATGGCACAACTTTACC

TCTGTGGGAGATGCAACACTGAGAGCCAAGGGGTGGG

AGTTGGGATAATTTTTATATAAAAGAAGTTTTTCCACT

TTGAATTGCTAAAAGTGGCATTTTTCCTATGTGCAGTC

ACTCCTCTCATTTCTAAAATAGGGACGTGGCCAGGCA

CGGTGGCTCATGCCTGTAATCCCAGCACTTTGGGAGG

CCGAGGCAGGCGGCTCACGAGGTCAGGAGATCGAGA

CTATCCTGGCTAACACGGTAAAACCCTGTCTCTACTAA

AAGTACAAAAAATTAGCTGGGCGTGGTGGTGGGCACC

TGTAGTCCCAGCTACTCGGGAGGCTGAGGCAGGAGAA

AGGCATGAATCCAAGAGGCAGAGCTTGCAGTGAGCTG

AGATCACGCCATTGCACTCCAGCCTGGGCAACAGTGT

TAAGACTCTGTCTCAAATATAAATAAATAAATAAATA

AATAAATAAATAAATAAAAATAAAGCGAGATGTTGCC

CTCAAA

3UTR-010
LRP1; low
GGCCCTGCCCCGTCGGACTGCCCCCAGAAAGCCTCCT
923

density
GCCCCCTGCCAGTGAAGTCCTTCAGTGAGCCCCTCCCC

lipoprotein
AGCCAGCCCTTCCCTGGCCCCGCCGGATGTATAAATGT

receptor-
AAAAATGAAGGAATTACATTTTATATGTGAGCGAGCA

related
AGCCGGCAAGCGAGCACAGTATTATTTCTCCATCCCCT

protein 1
CCCTGCCTGCTCCTTGGCACCCCCATGCTGCCTTCAGG

GAGACAGGCAGGGAGGGCTTGGGGCTGCACCTCCTAC

CCTCCCACCAGAACGCACCCCACTGGGAGAGCTGGTG

GTGCAGCCTTCCCCTCCCTGTATAAGACACTTTGCCAA

GGCTCTCCCCTCTCGCCCCATCCCTGCTTGCCCGCTCC

CACAGCTTCCTGAGGGCTAATTCTGGGAAGGGAGAGT

TCTTTGCTGCCCCTGTCTGGAAGACGTGGCTCTGGGTG

AGGTAGGCGGGAAAGGATGGAGTGTTTTAGTTCTTGG

GGGAGGCCACCCCAAACCCCAGCCCCAACTCCAGGGG

CACCTATGAGATGGCCATGCTCAACCCCCCTCCCAGA

CAGGCCCTCCCTGTCTCCAGGGCCCCCACCGAGGTTCC

CAGGGCTGGAGACTTCCTCTGGTAAACATTCCTCCAGC

CTCCCCTCCCCTGGGGACGCCAAGGAGGTGGGCCACA

CCCAGGAAGGGAAAGCGGGCAGCCCCGTTTTGGGGAC

GTGAACGTTTTAATAATTTTTGCTGAATTCCTTTACAA

CTAAATAACACAGATATTGTTATAAATAAAATTGT

3UTR-011
Nnt1;
ATATTAAGGATCAAGCTGTTAGCTAATAATGCCACCTC
924

cardio-
TGCAGTTTTGGGAACAGGCAAATAAAGTATCAGTATA

trophin-
CATGGTGATGTACATCTGTAGCAAAGCTCTTGGAGAA

like
AATGAAGACTGAAGAAAGCAAAGCAAAAACTGTATA

cytokine
GAGAGATTTTTCAAAAGCAGTAATCCCTCAATTTTAAA

factor 1
AAAGGATTGAAAATTCTAAATGTCTTTCTGTGCATATT

TTTTGTGTTAGGAATCAAAAGTATTTTATAAAAGGAG

AAAGAACAGCCTCATTTTAGATGTAGTCCTGTTGGATT

TTTTATGCCTCCTCAGTAACCAGAAATGTTTTAAAAAA

CTAAGTGTTTAGGATTTCAAGACAACATTATACATGGC

TCTGAAATATCTGACACAATGTAAACATTGCAGGCAC

CTGCATTTTATGTTTTTTTTTTCAACAAATGTGACTAAT

TTGAAACTTTTATGAACTTCTGAGCTGTCCCCTTGCAA

TTCAACCGCAGTTTGAATTAATCATATCAAATCAGTTT

TAATTTTTTAAATTGTACTTCAGAGTCTATATTTCAAG

GGCACATTTTCTCACTACTATTTTAATACATTAAAGGA

CTAAATAATCTTTCAGAGATGCTGGAAACAAATCATTT

GCTTTATATGTTTCATTAGAATACCAATGAAACATACA

ACTTGAAAATTAGTAATAGTATTTTTGAAGATCCCATT

TCTAATTGGAGATCTCTTTAATTTCGATCAACTTATAA

TGTGTAGTACTATATTAAGTGCACTTGAGTGGAATTCA

ACATTTGACTAATAAAATGAGTTCATCATGTTGGCAA

GTGATGTGGCAATTATCTCTGGTGACAAAAGAGTAAA

ATCAAATATTTCTGCCTGTTACAAATATCAAGGAAGA

CCTGCTACTATGAAATAGATGACATTAATCTGTCTTCA

CTGTTTATAATACGGATGGATTTTTTTTCAAATCAGTG

TGTGTTTTGAGGTCTTATGTAATTGATGACATTTGAGA

GAAATGGTGGCTTTTTTTAGCTACCTCTTTGTTCATTTA

AGCACCAGTAAAGATCATGTCTTTTTATAGAAGTGTA

GATTTTCTTTGTGACTTTGCTATCGTGCCTAAAGCTCT

AAATATAGGTGAATGTGTGATGAATACTCAGATTATTT

GTCTCTCTATATAATTAGTTTGGTACTAAGTTTCTCAA

AAAATTATTAACACATGAAAGACAATCTCTAAACCAG

AAAAAGAAGTAGTACAAATTTTGTTACTGTAATGCTC

GCGTTTAGTGAGTTTAAAACACACAGTATCTTTTGGTT

TTATAATCAGTTTCTATTTTGCTGTGCCTGAGATTAAG

ATCTGTGTATGTGTGTGTGTGTGTGTGTGCGTTTGTGT

GTTAAAGCAGAAAAGACTTTTTTAAAAGTTTTAAGTG

ATAAATGCAATTTGTTAATTGATCTTAGATCACTAGTA

AACTCAGGGCTGAATTATACCATGTATATTCTATTAGA

AGAAAGTAAACACCATCTTTATTCCTGCCCTTTTTCTT

CTCTCAAAGTAGTTGTAGTTATATCTAGAAAGAAGCA

ATTTTGATTTCTTGAAAAGGTAGTTCCTGCACTCAGTT

TAAACTAAAAATAATCATACTTGGATTTTATTTATTTT

TGTCATAGTAAAAATTTTAATTTATATATATTTTTATTT

AGTATTATCTTATTCTTTGCTATTTGCCAATCCTTTGTC

ATCAATTGTGTTAAATGAATTGAAAATTCATGCCCTGT

TCATTTTATTTTACTTTATTGGTTAGGATATTTAAAGG

ATTTTTGTATATATAATTTCTTAAATTAATATTCCAAA

AGGTTAGTGGACTTAGATTATAAATTATGGCAAAAAT

CTAAAAACAACAAAAATGATTTTTATACATTCTATTTC

ATTATTCCTCTTTTTCCAATAAGTCATACAATTGGTAG

ATATGACTTATTTTATTTTTGTATTATTCACTATATCTT

TATGATATTTAAGTATAAATAATTAAAAAAATTTATTG

TACCTTATAGTCTGTCACCAAAAAAAAAAAATTATCT

GTAGGTAGTGAAATGCTAATGTTGATTTGTCTTTAAGG

GCTTGTTAACTATCCTTTATTTTCTCATTTGTCTTAAAT

TAGGAGTTTGTGTTTAAATTACTCATCTAAGCAAAAAA

TGTATATAAATCCCATTACTGGGTATATACCCAAAGG

ATTATAAATCATGCTGCTATAAAGACACATGCACACG

TATGTTTATTGCAGCACTATTCACAATAGCAAAGACTT

GGAACCAACCCAAATGTCCATCAATGATAGACTTGAT

TAAGAAAATGTGCACATATACACCATGGAATACTATG

CAGCCATAAAAAAGGATGAGTTCATGTCCTTTGTAGG

GACATGGATAAAGCTGGAAACCATCATTCTGAGCAAA

CTATTGCAAGGACAGAAAACCAAACACTGCATGTTCT

CACTCATAGGTGGGAATTGAACAATGAGAACACTTGG

ACACAAGGTGGGGAACACCACACACCAGGGCCTGTCA

TGGGGTGGGGGGAGTGGGGAGGGATAGCATTAGGAG

ATATACCTAATGTAAATGATGAGTTAATGGGTGCAGC

ACACCAACATGGCACATGTATACATATGTAGCAAACC

TGCACGTTGTGCACATGTACCCTAGAACTTAAAGTATA

ATTAAAAAAAAAAAGAAAACAGAAGCTATTTATAAA

GAAGTTATTTGCTGAAATAAATGTGATCTTTCCCATTA

AAAAAATAAAGAAATTTTGGGGTAAAAAAACACAAT

ATATTGTATTCTTGAAAAATTCTAAGAGAGTGGATGTG

AAGTGTTCTCACCACAAAAGTGATAACTAATTGAGGT

AATGCACATATTAATTAGAAAGATTTTGTCATTCCACA

ATGTATATATACTTAAAAATATGTTATACACAATAAAT

ACATACATTAAAAAATAAGTAAATGTA

3UTR-012
Col6a1;
CCCACCCTGCACGCCGGCACCAAACCCTGTCCTCCCAC
925

collagen,
CCCTCCCCACTCATCACTAAACAGAGTAAAATGTGAT

type VI,
GCGAATTTTCCCGACCAACCTGATTCGCTAGATTTTTT

alpha 1
TTAAGGAAAAGCTTGGAAAGCCAGGACACAACGCTGC

TGCCTGCTTTGTGCAGGGTCCTCCGGGGCTCAGCCCTG

AGTTGGCATCACCTGCGCAGGGCCCTCTGGGGCTCAG

CCCTGAGCTAGTGTCACCTGCACAGGGCCCTCTGAGG

CTCAGCCCTGAGCTGGCGTCACCTGTGCAGGGCCCTCT

GGGGCTCAGCCCTGAGCTGGCCTCACCTGGGTTCCCC

ACCCCGGGCTCTCCTGCCCTGCCCTCCTGCCCGCCCTC

CCTCCTGCCTGCGCAGCTCCTTCCCTAGGCACCTCTGT

GCTGCATCCCACCAGCCTGAGCAAGACGCCCTCTCGG

GGCCTGTGCCGCACTAGCCTCCCTCTCCTCTGTCCCCA

TAGCTGGTTTTTCCCACCAATCCTCACCTAACAGTTAC

TTTACAATTAAACTCAAAGCAAGCTCTTCTCCTCAGCT

TGGGGCAGCCATTGGCCTCTGTCTCGTTTTGGGAAACC

AAGGTCAGGAGGCCGTTGCAGACATAAATCTCGGCGA

CTCGGCCCCGTCTCCTGAGGGTCCTGCTGGTGACCGGC

CTGGACCTTGGCCCTACAGCCCTGGAGGCCGCTGCTG

ACCAGCACTGACCCCGACCTCAGAGAGTACTCGCAGG

GGCGCTGGCTGCACTCAAGACCCTCGAGATTAACGGT

GCTAACCCCGTCTGCTCCTCCCTCCCGCAGAGACTGGG

GCCTGGACTGGACATGAGAGCCCCTTGGTGCCACAGA

GGGCTGTGTCTTACTAGAAACAACGCAAACCTCTCCTT

CCTCAGAATAGTGATGTGTTCGACGTTTTATCAAAGGC

CCCCTTTCTATGTTCATGTTAGTTTTGCTCCTTCTGTGT

TTTTTTCTGAACCATATCCATGTTGCTGACTTTTCCAAA

TAAAGGTTTTCACTCCTCTC

3UTR-013
Calr;
AGAGGCCTGCCTCCAGGGCTGGACTGAGGCCTGAGCG
926

calreticulin
CTCCTGCCGCAGAGCTGGCCGCGCCAAATAATGTCTCT

GTGAGACTCGAGAACTTTCATTTTTTTCCAGGCTGGTT

CGGATTTGGGGTGGATTTTGGTTTTGTTCCCCTCCTCC

ACTCTCCCCCACCCCCTCCCCGCCCTTTTTTTTTTTTTT

TTTTAAACTGGTATTTTATCTTTGATTCTCCTTCAGCCC

TCACCCCTGGTTCTCATCTTTCTTGATCAACATCTTTTC

TTGCCTCTGTCCCCTTCTCTCATCTCTTAGCTCCCCTCC

AACCTGGGGGGCAGTGGTGTGGAGAAGCCACAGGCCT

GAGATTTCATCTGCTCTCCTTCCTGGAGCCCAGAGGAG

GGCAGCAGAAGGGGGTGGTGTCTCCAACCCCCCAGCA

CTGAGGAAGAACGGGGCTCTTCTCATTTCACCCCTCCC

TTTCTCCCCTGCCCCCAGGACTGGGCCACTTCTGGGTG

GGGCAGTGGGTCCCAGATTGGCTCACACTGAGAATGT

AAGAACTACAAACAAAATTTCTATTAAATTAAATTTTG

TGTCTCC

3UTR-014
Col1a1;
CTCCCTCCATCCCAACCTGGCTCCCTCCCACCCAACCA
927

collagen,
ACTTTCCCCCCAACCCGGAAACAGACAAGCAACCCAA

type I, alpha
ACTGAACCCCCTCAAAAGCCAAAAAATGGGAGACAAT

1
TTCACATGGACTTTGGAAAATATTTTTTTCCTTTGCATT

CATCTCTCAAACTTAGTTTTTATCTTTGACCAACCGAA

CATGACCAAAAACCAAAAGTGCATTCAACCTTACCAA

AAAAAAAAAAAAAAAAAGAATAAATAAATAACTTTTT

AAAAAAGGAAGCTTGGTCCACTTGCTTGAAGACCCAT

GCGGGGGTAAGTCCCTTTCTGCCCGTTGGGCTTATGAA

ACCCCAATGCTGCCCTTTCTGCTCCTTTCTCCACACCC

CCCTTGGGGCCTCCCCTCCACTCCTTCCCAAATCTGTC

TCCCCAGAAGACACAGGAAACAATGTATTGTCTGCCC

AGCAATCAAAGGCAATGCTCAAACACCCAAGTGGCCC

CCACCCTCAGCCCGCTCCTGCCCGCCCAGCACCCCCAG

GCCCTGGGGGACCTGGGGTTCTCAGACTGCCAAAGAA

GCCTTGCCATCTGGCGCTCCCATGGCTCTTGCAACATC

TCCCCTTCGTTTTTGAGGGGGTCATGCCGGGGGAGCCA

CCAGCCCCTCACTGGGTTCGGAGGAGAGTCAGGAAGG

GCCACGACAAAGCAGAAACATCGGATTTGGGGAACGC

GTGTCAATCCCTTGTGCCGCAGGGCTGGGCGGGAGAG

ACTGTTCTGTTCCTTGTGTAACTGTGTTGCTGAAAGAC

TACCTCGTTCTTGTCTTGATGTGTCACCGGGGCAACTG

CCTGGGGGCGGGGATGGGGGCAGGGTGGAAGCGGCT

CCCCATTTTATACCAAAGGTGCTACATCTATGTGATGG

GTGGGGTGGGGAGGGAATCACTGGTGCTATAGAAATT

GAGATGCCCCCCCAGGCCAGCAAATGTTCCTTTTTGTT

CAAAGTCTATTTTTATTCCTTGATATTTTTCTTTTTTTTT

TTTTTTTTTTGTGGATGGGGACTTGTGAATTTTTCTAAA

GGTGCTATTTAACATGGGAGGAGAGCGTGTGCGGCTC

CAGCCCAGCCCGCTGCTCACTTTCCACCCTCTCTCCAC

CTGCCTCTGGCTTCTCAGGCCTCTGCTCTCCGACCTCT

CTCCTCTGAAACCCTCCTCCACAGCTGCAGCCCATCCT

CCCGGCTCCCTCCTAGTCTGTCCTGCGTCCTCTGTCCC

CGGGTTTCAGAGACAACTTCCCAAAGCACAAAGCAGT

TTTTCCCCCTAGGGGTGGGAGGAAGCAAAAGACTCTG

TACCTATTTTGTATGTGTATAATAATTTGAGATGTTTTT

AATTATTTTGATTGCTGGAATAAAGCATGTGGAAATG

ACCCAAACATAATCCGCAGTGGCCTCCTAATTTCCTTC

TTTGGAGTTGGGGGAGGGGTAGACATGGGGAAGGGG

CTTTGGGGTGATGGGCTTGCCTTCCATTCCTGCCCTTT

CCCTCCCCACTATTCTCTTCTAGATCCCTCCATAACCC

CACTCCCCTTTCTCTCACCCTTCTTATACCGCAAACCTT

TCTACTTCCTCTTTCATTTTCTATTCTTGCAATTTCCTT

GCACCTTTTCCAAATCCTCTTCTCCCCTGCAATACCAT

ACAGGCAATCCACGTGCACAACACACACACACACTCT

TCACATCTGGGGTTGTCCAAACCTCATACCCACTCCCC

TTCAAGCCCATCCACTCTCCACCCCCTGGATGCCCTGC

ACTTGGTGGCGGTGGGATGCTCATGGATACTGGGAGG

GTGAGGGGAGTGGAACCCGTGAGGAGGACCTGGGGG

CCTCTCCTTGAACTGACATGAAGGGTCATCTGGCCTCT

GCTCCCTTCTCACCCACGCTGACCTCCTGCCGAAGGAG

CAACGCAACAGGAGAGGGGTCTGCTGAGCCTGGCGAG

GGTCTGGGAGGGACCAGGAGGAAGGCGTGCTCCCTGC

TCGCTGTCCTGGCCCTGGGGGAGTGAGGGAGACAGAC

ACCTGGGAGAGCTGTGGGGAAGGCACTCGCACCGTGC

TCTTGGGAAGGAAGGAGACCTGGCCCTGCTCACCACG

GACTGGGTGCCTCGACCTCCTGAATCCCCAGAACACA

ACCCCCCTGGGCTGGGGTGGTCTGGGGAACCATCGTG

CCCCCGCCTCCCGCCTACTCCTTTTTAAGCTT

3UTR-015
Pld1;
TTGGCCAGGCCTGACCCTCTTGGACCTTTCTTCTTTGC
928

procollagen-
CGACAACCACTGCCCAGCAGCCTCTGGGACCTCGGGG

lysine, 2-
TCCCAGGGAACCCAGTCCAGCCTCCTGGCTGTTGACTT

oxoglutarate
CCCATTGCTCTTGGAGCCACCAATCAAAGAGATTCAA

5-
AGAGATTCCTGCAGGCCAGAGGCGGAACACACCTTTA

dioxygenase
TGGCTGGGGCTCTCCGTGGTGTTCTGGACCCAGCCCCT

1
GGAGACACCATTCACTTTTACTGCTTTGTAGTGACTCG

TGCTCTCCAACCTGTCTTCCTGAAAAACCAAGGCCCCC

TTCCCCCACCTCTTCCATGGGGTGAGACTTGAGCAGAA

CAGGGGCTTCCCCAAGTTGCCCAGAAAGACTGTCTGG

GTGAGAAGCCATGGCCAGAGCTTCTCCCAGGCACAGG

TGTTGCACCAGGGACTTCTGCTTCAAGTTTTGGGGTAA

AGACACCTGGATCAGACTCCAAGGGCTGCCCTGAGTC

TGGGACTTCTGCCTCCATGGCTGGTCATGAGAGCAAA

CCGTAGTCCCCTGGAGACAGCGACTCCAGAGAACCTC

TTGGGAGACAGAAGAGGCATCTGTGCACAGCTCGATC

TTCTACTTGCCTGTGGGGAGGGGAGTGACAGGTCCAC

ACACCACACTGGGTCACCCTGTCCTGGATGCCTCTGAA

GAGAGGGACAGACCGTCAGAAACTGGAGAGTTTCTAT

TAAAGGTCATTTAAACCA

3UTR-016
Nucb1;
TCCTCCGGGACCCCAGCCCTCAGGATTCCTGATGCTCC
929

nucleobindin
AAGGCGACTGATGGGCGCTGGATGAAGTGGCACAGTC

1
AGCTTCCCTGGGGGCTGGTGTCATGTTGGGCTCCTGGG

GCGGGGGCACGGCCTGGCATTTCACGCATTGCTGCCA

CCCCAGGTCCACCTGTCTCCACTTTCACAGCCTCCAAG

TCTGTGGCTCTTCCCTTCTGTCCTCCGAGGGGCTTGCC

TTCTCTCGTGTCCAGTGAGGTGCTCAGTGATCGGCTTA

ACTTAGAGAAGCCCGCCCCCTCCCCTTCTCCGTCTGTC

CCAAGAGGGTCTGCTCTGAGCCTGCGTTCCTAGGTGG

CTCGGCCTCAGCTGCCTGGGTTGTGGCCGCCCTAGCAT

CCTGTATGCCCACAGCTACTGGAATCCCCGCTGCTGCT

CCGGGCCAAGCTTCTGGTTGATTAATGAGGGCATGGG

GTGGTCCCTCAAGACCTTCCCCTACCTTTTGTGGAACC

AGTGATGCCTCAAAGACAGTGTCCCCTCCACAGCTGG

GTGCCAGGGGCAGGGGATCCTCAGTATAGCCGGTGAA

CCCTGATACCAGGAGCCTGGGCCTCCCTGAACCCCTG

GCTTCCAGCCATCTCATCGCCAGCCTCCTCCTGGACCT

CTTGGCCCCCAGCCCCTTCCCCACACAGCCCCAGAAG

GGTCCCAGAGCTGACCCCACTCCAGGACCTAGGCCCA

GCCCCTCAGCCTCATCTGGAGCCCCTGAAGACCAGTC

CCACCCACCTTTCTGGCCTCATCTGACACTGCTCCGCA

TCCTGCTGTGTGTCCTGTTCCATGTTCCGGTTCCATCCA

AATACACTTTCTGGAACAAA

3UTR-017
α-globin
GCTGGAGCCTCGGTGGCCATGCTTCTTGCCCCTTGGGC
930

CTCCCCCCAGCCCCTCCTCCCCTTCCTGCACCCGTACC

CCCGTGGTCTTTGAATAAAGTCTGAGTGGGCGGC

5′ UTR and Translation Initiation

Natural 5′UTRs bear features which play roles in translation initiation. They harbor signatures like Kozak sequences which are commonly known to be involved in the process by which the ribosome initiates translation of many genes. Kozak sequences have the consensus CCR(A/G)CCAUGG (SEQ ID NO: 965), where R is a purine (adenine or guanine) three bases upstream of the start codon (AUG), which is followed by another ‘G’. 5′UTR also have been known to form secondary structures which are involved in elongation factor binding.

By engineering the features typically found in abundantly expressed genes of specific target organs, one can enhance the stability and protein production of the polynucleotides of the invention. For example, introduction of 5′ UTR of liver-expressed mRNA, such as albumin, serum amyloid A, Apolipoprotein A/B/E, transferrin, alpha fetoprotein, erythropoietin, or Factor VIII, could be used to enhance expression of a nucleic acid molecule, such as a polynucleotides, in hepatic cell lines or liver. Likewise, use of 5′ UTR from other tissue-specific mRNA to improve expression in that tissue is possible for muscle (MyoD, Myosin, Myoglobin, Myogenin, Herculin), for endothelial cells (Tie-1, CD36), for myeloid cells (C/EBP, AML1, G-CSF, GM-CSF, CD11b, MSR, Fr-1, i-NOS), for leukocytes (CD45, CD18), for adipose tissue (CD36, GLUT4, ACRP30, adiponectin) and for lung epithelial cells (SP-A/B/C/D).

Untranslated regions useful in the design and manufacture of polynucleotides (e.g., antigen-encoding polynucleotides featured in the NAVs of the invention) include, but are not limited, to those disclosed in co-pending, co-owned US Provisional Application U.S. Ser. No. 61/829,372 (Attorney Docket Number M42.60), U.S. Provisional Application 61/829,372 (USSN) (Attorney Docket Number M42.61), and international Application, PCT/US14/21522 filed Mar. 7, 2014, the contents of each of which are incorporated herein by reference in its entirety.

Other non-UTR sequences may also be used as regions or subregions within the polynucleotides. For example, introns or portions of introns sequences may be incorporated into regions of the polynucleotides of the invention. Incorporation of intronic sequences may increase protein production as well as polynucleotide levels.

Combinations of features may be included in flanking regions and may be contained within other features. For example, the ORF may be flanked by a 5′ UTR which may contain a strong Kozak translational initiation signal and/or a 3′ UTR which may include an oligo(dT) sequence for templated addition of a poly-A tail. 5′UTR may comprise a first polynucleotide fragment and a second polynucleotide fragment from the same and/or different genes such as the 5′UTRs described in US Patent Application Publication No. 20100293625, herein incorporated by reference in its entirety.

Co-pending, co-owned US Provisional Application U.S. Ser. No. 61/829,372 (Attorney Docket Number M42.60) and U.S. Provisional Application 61/829,372 (USSN) (Attorney Docket Number M42.61) provides a listing of exemplary UTRs which may be utilized in the polynucleotide of the present invention as flanking regions. Variants of 5′ or 3′ UTRs may be utilized wherein one or more nucleotides are added or removed to the termini, including A, T, C or G.

It should be understood that any UTR from any gene may be incorporated into the regions of the polynucleotide. Furthermore, multiple wild-type UTRs of any known gene may be utilized. It is also within the scope of the present invention to provide artificial UTRs which are not variants of wild type regions. These UTRs or portions thereof may be placed in the same orientation as in the transcript from which they were selected or may be altered in orientation or location. Hence a 5′ or 3′ UTR may be inverted, shortened, lengthened, made with one or more other 5′ UTRs or 3′ UTRs. As used herein, the term “altered” as it relates to a UTR sequence, means that the UTR has been changed in some way in relation to a reference sequence. For example, a 3′ or 5′ UTR may be altered relative to a wild type or native UTR by the change in orientation or location as taught above or may be altered by the inclusion of additional nucleotides, deletion of nucleotides, swapping or transposition of nucleotides. Any of these changes producing an “altered” UTR (whether 3′ or 5′) comprise a variant UTR.

In one embodiment, a double, triple or quadruple UTR such as a 5′ or 3′ UTR may be used. As used herein, a “double” UTR is one in which two copies of the same UTR are encoded either in series or substantially in series. For example, a double beta-globin 3′ UTR may be used as described in US Patent publication 20100129877, the contents of which are incorporated herein by reference in its entirety.

It is also within the scope of the present invention to have patterned UTRs. As used herein “patterned UTRs” are those UTRs which reflect a repeating or alternating pattern, such as ABABAB or AABBAABBAABB or ABCABCABC or variants thereof repeated once, twice, or more than 3 times. In these patterns, each letter, A, B, or C represent a different UTR at the nucleotide level.

In one embodiment, flanking regions are selected from a family of transcripts whose proteins share a common function, structure, feature of property. For example, polypeptides of interest may belong to a family of proteins which are expressed in a particular cell, tissue or at some time during development. The UTRs from any of these genes may be swapped for any other UTR of the same or different family of proteins to create a new polynucleotide. As used herein, a “family of proteins” is used in the broadest sense to refer to a group of two or more polypeptides of interest which share at least one function, structure, feature, localization, origin, or expression pattern.

The untranslated region may also include translation enhancer elements (TEE). As a non-limiting example, the TEE may include those described in US Application No. 20090226470, herein incorporated by reference in its entirety, and those known in the art.

3′ UTR and the AU Rich Elements

Natural or wild type 3′ UTRs are known to have stretches of Adenosines and Uridines embedded in them. These AU rich signatures are particularly prevalent in genes with high rates of turnover. Based on their sequence features and functional properties, the AU rich elements (AREs) can be separated into three classes (Chen et al, 1995): Class I AREs contain several dispersed copies of an AUUUA motif within U-rich regions. C-Myc and MyoD contain class I AREs. Class II AREs possess two or more overlapping UUAUUUA(U/A)(U/A) nonamers. Molecules containing this type of AREs include GM-CSF and TNF-α. Class ITT ARES are less well defined. These U rich regions do not contain an AUULUA motif. c-Jun and Myogenin are two well-studied examples of this class. Most proteins binding to the AREs are known to destabilize the messenger, whereas members of the ELAV family, most notably HuR, have been documented to increase the stability of mRNA. HuR binds to AREs of all the three classes. Engineering the HuR specific binding sites into the 3′ UTR of nucleic acid molecules will lead to HuR binding and thus, stabilization of the message in vivo.

Introduction, removal or modification of 3′ UTR AU rich elements (AREs) can be used to modulate the stability of polynucleotides of the invention (e.g., antigen-encoding polynucleotides featured in the NAVs of the invention). When engineering specific polynucleotides, one or more copies of an ARE can be introduced to make polynucleotides of the invention less stable and thereby curtail translation and decrease production of the resultant protein. Likewise, AREs can be identified and removed or mutated to increase the intracellular stability and thus increase translation and production of the resultant protein. Transfection experiments can be conducted in relevant cell lines, using polynucleotides of the invention and protein production can be assayed at various time points post-transfection. For example, cells can be transfected with different ARE-engineering molecules and by using an ELISA kit to the relevant protein and assaying protein produced at 6 hour, 12 hour, 24 hour, 48 hour, and 7 days post-transfection.

microRNA Binding Sites

microRNAs (or miRNA) are 19-25 nucleotide long noncoding RNAs that bind to the 3′UTR of nucleic acid molecules and down-regulate gene expression either by reducing nucleic acid molecule stability or by inhibiting translation. The polynucleotides of the invention (e.g., antigen-encoding polynucleotides featured in the NAVs of the invention) may comprise one or more microRNA target sequences, microRNA sequences, or microRNA seeds. Such sequences may correspond to any known microRNA such as those taught in US Publication US2005/0261218 and US Publication US2005/0059005, the contents of which are incorporated herein by reference in their entirety.

A microRNA sequence comprises a “seed” region, i.e., a sequence in the region of positions 2-8 of the mature microRNA, which sequence has perfect Watson-Crick complementarity to the miRNA target sequence. A microRNA seed may comprise positions 2-8 or 2-7 of the mature microRNA. In some embodiments, a microRNA seed may comprise 7 nucleotides (e.g., nucleotides 2-8 of the mature microRNA), wherein the seed-complementary site in the corresponding miRNA target is flanked by an adenine (A) opposed to microRNA position 1. In some embodiments, a microRNA seed may comprise 6 nucleotides (e.g., nucleotides 2-7 of the mature microRNA), wherein the seed-complementary site in the corresponding miRNA target is flanked byan adenine (A) opposed to microRNA position 1. See for example, Grimson A, Farh K K, Johnston W K, Garrett-Engele P, Lim L P, Bartel D P; Mol Cell. 2007 Jul. 6; 27(1):91-105; each of which is herein incorporated by reference in their entirety. The bases of the microRNA seed have complete complementarity with the target sequence. By engineering microRNA target sequences into the polynucleotides (e.g., in a 3′UTR like region or other region) of the invention one can target the molecule for degradation or reduced translation, provided the microRNA in question is available. This process will reduce the hazard of off target effects upon nucleic acid molecule delivery. Identification of microRNA, microRNA target regions, and their expression patterns and role in biology have been reported (Bonauer et al., Curr Drug Targets 2010 11:943-949; Anand and Cheresh Cuff Opin Hematol 2011 18:171-176; Contreras and Rao Leukemia 2012 26:404-413 (2011 Dec. 20. doi: 10.1038/leu.2011.356); Bartel Cell 2009 136:215-233; Landgraf et al, Cell, 2007 129:1401-1414; each of which is herein incorporated by reference in its entirety).

For example, if the nucleic acid molecule is an mRNA and is not intended to be delivered to the liver but ends up there, then miR-122, a microRNA abundant in liver, can inhibit the expression of the gene of interest if one or multiple target sites of miR-122 are engineered into the 3′ UTR region of the polynucleotides. Introduction of one or multiple binding sites for different microRNA can be engineered to further decrease the longevity, stability, and protein translation of polynucleotides.

As used herein, the term “microRNA site” refers to a microRNA target site or a microRNA recognition site, or any nucleotide sequence to which a microRNA binds or associates. It should be understood that “binding” may follow traditional Watson-Crick hybridization rules or may reflect any stable association of the microRNA with the target sequence at or adjacent to the microRNA site.

Conversely, for the purposes of the polynucleotides of the present invention, microRNA binding sites can be engineered out of (i.e. removed from) sequences in which they occur, e.g., in order to increase protein expression in specific tissues. For example, miR-122 binding sites may be removed to improve protein expression in the liver. Regulation of expression in multiple tissues can be accomplished through introduction or removal or one or several microRNA binding sites.

Examples of tissues where microRNA are known to regulate mRNA, and thereby protein expression, include, but are not limited to, liver (miR-122), muscle (miR-133, miR-206, miR-208), endothelial cells (miR-17-92, miR-126), myeloid cells (miR-142-3p, miR-142-5p, miR-16, miR-21, miR-223, miR-24, miR-27), adipose tissue (let-7, miR-30c), heart (miR-1d, miR-149), kidney (miR-192, miR-194, miR-204), and lung epithelial cells (let-7, miR-133, miR-126). MicroRNA can also regulate complex biological processes such as angiogenesis (miR-132) (Anand and Cheresh Curr Opin Hematol 2011 18:171-176; herein incorporated by reference in its entirety).

Expression profiles, microRNA and cell lines useful in the present invention include those taught in for example, U.S. Provisional Application Nos 61/857,436 (Attorney Docket Number M39) and 61/857,304 (Attorney Docket Number M37) each filed Jul. 23, 2013, the contents of which are incorporated by reference in their entirety.

In the polynucleotides of the present invention, binding sites for microRNAs that are involved in such processes may be removed or introduced, in order to tailor the expression of the polynucleotides expression to biologically relevant cell types or to the context of relevant biological processes. A listing of microRNA, miR sequences and miR binding sites is listed in Table 9 of U.S. Provisional Application No. 61/753,661 filed Jan. 17, 2013, in Table 9 of U.S. Provisional Application No. 61/754,159 filed Jan. 18, 2013, and in Table 7 of U.S. Provisional Application No. 61/758,921 filed Jan. 31, 2013, each of which are herein incorporated by reference in their entireties.

Examples of use of microRNA to drive tissue or disease-specific gene expression are listed (Getner and Naldini, Tissue Antigens. 2012, 80:393-403; herein incoroporated by reference in its entirety). In addition, microRNA seed sites can be incorporated into mRNA to decrease expression in certain cells which results in a biological improvement. An example of this is incorporation of miR-142 sites into a UGTI A1-expressing lentiviral vector. The presence of miR-142 seed sites reduced expression in hematopoietic cells, and as a consequence reduced expression in antigen-presentating cells, leading to the absence of an immune response against the virally expressed UGT1 A1 (Schmitt et al., Gastroenterology 2010; 139:999-1007; Gonzalez-Asequinolaza et al. Gastroenterology 2010, 139:726-729; both herein incorporated by reference in its entirety). Incorporation of miR-142 sites into modified mRNA could not only reduce expression of the encoded protein in hematopoietic cells, but could also reduce or abolish immune responses to the mRNA-encoded protein. Incorporation of miR-142 seed sites (one or multiple) into mRNA would be important in the case of treatment of patients with complete protein deficiencies (UGT1 A1 type I, LDLR-deficient patients. CRIM-negative Pompe patients, etc.).

Lastly, through an understanding of the expression patterns of microRNA in different cell types, polynucleotides (e.g., antigen-encoding polynucleotides featured in the NAVs of the invention) can be engineered for more targeted expression in specific cell types or only under specific biological conditions. Through introduction of tissue-specific microRNA binding sites, polynucleotides could be designed that would be optimal for protein expression in a tissue or in the context of a biological condition.

Transfection experiments can be conducted in relevant cell lines, using engineered polynucleotides and protein production can be assayed at various time points post-transfection. For example, cells can be transfected with different microRNA binding site-engineering polynucleotides and by using an ELISA kit to the relevant protein and assaying protein produced at 6 hour, 12 hour, 24 hour, 48 hour, 72 hour and 7 days post-transfection. In vivo experiments can also be conducted using microRNA-binding site-engineered molecules to examine changes in tissue-specific expression of formulated polynucleotides.

Regions Having a 5′ Cap

The 5′ cap structure of a natural mRNA is involved in nuclear export, increasing mRNA stability and binds the mRNA Cap Binding Protein (CBP), which is responsible for mRNA stability in the cell and translation competency through the association of CBP with poly(A) binding protein to form the mature cyclic mRNA species. The cap further assists the removal of 5′ proximal introns removal during mRNA splicing.

Endogenous mRNA molecules may be 5′-end capped generating a 5′-ppp-5′-triphosphate linkage between a terminal guanosine cap residue and the 5′-terminal transcribed sense nucleotide of the mRNA molecule. This 5′-guanylate cap may then be methylated to generate an N7-methyl-guanylate residue. The ribose sugars of the terminal and/or anteterminal transcribed nucleotides of the 5′ end of the mRNA may optionally also be 2′-O-methylated. 5′-decapping through hydrolysis and cleavage of the guanylate cap structure may target a nucleic acid molecule, such as an mRNA molecule, for degradation.

In some embodiments, polynucleotides (e.g., antigen-encoding polynucleotides featured in the NAVs of the invention) may be designed to incorporate a cap moiety. Modifications to the polynucleotides of the present invention may generate a non-hydrolyzable cap structure preventing decapping and thus increasing mRNA half-life. Because cap structure hydrolysis requires cleavage of 5′-ppp-5′ phosphorodiester linkages, modified nucleotides may be used during the capping reaction. For example, a Vaccinia Capping Enzyme from New England Biolabs (Ipswich, MA) may be used with α-thio-guanosine nucleotides according to the manufacturer's instructions to create a phosphorothioate linkage in the 5′-ppp-5′ cap. Additional modified guanosine nucleotides may be used such as α-methyl-phosphonate and seleno-phosphate nucleotides.

Additional modifications include, but are not limited to, 2′-O-methylation of the ribose sugars of 5′-terminal and/or 5′-anteterminal nucleotides of the polynucleotide (as mentioned above) on the 2′-hydroxyl group of the sugar ring. Multiple distinct 5′-cap structures can be used to generate the 5′-cap of a nucleic acid molecule, such as a polynucleotide which functions as an mRNA molecule.

Cap analogs, which herein are also referred to as synthetic cap analogs, chemical caps, chemical cap analogs, or structural or functional cap analogs, differ from natural (i.e. endogenous, wild-type or physiological) 5′-caps in their chemical structure, while retaining cap function. Cap analogs may be chemically (i.e. non-enzymatically) or enzymatically synthesized and/or linked to the polynucleotides of the invention.

For example, the Anti-Reverse Cap Analog (ARCA) cap contains two guanines linked by a 5′-5′-triphosphate group, wherein one guanine contains an N7 methyl group as well as a 3′-O-methyl group (i.e., N7,3′-O-dimethyl-guanosine-5′-triphosphate-5′-guanosine (m⁷G-3′mppp-G; which may equivaliently be designated 3′ O-Me-m7G(5′)ppp(5′)G). The 3′-0 atom of the other, unmodified, guanine becomes linked to the 5′-terminal nucleotide of the capped polynucleotide. The N7- and 3′-O-methylated guanine provides the terminal moiety of the capped polynucleotide.

Another exemplary cap is mCAP, which is similar to ARCA but has a 2′-O-methyl group on guanosine (i.e., N7,2′-O-dimethyl-guanosine-5′-uiphosphate-5′-guanosine, m⁷Gm-ppp-G).

In one embodiment, the cap is a dinucleotide cap analog. As a non-limiting example, the dinucleotide cap analog may be modified at different phosphate positions with a boranophosphate group or a phosphoroselenoate group such as the dinucleotide cap analogs described in U.S. Pat. No. 8,519,110, the contents of which are herein incorporated by reference in its entirety.

In another embodiment, the cap is a cap analog is a N7-(4-chlorophenoxyethyl) substituted dicucleotide form of a cap analog known in the art and/or described herein. Non-limiting examples of a N7-(4-chlorophenoxyethyl) substituted dicucleotide form of a cap analog include a N7-(4-chlorophenoxyethyl)-G(5′)ppp(5′)G and a N7-(4-chlorophenoxyethyl)-m^3′-O-( )G(5′)ppp(5′)G cap analog (See e.g., the various cap analogs and the methods of synthesizing cap analogs described in Kore et al. Bioorganic & Medicinal Chemistry 2013 21:4570-4574; the contents of which are herein incorporated by reference in its entirety). In another embodiment, a cap analog of the present invention is a 4-chloro/bromophenoxyethyl analog.

While cap analogs allow for the concomitant capping of a polynucleotide or a region thereof, in an in vitro transcription reaction, up to 20% of transcripts can remain uncapped. This, as well as the structural differences of a cap analog from an endogenous 5′-cap structures of nucleic acids produced by the endogenous, cellular transcription machinery, may lead to reduced translational competency and reduced cellular stability.

Polynucleotides of the invention may also be capped post-manufacture (whether IVT or chemical synthesis), using enzymes, in order to generate more authentic 5′-cap structures. As used herein, the phrase “more authentic” refers to a feature that closely mirrors or mimics, either structurally or functionally, an endogenous or wild type feature. That is, a “more authentic” feature is better representative of an endogenous, wild-type, natural or physiological cellular function and/or structure as compared to synthetic features or analogs, etc., of the prior art, or which outperforms the corresponding endogenous, wild-type, natural or physiological feature in one or more respects. Non-limiting examples of more authentic 5′cap structures of the present invention are those which, among other things, have enhanced binding of cap binding proteins, increased half life, reduced susceptibility to 5′ endonucleases and/or reduced 5′decapping, as compared to synthetic 5′cap structures known in the art (or to a wild-type, natural or physiological 5′cap structure). For example, recombinant Vaccinia Virus Capping Enzyme and recombinant 2′-O-methyltransferase enzyme can create a canonical 5′-5′-triphosphate linkage between the 5′-terminal nucleotide of a polynucleotide and a guanine cap nucleotide wherein the cap guanine contains an N7 methylation and the 5′-terminal nucleotide of the mRNA contains a 2′-O-methyl. Such a structure is termed the Cap1 structure. This cap results in a higher translational-competency and cellular stability and a reduced activation of cellular pro-inflammatory cytokines, as compared, e.g., to other 5′cap analog structures known in the art. Cap structures include, but are not limited to, 7mG(5′)ppp(5′)N,pN2p (cap 0), 7mG(5′)ppp(5′)NlmpNp (cap 1), and 7mG(5′)-ppp(5′)NlmpN2mp (cap 2).

As a non-limiting example, capping chimeric polynucleotides post-manufacture may be more efficient as nearly 100% of the chimeric polynucleotides may be capped. This is in contrast to ˜80% when a cap analog is linked to a chimeric polynucleotide in the course of an in vitro transcription reaction.

According to the present invention, 5′ terminal caps may include endogenous caps or cap analogs. According to the present invention, a 5′ terminal cap may comprise a guanine analog. Useful guanine analogs include, but are not limited to, inosine, N1-methyl-guanosine, 2′fluoro-guanosine, 7-deaza-guanosine, 8-oxo-guanosine, 2-amino-guanosine, LNA-guanosine, and 2-azido-guanosine.

Viral Sequences

Additional viral sequences such as, but not limited to, the translation enhancer sequence of the barley yellow dwarf virus (BYDV-PAV), the Jaagsiekte sheep retrovirus (JSRV) and/or the Enzootic nasal tumor virus (See e.g., International Pub. No. WO2012129648; herein incorporated by reference in its entirety) can be engineered and inserted in the polynucleotides of the invention and can stimulate the translation of the construct in vitro and in vivo. Transfection experiments can be conducted in relevant cell lines at and protein production can be assayed by ELISA at 12 hr, 24 hr, 48 hr, 72 hr and day 7 post-transfection.

IRES Sequences

Further, provided are polynucleotides (e.g., antigen-encoding polynucleotides featured in the NAVs of the invention) which may contain an internal ribosome entry site (IRES). First identified as a feature Picoma virus RNA, IRES plays an important role in initiating protein synthesis in absence of the 5′ cap structure. An IRES may act as the sole ribosome binding site, or may serve as one of multiple ribosome binding sites of an mRNA. Polynucleotides containing more than one functional ribosome binding site may encode several peptides or polypeptides that are translated independently by the ribosomes (“multicistronic nucleic acid molecules”). When polynucleotides are provided with an IRES, further optionally provided is a second translatable region. Examples of IRES sequences that can be used according to the invention include without limitation, those from picornaviruses (e.g. FMDV), pest viruses (CFFV), polio viruses (PV), encephalomyocarditis viruses (ECMV), foot-and-mouth disease viruses (FMDV), hepatitis C viruses (HCV), classical swine fever viruses (CSFV), murine leukemia virus (MLV), simian immune deficiency viruses (SIV) or cricket paralysis viruses (CrPV).

Poly-A Tails

During RNA processing, a long chain of adenine nucleotides (poly-A tail) may be added to a polynucleotide such as an mRNA molecule in order to increase stability. Immediately after transcription, the 3′ end of the transcript may be cleaved to free a 3′ hydroxyl. Then poly-A polymerase adds a chain of adenine nucleotides to the RNA. The process, called polyadenylation, adds a poly-A tail that can be between, for example, approximately 80 to approximately 250 residues long, including approximately 80, 90, 100, 110, 120, 130, 140, 150, 160, 170, 180, 190, 200, 210, 220, 230, 240 or 250 residues long.

PolyA tails may also be added after the construct is exported from the nucleus.

According to the present invention, terminal groups on the poly A tail may be incorporated for stabilization into polynucleotides of the invention (e.g., antigen-encoding polynucleotides featured in the RNAVs of the invention). Polynucleotides of the present invention may incude des-3′ hydroxyl tails. They may also include structural moieties or 2′-Omethyl modifications as taught by Junjie Li, et al. (Current Biology, Vol. 15, 1501-1507, Aug. 23, 2005, the contents of which are incorporated herein by reference in its entirety).

The polynucleotides of the present invention (e.g., antigen-encoding polynucleotides featured in the NAVs of the invention) may be designed to encode transcripts with alternative polyA tail structures including histone mRNA. According to Norbury, “Terminal uridylation has also been detected on human replication-dependent histone mRNAs. The turnover of these mRNAs is thought to be important for the prevention of potentially toxic histone accumulation following the completion or inhibition of chromosomal DNA replication. These mRNAs are distinguished by their lack of a 3′ poly(A) tail, the function of which is instead assumed by a stable stem-loop structure and its cognate stem-loop binding protein (SLBP); the latter carries out the same functions as those of PABP on polyadenylated mRNAs” (Norbury, “Cytoplasmic RNA: a case of the tail wagging the dog,” Nature Reviews Molecular Cell Biology: AOP, published online 29 Aug. 2013; doi:10.1038/nrm3645) the contents of which are incorporated herein by reference in its entirety.

Unique poly-A tail lengths provide certain advantages to the polynucleotides of the present invention (e.g., antigen-encoding polynucleotides featured in the NAVs of the invention).

Generally, the length of a poly-A tail, when present, is greater than 30 nucleotides in length. In another embodiment, the poly-A tail is greater than 35 nucleotides in length (e.g., at least or greater than about 35, 40, 45, 50, 55, 60, 70, 80, 90, 100, 120, 140, 160, 180, 200, 250, 300, 350, 400, 450, 500, 600, 700, 800, 900, 1,000, 1,100, 1,200, 1,300, 1,400, 1,500, 1,600, 1,700, 1,800, 1,900, 2,000, 2,500, and 3,000 nucleotides). In some embodiments, the polynucleotide or region thereof includes from about 30 to about 3,000 nucleotides (e.g., from 30 to 50, from 30 to 100, from 30 to 250, from 30 to 500, from 30 to 750, from 30 to 1,000, from 30 to 1,500, from 30 to 2,000, from 30 to 2,500, from 50 to 100, from 50 to 250, from 50 to 500, from 50 to 750, from 50 to 1,000, from 50 to 1,500, from 50 to 2,000, from 50 to 2,500, from 50 to 3,000, from 100 to 500, from 100 to 750, from 100 to 1,000, from 100 to 1.500, from 100 to 2,000, from 100 to 2,500, from 100 to 3,000, from 500 to 750, from 500 to 1,000, from 500 to 1,500, from 500 to 2,000, from 500 to 2,500, from 500 to 3,000, from 1,000 to 1,500, from 1,000 to 2,000, from 1,000 to 2,500, from 1.000 to 3,000, from 1,500 to 2,000, from 1,500 to 2,500, from 1,500 to 3,000, from 2,000 to 3,000, from 2,000 to 2,500, and from 2,500 to 3,000).

In one embodiment, the poly-A tail is designed relative to the length of the overall polynucleotide or the length of a particular region of the polynucleotide. This design may be based on the length of a coding region, the length of a particular feature or region or based on the length of the ultimate product expressed from the polynucleotides.

In this context the poly-A tail may be 10, 20, 30, 40, 50, 60, 70, 80, 90, or 100% greater in length than the polynucleotide or feature thereof. The poly-A tail may also be designed as a fraction of the polynucleotides to which it belongs. In this context, the poly-A tail may be 10, 20, 30, 40, 50, 60, 70, 80, or 90% or more of the total length of the construct, a construct region or the total length of the construct minus the poly-A tail. Further, engineered binding sites and conjugation of polynucleotides for Poly-A binding protein may enhance expression.

Additionally, multiple distinct polynucleotides may be linked together via the PABP (Poly-A binding protein) through the Y-end using modified nucleotides at the 3′-terminus of the poly-A tail. Transfection experiments can be conducted in relevant cell lines at and protein production can be assayed by ELISA at 12 hr, 24 hr, 48 hr, 72 hr and day 7 post-transfection.

In one embodiment, the polynucleotides of the present invention (e.g., antigen-encoding polynucleotides featured in the NAVs of the invention) are designed to include a polyA-G Quartet region. The G-quartet is a cyclic hydrogen bonded array of four guanine nucleotides that can be formed by G-rich sequences in both DNA and RNA. In this embodiment, the G-quartet is incorporated at the end of the poly-A tail. The resultant polynucleotide is assayed for stability, protein production and other parameters including half-life at various time points. It has been discovered that the polyA-G quartet results in protein production from an mRNA equivalent to at least 75% of that seen using a poly-A tail of 120 nucleotides alone.

Start Codon Region

In some embodiments, the polynucleotides of the present invention (e.g., antigen-encoding polynucleotides featured in the NAVs of the invention) may have regions that are analogous to or function like a start codon region.

In one embodiment, the translation of a polynucleotide may initiate on a codon which is not the start codon AUG. Translation of the polynucleotide may initiate on an alternative start codon such as, but not limited to, ACG, AGG, AAG, CTG/CUG, GTG/GUG, ATA/AUA, ATT/AUU, TTG/UUG (see Touriol et al. Biology of the Cell 95 (2003) 169-178 and Matsuda and Mauro PLoS ONE, 2010 5:11; the contents of each of which are herein incorporated by reference in its entirety). As a non-limiting example, the translation of a polynucleotide begins on the alternative start codon ACG. As another non-limiting example, polynucleotide translation begins on the alternative start codon CTG or CUG. As yet another non-limiting example, the translation of a polynucleotide begins on the alternative start codon GTG or GUG.

Nucleotides flanking a codon that initiates translation such as, but not limited to, a start codon or an alternative start codon, are known to affect the translation efficiency, the length and/or the structure of the polynucleotide. (See e.g., Matsuda and Mauro PLoS ONE, 2010 5:11; the contents of which are herein incorporated by reference in its entirety). Masking any of the nucleotides flanking a codon that initiates translation may be used to alter the position of translation initiation, translation efficiency, length and/or structure of a polynucleotide.

In one embodiment, a masking agent may be used near the start codon or alternative start codon in order to mask or hide the codon to reduce the probability of translation initiation at the masked start codon or alternative start codon. Non-limiting examples of masking agents include antisense locked nucleic acids (LNA) polynucleotides and exon-junction complexes (EJCs) (See e.g., Matsuda and Mauro describing masking agents LNA polynucleotides and EJCs (PLoS ONE, 2010 5:11); the contents of which are herein incorporated by reference in its entirety).

In another embodiment, a masking agent may be used to mask a start codon of a polynucleotide in order to increase the likelihood that translation will initiate on an alternative start codon.

In one embodiment, a masking agent may be used to mask a first start codon or alternative start codon in order to increase the chance that translation will initiate on a start codon or alternative start codon downstream to the masked start codon or alternative start codon.

In one embodiment, a start codon or alternative start codon may be located within a perfect complement for a miR binding site. The perfect complement of a miR binding site may help control the translation, length and/or structure of the polynucleotide similar to a masking agent. As a non-limiting example, the start codon or alternative start codon may be located in the middle of a perfect complement for a miR-122 binding site. The start codon or alternative start codon may be located after the first nucleotide, second nucleotide, third nucleotide, fourth nucleotide, fifth nucleotide, sixth nucleotide, seventh nucleotide, eighth nucleotide, ninth nucleotide, tenth nucleotide, eleventh nucleotide, twelfth nucleotide, thirteenth nucleotide, fourteenth nucleotide, fifteenth nucleotide, sixteenth nucleotide, seventeenth nucleotide, eighteenth nucleotide, nineteenth nucleotide, twentieth nucleotide or twenty-first nucleotide.

In another embodiment, the start codon of a polynucleotide may be removed from the polynucleotide sequence in order to have the translation of the polynucleotide begin on a codon which is not the start codon. Translation of the polynucleotide may begin on the codon following the removed start codon or on a downstream start codon or an alternative start codon. In a non-limiting example, the start codon ATG or AUG is removed as the first 3 nucleotides of the polynucleotide sequence in order to have translation initiate on a downstream start codon or alternative start codon. The polynucleotide sequence where the start codon was removed may further comprise at least one masking agent for the downstream start codon and/or alternative start codons in order to control or attempt to control the initiation of translation, the length of the polynucleotide and/or the structure of the polynucleotide.

Stop Codon Region

In one embodiment, the polynucleotides of the present invention (e.g., antigen-encoding polynucleotides featured in the NAVs of the invention) may include at least two stop codons before the 3′ untranslated region (UTR). The stop codon may be selected from TGA, TAA and TAG. In one embodiment, the polynucleotides of the present invention include the stop codon TGA and one additional stop codon. In a further embodiment the addition stop codon may be TAA. In another embodiment, the polynucleotides of the present invention include three stop codons.

Signal Sequences

The polynucleotides of the invention (e.g., antigen-encoding polynucleotides featured in the NAVs of the invention) may also encode additional features which facilitate trafficking of the polypeptides to therapeutically relevant sites. One such feature which aids in protein trafficking is the signal sequence. As used herein, a “signal sequence” or “signal peptide” is a polynucleotide or polypeptide, respectively, which is from about 9 to 200 nucleotides (3-60 amino acids) in length which is incorporated at the 5′ (or N-terminus) of the coding region or polypeptide encoded, respectively. Addition of these sequences result in trafficking of the encoded polypeptide to the endoplasmic reticulum through one or more secretory pathways. Some signal peptides are cleaved from the protein by signal peptidase after the proteins are transported.

Additional signal sequences which may be utilized in the present invention include those taught in, for example, databases such as those found at http://www.signalpeptide.de/ or http://proline.bic.nus.edu.sg/spdb/. Those described in U.S. Pat. Nos. 8,124,379; 7,413,875 and 7,385,034 are also within the scope of the invention and the contents of each are incorporated herein by reference in their entirety.

Protein Cleavage Signals and Sites

In exemplary embodiments, polypeptides of the invention (e.g., antigen polypeptides) may include various protein cleavage signals and/or sites.

In one embodiment, the polypeptides of the present invention may include at least one protein cleavage signal containing at least one protein cleavage site. The protein cleavage site may be located at the N-terminus, the C-terminus, at any space between the N- and the C-termini such as, but not limited to, half-way between the N- and C-termini, between the N-terminus and the half way point, between the half way point and the C-terminus, and combinations thereof.

In one embodiment, the polynucleotides of the present invention may be engineered such that the polynucleotide contains at least one encoded protein cleavage signal. The encoded protein cleavage signal may be located in any region including but not limited to before the start codon, after the start codon, before the coding region, within the coding region such as, but not limited to, half way in the coding region, between the start codon and the half way point, between the half way point and the stop codon, after the coding region, before the stop codon, between two stop codons, after the stop codon and combinations thereof.

In one embodiment, the polynucleotides of the present invention may include at least one encoded protein cleavage signal containing at least one protein cleavage site. The encoded protein cleavage signal may include, but is not limited to, a proprotein convertase (or prohormone convertase), thrombin and/or Factor Xa protein cleavage signal.

As a non-limiting example, U.S. Pat. No. 7,374,930 and U.S. Pub. No. 20090227660, herein incorporated by reference in their entireties, use a furin cleavage site to cleave the N-terminal methionine of GLP-1 in the expression product from the Golgi apparatus of the cells. In one embodiment, the polypeptides of the present invention include at least one protein cleavage signal and/or site with the proviso that the polypeptide is not GLP-1.

Insertions and Substitutions

In exemplary embodiments, polynucleotides of the invention (e.g., antigen-encoding polynucleotides featured in the NAVs of the invention) can include various substitutions and/or insertions.

In one embodiment, the 5′UTR of the polynucleotide may be replaced by the insertion of at least one region and/or string of nucleosides of the same base. The region and/or string of nucleotides may include, but is not limited to, at least 3, at least 4, at least 5, at least 6, at least 7 or at least 8 nucleotides and the nucleotides may be natural and/or unnatural. As a non-limiting example, the group of nucleotides may include 5-8 adenine, cytosine, thymine, a string of any of the other nucleotides disclosed herein and/or combinations thereof.

In one embodiment, the 5′UTR of the polynucleotide may be replaced by the insertion of at least two regions and/or strings of nucleotides of two different bases such as, but not limited to, adenine, cytosine, thymine, any of the other nucleotides disclosed herein and/or combinations thereof. For example, the 5′UTR may be replaced by inserting 5-8 adenine bases followed by the insertion of 5-8 cytosine bases. In another example, the 5′UTR may be replaced by inserting 5-8 cytosine bases followed by the insertion of 5-8 adenine bases.

In one embodiment, the polynucleotide may include at least one substitution and/or insertion downstream of the transcription start site which may be recognized by an RNA polymerase. As a non-limiting example, at least one substitution and/or insertion may occur downstream the transcription start site by substituting at least one nucleic acid in the region just downstream of the transcription start site (such as, but not limited to, +1 to +6). Changes to region of nucleotides just downstream of the transcription start site may affect initiation rates, increase apparent nucleotide triphosphate (NTP) reaction constant values, and increase the dissociation of short transcripts from the transcription complex curing initial transcription (Brieba et al, Biochemistry (2002) 41: 5144-5149; herein incorporated by reference in its entirety). The modification, substitution and/or insertion of at least one nucleoside may cause a silent mutation of the sequence or may cause a mutation in the amino acid sequence.

In one embodiment, the polynucleotide may include the substitution of at least 1, at least 2, at least 3, at least 4, at least 5, at least 6, at least 7, at least 8, at least 9, at least 10, at least 11, at least 12 or at least 13 guanine bases downstream of the transcription start site.

In one embodiment, the polynucleotide may include the substitution of at least 1, at least 2, at least 3, at least 4, at least 5 or at least 6 guanine bases in the region just downstream of the transcription start site. As a non-limiting example, if the nucleotides in the region are GGGAGA the guanine bases may be substituted by at least 1, at least 2, at least 3 or at least 4 adenine nucleotides. In another non-limiting example, if the nucleotides in the region are GGGAGA the guanine bases may be substituted by at least 1, at least 2, at least 3 or at least 4 cytosine bases. In another non-limiting example, if the nucleotides in the region are GGGAGA the guanine bases may be substituted by at least 1, at least 2, at least 3 or at least 4 thymine, and/or any of the nucleotides described herein.

In one embodiment, the polynucleotide may include at least one substitution and/or insertion upstream of the start codon. For the purpose of clarity, one of skill in the art would appreciate that the start codon is the first codon of the protein coding region whereas the transcription start site is the site where transcription begins. The polynucleotide may include, but is not limited to, at least 1, at least 2, at least 3, at least 4, at least 5, at least 6, at least 7 or at least 8 substitutions and/or insertions of nucleotide bases. The nucleotide bases may be inserted or substituted at 1, at least 1, at least 2, at least 3, at least 4 or at least 5 locations upstream of the start codon. The nucleotides inserted and/or substituted may be the same base (e.g., all A or all C or all T or all G), two different bases (e.g., A and C, A and T, or C and T), three different bases (e.g., A, C and T or A, C and T) or at least four different bases. As a non-limiting example, the guanine base upstream of the coding region in the polynucleotide may be substituted with adenine, cytosine, thymine, or any of the nucleotides described herein. In another non-limiting example the substitution of guanine bases in the polynucleotide may be designed so as to leave one guanine base in the region downstream of the transcription start site and before the start codon (see Esvelt et al. Nature (2011) 472(7344):499-503; the contents of which is herein incorporated by reference in its entirety). As a non-limiting example, at least 5 nucleotides may be inserted at 1 location downstream of the transcription start site but upstream of the start codon and the at least 5 nucleotides may be the same base type.

Incorporating Post Transcriptional Control Modulators

In one embodiment, the polynucleotides of the present invention (e.g., antigen-encoding polynucleotides featured in the NAVs of the invention) may include at least one post transcriptional control modulator. These post transcriptional control modulators may be, but are not limited to, small molecules, compounds and regulatory sequences. As a non-limiting example, post transcriptional control may be achieved using small molecules identified by PTC Therapeutics Inc. (South Plainfield, NJ) using their GEMS™ (Gene Expression Modulation by Small-Molecules) screening technology.

The post transcriptional control modulator may be a gene expression modulator which is screened by the method detailed in or a gene expression modulator described in International Publication No. WO2006022712, herein incorporated by reference in its entirety. Methods identifying RNA regulatory sequences involved in translational control are described in International Publication No. WO2004067728, herein incorporated by reference in its entirety; methods identifying compounds that modulate untranslated region dependent expression of a gene are described in International Publication No. WO2004065561, herein incorporated by reference in its entirety.

In one embodiment, the polynucleotides of the present invention may include at least one post transcriptional control modulator is located in the 5′ and/or the 3′ untranslated region of the polynucleotides of the present invention.

In another embodiment, the polynucleotides of the present invention may include at least one post transcription control modulator to modulate premature translation termination. The post transcription control modulators may be compounds described in or a compound found by methods outlined in International Publication Nos. WO2004010106, WO2006044456, WO2006044682, WO2006044503 and WO2006044505, each of which is herein incorporated by reference in its entirety. As a non-limiting example, the compound may bind to a region of the 28S ribosomal RNA in order to modulate premature translation termination (See e.g., WO2004010106, herein incorporated by reference in its entirety).

In one embodiment, polynucleotides of the present invention may include at least one post transcription control modulator to alter protein expression. As a non-limiting example, the expression of VEGF may be regulated using the compounds described in or a compound found by the methods described in International Publication Nos. WO2005118857, WO2006065480, WO2006065479 and WO2006058088, each of which is herein incorporated by reference in its entirety.

The polynucleotides of the present invention may include at least one post transcription control modulator to control translation. In one embodiment, the post transcription control modulator may be a RNA regulatory sequence. As a non-limiting example, the RNA regulatory sequence may be identified by the methods described in International Publication No. WO2006071903, herein incorporated by reference in its entirety.

Codon Optimization

The polynucleotides contained in the NAVs of the invention, their regions or parts or subregions may be codon optimized. Codon optimization methods are known in the art and may be useful in efforts to achieve one or more of several goals. These goals include to match codon frequencies in target and host organisms to ensure proper folding, bias GC content to increase mRNA stability or reduce secondary structures, minimize tandem repeat codons or base runs that may impair gene construction or expression, customize transcriptional and translational control regions, insert or remove protein trafficking sequences, remove/add post translation modification sites in encoded protein (e.g. glycosylation sites), add, remove or shuffle protein domains, insert or delete restriction sites, modify ribosome binding sites and mRNA degradation sites, to adjust translational rates to allow the various domains of the protein to fold properly, or to reduce or eliminate problem secondary structures within the polynucleotide. Codon optimization tools, algorithms and services are known in the art, non-limiting examples include services from GeneArt (Life Technologies), DNA2.0 (Menlo Park CA) and/or proprietary methods. In one embodiment, the ORF sequence is optimized using optimization algorithms. Codon options for each amino acid are given in Table 21.

TABLE 21

Codon Options

Single

Amino Acid
Letter Code
Codon Options

Isoleucine
I
ATT, ATC, ATA

Leucine
L
CTT, CTC, CTA, CTG, TTA, TTG

Valine
V
GTT, GTC, GTA, GTG

Phenylalanine
F
TTT, TTC

Methionine
M
ATG

Cysteine
C
TGT, TGC

Alanine
A
GCT, GCC, GCA, GCG

Glycine
G
GGT, GGC, GGA, GGG

Proline
P
CCT, CCC, CCA, CCG

Threonine
T
ACT, ACC, ACA, ACG

Serine
S
TCT, TCC, TCA, TCG, AGT, AGC

Tyrosine
Y
TAT, TAC

Tryptophan
W
TGG

Glutamine
Q
CAA, CAG

Asparagine
N
AAT, AAC

Histidine
H
CAT, CAC

Glutamic acid
E
GAA, GAG

Aspartic acid
D
GAT, GAC

Lysine
K
AAA, AAG

Arginine
R
CGT, CGC, CGA, CGG, AGA, AGG

Selenocysteine
Sec
UGA in mRNA in presence of

Selenocystein insertion element

(SECIS)

Stop codons
Stop
TAA, TAG, TGA

Features, which may be considered beneficial in some embodiments of the present invention, may be encoded by regions of the polynucleotide and such regions may be upstream (5′) or downstream (3′) to a region which encodes a polypeptide. These regions may be incorporated into the polynucleotide before and/or after codon optimization of the protein encoding region or open reading frame (ORF). It is not required that a polynucleotide contain both a 5′ and 3′ flanking region. Examples of such features include, but are not limited to, untranslated regions (UTRs), Kozak sequences, an oligo(dT) sequence, and detectable tags and may include multiple cloning sites which may have XbaI recognition.

In some embodiments, a 5′ UTR and/or a 3′ UTR region may be provided as flanking regions. Multiple 5′ or 3′ UTRs may be included in the flanking regions and may be the same or of different sequences. Any portion of the flanking regions, including none, may be codon optimized and any may independently contain one or more different structural or chemical modifications, before and/or after codon optimization.

After optimization (if desired), the polynucleotides components are reconstituted and transformed into a vector such as, but not limited to, plasmids, viruses, cosmids, and artificial chromosomes. For example, the optimized polynucleotide may be reconstituted and transformed into chemically competent E. coli, yeast, neurospora, maize, drosophila, etc. where high copy plasmid-like or chromosome structures occur by methods described herein.

Synthetic polynucleotides and their nucleic acid analogs play an important role in the research and studies of biochemical processes. Various enzyme-assisted and chemical-based methods have been developed to synthesize polynucleotides and nucleic acids, in particular, polynucleotides and nucleic acids featured in the NAVs of the invention, as described infra.

Synthesis: Enzymatic Methods
In Vitro Transcription-Enzymatic Synthesis

cDNA encoding the polynucleotides described herein may be transcribed using an in vitro transcription (IVT) system. The system typically comprises a transcription buffer, nucleotide triphosphates (NTPs), an RNase inhibitor and a polymerase. The NTPs may be manufactured in house, may be selected from a supplier, or may be synthesized as described herein. The NTPs may be selected from, but are not limited to, those described herein including natural and unnatural (modified) NTPs. The polymerase may be selected from, but is not limited to, T7 RNA polymerase, T3 RNA polymerase and mutant polymerases such as, but not limited to, polymerases able to incorporate polynucleotides (e.g., modified nucleic acids).

RNA Polymerases Useful for Synthesis

Any number of RNA polymerases or variants may be used in the synthesis of the polynucleotides of the present invention.

RNA polymerases may be modified by inserting or deleting amino acids of the RNA polymerase sequence. As a non-limiting example, the RNA polymerase may be modified to exhibit an increased ability to incorporate a 2′-modified nucleotide triphosphate compared to an unmodified RNA polymerase (see International Publication WO2008078180 and U.S. Pat. No. 8,101,385; herein incorporated by reference in their entireties).

Variants may be obtained by evolving an RNA polymerase, optimizing the RNA polymerase amino acid and/or nucleic acid sequence and/or by using other methods known in the art. As a non-limiting example, T7 RNA polymerase variants may be evolved using the continuous directed evolution system set out by Esvelt et al. (Nature (2011) 472(7344):499-503; herein incorporated by reference in its entirety) where clones of T7 RNA polymerase may encode at least one mutation such as, but not limited to, lysine at position 93 substituted for threonine (K93T), 14M, A7T, E63V, V64D, A65E, D66Y, T76N, C125R, S128R, A136T, N165S, G175R, H176L, Y178H, F182L, L196F, G198V, D208Y, E222K, S228A, Q239R, T243N, G259D, M2671, G280C, H300R, D351A, A354S, E356D, L360P, A383V, Y385C, D388Y, S397R, M40 IT, N410S, K450R, P451T, G452V, E484A, H523L, H524N, G542V. E565K, K577E, K577M, N601 S, S684Y, L6991, K713E, N748D, Q754R, E775K, A827V, D851N or L864F. As another non-limiting example, T7 RNA polymerase variants may encode at least mutation as described in U.S. Pub. Nos. 20100120024 and 20070117112; herein incorporated by reference in their entireties. Variants of RNA polymerase may also include, but are not limited to, substitutional variants, conservative amino acid substitution, insertional variants, deletional variants and/or covalent derivatives.

In one embodiment, the polynucleotide may be designed to be recognized by the wild type or variant RNA polymerases. In doing so, the polynucleotide may be modified to contain sites or regions of sequence changes from the wild type or parent polynucleotide.

Polynucleotide or nucleic acid synthesis reactions may be carried out by enzymatic methods utilizing polymerases. Polymerases catalyze the creation of phosphodiester bonds between nucleotides in a polynucleotide or nucleic acid chain. Currently known DNA polymerases can be divided into different families based on amino acid sequence comparison and crystal structure analysis. DNA polymerase 1 (pol I) or A polymerase family, including the Klenow fragments of E. Coli, Bacillus DNA polymerase I, Thermus aquaticus (Taq) DNA polymerases, and the T7 RNA and DNA polymerases, is among the best studied of these families. Another large family is DNA polymerase a (pol a) or B polymerase family, including all eukaryotic replicating DNA polymerases and polymerases from phages T4 and RB69. Although they employ similar catalytic mechanism, these families of polymerases differ in substrate specificity, substrate analog-incorporating efficiency, degree and rate for primer extension, mode of DNA synthesis, exonuclease activity, and sensitivity against inhibitors.

DNA polymerases are also selected based on the optimum reaction conditions they require, such as reaction temperature, pH, and template and primer concentrations. Sometimes a combination of more than one DNA polymerases is employed to achieve the desired DNA fragment size and synthesis efficiency. For example, Cheng et al. increase pH, add glycerol and dimethyl sulfoxide, decrease denaturation times, increase extension times, and utilize a secondary thermostable DNA polymerase that possesses a 3′ to 5′ exonuclease activity to effectively amplify long targets from cloned inserts and human genomic DNA (Cheng et al., PNAS, Vol. 91, 5695-5699 (1994), the contents of which are incorporated herein by reference in their entirety). RNA polymerases from bacteriophage T3, T7, and SP6 have been widely used to prepare RNAs for biochemical and biophysical studies. RNA polymerases, capping enzymes, and poly-A polymerases are disclosed in the copending application No. PCT/US2013/054635 (M032), the contents of which are incorporated herein by reference in their entirety.

In one embodiment, the RNA polymerase which may be used in the synthesis of the chimeric polynucleotides described herein is a Syn5 RNA polymerase (see Zhu et al. Nucleic Acids Research 2013, the contents of which is herein incorporated by reference in its entirety). The Syn5 RNA polymerase was recently characterized from marine cyanophage Syn5 by Zhu et al. where they also identified the promoter sequence (see Zhu et al. Nucleic Acids Research 2013, the contents of which is herein incorporated by reference in its entirety). Zhu et al. found that Syn5 RNA polymerase catalyzed RNA synthesis over a wider range of temperatures and salinity as compared to T7 RNA polymerase. Additionally, the requirement for the initiating nucleotide at the promoter was found to be less stringent for Syn5 RNA polymerase as compared to the T7 RNA polymerase making Syn5 RNA polymerase promising for RNA synthesis.

In one embodiment, a Syn5 RNA polymerase may be used in the synthesis of the chimeric polynucleotides described herein. As a non-limiting example, a Syn5 RNA polymerase may be used in the synthesis of the chimeric polynucleotide requiring a precise 3′-termini.

In one embodiment, a Syn5 promoter may be used in the synthesis of the chimeric polynucleotides. As a non-limiting example, the Syn5 promoter may be 5′-ATTGGGCACCCGTAAGGG-3′ (SEQ ID NO: 966) as described by Zhu et al. (Nucleic Acids Research 2013, the contents of which is herein incorporated by reference in its entirety).

In one embodiment, a Syn5 RNA polymerase may be used in the synthesis of chimeric polynucleotides comprising at least one chemical modification described herein and/or known in the art. (see e.g., the incorporation of pseudo-UTP and 5Me-CTP described in Zhu et al. Nucleic Acids Research 2013, the contents of which is herein incorporated by reference in its entirety).

In one embodiment, the chimeric polynucleotides described herein may be synthesized using a Syn5 RNA polymerase which has been purified using modified and improved purification procedure described by Zhu et al. (Nucleic Acids Research 2013, the contents of which is herein incorporated by reference in its entirety).

Various tools in genetic engineering are based on the enzymatic amplification of a target gene which acts as a template. For the study of sequences of individual genes or specific regions of interest and other research needs, it is necessary to generate multiple copies of a target gene from a small sample of polynucleotides or nucleic acids. Such methods may be applied in the manufacture of the polynucleotides of the invention.

Polymerase chain reaction (PCR) has wide applications in rapid amplification of a target gene, as well as genome mapping and sequencing. The key components for synthesizing DNA comprise target DNA molecules as a template, primers complementary to the ends of target DNA strands, deoxynucleoside triphosphates (dNTPs) as building blocks, and a DNA polymerase. As PCR progresses through denaturation, annealing and extension steps, the newly produced DNA molecules can act as a template for the next circle of replication, achieving exponentially amplification of the target DNA. PCR requires a cycle of heating and cooling for denaturation and annealing. Variations of the basic PCR include, but are not limited to, asymmetric PCR (See e.g., Innis et al., PNAS, vol. 85, 9436-9440 (1988), the contents of which are incorporated herein by reference in their entirety), inverse PCR (see e.g., Ochman et al., Genetics, vol. 120(3), 621-623, (1988), the contents of which are incorporated herein by reference in their entirety), and reverse transcription PCR (RT-PCR) (see e.g., Freeman et al., BioTechniques, vol. 26(1), 112-22, 124-5 (1999), the contents of which are incorporated herein by reference in their entirety). In RT-PCR, a single stranded RNA is the desired target and is converted to a double stranded DNA first by reverse transcriptase.

A variety of isothermal in vitro nucleic acid amplification techniques have been developed as alternatives or complements of PCR. For example, strand displacement amplification (SDA) is based on the ability of a restriction enzyme to form a nick (Walker et al., PNAS, vol. 89, 392-396 (1992), the contents of which are incorporated herein by reference in their entirety). A restriction enzyme recognition sequence is inserted into an annealed primer sequence. Primers are extended by a DNA polymerase and dNTPs to form a duplex. Only one strand of the duplex is cleaved by the restriction enzyme. Each single strand chain is then available as a template for subsequent synthesis. SDA does not require the complicated temperature control cycle of PCR.

Nucleic acid sequence-based amplification (NASBA), also called transcription mediated amplification (TMA), is also an isothermal amplification method that utilizes a combination of DNA polymerase, reverse transcriptase, RNAse H, and T7 RNA polymerase (Compton, Nature, vol. 350, 91-92 (1991), the contents of which are incorporated herein by reference in their entirety). A target RNA is used as a template and a reverse transcriptase synthesizes its complementary DNA strand. RNAse H hydrolyzes the RNA template, making space for a DNA polymerase to synthesize a DNA strand complementary to the first DNA strand which is complementary to the RNA target, forming a DNA duplex. T7 RNA polymerase continuously generates complementary RNA strands of this DNA duplex. These RNA strands act as templates for new cycles of DNA synthesis, resulting in amplification of the target gene.

Rolling-circle amplification (RCA) amplifies a single stranded circular polynucleotide and involves numerous rounds of isothermal enzymatic synthesis where Φ29 DNA polymerase extends a primer by continuously progressing around the polynucleotide circle to replicate its sequence over and over again. Therefore, a linear copy of the circular template is achieved. A primer can then be annealed to this linear copy and its complementary chain can be synthesized (Lizardi et al., Nature Genetics, vol. 19, 225-232 (1998), the contents of which are incorporated herein by reference in their entirety). A single stranded circular DNA can also serve as a template for RNA synthesis in the presence of an RNA polymerase (Daubendiek et al., JACS, vol. 117, 7818-7819 (1995), the contents of which are incorporated herein by reference in their entirety). An inverse rapid amplification of cDNA ends (RACE) RCA is described by Polidoros et al. (BioTechniques, vol. 41, 35-42 (2006), the contents of which are incorporated herein by reference in their entirety). A messenger RNA (mRNA) is reverse transcribed into cDNA, followed by RNAse H treatment to separate the cDNA. The cDNA is then circularized by CircLigase into a circular DNA. The amplification of the resulting circular DNA is achieved with RCA.

Any of the foregoing methods may be utilized in the manufacture of one or more regions of the polynucleotides of the present invention (e.g., antigen-encoding polynucleotides featured in the NAVs of the invention).

Assembling polynucleotides or nucleic acids (e.g., antigen-encoding polynucleotides or nucleic acids) by a ligase is also widely used. DNA or RNA ligases promote intermolecular ligation of the 5′ and 3′ ends of polynucleotide chains through the formation of a phosphodiester bond. Ligase chain reaction (LCR) is a promising diagnosing technique based on the principle that two adjacent polynucleotide probes hybridize to one strand of a target gene and couple to each other by a ligase. If a target gene is not present, or if there is a mismatch at the target gene, such as a single-nucleotide polymorphism (SNP), the probes cannot ligase (Wiedmann et al., PCR Methods and Application, vol. 3 (4), s51-s64 (1994), the contents of which are incorporated herein by reference in their entirety). LCR may be combined with various amplification techniques to increase sensitivity of detection or to increase the amount of products if it is used in synthesizing polynucleotides and nucleic acids.

Several library preparation kits for nucleic acids are now commercially available. They include enzymes and buffers to convert a small amount of nucleic acid samples into an indexed library for downstream applications. For example, DNA fragments may be placed in a NEBNEXT® ULTRA™ DNA Library Prep Kit by NEWENGLAND BIOLABS® for end preparation, ligation, size selection, clean-up, PCR amplification and final clean-up.

Continued development is going on to improvement the amplification techniques. For example, U.S. Pat. No. 8,367,328 to Asada et al. the contents of which are incorporated herein by reference in their entirety, teaches utilizing a reaction enhancer to increase the efficiency of DNA synthesis reactions by DNA polymerases. The reaction enhancer comprises an acidic substance or cationic complexes of an acidic substance. U.S. Pat. No. 7,384,739 to Kitabayashi et al. the contents of which are incorporated herein by reference in their entirety, teaches a carboxylate ion-supplying substance that promotes enzymatic DNA synthesis, wherein the carboxylate ioin-supplying substance is selected from oxalic acid, malonic acid, esters of oxalic acid, esters of malonic acid, salts of malonic acid, and esters of maleic acid. U.S. Pat. No. 7,378,262 to Sobek et al. the contents of which are incorporated herein by reference in their entirety, discloses an enzyme composition to increase fidelity of DNA amplifications. The composition comprises one enzyme with 3′ exonuclease activity but no polymerase activity and another enzyme that is a polymerase. Both of the enzymes are thermostable and are reversibly modified to be inactive at lower temperatures.

U.S. Pat. No. 7,550,264 to Getts et al. teaches multiple round of synthesis of sense RNA molecules are performed by attaching oligodeoxynucleotides tails onto the 3′ end of cDNA molecules and initiating RNA transcription using RNA polymerase, the contents of which are incorporated herein by reference in their entirety. US Pat. Publication No. 2013/0183718 to Rohayem teaches RNA synthesis by RNA-dependent RNA polymerases (RdRp) displaying an RNA polymerase activity on single-stranded DNA templates, the contents of which are incorporated herein by reference in their entirety. Oligonucleotides with non-standard nucleotides may be synthesized with enzymatic polymerization by contacting a template compring non-standard nucleotides with a mixture of nucleotides that are complementary to the nucleotides of the template as disclosed in U.S. Pat. No. 6,617,106 to Benner, the contents of which are incorporated herein by reference in their entirety.

Synthesis: Solid-Phase Chemical Synthesis

Chimeric polynucleotides or circular polynucleotides of the present invention (e.g., antigen-encoding polynucleotides featured in the NAVs of the invention) may be manufactured in whole or in part using solid phase techniques.

Solid-phase chemical synthesis of polynucleotides or nucleic acids is an automated method wherein molecules are immobilized on a solid support and synthesized step by step in a reactant solution. Impurities and excess reagents are washed away and no purification is required after each step. The automation of the process is amenable on a computer-controlled solid-phase synthesizer. Solid-phase synthesis allows rapid production of polynucleotides or nucleic acids in a relatively large scale that leads to the commercial availability of some polynucleotides or nucleic acids. Furthermore, it is useful in site-specific introduction of chemical modifications in the polynucleotide or nucleic acid sequences. It is an indispensable tool in designing modified derivatives of natural nucleic acids.

In automated solid-phase synthesis, the chain is synthesized in 3′ to 5′ direction. The hydroxyl group in the 3′ end of a nucleoside is tethered to a solid support via a chemically cleavable or light-cleavable linker. Activated nucleoside monomers, such as 2′-deoxynucleosides (dA, dC, dG and T), ribonucleosides (A, C, G, and U), or chemically modified nucleosides, are added to the support-bound nucleoside sequentially. Currently most widely utilized monomers are the 3′-phophoramidite derivatives of nucleoside building blocks. The 3′ phosphorus atom of the activated monomer couples with the 5′ oxygen atom of the support-bound nucleoside to form a phosphite triester. To prevent side reactions, all functional groups not involved in the coupling reaction, such as the 5′ hydroxyl group, the hydroxyl group on the 3′ phosphorus atom, the 2′ hydroxyl group in ribonucleosides monomers, and the amino groups on the purine or pyrimidine bases, are all blocked with protection groups. The next step involves oxidation of the phosphite triester to form a phosphate triester or phosphotriester, where the phosphorus atom is pentavalent. The protection group on the 5′ hydroxyl group at the end of the growing chain is then removed, ready to couple with an incoming activated monomer building block. At the end of the synthesis, a cleaving agent such as ammonia or ammonium hydroxide is added to remove all the protecting groups and release the polynucleotide chains from the solid support. Light may also be applied to cleave the polynucleotide chain. The product can then be further purified with high pressure liquid chromatography (HPLC) or electrophoresis.

In solid-phase synthesis, the polynucleotide chain is covalently bound to the solid support via its 3′ hydroxyl group. The solid supports are insoluble particles also called resins, typically 50-200 μm in diameter. Many different kinds of resins are now available, as reviewed in “Solid-phase supports for polynucleotide synthesis” by Guzaev (Guzaev, Current Protocols in Nucleic Acid Chemistry, 3.1.1-3.1.60 (2013), the contents of which are incorporated herein by reference in their entirety). The most common materials for the resins include highly cross-linked polystyrene beads and controlled pore glass (CPG) beads. The surface of the beads may be treated to have functional groups, such as amino or aminomethyl groups that can be used as anchoring points for linkers to tether nucleosides. They can be implemented in columns, multi-well plates, microarrays or microchips. The column-based format allows relatively large scale synthesis of the polynucleotides or nucleic acids. The resins are held between filters in columns that enable all reagents and solvents to pass through freely. Multi-well plates, microarrays, or microchips are designed specifically for cost-effective small scale synthesis. Up to a million polynucleotides can be produced on a single microarray chip. However, the error rates of microchip-based synthesis are higher than traditional column-based methods (Borovkov et al., Nucleic Acids Research, vol. 38(19), e180 (2010), the contents of which are incorporated herein by reference in their entirety). Multi-well plates allow parallel synthesis of polynucleotides or nucleic acids with different sequences simultaneously (Sindelar, et al., Nucleic Acids Research, vol. 23, 982-987 (1995), the contents of which are incorporated herein by reference in their entirety). The loading on the solid supports is limited. In addition, as the extension progresses, the morphology and bulkiness of the growing chains on the solid supports might hinder the incoming monomers from reacting with the terminal group of the growing chains. Therefore, the number of monomers that can be added to the growing chain is also limited.

Linkers are attached to the solid support for further extension of the chain. They are stable to all the reagents used in the synthesis process, except in the end of the synthesis when the chain is detached from the solid support. Solid supports with a specific nucleoside linker, i.e., A, C, dT, G, or U, can be used to prepare polynucleotides with A, C, T, G, or U as the first nucleotide in the sequence, respectively. Universal solid supports with non-nucleoside linkers can be used for all polynucleotide sequences (U.S. Pat. No. 6,653,468 to Guzaev et al., the contents of which are incorporated herein by reference in their entirety). Various non-nucleoside linkers have been developed for universal supports, a lot of them with two vicinal hydroxyl groups. For example, a succinyl group is a frequently used linker.

As used herein, a linker refers to a group of atoms, e.g., 10-1,000 atoms, and can be comprised of the atoms or groups such as, but not limited to, carbon, amino, alkylamino, oxygen, sulfur, sulfoxide, sulfonyl, carbonyl, and imine. The linker can be attached to a modified nucleoside or nucleotide on the nucleobase or sugar moiety. A linker may be nucleic acid based or non-nucleosidic. The linker may be of sufficient length as to not interfere with incorporation into a nucleic acid sequence. The linker can be used for any useful purpose, such as to form multimers (e.g., through linkage of two or more chimeric polynucleotides molecules) or conjugates, as well as to administer a therapeutic molecule or incorporate a label, as described herein. Examples of chemical groups that can be incorporated into the linker include, but are not limited to, alkyl, alkenyl, alkynyl, amido, amino, ether, thioether, ester, alkylene, heteroalkylene, aryl, or heterocyclyl, each of which can be optionally substituted, as described herein. Examples of linkers include, but are not limited to, unsaturated alkanes, polyethylene glycols (e.g., ethylene or propylene glycol monomeric units, e.g., diethylene glycol, dipropylene glycol, triethylene glycol, tripropylene glycol, tetraethylene glycol, or tetraethylene glycol), and dextran polymers and derivatives thereof. Other examples include, but are not limited to, cleavable moieties within the linker, such as, for example, a disulfide bond (—S—S—) or an azo bond (—N═N—), which can be cleaved using a reducing agent or photolysis. Non-limiting examples of a selectively cleavable bond include an amido bond can be cleaved for example by the use of tris(2-carboxyethyl)phosphine (TCEP), or other reducing agents, and/or photolysis, as well as an ester bond can be cleaved for example by acidic or basic hydrolysis.)

Besides the functional groups on the activated monomer and the growing chain needed for the coupling reaction to extend the chain, all other functional groups need to be protected to avoid side reactions. The conditions for protection and deprotection, and the selection of appropriate protecting groups can be readily determined by one skilled in the art. The chemistry of protecting groups can be found and/or described, for example, in Greene, et al. (Protective Groups in Organic Synthesis, 2d. Ed., Wiley & Sons, 1991, the contents of which is incorporated herein by reference in its entirety.) For example, the 5′ hydroxyl group on the activated nucleoside phosphoramidite monomers may be protected with 4,4′-dimethoxytrityl (DMT) and the hydroxyl group on the phosphorus atom may be protected with 2-cyanoethyl. The exocyclic amino groups on the A, C, G bases may be protected with acyl groups.

In a solid-phase synthesis system, the reactivity of the activated monomers is important, because of the heterogeneity of the media. A majority of solid-phase synthesis uses phosphoramidite nucleosides, the mechanism of which is discussed above. Another activated monomer example is nucleoside H-phosphonates (Abramova, Molecules, vol. 18, 1063-1075 (2013), the contents of which are incorporated herein by reference in their entirety). A large excess of reagents, such as monomers, oxidizing agents, and deprotection agents, is required in order to ensure high yields in the solid-phase synthesis system.

Scientific studies and research are going on to further improve the solid-phase synthesis method. For example, instead of the well-established 3′-to-5′ synthesis, U.S. Pat. No. 8,309,707 and US Pat. Publication No. 2013/0072670 to Srivastava et al. disclosed a 5′-to-3′ synthesis of RNA utilizing a novel phosphoramidite and a novel nucleoside derivative, thereby allowing easy modifications of the synthetic RNA at the 3′ end. PCT application WO2013123125 to Church et al. the contents of which are incorporated herein by reference in their entirety, describes assembly of a target nucleic acid sequence from a plurality of subsequences, wherein resins with the subsequences are placed in an emulsion droplet. The subsequences are cleaved off the resins and assemble within the emulsion droplet. To reduce the cost of solid supports, a reusable CPG solid support has been developed with a hydroquinone-O, O′-diacetic acid linker (Q-linker) (Pon et al., Nucleic Acid Research, vol. 27, 1531-1538 (1999), the contents of which are incorporated herein by reference in their entirety).

New protecting groups for solid-phase synthesis have also been developed. Nagat et al. has successfully synthesized 110-nt-long RNA with the sequence of a candidate precursor microRNA by using 2-cyanoethoxymethyl (CEM) as the 2′-hydroxy protecting group (Shiba et al., Nucleic Acids Research, vol. 35, 3287-3296 (2007), the contents of which are incorporated herein by reference in their entirety). Also with CEM as 2′-O-protecting group, a 130-nt mRNA has been synthesized encoding a 33-amino acid peptide that includes the sequence of glucagon-like peptide-1 (GLP-1). The biological activity of the artificial 130-nt mRNA is shown by producing GLP-1 in a cell-free protein synthesis system and in Chinese hamster ovary (CHO) cells (Nagata et al., Nucleic Acids Research, vol. 38(21), 7845-7857 (2010), the contents of which are incorporated herein by reference in their entirety). Novel protecting groups for solid-phase synthesis monomers include, but are not limited to, carbonate protecting group disclosed in U.S. Pat. No. 8,309,706 to Dellinger et al., orthoester-type 2′ hydroxyl protecting group and an acyl carbonate-type hydroxyl protecting group disclosed in U.S. Pat. No. 8,242,258 to Dellinger et al., 2′-hydroxyl thiocarbon protecting group disclosed in U.S. Pat. No. 8,202,983 to Dellinger et al., 2′-silyl containing thiocarbonate protecting group disclosed in U.S. Pat. No. 7,999,087 to Dellinger et al., 9-fluorenylmethoxycarbonyl (FMOS) derivatives as an amino protecting group disclosed in U.S. Pat. No. 7,667,033 to Alvarado, fluoride-labile 5′silyl protecting group disclosed in U.S. Pat. No. 5,889,136 to Scaringe et al., and pixyl protecting groups disclosed in US Pat. Publication No. 2008/0119645 to Griffey et al., the contents of which are incorporated herein by reference in their entirety. US Pat. Publication No. 2011/0275793 to Debart et al. teaches RNA synthesis using a protecting group of the hyoxyls in position 2′ of the ribose that can be removed by a base, the contents of which are incorporated herein by reference in their entirety. Novel solid supports include polymers made from monomers comprising protected hydroxypolyC24 alkyleneoxy chain attached to a polymerizable unit taught in U.S. Pat. No. 7,476,709 to Moody et al., the contents of which are incorporated herein by reference in their entirety.

Synthesis: Liquid Phase Chemical Synthesis

The synthesis of chimeric polynucleotides or circular polynucleotides of the present invention (e.g., antigen-encoding polynucleotides featured in the NAVs of the invention) by the sequential addition of monomer building blocks may be carried out in a liquid phase. A covalent bond is formed between the monomers or between a terminal functional group of the growing chain and an incoming monomer. Functional groups not involved in the reaction must be temporarily protected. After the addition of each monomer building block, the reaction mixture has to be purified before adding the next monomer building block. The functional group at one terminal of the chain has to be deprotected to be able to react with the next monomer building blocks. A liquid phase synthesis is labor- and time-consuming and cannot not be automated. Despite the limitations, liquid phase synthesis is still useful in preparing short polynucleotides in a large scale. Because the system is homogenous, it does not require a large excess of reagents and is cost-effective in this respect.

Synthesis: Combination of Synthetic Methods

The synthetic methods discussed above each has its own advantages and limitations. Attempts have been conducted to combine these methods to overcome the limitations. Such combinations of methods are within the scope of the present invention.

Short polynucleotide chains with 2-4 nucleotides may be prepared in liquid phase followed by binding to a solid support for extension reactions by solid phase synthesis. A high efficiency liquid phase (HELP) synthesis is developed that uses monomethyl ether of polyethylene glycol (MPEG) beads as a support for the monomer building blocks. MPEG is soluble in methylene chloride and pyridine solvents but precipitates in a diethyl ether solvent. By choosing an appropriate solvent, the coupling reaction between monomers or between a growing chain and an incoming monomer bound on MPEG can be carried out in a homogenous liquid phase system. The mixture can then be washed with a diethyl ether solvent to easily precipitate and purify the product (Bonora et al., Nucleic Acids Research, vol. 18, 3155-3159 (1990), the contents of which are incorporated herein by reference in their entirety). U.S. Pat. No. 8,304,532 to Adamo et al., the contents of which are incorporated herein in their entirety, teaches a solution phase oligonucleotide synthesis where at least some of the reagents are solid supported.

The use of solid-phase or liquid-phase chemical synthesis in combination with enzymatic ligation provides an efficient way to generate long chain polynucleotides that cannot be obtained by chemical synthesis alone. Moore and Sharp describe preparing RNA fragments 10- to 20-nt long by chemical synthesis, to which site-specific modifications may be introduced, annealing the fragments to a cDNA bridge, and then assemble the fragments with T4 DNA ligase (Moore et al., Science, vol. 256, 992-997 (1992), the contents of which are incorporated herein by reference in their entirety).

A solid-phase synthesizer may produce enough polynucleotides or nucleic acids with good purity to preform PCR and other amplification techniques. Agilent Technologies have developed microarrays that are commercially available. Polynucleotides may be synthesized on a microarray substrate, cleaved by a strong base or light, followed by PCR amplification to generate a library of polynucleotides (Cleary et al., Nature Methods, vol. 1(3), 241-247 (2004), the contents of which are incorporated herein by reference in their entirety).

Synthesis: Small Region Synthesis

Regions or subregions of the polynucleotides of the present invention (e.g., antigen-encoding polynucleotides featured in the NAVs of the invention) may comprise small RNA molecules such as siRNA, and therefore may be synthesized in the same manner. There are several methods for preparing siRNA, such as chemical synthesis using appropriately protected ribonucleoside phosphoramidites, in vitro transcription, siRNA expression vectors, and PCR expression cassettes. Sigma-Aldrich® is one of the siRNA suppliers and synthesizes their siRNA using ribonucleoside phosphoramidite monomers protected at the 2′ position with a t-butylmethylsilyl (TBDMS) group. The solid-phase chemical synthesis is carried out with SIGMA-ALDRICH®'s Ultra Fast Parallel Synthesis (UFPS) and Ultra Fast Parallel Deprotection (UFPD) to achieve high coupling efficiency and fast deprotection. The final siRNA products may be purified with HPLC or PAGE. Such methods may be used to synthesize regions or subregions of chimeric polynucleotides.

In vitro transcription and expression from a vector or a PCR-generated siRNA cassette require appropriate templates to produce siRNAs. The commercially available AMBION® SILENCER® siRNA construction kit produces siRNA by in vitro transcription of DNA templates and contains the enzymes, buffers, primers needed. Such methods may be used to synthesize regions or subregions of chimeric polynucleotides.

Synthesis: Ligation of Polynucleotide Regions or Subregions

Polynucleotides of the invention (e.g., antigen-encoding polynucleotides featured in the NAVs of the invention) such as chimeric polynucleotides and/or circular polynucleotides may be prepared by ligation of one or more regions or subregions.

Ligation is an indispensable tool for assembling polynucleotide or nucleic acid fragments into larger constructs. DNA fragments can be joined by a ligase catalyzed reaction to create recombinant DNA with different functions. Two oligodeoxynucleotides, one with a 5′ phosphoryl group and another with a free 3′ hydroxyl group, serve as substrates for a DNA ligase. Oligodexoynucleotides with fluorescent or chemiluminescent labels may also serve as DNA ligase substrates (Martinelli et al., Clinical Chemistry, vol. 42, 14-18 (1996), the contents of which are incorporated herein by reference in their entirety). RNA ligases such as T4 RNA ligase catalyze the formation of a phosphodiester bond between two single stranded oligoribonucleotides or RNA fragments. Copies of large DNA constructs have been synthesized with a combination of polynucleotide fragments, thermostable DNA polymerases, and DNA ligases. US Pat. Publication No. 2009/0170090 to Ignatov et al., the contents of which are incorporated herein by reference in their entirety, discloses improving PCT, especially enhancing yield of a long distance PCR and/or a low copy DNA template PCR amplication, by using a DNA ligase in addition to a DNA polymerase.

Ligases may be used with other enzymes to prepare desired chimeric polynucleotide or nucleic acid molecules and to perform genome analysis. For example, ligation-mediated selective PCR amplification is disclosed in EP Pat. Pub. No. 0735144 to Kato. Complementary DNAs (cDNAs) reverse-transcribed from tissue- or cell-derived RNA or DNA are digested into fragments with type IIS restriction enzymes the contents of which are incorporated herein by reference in their entirety. Biotinylated adapter sequences are attached to the fragments by E. coli DNA ligases. The biotin-labeled DNA fragments are then immobilized onto streptavidin-coated beads for downstream analysis.

A ligation splint or a ligation splint oligo is an oligonucleotide that is used to provide an annealing site or a ligation template for joining two ends of one nucleic acid, i.e., intramolecular joining, or two ends of two nucleic acids, i.e., intermolecular joining, using a ligase or another enzyme with ligase activity. The ligation splint holds the ends adjacent to each other and creates a ligation junction between the 5′-phosphorylated and a 3′-hydroxylated ends that are to be ligated.

In one embodiment, a splint-mediated ligation or splint ligation method may be used to synthesize the chimeric polynucleotides described herein. The chimeric polynucleotide may be assembled using a method that does not rely on the presence of restriction endonuclease cleavage sites such as the method described in international Patent Publication No. WO2012138453, the contents of which are herein incorporated by reference in its entirety. Splint-mediated ligation allows for the rapid synthesis of the construct using controlled concatenation and without the need or with limited need for the introduction of restriction sites at the joining regions. As a non-limiting example, splint ligation may be used to add at least one untranslated region to a coding region of the chimeric polynucleotide. In one embodiment, splint ligation may be used in combination with other synthesis methods in the synthesis of the chimeric polynucleotides described herein.

If the 5′-phosphorylated and the 3′-hydroxyl ends of nucleic acids are ligated when the ends are annealed to a ligation splint so that the ends are adjacent, enzymes such as, but not limited to, T4 DNA ligase, AMPLIGASE® DNA Ligase (EPICENTRE® Technologies), Tth DNA ligase, TJ7 DNA ligase, or Tsc DNA Ligase (Prokaria) can be used. Farugui IN U.S. Pat. No. 6,368,801 (the contents of which is incorporated by reference in its entirety) describes that T4 RNA ligase can efficiently ligate ends of DNA molecules that are adjacent to each other when hybridized to an RNA splint. Thus, T4 RNA ligase is a suitable ligase for joining DNA ends with a ligation splint oligo comprising RNA or modified RNA. Examples of RNA splints include modified RNA containing 2′-fluorine-CTP (2′-F-dCTP) and 2′-fluorine-UTP (2′-F-dUTP) made using the DURASCRIBE® T7 Transcription Kit (EPICENTRE® Technologies) disclosed in U.S. Pat. No. 8,137,911 and US Pat. Publication 2012/0156679 to Dahl et al, the contents of each of which are incorporated herein by reference in their entirety. The modified RNA produced from DURASCRIBE® T7 Transcription kit is completely resistant to RNase A digestion. DNA splint and DNA ligase may be used to generate RNA-protein fusions disclosed in U.S. Pat. No. 6,258,558 to Szostak et al., the contents of which are incorporated herein by reference in their entirety.

For intramolecular ligation of linear ssDNA, U.S. Pat. No. 7,906,490 to Kool et al. teaches constructing a 83-nucleotide circle by making linear oligodeoxynucleotides fragments on a DNA synthesizer followed by ligation with T4 DNA ligase and two 30 nucleotide splint oligonucleotides. Circulation of linear sense promoter-containing cDNA is disclosed in US Pat. Publication No. 2012/0156679 to Dahl et al., the contents of which are incorporated herein by reference in their entirety. THERMOPHAGET ssDNA ligase (Prokazyme), which is derived from phage TS2126 that infects Thermus scotoductus, catalyzes ATP-dependent intra- and inter-molecular ligation of DNA and RNA.

The solid-phase chemical synthesis method that uses phosphoramidite monomers is limited to produce DNA molecules with short strands. The purity of the DNA products and the yield of reactions become poor when the length exceeds 150 bases. For the synthesis of long polynucleotides in high yields, it is more convenient to use enzymatic ligation method in tandem with chemical synthesis. For example, Moore and Sharp describe preparing RNA fragments 10- to 20-nt long by chemical synthesis, to which site-specific modifications may be introduced, annealing the fragments to a cDNAsplint, and then assemble the fragments with T4 DNA ligase (Moore et al., Science, vol. 256, 992-997 (1992), the contents of which are incorporated herein by reference in their entirety). Ligation reactions of oligoribonucleotides with T4 RNA ligase and a DNA splint or a polyribonucleotide to generate large, synthetic RNAs are described in Bain et al., Nucleic Acids Research, vol. 20(16), 4372 (1992), Stark et al., RNA, vol. 12, 2014-2019 (2006), and US Pat. Application No. 2005/0130201 to Deras et al., the contents of each of which are incorporated herein by reference in their entirety. 5′-cap and 3′-polyA tail are often added by enzymatic addition to an oligonucleotide synthesized with solid-phase methods. As a non-limiting example, a synthetic capped 42-mer mRNA has been synthesized in three fragments enzymatically ligated as described by Iwase et al. (Nucleic Acids Research, vol. 20, 1643-1648 (1992), the contents of which are incorporated herein by reference in their entirety). As another example, a 16.3-kilobase mouse mitochondrial genome has been produced from 600 overlapping 60-mer polynucleotides. The method cycles between in vitro recombination and amplification may be repeated until the desired length is reached (Gibson et al., Nature Methods, vol. 7, 901-903 (2010), the contents of which are incorporated herein by reference in their entirety). The assembly of a 1.08 megabase Mycoplasma mycoides JCVI-syn1.0 genome has also been reported. As a non-limiting example, 1080 bp cassettes are produced by assembling polynucleotide fragments chemically generated from a polynucleotide synthesizer. The genome is then assembled in three stages by transformation and homologous recombination in yeast (Gibson, et al., Science, vol. 329, 52-56 (2010), the contents of which are incorporated herein by reference in their entirety).

Studies have been conducted to join short DNA fragments with chemical linkers. ‘Click’ chemistry or ‘click’ ligation, the cycloaddition reaction between azide and alkyne, has gained a lot of interest because of its advantages such as mild reaction condition, high yields, and inoffensive byproducts. ‘Click’ chemistry is reviewed by Nwe et al. in Cancer Biotherapy and Radiopharmaceuticals, vol. 24(3), 289-302 (2009), the contents of which are incorporated here by reference for their entirety. DNA constructs up to 300 bases in length have been produced with click ligation and longer sequences are feasible. Demonstrated with PCR data, various DNA polymerases are able to amplify the synthesized DNA constructs made by click ligation despite the triazole linkers between the fragments resulting from the cycloaddition reaction. In vitro transcription and rolling circle amplification can also be performed on the synthesized DNA constructs. Hairpin ribozymes up to 100 nucleotides in length and cyclic mini-DNA duplexes have also been prepared with click ligation (EI-Sagheer et al., Accounts of Chemical Research, vol. 45(8), 1258-1267 (2012), the contents of which are incorporated herein by reference in their entirety).

Sequential ligation can be performed on a solid substrate. For example, initial linker DNA molecules modified with biotin at the end are attached to streptavidin-coated beads. The 3′-ends of the linker DNA molecules are complimentary with the 5′-ends of the incoming DNA fragments. The beads are washed and collected after each ligation step and the final linear constructs are released by a meganuclease. This method allows rapid and efficient assembly of genes in an optimized order and orientation. (Takita, DNA Research, vol. 20(4), 1-10 (2013), the contents of which are incorporated herein by reference in their entirety). Labeled polynucleotides synthesized on solid-supports are disclosed in US Pat. Pub. No. 2001/0014753 to Soloveichik et al. and US Pat. Pub. No. 2003/0191303 to Vinayak et al., the contents of which are incorporated herein by reference for their entirety.

Quantification

In one embodiment, the polynucleotides of the present invention (e.g., antigen-encoding polynucleotides featured in the NAVs of the invention) may be quantified in exosomes or when derived from one or more bodily fluid. As used herein “bodily fluids” include peripheral blood, serum, plasma, ascites, urine, cerebrospinal fluid (CSF), sputum, saliva, bone marrow, synovial fluid, aqueous humor, amniotic fluid, cerumen, breast milk, broncheoalveolar lavage fluid, semen, prostatic fluid, cowpers fluid or pre-ejaculatory fluid, sweat, fecal matter, hair, tears, cyst fluid, pleural and peritoneal fluid, pericardial fluid, lymph, chyme, chyle, bile, interstitial fluid, menses, pus, sebum, vomit, vaginal secretions, mucosal secretion, stool water, pancreatic juice, lavage fluids from sinus cavities, bronchopulmonary aspirates, blastocyl cavity fluid, and umbilical cord blood. Alternatively, exosomes may be retrieved from an organ selected from the group consisting of lung, heart, pancreas, stomach, intestine, bladder, kidney, ovary, testis, skin, colon, breast, prostate, brain, esophagus, liver, and placenta.

In the exosome quantification method, a sample of not more than 2 mL is obtained from the subject and the exosomes isolated by size exclusion chromatography, density gradient centrifugation, differential centrifugation, nanomembrane ultrafiltration, immunoabsorbent capture, affinity purification, microfluidic separation, or combinations thereof. In the analysis, the level or concentration of a polynucleotide may be an expression level, presence, absence, truncation or alteration of the administered construct. It is advantageous to correlate the level with one or more clinical phenotypes or with an assay for a human disease biomarker. The assay may be performed using construct specific probes, cytometry, qRT-PCR, real-time PCR. PCR, flow cytometry, electrophoresis, mass spectrometry, or combinations thereof while the exosomes may be isolated using immunohistochemical methods such as enzyme linked immunosorbent assay (ELISA) methods. Exosomes may also be isolated by size exclusion chromatography, density gradient centrifugation, differential centrifugation, nanomembrane ultrafiltration, immunoabsorbent capture, affinity purification, microfluidic separation, or combinations thereof.

These methods afford the investigator the ability to monitor, in real time, the level of polynucleotides remaining or delivered. This is possible because the polynucleotides of the present invention differ from the endogenous forms due to the structural or chemical modifications.

In one embodiment, the polynucleotide may be quantified using methods such as, but not limited to, ultraviolet visible spectroscopy (UV/Vis). A non-limiting example of a UV/Vis spectrometer is a NANODROP® spectrometer (ThermoFisher, Waltham, MA). The quantified polynucleotide may be analyzed in order to determine if the polynucleotide may be of proper size, check that no degradation of the polynucleotide has occurred. Degradation of the polynucleotide may be checked by methods such as, but not limited to, agarose gel electrophoresis, HPLC based purification methods such as, but not limited to, strong anion exchange HPLC, weak anion exchange HPLC, reverse phase HPLC (RP-HPLC), and hydrophobic interaction HPLC (HIC-HPLC), liquid chromatography-mass spectrometry (LCMS), capillary electrophoresis (CE) and capillary gel electrophoresis (CGE).

Purification

Purification of the polynucleotides of the invention (e.g., antigen-encoding polynucleotides featured in the NAVs of the invention) described herein may include, but is not limited to, polynucleotide clean-up, quality assurance and quality control. Clean-up may be performed by methods known in the arts such as, but not limited to, AGENCOURT® beads (Beckman Coulter Genomics, Danvers, MA), poly-T beads. LNA™ oligo-T capture probes (EXIQON® Inc, Vedbaek, Denmark) or HPLC based purification methods such as, but not limited to, strong anion exchange HPLC, weak anion exchange HPLC, reverse phase HPLC (RP-HPLC), and hydrophobic interaction HPLC (HIC-HPLC). The term “purified” when used in relation to a polynucleotide such as a “purified polynucleotide” refers to one that is separated from at least one contaminant. As used herein, a “contaminant” is any substance which makes another unfit, impure or inferior. Thus, a purified polynucleotide (e.g., DNA and RNA) is present in a form or setting different from that in which it is found in nature, or a form or setting different from that which existed prior to subjecting it to a treatment or purification method.

A quality assurance and/or quality control check may be conducted using methods such as, but not limited to, gel electrophoresis. UV absorbance, or analytical HPLC.

In another embodiment, the polynucleotides may be sequenced by methods including, but not limited to reverse-transcriptase-PCR.

IV. Modifications

In exemplary embodiments, polynucleotides of the invention (e.g., antigen-encoding polynucleotides featured in the NAVs of the invention) can include various substitutions and/or insertions.

The data presented in the Examples demonstrate significant enhanced immune responses using the formulations of the invention. The data demonstrated the effectiveness of both chemically modified and unmodified RNA vaccines of the invention. Surprisingly, in contrast to prior art reports that it was preferable to use chemically unmodified mRNA formulated in a carrier for the production of vaccines, it was discovered herein that chemically modified mRNA-LNP vaccines required a much lower effective mRNA dose than unmodified mRNA, i.e., tenfold less than unmodified mRNA.

Additionally, a study described herein involved intravenous (IV), intramuscular (IM), or intradermal (ID) vaccination of mice, followed by challenge with a lethal dose of virus. In addition to all of the vaccinated animals surviving the lethal dose, significantly stronger early immune responses were observed (anti-viral activity via virus neutralization assay and HA inhibition (HAI)) in comparison to protein antigen and other lipid based formulations (lipoplex). The data demonstrated that as early as 1 week after vaccination both groups of animals receiving a chemically modified mRNA-LNP formulation (ID or IM) displayed HAI titers over 40, at 60 and 114, respectively. An HAI titer of greater than 40 is deemed sufficient to protect from a lethal challenge of influenza. The rapid response was unexpected, particularly when compared to the response seen with protein antigen and mRNA vaccines formulated in other lipid carriers (lipoplex), which at one week and even at three weeks following vaccination continued to show ineffective HAI titers of less than 40.

Both the chemically modified and unmodified RNA vaccines of the invention produced better immune responses than did mRNA vaccines formulated in a different lipid carrier (lipoplex). At week 5 the non-chemically modified mRNA—lipoplex vaccine produced HAI titers of 197, in comparison to those achieved by the mRNA-LNP formulations of the invention (HAI titers of 635-10,152). At all other time points and for all of the chemically modified mRNA-lipoplex vaccines, none of the HAI titers reached the critical level of greater than 40. Additionally, the mRNA—lipoplex vaccine did not result in any detectable neutralizing activity in the microneutralization activity, even as late as five weeks after vaccination.

As used herein in a polynucleotide (such as a chimeric polynucleotide, IVT polynucleotide or a circular polynucleotide), the terms “chemical modification” or, as appropriate, “chemically modified” refer to modification with respect to adenosine (A), guanosine (G), uridine (U), thymidine (T) or cytidine (C) ribo- or deoxyribnucleosides in one or more of their position, pattern, percent or population. Generally, herein, these terms are not intended to refer to the ribonucleotide modifications in naturally occurring 5′-terminal mRNA cap moieties.

In a polypeptide, the term “modification” refers to a modification as compared to the canonical set of 20 amino acids.

The modifications may be various distinct modifications. In some embodiments, the regions may contain one, two, or more (optionally different) nucleoside or nucleotide modifications. In some embodiments, a modified polynucleotide, introduced to a cell may exhibit reduced degradation in the cell, as compared to an unmodified polynucleotide.

Modifications of the polynucleotides of the NAVs which are useful in the present invention include, but are not limited to those in Table 22. Noted in the table are the symbol of the modification, the nucleobase type and whether the modification is naturally occurring or not.

TABLE 22

Modifications

Naturally

Name
Symbol
Base
Occurring

2-methylthio-N6-(cis-
ms2i6A
A
YES

hydroxyisopentenyl)adenosine

2-methylthio-N6-methyladenosine
ms2m6A
A
YES

2-methylthio-N6-threonyl
ms2t6A
A
YES

carbamoyladenosine

N6-glycinylcarbamoyladenosine
g6A
A
YES

N6-isopentenyladenosine
i6A
A
YES

N6-methyladenosine
m6A
A
YES

N6-threonylcarbamoyladenosine
t6A
A
YES

1,2′-O-dimethyladenosine
m1Am
A
YES

1-methyladenosine
m1A
A
YES

2′-O-methyladenosine
Am
A
YES

2′-O-ribosyladenosine (phosphate)
Ar(p)
A
YES

2-methyladenosine
m2A
A
YES

2-methylthio-N6 isopentenyladenosine
ms2i6A
A
YES

2-methylthio-N6-hydroxynorvalyl
ms2hn6A
A
YES

carbamoyladenosine

2′-O-methyladenosine
m6A
A
YES

2′-O-ribosyladenosine (phosphate)
Ar(p)
A
YES

Isopentenyladenosine
Iga
A
YES

N6-(cis-hydroxyisopentenyl)adenosine
io6A
A
YES

N6,2′-O-dimethyladenosine
m6Am
A
YES

N⁶,2′-O-dimethyladenosine
m⁶Am
A
YES

N6,N6,2′-O-trimethyladenosine
m62Am
A
YES

N6,N6-dimethyladenosine
m62A
A
YES

N6-acetyladenosine
ac6A
A
YES

N6-hydroxynorvalylcarbamoyladenosine
hn6A
A
YES

N6-methyl-N6-
m6t6A
A
YES

threonylcarbamoyladenosine

2-methyladenosine
m²A
A
YES

2-methylthio-N⁶-isopentenyladenosine
ms²i⁶A
A
YES

7-deaza-adenosine
—
A
NO

N1-methyl-adenosine
—
A
NO

N6,N6 (dimethyl)adenine
—
A
NO

N6-cis-hydroxy-isopentenyl-adenosine
—
A
NO

α-thio-adenosine
—
A
NO

2 (amino)adenine
—
A
NO

2 (aminopropyl)adenine
—
A
NO

2 (methylthio) N6 (isopentenyl)adenine
—
A
NO

2-(alkyl)adenine
—
A
NO

2-(aminoalkyl)adenine
—
A
NO

2-(aminopropyl)adenine
—
A
NO

2-(halo)adenine
—
A
NO

2-(halo)adenine
—
A
NO

2-(propyl)adenine
—
A
NO

2′-Amino-2′-deoxy-ATP
—
A
NO

2′-Azido-2′-deoxy-ATP
—
A
NO

2′-Deoxy-2′-a-aminoadenosine TP
—
A
NO

2′-Deoxy-2′-a-azidoadenosine TP
—
A
NO

6 (alkyl)adenine
—
A
NO

6 (methyl)adenine
—
A
NO

6-(alkyl)adenine
—
A
NO

6-(methyl)adenine
—
A
NO

7 (deaza)adenine
—
A
NO

8 (alkenyl)adenine
—
A
NO

8 (alkynyl)adenine
—
A
NO

8 (amino)adenine
—
A
NO

8 (thioalkyl)adenine
—
A
NO

8-(alkenyl)adenine
—
A
NO

8-(alkyl)adenine
—
A
NO

8-(alkynyl)adenine
—
A
NO

8-(amino)adenine
—
A
NO

8-(halo)adenine
—
A
NO

8-(hydroxyl)adenine
—
A
NO

8-(thioalkyl)adenine
—
A
NO

8-(thiol)adenine
—
A
NO

8-azido-adenosine
—
A
NO

aza adenine
—
A
NO

deaza adenine
—
A
NO

N6 (methyl)adenine
—
A
NO

N6-(isopentyl)adenine
—
A
NO

7-deaza-8-aza-adenosine
—
A
NO

7-methyladenine
—
A
NO

1-Deazaadenosine TP
—
A
NO

2′Fluoro-N6-Bz-deoxyadenosine TP
—
A
NO

2′-OMe-2-Amino-ATP
—
A
NO

2′O-methyl-N6-Bz-deoxyadenosine TP
—
A
NO

2′-a-Ethynyladenosine TP
—
A
NO

2-aminoadenine
—
A
NO

2-Aminoadenosine TP
—
A
NO

2-Amino-ATP
—
A
NO

2′-a-Trifluoromethyladenosine TP
—
A
NO

2-Azidoadenosine TP
—
A
NO

2′-b-Ethynyladenosine TP
—
A
NO

2-Bromoadenosine TP
—
A
NO

2′-b-Trifluoromethyladenosine TP
—
A
NO

2-Chloroadenosine TP
—
A
NO

2′-Deoxy-2′,2′-difluoroadenosine TP
—
A
NO

2′-Deoxy-2′-a-mercaptoadenosine TP
—
A
NO

2′-Deoxy-2′-a-thiomethoxyadenosine TP
—
A
NO

2′-Deoxy-2′-b-aminoadenosine TP
—
A
NO

2′-Deoxy-2′-b-azidoadenosine TP
—
A
NO

2′-Deoxy-2′-b-bromoadenosine TP
—
A
NO

2′-Deoxy-2′-b-chloroadenosine TP
—
A
NO

2′-Deoxy-2′-b-fluoroadenosine TP
—
A
NO

2′-Deoxy-2′-b-iodoadenosine TP
—
A
NO

2′-Deoxy-2′-b-mercaptoadenosine TP
—
A
NO

2′-Deoxy-2′-b-thiomethoxyadenosine TP
—
A
NO

2-Fluoroadenosine TP
—
A
NO

2-Iodoadenosine TP
—
A
NO

2-Mercaptoadenosine TP
—
A
NO

2-methoxy-adenine
—
A
NO

2-methylthio-adenine
—
A
NO

2-Trifluoromethyladenosine TP
—
A
NO

3-Deaza-3-bromoadenosine TP
—
A
NO

3-Deaza-3-chloroadenosine TP
—
A
NO

3-Deaza-3-fluoroadenosine TP
—
A
NO

3-Deaza-3-iodoadenosine TP
—
A
NO

3-Deazaadenosine TP
—
A
NO

4′-Azidoadenosine TP
—
A
NO

4′-Carbocyclic adenosine TP
—
A
NO

4′-Ethynyladenosine TP
—
A
NO

5′-Homo-adenosine TP
—
A
NO

8-Aza-ATP
—
A
NO

8-bromo-adenosine TP
—
A
NO

8-Trifluoromethyladenosine TP
—
A
NO

9-Deazaadenosine TP
—
A
NO

2-aminopurine
—
A/G
NO

7-deaza-2,6-diaminopurine
—
A/G
NO

7-deaza-8-aza-2,6-diaminopurine
—
A/G
NO

7-deaza-8-aza-2-aminopurine
—
A/G
NO

2,6-diaminopurine
—
A/G
NO

7-deaza-8-aza-adenine, 7-deaza-2-
—
A/G
NO

aminopurine

2-thiocytidine
s2C
C
YES

3-methylcytidine
m3C
C
YES

5-formylcytidine
f5C
C
YES

5-hydroxymethylcytidine
hm5C
C
YES

5-methylcytidine
m5C
C
YES

N4-acetylcytidine
ac4C
C
YES

2′-O-methylcytidine
Cm
C
YES

2′-O-methylcytidine
Cm
C
YES

5,2′-O-dimethylcytidine
m5 Cm
C
YES

5-formyl-2′-O-methylcytidine
f5Cm
C
YES

Lysidine
k2C
C
YES

N4,2′-O-dimethylcytidine
m4Cm
C
YES

N4-acetyl-2′-O-methylcytidine
ac4Cm
C
YES

N4-methylcytidine
m4C
C
YES

N4,N4-Dimethyl-2′-O-OMe-Cytidine TP
—
C
YES

4-methylcytidine
—
C
NO

5-aza-cytidine
—
C
NO

Pseudo-iso-cytidine
—
C
NO

pyrrolo-cytidine
—
C
NO

α-thio-cytidine
—
C
NO

2-(thio)cytosine
—
C
NO

2′-Amino-2′-deoxy-CTP
—
C
NO

2′-Azido-2′-deoxy-CTP
—
C
NO

2′-Deoxy-2′-a-aminocytidine TP
—
C
NO

2′-Deoxy-2′-a-azidocytidine TP
—
C
NO

3 (deaza) 5 (aza)cytosine
—
C
NO

3 (methyl)cytosine
—
C
NO

3-(alkyl)cytosine
—
C
NO

3-(deaza) 5 (aza)cytosine
—
C
NO

3-(methyl)cytidine
—
C
NO

4,2′-O-dimethylcytidine
—
C
NO

5 (halo)cytosine
—
C
NO

5 (methyl)cytosine
—
C
NO

5 (propynyl)cytosine
—
C
NO

5 (trifluoromethyl)cytosine
—
C
NO

5-(alkyl)cytosine
—
C
NO

5-(alkynyl)cytosine
—
C
NO

5-(halo)cytosine
—
C
NO

5-(propynyl)cytosine
—
C
NO

5-(trifluoromethyl)cytosine
—
C
NO

5-bromo-cytidine
—
C
NO

5-iodo-cytidine
—
C
NO

5-propynyl cytosine
—
C
NO

6-(azo)cytosine
—
C
NO

6-aza-cytidine
—
C
NO

aza cytosine
—
C
NO

deaza cytosine
—
C
NO

N4 (acetyl)cytosine
—
C
NO

1-methyl-1-deaza-pseudoisocytidine
—
C
NO

1-methyl-pseudoisocytidine
—
C
NO

2-methoxy-5-methyl-cytidine
—
C
NO

2-methoxy-cytidine
—
C
NO

2-thio-5-methyl-cytidine
—
C
NO

4-methoxy-1-methyl-pseudoisocytidine
—
C
NO

4-methoxy-pseudoisocytidine
—
C
NO

4-thio-1-methyl-1-deaza-
—
C
NO

pseudoisocytidine

4-thio-1-methyl-pseudoisocytidine
—
C
NO

4-thio-pseudoisocytidine
—
C
NO

5-aza-zebularine
—
C
NO

5-methyl-zebularine
—
C
NO

pyrrolo-pseudoisocytidine
—
C
NO

Zebularine
—
C
NO

(E)-5-(2-Bromo-vinyl)cytidine TP
—
C
NO

2,2′-anhydro-cytidine TP hydrochloride
—
C
NO

2′Fluor-N4-Bz-cytidine TP
—
C
NO

2′Fluoro-N4-Acetyl-cytidine TP
—
C
NO

2′-O-Methyl-N4-Acetyl-cytidine TP
—
C
NO

2′O-methyl-N4-Bz-cytidine TP
—
C
NO

2′-a-Ethynylcytidine TP
—
C
NO

2′-a-Trifluoromethylcytidine TP
—
C
NO

2′-b-Ethynylcytidine TP
—
C
NO

2′-b-Trifluoromethylcytidine TP
—
C
NO

2′-Deoxy-2′,2′-difluorocytidine TP
—
C
NO

2′-Deoxy-2′-a-mercaptocytidine TP
—
C
NO

2′-Deoxy-2′-a-thiomethoxycytidine TP
—
C
NO

2′-Deoxy-2′-b-aminocytidine TP
—
C
NO

2′-Deoxy-2′-b-azidocytidine TP
—
C
NO

2′-Deoxy-2′-b-bromocytidine TP
—
C
NO

2′-Deoxy-2′-b-chlorocytidine TP
—
C
NO

2′-Deoxy-2′-b-fluorocytidine TP
—
C
NO

2′-Deoxy-2′-b-iodocytidine TP
—
C
NO

2′-Deoxy-2′-b-mercaptocytidine TP
—
C
NO

2′-Deoxy-2′-b-thiomethoxycytidine TP
—
C
NO

2′-O-Methyl-5-(1-propynyl)cytidine TP
—
C
NO

3′-Ethynylcytidine TP
—
C
NO

4′-Azidocytidine TP
—
C
NO

4′-Carbocyclic cytidine TP
—
C
NO

4′-Ethynylcytidine TP
—
C
NO

5-(1-Propynyl)ara-cytidine TP
—
C
NO

5-(2-Chloro-phenyl)-2-thiocytidine TP
—
C
NO

5-(4-Amino-phenyl)-2-thiocytidine TP
—
C
NO

5-Aminoallyl-CTP
—
C
NO

5-Cyanocytidine TP
—
C
NO

5-Ethynylara-cytidine TP
—
C
NO

5-Ethynylcytidine TP
—
C
NO

5′-Homo-cytidine TP
—
C
NO

5-Methoxycytidine TP
—
C
NO

5-Trifluoromethyl-Cytidine TP
—
C
NO

N4-Amino-cytidine TP
—
C
NO

N4-Benzoyl-cytidine TP
—
C
NO

Pseudoisocytidine
—
C
NO

7-methylguanosine
m7G
G
YES

N2,2′-O-dimethylguanosine
m2Gm
G
YES

N2-methylguanosine
m2G
G
YES

Wyosine
imG
G
YES

1,2′-O-dimethylguanosine
m1Gm
G
YES

1-methylguanosine
m1G
G
YES

2′-O-methylguanosine
Gm
G
YES

2′-O-ribosylguanosine (phosphate)
Gr(p)
G
YES

2′-O-methylguanosine
Gm
G
YES

2′-O-ribosylguanosine (phosphate)
Gr(p)
G
YES

7-aminomethyl-7-deazaguanosine
preQ1
G
YES

7-cyano-7-deazaguanosine
preQ0
G
YES

Archaeosine
G+
G
YES

Methylwyosine
mimG
G
YES

N2,7-dimethylguanosine
m2,7G
G
YES

N2,N2,2′-O-trimethylguanosine
m22Gm
G
YES

N2,N2,7-trimethylguanosine
m2,2,7G
G
YES

N2,N2-dimethylguanosine
m22G
G
YES

N²,7,2′-O-trimethylguanosine
m^2,7Gm
G
YES

6-thio-guanosine
—
G
NO

7-deaza-guanosine
—
G
NO

8-oxo-guanosine
—
G
NO

N1-methyl-guanosine
—
G
NO

α-thio-guanosine
—
G
NO

2 (propyl)guanine
—
G
NO

2-(alkyl)guanine
—
G
NO

2′-Amino-2′-deoxy-GTP
—
G
NO

2′-Azido-2′-deoxy-GTP
—
G
NO

2′-Deoxy-2′-a-aminoguanosine TP
—
G
NO

2′-Deoxy-2′-a-azidoguanosine TP
—
G
NO

6 (methyl)guanine
—
G
NO

6-(alkyl)guanine
—
G
NO

6-(methyl)guanine
—
G
NO

6-methyl-guanosine
—
G
NO

7 (alkyl)guanine
—
G
NO

7 (deaza)guanine
—
G
NO

7 (methyl)guanine
—
G
NO

7-(alkyl)guanine
—
G
NO

7-(deaza)guanine
—
G
NO

7-(methyl)guanine
—
G
NO

8 (alkyl)guanine
—
G
NO

8 (alkynyl)guanine
—
G
NO

8 (halo)guanine
—
G
NO

8 (thioalkyl)guanine
—
G
NO

8-(alkenyl)guanine
—
G
NO

8-(alkyl)guanine
—
G
NO

8-(alkynyl)guanine
—
G
NO

8-(amino)guanine
—
G
NO

8-(halo)guanine
—
G
NO

8-(hydroxyl)guanine
—
G
NO

8-(thioalkyl)guanine
—
G
NO

8-(thiol)guanine
—
G
NO

aza guanine
—
G
NO

deaza guanine
—
G
NO

N (methyl)guanine
—
G
NO

N-(methyl)guanine
—
G
NO

1-methyl-6-thio-guanosine
—
G
NO

6-methoxy-guanosine
—
G
NO

6-thio-7-deaza-8-aza-guanosine
—
G
NO

6-thio-7-deaza-guanosine
—
G
NO

6-thio-7-methyl-guanosine
—
G
NO

7-deaza-8-aza-guanosine
—
G
NO

7-methyl-8-oxo-guanosine
—
G
NO

N2,N2-dimethyl-6-thio-guanosine
—
G
NO

N2-methyl-6-thio-guanosine
—
G
NO

1-Me-GTP
—
G
NO

2′Fluoro-N2-isobutyl-guanosine TP
—
G
NO

2′O-methyl-N2-isobutyl-guanosine TP
—
G
NO

2′-a-Ethynylguanosine TP
—
G
NO

2′-a-Trifluoromethylguanosine TP
—
G
NO

2′-b-Ethynylguanosine TP
—
G
NO

2′-b-Trifluoromethylguanosine TP
—
G
NO

2′-Deoxy-2′,2′-difluoroguanosine TP
—
G
NO

2′-Deoxy-2′-a-mercaptoguanosine TP
—
G
NO

2′-Deoxy-2′-a-thiomethoxyguanosine TP
—
G
NO

2′-Deoxy-2′-b-aminoguanosine TP
—
G
NO

2′-Deoxy-2′-b-azidoguanosine TP
—
G
NO

2′-Deoxy-2′-b-bromoguanosine TP
—
G
NO

2′-Deoxy-2′-b-chloroguanosine TP
—
G
NO

2′-Deoxy-2′-b-fluoroguanosine TP
—
G
NO

2′-Deoxy-2′-b-iodoguanosine TP
—
G
NO

2′-Deoxy-2′-b-mercaptoguanosine TP
—
G
NO

2′-Deoxy-2′-b-thiomethoxyguanosine TP
—
G
NO

4′-Azidoguanosine TP
—
G
NO

4′-Carbocyclic guanosine TP
—
G
NO

4′-Ethynylguanosine TP
—
G
NO

5′-Homo-guanosine TP
—
G
NO

8-bromo-guanosine TP
—
G
NO

9-Deazaguanosine TP
—
G
NO

N2-isobutyl-guanosine TP
—
G
NO

1-methylinosine
m1I
I
YES

Inosine
I
I
YES

1,2′-O-dimethylinosine
m1Im
I
YES

2′-O-methylinosine
Im
I
YES

7-methylinosine

I
NO

2′-O-methylinosine
Im
I
YES

Epoxyqueuosine
oQ
Q
YES

galactosyl-queuosine
galQ
Q
YES

Mannosylqueuosine
manQ
Q
YES

Queuosine
Q
Q
YES

allyamino-thymidine
—
T
NO

aza thymidine
—
T
NO

deaza thymidine
—
T
NO

deoxy-thymidine
—
T
NO

2′-O-methyluridine
—
U
YES

2-thiouridine
s2U
U
YES

3-methyluridine
m3U
U
YES

5-carboxymethyluridine
cm5U
U
YES

5-hydroxyuridine
ho5U
U
YES

5-methyluridine
m5U
U
YES

5-taurinomethyl-2-thiouridine
τm5s2U
U
YES

5-taurinomethyluridine
τm5U
U
YES

Dihydrouridine
D
U
YES

Pseudouridine
Ψ
U
YES

(3-(3-amino-3-carboxypropyl)uridine
acp3U
U
YES

1-methyl-3-(3-amino-5-
m1acp3Ψ
U
YES

carboxypropyl)pseudouridine

1-methylpseduouridine
m1Ψ
U
YES

1-methyl-pseudouridine
—
U
YES

2′-O-methyluridine
Um
U
YES

2′-O-methylpseudouridine
Ψm
U
YES

2′-O-methyluridine
Um
U
YES

2-thio-2′-O-methyluridine
s2Um
U
YES

3-(3-amino-3-carboxypropyl)uridine
acp3U
U
YES

3,2′-O-dimethyluridine
m3Um
U
YES

3-Methyl-pseudo-Uridine TP
—
U
YES

4-thiouridine
s4U
U
YES

5-(carboxyhydroxymethyl)uridine
chm5U
U
YES

5-(carboxyhydroxymethyl)uridine methyl
mchm5U
U
YES

ester

5,2′-O-dimethyluridine
m5Um
U
YES

5,6-dihydro-uridine
—
U
YES

5-aminomethyl-2-thiouridine
nm5s2U
U
YES

5-carbamoylmethyl-2′-O-methyluridine
ncm5Um
U
YES

5-carbamoylmethyluridine
ncm5U
U
YES

5-carboxyhydroxymethyluridine
—
U
YES

5-carboxyhydroxymethyluridine methyl
—
U
YES

ester

5-carboxymethylaminomethyl-2′-O-
cmnm5Um
U
YES

methyluridine

5-carboxymethylaminomethyl-2-
cmnm5s2U
U
YES

thiouridine

5-carboxymethylaminomethyl-2-
—
U
YES

thiouridine

5-carboxymethylaminomethyluridine
cmnm5U
U
YES

5-carboxymethylaminomethyluridine
—
U
YES

5-Carbamoylmethyluridine TP
—
U
YES

5-methoxycarbonylmethyl-2′-O-
mcm5Um
U
YES

methyluridine

5-methoxycarbonylmethyl-2-thiouridine
mcm5s2U
U
YES

5-methoxycarbonylmethyluridine
mcm5U
U
YES

5-methoxyuridine
mo5U
U
YES

5-methyl-2-thiouridine
m5s2U
U
YES

5-methylaminomethyl-2-selenouridine
mnm5se2U
U
YES

5-methylaminomethyl-2-thiouridine
mnm5s2U
U
YES

5-methylaminomethyluridine
mnm5U
U
YES

5-Methyldihydrouridine
—
U
YES

5-Oxyacetic acid-Uridine TP
—
U
YES

5-Oxyacetic acid-methyl ester-Uridine TP
—
U
YES

N1-methyl-pseudo-uridine
—
U
YES

uridine 5-oxyacetic acid
cmo5U
U
YES

uridine 5-oxyacetic acid methyl ester
mcmo5U
U
YES

3-(3-Amino-3-carboxypropyl)-Uridine TP
—
U
YES

5-(iso-Pentenylaminomethyl)-2-
—
U
YES

thiouridine TP

5-(iso-Pentenylaminomethyl)-2′-O-
—
U
YES

methyluridine TP

5-(iso-Pentenylaminomethyl)uridine TP
—
U
YES

5-propynyl uracil
—
U
NO

α-thio-uridine
—
U
NO

1 (aminoalkylamino-carbonylethylenyl)-
—
U
NO

2(thio)-pseudouracil

1 (aminoalkylaminocarbonylethylenyl)-
—
U
NO

2,4-(dithio)pseudouracil

1 (aminoalkylaminocarbonylethylenyl)-4
—
U
NO

(thio)pseudouracil

1 (aminoalkylaminocarbonylethylenyl)-
—
U
NO

pseudouracil

1 (aminocarbonylethylenyl)-2(thio)-
—
U
NO

pseudouracil

1 (aminocarbonylethylenyl)-2,4-
—
U
NO

(dithio)pseudouracil

1 (aminocarbonylethylenyl)-4
—
U
NO

(thio)pseudouracil

1 (aminocarbonylethylenyl)-pseudouracil
—
U
NO

1 substituted 2(thio)-pseudouracil
—
U
NO

1 substituted 2,4-(dithio)pseudouracil
—
U
NO

1 substituted 4 (thio)pseudouracil
—
U
NO

1 substituted pseudouracil
—
U
NO

1-(aminoalkylamino-carbonylethylenyl)-2-
—
U
NO

(thio)-pseudouracil

1-Methyl-3-(3-amino-3-carboxypropyl)
—
U
NO

pseudouridine TP

1-Methyl-3-(3-amino-3-
—
U
NO

carboxypropyl)pseudo-UTP

1-Methyl-pseudo-UTP
—
U
NO

2 (thio)pseudouracil
—
U
NO

2′ deoxy uridine
—
U
NO

2′ fluorouridine
—
U
NO

2-(thio)uracil
—
U
NO

2,4-(dithio)psuedouracil
—
U
NO

2′ methyl, 2′amino, 2′azido, 2′fluro-
—
U
NO

guanosine

2′-Amino-2′-deoxy-UTP
—
U
NO

2′-Azido-2′-deoxy-UTP
—
U
NO

2′-Azido-deoxyuridine TP
—
U
NO

2′-O-methylpseudouridine
—
U
NO

2′ deoxy uridine
2′ dU
U
NO

2′ fluorouridine
—
U
NO

2′-Deoxy-2′-a-aminouridine TP
—
U
NO

2′-Deoxy-2′-a-azidouridine TP
—
U
NO

2-methylpseudouridine
m3Ψ
U
NO

3 (3 amino-3 carboxypropyl)uracil
—
U
NO

4 (thio)pseudouracil
—
U
NO

4-(thio)pseudouracil
—
U
NO

4-(thio)uracil
—
U
NO

4-thiouracil
—
U
NO

5 (1,3-diazole-1-alkyl)uracil
—
U
NO

5 (2-aminopropyl)uracil
—
U
NO

5 (aminoalkyl)uracil
—
U
NO

5 (dimethylaminoalkyl)uracil
—
U
NO

5 (guanidiniumalkyl)uracil
—
U
NO

5 (methoxycarbonylmethyl)-2-(thio)uracil
—
U
NO

5 (methoxycarbonyl-methyl)uracil
—
U
NO

5 (methyl) 2 (thio)uracil
—
U
NO

5 (methyl) 2,4 (dithio)uracil
—
U
NO

5 (methyl) 4 (thio)uracil
—
U
NO

5 (methylaminomethyl)-2 (thio)uracil
—
U
NO

5 (methylaminomethyl)-2,4 (dithio)uracil
—
U
NO

5 (methylaminomethyl)-4 (thio)uracil
—
U
NO

5 (propynyl)uracil
—
U
NO

5 (trifluoromethyl)uracil
—
U
NO

5-(2-aminopropyl)uracil
—
U
NO

5-(alkyl)-2-(thio)pseudouracil
—
U
NO

5-(alkyl)-2,4 (dithio)pseudouracil
—
U
NO

5-(alkyl)-4 (thio)pseudouracil
—
U
NO

5-(alkyl)pseudouracil
—
U
NO

5-(alkyl)uracil
—
U
NO

5-(alkynyl)uracil
—
U
NO

5-(allylamino)uracil
—
U
NO

5-(cyanoalkyl)uracil
—
U
NO

5-(dialkylaminoalkyl)uracil
—
U
NO

5-(dimethylaminoalkyl)uracil
—
U
NO

5-(guanidiniumalkyl)uracil
—
U
NO

5-(halo)uracil
—
U
NO

5-(1,3-diazole-1-alkyl)uracil
—
U
NO

5-(methoxy)uracil
—
U
NO

5-(methoxycarbonylmethyl)-2-(thio)uracil
—
U
NO

5-(methoxycarbonyl-methyl)uracil
—
U
NO

5-(methyl) 2(thio)uracil
—
U
NO

5-(methyl) 2,4 (dithio)uracil
—
U
NO

5-(methyl) 4 (thio)uracil
—
U
NO

5-(methyl)-2-(thio)pseudouracil
—
U
NO

5-(methyl)-2,4 (dithio)pseudouracil
—
U
NO

5-(methyl)-4 (thio)pseudouracil
—
U
NO

5-(methyl)pseudouracil
—
U
NO

5-(methylaminomethyl)-2 (thio)uracil
—
U
NO

5-(methylaminomethyl)-2,4(dithio)uracil
—
U
NO

5-(methylaminomethyl)-4-(thio)uracil
—
U
NO

5-(propynyl)uracil
—
U
NO

5-(trifluoromethyl)uracil
—
U
NO

5-aminoallyl-uridine
—
U
NO

5-bromo-uridine
—
U
NO

5-iodo-uridine
—
U
NO

5-uracil
—
U
NO

6 (azo)uracil
—
U
NO

6-(azo)uracil
—
U
NO

6-aza-uridine
—
U
NO

allyamino-uracil
—
U
NO

aza uracil
—
U
NO

deaza uracil
—
U
NO

N3 (methyl)uracil
—
U
NO

Pseudo-UTP-1-2-ethanoic acid
—
U
NO

Pseudouracil
—
U
NO

4-Thio-pseudo-UTP
—
U
NO

1-carboxymethyl-pseudouridine
—
U
NO

1-methyl-1-deaza-pseudouridine
—
U
NO

1-propynyl-uridine
—
U
NO

1-taurinomethyl-1-methyl-uridine
—
U
NO

1-taurinomethyl-4-thio-uridine
—
U
NO

1-taurinomethyl-pseudouridine
—
U
NO

2-methoxy-4-thio-pseudouridine
—
U
NO

2-thio-1-methyl-1-deaza-pseudouridine
—
U
NO

2-thio-1-methyl-pseudouridine
—
U
NO

2-thio-5-aza-uridine
—
U
NO

2-thio-dihydropseudouridine
—
U
NO

2-thio-dihydrouridine
—
U
NO

2-thio-pseudouridine
—
U
NO

4-methoxy-2-thio-pseudouridine
—
U
NO

4-methoxy-pseudouridine
—
U
NO

4-thio-1-methyl-pseudouridine
—
U
NO

4-thio-pseudouridine
—
U
NO

5-aza-uridine
—
U
NO

Dihydropseudouridine
—
U
NO

(±)1-(2-Hydroxypropyl)pseudouridine TP
—
U
NO

(2R)-1-(2-Hydroxypropyl)pseudouridine
—
U
NO

TP

(2S)-1-(2-Hydroxypropyl)pseudouridine
—
U
NO

TP

(E)-5-(2-Bromo-vinyl)ara-uridine TP
—
U
NO

(E)-5-(2-Bromo-vinyl)uridine TP
—
U
NO

(Z)-5-(2-Bromo-vinyl)ara-uridine TP
—
U
NO

(Z)-5-(2-Bromo-vinyl)uridine TP
—
U
NO

1-(2,2,2-Trifluoroethyl)-pseudo-UTP
—
U
NO

1-(2,2,3,3,3-Pentafluoropropyl)
—
U
NO

pseudouridine TP

1-(2,2-Diethoxyethyl)pseudouridine TP
—
U
NO

1-(2,4,6-Trimethylbenzyl)pseudouridine
—
U
NO

TP

1-(2,4,6-Trimethyl-benzyl)pseudo-UTP
—
U
NO

1-(2,4,6-Trimethyl-phenyl)pseudo-UTP
—
U
NO

1-(2-Amino-2-carboxyethyl)pseudo-UTP
—
U
NO

1-(2-Amino-ethyl)pseudo-UTP
—
U
NO

1-(2-Hydroxyethyl)pseudouridine TP
—
U
NO

1-(2-Methoxyethyl)pseudouridine TP
—
U
NO

1-(3,4-Bis-trifluoromethoxybenzyl)
—
U
NO

pseudouridine TP

1-(3,4-Dimethoxybenzyl)pseudouridine
—
U
NO

TP

1-(3-Amino-3-carboxypropyl)pseudo-UTP
—
U
NO

1-(3-Amino-propyl)pseudo-UTP
—
U
NO

1-(3-Cyclopropyl-prop-2-
—
U
NO

ynyl)pseudouridine TP

1-(4-Amino-4-carboxybutyl)pseudo-UTP
—
U
NO

1-(4-Amino-benzyl)pseudo-UTP
—
U
NO

1-(4-Amino-butyl)pseudo-UTP
—
U
NO

1-(4-Amino-phenyl)pseudo-UTP
—
U
NO

1-(4-Azidobenzyl)pseudouridine TP
—
U
NO

1-(4-Bromobenzyl)pseudouridine TP
—
U
NO

1-(4-Chlorobenzyl)pseudouridine TP
—
U
NO

1-(4-Fluorobenzyl)pseudouridine TP
—
U
NO

1-(4-Iodobenzyl)pseudouridine TP
—
U
NO

1-(4-Methanesulfonylbenzyl)
—
U
NO

pseudouridine TP

1-(4-Methoxybenzyl)pseudouridine TP
—
U
NO

1-(4-Methoxy-benzyl)pseudo-UTP
—
U
NO

1-(4-Methoxy-phenyl)pseudo-UTP
—
U
NO

1-(4-Methylbenzyl)pseudouridine TP
—
U
NO

1-(4-Methyl-benzyl)pseudo-UTP
—
U
NO

1-(4-Nitrobenzyl)pseudouridine TP
—
U
NO

1-(4-Nitro-benzyl)pseudo-UTP
—
U
NO

1 (4-Nitro-phenyl)pseudo-UTP
—
U
NO

1-(4-Thiomethoxybenzyl)pseudouridine
—
U
NO

TP

1-(4-Trifluoromethoxybenzyl)
—
U
NO

pseudouridine TP

1-(4-Trifluoromethylbenzyl)pseudouridine
—
U
NO

TP

1-(5-Amino-pentyl)pseudo-UTP
—
U
NO

1-(6-Amino-hexyl)pseudo-UTP
—
U
NO

1,6-Dimethyl-pseudo-UTP
—
U
NO

1-[3-(2-{2-[2-(2-Aminoethoxy)-ethoxy]-
—
U
NO

ethoxy}-ethoxy)-propionyl]pseudouridine

TP

1-{3-[2-(2-Aminoethoxy)-ethoxy]-
—
U
NO

propionyl} pseudouridine TP

1-Acetylpseudouridine TP
—
U
NO

1-Alkyl-6-(1-propynyl)-pseudo-UTP
—
U
NO

1-Alkyl-6-(2-propynyl)-pseudo-UTP
—
U
NO

1-Alkyl-6-allyl-pseudo-UTP
—
U
NO

1-Alkyl-6-ethynyl-pseudo-UTP
—
U
NO

1-Alkyl-6-homoallyl-pseudo-UTP
—
U
NO

1-Alkyl-6-vinyl-pseudo-UTP
—
U
NO

1-Allylpseudouridine TP
—
U
NO

1-Aminomethyl-pseudo-UTP
—
U
NO

1-Benzoylpseudouridine TP
—
U
NO

1-Benzyloxymethylpseudouridine TP
—
U
NO

1-Benzyl-pseudo-UTP
—
U
NO

1-Biotinyl-PEG2-pseudouridine TP
—
U
NO

1-Biotinylpseudouridine TP
—
U
NO

1-Butyl-pseudo-UTP
—
U
NO

1-Cyanomethylpseudouridine TP
—
U
NO

1-Cyclobutylmethyl-pseudo-UTP
—
U
NO

1-Cyclobutyl-pseudo-UTP
—
U
NO

1-Cycloheptylmethyl-pseudo-UTP
—
U
NO

1-Cycloheptyl-pseudo-UTP
—
U
NO

1-Cyclohexylmethyl-pseudo-UTP
—
U
NO

1-Cyclohexyl-pseudo-UTP
—
U
NO

1-Cyclooctylmethyl-pseudo-UTP
—
U
NO

1-Cyclooctyl-pseudo-UTP
—
U
NO

1-Cyclopentylmethyl-pseudo-UTP
—
U
NO

1-Cyclopentyl-pseudo-UTP
—
U
NO

1-Cyclopropylmethyl-pseudo-UTP
—
U
NO

1-Cyclopropyl-pseudo-UTP
—
U
NO

1-Ethyl-pseudo-UTP
—
U
NO

1-Hexyl-pseudo-UTP
—
U
NO

1-Homoallylpseudouridine TP
—
U
NO

1-Hydroxymethylpseudouridine TP
—
U
NO

1-iso-propyl-pseudo-UTP
—
U
NO

1-Me-2-thio-pseudo-UTP
—
U
NO

1-Me-4-thio-pseudo-UTP
—
U
NO

1-Me-alpha-thio-pseudo-UTP
—
U
NO

1-Methane sulfonylmethylpseudouridine
—
U
NO

TP

1-Methoxymethylpseudouridine TP
—
U
NO

1-Methyl-6-(2,2,2-Trifluoroethyl)pseudo-
—
U
NO

UTP

1-Methyl-6-(4-morpholino)-pseudo-UTP
—
U
NO

1-Methyl-6-(4-thiomorpholino)-pseudo-
—
U
NO

UTP

1-Methyl-6-(substituted phenyl)pseudo-
—
U
NO

UTP

1-Methyl-6-amino-pseudo-UTP
—
U
NO

1-Methyl-6-azido-pseudo-UTP
—
U
NO

1-Methyl-6-bromo-pseudo-UTP
—
U
NO

1-Methyl-6-butyl-pseudo-UTP
—
U
NO

1-Methyl-6-chloro-pseudo-UTP
—
U
NO

1-Methyl-6-cyano-pseudo-UTP
—
U
NO

1-Methyl-6-dimethylamino-pseudo-UTP
—
U
NO

1-Methyl-6-ethoxy-pseudo-UTP
—
U
NO

1-Methyl-6-ethylcarboxylate-pseudo-UTP
—
U
NO

1-Methyl-6-ethyl-pseudo-UTP
—
U
NO

1-Methyl-6-fluoro-pseudo-UTP
—
U
NO

1-Methyl-6-formyl-pseudo-UTP
—
U
NO

1-Methyl-6-hydroxyamino-pseudo-UTP
—
U
NO

1-Methyl-6-hydroxy-pseudo-UTP
—
U
NO

1-Methyl-6-iodo-pseudo-UTP
—
U
NO

1-Methyl-6-iso-propyl-pseudo-UTP
—
U
NO

1-Methyl-6-methoxy-pseudo-UTP
—
U
NO

1-Methyl-6-methylamino-pseudo-UTP
—
U
NO

1-Methyl-6-phenyl-pseudo-UTP
—
U
NO

1-Methyl-6-propyl-pseudo-UTP
—
U
NO

1-Methyl-6-tert-butyl-pseudo-UTP
—
U
NO

1-Methyl-6-trifluoromethoxy-pseudo-UTP
—
U
NO

1-Methyl-6-trifluoromethyl-pseudo-UTP
—
U
NO

1-Morpholinomethylpseudouridine TP
—
U
NO

1-Pentyl-pseudo-UTP
—
U
NO

1-Phenyl-pseudo-UTP
—
U
NO

1-Pivaloylpseudouridine TP
—
U
NO

1-Propargylpseudouridine TP
—
U
NO

1-Propyl-pseudo-UTP
—
U
NO

1-propynyl-pseudouridine
—
U
NO

1-p-tolyl-pseudo-UTP
—
U
NO

1-tert-Butyl-pseudo-UTP
—
U
NO

1-Thiomethoxymethylpseudouridine TP
—
U
NO

1-Thiomorpholinomethylpseudouridine TP
—
U
NO

1-Trifluoroacetylpseudouridine TP
—
U
NO

1-Trifluoromethyl-pseudo-UTP
—
U
NO

1-Vinylpseudouridine TP
—
U
NO

2,2′-anhydro-uridine TP
—
U
NO

2′-bromo-deoxyuridine TP
—
U
NO

2′-F-5-Methyl-2′-deoxy-UTP
—
U
NO

2′-OMe-5-Me-UTP
—
U
NO

2′-OMe-pseudo-UTP
—
U
NO

2′-a-Ethynyluridine TP
—
U
NO

2′-a-Trifluoromethyluridine TP
—
U
NO

2′-b-Ethynyluridine TP
—
U
NO

2′-b-Trifluoromethyluridine TP
—
U
NO

2′-Deoxy-2′,2′-difluorouridine TP
—
U
NO

2′-Deoxy-2′-a-mercaptouridine TP
—
U
NO

2′-Deoxy-2′-a-thiomethoxyuridine TP
—
U
NO

2′-Deoxy-2′-b-aminouridine TP
—
U
NO

2′-Deoxy-2′-b-azidouridine TP
—
U
NO

2′-Deoxy-2′-b-bromouridine TP
—
U
NO

2′-Deoxy-2′-b-chlorouridine TP
—
U
NO

2′-Deoxy-2′-b-fluorouridine TP
—
U
NO

2′-Deoxy-2′-b-iodouridine TP
—
U
NO

2′-Deoxy-2′-b-mercaptouridine TP
—
U
NO

2′-Deoxy-2′-b-thiomethoxyuridine TP
—
U
NO

2-methoxy-4-thio-uridine
—
U
NO

2-methoxyuridine
—
U
NO

2′-O-Methyl-5-(1-propynyl)uridine TP
—
U
NO

3-Alkyl-pseudo-UTP
—
U
NO

4′-Azidouridine TP
—
U
NO

4′-Carbocyclic uridine TP
—
U
NO

4′-Ethynyluridine TP
—
U
NO

5-(1-Propynyl)ara-uridine TP
—
U
NO

5-(2-Furanyl)uridine TP
—
U
NO

5-Cyanouridine TP
—
U
NO

5-Dimethylaminouridine TP
—
U
NO

5′-Homo-uridine TP
—
U
NO

5-iodo-2′-fluoro-deoxyuridine TP
—
U
NO

5-Phenylethynyluridine TP
—
U
NO

5-Trideuteromethyl-6-deuterouridine TP
—
U
NO

5-Trifluoromethyl-Uridine TP
—
U
NO

5-Vinylarauridine TP
—
U
NO

6-(2,2,2-Trifluoroethyl)-pseudo-UTP
—
U
NO

6-(4-Morpholino)-pseudo-UTP
—
U
NO

6-(4-Thiomorpholino)-pseudo-UTP
—
U
NO

6-(Substituted-Phenyl)-pseudo-UTP
—
U
NO

6-Amino-pseudo-UTP
—
U
NO

6-Azido-pseudo-UTP
—
U
NO

6-Bromo-pseudo-UTP
—
U
NO

6-Butyl-pseudo-UTP
—
U
NO

6-Chloro-pseudo-UTP
—
U
NO

6-Cyano-pseudo-UTP
—
U
NO

6-Dimethylamino-pseudo-UTP
—
U
NO

6-Ethoxy-pseudo-UTP
—
U
NO

6-Ethylcarboxylate-pseudo-UTP
—
U
NO

6-Ethyl-pseudo-UTP
—
U
NO

6-Fluoro-pseudo-UTP
—
U
NO

6-Formyl-pseudo-UTP
—
U
NO

6-Hydroxyamino-pseudo-UTP
—
U
NO

6-Hydroxy-pseudo-UTP
—
U
NO

6-Iodo-pseudo-UTP
—
U
NO

6-iso-Propyl-pseudo-UTP
—
U
NO

6-Methoxy-pseudo-UTP
—
U
NO

6-Methylamino-pseudo-UTP
—
U
NO

6-Methyl-pseudo-UTP
—
U
NO

6-Phenyl-pseudo-UTP
—
U
NO

6-Phenyl-pseudo-UTP
—
U
NO

6-Propyl-pseudo-UTP
—
U
NO

6-tert-Butyl-pseudo-UTP
—
U
NO

6-Trifluoromethoxy-pseudo-UTP
—
U
NO

6-Trifluoromethyl-pseudo-UTP
—
U
NO

Alpha-thio-pseudo-UTP
—
U
NO

Pseudouridine 1-(4-
—
U
NO

methylbenzenesulfonic acid) TP

Pseudouridine 1-(4-methylbenzoic acid)
—
U
NO

TP

Pseudouridine TP 1-[3-(2-
—
U
NO

ethoxy)]propionic acid

Pseudouridine TP 1-[3-{2-(2-[2-(2-
—
U
NO

ethoxy)-ethoxy]-ethoxy)-ethoxy}]

propionic acid

Pseudouridine TP 1-[3-{2-(2-[2-{2-(2-
—
U
NO

ethoxy)-ethoxy}-ethoxy]-ethoxy)-

ethoxyl}]propionic acid

Pseudouridine TP 1-[3-{2-(2-[2-ethoxy]-
—
U
NO

ethoxy)-ethoxy}]propionic acid

Pseudouridine TP 1-[3-{2-(2-ethoxy)-
—
U
NO

ethoxy}] propionic acid

Pseudouridine TP 1-methylphosphonic
—
U
NO

acid

Pseudouridine TP 1-methylphosphonic
—
U
NO

acid diethyl ester

Pseudo-UTP-N1-3-propionic acid
—
U
NO

Pseudo-UTP-N1-4-butanoic acid
—
U
NO

Pseudo-UTP-N1-5-pentanoic acid
—
U
NO

Pseudo-UTP-N1-6-hexanoic acid
—
U
NO

Pseudo-UTP-N1-7-heptanoic acid
—
U
NO

Pseudo-UTP-N1-methyl-p-benzoic acid
—
U
NO

Pseudo-UTP-N1-p-benzoic acid
—
U
NO

Wybutosine
yW
W
YES

Hydroxywybutosine
OHyW
W
YES

Isowyosine
imG2
W
YES

Peroxywybutosine
o2yW
W
YES

undermodified hydroxywybutosine
OHyW*
W
YES

4-demethylwyosine
imG-14
W
YES

Other modifications which may be useful in the polynucleotides of the NAVs of the present invention are listed in Table 23.

TABLE 23

Additional Modification types

Name
Type

2,6-(diamino)purine
Other

1-(aza)-2-(thio)-3-(aza)-phenoxazin-1-yl
Other

1,3-(diaza)-2-(oxo)-phenthiazin-1-yl
Other

1,3-(diaza)-2-(oxo)-phenoxazin-1-yl
Other

1,3,5-(triaza)-2,6-(dioxa)-naphthalene
Other

2 (amino)purine
Other

2,4,5-(trimethyl)phenyl
Other

2′methyl, 2′amino, 2′azido, 2′fluro-cytidine
Other

2′methyl, 2′amino, 2′azido, 2′fluro-adenine
Other

2′methyl, 2′amino, 2′azido, 2′fluro-uridine
Other

2′-amino-2′-deoxyribose
Other

2-amino-6-Chloro-purine
Other

2-aza-inosinyl
Other

2′-azido-2′-deoxyribose
Other

2′fluoro-2′-deoxyribose
Other

2′-fluoro-modified bases
Other

2′-O-methyl-ribose
Other

2-oxo-7-aminopyridopyrimidin-3-yl
Other

2-oxo-pyridopyrimidine-3-yl
Other

2-pyridinone
Other

3 nitropyrrole
Other

3-(methyl)-7-(propynyl)isocarbostyrilyl
Other

3-(methyl)isocarbostyrilyl
Other

4-(fluoro)-6-(methyl)benzimidazole
Other

4-(methyl)benzimidazole
Other

4-(methyl)indolyl
Other

4,6-(dimethyl)indolyl
Other

5 nitroindole
Other

5 substituted pyrimidines
Other

5-(methyl)isocarbostyrilyl
Other

5-nitroindole
Other

6-(aza)pyrimidine
Other

6-(azo)thymine
Other

6-(methyl)-7-(aza)indolyl
Other

6-chloro-purine
Other

6-phenyl-pyrrolo-pyrimidin-2-on-3-yl
Other

7-(aminoalkylhydroxy)-1-(aza)-2-(thio)-3-(aza)-phenthiazin-1-yl
Other

7-(aminoalkylhydroxy)-1-(aza)-2-(thio)-3-(aza)-phenoxazin-1-yl
Other

7-(aminoalkylhydroxy)-1,3-(diaza)-2-(oxo)-phenoxazin-1-yl
Other

7-(aminoalkylhydroxy)-1,3-(diaza)-2-(oxo)-phenthiazin-1-yl
Other

7-(aminoalkylhydroxy)-1,3-(diaza)-2-(oxo)-phenoxazin-1-yl
Other

7-(aza)indolyl
Other

7-(guanidiniumalkylhydroxy)-1-(aza)-2-(thio)-
Other

3-(aza)-phenoxazinl-yl

7-(guanidiniumalkylhydroxy)-1-(aza)-2-(thio)-
Other

3-(aza)-phenthiazin-1-yl

7-(guanidiniumalkylhydroxy)-1-(aza)-2-(thio)-3-(aza)-
Other

phenoxazin-1-yl

7-(guanidiniumalkylhydroxy)-1,3-(diaza)-
Other

2-(oxo)-phenoxazin-1-yl

7-(guanidiniumalkyl-hydroxy)-1,3-(diaza)-
Other

2-(oxo)-phenthiazin-1-yl

7-(guanidiniumalkylhydroxy)-1,3-(diaza)-
Other

2-(oxo)-phenoxazin-1-yl

7-(propynyl)isocarbostyrilyl
Other

7-(propynyl)isocarbostyrilyl, propnyl-7-(aza)indolyl
Other

7-deaza-inosinyl
Other

7-substituted 1-(aza)-2-(thio)-3-(aza)-phenoxazin-1-yl
Other

7-substituted 1,3-(diaza)-2-(oxo)-phenoxazin-1-yl
Other

9-(methyl)-imidizopyridinyl
Other

Aminoindolyl
Other

Anthracenyl
Other

bis-ortho-(aminoalkylhydroxy)-6-phenyl-
Other

pyrrolo-pyrimidin-2-on-3-yl

bis-ortho-substituted-6-phenyl-pyrrolo-
Other

pyrimidin-2-on-3-yl

Difluorotolyl
Other

Hypoxanthine
Other

Imidizopyridinyl
Other

Inosinyl
Other

Isocarbostyrilyl
Other

Isoguanisine
Other

N2-substituted purines
Other

N6-methyl-2-amino-purine
Other

N6-substituted purines
Other

N-alkylated derivative
Other

Napthalenyl
Other

Nitrobenzimidazolyl
Other

Nitroimidazolyl
Other

Nitroindazolyl
Other

Nitropyrazolyl
Other

Nubularine
Other

O6-substituted purines
Other

O-alkylated derivative
Other

ortho-(aminoalkylhydroxy)-6-phenyl-
Other

pyrrolo-pyrimidin-2-on-3-yl

ortho-sub stituted-6-phenyl-
Other

pyrrolo-pyrimidin-2-on-3-yl

Oxoformycin TP
Other

para-(aminoalkylhydroxy)-6-phenyl-
Other

pyrrolo-pyrimidin-2-on-3-yl

para-substituted-6-phenyl-
Other

pyrrolo-pyrimidin-2-on-3-yl

Pentacenyl
Other

Phenanthracenyl
Other

Phenyl
Other

propynyl-7-(aza)indolyl
Other

Pyrenyl
Other

pyridopyrimidin-3-yl
Other

pyridopyrimidin-3-yl, 2-oxo-7-amino-
Other

pyridopyrimidin-3-yl

pyrrolo-pyrimidin-2-on-3-yl
Other

Pyrrolopyrimidinyl
Other

Pyrrolopyrizinyl
Other

Stilbenzyl
Other

substituted 1,2,4-triazoles
Other

Tetracenyl
Other

Tubercidine
Other

Xanthine
Other

Xanthosine-5′-TP
Other

2-thio-zebularine
Other

5-aza-2-thio-zebularine
Other

7-deaza-2-amino-purine
Other

pyridin-4-one ribonucleoside
Other

2-Amino-riboside-TP
Other

Formycin A TP
Other

Formycin B TP
Other

Pyrrolosine TP
Other

2′-OH-ara-adenosine TP
Other

2′-OH-ara-cytidine TP
Other

2′-OH-ara-uridine TP
Other

2′-OH-ara-guanosine TP
Other

5-(2-carbomethoxyvinyl)uridine TP
Other

N6-(19-Amino-pentaox anonadecyl)adenoine TP
Other

The polynucleotides of the NAVs can include any useful linker between the nucleosides. Such linkers, including backbone modifications are given in Table

TABLE 24

Linker modifications

Name
TYPE

3′-alkylene phosphonates
Linker

3′-amino phosphoramidate
Linker

alkene containing backbones
Linker

Aminoalkylphosphoramidates
Linker

Aminoalkylphosphotriesters
Linker

Boranophosphates
Linker

—CH2-0-N(CH3)—CH2—
Linker

—CH2—N(CH3)—N(CH3)—CH2—
Linker

—CH2—NH—CH2—
Linker

chiral phosphonates
Linker

chiral phosphorothioates
Linker

formacetyl and thioformacetyl backbones
Linker

methylene (methylimino)
Linker

methylene formacetyl and
Linker

thioformacetyl backbones

methyleneimino and
Linker

methylenehydrazino backbones

morpholino linkages
Linker

—N(CH3)—CH2—CH2—
Linker

oligonucleosides with heteroatom
Linker

internucleoside linkage

Phosphinates
Linker

phosphoramidates
Linker

Phosphorodithioates
Linker

phosphorothioate internucleoside
Linker

linkages

Phosphorothioates
Linker

Phosphotriesters
Linker

PNA
Linker

siloxane backbones
Linker

sulfamate backbones
Linker

sulfide sulfoxide and sulfone backbones
Linker

sulfonate and sulfonamide backbones
Linker

Thionoalkylphosphonates
Linker

Thionoalkylphosphotriesters
Linker

Thionophosphoramidates
Linker

The polynucleotides of the NAVs of the invention can include any useful modification, such as to the sugar, the nucleobase, or the internucleoside linkage (e.g. to a linking phosphate/to a phosphodiester linkage/to the phosphodiester backbone). One or more atoms of a pyrimidine nucleobase may be replaced or substituted with optionally substituted amino, optionally substituted thiol, optionally substituted alkyl (e.g., methyl or ethyl), or halo (e.g., chloro or fluoro). In certain embodiments, modifications (e.g., one or more modifications) are present in each of the sugar and the internucleoside linkage. Modifications according to the present invention may be modifications of ribonucleic acids (RNAs) to deoxyribonucleic acids (DNAs), threose nucleic acids (TNAs), glycol nucleic acids (GNAs), peptide nucleic acids (PNAs), locked nucleic acids (LNAs) or hybrids thereof). Additional modifications are described herein.

Non-natural modified nucleotides may be introduced to polynucleotides, e.g., of the NAVs of the invention, or nucleic acids during synthesis or post-synthesis of the chains to achieve desired functions or properties. The modifications may be on internucleotide lineage, the purine or pyrimidine bases, or sugar. The modification may be introduced at the terminal of a chain or anywhere else in the chain; with chemical synthesis or with a polymerase enzyme. For example, hexitol nucleic acids (HNAs) are nuclease resistant and provide strong hybridization to RNA. Short messenger RNAs (mRNAs) with hexitol residues in two codons have been constructed (Lavrik et al., Biochemistry, 40, 11777-11784 (2001), the contents of which are incorporated herein by reference in their entirety). The antisense effects of a chimeric HNA gapmer oligonucleotide comprising a phosphorothioate central sequence flanked by 5′ and 3′ HNA sequences have also been studied (See e.g., Kang et al., Nucleic Acids Research, vol. 32(4), 4411-4419 (2004), the contents of which are incorporated herein by reference in their entirety). The preparation and uses of modified nucleotides comprising 6-member rings in RNA interference, antisense therapy or other applications are disclosed in US Pat. Application No. 2008/0261905, US Pat. Application No. 2010/0009865, and PCT Application No. WO97/30064 to Herdewijn et al.; the contents of each of which are herein incorporated by reference in their entireties). Modified nucleic acids and their synthesis are disclosed in copending PCT applications No. PCT/US2012/058519 (Attorney Docket Number M09), the contents of which are incorporated herein by reference for their entirety. The synthesis and strategy of modified polynucleotides is reviewed by Verma and Eckstein in Annual Review of Biochemistry, vol. 76, 99-134 (1998), the contents of which are incorporated herein by reference in their entirety.

Either enzymatic or chemical ligation methods can be used to conjugate polynucleotides or their regions with different functional blocks, such as fluorescent labels, liquids, nanoparticles, delivery agents, etc. The conjugates of polynucleotides and modified polynucleotides are reviewed by Goodchild in Bioconjugate Chemistry, vol. 1(3), 165-187 (1990), the contents of which are incorporated herein by reference in their entirety. U.S. Pat. Nos. 6,835,827 and 6,525,183 to Vinayak et al. (the contents of each of which are herein incorporated by reference in their entireties) teach synthesis of labeled oligonucleotides using a labeled solid support.

In certain embodiments, it may desirable to intracellularly degrade a polynucleotide introduced into the cell. For example, degradation of a polynucleotide may be preferable if precise timing of protein production is desired. Thus, in some embodiments, the invention provides a polynucleotide containing a degradation domain, which is capable of being acted on in a directed manner within a cell.

Any of the regions of the polynucleotides may be chemically modified as taught herein or as taught in International Application Number PCT/2012/058519 filed Oct. 3, 2012 (Attorney Docket Number M9) and U.S. Provisional Application No. 61/837,297 filed Jun. 20, 2013 (Attorney Docket Number M36) the contents of each of which are incorporated herein by reference in its entirety.

Modified Polynucleotide Molecules

The present invention also includes building blocks, e.g., modified ribonucleosides, and modified ribonucleotides, of polynucleotide molecules, e.g., of the NAVs of the invention. For example, these building blocks can be useful for preparing the polynucleotides of the invention. Such building blocks are taught in International Application Number PCT/2012/058519 filed Oct. 3, 2012 (Attorney Docket Number M9) and U.S. Provisional Application No. 61/837,297 filed Jun. 20, 2013 (Attorney Docket Number M36) the contents of each of which are incorporated herein by reference in its entirety.

Modifications on the Sugar

The modified nucleosides and nucleotides (e.g., building block molecules), which may be incorporated into a polynucleotide (e.g., RNA or mRNA, as described herein), can be modified on the sugar of the ribonucleic acid. For example, the 2′ hydroxyl group (OH) can be modified or replaced with a number of different substituents. Exemplary substitutions at the 2′-position include, but are not limited to, H, halo, optionally substituted C_1-6alkyl: optionally substituted C_1-6alkoxy; optionally substituted C_6-10aryloxy; optionally substituted C_3-10cycloalkyl; optionally substituted C_3-8cycloalkoxy; optionally substituted C_6-10aryloxy; optionally substituted C_6-10aryl-C_1-6alkoxy, optionally substituted C_1-12(heterocyclyl)oxy; a sugar (e.g., ribose, pentose, or any described herein); a polyethyleneglycol (PEG), —O(CH₂CH₂O)_nCH₂CH₂OR, where R is H or optionally substituted alkyl, and n is an integer from 0 to 20 (e.g., from 0 to 4, from 0 to 8, from 0 to 10, from 0 to 16, from 1 to 4, from 1 to 8, from 1 to 10, from 1 to 16, from 1 to 20, from 2 to 4, from 2 to 8, from 2 to 10, from 2 to 16, from 2 to 20, from 4 to 8, from 4 to 10, from 4 to 16, and from 4 to 20); “locked” nucleic acids (LNA) in which the 2′-hydroxyl is connected by a C_1-6alkylene or C_1-6heteroalkylene bridge to the 4′-carbon of the same ribose sugar, where exemplary bridges included methylene, propylene, ether, or amino bridges; aminoalkyl, as defined herein; aminoalkoxy, as defined herein; amino as defined herein; and amino acid, as defined herein

Generally, RNA includes the sugar group ribose, which is a 5-membered ring having an oxygen. Exemplary, non-limiting modified nucleotides include replacement of the oxygen in ribose (e.g., with S, Se. or alkylene, such as methylene or ethylene); addition of a double bond (e.g., to replace ribose with cyclopentenyl or cyclohexenyl); ring contraction of ribose (e.g., to form a 4-membered ring of cyclobutane or oxetane); ring expansion of ribose (e.g., to form a 6- or 7-membered ring having an additional carbon or heteroatom, such as for anhydrohexitol, ahritol, mannitol, cyclohexanyl, cyclohexenyl, and morpholino that also has a phosphoramidate backbone); multicyclic forms (e.g., tricyclo; and “unlocked” forms, such as glycol nucleic acid (GNA) (e.g., R-GNA or S-GNA, where ribose is replaced by glycol units attached to phosphodiester bonds), threose nucleic acid (TNA, where ribose is replace with α-L-threofuranosyl-(3′-+2′)), and peptide nucleic acid (PNA, where 2-amino-ethyl-glycine linkages replace the ribose and phosphodiester backbone). The sugar group can also contain one or more carbons that possess the opposite stereochemical configuration than that of the corresponding carbon in ribose. Thus, a polynucleotide molecule can include nucleotides containing, e.g., arabinose, as the sugar. Such sugar modifications are taught International Application Number PCT/2012/058519 filed Oct. 3, 2012 (Attorney Docket Number M9) and U.S. Provisional Application No. 61/837,297 filed Jun. 20, 2013 (Attorney Docket Number M36) the contents of each of which are incoroporated herein by reference in its entirety.

Modifications on the Nucleobase

The present disclosure provides for modified nucleosides and nucleotides. As described herein “nucleoside” is defined as a compound containing a sugar molecule (e.g., a pentose or ribose) or a derivative thereof in combination with an organic base (e.g., a purine or pyrimidine) or a derivative thereof (also referred to herein as “nucleobase”). As described herein, “nucleotide” is defined as a nucleoside including a phosphate group. The modified nucleotides may by synthesized by any useful method, as described herein (e.g., chemically, enzymatically, or recombinantly to include one or more modified or non-natural nucleosides). The polynucleotides may comprise a region or regions of linked nucleosides. Such regions may have variable backbone linkages. The linkages may be standard phosphoester linkages, in which case the polynucleotides would comprise regions of nucleotides.

The modified nucleotide base pairing encompasses not only the standard adenosine-thymine, adenosine-uracil, or guanosine-cytosine base pairs, but also base pairs formed between nucleotides and/or modified nucleotides comprising non-standard or modified bases, wherein the arrangement of hydrogen bond donors and hydrogen bond acceptors permits hydrogen bonding between a non-standard base and a standard base or between two complementary non-standard base structures. One example of such non-standard base pairing is the base pairing between the modified nucleotide inosine and adenine, cytosine or uracil.

The modified nucleosides and nucleotides can include a modified nucleobase. Examples of nucleobases found in RNA include, but are not limited to, adenine, guanine, cytosine, and uracil. Examples of nucleobase found in DNA include, but are not limited to, adenine, guanine, cytosine, and thymine. Such modified nucleobases (including the distinctions between naturally occurring and non-naturally occurring) are taught in International Application Number PCT/2012/058519 filed Oct. 3, 2012 (Attorney Docket Number M9) and U.S. Provisional Application No. 61/837,297 filed Jun. 20, 2013 (Attorney Docket Number M36) the contents of each of which are incoroporated herein by reference in its entirety.

Combinations of Modified Sugars, Nucleobases, and Internucleoside Linkages

The polynucleotides of the invention, e.g., the NAVs of the invention, can include a combination of modifications to the sugar, the nucleobase, and/or the internucleoside linkage. These combinations can include any one or more modifications described herein.

Examples of modified nucleotides and modified nucleotide combinations are provided below in Table 25. These combinations of modified nucleotides can be used to form the polynucleotides of the invention. Unless otherwise noted, the modified nucleotides may be completely substituted for the natural nucleotides of the polynucleotides of the invention. As a non-limiting example, the natural nucleotide uridine may be substituted with a modified nucleoside described herein. In another non-limiting example, the natural nucleotide uridine may be partially substituted (e.g., about 0.1%, 1%, 5%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95% or 99.9%) with at least one of the modified nucleoside disclosed herein. Any combination of base/sugar or linker may be incorporated into the polynucleotides of the invention and such modifications are taught in International Application Number PCT/2012/058519 filed Oct. 3, 2012 (Attorney Docket Number M9) and U.S. Provisional Application No. 61/837,297 filed Jun. 20, 2013 (Attorney Docket Number M36) the contents of each of which are incorporated herein by reference in its entirety.

TABLE 25

Combinations

Modified

Nucleotide
Modified Nucleotide Combination

α-thio-cytidine
α-thio-cytidine/5-iodo-uridine

α-thio-cytidine/N1-methyl-pseudouridine

α-thio-cytidine/α-thio-uridine

α-thio-cytidine/5-methyl-uridine

α-thio-cytidine/pseudo-uridine

about 50% of the cytosines are α-thio-cytidine

Pseudoisocytidine
pseudoisocytidine/5-iodo-uridine

pseudoisocytidine/N1-methyl-pseudouridine

pseudoisocytidine/α-thio-uridine

pseudoisocytidine/5-methyl-uridine

pseudoisocytidine/pseudouridine

about 25% of cytosines are pseudoisocytidine

pseudoisocytidine/about 50% of uridines are

N1-methyl-pseudouridine and about 50%

of uridines are pseudouridine

pseudoisocytidine/about 25% of uridines are

N1-methyl-pseudouridine and about

25% of uridines are pseudouridine

pyrrolo-cytidine
pyrrolo-cytidine/5-iodo-uridine

pyrrolo-cytidine/N1-methyl-pseudouridine

pyrrolo-cytidine/α-thio-uridine

pyrrolo-cytidine/5-methyl-uridine

pyrrolo-cytidine/pseudouridine

about 50% of the cytosines are pyrrolo-cytidine

5-methyl-cytidine
5-methyl-cytidine/5-iodo-uridine

5-methyl-cytidine/N1-methyl-pseudouridine

5-methyl-cytidine/α-thio-uridine

5-methyl-cytidine/5-methyl-uridine

5-methyl-cytidine/pseudouridine

about 25% of cytosines are 5-methyl-cytidine

about 50% of cytosines are 5-methyl-cytidine

5-methyl-cytidine/5-methoxy-uridine

5-methyl-cytidine/5-bromo-uridine

5-methyl-cytidine/2-thio-uridine

5-methyl-cytidine/about 50% of uridines

are 2-thio-uridine

about 50% of uridines are 5-methyl-cytidine/about

50% of uridines are 2-thio-uridine

N4-acetyl-cytidine
N4-acetyl-cytidine/5-iodo-uridine

N4-acetyl-cytidine/N1-methyl-pseudouridine

N4-acetyl-cytidine/α-thio-uridine

N4-acetyl-cytidine/5-methyl-uridine

N4-acetyl-cytidine/pseudouridine

about 50% of cytosines are N4-acetyl-cytidine

about 25% of cytosines are N4-acetyl-cytidine

N4-acetyl-cytidine/5-methoxy-uridine

N4-acetyl-cytidine/5-bromo-uridine

N4-acetyl-cytidine/2-thio-uridine

about 50% of cytosines are N4-acetyl-cytidine/

about 50% of uridines are 2-thio-uridine

V. Pharmaceutical Vaccine Compositions

Formulation, Administration, Delivery and Dosing

The present invention provides pharmaceutical compositions including NAVs and NAV compositions and/or complexes optionally in combination with one or more pharmaceutically acceptable excipients.

The present inventors have discovered that NAVs are superior to current vaccines in several ways. First, subcutaneous and/or intradermal injection is better than intramuscular administration as a route of delivery. Second, the lipid nanoparticle delivery is superior to other formulations including the protamine approach in the literature by a factor of between 10-100 fold and no additional adjuvants were found to be necessary. Third modified and formulated NAVs were superior to unmodified formulated NAVs by a factor of 50 fold.

The present invention provides NAVs and NAV pharmaceutical compositions and complexes optionally in combination with one or more pharmaceutically acceptable excipients. Pharmaceutical compositions may optionally comprise one or more additional active substances, e.g. therapeutically and/or prophylactically active substances. Pharmaceutical compositions of the present invention may be sterile and/or pyrogen-free. General considerations in the formulation and/or manufacture of pharmaceutical agents may be found, for example, in Remington: The Science and Practice of Pharmacy 21^sted., Lippincott Williams & Wilkins, 2005 (incorporated herein by reference in its entirety).

In some embodiments, compositions are administered to humans, human patients or subjects. For the purposes of the present disclosure, the phrase “active ingredient” generally refers to the NAVs or the polynucleotides contained therein, e.g., antigen-encoding polynucleotides, for example, RNA polynucleotides, to be delivered as described herein.

Although the descriptions of pharmaceutical compositions provided herein are principally directed to pharmaceutical compositions which are suitable for administration to humans, it will be understood by the skilled artisan that such compositions are generally suitable for administration to any other animal, e.g., to non-human animals, e.g. non-human mammals. Modification of pharmaceutical compositions suitable for administration to humans in order to render the compositions suitable for administration to various animals is well understood, and the ordinarily skilled veterinary pharmacologist can design and/or perform such modification with merely ordinary, if any, experimentation. Subjects to which administration of the pharmaceutical compositions is contemplated include, but are not limited to, humans and/or other primates; mammals, including commercially relevant mammals such as cattle, pigs, horses, sheep, cats, dogs, mice, and/or rats; and/or birds, including commercially relevant birds such as poultry, chickens, ducks, geese, and/or turkeys.

Formulations of the pharmaceutical compositions described herein may be prepared by any method known or hereafter developed in the art of pharmacology. In general, such preparatory methods include the step of bringing the active ingredient into association with an excipient and/or one or more other accessory ingredients, and then, if necessary and/or desirable, dividing, shaping and/or packaging the product into a desired single- or multi-dose unit.

Relative amounts of the active ingredient, the pharmaceutically acceptable excipient, and/or any additional ingredients in a pharmaceutical composition in accordance with the invention will vary, depending upon the identity, size, and/or condition of the subject treated and further depending upon the route by which the composition is to be administered. By way of example, the composition may comprise between 0.1% and 100%. e.g., between 0.5 and 50%, between 1-30%, between 5-80%, at least 80% (w/w) active ingredient.

Formulations

The NAVs of the invention can be formulated using one or more excipients to: (1) increase stability; (2) increase cell transfection; (3) permit the sustained or delayed release (e.g., from a depot formulation); (4) alter the biodistribution (e.g., target to specific tissues or cell types); (5) increase the translation of encoded protein in vivo; and/or (6) alter the release profile of encoded protein (antigen) in vivo. In addition to traditional excipients such as any and all solvents, dispersion media, diluents, or other liquid vehicles, dispersion or suspension aids, surface active agents, isotonic agents, thickening or emulsifying agents, preservatives, excipients of the present invention can include, without limitation, lipidoids, liposomes, lipid nanoparticles, polymers, lipoplexes, core-shell nanoparticles, peptides, proteins, cells transfected with NAVs (e.g., for transplantation into a subject), hyaluronidase, nanoparticle mimics and combinations thereof.

Accordingly, the formulations of the invention can include one or more excipients, each in an amount that may increases the stability of the NAV, increases cell transfection by the NAV, increases the expression of polynucleotides encoded protein, and/or alters the release profile of polynucleotide encoded proteins. Further, the polynucleotides of the present invention may be formulated using self-assembled nucleic acid nanoparticles.

A pharmaceutical composition in accordance with the present disclosure may be prepared, packaged, and/or sold in bulk, as a single unit dose, and/or as a plurality of single unit doses. As used herein, a “unit dose” refers to a discrete amount of the pharmaceutical composition comprising a predetermined amount of the active ingredient. The amount of the active ingredient is generally equal to the dosage of the active ingredient which would be administered to a subject and/or a convenient fraction of such a dosage such as, for example, one-half or one-third of such a dosage.

Relative amounts of the active ingredient, the pharmaceutically acceptable excipient, and/or any additional ingredients in a pharmaceutical composition in accordance with the present disclosure may vary, depending upon the identity, size, and/or condition of the subject being treated and further depending upon the route by which the composition is to be administered. For example, the composition may comprise between 0.1% and 99% (w/w) of the active ingredient. By way of example, the composition may comprise between 0.1% and 100%, e.g., between 0.5 and 50%, between 1-30%, between 5-80%, at least 80% (w/w) active ingredient.

In some embodiments, the formulations described herein may contain at least one polynucleotide, e.g., antigen-encoding polynucleotide. As a non-limiting example, the formulations may contain 1, 2, 3, 4 or 5 polynucleotides.

In one embodiment, the formulations described herein may comprise more than one type of polynucleotide, e.g., antigen-encoding polynucleotide. In one embodiment, the formulation may comprise a chimeric polynucleotide in linear and circular form. In another embodiment, the formulation may comprise a circular polynucleotide and an IVT polynucleotide. In yet another embodiment, the formulation may comprise an IVT polynucleotide, a chimeric polynucleotide and a circular polynucleotide.

In one embodiment the formulation may contain polynucleotide encoding proteins selected from categories such as, but not limited to, human proteins, veterinary proteins, bacterial proteins, biological proteins, antibodies, immunogenic proteins, therapeutic peptides and proteins, secreted proteins, plasma membrane proteins, cytoplasmic and cytoskeletal proteins, intracellular membrane bound proteins, nuclear proteins, proteins associated with human disease and/or proteins associated with non-human diseases. In one embodiment, the formulation contains at least three polynucleotides encoding proteins. In one embodiment, the formulation contains at least five polynucleotide encoding proteins.

Pharmaceutical formulations may additionally comprise a pharmaceutically acceptable excipient, which, as used herein, includes, but is not limited to, any and all solvents, dispersion media, diluents, or other liquid vehicles, dispersion or suspension aids, surface active agents, isotonic agents, thickening or emulsifying agents, preservatives, and the like, as suited to the particular dosage form desired. Various excipients for formulating pharmaceutical compositions and techniques for preparing the composition are known in the art (see Remington: The Science and Practice of Pharmacy, 21^stEdition, A. R. Gennaro, Lippincott, Williams & Wilkins, Baltimore, MD, 2006; incorporated herein by reference in its entirety). The use of a conventional excipient medium may be contemplated within the scope of the present disclosure, except insofar as any conventional excipient medium may be incompatible with a substance or its derivatives, such as by producing any undesirable biological effect or otherwise interacting in a deleterious manner with any other component(s) of the pharmaceutical composition.

In some embodiments, the particle size of the lipid nanoparticle may be increased and/or decreased. The change in particle size may be able to help counter biological reaction such as, but not limited to, inflammation or may increase the biological effect of the modified mRNA delivered to mammals.

Pharmaceutically acceptable excipients used in the manufacture of pharmaceutical compositions include, but are not limited to, inert diluents, surface active agents and/or emulsifiers, preservatives, buffering agents, lubricating agents, and/or oils. Such excipients may optionally be included in the pharmaceutical formulations of the invention.

Lipidoids

The synthesis of lipidoids has been extensively described and formulations containing these compounds are particularly suited for delivery of polynucleotides (see Mahon et al., Bioconjug Chem. 2010 21:1448-1454; Schroeder et al., J Intern Med. 2010 267:9-21; Akinc et al., Nat Biotechnol. 2008 26:561-569; Love et al., Proc Natl Acad Sci USA. 2010 107:1864-1869; Siegwart et al., Proc Natl Acad Sci USA. 2011 108:12996-3001: all of which are incorporated herein in their entireties).

While these lipidoids have been used to effectively deliver double stranded small interfering RNA molecules in rodents and non-human primates (see Akinc et al., Nat Biotechnol. 2008 26:561-569; Frank-Kamenetsky et al., Proc Natl Acad Sci USA. 2008 105:11915-11920; Akinc et al., Mol Ther. 2009 17:872-879; Love et al., Proc Natl Acad Sci USA. 2010 107:1864-1869; Leuschner et al., Nat Biotechnol. 2011 29:1005-1010; all of which is incorporated herein in their entirety), the present disclosure describes their formulation and use in delivering NAVs or polynucleotides contained therein.

Complexes, micelles, liposomes or particles can be prepared containing these lipidoids and therefore, can result in an effective delivery of the polynucleotide, as judged by the production of an encoded protein, following the injection of a lipidoid formulation via localized and/or systemic routes of administration. Lipidoid complexes of polynucleotides can be administered by various means including, but not limited to, intravenous, intramuscular, or subcutaneous routes.

In vivo delivery of nucleic acids may be affected by many parameters, including, but not limited to, the formulation composition, nature of particle PEGylation, degree of loading, polynucleotide to lipid ratio, and biophysical parameters such as, but not limited to, particle size (Akinc et al., Mol Ther. 2009 17:872-879; herein incorporated by reference in its entirety). As an example, small changes in the anchor chain length of poly(ethylene glycol) (PEG) lipids may result in significant effects on in vivo efficacy. Formulations with the different lipidoids, including, but not limited to penta[3-(1-laurylaminopropionyl)]-triethylenetetramine hydrochloride (TETA-5LAP; aka 98N12-5, see Murugaiah et al., Analytical Biochemistry, 401:61 (2010); herein incorporated by reference in its entirety), C12-200 (including derivatives and variants), and MD1, can be tested for in vivo activity.

The lipidoid referred to herein as “98N12-5” is disclosed by Akinc et al., Mol Ther. 2009 17:872-879 and is incorporated by reference in its entirety.

The lipidoid referred to herein as “C12-200” is disclosed by Love et al., Proc Natl Acad Sci USA. 2010 107:1864-1869 and Liu and Huang, Molecular Therapy. 2010 669-670; both of which are herein incorporated by reference in their entirety. The lipidoid formulations can include particles comprising either 3 or 4 or more components in addition to polynucleotides. As an example, formulations with certain lipidoids, include, but are not limited to, 98N12-5 and may contain 42% lipidoid, 48% cholesterol and 10% PEG (C14 alkyl chain length). As another example, formulations with certain lipidoids, include, but are not limited to, C12-200 and may contain 50% lipidoid, 10% disteroylphosphatidyl choline, 38.5% cholesterol, and 1.5% PEG-DMG.

In one embodiment, a polynucleotide formulated with a lipidoid for systemic intravenous administration can target the liver. For example, a final optimized intravenous formulation using polynucleotides, and comprising a lipid molar composition of 42% 98N12-5, 48% cholesterol, and 10% PEG-lipid with a final weight ratio of about 7.5 to 1 total lipid to polynucleotides, and a C14 alkyl chain length on the PEG lipid, with a mean particle size of roughly 50-60 nm, can result in the distribution of the formulation to be greater than 90% to the liver. (see, Akinc et al., Mol Ther. 2009 17:872-879; herein incorporated by reference in its entirety). In another example, an intravenous formulation using a C12-200 (see U.S. provisional application 61/175,770 and published international application WO2010129709, each of which is herein incorporated by reference in their entirety) lipidoid may have a molar ratio of 50/10/38.5/1.5 of C12-200/disteroylphosphatidyl choline/cholesterol/PEG-DMG, with a weight ratio of 7 to 1 total lipid to polynucleotides, and a mean particle size of 80 nm may be effective to deliver polynucleotides to hepatocytes (see, Love et al., Proc Natd Acad Sci USA. 2010 107:1864-1869 herein incorporated by reference in its entirety). In another embodiment, an MD1 lipidoid-containing formulation may be used to effectively deliver polynucleotides to hepatocytes in vivo.

The characteristics of optimized lipidoid formulations for intramuscular or subcutaneous routes may vary significantly depending on the target cell type and the ability of formulations to diffuse through the extracellular matrix into the blood stream. While a particle size of less than 150 nm may be desired for effective hepatocyte delivery due to the size of the endothelial fenestrae (see, Akinc et al., Mol Ther. 2009 17:872-879 herein incorporated by reference in its entirety), use of a lipidoid-formulated NAVs to deliver the formulation to other cells types including, but not limited to, endothelial cells, myeloid cells, and muscle cells may not be similarly size-limited.

Use of lipidoid formulations to deliver siRNA in vivo to other non-hepatocyte cells such as myeloid cells and endothelium has been reported (see Akinc et al., Nat Biotechnol. 2008 26:561-569; Leuschner et al., Nat Biotechnol. 2011 29:1005-1010; Cho et al. Adv. Funct. Mater. 2009 19:3112-3118; 8^thInternational Judah Folkman Conference, Cambridge, MA Oct. 8-9, 2010; each of which is herein incorporated by reference in its entirety). Effective delivery to myeloid cells, such as monocytes, lipidoid formulations may have a similar component molar ratio. Different ratios of lipidoids and other components including, but not limited to, disteroylphosphatidyl choline, cholesterol and PEG-DMG, may be used to optimize the formulation of the RNAVs for delivery to different cell types including, but not limited to, hepatocytes, myeloid cells, muscle cells, etc. For example, the component molar ratio may include, but is not limited to, 50% C12-200, 10% disteroylphosphatidyl choline, 38.5% cholesterol, and %1.5 PEG-DMG (see Leuschner et al., Nat Biotechnol 2011 29:1005-1010: herein incorporated by reference in its entirety). The use of lipidoid formulations for the localized delivery of nucleic acids to cells (such as, but not limited to, adipose cells and muscle cells) via either subcutaneous or intramuscular delivery, may not require all of the formulation components desired for systemic delivery, and as such may comprise only the lipidoid and the NAV.

Combinations of different lipidoids may be used to improve the efficacy of polynucleotides directed protein production as the lipidoids may be able to increase cell transfection by the RNAV; and/or increase the translation of encoded protein (see Whitehead et al., Mol. Ther. 2011, 19:1688-1694, herein incorporated by reference in its entirety).

Liposomes, Lipoplexes, and Lipid Nanoparticles

The NAVs of the invention can be formulated using one or more liposomes, lipoplexes, or lipid nanoparticles. In one embodiment, pharmaceutical compositions of NAVs include liposomes. Liposomes are artificially-prepared vesicles which may primarily be composed of a lipid bilayer and may be used as a delivery vehicle for the administration of nutrients and pharmaceutical formulations. Liposomes can be of different sizes such as, but not limited to, a multilamellar vesicle (MLV) which may be hundreds of nanometers in diameter and may contain a series of concentric bilayers separated by narrow aqueous compartments, a small unicellular vesicle (SUV) which may be smaller than 50 nm in diameter, and a large unilamellar vesicle (LUV) which may be between 50 and 500 nm in diameter. Liposome design may include, but is not limited to, opsonins or ligands in order to improve the attachment of liposomes to unhealthy tissue or to activate events such as, but not limited to, endocytosis. Liposomes may contain a low or a high pH in order to improve the delivery of the pharmaceutical formulations.

The formation of liposomes may depend on the physicochemical characteristics such as, but not limited to, the pharmaceutical formulation entrapped and the liposomal ingredients, the nature of the medium in which the lipid vesicles are dispersed, the effective concentration of the entrapped substance and its potential toxicity, any additional processes involved during the application and/or delivery of the vesicles, the optimization size, polydispersity and the shelf-life of the vesicles for the intended application, and the batch-to-batch reproducibility and possibility of large-scale production of safe and efficient liposomal products.

As a non-limiting example, liposomes such as synthetic membrane vesicles may be prepared by the methods, apparatus and devices described in US Patent Publication No. US20130177638, US20130177637, US20130177636, US20130177635, US20130177634, US20130177633. US20130183375, US20130183373 and US20130183372, the contents of each of which are herein incorporated by reference in its entirety.

In one embodiment, pharmaceutical compositions described herein may include, without limitation, liposomes such as those formed from 1,2-dioleyloxy-N,N-dimethylaminopropane (DODMA) liposomes, DiLa2 liposomes from Marina Biotech (Bothell, WA), 1,2-dilinoleyloxy-3-dimethylaminopropane (DLin-DMA), 2,2-dilinoleyl-4-(2-dimethylaminoethyl)-[1,3]-dioxolane (DLin-KC2-DMA), and MC3 (US20100324120; herein incorporated by reference in its entirety) and liposomes which may deliver small molecule drugs such as, but not limited to, DOXIL® from Janssen Biotech, Inc. (Horsham, PA).

In one embodiment, pharmaceutical compositions described herein may include, without limitation, liposomes such as those formed from the synthesis of stabilized plasmid-lipid particles (SPLP) or stabilized nucleic acid lipid particle (SNALP) that have been previously described and shown to be suitable for oligonucleotide delivery in vitro and in vivo (see Wheeler et al. Gene Therapy. 1999 6:271-281; Zhang et al. Gene Therapy. 1999 6:1438-1447; Jeffs et al. Pharm Res. 2005 22:362-372; Morrissey et al., Nat Biotechnol. 2005 2:1002-1007; Zimmermann et al., Nature. 2006 441:111-114; Heyes et al. J Contr Rel. 2005 107:276-287; Semple et al. Nature Biotech. 2010 28:172-176; Judge et al. J Clin Invest. 2009 119:661-673; deFougerolles Hum Gene Ther. 2008 19:125-132; U.S. Patent Publication No US20130122104; all of which are incorporated herein in their entireties). The original manufacture method by Wheeler et al. was a detergent dialysis method, which was later improved by Jeffs et al. and is referred to as the spontaneous vesicle formation method. The liposome formulations are composed of 3 to 4 lipid components in addition to the polynucleotide. As an example a liposome can contain, but is not limited to, 55% cholesterol, 20% disteroylphosphatidyl choline (DSPC), 10% PEG-S-DSG, and 15% 1,2-dioleyloxy-N,N-dimethylaminopropane (DODMA), as described by Jeffs et al. As another example, certain liposome formulations may contain, but are not limited to, 48% cholesterol, 20% DSPC, 2% PEG-c-DMA, and 30% cationic lipid, where the cationic lipid can be 1,2-distearloxy-N,N-dimethylaminopropane (DSDMA), DODMA, DLin-DMA, or 1,2-dilinolenyloxy-3-dimethylaminopropane (DLenDMA), as described by Heyes et al.

In some embodiments, liposome formulations may comprise from about about 25.0% cholesterol to about 40.0% cholesterol, from about 30.0% cholesterol to about 45.0% cholesterol, from about 35.0% cholesterol to about 50.0% cholesterol and/or from about 48.5% cholesterol to about 60% cholesterol. In a preferred embodiment, formulations may comprise a percentage of cholesterol selected from the group consisting of 28.5%, 31.5%, 33.5%, 36.5%, 37.0%, 38.5%, 39.0% and 43.5%. In some embodiments, formulations may comprise from about 5.0% to about 10.0% DSPC and/or from about 7.0% to about 15.0% DSPC.

In one embodiment, pharmaceutical compositions may include liposomes which may be formed to deliver polynucleotides which may encode at least one immunogen (antigen) or any other polypeptide of interest. The NAV may be encapsulated by the liposome and/or it may be contained in an aqueous core which may then be encapsulated by the liposome (see International Pub. Nos. WO2012031046, WO2012031043, WO2012030901 and WO2012006378 and US Patent Publication No. US20130189351, US20130195969 and US20130202684; the contents of each of which are herein incorporated by reference in their entirety).

In another embodiment, liposomes may be formulated for targeted delivery. As a non-limiting example, the liposome may be formulated for targeted delivery to the liver. The liposome used for targeted delivery may include, but is not limited to, the liposomes described in and methods of making liposomes described in US Patent Publication No. US20130195967, the contents of which are herein incorporated by reference in its entirety.

In another embodiment, the polynucleotide which may encode an immunogen (antigen) may be formulated in a cationic oil-in-water emulsion where the emulsion particle comprises an oil core and a cationic lipid which can interact with the polynucleotide anchoring the molecule to the emulsion particle (see International Pub. No. WO2012006380; herein incorporated by reference in its entirety).

In one embodiment, the NAVs may be formulated in a water-in-oil emulsion comprising a continuous hydrophobic phase in which the hydrophilic phase is dispersed. As a non-limiting example, the emulsion may be made by the methods described in International Publication No. WO201087791, the contents of which are herein incorporated by reference in its entirety.

In another embodiment, the lipid formulation may include at least cationic lipid, a lipid which may enhance transfection and a least one lipid which contains a hydrophilic head group linked to a lipid moiety (International Pub. No. WO2011076807 and U.S. Pub. No. 20110200582; the contents of each of which is herein incorporated by reference in their entirety). In another embodiment, the polynucleotides encoding an immunogen may be formulated in a lipid vesicle which may have crosslinks between functionalized lipid bilayers (see U.S. Pub. No. 20120177724, the contents of which is herein incorporated by reference in its entirety).

In one embodiment, the polynucleotides may be formulated in a liposome as described in International Patent Publication No. WO2013086526, the contents of which is herein incorporated by reference in its entirety. The NAVs may be encapsulated in a liposome using reverse pH gradients and/or optimized internal buffer compositions as described in International Patent Publication No. WO2013086526, the contents of which is herein incorporated by reference in its entirety.

In one embodiment, the NAV pharmaceutical compositions may be formulated in liposomes such as, but not limited to, DiLa2 liposomes (Marina Biotech, Bothell, WA), SMARTICLES® (Marina Biotech, Bothell, WA), neutral DOPC (1,2-dioleoyl-sn-glycero-3-phosphocholine) based liposomes (e.g., siRNA delivery for ovarian cancer (Landen et al. Cancer Biology & Therapy 2006 5(12)1708-1713); herein incorporated by reference in its entirety) and hyaluronan-coated liposomes (Quiet Therapeutics, Israel).

In one embodiment, the cationic lipid may be a low molecular weight cationic lipid such as those described in US Patent Application No. 20130090372, the contents of which are herein incorporated by reference in its entirety.

In one embodiment, the NAVs may be formulated in a lipid vesicle which may have crosslinks between functionalized lipid bilayers.

In one embodiment, the NAVs may be formulated in a liposome comprising a cationic lipid. The liposome may have a molar ratio of nitrogen atoms in the cationic lipid to the phophates in the RNA (N:P ratio) of between 1:1 and 20:1 as described in International Publication No. WO2013006825, herein incorporated by reference in its entirety. In another embodiment, the liposome may have a N:P ratio of greater than 20:1 or less than 1:1.

In one embodiment, the NAVs may be formulated in a lipid-polycation complex. The formation of the lipid-polycation complex may be accomplished by methods known in the art and/or as described in U.S. Pub. No. 20120178702, herein incorporated by reference in its entirety. As a non-limiting example, the polycation may include a cationic peptide or a polypeptide such as, but not limited to, polylysine, polyornithine and/or polyarginine and the cationic peptides described in International Pub. No. WO2012013326 or US Patent Pub. No. US20130142818; each of which is herein incorporated by reference in its entirety. In another embodiment, the NAVs may be formulated in a lipid-polycation complex which may further include a non-cationic lipid such as, but not limited to, cholesterol or dioleoyl phosphatidylethanolamine (DOPE).

In one embodiment, the NAVs may be formulated in an aminoalcohol lipidoid. Aminoalcohol lipidoids which may be used in the present invention may be prepared by the methods described in U.S. Pat. No. 8,450,298, herein incorporated by reference in its entirety.

The liposome formulation may be influenced by, but not limited to, the selection of the cationic lipid component, the degree of cationic lipid saturation, the nature of the PEGylation, ratio of all components and biophysical parameters such as size. In one example by Semple et al. (Semple et al. Nature Biotech. 2010 28:172-176; herein incorporated by reference in its entirety), the liposome formulation was composed of 57.1% cationic lipid, 7.1% dipalmitoylphosphatidylcholine, 34.3% cholesterol, and 1.4% PEG-c-DMA. As another example, changing the composition of the cationic lipid could more effectively deliver siRNA to various antigen presenting cells (Basha et al. Mol Ther. 2011 19:2186-2200; herein incorporated by reference in its entirety). In some embodiments, liposome formulations may comprise from about 35 to about 45% cationic lipid, from about 40% to about 50% cationic lipid, from about 50% to about 60% cationic lipid and/or from about 55% to about 65% cationic lipid. In some embodiments, the ratio of lipid to mRNA in liposomes may be from about about 5:1 to about 20:1, from about 10:1 to about 25:1, from about 15:1 to about 30:1 and/or at least 30:1.

In some embodiments, the ratio of PEG in the lipid nanoparticle (LNP) formulations may be increased or decreased and/or the carbon chain length of the PEG lipid may be modified from C14 to C18 to alter the pharmacokinetics and/or biodistribution of the LNP formulations. As a non-limiting example, LNP formulations may contain from about 0.5% to about 3.0%, from about 1.0% to about 3.5%, from about 1.5% to about 4.0%, from about 2.0% to about 4.5%, from about 2.5% to about 5.0% and/or from about 3.0% to about 6.0% of the lipid molar ratio of PEG-c-DOMG (R-3-[(w-methoxy-poly(ethyleneglycol)2000)carbamoyl)]-1,2-dimyristyloxypropyl-3-amine) (also referred to herein as PEG-DOMG) as compared to the cationic lipid, DSPC and cholesterol. In another embodiment the PEG-c-DOMG may be replaced with a PEG lipid such as, but not limited to, PEG-DSG (1,2-Disteamyl-sn-glycerol, methoxypolyethylene glycol), PEG-DMG (1,2-Dimyristoyl-sn-glycerol) and/or PEG-DPG (1,2-Dipalmitoyl-sn-glycerol, methoxypolyethylene glycol). The cationic lipid may be selected from any lipid known in the art such as, but not limited to, DLin-MC3-DMA, DLin-DMA, C12-200 and DLin-KC2-DMA.

In one embodiment, the NAVs may be formulated in a lipid nanoparticle such as those described in International Publication No. WO2012170930, the contents of which is herein incorporated by reference in its entirety.

In one embodiment, the NAV formulation comprising the polynucleotide is a nanoparticle which may comprise at least one lipid. The lipid may be selected from, but is not limited to, DLin-DMA, DLin-K-DMA, 98N12-5, C12-200, DLin-MC3-DMA, DLin-KC2-DMA, DODMA, PLGA, PEG, PEG-DMG, PEGylated lipids and amino alcohol lipids. In another aspect, the lipid may be a cationic lipid such as, but not limited to, DLin-DMA, DLin-D-DMA, DLin-MC3-DMA, DLin-KC2-DMA, DODMA and amino alcohol lipids. The amino alcohol cationic lipid may be the lipids described in and/or made by the methods described in US Patent Publication No. US20130150625, herein incorporated by reference in its entirety. As a non-limiting example, the cationic lipid may be 2-amino-3-[(9Z,12Z)-octadeca-9,12-dien-1-yloxy]-2-{[(9Z,2Z)-octadeca-9,12-dien-1-yloxy]methyl}propan-1-ol (Compound 1 in US20130150625); 2-amino-3-[(9Z)-octadec-9-en-1-yloxy]-2-{[(9Z)-octadec-9-en-1-yloxy]methyl}propan-1-ol (Compound 2 in US20130150625); 2-amino-3-[(9Z,12Z)-octadeca-9,12-dien-1-yloxy]-2-[(octyloxy)methyl]propan-1-ol (Compound 3 in US20130150625); and 2-(dimethylamino)-3-[(9Z,12Z)-octadeca-9,12-dien-1-yloxy]-2-{[(9Z,12Z)-octadeca-9,12-dien-1-yloxy]methyl}propan-1-ol (Compound 4 in US20130150625); or any pharmaceutically acceptable salt or stereoisomer thereof.

Lipid nanoparticle formulations typically comprise a lipid, in particular, an ionizable cationic lipid, for example, 2,2-dilinoleyl-4-dimethylaminoethyl-[1,3]-dioxolane (DLin-KC2-DMA), dilinoleyl-methyl-4-dimethylaminobutyrate (DLin-MC3-DMA), or di((Z)-non-2-en-1-yl) 9-((4-(dimethylamino)butanoyl)oxy)heptadecanedioate (L319), and further comprise a neutral lipid, a sterol and a molecule capable of reducing particle aggregation, for example a PEG or PEG-modified lipid.

In one embodiment, the lipid nanoparticle formulation consists essentially of (i) at least one lipid selected from the group consisting of 2,2-dilinoleyl-4-dimethylaminoethyl-[1,3]-dioxolane (DLin-KC2-DMA), dilinoleyl-methyl-4-dimethylaminobutyrate (DLin-MC3-DMA), and di((Z)-non-2-en-1-yl) 9-((4-(dimethylamino)butanoyl)oxy)heptadecanedioate (L319); (ii) a neutral lipid selected from DSPC, DPPC, POPC, DOPE and SM; (iii) a sterol, e.g., cholesterol; and (iv) a PEG-lipid, e.g., PEG-DMG or PEG-cDMA, in a molar ratio of about 20-60% cationic lipid: 5-25% neutral lipid: 25-55% sterol; 0.5-15% PEG-lipid.

In one embodiment, the formulation includes from about 25% to about 75% on a molar basis of a cationic lipid selected from 2,2-dilinoleyl-4-dimethylaminoethyl-[1,3]-dioxolane (DLin-KC2-DMA), dilinoleyl-methyl-4-dimethylaminobutyrate (DLin-MC3-DMA), and di((Z)-non-2-en-1-yl) 9-((4-(dimethylamino)butanoyl)oxy)heptadecanedioate (1319), e.g., from about 35 to about 65%, from about 45 to about 65%, about 60%, about 57.5%, about 50% or about 40% on a molar basis.

In one embodiment, the formulation includes from about 0.5% to about 15% on a molar basis of the neutral lipid e.g., from about 3 to about 12%, from about 5 to about 10% or about 15%, about 10%, or about 7.5% on a molar basis. Exemplary neutral lipids include, but are not limited to, DSPC, POPC, DPPC, DOPE and SM. In one embodiment, the formulation includes from about 5% to about 50% on a molar basis of the sterol (e.g., about 15 to about 45%, about 20 to about 40%, about 40%, about 38.5%, about 35%, or about 31% on a molar basis. An exemplary sterol is cholesterol. In one embodiment, the formulation includes from about 0.5% to about 20% on a molar basis of the PEG or PEG-modified lipid (e.g., about 0.5 to about 10%, about 0.5 to about 5%, about 1.5%, about 0.5%, about 1.5%, about 3.5%, or about 5% on a molar basis. In one embodiment, the PEG or PEG modified lipid comprises a PEG molecule of an average molecular weight of 2,000 Da. In other embodiments, the PEG or PEG modified lipid comprises a PEG molecule of an average molecular weight of less than 2,000, for example around 1,500 Da, around 1,000 Da, or around 500 Da. Exemplary PEG-modified lipids include, but are not limited to, PEG-distearoyl glycerol (PEG-DMG) (also referred herein as PEG-C₁₄or C₁₄-PEG), PEG-cDMA (further discussed in Reyes et al. J. Controlled Release, 107, 276-287 (2005) the contents of which are herein incorporated by reference in its entirety)

In one embodiment, the formulations of the inventions include 25-75% of a cationic lipid selected from 2,2-dilinoleyl-4-dimethylaminoethyl-[1,3]-dioxolane (DLin-KC2-DMA), dilinoleyl-methyl-4-dimethylaminobutyrate (DLin-MC3-DMA), and di((Z)-non-2-en-1-yl) 9-((4-(dimethylamino)butanoyl)oxy)heptadecanedioate (L319), 0.5-15% of the neutral lipid, 5-50% of the sterol, and 0.5-20% of the PEG or PEG-modified lipid on a molar basis.

In one embodiment, the formulations of the inventions include 35-65% of a cationic lipid selected from 2,2-dilinoleyl-4-dimethylaminoethyl-[1,3]-dioxolane (DLin-KC2-DMA), dilinoleyl-methyl-4-dimethylaminobutyrate (DLin-MC3-DMA), and di((Z)-non-2-en-1-yl) 9-((4-(dimethylamino)butanoyl)oxy)heptadecanedioate (L319), 3-12% of the neutral lipid, 15-45% of the sterol, and 0.5-10% of the PEG or PEG-modified lipid on a molar basis.

In one embodiment, the formulations of the inventions include 45-65% of a cationic lipid selected from 2,2-dilinoleyl-4-dimethylaminoethyl-[1,3]-dioxolane (DLin-KC2-DMA), dilinoleyl-methyl-4-dimethylaminobutyrate (DLin-MC3-DMA), and di((Z)-non-2-en-1-yl) 9-((4-(dimethylamino)butanoyl)oxy)heptadecanedioate (L319), 5-10% of the neutral lipid, 25-40% of the sterol, and 0.5-10% of the PEG or PEG-modified lipid on a molar basis.

In one embodiment, the formulations of the inventions include about 60% of a cationic lipid selected from 2,2-dilinoleyl-4-dimethylaminoethyl-[1,3]-dioxolane (DLin-KC2-DMA), dilinoleyl-methyl-4-dimethylaminobutyrate (DLin-MC3-DMA), and di((Z)-non-2-en-1-yl) 9-((4-(dimethylamino)butanoyl)oxy)heptadecanedioate (1319), about 7.5% of the neutral lipid, about 31% of the sterol, and about 1.5% of the PEG or PEG-modified lipid on a molar basis.

In one embodiment, the formulations of the inventions include about 50% of a cationic lipid selected from 2,2-dilinoleyl-4-dimethylaminoethyl-[1,3]-dioxolane (DLin-KC2-DMA), dilinoleyl-methyl-4-dimethylaminobutyrate (DLin-MC3-DMA), and di((Z)-non-2-en-1-yl) 9-((4-(dimethylamino)butanoyl)oxy)heptadecanedioate (L319), about 10% of the neutral lipid, about 38.5% of the sterol, and about 1.5% of the PEG or PEG-modified lipid on a molar basis.

In one embodiment, the formulations of the inventions include about 50% of a cationic lipid selected from 2,2-dilinoleyl-4-dimethylaminoethyl-[1,3]-dioxolane (DLin-KC2-DMA), dilinoleyl-methyl-4-dimethylaminobutyrate (DLin-MC3-DMA), and di((Z)-non-2-en-1-yl) 9-((4-(dimethylamino)butanoyl)oxy)heptadecanedioate (L319), about 10% of the neutral lipid, about 35% of the sterol, about 4.5% or about 5% of the PEG or PEG-modified lipid, and about 0.5% of the targeting lipid on a molar basis.

In one embodiment, the formulations of the inventions include about 40% of a cationic lipid selected from 2,2-dilinoleyl-4-dimethylaminoethyl-[1,3]-dioxolane (DLin-KC2-DMA), dilinoleyl-methyl-4-dimethylaminobutyrate (DLin-MC3-DMA), and di((Z)-non-2-en-1-yl) 9-((4-(dimethylamino)butanoyl)oxy)heptadecanedioate (L319), about 15% of the neutral lipid, about 40% of the sterol, and about 5% of the PEG or PEG-modified lipid on a molar basis.

In one embodiment, the formulations of the inventions include about 57.2% of a cationic lipid selected from 2,2-dilinoleyl-4-dimethylaminoethyl-[1,3]-dioxolane (DLin-KC2-DMA), dilinoleyl-methyl-4-dimethylaminobutyrate (DLin-MC3-DMA), and di((Z)-non-2-en-1-yl) 9-((4-(dimethylamino)butanoyl)oxy)heptadecanedioate (L319), about 7.1% of the neutral lipid, about 34.3% of the sterol, and about 1.4% of the PEG or PEG-modified lipid on a molar basis.

In one embodiment, the formulations of the inventions include about 57.5% of a cationic lipid selected from the PEG lipid is PEG-cDMA (PEG-cDMA is further discussed in Reyes et al. (J. Controlled Release, 107, 276-287 (2005), the contents of which are herein incorporated by reference in its entirety), about 7.5% of the neutral lipid, about 31.5% of the sterol, and about 3.5% of the PEG or PEG-modified lipid on a molar basis.

In preferred embodiments, lipid nanoparticle formulation consists essentially of a lipid mixture in molar ratios of about 20-70% cationic lipid: 5-45% neutral lipid: 20-55% cholesterol: 0.5-15% PEG-modified lipid; more preferably in a molar ratio of about 20-60% cationic lipid: 5-25% neutral lipid: 25-55% cholesterol: 0.5-15% PEG-modified lipid.

In particular embodiments, the molar lipid ratio is approximately 50/10/38.5/1.5 (mol % cationic lipid/neutral lipid, e.g., DSPC/Chol/PEG-modified lipid, e.g., PEG-DMG, PEG-DSG or PEG-DPG), 57.2/7.1134.3/1.4 (mol % cationic lipid/ neutral lipid, e.g., DPPC/Chol/PEG-modified lipid, e.g., PEG-cDMA), 40/15/40/5 (mol % cationic lipid/neutral lipid, e.g., DSPC/Cho/PEG-modified lipid, e.g., PEG-DMG), 50/10/35/4.5/0.5 (mol % cationic lipid/neutral lipid, e.g., DSPC/Chol/PEG-modified lipid, e.g., PEG-DSG), 50/10/35/5 (cationic lipid/neutral lipid, e.g., DSPC/Chol/PEG-modified lipid, e.g., PEG-DMG), 40/10/40/10 (mol % cationic lipid/neutral lipid, e.g., DSPC/Chol/PEG-modified lipid, e.g., PEG-DMG or PEG-cDMA), 35/15/40/10 (mol % cationic lipid/neutral lipid, e.g., DSPC/Chol/PEG-modified lipid, e.g., PEG-DMG or PEG-cDMA) or 52/13/30/5 (mol % cationic lipid/neutral lipid, e.g., DSPC/Cho/PEG-modified lipid, e.g., PEG-DMG or PEG-cDMA).

Exemplary lipid nanoparticle compositions and methods of making same are described, for example, in Semple et al. (2010) Nat. Biotechnol. 28:172-176; Jayarama et al. (2012), Angew. Chen. Int. Ed., 51: 8529-8533; and Maier et al. (2013) Molecular Therapy 21, 1570-1578 (the contents of each of which are incorporated herein by reference in their entirety).

In one embodiment, the lipid nanoparticle formulations described herein may comprise a cationic lipid, a PEG lipid and a structural lipid and optionally comprise a non-cationic lipid. As a non-limiting example, the lipid nanoparticle may comprise about 40-60% of cationic lipid, about 5-15% of a non-cationic lipid, about 1-2% of a PEG lipid and about 30-50% of a structural lipid. As another non-limiting example, the lipid nanoparticle may comprise about 50% cationic lipid, about 10% non-cationic lipid, about 1.5% PEG lipid and about 38.5% structural lipid. As yet another non-limiting example, the lipid nanoparticle may comprise about 55% cationic lipid, about 10% non-cationic lipid, about 2.5% PEG lipid and about 32.5% structural lipid. In one embodiment, the cationic lipid may be any cationic lipid described herein such as, but not limited to, DLin-KC2-DMA, DLin-MC3-DMA and L319.

In one embodiment, the lipid nanoparticle formulations described herein may be 4 component lipid nanoparticles. The lipid nanoparticle may comprise a cationic lipid, a non-cationic lipid, a PEG lipid and a structural lipid. As a non-limiting example, the lipid nanoparticle may comprise about 40-60% of cationic lipid, about 5-15% of a non-cationic lipid, about 1-2% of a PEG lipid and about 30-50% of a structural lipid. As another non-limiting example, the lipid nanoparticle may comprise about 50% cationic lipid, about 10% non-cationic lipid, about 1.5% PEG lipid and about 38.5% structural lipid. As yet another non-limiting example, the lipid nanoparticle may comprise about 55% cationic lipid, about 10% non-cationic lipid, about 2.5% PEG lipid and about 32.5% structural lipid. In one embodiment, the cationic lipid may be any cationic lipid described herein such as, but not limited to, DLin-KC2-DMA, DLin-MC3-DMA and L319.

In one embodiment, the lipid nanoparticle formulations described herein may comprise a cationic lipid, a non-cationic lipid, a PEG lipid and a structural lipid. As a non-limiting example, the lipid nanoparticle comprise about 50% of the cationic lipid DLin-KC2-DMA, about 10% of the non-cationic lipid DSPC, about 1.5% of the PEG lipid PEG-DOMG and about 38.5% of the structural lipid cholesterol. As a non-limiting example, the lipid nanoparticle comprise about 50% of the cationic lipid DLin-MC3-DMA, about 10% of the non-cationic lipid DSPC, about 1.5% of the PEG lipid PEG-DOMG and about 38.5% of the structural lipid cholesterol. As a non-limiting example, the lipid nanoparticle comprise about 50% of the cationic lipid DLin-MC3-DMA, about 10% of the non-cationic lipid DSPC, about 1.5% of the PEG lipid PEG-DMG and about 38.5% of the structural lipid cholesterol. As yet another non-limiting example, the lipid nanoparticle comprise about 55% of the cationic lipid L319, about 10% of the non-cationic lipid DSPC, about 2.5% of the PEG lipid PEG-DMG and about 32.5% of the structural lipid cholesterol.

In one embodiment, the cationic lipid may be selected from, but not limited to, a cationic lipid described in International Publication Nos. WO2012040184, WO2011153120, WO2011149733, WO2011090965, WO2011043913, WO2011022460, WO2012061259, WO2012054365, WO2012044638, WO2010080724, WO201021865, WO2008103276, WO2013086373 and WO2013086354, U.S. Pat. Nos. 7,893,302, 7,404,969, 8,283,333, and 8,466,122 and US Patent Publication No. US20100036115, US20120202871, US20130064894, US20130129785. US20130150625, US20130178541 and US20130225836; the contents of each of which are herein incorporated by reference in their entirety. In another embodiment, the cationic lipid may be selected from, but not limited to, formula A described in International Publication Nos. WO2012040184, WO2011153120, WO2011149733, WO2011090965, WO2011043913, WO2011022460, WO2012061259, WO2012054365, WO2012044638 and WO2013116126 or US Patent Publication No. US20130178541 and US20130225836; the contents of each of which is herein incorporated by reference in their entirety. In yet another embodiment, the cationic lipid may be selected from, but not limited to, formula CLI-CLXXIX of International Publication No. WO2008103276, formula CLI-CLXXIX of U.S. Pat. No. 7,893,302, formula CLI-CLXXXXII of U.S. Pat. No. 7,404,969 and formula I-VI of US Patent Publication No. US20100036115, formula I of US Patent Publication No US20130123338; each of which is herein incorporated by reference in their entirety. As a non-limiting example, the cationic lipid may be selected from (20Z,23Z)—N,N-dimethylnonacosa-20,23-dien-10-amine, (17Z,20Z)—N,N-dimemylhexacosa-17,20-dien-9-amine, (1Z,19Z)—N5N-dimethylpentacosa-16, 19-dien-8-amine, (13Z,16Z)—N,N-dimethyldocosa-13,16-dien-5-amine, (12Z,15Z)—N,N-dimethylhenicosa-12,15-dien-4-amine, (14Z,17Z)—N,N-dimethyluricosa-14,17-dien-6-amine, (15Z,18Z)—N,N-dimethyltetracosa-15,18-dien-7-amine, (18Z,21Z)—N,N-dimethylheptacosa-18,21-dien-10-amine, (15Z,18Z)—N,N-dimethyltetracosa-15,18-dien-5-amine, (14Z,17Z)—N,N-dimethyltricosa-14,17-dien-4-amine, (19Z,22Z)—N,N-dimeihyloctacosa-19,22-dien-9-amine, (18Z,21 Z)—N,N-dimethylheptacosa-18,21-dien-8-amine, (17Z,20Z)—N,N-dimethylhexacosa-17,20-dien-7-amine, (16Z,19Z)—N,N-dimethylpentacosa-16,19-dien-6-amine, (22Z,25Z)—N,N-dimethylhentriaconta-22,25-dien-10-amine, (21 Z,24Z)—N,N-dimethyltriaconta-21,24-dien-9-amine, (18Z)—N,N-dimetylheptacos-18-en-10-amine, (17Z)—N,N-dimethylhexacos-17-en-9-amine, (19Z,22Z)—N,N-dimethyloctacosa-19,22-dien-7-amine, N,N-dimethylheptacosan-10-amine, (20Z,23Z)—N-ethyl-N-methylnonacosa-20,23-dien-10-amine, 1-[(11Z,14Z)-1-nonylicosa-11,14-dien-1-yl] pyrrolidine, (20Z)—N,N-dimethylheptacos-20-en-1 O-amine, (15Z)—N,N-dimethyl eptacos-15-en-10-amine, (14Z)—N,N-dimethylnonacos-14-en-10-amine, (17Z)—N,N-dimethylnonacos-17-en-10-amine. (24Z)—N,N-dimethyltritriacont-24-en-10-amine, (20Z)—N,N-dimethylnonacos-20-en-1 O-amine, (22Z)—N,N-dimethylhentriacont-22-en-10-amine, (16Z)—N,N-dimethylpentacos-16-en-8-amine, (12Z,15Z)—N,N-dimethyl-2-nonylhenicosa-12,15-dien-1-amine, (13Z,16Z)—N,N-dimethyl-3-nonyldocosa-13,16-dien-1-amine, N,N-dimethyl-1-[(1S,2R)-2-octylcyclopropyl] eptadecan-8-amine, 1-[(1S,2R)-2-hexylcyclopropyll-N,N-dimethylnonadecan-10-amine, N,N-dimethyl-1-1(1S,2R)-2-octylcyclopropyl]nonadecan-10-amine, N,N-dimethyl-21-[(1S,2R)-2-octylcyclopropyl]henicosan-O-amine,N,N-dimethyl-1-[(1S,2S)-2-{[(1R,2R)-2-pentylcyclopropyl]methyl}cyclopropyl]nonadecan-10-amine,N,N-dimethyl-1-[(1S,2R)-2-octylcyclopropyl]hexadecan-8-amine, N,N-dimethyl-[(1R,2S)-2-undecylcyclopropyl]tetradecan-5-amine. N,N-dimethyl-3-{7-[(1S,2R)-2-octylcyclopropyl]heptyl} dodecan-1-amine, 1-[(1R,2S)-2-hepty lcyclopropyll-N,N-dimethyloctadecan-9-amine, 1-[(1S,2R)-2-decylcyclopropyl]-N,N-dimethylpentadecan-6-amine, N,N-dimethyl-1-[(1S,2R)-2-octylcyclopropyl]pentadecan-8-amine, R—N,N-dimethyl-1-[(9Z,12Z)-octadeca-9,12-dien-1-yloxy]-3-(octyloxy)propan-2-amine, S—N,N-dimethyl-1-[(9Z,12Z)-octadeca-9,12-dien-1-yloxy]-3-(octyloxy)propan-2-amine, 1-{2-[(9Z,12Z)-octadeca-9,12-dien-1-yloxy]-1-[(octyloxy)methyl]ethyl}pyrrolidine, (2S)—N,N-dimethyl-1-[(9Z,12Z)-octadeca-9,12-dien-1-yloxy]-3-[(5Z)-oct-5-en-1-yloxy]propan-2-amine, 1-{2-[(9Z,12Z)-octadeca-9,12-dien-1-yloxy]-1-[(octyloxy)methyl]ethyl}azetidine, (2S)-1-(hexyloxy)-N,N-dimethyl-3-[(9Z,12Z)-octadeca-9,12-dien-1-yloxy]propan-2-amine, (2S)-1-(heptyloxy)-N,N-dimethyl-3-1(9Z,12Z)-octadeca-9,12-dien-1-yloxy]propan-2-amine, N,N-dimethyl-1-(nonyloxy)-3-[(9Z,12Z)-octadeca-9,12-dien-1-yloxy]propan-2-amine. N,N-dimethyl-1-[(9Z)-octadec-9-en-1-yloxy]-3-(octyloxy)propan-2-amine; (2S)—N,N-dimethyl-1-1(6Z,9Z,12Z)-octadeca-6,9,12-trien-1-yloxyl-3-(octyloxy)propan-2-amine, (2S)-1-[(11Z,14Z)-icosa-11,14-dien-1-yloxy]-N,N-dimethyl-3-(pentyloxy)propan-2-amine, (2S)-1-(hexyloxy)-3-[(11Z,14Z)-icosa-11,14-dien-1-yloxy]-N,N-dimethylpropan-2-amine, 1-[(11Z,14Z)-icosa-11,14-dien-1-yloxy]-N,N-dimethyl-3-(octyloxy)propan-2-amine, 1-[(13Z,16Z)-docosa-13,16-dien-1-yloxy]-N,N-dimethyl-3-(octyloxy)propan-2-amine, (2S)-1-[(13Z,16Z)-docosa-13,16-dien-1-yloxy]-3-(hexyloxy)-N,N-dimethylpropan-2-amine, (2S)-1-[(13Z)-docos-13-en-1-yloxy]-3-(hexyloxy)-N,N-dimethylpropan-2-amine, 1-[(13Z)-docos-13-en-1-yloxy]-N,N-dimethyl-3-(octyloxy)propan-2-amine, 1-[(9Z)-hexadec-9-en-1-yloxy]-N,N-dimethyl-3-(octyloxy)propan-2-amine, (2R)—N,N-dimethyl-H(1-metoyloctyl)oxyl-3-[(9Z,12Z)-octadeca-9,12-dien-1-yloxy]propan-2-amine, (2R)-1-[(3,7-dimethyloctyl)oxy]-N,N-dimethyl-3-[(9Z,12Z)-octadeca-9,12-dien-1-yloxy]propan-2-amine, N,N-dimethyl-1-(octyloxy)-3-({8-[(1S,2S)-2-{[(1R,2R)-2-pentylcyclopropyl]methyl}cyclopropyl]octyl}oxy)propan-2-amine, N,N-dimethyl-1-{[8-(2-oc1ylcyclopropyl)octyl]oxy}-3-(octyloxy)propan-2-amine and (11E,20Z,23Z)—N,N-dimethylnonacosa-11,20,2-trien-10-amine or a pharmaceutically acceptable salt or stereoisomer thereof.

In one embodiment, the lipid may be a cleavable lipid such as those described in international Publication No. WO2012170889, herein incorporated by reference in its entirety.

In another embodiment, the lipid may be a cationic lipid such as, but not limited to, Formula (I) of U.S. Patent Application No. US20130064894, the contents of which are herein incorporated by reference in its entirety.

In one embodiment, the cationic lipid may be synthesized by methods known in the art and/or as described in International Publication Nos. WO2012040184, WO2011153120, WO2011149733, WO2011090965, WO2011043913, WO2011022460, WO2012061259. WO2012054365, WO2012044638, WO2010080724. WO201021865, WO2013086373 and WO2013086354; the contents of each of which are herein incorporated by reference in their entirety.

In another embodiment, the cationic lipid may be a trialkyl cationic lipid. Non-limiting examples of trialkyl cationic lipids and methods of making and using the trialkyl cationic lipids are described in International Patent Publication No. WO2013126803, the contents of which are herein incorporated by reference in its entirety.

In one embodiment, the LNP formulations of the NAVs may contain PEG-c-DOMG at 3% lipid molar ratio. In another embodiment, the LNP formulations RNAVs may contain PEG-c-DOMG at 1.5% lipid molar ratio.

In one embodiment, the pharmaceutical compositions of the NAVs may include at least one of the PEGylated lipids described in International Publication No. WO2012099755, the contents of which is herein incorporated by reference in its entirety.

In one embodiment, the LNP formulation may contain PEG-DMG 2000 (1,2-dimyristoyl-sn-glycero-3-phophoethanolamine-N-[methoxy(polyethylene glycol)-2000). In one embodiment, the LNP formulation may contain PEG-DMG 2000, a cationic lipid known in the art and at least one other component. In another embodiment, the LNP formulation may contain PEG-DMG 2000, a cationic lipid known in the art. DSPC and cholesterol. As a non-limiting example, the LNP formulation may contain PEG-DMG 2000, DLin-DMA, DSPC and cholesterol. As another non-limiting example the LNP formulation may contain PEG-DMG 2000, DLin-DMA, DSPC and cholesterol in a molar ratio of 2:40:10:48 (see e.g., Geall et al., Nonviral delivery of self-amplifying RNA vaccines, PNAS 2012; PMID: 22908294; herein incorporated by reference in its entirety).

In one embodiment, the LNP formulation may be formulated by the methods described in International Publication Nos. WO2011127255 or WO2008103276, the contents of each of which is herein incorporated by reference in their entirety. As a non-limiting example, the NAVs described herein may be encapsulated in LNP formulations as described in WO2011127255 and/or WO2008103276; each of which is herein incorporated by reference in their entirety.

In one embodiment, the NAVs described herein may be formulated in a nanoparticle to be delivered by a parenteral route as described in U.S. Pub. No. US20120207845; the contents of which are herein incorporated by reference in its entirety.

In one embodiment, the NAVs may be formulated in a lipid nanoparticle made by the methods described in US Patent Publication No US20130156845 or International Publication No WO2013093648 or WO2012024526, each of which is herein incorporated by reference in its entirety.

The lipid nanoparticles described herein may be made in a sterile environment by the system and/or methods described in US Patent Publication No. US20130164400, herein incorporated by reference in its entirety.

In one embodiment, the LNP formulation may be formulated in a nanoparticle such as a nucleic acid-lipid particle described in U.S. Pat. No. 8,492,359, the contents of which are herein incorporated by reference in its entirety. As a non-limiting example, the lipid particle may comprise one or more active agents or therapeutic agents; one or more cationic lipids comprising from about 50 mol % to about 85 mol % of the total lipid present in the particle; one or more non-cationic lipids comprising from about 13 mol % to about 49.5 mol % of the total lipid present in the particle; and one or more conjugated lipids that inhibit aggregation of particles comprising from about 0.5 mol % to about 2 mol % of the total lipid present in the particle. The nucleic acid in the nanoparticle may be the polynucleotides described herein and/or are known in the art.

In one embodiment, the LNP formulation may be formulated by the methods described in International Publication Nos. WO2011127255 or WO2008103276, the contents of each of which are herein incorporated by reference in their entirety. As a non-limiting example, modified RNA described herein may be encapsulated in LNP formulations as described in WO2011127255 and/or WO2008103276; the contents of each of which are herein incorporated by reference in their entirety.

In one embodiment, LNP formulations described herein may comprise a polycationic composition. As a non-limiting example, the polycationic composition may be selected from formula 1-60 of US Patent Publication No. US20050222064; the content of which is herein incorporated by reference in its entirety. In another embodiment, the LNP formulations comprising a polycationic composition may be used for the delivery of the modified RNA described herein in vivo and/or in vitro.

In one embodiment, the LNP formulations described herein may additionally comprise a permeability enhancer molecule. Non-limiting permeability enhancer molecules are described in US Patent Publication No. US20050222064; the content of which is herein incorporated by reference in its entirety.

In one embodiment, the NAV pharmaceutical compositions may be formulated in liposomes such as, but not limited to. DiLa2 liposomes (Marina Biotech, Bothell, WA), SMARTICLES® (Marina Biotech, Bothell, WA), neutral DOPC (1,2-dioleoyl-sn-glycero-3-phosphocholine) based liposomes (e.g., siRNA delivery for ovarian cancer (Landen et al. Cancer Biology & Therapy 2006 5(12)1708-1713); herein incorporated by reference in its entirety) and hyaluronan-coated liposomes (Quiet Therapeutics, Israel).

In one embodiment, the NAVs may be formulated in a lyophilized gel-phase liposomal composition as described in US Publication No. US2012060293, herein incorporated by reference in its entirety.

The nanoparticle formulations may comprise a phosphate conjugate. The phosphate conjugate may increase in vivo circulation times and/or increase the targeted delivery of the nanoparticle. Phosphate conjugates for use with the present invention may be made by the methods described in International Application No. WO2013033438 or US Patent Publication No. US20130196948, the contents of each of which are herein incorporated by reference in its entirety. As a non-limiting example, the phosphate conjugates may include a compound of any one of the formulas described in International Application No. WO2013033438, herein incorporated by reference in its entirety.

The nanoparticle formulation may comprise a polymer conjugate. The polymer conjugate may be a water soluble conjugate. The polymer conjugate may have a structure as described in U.S. Patent Application No. 20130059360, the contents of which are herein incorporated by reference in its entirety. In one aspect, polymer conjugates with the polynucleotides of the present invention may be made using the methods and/or segmented polymeric reagents described in U.S. Patent Application No. 20130072709, herein incorporated by reference in its entirety. In another aspect, the polymer conjugate may have pendant side groups comprising ring moieties such as, but not limited to, the polymer conjugates described in US Patent Publication No. US20130196948, the contents of which is herein incorporated by reference in its entirety.

The nanoparticle formulations may comprise a conjugate to enhance the delivery of nanoparticles of the present invention in a subject. Further, the conjugate may inhibit phagocytic clearance of the nanoparticles in a subject. In one aspect, the conjugate may be a “self” peptide designed from the human membrane protein CD47 (e.g., the “self” particles described by Rodriguez et al (Science 2013 339, 971-975), herein incorporated by reference in its entirety). As shown by Rodriguez et al. the self peptides delayed macrophage-mediated clearance of nanoparticles which enhanced delivery of the nanoparticles. In another aspect, the conjugate may be the membrane protein CD47 (e.g., see Rodriguez et al. Science 2013 339, 971-975, herein incorporated by reference in its entirety). Rodriguez et al. showed that, similarly to “self” peptides, CD47 can increase the circulating particle ratio in a subject as compared to scrambled peptides and PEG coated nanoparticles.

In one embodiment, the NAVs of the present invention are formulated in nanoparticles which comprise a conjugate to enhance the delivery of the nanoparticles of the present invention in a subject. The conjugate may be the CD47 membrane or the conjugate may be derived from the CD47 membrane protein, such as the “self” peptide described previously. In another aspect the nanoparticle may comprise PEG and a conjugate of CD47 or a derivative thereof. In yet another aspect, the nanoparticle may comprise both the “self” peptide described above and the membrane protein CD47.

In another aspect, a “self” peptide and/or CD47 protein may be conjugated to a virus-like particle or pseudovirion, as described herein for delivery of the NAVs of the present invention.

In another embodiment, NAV pharmaceutical compositions comprising the polynucleotides of the present invention and a conjugate which may have a degradable linkage. Non-limiting examples of conjugates include an aromatic moiety comprising an ionizable hydrogen atom, a spacer moiety, and a water-soluble polymer. As a non-limiting example, pharmaceutical compositions comprising a conjugate with a degradable linkage and methods for delivering such pharmaceutical compositions are described in US Patent Publication No. US20130184443, the contents of which are herein incorporated by reference in its entirety.

The nanoparticle formulations may be a carbohydrate nanoparticle comprising a carbohydrate carrier and a NAV. As a non-limiting example, the carbohydrate carrier may include, but is not limited to, an anhydride-modified phytoglycogen or glycogen-type material, phytoglycogen octenyl succinate, phytoglycogen beta-dextrin, anhydride-modified phytoglycogen beta-dextrin. (See e.g., International Publication No. WO2012109121; the contents of which are herein incorporated by reference in its entirety).

Nanoparticle formulations of the present invention may be coated with a surfactant or polymer in order to improve the delivery of the particle. In one embodiment, the nanoparticle may be coated with a hydrophilic coating such as, but not limited to, PEG coatings and/or coatings that have a neutral surface charge. The hydrophilic coatings may help to deliver nanoparticles with larger payloads such as, but not limited to, NAVs within the central nervous system. As a non-limiting example nanoparticles comprising a hydrophilic coating and methods of making such nanoparticles are described in US Patent Publication No. US20130183244, the contents of which are herein incorporated by reference in its entirety.

In one embodiment, the lipid nanoparticles of the present invention may be hydrophilic polymer particles. Non-limiting examples of hydrophilic polymer particles and methods of making hydrophilic polymer particles are described in US Patent Publication No. US20130210991, the contents of which are herein incorporated by reference in its entirety.

In another embodiment, the lipid nanoparticles of the present invention may be hydrophobic polymer particles.

Lipid nanoparticle formulations may be improved by replacing the cationic lipid with a biodegradable cationic lipid which is known as a rapidly eliminated lipid nanoparticle (reLNP). Ionizable cationic lipids, such as, but not limited to, DLinDMA, DLin-KC2-DMA, and DLin-MC3-DMA, have been shown to accumulate in plasma and tissues over time and may be a potential source of toxicity. The rapid metabolism of the rapidly eliminated lipids can improve the tolerability and therapeutic index of the lipid nanoparticles by an order of magnitude from a 1 mg/kg dose to a 10 mg/kg dose in rat. Inclusion of an enzymatically degraded ester linkage can improve the degradation and metabolism profile of the cationic component, while still maintaining the activity of the reLNP formulation. The ester linkage can be internally located within the lipid chain or it may be terminally located at the terminal end of the lipid chain. The internal ester linkage may replace any carbon in the lipid chain.

In one embodiment, the internal ester linkage may be located on either side of the saturated carbon.

In one embodiment, an immune response may be elicited by delivering a lipid nanoparticle which may include a nanospecies, a polymer and an immunogen. (U.S. Publication No. 20120189700 and International Publication No. WO20l2099805; each of which is herein incorporated by reference in their entirety). The polymer may encapsulate the nanospecies or partially encapsulate the nanospecies. The immunogen may be a recombinant protein, a modified RNA and/or a polynucleotide described herein. In one embodiment, the lipid nanoparticle may be formulated for use in a vaccine such as, but not limited to, against a pathogen.

Lipid nanoparticles may be engineered to alter the surface properties of particles so the lipid nanoparticles may penetrate the mucosal barrier. Mucus is located on mucosal tissue such as, but not limited to, oral (e.g., the buccal and esophageal membranes and tonsil tissue), ophthalmic, gastrointestinal (e.g., stomach, small intestine, large intestine, colon, rectum), nasal, respiratory (e.g., nasal, pharyngeal, tracheal and bronchial membranes), genital (e.g., vaginal, cervical and urethral membranes). Nanoparticles larger than 10-200 nm which are preferred for higher drug encapsulation efficiency and the ability to provide the sustained delivery of a wide array of drugs have been thought to be too large to rapidly diffuse through mucosal barriers. Mucus is continuously secreted, shed, discarded or digested and recycled so most of the trapped particles may be removed from the mucosla tissue within seconds or within a few hours. Large polymeric nanoparticles (200 nm-500 nm in diameter) which have been coated densely with a low molecular weight polyethylene glycol (PEG) diffused through mucus only 4 to 6-fold lower than the same particles diffusing in water (Lai et al. PNAS 2007 104(5):1482-487; Lai et al. Adv Drug Deliv Rev. 2009 61(2): 158-171; each of which is herein incorporated by reference in their entirety). The transport of nanoparticles may be determined using rates of permeation and/or fluorescent microscopy techniques including, but not limited to, fluorescence recovery after photobleaching (FRAP) and high resolution multiple particle tracking (MPT). As a non-limiting example, compositions which can penetrate a mucosal barrier may be made as described in U.S. Pat. No. 8,241,670 or International Patent Publication No. WO2013110028, the contents of each of which are herein incorporated by reference in its entirety.

The lipid nanoparticle engineered to penetrate mucus may comprise a polymeric material (i.e. a polymeric core) and/or a polymer-vitamin conjugate and/or a tri-block co-polymer. The polymeric material may include, but is not limited to, polyamines, polyethers, polyamides, polyesters, polycarbamates, polyureas, polycarbonates, poly(styrenes), polyimides, polysulfones, polyurethanes, polyacetylenes, polyethylenes, polyethyeneimines, polyisocyanates, polyacrylates, polymethacrylates, polyacrylonitriles, and polyarylates. The polymeric material may be biodegradable and/or biocompatible. Non-limiting examples of biocompatible polymers are described in International Patent Publication No. WO2013116804, the contents of which are herein incorporated by reference in its entirety. The polymeric material may additionally be irradiated. As a non-limiting example, the polymeric material may be gamma irradiated (See e.g., International App. No. WO201282165, herein incorporated by reference in its entirety). Non-limiting examples of specific polymers include poly(caprolactone) (PCL), ethylene vinyl acetate polymer (EVA), poly(lactic acid) (PLA), poly(L-lactic acid) (PLLA), poly(glycolic acid) (PGA), poly(lactic acid-co-glycolic acid) (PLGA), poly(L-lactic acid-co-glycolic acid) (PLLGA), poly(D,L-lactide) (PDLA), poly(L-lactide) (PLLA), poly(D,L-lactide-co-caprolactone), poly(D,L-lactide-co-caprolactone-co-glycolide), poly(D,L-lactide-co-PEO-co-D,L-lactide), poly(D,L-lactide-co-PPO-co-D,L-lactide), polyalkyl cyanoacralate, polyurethane, poly-L-lysine (PLL), hydroxypropyl methacrylate (HPMA), polyethyleneglycol, poly-L-glutamic acid, poly(hydroxy acids), polyanhydrides, polyorthoesters, poly(ester amides), polyamides, poly(ester ethers), polycarbonates, polyalkylenes such as polyethylene and polypropylene, polyalkylene glycols such as poly(ethylene glycol) (PEG), polyalkylene oxides (PEO), polyalkylene terephthalates such as poly(ethylene terephthalate), polyvinyl alcohols (PVA), polyvinyl ethers, polyvinyl esters such as poly(vinyl acetate), polyvinyl halides such as poly(vinyl chloride) (PVC), polyvinylpyrrolidone, polysiloxanes, polystyrene (PS), polyurethanes, derivatized celluloses such as alkyl celluloses, hydroxyalkyl celluloses, cellulose ethers, cellulose esters, nitro celluloses, hydroxypropylcellulose, carboxymethylcellulose, polymers of acrylic acids, such as poly(methyl(meth)acrylate) (PMMA), poly(ethyl(meth)acrylate), poly(butyl(meth)acrylate), poly(isobutyl(meth)acrylate), poly(hexyl(meth)acrylate), poly(isodecyl(meth)acrylate), poly(lauryl(meth)acrylate), poly(phenyl(meth)acrylate), poly(methyl acrylate), poly(isopropyl acrylate), poly(isobutyl acrylate), poly(octadecyl acrylate) and copolymers and mixtures thereof, polydioxanone and its copolymers, polyhydroxyalkanoates, polypropylene fumarate, polyoxymethylene, poloxamers, poly(ortho)esters, poly(butyric acid), poly(valeric acid), poly(lactide-co-caprolactone), PEG-PLGA-PEG and trimethylene carbonate, polyvinylpyrrolidone. The lipid nanoparticle may be coated or associated with a co-polymer such as, but not limited to, a block co-polymer (such as a branched polyether-polyamide block copolymer described in International Publication No. WO2013012476, herein incorporated by reference in its entirety), and (poly(ethylene glycol))-(poly(propylene oxide))-(poly(ethylene glycol)) triblock copolymer (see e.g., US Publication 20120121718 and US Publication 20100003337 and U.S. Pat. No. 8,263,665; each of which is herein incorporated by reference in their entirety). The co-polymer may be a polymer that is generally regarded as safe (GRAS) and the formation of the lipid nanoparticle may be in such a way that no new chemical entities are created. For example, the lipid nanoparticle may comprise poloxamers coating PLDA nanoparticles without forming new chemical entities which are still able to rapidly penetrate human mucus (Yang et al. Angew. Chem. Int. Ed. 2011 50:2597-2600; the contents of which are herein incorporated by reference in its entirety). A non-limiting scalable method to produce nanoparticles which can penetrate human mucus is described by Xu et al. (See e.g., J Control Release 2013, 170(2):279-86; the contents of which are herein incorporated by reference in its entirety).

The vitamin of the polymer-vitamin conjugate may be vitamin E. The vitamin portion of the conjugate may be substituted with other suitable components such as, but not limited to, vitamin A, vitamin E, other vitamins, cholesterol, a hydrophobic moiety, or a hydrophobic component of other surfactants (e.g., sterol chains, fatty acids, hydrocarbon chains and alkylene oxide chains).

The lipid nanoparticle engineered to penetrate mucus may include surface altering agents such as, but not limited to, polynucleotides, anionic proteins (e.g., bovine serum albumin), surfactants (e.g., cationic surfactants such as for example dimethyldioctadecyl-ammonium bromide), sugars or sugar derivatives (e.g., cyclodextrin), nucleic acids, polymers (e.g., heparin, polyethylene glycol and poloxamer), mucolytic agents (e.g., N-acetylcysteine, mugwort, bromelain, papain, clerodendrum, acetylcysteine, bromhexine, carbocisteine, eprazinone, mesna, ambroxol, sobrerol, domiodol, letosteine, stepronin, tiopronin, gelsolin, thymosin β4 dornase alfa, neltenexine, erdosteine) and various DNases including rhDNase. The surface altering agent may be embedded or enmeshed in the particle's surface or disposed (e.g., by coating, adsorption, covalent linkage, or other process) on the surface of the lipid nanoparticle. (see e.g., US Publication 20100215580 and US Publication 20080166414 and US20130164343; the contents of each of which is herein incorporated by reference in their entirety).

In one embodiment, the mucus penetrating lipid nanoparticles may comprise at least one polynucleotide described herein. The polynucleotide may be encapsulated in the lipid nanoparticle and/or disposed on the surface of the paricle. The polynucleotide may be covalently coupled to the lipid nanoparticle. Formulations of mucus penetrating lipid nanoparticles may comprise a plurality of nanoparticles. Further, the formulations may contain particles which may interact with the mucus and alter the structural and/or adhesive properties of the surrounding mucus to decrease mucoadhesion which may increase the delivery of the mucus penetrating lipid nanoparticles to the mucosal tissue.

In another embodiment, the mucus penetrating lipid nanoparticles may be a hypotonic formulation comprising a mucosal penetration enhancing coating. The formulation may be hypotonice for the epithelium to which it is being delivered. Non-limiting examples of hypotonic formulations may be found in International Patent Publication No. WO2013110028, the contents of which are herein incorporated by reference in its entirety.

In one embodiment, in order to enhance the delivery through the mucosal barrier the NAV formulation may comprise or be a hypotonic solution. Hypotonic solutions were found to increase the rate at which mucoinert particles such as, but not limited to, mucus-penetrating particles, were able to reach the vaginal epithelial surface (See e.g., Ensign et al. Biomaterials 2013 34(28):6922-9; the contents of which is herein incorporated by reference in its entirety).

In one embodiment, the NAV is formulated as a lipoplex, such as, without limitation, the ATUPLEX™ system, the DACC system, the DBTC system and other siRNA-lipoplex technology from Silence Therapeutics (London, United Kingdom), STEMFECT™ from STEMGENT® (Cambridge, MA), and polyethylenimine (PEI) or protamine-based targeted and non-targeted delivery of nucleic acids acids (Aleku et al. Cancer Res. 2008 68:9788-9798; Strumberg et al. Int J Clin Pharmacol Ther 2012 50:76-78; Santel et al., Gene Ther 2006 13:1222-1234; Santel et al., Gene Ther 2006 13:1360-1370; Gutbier et al., Pulm Pharmacol. Ther. 2010 23:334-344; Kaufmann et al. Microvasc Res 2010 80:286-293Weide et al. J Immunother. 2009 32:498-507; Weide et al. J Immunother. 2008 31:180-188; Pascolo Expert Opin. Biol. Ther. 4:1285-1294; Fotin-Mleczek et al., 2011 J. Immunother. 34:1-15; Song et al., Nature Biotechnol. 2005, 23:709-717; Peer et al., Proc Nati Acad Sci USA. 2007 6; 104:4095-4100; deFougerolles Hum Gene Ther. 2008 19:125-132; all of which are incorporated herein by reference in its entirety).

In one embodiment such formulations may also be constructed or compositions altered such that they passively or actively are directed to different cell types in vivo, including but not limited to hepatocytes, immune cells, tumor cells, endothelial cells, antigen presenting cells, and leukocytes (Akinc et al. Mol Ther. 2010 18:1357-1364; Song et al., Nat Biotechnol. 2005 23:709-717; Judge et al., J Clin invest. 2009 119:661-673; Kaufmann et al., Microvasc Res 2010 80:286-293; Santel et al., Gene Ther 2006 13:1222-1234; Santel et al., Gene Ther 2006 13:1360-1370; Gutbier et al., Pulm Pharmacol. Ther. 2010 23:334-344; Basha et al., Mol. Ther. 2011 19:2186-2200; Fenske and Cullis, Expert Opin Drug Deliv. 2008 5:25-44; Peer et al., Science. 2008 319:627-630; Peer and Lieberman, Gene Ther. 2011 18:1127-1133; all of which are incorporated herein by reference in its entirety). One example of passive targeting of formulations to liver cells includes the DLin-DMA, DLin-KC2-DMA and DLin-MC3-DMA-based lipid nanoparticle formulations which have been shown to bind to apolipoprotein E and promote binding and uptake of these formulations into hepatocytes in vivo (Akinc et al. Mol Ther. 2010 18:1357-1364; herein incorporated by reference in its entirety). Formulations can also be selectively targeted through expression of different ligands on their surface as exemplified by, but not limited by, folate, transferrin, N-acetylgalactosamine (GalNAc), and antibody targeted approaches (Kolhatkar et al., Curr Drug Discov Technol. 2011 8:197-206; Musacchio and Torchilin, Front Biosci. 2011 16:1388-1412; Yu et al., Mol Membr Biol. 2010 27:286-298; Patil et al., Crit Rev Ther Drug Carrier Syst. 2008 25:1-61; Benoit et al., Biomacromolecules. 2011 12:2708-2714; Zhao et al., Expert Opin Drug Deliv. 2008 5:309-319; Akinc et al., Mol Ther. 2010 18:1357-1364; Srinivasan et al., Methods Mol Biol. 2012 820:105-116; Ben-Arie et al., Methods Mol Biol. 2012 757:497-507; Peer 2010 J Control Release. 20:63-68; Peer et al., Proc Natl Acad Sci USA. 2007 104:4095-4100; Kim et al., Methods Mol Biol. 2011 721:339-353; Subramanya et al., Mol Ther. 2010 18:2028-2037; Song et al., Nat Biotechnol. 2005 23:709-717; Peer et al., Science. 2008 319:627-630; Peer and Lieberman, Gene Ther. 2011 18:1127-1133; all of which are incorporated herein by reference in its entirety).

In one embodiment, the NAV is formulated as a solid lipid nanoparticle. A solid lipid nanoparticle (SLN) may be spherical with an average diameter between 10 to 1000 nm. SLN possess a solid lipid core matrix that can solubilize lipophilic molecules and may be stabilized with surfactants and/or emulsifiers. In a further embodiment, the lipid nanoparticle may be a self-assembly lipid-polymer nanoparticle (see Zhang et al., ACS Nano, 2008, 2 (8), pp 1696-1702; the contents of which are herein incorporated by reference in its entirety). As a non-limiting example, the SLN may be the SLN described in International Patent Publication No. WO2013105101, the contents of which are herein incorporated by reference in its entirety. As another non-limiting example, the SLN may be made by the methods or processes described in International Patent Publication No. WO2013105101, the contents of which are herein incorporated by reference in its entirety.

Liposomes, lipoplexes, or lipid nanoparticles may be used to improve the efficacy of polynucleotides directed protein production as these formulations may be able to increase cell transfection by the NAV; and/or increase the translation of encoded protein. One such example involves the use of lipid encapsulation to enable the effective systemic delivery of polyplex plasmid DNA (Heyes et al., Mol Ther. 2007 15:713-720; herein incorporated by reference in its entirety). The liposomes, lipoplexes, or lipid nanoparticles may also be used to increase the stability of the polynucleotide.

In one embodiment, the NAVs of the present invention can be formulated for controlled release and/or targeted delivery. As used herein, “controlled release” refers to a pharmaceutical composition or compound release profile that conforms to a particular pattern of release to effect a therapeutic outcome. In one embodiment, the RNAVs may be encapsulated into a delivery agent described herein and/or known in the art for controlled release and/or targeted delivery. As used herein, the term “encapsulate” means to enclose, surround or encase. As it relates to the formulation of the compounds of the invention, encapsulation may be substantial, complete or partial. The term “substantially encapsulated” means that at least greater than 50, 60, 70, 80, 85, 90, 95, 96, 97, 98, 99, 99.9, 99.9 or greater than 99.999% of the pharmaceutical composition or compound of the invention may be enclosed, surrounded or encased within the delivery agent. “Partially encapsulation” means that less than 10, 10, 20, 30, 40 50 or less of the pharmaceutical composition or compound of the invention may be enclosed, surrounded or encased within the delivery agent. Advantageously, encapsulation may be determined by measuring the escape or the activity of the pharmaceutical composition or compound of the invention using fluorescence and/or electron micrograph. For example, at least 1, 5, 10, 20, 30, 40, 50, 60, 70, 80, 85, 90, 95, 96, 97, 98, 99, 99.9, 99.99 or greater than 99.99% of the pharmaceutical composition or compound of the invention are encapsulated in the delivery agent.

In one embodiment, the controlled release formulation may include, but is not limited to, tri-block co-polymers. As a non-limiting example, the formulation may include two different types of tri-block co-polymers (International Pub. No. WO2012131104 and WO2012131106; the contents of each of which is herein incorporated by reference in its entirety).

In another embodiment, the NAVs may be encapsulated into a lipid nanoparticle or a rapidly eliminated lipid nanoparticle and the lipid nanoparticles or a rapidly eliminated lipid nanoparticle may then be encapsulated into a polymer, hydrogel and/or surgical sealant described herein and/or known in the art. As a non-limiting example, the polymer, hydrogel or surgical sealant may be PLGA, ethylene vinyl acetate (EVAc), poloxamer, GELSITE® (Nanotherapeutics, Inc. Alachua, FL), HYLENEX® (Halozyme Therapeutics, San Diego CA), surgical sealants such as fibrinogen polymers (Ethicon Inc. Cornelia, GA), TISSELL® (Baxter International, Inc Deerfield, IL), PEG-based sealants, and COSEAL® (Baxter International, Inc Deerfield, IL).

In another embodiment, the lipid nanoparticle may be encapsulated into any polymer known in the art which may form a gel when injected into a subject. As another non-limiting example, the lipid nanoparticle may be encapsulated into a polymer matrix which may be biodegradable.

In one embodiment, the NAV formulation for controlled release and/or targeted delivery may also include at least one controlled release coating. Controlled release coatings include, but are not limited to, OPADRY®, polyvinylpyrrolidone/vinyl acetate copolymer, polyvinylpyrrolidone, hydroxypropyl methylcellulose, hydroxypropyl cellulose, hydroxyethyl cellulose, EUDRAGIT RL®, EUDRAGIT RS® and cellulose derivatives such as ethylcellulose aqueous dispersions (AQUACOAT® and SURELEASE®).

In one embodiment, the NAV controlled release and/or targeted delivery formulation may comprise at least one degradable polyester which may contain polycationic side chains. Degradeable polyesters include, but are not limited to, poly(serine ester), poly(L-lactide-co-L-lysine), poly(4-hydroxy-L-proline ester), and combinations thereof. In another embodiment, the degradable polyesters may include a PEG conjugation to form a PEGylated polymer.

In one embodiment, the NAV controlled release and/or targeted delivery formulation comprising at least one polynucleotide may comprise at least one PEG and/or PEG related polymer derivatives as described in U.S. Pat. No. 8,404,222, herein incorporated by reference in its entirety.

In another embodiment, the NAV controlled release delivery formulation comprising at least one polynucleotide may be the controlled release polymer system described in US20130130348, herein incorporated by reference in its entirety.

In one embodiment, the NAVs of the present invention may be encapsulated in a therapeutic nanoparticle, referred to herein as “therapeutic nanoparticle RNAVs.” Therapeutic nanoparticles may be formulated by methods described herein and known in the art such as, but not limited to, International Pub Nos. WO2010005740, WO2010030763, WO2010005721. WO2010005723, WO2012054923, US Pub. Nos. US20110262491, US20100104645, US20100087337, US20100068285, US20110274759, US20100068286, US20120288541, US20130123351 and US20130230567 and U.S. Pat. Nos. 8,206,747, 8,293,276, 8,318,208 and 8,318,211; the contents of each of which are herein incorporated by reference in their entirety. In another embodiment, therapeutic polymer nanoparticles may be identified by the methods described in US Pub No. US20120140790, the contents of which is herein incorporated by reference in its entirety.

In one embodiment, the therapeutic nanoparticle NAV may be formulated for sustained release. As used herein, “sustained release” refers to a pharmaceutical composition or compound that conforms to a release rate over a specific period of time. The period of time may include, but is not limited to, hours, days, weeks, months and years. As a non-limiting example, the sustained release nanoparticle may comprise a polymer and a therapeutic agent such as, but not limited to, the polynucleotides of the present invention (see International Pub No. 2010075072 and US Pub No. US20100216804, US20110217377 and US20120201859, each of which is herein incorporated by reference in their entirety). In another non-limiting example, the sustained release formulation may comprise agents which permit persistent bioavailability such as, but not limited to, crystals, macromolecular gels and/or particulate suspensions (see US Patent Publication No US20130150295, the contents of which is herein incorporated by reference in its entirety).

In one embodiment, the therapeutic nanoparticle NAVs may be formulated to be target specific. As a non-limiting example, the therapeutic nanoparticles may include a corticosteroid (see International Pub. No. WO2011084518; herein incorporated by reference in its entirety). As a non-limiting example, the therapeutic nanoparticles may be formulated in nanoparticles described in international Pub No. WO2008121949, WO2010005726, WO2010005725, WO2011084521 and US Pub No. US20100069426, US20120004293 and US20100104655, each of which is herein incorporated by reference in their entirety.

In one embodiment, the nanoparticles of the present invention may comprise a polymeric matrix. As a non-limiting example, the nanoparticle may comprise two or more polymers such as, but not limited to, polyethylenes, polycarbonates, polyanhydrides, polyhydroxyacids, polypropylfumerates, polycaprolactones, polyamides, polyacetals, polyethers, polyesters, poly(orthoesters), polycyanoacrylates, polyvinyl alcohols, polyurethanes, polyphosphazenes, polyacrylates, polymethacrylates, polycyanoacrylates, polyureas, polystyrenes, polyamines, polylysine, poly(ethylene imine), poly(serine ester), poly(L-lactide-co-L-lysine), poly(4-hydroxy-L-proline ester) or combinations thereof.

In one embodiment, the therapeutic nanoparticle comprises a diblock copolymer. In one embodiment, the diblock copolymer may include PEG in combination with a polymer such as, but not limited to, polyethylenes, polycarbonates, polyanhydrides, polyhydroxyacids, polypropylfumerates, polycaprolactones, polyamides, polyacetals, polyethers, polyesters, poly(orthoesters), polycyanoacrylates, polyvinyl alcohols, polyurethanes, polyphosphazenes, polyacrylates, polymethacrylates, polycyanoacrylates, polyureas, polystyrenes, polyamines, polylysine, poly(ethylene imine), poly(serine ester), poly(L-lactide-co-L-lysine), poly(4-hydroxy-L-proline ester) or combinations thereof. In another embodiment, the diblock copolymer may comprise the diblock copolymers described in European Patent Publication No. the contents of which are herein incorporated by reference in its entirety. In yet another embodiment, the diblock copolymer may be a high-X diblock copolymer such as those described in International Patent Publication No. WO2013120052, the contents of which are herein incorporated by reference in its entirety.

As a non-limiting example the therapeutic nanoparticle comprises a PLGA-PEG block copolymer (see US Pub. No. US20120004293 and U.S. Pat. No. 8,236,330, each of which is herein incorporated by reference in their entirety). In another non-limiting example, the therapeutic nanoparticle is a stealth nanoparticle comprising a diblock copolymer of PEG and PLA or PEG and PLGA (see U.S. Pat. No. 8,246,968 and International Publication No. WO2012166923, the contents of each of which are herein incorporated by reference in its entirety). In yet another non-limiting example, the therapeutic nanoparticle is a stealth nanoparticle or a target-specific stealth nanoparticle as described in US Patent Publication No. US20130172406, the contents of which are herein incorporated by reference in its entirety.

In one embodiment, the therapeutic nanoparticle may comprise a multiblock copolymer (See e.g., U.S. Pat. No. 8,263,665 and 8287,910 and US Patent Pub. No. US20130195987; the contents of each of which are herein incorporated by reference in its entirety).

In yet another non-limiting example, the lipid nanoparticle comprises the block copolymer PEG-PLGA-PEG (see e.g., the thermosensitive hydrogel (PEG-PLGA-PEG) was used as a TGF-beta1 gene delivery vehicle in Lee et al. Thermosensitive Hydrogel as a Tgf-β1 Gene Delivery Vehicle Enhances Diabetic Wound Healing. Pharmaceutical Research, 2003 20(12): 1995-2000; as a controlled gene delivery system in Li et al. Controlled Gene Delivery System Based on Thermosensitive Biodegradable Hydrogel. Pharmaceutical Research 2003 20(6):884-888; and Chang et al., Non-ionic amphiphilic biodegradable PEG-PLGA-PEG copolymer enhances gene delivery efficiency in rat skeletal muscle. J Controlled Release. 2007 118:245-253; each of which is herein incorporated by reference in its entirety). The NAVs of the present invention may be formulated in lipid nanoparticles comprising the PEG-PLGA-PEG block copolymer.

In one embodiment, the therapeutic nanoparticle may comprise a multiblock copolymer (See e.g., U.S. Pat. Nos. 8,263,665 and 8,287,910 and US Patent Pub. No. US20130195987; the contents of each of which are herein incorporated by reference in its entirety).

In one embodiment, the block copolymers described herein may be included in a polyion complex comprising a non-polymeric micelle and the block copolymer. (See e.g., U.S. Pub. No. 20120076836; herein incorporated by reference in its entirety).

In one embodiment, the therapeutic nanoparticle may comprise at least one acrylic polymer. Acrylic polymers include but are not limited to, acrylic acid, methacrylic acid, acrylic acid and methacrylic acid copolymers, methyl methacrylate copolymers, ethoxyethyl methacrylates, cyanoethyl methacrylate, amino alkyl methacrylate copolymer, poly(acrylic acid), poly(methacrylic acid), polycyanoacrylates and combinations thereof.

In one embodiment, the therapeutic nanoparticles may comprise at least one poly(vinyl ester) polymer. The poly(vinyl ester) polymer may be a copolymer such as a random copolymer. As a non-limiting example, the random copolymer may have a structure such as those described in International Application No. WO2013032829 or US Patent Publication No US20130121954, the contents of which are herein incorporated by reference in its entirety. In one aspect, the poly(vinyl ester) polymers may be conjugated to the polynucleotides described herein. In another aspect, the poly(vinyl ester) polymer which may be used in the present invention may be those described in, herein incorporated by reference in its entirety.

In one embodiment, the therapeutic nanoparticle may comprise at least one diblock copolymer. The diblock copolymer may be, but it not limited to, a poly(lactic) acid-poly(ethylene)glycol copolymer (see e.g., International Patent Publication No. WO2013044219; herein incorporated by reference in its entirety). As a non-limiting example, the therapeutic nanoparticle may be used to treat cancer (see International publication No. WO2013044219; herein incorporated by reference in its entirety).

In one embodiment, the therapeutic nanoparticles may comprise at least one cationic polymer described herein and/or known in the art.

In one embodiment, the therapeutic nanoparticles may comprise at least one amine-containing polymer such as, but not limited to polylysine, polyethylene imine, poly(amidoamine) dendrimers, poly(beta-amino esters) (See e.g., U.S. Pat. No. 8,287,849; herein incorporated by reference in its entirety) and combinations thereof.

In another embodiment, the nanoparticles described herein may comprise an amine cationic lipid such as those described in International Patent Application No. WO2013059496, the contents of which are herein incorporated by reference in its entirety. In one aspect the cationic lipids may have an amino-amine or an amino-amide moiety.

In one embodiment, the therapeutic nanoparticles may comprise at least one degradable polyester which may contain polycationic side chains. Degradeable polyesters include, but are not limited to, poly(serine ester), poly(L-lactide-co-L-lysine), poly(4-hydroxy-L-proline ester), and combinations thereof. In another embodiment, the degradable polyesters may include a PEG conjugation to form a PEGylated polymer.

In another embodiment, the therapeutic nanoparticle may include a conjugation of at least one targeting ligand. The targeting ligand may be any ligand known in the art such as, but not limited to, a monoclonal antibody. (Kirpotin et al, Cancer Res. 2006 66:6732-6740; herein incorporated by reference in its entirety).

In one embodiment, the therapeutic nanoparticle may be formulated in an aqueous solution which may be used to target cancer (see International Pub No. WO2011084513 and US Pub No. US20110294717, each of which is herein incorporated by reference in their entirety).

In one embodiment, the therapeutic nanoparticle NAVs, e.g., therapeutic nanoparticles comprising at least one NAV may be formulated using the methods described by Podobinski et al in U.S. Pat. No. 8,404,799, the contents of which are herein incorporated by reference in its entirety.

In one embodiment, the NAVs may be encapsulated in, linked to and/or associated with synthetic nanocarriers. Synthetic nanocarriers include, but are not limited to, those described in International Pub. Nos. WO2010005740, WO2010030763, WO201213501, WO2012149252, WO2012149255, WO2012149259, WO2012149265, WO2012149268, WO2012149282, WO2012149301, WO2012149393, WO2012149405, WO2012149411, WO2012149454 and WO2013019669, and US Pub. Nos. US20110262491, US20100104645, US20100087337 and US20120244222, each of which is herein incorporated by reference in their entirety. The synthetic nanocarriers may be formulated using methods known in the art and/or described herein. As a non-limiting example, the synthetic nanocarriers may be formulated by the methods described in International Pub Nos. WO2010005740, WO2010030763 and WO201213501 and US Pub. Nos. US20110262491, US20100104645, US20100087337 and US2012024422, each of which is herein incorporated by reference in their entirety. In another embodiment, the synthetic nanocarrier formulations may be lyophilized by methods described in International Pub. No. WO2011072218 and U.S. Pat. No. 8,211,473; the content of each of which is herein incorporated by reference in their entirety. In yet another embodiment, formulations of the present invention, including, but not limited to, synthetic nanocarriers, may be lyophilized or reconstituted by the methods described in US Patent Publication No. US20130230568, the contents of which are herein incorporated by reference in its entirety.

In one embodiment, the synthetic nanocarriers may contain reactive groups to release the polynucleotides described herein (see International Pub. No. WO20120952552 and US Pub No. US20120171229, each of which is herein incorporated by reference in their entirety).

In one embodiment, the synthetic nanocarriers may contain an immunostimulatory agent to enhance the immune response from delivery of the synthetic nanocarrier. As a non-limiting example, the synthetic nanocarrier may comprise a Th1 immunostimulatory agent which may enhance a Th1-based response of the immune system (see International Pub No. WO2010123569 and US Pub. No. US20110223201, each of which is herein incorporated by reference in its entirety).

In one embodiment, the synthetic nanocarriers may be formulated for targeted release. In one embodiment, the synthetic nanocarrier is formulated to release the polynucleotides at a specified pH and/or after a desired time interval. As a non-limiting example, the synthetic nanoparticle may be formulated to release the NAVs after 24 hours and/or at a pH of 4.5 (see International Pub. Nos. WO2010138193 and WO2010138194 and US Pub Nos. US20110020388 and US20110027217, each of which is herein incorporated by reference in their entireties).

In one embodiment, the synthetic nanocarriers may be formulated for controlled and/or sustained release of the polynucleotides described herein. As a non-limiting example, the synthetic nanocarriers for sustained release may be formulated by methods known in the art, described herein and/or as described in International Pub No. WO2010138192 and US Pub No. 20100303850, each of which is herein incorporated by reference in their entirety.

In one embodiment, the NAV may be formulated for controlled and/or sustained release wherein the formulation comprises at least one polymer that is a crystalline side chain (CYSC) polymer. CYSC polymers are described in U.S. Pat. No. 8,399,007, herein incorporated by reference in its entirety.

In one embodiment, the synthetic nanocarrier may be formulated for use as a vaccine. In one embodiment, the synthetic nanocarrier may encapsulate at least one polynucleotide which encode at least one antigen. As a non-limiting example, the synthetic nanocarrier may include at least one antigen and an excipient for a vaccine dosage form (see International Pub No. WO2011150264 and US Pub No. US20110293723, each of which is herein incorporated by reference in their entirety). As another non-limiting example, a vaccine dosage form may include at least two synthetic nanocarriers with the same or different antigens and an excipient (see International Pub No. WO2011150249 and US Pub No. US20110293701, each of which is herein incorporated by reference in their entirety). The vaccine dosage form may be selected by methods described herein, known in the art and/or described in international Pub No. WO2011150258 and US Pub No. US20120027806, each of which is herein incorporated by reference in their entirety).

In one embodiment, the synthetic nanocarrier may comprise at least one polynucleotide which encodes at least one adjuvant. As non-limiting example, the adjuvant may comprise dimethyldioctadecylammonium-bromide, dimethyldioctadecylammonium-chloride, dimethyldioctadecylammonium-phosphate or dimethyldioctadecylammonium-acetate (DDA) and an apolar fraction or part of said apolar fraction of a total lipid extract of a mycobacterium (See e.g, U.S. Pat. No. 8,241,610; herein incorporated by reference in its entirety). In another embodiment, the synthetic nanocarrier may comprise at least one polynucleotide and an adjuvant. As a non-limiting example, the synthetic nanocarrier comprising and adjuvant may be formulated by the methods described in International Pub No. WO2011150240 and US Pub No. US20110293700, each of which is herein incorporated by reference in its entirety.

In one embodiment, the synthetic nanocarrier may encapsulate at least one polynucleotide which encodes a peptide, fragment or region from a virus. As a non-limiting example, the synthetic nanocarrier may include, but is not limited to, the nanocarriers described in International Pub No. WO2012024621, WO201202629, WO2012024632 and US Pub No. US20120064110, US20120058153 and US20120058154, each of which is herein incorporated by reference in their entirety.

In one embodiment, the synthetic nanocarrier may be coupled to a polynucleotide which may be able to trigger a humoral and/or cytotoxic T lymphocyte (CTL) response (See e.g., International Publication No. WO2013019669, herein incorporated by reference in its entirety).

In one embodiment, the NAV may be encapsulated in, linked to and/or associated with zwitterionic lipids. Non-limiting examples of zwitterionic lipids and methods of using zwitterionic lipids are described in US Patent Publication No. US20130216607, the contents of which are herein incorporated by reference in its entirety. In one aspect, the zwitterionic lipids may be used in the liposomes and lipid nanoparticles described herein.

In one embodiment, the NAV may be formulated in colloid nanocarriers as described in US Patent Publication No. US20130197100, the contents of which are herein incorporated by reference in its entirety.

In one embodiment, the nanoparticle may be optimized for oral administration. The nanoparticle may comprise at least one cationic biopolymer such as, but not limited to, chitosan or a derivative thereof. As a non-limiting example, the nanoparticle may be formulated by the methods described in U.S. Pub. No. 20120282343; herein incorporated by reference in its entirety.

In some embodiments, LNPs comprise the lipid KL52 (an amino-lipid disclosed in U.S. Application Publication No. 2012/0295832 expressly incorporated herein by reference in its entirety). Activity and/or safety (as measured by examining one or more of ALT/AST, white blood cell count and cytokine induction) of LNP administration may be improved by incorporation of such lipids. LNPs comprising KL52 may be administered intravenously and/or in one or more doses. In some embodiments, administration of LNPs comprising KL52 results in equal or improved mRNA and/or protein expression as compared to LNPs comprising MC3.

In some embodiments, NAV may be delivered using smaller LNPs. Such particles may comprise a diameter from below 0.1 um up to 100 nm such as, but not limited to, less than 0.1 um, less than 1.0 um, less than 5 um, less than 10 um, less than 15 um, less than 20 um, less than 25 um, less than 30 um, less than 35 um, less than 40 um, less than 50 um, less than 55 um, less than 60 um, less than 65 um, less than 70 um, less than 75 um, less than 80 um, less than 85 um, less than 90 um, less than 95 um, less than 100 um, less than 125 um, less than 150 um, less than 175 um, less than 200 um, less than 225 um, less than 250 um, less than 275 um, less than 300 um, less than 325 um, less than 350 um, less than 375 um, less than 400 um, less than 425 um, less than 450 um, less than 475 um, less than 500 um, less than 525 um, less than 550 um, less than 575 um, less than 600 um, less than 625 um, less than 650 um, less than 675 um, less than 700 um, less than 725 um, less than 750 um, less than 775 um, less than 800 um, less than 825 um, less than 850 um, less than 875 um, less than 900 um, less than 925 um, less than 950 um, less than 975 um,

In another embodiment, NAVs may be delivered using smaller LNPs which may comprise a diameter from about 1 nm to about 100 nm, from about 1 nm to about 10 nm, about 1 nm to about 20 nm, from about 1 nm to about 30 nm, from about 1 nm to about 40 nm, from about 1 nm to about 50 nm, from about 1 nm to about 60 nm, from about 1 nm to about 70 nm, from about 1 nm to about 80 nm, from about 1 nm to about 90 nm, from about 5 nm to about from 100 nm, from about 5 nm to about 10 nm, about 5 nm to about 20 nm, from about 5 nm to about 30 nm, from about 5 nm to about 40 nm, from about 5 nm to about 50 nm, from about 5 nm to about 60 nm, from about 5 nm to about 70 nm, from about 5 nm to about 80 nm, from about 5 nm to about 90 nm, about 10 to about 50 nM, from about 20 to about 50 nm, from about 30 to about 50 nm, from about 40 to about 50 nm, from about 20 to about 60 nm, from about 30 to about 60 nm, from about 40 to about 60 nm, from about 20 to about 70 nm, from about 30 to about 70 nm, from about 40 to about 70 nm, from about 50 to about 70 nm, from about 60 to about 70 nm, from about 20 to about 80 nm, from about 30 to about 80 nm, from about 40 to about 80 nm, from about 50 to about 80 nm, from about 60 to about 80 nm, from about 20 to about 90 nm, from about 30 to about 90 nm, from about 40 to about 90 nm, from about 50 to about 90 nm, from about 60 to about 90 nm and/or from about 70 to about 90 rnm.

In some embodiments, such LNPs are synthesized using methods comprising microfluidic mixers. Exemplary microfluidic mixers may include, but are not limited to a slit interdigitial micromixer including, but not limited to those manufactured by Microinnova (Allerheiligen bei Wildon, Austria) and/or a staggered herringbone micromixer (SHM) (Zhigaltsev, I. V. et al., Bottom-up design and synthesis of limit size lipid nanoparticle systems with aqueous and triglyceride cores using millisecond microfluidic mixing have been published (Langmuir. 2012. 28:3633-40; Belliveau, N. M. et al., Microfluidic synthesis of highly potent limit-size lipid nanoparticles for in vivo delivery of siRNA. Molecular Therapy-Nucleic Acids. 2012. 1:e37; Chen, D. et al., Rapid discovery of potent siRNA-containing lipid nanoparticles enabled by controlled microfluidic formulation. J Am Chem Soc. 2012. 134(16):6948-51; each of which is herein incorporated by reference in its entirety). In some embodiments, methods of LNP generation comprising SHM, further comprise the mixing of at least two input streams wherein mixing occurs by microstructure-induced chaotic advection (MICA). According to this method, fluid streams flow through channels present in a herringbone pattern causing rotational flow and folding the fluids around each other. This method may also comprise a surface for fluid mixing wherein the surface changes orientations during fluid cycling. Methods of generating LNPs using SHM include those disclosed in U.S. Application Publication Nos. 2004/0262223 and 2012/0276209, each of which is expressly incorporated herein by reference in their entirety.

In one embodiment, the NAV of the present invention may be formulated in lipid nanoparticles created using a micromixer such as, but not limited to, a Slit Interdigital Microstnuctured Mixer (SIMM-V2) or a Standard Slit Interdigital Micro Mixer (SSIMM) or Caterpillar (CPMM) or Impinging-jet (UMM) from the Institut for Mikrotechnik Mainz GmbH, Mainz Germany).

In one embodiment, the NAVs of the present invention may be formulated in lipid nanoparticles created using microfluidic technology (see Whitesides, George M. The Origins and the Future of Microfluidics. Nature, 2006 442: 368-373; and Abraham et al. Chaotic Mixer for Microchannels. Science, 2002 295: 647-651; each of which is herein incorporated by reference in its entirety). As a non-limiting example, controlled microfluidic formulation includes a passive method for mixing streams of steady pressure-driven flows in micro channels at a low Reynolds number (See e.g., Abraham et al. Chaotic Mixer for Microchannels. Science, 2002 295: 647-651; which is herein incorporated by reference in its entirety).

In one embodiment, the NAVs of the present invention may be formulated in lipid nanoparticles created using a micromixer chip such as, but not limited to, those from Harvard Apparatus (Holliston, MA) or Dolomite Microfluidics (Royston, UK). A micromixer chip can be used for rapid mixing of two or more fluid streams with a split and recombine mechanism.

In one embodiment, the NAVs of the invention may be formulated for delivery using the drug encapsulating microspheres described in International Patent Publication No. WO2013063468 or U.S. Pat. No. 8,440,614, each of which is herein incorporated by reference in its entirety. The microspheres may comprise a compound of the formula (I), (II), (III), (IV). (V) or (VI) as described in International Patent Publication No. WO2013063468, the contents of which are herein incorporated by reference in its entirety. In another aspect, the amino acid, peptide, polypeptide, lipids (APPL) are useful in delivering the NAVs of the invention to cells (see International Patent Publication No. WO2013063468, the contents of which is herein incorporated by reference in its entirety).

In one embodiment, the NAVs of the invention may be formulated in lipid nanoparticles having a diameter from about 10 to about 100 nm such as, but not limited to, about 10 to about 20 nm, about 10 to about 30 nm, about 10 to about 40 nm, about 10 to about 50 nm, about 10 to about 60 nm, about 10 to about 70 nm, about 10 to about 80 nm, about 10 to about 90 nm, about 20 to about 30 nm, about 20 to about 40 nm, about 20 to about 50 nm, about 20 to about 60 nm, about 20 to about 70 nm, about 20 to about 80 nm, about 20 to about 90 nm, about 20 to about 100 nm, about 30 to about 40 nm, about 30 to about 50 nm, about 30 to about 60 nm, about 30 to about 70 nm, about 30 to about 80 nm, about 30 to about 90 nm, about 30 to about 100 nm, about 40 to about 50 nm, about 40 to about 60 nm, about 40 to about 70 nm, about 40 to about 80 nm, about 40 to about 90 nm, about 40 to about 100 nm, about 50 to about 60 nm, about 50 to about 70 nm about 50 to about 80 nm, about 50 to about 90 nm, about 50 to about 100 nm, about 60 to about 70 nm, about 60 to about 80 nm, about 60 to about 90 nm, about 60 to about 100 nm, about 70 to about 80 nm, about 70 to about 90 nm, about 70 to about 100 nm, about 80 to about 90 nm, about 80 to about 100 nm and/or about 90 to about 100 nm.

In one embodiment, the lipid nanoparticles may have a diameter from about 10 to 500 nm.

In one embodiment, the lipid nanoparticle may have a diameter greater than 100 nm, greater than 150 nm, greater than 200 nm, greater than 250 nm, greater than 300 nm, greater than 350 nm, greater than 400 nm, greater than 450 nm, greater than 500 nm, greater than 550 nm, greater than 600 nm, greater than 650 nm, greater than 700 nm, greater than 750 nm, greater than 800 nm, greater than 850 nm, greater than 900 nm, greater than 950 nm or greater than 1000 nm.

In one aspect, the lipid nanoparticle may be a limit size lipid nanoparticle described in International Patent Publication No. WO2013059922, the contents of which are herein incorporated by reference in its entirety. The limit size lipid nanoparticle may comprise a lipid bilayer surrounding an aqueous core or a hydrophobic core; where the lipid bilayer may comprise a phospholipid such as, but not limited to, diacylphosphatidylcholine, a diacylphosphatidylethanolamine, a ceramide, a sphingomyelin, a dihydrosphingomyelin, a cephalin, a cerebroside, a C8-C20 fatty acid diacylphophatidylcholine, and 1-palmitoyl-2-oleoyl phosphatidylcholine (POPC). In another aspect the limit size lipid nanoparticle may comprise a polyethylene glycol-lipid such as, but not limited to, DLPE-PEG, DMPE-PEG, DPPC-PEG and DSPE-PEG.

In one embodiment, the NAVs may be delivered, localized and/or concentrated in a specific location using the delivery methods described in International Patent Publication No. WO2013063530, the contents of which are herein incorporated by reference in its entirety. As a non-limiting example, a subject may be administered an empty polymeric particle prior to, simultaneously with or after delivering the NAVs to the subject. The empty polymeric particle undergoes a change in volume once in contact with the subject and becomes lodged, embedded, immobilized or entrapped at a specific location in the subject.

In one embodiment, the NAVs may be formulated in an active substance release system (See e.g., US Patent Publication No. US20130102545, the contents of which is herein incorporated by reference in its entirety). The active substance release system may comprise 1) at least one nanoparticle bonded to an oligonucleotide inhibitor strand which is hybridized with a catalytically active nucleic acid and 2) a compound bonded to at least one substrate molecule bonded to a therapeutically active substance (e.g., polynucleotides described herein), where the therapeutically active substance is released by the cleavage of the substrate molecule by the catalytically active nucleic acid.

In one embodiment, the NAVs may be formulated in a nanoparticle comprising an inner core comprising a non-cellular material and an outer surface comprising a cellular membrane. The cellular membrane may be derived from a cell or a membrane derived from a virus. As a non-limiting example, the nanoparticle may be made by the methods described in International Patent Publication No. WO2013052167, herein incorporated by reference in its entirety. As another non-limiting example, the nanoparticle described in International Patent Publication No. WO2013052167, herein incorporated by reference in its entirety, may be used to deliver the NAVs described herein.

In one embodiment, the NAVs may be formulated in porous nanoparticle-supported lipid bilayers (protocells). Protocells are described in International Patent Publication No. WO2013056132, the contents of which are herein incorporated by reference in its entirety.

In one embodiment, the NAVs described herein may be formulated in polymeric nanoparticles as described in or made by the methods described in U.S. Pat. Nos. 8,420,123 and 8,518,963 and European Patent No. EP2073848B1, the contents of each of which are herein incorporated by reference in their entirety. As a non-limiting example, the polymeric nanoparticle may have a high glass transition temperature such as the nanoparticles described in or nanoparticles made by the methods described in U.S. Pat. No. 8,518,963, the contents of which are herein incorporated by reference in its entirety. As another non-limiting example, the polymer nanoparticle for oral and parenteral formulations may be made by the methods described in European Patent No. EP2073848B1, the contents of which are herein incorporated by reference in its entirety.

In another embodiment, the NAVs described herein may be formulated in nanoparticles used in imaging. The nanoparticles may be liposome nanoparticles such as those described in US Patent Publication No US20130129636, herein incorporated by reference in its entirety. As a non-limiting example, the liposome may comprise gadolinium(II)2-{4,7-bis-carboxymethyl-10-[(N,N-distearylamidomethyl-N′-amido-methyl]-1,4,7,10-tetra-azacyclododec-1-yl}-acetic acid and a neutral, fully saturated phospholipid component (see e.g., US Patent Publication No US20130129636, the contents of which is herein incorporated by reference in its entirety).

In one embodiment, the nanoparticles which may be used in the present invention are formed by the methods described in U.S. Patent Application No. US20130130348, the contents of which is herein incorporated by reference in its entirety.

The nanoparticles of the present invention may further include nutrients such as, but not limited to, those which deficiencies can lead to health hazards from anemia to neural tube defects (see e.g, the nanoparticles described in International Patent Publication No WO2013072929, the contents of which is herein incorporated by reference in its entirety). As a non-limiting example, the nutrient may be iron in the form of ferrous, ferric salts or elemental iron, iodine, folic acid, vitamins or micronutrients.

In one embodiment, the NAVs of the present invention may be formulated in a swellable nanoparticle. The swellable nanoparticle may be, but is not limited to, those described in U.S. Pat. No. 8,440,231, the contents of which is herein incorporated by reference in its entirety. As a non-limiting embodiment, the swellable nanoparticle may be used for delivery of the NAVs of the present invention to the pulmonary system (see e.g., U.S. Pat. No. 8,440,231, the contents of which is herein incorporated by reference in its entirety).

The NAVs of the present invention may be formulated in polyanhydride nanoparticles such as, but not limited to, those described in U.S. Pat. No. 8,449,916, the contents of which is herein incorporated by reference in its entirety.

The nanoparticles and microparticles of the present invention may be geometrically engineered to modulate macrophage and/or the immune response. In one aspect, the geometrically engineered particles may have varied shapes, sizes and/or surface charges in order to incorporated the polynucleotides of the present invention for targeted delivery such as, but not limited to, pulmonary delivery (see e.g., International Publication No WO2013082111, the contents of which is herein incorporated by reference in its entirety). Other physical features the geometrically engineering particles may have include, but are not limited to, fenestrations, angled arms, asymmetry and surface roughness, charge which can alter the interactions with cells and tissues. As a non-limiting example, nanoparticles of the present invention may be made by the methods described in International Publication No WO2013082111, the contents of which is herein incorporated by reference in its entirety.

In one embodiment, the nanoparticles of the present invention may be water soluble nanoparticles such as, but not limited to, those described in International Publication No. WO2013090601, the contents of which is herein incorporated by reference in its entirety. The nanoparticles may be inorganic nanoparticles which have a compact and zwitterionic ligand in order to exhibit good water solubility. The nanoparticles may also have small hydrodynamic diameters (HD), stability with respect to time, pH, and salinity and a low level of non-specific protein binding.

In one embodiment the nanoparticles of the present invention may be developed by the methods described in US Patent Publication No. US20130172406, the contents of which are herein incorporated by reference in its entirety.

In one embodiment, the nanoparticles of the present invention are stealth nanoparticles or target-specific stealth nanoparticles such as, but not limited to, those described in US Patent Publication No. US20130172406: the contents of which is herein incorporated by reference in its entirety. The nanoparticles of the present invention may be made by the methods described in US Patent Publication No. US20130172406, the contents of which are herein incorporated by reference in its entirety.

In another embodiment, the stealth or target-specific stealth nanoparticles may comprise a polymeric matrix. The polymeric matrix may comprise two or more polymers such as, but not limited to, polyethylenes, polycarbonates, polyanhydrides, polyhydroxyacids, polypropylfumerates, polycaprolactones, polyamides, polyacetals, polyethers, polyesters, poly(orthoesters), polycyanoacrylates, polyvinyl alcohols, polyurethanes, polyphosphazenes, polyacrylates, polymethacrylates, polycyanoacrylates, polyureas, polystyrenes, polyamines, polyesters, polyanhydrides, polyethers, polyurethanes, polymethacrylates, polyacrylates, polycyanoacrylates or combinations thereof.

In one embodiment, the nanoparticle may be a nanoparticle-nucleic acid hybrid structure having a high density nucleic acid layer. As a non-limiting example, the nanoparticle-nucleic acid hybrid structure may made by the methods described in US Patent Publication No. US20130171646, the contents of which are herein incorporated by reference in its entirety. The nanoparticle may comprise a nucleic acid such as, but not limited to, polynucleotides described herein and/or known in the art.

At least one of the nanoparticles of the present invention may be embedded in in the core a nanostructure or coated with a low density porous 3-D structure or coating which is capable of carrying or associating with at least one payload within or on the surface of the nanostructure. Non-limiting examples of the nanostructures comprising at least one nanoparticle are described in International Patent Publication No. WO2013123523, the contents of which are herein incorporated by reference in its entirety.

Polymers, Biodegradable Nanoparticles, and Core-Shell Nanoparticles

The NAVs of the invention can be formulated using natural and/or synthetic polymers. Non-limiting examples of polymers which may be used for delivery include, but are not limited to, DYNAMIC POLYCONJUGATE® (Arrowhead Research Corp., Pasadena, CA) formulations from MIRUS® Bio (Madison, WI) and Roche Madison (Madison, WI), PHASERX™ polymer formulations such as, without limitation, SMARTT POLYMER TECHNOLOGY™ (PHASERX®, Seattle, WA), DMRI/DOPE, poloxamer, VAXFECTIN® adjuvant from Vical (San Diego, CA), chitosan, cyclodextrin from Calando Pharmaceuticals (Pasadena, CA), dendrimers and poly(lactic-co-glycolic acid) (PLGA) polymers. RONDEL™ (RNAi/Oligonucleotide Nanoparticle Delivery) polymers (Arrowhead Research Corporation, Pasadena, CA) and pH responsive co-block polymers such as, but not limited to, PHASERX® (Seattle, WA).

A non-limiting example of chitosan formulation includes a core of positively charged chitosan and an outer portion of negatively charged substrate (U.S. Pub. No. 20120258176; herein incorporated by reference in its entirety). Chitosan includes, but is not limited to N-trimethyl chitosan, mono-N-carboxymethyl chitosan (MCC), N-palmitoyl chitosan (NPCS), EDTA-chitosan, low molecular weight chitosan, chitosan derivatives, or combinations thereof.

In one embodiment, the polymers used in the present invention have undergone processing to reduce and/or inhibit the attachement of unwanted substances such as, but not limited to, bacteria, to the surface of the polymer. The polymer may be processed by methods known and/or described in the art and/or described in International Pub. No. WO2012150467, herein incorporated by reference in its entirety.

A non-limiting example of PLGA formulations include, but are not limited to, PLGA injectable depots (e.g., ELIGARD® which is formed by dissolving PLGA in 66% N-methyl-2-pyrrolidone (NMP) and the remainder being aqueous solvent and leuprolide. Once injected, the PLGA and leuprolide peptide precipitates into the subcutaneous space).

Many of these polymer approaches have demonstrated efficacy in delivering oligonucleotides in vivo into the cell cytoplasm (reviewed in deFougerolles Hum Gene Ther. 2008 19:125-132; herein incorporated by reference in its entirety). Two polymer approaches that have yielded robust in vivo delivery of nucleic acids, in this case with small interfering RNA (siRNA), are dynamic polyconjugates and cyclodextrin-based nanoparticles (see e.g., US Patent Publication No. US20130156721, herein incorporated by reference in its entirety). The first of these delivery approaches uses dynamic polyconjugates and has been shown in vivo in mice to effectively deliver siRNA and silence endogenous target mRNA in hepatocytes (Rozema et al., Proc Natl Acad Sci USA. 2007 104:12982-12887; herein incorporated by reference in its entirety). This particular approach is a multicomponent polymer system whose key features include a membrane-active polymer to which nucleic acid, in this case siRNA, is covalently coupled via a disulfide bond and where both PEG (for charge masking) and N-acetylgalactosamine (for hepatocyte targeting) groups are linked via pH-sensitive bonds (Rozema et al., Proc Natl Acad Sci USA. 2007 104:12982-12887; herein incorporated by reference in its entirety). On binding to the hepatocyte and entry into the endosome, the polymer complex disassembles in the low-pH environment, with the polymer exposing its positive charge, leading to endosomal escape and cytoplasmic release of the siRNA from the polymer. Through replacement of the N-acetylgalactosamine group with a mannose group, it was shown one could alter targeting from asialoglycoprotein receptor-expressing hepatocytes to sinusoidal endothelium and Kupffer cells. Another polymer approach involves using transferrin-targeted cyclodextrin-containing polycation nanoparticles. These nanoparticles have demonstrated targeted silencing of the EWS-FLIJ gene product in transferrin receptor-expressing Ewing's sarcoma tumor cells (Hu-Lieskovan et al., Cancer Res. 2005 65: 8984-8982; herein incorporated by reference in its entirety) and siRNA formulated in these nanoparticles was well tolerated in non-human primates (Heidel et al., Proc Natl Acad Sci USA 2007 104:5715-21; herein incorporated by reference in its entirety). Both of these delivery strategies incorporate rational approaches using both targeted delivery and endosomal escape mechanisms.

The polymer formulation can permit the sustained or delayed release of polynucleotides (e.g., following intramuscular or subcutaneous injection). The altered release profile for the polynucleotide can result in, for example, translation of an encoded protein over an extended period of time. The polymer formulation may also be used to increase the stability of the polynucleotide. Biodegradable polymers have been previously used to protect nucleic acids other than polynucleotide from degradation and been shown to result in sustained release of payloads in vivo (Rozema et al., Proc Natl Acad Sci USA. 2007 104:12982-12887; Sullivan et al., Expert Opin Drug Deliv. 2010 7:1433-1446; Convertine et al., Biomacromolecules. 2010 Oct. 1; Chu et al., Acc Chem Res. 2012 Jan. 13; Manganiello et al., Biomaterials. 2012 33:2301-2309; Benoit et al., Biomacromolecules. 2011 12:2708-2714; Singha et al., Nucleic Acid Ther. 2011 2:133-147; deFougerolles Hum Gene Ther. 2008 19:125-132; Schaffert and Wagner, Gene Ther. 2008 16:1131-1138; Chaturvedi et al., Expert Opin Drug Deliv. 2011 8:1455-1468; Davis, Mol Pharm. 2009 6:659-668; Davis, Nature 2010 464:1067-1070; each of which is herein incorporated by reference in its entirety).

In one embodiment, the NAV pharmaceutical compositions may be sustained release formulations. In a further embodiment, the sustained release formulations may be for subcutaneous delivery. Sustained release formulations may include, but are not limited to, PLGA microspheres, ethylene vinyl acetate (EVAc), poloxamer, GELSITE® (Nanotherapeutics, Inc. Alachua, FL), HYLENEX® (Halozyme Therapeutics, San Diego CA), surgical sealants such as fibrinogen polymers (Ethicon Inc. Cornelia, GA), TISSELL® (Baxter International, Inc Deerfield, IL), PEG-based sealants, and COSEAL® (Baxter International, Inc Deerfield, IL).

As a non-limiting example NAVs may be formulated in PLGA microspheres by preparing the PLGA microspheres with tunable release rates (e.g., days and weeks) and encapsulating the modified mRNA in the PLGA microspheres while maintaining the integrity of the modified mRNA during the encapsulation process. EVAc are non-biodegradeable, biocompatible polymers which are used extensively in pre-clinical sustained release implant applications (e.g., extended release products Ocusert a pilocarpine ophthalmic insert for glaucoma or progestasert a sustained release progesterone intrauterine deivce; transdermal delivery systems Testoderm, Duragesic and Selegiline; catheters). Poloxamer F-407 NF is a hydrophilic, non-ionic surfactant triblock copolymer of polyoxyethylene-polyoxypropylene-polyoxyethylene having a low viscosity at temperatures less than 5° C. and forms a solid gel at temperatures greater than 15° C. PEG-based surgical sealants comprise two synthetic PEG components mixed in a delivery device which can be prepared in one minute, seals in 3 minutes and is reabsorbed within 30 days. GELSITE® and natural polymers are capable of in-situ gelation at the site of administration. They have been shown to interact with protein and peptide therapeutic candidates through ionic ineraction to provide a stabilizing effect.

Polymer formulations can also be selectively targeted through expression of different ligands as exemplified by, but not limited by, folate, transferrin, and N-acetylgalactosamine (GalNAc) (Benoit et al., Biomacromolecules. 2011 12:2708-2714; Rozema et al., Proc Natl Acad Sci USA. 2007 104:12982-12887; Davis, Mol Pharm. 2009 6:659-668; Davis, Nature 2010 464:1067-1070; each of which is herein incorporated by reference in its entirety).

The NAVs of the invention may be formulated with or in a polymeric compound. The polymer may include at least one polymer such as, but not limited to, polyethenes, polyethylene glycol (PEG), poly(l-lysine)(PLL), PEG grafted to PLL, cationic lipopolymer, biodegradable cationic lipopolymer, polyethyleneimine (PEI), cross-linked branched poly(alkylene imines), a polyamine derivative, a modified poloxamer, a biodegradable polymer, elastic biodegradable polymer, biodegradable block copolymer, biodegradable random copolymer, biodegradable polyester copolymer, biodegradable polyester block copolymer, biodegradable polyester block random copolymer, multiblock copolymers, linear biodegradable copolymer, poly[α-(4-aminobutyl)-L-glycolic acid) (PAGA), biodegradable cross-linked cationic multi-block copolymers, polycarbonates, polyanhydrides, polyhydroxyacids, polypropylfumerates, polycaprolactones, polyamides, polyacetals, polyethers, polyesters, poly(orthoesters), polycyanoacrylates, polyvinyl alcohols, polyurethanes, polyphosphazenes, polyacrylates, polymethacrylates, polycyanoacrylates, polyureas, polystyrenes, polyamines, polylysine, poly(ethylene imine), poly(serine ester), poly(L-lactide-co-L-lysine), poly(4-hydroxy-L-proline ester), acrylic polymers, amine-containing polymers, dextran polymers, dextran polymer derivatives or or combinations thereof.

As a non-limiting example, the NAVs of the invention may be formulated with the polymeric compound of PEG grafted with PLL as described in U.S. Pat. No. 6,177,274; herein incorporated by reference in its entirety. The formulation may be used for transfecting cells in vitro or for in vivo delivery of polynucleotides. In another example, the polynucleotide may be suspended in a solution or medium with a cationic polymer, in a dry pharmaceutical composition or in a solution that is capable of being dried as described in U.S. Pub. Nos. 20090042829 and 20090042825: each of which are herein incorporated by reference in their entireties.

As another non-limiting example the NAVs of the invention may be formulated with a PLGA-PEG block copolymer (see US Pub. No. US20120004293 and U.S. Pat. No. 8,236,330, herein incorporated by reference in their entireties) or PLGA-PEG-PLGA block copolymers (See U.S. Pat. No. 6,004,573, herein incorporated by reference in its entirety). As a non-limiting example, the NAVs of the invention may be formulated with a diblock copolymer of PEG and PLA or PEG and PLGA (see U.S. Pat. No. 8,246,968, herein incorporated by reference in its entirety).

A polyamine derivative may be used to deliver nucleic acids or to treat and/or prevent a disease or to be included in an implantable or injectable device (U.S. Pub. No. 20100260817 (now U.S. Pat. No. 8,460,696) the contents of each of which is herein incorporated by reference in its entirety). As a non-limiting example, a pharmaceutical composition may include the NAV and the polyamine derivative described in U.S. Pub. No. 20100260817 (now U.S. Pat. No. 8,460,696; the contents of which are incorporated herein by reference in its entirety. As a non-limiting example the NAVs of the present invention may be delivered using a polyaminde polymer such as, but not limited to, a polymer comprising a 1,3-dipolar addition polymer prepared by combining a carbohydrate diazide monomer with a dilkyne unite comprising oligoamines (U.S. Pat. No. 8,236,280; herein incorporated by reference in its entirety).

The NAVs of the invention may be formulated with at least one acrylic polymer. Acrylic polymers include but are not limited to, acrylic acid, methacrylic acid, acrylic acid and methacrylic acid copolymers, methyl methacrylate copolymers, ethoxyethyl methacrylates, cyanoethyl methacrylate, amino alkyl methacrylate copolymer, poly(acrylic acid), poly(methacrylic acid), polycyanoacrylates and combinations thereof.

In one embodiment, the NAVs of the present invention may be formulated with at least one polymer and/or derivatives thereof described in International Publication Nos. WO2011115862, WO2012082574 and WO2012068187 and U.S. Pub. No. 20120283427, each of which are herein incorporated by reference in their entireties.

In another embodiment, the NAVs of the present invention may be formulated with a polymer of formula Z as described in WO2011115862, herein incorporated by reference in its entirety. In yet another embodiment, the NAVs may be formulated with a polymer of formula Z, Z′ or Z″ as described in International Pub. Nos. WO2012082574 or WO2012068187 and U.S. Pub. No. 2012028342, each of which are herein incorporated by reference in their entireties. The polymers formulated with the modified RNA of the present invention may be synthesized by the methods described in International Pub. Nos. WO2012082574 or WO2012068187, each of which are herein incorporated by reference in their entireties.

Formulations of NAVs of the invention may include at least one amine-containing polymer such as, but not limited to polylysine, polyethylene imine, poly(amidoamine) dendrimers, poly(amine-co-esters) or combinations thereof. As a non-limiting example, the poly(amine-co-esters) may be the polymers described in and/or made by the methods described in International Publication No WO2013082529, the contents of which are herein incorporated by reference in its entirety.

For example, the NAVs of the invention may be formulated in a pharmaceutical compound including a poly(alkylene imine), a biodegradable cationic lipopolymer, a biodegradable block copolymer, a biodegradable polymer, or a biodegradable random copolymer, a biodegradable polyester block copolymer, a biodegradable polyester polymer, a biodegradable polyester random copolymer, a linear biodegradable copolymer, PAGA, a biodegradable cross-linked cationic multi-block copolymer or combinations thereof. The biodegradable cationic lipopolymer may be made by methods known in the art and/or described in U.S. Pat. No. 6,696,038, U.S. App. Nos. 20030073619 and 20040142474 each of which is herein incorporated by reference in their entireties. The poly(alkylene imine) may be made using methods known in the art and/or as described in U.S. Pub. No. 20100004315, herein incorporated by reference in its entirety. The biodegradabale polymer, biodegradable block copolymer, the biodegradable random copolymer, biodegradable polyester block copolymer, biodegradable polyester polymer, or biodegradable polyester random copolymer may be made using methods known in the art and/or as described in U.S. Pat. Nos. 6,517,869 and 6,267,987, the contents of which are each incorporated herein by reference in their entirety. The linear biodegradable copolymer may be made using methods known in the art and/or as described in U.S. Pat. No. 6,652,886. The PAGA polymer may be made using methods known in the art and/or as described in U.S. Pat. No. 6,217,912 herein incorporated by reference in its entirety. The PAGA polymer may be copolymerized to form a copolymer or block copolymer with polymers such as but not limited to, poly-L-lysine, polyargine, polyornithine, histones, avidin, protamines, polylactides and poly(lactide-co-glycolides). The biodegradable cross-linked cationic multi-block copolymers may be made my methods known in the art and/or as described in U.S. Pat. Nos. 8,057,821, 8,444,992 or U.S. Pub. No. 2012009145 each of which are herein incorporated by reference in their entireties. For example, the multi-block copolymers may be synthesized using linear polyethyleneimine (LPEI) blocks which have distinct patterns as compared to branched polyethyleneimines. Further, the composition or pharmaceutical composition may be made by the methods known in the art, described herein, or as described in U.S. Pub. No. 20100004315 or U.S. Pat. Nos. 6,267,987 and 6,217,912 each of which are herein incorporated by reference in their entireties.

The NAVs of the invention may be formulated with at least one degradable polyester which may contain polycationic side chains. Degradeable polyesters include, but are not limited to, poly(serine ester), poly(L-lactide-co-L-lysine), poly(4-hydroxy-L-proline ester), and combinations thereof. In another embodiment, the degradable polyesters may include a PEG conjugation to form a PEGylated polymer.

The NAVs of the invention may be formulated with at least one crosslinkable polyester. Crosslinkable polyesters include those known in the art and described in US Pub. No. 20120269761, the contents of which is herein incorporated by reference in its entirety.

The NAVs of the invention may be formulated in or with at least one cyclodextrin polymer. Cyclodextrin polymers and methods of making cyclodextrin polymers include those known in the art and described in US Pub. No. 20130184453, the contents of which are herein incorporated by reference in its entirety.

In one embodiment, the NAVs of the invention may be formulated in or with at least one crosslinked cation-binding polymers. Crosslinked cation-binding polymers and methods of making crosslinked cation-binding polymers include those known in the art and described in International Patent Publication No. WO2013106072, WO2013106073 and WO2013106086, the contents of each of which are herein incorporated by reference in its entirety.

In one embodiment, the NAVs of the invention may be formulated in or with at least one branched polymer. Branched polymers and methods of making branched polymers include those known in the art and described in International Patent Publication No. WO2013113071, the contents of each of which are herein incorporated by reference in its entirety.

In one embodiment, the NAVs of the invention may be formulated in or with at least PEGylated albumin polymer. PEGylated albumin polymer and methods of making PEGylated albumin polymer include those known in the art and described in US Patent Publication No. US20130231287, the contents of each of which are herein incorporated by reference in its entirety.

In one embodiment, the polymers described herein may be conjugated to a lipid-terminating PEG. As a non-limiting example, PLGA may be conjugated to a lipid-terminating PEG forming PLGA-DSPE-PEG. As another non-limiting example, PEG conjugates for use with the present invention are described in International Publication No. WO2008103276, herein incorporated by reference in its entirety. The polymers may be conjugated using a ligand conjugate such as, but not limited to, the conjugates described in U.S. Pat. No. 8,273,363, herein incorporated by reference in its entirety.

In one embodiment, the NAVs disclosed herein may be mixed with the PEGs or the sodium phosphate/sodium carbonate solution prior to administration.

In another embodiment, a polynucleotides encoding a protein of interest may be mixed with the PEGs and also mixed with the sodium phosphate/sodium carbonate solution.

In yet another embodiment, polynucleotides encoding a protein of interest may be mixed with the PEGs and a polynucleotides encoding a second protein of interest may be mixed with the sodium phosphate/sodium carbonate solution.

In one embodiment, the NAVs described herein may be conjugated with another compound. Non-limiting examples of conjugates are described in U.S. Pat. Nos. 7,964,578 and 7,833,992, each of which are herein incorporated by reference in their entireties. In another embodiment, the NAVs of the present invention may be conjugated with conjugates of formula 1-122 as described in U.S. Pat. Nos. 7,964,578 and 7,833,992, each of which are herein incorporated by reference in their entireties. The NAVs described herein may be conjugated with a metal such as, but not limited to, gold. (See e.g., Giljohann et al. Journ. Amer. Chem. Soc. 2009 131(6): 2072-2073; herein incorporated by reference in its entirety). In another embodiment, the NAVs described herein may be conjugated and/or encapsulated in gold-nanoparticles. (International Pub. No. WO201216269 and U.S. Pub. No. 20120302940 and US20130177523; the contents of each of which is herein incorporated by reference in its entirety).

As described in U.S. Pub. No. 20100004313, herein incorporated by reference in its entirety, a gene delivery composition may include a nucleotide sequence and a poloxamer. For example, the NAVs of the present invention may be used in a gene delivery composition with the poloxamer described in U.S. Pub. No. 20100004313, the contents of which are herein incorporated by reference in its entirety.

In one embodiment, the polymer formulation of the present invention may be stabilized by contacting the polymer formulation, which may include a cationic carrier, with a cationic lipopolymer which may be covalently linked to cholesterol and polyethylene glycol groups. The polymer formulation may be contacted with a cationic lipopolymer using the methods described in U.S. Pub. No. 20090042829 herein incorporated by reference in its entirety. The cationic carrier may include, but is not limited to, polyethylenimine, poly(trimethylenimine), poly(tetramethylenimine), polypropylenimine, aminoglycoside-polyamine, dideoxy-diamino-b-cyclodexuin, spermine, spermidine, poly(2-dimethylamino)ethyl methacrylate, poly(lysine), poly(histidine), poly(arginine), cationized gelatin, dendrimers, chitosan, 1,2-Dioleoyl-3-Trimethylammonium-Propane(DOTAP), N-[l-(2,3-dioleoyloxy)propyl]-N,N,N-trimethylammonium chloride (DOTMA), 1-[2-(oleoyloxy)ethyl]-2-oleyl-3-(2-hydroxyethyl)imidazolinium chloride (DOTIM), 2,3-dioleyloxy-N-[2(sperminecarboxamido)ethyl]-N,N-dimethyl-1-propanaminium trifluoroacetate (DOSPA), 3B—[N—(N′,N′-Dimethylaminoethane)-carbamoyl]Cholesterol Hydrochloride (DC-Cholesterol HCl) diheptadecylamidoglycyl spermidine (DOGS), N,N-distearyl-N,N-dimethylammonium bromide (DDAB), N-(1,2-dimyristyloxyprop-3-yl)-N,N-dimethyl-N-hydroxyethyl ammonium bromide (DMRIE), N,N-dioleyl-N,N-dimethylammonium chloride DODAC) and combinations thereof. As a non-limiting example, the NAVs may be formulated with a cationic lipopolymer such as those described in U.S. Patent Application No. 20130065942, the contents of which are herein incorporated by reference in its entirety.

The NAVs of the invention may be formulated in a polyplex of one or more polymers (See e.g., U.S. Pat. No. 8,501,478, U.S. Pub. No. 20120237565 and 20120270927 and 20130149783 and International Patent Pub. No. WO2013090861; the contents of each of which is herein incorporated by reference in its entirety). As a non-limiting example, the polyplex may be formed using the noval alpha-aminoamidine polymers described in International Publication No. WO2013090861, the contents of which are herein incorporated by reference in its entirety. As another non-limiting example, the polyplex may be formed using the click polymers described in U.S. Pat. No. 8,501,478, the contents of which is herein incorporated by reference in its entirety.

In one embodiment, the polyplex comprises two or more cationic polymers. The catioinic polymer may comprise a poly(ethylene imine) (PEI) such as linear PEI. In another embodiment, the polyplex comprises p(TETA/CBA) its PEGylated analog p(TETA/CBA)-g-PEG2k and mixtures thereof (see e.g., US Patent Publication No. US20130149783, the contents of which are herein incorporated by reference in its entirety.

The NAVs of the invention can also be formulated as a nanoparticle using a combination of polymers, lipids, and/or other biodegradable agents, such as, but not limited to, calcium phosphate. Components may be combined in a core-shell, hybrid, and/or layer-by-layer architecture, to allow for fine-tuning of the nanoparticle so to delivery of the NAV, may be enhanced (Wang et al., Nat Mater. 2006 5:791-796; Fuller et al., Biomaterials. 2008 29:1526-1532; DeKoker et al., Adv Drug Deliv Rev. 2011 63:748-761; Endres et al., Biomaterials. 2011 32:7721-7731; Su et al., Mol Pharm. 2011 Jun. 6; 8(3):774-87; herein incorporated by reference in its entirety). As a non-limiting example, the nanoparticle may comprise a plurality of polymers such as, but not limited to hydrophilic-hydrophobic polymers (e.g., PEG-PLGA), hydrophobic polymers (e.g., PEG) and/or hydrophilic polymers (International Pub. No. WO20120225129; the contents of which is herein incorporated by reference in its entirety).

As another non-limiting example the nanoparticle comprising hydrophilic polymers for the NAVs may be those described in or made by the methods described in International Patent Publication No. WO2013119936, the contents of which are herein incorporated by reference in its entirety.

In one embodiment, the biodegradable polymers which may be used in the present invention are poly(ether-anhydride) block copolymers. As a non-limiting example, the biodegradable polymers used herein may be a block copolymer as described in International Patent Publication No WO2006063249, herein incorporated by reference in its entirety, or made by the methods described in International Patent Publication No WO2006063249, herein incorporated by reference in its entirety.

In another embodiment, the biodegradable polymers which may be used in the present invention are alkyl and cycloalkyl terminated biodegradable lipids. As a non-limiting example, the alkyl and cycloalkyl terminated biodegradable lipids may be those described in International Publication No. WO2013086322 and/or made by the methods described in international Publication No. WO2013086322; the contents of which are herein incorporated by reference in its entirety.

In yet another embodiment, the biodegradable polymers which may be used in the present invention are cationic lipids having one or more biodegradable group located in a lipid moiety. As a non-limiting example, the biodegradable lipids may be those described in US Patent Publication No. US20130195920, the contents of which are herein incorporated by reference in its entirety.

Biodegradable calcium phosphate nanoparticles in combination with lipids and/or polymers have been shown to deliver polynucleotides in vivo. In one embodiment, a lipid coated calcium phosphate nanoparticle, which may also contain a targeting ligand such as anisamide, may be used to deliver the NAVof the present invention. For example, to effectively deliver siRNA in a mouse metastatic lung model a lipid coated calcium phosphate nanoparticle was used (Li et al., J Contr Rel. 2010 142: 416-421; Li et al., J Contr Rel. 2012 158:108-114; Yang et al., Mol Ther. 2012 20:609-615; herein incorporated by reference in its entirety). This delivery system combines both a targeted nanoparticle and a component to enhance the endosomal escape, calcium phosphate, in order to improve delivery of the siRNA.

In one embodiment, calcium phosphate with a PEG-polyanion block copolymer may be used to delivery NAVs (Kazikawa et al., J Contr Rel. 2004 97:345-356: Kazikawa et al., J Contr Rel. 2006 111:368-370; the contents of each of which are herein incorporated by reference in its entirety).

In one embodiment, a PEG-charge-conversional polymer (Pitella et al., Biomaterials. 2011 32:3106-3114; the contents of which are herein incorporated by reference in its entirety) may be used to form a nanoparticle to deliver the NAVs of the present invention. The PEG-charge-conversional polymer may improve upon the PEG-polyanion block copolymers by being cleaved into a polycation at acidic pH, thus enhancing endosomal escape.

In one embodiment, a polymer used in the present invention may be a pentablock polymer such as, but not limited to, the pentablock polymers described in International Patent Publication No. WO2013055331, herein incorporated by reference in its entirety. As a non-limiting example, the pentablock polymer comprises PGA-PCL-PEG-PCL-PGA, wherein PEG is polyethylene glycol, PCL is poly(E-caprolactone), PGA is poly(glycolic acid), and PLA is poly(lactic acid). As another non-limiting example, the pentablock polymer comprises PEG-PCL-PLA-PCL-PEG, wherein PEG is polyethylene glycol, PCL is poly(E-caprolactone), PGA is poly(glycolic acid), and PLA is poly(lactic acid).

In one embodiment, a polymer which may be used in the present invention comprises at least one diepoxide and at least one aminoglycoside (See e.g., International Patent Publication No. WO2013055971, the contents of which are herein incorporated by reference in its entirety). The diepoxide may be selected from, but is not limited to, 1,4 butanediol diglycidyl ether (1,4 B), 1,4-cyclohexanedimethanol diglycidyl ether (1,4 C), 4-vinylcyclohexene diepoxide (4VCD), ethyleneglycol diglycidyl ether (EDGE), glycerol diglycidyl ether (GDE), neopentylglycol diglycidyl ether (NPDGE), poly(ethyleneglycol) diglycidyl ether (PEGDE), poly(propyleneglycol) diglycidyl ether (PPGDE) and resorcinol diglycidyl ether (RDE). The aminoglycoside may be selected from, but is not limited to, streptomycin, neomycin, framycetin, paromomycin, ribostamycin, kanamycin, amikacin, arbekacin, bekanamycin, dibekacin, tobramycin, spectinomycin, hygromycin, gentamicin, netilmicin, sisomicin, isepamicin, verdamicin, astromicin, and apramycin. As a non-limiting example, the polymers may be made by the methods described in International Patent Publication No. WO2013055971, the contents of which are herein incorporated by reference in its entirety. As another non-limiting example, compositions comprising any of the polymers comprising at least one least one diepoxide and at least one aminoglycoside may be made by the methods described in International Patent Publication No. WO2013055971, the contents of which are herein incorporated by reference in its entirety.

In one embodiment, a polymer which may be used in the present invention may be a cross-linked polymer. As a non-limiting example, the cross-linked polymers may be used to form a particle as described in U.S. Pat. No. 8,414,927, the contents of which are herein incorporated by reference in its entirety. As another non-limiting example, the cross-linked polymer may be obtained by the methods described in US Patent Publication No. US20130172600, the contents of which are herein incorporated by reference in its entirety.

In another embodiment, a polymer which may be used in the present invention may be a cross-linked polymer such as those described in U.S. Pat. No. 8,461,132, the contents of which are herein incorporated by reference in its entirety. As a non-limiting example, the cross-linked polymer may be used in a therapeutic composition for the treatment of a body tissue. The therapeutic composition may be administered to damaged tissue using various methods known in the art and/or described herein such as injection or catheterization.

In one embodiment, a polymer which may be used in the present invention may be a di-alphatic substituted pegylated lipid such as, but not limited to, those described in International Patent Publication No. WO2013049328, the contents of which are herein incorporated by reference in its entirety.

In one embodiment, a block copolymer is PEG-PLGA-PEG (see e.g., the thermosensitive hydrogel (PEG-PLGA-PEG) was used as a TGF-beta1 gene delivery vehicle in Lee et al. Thermosensitive Hydrogel as a Tgf-β1 Gene Delivery Vehicle Enhances Diabetic Wound Healing. Pharmaceutical Research, 2003 20(12): 1995-2000; as a controlled gene delivery system in Li et al. Controlled Gene Delivery System Based on Thermosensitive Biodegradable Hydrogel. Pharmaceutical Research 2003 20(6):884-888; and Chang et al., Non-ionic amphiphilic biodegradable PEG-PLGA-PEG copolymer enhances gene delivery efficiency in rat skeletal muscle. J Controlled Release. 2007 118:245-253; each of which is herein incorporated by reference in its entirety) may be used in the present invention. The present invention may be formulated with PEG-PLGA-PEG for administration such as, but not limited to, intramuscular and subcutaneous administration.

In another embodiment, the PEG-PLGA-PEG block copolymer is used in the present invention to develop a biodegradable sustained release system. In one aspect, the NAVs of the present invention are mixed with the block copolymer prior to administration. In another aspect, the NAVs of the present invention are co-administered with the block copolymer.

In one embodiment, the polymer used in the present invention may be a multi-functional polymer derivative such as, but not limited to, a multi-functional N-maleimidyl polymer derivatives as described in U.S. Pat. No. 8,454,946, the contents of which are herein incorporated by reference in its entirety.

The use of core-shell nanoparticles has additionally focused on a high-throughput approach to synthesize cationic cross-linked nanogel cores and various shells (Siegwart et al., Proc Natl Acad Sci USA. 2011 108:12996-13001; the contents of which are herein incorporated by reference in its entirety). The complexation, delivery, and internalization of the polymeric nanoparticles can be precisely controlled by altering the chemical composition in both the core and shell components of the nanoparticle. For example, the core-shell nanoparticles may efficiently deliver siRNA to mouse hepatocytes after they covalently attach cholesterol to the nanoparticle.

In one embodiment, a hollow lipid core comprising a middle PLGA layer and an outer neutral lipid layer containing PEG may be used to delivery of the NAV of the present invention. As a non-limiting example, in mice bearing a luciferease-expressing tumor, it was determined that the lipid-polymer-lipid hybrid nanoparticle significantly suppressed luciferase expression, as compared to a conventional lipoplex (Shi et al, Angew Chem Int Ed. 2011 50:7027-7031; herein incorporated by reference in its entirety).

In one embodiment, the lipid nanoparticles may comprise a core of the NAVs disclosed herein and a polymer shell. The polymer shell may be any of the polymers described herein and are known in the art. In an additional embodiment, the polymer shell may be used to protect the polynucleotides in the core.

Core-shell nanoparticles for use with the NAVs of the present invention are described and may be formed by the methods described in U.S. Pat. No. 8,313,777 or International Patent Publication No. WO2013124867, the contents of each of which are herein incorporated by reference in their entirety.

In one embodiment, the polymer used with the formulations described herein may be a modified polymer (such as, but not limited to, a modified polyacetal) as described in International Publication No. WO2011120053, the contents of which are herein incorporated by reference in its entirety.

In one embodiment, the formulation may be a polymeric carrier cargo complex comprising a polymeric carrier and at least one nucleic acid molecule. Non-limiting examples of polymeric carrier cargo complexes are described in International Patent Publications Nos. WO2013113326, WO2013113501, WO2013113325, WO2013113502 and WO2013113736 and European Patent Publication No. EP2623121, the contents of each of which are herein incorporated by reference in their entireties. In one aspect the polymeric carrier cargo complexes may comprise a negatively charged nucleic acid molecule such as, but not limited to, those described in International Patent Publication Nos. WO2013113325 and WO2013113502, the contents of each of which are herein incorporated by reference in its entirety.

In one embodiment, a pharmaceutical composition may comprise NAVs of the invention and a polymeric carrier cargo complex. The polynucleotides may encode a protein of interest such as, but not limited to, an antigen from a pathogen associated with infectious disease, an antigen associated with allergy or allergic disease, an antigen associated with autoimmune disease or an antigen associated with cancer or tumour disease (See e.g., the antigens described in International Patent Publications Nos. WO2013113326, WO2013113501, WO2013113325, WO2013113502 and WO2013113736 and European Patent Publication No. EP2623121, the contents of each of which are herein incorporated by reference in their entireties).

As a non-limiting example, the core-shell nanoparticle may be used to treat an eye disease or disorder (See e.g. US Publication No. 20120321719, the contents of which are herein incorporated by reference in its entirety).

Peptides and Proteins

The NAVs of the invention can be formulated with peptides and/or proteins in order to increase transfection of cells by the polynucleotide. In one embodiment, peptides such as, but not limited to, cell penetrating peptides and proteins and peptides that enable intracellular delivery may be used to deliver pharmaceutical formulations. A non-limiting example of a cell penetrating peptide which may be used with the pharmaceutical formulations of the present invention includes a cell-penetrating peptide sequence attached to polycations that facilitates delivery to the intracellular space, e.g., HIV-derived TAT peptide, penetratins, transportans, or hCT derived cell-penetrating peptides (see, e.g., Caron et al., Mol. Ther. 3(3):310-8 (2001); Langel, Cell-Penetrating Peptides: Processes and Applications (CRC Press, Boca Raton FL, 2002); El-Andaloussi et al., Curr. Pharm. Des. 1 1(28):3597-611 (2003); and Deshayes et al., Cell. Mol. Life Sci. 62(16):1839-49 (2005), all of which are incorporated herein by reference in their entirety). The compositions can also be formulated to include a cell penetrating agent, e.g., liposomes, which enhance delivery of the compositions to the intracellular space. NAVs of the invention may be complexed to peptides and/or proteins such as, but not limited to, peptides and/or proteins from Aileron Therapeutics (Cambridge, MA) and Permeon Biologics (Cambridge, MA) in order to enable intracellular delivery (Cronican et al., ACS Chem. Biol. 2010 5:747-752; McNaughton et al., Proc. Natl. Acad. Sci. USA 2009 106:6111-6116; Sawyer, Chem Biol Drug Des. 2009 73:3-6; Verdine and Hilinski, Methods Enzymol. 2012; 503:3-33; all of which are herein incorporated by reference in its entirety).

In one embodiment, the cell-penetrating polypeptide may comprise a first domain and a second domain. The first domain may comprise a supercharged polypeptide. The second domain may comprise a protein-binding partner. As used herein, “protein-binding partner” includes, but are not limited to, antibodies and functional fragments thereof, scaffold proteins, or peptides. The cell-penetrating polypeptide may further comprise an intracellular binding partner for the protein-binding partner. The cell-penetrating polypeptide may be capable of being secreted from a cell where the polynucleotide may be introduced.

Formulations of the including peptides or proteins may be used to increase cell transfection by the NAV, alter the biodistribution of the polynucleotide (e.g., by targeting specific tissues or cell types), and/or increase the translation of encoded protein. (See e.g., International Pub. No. WO2012110636 and WO2013123298; the contents of which are herein incorporated by reference in its entirety).

In one embodiment, the cell penetrating peptide may be, but is not limited to, those described in US Patent Publication No US20130129726, US20130137644 and US20130164219, each of which is herein incorporated by reference in its entirety.

Cells

The NAVs of the invention can be transfected ex vivo into cells, which are subsequently transplanted into a subject.

As one non-limiting example, a sample of blood from a patient or subject may be treated with an antigen or adjuvant or both where one or more are encoded by the NAVs of the invention to activate the PBMC population. This activated sample or a subset of specific cells may then be given back to the donor patient thereby activating the immune system. This activated PBMC vaccine may be designed using any of the NAVs of the present disclosure.

As non-limiting examples, the pharmaceutical compositions may include red blood cells to deliver modified RNA to liver and myeloid cells, virosomes to deliver modified RNA in virus-like particles (VLPs), and electroporated cells such as, but not limited to, from MAXCYTE® (Gaithersburg, MD) and from ERYTECH® (Lyon, France) to deliver modified RNA. Examples of use of red blood cells, viral particles and electroporated cells to deliver payloads other than polynucleotides have been documented (Godfrin et al., Expert Opin Biol Ther. 2012 12:127-133; Fang et al., Expert Opin Biol Ther. 2012 12:385-389; Hu et al., Proc Natd Acad Sci USA. 2011 108:10980-10985; Lund et al., Pharm Res. 2010 27:400-420; Huckriede et al., J Liposome Res. 2007; 17:39-47; Cusi, Hum Vaccin. 2006 2:1-7; de Jonge et al., Gene Ther. 2006 13:400-411; all of which are herein incorporated by reference in its entirety).

The NAVs may be delivered in synthetic VLPs synthesized by the methods described in International Pub No. WO2011085231 and WO2013116656 and US Pub No. 20110171248, the contents of each of which are herein incorporated by reference in their entireties.

Cell-based formulations of the NAVs of the invention may be used to ensure cell transfection (e.g., in the cellular carrier), alter the biodistribution of the polynucleotide (e.g., by targeting the cell carrier to specific tissues or cell types), and/or increase the translation of encoded protein.

Introduction into Cells

A variety of methods are known in the art and suitable for introduction of nucleic acid into a cell, including viral and non-viral mediated techniques and any of these may be used to introduce the NAVs of the present invention. Examples of typical non-viral mediated techniques include, but are not limited to, electroporation, calcium phosphate mediated transfer, nucleofection, sonoporation, heat shock, magnetofection, liposome mediated transfer, microinjection, microprojectile mediated transfer (nanoparticles), cationic polymer mediated transfer (DEAE-dextran, polyethylenimine, polyethylene glycol (PEG) and the like) or cell fusion.

The technique of sonoporation, or cellular sonication, is the use of sound (e.g., ultrasonic frequencies) for modifying the permeability of the cell plasma membrane. Sonoporation methods are known to those in the art and are used to deliver nucleic acids in vivo (Yoon and Park, Expert Opin Drug Deliv. 2010 7:321-330; Postema and Gilja, Curr Pharm Biotechnol. 2007 8:355-361; Newman and Bettinger, Gene Ther. 2007 14:465-475; all herein incorporated by reference in their entirety). Sonoporation methods are known in the art and are also taught for example as it relates to bacteria in US Patent Publication 20100196983 and as it relates to other cell types in, for example, US Patent Publication 20100009424, each of which are incorporated herein by reference in their entirety.

Electroporation techniques are also well known in the art and are used to deliver nucleic acids in vivo and clinically (Andre et al., Cuff Gene Ther. 2010 10:267-280; Chiarella et al., Curr Gene Ther. 2010 10:281-286; Hojman, Curr Gene Ther. 2010 10:128-138; all herein incorporated by reference in their entirety). Electroporation devices are sold by many companies worldwide including, but not limited to BTX® Instruments (Holliston, MA) (e.g., the AgilePulse In Vivo System) and Inovio (Blue Bell, PA) (e.g., Inovio SP-5P intramuscular delivery device or the CELLECTRA® 3000 intradermal delivery device). In one embodiment, NAVs may be delivered by electroporation as described in Example 9.

Micro-Organ

The NAVs may be contained in a micro-organ which can then express an encoded polypeptide of interest in a long-lasting therapeutic formulation. In one aspect, the micro-organ may comprise a vector comprising a nucleic acid sequence (e.g., a polynucleotides of the present invention) encoding a polypeptide of interest, operably linked to one or more regulatory sequences. As a non-limiting example, the long-lasting therapeutic micro-organ used with the present invention may be those described in U.S. Pat. No. 845,948, the contents of which are herein incorporated by reference in its entirety. As another non-limiting example, the micro-organ may be used to maintain a desired level of a polypeptide of interest for a sustained period of time (e.g., maintaining physiological hemoglobin levels as described in U.S. Pat. No. 845,948, the contents of which are herein incorporated by reference in its entirety).

The micro-organ may be able to produce the polypeptide of interest for at least a day, at least two days, at least three days, at least four days, at least five days, at least six days, a least 7 days, at least 8 days, at least 9 days, at least 10 days, at least 11 days, at least 12 days, at least 13 days, at least 14 days, at least 3 weeks, at least 1 month and/or at least 2 months, at least 3 months, at least 4 months, at least 5 months, at least 6 months or greater than 6 months.

In one embodiment, the micro-organ may have a diameter of at least 0.5 mm to at least 20 mm such as, but not limited to, at least 0.5 mm, at least 1 mm, at least 1.5 mm, at least 2 mm, at least 2.5 mm, at least 3 mm, at least 3.5 mm, at least 4 mm, at least 4.5 mm, at least 5 mm, at least 5.5 mm, at least 6 mm, at least 6.5 mm, at least 7 mm, at least 7.5 mm, at least 8 mm, at least 8.5 mm, at least 9 mm, at least 9.5 mm, at least 10 mm, at least 10.5 mm, at least 11 mm, at least 11.5 mm, at least 12 mm, at least 12.5 mm, at least 13 mm, at least 13.5 mm, at least 14 mm, at least 14.5 mm, at least 15 mm, at least 15.5. mm, at least 16 mm, at least 16.5 mm, at least 17 mm, at least 17.5 mm, at least 18 mm, at least 18.5 mm, at least 19 mm, at least 19.5 mm or at least 20 mm. In another embodiment, the micro-organ may have a diameter of 0.5-2.5 mm, 1-2.5 mm, 1.5-2.5 mm, 0.5-3 mm, 1-3 mm, 1.5-3 mm, 0.5-3.5 mm, 1-3.5 mm, 1.5-3.5 mm, 0.5-4 mm, 1-4 mm, 1.5-4 mm, 2-4 mm, 0.5-5 mm, 1-5 mm, 1.5-5 mm, 2-5 mm, 2.5-5 mm, 3-5 mm, 0.5-6 mm, 1-6 mm, 1.5-6 mm, 2-6 mm, 2.5-6 mm, 3-6 mm, 3.5-6 mm, 4-6 mm, 0.5-7 mm, 1-7 mm, 1.5-7 mm, 2-7 mm, 2.5-7 mm, 3-7 mm, 3.5-7 mm, 4-7 mm, 4.5-7 mm, 5-7 mm, 0.5-8 mm, 1-8 mm, 1.5-8 mm, 2-8 mm, 2.5-8 mm, 3-8 mm, 3.5-8 mm, 4-8 mm, 4.5-8 mm, 5-8 mm, 5.5-8 mm, 6-8 mm, 0.5-9 mm, 1-9 mm, 1.5-9 mm, 2-9 mm, 2.5-9 mm, 3-9 mm, 3.5-9 mm, 4-9 mm, 4.5-9 mm, 5-9 mm, 5.5-9 mm, 6-9 mm, 6.5-9 mm, 7-9 mm, 0.5-10 mm, 1-10 mm, 1.5-10 mm, 2-10 mm, 2.5-10 mm, 3-10 mm, 3.5-10 mm, 4-10 mm, 4.5-10 mm, 5-10 mm, 5.5-10 mm, 6-10 mm, 6.5-10 mm, 7-10 mm, 7.5-10 nm or 8-10 nm.

In one embodiment, the micro-organ may have a length of at least 2 mm to at least 150 mm such as, but not limited to, at least 2 mm, at least 3 mm, at least 4 mm, at least 5 mm, at least 6 mm, at least 7 mm, at least 8 mm, at least 9 mm, at least 10 mm, at least 15 mm, at least 20 mm, at least 25 mm, at least 30 mm, at least 35 mm, at least 40 mm, at least 45 mm, at least 50 mm, at least 55 mm, at least 60 mm, at least 65 mm, at least 70 mm, at least 75 mm, at least 80 mm, at least 85 mm, at least 90 mm, at least 95 mm, at least 100 mm, at least 105 mm, at least 110 mm, at least 115 mm, at least 120 mm, at least 125 mm, at least 130 mm, at least 135 mm, at least 140 mm, at least 145 mm or at least 150 mm. In another embodiment, the micro-organ may have a length of 5-100 mm, 10-100 mm, 15-100 mm, 20-100 mm, 25-10 mm, 30-100 mm, 35-100 mm, 40-100 mm, 45-100 mm, 50-100 mm, 55-100 mm, 60-100 mm, 65-100 mm, 70-100 mm, 75-100 mm, 80-100 mm, 85-100 mm, 90-100 mm, 5-90 mm, 10-90 mm, 15-90 mm, 20-90 mm, 25-10 mm, 30-90 mm, 35-90 mm, 40-90 mm, 45-90 mm, 50-90 mm, 55-90 mm, 60-90 mm, 65-90 mm, 70-90 mm, 75-90 mm, 80-90 mm, 5-80 mm, 10-80 mm, 15-80 mm, 20-80 mm, 25-10 mm, 30-80 mm, 35-80 mm, 40-80 mm, 45-80 mm, 50-80 mm, 55-80 mm, 60-80 mm, 65-80 mm, 70-80 mm, 5-70 mm, 10-70 mm, 15-70 mm, 20-70 mm, 25-10 mm, 30-70 mm, 35-70 mm, 40-70 mm, 45-70 mm, 50-70 mm, 55-70 mm, 60-70 mm, 5-60 mm, 10-60 mm, 15-60 mm, 20-60 mm, 25-10 mm, 30-60 mm, 35-60 mm, 40-60 mm, 45-60 mm, 50-60 mm, 5-50 mm, 10-50 mm, 15-50 mm, 20-50 mm, 25-10 mm, 30-50 mm, 35-50 mm, 40-50 mm, 5-40 mm, 10-40 mm, 15-40 mm, 20-40 mm, 25-10 mm, 30-40 mm, 5-30 mm, 10-30 mm, 15-30 mm, 20-30 mm, 5-20 mm, 10-20 mm or 5-10 mm.

Hyaluronidase

The intramuscular or subcutaneous localized injection of NAVs of the invention can include hyaluronidase, which catalyzes the hydrolysis of hyaluronan. By catalyzing the hydrolysis of hyaluronan, a constituent of the interstitial barrier, hyaluronidase lowers the viscosity of hyaluronan, thereby increasing tissue permeability (Frost, Expert Opin. Drug Deliv. (2007) 4:427-440; herein incorporated by reference in its entirety). It is useful to speed their dispersion and systemic distribution of encoded proteins produced by transfected cells. Alternatively, the hyaluronidase can be used to increase the number of cells exposed to a polynucleotide of the invention administered intramuscularly or subcutaneously.

Nanoparticle Mimics

The NAVs of the invention may be encapsulated within and/or absorbed to a nanoparticle mimic. A nanoparticle mimic can mimic the delivery function organisms or particles such as, but not limited to, pathogens, viruses, bacteria, fungus, parasites, prions and cells. As a non-limiting example the NAVs of the invention may be encapsulated in a non-viron particle which can mimic the delivery function of a virus (see International Pub. No. WO2012006376 and US Patent Publication No. US20130171241 and US20130195968, the contents of each of which are herein incorporated by reference in its entirety).

Nanotubes

The NAVs of the invention can be attached or otherwise bound to at least one nanotube such as, but not limited to, rosette nanotubes, rosette nanotubes having twin bases with a linker, carbon nanotubes and/or single-walled carbon nanotubes. The NAVs may be bound to the nanotubes through forces such as, but not limited to, steric, ionic, covalent and/or other forces.

In one embodiment, the nanotube can release one or more NAVs into cells. The size and/or the surface structure of at least one nanotube may be altered so as to govern the interaction of the nanotubes within the body and/or to attach or bind to the NAVs disclosed herein. In one embodiment, the building block and/or the functional groups attached to the building block of the at least one nanotube may be altered to adjust the dimensions and/or properties of the nanotube. As a non-limiting example, the length of the nanotubes may be altered to hinder the nanotubes from passing through the holes in the walls of normal blood vessels but still small enough to pass through the larger holes in the blood vessels of tumor tissue.

In one embodiment, at least one nanotube may also be coated with delivery enhancing compounds including polymers, such as, but not limited to, polyethylene glycol. In another embodiment, at least one nanotube and/or the NAVs may be mixed with pharmaceutically acceptable excipients and/or delivery vehicles.

In one embodiment, the NAVs are attached and/or otherwise bound to at least one rosette nanotube. The rosette nanotubes may be formed by a process known in the art and/or by the process described in international Publication No. WO2012094304, herein incorporated by reference in its entirety. At least one NAV may be attached and/or otherwise bound to at least one rosette nanotube by a process as described in International Publication No. WO2012094304, herein incorporated by reference in its entirety, where rosette nanotubes or modules forming rosette nanotubes are mixed in aqueous media with at least one NAV under conditions which may cause at least one RNAVs to attach or otherwise bind to the rosette nanotubes.

In one embodiment, the NAVs may be attached to and/or otherwise bound to at least one carbon nanotube. As a non-limiting example, the NAVs may be bound to a linking agent and the linked agent may be bound to the carbon nanotube (See e.g., U.S. Pat. No. 8,246,995; herein incorporated by reference in its entirety). The carbon nanotube may be a single-walled nanotube (See e.g., U.S. Pat. No. 8,246,995; herein incorporated by reference in its entirety).

Conjugates

The NAVs of the invention include conjugates, such as a polynucleotide covalently linked to a carrier or targeting group, or including two encoding regions that together produce a fusion protein (e.g., bearing a targeting group and therapeutic protein or peptide).

The conjugates of the invention include a naturally occurring substance, such as a protein (e.g., human serum albumin (HSA), low-density lipoprotein (LDL), high-density lipoprotein (HDL), or globulin); an carbohydrate (e.g., a dextran, pullulan, chitin, chitosan, inulin, cyclodextrin or hyaluronic acid); or a lipid. The ligand may also be a recombinant or synthetic molecule, such as a synthetic polymer, e.g., a synthetic polyamino acid, an oligonucleotide (e.g. an aptamer). Examples of polyamino acids include polyamino acid is a polylysine (PLL), poly L-aspartic acid, poly L-glutamic acid, styrene-maleic acid anhydride copolymer, poly(L-lactide-co-glycolied) copolymer, divinyl ether-maleic anhydride copolymer, N-(2-hydroxypropyl)methacrylamide copolymer (HMPA), polyethylene glycol (PEG), polyvinyl alcohol (PVA), polyurethane, poly(2-ethylacryllic acid), N-isopropylacrylamide polymers, or polyphosphazine. Example of polyamines include: polyethylenimine, polylysine (PLL), spermine, spermidine, polyamine, pseudopeptide-polyamine, peptidomimetic polyamine, dendrimer polyamine, arginine, amidine, protamine, cationic lipid, cationic porphyrin, quaternary salt of a polyamine, or an alpha helical peptide.

Representative U.S. patents that teach the preparation of polynucleotide conjugates, particularly to RNA, include, but are not limited to, U.S. Pat. Nos. 4,828,979; 4,948,882; 5,218,105; 5,525,465; 5,541,313; 5,545,730; 5,552,538; 5,578,717, 5,580,731; 5,591,584; 5,109,124; 5,118,802; 5,138,045; 5,414,077; 5,486,603; 5,512,439; 5,578,718; 5,608,046; 4,587,044; 4,605,735; 4,667,025; 4,762,779; 4,789,737; 4,824,941; 4,835,263; 4,876,335; 4,904,582; 4,958,013; 5,082,830; 5,112,963; 5,214,136; 5,082,830; 5,112,963; 5,214,136; 5,245,022; 5,254,469; 5,258,506; 5,262,536; 5,272,250; 5,292,873; 5,317,098; 5,371,241, 5,391,723; 5,416,203, 5,451,463; 5,510,475; 5,512,667; 5,514,785; 5,565,552; 5,567,810; 5,574,142; 5,585,481; 5,587,371; 5,595,726; 5,597,696; 5,599,923; 5,599,928 and 5,688,941; 6,294,664; 6,320,017; 6,576,752; 6,783,931; 6,900,297; 7,037,646; each of which is herein incorporated by reference in their entireties.

In one embodiment, the conjugate of the present invention may function as a carrier for the NAVs of the present invention. The conjugate may comprise a cationic polymer such as, but not limited to, polyamine, polylysine, polyalkylenimine, and polyethylenimine which may be grafted to with poly(ethylene glycol). As a non-limiting example, the conjugate may be similar to the polymeric conjugate and the method of synthesizing the polymeric conjugate described in U.S. Pat. No. 6,586,524 herein incorporated by reference in its entirety.

A non-limiting example of a method for conjugation to a substrate is described in US Patent Publication No. US20130211249, the contents of which are herein incorporated by reference in its entirety. The method may be used to make a conjugated polymeric particle comprising a NAV.

The conjugates can also include targeting groups, e.g., a cell or tissue targeting agent, e.g., a lectin, glycoprotein, lipid or protein, e.g., an antibody, that binds to a specified cell type such as a kidney cell. A targeting group can be a thyrotropin, melanotropin, lectin, glycoprotein, surfactant protein A, Mucin carbohydrate, multivalent lactose, multivalent galactose, N-acetyl-galactosamine, N-acetyl-gulucosamine multivalent mannose, multivalent fucose, glycosylated polyaminoacids, multivalent galactose, transferrin, bisphosphonate, polyglutamate, polyaspartate, a lipid, cholesterol, a steroid, bile acid, folate, vitamin B12, biotin, an RGD peptide, an ROD peptide mimetic or an aptamer.

Targeting groups can be proteins, e.g., glycoproteins, or peptides, e.g., molecules having a specific affinity for a co-ligand, or antibodies e.g., an antibody, that binds to a specified cell type such as a cancer cell, endothelial cell, or bone cell. Targeting groups may also include hormones and hormone receptors. They can also include non-peptidic species, such as lipids, lectins, carbohydrates, vitamins, cofactors, multivalent lactose, multivalent galactose, N-acetyl-galactosamine, N-acetyl-gulucosamine multivalent mannose, multivalent fucose, or aptamers. The ligand can be, for example, a lipopolysaccharide, or an activator of p38 MAP kinase.

The targeting group can be any ligand that is capable of targeting a specific receptor. Examples include, without limitation, folate, GalNAc, galactose, mannose, mannose-6P, apatamers, integrin receptor ligands, chemokine receptor ligands, transferrin, biotin, serotonin receptor ligands, PSMA, endothelin, GCPTT, somatostatin, LDL, and HDL ligands. In particular embodiments, the targeting group is an aptamer. The aptamer can be unmodified or have any combination of modifications disclosed herein.

As a non-limiting example, the targeting group may be a glutathione receptor (GR)-binding conjugate for targeted delivery across the blood-central nervious system barrier (See e.g., US Patent Publication No. US2013021661012, the contents of which are herein incorporated by reference in its entirety.

In one embodiment, the conjugate of the present invention may be a synergistic biomolecule-polymer conjugate. The synergistic biomolecule-polymer conjugate may be long-acting continuous-release system to provide a greater therapeutic efficacy. The synergistic biomolecule-polymer conjugate may be those described in US Patent Publication No. US20130195799, the contents of which are herein incorporated by reference in its entirety.

In another embodiment, the conjugate which may be used in the present invention may be an aptamer conjugate. Non-limiting examples of apatamer conjugates are described in International Patent Publication No. WO2012040524, the contents of which are herein incorporated by reference in its entirety. The aptamer conjugates may be used to provide targeted delivery of formulations comprising NAVs.

In one embodiment, the conjugate which may be used in the present invention may be an amine containing polymer conjugate. Non-limiting examples of amine containing polymer conjugate are described in U.S. Pat. No. 8,507,653, the contents of which are herein incorporated by reference in its entirety. The factor IX moiety polymer conjugate may be comprise releasable linkages to release the NAVs upon and/or after delivery to a subject.

In one embodiment, pharmaceutical compositions of the present invention may include chemical modifications such as, but not limited to, modifications similar to locked nucleic acids.

Representative U.S. patents that teach the preparation of locked nucleic acid (LNA) such as those from Santaris, include, but are not limited to, the following: U.S. Pat. Nos. 6,268,490; 6,670,461; 6,794,499; 6,998,484; 7,053,207; 7,084,125; and 7,399,845, each of which is herein incorporated by reference in its entirety.

Representative U.S. patents that teach the preparation of PNA compounds include, but are not limited to, U.S. Pat. Nos. 5,539,082; 5,714,331; and 5,719,262, each of which is herein incorporated by reference. Further teaching of PNA compounds can be found, for example, in Nielsen et al., Science, 1991, 254, 1497-1500.

Some embodiments featured in the invention include polynucleotides with phosphorothioate backbones and oligonucleosides with other modified backbones, and in particular —CH₂—NH—CH₂—, —CH₂—N(CH₃)—O—CH₂— [known as a methylene (methylimino) or MMI backbone], —CH₂—O—N(CH₃)—CH₂—, —CH₂—N(CH₃)—N(CH₃)—CH₂— and —N(CH₃)—CH₂—CH₂— [wherein the native phosphodiester backbone is represented as —O—P(O)₂—O—CH₂—] of the above-referenced U.S. Pat. No. 5,489,677, and the amide backbones of the above-referenced U.S. Pat. No. 5,602,240. In some embodiments, the polynucletotides featured herein have morpholino backbone structures of the above-referenced U.S. Pat. No. 5,034,506.

Modifications at the 2′ position may also aid in delivery. Preferably, modifications at the 2′ position are not located in a polypeptide-coding sequence, i.e., not in a translatable region. Modifications at the 2′ position may be located in a 5′UTR, a 3′UTR and/or a tailing region. Modifications at the 2′ position can include one of the following at the 2′ position: H (i.e., 2′-deoxy); F; O—, S—, or N-alkyl; O-, S-, or N-alkenyl; O-, S- or N-alkynyl; or O-alkyl-O-alkyl, wherein the alkyl, alkenyl and alkynyl may be substituted or unsubstituted C₁to C₁₀alkyl or C₂to C₁₀alkenyl and alkynyl. Exemplary suitable modifications include O[(CH₂)_nO]_mCH₃, O(CH₂)·_nOCH₃, O(CH₂)_nNH₂, O(CH₂)_nCH₃, O(CH₂)_nONH₂, and O(CH₂)_nON[(CH₂)_nCH₃)]₂, where n and m are from 1 to about 10. In other embodiments, the polynucleotides include one of the following at the 2′ position: C₁to C₁₀lower alkyl, substituted lower alkyl, alkaryl, aralkyl, O-alkaryl or O-aralkyl, SH, SCH₃, OCN, Cl, Br, CN, CF₃, OCF₃, SOCH₃, SO₂CH₃, ONO₂, NO₂, N₃, NH₂, heterocycloalkyl, heterocycloalkaryl, aminoalkylamino, polyalkylamino, substituted silyl, an RNA cleaving group, a reporter group, an intercalator, a group for improving the pharmacokinetic properties, or a group for improving the pharmacodynamic properties, and other substituents having similar properties. In some embodiments, the modification includes a 2-methoxyethoxy (2′-O—CH₂CH₂OCH₃, also known as 2′-O-(2-methoxyethyl) or 2′-MOE) (Martin et al., Helv. Chin. Acta, 1995, 78:486-504) i.e., an alkoxy-alkoxy group. Another exemplary modification is 2′-dimethylaminooxyethoxy, i.e., a O(CH₂)₂ON(CH₃)₂group, also known as 2′-DMAOE, as described in examples herein below, and 2′-dimethylaminoethoxyethoxy (also known in the art as 2′-O-dimethylaminoethoxyethyl or 2′-DMAEOE), i.e., 2′-O—CH₂—O—CH₂—N(CH₂)₂, also described in examples herein below. Other modifications include 2′-methoxy (2′-OCH₃), 2′-aminopropoxy (2′-OCH₂CH₂CH₂NH₂) and 2′-fluoro (2′-F). Similar modifications may also be made at other positions, particularly the 3′ position of the sugar on the 3′ terminal nucleotide or in 2′-5′ linked dsRNAs and the 5′ position of 5′ terminal nucleotide. Polynucleotides of the invention may also have sugar mimetics such as cyclobutyl moieties in place of the pentofuranosyl sugar. Representative U.S. patents that teach the preparation of such modified sugar structures include, but are not limited to, U.S. Pat. Nos. 4,981,957; 5,118,800; 5,319,080; 5,359,044; 5,393,878; 5,446,137; 5,466,786; 5,514,785; 5,519,134; 5,567,811; 5,576,427; 5,591,722; 5,597,909; 5,610,300; 5,627,053; 5,639,873; 5,646,265; 5,658,873; 5,670,633; and 5,700,920; the contents of each of which is herein incorporated by reference in their entirety.

In one embodiment, the NAVs may be conjugated to an agent to enhance delivery. As a non-limiting example, the agent may be a monomer or polymer such as a targeting monomer or a polymer having targeting blocks as described in international Publication No. WO2011062965, herein incorporated by reference in its entirety. In another non-limiting example, the agent may be a transport agent covalently coupled to the polynucleotides of the present invention (See e.g., U.S. Pat. Nos. 6,835,393 and 7,374,778, each of which is herein incorporated by reference in its entirety). In yet another non-limiting example, the agent may be a membrane barrier transport enhancing agent such as those described in U.S. Pat. Nos. 7,737,108 and 8,003,129, each of which is herein incorporated by reference in its entirety.

In another embodiment, polynucleotides may be conjugated to SMARTT POLYMER TECHNOLOGY® (PHASERX®, Inc. Seattle, WA).

In another aspect, the conjugate may be a peptide that selectively directs the nanoparticle to neurons in a tissue or organism. As a non-limiting example, the peptide used may be, but is not limited to, the peptides described in US Patent Publication No US20130129627, herein incorporated by reference in its entirety.

In yet another aspect, the conjugate may be a peptide that can assist in crossing the blood-brain barrier.

Self-Assembled Nanoparticles

Nucleic Acid Self-Assembled Nanoparticles Self-assembled nanoparticles have a well-defined size which may be precisely controlled as the nucleic acid strands may be easily reprogrammable. For example, the optimal particle size for a cancer-targeting nanodelivery carrier is 20-100 nm as a diameter greater than 20 nm avoids renal clearance and enhances delivery to certain tumors through enhanced permeability and retention effect. (Lee et al., Nature Nanotechnology 2012 7:389-393; herein incorporated by reference in its entirety). Such self-assembling nanoparticles may be useful in formulating the NAVs of the invention.

In one embodiment, the NAVs disclosed herein may be formulated as self-assembled nanoparticles. As a non-limiting example, nucleic acids may be used to make nanoparticles which may be used in a delivery system for the NAVs of the present invention (See e.g., International Pub. No. WO2012125987; herein incorporated by reference in its entirety).

In one embodiment, the nucleic acid self-assembled nanoparticles may comprise a core of the NAVs disclosed herein and a polymer shell. The polymer shell may be any of the polymers described herein and are known in the art. In an additional embodiment, the polymer shell may be used to protect the NAVs in the core.

The metallic nanoparticle which may be used in the present invention may be a pH-sensitive nanoparticle such as, but not limited to, those described in US Patent Publication No US20130138032, herein incorporated by reference in its entirety.

In one aspect, the metallic and/or metal-allow nanoparticles may be made by the methods described in US Patent Publication No US20130133483, herein incorporated by reference in its entirety

Polymer-Based Self-Assembled Nanoparticles

Polymers may be used to form sheets which self-assembled into nanoparticles. These nanoparticles may be used to deliver the NAVs of the present invention. In one embodiment, these self-assembled nanoparticles may be microsponges formed of long polymers of RNA hairpins which form into crystalline ‘pleated’ sheets before self-assembling into microsponges. These microsponges are densely-packed sponge like microparticles which may function as an efficient carrier and may be able to deliver cargo to a cell. The microsponges may be from 1 μm to 300 nm in diameter. The microsponges may be complexed with other agents known in the art to form larger microsponges. As a non-limiting example, the microsponge may be complexed with an agent to form an outer layer to promote cellular uptake such as polycation polyethyleneime (PEI). This complex can form a 250-nm diameter particle that can remain stable at high temperatures (150° C.) (Grabow and Jaegar, Nature Materials 2012, 11:269-269; herein incorporated by reference in its entirety). Additionally these microsponges may be able to exhibit an extraordinary degree of protection from degradation by ribonucleases.

In another embodiment, the polymer-based self-assembled nanoparticles such as, but not limited to, microsponges, may be fully programmable nanoparticles. The geometry, size and stoichiometry of the nanoparticle may be precisely controlled to create the optimal nanoparticle for delivery of cargo such as, but not limited to, NAVs.

In yet another embodiment, the polymer based nanoparticle may comprise a non-nucleic acid polymer comprising a plurality of heterogenous monomers such as those described in International Publication No. WO2013009736, the contents of which are herein incorporated by reference in its entirety.

Self-Assembled Macromolecules

The NAVs may be formulated in amphiphilic macromolecules (AMs) for delivery. AMs comprise biocompatible amphiphilic polymers which have an alkylated sugar backbone covalently linked to poly(ethylene glycol). In aqueous solution, the AMs self-assemble to form micelles. Non-limiting examples of methods of forming AMs and AMs are described in US Patent Publication No. US20130217753, the contents of which are herein incorporated by reference in its entirety.

Inorganic Nanoparticles

The NAVs of the present invention may be formulated in inorganic nanoparticles (U.S. Pat. No. 8,257,745, herein incorporated by reference in its entirety). The inorganic nanoparticles may include, but are not limited to, clay substances that are water swellable. As a non-limiting example, the inorganic nanoparticle may include synthetic smectite clays which are made from simple silicates (See e.g., U.S. Pat. Nos. 5,585,108 and 8,257,745 each of which are herein incorporated by reference in their entirety).

In one embodiment, the inorganic nanoparticles may comprise a core of the NAVs disclosed herein and a polymer shell. The polymer shell may be any of the polymers described herein and are known in the art. In an additional embodiment, the polymer shell may be used to protect the NAVs in the core.

Semi-conductive and Metallic Nanoparticles

The NAVs of the present invention may be formulated in water-dispersible nanoparticle comprising a semiconductive or metallic material (U.S. Pub. No. 20120228565: herein incorporated by reference in its entirety) or formed in a magnetic nanoparticle (U.S. Pub. No. 20120265001 and 20120283503; each of which is herein incorporated by reference in its entirety). The water-dispersible nanoparticles may be hydrophobic nanoparticles or hydrophilic nanoparticles.

In one embodiment, the semi-conductive and/or metallic nanoparticles may comprise a core of the NAVs disclosed herein and a polymer shell. The polymer shell may be any of the polymers described herein and are known in the art. In an additional embodiment, the polymer shell may be used to protect the NAVs in the core.

Surgical Sealants: Gels and Hydrogels

In one embodiment, the NAVs disclosed herein may be encapsulated into any hydrogel known in the art which may form a gel when injected into a subject. Hydrogels are a network of polymer chains that are hydrophilic, and are sometimes found as a colloidal gel in which water is the dispersion medium. Hydrogels are highly absorbent (they can contain over 99% water) natural or synthetic polymers. Hydrogels also possess a degree of flexibility very similar to natural tissue, due to their significant water content. The hydrogel described herein may used to encapsulate lipid nanoparticles which are biocompatible, biodegradable and/or porous. A hydrogel can be made in situ from solution injection or implanted.

As a non-limiting example, the hydrogel may be an aptamer-functionalized hydrogel. The aptamer-functionalized hydrogel may be programmed to release one or more polynucleotides using nucleic acid hybridization. (Battig et al., J. Am. Chem. Society. 2012 134:12410-12413; the contents of which is herein incorporated by reference in its entirety).

As another non-limiting example, the hydrogel may be a shaped as an inverted opal. The opal hydrogels exhibit higher swelling ratios and the swelling kinetics is an order of magnitude faster than conventional hydrogels as well. Methods of producing opal hydrogels and description of opal hydrogels are described in International Pub. No. WO2012148684, the contents of which is herein incorporated by reference in its entirety.

In yet another non-limiting example, the hydrogel may be an antibacterial hydrogel. The antibacterial hydrogel may comprise a pharmaceutical acceptable salt or organic material such as, but not limited to pharmaceutical grade and/or medical grade silver salt and aloe vera gel or extract. (International Pub. No. WO2012151438, the contents of which are herein incorporated by reference in its entirety).

In one embodiment, a NAV may be encapsulated in a lipid nanoparticle and then the lipid nanoparticle may be encapsulated into a hydrogel.

In one embodiment, the NAVs disclosed herein may be encapsulated into any gel known in the art. As a non-limiting example the gel may be a fluorouracil injectable gel or a fluorouracil injectable gel containing a chemical compound and/or drug known in the art. As another example, the NAVs may be encapsulated in a fluorouracil gel containing epinephrine (See e.g., Smith et al. Cancer Chemotherapty and Pharmacology, 1999 44(4):267-274; the contents of which are herein incorporated by reference in its entirety).

In one embodiment, the NAVs disclosed herein may be encapsulated into a fibrin gel, fibrin hydrogel or fibrin glue.

In another embodiment, the NAVs may be formulated in a lipid nanoparticle or a rapidly eliminated lipid nanoparticle prior to being encapsulated into a fibrin gel, fibrin hydrogel or a fibrin glue. In yet another embodiment, the NAVs may be formulated as a lipoplex prior to being encapsulated into a fibrin gel, hydrogel or a fibrin glue. Fibrin gels, hydrogels and glues comprise two components, a fibrinogen solution and a thrombin solution which is rich in calcium (See e.g., Spicer and Mikos, Journal of Controlled Release 2010. 148: 49-55; Kidd et al. Journal of Controlled Release 2012. 157:80-85: each of which is herein incorporated by reference in its entirety). The concentration of the components of the fibrin gel, hydrogel and/or glue can be altered to change the characteristics, the network mesh size, and/or the degradation characteristics of the gel, hydrogel and/or glue such as, but not limited to changing the release characteristics of the fibrin gel, hydrogel and/or glue. (See e.g., Spicer and Mikos, Journal of Controlled Release 2010. 148: 49-55; Kidd et al. Journal of Controlled Release 2012. 157:80-85; Catelas et al. Tissue Engineering 2008. 14:119-128; each of which is herein incorporated by reference in its entirety). This feature may be advantageous when used to deliver the modified mRNA disclosed herein. (See e.g., Kidd et al. Journal of Controlled Release 2012. 157:80-85; Catelas et al. Tissue Engineering 2008. 14:119-128; each of which is herein incorporated by reference in its entirety).

In one embodiment, the NAVs disclosed herein may be used with hydrogels such as, but not limited to, the hydrogels described in U.S. Patent Application No. 20130071450 or 20130211249, the contents of each of which is herein incorporated by reference in its entirety.

As a non-limiting example, the hydrogels which may be used in the present invention may be made by the methods described in International Patent Publication No. WO2013124620, the contents of which are herein incorporated by reference in its entirety.

In another embodiment, the NAVs disclosed herein may be formulated for transdermal delivery. The formulation may comprise at least one hydrogel described in U.S. Patent Application No. 20130071450, the contents of which are herein incorporated by reference in its entirety.

In one embodiment, the hydrogel which may be used in the present invention is described in U.S. Pat. Nos. 8,420,605, 8,415,325 and/or International Patent Publication No. WO2013091001 and WO2013124620, the contents of each of which are herein incorporated by reference in its entirety.

In one embodiment, the hydrogel which may be used in the present invention may be, but is not limited to. ATRIGEL® (QLT Inc. Vancouver, British Columbia), chitosan, aliginate, collagen or hyaluronic acid hydrogel.

In another embodiment, the hydrogel which may be used in the present invention is a crosslinked methacrylate. As a non-limiting example, the hydrogel of the present invention may be used in wound dressings.

The hydrogel which may be used in the present invention may also be complexed with agents and excipients described herein including, but not limited to PEI, PVA, poly-lysine, Poloxamer 124, Poloxamer 181, Poloxamer 182, Poloxamer 407. Poloxamer 237, Poloxamer 331 and Poloxamer 338. Complexing the hydrogel with agents and/or excipients may help improve mRNA stability and uptake in a cell, tissue and/or organism. As a non-limiting example, a hydrogel may be complexed with Poloxamer 188 to improve the stability and uptake of mRNA.

In one embodiment, the NAVs disclosed herein may be formulated in a surgical sealant. The surgical sealant may be, but is not limited to, fibrinogen polymer based sealants (Ethicon Inc. Cornelia, GA), TISSELL® (Baxter International, Inc Deerfield, IL) or PEG-based sealants such as, but not limited to, COSEAL® (Baxter International, Inc Deerfield, IL) and DURASEAL™ (trilysine amine/PEG-ester) (Covidien, Waltham, MA).

In one embodiment, NAVs may be formulated in COSEAL® or co-administered with or administered after a cell, tissue or organism is administered COSEAL®. COSEAL® comprises two synthetic polyethylene glycols (PEGs) (pentaerythritol PEG ester tetra-succinimidyl and pentaerythritol PEG ether tetra-thiol), a dilute hydrogen chloride solution, and a sodium phosphate/sodium carbonate solution. The PEGs are kept separate from the sodium phosphate/sodium carbonate solution in the dilute hydrogen chloride solution until administration. After administration a hydrogel is formed, which may adhere to tissue, and forms a stiff gel in seconds which is resorbed within 30 days.

In another embodiment, the NAVs disclosed herein may be formulated in a hydrogel comprising a macromolecular matrix. The macromolecular matrix may comprise a hyaluronic acid component which may be crosslinked to a collagent component. The hydrogel used in the present invention may be, but is not limited to, the hydrogels described in International Patent Publication No. WO2013106715, the contents of which are herein incorporated by reference in its entirety.

In yet another embodiment, the NAVs disclosed herein may be formulated in a chitosan glycerophosphate (CGP) hydrogel. The formulation may further comprise a chitosanase in an effect amount to dissolve the COP hydrogel and release the NAVs associated with the COP hydrogel. As a non-limiting example, the NAVs may be formulated in the controlled release delivery system comprising a COP hydrogel described in US Patent Publication No. US20130189241, the contents of which are herein incorporated by reference in its entirety.

In one embodiment, the NAVs disclosed herein may be formulated in a hydrogel formulated for controlled release such as, but not limited to, the porous matrix composites and formulations described in US Patent Publication No. US20130196915, the contents of which are herein incorporated by reference in its entirety.

In another embodiment, the NAVs disclosed herein may be formulated in a hydrogel comprising heterobifunctional poly(alkylene oxides) which may have degradable linkages. Non-limiting examples of heterobifunctional poly(alkylene oxides) are described in U.S. Pat. No. 8,497,357, the contents of which are herein incorporated by reference in its entirety.

In yet another embodiment, the NAVs may be formulated in a hydrogel which may be used as an insulin delivery system. As a non-limiting example, the hydrogel may be a glucose binding amphiphilic peptide hydrogel as described in International Patent Publication No. WO2013123491, the contents of which are herein incorporated by reference in its entirety. As another non-limiting example, the hydrogel may be a microgel such as the glucose-responsive microgels described in International Patent Publication No. WO2013123492, the contents of which are herein incorporated by reference in its entirety.

In one embodiment, the NAVs may be formulated in a hydrogel system such as, but not limited to, a multi-compartment hydrogel. A non-limiting example of a multi-compartment hydrogel and methods of making the hydrogel is described in International Patent Publication No. WO2013124855, the contents of which are herein incorporated by reference in its entirety. The multi-compartment hydrogel may be used to repair or regenerate damaged tissue in a subject.

In another embodiment, the NAVs may be formulated in a cucurbituril-based hydrogel. A non-limiting example of a cucurbituril-based hydrogel is described in international Patent Publication No. WO2013124654, the contents of which are herein incorporated by reference in its entirety.

In one embodiment, the NAVs disclosed herein may be formulated in a PEG-based surgical sealant or hydrogel.

In one embodiment, the surgical sealant or hydrogel may include at least one, at least two, at least three, at least four, at least five, at least six or more than six PEG lipids. The PEG lipids may be selected from, but are not limited to, pentaerythritol PEG ester tetra-succinimidyl and pentaerythritol PEG ether tetra-thiol, PEG-c-DOMG, PEG-DMG (1,2-Dimyristoyl-sn-glycerol, methoxypolyethylene Glycol), PEG-DSG (1,2-Distearoyl-sn-glycerol, methoxypolyethylene Glycol), PEG-DPG (1,2-Dipalmitoyl-sn-glycerol, methoxypolyethylene glycol), PEG-DSA (PEG coupled to 1,2-distearyloxypropyl-3-amine), PEG-DMA (PEG coupled to 1,2-dimyristyloxypropyl-3-amine, PEG-c-DNA, PEG-c-DMA, PEG-S-DSG, PEG-c-DMA, PEG-DPG, PEG-DMG 2000 and those described herein and/or known in the art. The concentration and/or ratio of the PEG lipids in the surgical sealant or hydrogel may be varied in order to optimize the formulation for delivery and/or administration.

The amount of buffer and/or acid used in combination with the PEG lipids of the surgical sealant or hydrogel may also be varied. In one non-limiting example, the ratio of buffer and/or acid with PEG lipids is 1:1. As a non-limiting example, the amount of buffer and/or acid used with the PEG lipids may be increased to alter the ratio of buffer/acid to PEG in order to optimize the surgical sealant or hydrogel. As another non-limiting example, the amount of buffer and/or acid used with the PEG lipids may be decreased to alter the ratio of buffer/acid to PEG in order to optimize the surgical sealant or hydrogel.

The amount of NAVs loaded into the buffer, acid and/or PEG lipid may be varied. The amount of NAVs loaded into the buffer, acid and/or PEG lipid may be, but is not limited to, at least 1 uL, at least 2 uL, at least 5 uL, at least 10 uL, at least 15 uL, at least 20 uL, at least 25 uL, at least 30 uL, at least 35 uL, at least 40 uL, at least 45 ul, at least 50 uL, at least 55 uL, at least 60 uL, at least 65 uL, at least 70 uL, at least 75 uL, at least 80 uL, at least 85 uL, at least 90 uL, at least 100 uL, at least 125 uL, at least 150 uL, at least 200 uL, at least 250 uL, at least 300 uL, at least 350 uL, at least 400 uL, at least 450 uL, at least 500 uL or more than 500 uL.

In one embodiment, the NAVs of the present invention may be loaded in PEGs and also in the buffer or the acid. The amount of NAVs loaded in the PEG may be the same, greater or less than the amount loaded in the buffer or acid. In another embodiment, the NAVs may be formulated, by the methods described herein and/or known in the art, prior to loading in the PEGs, buffer or acid.

A non-limiting example of a PEG-based hydrogel which may be used in the present invention is described in U.S. Pat. No. 8,524,215, the contents of which is herein incorporated by reference in its entirety. The PEG-based hyrdrogel may be an absorbable hydrogel prepared from a multi-arm PEG-vinylsulfone having about 3 to about 8 arms and a multi-arm-PEG-R-sulfhydryl having about 3 to about 8 arms (See e.g., U.S. Pat. No. 8,524,215). In one embodiment, the PEG-based hydrogel may be an absorbable hydrogel. While not wishing to be bound by theory, an absorbable PEG-based hydrogel may be beneficial to reduce the permanent chronic foreign body reaction since the absorbable hydrogel can be absorbed and passed by the body.

In one embodiment, the hydrogel may be a thermosensitive hydrogel. In one aspect the thermosensitive hydrogel may be, but is not limited to, a triblock polymer such as those described herein and known in the art. As a non-limiting example, the tri-block polymer may be PEG-PLGA-PEG (see e.g., the thermosensitive hydrogel (PEG-PLGA-PEG) was used as a TGF-beta1 gene delivery vehicle in Lee et al. Thermosensitive Hydrogel as a Tgf-β1 Gene Delivery Vehicle Enhances Diabetic Wound Healing. Pharmaceutical Research, 2003 20(12): 1995-2000; as a controlled gene delivery system in Li et al. Controlled Gene Delivery System Based on Thermosensitive Biodegradable Hydrogel. Pharmaceutical Research 2003 20(6):884-888; and Chang et al., Non-ionic amphiphilic biodegradable PEG-PLGA-PEG copolymer enhances gene delivery efficiency in rat skeletal muscle. J Controlled Release. 2007 118:245-253; each of which is herein incorporated by reference in its entirety). As a non-limiting example, the thermosensitive hydrogel may be used to make nanoparticles and liposomes by the methods described in International Publication No. WO2013123407, the contents of which are herein incorporated by reference in its entirety.

In another embodiment, the hydrogel may be a biodegradable copolymer hydrogel (see e.g., the biodegradable hydrogels described by Nguyen and Lee (Injectable Biodegradable Hydrogels. Macromolecular Bioscience. 2010 10:563-579), herein incorporated by reference in its entirety). These hydrogels may exhibit a sol-gel phase transition that respond to external stimuli such as, but not limited to, temperature changes, pH alternations or both. Non-limiting examples of biodegradable copolymer hydrogels include triblock copolymers PEG-PLLA-PEG, PEG-PLA-PEG (see e.g., Chang et al., Non-ionic amphiphilic biodegradable PEG-PLGA-PEG copolymer enhances gene delivery efficiency in rat skeletal muscle. J Controlled Release. 2007 118:245-253, herein incorporated by reference in its entirety), PLGA-PEG-PLGA, PEG-PCL-PEG, PCL-PEG-PCL, polyesters such as poly[(R)-3-hydroxybutyrate] (PHB), polyphosphazenes such as L-sioleucine ethyl ester (IIeOEt), D,L-leucine ethyl ester (LeuOEt), L-valine ethyl ester (ValOEt), or di-, tri- and oligo-peptides, polypeptides and chitosan. Temperature and pH sensitive polymers which may be used to form the biodegradable copolymer hydrogels include, but are not limited to, sulfamethazine-, poly(O-amino ester)-, poly(amino urethane)-, and poly(amidoamine)-based polymers. Formulations of the biodegradable copolymer hydrogels and NAVs may be administered using site-specific control of release behavior.

In one embodiment, the hydrogel used in the present invention may be a PEG based hydrogel such as, but not limited to, those described in International Patent Publication No WO2013082590, herein incorporated by reference in its entirety. The PEG based hydrogel may have, but is not limited to, an overall polymer weight concentration of less than or equal to 50% at the time of curing. As a non-limiting example, the PEG based hydrogel may be made by the methods described in International Patent Publication No WO2013082590, the contents of which are herein incorporated by reference in its entirety.

In another embodiment, the NAVs may be formulated in a nanostructured gel composition. The nanostructured gel may be capable of controlled release of the encapsulated NAVs. Non-limiting examples of nanostructed gels or self-assembled gels are described in International Patent Publication No. WO2012040623, the contents of which are herein incorporated by reference in its entirety.

In one embodiment, the concentration of the NAVs of the present invention in the surgical sealants, gels and/or hydrogels may be selected to provide a dosage within the range to have the desired therapeutic effect.

In one embodiment, the concentration of the polynucleotides of the NAV of the present invention in the surgical sealants, gels and/or hydrogels may be at least 0.001 mg to at least 150 mg in at least 0.1 ml to at least 30 ml of the surgical sealant, gel or hydrogel. The concentration of the polynucleotides of the present invention may be at least 0.001 mg, at least 0.005 mg, at least 0.01 mg, at least 0.05 mg, at least 0.1 mg, at least 0.5 mg, at least 1 mg, at least 5 mg, at least 7 mg, at least 10 mg, at least 12, at least 15 mg, at least 17 mg, at least 20 mg, at least 22 mg, at least 25 mg, at least 27 mg, at least 30 mg, at least 32 mg, at least 35 mg, at least 40 mg, at least 45 mg, at least 50 mg, at least 55 mg, at least 60 mg, at least 65 mg, at least 70 mg, at least 75 mg, at least 80 mg, at least 85 mg, at least 90 mg, at least 95 mg, at least 100 mg, at least 105 mg, at least 110 mg, at least 115 mg, at least 120 mg, at least 125 mg, at least 130 mg, at least 135 mg, at least 140 mg, at least 145 mg or at least 150 mg in at least 0.1 ml, at least 0.2 ml, at least 0.3 ml, at least 0.4 ml, at least 0.5 ml, at least 0.6 ml, at least 0.7 ml, at least 0.8 ml, at least 0.9 ml, at least 1 ml, at least 2 ml, at least 3 ml, at least 4 ml, at least 5 ml, at least 6 ml, at least 7 ml, at least 8 ml, at least 9 ml, at least 10 ml, at least 11 ml, at least 12 ml, at least 13 ml, at least 14 ml, at least 15 ml, at least 16 ml, at least 17 ml, at least 18 ml, at least 19 ml, at least 20 ml, at least 21 ml, at least 22 ml, at least 23 ml, at least 24 ml, at least 25 ml, at least 26 ml, at least 27 ml, at least 28 ml, at least 29 ml or at least 30 ml of the surgical sealant, gel or hydrogel.

In another embodiment, concentration of the polynucleotides of the NAV of the present invention in the surgical sealants, gels and/or hydrogels may be at least 0.001 mg/ml at least 0.005 mg/ml, at least 0.01 mg/ml, at least 0.05 mg/ml, at least 0.1 mg/ml, at least 0.5 mg/ml, at least 1 mg/ml, at least 5 mg/ml, at least 7 mg/ml, at least 10 mg/ml, at least 12, at least 15 mg/ml, at least 17 mg/ml, at least 20 mg/ml, at least 22 mg/ml, at least 25 mg/ml, at least 27 mg/ml, at least 30 mg/ml, at least 32 mg/ml, at least 35 mg/ml, at least 40 mg/ml, at least 45 mg/ml or at least 50 mg/ml.

Technology allowing for large subcutaneous infusion volumes which are known in the art, such as, but not limited to, HYLENEX® (Halozyme Therapeutics, San Diego, CA) may also be used. The dispersion and/or adsorption of the modified mRNA described herein may be increased with the use of HYLENEX® as HYLENEX® temporarily breaks down hyaluronic acid causing a temporty degradation in the subcutaneous space (for about 24 hours) just beneath the outside surface of the skin opening microscopic channels and allowing fluid or drugs to be dispersed and absorbed in the body.

Suspension Formulations

In some embodiments, suspension formulations are provided comprising NAVs, water immiscible oil depots, surfactants and/or co-surfactants and/or co-solvents. Combinations of oils and surfactants may enable suspension formulation with NAVs. Delivery of NAVs in a water immiscible depot may be used to improve bioavailability through sustained release of NAVs from the depot to the surrounding physiologic environment and prevent polynucleotides degradation by nucleases.

In some embodiments, suspension formulations of NAV may be prepared using combinations of polynucleotides, oil-based solutions and surfactants. Such formulations may be prepared as a two-part system comprising an aqueous phase comprising polynucleotides and an oil-based phase comprising oil and surfactants. Exemplary oils for suspension formulations may include, but are not limited to sesame oil and Miglyol (comprising esters of saturated coconut and palmkernel oil-derived caprylic and capric fatty acids and glycerin or propylene glycol), corn oil, soybean oil, peanut oil, beeswax and/or palm seed oil. Exemplary surfactants may include, but are not limited to Cremophor, polysorbate 20, polysorbate 80, polyethylene glycol, transcutol, Capmul®, labrasol, isopropyl myristate, and/or Span 80. In some embodiments, suspensions may comprise co-solvents including, but not limited to ethanol, glycerol and/or propylene glycol.

Suspensions may be formed by first preparing NAV formulation comprising an aqueous solution of polynucleotide and an oil-based phase comprising one or more surfactants. Suspension formation occurs as a result of mixing the two phases (aqueous and oil-based). In some embodiments, such a suspension may be delivered to an aqueous phase to form an oil-in-water emulsion. In some embodiments, delivery of a suspension to an aqueous phase results in the formation of an oil-in-water emulsion in which the oil-based phase comprising polynucleotides forms droplets that may range in size from nanometer-sized droplets to micrometer-sized droplets.

In some embodiments, specific combinations of oils, surfactants, cosurfactants and/or co-solvents may be utilized to suspend NAVs in the oil phase and/or to form oil-in-water emulsions upon delivery into an aqueous environment.

In some embodiments, suspensions may provide modulation of the release of NAVs into the surrounding environment. In such embodiments, NAV release may be modulated by diffusion from a water immiscible depot followed by resolubilization into a surrounding environment (e.g. an aqueous environment).

In some embodiments, NAVs within a water immiscible depot (e.g. suspended within an oil phase) may result in altered polynucleotides stability (e.g. altered degradation by nucleases).

In some embodiments, NAVs may be formulated such that upon injection, an emulsion forms spontaneously (e.g. when delivered to an aqueous phase). Such particle formation may provide a high surface area to volume ratio for release of polynucleotides from an oil phase to an aqueous phase.

In one embodiment, the NAVs may be formulated in a nanoemulsion such as, but not limited to, the nanoemulsions described in U.S. Pat. No. 8,496,945, the contents of which are herein incorporated by reference in its entirety. The nanoemulsions may comprise nanoparticles described herein. As a non-limiting example, the nanoparticles may comprise a liquid hydrophobic core which may be surrounded or coated with a lipid or surfactant layer. The lipid or surfactant layer may comprise at least one membrane-integrating peptide and may also comprise a targeting ligand (see e.g., U.S. Pat. No. 8,496,945, the contents of which are herein incorporated by reference in its entirety).

Cations and Anions

Formulations of NAVs disclosed herein may include cations or anions. In one embodiment, the formulations include metal cations such as, but not limited to, Zn2+, Ca2+, Cu2+, Mg+ and combinations thereof. As a non-limiting example, formulations may include polymers and a RNAV complexed with a metal cation (See e.g., U.S. Pat. Nos. 6,265,389 and 6,555,525, each of which is herein incorporated by reference in its entirety).

In some embodiments, cationic nanoparticles comprising combinations of divalent and monovalent cations may be formulated with NAVs. Such nanoparticles may form spontaneously in solution over a give period (e.g. hours, days, etc). Such nanoparticles do not form in the presence of divalent cations alone or in the presence of monovalent cations alone. The delivery of NAVs in cationic nanoparticles or in one or more depot comprising cationic nanoparticles may improve NAV bioavailability by acting as a long-acting depot and/or reducing the rate of degradation by nucleases.

Molded Nanoparticles and Microparticles

The NAVs disclosed herein may be formulated in nanoparticles and/or microparticles. These nanoparticles and/or microparticles may be molded into any size shape and chemistry. As an example, the nanoparticles and/or microparticles may be made using the PRINT® technology by LIQUIDA TECHNOLOGIES® (Morrisville, NC) (See e.g., International Pub. No. WO2007024323; the contents of which are herein incorporated by reference in its entirety).

In one embodiment, the molded nanoparticles may comprise a core of the NAVs disclosed herein and a polymer shell. The polymer shell may be any of the polymers described herein and are known in the art. In an additional embodiment, the polymer shell may be used to protect the NAVs in the core.

In one embodiment, the NAVs of the present invention may be formulated in microparticles. The microparticles may contain a core of the NAVs and a cortext of a biocompatible and/or biodegradable polymer. As a non-limiting example, the microparticles which may be used with the present invention may be those described in U.S. Pat. No. 8,460,709, U.S. Patent Publication No. US20130129830 and International Patent Publication No WO2013075068, each of which is herein incorporated by reference in its entirety. As another non-limiting example, the microparticles may be designed to extend the release of the NAVs of the present invention over a desired period of time (see e.g, extended release of a therapeutic protein in U.S. Patent Publication No. US20130129830, herein incorporated by reference in its entirety).

The microparticle for use with the present invention may have a diameter of at least 1 micron to at least 100 microns (e.g., at least 1 micron, at least 5 micron, at least 10 micron, at least 15 micron, at least 20 micron, at least 25 micron, at least 30 micron, at least 35 micron, at least 40 micron, at least 45 micron, at least 50 micron, at least 55 micron, at least 60 micron, at least 65 micron, at least 70 micron, at least 75 micron, at least 80 micron, at least 85 micron, at least 90 micron, at least 95 micron, at least 97 micron, at least 99 micron, and at least 100 micron).

NanoJackets and NanoLiposomes

The NAVs disclosed herein may be formulated in NanoJackets and NanoLiposomes by Keystone Nano (State College, PA). NanoJackets are made of compounds that are naturally found in the body including calcium, phosphate and may also include a small amount of silicates. Nanojackets may range in size from 5 to 50 nm and may be used to deliver hydrophilic and hydrophobic compounds such as, but not limited to, NAVs.

NanoLiposomes are made of lipids such as, but not limited to, lipids which naturally occur in the body. NanoLiposomes may range in size from 60-80 nm and may be used to deliver hydrophilic and hydrophobic compounds such as, but not limited to, NAVs. In one aspect, the NAVs disclosed herein are formulated in a NanoLiposome such as, but not limited to, Ceramide NanoLiposomes.

Pseudovirions

In one embodiment, the NAVs disclosed herein may be formulated in Pseudovirions (e.g., pseudo-virions). As a non-limiting example, the pseudovirions may be those developed and/or are described by Aura Biosciences (Cambridge, MA). In one aspect, the pseudovirion may be developed to deliver drugs to keratinocytes and basal membranes (See e.g., US Patent Publication Nos. US20130012450, US20130012566, US21030012426 and US20120207840 and International Publication No. WO2013009717, each of which is herein incorporated by reference in its entirety).

In one embodiment, the pseudovirion used for delivering the NAVs of the present invention may be derived from viruses such as, but not limited to, herpes and papillomaviruses (See e.g., US Patent Publication Nos. US Patent Publication Nos. US20130012450, US20130012566, US21030012426 and US20120207840 and International Publication No. WO2013009717, each of which is herein incorporated by reference in its entirety; and Ma et al. HPV pseudovirions as DNA delivery vehicles. Ther Deliv. 2011: 2(4): 427-430; Kines et al. The initial steps leading to papillomavirus infection occur on the basement membrane prior to cell surface binding. PNAS 2009:106(48), 20458-20463; Roberts et al. Genital transmission of HPV in a mouse model is potentiated by nonoxynol-9 and inhibited by carrageenan. Nature Medicine. 2007:13(7) 857-861; Gordon et al., Targeting the Vaginal Mucosa with Human Papillomavirus Psedudovirion Vaccines delivering SIV DNA. J Immunol. 2012 188(2) 714-723; Cuburu et al., Intravaginal immunization with HPV vectors induces tissue-resident CD8+ T cell responses. The Journal of Clinical Investigation. 2012: 122(12) 4606-4620; Hung et al., Ovarian Cancer Gene Therapy Using HPV-16 Psedudovirion Carrying the HSV-tk Gene. PLoS ONE. 2012: 7(7) e40983; Johnson et al., Role of Heparan Sulfate in Attachment to and Infection of the Murine Femal Genital Tract by Human Papillomavirus. J Virology. 2009: 83(5) 2067-2074; each of which is herein incorporated by reference in its entirety).

The pseudovirion may be a virus-like particle (VLP) prepared by the methods described in US Patent Publication No. US20120015899 and US20130177587 and International Patent Publication No. WO2010047839 WO2013116656, WO2013106525 and WO2013122262, the contents of each of which is herein incorporated by reference in its entirety. In one aspect, the VLP may be, but is not limited to, bacteriophages MS, Qp, R17, fr. GA, Sp, MI, I, MXI, NL95, AP205, f2, PP7, and the plant viruses Turnip crinkle virus (TCV), Tomato bushy stunt virus (TBSV), Southern bean mosaic virus (SBMV) and members of the genus Bromovirus including Broad bean mottle virus, Brome mosaic virus, Cassia yellow blotch virus, Cowpea chlorotic mottle virus (CCMV), Melandrium yellow fleck virus, and Spring beauty latent virus. In another aspect, the VLP may be derived from the influenza virus as described in US Patent Publication No. US20130177587 or U.S. Pat. No. 8,506,967, the contents of each of which are herein incorporated by reference in its entirety. In yet another aspect, the VLP may comprise a B7-1 and/or B7-2 molecule anchored to a lipid membrane or the exterior of the particle such as described in International Patent Publication No. WO2013116656, the contents of which are herein incorporated by reference in its entirety. In one aspect, the VLP may be derived from norovirus, rotavirus recombinant VP6 protein or double layered VP2/VP6 such as the VLP described in International Patent Publication No. WO2012049366, the contents of which are herein incorporated by reference in its entirety.

The pseudovirion may be a human papilloma virus-like particle such as, but not limited to, those described in International Publication No. WO2010120266 and US Patent Publication No. US20120171290, each of which is herein incorporated by reference in its entirety and Ma et al. HPV pseudovirions as DNA delivery vehicles. Ther Deliv. 2011: 2(4): 427-430; Kines et al. The initial steps leading to papillomavirus infection occur on the basement membrane prior to cell surface binding. PNAS 2009:106(48), 20458-20463; Roberts et al. Genital transmission of HPV in a mouse model is potentiated by nonoxynol-9 and inhibited by carrageenan. Nature Medicine. 2007:13(7) 857-861; Gordon et al., Targeting the Vaginal Mucosa with Human Papillomavirus Psedudovirion Vaccines delivering SIV DNA. J Immunol. 2012 188(2) 714-723; Cuburu et al., Intravaginal immunization with HPV vectors induces tissue-resident CD8+ T cell responses. The Journal of Clinical Investigation. 2012: 122(12) 4606-4620; Hung et al., Ovarian Cancer Gene Therapy Using HPV-16 Psedudovirion Carrying the HSV-tk Gene. PLoS ONE. 2012: 7(7) e40983; Johnson et al., Role of Heparan Sulfate in Attachment to and Infection of the Murine Femal Genital Tract by Human Papillomavirus. J Virology. 2009: 83(5) 2067-2074; each of which is herein incorporated by reference in its entirety.

In one aspect, the pseudovirions may be virion derived nanoparticles such as, but not limited to, those described in US Patent Publication No. US20130116408 and US20130115247, each of which is herein incorporated by reference in their entirety. As a non-limiting example, the virion derived nanoparticles may be used to deliver NAVs which may be used in the treatment for cancer and/or enhance the immune system's recognition of the tumor. As a non-limiting example, the virion-derived nanoparticle which may selectively deliver an agent to at least one tumor may be the papilloma-derived particles described in International Patent Publication No. WO2013119877, the contents of which are herein incorporated by reference in its entirety. The virion derived nanoparticles may be made by the methods described in US Patent Publication No. US20130116408 and US20130115247 or international Patent Publication No. WO2013119877, each of which is herein incorporated by reference in their entirety.

In one embodiment, the virus-like particle (VLP) may be a self-assembled particle. Non-limiting examples of self-assembled VLPs and methods of making the self-assembled VLPs are described in International Patent Publication No. WO2013122262, the contents of which are herein incorporated by reference in its entirety.

Minicells

In one aspect, the NAVs may be formulated in bacterial minicells. As a non-limiting example, bacterial minicells may be those described in international Publication No. WO2013088250 or US Patent Publication No. US20130177499, the contents of each of which are herein incorporated by reference in its entirety. The bacterial minicells comprising therapeutic agents such as NAVs described herein may be used to deliver the therapeutic agents to brain tumors.

Semi-Solid Compositions

In one embodiment, the NAVs may be formulated with a hydrophobic matrix to form a semi-solid composition. As a non-limiting example, the semi-solid composition or paste-like composition may be made by the methods described in International Patent Publication No WO201307604, herein incorporated by reference in its entirety. The semi-solid composition may be a sustained release formulation as described in International Patent Publication No WO201307604, herein incorporated by reference in its entirety.

In another embodiment, the semi-solid composition may further have a micro-porous membrane or a biodegradable polymer formed around the composition (see e.g., International Patent Publication No WO201307604, herein incorporated by reference in its entirety).

The semi-solid composition using the NAVs of the present invention may have the characteristics of the semi-solid mixture as described in International Patent Publication No WO201307604, herein incorporated by reference in its entirety (e.g., a modulus of elasticity of at least 10⁻⁴N·mm⁻², and/or a viscosity of at least 100 mPa·s).

Exosomes

In one embodiment, the NAVs may be formulated in exosomes. The exosomes may be loaded with at least one NAV and delivered to cells, tissues and/or organisms. As a non-limiting example, the NAVs may be loaded in the exosomes described in International Publication No. WO2013084000, herein incorporated by reference in its entirety.

Silk-Based Delivery

In one embodiment, the NAVs may be formulated in a sustained release silk-based delivery system. The silk-based delivery system may be formed by contacting a silk fibroin solution with a therapeutic agent such as, but not limited to, the NAVs described herein and/or known in the art. As a non-limiting example, the sustained release silk-based delivery system which may be used in the present invention and methods of making such system are described in US Patent Publication No. US20130177611, the contents of which are herein incorporated by reference in its entirety.

Microparticles

In one embodiment, formulations comprising NAVs may comprise microparticles. The microparticles may comprise a polymer described herein and/or known in the art such as, but not limited to, poly(α-hydroxy acid), a polyhydroxy butyric acid, a polycaprolactone, a polyorthoester and a polyanhydride. The microparticle may have adsorbent surfaces to adsorb biologically active molecules such as NAVs. As a non-limiting example microparticles for use with the present invention and methods of making microparticles are described in US Patent Publication No. US2013195923 and US20130195898 and U.S. Pat. Nos. 8,309,139 and 8,206,749, the contents of each of which are herein incorporated by reference in its entirety.

In another embodiment, the formulation may be a microemulsion comprising microparticles and NAVs. As a non-limiting example, microemulsions comprising microparticles are described in US Patent Publication No. US2013195923 and US20130195898 and U.S. Pat. Nos. 8,309,139 and 8,206,749, the contents of each of which are herein incorporated by reference in its entirety.

Amino Acid Lipids

In one embodiment, the NAVs may be formulated in amino acid lipids. Amino acid lipids are lipophilic compounds comprising an amino acid residue and one or more lipophilic tails. Non-limiting examples of amino acid lipids and methods of making amino acid lipids are described in U.S. Pat. No. 8,501,824, the contents of which are herein incorporated by reference in its entirety.

In one embodiment, the amino acid lipids have a hydrophilic portion and a lipophilic portion. The hydrophilic portion may be an amino acid residue and a lipophilic portion may comprise at least one lipophilic tail.

In one embodiment, the amino acid lipid formulations may be used to deliver the NAVs to a subject.

In another embodiment, the amino acid lipid formulations may deliver a NAV in releasable form which comprises an amino acid lipid that binds and releases the NAV. As a non-limiting example, the release of the NAVs may be provided by an acid-labile linker such as, but not limited to, those described in U.S. Pat. Nos. 7,098,032, 6,897,196, 6,426,086, 7,138,382, 5,563,250, and 5,505,931, the contents of each of which are herein incorporated by reference in its entirety.

Microvesicles

In one embodiment, NAVs may be formulated in microvesicles. Non-limiting examples of microvesicles include those described in US Patent Publication No. US20130209544, the contents of which are herein incorporated by reference in its entirety.

In one embodiment, the microvesicle is an ARRDC1-mediated microvesicles (ARMMs). Non-limiting examples of ARMMs and methods of making ARMMs are described in International Patent Publication No. WO2013119602, the contents of which are herein incorporated by reference in its entirety.

Interpolyelectrolyte Complexes

In one embodiment, the NAVs may be formulated in an interpolyelectrolyte complex. Interpolyelectrolyte complexes are formed when charge-dynamic polymers are complexed with one or more anionic molecules. Non-limiting examples of charge-dynamic polymers and interpolyelectrolyte complexes and methods of making interpolyelectrolyte complexes are described in U.S. Pat. No. 8,524,368, the contents of which is herein incorporated by reference in its entirety.

Crystalline Polymeric Systems

In one embodiment, the NAVs may be formulated in crystalline polymeric systems. Crystalline polymeric systems are polymers with crystalline moieties and/or terminal units comprising crystalline moieties. Non-limiting examples of polymers with crystalline moieties and/or terminal units comprising crystalline moieties termed “CYC polymers,” crystalline polymer systems and methods of making such polymers and systems are described in U.S. Pat. No. 8,524,259, the contents of which are herein incorporated by reference in its entirety.

Excipients

NAV pharmaceutical formulations may additionally comprise a pharmaceutically acceptable excipient, which, as used herein, includes, but are not limited to, any and all solvents, dispersion media, diluents, or other liquid vehicles, dispersion or suspension aids, surface active agents, isotonic agents, thickening or emulsifying agents, preservatives, solid binders, lubricants, flavoring agents, stabilizers, antioxidants, osmolality adjusting agents. pH adjusting agents and the like, as suited to the particular dosage form desired. Various excipients for formulating pharmaceutical compositions and techniques for preparing the composition are known in the art (see Remington: The Science and Practice of Pharmacy, 21^stEdition, A. R. Gennaro (Lippincott, Williams & Wilkins, Baltimore, MD, 2006; incorporated herein by reference in its entirety). The use of a conventional excipient medium may be contemplated within the scope of the present disclosure, except insofar as any conventional excipient medium is incompatible with a substance or its derivatives, such as by producing any undesirable biological effect or otherwise interacting in a deleterious manner with any other component(s) of the pharmaceutical composition, its use is contemplated to be within the scope of this invention.

In some embodiments, a pharmaceutically acceptable excipient may be at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% pure. In some embodiments, an excipient is approved for use for humans and for veterinary use. In some embodiments, an excipient may be approved by United States Food and Drug Administration. In some embodiments, an excipient may be of pharmaceutical grade. In some embodiments, an excipient may meet the standards of the United States Pharmacopoeia (USP), the European Pharmacopoeia (EP), the British Pharmacopoeia, and/or the International Pharmacopoeia.

Pharmaceutically acceptable excipients used in the manufacture of pharmaceutical compositions include, but are not limited to, inert diluents, dispersing and/or granulating agents, surface active agents and/or emulsifiers, disintegrating agents, binding agents, preservatives, buffering agents, lubricating agents, and/or oils. Such excipients may optionally be included in pharmaceutical compositions. The composition may also include excipients such as cocoa butter and suppository waxes, coloring agents, coating agents, sweetening, flavoring, and/or perfuming agents.

Exemplary diluents include, but are not limited to, calcium carbonate, sodium carbonate, calcium phosphate, dicalcium phosphate, calcium sulfate, calcium hydrogen phosphate, sodium phosphate lactose, sucrose, cellulose, microcrystalline cellulose, kaolin, mannitol, sorbitol, inositol, sodium chloride, dry starch, cornstarch, powdered sugar, etc., and/or combinations thereof.

Exemplary granulating and/or dispersing agents include, but are not limited to, potato starch, corn starch, tapioca starch, sodium starch glycolate, clays, alginic acid, guar gum, citrus pulp, agar, bentonite, cellulose and wood products, natural sponge, cation-exchange resins, calcium carbonate, silicates, sodium carbonate, cross-linked poly(vinyl-pyrrolidone) (crospovidone), sodium carboxymethyl starch (sodium starch glycolate), carboxymethyl cellulose, cross-linked sodium carboxymethyl cellulose (croscarmellose), methylcellulose, pregelatinized starch (starch 1500), microcrystalline starch, water insoluble starch, calcium carboxymethyl cellulose, magnesium aluminum silicate (VEEGUM®), sodium lauryl sulfate, quaternary ammonium compounds, etc., and/or combinations thereof.

Exemplary surface active agents and/or emulsifiers include, but are not limited to, natural emulsifiers (e.g. acacia, agar, alginic acid, sodium alginate, tragacanth, chondrux, cholesterol, xanthan, pectin, gelatin, egg yolk, casein, wool fat, cholesterol, wax, and lecithin), colloidal clays (e.g. bentonite [aluminum silicate] and VEEGUM® [magnesium aluminum silicate]), long chain amino acid derivatives, high molecular weight alcohols (e.g. stearyl alcohol, cetyl alcohol, oleyl alcohol, triacetin monostearate, ethylene glycol distearate, glyceryl monostearate, and propylene glycol monostearate, polyvinyl alcohol), carbomers (e.g. carboxy polymethylene, polyacrylic acid, acrylic acid polymer, and carboxyvinyl polymer), carrageenan, cellulosic derivatives (e.g. carboxymethylcellulose sodium, powdered cellulose, hydroxymethyl cellulose, hydroxypropyl cellulose, hydroxypropyl methylcellulose, methylcellulose), sorbitan fatty acid esters (e.g. polyoxyethylene sorbitan monolaurate [TWEEN®20], polyoxyethylene sorbitan [TWEEN®60], polyoxyethylene sorbitan monooleate [TWEEN®80], sorbitan monopalmitate [SPAN®40], sorbitan monostearate [SPAN®60], sorbitan tristearate [SPAN®65], glyceryl monooleate, sorbitan monooleate [SPAN®80]), polyoxyethylene esters (e.g. polyoxyethylene monostearate [MYRJ®45], polyoxyethylene hydrogenated castor oil, polyethoxylated castor oil, polyoxymethylene stearate, and SOLUTOL®), sucrose fatty acid esters, polyethylene glycol fatty acid esters (e.g. CREMOPHOR®), polyoxyethylene ethers, (e.g. polyoxyethylene lauryl ether [BRU®30]), poly(vinyl-pyrrolidone), diethylene glycol monolaurate, triethanolamine oleate, sodium oleate, potassium oleate, ethyl oleate, oleic acid, ethyl laurate, sodium lauryl sulfate, PLUORINC®F 68, POLOXAMER®188, cetrimonium bromide, cetylpyridinium chloride, benzalkonium chloride, docusate sodium, etc. and/or combinations thereof.

Exemplary binding agents include, but are not limited to, starch (e.g. cornstarch and starch paste); gelatin; sugars (e.g. sucrose, glucose, dextrose, dextrin, molasses, lactose, lactitol, mannitol); amino acids (e.g., glycine); natural and synthetic gums (e.g. acacia, sodium alginate, extract of Irish moss, panwar gum, ghatti gum, mucilage of isapol husks, carboxymethylcellulose, methylcellulose, ethylcellulose, hydroxyethylcellulose, hydroxypropyl cellulose, hydroxypropyl methylcellulose, microcrystalline cellulose, cellulose acetate, poly(vinyl-pyrrolidone), magnesium aluminum silicate (VEEGUM®), and larch arabogalactan); alginates; polyethylene oxide; polyethylene glycol; inorganic calcium salts; silicic acid; polymethacrylates; waxes; water, alcohol; etc.; and combinations thereof.

Exemplary preservatives may include, but are not limited to, antioxidants, chelating agents, antimicrobial preservatives, antifungal preservatives, alcohol preservatives, acidic preservatives, and/or other preservatives. Oxidation is a potential degradation pathway for mRNA, especially for liquid mRNA formulations. In order to prevent oxidation, antioxidants can be added to the formulation. Exemplary antioxidants include, but are not limited to, alpha tocopherol, ascorbic acid, acorbyl palmitate, benzyl alcohol, butylated hydroxyanisole, EDTA, m-cresol, methionine, butylated hydroxytoluene, monothioglycerol, potassium metabisulfite, propionic acid, propyl gallate, sodium ascorbate, sodium bisulfite, sodium metabisulfite, thioglycerol and/or sodium sulfite. Exemplary chelating agents include ethylenediaminetetraacetic acid (EDTA), citric acid monohydrate, disodium edetate, dipotassium edetate, edetic acid, fumaric acid, malic acid, phosphoric acid, sodium edetate, tartaric acid, and/or trisodium edetate. Exemplary antimicrobial preservatives include, but are not limited to, benzalkonium chloride, benzethonium chloride, benzyl alcohol, bronopol, cetrimide, cetylpyridinium chloride, chlorhexidine, chlorobutanol, chlorocresol, chloroxylenol, cresol, ethyl alcohol, glycerin, hexetidine, imidurea, phenol, phenoxyethanol, phenylethyl alcohol, phenylmercuric nitrate, propylene glycol, and/or thimerosal. Exemplary antifungal preservatives include, but are not limited to, butyl paraben, methyl paraben, ethyl paraben, propyl paraben, benzoic acid, hydroxybenzoic acid, potassium benzoate, potassium sorbate, sodium benzoate, sodium propionate, and/or sorbic acid. Exemplary alcohol preservatives include, but are not limited to, ethanol, polyethylene glycol, phenol, phenolic compounds, bisphenol, chlorobutanol, hydroxybenzoate, and/or phenylethyl alcohol. Exemplary acidic preservatives include, but are not limited to, vitamin A, vitamin C, vitamin E, beta-carotene, citric acid, acetic acid, dehydroacetic acid, ascorbic acid, sorbic acid, and/or phytic acid. Other preservatives include, but are not limited to, tocopherol, tocopherol acetate, deteroxime mesylate, cetrimide, butylated hydroxyanisol (BHA), butylated hydroxytoluened (BHT), ethylenediamine, sodium lauryl sulfate (SLS), sodium lauryl ether sulfate (SLES), sodium bisulfite, sodium metabisulfite, potassium sulfite, potassium metabisulfite, GLYDANT PLUS*, PHENONIP*, methylparaben, GERMALL®115, GERMABEN®II, NEOLONE™, KATHON™, and/or EUXYL®.

In some embodiments, the pH of the NAV solutions are maintained between pH 5 and pH 8 to improve stability. Exemplary buffers to control pH may include, but are not limited to sodium phosphate, sodium citrate, sodium succinate, histidine (or histidine-HCl), sodium carbonate, and/or sodium malate. In another embodiment, the exemplary buffers listed above may be used with additional monovalent counterions (including, but not limited to potassium). Divalent cations may also be used as buffer counterions; however, these are not preferred due to complex formation and/or mRNA degradation.

Exemplary buffering agents may also include, but are not limited to, citrate buffer solutions, acetate buffer solutions, phosphate buffer solutions, ammonium chloride, calcium carbonate, calcium chloride, calcium citrate, calcium glubionate, calcium gluceptate, calcium gluconate, D-gluconic acid, calcium glycerophosphate, calcium lactate, propanoic acid, calcium levulinate, pentanoic acid, dibasic calcium phosphate, phosphoric acid, tribasic calcium phosphate, calcium hydroxide phosphate, potassium acetate, potassium chloride, potassium gluconate, potassium mixtures, dibasic potassium phosphate, monobasic potassium phosphate, potassium phosphate mixtures, sodium acetate, sodium bicarbonate, sodium chloride, sodium citrate, sodium lactate, dibasic sodium phosphate, monobasic sodium phosphate, sodium phosphate mixtures, tromethamine, magnesium hydroxide, aluminum hydroxide, alginic acid, pyrogen-free water, isotonic saline, Ringer's solution, ethyl alcohol, etc., and/or combinations thereof.

Exemplary lubricating agents include, but are not limited to, magnesium stearate, calcium stearate, stearic acid, silica, talc, malt, glyceryl behanate, hydrogenated vegetable oils, polyethylene glycol, sodium benzoate, sodium acetate, sodium chloride, leucine, magnesium lauryl sulfate, sodium lauryl sulfate, etc., and combinations thereof.

Exemplary oils include, but are not limited to, almond, apricot kernel, avocado, babassu, bergamot, black current seed, borage, cade, camomile, canola, caraway, carnauba, castor, cinnamon, cocoa butter, coconut, cod liver, coffee, corn, cotton seed, emu, eucalyptus, evening primrose, fish, flaxseed, geraniol, gourd, grape seed, hazel nut, hyssop, isopropyl myristate, jojoba, kukui nut, lavandin, lavender, lemon, Litsea cubeba, macademia nut, mallow, mango seed, meadowfoam seed, mink, nutmeg, olive, orange, orange roughy, palm, palm kernel, peach kernel, peanut, poppy seed, pumpkin seed, rapeseed, rice bran, rosemary, safflower, sandalwood, sasquana, savoury, sea buckthorn, sesame, shea butter, silicone, soybean, sunflower, tea tree, thistle, tsubaki, vetiver, walnut, and wheat germ oils. Exemplary oils include, but are not limited to, butyl stearate, caprylic triglyceride, capric triglyceride, cyclomethicone, diethyl sebacate, dimethicone 360, isopropyl myristate, mineral oil, octyldodecanol, oleyl alcohol, silicone oil, and/or combinations thereof.

Excipients such as cocoa butter and suppository waxes, coloring agents, coating agents, sweetening, flavoring, and/or perfuming agents can be present in the composition, according to the judgment of the formulator.

Exemplary additives include physiologically biocompatible buffers (e.g., trimethylamine hydrochloride), addition of chelants (such as, for example, DTPA or DTPA-bisamide) or calcium chelate complexes (as for example calcium DTPA, CaNaDTPA-bisamide), or, optionally, additions of calcium or sodium salts (for example, calcium chloride, calcium ascorbate, calcium gluconate or calcium lactate). In addition, antioxidants and suspending agents can be used.

Cryoprotectants

In some embodiments, NAV formulations may comprise cyroprotectants. As used herein, there term “cryoprotectant” refers to one or more agent that when combined with a given substance, helps to reduce or eliminate damage to that substance that occurs upon freezing. In some embodiments, cryoprotectants are combined with NAVs in order to stabilize them during freezing. Frozen storage of NAVs between −20° C. and −80° C. may be advantageous for long term (e.g. 36 months) stability of polynucleotide. In some embodiments, cryoprotectants are included in NAV formulations to stabilize polynucleotide through freeze/thaw cycles and under frozen storage conditions. Cryoprotectants of the present invention may include, but are not limited to sucrose, trehalose, lactose, glycerol, dextrose, raffinose and/or mannitol. Trehalose is listed by the Food and Drug Administration as being generally regarded as safe (GRAS) and is commonly used in commercial pharmaceutical formulations.

Bulking Agents

In some embodiments, NAV formulations may comprise bulking agents. As used herein, the term “bulking agent” refers to one or more agents included in formulations to impart a desired consistency to the formulation and/or stabilization of formulation components. In some embodiments, bulking agents are included in lyophilized NAV formulations to yield a “pharmaceutically elegant” cake, stabilizing the lyophilized NAVs during long term (e.g. 36 month) storage. Bulking agents of the present invention may include, but are not limited to sucrose, trehalose, mannitol, glycine, lactose and/or raffinose. In some embodiments, combinations of cryoprotectants and bulking agents (for example, sucrose/glycine or trehalose/mannitol) may be included to both stabilize NAVs during freezing and provide a bulking agent for lyophilization.

Non-limiting examples of formulations and methods for formulating the NAVs of the present invention are also provided in International Publication No WO2013090648 filed Dec. 14, 2012, the contents of which are incorporated herein by reference in their entirety.

Inactive Ingredients

In some embodiments, NAV formulations may comprise at least one excipient which is an inactive ingredient. As used herein, the term “inactive ingredient” refers to one or more inactive agents included in formulations. In some embodiments, all, none or some of the inactive ingredients which may be used in the formulations of the present invention may be approved by the US Food and Drug Administration (FDA). A non-exhaustive list of inactive ingredients and the routes of administration the inactive ingredients may be formulated in are described in Table 26. In Table 26, “AN” means anesthetic, “CNBLK” means cervical nerve block, “NBLK” means nerve block, “IV” means intravenous, “IM” means intramuscular and “SC” means subcutaneous

TABLE 26

Inactive Ingredients

Inactive Ingredient
Route of Administration

Alpha-Terpineol
Topical

Alpha-Tocopherol
Intravenous; Topical

Alpha-Tocopherol Acetate, Dl-
Topical

Alpha-Tocopherol, Dl-
Intravenous; Topical

1,2,6-Hexanetriol
Topical

1,2-Dimyristoyl-Sn-Glycero-3-(Phospho-S-
Intravenous; Infusion (IV)

(1-Glycerol))

1,2-Dimyristoyl-Sn-Glycero-3-
Intravenous; Infusion (IV)

Phosphocholine

1,2-Dioleoyl-Sn-Glycero-3-Phosphocholine
Epidural

1,2-Dipalmitoyl-Sn-Glycero-3-(Phospho-
Epidural

Rac-(1-Glycerol))

1,2-Distearoyl-Sn-Glycero-3-(Phospho-Rac-
Intravenous

(1-Glycerol))

1,2-Distearoyl-Sn-Glycero-3-Phosphocholine
Intravenous

1-O-Tolylbiguanide
Topical

2-Ethyl-1,6-Hexanediol
Topical

Acetic Acid
Infiltration; Auricular (Otic); Extracorporeal;

Intramuscular; Intravenous; Subcutaneous; Intra-

articualr; Intralesional; Intramuscular; Intrasynovial;

Intratracheal; Intravenous; Irrigation; Infusion (IV);

Nasal; Nerve block; Ophthalmic; Photopheresis; Soft

Tissue; Submucosal; Topical

Acetic Acid, Glacial
Intravenous; Infusion (IV); Subcutaneous

Acetic Anhydride
Intravenous

Acetone
Implantation; Topical

Acetone Sodium Bisulfite
Intrathecal (AN, CNBLK); Infiltration (AN); Dental;

Inhalation; Nerve Block

Acetylated Lanolin Alcohols
Topical

Acetylated Monoglycerides
Intravenous

Acetylcysteine
Inhalation

Acetyltryptophan, DL-
Intravenous

Acrylates Copolymer
Topical; Transdermal

Acrylic Acid-Isooctyl Acrylate Copolymer
Transdermal

Acrylic Adhesive 788
Transdermal

Activated Charcoal
Intramuscular; Intravenous; Irrigation; Infusion (IV)

Adcote 72A103
Transdermal

Adhesive Tape
Topical

Adipic Acid
Intramuscular; Vaginal

Aerotex Resin 3730
Transdermal

Alanine
Infusion (IV)

Albumin Aggregated
Intravenous

Albumin Colloidal
Intravenous

Albumin Human
Intravenous; Infusion (IV); Subcutaneous

Alcohol
Dental; Intramuscular; Intravenous; Subcutaneous;

Inhalation; Intravascular; Infusion (IV); Ophthalmic;

Rectal; Respiratory (Inhalation); Topical;

Transdermal

Alcohol, Dehydrated
Dental; Extracorporeal; Intramuscular; Intravenous;

Subcutaneous; Inhalation; Intracavitary;

Intravascular; Intravesical; Nasal, Ophthalmic;

Photopheresis, Rectal; Respiratory (Inhalation);

Sublingual; Topical; Transdermal

Alcohol, Denatured
Denatal; Intravenous; Topical; Vaginal

Alcohol, Diluted
Intramuscular; Intravenous; Topical

Alfadex
Intracavitary

Alginic Acid
Ophthalmic

Alkyl Ammonium Sulfonic Acid Betaine
Topical

Alkyl Aryl Sodium Sulfonate
Topical

Allantoin
Topical; Vaginal

Allyl.Alpha.-Ionone
Nasal

Almond Oil
Topical

Aluminum Acetate
Auricular (Otic); Topical

Aluminum Chlorhydroxy Allantoinate
Topical

Aluminum Hydroxide
Topical

Aluminum Hydroxide-Sucrose, Hydrated
Topical

Aluminum Hydroxide Gel
Topical

Aluminum Hydroxide Gel F 500
Topical

Aluminum Hydroxide Gel F 5000
Topical

Aluminum Monostearate
Topical

Aluminum Oxide
Topical

Aluminum Polyester
Transdermal

Aluminum Silicate
Topical

Aluminum Starch Octenylsuccinate
Topical

Aluminum Stearate
Topical

Aluminum Subacetate
Rectal

Aluminum Sulfate Anhydrous
Auricular (Otic); Topical

Amerchol C
Topical

Amerchol-Cab
Ophthalmic; Topical

Aminomethylpropanol
Topical

Ammonia
Inhalation

Ammonia Solution
Topical

Ammonia Solution, Strong
Topical

Ammonium Acetate
Intramuscular; Intravenous; Infusion (IV)

Ammonium Hydroxide
Intravenous; Ophthalmic; Subcutaneous; Topical

Ammonium Lauryl Sulfate
Topical

Ammonium Nonoxynol-4 Sulfate
Topical

Ammonium Salt Of C-12-C-15 Linear
Topical

Primary Alcohol Ethoxylate

Ammonium Sulfate
Intravenous

Ammonyx
Topical

Amphoteric-2
Topical

Amphoteric-9
Topical

Anethole
Dental

Anhydrous Citric Acid
Intravenous; Infusion (IV); Rectal; Topical

Anhydrous Dextrose
Intramuscular; Intravenous; Subcutaneous; Infusion

(IV); Nasal; Spinal

Anhydrous Lactose
Intramuscular; Intravenous; Intracavitary;

Intravenous; Infusion (IV); Vaginal

Anhydrous Trisodium Citrate
Intramuscular; Intravenous; Intra-arterial; Intra-

articular; Intrabursal; Infusion (IV); Nasal;

Ophthalmic; Soft Tissue; Topical

Aniseed Oil
Rectal

Anoxid Sbn
Topical

Antifoam
Topical

Antipyrine
Ophthalmic

Apaflurane
Respiratory (Inhalation)

Apricot Kernel Oil Peg-6 Esters
Topical; Vaginal

Aquaphor
Topical

Arginine
Intramuscular; Intravenous; Infusion (IV)

Arlacel
Topical

Ascorbic Acid
Infiltration (AN); Caudal Block; Epidural;

Intramuscular; Intravenous; Inhalation; Infusion

(IV); Nerve Block; Rectal; Subctaneous; Topical

Ascorbyl Palmitate
Rectal; Topical

Aspartic Acid
Infusion (IV)

Balsam Peru
Rectal

Barium Sulfate
Intrauterine; Vaginal

Beeswax
Topical; Vaginal

Beeswax, Synthetic
Topical

Beheneth-10
Topical

Bentonite
Topical; Transdermal; Vaginal

Benzalkonium Chloride
Auricular (Otic); Inhalation; Intra-Articular;

Intrabursal; Intradermal; Intralesional; Intramuscular;

Intraocular; Nasal; Ophthalmic; Respiratory

(Inhalation); Topical

Benzenesulfonic Acid
Intravenous; Infusion (IV)

Benzethonium Chloride
Auricular (Otic); Intramuscular; Intravenous;

Infusion (IV); Nasal; Ophthalmic

Benzododecinium Bromide
Ophthalmic

Benzoic Acid
Intramuscular; Intravenous; Irrigation; Infusion (IV);

Rectal; Topical; Vaginal

Benzyl Alcohol
Infiltration (AN); Auricular (Otic); Dental; Epidural;

Extracorporeal; Interstitial; Intra-Arterial; Intra-

Articular; Intrabursal; Intracavitary; Intradermal;

Intralesional; Intramuscular; Intraperitoneal;

Intrapleural; Intrasynovial; Intrathecal; Intratracheal;

Intratumor; Intravenous; Infusion(IV); Nasal; Nerve

Block; Rectal; Soft Tissue; Subconjunctival;

Subcutaneous; Topical; Ureteral; Vaginal

Benzyl Benzoate
Intramuscular

Benzyl Chloride
Intravenous

Betadex
Topical

Bibapcitide
Intravenous

Bismuth Subgallate
Rectal

Boric Acid
Auricular (Otic); Intravenous; Ophthalmic; Topical

Brocrinat
Infusion (IV)

Butane
Topical

Butyl Alcohol
Topical

Butyl Ester Of Vinyl Methyl Ether/Maleic
Topical

Anhydride Copolymer (125000 Mw)

Butyl Stearate
Topical

Butylated Hydroxyanisole
Intramuscular; Infusion (IV); Nasal; Rectal; Topical;

Vaginal

Butylated Hydroxytoluene
Intramuscular; Intravenous; Infusion (IV); Nasal;

Rectal; Topical; Transdermal; Vaginal

Butylene Glycol
Topical; Transdermal

Butylparaben
Intramuscular; Rectal; Topical

Butyric Acid
Transdermal

C20-40 Pareth-24
Topical

Caffeine
Nasal; Ophthalmic

Calcium
Intramuscular

Calcium Carbonate
Auricular (Otic); Respiratory (Inhalation)

Calcium Chloride
Infiltration (AN); Caudal Block; Epidural;

Intramuscular; Intravenous; Intraocular;

Intraperitoneal; Intravascular; Intravitreal; Nerve

Block; Ophthalmic; Subctaneous; Topical

Calcium Gluceptate
Intravenous

Calcium Hydroxide
Intravenous; Subcutaneous; Topical

Calcium Lactate
Vaginal

Calcobutrol
Intravenous

Caldiamide Sodium
Intravenous

Caloxetate Trisodium
Intravenous

Calteridol Calcium
Intravenous

Canada Balsam
Topical

Caprylic/Capric Triglyceride
Topical; Transdermal

Caprylic/Capric/Stearic Triglyceride
Topical

Captan
Topical

Captisol
Intravenous

Caramel
Rectal; Topical

Carbomer 1342
Ophthalmic; Topical; Transdermal

Carbomer 1382
Topical

Carbomer 934
Rectal; Topical; Vaginal

Carbomer 934p
Ophthalmic; Rectal; Topical; Vaginal

Carbomer 940
Ophthalmic; Topical; Transdermal

Carbomer 941
Topical

Carbomer 980
Topical; Transdermal

Carbomer 981
Topical

Carbomer Homopolymer Type B (Allyl
Ophthalmic; Topical

Pentaerythritol Crosslinked)

Carbomer Homopolymer Type C (Allyl
Topical

Pentaerythritol Crosslinked)

Carbon Dioxide
Infiltration (AN); Intramuscular (IM); Infusion (IV);

Inhalation; Intra-arterial; Intracardiac; Intrathecal;

Intravascular; Intravenous

Carboxy Vinyl Copolymer
Topical

Carboxymethylcellulose
Intra-articular; Intrabursal; Intralesional;

Intramuscular; Soft tissue; Topical

Carboxymethylcellulose Sodium
Dental; Intra-articular; Intrabursal; Intradermal;

Intramuscular; Intrasynovial; Intratracheal; Nasal;

Ophthalmic; Soft tissue; Subcutaneous; Topical

Carboxypolymethylene
Rectal; Topical

Carrageenan
Dental; Topical; Transdermal

Carrageenan Salt
Topical

Castor Oil
Intramuscular; Ophthalmic; Topical

Cedar Leaf Oil
Topical

Cellulose
Topical

Cellulose, Microcrystalline
Intra-articular; Intramuscular; Intravenous;

Intravitreal; Nasal; Vaginal

Cerasynt-Se
Rectal; Topical

Ceresin
Topical

Ceteareth-12
Topical

Ceteareth-15
Topical

Ceteareth-30
Topical

Cetearyl Alcohol/Ceteareth-20
Topical

Cetearyl Ethylhexanoate
Topical

Ceteth-10
Topical

Ceteth-2
Topical

Ceteth-20
Topical; Vaginal

Ceteth-23
Topical

Cetostearyl Alcohol
Topical; Vaginal

Cetrimonium Chloride
Topical

Cetyl Alcohol
Auricular (Otic); Ophthalmic; Rectal; Topical;

Vaginal

Cetyl Esters Wax
Topical; Vaginal

Cetyl Palmitate
Topical; Vaginal

Cetylpyridinium Chloride
Inhalation; Iontophoresis; Transdermal

Chlorobutanol
Infiltration (AN); Auricular (Otic); Intramuscular

(IM); Infusion (IV); Subcutaneous (SC); Inhalation;

Intravenous; Nasal; Nerve Block; Ophthalmic;

Topical

Chlorobutanol Hemihydrate
Intramuscular; Intravenous

Chlorobutanol, Anhydrous
Intramuscular; Intravenous; Ophthalmic

Chlorocresol
Topical

Chloroxylenol
Auricular (Otic); Topical

Cholesterol
Epidural; Infiltration; Intravecous; Ophthalmic;

Topical; Vaginal

Choleth
Vaginal

Choleth-24
Topical

Citrate
Intravenous

Citric Acid
Intrathecal (AN, CNBLK); Infiltration (AN);

Auricular (Otic); Caudal Block; Epidural;

Intramuscular (IM); Infusion (IV); Subcutaneous

(SC); Infiltration; Inhalation; Intra-amniotic; Intra-

arterial; Intra-articular; Intrabursal; Intracardiac;

Intralesional; Iintrapleural; Intrasynovial; Intrathecal;

Intravascular; Intravenous; Iontophoresis; Nasal;

Nerve Block; Ophthalmic; Peridural; Soft tissue;

Topical; Transdermal; Vaginal

Citric Acid Monohydrate
Infiltration (AN); Intramuscular (IM); Infusion (IV);

Subcutaneous (SC); Intracardiac; Intraocular;

Intravenous; Nasal; Nerve Block; Ophthalmic;

Topical; Vaginal

Citric Acid, Hydrous
Intramuscular (IM); Infusion (IV); Subcutaneous

(SC); Intravenous

Cocamide Ether Sulfate
Topical

Cocamine Oxide
Topical

Coco Betaine
Topical

Coco Diethanolamide
Topical

Coco Monoethanolamide
Topical

Cocoa Butter
Rectal; Topical

Coco-Glycerides
Topical

Coconut Oil
Topical

Coconut Oil, Hydrogenated
Rectal

Coconut Oil/Palm Kernel Oil Glycerides,
Rectal; Vaginal

Hydrogenated

Cocoyl Caprylocaprate
Topical

Cola Nitida Seed Extract
Rectal

Collagen
Topical

Coloring Suspension
Topical

Corn Oil
Intramuscular

Cottonseed Oil
Intramuscular

Cream Base
Topical

Creatine
Intra-articular; Intralesional; Intramuscular

Creatinine
Auricular (Otic); Intramuscular (IM); Infusion (IV);

Subcutaneous (SC); Intra-articular; Intrabursal;

Intradermal; Intralesional; Intrasynovial;

Ophthalmic; Soft tissue; Topical

Cresol
Subcutaneous

Croscarmellose Sodium
Intramuscular

Crospovidone
Implantation; Intra-articluar; Intramuscular;

Intrauterine; Topical; Transdermal; Vagiinal

Cupric Sulfate
Auricular (Otic)

Cupric Sulfate Anhydrous
Auricular (Otic)

Cyclomethicone
Topical

Cyclomethicone/Dimethicone Copolyol
Topical

Cysteine
Intramuscular (IM); Subcutaneous (SC);

Intravenous; Infusion (IV)

Cysteine Hydrochloride
Intravenous; Infusion (IV)

Cysteine Hydrochloride Anhydrous
Intradiscal

Cysteine, Dl-
Intradiscal

D&C Red No. 28
Topical

D&C Red No. 33
Topical

D&C Red No. 36
Topical

D&C Red No. 39
Topical

D&C Yellow No. 10
Dental; Inhalation; Rectal; Topical

Dalfampridine
Intravenous

Daubert 1-5 Pestr (Matte) 164z
Transdermal

Decyl Methyl Sulfoxide
Topical

Dehydag Wax Sx
Topical

Dehydroacetic Acid
Topical

Dehymuls E
Topical

Denatonium Benzoate
Topical

Deoxycholic Acid
Infusion (IV)

Dextran
Intravenous

Dextran 40
Intravenous

Dextrin
Topical

Dextrose
Intramuscular (IM); Infusion (IV); Subcutaneous

(SC); Interstitial; Intracavitary; Intraperitoneal;

Intrapleural; Intraspinal; Intravenous; Nasal; Spinal

Dextrose Monohydrate
Intravenous

Dextrose Solution
Intravenous; Infusion (IV)

Diatrizoic Acid
Intra-arterial; Intra-articular; Intracardiac;

Intradiscal; Intramuscular; Intrauterine;

Intravascular; Intravenous; Infusion (IV);

Periarticular; Subcutaneous; Ureteral; Urethral

Diazolidinyl Urea
Topical

Dichlorobenzyl Alcohol
Topical

Dichlorodifluoromethane
Inhalation; Intrapleural; Nasal; Rectal; Topical

Dichlorotetrafluoroethane
Inhalation; Nasal; Rectal; Topical

Diethanolamine
Infusion (IV); Ophthalmic; Topical

Diethyl Pyrocarbonate
Inflitration

Diethyl Sebacate
Topical

Diethylene Glycol Monoethyl Ether
Topical; Transdermal

Diethylhexyl Phthalate
Ophthalmic; Transdermal

Dihydroxyaluminum Aminoacetate
Topical

Diisopropanolamine
Topical

Diisopropyl Adipate
Topical

Diisopropyl Dilinoleate
Topical

Dimethicone 350
Topical

Dimethicone Copolyol
Topical; Transermal

Dimethicone Mdx4-4210
Transdermal

Dimethicone Medical Fluid 360
Dental; Intravenous; Topical; Transdermal

Dimethyl Isosorbide
Topical

Dimethyl Sulfoxide
Infusion (IV); Subcutanous; Topical

Dimethylaminoethyl Methacrylate-Butyl
Transdermal

Methacrylate-Methyl Methacrylate

Copolymer

Dimethyldioctadecylammonium Bentonite
Rectal

Dimethylsiloxane/Methylvinylsiloxane
Implantation; Intrauterine

Copolymer

Dinoseb Ammonium Salt
Topical

Dipalmitoylphosphatidylglycerol, Dl-
Inflitration

Dipropylene Glycol
Transdermal

Disodium Cocoamphodiacetate
Topical

Disodium Laureth Sulfosuccinate
Topical

Disodium Lauryl Sulfosuccinate
Topical

Disodium Sulfosalicylate
Topical

Disofenin
Topical

Divinylbenzene Styrene Copolymer
Ophthalmic

Dmdm Hydantoin
Topical

Docosanol
Topical

Docusate Sodium
Intramuscular; Topical

Duro-Tak 280-2516
Transdermal

Duro-Tak 387-2516
Transdermal

Duro-Tak 80-1196
Transdermal

Duro-Tak 87-2070
Transdermal

Duro-Tak 87-2194
Transdermal

Duro-Tak 87-2287
Percutaneous; Transdermal

Duro-Tak 87-2296
Transdermal

Duro-Tak 87-2888
Transdermal

Duro-Tak 87-2979
Transdermal

Edetate Calcium Disodium
Infiltration (AN); Caudal Block; Epidural;

Intramuscular (IM); Infusion (IV); Intra-articular;

Intra-arterial; Intracardiac; Intradiscal;

Intraperitoneal; Intrathecal; Intrauterine;

Intravascular; Intravenous; Intravesical; Nerve

Block; Periarticular; Rectal; Subcutaneous; Ureteral;

Urethral

Edetate Disodium
Infiltration (AN), Auricular (Otic); Caudal Block;

Epidural; Intramuscular (IM); Infusion (IV);

Subcutaneous (SC); Inhalation; Intra-arterial; Intra-

articular; Intrabursal; Intracardiac; Intradermal;

Intradiscal; Intralesional; Intrasynovial; Intrauterine;

Intravascular; Intravenous; Iontophoresis; Nasal;

Nerve Block; Ophthalmic; Rectal; Respiratory

(Inhalation); Soft tissue; Topical; Transdermal;

Ureteral; Urethral; Vaginal

Edetate Disodium Anhydrous
Intra-amniotic; Intramuscular; Intravenous; Infusion

(IV); Ophthalmic

Edetate Sodium
Intramuscular (IM); Infusion (IV); Subcutaneous

(SC); Inhalation; Ophthalmic; Topical

Edetic Acid
Auricular (Otic); Rectal; Submucosal; Topical

Egg Phospholipids
Intravenous; Infusion (IV)

Entsufon
Topical

Entsufon Sodium
Topical

Epilactose
Rectal

Epitetracycline Hydrochloride
Topical

Essence Bouquet 9200
Topical

Ethanolamine Hydrochloride
Intravenous

Ethyl Acetate
Intramuscular; Topical; Transdermal

Ethyl Oleate
Transdermal

Ethylcelluloses
Topical; Transdermal; Vaginal

Ethylene Glycol
Topical

Ethylene Vinyl Acetate Copolymer
Implantation; Intrauerine; Ophthalmic; Periodontal;

Subcutaneous; Transdermal

Ethylenediamine
Intravenous; Infusion (IV); Rectal; Topical

Ethylenediamine Dihydrochloride
Topical

Ethylene-Propylene Copolymer
Transdermal

Ethylene-Vinyl Acetate Copolymer
Vaginal

(28% Vinyl Acetate)

Ethylene-Vinyl Acetate Copolymer
Vaginal

(9% Vinylacetate)

Ethylhexyl Hydroxystearate
Topical

Ethylparaben
Topical

Eucalyptol
Dental

Exametazime
Intravenous

Fat, Edible
Rectal

Fat, Hard
Rectal

Fatty Acid Esters
Transdermal

Fatty Acid Pentaerythriol Ester
Topical

Fatty Acids
Topical

Fatty Alcohol Citrate
Topical

Fatty Alcohols
Vaginal

Fd&C Blue No. 1
Dental; Rectal; Topical

Fd&C Green No. 3
Dental; Rectal

Fd&C Red No. 4
Topical

Fd&C Red No. 40
Topical

Fd&C Yellow No. 10 (Delisted)
Topical

Fd&C Yellow No. 5
Topical; Vaginal

Fd&C Yellow No. 6
Inhalation; Rectal; Topical

Ferric Chloride
Intravenous

Ferric Oxide
Topical

Flavor 89-186
Dental

Flavor 89-259
Dental

Flavor Df-119
Dental

Flavor Df-1530
Dental

Flavor Enhancer
Dental

Flavor Fig 827118
Rectal

Flavor Raspberry Pfc-8407
Rectal

Flavor Rhodia Pharmaceutical No. Rf 451
Topical

Fluorochlorohydrocarbons
Inhalation

Formaldehyde
Topical

Formaldehyde Solution
Topical

Fractionated Coconut Oil
Topical

Fragrance 3949-5
Topical

Fragrance 520a
Topical

Fragrance 6.007
Topical

Fragrance 91-122
Topical

Fragrance 9128-Y
Topical

Fragrance 93498g
Topical

Fragrance Balsam Pine No. 5124
Topical

Fragrance Bouquet 10328
Topical

Fragrance Chemoderm 6401-B
Topical

Fragrance Chemoderm 6411
Topical

Fragrance Cream No. 73457
Topical

Fragrance Cs-28197
Topical

Fragrance Felton 066m
Topical

Fragrance Firmenich 47373
Topical

Fragrance Givaudan Ess 9090/1c
Topical

Fragrance H-6540
Topical

Fragrance Herbal 10396
Topical

Fragrance Nj-1085
Topical

Fragrance P O Fl-147
Topical

Fragrance Pa 52805
Topical

Fragrance Pera Derm D
Topical

Fragrance Rbd-9819
Topical

Fragrance Shaw Mudge U-7776
Topical

Fragrance Tf 044078
Topical

Fragrance Ungerer Honeysuckle K 2771
Topical

Fragrance Ungerer N5195
Topical

Fructose
Infusion (IV); Rectal

Gadolinium Oxide
Intravenous

Galactose
Rectal

Gamma Cyclodextrin
Intravenous

Gelatin
Dental; Intramuscular (IM); Infusion (IV);

Subcutaneous (SC); Intravenous; Respiratory

(Inhalation); Topical; Vaginal

Gelatin, Crosslinked
Dental

Gelfoam Sponge
N/A

GelIan Gum (Low Acyl)
Ophthalmic

Gelva 737
Transdermal

Gentisic Acid
Intravenous

Gentisic Acid Ethanolamide
Infusion (IV)

Gluceptate Sodium
Intravenous

Gluceptate Sodium Dihydrate
Intravenous

Gluconolactone
Intramuscular (IM); Infusion (IV); Intravesou;

Topical

Glucuronic Acid
Intravenous

Glutamic Acid, Dl-
Vaginal

Glutathione
Intramuscular

Glycerin
Auricular (Otic); Dental; Intramuscular; Infusion

(IV); Subcutaneous (SC); Inhalation; Intradermal;

Intravenous; Iontophoresis; Nasal; Ophthalmic;

Perfusion; Biliary; Rectal; Topical; Transdermal;

Vaginal

Glycerol Ester Of Hydrogenated Rosin
Nasal

Glyceryl Citrate
Topical

Glyceryl Isostearate
Topical; Vaginal

Glyceryl Laurate
Transdermal

Glyceryl Monostearate
Topical; Vaginal

Glyceryl Oleate
Topical; Transdermal

Glyceryl Oleate/Propylene Glycol
Topical

Glyceryl Palmitate
Rectal; Topical

Glyceryl Ricinoleate
Topical

Glyceryl Stearate
Auricular (Otic); Dental; Ophthalmic; Rectal;

Topical; Vaginal

Glyceryl Stearate-Laureth-23
Topical

Glyceryl Stearate/Peg Stearate
Rectal

Glyceryl Stearate/Peg-100 Stearate
Topical

Glyceryl Stearate/Peg-40 Stearate
Rectal

Glyceryl Stearate-Stearamidoethyl
Topical

Diethylamine

Glyceryl Trioleate
Epidural

Glycine
Intramuscular (IM); Infusion (IV); Subcutaneous

(SC); Intravenous; Rectal; Respiratory (Inhalation)

Glycine Hydrochloride
Subcutaneous

Glycol Distearate
Topical

Glycol Stearate
Topical

Guanidine Hydrochloride
Intravenous

Guar Gum
Topical; Vaginal

Hair Conditioner (18n195-1m)
Topical

Heptane
Transdermal

Hetastarch
Intravenous

Hexylene Glycol
Topical

High Density Polyethylene
Dental; Intrauterine; Ophthalmic; Topical;

Transdermal; Vaginal

Histidine
Intravenous; Infusion (IV); Subcutaneous

Human Albumin Microspheres
Intravenous

Hyaluronate Sodium
Intra-articular; Intramuscular; Intravitreal; Topical

Hydrocarbon
Rectal

Hydrocarbon Gel, Plasticized
Dental; Ophthalmic; Topical

Hydrochloric Acid
Intrathecal (AN, CNBLK); Inflitration (AN);

Sympathetic (AN, NBLK); Auricular (Otic); Caudal

Block; Dental; Diagnostic; Epidural; Extracorporeal;

Intramuscular (IM); Infusion (IV); Subcutaneous

(SC); Inflitration; Inhalationi; Interstitial; Intra-

amniotic; Intra-arterial; Intra-articular; Intrabursal;

Intracardiac; Intracaudal; Intracavitary; Intradermal;

Intralesional; Intraocular; Intraperitoneal;

Intrapleural; Intraspinal; Intrasynovial; Intrathecal;

Intratracheal; Intratumor; Intravascular; Intravenous;

Intravesical; Intravitreal; Iontophoresis; Irrigation;

Nasal; Nerve Block, Ophthalmic; Parenteral;

Perfusion, Cardiac; Peridural; Perineural;

Periodontal; Pectal; Respiratory (Inhalation);

Retrobulbar; Soft tissue; Spinal; Subarachnoid;

Subconjunctival; Subcutaneous; Topical;

Transdermal; Ureteral; Urethral

Hydrochloric Acid, Diluted
Infiltration (AN); Intramuscular (IM); Infusion (IV);

Subcutaneous (SC); Inhalation; Intra-arterial;

Intravascular; Intravenous; Nerve Block;

Ophthalmic; Topical

Hydrocortisone
Auricular (Otic)

Hydrogel Polymer
Vaginal

Hydrogen Peroxide
Topical

Hydrogenated Castor Oil
Topical

Hydrogenated Palm Oil
Rectal; Vaginal

Hydrogenated Palm/Palm Kernel Oil Peg-6
Topical

Esters

Hydrogenated Polybutene 635-690
Transdermal

Hydroxide Ion
Intramuscular; Infusion (IV)

Hydroxyethyl Cellulose
Auricular (Otic); Ophthalmic; Topical; Transdermal

Hydroxyethylpiperazine Ethane Sulfonic
Intravenous

Acid

Hydroxymethyl Cellulose
Topical

Hydroxyoctacosanyl Hydroxystearate
Topical

Hydroxypropyl Cellulose
Topical

Hydroxypropyl Methylcellulose 2906
Ophthalmic

Hydroxypropyl-Bcyclodextrin
Intravenous; Infusion (IV)

Hypromellose 2208 (15000 Mpa · S)
Vaginal

Hypromellose 2910 (15000 Mpa · S)
Nasal; Ophthalmic

Hypromelloses
Irrigation; Ophthalmic; Rectal; Topical; Vaginal

Imidurea
Topical

Iodine
Intra-arterial; Intra-articular; Intracardiac;

Intradiscal; Intravascular; Intravenous; Periarticular

Iodoxamic Acid
Intravenous

Iofetamine Hydrochloride
Intravenous

Irish Moss Extract
Topical

Isobutane
Topical

Isoceteth-20
Topical

Isoleucine
Infusion (IV)

Isooctyl Acrylate
Topical

Isopropyl Alcohol
Intravenous; Topical

Isopropyl Isostearate
Topical

Isopropyl Myristate
Auricular (Otic); Topical; Transdermal; Vaginal

Isopropyl Myristate-Myristyl Alcohol
Topical

Isopropyl Palmitate
Topical; Transdermal

Isopropyl Stearate
Topical

Isostearic Acid
Topical

Isostearyl Alcohol
Topical

Isotonic Sodium Chloride Solution
Epidural; Intratracheal; Intravenous; Infusion (IV)

Jelene
Ophthalmic; Topical

Kaolin
Topical

Kathon Cg
Topical

Kathon Cg II
Topical

Lactate
Topical

Lactic Acid
Infiltration (AN); Auricular (Otic); Intramuscular

(IM); Infusion (IV); Subcutaneous (SC);

Intracardiac; Intravenous; Nerve Block; Topical;

Vaginal

Lactic Acid, Dl-
Intramuscular (IM); Infusion (IV); Intravesou;

Topical; Vaginal

Lactic Acid, L-
Intravenous; Subcutanous

Lactobionic Acid
Intravenous; Infusion (IV)

Lactose
Intramuscular (IM); Infusion (IV); Subcutaneous

(SC); Inhalation; Intracavitary; Intravenous; Rectal;

Transdermal; Vaginal

Lactose Monohydrate
Intramuscular (IM); Infusion (IV); Subcutaneous

(SC); Intracavitary; Intravenous; Respiratory

(Inhalation); Vaginal

Lactose, Hydrous
Intramuscular (IM); Infusion (IV); Intravenous;

Vaginal

Laneth
Topical

Lanolin
Ophthalmic; Rectal; Topical; Vaginal

Lanolin Alcohol-Mineral Oil
Topical

Lanolin Alcohols
Ophthalmic; Topical

Lanolin Anhydrous
Ophthalmic; Topical; Transdermal; Vaginal

Lanolin Cholesterols
Topical

Lanolin Nonionic Derivatives
Ophthalmic

Lanolin, Ethoxylated
Topical

Lanolin, Hydrogenated
Topical

Lauralkonium Chloride
Ophthalmic

Lauramine Oxide
Topical

Laurdimonium Hydrolyzed Animal Collagen
Topical

Laureth Sulfate
Topical

Laureth-2
Topical

Laureth-23
Topical

Laureth-4
Topical

Lauric Diethanolamide
Topical

Lauric Myristic Diethanolamide
Topical

Lauroyl Sarcosine
Ophthalmic

Lauryl Lactate
Transdermal

Lauryl Sulfate
Topical

Lavandula
Angustifolia Flowering Top
Topical

Lecithin
Inhalation; Intramuscular; Rectal; Topical;

Transdermal; Vaginal

Lecithin Unbleached
Topical

Lecithin, Egg
Intravenous

Lecithin, Hydrogenated
Auricular (Otic)

Lecithin, Hydrogenated Soy
Inhalation; Intravenous

Lecithin, Soybean
Inhalation; Vaginal

Lemon Oil
Topical

Leucine
Infusion (IV)

Levulinic Acid
Transdermal

Lidofenin
Intravenous

Light Mineral Oil
Ophthalmic; Rectal; Topical; Vaginal; Transdermal

Light Mineral Oil (85 Ssu)
Topical

Limonene, (+/−)-
Topical

Lipocol Sc-15
Topical

Lysine
Intramuscular (IM); Infusion (IV)

Lysine Acetate
Infusion (IV)

Lysine Monohydrate
Respiratory (Inhalation)

Magnesium Aluminum Silicate
Rectal; Topical; Vaginal

Magnesium Aluminum Silicate Hydrate
Rectal; Topical; Vaginal

Magnesium Chloride
Intramuscular; Intraocular; Intraperitoneal;

Intravitreal; Infusion (IV); Ophthalmic;

Subcutaneous

Magnesium Nitrate
Topical

Magnesium Stearate
Implantation; Intravitreal; Subcutaneous; Topical;

Transmucosal; Vaginal

Maleic Acid
Intramuscular; Infusion (IV)

Mannitol
Intramuscular (IM); Infusion (IV); Subcutanous

(SC); Intravenous; Ophthalmic; Parenteral;

Respiratory (Inhalation); Submucosal; Topical;

Transdermal

Maprofix
Topical

Mebrofenin
Intravenous

Medical Adhesive Modified S-15
Transdermal

Medical Antiform A-F Emulsion
Topical

Medronate Disodium
Intravenous

Medronic Acid
Intravenous

Meglumine
Intra-arterial; Intra-articular; Intracardiac;

Intradiscal; Intramuscular; Intrauterine;

Intravascular; Intravenous; Infusion (IV);

Periarticular; Ureteral; Urethral

Menthol
Detanl; Inhalation; Topical

Metacresol
Intramuscular (IM); Infusion (IV); Subcutanous

(SC); Intradermal

Metaphosphoric Acid
Infusion (IV)

Methanesulfonic Acid
Intramuscular (IM); Infusion (IV); Subcutaneous

(SC)

Methionine
Intramuscular; Intrathecal; Intravenous; Infusion

(IV); Subcutaneous

Methyl Alcohol
Transdermal

Methyl Gluceth-10
Topical

Methyl Gluceth-20
Topical

Methyl Gluceth-20 Sesquistearate
Topical

Methyl Glucose Sesquistearate
Topical

Methyl Laurate
Transdermal

Methyl Pyrrolidone
Periodontal; Subcutaneous

Methyl Salicylate
Topical

Methyl Stearate
Topical; Vaginal

Methylboronic Acid
Intravenous

Methylcellulose (4000 Mpa · S)
Ophthalmic

Methylcelluloses
Intra-articular; Intralesional; Intramuscular;

Intrasynovial; Nasal; Ophthalmic; Soft tissue;

Topical

Methylchloroisothiazolinone
Topical

Methylene Blue
Intravenous

Methylisothiazolinone
Topical

Methylparaben
Infiltration (AN); Auricular (Otic); Caudal Block;

Epidural; Intramuscular (IM); Infusion (IV);

Subcutaneous (SC); Inhalation; Intra-arterial; Intra-

articular; Intrabursal; Intradermal; Intralesional;

Intrasynovial; Intravenous; Iontophoresis; Irrigation;

Nasal; Nerve Block; Ophthalmic; Peridural; Rectal;

Soft tissue; Topical; Ureteral; Urethral; Vaginal

Microcrystalline Wax
Topical; Vaginal

Mineral Oil
Auricular (Otic); Dental; Ophthalmic; Topical;

Transdermal; Vaginal

Mono And Diglyceride
Topical

Monostearyl Citrate
Topical

Monothioglycerol
Infiltration (AN); Caudal Block; Epidural;

Intramuscular (IM); Infusion (IV); Subcutanous

(SC); Intravenous; Nerve Block

Multisterol Extract
Topical

Myristyl Alcohol
Topical

Myristyl Lactate
Topical

Myristyl-.Gamma.-Picolinium Chloride
Intra-articular; Intralesional; Intramuscular;

Intrasynovial; Soft tissue

N-(Carbamoyl-Methoxy Peg-40)-1,2-
Intravenous

Distearoyl-Cephalin Sodium

N,N-Dimethylacetamide
Intramuscular; Intravenous; Infusion (IV)

Niacinamide
Intramuscular; Infusion (IV); Intra-articular;

Intralesional; Intrasynovial; Topical

Nioxime
Intravenous

Nitric Acid
Inhalation; Infusion (IV); Ophthalmic; Topical;

Vaginal

Nitrogen
Infiltration (AN); Caudal Block; Dental; Epidural;

Intramuscular; Infusion (IV); Subcutanous (SC);

Inhalation; Intra-arterial; Intracavitary; Intramuscular

(IM); Intrathecal; Intratumor; Intravascular;

Intravenous; Intravesical; Irrigation; Nasal; Nerve

Block; Ophthalmic; Parenteral; Submucosal;

Topical; Transdermal

Nonoxynol Iodine
Topical

Nonoxynol-15
Topical

Nonoxynol-9
Ophthalmic; Topical

Norflurane
Inhalation; Nasal; Respiratory (Inhalation)

Oatmeal
Topical

Octadecene-1/MaleicAcid Copolymer
Topical

Octanoic Acid
Intravenous

Octisalate
Transdermal

Octoxynol-1
Topical

Octoxynol-40
Ophthalmic

Octoxynol-9
Topical

Octyldodecanol
Topical; Transdermal; Vaginal

Octylphenol Polymethylene
Ophthalmic

Oleic Acid
Inhalation; Nasal; Respiratory (Inhalation);

Topical; Transdermal

Oleth-10/Oleth-5
Topical

Oleth-2
Topical

Oleth-20
Topical

Oleyl Alcohol
Topical; Transdermal

Oleyl Oleate
Topical; Transdermal

Olive Oil
Topical

Oxidronate Disodium
Intravenous

Oxyquinoline
Intravenous

Palm Kernel Oil
Rectal

Palmitamine Oxide
Topical

Parabens
Topical

Paraffin
Rectal; Topical

Paraffin, White Soft
Topical

Parfum Creme 45/3
Topical

Peanut Oil
Intramuscular; Intratracheal; Topical; Vaginal

Peanut Oil, Refined
Topical

Pectin
Dental; Topical

Peg 6-32 Stearate/Glycol Stearate
Topical; Vaginal

Peg Vegetable Oil
Intramuscular (IM); Infusion (IV);

Subcutaneous (SC)

Peg-100 Stearate
Topical; Vaginal

Peg-12 Glyceryl Laurate
Topical

Peg-120 Glyceryl Stearate
Topical; Vaginal

Peg-120 Methyl Glucose Dioleate
Topical

Peg-15 Cocamine
Topical

Peg-150 Distearate
Topical

Peg-2 Stearate
Topical; Vaginal

Peg-20 Sorbitan Isostearate
Intramuscular

Peg-22 Methyl Ether/Dodecyl Glycol
Topical

Copolymer

Peg-25 Propylene Glycol Stearate
Topical

Peg-4 Dilaurate
Topical

Peg-4 Laurate
Topical

Peg-40 Castor Oil
Intramuscular (IM); Subcutaneous (SC);

Infusion (IV)

Peg-40 Sorbitan Diisostearate
Dental

Peg-45/Dodecyl Glycol Copolymer
Topical

Peg-5 Oleate
Topical; Vaginal

Peg-50 Stearate
Topical

Peg-54 Hydrogenated Castor Oil
Topical

Peg-6 Isostearate
Topical

Peg-60 Castor Oil
Infusion (IV)

Peg-60 Hydrogenated Castor Oil
Topical

Peg-7 Methyl Ether
Topical

Peg-75 Lanolin
Topical

Peg-8 Laurate
Topical

Peg-8 Stearate
Topical

Pegoxol 7 Stearate
Topical; Vaginal

Pentadecalactone
Transdermal

Pentaerythritol Cocoate
Topical

Pentasodium Pentetate
Intravenous

Pentetate Calcium Trisodium
Intrathecal; Intravenous; Infusion (IV)

Pentetic Acid
Intrathecal; Intravenous

Peppermint Oil
Dental; Topical

Perflutren
Intravenous

Perfume 25677
Topical

Perfume Bouquet
Topical

Perfume E-1991
Topical

Perfume Gd 5604
Topical

Perfume Tana 90/42 Scba
Topical

Perfume W-1952-1
Topical

Petrolatum
Auricular (Otic); Ophthalmic; Topical

Petrolatum, White
Auricular (Otic); Dental; Nasal; Ophthalmic; Rectal;

Topical; Transdermal; Vaginal

Petroleum Distillates
Topical

Phenol
Intramuscular (IM); Infusion (IV); Subcutaneous

(SC); Intra-articular; Intradermal; Intralesional;

Intrasynovial; Intravenous; Soft tissue

Phenol, Liquefied
Intramuscular (IM); Infusion (IV); Subcutaneous

(SC); Intravenous

Phenonip
Iontophoresis; Topical

Phenoxyethanol
Topical

Phenylalanine
Infusion (IV)

Phenylethyl Alcohol
Auricular (Otic); Nasal; Ophthalmic

Phenylmercuric Acetate
Ophthalmic; Topical; Vaginal

Phenylmercuric Nitrate
Intramuscular; Ophthalmic

Phosphatidyl Glycerol, Egg
Intravenous

Phospholipid
Infusion (IV)

Phospholipid, Egg
Intravenous; Infusion (IV)

Phospholipon 90 g
Vagianl

Phosphoric Acid
Intramuscular (IM); Infusion (IV); Subcutaneous

(SC); Infiltration; Intra-articular; Intralesional;

Intravenous; Ophthalmic; Soft tissue; Topical;

Vaginal

Pine Needle Oil (PinusSylvestris)
Topical

Piperazine Hexahydrate
Vagianl

Plastibase-50w
Dental; Topical

Polacrilin
Iontophoresis; Transdermal

Polidronium Chloride
Ophthalmic; Topical

Poloxamer 124
Topical

Poloxamer 181
Topical

Poloxamer 182
Topical

Poloxamer 188
Intravenous; Ophthalmic; Peridontal; Subcutaneous;

Topical

Poloxamer 237
Topical

Poloxamer 407
Ophthalmic; Peridontal; Topical

Poly(Bis(P-Carboxyphenoxy)Propane
Implantation

Anhydride):Sebacic Acid

Poly(Dimethylsiloxane/Methylvinylsiloxane/
Vagianl

Methylhydrogensiloxane) Dimethylvinyl Or

Dimethylhydroxy Or Trimethyl Endblocked

Poly(Dl-Lactic-Co-Glycolic Acid), (50:50
N/A

Poly(Dl-Lactic-Co-Glycolic Acid), Ethyl
N/A

Ester Terminated, (50:50

Polyacrylic Acid (250000 Mw)
Transdermal

Polybutene (1400 Mw)
Transdermal

Polycarbophil
Ophthalmic; Topical; Vaginal

Polyester
Transdermal; Vaginal

Polyester Polyamine Copolymer
Transdermal

Polyester Rayon
Transdermal

Polyethylene Glycol 1000
Rectal; Respiratory (Inhalation); Topical; Vaginal

Polyethylene Glycol 1450
Topical; Urethral

Polyethylene Glycol 1500
Topical

Polyethylene Glycol 1540
Dental; Rectal; Topical

Polyethylene Glycol 200
Intramuscular; Topical

Polyethylene Glycol 300
Intramuscular (IM); Infusion (IV); Intravenous;

Ophthalmic; Topical

Polyethylene Glycol 300-1600
Topical

Polyethylene Glycol 3350
Intra-articular; Intralesional; Intramuscular;

Intrasynovial; Nasal; Rectal; Soft tissue;

Subcutaneous; Topical; Vaginal

Polyethylene Glycol 400
Intramuscular (IM); Infusion (IV); Intravenous;

Nasal; Ophthalmic; Rectal; Topical; Vaginal

Polyethylene Glycol 4000
Intra-articular; Intralesional; Intramuscular;

Intrasynovial; Rectal; Soft tissue; Topical; Vaginal

Polyethylene Glycol 540
Topical

Polyethylene Glycol 600
Intravenous; Topical

Polyethylene Glycol 6000
Rectal; Topical; Vaginal

Polyethylene Glycol 8000
Ophthalmic; Rectal; Topical; Vaginal

Polyethylene Glycol 900
Topical

Polyethylene High Density Containing
Intrauterine

Ferric Oxide Black (<1%)

Polyethylene Low Density Containing
Initrauterine

Barium Sulfate (20-24%)

Polyethylene T
Initrauterine

Polyethylene Terephthalates
Transdermal

Polyglactin
Dental; Implantation; Intramuscular; Subcutaneous

Polyglyceryl-3 Oleate
Vagianl

Polyglyceryl-4 Oleate
Vagianl

Polyhydroxyethyl Methacrylate
Topical

Polyisobutylene
Topical; Transdermal

Polyisobutylene (1100000 Mw)
Topical; Transdermal

Polyisobutylene (35000 Mw)
Transdermal

Polyisobutylene 178-236
Transdermal

Polyisobutylene 241-294
Transdermal

Polyisobutylene 35-39
Transdermal

Polyisobutylene Low Molecular Weight
Transdermal

Polyisobutylene Medium Molecular Weight
Transdermal

Polyisobutylene/Polybutene Adhesive
Transdermal

Polylactide
Intramuscular; Peridontal

Polyols
Dental

Polyoxyethylene-Polyoxypropylene 1800
Ophthalmic; Topical

Polyoxyethylene Alcohols
Topical

Polyoxyethylene Fatty Acid Esters
Intramuscular (IM); Infusion (IV); Subcutaneous

(SC); Topical

Polyoxyethylene Propylene
Topical

Polyoxyl 20 Cetostearyl Ether
Topical

Polyoxyl 35 Castor Oil
Intravesical; Infusion (IV); Ophthalmic

Polyoxyl 40 Hydrogenated Castor Oil
Dental; Ophthalmic; Topical

Polyoxyl 40 Stearate
Auricular (Otic); Dental; Ophthalmic; Topical

Polyoxyl 400 Stearate
Nasal; Topical

Polyoxyl 6 And Polyoxyl 32 Palmitostearate
Topical

Polyoxyl Distearate
Topical

Polyoxyl Glyceryl Stearate
Topical

Polyoxyl Lanolin
Topical

Polyoxyl Palmitate
Vagianl

Polyoxyl Stearate
Auricular (Otic); Topical

Polypropylene
Intrauterine; Topical; Transdermal

Polypropylene Glycol
Intramuscular (IM); Infusion (IV); Ophthalmic

Polyquaternium-10
Topical

Polyquaternium-7 (70/30
N/A

Acrylamide/Dadmac

Polysiloxane
Intravenous

Polysorbate 20
Auricular (Otic); Intramuscular (IM); Subcutaneous

(SC); Intravenous; Infusion (IV); Nasal; Ophthalmic;

Topical; Vaginal

Polysorbate 40
Intramuscular (IM); Infusion (IV); Topical

Polysorbate 60
Ophthalmic; Rectal; Topical; Vaginal

Polysorbate 65
Topical

Polysorbate 80
Auricular (Otic); Intra-articular; Intrabursal;

Intradermal; Intralesional; Intramuscular;

Intrasynovial; Intravenous; Infusion (IV); Nasal;

Ophthalmic; Rectal; Soft tissue; Subcutaneous;

Topical; Vaginal

Polyurethane
Vagianl

Polyvinyl Acetate
Transdermal

Polyvinyl Alcohol
Auricular (Otic); Intramuscular; Intraocular;

Intravitreal; Iontophoresis; Ophthalmic; Topical;

Transdermal

Polyvinyl Chloride
Transdermal

Polyvinyl Chloride-Polyvinyl Acetate
Transdermal

Copolymer

Polyvinylpyridine
Transdermal

Poppy Seed Oil
Intralymphatic; Intrauterine

Potash
Topical

Potassium Acetate
Ophthalmic; Rectal

Potassium Alum
Vagianl

Potassium Bicarbonate
Transmucosal

Potassium Bisulfite
Intravenous

Potassium Chloride
Infiltration (AN); Caudal Block; Epidural;

Intraocular; Intravenous; Intravitreal; Infusion (IV);

Nerve Block; Ophthalmic

Potassium Citrate
Topical

Potassium Hydroxide
Intravascular; Intravenous; Infusion (IV); Topical;

Vaginal

Potassium Metabisulfite
Infiltration (AN); Auricular (Otic); Intramuscular

(IM); Infusion (IV); Nerve Block; Rectal

Potassium Phosphate, Dibasic
Intra-articular; Intramuscular; Intravenous; Infusion

(IV); Subcutaneous

Potassium Phosphate, Monobasic
Infiltration (AN); Auricular (Otic); Intramuscular

(IM); Infusion (IV); Intra-articular; Intramuterine;

Intravenous; Intravesical; Nasal; Nerve Block;

Ophthalmic; Subcutaneous

Potassium Soap
Topical

Potassium Sorbate
Nasal; Ophthalmic; Topical

Povidone Acrylate Copolymer
Topical

Povidone Hydrogel
Iontophoresis; Topical

Povidone K17
Subcutaneous

Povidone K25
Respiratory (Inhalation)

Povidone K29/32
Ophthalmic; Transdermal; Vaginal

Povidone K30
Ophthalmic

Povidone K90
Ophthalmic; Topical

Povidone K90f
Auricular (Otic)

Povidone/Eicosene Copolymer
Topical

Povidones
Auricular (Otic); Intramuscular; Intravenous;

Infusion (IV); Ophthalmic; Subcutaneous; Topical;

Transdermal; Vaginal

Ppg-12/Smdi Copolymer
Topical

Ppg-15 Stearyl Ether
Topical

Ppg-20 Methyl Glucose Ether Distearate
Topical

Ppg-26 Oleate
Topical

Product Wat
Topical

Proline
Infusion (IV)

Promulgen D
Topical; Vaginal

Promulgen G
Topical

Propane
Topical

Propellant A-46
Topical

Propyl Gallate
Topical; Intramuscular

Propylene Carbonate
Topical

Propylene Glycol
Auricular (Otic); Dental; Extracorporeal;

Intramuscular (IM); Infusion (IV); Inhalation;

Intravenous; Nasal; Ophthalmic; Photopheresis;

Rectal; Subcutaneous; Topical; Transdermal;

Vaginal

Propylene Glycol Diacetate
Auricular (Otic); Topical

Propylene Glycol Dicaprylate
Topical

Propylene Glycol Monolaurate
Transdermal

Propylene Glycol Monopalmitostearate
Topical; Vaginal

Propylene Glycol Palmitostearate
Topical

Propylene Glycol Ricinoleate
Topical

Propylene Glycol/Diazolidinyl
Topical

Urea/Methylparaben/Propylparben

Propylparaben
Inflitration (AN); Auricular (Otic); Intramuscular

(IM); Infusion (IV); Subcutaneous (SC); Inhalation;

Intra-arterial; Intra-articular; Intrabursal;

Intralesional; Intrasynovial; Intravenous; Nasal;

Nerve Block; Ophthalmic; Rectal; Soft tissue;

Topical; Ureteral; Urethral; Vaginal

Protamine Sulfate
Intramuscular (IM); Subcutaneous (SC); Intradermal

Protein Hydrolysate
Topical

Pvm/Ma Copolymer
Dental

Quaternium-15
Topical

Quaternium-15 Cis-Form
Topical; Vaginal

Quaternium-52
Topical

Ra-2397
Transdermal

Ra-3011
Transdermal

Saccharin
Inhalation; Topical

Saccharin Sodium
Dental; Intramuscular (IM); Infusion (IV);

Inhalation; Intravenous; Rectal; Topical

Saccharin Sodium Anhydrous
Intramuscular (IM); Infusion (IV); Rectal

Safflower Oil
Topical

Sd Alcohol 3a
Topical

Sd Alcohol 40
Topical

Sd Alcohol 40-2
Topical

Sd Alcohol 40b
Topical

Sepineo P 600
Topical

Serine
Infusion (IV)

Sesame Oil
Intramuscular (IM); Subcutaneous (SC)

Shea Butter
Topical

Silastic Brand Medical Grade Tubing
Implantation

Silastic Medical Adhesive, Silicone Type A
Implantation

Silica, Dental
Dental

Silicon
Topical; Transdermal

Silicon Dioxide
Dental; Topical; Vaginal

Silicon Dioxide, Colloidal
Endocervical; Rectal; Respiratory (Inhalation);

Transdermal; Vaginal

Silicone
Intramuscular (IM); Infusion (IV); Intrauterine;

Topical; Transdermal; Vaginal

Silicone Adhesive 4102
Percutaneous; Transdermal

Silicone Adhesive 4502
Transdermal

Silicone Adhesive Bio-Psa Q7-4201
Transdermal; Topical

Silicone Adhesive Bio-Psa Q7-4301
Transdermal; Topical

Silicone Emulsion
Topical

Silicone/Polyester Film Strip
Transdermal

Simethicone
Intramuscular (IM); Infusion (IV); Rectal; Topical

Simethicone Emulsion
Topical

Sipon Ls 20 np
Topical

Soda Ash
Ophthalmic

Sodium Acetate
Auricular (Otic); Extracorporeal; Intramuscular

(IM); Infusion (IV); Subcutaneous (SC); Interstitial;

Intra-articular; Intracavitary; Intradermal;

Intralesional; Intraocular; Intraperitoneal;

Intrapleural; Intrasynovial; Intravenous; Intravitreal;

Nasal; Ophthalmic; Parenteral; Phtotpheresis; Soft

tissue; Submucosal; Topical

Sodium Acetate Anhydrous
Intramuscular (IM); Infusion (IV); Subcutaneous

(SC); Intravenous; Topical

Sodium Alkyl Sulfate
Topical

Sodium Ascorbate
Intravenous

Sodium Benzoate
Dental; Intramuscular (IM); Infusion (IV);

Intravenous; Rectal; Topical

Sodium Bicarbonate
Intramuscular (IM); Infusion (IV); Intraperitoneal;

Intrathecal; Intratracheal; Intravenous; Intravitreal;

Subcutaneous; Vaginal

Sodium Bisulfate
Intramuscular (IM); Infusion (IV); Subcutaneous

(SC); Inhalation; Ophthalmic

Sodium Bisulfite
Inflitration (AN); Auricular (Otic); Intramuscular

(IM); Infusion (IV); Subcutaneous (SC); Epidural;

Inhalation; Intra-arterial; Intra-articular; Intrabursal;

Intracardiac; Intradermal; Intradiscal; Intralesional;

Intraperitoneal; Intrasynovial; Iontophoresis;

Irrigation; Intravenous; Nerve Block; Ophthalmic;

soft tissue; Topical

Sodium Borate
Auricular (Otic); Ophthalmic; Topical

Sodium Borate Decahydrate
Ophthalmic

Sodium Carbonate
Infiltration (AN); Intramuscular (IM); Infusion (IV);

Intra-arterial; Intraperitoneal; Intrapleural;

Intratumor; Intravascular; Intravenous; Intravitreal;

Nerve Block; Ophthalmic; Rectal

Sodium Carbonate Decahydrate
Intravenous

Sodium Carbonate Monohydrate
Intra-arterial; Intracardiac; Intravenous; Ophthalmic

Sodium Cetostearyl Sulfate
Topical

Sodium Chlorate
Infiltration (AN); Intramuscular; Infusion (IV);

Nerve Block

Sodium Chloride
Infiltration; Inhalation; Intra-arterial; Intra-articular;

Intrabursal; Intracardiac; Intracaudal; Intracavitary;

Intradermal; Intralesional; Intramuscular;

Intraocular; Intraperitoneal; Intrapleural;

Intrasynovial; Intrathecal; Intratracheal; Intratumor;

Intravascular; Intravenous; Intravenous bolus;

Intravesical; Intravitreal; Iontophoresis; Infusion

(IV); Intramuscular (IM); Subcutaneous (SC); Nasal;

Nerve Block; Ophthalmic; Parenteral; Peridural;

Photopheresis; Rectal; Respiratory (Inhalation); Soft

tissue; Subarachnoid; Submucosal; Topical;

Transermal

Sodium Chloride Injection
Intramuscular

Sodium Chloride Injection, Bacteriostatic
Intraveous

Sodium Cholesteryl Sulfate
Infusion (IV)

Sodium Citrate
Infiltration (AN); Auricular (Otic); Epidural;

Intramuscular (IM); Infusion (IV); Subcutaneous

(SC); Inhalation; Intra-arterial; Intra-articular;

Intracardiac; Intravacitary; Intralesional; Intraocular;

Iintraperitoneal; Intrapleural; Intrasynovial;

Intrathecal; Intratracheal; Intrauterine; Intravasular;

Intravenous; Iontophoresis; Irrigation; Nasal; Nerve

Block; Ophthalmic; Rectal; Respiratory (Inhalation);

Soft tissue; Topical; Transdermal; Ureteral; Vaginal

Sodium Cocoyl Sarcosinate
Topical

Sodium Desoxycholate
Infusion (IV)

Sodium Dithionite
Intramuscular (IM); Infusion (IV); Subcutaneous

(SC); Intravenous

Sodium Dodecylbenzenesulfonate
Topical

Sodium Formaldehyde Sulfoxylate
Intramuscular (IM); Infusion (IV); Subcutaneous

(SC); Topical

Sodium Gluconate
Intravenous; Infusion (IV)

Sodium Hydroxide
Intrathecal (AN, CNBLK); Inflitration (AN);

Sympathetic (AN, NBLK); Auricular (Otic); Caudal

Block; Dental; Epidural; Extracorporeal;

Intramuscular (IM); Infusion (IV); Subcutaneous

(SC); Inflitration; Inhalationi; Interstitial; Intra-

amniotic; Intra-arterial; Intra-articular; Intrabursal;

Intracardiac; Intracaudl; Intracavitary; Intradermal;

Intradiscal; Intralesional; Intraocular; Intraperioneal;

Intrapleural; Intraspinal; Intrasynovial; Intrathecal;

Intratracheal; Intratumor; Intrauterine; Intravascular;

Intravenous; Intravitreal; Iontophoresis; Irrigation;

Nasal; Nerve Block; Ophthalmic; Parenteral;

Perfusion, cardiac; Peridural; Perineural;

Photopheresis; Rectal; Respiratory (Inhalation);

Retrobular; Soft tissue; Spinal; Subarachnoid;

Subconjunctival; Submucosal; Topical; Transdermal;

Ureteral; Urethral; Vaginal

Sodium Hypochlorite
Infusion (IV)

Sodium Iodide
Intravenous; Topical

Sodium Lactate
Infiltration (AN); Caudal Black; Intramuscular (IM);

Infusion (IV); Subcutaneous (SC); Intracardiac;

Intraperitoneal; Intravenous; Nerve Block; Topical

Sodium Lactate, L-
Epidural; Intramuscular (IM); Infusion (IV);

Subcutaneous (SC); Intracardiac; Nerve Block

Sodium Laureth-2 Sulfate
Topical

Sodium Laureth-3 Sulfate
Topical

Sodium Laureth-5 Sulfate
Topical

Sodium Lauroyl Sarcosinate
Topical

Sodium Lauryl Sulfate
Dental; Respiratory (Inhalation); Topical; Vaginal

Sodium Lauryl Sulfoacetate
Topical

Sodium Metabisulfite
Intrathecal (AN, CNBLK); Infiltration (AN); Cardal

Block; Dental; Epidural; Intramuscular (IM);

Infusion (IV); Subcutaneous (SC); Inflitration;

Inhalation; Intra-articular; Initrabursal; Intracardiac;

Intramuscular; Intraperitoneal; Intravenous;

Iontophoresis; Nerve Block; Ophthalmic; Peridural;

Rectal; Submucosal; Topical; Vaginal

Sodium Nitrate
Ophthalmic

Sodium Phosphate
Intramuscular (IM); Infusion (IV); Intra-articular;

Intrabursal; Intradermal; Intralesional; Nasal; Nerve

Block; Ophthalmic; Soft tissue; Subcutanesou;

Topical

Sodium Phosphate Dihydrate
Intramuscular (IM); Subcutaneous (SC); Ophthalmic

Sodium Phosphate, Dibasic
Intramuscular (IM); Infusion (IV); Intradermal;

Intralesional; Intrasynovial; Intravenous; Nasal;

Ophthalmic; Soft tissue; Topical; Subcutaneous (SC)

Sodium Phosphate, Dibasic, Anhydrous
Auricular (Otic); Intramuscular (IM); Infusion (IV);

Subcutaneous (SC); Intra-articular; Intralesional;

Intramuscular; Intravenous; Intravesical; Nasal;

Ophthalmic; Topical; Vaginal

Sodium Phosphate, Dibasic, Dihydrate
Intramuscular (IM); Infusion (IV); Intravenous;

Nasal; Ophthalmic; Subcutaneous; Topical

Sodium Phosphate, Dibasic, Dodecahydrate
Nasal

Sodium Phosphate, Dibasic, Heptahydrate
Infiltration (AN); Auricular (Otic); Intramuscular

(IM); Infusion (IV); Subcutaneous (SC); Iintra-

articular; Intrabursal; Intradermal; Intralesional;

Intramuscular; Intrasynovial; Intravenous;

Intravitreal; Nasal; Nerve Block; Ophthalmic; Soft

tissue; Topical; Urethral

Sodium Phosphate, Monobasic
Intramuscular (IM); Infusion (IV); Intralesional;

Intrasynovial; Iontophoresis; Ophthalmic; Soft

tissue; Subcutaneous; Topical

Sodium Phosphate, Monobasic, Anhydrous
Auricular (Otic); Intramuscular (IM); Infusion (IV);

Intrabursal; Intradermal; Intralesional; Intrasynovial;

Intravascular; Intravenous; Intravesical; Nasal;

Ophthalmic; Soft tissue; Subcutaneous; Topical;

Vaginal

Sodium Phosphate, Monobasic, Dihydrate
Intravenous; Infusion (IV); Nasal; Ophthalmic;

Subcutaneous; Topical

Sodium Phosphate, Monobasic,
Intramuscular (IM); Infusion (IV); Intra-articular;

Monohydrate
Intralesional; Intravascular; Intravenous; Intravitreal;

Ophthalmic; Subcutaneous; Topical

Sodium Polyacrylate (2500000 Mw)
Topical

Sodium Pyrophosphate
Intravenous

Sodium Pyrrolidone Carboxylate
Topical

Sodium Starch Glycolate
Transmucosal

Sodium Succinate Hexahydrate
Intravenous

Sodium Sulfate
Intramuscular (IM); Infusion (IV); Ophthalmic

Sodium Sulfate Anhydrous
Inhalation; Iintramuscular; Ophthalmic

Sodium Sulfate Decahydrate
Ophthalmic

Sodium Sulfite
Auricular (Otic); Epidural; Intramuscular (IM);

Infusion (IV); Inhalation; Intra-articular;

Intralesional; Intravenous; Ophthalmic; Soft tissue;

Subcutaneous; Topical

Sodium Sulfosuccinated Undecyclenic
Topical

Monoalkylolamide

Sodium Tartrate
Intramuscual (IM); Infusion (IV); Intravenous

Sodium Thioglycolate
Subcutaneous

Sodium Thiomalate
Intramuscular (IM); Infusion (IV)

Sodium Thiosulfate
Intravenous; Ophthalmic; Topical

Sodium Thiosulfate Anhydrous
Intravenous

Sodium Trimetaphosphate
Intravenous

Sodium Xylenesulfonate
Topical

Somay 44
Topical

Sorbic Acid
Ophthalmic; Topical; Vaginal

Sorbitan
Topical

Sorbitan Isostearate
Topical

Sorbitan Monolaurate
Ophthalmic; Topical

Sorbitan Monooleate
Rectal; Topical; Transdermal

Sorbitan Monopalmitate
Intramuscular; Topical

Sorbitan Monostearate
Topical; Vaginal

Sorbitan Sesquioleate
Rectal; Topical

Sorbitan Trioleate
Inhalation; Nasal

Sorbitan Tristearate
Topical

Sorbitol
Dental; Intra-articular; Intralesional; Intramuscular;

Intrasynovial; Intravenous; Infusion (IV); Nasal;

Ophthalmic; Rectal; Topical; Vaginal

Sorbitol Solution
Intra-articular; Intralesional; Intramuscular;

Intravenous; Infusion (IV); Nasal; Ophthalmic;

Rectal; Topical; Vaginal

Soybean Flour
Topical

Soybean Oil
Intraveous; Infusion (IV); Topical

Spearmint Oil
Topical

Spermaceti
Topical; Vaginal

Squalane
Topical

Stabilized Oxychloro Complex
Ophthalmic

Stannous 2-Ethylhexanoate
Vagianl

Stannous Chloride
Intravenous; Infusion (IV)

Stannous Chloride Anhydrous
Intravenous; Infusion (IV)

Stannous Fluoride
Intravenous

Stannous Tartrate
Intravenous

Starch
Intramuscular; Rectal; Topical; Vaginal

Starch 1500, Pregelatinized
Vagianl

Starch, Corn
Vagianl

Stearalkonium Chloride
Topical

Stearalkonium Hectorite/Propylene
Transdermal

Carbonate

Stearamidoethyl Diethylamine
Topical; Vaginal

Steareth-10
Rectal; Topical

Steareth-100
Topical

Steareth-2
Topical

Steareth-20
Topical

Steareth-21
Topical

Steareth-40
Topical; Rectal

Stearic Acid
Implantation; Subcutaneous; Topical; Vaginal

Stearic Diethanolamide
Topical

Stearoxytrimethylsilane
Topical

Steartrimonium Hydrolyzed Animal
Topical

Collagen

Stearyl Alcohol
Topical; Vaginal

Sterile Water For Inhalation
Infusion (IV)

Styrene/Isoprene/Styrene Block Copolymer
Topical

Succimer
Intravenous

Succinic Acid
Intramuscular (IM); Infusion (IV); Intravenous

Sucralose
Nasa

Sucrose
Intramuscular; Intravenous; Infusion (IV); Rectal;

Subcutaneous; Topical

Sucrose Distearate
Topical

Sucrose Polyesters
Topical

Sulfacetamide Sodium
Topical

Sulfobutylether.Beta.-Cyclodextrin
Intramuscular; Intravenous; Infusion (IV)

Sulfur Dioxide
Infusion (IV)

Sulfuric Acid
Auricular (Otic); Epidural; Intramuscular (IM);

Infusion (IV); Inhalation; Intraperitoneal;

Intravenous; Irrigation; Nasal; Ophthalmic;

Respiratory (Inhalation); Topical

Sulfurous Acid
Intramuscular

Surfactol Qs
Topical

Tagatose, D-
Rectal

Talc
Topical

Tall Oil
Topical

Tallow Glycerides
Topical

Tartaric Acid
Intramuscular; Intravenous; Infusion (IV); Topical

Tartaric Acid, Dl-
Intramuscular (IM); Infusion (IV); Intravenous;

Rectal; Vaginal

Tenox
Topical

Tenox-2
Topical

Tert-Butyl Alcohol
Intravenous; Infusion (IV); Topical

Tert-Butyl Hydroperoxide
Topical

Tert-Butylhydroquinone
Vagianl

Tetrakis(2-
Intravenous

Methoxyisobutylisocyanide)Copper(I)

Tetrafluoroborate

Tetrapropyl Orthosilicate
Vagianl

Tetrofosmin
Infusion (IV)

Theophylline
Intravenous; Infusion (IV)

Thimerosal
Auricular (Otic); Intramuscular (IM); Infusion (IV);

Subcutaneous (SC); Intravenous; Ophthalmic;

Topical

Threonine
Intravenous; Infusion (IV)

Thymol
Inhalation

Tin
Intravenous

Titanium Dioxide
Dental; Intrauterine; Ophthalmic; Respiratory

(Inhalation); Topical; Transdermal

Tocopherol
Topical

Tocophersolan
Ophthalmic; Topical

Triacetin
Endocervical; Transdermal

Tricaprylin
Epidural; Infiltration

Trichloromonofluoromethane
Inhalation; Nasal; Topical

Trideceth-10
Topical

Triethanolamine Lauryl Sulfate
Topical

Trifluoroacetic Acid
Infusion (IV)

Triglycerides, Medium Chain
Topical

Trihydroxystearin
Topical

Trilaneth-4 Phosphate
Topical

Trilaureth-4 Phosphate
Topical

Trisodium Citrate Dihydrate
Intramuscular (IM); Infusion (IV); Intravenous;

Intravitreal; Nasal; Ophthalmic; Topical

Trisodium Hedta
Topical

Triton 720
Ophthalmic

Triton X-200
Topical

Trolamine
Rectal; Topical; Transdermal; Vaginal

Tromantadine
Intramuscular; Intravenous

Tromethamine
Intramuscular (IM); Infusion (IV); Intra-arterial;

Intrathecal; Intratracheal; Intravasular; Intravenous;

Ophthalmic; Rectal; Respiratory (Inhalation);

Subcutaneous; Topical; Transdermal; Urethral

Tryptophan
Infusion (IV)

Tyloxapol
Ophthalmic; Topical

Tyrosine
Infusion (IV)

Undecylenic Acid
Topical

Union 76 Amsco-Res 6038
Transdermal

Urea
Intramuscular; Vaginal

Valine
Infusion (IV)

Vegetable Oil
Topical

Vegetable Oil Glyceride, Hydrogenated
Rectal

Vegetable Oil, Hydrogenated
Rectal; Topical; Vaginal

Versetamide
Intravenous

Viscarin
Topical

Viscose/Cotton
Transdermal

Vitamin E
Topical

Wax, Emulsifying
Rectal; Topical

Wecobee Fs
Topical; Vaginal

White Ceresin Wax
Vagianl

White Wax
Rectal; Topical; Vaginal

Xanthan Gum
Rectal; Topical

Zinc
Subcutaneous

Zinc Acetate
Subcutaneous, Topical

Zinc Carbonate
Subcutaneous

Zinc Chloride
Intramuscular (IM); Subcutaneous (SC); Intradermal;

Ophthalmic

Zinc Oxide
Intramuscular (IM); Subcutaneous (SC); Rectal;

Respiratory (Inhalation)

Delivery

The present disclosure encompasses the delivery of NAVs for any of therapeutic, pharmaceutical, diagnostic or imaging by any appropriate route taking into consideration likely advances in the sciences of drug delivery. Delivery may be naked or formulated.

Naked Delivery

The NAVs of the present invention may be delivered to a cell naked. As used herein in, “naked” refers to delivering NAVs free from agents which promote transfection. For example, the NAVs delivered to the cell may contain no modifications. The naked NAVs may be delivered to the cell using routes of administration known in the art and described herein.

Formulated Delivery

The NAVs of the present invention may be formulated, using the methods described herein. The formulations may contain polynucleotides which may be modified and/or unmodified. The formulations may further include, but are not limited to, cell penetration agents, a pharmaceutically acceptable carrier, a delivery agent, a bioerodible or biocompatible polymer, a solvent, and a sustained-release delivery depot. The formulated NAVs may be delivered to the cell using routes of administration known in the art and described herein.

The compositions may also be formulated for direct delivery to an organ or tissue in any of several ways in the art including, but not limited to, direct soaking or bathing, via a catheter, by gels, powder, ointments, creams, gels, lotions, and/or drops, by using substrates such as fabric or biodegradable materials coated or impregnated with the compositions, and the like.

Administration

The NAVs of the present invention may be administered by any route which results in a therapeutically effective outcome. These include, but are not limited to enteral (into the intestine), gastroenteral, epidural (into the dura matter), oral (by way of the mouth), transdermal, peridural, intracerebral (into the cerebrum), intracerebroventricular (into the cerebral ventricles), epicutaneous (application onto the skin), intradermal, (into the skin itself), subcutaneous (under the skin), nasal administration (through the nose), intravenous (into a vein), intravenous bolus, intravenous drip, intraarterial (into an artery), intramuscular (into a muscle), intracardiac (into the heart), intraosseous infusion (into the bone marrow), intrathecal (into the spinal canal), intraperitoneal. (infusion or injection into the peritoneum), intravesical infusion, intravitreal, (through the eye), intracavernous injection (into a pathologic cavity) intracavitary (into the base of the penis), intravaginal administration, intrauterine, extra-amniotic administration, transdermal (diffusion through the intact skin for systemic distribution), transmucosal (diffusion through a mucous membrane), transvaginal, insufflation (snorting), sublingual, sublabial, enema, eye drops (onto the conjunctiva), in ear drops, auricular (in or by way of the ear), buccal (directed toward the cheek), conjunctival, cutaneous, dental (to a tooth or teeth), electro-osmosis, endocervical, endosinusial, endotracheal, extracorporeal, hemodialysis, infiltration, interstitial, intra-abdominal, intra-amniotic, intra-articular, intrabiliary, intrabronchial, intrabursal, intracartilaginous (within a cartilage), intracaudal (within the cauda equine), intracisternal (within the cisterna magna cerebellomedularis), intracorneal (within the cornea), dental intracornal, intracoronary (within the coronary arteries), intracorporus cavernosum (within the dilatable spaces of the corporus cavernosa of the penis), intradiscal (within a disc), intraductal (within a duct of a gland), intraduodenal (within the duodenum), intradural (within or beneath the dura), intraepidermal (to the epidermis), intraesophageal (to the esophagus), intragastric (within the stomach), intragingival (within the gingivae), intraileal (within the distal portion of the small intestine), intralesional (within or introduced directly to a localized lesion), intraluminal (within a lumen of a tube), intralymphatic (within the lymph), intramedullary (within the marrow cavity of a bone), intrameningeal (within the meninges), intraocular (within the eye), intraovarian (within the ovary), intrapericardial (within the pericardium), intrapleural (within the pleura), intraprostatic (within the prostate gland), intrapulmonary (within the lungs or its bronchi), intrasinal (within the nasal or periorbital sinuses), intraspinal (within the vertebral column), intrasynovial (within the synovial cavity of a joint), intratendinous (within a tendon), intratesticular (within the testicle), intrathecal (within the cerebrospinal fluid at any level of the cerebrospinal axis), intrathoracic (within the thorax), intratubular (within the tubules of an organ), intratumor (within a tumor), intratympanic (within the aurus media), intravascular (within a vessel or vessels), intraventricular (within a ventricle), iontophoresis (by means of electric current where ions of soluble salts migrate into the tissues of the body), irrigation (to bathe or flush open wounds or body cavities), laryngeal (directly upon the larynx), nasogastric (through the nose and into the stomach), occlusive dressing technique, ophthalmic (to the external eye), oropharyngeal (directly to the mouth and pharynx), parenteral, percutaneous, periarticular, peridural, perineural, periodontal, rectal, respiratory (within the respiratory tract by inhaling orally or nasally for local or systemic effect), retrobulbar (behind the pons or behind the eyeball), intramyocardial (entering the myocardium), soft tissue, subarachnoid, subconjunctival, submucosal, transplacental (through or across the placenta), transtracheal (through the wall of the trachea), transtympanic (across or through the tympanic cavity), ureteral (to the ureter), urethral (to the urethra), vaginal, caudal block, diagnostic, nerve block, biliary perfusion, cardiac perfusion, photopheresis or spinal. In specific embodiments, compositions may be administered in a way which allows them cross the blood-brain barrier, vascular barrier, or other epithelial barrier. In one embodiment, a formulation for a route of administration may include at least one inactive ingredient. Non-limiting examples of routes of administration and inactive ingredients which may be included in formulations for the specific route of administration is shown in Table 20. In Table 27, “AN” means anesthetic, “CNBLK” means cervical nerve block, “NBLK” means nerve block, “IV” means intravenous, “IM” means intramuscular and “SC” means subcutaneous.

TABLE 27

Routes of Adminsitration and Inactive Ingredients

Route of Administration
Inactive Ingredient

Intrathecal
Acetone Sodium Bisulfite; Citric Acid; Hydrochloric Acid;

(AN, CNBLK)
Sodium Chloride; Sodium Hydroxide; Sodium Metabisulfite

Infiltration (AN)
Acetic Acid; Acetone Sodium Bisulfite; Ascorbic Acid; Benzyl

Alcohol; Calcium Chloride; Carbon Dioxide; Chlorobutanol; Citric

Acid; Citric Acid Monohydrate; Edetate Calcium Disodium; Edetate

Disodium; Hydrochloric Acid; Hydrochloric Acid, Diluted; Lactic Acid;

Methylparaben; Monothioglycerol; Nitrogen; Potassium Chloride;

Potassium Metabisulfite; Potassium Phosphate, Monobasic;

Propylparaben; Sodium Bisulfite; Sodium Carbonate; Sodium Chlorate;

Sodium Chloride; Sodium Citrate; Sodium Hydroxide; Sodium Lactate;

Sodium Metabisulfite; Sodium Phosphate, Dibasic, Heptahydrate

Sympathetic NBLK(AN)
Hydrochloric Acid; Sodium Chloride; Sodium Hydroxide

Auricular (Otic)
Acetic Acid; Aluminum Acetate; Aluminum Sulfate Anhydrous;

Benzalkonium Chloride; Benzethonium Chloride; Benzyl Alcohol;

Boric Acid; Calcium Carbonate; Cetyl Alcohol; Chlorobutanol;

Chloroxylenol; Citric Acid; Creatinine; Cupric Sulfate; Cupric Sulfate

Anhydrous; Edetate Disodium; Edetic Acid; Glycerin; Glyceryl

Stearate; Hydrochloric Acid; Hydrocortisone; Hydroxyethyl Cellulose;

Isopropyl Myristate; Lactic Acid; Lecithin, Hydrogenated;

Methylparaben; Mineral Oil; Petrolatum; Petrolatum, White;

Phenylethyl Alcohol; Polyoxyl 40 Stearate; Polyoxyl Stearate;

Polysorbate 20; Polysorbate 80; Polyvinyl Alcohol; Potassium

Metabisulfite; Potassium Phosphate, Monobasic; Povidone K90f;

Povidones; Propylene Glycol; Propylene Glycol Diacetate;

Propylparaben; Sodium Acetate; Sodium Bisulfite; Sodium Borate;

Sodium Chloride; Sodium Citrate; Sodium Hydroxide; Sodium

Phosphate, Dibasic, Anhydrous; Sodium Phosphate, Dibasic,

Heptahydrate; Sodium Phosphate, Monobasic, Anhydrous; Sodium

Sulfite; Sulfuric Acid; Thimerosal

Caudal Block
Ascorbic Acid; Calcium Chloride; Citric Acid; Edetate Calcium

Disodium; Edetate Disodium; Hydrochloric Acid; Methylparaben;

Monothioglycerol; Nitrogen; Potassium Chloride; Sodium Chloride;

Sodium Hydroxide; Sodium Lactate; Sodium Metabisulfite

Dental
Acetone Sodium Bisulfite; Alcohol; Alcohol, Dehydrated; Alcohol,

Denatured; Anethole; Benzyl Alcohol; Carboxymethylcellulose

Sodium; Carrageenan; D&C Yellow No. 10; Dimethicone Medical

Fluid 360; Eucalyptol; Fd&C Blue No. 1; Fd&C Green No. 3; Flavor

89-186; Flavor 89-259; Flavor Df-119; Flavor Df-1530; Flavor

Enhancer; Gelatin; Gelatin, Crosslinked; Glycerin; Glyceryl Stearate;

High Density Polyethylene; Hydrocarbon Gel, Plasticized; Hydrochloric

Acid; Menthol; Mineral Oil; Nitrogen; Pectin; Peg-40 Sorbitan

Diisostearate; Peppermint Oil; Petrolatum, White; Plastibase-50w;

Polyethylene Glycol 1540; Polyglactin; Polyols; Polyoxyl 40

Hydrogenated Castor Oil; Polyoxyl 40 Stearate; Propylene Glycol;

Pvm/Ma Copolymer; Saccharin Sodium; Silica, Dental; Silicon

Dioxide; Sodium Benzoate; Sodium Chloride; Sodium Hydroxide;

Sodium Lauryl Sulfate; Sodium Metabisulfite; Sorbitol; Titanium

Dioxide

Diagnostic
Hydrochloric Acid

Endocervical
Colloidal Silicon Dioxide; Triacetin

Epidural
1,2-Dioleoyl-Sn-Glycero-3-Phosphocholine; 1,2-Dipalmitoyl-Sn-

Glycero-3-(Phospho-Rac-(1-Glycerol)); Ascorbic Acid; Benzyl

Alcohol; Calcium Chloride; Cholesterol; Citric Acid; Edetate Calcium

Disodium; Edetate Disodium; Glyceryl Trioleate; Hydrochloric Acid;

Isotonic Sodium Chloride Solution; Methylparaben; Monothioglycerol;

Nitrogen; Potassium Chloride; Sodium Bisulfite; Sodium Chloride;

Sodium Citrate; Sodium Hydroxide; Sodium Lactate, L-; Sodium

Metabisulfite; Sodium Sulfite; Sulfuric Acid; Tricaprylin

Extracorporeal
Acetic Acid; Alcohol, Dehydrated; Benzyl Alcohol; Hydrochloric Acid;

Propylene Glycol; Sodium Acetate; Sodium Chloride; Sodium

Hydroxide

Intramuscular-
Acetic Acid; Alcohol; Alcohol, Dehydrated; Alcohol, Diluted;

Intravenous
Anhydrous Dextrose; Anhydrous Lactose; Anhydrous Trisodium

Citrate; Arginine; Ascorbic Acid; Benzethonium Chloride; Benzoic

Acid; Benzyl Alcohol; Calcium Chloride; Carbon Dioxide;

Chlorobutanol; Citric Acid; Citric Acid Monohydrate; Creatinine;

Dextrose; Edetate Calcium Disodium; Edetate Disodium; Edetate

Sodium; Gluconolactone; Glycerin; Hydrochloric Acid; Hydrochloric

Acid, Diluted; Lactic Acid; Lactic Acid, Dl-; Lactose; Lactose

Monohydrate; Lactose, Hydrous; Lysine; Mannitol; Methylparaben;

Monothioglycerol; Niacinamide; Nitrogen; Phenol; Phenol, Liquefied;

Phosphoric Acid; Polyethylene Glycol 300; Polyethylene Glycol 400;

Polypropylene Glycol; Polysorbate 40; Potassium Metabisulfite;

Potassium Phosphate, Monobasic; Propylene Glycol; Propylparaben;

Saccharin Sodium; Saccharin Sodium Anhydrous; Silicone;

Simethicone; Sodium Acetate; Sodium Acetate Anhydrous; Sodium

Benzoate; Sodium Bicarbonate; Sodium Bisulfate; Sodium Bisulfite;

Sodium Carbonate; Sodium Chloride; Sodium Citrate; Sodium

Formaldehyde Sulfoxylate; Sodium Hydroxide; Sodium Lactate, L-;

Sodium Metabisulfite; Sodium Phosphate; Sodium Phosphate, Dibasic;

Sodium Phosphate, Dibasic, Anhydrous; Sodium Phosphate, Dibasic,

Dihydrate; Sodium Phosphate, Dibasic, Heptahydrate; Sodium

Phosphate, Monobasic; Sodium Phosphate, Monobasic, Anhydrous;

Sodium Phosphate, Monobasic, Monohydrate; Sodium Sulfate; Sodium

Sulfite; Sodium Tartrate; Sodium Thiomalate; Succinic Acid; Sulfuric

Acid; Tartaric Acid, Dl-; Thimerosal; Trisodium Citrate Dihydrate;

Tromethamine

Intramuscular-
Acetic Acid; Alcohol; Alcohol, Dehydrated; Benzyl Alcohol;

Intravenous-
Chlorobutanol; Citric Acid; Citric Acid Monohydrate; Citric Acid,

Subcutaneous
Hydrous; Creatinine; Dextrose; Edetate Disodium; Edetate Sodium;

Gelatin; Glycerin; Glycine; Hydrochloric Acid; Hydrochloric Acid,

Diluted; Lactic Acid; Lactose; Lactose Monohydrate; Metacresol;

Methanesulfonic Acid; Methylparaben; Monothioglycerol; Nitrogen;

Phenol; Phosphoric Acid; Polyoxyethylene Fatty Acid Esters;

Propylparaben; Sodium Acetate; Sodium Bisulfate; Sodium Bisulfite;

Sodium Chloride; Sodium Citrate; Sodium Dithionite; Sodium

Hydroxide; Sodium Lactate; Sodium Lactate, L-; Sodium Metabisulfite;

Sodium Phosphate, Dibasic, Heptahydrate; Thimerosal

Intramuscular-
Acetic Acid; Anhydrous Dextrose; Benzyl Alcohol; Chlorobutanol;

Subcutaneous
Citric Acid; Cysteine; Edetate Disodium; Gelatin; Glycerin; Glycine;

Hydrochloric Acid; Lactose Monohydrate; Mannitol; Metacresol;

Methylparaben; Nitrogen; Peg Vegetable Oil; Peg-40 Castor Oil;

Phenol; Phenol, Liquefied; Phosphoric Acid; Polyoxyethylene Fatty

Acid Esters; Polysorbate 20; Propylparaben; Protamine Sulfate; Sesame

Oil; Sodium Acetate; Sodium Acetate Anhydrous; Sodium Chloride;

Sodium Citrate; Sodium Formaldehyde Sulfoxylate; Sodium Hydroxide;

Sodium Phosphate Dihydrate; Sodium Phosphate, Dibasic,

Heptahydrate; Sulfuric Acid; Thimerosal; Zinc Chloride; Zinc Oxide

Implantation
Acetone; Crospovidone; Dimethylsiloxane/Methylvinylsiloxane

Copolymer; Ethylene Vinyl Acetate Copolymer; Magnesium Stearate;

Poly(Bis(P-Carboxyphenoxy)Propane Anhydride):Sebacic Acid;

Polyglactin; Silastic Brand Medical Grade Tubing; Silastic Medical

Adhesive, Silicone Type A; Stearic Acid

Infiltration
Cholesterol; Citric Acid; Diethyl Pyrocarbonate;

Dipalmitoylphosphatidylglycerol, Dl-; Hydrochloric Acid; Nitrogen;

Phosphoric Acid; Sodium Chloride; Sodium Hydroxide; Sodium

Metabisulfite; Tricaprylin

Inhalation
Acetone Sodium Bisulfite; Acetylcysteine; Alcohol; Alcohol,

Dehydrated; Ammonia; Ascorbic Acid; Benzalkonium Chloride;

Carbon Dioxide; Cetylpyridinium Chloride; Chlorobutanol; Citric Acid;

D&C Yellow No. 10; Dichlorodifluoromethane;

Dichlorotetrafluoroethane; Edetate Disodium; Edetate Sodium; Fd&C

Yellow No. 6; Fluorochlorohydrocarbons; Glycerin; Hydrochloric Acid;

Hydrochloric Acid, Diluted; Lactose; Lecithin; Lecithin, Hydrogenated

Soy; Lecithin, Soybean; Menthol; Methylparaben; Nitric Acid;

Nitrogen; Norflurane; Oleic Acid; Propylene Glycol; Propylparaben;

Saccharin; Saccharin Sodium; Sodium Bisulfate; Sodium Bisulfite;

Sodium Chloride; Sodium Citrate; Sodium Hydroxide; Sodium

Metabisulfite; Sodium Sulfate Anhydrous; Sodium Sulfite; Sorbitan

Trioleate; Sulfuric Acid; Thymol; Trichloromonofluoromethane

Interstitial
Benzyl Alcohol; Dextrose; Hydrochloric Acid; Sodium Acetate;

Sodium Hydroxide

Intra-amniotic
Citric Acid; Edetate Disodium Anhydrous; Hydrochloric Acid; Sodium

Hydroxide

Intra-arterial
Anhydrous Trisodium Citrate; Benzyl Alcohol; Carbon Dioxide; Citric

Acid; Diatrizoic Acid; Edetate Calcium Disodium; Edetate Disodium;

Hydrochloric Acid; Hydrochloric Acid, Diluted; Iodine; Meglumine;

Methylparaben; Nitrogen; Propylparaben; Sodium Bisulfite; Sodium

Carbonate; Sodium Carbonate Monohydrate; Sodium Chloride; Sodium

Citrate; Sodium Hydroxide; Tromethamine

Intra-articular
Acetic Acid; Anhydrous Trisodium Citrate; Benzalkonium Chloride;

Benzyl Alcohol; Carboxymethylcellulose; Carboxymethylcellulose

Sodium; Cellulose, Microcrystalline; Citric Acid; Creatine; Creatinine;

Crospovidone; Diatrizoic Acid; Edetate Calcium Disodium; Edetate

Disodium; Hyaluronate Sodium; Hydrochloric Acid; Iodine;

Meglumine; Methylcelluloses; Methylparaben; Myristyl-.Gamma.-

Picolinium Chloride; Niacinamide; Phenol; Phosphoric Acid;

Polyethylene Glycol 3350; Polyethylene Glycol 4000; Polysorbate 80;

Potassium Phosphate, Dibasic; Potassium Phosphate, Monobasic;

Propylparaben; Sodium Acetate; Sodium Bisulfite; Sodium Chloride;

Sodium Citrate; Sodium Hydroxide; Sodium Metabisulfite; Sodium

Phosphate; Sodium Phosphate, Dibasic, Anhydrous; Sodium Phosphate,

Dibasic, Heptahydrate; Sodium Phosphate, Monobasic, Anhydrous;

Sodium Phosphate, Monobasic, Monohydrate; Sodium Sulfite; Sorbitol;

Sorbitol Solution

Intrabursal
Anhydrous Trisodium Citrate; Benzalkonium Chloride; Benzyl Alcohol;

Carboxymethylcellulose; Carboxymethylcellulose Sodium; Citric Acid;

Creatinine; Edetate Disodium; Hydrochloric Acid; Methylparaben;

Polysorbate 80; Propylparaben; Sodium Bisulfite; Sodium Chloride;

Sodium Hydroxide; Sodium Metabisulfite; Sodium Phosphate; Sodium

Phosphate, Dibasic, Heptahydrate; Sodium Phosphate, Monobasic,

Anhydrous

Intracardiac
Carbon Dioxide; Citric Acid; Citric Acid Monohydrate; Diatrizoic Acid;

Edetate Calcium Disodium; Edetate Disodium; Hydrochloric Acid;

Iodine; Lactic Acid; Meglumine; Sodium Bisulfite; Sodium Carbonate

Monohydrate; Sodium Chloride; Sodium Citrate; Sodium Hydroxide;

Sodium Lactate; Sodium Lactate, L-; Sodium Metabisulfite

Intracaudal
Hydrochloric Acid; Sodium Chloride; Sodium Hydroxide

Intracavitary
Alcohol, Dehydrated; Alfadex; Anhydrous Lactose; Benzyl Alcohol;

Dextrose; Hydrochloric Acid; Lactose; Lactose Monohydrate; Nitrogen;

Sodium Acetate; Sodium Chloride; Sodium Citrate; Sodium Hydroxide

Intradermal
Benzalkonium Chloride; Benzyl Alcohol; Carboxymethylcellulose

Sodium; Creatinine; Edetate Disodium; Glycerin; Hydrochloric Acid;

Metacresol; Methylparaben; Phenol; Polysorbate 80; Protamine Sulfate;

Sodium Acetate; Sodium Bisulfite; Sodium Chloride; Sodium

Hydroxide; Sodium Phosphate; Sodium Phosphate, Dibasic; Sodium

Phosphate, Dibasic, Heptahydrate; Sodium Phosphate, Monobasic,

Anhydrous; Zinc Chloride

Intradiscal
Cysteine Hydrochloride Anhydrous; Cysteine, Dl-; Diatrizoic Acid;

Edetate Calcium Disodium; Edetate Disodium; Iodine; Meglumine;

Sodium Bisulfite; Sodium Hydroxide

Intralesional
Acetic Acid; Benzalkonium Chloride; Benzyl Alcohol;

Carboxymethylcellulose; Carboxymethylcellulose Sodium; Citric Acid;

Creatine; Creatinine; Edetate Disodium; Hydrochloric Acid;

Methylcelluloses; Methylparaben; Myristyl-.Gamma.-Picolinium

Chloride; Niacinamide; Phenol; Phosphoric Acid; Polyethylene Glycol

3350; Polyethylene Glycol 4000; Polysorbate 80; Propylparaben;

Sodium Acetate; Sodium Bisulfite; Sodium Chloride; Sodium Citrate;

Sodium Hydroxide; Sodium Phosphate; Sodium Phosphate, Dibasic;

Sodium Phosphate, Dibasic, Anhydrous; Sodium Phosphate, Dibasic,

Heptahydrate; Sodium Phosphate, Monobasic; Sodium Phosphate,

Monobasic, Anhydrous; Sodium Phosphate, Monobasic, Monohydrate;

Sodium Sulfite; Sorbitol; Sorbitol Solution

Intralymphatic
Poppy Seed Oil

Intramuscular
Acetic Acid; Activated Charcoal; Adipic Acid; Alcohol; Alcohol,

Dehydrated; Ammonium Acetate; Anhydrous Dextrose; Ascorbic Acid;

Benzalkonium Chloride; Benzethonium Chloride; Benzoic Acid; Benzyl

Alcohol; Benzyl Benzoate; Butylated Hydroxyanisole; Butylated

Hydroxytoluene; Butylparaben; Calcium; Calcium Chloride; Carbon

Dioxide; Carboxymethylcellulose; Carboxymethylcellulose Sodium;

Castor Oil; Cellulose, Microcrystalline; Chlorobutanol; Chlorobutanol

Hemihydrate; Chlorobutanol, Anhydrous; Citric Acid; Citric Acid

Monohydrate; Corn Oil; Cottonseed Oil; Creatine; Creatinine;

Croscarmellose Sodium; Crospovidone; Dextrose; Diatrizoic Acid;

Docusate Sodium; Edetate Calcium Disodium; Edetate Disodium;

Edetate Disodium Anhydrous; Edetate Sodium; Ethyl Acetate; Gelatin;

Glutathione; Glycerin; Glycine; Hyaluronate Sodium; Hydrochloric

Acid; Hydroxide Ion; Lactic Acid; Lactic Acid, Dl-; Lactose; Lactose

Monohydrate; Lactose, Hydrous; Lecithin; Magnesium Chloride;

Maleic Acid; Mannitol; Meglumine; Metacresol; Methionine;

Methylcelluloses; Methylparaben; Monothioglycerol; Myristyl-

.Gamma.-Picolinium Chloride; N,N-Dimethylacetamide; Niacinamide;

Nitrogen; Peanut Oil; Peg-20 Sorbitan Isostearate; Phenol;

Phenylmercuric Nitrate; Phosphoric Acid; Polyethylene Glycol 200;

Polyethylene Glycol 300; Polyethylene Glycol 3350; Polyethylene

Glycol 4000; Polyglactin; Polylactide; Polysorbate 20; Polysorbate 40;

Polysorbate 80; Polyvinyl Alcohol; Potassium Phosphate, Dibasic;

Potassium Phosphate, Monobasic; Povidones; Propyl Gallate; Propylene

Glycol; Propylparaben; Saccharin Sodium; Saccharin Sodium

Anhydrous; Sesame Oil; Sodium Acetate; Sodium Acetate Anhydrous;

Sodium Benzoate; Sodium Bicarbonate; Sodium Bisulfite; Sodium

Carbonate; Sodium Chlorate; Sodium Chloride; Sodium Chloride

Injection; Sodium Citrate; Sodium Formaldehyde Sulfoxylate; Sodium

Hydroxide; Sodium Metabisulfite; Sodium Phosphate; Sodium

Phosphate, Dibasic; Sodium Phosphate, Dibasic, Anhydrous; Sodium

Phosphate, Dibasic, Heptahydrate; Sodium Phosphate, Monobasic;

Sodium Phosphate, Monobasic, Anhydrous; Sodium Phosphate,

Monobasic, Monohydrate; Sodium Sulfate Anhydrous; Sodium Sulfite;

Sodium Tartrate; Sorbitan Monopalmitate; Sorbitol; Sorbitol Solution;

Starch; Sucrose; Sulfobutylether .Beta.-Cyclodextrin; Sulfuric Acid;

Sulfurous Acid; Tartaric Acid; Thimerosal; Tromantadine;

Tromethamine; Urea

Intraocular
Benzalkonium Chloride; Calcium Chloride; Citric Acid Monohydrate;

Hydrochloric Acid; Magnesium Chloride; Polyvinyl Alcohol; Potassium

Chloride; Sodium Acetate; Sodium Chloride; Sodium Citrate; Sodium

Hydroxide

Intraperitoneal
Benzyl Alcohol; Calcium Chloride; Dextrose; Edetate Calcium

Disodium; Hydrochloric Acid; Magnesium Chloride; Sodium Acetate;

Sodium Bicarbonate; Sodium Bisulfite; Sodium Carbonate; Sodium

Chloride; Sodium Citrate; Sodium Hydroxide; Sodium Lactate; Sodium

Metabisulfite; Sulfuric Acid

Intrapleural
Benzyl Alcohol; Citric Acid; Dextrose; Dichlorodifluoromethane;

Hydrochloric Acid; Sodium Acetate; Sodium Carbonate; Sodium

Chloride; Sodium Citrate; Sodium Hydroxide

Intraspinal
Dextrose; Hydrochloric Acid; Sodium Hydroxide

Intrasynovial
Acetic Acid; Benzyl Alcohol; Carboxymethylcellulose Sodium; Citric

Acid; Creatinine; Edetate Disodium; Hydrochloric Acid;

Methylcelluloses; Methylparaben; Myristyl-.Gamma-Picolinium

Chloride; Niacinamide; Phenol; Polyethylene Glycol 3350;

Polyethylene Glycol 4000; Polysorbate 80; Propylparaben; Sodium

Acetate; Sodium Bisulfite; Sodium Chloride; Sodium Citrate; Sodium

Hydroxide; Sodium Phosphate, Dibasic; Sodium Phosphate, Dibasic,

Heptahydrate; Sodium Phosphate, Monobasic; Sodium Phosphate,

Monobasic, Anhydrous; Sorbitol

Intrathecal
Benzyl Alcohol; Carbon Dioxide; Citric Acid; Edetate Calcium

Disodium; Hydrochloric Acid; Methionine; Nitrogen; Pentetate Calcium

Trisodium; Pentetic Acid; Sodium Bicarbonate; Sodium Chloride;

Sodium Citrate; Sodium Hydroxide; Sulfuric Acid; Tromethamine

Intratracheal
Acetic Acid; Benzyl Alcohol; Carboxymethylcellulose Sodium;

Hydrochloric Acid; Isotonic Sodium Chloride Solution; Peanut Oil;

Sodium Bicarbonate; Sodium Chloride; Sodium Citrate; Sodium

Hydroxide; Tromethamine

Intratumor
Benzyl Alcohol; Hydrochloric Acid; Nitrogen; Sodium Carbonate;

Sodium Chloride; Sodium Hydroxide

Intrauterine
Barium Sulfate; Crospovidone; Diatrizoic Acid;

Dimethylsiloxane/Methylvinylsiloxane Copolymer; Edetate Calcium

Disodium; Edetate Disodium; Ethylene Vinyl Acetate Copolymer; High

Density Polyethylene; Meglumine; Polyethylene High Density

Containing Ferric Oxide Black (<1%); Polyethylene Low Density

Containing Barium Sulfate (20-24%); Polyethylene T; Polypropylene;

Poppy Seed Oil; Potassium Phosphate, Monobasic; Silicone; Sodium

Citrate; Sodium Hydroxide; Titanium Dioxide

Intravascular
Alcohol; Alcohol, Dehydrated; Calcium Chloride; Carbon Dioxide;

Citric Acid; Diatrizoic Acid; Edetate Calcium Disodium; Edetate

Disodium; Hydrochloric Acid; Hydrochloric Acid, Diluted; Iodine;

Meglumine; Nitrogen; Potassium Hydroxide; Sodium Carbonate;

Sodium Chloride; Sodium Citrate; Sodium Hydroxide; Sodium

Phosphate, Monobasic, Anhydrous; Sodium Phosphate, Monobasic,

Monohydrate; Tromethamine

Intravenous
Alpha-Tocopherol; Alpha-Tocopherol, Dl-; 1,2-Dimyristoyl-Sn-

Glycero-3-Phosphocholine; 1,2-Distearoyl-Sn-Glycero-3-(Phospho-

Rac-(1-Glycerol)); 1,2-Distearoyl-Sn-Glycero-3-Phosphocholine;

Acetic Acid; Acetic Acid, Glacial; Acetic Anhydride; Acetylated

Monoglycerides; Acetyltryptophan, Dl-; Activated Charcoal; Albumin

Aggregated; Albumin Colloidal; Albumin Human; Alcohol; Alcohol,

Dehydrated; Alcohol, Denatured; Ammonium Acetate; Ammonium

Hydroxide; Ammonium Sulfate; Anhydrous Citric Acid; Anhydrous

Dextrose; Anhydrous Lactose; Anhydrous Trisodium Citrate; Arginine;

Ascorbic Acid; Benzenesulfonic Acid; Benzethonium Chloride;

Benzoic Acid; Benzyl Alcohol; Benzyl Chloride; Bibapcitide; Boric

Acid; Butylated Hydroxytoluene; Calcium Chloride; Calcium

Gluceptate; Calcium Hydroxide; Calcobutrol; Caldiamide Sodium;

Caloxetate Trisodium; Calteridol Calcium; Captisol; Carbon Dioxide;

Cellulose, Microcrystalline; Chlorobutanol; Chlorobutanol

Hemihydrate; Chlorobutanol, Anhydrous; Cholesterol; Citrate; Citric

Acid; Citric Acid Monohydrate; Citric Acid, Hydrous; Cysteine;

Cysteine Hydrochloride; Dalfampridine; Dextran; Dextran 40;

Dextrose; Dextrose Monohydrate; Dextrose Solution; Diatrizoic Acid;

Dimethicone Medical Fluid 360; Edetate Calcium Disodium; Edetate

Disodium; Edetate Disodium Anhydrous; Egg Phospholipids;

Ethanolamine Hydrochloride; Ethylenediamine; Exametazime; Ferric

Chloride; Gadolinium Oxide; Gamma Cyclodextrin; Gelatin; Gentisic

Acid; Gluceptate Sodium; Gluceptate Sodium Dihydrate;

Gluconolactone; Glucuronic Acid; Glycerin; Glycine; Guanidine

Hydrochloride; Hetastarch; Histidine; Human Albumin Microspheres;

Hydrochloric Acid; Hydrochloric Acid, Diluted;

Hydroxyethylpiperazine Ethane Sulfonic Acid; Hydroxypropyl-

Bcyclodextrin; Iodine; Iodoxamic Acid; Iofetamine Hydrochloride;

Isopropyl Alcohol; Isotonic Sodium Chloride Solution; Lactic Acid;

Lactic Acid, Dl-; Lactic Acid, L-; Lactobionic Acid; Lactose; Lactose

Monohydrate; Lactose, Hydrous; Lecithin, Egg; Lecithin, Hydrogenated

Soy; Lidofenin; Mannitol; Mebrofenin; Medronate Disodium; Medronic

Acid; Meglumine; Methionine; Methylboronic Acid; Methylene Blue;

Methylparaben; Monothioglycerol; N-(Carbamoyl-Methoxy Peg-40)-

1,2-Distearoyl-Cephalin Sodium; N,N-Dimethylacetamide; Nioxime;

Nitrogen; Octanoic Acid; Oxidronate Disodium; Oxyquinoline;

Pentasodium Pentetate; Pentetate Calcium Trisodium; Pentetic Acid;

Perflutren; Phenol; Phenol, Liquefied; Phosphatidyl Glycerol, Egg;

Phospholipid, Egg; Phosphoric Acid; Poloxamer 188; Polyethylene

Glycol 300; Polyethylene Glycol 400; Polyethylene Glycol 600;

Polysiloxane; Polysorbate 20; Polysorbate 80; Potassium Bisulfite;

Potassium Chloride; Potassium Hydroxide; Potassium Metabisulfite;

Potassium Phosphate, Dibasic; Potassium Phosphate, Monobasic;

Povidones; Propylene Glycol; Propylparaben; Saccharin Sodium;

Sodium Acetate; Sodium Acetate Anhydrous; Sodium Ascorbate;

Sodium Benzoate; Sodium Bicarbonate; Sodium Bisulfite; Sodium

Carbonate; Sodium Carbonate Decahydrate; Sodium Carbonate

Monohydrate; Sodium Chloride; Sodium Chloride Injection,

Bacteriostatic; Sodium Citrate; Sodium Dithionite; Sodium Gluconate;

Sodium Hydroxide; Sodium Iodide; Sodium Lactate; Sodium

Metabisulfite; Sodium Phosphate; Sodium Phosphate, Dibasic; Sodium

Phosphate, Dibasic, Anhydrous; Sodium Phosphate, Dibasic, Dihydrate;

Sodium Phosphate, Dibasic, Heptahydrate; Sodium Phosphate,

Monobasic, Anhydrous; Sodium Phosphate, Monobasic, Dihydrate;

Sodium Phosphate, Monobasic, Monohydrate; Sodium Pyrophosphate;

Sodium Succinate Hexahydrate; Sodium Sulfite; Sodium Tartrate;

Sodium Thiosulfate; Sodium Thiosulfate Anhydrous; Sodium

Trimetaphosphate; Sorbitol; Sorbitol Solution; Soybean Oil; Stannous

Chloride; Stannous Chloride Anhydrous; Stannous Fluoride; Stannous

Tartrate; Succimer; Succinic Acid; Sucrose; Sulfobutylether .Beta.-

Cyclodextrin; Sulfuric Acid; Tartaric Acid; Tartaric Acid, Dl-; Tert-

Butyl Alcohol; Tetrakis(2-Methoxyisobutylisocyanide)Copper(I)

Tetrafluoroborate; Theophylline; Thimerosal; Threonine; Tin;

Trisodium Citrate Dihydrate; Tromantadine; Tromethamine;

Versetamide

Intravenous Bolus
Sodium Chloride

Intravesical
Alcohol, Dehydrated; Edetate Calcium Disodium; Hydrochloric Acid;

Nitrogen; Polyoxyl 35 Castor Oil; Potassium Phosphate, Monobasic;

Sodium Chloride; Sodium Hydroxide; Sodium Phosphate, Dibasic,

Anhydrous; Sodium Phosphate, Monobasic, Anhydrous

Intravitreal
Calcium Chloride; Carboxymethylcellulose Sodium; Cellulose,

Microcrystalline; Hyaluronate Sodium; Hydrochloric Acid; Magnesium

Chloride; Magnesium Stearate; Polysorbate 80; Polyvinyl Alcohol;

Potassium Chloride; Sodium Acetate; Sodium Bicarbonate; Sodium

Carbonate; Sodium Chloride; Sodium Hydroxide; Sodium Phosphate,

Dibasic, Heptahydrate; Sodium Phosphate, Monobasic, Monohydrate;

Trisodium Citrate Dihydrate

Iontophoresis
Cetylpyridinium Chloride; Citric Acid; Edetate Disodium; Glycerin;

Hydrochloric Acid; Methylparaben; Phenonip; Polacrilin; Polyvinyl

Alcohol; Povidone Hydrogel; Sodium Bisulfite; Sodium Chloride;

Sodium Citrate; Sodium Hydroxide; Sodium Metabisulfite; Sodium

Phosphate, Monobasic

Irrigation
Acetic Acid; Activated Charcoal; Benzoic Acid; Hydrochloric Acid;

Hypromelloses; Methylparaben; Nitrogen; Sodium Bisulfite; Sodium

Citrate; Sodium Hydroxide; Sulfuric Acid

Intravenous-
Acetic Acid; Alcohol; Benzyl Alcohol; Calcium Hydroxide;

Subcutaneous
Chlorobutanol; Glycerin; Hydrochloric Acid; Lactose Monohydrate;

Methylparaben; Nitrogen; Phenol; Phenol, Liquefied; Phosphoric Acid;

Propylparaben; Sodium Acetate; Sodium Carbonate; Sodium Chloride;

Sodium Hydroxide

Intravenous
1,2-Dimyristoyl-Sn-Glycero-3-(Phospho-S-(1-Glycerol)); 1,2-

(Infusion)
Dimyristoyl-Sn-Glycero-3-Phosphocholine; Acetic Acid; Acetic Acid,

Glacial; Activated Charcoal; Alanine; Albumin Human; Alcohol;

Alcohol, Dehydrated; Ammonium Acetate; Anhydrous Citric Acid;

Anhydrous Dextrose; Anhydrous Lactose; Anhydrous Trisodium

Citrate; Arginine; Ascorbic Acid; Aspartic Acid; Benzenesulfonic Acid;

Benzethonium Chloride; Benzoic Acid; Benzyl Alcohol; Brocrinat;

Butylated Hydroxyanisole; Butylated Hydroxytoluene; Carbon Dioxide;

Chlorobutanol; Citric Acid; Citric Acid Monohydrate; Citric Acid,

Hydrous; Cysteine; Cysteine Hydrochloride; Deoxycholic Acid;

Dextrose; Dextrose Solution; Diatrizoic Acid; Diethanolamine;

Dimethyl Sulfoxide; Disodium Sulfosalicylate; Disofenin; Edetate

Calcium Disodium; Edetate Disodium; Edetate Disodium Anhydrous;

Edetate Sodium; Egg Phospholipids; Ethylenediamine; Fructose;

Gelatin; Gentisic Acid Ethanolamide; Glycerin; Glycine; Histidine;

Hydrochloric Acid; Hydrochloric Acid, Diluted; Hydroxide Ion;

Hydroxypropyl-Bcyclodextrin; Isoleucine; Isotonic Sodium Chloride

Solution; Lactic Acid; Lactic Acid, Dl-; Lactobionic Acid; Lactose;

Lactose Monohydrate; Lactose, Hydrous; Leucine; Lysine; Lysine

Acetate; Magnesium Chloride; Maleic Acid; Mannitol; Meglumine;

Metacresol; Metaphosphoric Acid; Methanesulfonic Acid; Methionine;

Methylparaben; Monothioglycerol; N,N-Dimethylacetamide; Nitric

Acid; Nitrogen; Peg Vegetable Oil; Peg-40 Castor Oil; Peg-60 Castor

Oil; Pentetate Calcium Trisodium; Phenol; Phenylalanine;

Phospholipid; Phospholipid, Egg; Phosphoric Acid; Polyethylene

Glycol 300; Polyethylene Glycol 400; Polyoxyl 35 Castor Oil;

Polysorbate 20; Polysorbate 80; Potassium Chloride; Potassium

Hydroxide; Potassium Metabisulfite; Potassium Phosphate, Dibasic;

Potassium Phosphate, Monobasic; Povidones; Proline; Propylene

Glycol; Propylparaben; Saccharin Sodium; Saccharin Sodium

Anhydrous; Serine; Sodium Acetate; Sodium Acetate Anhydrous;

Sodium Benzoate; Sodium Bicarbonate; Sodium Bisulfite; Sodium

Carbonate; Sodium Chlorate; Sodium Chloride; Sodium Cholesteryl

Sulfate; Sodium Citrate; Sodium Desoxycholate; Sodium Dithionite;

Sodium Formaldehyde Sulfoxylate; Sodium Gluconate; Sodium

Hydroxide; Sodium Hypochlorite; Sodium Lactate; Sodium Lactate, L-;

Sodium Metabisulfite; Sodium Phosphate; Sodium Phosphate, Dibasic;

Sodium Phosphate, Dibasic, Anhydrous; Sodium Phosphate, Dibasic,

Dihydrate; Sodium Phosphate, Dibasic, Heptahydrate; Sodium

Phosphate, Monobasic; Sodium Phosphate, Monobasic, Anhydrous;

Sodium Phosphate, Monobasic, Dihydrate; Sodium Phosphate,

Monobasic, Monohydrate; Sodium Sulfite; Sodium Tartrate; Sorbitol;

Sorbitol Solution; Soybean Oil; Stannous Chloride; Stannous Chloride

Anhydrous; Sterile Water For Inhalation; Sucrose; Sulfobutylether

.Beta.-Cyclodextrin; Sulfur Dioxide; Sulfuric Acid; Tartaric Acid;

Tartaric Acid, Dl-; Tert-Butyl Alcohol; Tetrofosmin; Theophylline;

Threonine; Trifluoroacetic Acid; Trisodium Citrate Dihydrate;

Tromethamine; Tryptophan; Tyrosine; Valine

Any Delivery Route
Alcohol; Benzyl Alcohol; Citric Acid Monohydrate; Gelfoam Sponge;

Hydrochloric Acid; Methylparaben; Poly(Dl-Lactic-Co-Glycolic Acid),

(50:50; Poly(Dl-Lactic-Co-Glycolic Acid), Ethyl Ester Terminated,

(50:50; Polyquaternium-7 (70/30 Acrylamide/Dadmac; Propylene

Glycol; Propylparaben; Sodium Chloride; Sodium Citrate; Sodium

Hydroxide; Sodium Lactate; Sodium Phosphate, Monobasic,

Monohydrate

Nasal
Acetic Acid; Alcohol, Dehydrated; Allyl .Alpha.-Ionone; Anhydrous

Dextrose; Anhydrous Trisodium Citrate; Benzalkonium Chloride;

Benzethonium Chloride; Benzyl Alcohol; Butylated Hydroxyanisole;

Butylated Hydroxytoluene; Caffeine; Carbon Dioxide;

Carboxymethylcellulose Sodium; Cellulose, Microcrystalline;

Chlorobutanol; Citric Acid; Citric Acid Monohydrate; Dextrose;

Dichlorodifluoromethane; Dichlorotetrafluoroethane; Edetate

Disodium; Glycerin; Glycerol Ester Of Hydrogenated Rosin;

Hydrochloric Acid; Hypromellose 2910 (15000 Mpa · S);

Methylcelluloses; Methylparaben; Nitrogen; Norflurane; Oleic Acid;

Petrolatum, White; Phenylethyl Alcohol; Polyethylene Glycol 3350;

Polyethylene Glycol 400; Polyoxyl 400 Stearate; Polysorbate 20;

Polysorbate 80; Potassium Phosphate, Monobasic; Potassium Sorbate;

Propylene Glycol; Propylparaben; Sodium Acetate; Sodium Chloride;

Sodium Citrate; Sodium Hydroxide; Sodium Phosphate; Sodium

Phosphate, Dibasic; Sodium Phosphate, Dibasic, Anhydrous; Sodium

Phosphate, Dibasic, Dihydrate; Sodium Phosphate, Dibasic,

Dodecahydrate; Sodium Phosphate, Dibasic, Heptahydrate; Sodium

Phosphate, Monobasic, Anhydrous; Sodium Phosphate, Monobasic,

Dihydrate; Sorbitan Trioleate; Sorbitol; Sorbitol Solution; Sucralose;

Sulfuric Acid; Trichloromonofluoromethane; Trisodium Citrate

Dihydrate

Nerve Block
Acetic Acid; Acetone Sodium Bisulfite; Ascorbic Acid; Benzyl

Alcohol; Calcium Chloride; Carbon Dioxide; Chlorobutanol; Citric

Acid; Citric Acid Monohydrate; Edetate Calcium Disodium; Edetate

Disodium; Hydrochloric Acid; Hydrochloric Acid, Diluted; Lactic Acid;

Methylparaben; Monothioglycerol; Nitrogen; Potassium Chloride;

Potassium Metabisulfite; Potassium Phosphate, Monobasic;

Propylparaben; Sodium Bisulfite; Sodium Carbonate; Sodium Chlorate;

Sodium Chloride; Sodium Citrate; Sodium Hydroxide; Sodium Lactate;

Sodium Lactate, L-; Sodium Metabisulfite; Sodium Phosphate; Sodium

Phosphate, Dibasic, Heptahydrate

Ophthalmic
Acetic Acid; Alcohol; Alcohol, Dehydrated; Alginic Acid; Amerchol-

Cab; Ammonium Hydroxide; Anhydrous Trisodium Citrate; Antipyrine;

Benzalkonium Chloride; Benzethonium Chloride; Benzododecinium

Bromide; Boric Acid; Caffeine; Calcium Chloride; Carbomer 1342;

Carbomer 934p; Carbomer 940; Carbomer Homopolymer Type B (Allyl

Pentaerythritol Crosslinked); Carboxymethylcellulose Sodium; Castor

Oil; Cetyl Alcohol; Chlorobutanol; Chlorobutanol, Anhydrous;

Cholesterol; Citric Acid; Citric Acid Monohydrate; Creatinine;

Diethanolamine; Diethylhexyl Phthalate **See Cder Guidance:

Limiting The Use Of Certain Phthalates As Excipients In Cder-

Regulated Products; Divinylbenzene Styrene Copolymer; Edetate

Disodium; Edetate Disodium Anhydrous; Edetate Sodium; Ethylene

Vinyl Acetate Copolymer; Gellan Gum (Low Acyl); Glycerin; Glyceryl

Stearate; High Density Polyethylene; Hydrocarbon Gel, Plasticized;

Hydrochloric Acid; Hydrochloric Acid, Diluted; Hydroxyethyl

Cellulose; Hydroxypropyl Methylcellulose 2906; Hypromellose 2910

(15000 Mpa · S); Hypromelloses; Jelene; Lanolin; Lanolin Alcohols;

Lanolin Anhydrous; Lanolin Nonionic Derivatives; Lauralkonium

Chloride; Lauroyl Sarcosine; Light Mineral Oil; Magnesium Chloride;

Mannitol; Methylcellulose (4000 Mpa · S); Methylcelluloses;

Methylparaben; Mineral Oil; Nitric Acid; Nitrogen; Nonoxynol-9;

Octoxynol-40; Octylphenol Polymethylene; Petrolatum; Petrolatum,

White; Phenylethyl Alcohol; Phenylmercuric Acetate; Phenylmercuric

Nitrate; Phosphoric Acid; Polidronium Chloride; Poloxamer 188;

Poloxamer 407; Polycarbophil; Polyethylene Glycol 300; Polyethylene

Glycol 400; Polyethylene Glycol 8000; Polyoxyethylene-

Polyoxypropylene 1800; Polyoxyl 35 Castor Oil; Polyoxyl 40

Hydrogenated Castor Oil; Polyoxyl 40 Stearate; Polypropylene Glycol;

Polysorbate 20; Polysorbate 60; Polysorbate 80; Polyvinyl Alcohol;

Potassium Acetate; Potassium Chloride; Potassium Phosphate,

Monobasic; Potassium Sorbate; Povidone K29/32; Povidone K30;

Povidone K90; Povidones; Propylene Glycol; Propylparaben; Soda Ash;

Sodium Acetate; Sodium Bisulfate; Sodium Bisulfite; Sodium Borate;

Sodium Borate Decahydrate; Sodium Carbonate; Sodium Carbonate

Monohydrate; Sodium Chloride; Sodium Citrate; Sodium Hydroxide;

Sodium Metabisulfite; Sodium Nitrate; Sodium Phosphate; Sodium

Phosphate Dihydrate; Sodium Phosphate, Dibasic; Sodium Phosphate,

Dibasic, Anhydrous; Sodium Phosphate, Dibasic, Dihydrate; Sodium

Phosphate, Dibasic, Heptahydrate; Sodium Phosphate, Monobasic;

Sodium Phosphate, Monobasic, Anhydrous; Sodium Phosphate,

Monobasic, Dihydrate; Sodium Phosphate, Monobasic, Monohydrate;

Sodium Sulfate; Sodium Sulfate Anhydrous; Sodium Sulfate

Decahydrate; Sodium Sulfite; Sodium Thiosulfate; Sorbic Acid;

Sorbitan Monolaurate; Sorbitol; Sorbitol Solution; Stabilized Oxychloro

Complex; Sulfuric Acid; Thimerosal; Titanium Dioxide;

Tocophersolan; Trisodium Citrate Dihydrate; Triton 720;

Tromethamine; Tyloxapol; Zinc Chloride

Parenteral
Hydrochloric Acid; Mannitol; Nitrogen; Sodium Acetate; Sodium

Chloride; Sodium Hydroxide

Percutaneous
Duro-Tak 87-2287; Silicone Adhesive 4102

Perfusion, Biliary
Glycerin

Perfusion, Cardiac
Hydrochloric Acid; Sodium Hydroxide

Periarticular
Diatrizoic Acid; Edetate Calcium Disodium; Iodine; Meglumine

Peridural
Citric Acid; Hydrochloric Acid; Methylparaben; Sodium Chloride;

Sodium Hydroxide; Sodium Metabisulfite

Perineural
Hydrochloric Acid; Sodium Chloride; Sodium Hydroxide

Periodontal
Ethylene Vinyl Acetate Copolymer; Hydrochloric Acid; Methyl

Pyrrolidone; Poloxamer 188; Poloxamer 407; Polylactide

Photopheresis
Acetic Acid; Alcohol, Dehydrated; Propylene Glycol; Sodium Acetate;

Sodium Chloride; Sodium Hydroxide

Rectal
Alcohol; Alcohol, Dehydrated; Aluminum Subacetate; Anhydrous

Citric Acid; Aniseed Oil; Ascorbic Acid; Ascorbyl Palmitate; Balsam

Peru; Benzoic Acid; Benzyl Alcohol; Bismuth Subgallate; Butylated

Hydroxyanisole; Butylated Hydroxytoluene; Butylparaben; Caramel;

Carbomer 934; Carbomer 934p; Carboxypolymethylene; Cerasynt-Se;

Cetyl Alcohol; Cocoa Butter; Coconut Oil, Hydrogenated; Coconut

Oil/Palm Kernel Oil Glycerides, Hydrogenated; Cola Nitida Seed

Extract; D&C Yellow No. 10; Dichlorodifluoromethane;

Dichlorotetrafluoroethane; Dimethyldioctadecylammonium Bentonite;

Edetate Calcium Disodium; Edetate Disodium; Edetic Acid; Epilactose;

Ethylenediamine; Fat, Edible; Fat, Hard; Fd&C Blue No. 1; Fd&C

Green No. 3; Fd&C Yellow No. 6; Flavor Fig 827118; Flavor

Raspberry Pfc-8407; Fructose; Galactose; Glycerin; Glyceryl Palmitate;

Glyceryl Stearate; Glyceryl Stearate/Peg Stearate; Glyceryl

Stearate/Peg-40 Stearate; Glycine; Hydrocarbon; Hydrochloric Acid;

Hydrogenated Palm Oil; Hypromelloses; Lactose; Lanolin; Lecithin;

Light Mineral Oil; Magnesium Aluminum Silicate; Magnesium

Aluminum Silicate Hydrate; Methylparaben; Nitrogen; Palm Kernel

Oil; Paraffin; Petrolatum, White; Polyethylene Glycol 1000;

Polyethylene Glycol 1540; Polyethylene Glycol 3350; Polyethylene

Glycol 400; Polyethylene Glycol 4000; Polyethylene Glycol 6000;

Polyethylene Glycol 8000; Polysorbate 60; Polysorbate 80; Potassium

Acetate; Potassium Metabisulfite; Propylene Glycol; Propylparaben;

Saccharin Sodium; Saccharin Sodium Anhydrous; Silicon Dioxide,

Colloidal; Simethicone; Sodium Benzoate; Sodium Carbonate; Sodium

Chloride; Sodium Citrate; Sodium Hydroxide; Sodium Metabisulfite;

Sorbitan Monooleate; Sorbitan Sesquioleate; Sorbitol; Sorbitol Solution;

Starch; Steareth-10; Steareth-40; Sucrose; Tagatose, D-; Tartaric Acid,

Dl-; Trolamine; Tromethamine; Vegetable Oil Glyceride,

Hydrogenated; Vegetable Oil, Hydrogenated; Wax, Emulsifying; White

Wax; Xanthan Gum; Zinc Oxide

Respiratory
Alcohol; Alcohol, Dehydrated; Apaflurane; Benzalkonium Chloride;

(Inhalation)
Calcium Carbonate; Edetate Disodium; Gelatin; Glycine; Hydrochloric

Acid; Lactose Monohydrate; Lysine Monohydrate; Mannitol;

Norflurane; Oleic Acid; Polyethylene Glycol 1000; Povidone K25;

Silicon Dioxide, Colloidal; Sodium Chloride; Sodium Citrate; Sodium

Hydroxide; Sodium Lauryl Sulfate; Sulfuric Acid; Titanium Dioxide;

Tromethamine; Zinc Oxide

Retrobulbar
Hydrochloric Acid; Sodium Hydroxide

Soft Tissue
Acetic Acid; Anhydrous Trisodium Citrate; Benzyl Alcohol;

Carboxymethylcellulose; Carboxymethylcellulose Sodium; Citric Acid;

Creatinine; Edetate Disodium; Hydrochloric Acid; Methylcelluloses;

Methylparaben; Myristyl-.Gamma.-Picolinium Chloride; Phenol;

Phosphoric Acid; Polyethylene Glycol 3350; Polyethylene Glycol 4000;

Polysorbate 80; Propylparaben; Sodium Acetate; Sodium Bisulfite;

Sodium Chloride; Sodium Citrate; Sodium Hydroxide; Sodium

Phosphate; Sodium Phosphate, Dibasic; Sodium Phosphate, Dibasic,

Heptahydrate; Sodium Phosphate, Monobasic; Sodium Phosphate,

Monobasic, Anhydrous; Sodium Sulfite

Spinal
Anhydrous Dextrose; Dextrose; Hydrochloric Acid; Sodium Hydroxide

Subarachnoid
Hydrochloric Acid; Sodium Chloride; Sodium Hydroxide

Subconjunctival
Benzyl Alcohol; Hydrochloric Acid; Sodium Hydroxide

Subcutaneous
Acetic Acid; Acetic Acid, Glacial; Albumin Human; Ammonium

Hydroxide; Ascorbic Acid; Benzyl Alcohol; Calcium Chloride;

Carboxymethylcellulose Sodium; Chlorobutanol; Cresol; Diatrizoic

Acid; Dimethyl Sulfoxide; Edetate Calcium Disodium; Edetate

Disodium; Ethylene Vinyl Acetate Copolymer; Glycerin; Glycine;

Glycine Hydrochloride; Histidine; Hydrochloric Acid; Lactic Acid;

Lactic Acid, L-; Lactose; Magnesium Chloride; Magnesium Stearate;

Mannitol; Metacresol; Methanesulfonic Acid; Methionine; Methyl

Pyrrolidone; Methylparaben; Nitrogen; Phenol; Phenol, Liquefied;

Phosphoric Acid; Poloxamer 188; Polyethylene Glycol 3350;

Polyglactin; Polysorbate 20; Polysorbate 80; Potassium Phosphate,

Dibasic; Potassium Phosphate, Monobasic; Povidone K17; Povidones;

Propylene Glycol; Propylparaben; Protamine Sulfate; Sodium Acetate;

Sodium Acetate Anhydrous; Sodium Bicarbonate; Sodium Bisulfite;

Sodium Chloride; Sodium Citrate; Sodium Hydroxide; Sodium

Metabisulfite; Sodium Phosphate; Sodium Phosphate Dihydrate;

Sodium Phosphate, Dibasic; Sodium Phosphate, Dibasic, Anhydrous;

Sodium Phosphate, Dibasic, Dihydrate; Sodium Phosphate, Dibasic,

Heptahydrate; Sodium Phosphate, Monobasic; Sodium Phosphate,

Monobasic, Anhydrous; Sodium Phosphate, Monobasic, Dihydrate;

Sodium Phosphate, Monobasic, Monohydrate; Sodium Sulfite; Sodium

Thioglycolate; Stearic Acid; Sucrose; Thimerosal; Tromethamine; Zinc;

Zinc Acetate; Zinc Carbonate; Zinc Chloride; Zinc Oxide

Sublingual
Alcohol, Dehydrated

Submucosal
Acetic Acid; Edetic Acid; Mannitol; Nitrogen; Sodium Acetate; Sodium

Chloride; Sodium Hydroxide; Sodium Metabisulfite

Topical
.Alpha.-Terpineol; .Alpha.-Tocopherol; .Alpha.-Tocopherol Acetate,

Dl-; .Alpha.-Tocopherol, Dl-; 1,2,6-Hexanetriol; 1-O-Tolylbiguanide;

2-Ethyl-1,6-Hexanediol; Acetic Acid; Acetone; Acetylated Lanolin

Alcohols; Acrylates Copolymer; Adhesive Tape; Alcohol; Alcohol,

Dehydrated; Alcohol, Denatured; Alcohol, Diluted; Alkyl Ammonium

Sulfonic Acid Betaine; Alkyl Aryl Sodium Sulfonate; Allantoin;

Almond Oil; Aluminum Acetate; Aluminum Chlorhydroxy

Allantoinate; Aluminum Hydroxide; Aluminum Hydroxide-Sucrose,

Hydrated; Aluminum Hydroxide Gel; Aluminum Hydroxide Gel F 500;

Aluminum Hydroxide Gel F 5000; Aluminum Monostearate; Aluminum

Oxide; Aluminum Silicate; Aluminum Starch Octenylsuccinate;

Aluminum Stearate; Aluminum Sulfate Anhydrous; Amerchol C;

Amerchol-Cab; Aminomethylpropanol; Ammonia Solution; Ammonia

Solution, Strong; Ammonium Hydroxide; Ammonium Lauryl Sulfate;

Ammonium Nonoxynol-4 Sulfate; Ammonium Salt Of C-12-C-15

Linear Primary Alcohol Ethoxylate; Ammonyx; Amphoteric-2;

Amphoteric-9; Anhydrous Citric Acid; Anhydrous Trisodium Citrate;

Anoxid Sbn; Antifoam; Apricot Kernel Oil Peg-6 Esters; Aquaphor;

Arlacel; Ascorbic Acid; Ascorbyl Palmitate; Beeswax; Beeswax,

Synthetic; Beheneth-10; Bentonite; Benzalkonium Chloride; Benzoic

Acid; Benzyl Alcohol; Betadex; Boric Acid; Butane; Butyl Alcohol;

Butyl Ester Of Vinyl Methyl Ether/Maleic Anhydride Copolymer

(125000 Mw); Butyl Stearate; Butylated Hydroxyanisole; Butylated

Hydroxytoluene; Butylene Glycol; Butylparaben; C20-40 Pareth-24;

Calcium Chloride; Calcium Hydroxide; Canada Balsam;

Caprylic/Capric Triglyceride; Caprylic/Capric/Stearic Triglyceride;

Captan; Caramel; Carbomer 1342; Carbomer 1382; Carbomer 934;

Carbomer 934p; Carbomer 940; Carbomer 941; Carbomer 980;

Carbomer 981; Carbomer Homopolymer Type B (Allyl Pentaerythritol

Crosslinked); Carbomer Homopolymer Type C (Allyl Pentaerythritol

Crosslinked); Carboxy Vinyl Copolymer; Carboxymethylcellulose;

Carboxymethylcellulose Sodium; Carboxypolymethylene; Carrageenan;

Carrageenan Salt; Castor Oil; Cedar Leaf Oil; Cellulose; Cerasynt-Se;

Ceresin; Ceteareth-12; Ceteareth-15; Ceteareth-30; Cetearyl

Alcohol/Ceteareth-20; Cetearyl Ethylhexanoate; Ceteth-10; Ceteth-2;

Ceteth-20; Ceteth-23; Cetostearyl Alcohol; Cetrimonium Chloride;

Cetyl Alcohol; Cetyl Esters Wax; Cetyl Palmitate; Chlorobutanol;

Chlorocresol; Chloroxylenol; Cholesterol; Choleth-24; Citric Acid;

Citric Acid Monohydrate; Cocamide Ether Sulfate; Cocamine Oxide;

Coco Betaine; Coco Diethanolamide; Coco Monoethanolamide; Cocoa

Butter; Coco-Glycerides; Coconut Oil; Cocoyl Caprylocaprate;

Collagen; Coloring Suspension; Cream Base; Creatinine; Crospovidone;

Cyclomethicone; Cyclomethicone/Dimethicone Copolyol; D&C Red

No. 28; D&C Red No. 33; D&C Red No. 36; D&C Red No. 39; D&C

Yellow No. 10; Decyl Methyl Sulfoxide; Dehydag Wax Sx;

Dehydroacetic Acid; Dehymuls E; Denatonium Benzoate; Dextrin;

Diazolidinyl Urea; Dichlorobenzyl Alcohol; Dichlorodifluoromethane;

Dichlorotetrafluoroethane; Diethanolamine; Diethyl Sebacate;

Diethylene Glycol Monoethyl Ether; Dihydroxyaluminum

Aminoacetate; Diisopropanolamine; Diisopropyl Adipate; Diisopropyl

Dilinoleate; Dimethicone 350; Dimethicone Copolyol; Dimethicone

Medical Fluid 360; Dimethyl Isosorbide; Dimethyl Sulfoxide; Dinoseb

Ammonium Salt; Disodium Cocoamphodiacetate; Disodium Laureth

Sulfosuccinate; Disodium Lauryl Sulfosuccinate; Dmdm Hydantoin;

Docosanol; Docusate Sodium; Edetate Disodium; Edetate Sodium;

Edetic Acid; Entsufon; Entsufon Sodium; Epitetracycline

Hydrochloride; Essence Bouquet 9200; Ethyl Acetate; Ethylcelluloses;

Ethylene Glycol; Ethylenediamine; Ethylenediamine Dihydrochloride;

Ethylhexyl Hydroxystearate; Ethylparaben; Fatty Acid Pentaerythriol

Ester; Fatty Acids; Fatty Alcohol Citrate; Fd&C Blue No. 1; Fd&C Red

No. 4; Fd&C Red No. 40; Fd&C Yellow No. 10 (Delisted); Fd&C

Yellow No. 5; Fd&C Yellow No. 6; Ferric Oxide; Flavor Rhodia

Pharmaceutical No. Rf 451; Formaldehyde; Formaldehyde Solution;

Fractionated Coconut Oil; Fragrance 3949-5; Fragrance 520a; Fragrance

6.007; Fragrance 91-122; Fragrance 9128-Y; Fragrance 93498g;

Fragrance Balsam Pine No. 5124; Fragrance Bouquet 10328; Fragrance

Chemoderm 6401-B; Fragrance Chemoderm 6411; Fragrance Cream

No. 73457; Fragrance Cs-28197; Fragrance Felton 066m; Fragrance

Firmenich 47373; Fragrance Givaudan Ess 9090/1c; Fragrance H-6540;

Fragrance Herbal 10396; Fragrance Nj-1085; Fragrance P O Fl-147;

Fragrance Pa 52805; Fragrance Pera Derm D; Fragrance Rbd-9819;

Fragrance Shaw Mudge U-7776; Fragrance Tf 044078; Fragrance

Ungerer Honeysuckle K 2771; Fragrance Ungerer N5195; Gelatin;

Gluconolactone; Glycerin; Glyceryl Citrate; Glyceryl Isostearate;

Glyceryl Monostearate; Glyceryl Oleate; Glyceryl Oleate/Propylene

Glycol; Glyceryl Palmitate; Glyceryl Ricinoleate; Glyceryl Stearate;

Glyceryl Stearate-Laureth-23; Glyceryl Stearate/Peg-100 Stearate;

Glyceryl Stearate-Stearamidoethyl Diethylamine; Glycol Distearate;

Glycol Stearate; Guar Gum; Hair Conditioner (18n195-1m); Hexylene

Glycol; High Density Polyethylene; Hyaluronate Sodium; Hydrocarbon

Gel, Plasticized; Hydrochloric Acid; Hydrochloric Acid, Diluted;

Hydrogen Peroxide; Hydrogenated Castor Oil; Hydrogenated

Palm/Palm Kernel Oil Peg-6 Esters; Hydroxyethyl Cellulose;

Hydroxymethyl Cellulose; Hydroxyoctacosanyl Hydroxystearate;

Hydroxypropyl Cellulose; Hypromelloses; Imidurea; Irish Moss

Extract; Isobutane; Isoceteth-20; Isooctyl Acrylate; Isopropyl Alcohol;

Isopropyl Isostearate; Isopropyl Myristate; Isopropyl Myristate-

Myristyl Alcohol; Isopropyl Palmitate; Isopropyl Stearate; Isostearic

Acid; Isostearyl Alcohol; Jelene; Kaolin; Kathon Cg; Kathon Cg Ii;

Lactate; Lactic Acid; Lactic Acid, Dl-; Laneth; Lanolin; Lanolin

Alcohol-Mineral Oil; Lanolin Alcohols; Lanolin Anhydrous; Lanolin

Cholesterols; Lanolin, Ethoxylated; Lanolin, Hydrogenated; Lauramine

Oxide; Laurdimonium Hydrolyzed Animal Collagen; Laureth Sulfate;

Laureth-2; Laureth-23; Laureth-4; Lauric Diethanolamide; Lauric

Myristic Diethanolamide; Lauryl Sulfate; Lavandula Angustifolia

Flowering Top; Lecithin; Lecithin Unbleached; Lemon Oil; Light

Mineral Oil; Light Mineral Oil (85 Ssu); Limonene, (+/−)-; Lipocol Sc-

15; Magnesium Aluminum Silicate; Magnesium Aluminum Silicate

Hydrate; Magnesium Nitrate; Magnesium Stearate; Mannitol; Maprofix;

Medical Antiform A-F Emulsion; Menthol; Methyl Gluceth-10; Methyl

Gluceth-20; Methyl Gluceth-20 Sesquistearate; Methyl Glucose

Sesquistearate; Methyl Salicylate; Methyl Stearate; Methylcelluloses;

Methylchloroisothiazolinone; Methylisothiazolinone; Methylparaben;

Microcrystalline Wax; Mineral Oil; Mono And Diglyceride;

Monostearyl Citrate; Multisterol Extract; Myristyl Alcohol; Myristyl

Lactate; Niacinamide; Nitric Acid; Nitrogen; Nonoxynol Iodine;

Nonoxynol-15; Nonoxynol-9; Oatmeal; Octadecene-1/Maleic Acid

Copolymer; Octoxynol-1; Octoxynol-9; Octyldodecanol; Oleic Acid;

Oleth-10/Oleth-5; Oleth-2; Oleth-20; Oleyl Alcohol; Oleyl Oleate;

Olive Oil; Palmitamine Oxide; Parabens; Paraffin; Paraffin, White Soft;

Parfum Creme 45/3; Peanut Oil; Peanut Oil, Refined; Pectin; Peg 6-32

Stearate/Glycol Stearate; Peg-100 Stearate; Peg-12 Glyceryl Laurate;

Peg-120 Glyceryl Stearate; Peg-120 Methyl Glucose Dioleate; Peg-15

Cocamine; Peg-150 Distearate; Peg-2 Stearate; Peg-22 Methyl

Ether/Dodecyl Glycol Copolymer; Peg-25 Propylene Glycol Stearate;

Peg-4 Dilaurate; Peg-4 Laurate; Peg-45/Dodecyl Glycol Copolymer;

Peg-5 Oleate; Peg-50 Stearate; Peg-54 Hydrogenated Castor Oil; Peg-6

Isostearate; Peg-60 Hydrogenated Castor Oil; Peg-7 Methyl Ether; Peg-

75 Lanolin; Peg-8 Laurate; Peg-8 Stearate; Pegoxol 7 Stearate;

Pentaerythritol Cocoate; Peppermint Oil; Perfume 25677; Perfume

Bouquet; Perfume E-1991; Perfume Gd 5604; Perfume Tana 90/42

Scba; Perfume W-1952-1; Petrolatum; Petrolatum, White; Petroleum

Distillates; Phenonip; Phenoxyethanol; Phenylmercuric Acetate;

Phosphoric Acid; Pine Needle Oil (Pinus Sylvestris); Plastibase-50w;

Polidronium Chloride; Poloxamer 124; Poloxamer 181; Poloxamer 182;

Poloxamer 188; Poloxamer 237; Poloxamer 407; Polycarbophil;

Polyethylene Glycol 1000; Polyethylene Glycol 1450; Polyethylene

Glycol 1500; Polyethylene Glycol 1540; Polyethylene Glycol 200;

Polyethylene Glycol 300; Polyethylene Glycol 300-1600; Polyethylene

Glycol 3350; Polyethylene Glycol 400; Polyethylene Glycol 4000;

Polyethylene Glycol 540; Polyethylene Glycol 600; Polyethylene

Glycol 6000; Polyethylene Glycol 8000; Polyethylene Glycol 900;

Polyhydroxyethyl Methacrylate; Polyisobutylene; Polyisobutylene

(1100000 Mw); Polyoxyethylene-Polyoxypropylene 1800;

Polyoxyethylene Alcohols; Polyoxyethylene Fatty Acid Esters;

Polyoxyethylene Propylene; Polyoxyl 20 Cetostearyl Ether; Polyoxyl 40

Hydrogenated Castor Oil; Polyoxyl 40 Stearate; Polyoxyl 400 Stearate;

Polyoxyl 6 And Polyoxyl 32 Palmitostearate; Polyoxyl Distearate;

Polyoxyl Glyceryl Stearate; Polyoxyl Lanolin; Polyoxyl Stearate;

Polypropylene; Polyquaternium-10; Polysorbate 20; Polysorbate 40;

Polysorbate 60; Polysorbate 65; Polysorbate 80; Polyvinyl Alcohol;

Potash; Potassium Citrate; Potassium Hydroxide; Potassium Soap;

Potassium Sorbate; Povidone Acrylate Copolymer; Povidone Hydrogel;

Povidone K90; Povidone/Eicosene Copolymer; Povidones; Ppg-

12/Smdi Copolymer; Ppg-15 Stearyl Ether; Ppg-20 Methyl Glucose

Ether Distearate; Ppg-26 Oleate; Product Wat; Promulgen D;

Promulgen G; Propane; Propellant A-46; Propyl Gallate; Propylene

Carbonate; Propylene Glycol; Propylene Glycol Diacetate; Propylene

Glycol Dicaprylate; Propylene Glycol Monopalmitostearate; Propylene

Glycol Palmitostearate; Propylene Glycol Ricinoleate; Propylene

Glycol/Diazolidinyl Urea/Methylparaben/Propylparben; Propylparaben;

Protein Hydrolysate; Quaternium-15; Quaternium-15 Cis-Form;

Quaternium-52; Saccharin; Saccharin Sodium; Safflower Oil; Sd

Alcohol 3a; Sd Alcohol 40; Sd Alcohol 40-2; Sd Alcohol 40b; Sepineo

P 600; Shea Butter; Silicon; Silicon Dioxide; Silicone; Silicone

Adhesive Bio-Psa Q7-4201; Silicone Adhesive Bio-Psa Q7-4301;

Silicone Emulsion; Simethicone; Simethicone Emulsion; Sipon Ls

20 np; Sodium Acetate; Sodium Acetate Anhydrous; Sodium Alkyl

Sulfate; Sodium Benzoate; Sodium Bisulfite; Sodium Borate; Sodium

Cetostearyl Sulfate; Sodium Chloride; Sodium Citrate; Sodium Cocoyl

Sarcosinate; Sodium Dodecylbenzenesulfonate; Sodium Formaldehyde

Sulfoxylate; Sodium Hydroxide; Sodium Iodide; Sodium Lactate;

Sodium Laureth-2 Sulfate; Sodium Laureth-3 Sulfate; Sodium Laureth-5

Sulfate; Sodium Lauroyl Sarcosinate; Sodium Lauryl Sulfate; Sodium

Lauryl Sulfoacetate; Sodium Metabisulfite; Sodium Phosphate; Sodium

Phosphate, Dibasic; Sodium Phosphate, Dibasic, Anhydrous; Sodium

Phosphate, Dibasic, Dihydrate; Sodium Phosphate, Dibasic,

Heptahydrate; Sodium Phosphate, Monobasic; Sodium Phosphate,

Monobasic, Anhydrous; Sodium Phosphate, Monobasic, Dihydrate;

Sodium Phosphate, Monobasic, Monohydrate; Sodium Polyacrylate

(2500000 Mw); Sodium Pyrrolidone Carboxylate; Sodium Sulfite;

Sodium Sulfosuccinated Undecyclenic Monoalkylolamide; Sodium

Thiosulfate; Sodium Xylenesulfonate; Somay 44; Sorbic Acid;

Sorbitan; Sorbitan Isostearate; Sorbitan Monolaurate; Sorbitan

Monooleate; Sorbitan Monopalmitate; Sorbitan Monostearate; Sorbitan

Sesquioleate; Sorbitan Tristearate; Sorbitol; Sorbitol Solution; Soybean

Flour; Soybean Oil; Spearmint Oil; Spermaceti; Squalane; Starch;

Stearalkonium Chloride; Stearamidoethyl Diethylamine; Steareth-10;

Steareth-100; Steareth-2; Steareth-20; Steareth-21; Steareth-40; Stearic

Acid; Stearic Diethanolamide; Stearoxytrimethylsilane; Steartrimonium

Hydrolyzed Animal Collagen; Stearyl Alcohol;

Styrene/Isoprene/Styrene Block Copolymer; Sucrose; Sucrose

Distearate; Sucrose Polyesters; Sulfacetamide Sodium; Sulfuric Acid;

Surfactol Qs; Talc; Tall Oil; Tallow Glycerides; Tartaric Acid; Tenox;

Tenox-2; Tert-Butyl Alcohol; Tert-Butyl Hydroperoxide; Thimerosal;

Titanium Dioxide; Tocopherol; Tocophersolan;

Trichloromonofluoromethane; Trideceth-10; Triethanolamine Lauryl

Sulfate; Triglycerides, Medium Chain; Trihydroxystearin; Trilaneth-4

Phosphate; Trilaureth-4 Phosphate; Trisodium Citrate Dihydrate;

Trisodium Hedta; Triton X-200; Trolamine; Tromethamine; Tyloxapol;

Undecylenic Acid; Vegetable Oil; Vegetable Oil, Hydrogenated;

Viscarin; Vitamin E; Wax, Emulsifying; Wecobee Fs; White Wax;

Xanthan Gum; Zinc Acetate

Transdermal
Acrylates Copolymer; Acrylic Acid-Isooctyl Acrylate Copolymer;

Acrylic Adhesive 788; Adcote 72a103; Aerotex Resin 3730; Alcohol;

Alcohol, Dehydrated; Aluminum Polyester; Bentonite; Butylated

Hydroxytoluene; Butylene Glycol; Butyric Acid; Caprylic/Capric

Triglyceride; Carbomer 1342; Carbomer 940; Carbomer 980;

Carrageenan; Cetylpyridinium Chloride; Citric Acid; Crospovidone;

Daubert 1-5 Pestr (Matte) 164z; Diethylene Glycol Monoethyl Ether;

Diethylhexyl Phthalate **See Cder Guidance: Limiting The Use Of

Certain Phthalates As Excipients In Cder-Regulated Products;

Dimethicone Copolyol; Dimethicone Mdx4-4210; Dimethicone Medical

Fluid 360; Dimethylaminoethyl Methacrylate-Butyl Methacrylate-

Methyl Methacrylate Copolymer; Dipropylene Glycol; Duro-Tak 280-

2516; Duro-Tak 387-2516; Duro-Tak 80-1196; Duro-Tak 87-2070;

Duro-Tak 87-2194; Duro-Tak 87-2287; Duro-Tak 87-2296; Duro-Tak

87-2888; Duro-Tak 87-2979; Edetate Disodium; Ethyl Acetate; Ethyl

Oleate; Ethylcelluloses; Ethylene Vinyl Acetate Copolymer; Ethylene-

Propylene Copolymer; Fatty Acid Esters; Gelva 737; Glycerin; Glyceryl

Laurate; Glyceryl Oleate; Heptane; High Density Polyethylene;

Hydrochloric Acid; Hydrogenated Polybutene 635-690; Hydroxyethyl

Cellulose; Hydroxypropyl Cellulose; Isopropyl Myristate; Isopropyl

Palmitate; Lactose; Lanolin Anhydrous; Lauryl Lactate; Lecithin;

Levulinic Acid; Light Mineral Oil; Medical Adhesive Modified S-15;

Methyl Alcohol; Methyl Laurate; Mineral Oil; Nitrogen; Octisalate;

Octyldodecanol; Oleic Acid; Oleyl Alcohol; Oleyl Oleate;

Pentadecalactone; Petrolatum, White; Polacrilin; Polyacrylic Acid

(250000 Mw); Polybutene (1400 Mw); Polyester; Polyester Polyamine

Copolymer; Polyester Rayon; Polyethylene Terephthalates;

Polyisobutylene; Polyisobutylene (1100000 Mw); Polyisobutylene

(35000 Mw); Polyisobutylene 178-236; Polyisobutylene 241-294;

Polyisobutylene 35-39; Polyisobutylene Low Molecular Weight;

Polyisobutylene Medium Molecular Weight;

Polyisobutylene/Polybutene Adhesive; Polypropylene; Polyvinyl

Acetate; Polyvinyl Alcohol; Polyvinyl Chloride; Polyvinyl Chloride-

Polyvinyl Acetate Copolymer; Polyvinylpyridine; Povidone K29/32;

Povidones; Propylene Glycol; Propylene Glycol Monolaurate; Ra-2397;

Ra-3011; Silicon; Silicon Dioxide, Colloidal; Silicone; Silicone

Adhesive 4102; Silicone Adhesive 4502; Silicone Adhesive Bio-Psa

Q7-4201; Silicone Adhesive Bio-Psa Q7-4301; Silicone/Polyester Film

Strip; Sodium Chloride; Sodium Citrate; Sodium Hydroxide; Sorbitan

Monooleate; Stearalkonium Hectorite/Propylene Carbonate; Titanium

Dioxide; Triacetin; Trolamine; Tromethamine; Union 76 Amsco-Res

6038; Viscose/Cotton

Transmucosal
Magnesium Stearate; Mannitol; Potassium Bicarbonate; Sodium Starch

Glycolate

Ureteral
Benzyl Alcohol; Diatrizoic Acid; Edetate Calcium Disodium; Edetate

Disodium; Hydrochloric Acid; Meglumine; Methylparaben;

Propylparaben; Sodium Citrate; Sodium Hydroxide

Urethral
Diatrizoic Acid; Edetate Calcium Disodium; Edetate Disodium;

Hydrochloric Acid; Meglumine; Methylparaben; Polyethylene Glycol

1450; Propylparaben; Sodium Hydroxide; Sodium Phosphate, Dibasic,

Heptahydrate; Tromethamine

Vaginal
Adipic Acid; Alcohol, Denatured; Allantoin; Anhydrous Lactose;

Apricot Kernel Oil Peg-6 Esters; Barium Sulfate; Beeswax; Bentonite;

Benzoic Acid; Benzyl Alcohol; Butylated Hydroxyanisole; Butylated

Hydroxytoluene; Calcium Lactate; Carbomer 934; Carbomer 934p;

Cellulose, Microcrystalline; Ceteth-20; Cetostearyl Alcohol; Cetyl

Alcohol; Cetyl Esters Wax; Cetyl Palmitate; Cholesterol; Choleth;

Citric Acid; Citric Acid Monohydrate; Coconut Oil/Palm Kernel Oil

Glycerides, Hydrogenated; Crospovidone; Edetate Disodium;

Ethylcelluloses; Ethylene-Vinyl Acetate Copolymer (28% Vinyl

Acetate); Ethylene-Vinyl Acetate Copolymer (9% Vinylacetate); Fatty

Alcohols; Fd&C Yellow No. 5; Gelatin; Glutamic Acid, Dl-; Glycerin;

Glyceryl Isostearate; Glyceryl Monostearate; Glyceryl Stearate; Guar

Gum; High Density Polyethylene; Hydrogel Polymer; Hydrogenated

Palm Oil; Hypromellose 2208 (15000 Mpa · S); Hypromelloses;

Isopropyl Myristate; Lactic Acid; Lactic Acid, Dl-; Lactose; Lactose

Monohydrate; Lactose, Hydrous; Lanolin; Lanolin Anhydrous;

Lecithin; Lecithin, Soybean; Light Mineral Oil; Magnesium Aluminum

Silicate; Magnesium Aluminum Silicate Hydrate; Magnesium Stearate;

Methyl Stearate; Methylparaben; Microcrystalline Wax; Mineral Oil;

Nitric Acid; Octyldodecanol; Peanut Oil; Peg 6-32 Stearate/Glycol

Stearate; Peg-100 Stearate; Peg-120 Glyceryl Stearate; Peg-2 Stearate;

Peg-5 Oleate; Pegoxol 7 Stearate; Petrolatum, White; Phenylmercuric

Acetate; Phospholipon 90 g; Phosphoric Acid; Piperazine Hexahydrate;

Poly(Dimethylsiloxane/Methylvinylsiloxane/Methylhydrogensiloxane)

Dimethylvinyl Or Dimethylhydroxy Or Trimethyl Endblocked;

Polycarbophil; Polyester; Polyethylene Glycol 1000; Polyethylene

Glycol 3350; Polyethylene Glycol 400; Polyethylene Glycol 4000;

Polyethylene Glycol 6000; Polyethylene Glycol 8000; Polyglyceryl-3

Oleate; Polyglyceryl-4 Oleate; Polyoxyl Palmitate; Polysorbate 20;

Polysorbate 60; Polysorbate 80; Polyurethane; Potassium Alum;

Potassium Hydroxide; Povidone K29/32; Povidones; Promulgen D;

Propylene Glycol; Propylene Glycol Monopalmitostearate;

Propylparaben; Quaternium-15 Cis-Form; Silicon Dioxide; Silicon

Dioxide, Colloidal; Silicone; Sodium Bicarbonate; Sodium Citrate;

Sodium Hydroxide; Sodium Lauryl Sulfate; Sodium Metabisulfite;

Sodium Phosphate, Dibasic, Anhydrous; Sodium Phosphate,

Monobasic, Anhydrous; Sorbic Acid; Sorbitan Monostearate; Sorbitol;

Sorbitol Solution; Spermaceti; Stannous 2-Ethylhexanoate; Starch;

Starch 1500, Pregelatinized; Starch, Corn; Stearamidoethyl

Diethylamine; Stearic Acid; Stearyl Alcohol; Tartaric Acid, Dl-; Tert-

Butylhydroquinone; Tetrapropyl Orthosilicate; Trolamine; Urea;

Vegetable Oil, Hydrogenated; Wecobee Fs; White Ceresin Wax; White

Wax

Non-limiting routes of administration for the NAVs of the present invention are described below.

Parenteral and Injectable Administration

Liquid dosage forms for parenteral administration include, but are not limited to, pharmaceutically acceptable emulsions, microemulsions, solutions, suspensions, syrups, and/or elixirs. In addition to active ingredients, liquid dosage forms may comprise inert diluents commonly used in the art such as, for example, water or other solvents, solubilizing agents and emulsifiers such as ethyl alcohol, isopropyl alcohol, ethyl carbonate, ethyl acetate, benzyl alcohol, benzyl benzoate, propylene glycol, 1,3-butylene glycol, dimethylformamide, oils (in particular, cottonseed, groundnut, corn, germ, olive, castor, and sesame oils), glycerol, tetrahydrofurfuryl alcohol, polyethylene glycols and fatty acid esters of sorbitan, and mixtures thereof. Besides inert diluents, oral compositions can include adjuvants such as wetting agents, emulsifying and suspending agents, sweetening, flavoring, and/or perfuming agents. In certain embodiments for parenteral administration, compositions are mixed with solubilizing agents such as CREMOPHOR*, alcohols, oils, modified oils, glycols, polysorbates, cyclodextrins, polymers, and/or combinations thereof.

A pharmaceutical composition for parenteral administration may comprise at least one inactive ingredient. Any or none of the inactive ingredients used may have been approved by the US Food and Drug Administration (FDA). A non-exhaustive list of inactive ingredients for use in pharmaceutical compositions for parenteral administration includes hydrochloric acid, mannitol, nitrogen, sodium acetate, sodium chloride and sodium hydroxide.

Injectable preparations, for example, sterile injectable aqueous or oleaginous suspensions may be formulated according to the known art using suitable dispersing agents, wetting agents, and/or suspending agents. Sterile injectable preparations may be sterile injectable solutions, suspensions, and/or emulsions in nontoxic parenterally acceptable diluents and/or solvents, for example, as a solution in 1,3-butanediol. Among the acceptable vehicles and solvents that may be employed are water, Ringer's solution, U.S.P., and isotonic sodium chloride solution. Sterile, fixed oils are conventionally employed as a solvent or suspending medium. For this purpose any bland fixed oil can be employed including synthetic mono- or diglycerides. Fatty acids such as oleic acid can be used in the preparation of injectables. The sterile formulation may also comprise adjuvants such as local anesthetics, preservatives and buffering agents.

Injectable formulations can be sterilized, for example, by filtration through a bacterial-retaining filter, and/or by incorporating sterilizing agents in the form of sterile solid compositions which can be dissolved or dispersed in sterile water or other sterile injectable medium prior to use.

Injectable formulations may be for direct injection into a region of a tissue, organ and/or subject. As a non-limiting example, a tissue, organ and/or subject may be directly injected a formulation by intramyocardial injection into the ischemic region. (See e.g., Zangi et al. Nature Biotechnology 2013; the contents of which are herein incorporated by reference in its entirety).

In order to prolong the effect of an active ingredient, it is often desirable to slow the absorption of the active ingredient from subcutaneous or intramuscular injection. This may be accomplished by the use of a liquid suspension of crystalline or amorphous material with poor water solubility. The rate of absorption of the drug then depends upon its rate of dissolution which, in turn, may depend upon crystal size and crystalline form. Alternatively, delayed absorption of a parenterally administered drug form is accomplished by dissolving or suspending the drug in an oil vehicle. Injectable depot forms are made by forming microencapsule matrices of the drug in biodegradable polymers such as polylactide-polyglycolide. Depending upon the ratio of drug to polymer and the nature of the particular polymer employed, the rate of drug release can be controlled. Examples of other biodegradable polymers include poly(orthoesters) and poly(anhydrides). Depot injectable formulations are prepared by entrapping the drug in liposomes or microemulsions which are compatible with body tissues.

Rectal and Vaginal Administration

Compositions for rectal or vaginal (e.g., transvaginal) administration are typically suppositories which can be prepared by mixing compositions with suitable non-irritating excipients such as cocoa butter, polyethylene glycol or a suppository wax which are solid at ambient temperature but liquid at body temperature and therefore melt in the rectum or vaginal cavity and release the active ingredient.

As a non-limiting example, the formulations for rectal and/or vaginal administration may be prepared by mixing the drug with a suitable non-irritating excipient that is solid at ordinary temperatures but liquid at the rectal temperature and will therefore melt in the rectum and/or vagina to release the drug. Such materials include cocoa butter and polyethylene glycols.

A pharmaceutical composition for rectal administration may comprise at least one inactive ingredient. Any or none of the inactive ingredients used may have been approved by the US Food and Drug Administration (FDA). A non-exhaustive list of inactive ingredients for use in pharmaceutical compositions for rectal administration includes alcohol, alcohol, dehydrated, aluminum subacetate, anhydrous citric acid, aniseed oil, ascorbic acid, ascorbyl palmitate, balsam peru, benzoic acid, benzyl alcohol, bismuth subgallate, butylated hydroxyanisole, butylated hydroxytoluene, butylparaben, caramel, carbomer 934, carbomer 934p, carboxypolymethylene, cerasynt-se, cetyl alcohol, cocoa butter, coconut oil, hydrogenated, coconut oil/palm kernel oil glycerides, hydrogenated, cola nitida seed extract, d&c yellow no. 10, dichlorodifluoromethane, dichlorotetrafluoroethane, dimethyldioctadecylammonium bentonite, edetate calcium disodium, edetate disodium, edetic acid, epilactose, ethylenediamine, fat, edible, fat, hard, fd&c blue no. 1, fd&c green no. 3, fd&c yellow no. 6, flavor fig 827118, flavor raspberry pfc-8407, fructose, galactose, glycerin, glyceryl palmitate, glyceryl stearate, glyceryl stearate/peg stearate, glyceryl stearate/peg-40 stearate, glycine, hydrocarbon, hydrochloric acid, hydrogenated palm oil, hypromelloses, lactose, lanolin, lecithin, light mineral oil, magnesium aluminum silicate, magnesium aluminum silicate hydrate, methylparaben, nitrogen, palm kernel oil, paraffin, petrolatum, white, polyethylene glycol 1000, polyethylene glycol 1540, polyethylene glycol 3350, polyethylene glycol 400, polyethylene glycol 4000, polyethylene glycol 6000, polyethylene glycol 8000, polysorbate 60, polysorbate 80, potassium acetate, potassium metabisultite, propylene glycol, propylparaben, saccharin sodium, saccharin sodium anhydrous, silicon dioxide, colloidal, simethicone, sodium benzoate, sodium carbonate, sodium chloride, sodium citrate, sodium hydroxide, sodium metabisulfite, sorbitan monooleate, sorbitan sesquioleate, sorbitol, sorbitol solution, starch, steareth-10, steareth-40, sucrose, tagatose, d-, tartaric acid, dl-, trolamine, tromethamine, vegetable oil glyceride, hydrogenated, vegetable oil, hydrogenated, wax, emulsifying, white wax, xanthan gum and zinc oxide.

A pharmaceutical composition for vaginal administration may comprise at least one inactive ingredient. Any or none of the inactive ingredients used may have been approved by the US Food and Drug Administration (FDA). A non-exhaustive list of inactive ingredients for use in pharmaceutical compositions for vaginal administration includes adipic acid, alcohol, denatured, allantoin, anhydrous lactose, apricot kernel oil peg-6 esters, barium sulfate, beeswax, bentonite, benzoic acid, benzyl alcohol, butylated hydroxyanisole, butylated hydroxytoluene, calcium lactate, carbomer 934, carbomer 934p, cellulose, microcrystalline, ceteth-20, cetostearyl alcohol, cetyl alcohol, cetyl esters wax, cetyl palmitate, cholesterol, choleth, citric acid, citric acid monohydrate, coconut oil/palm kernel oil glycerides, hydrogenated, crospovidone, edetate disodium, ethylcelluloses, ethylene-vinyl acetate copolymer (28% vinyl acetate), ethylene-vinyl acetate copolymer (9% vinylacetate), fatty alcohols, fd&c yellow no. 5, gelatin, glutamic acid, dl-, glycerin, glyceryl isostearate, glyceryl monostearate, glyceryl stearate, guar gum, high density polyethylene, hydrogel polymer, hydrogenated palm oil, hypromellose 2208 (15000 mpa·s), hypromelloses, isopropyl myristate, lactic acid, lactic acid, dl-, lactose, lactose monohydrate, lactose, hydrous, lanolin, lanolin anhydrous, lecithin, lecithin, soybean, light mineral oil, magnesium aluminum silicate, magnesium aluminum silicate hydrate, magnesium stearate, methyl stearate, methylparaben, microcrystalline wax, mineral oil, nitric acid, octyldodecanol, peanut oil, peg 6-32 stearate/glycol stearate, peg-100 stearate, peg-120 glyceryl stearate, peg-2 stearate, peg-5 oleate, pegoxol 7 stearate, petrolatum, white, phenylmercuric acetate, phospholipon 90 g, phosphoric acid, piperazine hexahydrate, poly(dimethylsiloxane/methylvinylsiloxanelmethylhydrogensiloxane) dimethylvinyl or dimethylhydroxy or trimethyl endblocked, polycarbophil, polyester, polyethylene glycol 1000, polyethylene glycol 3350, polyethylene glycol 400, polyethylene glycol 4000, polyethylene glycol 6000, polyethylene glycol 8000, polyglyceryl-3 oleate, polyglyceryl-4 oleate, polyoxyl palmitate, polysorbate 20, polysorbate 60, polysorbate 80, polyurethane, potassium alum, potassium hydroxide, povidone k29/32, povidones, promulgen d, propylene glycol, propylene glycol monopalmitostearate, propylparaben, quaternium-15 cis-form, silicon dioxide, silicon dioxide, colloidal, silicone, sodium bicarbonate, sodium citrate, sodium hydroxide, sodium lauryl sulfate, sodium metabisulfite, sodium phosphate, dibasic, anhydrous, sodium phosphate, monobasic, anhydrous, sorbic acid, sorbitan monostearate, sorbitol, sorbitol solution, spermaceti, stannous 2-ethylhexanoate, starch, starch 1500, pregelatinized, starch, corn, stearamidoethyl diethylamine, stearic acid, stearyl alcohol, tartaric acid, dl-, tert-butylhydroquinone, tetrapropyl orthosilicate, trolamine, urea, vegetable oil, hydrogenated, wecobee fs, white ceresin wax and white wax.

Oral Administration

Liquid dosage forms for oral administration include, but are not limited to, pharmaceutically acceptable emulsions, microemulsions, solutions, suspensions, syrups, and/or elixirs. In addition to active ingredients, liquid dosage forms may comprise inert diluents and/or excipients commonly used in the art such as, for example, water or other solvents, solubilizing agents and emulsifiers such as ethyl alcohol, isopropyl alcohol, ethyl carbonate, ethyl acetate, benzyl alcohol, benzyl benzoate, propylene glycol, 1,3-butylene glycol, dimethylformamide, oils (in particular, cottonseed, groundnut, corn, germ, olive, castor, and sesame oils), glycerol, tetrahydrofurfuryl alcohol, polyethylene glycols and fatty acid esters of sorbitan, and mixtures thereof. Besides inert diluents, oral compositions can include adjuvants such as wetting agents, emulsifying and suspending agents, sweetening, flavoring, and/or perfuming agents. In certain embodiments for parenteral administration, compositions are mixed with solubilizing agents such as CREMOPHOR*, alcohols, oils, modified oils, glycols, polysorbates, cyclodextrins, polymers, and/or combinations thereof.

Syrups and elixirs can be formulated with sweetening agents, for example glycerol, propylene glycol, sorbitol, glucose or sucrose. Such formulations can also contain a demulcent, a preservative and flavoring and coloring agents. The pharmaceutical compositions can be in the form of a sterile injectable aqueous or oleaginous suspension. This suspension can be formulated according to the known art using those suitable dispersing or wetting agents and suspending agents that have been mentioned above. The sterile injectable preparation can also be a sterile injectable solution or suspension in a non-toxic parentally acceptable diluent or solvent, for example as a solution in 1,3-butanediol. Among the acceptable vehicles and solvents that can be employed are water, Ringer's solution and isotonic sodium chloride solution. In addition, sterile, fixed oils are conventionally employed as a solvent or suspending medium. For this purpose, any bland fixed oil can be employed including synthetic mono- or diglycerides. In addition, fatty acids such as oleic acid find use in the preparation of injectables.

Suspensions for oral dosage may contain the active materials in a mixture with excipients suitable for the manufacture of aqueous suspensions. Such excipients may be suspending agents, as a non-limiting example the suspending agents may be sodium carboxymethylcellulose, methylcellulose, hydropropyl-methylcellulose, sodium alginate, polyvinylpyrrolidone, gum tragacanth and gum acacia; dispersing or wetting agents can be a naturally-occurring phosphatide, for example, lecithin, or condensation products of an alkylene oxide with fatty acids, for example polyoxyethylene stearate; or condensation products of ethylene oxide with long chain aliphatic alcohols, for example heptadecaethyleneoxycetanol, or condensation products of ethylene oxide with partial esters derived from fatty acids and a hexitol such as polyoxyethylene sorbitol monooleate, or condensation products of ethylene oxide with partial esters derived from fatty acids and hexitol anhydrides, for example polyethylene sorbitan monooleate. The aqueous suspensions may also contain one or more preservatives, for example ethyl, or n-propyl p-hydroxybenzoate, one or more coloring agents, one or more flavoring agents, and one or more sweetening agents, such as sucrose or saccharin.

Oily suspensions for oral dosage can be formulated by suspending the active ingredients in a vegetable oil, for example arachis oil, olive oil, sesame oil or coconut oil, or in a mineral oil such as liquid paraffin. The oily suspensions can contain a thickening agent, for example beeswax, hard paraffin or cetyl alcohol. Sweetening agents and flavoring agents can be added to provide palatable oral preparations. These compositions can be preserved by the addition of an anti-oxidant such as ascorbic acid

The oral dosage may also be in the form of oil-in-water emulsions. The oily phase can be a vegetable oil or a mineral oil or mixtures of these. Suitable emulsifying agents can be naturally-occurring gums, for example gum acacia or gum tragacanth, naturally-occurring phosphatides, for example soy bean, lecithin, and esters or partial esters derived from fatty acids and hexitol, anhydrides, for example sorbitan monooleate, and condensation products of the said partial esters with ethylene oxide, for example polyoxyethylene sorbitan monooleate. The emulsions may also contain sweetening and flavoring agents.

Solid dosage forms for oral administration include capsules, tablets, pills, powders, and granules. In such solid dosage forms, an active ingredient is mixed with at least one inert, pharmaceutically acceptable excipient such as sodium citrate or dicalcium phosphate and/or fillers or extenders (e.g. starches, lactose, sucrose, glucose, mannitol, and silicic acid), binders (e.g. carboxymethylcellulose, alginates, gelatin, polyvinylpyrrolidinone, sucrose, and acacia), humectants (e.g. glycerol), disintegrating agents (e.g. agar, calcium carbonate, potato or tapioca starch, alginic acid, certain silicates, and sodium carbonate), solution retarding agents (e.g. paraffin), absorption accelerators (e.g. quaternary ammonium compounds), wetting agents (e.g. cetyl alcohol and glycerol monostearate), absorbents (e.g. kaolin and bentonite clay), and lubricants (e.g. talc, calcium stearate, magnesium stearate, solid polyethylene glycols, sodium lauryl sulfate), and mixtures thereof. In the case of capsules, tablets and pills, the dosage form may comprise buffering agents. The solid dosage forms may also dissolve once they come in contact with liquid such as, but not limited to, salvia and bile.

Compositions intended for oral use can be prepared according to any method known to the art for the manufacture of pharmaceutical compositions and such compositions can contain one or more such sweetening agents, flavoring agents, coloring agents or preservative agents in order to provide pharmaceutically elegant and palatable preparations.

Solid dosage forms may be uncoated or they can be coated by known techniques. In some cases such coatings can be prepared by known techniques to delay disintegration and absorption in the gastrointestinal tract and thereby provide a sustained action over a longer period. For example, a time delay material such as glyceryl monosterate or glyceryl distearate can be employed.

Formulations for oral use can also be presented as hard gelatin capsules wherein the active ingredient is mixed with an inert solid diluent, for example, calcium carbonate, calcium phosphate or kaolin, or as soft gelatin capsules wherein the active ingredient is mixed with water or an oil medium, for example peanut oil, liquid paraffin or olive oil.

Dosage forms for oral delivery may also be chewable or may be suckable (e.g., lozenge form). The chewable dosages forms may be sustained release formulations such as, but not limited to, the sustained release compositions described in International Publication No WO2013082470 and US Publication No US20130142876, each of which is herein incorporated by reference in its entirety. The chewable dosage forms may comprise amphipathic lipids such as, but not limited to, those described in International Publication No WO2013082470 and US Publication No US20130142876, each of which is herein incorporated by reference in its entirety.

Topical or Transdermal Administration

As described herein, compositions containing the NAVs of the invention may be formulated for administration transdermally. The skin may be an ideal target site for delivery as it is readily accessible. Gene expression may be restricted not only to the skin, potentially avoiding nonspecific toxicity, but also to specific layers and cell types within the skin.

The site of cutaneous expression of the delivered compositions will depend on the route of nucleic acid delivery. Two routes are commonly considered to deliver NAVs to the skin: (ii) intradermal injection; and (iii) systemic delivery (e.g. for treatment of dermatologic diseases that affect both cutaneous and extracutaneous regions). NAVs can be delivered to the skin by several different approaches known in the art. After delivery of the nucleic acid, gene products have been detected in a number of different skin cell types, including, but not limited to, basal keratinocytes, sebaceous gland cells, dermal fibroblasts and dermal macrophages.

In one embodiment, the invention provides for the NAV compositions to be delivered in more than one injection.

In one embodiment, before transdermal administration at least one area of tissue, such as skin, may be subjected to a device and/or solution which may increase permeability. In one embodiment, the tissue may be subjected to an abrasion device to increase the permeability of the skin (see U.S. Patent Publication No. 20080275468, herein incorporated by reference in its entirety). In another embodiment, the tissue may be subjected to an ultrasound enhancement device. An ultrasound enhancement device may include, but is not limited to, the devices described in U.S. Publication No. 20040236268 and U.S. Pat. Nos. 6,491,657 and 6,234,990; each of which are herein incorporated by reference in their entireties. Methods of enhancing the permeability of tissue are described in U.S. Publication Nos. 20040171980 and 20040236268 and U.S. Pat. No. 6,190,315; each of which are herein incorporated by reference in their entireties.

In one embodiment, a device may be used to increase permeability of tissue before delivering formulations of modified mRNA described herein. The permeability of skin may be measured by methods known in the art and/or described in U.S. Pat. No. 6,190,315, herein incorporated by reference in its entirety. As a non-limiting example, a modified mRNA formulation may be delivered by the drug delivery methods described in U.S. Pat. No. 6,190,315, herein incorporated by reference in its entirety.

In another non-limiting example tissue may be treated with a eutectic mixture of local anesthetics (EMLA) cream before, during and/or after the tissue may be subjected to a device which may increase permeability. Katz et al. (Anesth Analg (2004); 98:371-76; herein incorporated by reference in its entirety) showed that using the EMLA cream in combination with a low energy, an onset of superficial cutaneous analgesia was seen as fast as 5 minutes after a pretreatment with a low energy ultrasound.

In one embodiment, enhancers may be applied to the tissue before, during, and/or after the tissue has been treated to increase permeability. Enhancers include, but are not limited to, transport enhancers, physical enhancers, and cavitation enhancers. Non-limiting examples of enhancers are described in U.S. Pat. No. 6,190,315, herein incorporated by reference in its entirety.

In one embodiment, a device may be used to increase permeability of tissue before delivering formulations of NAVs described herein, which may further contain a substance that invokes an immune response. In another non-limiting example, a formulation containing a substance to invoke an immune response may be delivered by the methods described in U.S. Publication Nos. 20040171980 and 20040236268; each of which are herein incorporated by reference in their entireties.

Dosage forms for transdermal administration of a composition may include ointments, pastes, creams, lotions, gels, powders, solutions, sprays, inhalants and/or patches. Generally, an active ingredient is admixed under sterile conditions with a pharmaceutically acceptable excipient and/or any needed preservatives and/or buffers as may be required.

Additionally, the present invention contemplates the use of transdermal patches, which often have the added advantage of providing controlled delivery of a compound to the body. Such dosage forms may be prepared, for example, by dissolving and/or dispensing the compound in the proper medium. Alternatively or additionally, rate may be controlled by either providing a rate controlling membrane and/or by dispersing the compound in a polymer matrix and/or gel.

A pharmaceutical NAV composition for transdermal administration may comprise at least one inactive ingredient. Any or none of the inactive ingredients used may have been approved by the US Food and Drug Administration (FDA). A non-exhaustive list of inactive ingredients for use in pharmaceutical compositions for transdermal administration includes acrylates copolymer, acrylic acid-isooctyl acrylate copolymer, acrylic adhesive 788, adcote 72a103, aerotex resin 3730, alcohol, alcohol, dehydrated, aluminum polyester, bentonite, butylated hydroxytoluene, butylene glycol, butyric acid, caprylic/capric triglyceride, carbomer 1342, carbomer 940, carbomer 980, carrageenan, cetylpyridinium chloride, citric acid, crospovidone, daubert 1-5 pestr (matte) 164z, diethylene glycol monoethyl ether, diethylhexyl phthalate, dimethicone copolyol, dimethicone mdx4-4210, dimethicone medical fluid 360, dimethylaminoethyl methacrylate-butyl methacrylate-methyl methacrylate copolymer, dipropylene glycol, duro-tak 280-2516, duro-tak 387-2516, duro-tak 80-1196, duro-tak 87-2070, duro-tak 87-2194, duro-tak 87-2287, duro-tak 87-2296, duro-tak 87-2888, duro-tak 87-2979, edetate disodium, ethyl acetate, ethyl oleate, ethylcelluloses, ethylene vinyl acetate copolymer, ethylene-propylene copolymer, fatty acid esters, gelva 737, glycerin, glyceryl laurate, glyceryl oleate, heptane, high density polyethylene, hydrochloric acid, hydrogenated polybutene 635-690, hydroxyethyl cellulose, hydroxypropyl cellulose, isopropyl myristate, isopropyl palmitate, lactose, lanolin anhydrous, lauryl lactate, lecithin, levulinic acid, light mineral oil, medical adhesive modified s-15, methyl alcohol, methyl laurate, mineral oil, nitrogen, octisalate, octyldodecanol, oleic acid, oleyl alcohol, oleyl oleate, pentadecalactone, petrolatum, white, polacrilin, polyacrylic acid (250000 mw), polybutene (1400 mw), polyester, polyester polyamine copolymer, polyester rayon, polyethylene terephthalates, polyisobutylene, polyisobutylene (1100000 mw), polyisobutylene (35000 mw), polyisobutylene 178-236, polyisobutylene 241-294, polyisobutylene 35-39, polyisobutylene low molecular weight, polyisobutylene medium molecular weight, polyisobutylene/polybutene adhesive, polypropylene, polyvinyl acetate, polyvinyl alcohol, polyvinyl chloride, polyvinyl chloride-polyvinyl acetate copolymer, polyvinylpyridine, povidone k29/32, povidones, propylene glycol, propylene glycol monolaurate, ra-2397, ra-3011, silicon, silicon dioxide, colloidal, silicone, silicone adhesive 4102, silicone adhesive 4502, silicone adhesive bio-psa q7-4201, silicone adhesive bio-psa q7-4301, silicone/polyester tilm strip, sodium chloride, sodium citrate, sodium hydroxide, sorbitan monooleate, stearalkonium hectorite/propylene carbonate, titanium dioxide, triacetin, trolamine, tromethamine, union 76 amsco-res 6038 and viscose/cotton.

A pharmaceutical NAV composition for intradermal administration may comprise at least one inactive ingredient. Any or none of the inactive ingredients used may have been approved by the US Food and Drug Administration (FDA). A non-exhaustive list of inactive ingredients for use in pharmaceutical compositions for intradermal administration includes benzalkonium chloride, benzyl alcohol, carboxymethylcellulose sodium, creatinine, edetate disodium, glycerin, hydrochloric acid, metacresol, methylparaben, phenol, polysorbate 80, protamine sulfate, sodium acetate, sodium bisulfite, sodium chloride, sodium hydroxide, sodium phosphate, sodium phosphate, dibasic, sodium phosphate, dibasic, heptahydrate, sodium phosphate, monobasic, anhydrous and zinc chloride.

Depot Administration

As described herein, in some embodiments, the composition is formulated in depots for extended release. Generally, a specific organ or tissue (a “target tissue”) is targeted for administration.

In some aspects of the invention, the NAVs are spatially retained within or proximal to a target tissue. Provided are method of providing a composition to a target tissue of a mammalian subject by contacting the target tissue (which contains one or more target cells) with the composition under conditions such that the composition, in particular the nucleic acid component(s) of the composition, is substantially retained in the target tissue, meaning that at least 10, 20, 30, 40, 50, 60, 70, 80, 85, 90, 95, 96, 97, 98, 99, 99.9, 99.99 or greater than 99.99% of the composition is retained in the target tissue. Advantageously, retention is determined by measuring the amount of the nucleic acid present in the composition that enters one or more target cells. For example, at least 1, 5, 10, 20, 30, 40, 50, 60, 70, 80, 85, 90, 95, 96, 97, 98, 99, 99.9, 99.99 or greater than 99.99% of the nucleic acids administered to the subject are present intracellularly at a period of time following administration. For example, intramuscular injection to a mammalian subject is performed using an aqueous composition containing a ribonucleic acid and a transfection reagent, and retention of the composition is determined by measuring the amount of the ribonucleic acid present in the muscle cells.

Aspects of the invention are directed to methods of providing a composition to a target tissue of a mammalian subject, by contacting the target tissue (containing one or more target cells) with the composition under conditions such that the composition is substantially retained in the target tissue. The composition contains an effective amount of a polynucleotides such that the polypeptide of interest is produced in at least one target cell. The compositions generally contain a cell penetration agent, although “naked” NAV (such as nucleic acids without a cell penetration agent or other agent) is also contemplated, and a pharmaceutically acceptable carrier.

In some circumstances, the amount of a protein produced by cells in a tissue is desirably increased. Preferably, this increase in protein production is spatially restricted to cells within the target tissue. Thus, provided are methods of increasing production of a protein of interest in a tissue of a mammalian subject. A composition is provided that contains polynucleotides characterized in that a unit quantity of composition has been determined to produce the polypeptide of interest in a substantial percentage of cells contained within a predetermined volume of the target tissue.

In some embodiments, the NAV composition includes a plurality of different polynucleotides, where one or more than one of the polynucleotides encodes a polypeptide of interest. Optionally, the composition also contains a cell penetration agent to assist in the intracellular delivery of the composition. A determination is made of the dose of the composition required to produce the polypeptide of interest in a substantial percentage of cells contained within the predetermined volume of the target tissue (generally, without inducing significant production of the polypeptide of interest in tissue adjacent to the predetermined volume, or distally to the target tissue). Subsequent to this determination, the determined dose is introduced directly into the tissue of the mammalian subject.

In one embodiment, the invention provides for the NAVs to be delivered in more than one injection or by split dose injections.

In one embodiment, the invention may be retained near target tissue using a small disposable drug reservoir, patch pump or osmotic pump. Non-limiting examples of patch pumps include those manufactured and/or sold by BD® (Franklin Lakes, NJ), Insulet Corporation (Bedford, MA), SteadyMed Therapeutics (San Francisco, CA), Medtronic (Minneapolis, MN) (e.g., MiniMed), UniLife (York, PA), Valeritas (Bridgewater, NJ), and SpringLeaf Therapeutics (Boston, MA). A non-limiting example of an osmotic pump include those manufactured by DURECT® (Cupertino, CA) (e.g., DUROS® and ALZET®).

Pulmonary Administration

A pharmaceutical composition may be prepared, packaged, and/or sold in a formulation suitable for pulmonary administration via the buccal cavity. Such a formulation may comprise dry particles which comprise the active ingredient and which have a diameter in the range from about 0.5 nm to about 7 nm or from about 1 nm to about 6 nm. Such compositions are suitably in the form of dry powders for administration using a device comprising a dry powder reservoir to which a stream of propellant may be directed to disperse the powder and/or using a self propelling solvent/powder dispensing container such as a device comprising the active ingredient dissolved and/or suspended in a low-boiling propellant in a sealed container. Such powders comprise particles wherein at least 98% of the particles by weight have a diameter greater than 0.5 nm and at least 95% of the particles by number have a diameter less than 7 nm. Alternatively, at least 95% of the particles by weight have a diameter greater than 1 nm and at least 90% of the particles by number have a diameter less than 6 nm. Dry powder compositions may include a solid fine powder diluent such as sugar and are conveniently provided in a unit dose form.

Low boiling propellants generally include liquid propellants having a boiling point of below 65° F. at atmospheric pressure. Generally the propellant may constitute 50% to 99.9% (w/w) of the composition, and active ingredient may constitute 0.1% to 20% (w/w) of the composition. A propellant may further comprise additional ingredients such as a liquid non-ionic and/or solid anionic surfactant and/or a solid diluent (which may have a particle size of the same order as particles comprising the active ingredient).

As a non-limiting example, the NAVs described herein may be formulated for pulmonary delivery by the methods described in U.S. Pat. No. 8,257,685; herein incorporated by reference in its entirety.

Pharmaceutical NAV compositions formulated for pulmonary delivery may provide an active ingredient in the form of droplets of a solution and/or suspension. Such formulations may be prepared, packaged, and/or sold as aqueous and/or dilute alcoholic solutions and/or suspensions, optionally sterile, comprising active ingredient, and may conveniently be administered using any nebulization and/or atomization device. Such formulations may further comprise one or more additional ingredients including, but not limited to, a flavoring agent such as saccharin sodium, a volatile oil, a buffering agent, a surface active agent, and/or a preservative such as methylhydroxybenzoate. Droplets provided by this route of administration may have an average diameter in the range from about 0.1 nm to about 200 nm.

The compositions and formulations provided herein which may be used for pulmonary delivery may further comprise one or more surfactants. Suitable surfactants or surfactant components for enhancing the uptake of the compositions of the invention include synthetic and natural as well as full and truncated forms of surfactant protein A, surfactant protein B, surfactant protein C, surfactant protein D and surfactant Protein E, di-saturated phosphatidylcholine (other than dipalmitoyl), dipalmitoylphosphatidylcholine, phosphatidylcholine, phosphatidylglycerol, phosphatidylinositol, phosphatidylethanolamine, phosphatidylserine; phosphatidic acid, ubiquinones, lysophosphatidylethanolamine, lysophosphatidylcholine, palmitoyl-lysophosphatidylcholine, dehydroepiandrosterone, dolichols, sulfatidic acid, glycerol-3-phosphate, dihydroxyacetone phosphate, glycerol, glycero-3-phosphocholine, dihydroxyacetone, palmitate, cytidine diphosphate (CDP) diacylglycerol, CDP choline, choline, choline phosphate; as well as natural and artificial lamellar bodies which are the natural carrier vehicles for the components of surfactant, omega-3 fatty acids, polyenic acid, polyenoic acid, lecithin, palmitinic acid, non-ionic block copolymers of ethylene or propylene oxides, polyoxypropylene, monomeric and polymeric, polyoxyethylene, monomeric and polymeric, poly(vinyl amine) with dextran and/or alkanoyl side chains, Brij 35. Triton X-100 and synthetic surfactants ALEC, Exosurf, Survan and Atovaquone, among others. These surfactants can be used either as single or part of a multiple component surfactant in a formulation, or as covalently bound additions to the 5′ and/or 3′ ends of the nucleic acid component of a pharmaceutical composition herein.

Intranasal, Nasal and Buccal Administration

Formulations described herein as being useful for pulmonary delivery are useful for intranasal delivery of a NAV pharmaceutical composition. Another formulation suitable for intranasal administration is a coarse powder comprising the active ingredient and having an average particle from about 0.2 sm to 500 μm. Such a formulation is administered in the manner in which snuff is taken, i.e. by rapid inhalation through the nasal passage from a container of the powder held close to the nose.

Formulations suitable for nasal administration may, for example, comprise from about as little as 0.1% (w/w) and as much as 100% (w/w) of active ingredient, and may comprise one or more of the additional ingredients described herein. A pharmaceutical composition may be prepared, packaged, and/or sold in a formulation suitable for buccal administration. Such formulations may, for example, be in the form of tablets and/or lozenges made using conventional methods and may, for example, 0.1% to 20% (w/w) active ingredient, the balance comprising an orally dissolvable and/or degradable composition and, optionally, one or more of the additional ingredients described herein. Alternately, formulations suitable for buccal administration may comprise a powder and/or an aerosolized and/or atomized solution and/or suspension comprising active ingredient. Such powdered, aerosolized, and/or aerosolized formulations, when dispersed, may have an average particle and/or droplet size in the range from about 0.1 nm to about 200 nm, and may further comprise one or more of any additional ingredients described herein.

A pharmaceutical NAV composition for inhalation (respiratory) administration may comprise at least one inactive ingredient. Any or none of the inactive ingredients used may have been approved by the US Food and Drug Administration (FDA). A non-exhaustive list of inactive ingredients for use in pharmaceutical compositions for inhalation (respiratory) administration includes acetone sodium bisulfite, acetylcysteine, alcohol, alcohol, dehydrated, ammonia, apaflurane, ascorbic acid, benzalkonium chloride, calcium carbonate, carbon dioxide, cetylpyridinium chloride, chlorobutanol, citric acid, d&c yellow no. 10, dichlorodifluoromethane, dichlorotetrafluoroethane, edetate disodium, edetate sodium, fd&c yellow no. 6, fluorochlorohydrocarbons, gelatin, glycerin, glycine, hydrochloric acid, hydrochloric acid, diluted, lactose, lactose monohydrate, lecithin, lecithin, hydrogenated soy, lecithin, soybean, lysine monohydrate, mannitol, menthol, methylparaben, nitric acid, nitrogen, norflurane, oleic acid, polyethylene glycol 1000, povidone k25, propylene glycol, propylparaben, saccharin, saccharin sodium, silicon dioxide, colloidal, sodium bisulfate, sodium bisulfite, sodium chloride, sodium citrate, sodium hydroxide, sodium lauryl sulfate, sodium metabisulfite, sodium sulfate anhydrous, sodium sulfite, sorbitan trioleate, sulfuric acid, thymol, titanium dioxide, trichloromonofluoromethane, tromethamine and zinc oxide.

A pharmaceutical NAV composition for nasal administration may comprise at least one inactive ingredient. Any or none of the inactive ingredients used may have been approved by the US Food and Drug Administration (FDA). A non-exhaustive list of inactive ingredients for use in pharmaceutical compositions for nasal administration includes acetic acid, alcohol, dehydrated, allyl .alpha.-ionone, anhydrous dextrose, anhydrous trisodium citrate, benzalkonium chloride, benzethonium chloride, benzyl alcohol, butylated hydroxyanisole, butylated hydroxytoluene, caffeine, carbon dioxide, carboxymethylcellulose sodium, cellulose, microcrystalline, chlorobutanol, citric acid, citric acid monohydrate, dextrose, dichlorodifluoromethane, dichlorotetrafluoroethane, edetate disodium, glycerin, glycerol ester of hydrogenated rosin, hydrochloric acid, hypromellose 2910 (15000 mpa·s), methylcelluloses, methylparaben, nitrogen, norflurane, oleic acid, petrolatum, white, phenylethyl alcohol, polyethylene glycol 3350, polyethylene glycol 400, polyoxyl 400 stearate, polysorbate 20, polysorbate 80, potassium phosphate, monobasic, potassium sorbate, propylene glycol, propylparaben, sodium acetate, sodium chloride, sodium citrate, sodium hydroxide, sodium phosphate, sodium phosphate, dibasic, sodium phosphate, dibasic, anhydrous, sodium phosphate, dibasic, dihydrate, sodium phosphate, dibasic, dodecahydrate, sodium phosphate, dibasic, heptahydrate, sodium phosphate, monobasic, anhydrous, sodium phosphate, monobasic, dihydrate, sorbitan trioleate, sorbitol, sorbitol solution, sucralose, sulfuric acid, trichloromonofluoromethane and trisodium citrate dihydrate.

Ophthalmic and Auricular (Otic) Administration

A pharmaceutical NAV composition may be prepared, packaged, and/or sold in a formulation suitable for delivery to and/or around the eye and/or delivery to the ear (e.g., auricular (otic) administration). Non-limiting examples of route of administration for delivery to and/or around the eye include retrobulbar, conjuctival, intracorneal, intraocular, intravitreal, ophthlamic and subconjuctiva. Such formulations may, for example, be in the form of eye drops or ear drops including, for example, a 0.1/1.0% (w/w) solution and/or suspension of the active ingredient in an aqueous or oily liquid excipient. Such drops may further comprise buffering agents, salts, and/or one or more other of any additional ingredients described herein. Other ophthalmically-administrable formulations which are useful include those which comprise the active ingredient in microcrystalline form and/or in a liposomal preparation. Ear drops and/or eye drops are contemplated as being within the scope of this invention. A multilayer thin film device may be prepared to contain a pharmaceutical composition for delivery to the eye and/or surrounding tissue.

A pharmaceutical NAV composition for ophthalmic administration may comprise at least one inactive ingredient. Any or none of the inactive ingredients used may have been approved by the US Food and Drug Administration (FDA). A non-exhaustive list of inactive ingredients for use in pharmaceutical compositions for ophthalmic administration includes acetic acid, alcohol, alcohol, dehydrated, alginic acid, amerchol-cab, ammonium hydroxide, anhydrous trisodium citrate, antipyrine, benzalkonium chloride, benzethonium chloride, benzododecinium bromide, boric acid, caffeine, calcium chloride, carbomer 1342, carbomer 934p, carbomer 940, carbomer homopolymer type b (allyl pentaerythritol crosslinked), carboxymethylcellulose sodium, castor oil, cetyl alcohol, chlorobutanol, chlorobutanol, anhydrous, cholesterol, citric acid, citric acid monohydrate, creatinine, diethanolamine, diethylhexyl phthalate, divinylbenzene styrene copolymer, edetate disodium, edetate disodium anhydrous, edetate sodium, ethylene vinyl acetate copolymer, gellan gum (low acyl), glycerin, glyceryl stearate, high density polyethylene, hydrocarbon gel, plasticized, hydrochloric acid, hydrochloric acid, diluted, hydroxyethyl cellulose, hydroxypropyl methylcellulose 2906, hypromellose 2910 (15000 mpa·s), hypromelloses, jelene, lanolin, lanolin alcohols, lanolin anhydrous, lanolin nonionic derivatives, lauralkonium chloride, lauroyl sarcosine, light mineral oil, magnesium chloride, mannitol, methylcellulose (4000 mpa·s), methylcelluloses, methylparaben, mineral oil, nitric acid, nitrogen, nonoxynol-9, octoxynol-40, octylphenol polymethylene, petrolatum, petrolatum, white, phenylethyl alcohol, phenylmercuric acetate, phenylmercuric nitrate, phosphoric acid, polidronium chloride, poloxamer 188, poloxamer 407, polycarbophil, polyethylene glycol 300, polyethylene glycol 400, polyethylene glycol 8000, polyoxyethylene-polyoxypropylene 1800, polyoxyl 35 castor oil, polyoxyl 40 hydrogenated castor oil, polyoxyl 40 stearate, polypropylene glycol, polysorbate 20, polysorbate 60, polysorbate 80, polyvinyl alcohol, potassium acetate, potassium chloride, potassium phosphate, monobasic, potassium sorbate, povidone k29/32, povidone k30, povidone k90, povidones, propylene glycol, propylparaben, soda ash, sodium acetate, sodium bisulfate, sodium bisulfite, sodium borate, sodium borate decahydrate, sodium carbonate, sodium carbonate monohydrate, sodium chloride, sodium citrate, sodium hydroxide, sodium metabisulfite, sodium nitrate, sodium phosphate, sodium phosphate dihydrate, sodium phosphate, dibasic, sodium phosphate, dibasic, anhydrous, sodium phosphate, dibasic, dihydrate, sodium phosphate, dibasic, heptahydrate, sodium phosphate, monobasic, sodium phosphate, monobasic, anhydrous, sodium phosphate, monobasic, dihydrate, sodium phosphate, monobasic, monohydrate, sodium sulfate, sodium sulfate anhydrous, sodium sulfate decahydrate, sodium sulfite, sodium thiosulfate, sorbic acid, sorbitan monolaurate, sorbitol, sorbitol solution, stabilized oxychloro complex, sulfuric acid, thimerosal, titanium dioxide, tocophersolan, trisodium citrate dihydrate, triton 720, tromethamine, tyloxapol and zinc chloride.

A pharmaceutical NAV composition for retrobulbar administration may comprise at least one inactive ingredient. Any or none of the inactive ingredients used may have been approved by the US Food and Drug Administration (FDA). A non-exhaustive list of inactive ingredients for use in pharmaceutical compositions for retrobulbar administration includes hydrochloric acid and sodium hydroxide.

A pharmaceutical NAV composition for intraocular administration may comprise at least one inactive ingredient. Any or none of the inactive ingredients used may have been approved by the US Food and Drug Administration (FDA). A non-exhaustive list of inactive ingredients for use in pharmaceutical compositions for intraocular administration includes benzalkonium chloride, calcium chloride, citric acid monohydrate, hydrochloric acid, magnesium chloride, polyvinyl alcohol, potassium chloride, sodium acetate, sodium chloride, sodium citrate and sodium hydroxide.

A pharmaceutical NAV composition for intravitreal administration may comprise at least one inactive ingredient. Any or none of the inactive ingredients used may have been approved by the US Food and Drug Administration (FDA). A non-exhaustive list of inactive ingredients for use in pharmaceutical compositions for intravitreal administration includes calcium chloride, carboxymethylcellulose sodium, cellulose, microcrystalline, hyaluronate sodium, hydrochloric acid, magnesium chloride, magnesium stearate, polysorbate 80, polyvinyl alcohol, potassium chloride, sodium acetate, sodium bicarbonate, sodium carbonate, sodium chloride, sodium hydroxide, sodium phosphate dibasic heptahydrate, sodium phosphate monobasic monohydrate and trisodium citrate dehydrate.

A pharmaceutical NAV composition for subconjunctival administration may comprise at least one inactive ingredient. Any or none of the inactive ingredients used may have been approved by the US Food and Drug Administration (FDA). A non-exhaustive list of inactive ingredients for use in pharmaceutical compositions for subconjunctival administration includes benzyl alcohol, hydrochloric acid and sodium hydroxide.

A pharmaceutical NAV composition for auricular administration may comprise at least one inactive ingredient. Any or none of the inactive ingredients used may have been approved by the US Food and Drug Administration (FDA). A non-exhaustive list of inactive ingredients for use in pharmaceutical compositions for auricular administration includes acetic acid, aluminum acetate, aluminum sulfate anhydrous, benzalkonium chloride, benzethonium chloride, benzyl alcohol, boric acid, calcium carbonate, cetyl alcohol, chlorobutanol, chloroxylenol, citric acid, creatinine, cupric sulfate, cupric sulfate anhydrous, edetate disodium, edetic acid, glycerin, glyceryl stearate, hydrochloric acid, hydrocortisone, hydroxyethyl cellulose, isopropyl myristate, lactic acid, lecithin, hydrogenated, methylparaben, mineral oil, petrolatum, petrolatum, white, phenylethyl alcohol, polyoxyl 40 stearate, polyoxyl stearate, polysorbate 20, polysorbate 80, polyvinyl alcohol, potassium metabisulfite, potassium phosphate, monobasic, povidone k90f, povidones, propylene glycol, propylene glycol diacetate, propylparaben, sodium acetate, sodium bisulfite, sodium borate, sodium chloride, sodium citrate, sodium hydroxide, sodium phosphate, dibasic, anhydrous, sodium phosphate, dibasic, heptahydrate, sodium phosphate, monobasic, anhydrous, sodium sulfite, sulfuric acid and thimerosal.

Payload Administration: Detectable Agents and Therapeutic Agents

The NAVs described herein can be used in a number of different scenarios in which delivery of a substance (the “payload”) to a biological target is desired, for example delivery of detectable substances for detection of the target, or delivery of a therapeutic agent. Detection methods can include, but are not limited to, both imaging in vitro and in vivo imaging methods, e.g., immunohistochemistry, bioluminescence imaging (BLI), Magnetic Resonance Imaging (MRI), positron emission tomography (PET), electron microscopy, X-ray computed tomography, Raman imaging, optical coherence tomography, absorption imaging, thermal imaging, fluorescence reflectance imaging, fluorescence microscopy, fluorescence molecular tomographic imaging, nuclear magnetic resonance imaging, X-ray imaging, ultrasound imaging, photoacoustic imaging, lab assays, or in any situation where tagging/staining/imaging is required.

NAVs described herein can be used in intracellular targeting of a payload, e.g., detectable or therapeutic agent, to specific organelle. Exemplary intracellular targets can include, but are not limited to, the nuclear localization for advanced mRNA processing, or a nuclear localization sequence (NLS) linked to the mRNA containing an inhibitor.

In addition, the NAVs described herein can be used to deliver therapeutic agents to cells or tissues, e.g., in living animals. For example, the NAVs described herein can be used to deliver highly polar chemotherapeutics agents to kill cancer cells. The NAVs attached to the therapeutic agent through a linker can facilitate member permeation allowing the therapeutic agent to travel into a cell to reach an intracellular target.

In some embodiments, the payload may be a therapeutic agent such as a cytotoxin, radioactive ion, chemotherapeutic, or other therapeutic agent. A cytotoxin or cytotoxic agent includes any agent that may be detrimental to cells. Examples include, but are not limited to, taxol, cytochalasin B, gramicidin D, ethidium bromide, emetine, mitomycin, etoposide, teniposide, vincristine, vinblastine, colchicine, doxorubicin, daunorubicin, dihydroxyanthracinedione, mitoxantrone, mithramycin, actinomycin D, 1-dehydrotestosterone, glucocorticoids, procaine, tetracaine, lidocaine, propranolol, puromycin, maytansinoids, e.g., maytansinol (see U.S. Pat. No. 5,208,020 incorporated herein in its entirety), rachelmycin (CC-1065, see U.S. Pat. Nos. 5,475,092, 5,585,499, and 5,846,545, all of which are incorporated herein by reference), and analogs or homologs thereof. Radioactive ions include, but are not limited to iodine (e.g., iodine 125 or iodine 131), strontium 89, phosphorous, palladium, cesium, iridium, phosphate, cobalt, yttrium 90, samarium 153, and praseodymium. Other therapeutic agents include, but are not limited to, antimetabolites (e.g., methotrexate, 6-mercaptopurine, 6-thioguanine, cytarabine, 5-fluorouracil decarbazine), alkylating agents (e.g., mechlorethamine, thiotepa chlorambucil, rachelmycin (CC-1065), melphalan, carmustine (BSNU), lomustine (CCNU), cyclophosphamide, busulfan, dibromomannitol, streptozotocin, mitomycin C, and cis-dichlorodiamine platinum (11) (DDP) cisplatin), anthracyclines (e.g., daunorubicin (formerly daunomycin) and doxorubicin), antibiotics (e.g., dactinomycin (formerly actinomycin), bleomycin, mithramycin, and anthramycin (AMC)), and anti-mitotic agents (e.g., vincristine, vinblastine, taxol and maytansinoids).

In some embodiments, the payload may be a detectable agent, such as various organic small molecules, inorganic compounds, nanoparticles, enzymes or enzyme substrates, fluorescent materials, luminescent materials (e.g., luminol), bioluminescent materials (e.g., luciferase, luciferin, and aequorin), chemiluminescent materials, radioactive materials (e.g., ¹⁸F, ⁶⁷Ga, ^81mKr, ⁸²Rb, ¹¹¹In, ¹²³I, ³³Xe, ²⁰¹Tl, ¹²⁵I, ³⁵S, ¹⁴C, ³H, or ^99mTc (e.g., as pertechnetate (technetate(VII), TcO₄⁻), and contrast agents (e.g., gold (e.g., gold nanoparticles), gadolinium (e.g., chelated Gd), iron oxides (e.g., superparamagnetic iron oxide (SPIO), monocrystalline iron oxide nanoparticles (MIONs), and ultrasmall superparamagnetic iron oxide (USPIO)), manganese chelates (e.g., Mn-DPDP), barium sulfate, iodinated contrast media (iohexol), microbubbles, or perfluorocarbons). Such optically-detectable labels include for example, without limitation, 4-acetamido-4′-isothiocyanatostilbene-2,2′disulfonic acid; acridine and derivatives (e.g., acridine and acridine isothiocyanate); 5-(2′-aminoethyl)aminonaphthalene-1-sulfonic acid (EDANS); 4-amino-N-[3-vinylsulfonyl)phenyl]naphthalimide-3,5 disulfonate; N-(4-anilino-1-naphthyl)maleimide; anthranilamide; BODIPY; Brilliant Yellow; coumarin and derivatives (e.g., coumarin, 7-amino-4-methylcoumarin (AMC, Coumarin 120), and 7-amino-4-trifluoromethylcoumarin (Coumarin 151)); cyanine dyes; cyanosine; 4′,6-diaminidino-2-phenylindole (DAPI); 5′ 5″-dibromopyrogallol-sulfonaphthalein (Bromopyrogallol Red); 7-diethylamino-3-(4′-isothiocyanatophenyl)-4-methylcoumarin; diethylenetriamine pentaacetate; 4,4′-diisothiocyanatodihydro-stilbene-2,2′-disulfonic acid; 4,4′-diisothiocyanatostilbene-2,2′-disulfonic acid; 5-[dimethylamino]-naphthalene-1-sulfonyl chloride (DNS, dansylchloride); 4-dimethylaminophenylazophenyl-4′-isothiocyanate (DABITC); eosin and derivatives (e.g., eosin and eosin isothiocyanate); erythrosin and derivatives (e.g., erythrosin B and erythrosin isothiocyanate); ethidium; fluorescein and derivatives (e.g., 5-carboxyfluorescein (FAM), 5-(4,6-dichlorotriazin-2-yl)aminofluorescein (DTAF), 2′,7′-dimethoxy-4′5′-dichloro-6-carboxyfluorescein, fluorescein, fluorescein isothiocyanate, X-rhodamine-5-(and-6)-isothiocyanate (QFITC or XRITC), and fluorescamine); 2-[2-[3-[[1,3-dihydro-1,1-dimethyl-3-(3-sulfopropyl)-2H-benz[e]indol-2-ylidene]ethylidene]-2-[4-(ethoxycarbonyl)-1-piperazinyl]-1-cyclopenten-1-yl]ethenyl]-1,1-dimethyl-3-(3-sulforpropyl)-1H-benz[e]indolium hydroxide, inner salt, compound with n,n-diethylethanamine(1:1) (IR144); 5-chloro-2-[2-[3-[(5-chloro-3-ethyl-2(3H)-benzothiazol-ylidene)ethylidene]-2-(diphenylamino)-1-cyclopenten-1-yl]ethenyl]-3-ethyl benzothiazolium perchlorate (IR140); Malachite Green isothiocyanate; 4-methylumbelliferone orthocresolphthalein; nitrotyrosine; pararosaniline; Phenol Red; B-phycoerythrin; o-phthaldialdehyde; pyrene and derivatives (e.g., pyrene, pyrene butyrate, and succinimidyl 1-pyrene); butyrate quantum dots; Reactive Red 4 (CIBACRON™ Brilliant Red 3B-A); rhodamine and derivatives (e.g., 6-carboxy-X-rhodamine (ROX), 6-carboxyrhodamine (R6G), lissamine rhodamine B sulfonyl chloride rhodarnine (Rhod), rhodamine B, rhodamine 123, rhodamine X isothiocyanate, sulforhodamine B, sulforhodamine 101, sulfonyl chloride derivative of sulforhodamine 101 (Texas Red), N,N,N′,N′tetramethyl-6-carboxyrhodamine (TAMRA) tetramethyl rhodamine, and tetramethyl rhodamine isothiocyanate (TRITC)); riboflavin; rosolic acid; terbium chelate derivatives; Cyanine-3 (Cy3); Cyanine-5 (Cy5); cyanine-5.5 (Cy5.5), Cyanine-7 (Cy7); IRD 700; IRD 800; Alexa 647; La Jolta Blue; phthalo cyanine; and naphthalo cyanine.

In some embodiments, the detectable agent may be a non-detectable precursor that becomes detectable upon activation (e.g., fluorogenic tetrazine-fluorophore constructs (e.g., tetrazine-BODIPY FL, tetrazine-Oregon Green 488, or tetrazine-BODIPY TMR-X) or enzyme activatable fluorogenic agents (e.g., PROSENSE® (VisEn Medical))). In vitro assays in which the enzyme labeled compositions can be used include, but are not limited to, enzyme linked immunosorbent assays (ELISAs), immunoprecipitation assays, immunofluorescence, enzyme immunoassays (EIA), radioimmunoassays (RIA), and Western blot analysis.

Combinations

The NAVs may be used in combination with one or more other therapeutic, prophylactic, diagnostic, or imaging agents. By “in combination with,” it is not intended to imply that the agents must be administered at the same time and/or formulated for delivery together, although these methods of delivery are within the scope of the present disclosure. Compositions can be administered concurrently with, prior to, or subsequent to, one or more other desired therapeutics or medical procedures. In general, each agent will be administered at a dose and/or on a time schedule determined for that agent. In some embodiments, the present disclosure encompasses the delivery of pharmaceutical, prophylactic, diagnostic, or imaging compositions in combination with agents that may improve their bioavailability, reduce and/or modify their metabolism, inhibit their excretion, and/or modify their distribution within the body.

The combinations can conveniently be presented for use in the form of a pharmaceutical formulation and thus pharmaceutical compositions comprising a combination as defined above together with a pharmaceutically acceptable diluent or carrier represent a further aspect of the invention.

The individual compounds of such combinations can be administered either sequentially or simultaneously in separate or combined pharmaceutical formulations. In one embodiment, the individual compounds will be administered simultaneously in a combined pharmaceutical formulation.

It will further be appreciated that therapeutically, prophylactically, diagnostically, or imaging active agents utilized in combination may be administered together in a single composition or administered separately in different compositions. In general, it is expected that agents utilized in combination with be utilized at levels that do not exceed the levels at which they are utilized individually. In some embodiments, the levels utilized in combination will be lower than those utilized individually. In one embodiment, the combinations, each or together may be administered according to the split dosing regimens described herein.

Dosing

The present invention provides methods comprising administering NAVs and in accordance with the invention to a subject in need thereof. The exact amount required will vary from subject to subject, depending on the species, age, and general condition of the subject, the severity of the disease, the particular composition, its mode of administration, its mode of activity, and the like. Compositions in accordance with the invention are typically formulated in dosage unit form for ease of administration and uniformity of dosage. It will be understood, however, that the total daily usage of the compositions of the present invention may be decided by the attending physician within the scope of sound medical judgment. The specific therapeutically effective, prophylactically effective, or appropriate imaging dose level for any particular patient will depend upon a variety of factors including the disorder being treated and the severity of the disorder; the activity of the specific compound employed; the specific composition employed; the age, body weight, general health, sex and diet of the patient; the time of administration, route of administration, and rate of excretion of the specific compound employed; the duration of the treatment; drugs used in combination or coincidental with the specific compound employed; and like factors well known in the medical arts.

In certain embodiments, compositions in accordance with the present invention may be administered at dosage levels sufficient to deliver from about 0.0001 mg/kg to about 100 mg/kg, from about 0.001 mg/kg to about 0.05 mg/kg, from about 0.005 mg/kg to about 0.05 mg/kg, from about 0.001 mg/kg to about 0.005 mg/kg, from about 0.05 mg/kg to about 0.5 mg/kg, from about 0.01 mg/kg to about 50 mg/kg, from about 0.1 mg/kg to about 40 mg/kg, from about 0.5 mg/kg to about 30 mg/kg, from about 0.01 mg/kg to about 10 mg/kg, from about 0.1 mg/kg to about 10 mg/kg, or from about 1 mg/kg to about 25 mg/kg, of subject body weight per day, one or more times a day, to obtain the desired therapeutic, diagnostic, prophylactic, or imaging effect (see e.g., the range of unit doses described in International Publication No WO2013078199, herein incorporated by reference in its entirety). The desired dosage may be delivered three times a day, two times a day, once a day, every other day, every third day, every week, every two weeks, every three weeks, or every four weeks. In certain embodiments, the desired dosage may be delivered using multiple administrations (e.g., two, three, four, five, six, seven, eight, nine, ten, eleven, twelve, thirteen, fourteen, or more administrations). When multiple administrations are employed, split dosing regimens such as those described herein may be used.

According to the present invention, NAVs may be administered in split-dose regimens. As used herein, a “split dose” is the division of single unit dose or total daily dose into two or more doses, e.g, two or more administrations of the single unit dose. As used herein, a “single unit dose” is a dose of any therapeutic administered in one dose/at one time/single route/single point of contact, i.e., single administration event. As used herein, a “total daily dose” is an amount given or prescribed in 24 hr period. It may be administered as a single unit dose. In one embodiment, the NAVs of the present invention are administered to a subject in split doses. The NAVs may be formulated in buffer only or in a formulation described herein.

Dosage Forms

A NAV pharmaceutical composition described herein can be formulated into a dosage form described herein, such as an intranasal, intratracheal, or injectable (e.g., intravenous, intraocular, intravitreal, intramuscular, intracardiac, intraperitoneal, subcutaneous).

Liquid Dosage Forms

Liquid dosage forms for parenteral administration include, but are not limited to, pharmaceutically acceptable emulsions, microemulsions, solutions, suspensions, syrups, and/or elixirs. In addition to active ingredients, liquid dosage forms may comprise inert diluents commonly used in the art including, but not limited to, water or other solvents, solubilizing agents and emulsifiers such as ethyl alcohol, isopropyl alcohol, ethyl carbonate, ethyl acetate, benzyl alcohol, benzyl benzoate, propylene glycol, 1,3-butylene glycol, dimethylformamide, oils (in particular, cottonseed, groundnut, corn, germ, olive, castor, and sesame oils), glycerol, tetrahydrofurfuryl alcohol, polyethylene glycols and fatty acid esters of sorbitan, and mixtures thereof. In certain embodiments for parenteral administration, compositions may be mixed with solubilizing agents such as CREMOPHOR*, alcohols, oils, modified oils, glycols, polysorbates, cyclodextrins, polymers, and/or combinations thereof.

Injectable

Injectable preparations, for example, sterile injectable aqueous or oleaginous suspensions may be formulated according to the known art and may include suitable dispersing agents, wetting agents, and/or suspending agents. Sterile injectable preparations may be sterile injectable solutions, suspensions, and/or emulsions in nontoxic parenterally acceptable diluents and/or solvents, for example, a solution in 1,3-butanediol. Among the acceptable vehicles and solvents that may be employed include, but are not limited to, water, Ringer's solution. U.S.P., and isotonic sodium chloride solution. Sterile, fixed oils are conventionally employed as a solvent or suspending medium. For this purpose any bland fixed oil can be employed including synthetic mono- or diglycerides. Fatty acids such as oleic acid can be used in the preparation of injectables.

In order to prolong the effect of an active ingredient, it may be desirable to slow the absorption of the active ingredient from subcutaneous or intramuscular injection. This may be accomplished by the use of a liquid suspension of crystalline or amorphous material with poor water solubility. The rate of absorption of the NAVs then depends upon its rate of dissolution which, in turn, may depend upon crystal size and crystalline form. Alternatively, delayed absorption of a parenterally administered NAV may be accomplished by dissolving or suspending the NAVs in an oil vehicle. Injectable depot forms are made by forming microencapsule matrices of the NAVs in biodegradable polymers such as polylactide-polyglycolide. Depending upon the ratio of NAVs to polymer and the nature of the particular polymer employed, the rate of polynucleotides release can be controlled. Examples of other biodegradable polymers include, but are not limited to, poly(orthoesters) and poly(anhydrides). Depot injectable formulations may be prepared by entrapping the NAVs in liposomes or microemulsions which are compatible with body tissues.

Pulmonary

Formulations described herein as being useful for pulmonary delivery may also be used for intranasal delivery of a pharmaceutical composition. Another formulation suitable for intranasal administration may be a coarse powder comprising the active ingredient and having an average particle from about 0.2 μm to 500 μm. Such a formulation may be administered in the manner in which snuff is taken, i.e. by rapid inhalation through the nasal passage from a container of the powder held close to the nose.

Formulations suitable for nasal administration may, for example, comprise from about as little as 0.1% (w/w) and as much as 100% (w/w) of active ingredient, and may comprise one or more of the additional ingredients described herein. A pharmaceutical composition may be prepared, packaged, and/or sold in a formulation suitable for buccal administration. Such formulations may, for example, be in the form of tablets and/or lozenges made using conventional methods, and may, for example, contain about 0.1% to 20% (w/w) active ingredient, where the balance may comprise an orally dissolvable and/or degradable composition and, optionally, one or more of the additional ingredients described herein. Alternately, formulations suitable for buccal administration may comprise a powder and/or an aerosolized and/or atomized solution and/or suspension comprising active ingredient. Such powdered, aerosolized, and/or aerosolized formulations, when dispersed, may have an average particle and/or droplet size in the range from about 0.1 nm to about 200 nm, and may further comprise one or more of any additional ingredients described herein.

General considerations in the formulation and/or manufacture of pharmaceutical agents may be found, for example, in Remington: The Science and Practice of Pharmacy 21^sted., Lippincott Williams & Wilkins, 2005 (incorporated herein by reference in its entirety).

Coatings or Shells

Solid dosage forms of tablets, dragees, capsules, pills, and granules can be prepared with coatings and shells such as enteric coatings and other coatings well known in the pharmaceutical formulating art. They may optionally comprise opacifying agents and can be of a composition that they release the active ingredient(s) only, or preferentially, in a certain part of the intestinal tract, optionally, in a delayed manner. Examples of embedding compositions which can be used include polymeric substances and waxes. Solid compositions of a similar type may be employed as fillers in soft and hard-filled gelatin capsules using such excipients as lactose or milk sugar as well as high molecular weight polyethylene glycols and the like.

Multi-Dose and Repeat-Dose Administration

In some embodiments, NAV compounds and/or compositions of the present invention may be administered in two or more doses (referred to herein as “multi-dose administration”). Such doses may comprise the same components or may comprise components not included in a previous dose. Such doses may comprise the same mass and/or volume of components or an altered mass and/or volume of components in comparison to a previous dose. In some embodiments, multi-dose administration may comprise repeat-dose administration. As used herein, the term “repeat-dose administration” refers to two or more doses administered consecutively or within a regimen of repeat doses comprising substantially the same components provided at substantially the same mass and/or volume. In some embodiments, subjects may display a repeat-dose response. As used herein, the term “repeat-dose response” refers to a response in a subject to a repeat-dose that differs from that of another dose administered within a repeat-dose administration regimen. In some embodiments, such a response may be the expression of a protein in response to a repeat-dose comprising NAV. In such embodiments, protein expression may be elevated in comparison to another dose administered within a repeat-dose administration regimen or protein expression may be reduced in comparison to another dose administered within a repeat-dose administration regimen. Alteration of protein expression may be from about 1% to about 20%, from about 5% to about 50% from about 10% to about 60%, from about 25% to about 75%, from about 40% to about 100% and/or at least 100%. A reduction in expression of mRNA administered as part of a repeat-dose regimen, wherein the level of protein translated from the administered RNA is reduced by more than 40% in comparison to another dose within the repeat-dose regimen is referred to herein as “repeat-dose resistance.”

Properties of the Pharmaceutical Compositions

The NAV pharmaceutical compositions described herein can be characterized by one or more of the following properties:

Bioavailability

The NAVs, when formulated into a composition with a delivery agent as described herein, can exhibit an increase in bioavailability as compared to a composition lacking a delivery agent as described herein. As used herein, the term “bioavailability” refers to the systemic availability of a given amount of NAVs administered to a mammal. Bioavailability can be assessed by measuring the area under the curve (AUC) or the maximum serum or plasma concentration (C_max) of the unchanged form of a compound following administration of the compound to a mammal. AUC is a determination of the area under the curve plotting the serum or plasma concentration of a compound along the ordinate (Y-axis) against time along the abscissa (X-axis). Generally, the AUC for a particular compound can be calculated using methods known to those of ordinary skill in the art and as described in G. S. Banker, Modern Pharmaceutics, Drugs and the Pharmaceutical Sciences, v. 72, Marcel Dekker, New York, Inc., 1996, herein incorporated by reference in its entirety.

The C_maxvalue is the maximum concentration of the compound achieved in the serum or plasma of a mammal following administration of the compound to the mammal. The Cam value of a particular compound can be measured using methods known to those of ordinary skill in the art. The phrases “increasing bioavailability” or “improving the pharmacokinetics,” as used herein mean that the systemic availability of a first NAV, measured as AUC, C_max, or C_minin a mammal is greater, when co-administered with a delivery agent as described herein, than when such co-administration does not take place. In some embodiments, the bioavailability of the NAVs can increase by at least about 2%, at least about 5%, at least about 10%, at least about 15%, at least about 20%, at least about 25%, at least about 30%, at least about 35%, at least about 40%, at least about 45%, at least about 50%, at least about 55%, at least about 60%, at least about 65%, at least about 70%, at least about 75%, at least about 80%, at least about 85%, at least about 90%, at least about 95%, or about 100%.

In some embodiments, liquid formulations of NAVs may have varying in vivo half-life, requiring modulation of doses to yield a therapeutic effect. To address this, in some embodiments of the present invention, NAV formulations may be designed to improve bioavailability and/or therapeutic effect during repeat administrations. Such formulations may enable sustained release of NAVs and/or reduce NAV degradation rates by nucleases. In some embodiments, suspension formulations are provided comprising NAVs, water immiscible oil depots, surfactants and/or co-surfactants and/or co-solvents. Combinations of oils and surfactants may enable suspension formulation with NAVs. Delivery of NAVs in a water immiscible depot may be used to improve bioavailability through sustained release of polynucleotides from the depot to the surrounding physiologic environment and/or prevent polynucleotide degradation by nucleases.

In some embodiments, cationic nanoparticles comprising combinations of divalent and monovalent cations may be formulated with NAVs. Such nanoparticles may form spontaneously in solution over a given period (e.g. hours, days, etc). Such nanoparticles do not form in the presence of divalent cations alone or in the presence of monovalent cations alone. The delivery of NAVs in cationic nanoparticles or in one or more depot comprising cationic nanoparticles may improve NAV bioavailability by acting as a long-acting depot and/or reducing the rate of degradation by nucleases.

Therapeutic Window

The NAVs, when formulated into a composition with a delivery agent as described herein, can exhibit an increase in the therapeutic window of the administered NAV composition as compared to the therapeutic window of the administered NAV composition lacking a delivery agent as described herein. As used herein “therapeutic window” refers to the range of plasma concentrations, or the range of levels of therapeutically active substance at the site of action, with a high probability of eliciting a therapeutic effect. In some embodiments, the therapeutic window of the NAVs when co-administered with a delivery agent as described herein can increase by at least about 2%, at least about 5%, at least about 10%, at least about 15%, at least about 20%, at least about 25%, at least about 30%, at least about 35%, at least about 40%, at least about 45%, at least about 50%, at least about 55%, at least about 60%, at least about 65%, at least about 70%, at least about 75%, at least about 80%, at least about 85%, at least about 90%, at least about 95%, or about 100%.

Volume of Distribution

The NAVs, when formulated into a composition with a delivery agent as described herein, can exhibit an improved volume of distribution (V_dist), e.g., reduced or targeted, relative to a composition lacking a delivery agent as described herein. The volume of distribution (Vdist) relates the amount of the drug in the body to the concentration of the drug in the blood or plasma. As used herein, the term “volume of distribution” refers to the fluid volume that would be required to contain the total amount of the drug in the body at the same concentration as in the blood or plasma: Vdist equals the amount of drug in the body/concentration of drug in blood or plasma. For example, for a 10 mg dose and a plasma concentration of 10 mg/L, the volume of distribution would be 1 liter. The volume of distribution reflects the extent to which the drug is present in the extravascular tissue. A large volume of distribution reflects the tendency of a compound to bind to the tissue components compared with plasma protein binding. In a clinical setting, Vdist can be used to determine a loading dose to achieve a steady state concentration. In some embodiments, the volume of distribution of the NAVs when co-administered with a delivery agent as described herein can decrease at least about 2%, at least about 5%, at least about 10%, at least about 15%, at least about 20%, at least about 25%, at least about 30%, at least about 35%, at least about 40%, at least about 45%, at least about 50%, at least about 55%, at least about 60%, at least about 65%, at least about 70%.

Biological Effect

In one embodiment, the biological effect of the NAV delivered to the animals may be categorized by analyzing the protein expression in the animals. The protein expression may be determined from analyzing a biological sample collected from a mammal administered the NAV of the present invention

Detection of Polynucleotides by Mass Spectrometry

Mass spectrometry (MS) is an analytical technique that can provide structural and molecular mass/concentration information on molecules after their conversion to ions. The molecules are first ionized to acquire positive or negative charges and then they travel through the mass analyzer to arrive at different areas of the detector according to their mass/charge (m/z) ratio.

Mass spectrometry is performed using a mass spectrometer which includes an ion source for ionizing the fractionated sample and creating charged molecules for further analysis. For example ionization of the sample may be performed by electrospray ionization (ESI), atmospheric pressure chemical ionization (APCI), photoionization, electron ionization, fast atom bombardment (FAB)/liquid secondary ionization (LSIMS), matrix assisted laser desorption/ionization (MALDI), field ionization, field desorption, thermospray/plasmaspray ionization, and particle beam ionization. The skilled artisan will understand that the choice of ionization method can be determined based on the analyte to be measured, type of sample, the type of detector, the choice of positive versus negative mode, etc.

After the sample has been ionized, the positively charged or negatively charged ions thereby created may be analyzed to determine a mass-to-charge ratio (i.e., m/z). Suitable analyzers for determining mass-to-charge ratios include quadropole analyzers, ion traps analyzers, and time-of-flight analyzers. The ions may be detected using several detection modes. For example, selected ions may be detected (i.e., using a selective ion monitoring mode (SIM)), or alternatively, ions may be detected using a scanning mode, e.g., multiple reaction monitoring (MRM) or selected reaction monitoring (SRM).

Liquid chromatography-multiple reaction monitoring (LC-MS/MRM) coupled with stable isotope labeled dilution of peptide standards has been shown to be an effective method for protein verification (e.g., Keshishian et al., Mol Cell Proteomics 2009 8: 2339-2349; Kuhn et al., Clin Chem 2009 55:1108-1117; Lopez et al., Clin Chem 2010 56:281-290; each of which are herein incorporated by reference in its entirety). Unlike untargeted mass spectrometry frequently used in biomarker discovery studies, targeted MS methods are peptide sequence-based modes of MS that focus the full analytical capacity of the instrument on tens to hundreds of selected peptides in a complex mixture. By restricting detection and fragmentation to only those peptides derived from proteins of interest, sensitivity and reproducibility are improved dramatically compared to discovery-mode MS methods. This method of mass spectrometry-based multiple reaction monitoring (MRM) quantitation of proteins can dramatically impact the discovery and quantitation of biomarkers via rapid, targeted, multiplexed protein expression profiling of clinical samples.

In one embodiment, a biological sample which may contain at least one protein encoded by at least one modified mRNA of the present invention may be analyzed by the method of MRM-MS. The quantification of the biological sample may further include, but is not limited to, isotopically labeled peptides or proteins as internal standards.

According to the present invention, the biological sample, once obtained from the subject, may be subjected to enzyme digestion. As used herein, the term “digest” means to break apart into shorter peptides. As used herein, the phrase “treating a sample to digest proteins” means manipulating a sample in such a way as to break down proteins in a sample. These enzymes include, but are not limited to, trypsin, endoproteinase Glu-C and chymotrypsin. In one embodiment, a biological sample which may contain at least one protein encoded by at least one modified mRNA of the present invention may be digested using enzymes.

In one embodiment, a biological sample which may contain protein encoded by modified mRNA of the present invention may be analyzed for protein using electrospray ionization. Electrospray ionization (ESI) mass spectrometry (ESIMS) uses electrical energy to aid in the transfer of ions from the solution to the gaseous phase before they are analyzed by mass spectrometry. Samples may be analyzed using methods known in the art (e.g., Ho et al., Clin Biochem Rev. 2003 24(1):3-12; herein incorporated by reference in its entirety). The ionic species contained in solution may be transferred into the gas phase by dispersing a fine spray of charge droplets, evaporating the solvent and ejecting the ions from the charged droplets to generate a mist of highly charged droplets. The mist of highly charged droplets may be analyzed using at least 1, at least 2, at least 3 or at least 4 mass analyzers such as, but not limited to, a quadropole mass analyzer. Further, the mass spectrometry method may include a purification step. As a non-limiting example, the first quadrapole may be set to select a single m/z ratio so it may filter out other molecular ions having a different m/z ratio which may eliminate complicated and time-consuming sample purification procedures prior to MS analysis.

In one embodiment, a biological sample which may contain protein encoded by modified mRNA of the present invention may be analyzed for protein in a tandem ESIMS system (e.g., MS/MS). As non-limiting examples, the droplets may be analyzed using a product scan (or daughter scan) a precursor scan (parent scan) a neutral loss or a multiple reaction monitoring.

In one embodiment, a biological sample which may contain protein encoded by modified mRNA of the present invention may be analyzed using matrix-assisted laser desorption/ionization (MALDI) mass spectrometry (MALDIMS). MALDI provides for the nondestructive vaporization and ionization of both large and small molecules, such as proteins. In MALDI analysis, the analyte is first co-crystallized with a large molar excess of a matrix compound, which may also include, but is not limited to, an ultraviolet absorbing weak organic acid. Non-limiting examples of matrices used in MALDI are α-cyano-4-hydroxycinnamic acid, 3,5-dimethoxy-4-hydroxycinnamic acid and 2,5-dihydroxybenzoic acid. Laser radiation of the analyte-matrix mixture may result in the vaporization of the matrix and the analyte. The laser induced desorption provides high ion yields of the intact analyte and allows for measurement of compounds with high accuracy. Samples may be analyzed using methods known in the art (e.g., Lewis, Wei and Siuzdak, Encyclopedia of Analytical Chemistry 2000:5880-5894; herein incorporated by reference in its entirety). As non-limiting examples, mass analyzers used in the MALDI analysis may include a linear time-of-flight (TOF), a TOF reflectron or a Fourier transform mass analyzer.

In one embodiment, the analyte-matrix mixture may be formed using the dried-droplet method. A biologic sample is mixed with a matrix to create a saturated matrix solution where the matrix-to-sample ratio is approximately 5000:1. An aliquot (approximately 0.5-2.0 uL) of the saturated matrix solution is then allowed to dry to form the analyte-matrix mixture.

In one embodiment, the analyte-matrix mixture may be formed using the thin-layer method. A matrix homogeneous film is first formed and then the sample is then applied and may be absorbed by the matrix to form the analyte-matrix mixture.

In one embodiment, the analyte-matrix mixture may be formed using the thick-layer method. A matrix homogeneous film is formed with a nitro-cellulose matrix additive. Once the uniform nitro-cellulose matrix layer is obtained the sample is applied and absorbed into the matrix to form the analyte-matrix mixture.

In one embodiment, the analyte-matrix mixture may be formed using the sandwich method. A thin layer of matrix crystals is prepared as in the thin-layer method followed by the addition of droplets of aqueous trifluoroacetic acid, the sample and matrix. The sample is then absorbed into the matrix to form the analyte-matrix mixture.

VI. Kits and Devices
Kits

The invention provides a variety of kits for conveniently and/or effectively carrying out methods of the present invention. Typically kits will comprise sufficient amounts and/or numbers of components to allow a user to perform multiple treatments of a subject(s) and/or to perform multiple experiments.

In one aspect, the present invention provides kits comprising the NAV molecules (including any proteins or polynucleotides) of the invention. In one embodiment, the kit comprises one or more functional antigens or function fragments thereof.

The kits can be for protein production, comprising a first polynucleotides comprising a translatable region of an antigen. The kit may further comprise packaging and instructions and/or a delivery agent to form a formulation composition. The delivery agent may comprise a saline, a buffered solution, a lipidoid or any delivery agent disclosed herein.

In one embodiment, the buffer solution may include sodium chloride, calcium chloride, phosphate and/or EDTA. In another embodiment, the buffer solution may include, but is not limited to, saline, saline with 2 mM calcium, 5% sucrose, 5% sucrose with 2 mM calcium, 5% Mannitol, 5% Mannitol with 2 mM calcium, Ringer's lactate, sodium chloride, sodium chloride with 2 mM calcium and mannose (See e.g., U.S. Pub. No. 20120258046; herein incorporated by reference in its entirety). In a further embodiment, the buffer solutions may be precipitated or it may be lyophilized. The amount of each component may be varied to enable consistent, reproducible higher concentration saline or simple buffer formulations.

The components may also be varied in order to increase the stability of polynucleotides in the buffer solution over a period of time and/or under a variety of conditions.

In one aspect, the present invention provides kits for protein production, comprising: a polynucleotide comprising a translatable region, provided in an amount effective to produce a desired amount of a protein encoded by the translatable region when introduced into a target cell; a second polynucleotide comprising an inhibitory nucleic acid, provided in an amount effective to substantially inhibit the innate immune response of the cell; and packaging and instructions.

In one aspect, the present invention provides kits for protein production, comprising a polynucleotide comprising a translatable region, wherein the polynucleotide exhibits reduced degradation by a cellular nuclease, and packaging and instructions.

Devices

The present invention provides for devices which may incorporate RNAVs comprising polynucleotides that encode polypeptides of interest, e.g., encode antigenic polypeptides. These devices contain in a stable formulation the reagents to synthesize a polynucleotide in a formulation available to be immediately delivered to a subject in need thereof, such as a human patient.

Devices for administration may be employed to deliver the NAVs of the present invention according to single, multi- or split-dosing regimens taught herein. Such devices are taught in, for example, International Application PCT/US2013/30062 filed Mar. 9, 2013 (Attorney Docket Number M300), the contents of which are incorporated herein by reference in their entirety.

Method and devices known in the art for multi-administration to cells, organs and tissues are contemplated for use in conjunction with the methods and compositions disclosed herein as embodiments of the present invention. These include, for example, those methods and devices having multiple needles, hybrid devices employing for example lumens or catheters as well as devices utilizing heat, electric current or radiation driven mechanisms.

According to the present invention, these multi-administration devices may be utilized to deliver the single, multi- or split doses contemplated herein. Such devices are taught for example in, International Application PCT/US2013/30062 filed Mar. 9, 2013 (Attorney Docket Number M300), the contents of which are incorporated herein by reference in their entirety.

In one embodiment, the NAV is administered subcutaneously or intramuscularly via at least 3 needles to three different, optionally adjacent, sites simultaneously, or within a 60 minutes period (e.g., administration to 4, 5, 6, 7, 8, 9, or 10 sites simultaneously or within a 60 minute period).

Methods and Devices Utilizing Catheters and/or Lumens

Methods and devices using catheters and lumens may be employed to administer the NAVs of the present invention on a single, multi- or split dosing schedule. Such methods and devices are described in International Application PCT/US2013/30062 filed Mar. 9, 2013 (Attorney Docket Number M300), the contents of which are incorporated herein by reference in their entirety.

Methods and Devices Utilizing Electrical Current

Methods and devices utilizing electric current may be employed to deliver the NAVs of the present invention according to the single, multi- or split dosing regimens taught herein. Such methods and devices are described in International Application PCT/US2013/30062 filed Mar. 9, 2013 (Attorney Docket Number M300), the contents of which are incorporated herein by reference in their entirety.

VII. Definitions

At various places in the present specification, substituents of compounds of the present disclosure are disclosed in groups or in ranges. It is specifically intended that the present disclosure include each and every individual subcombination of the members of such groups and ranges. For example, the term “C_1-6alkyl” is specifically intended to individually disclose methyl, ethyl, C₃alkyl, C₄alkyl, Cs alkyl, and C₆alkyl. Herein a phrase of the form “optionally substituted X” (e.g., optionally substituted alkyl) is intended to be equivalent to “X, wherein X is optionally substituted” (e.g., “alkyl, wherein said alkyl is optionally substituted”). It is not intended to mean that the feature “X” (e.g. alkyl) per se is optional.

About: As used herein, the term “about” means+/−10% of the recited value.

Administered in combination: As used herein, the term “administered in combination” or “combined administration” means that two or more agents are administered to a subject at the same time or within an interval such that there may be an overlap of an effect of each agent on the patient. In some embodiments, they are administered within about 60, 30, 15, 10, 5, or 1 minute of one another. In some embodiments, the administrations of the agents are spaced sufficiently closely together such that a combinatorial (e.g., a synergistic) effect is achieved.

Adjuvant: As used herein, the term “adjuvant” means a substance that enhances a subject's immune response to an antigen. The NAVs of the present invention may optionally comprise one or more adjuvants.

Animal: As used herein, the term “animal” refers to any member of the animal kingdom. In some embodiments, “animal” refers to humans at any stage of development. In some embodiments, “animal” refers to non-human animals at any stage of development. In certain embodiments, the non-human animal is a mammal (e.g., a rodent, a mouse, a rat, a rabbit, a monkey, a dog, a cat, a sheep, cattle, a primate, or a pig). In some embodiments, animals include, but are not limited to, mammals, birds, reptiles, amphibians, fish, and worms. In some embodiments, the animal is a transgenic animal, genetically-engineered animal, or a clone.

Antigen: As defined herein, the term “antigen” or “antibody generator” (“Ag”) refers to a composition, for example, a substance or agent which causes an immune response in an organism, e.g., causes the immune response of the organism to produce antibodies against the substance or agent in particular, which provokes an adaptive immune response in an organism. Antigens can be any immunogenic substance including, in particular, proteins, polypeptides, polysaccharides, nucleic acids, lipids and the like. Exemplary antigens are derived from infectious agents. Such agents can include parts or subunits of infectious agents, for example, coats, coat components, e.g., coat protein or polypeptides, surface components, e.g., surface proteins or polypeptides, capsule components, cell wall components, flagella, fimbrae, and/or toxins or toxoids) of infectious agents, for example, bacteria, viruses, and other microorganisms. Certain antigens, for example, lipids and/or nucleic acids are antigenic, preferably, when combined with proteins and/or polysaccharides.

Antigens of interest or desired antigens: As used herein, the terms “antigens of interest” or “desired antigens” include those proteins and other biomolecules provided herein that are components of or encoded by polynucleotides which are components of one or more NAVs.

Approximately: As used herein, the term “approximately” or “about,” as applied to one or more values of interest, refers to a value that is similar to a stated reference value. In certain embodiments, the term “approximately” or “about” refers to a range of values that fall within 25%, 20%, 19%, 18%, 17%, 16%, 15%, 14%, 13%, 12%, 11%, 10%, 9%, 8%, 7%, 6%, 5%, 4%, 3%, 2%, 1%, or less in either direction (greater than or less than) of the stated reference value unless otherwise stated or otherwise evident from the context (except where such number would exceed 100% of a possible value).

Associated with: As used herein, the terms “associated with,” “conjugated,” “linked,” “attached,” and “tethered,” when used with respect to two or more moieties, means that the moieties are physically associated or connected with one another, either directly or via one or more additional moieties that serves as a linking agent, to form a structure that is sufficiently stable so that the moieties remain physically associated under the conditions in which the structure is used, e.g., physiological conditions. An “association” need not be strictly through direct covalent chemical bonding. It may also suggest ionic or hydrogen bonding or a hybridization based connectivity sufficiently stable such that the “associated” entities remain physically associated.

Bifunctional: As used herein, the term “bifunctional” refers to any substance, molecule or moiety which is capable of or maintains at least two functions. The functions may effect the same outcome or a different outcome. The structure that produces the function may be the same or different. For example, bifunctional modified RNAs of the present invention may encode a cytotoxic peptide (a first function) while those nucleosides which comprise the encoding RNA are, in and of themselves, cytotoxic (second function). In this example, delivery of the bifunctional modified RNA to a cancer cell would produce not only a peptide or protein molecule which may ameliorate or treat the cancer but would also deliver a cytotoxic payload of nucleosides to the cell should degradation, instead of translation of the modified RNA, occur.

Biocompatible: As used herein, the term “biocompatible” means compatible with living cells, tissues, organs or systems posing little to no risk of injury, toxicity or rejection by the immune system.

Biodegradable: As used herein, the term “biodegradable” means capable of being broken down into innocuous products by the action of living things.

Biologically active: As used herein, the phrase “biologically active” refers to a characteristic of any substance that has activity in a biological system and/or organism. For instance, a substance that, when administered to an organism, has a biological effect on that organism, is considered to be biologically active. In particular embodiments, a polynucleotide of the present invention may be considered biologically active if even a portion of the polynucleotides is biologically active or mimics an activity considered biologically relevant.

Cancer stem cells: As used herein, “cancer stem cells” are cells that can undergo self-renewal and/or abnormal proliferation and differentiation to form a tumor.

Chemical terms: The following provides the definition of various chemical terms from “acyl” to “thiol.”

The term “acyl,” as used herein, represents a hydrogen or an alkyl group (e.g., a haloalkyl group), as defined herein, that is attached to the parent molecular group through a carbonyl group, as defined herein, and is exemplified by formyl (i.e., a carboxyaldehyde group), acetyl, trifluoroacetyl, propionyl, butanoyl and the like. Exemplary unsubstituted acyl groups include from 1 to 7, from 1 to 11, or from 1 to 21 carbons. In some embodiments, the alkyl group is further substituted with 1, 2, 3, or 4 substituents as described herein.

Non-limiting examples of optionally substituted acyl groups include, alkoxycarbonyl, alkoxycarbonylacyl, arylalkoxycarbonyl, aryloyl, carbamoyl, carboxyaldehyde, (heterocyclyl) imino, and (heterocyclyl)oyl:

The “alkoxycarbonyl” group, which as used herein, represents an alkoxy, as defined herein, attached to the parent molecular group through a carbonyl atom (e.g., —C(O)—OR, where R is H or an optionally substituted C_1-6, C_1-10, or C_1-20alkyl group). Exemplary unsubstituted alkoxycarbonyl include from 1 to 21 carbons (e.g., from 1 to 11 or from 1 to 7 carbons). In some embodiments, the alkoxy group is further substituted with 1, 2, 3, or 4 substituents as described herein.

The “alkoxycarbonylacyl” group, which as used herein, represents an acyl group, as defined herein, that is substituted with an alkoxycarbonyl group, as defined herein (e.g., —C(O)-alkyl-C(O)—OR, where R is an optionally substituted C_1-6, C_1-10, or C_1-20alkyl group). Exemplary unsubstituted alkoxycarbonylacyl include from 3 to 41 carbons (e.g., from 3 to 10, from 3 to 13, from 3 to 17, from 3 to 21, or from 3 to 31 carbons, such as C_1-6alkoxycarbonyl-C_1-6acyl, C_1-10alkoxycarbonyl-C_1-10acyl, or C_1-20alkoxycarbonyl-C_1-20acyl). In some embodiments, each alkoxy and alkyl group is further independently substituted with 1, 2, 3, or 4 substituents, as described herein (e.g., a hydroxy group) for each group.

The “arylalkoxycarbonyl” group, which as used herein, represents an arylalkoxy group, as defined herein, attached to the parent molecular group through a carbonyl (e.g., —C(O)—O-alkyl-aryl). Exemplary unsubstituted arylalkoxy groups include from 8 to 31 carbons (e.g., from 8 to 17 or from 8 to 21 carbons, such as C_6-10aryl-C_1-6alkoxy-carbonyl, C_6-10aryl-C_1-10alkoxy-carbonyl, or C_6-10aryl-C_1-20alkoxy-carbonyl). In some embodiments, the arylalkoxycarbonyl group can be substituted with 1, 2, 3, or 4 substituents as defined herein.

The “aryloyl” group, which as used herein, represents an aryl group, as defined herein, that is attached to the parent molecular group through a carbonyl group. Exemplary unsubstituted aryloyl groups are of 7 to 11 carbons. In some embodiments, the aryl group can be substituted with 1, 2, 3, or 4 substituents as defined herein.

The “carbamoyl” group, which as used herein, represents —C(O)—N(R^N1)₂, where the meaning of each R^N1is found in the definition of “amino” provided herein.

The “carboxyaldehyde” group, which as used herein, represents an acyl group having the structure —CHO.

The “(heterocyclyl) imino” group, which as used herein, represents a heterocyclyl group, as defined herein, attached to the parent molecular group through an imino group. In some embodiments, the heterocyclyl group can be substituted with 1, 2, 3, or 4 substituent groups as defined herein.

The “(heterocyclyl)oyl” group, which as used herein, represents a heterocyclyl group, as defined herein, attached to the parent molecular group through a carbonyl group. In some embodiments, the heterocyclyl group can be substituted with 1, 2, 3, or 4 substituent groups as defined herein.

The term “alkyl,” as used herein, is inclusive of both straight chain and branched chain saturated groups from 1 to 20 carbons (e.g., from 1 to 10 or from 1 to 6), unless otherwise specified. Alkyl groups are exemplified by methyl, ethyl, n- and iso-propyl, n-, sec-, iso- and tert-butyl, neopentyl, and the like, and may be optionally substituted with one, two, three, or, in the case of alkyl groups of two carbons or more, four substituents independently selected from the group consisting of: (1) C_1-6alkoxy; (2) C_1-6alkylsulfinyl; (3) amino, as defined herein (e.g., unsubstituted amino (i.e., —NH₂) or a substituted amino (i.e., —N(R^N1)₂, where R^N1is as defined for amino); (4) C_6-10aryl-C_1-6alkoxy; (5) azido; (6) halo; (7) (C_2-9heterocyclyl)oxy; (8) hydroxy, optionally substituted with an O-protecting group; (9) nitro; (10) oxo (e.g., carboxyaldehyde or acyl): (11) C_1-7spirocyclyl: (12) thioalkoxy; (13) thiol; (14) —CO₂R^A′, optionally substituted with an O-protecting group and where R^A′ is selected from the group consisting of (a) C_1-20alkyl (e.g., C_1-6alkyl), (b) C_2-20alkenyl (e.g., C_2-6alkenyl), (c) C_6-10aryl, (d) hydrogen, (e) C_1-6alk-C_6-10aryl, (f) amino-C_1-20alkyl, (g) polyethylene glycol of —(CH₂)_s2(OCH₂CH₂)_s1(CH₂)_s3OR′, wherein s1 is an integer from 1 to 10 (e.g., from 1 to 6 or from 1 to 4), each of s2 and s3, independently, is an integer from 0 to 10 (e.g., from 0 to 4, from 0 to 6, from 1 to 4, from 1 to 6, or from 1 to 10), and R′ is H or C_1-20alkyl, and (h) amino-polyethylene glycol of —NR^N1(CH₂)_s2(CH₂CH₂O)(CH₂)_s3NR^N1, wherein s1 is an integer from 1 to 10 (e.g., from 1 to 6 or from 1 to 4), each of s2 and s3, independently, is an integer from 0 to 10 (e.g., from 0 to 4, from 0 to 6, from 1 to 4, from 1 to 6, or from 1 to 10), and each R^N1is, independently, hydrogen or optionally substituted C_1-6alkyl;

- (15) —C(O)NR^B′R^C′, where each of R^B′ and R^C′ is, independently, selected from the group consisting of (a) hydrogen, (b) C_1-6alkyl, (c) C_6-10aryl, and (d) C_1-6alk-C_6-10aryl; (16) —SO₂R^D′, where R^D′ is selected from the group consisting of (a) C_1-6alkyl, (b) C_6-10aryl, (c) C_1-6alk-C_6-10aryl, and (d) hydroxy; (17) —SO₂NR^E′R^F′, where each of R^E′and R^F′is, independently, selected from the group consisting of (a) hydrogen, (b) C_1-6alkyl, (c) C_6-10aryl and (d) C_1-6alk-C_6-10aryl; (18) —C(O)R^G′, where R^G′ is selected from the group consisting of (a) C_1-20alkyl (e.g., C_1-6alkyl), (b) C_2-20alkenyl (e.g., C_2-6alkenyl), (c) C_6-10, aryl, (d) hydrogen. (e) C_1-6alk-C(Oo aryl, (f) amino-C_1-20alkyl, (g) polyethylene glycol of —(CH₂)_s2(OCH₂CH₂)_s1(CH₂)_s3OR′, wherein s1 is an integer from 1 to 10 (e.g., from 1 to 6 or from 1 to 4), each of s2 and s3, independently, is an integer from 0 to 10 (e.g., from 0 to 4, from 0 to 6, from 1 to 4, from 1 to 6, or from 1 to 10), and R′ is H or C_1-20alkyl, and (h) amino-polyethylene glycol of —NR^N1(CH₂)_s2(CH₂CH₂O)_s1(CH₂)_s3NR^N1, wherein s1 is an integer from 1 to 10 (e.g., from 1 to 6 or from 1 to 4), each of s2 and s3, independently, is an integer from 0 to 10 (e.g., from 0 to 4, from 0 to 6, from 1 to 4, from 1 to 6, or from 1 to 10), and each R^N1is, independently, hydrogen or optionally substituted C_1-6alkyl; (19) —NR^H′C(O)R^I′, wherein R^H′ is selected from the group consisting of (a1) hydrogen and (b1) C_1-6alkyl, and R^I′ is selected from the group consisting of (a2) C_1-20alkyl (e.g., C_1-6alkyl), (b2) C_2-20alkenyl (e.g., C_2-6alkenyl), (c2) C_6-10aryl, (d2) hydrogen, (e2) C_1-6alk-C_6-10aryl, (12) amino-C_1-20alkyl, (g2) polyethylene glycol of —(CH₂)_s2(OCH₂CH₂)_s1(CH₂)_s3OR′, wherein s1 is an integer from 1 to 10 (e.g., from 1 to 6 or from 1 to 4), each of s2 and s3, independently, is an integer from 0 to 10 (e.g., from 0 to 4, from 0 to 6, from 1 to 4, from 1 to 6, or from 1 to 10), and R′ is H or C_1-20alkyl, and (h2) amino-polyethylene glycol of —NR^N1(CH₂)_s2(CH₂CH₂O)_s1(CH₂)_s3NR^N1, wherein s1 is an integer from 1 to 10 (e.g., from 1 to 6 or from 1 to 4), each of s2 and s3, independently, is an integer from 0 to 10 (e.g., from 0 to 4, from 0 to 6, from 1 to 4, from 1 to 6, or from 1 to 10), and each R^N1is, independently, hydrogen or optionally substituted C_1-6alkyl; (20) —NR^J′C(O)OR^K′, wherein R^J′ is selected from the group consisting of (a1) hydrogen and (b1) C_1-6alkyl, and R^K′ is selected from the group consisting of (a2) C_1-20alkyl (e.g., C_1-6alkyl), (b2) C_2-20alkenyl (e.g., C_2-6alkenyl), (c2) C_6-10aryl, (d2) hydrogen, (e2) C_1-6alk-C_6-10aryl, (f2) amino-C_1-20alkyl, (g2) polyethylene glycol of —(CH₂)_s2(OCH₂CH₂)_s1(CH₂)_s3OR′, wherein s1 is an integer from 1 to 10 (e.g., from 1 to 6 or from 1 to 4), each of s2 and s3, independently, is an integer from 0 to 10 (e.g., from 0 to 4, from 0 to 6, from 1 to 4, from 1 to 6, or from 1 to 10), and R′ is H or C_1-20alkyl, and (h2) amino-polyethylene glycol of —NR^N1(CH₂)_s2(CH₂CH₂O)_s1(CH₂)_s3NR^N1, wherein s1 is an integer from 1 to 10 (e.g., from 1 to 6 or from 1 to 4), each of s2 and s3, independently, is an integer from 0 to 10 (e.g., from 0 to 4, from 0 to 6, from 1 to 4, from 1 to 6, or from 1 to 10), and each R^N1is, independently, hydrogen or optionally substituted C_1-6alkyl; and (21) amidine. In some embodiments, each of these groups can be further substituted as described herein. For example, the alkylene group of a C₁-alkaryl can be further substituted with an oxo group to afford the respective aryloyl substituent.

The term “alkylene,” as used herein, represent a saturated divalent hydrocarbon group derived from a straight or branched chain saturated hydrocarbon by the removal of two hydrogen atoms, and is exemplified by methylene, ethylene, isopropylene, and the like. The term “C_x-yalkylene” and the prefix “C_x-yalk-” represent alkylene groups having between x and y carbons. Exemplary values for x are 1, 2, 3, 4, 5, and 6, and exemplary values for y are 2, 3, 4, 5, 6, 7, 8, 9, 10, 12, 14, 16, 18, or 20 (e.g., C_1-6, C_1-10, C_2-20, C_2-6, C_2-10, or C_2-20alkylene). In some embodiments, the alkylene can be further substituted with 1, 2, 3, or 4 substituent groups as defined herein for an alkyl group. Similarly, the suffix “-ene” appended to any group indicates that the group is a divalent group.

Non-limiting examples of optionally substituted alkyl and alkylene groups include acylaminoalkyl, acyloxyalkyl, alkoxyalkyl, alkoxycarbonylalkyl, alkylsulfinyl, alkylsulfinylalkyl, aminoalkyl, carbamoylalkyl, carboxyalkyl, carboxyaminoalkyl, haloalkyl, hydroxyalkyl, pertluoroalkyl, and sulfoalkyl:

The “acylaminoalkyl” group, which as used herein, represents an acyl group, as defined herein, attached to an amino group that is in turn attached to the parent molecular group through an alkylene group, as defined herein (i.e., -alkyl-N(R^N1)—C(O)—R, where R is H or an optionally substituted C_1-6, C_1-10, or C_1-20alkyl group (e.g., haloalkyl) and R^N1is as defined herein). Exemplary unsubstituted acylaminoalkyl groups include from 1 to 41 carbons (e.g., from 1 to 7, from 1 to 13, from 1 to 21, from 2 to 7, from 2 to 13, from 2 to 21, or from 2 to 41 carbons). In some embodiments, the alkylene group is further substituted with 1, 2, 3, or 4 substituents as described herein, and/or the amino group is —NH₂or —NHR^N1, wherein R^N1is, independently, OH, NO₂, NH₂, NR^N2₂, SO₂OR^N2, SO₂R^N2, SOR^N2, alkyl, aryl, acyl (e.g., acetyl, trifluoroacetyl, or others described herein), or alkoxycarbonylalkyl, and each R^N2can be H, alkyl, or aryl.

The “acyloxyalkyl” group, which as used herein, represents an acyl group, as defined herein, attached to an oxygen atom that in turn is attached to the parent molecular group though an alkylene group (i.e., -alkyl-O—C(O)—R, where R is H or an optionally substituted C_1-6, C_1-10, or C_1-20alkyl group). Exemplary unsubstituted acyloxyalkyl groups include from 1 to 21 carbons (e.g., from 1 to 7 or from 1 to 11 carbons). In some embodiments, the alkylene group is, independently, further substituted with 1, 2, 3, or 4 substituents as described herein.

The “alkoxyalkyl” group, which as used herein, represents an alkyl group that is substituted with an alkoxy group. Exemplary unsubstituted alkoxyalkyl groups include between 2 to 40 carbons (e.g., from 2 to 12 or from 2 to 20 carbons, such as C_1-6alkoxy-C_1-6alkyl, C_1-10alkoxy-C_1-10alkyl, or C_1-20alkoxy-C_1-20alkyl). In some embodiments, the alkyl and the alkoxy each can be further substituted with 1, 2, 3, or 4 substituent groups as defined herein for the respective group.

The “alkoxycarbonylalkyl” group, which as used herein, represents an alkyl group, as defined herein, that is substituted with an alkoxycarbonyl group, as defined herein (e.g., -alkyl-C(O)—OR, where R is an optionally substituted C_1-20, C_1-10, or C_1-6alkyl group). Exemplary unsubstituted alkoxycarbonylalkyl include from 3 to 41 carbons (e.g., from 3 to 10, from 3 to 13, from 3 to 17, from 3 to 21, or from 3 to 31 carbons, such as C_1-6alkoxycarbonyl-C_1-6alkyl, C_1-10alkoxycarbonyl-C_1-10alkyl, or C_1-20alkoxycarbonyl-C_1-20alkyl). In some embodiments, each alkyl and alkoxy group is further independently substituted with 1, 2, 3, or 4 substituents as described herein (e.g., a hydroxy group).

The “alkylsulfinylalkyl” group, which as used herein, represents an alkyl group, as defined herein, substituted with an alkylsulfinyl group. Exemplary unsubstituted alkylsulfinylalkyl groups are from 2 to 12, from 2 to 20, or from 2 to 40 carbons. In some embodiments, each alkyl group can be further substituted with 1, 2, 3, or 4 substituent groups as defined herein.

The “aminoalkyl” group, which as used herein, represents an alkyl group, as defined herein, substituted with an amino group, as defined herein. The alkyl and amino each can be further substituted with 1, 2, 3, or 4 substituent groups as described herein for the respective group (e.g., CO₂R^A′, where R^A′ is selected from the group consisting of (a) C_1-6alkyl, (b) C_6-10aryl, (c) hydrogen, and (d) C_1-6alk-C_6-10aryl, e.g., carboxy, and/or an N-protecting group).

The “carbamoylalkyl” group, which as used herein, represents an alkyl group, as defined herein, substituted with a carbamoyl group, as defined herein. The alkyl group can be further substituted with 1, 2, 3, or 4 substituent groups as described herein.

The “carboxyalkyl” group, which as used herein, represents an alkyl group, as defined herein, substituted with a carboxy group, as defined herein. The alkyl group can be further substituted with 1, 2, 3, or 4 substituent groups as described herein, and the carboxy group can be optionally substituted with one or more 0-protecting groups.

The “carboxyaminoalkyl” group, which as used herein, represents an aminoalkyl group, as defined herein, substituted with a carboxy, as defined herein. The carboxy, alkyl, and amino each can be further substituted with 1, 2, 3, or 4 substituent groups as described herein for the respective group (e.g., CO₂R^A′, where R^A′ is selected from the group consisting of (a) C_1-6alkyl, (b) C_6-10aryl, (c) hydrogen, and (d) C₄, alk-C_6-10aryl, e.g., carboxy, and/or an N-protecting group, and/or an O-protecting group).

The “haloalkyl” group, which as used herein, represents an alkyl group, as defined herein, substituted with a halogen group (i.e., F, Cl, Br, or 1). A haloalkyl may be substituted with one, two, three, or, in the case of alkyl groups of two carbons or more, four halogens. Haloalkyl groups include perfluoroalkyls (e.g., —CF₃), —CHF₂, —CH₂F, —CCl₃, —CH₂CH₂Br, —CH₂CH(CH₂CH₂Br)CH₃, and —CHICH₃. In some embodiments, the haloalkyl group can be further substituted with 1, 2, 3, or 4 substituent groups as described herein for alkyl groups.

The “hydroxyalkyl” group, which as used herein, represents an alkyl group, as defined herein, substituted with one to three hydroxy groups, with the proviso that no more than one hydroxy group may be attached to a single carbon atom of the alkyl group, and is exemplified by hydroxymethyl, dihydroxypropyl, and the like. In some embodiments, the hydroxyalkyl group can be substituted with 1, 2, 3, or 4 substituent groups (e.g., O-protecting groups) as defined herein for an alkyl.

The “perfluoroalkyl” group, which as used herein, represents an alkyl group, as defined herein, where each hydrogen radical bound to the alkyl group has been replaced by a fluoride radical. Perfluoroalkyl groups are exemplified by trifluoromethyl, pentafluoroethyl, and the like.

The “sulfoalkyl” group, which as used herein, represents an alkyl group, as defined herein, substituted with a sulfo group of —SO₃H. In some embodiments, the alkyl group can be further substituted with 1, 2, 3, or 4 substituent groups as described herein, and the sulfo group can be further substituted with one or more O-protecting groups (e.g., as described herein).

The term “alkenyl,” as used herein, represents monovalent straight or branched chain groups of, unless otherwise specified, from 2 to 20 carbons (e.g., from 2 to 6 or from 2 to 10 carbons) containing one or more carbon-carbon double bonds and is exemplified by ethenyl, 1-propenyl, 2-propenyl, 2-methyl-1-propenyl, 1-butenyl, 2-butenyl, and the like. Alkenyls include both cis and trans isomers. Alkenyl groups may be optionally substituted with 1, 2, 3, or 4 substituent groups that are selected, independently, from amino, aryl, cycloalkyl, or heterocyclyl (e.g., heteroaryl), as defined herein, or any of the exemplary alkyl substituent groups described herein.

Non-limiting examples of optionally substituted alkenyl groups include, alkoxycarbonylalkenyl, aminoalkenyl, and hydroxyalkenyl:

The “alkoxycarbonylalkenyl” group, which as used herein, represents an alkenyl group, as defined herein, that is substituted with an alkoxycarbonyl group, as defined herein (e.g., -alkenyl-C(O)—OR, where R is an optionally substituted C_1-20, C_1-10, or C_1-6alkyl group). Exemplary unsubstituted alkoxycarbonylalkenyl include from 4 to 41 carbons (e.g., from 4 to 10, from 4 to 13, from 4 to 17, from 4 to 21, or from 4 to 31 carbons, such as C_1-6alkoxycarbonyl-C₂-6 alkenyl, C₁-10 alkoxycarbonyl-C₂-10 alkenyl, or C_1-20alkoxycarbonyl-C₂-20 alkenyl). In some embodiments, each alkyl, alkenyl, and alkoxy group is further independently substituted with 1, 2, 3, or 4 substituents as described herein (e.g., a hydroxy group).

The “aminoalkenyl” group, which as used herein, represents an alkenyl group, as defined herein, substituted with an amino group, as defined herein. The alkenyl and amino each can be further substituted with 1, 2, 3, or 4 substituent groups as described herein for the respective group (e.g., CO₂R^A′, where R^A′ is selected from the group consisting of (a) C_1-6alkyl, (b) C_6-10aryl, (c) hydrogen, and (d) C_1-6alk-C_6-10aryl, e.g., carboxy, and/or an N-protecting group).

The “hydroxyalkenyl” group, which as used herein, represents an alkenyl group, as defined herein, substituted with one to three hydroxy groups, with the proviso that no more than one hydroxy group may be attached to a single carbon atom of the alkyl group, and is exemplified by dihydroxypropenyl, hydroxyisopentenyl, and the like. In some embodiments, the hydroxyalkenyl group can be substituted with 1, 2, 3, or 4 substituent groups (e.g., O-protecting groups) as defined herein for an alkyl.

The term “alkynyl,” as used herein, represents monovalent straight or branched chain groups from 2 to 20 carbon atoms (e.g., from 2 to 4, from 2 to 6, or from 2 to 10 carbons) containing a carbon-carbon triple bond and is exemplified by ethynyl, I-propynyl, and the like. Alkynyl groups may be optionally substituted with 1, 2, 3, or 4 substituent groups that are selected, independently, from aryl, cycloalkyl, or heterocyclyl (e.g., heteroaryl), as defined herein, or any of the exemplary alkyl substituent groups described herein.

Non-limiting examples of optionally substituted alkynyl groups include alkoxycarbonylalkynyl, aminoalkynyl, and hydroxyalkynyl:

The “alkoxycarbonylalkynyl” group, which as used herein, represents an alkynyl group, as defined herein, that is substituted with an alkoxycarbonyl group, as defined herein (e.g., -alkynyl-C(O)—OR, where R is an optionally substituted C_1-20, C_1-10, or C_1-6alkyl group). Exemplary unsubstituted alkoxycarbonylalkynyl include from 4 to 41 carbons (e.g., from 4 to 10, from 4 to 13, from 4 to 17, from 4 to 21, or from 4 to 31 carbons, such as C_1-6alkoxycarbonyl-C_2-6alkynyl, C_1-10alkoxycarbonyl-C_2-10alkynyl, or C_1-20alkoxycarbonyl-C_2-20alkynyl). In some embodiments, each alkyl, alkynyl, and alkoxy group is further independently substituted with 1, 2, 3, or 4 substituents as described herein (e.g., a hydroxy group).

The “aminoalkynyl” group, which as used herein, represents an alkynyl group, as defined herein, substituted with an amino group, as defined herein. The alkynyl and amino each can be further substituted with 1, 2, 3, or 4 substituent groups as described herein for the respective group (e.g., CO₂R^A′, where R^A′ is selected from the group consisting of (a) C_1-6alkyl, (b) C_6-10aryl, (c) hydrogen, and (d) C_1-6alk-C_6-10aryl, e.g., carboxy, and/or an N-protecting group).

The “hydroxyalkynyl” group, which as used herein, represents an alkynyl group, as defined herein, substituted with one to three hydroxy groups, with the proviso that no more than one hydroxy group may be attached to a single carbon atom of the alkyl group. In some embodiments, the hydroxyalkynyl group can be substituted with 1, 2, 3, or 4 substituent groups (e.g., O-protecting groups) as defined herein for an alkyl.

The term “amino,” as used herein, represents —N(R^N1)₂, wherein each R^N1is, independently, H, OH, NO₂, N(R^N2)₂, SO₂OR^N2, SO₂R^N2, SOR^N2, an N-protecting group, alkyl, alkenyl, alkynyl, alkoxy, aryl, alkaryl, cycloalkyl, alkcycloalkyl, carboxyalkyl (e.g., optionally substituted with an O-protecting group, such as optionally substituted arylalkoxycarbonyl groups or any described herein), sulfoalkyl, acyl (e.g., acetyl, trifluoroacetyl, or others described herein), alkoxycarbonylalkyl (e.g., optionally substituted with an O-protecting group, such as optionally substituted arylalkoxycarbonyl groups or any described herein), heterocyclyl (e.g., heteroaryl), or alkheterocyclyl (e.g., alkheteroaryl), wherein each of these recited R^N1groups can be optionally substituted, as defined herein for each group; or two R^N1combine to form a heterocyclyl or an N-protecting group, and wherein each R^N2 is, independently, H, alkyl, or aryl. The amino groups of the invention can be an unsubstituted amino (i.e., —NH₂) or a substituted amino (i.e., —N(R^N1)₂). In a preferred embodiment, amino is —NH₂or —NHR^N1, wherein R^N1is, independently, OH, NO₂, NH₂, NR^N2₂, SO₂ORN², SO₂R^N2, SOR^N2, alkyl, carboxyalkyl, sulfoalkyl, acyl (e.g., acetyl, trifluoroacetyl, or others described herein), alkoxycarbonylalkyl (e.g., t-butoxycarbonylalkyl) or aryl, and each R^N2can be H, C_1-20alkyl (e.g., C_1-6alkyl), or C_6-10aryl.

Non-limiting examples of optionally substituted amino groups include acylamino and carbamyl:

The “acylamino” group, which as used herein, represents an acyl group, as defined herein, attached to the parent molecular group though an amino group, as defined herein (i.e., —N(R^N1)—C(O)—R, where R is H or an optionally substituted C_1-6, C_1-10, or C_1-2alkyl group (e.g., haloalkyl) and R^N1is as defined herein). Exemplary unsubstituted acylamino groups include from 1 to 41 carbons (e.g., from 1 to 7, from 1 to 13, from 1 to 21, from 2 to 7, from 2 to 13, from 2 to 21, or from 2 to 41 carbons). In some embodiments, the alkyl group is further substituted with 1, 2, 3, or 4 substituents as described herein, and/or the amino group is —NH₂or —NHR^N1, wherein R^N1is, independently, OH, NO₂, NH₂, NR^N2₂, SO₂OR^N2, SO₂R^N2, SOR^N2, alkyl, aryl, acyl (e.g., acetyl, trifluoroacetyl, or others described herein), or alkoxycarbonylalkyl, and each R^N2can be H, alkyl, or aryl.

The “carbamyl” group, which as used herein, refers to a carbamate group having the structure —NR^N1C(═O)OR or —OC(═O)N(R^N1)₂, where the meaning of each R^N1is found in the definition of “amino” provided herein, and R is alkyl, cycloalkyl, alkcycloalkyl, aryl, alkaryl, heterocyclyl (e.g., heteroaryl), or alkheterocyclyl (e.g., alkheteroaryl), as defined herein.

The term “amino acid,” as described herein, refers to a molecule having a side chain, an amino group, and an acid group (e.g., a carboxy group of —CO₂H or a sulfo group of —SO₃H), wherein the amino acid is attached to the parent molecular group by the side chain, amino group, or acid group (e.g., the side chain). In some embodiments, the amino acid is attached to the parent molecular group by a carbonyl group, where the side chain or amino group is attached to the carbonyl group. Exemplary side chains include an optionally substituted alkyl, aryl, heterocyclyl, alkaryl, alkheterocyclyl, aminoalkyl, carbamoylalkyl, and carboxyalkyl. Exemplary amino acids include alanine, arginine, asparagine, aspartic acid, cysteine, glutamic acid, glutamine, glycine, histidine, hydroxynorvaline, isoleucine, leucine, lysine, methionine, norvaline, ornithine, phenylalanine, proline, pyrrolysine, selenocysteine, serine, taurine, threonine, tryptophan, tyrosine, and valine. Amino acid groups may be optionally substituted with one, two, three, or, in the case of amino acid groups of two carbons or more, four substituents independently selected from the group consisting of: (1) C_1-6alkoxy; (2) C_1-6alkylsulfinyl; (3) amino, as defined herein (e.g., unsubstituted amino (i.e., —NH₂) or a substituted amino (i.e., —N(R^N1)₂, where R^N1is as defined for amino); (4) C_6-10aryl-C_1-6alkoxy; (5) azido; (6) halo; (7) (C_2-9heterocyclyl)oxy; (8) hydroxy; (9) nitro; (10) oxo (e.g., carboxyaldehyde or acyl); (11) C_1-7spirocyclyl; (12) thioalkoxy; (13) thiol; (14) —CO₂R^A′, where R^A′ is selected from the group consisting of (a) C_1-20alkyl (e.g., C_1-6alkyl), (b) C_2-20alkenyl (e.g., C_2-6alkenyl), (c) C_6-10aryl, (d) hydrogen, (e) C_1-6alk-C_6-10aryl, (f) amino-C_1-20alkyl, (g) polyethylene glycol of —(CH₂)_s2(OCH₂CH₂)_s1(CH₂)_s3OR′, wherein s1 is an integer from 1 to 10 (e.g., from 1 to 6 or from 1 to 4), each of s2 and s3, independently, is an integer from 0 to 10 (e.g., from 0 to 4, from 0 to 6, from 1 to 4, from 1 to 6, or from 1 to 10), and R′ is H or C_1-20alkyl, and (h) amino-polyethylene glycol of —NR^N1(CH₂)_s2(CH₂CH₂O)_s1(CH₂)_s3NR^N1, wherein s1 is an integer from 1 to 10 (e.g., from 1 to 6 or from 1 to 4), each of s2 and s3, independently, is an integer from 0 to 10 (e.g., from 0 to 4, from 0 to 6, from 1 to 4, from 1 to 6, or from 1 to 10), and each R^N1is, independently, hydrogen or optionally substituted C_1-6alkyl; (15) —C(O)NR^B′R^C′, where each of R^B′ and R^C′ is, independently, selected from the group consisting of (a) hydrogen, (b) C_1-6alkyl, (c) C_6-10aryl, and (d) C_1-6alk-C_6-10aryl; (16) —SO₂R^D′, where R^D′ is selected from the group consisting of (a) C_1-6alkyl, (b) C_6-10aryl, (c) C_1-6alk-C_6-10aryl, and (d) hydroxy; (17) —SO₂NR^E′R^F′, where each of R^E′ and R^F′ is, independently, selected from the group consisting of (a) hydrogen, (b) C_1-6alkyl, (c) C_6-10aryl and (d) C_1-6alk-C_6-10aryl; (18) —C(O)R^G′—, where R^G′ is selected from the group consisting of (a) C_1-20alkyl (e.g., C_1-6alkyl), (b) C_2-20alkenyl (e.g., C_2-6alkenyl), (c) C_6-10aryl, (d) hydrogen, (e) C_1-6alk-C_6-10aryl, (f) amino-C_1-20alkyl, (g) polyethylene glycol of —(CH₂)_s2(OCH₂CH₂)_s1(CH₂)_s3OR′, wherein s1 is an integer from 1 to 10 (e.g., from 1 to 6 or from 1 to 4), each of s2 and s3, independently, is an integer from 0 to 10 (e.g., from 0 to 4, from 0 to 6, from 1 to 4, from 1 to 6, or from 1 to 10), and R′ is H or C_1-20alkyl, and (h) amino-polyethylene glycol of —NR^N1(CH₂)_s2(CH₂CH₂O)_s1(CH₂)_s3NR^N1, wherein s1 is an integer from 1 to 10 (e.g., from 1 to 6 or from 1 to 4), each of s2 and s3, independently, is an integer from 0 to 10 (e.g., from 0 to 4, from 0 to 6, from 1 to 4, from 1 to 6, or from 1 to 10), and each R^N1is, independently, hydrogen or optionally substituted C_1-6alkyl; (19) —NR^H′C(O)R^I′, wherein R^H′ is selected from the group consisting of (al) hydrogen and (b1) C_1-6alkyl, and R^H′ is selected from the group consisting of (a2) C_1-20alkyl (e.g., C_1-6alkyl), (b2) C_2-20alkenyl (e.g., C_2-6alkenyl), (c2) C_6-10aryl, (d2) hydrogen, (e2) C_1-6alk-C_6-10aryl, (f2) amino-C_1-20alkyl, (g2) polyethylene glycol of —(CH₂)_s2(OCH₂CH₂)_s1(CH₂)_s3OR′, wherein s1 is an integer from 1 to 10 (e.g., from 1 to 6 or from 1 to 4), each of s2 and s3, independently, is an integer from 0 to 10 (e.g., from 0 to 4, from 0 to 6, from 1 to 4, from 1 to 6, or from 1 to 10), and R′ is H or C_1-20alkyl, and (h2) amino-polyethylene glycol of —NR^N1(CH₂)_s2(CH₂CH₂O)_s1(CH₂)_s3NR^N1, wherein s1 is an integer from 1 to 10 (e.g., from 1 to 6 or from 1 to 4), each of s2 and s3, independently, is an integer from 0 to 10 (e.g., from 0 to 4, from 0 to 6, from 1 to 4, from 1 to 6, or from 1 to 10), and each R^N1is, independently, hydrogen or optionally substituted C_1-6alkyl; (20) —NR^J′C(O)OR^K′, wherein R^J′ is selected from the group consisting of (a1) hydrogen and (b1) C_1-6alkyl, and R^K′is selected from the group consisting of (a2) C_1-20alkyl (e.g., C_1-6alkyl), (b2) C_2-20alkenyl (e.g., C_2-6alkenyl), (c2) C_6-10aryl, (d2) hydrogen, (e2) C_1-6alk-C_6-10aryl, (f2) amino-C_1-20alkyl, (g2) polyethylene glycol of —(CH₂)_s2(OCH₂CH₂)_s1(CH₂)_s3OR′, wherein s1 is an integer from 1 to 10 (e.g., from 1 to 6 or from 1 to 4), each of s2 and s3, independently, is an integer from 0 to 10 (e.g., from 0 to 4, from 0 to 6, from 1 to 4, from 1 to 6, or from 1 to 10), and R′ is H or C_1-20alkyl, and (h2) amino-polyethylene glycol of —NR^N1(CH₂)_s2(CH₂CH₂O)_s1(CH₂)_s3NR^N1, wherein s1 is an integer from 1 to 10 (e.g., from 1 to 6 or from 1 to 4), each of s2 and s3, independently, is an integer from 0 to 10 (e.g., from 0 to 4, from 0 to 6, from 1 to 4, from 1 to 6, or from 1 to 10), and each R^N1is, independently, hydrogen or optionally substituted C_1-6alkyl; and (21) amidine. In some embodiments, each of these groups can be further substituted as described herein.

The term “aryl,” as used herein, represents a mono-, bicyclic, or multicyclic carbocyclic ring system having one or two aromatic rings and is exemplified by phenyl, naphthyl, 1,2-dihydronaphthyl, 1,2,3,4-tetrahydronaphthyl, anthracenyl, phenanthrenyl, fluorenyl, indanyl, indenyl, and the like, and may be optionally substituted with 1, 2, 3, 4, or 5 substituents independently selected from the group consisting of: (1) C_1-7acyl (e.g., carboxyaldehyde); (2) C_1-20alkyl (e.g., C_1-6alkyl, C_1-6alkoxy-C_1-6alkyl, C_1-6alkylsulfinyl-C_1-6alkyl, amino-C_1-6alkyl, azido-C_1-6alkyl, (carboxyaldehyde)-C_1-6alkyl, halo-C_1-6alkyl (e.g., pertluoroalkyl), hydroxy-C_1-6alkyl, nitro-C_1-6alkyl, or C_1-6thioalkoxy-C_1-6alkyl); (3) C_1-20alkoxy (e.g., C_1-6alkoxy, such as perfluoroalkoxy); (4) C_1-6alkylsulfinyl; (5) C_6-10aryl; (6) amino; (7) C_1-6alk-C_6-10aryl; (8) azido; (9) C_3-8cycloalkyl; (10) C_1-6alk-C_3-8cycloalkyl; (11) halo; (12) C_1-12heterocyclyl (e.g., C_1-12heteroaryl); (13) (C_1-12heterocyclyl)oxy; (14) hydroxy; (15) nitro; (16) C_1-20thioalkoxy (e.g., C_1-6thioalkoxy); (17) —(CH₂)_qCO₂R^A′, where q is an integer from zero to four, and R^A′ is selected from the group consisting of (a) C_1-6alkyl, (b) C_6-10aryl, (c) hydrogen, and (d) C_1-6alk-C_6-10aryl; (18) —(CH₂)_qCONR^B′R^C′, where q is an integer from zero to four and where R^B′ and R^C′ are independently selected from the group consisting of (a) hydrogen, (b) C_1-6alkyl, (c) C_6-10aryl, and (d) C_1-6alk-C_6-10aryl; (19) —(CH₂)_qSO₂R^D′, where q is an integer from zero to four and where R^D′ is selected from the group consisting of (a) alkyl, (b) C_6-10aryl, and (c) alk-C_6-10aryl; (20) —(CH₂)_qSO₂NR^E′R^F′, where q is an integer from zero to four and where each of R^E′ and R^F′ is, independently, selected from the group consisting of (a) hydrogen, (b) C_1-6alkyl, (c) C_6-10aryl, and (d) C_1-6alk-C_6-10aryl; (21) thiol; (22) C_6-10aryloxy; (23) C_3-8cycloalkoxy; (24) C_6-10aryl-C_1-6alkoxy; (25) C_1-6alk-C_1-12heterocyclyl (e.g., C_1-6alk-C_1-12heteroaryl): (26) C_2-20alkenyl; and (27) C_2-20alkynyl. In some embodiments, each of these groups can be further substituted as described herein. For example, the alkylene group of a C₁-alkaryl or a C₁-alkheterocyclyl can be further substituted with an oxo group to afford the respective aryloyl and (heterocyclyl)oyl substituent group.

The “arylalkyl” group, which as used herein, represents an aryl group, as defined herein, attached to the parent molecular group through an alkylene group, as defined herein. Exemplary unsubstituted arylalkyl groups are from 7 to 30 carbons (e.g., from 7 to 16 or from 7 to 20 carbons, such as C_1-6alk-C_6-10aryl, C_1-10alk-C_6-10aryl, or C_1-20alk-C_6-10aryl). In some embodiments, the alkylene and the aryl each can be further substituted with 1, 2, 3, or 4 substituent groups as defined herein for the respective groups. Other groups preceded by the prefix “alk-” are defined in the same manner, where “alk” refers to a C_1-6alkylene, unless otherwise noted, and the attached chemical structure is as defined herein.

The term “azido” represents an —N₃group, which can also be represented as —N═N═N.

The term “bicyclic,” as used herein, refer to a structure having two rings, which may be aromatic or non-aromatic. Bicyclic structures include spirocyclyl groups, as defined herein, and two rings that share one or more bridges, where such bridges can include one atom or a chain including two, three, or more atoms. Exemplary bicyclic groups include a bicyclic carbocyclyl group, where the first and second rings are carbocyclyl groups, as defined herein; a bicyclic aryl groups, where the first and second rings are aryl groups, as defined herein; bicyclic heterocyclyl groups, where the first ring is a heterocyclyl group and the second ring is a carbocyclyl (e.g., aryl) or heterocyclyl (e.g., heteroaryl) group; and bicyclic heteroaryl groups, where the first ring is a heteroaryl group and the second ring is a carbocyclyl (e.g., aryl) or heterocyclyl (e.g., heteroaryl) group. In some embodiments, the bicyclic group can be substituted with 1, 2, 3, or 4 substituents as defined herein for cycloalkyl, heterocyclyl, and aryl groups.

The term “boranyl,” as used herein, represents —B(R^B1)₃, where each RB¹is, independently, selected from the group consisting of H and optionally substituted alkyl. In some embodiments, the boranyl group can be substituted with 1, 2, 3, or 4 substituents as defined herein for alkyl.

The terms “carbocyclic” and “carbocyclyl,” as used herein, refer to an optionally substituted C_3-12monocyclic, bicyclic, or tricyclic structure in which the rings, which may be aromatic or non-aromatic, are formed by carbon atoms. Carbocyclic structures include cycloalkyl, cycloalkenyl, cycloalkynyl, and aryl groups.

The term “carbonyl,” as used herein, represents a C(O) group, which can also be represented as C═O.

The term “carboxy,” as used herein, means —CO₂H.

The term “cyano,” as used herein, represents an —CN group.

The term “cycloalkyl,” as used herein represents a monovalent saturated or unsaturated non-aromatic cyclic hydrocarbon group from three to eight carbons, unless otherwise specified, and is exemplified by cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, bicycle heptyl, and the like. When what would otherwise be a cycloalkyl group includes one or more carbon-carbon double bonds, the group is referred to as a “cycloalkenyl” group. For the purposes of this invention, cycloalkenyl excludes aryl groups. When what would otherwise be a cycloalkyl group includes one or more carbon-carbon triple bonds, the group is referred to as a “cycloalkynyl” group. Exemplary cycloalkenyl groups include cyclopentenyl, cyclohexenyl, and the like. The cycloalkyl groups of this invention can be optionally substituted with: (1) C_1-7acyl (e.g., carboxyaldehyde); (2) C_1-20alkyl (e.g., C_1-6alkyl, C_1-6alkoxy-C_1-6alkyl, C_1-6alkylsulfinyl-C_1-6alkyl, amino-C_1-6alkyl, azido-C_1-6alkyl, (carboxyaldehyde)-C_1-6alkyl, halo-C_1-6alkyl (e.g., perfluoroalkyl), hydroxy-C_1-6alkyl, nitro-C_1-6alkyl, or C_1-6thioalkoxy-C_1-6alkyl); (3) C_1-20alkoxy (e.g., C_1-6alkoxy, such as perfluoroalkoxy); (4) C_1-6alkylsulfinyl; (5) C_6-10aryl; (6) amino; (7) C_1-6alk-C_6-10aryl; (8) azido; (9) C_3-8cycloalkyl; (10) C_1-6alk-C_3-8cycloalkyl; (11) halo; (12) C_1-12heterocyclyl (e.g., C_1-12heteroaryl); (13) (C_1-12heterocyclyl)oxy; (14) hydroxy; (15) nitro; (16) C_1-20thioalkoxy (e.g., C_1-6thioalkoxy); (17) —(CH₂)_qCO₂R^A′, where q is an integer from zero to four, and R^A′ is selected from the group consisting of (a) C_1-6alkyl, (b) C_6-10aryl, (c) hydrogen, and (d) C_1-6alk-C_6-10aryl; (18) —(CH₂)_qCONR^B′R^C′, where q is an integer from zero to four and where R^B′ and R^C′ are independently selected from the group consisting of (a) hydrogen, (b) C_6-10alkyl, (c) C_6-10aryl, and (d) C_1-6alk-C_6-10aryl; (19) —(CH₂)_qSO₂R^D′, where q is an integer from zero to four and where R^D′ is selected from the group consisting of (a) C_6-10alkyl, (b) C_6-10aryl, and (c) C_1-6alk-C_6-10aryl; (20) —(CH₂)_qSO₂NR^E′R^F′, where q is an integer from zero to four and where each of R^E′ and R^F′ is, independently, selected from the group consisting of (a) hydrogen, (b) C_6-10alkyl, (c) C_6-10aryl, and (d) C_1-6alk-C_6-10aryl; (21) thiol; (22) C_6-10aryloxy; (23) C_3-8cycloalkoxy; (24) C_6-10aryl-C_1-6alkoxy; (25) C_1-6alk-C_1-12heterocyclyl (e.g., C_1-6alk-C_1-12heteroaryl); (26) oxo; (27) C_2-20alkenyl; and (28) C_2-20alkynyl. In some embodiments, each of these groups can be further substituted as described herein. For example, the alkylene group of a C₁-alkaryl or a C₁-alkheterocyclyl can be further substituted with an oxo group to afford the respective aryloyl and (heterocyclyl)oyl substituent group.

The “cycloalkylalkyl” group, which as used herein, represents a cycloalkyl group, as defined herein, attached to the parent molecular group through an alkylene group, as defined herein (e.g., an alkylene group of from 1 to 4, from 1 to 6, from 1 to 10, or form 1 to 20 carbons). In some embodiments, the alkylene and the cycloalkyl each can be further substituted with 1, 2, 3, or 4 substituent groups as defined herein for the respective group.

The term “halo,” as used herein, represents a halogen selected from bromine, chlorine, iodine, or fluorine.

The term “heteroalkyl,” as used herein, refers to an alkyl group, as defined herein, in which one or two of the constituent carbon atoms have each been replaced by nitrogen, oxygen, or sulfur. In some embodiments, the heteroalkyl group can be further substituted with 1, 2, 3, or 4 substituent groups as described herein for alkyl groups. The terms “heteroalkenyl” and heteroalkynyl,” as used herein refer to alkenyl and alkynyl groups, as defined herein, respectively, in which one or two of the constituent carbon atoms have each been replaced by nitrogen, oxygen, or sulfur. In some embodiments, the heteroalkenyl and heteroalkynyl groups can be further substituted with 1, 2, 3, or 4 substituent groups as described herein for alkyl groups.

Non-limiting examples of optionally substituted heteroalkyl, heteroalkenyl, and heteroalkynyl groups include acyloxy, alkenyloxy, alkoxy, alkoxyalkoxy, alkoxycarbonylalkoxy, alkynyloxy, aminoalkoxy, arylalkoxy, carboxyalkoxy, cycloalkoxy, haloalkoxy, (heterocyclyl)oxy, perfluoroalkoxy, thioalkoxy, and thioheterocyclylalkyl:

The “acyloxy” group, which as used herein, represents an acyl group, as defined herein, attached to the parent molecular group though an oxygen atom (i.e., —O—C(O)—R, where R is H or an optionally substituted C_1-6, C_1-10, or C_1-20alkyl group). Exemplary unsubstituted acyloxy groups include from 1 to 21 carbons (e.g., from 1 to 7 or from 1 to 11 carbons). In some embodiments, the alkyl group is further substituted with 1, 2, 3, or 4 substituents as described herein.

The “alkenyloxy” group, which as used here, represents a chemical substituent of formula —OR, where R is a C_2-20alkenyl group (e.g., C_2-6or C_2-10alkenyl), unless otherwise specified. Exemplary alkenyloxy groups include ethenyloxy, propenyloxy, and the like. In some embodiments, the alkenyl group can be further substituted with 1, 2, 3, or 4 substituent groups as defined herein (e.g., a hydroxy group).

The “alkoxy” group, which as used herein, represents a chemical substituent of formula —OR, where R is a C_1-20alkyl group (e.g., C_1-6or C_1-10alkyl), unless otherwise specified. Exemplary alkoxy groups include methoxy, ethoxy, propoxy (e.g., n-propoxy and isopropoxy), t-butoxy, and the like. In some embodiments, the alkyl group can be further substituted with 1, 2, 3, or 4 substituent groups as defined herein (e.g., hydroxy or alkoxy).

The “alkoxyalkoxy” group, which as used herein, represents an alkoxy group that is substituted with an alkoxy group. Exemplary unsubstituted alkoxyalkoxy groups include between 2 to 40 carbons (e.g., from 2 to 12 or from 2 to 20 carbons, such as C_2-6alkoxy-C_1-6alkoxy, C_1-10alkoxy-C_1-10alkoxy, or C_1-20alkoxy-C_1-20alkoxy). In some embodiments, the each alkoxy group can be further substituted with 1, 2, 3, or 4 substituent groups as defined herein.

The “alkoxycarbonylalkoxy” group, which as used herein, represents an alkoxy group, as defined herein, that is substituted with an alkoxycarbonyl group, as defined herein (e.g., —O-alkyl-C(O)—OR, where R is an optionally substituted C_1-6, C_1-10, or C_1-20alkyl group). Exemplary unsubstituted alkoxycarbonylalkoxy include from 3 to 41 carbons (e.g., from 3 to 10, from 3 to 13, from 3 to 17, from 3 to 21, or from 3 to 31 carbons, such as C_1-6alkoxycarbonyl-C_1-6alkoxy, C_1-10alkoxycarbonyl-C_1-10alkoxy, or C_1-20alkoxycarbonyl-C_1-20alkoxy). In some embodiments, each alkoxy group is further independently substituted with 1, 2, 3, or 4 substituents, as described herein (e.g., a hydroxy group).

The “alkynyloxy” group, which as used herein, represents a chemical substituent of formula —OR, where R is a C_2-20alkynyl group (e.g., C_2-6or C_2-10alkynyl), unless otherwise specified. Exemplary alkynyloxy groups include ethynyloxy, propynyloxy, and the like. In some embodiments, the alkynyl group can be further substituted with 1, 2, 3, or 4 substituent groups as defined herein (e.g., a hydroxy group).

The “aminoalkoxy” group, which as used herein, represents an alkoxy group, as defined herein, substituted with an amino group, as defined herein. The alkyl and amino each can be further substituted with 1, 2, 3, or 4 substituent groups as described herein for the respective group (e.g., CO₂R^A′, where R^A′ is selected from the group consisting of (a) C_1-6alkyl, (b) C_6-10aryl, (c) hydrogen, and (d) C_1-6alk-C_6-10aryl, e.g., carboxy).

The “arylalkoxy” group, which as used herein, represents an alkaryl group, as defined herein, attached to the parent molecular group through an oxygen atom. Exemplary unsubstituted arylalkoxy groups include from 7 to 30 carbons (e.g., from 7 to 16 or from 7 to 20 carbons, such as C_6-10aryl-C_1-6alkoxy, C_6-10aryl-C_1-10alkoxy, or C_6-10aryl-C_1-20alkoxy). In some embodiments, the arylalkoxy group can be substituted with 1, 2, 3, or 4 substituents as defined herein.

The “aryloxy” group, which as used herein, represents a chemical substituent of formula —OR′, where R′ is an aryl group of 6 to 18 carbons, unless otherwise specified. In some embodiments, the aryl group can be substituted with 1, 2, 3, or 4 substituents as defined herein.

The “carboxyalkoxy” group, which as used herein, represents an alkoxy group, as defined herein, substituted with a carboxy group, as defined herein. The alkoxy group can be further substituted with 1, 2, 3, or 4 substituent groups as described herein for the alkyl group, and the carboxy group can be optionally substituted with one or more 0-protecting groups.

The “cycloalkoxy” group, which as used herein, represents a chemical substituent of formula —OR, where R is a C_3-8cycloalkyl group, as defined herein, unless otherwise specified. The cycloalkyl group can be further substituted with 1, 2, 3, or 4 substituent groups as described herein. Exemplary unsubstituted cycloalkoxy groups are from 3 to 8 carbons. In some embodiment, the cycloalkyl group can be further substituted with 1, 2, 3, or 4 substituent groups as described herein.

The “haloalkoxy” group, which as used herein, represents an alkoxy group, as defined herein, substituted with a halogen group (i.e., F, Cl, Br, or I). A haloalkoxy may be substituted with one, two, three, or, in the case of alkyl groups of two carbons or more, four halogens. Haloalkoxy groups include perfluoroalkoxys (e.g., —OCF₃), —OCHF₂, —OCH₂F, —OCCl₃, —OCH₂CH₂Br, —OCH₂CH(CH₂CH₂Br)CH₃, and —OCHICH₃. In some embodiments, the haloalkoxy group can be further substituted with 1, 2, 3, or 4 substituent groups as described herein for alkyl groups.

The “(heterocyclyl)oxy” group, which as used herein, represents a heterocyclyl group, as defined herein, attached to the parent molecular group through an oxygen atom. In some embodiments, the heterocyclyl group can be substituted with 1, 2, 3, or 4 substituent groups as defined herein.

The “perfluoroalkoxy” group, which as used herein, represents an alkoxy group, as defined herein, where each hydrogen radical bound to the alkoxy group has been replaced by a fluoride radical. Perfluoroalkoxy groups are exemplified by trifluoromethoxy, pentafluoroethoxy, and the like.

The “alkylsulfinyl” group, which as used herein, represents an alkyl group attached to the parent molecular group through an —S(O)—group. Exemplary unsubstituted alkylsulfinyl groups are from 1 to 6, from 1 to 10, or from 1 to 20 carbons. In some embodiments, the alkyl group can be further substituted with 1, 2, 3, or 4 substituent groups as defined herein.

The “thioarylalkyl” group, which as used herein, represents a chemical substituent of formula —SR, where R is an arylalkyl group. In some embodiments, the arylalkyl group can be further substituted with 1, 2, 3, or 4 substituent groups as described herein.

The “thioalkoxy” group as used herein, represents a chemical substituent of formula —SR, where R is an alkyl group, as defined herein. In some embodiments, the alkyl group can be further substituted with 1, 2, 3, or 4 substituent groups as described herein.

The “thioheterocyclylalkyl” group, which as used herein, represents a chemical substituent of formula —SR, where R is an heterocyclylalkyl group. In some embodiments, the heterocyclylalkyl group can be further substituted with 1, 2, 3, or 4 substituent groups as described herein.

The term “heteroaryl,” as used herein, represents that subset of heterocyclyls, as defined herein, which are aromatic: i.e., they contain 4n+2 pi electrons within the mono- or multicyclic ring system. Exemplary unsubstituted heteroaryl groups are of 1 to 12 (e.g., 1 to 11, 1 to 10, 1 to 9, 2 to 12, 2 to 11, 2 to 10, or 2 to 9) carbons. In some embodiment, the heteroaryl is substituted with 1, 2, 3, or 4 substituents groups as defined for a heterocyclyl group.

The term “heteroarylalkyl” refers to a heteroaryl group, as defined herein, attached to the parent molecular group through an alkylene group, as defined herein. Exemplary unsubstituted heteroarylalkyl groups are from 2 to 32 carbons (e.g., from 2 to 22, from 2 to 18, from 2 to 17, from 2 to 16, from 3 to 15, from 2 to 14, from 2 to 13, or from 2 to 12 carbons, such as C_1-6alk-C_1-12heteroaryl, C_1-10alk-C_1-12heteroaryl, or C_1-20alk-C_1-12heteroaryl). In some embodiments, the alkylene and the heteroaryl each can be further substituted with 1, 2, 3, or 4 substituent groups as defined herein for the respective group. Heteroarylalkyl groups are a subset of heterocyclylalkyl groups.

The term “heterocyclyl,” as used herein represents a 5-, 6- or 7-membered ring, unless otherwise specified, containing one, two, three, or four heteroatoms independently selected from the group consisting of nitrogen, oxygen, and sulfur. The 5-membered ring has zero to two double bonds, and the 6- and 7-membered rings have zero to three double bonds. Exemplary unsubstituted heterocyclyl groups are of 1 to 12 (e.g., 1 to 11, 1 to 10, 1 to 9, 2 to 12, 2 to 10, or 2 to 9) carbons. The term “heterocyclyl” also represents a heterocyclic compound having a bridged multicyclic structure in which one or more carbons and/or heteroatoms bridges two non-adjacent members of a monocyclic ring, e.g., a quinuclidinyl group. The term “heterocyclyl” includes bicyclic, tricyclic, and tetracyclic groups in which any of the above heterocyclic rings is fused to one, two, or three carbocyclic rings, e.g., an aryl ring, a cyclohexane ring, a cyclohexene ring, a cyclopentane ring, a cyclopentene ring, or another monocyclic heterocyclic ring, such as indolyl, quinolyl, isoquinolyl, tetrahydroquinolyl, benzofuryl, benzothienyl and the like. Examples of fused heterocyclyls include tropanes and 1,2,3,5,8,8a-hexahydroindolizine. Heterocyclics include pyrrolyl, pyrrolinyl, pyrrolidinyl, pyrazolyl, pyrazolinyl, pyrazolidinyl, imidazolyl, imidazolinyl, imidazolidinyl, pyridyl, piperidinyl, homopiperidinyl, pyrazinyl, piperazinyl, pyrimidinyl, pyridazinyl, oxazolyl, oxazolidinyl, isoxazolyl, isoxazolidiniyl, morpholinyl, thiomorpholinyl, thiazolyl, thiazolidinyl, isothiazolyl, isothiazolidinyl, indolyl, indazolyl, quinolyl, isoquinolyl, quinoxalinyl, dihydroquinoxalinyl, quinazolinyl, cinnolinyl, phthalazinyl, benzimidazolyl, benzothiazolyl, benzoxazolyl, benzothiadiazolyl, furyl, thienyl, thiazolidinyl, isothiazolyl, triazolyl, tetrazolyl, oxadiazolyl (e.g., 1,2,3-oxadiazolyl), purinyl, thiadiazolyl (e.g., 1,2,3-thiadiazolyl), tetrahydrofuranyl, dihydrofuranyl, tetrahydrothienyl, dihydrothienyl, dihydroindolyl, dihydroquinolyl, tetrahydroquinolyl, tetrahydroisoquinolyl, dihydroisoquinolyl, pyranyl, dihydropyranyl, dithiazolyl, benzofuranyl, isobenzofuranyl, benzothienyl, and the like, including dihydro and tetrahydro forms thereof, where one or more double bonds are reduced and replaced with hydrogens. Still other exemplary heterocyclyls include: 2,3,4,5-tetrahydro-2-oxo-oxazolyl; 2,3-dihydro-2-oxo-1H-imidazolyl; 2,3,4,5-tetrahydro-5-oxo-1H-pyrazolyl (e.g., 2,3,4,5-tetrahydro-2-phenyl-5-oxo-1H-pyrazolyl); 2,3,4,5-tetrahydro-2,4-dioxo-1H-imidazolyl (e.g., 2,3,4,5-tetrahydro-2,4-dioxo-5-methyl-5-phenyl-1H-imidazolyl); 2,3-dihydro-2-thioxo-1,3,4-oxadiazolyl (e.g., 2,3-dihydro-2-thioxo-5-phenyl-1,3,4-oxadiazolyl); 4,5-dihydro-5-oxo-1H-triazolyl (e.g., 4,5-dihydro-3-methyl-4-amino 5-oxo-1H-triazolyl); 1,2,3,4-tetrahydro-2,4-dioxopyridinyl (e.g., 1,2,3,4-tetrahydro-2,4-dioxo-3,3-diethylpyridinyl); 2,6-dioxo-piperidinyl (e.g., 2,6-dioxo-3-ethyl-3-phenylpiperidinyl); 1,6-dihydro-6-oxopyridiminyl; 1,6-dihydro-4-oxopyrimidinyl (e.g., 2-(methylthio)-1,6-dihydro-4-oxo-5-methylpyrimidin-1-yl); 1,2,3,4-tetrahydro-2,4-dioxopyrimidinyl (e.g., 1,2,3,4-tetrahydro-2,4-dioxo-3-ethylpyrimidinyl); 1,6-dihydro-6-oxo-pyridazinyl (e.g., 1,6-dihydro-6-oxo-3-ethylpyridazinyl): 1,6-dihydro-6-oxo-1,2,4-triazinyl (e.g., 1,6-dihydro-5-isopropyl-6-oxo-1,2,4-triazinyl); 2,3-dihydro-2-oxo-1H-indolyl (e.g., 3,3-dimethyl-2,3-dihydro-2-oxo-1H-indolyl and 2,3-dihydro-2-oxo-3,3′-spiropropane-1H-indol-1-yl); 1,3-dihydro-1-oxo-2H-iso-indolyl; 1,3-dihydro-1,3-dioxo-2H-iso-indolyl; 1H-benzopyrazolyl (e.g., 1-(ethoxycarbonyl)-1H-benzopyrazolyl); 2,3-dihydro-2-oxo-1H-benzimidazolyl (e.g., 3-ethyl-2,3-dihydro-2-oxo-1H-benzimidazolyl); 2,3-dihydro-2-oxo-benzoxazolyl (e.g., 5-chloro-2,3-dihydro-2-oxo-benzoxazolyl); 2,3-dihydro-2-oxo-benzoxazolyl: 2-oxo-2H-benzopyranyl; 1,4-benzodioxanyl; 1,3-benzodioxanyl; 2,3-dihydro-3-oxo,4H-1,3-benzothiazinyl; 3,4-dihydro-4-oxo-3H-quinazolinyl (e.g., 2-methyl-3,4-dihydro-4-oxo-3H-quinazolinyl); 1,2,3,4-tetrahydro-2,4-dioxo-3H-quinazolyl (e.g., 1-ethyl-1,2,3,4-tetrahydro-2,4-dioxo-3H-quinazolyl); 1,2,3,6-tetrahydro-2,6-dioxo-7H-purinyl (e.g., 1,2,3,6-tetrahydro-1,3-dimethyl-2,6-dioxo-7H-purinyl); 1,2,3,6-tetrahydro-2,6-dioxo-1H-purinyl (e.g., 1,2,3,6-tetrahydro-3,7-dimethyl-2,6-dioxo-1H-purinyl); 2-oxobenz[c,d]indolyl; 1,1-dioxo-2H-naphth[1,8-c,d]isothiazolyl; and 1,8-naphthylenedicarboxamido. Additional heterocyclics include 3,3a,4,5,6,6a-hexahydro-pyrrolo[3,4-b]pyrrol-(2H)-yl, and 2,5-diazabicyclo[2.2.1]heptan-2-yl, homopiperazinyl (or diazepanyl), tetrahydropyranyl, dithiazolyl, benzofuranyl, benzothienyl, oxepanyl, thiepanyl, azocanyl, oxecanyl, and thiocanyl. Heterocyclic groups also include groups of the formula

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where

- E′ is selected from the group consisting of —N— and —CH—; F′ is selected from the group consisting of —N═CH—, —NH—CH₂—, —NH—C(O)—, —NH—, —CH═N—, —CH₂—NH—. —C(O)—NH—, —CH═CH—, —CH₂—, —CH₂CH₂—, —CH₂O—, —OCH₂—, —O—, and —S—; and G′ is selected from the group consisting of —CH— and —N—. Any of the heterocyclyl groups mentioned herein may be optionally substituted with one, two, three, four or five substituents independently selected from the group consisting of: (1) C_1-7acyl (e.g., carboxyaldehyde); (2) C_1-20alkyl (e.g., C_1-6alkyl, C_1-6alkoxy-C_1-6alkyl, C_1-6alkylsulfinyl-C_1-6alkyl, amino-C_1-6, alkyl, azido-C_1-6, alkyl, (carboxyaldehyde)-C_1-6alkyl, halo-C_1-6alkyl (e.g., perfluoroalkyl), hydroxy-C_1-6alkyl, nitro-C_1-6alkyl, or C_1-6thioalkoxy-C_1-6alkyl); (3) C_1-20alkoxy (e.g., C_1-6alkoxy, such as perfluoroalkoxy); (4) C_1-6alkylsulfinyl; (5) C_1-10aryl; (6) amino; (7) C_1-6alk-C_1-10aryl; (8) azido; (9) C_3-8cycloalkyl; (10) C_1-6alk-C_3-8cycloalkyl; (11) halo; (12) C_1-12heterocyclyl (e.g., C_2-12heteroaryl); (13) (C_1-12heterocyclyl)oxy; (14) hydroxy; (15) nitro; (16) C_1-20thioalkoxy (e.g., C_1-6thioalkoxy); (17) —(CH₂)_qCO₂R^A′, where q is an integer from zero to four, and R^A′ is selected from the group consisting of (a) C_1-6alkyl, (b) C_6-10aryl, (c) hydrogen, and (d) C_1-6alk-C_6-10aryl; (18) —(CH₂)_qCONR^B′R^C′, where q is an integer from zero to four and where R^B′ and R^C′ are independently selected from the group consisting of (a) hydrogen, (b) C_1-6alkyl, (c) C_6-10aryl, and (d) C_1-6alk-C_6-10aryl; (19) —(CH2)_qSO₂R^D′, where q is an integer from zero to four and where R^D′is selected from the group consisting of (a) C_1-6alkyl, (b) C_6-10aryl, and (c) C_1-6alk-C_6-10aryl; (20) —(CH₂)_qSO₂NR^E′R^F′, where q is an integer from zero to four and where each of R^E′ and R^F′ is, independently, selected from the group consisting of (a) hydrogen, (b) C_1-6alkyl, (c) C_6-10aryl, and (d) C_1-6alk-C_6-10aryl; (21) thiol; (22) C_6-10aryloxy; (23) C_3-8cycloalkoxy; (24) arylalkoxy; (25) C_1-6alk-C_1-12heterocyclyl (e.g., C_1-6alk-C_1-12heteroaryl); (26) oxo; (27) (C_1-12heterocyclyl)imino; (28) C_2-20alkenyl; and (29) C_2-20alkynyl. In some embodiments, each of these groups can be further substituted as described herein. For example, the alkylene group of a C₁-alkaryl or a C₁-alkheterocyclyl can be further substituted with an oxo group to afford the respective aryloyl and (heterocyclyl)oyl substituent group.

The “heterocyclylalkyl” group, which as used herein, represents a heterocyclyl group, as defined herein, attached to the parent molecular group through an alkylene group, as defined herein. Exemplary unsubstituted heterocyclylalkyl groups are from 2 to 32 carbons (e.g., from 2 to 22, from 2 to 18, from 2 to 17, from 2 to 16, from 3 to 15, from 2 to 14, from 2 to 13, or from 2 to 12 carbons, such as C_1-6alk-C_1-12heterocyclyl, C_1-10alk-C_1-12heterocyclyl, or C_1-20alk-C_1-12heterocyclyl). In some embodiments, the alkylene and the heterocyclyl each can be further substituted with 1, 2, 3, or 4 substituent groups as defined herein for the respective group.

The term “hydrocarbon,” as used herein, represents a group consisting only of carbon and hydrogen atoms.

The term “hydroxy,” as used herein, represents an —OH group.

The term “N-protected amino,” as used herein, refers to an amino group, as defined herein, to which is attached one or two N-protecting groups, as defined herein.

The term “N-protecting group,” as used herein, represents those groups intended to protect an amino group against undesirable reactions during synthetic procedures. Commonly used N-protecting groups are disclosed in Greene, “Protective Groups in Organic Synthesis,” 3^rdEdition (John Wiley & Sons, New York, 1999), which is incorporated herein by reference. N-protecting groups include acyl, aryloyl, or carbamyl groups such as formyl, acetyl, propionyl, pivaloyl, t-butylacetyl, 2-chloroacetyl, 2-bromoacetyl, trifluoroacetyl, trichloroacetyl, phthalyl, o-nitrophenoxyacetyl, α-chlorobutyryl, benzoyl, 4-chlorobenzoyl, 4-bromobenzoyl, 4-nitrobenzoyl, and chiral auxiliaries such as protected or unprotected D, L or D. L-amino acids such as alanine, leucine, phenylalanine, and the like; sulfonyl-containing groups such as benzenesulfonyl, p-toluenesulfonyl, and the like; carbamate forming groups such as benzyloxycarbonyl, p-chlorobenzyloxycarbonyl, p-methoxybenzyloxycarbonyl, p-nitrobenzyloxycarbonyl, 2-nitrobenzyloxycarbonyl, p-bromobenzyloxycarbonyl, 3,4-dimethoxybenzyloxycarbonyl, 3,5-dimethoxybenzyloxycarbonyl, 2,4-dimethoxybenzyloxycarbonyl, 4-methoxybenzyloxycarbonyl, 2-nitro-4,5-dimethoxybenzyloxycarbonyl, 3,4,5-trimethoxybenzyloxycarbonyl, 1-(p-biphenylyl)-1-methylethoxycarbonyl, α,α-dimethyl-3,5-dimethoxybenzyloxycarbonyl, benzhydryloxy carbonyl, t-butyloxycarbonyl, diisopropylmethoxycarbonyl, isopropyloxycarbonyl, ethoxycarbonyl, methoxycarbonyl, allyloxycarbonyl, 2,2,2,-trichloroethoxycarbonyl, phenoxycarbonyl, 4-nitrophenoxy carbonyl, fluorenyl-9-methoxycarbonyl, cyclopentyloxycarbonyl, adamantyloxycarbonyl, cyclohexyloxycarbonyl, phenylthiocarbonyl, and the like, alkaryl groups such as benzyl, uiphenylmethyl, benzyloxymethyl, and the like and silyl groups, such as trimethylsilyl, and the like. Preferred N-protecting groups are formyl, acetyl, benzoyl, pivaloyl, t-butylacetyl, alanyl, phenylsulfonyl, benzyl, t-butyloxycarbonyl (Boc), and benzyloxycarbonyl (Cbz).

The term “nitro,” as used herein, represents an —NO₂group.

The term “O-protecting group,” as used herein, represents those groups intended to protect an oxygen containing (e.g., phenol, hydroxyl, or carbonyl) group against undesirable reactions during synthetic procedures. Commonly used 0-protecting groups are disclosed in Greene, “Protective Groups in Organic Synthesis.” 3^rdEdition (John Wiley & Sons. New York, 1999), which is incorporated herein by reference. Exemplary 0-protecting groups include acyl, aryloyl, or carbamyl groups, such as formyl, acetyl, propionyl, pivaloyl, t-butylacetyl, 2-chloroacetyl, 2-bromoacetyl, trifluoroacetyl, trichloroacetyl, phthalyl, o-nitrophenoxyacetyl, α-chlorobutyryl, benzoyl, 4-chlorobenzoyl, 4-bromobenzoyl, t-butyldimethylsilyl, tri-iso-propylsilyloxymethyl, 4,4′-dimethoxytrityl, isobutyryl, phenoxyacetyl, 4-isopropylpehenoxyacetyl, dimethylformamidino, and 4-nitrobenzoyl; alkylcarbonyl groups, such as acyl, acetyl, propionyl, pivaloyl, and the like; optionally substituted arylcarbonyl groups, such as benzoyl; silyl groups, such as trimethylsilyl (TMS), tert-butyldimethylsilyl (TBDMS), tri-iso-propylsilyloxymethyl (TOM), triisopropylsilyl (TIPS), and the like; ether-forming groups with the hydroxyl, such methyl, methoxymethyl, tetrahydropyranyl, benzyl, p-methoxybenzyl, trityl, and the like; alkoxycarbonyls, such as methoxycarbonyl, ethoxycarbonyl, isopropoxycarbonyl, n-isopropoxycarbonyl, n-butyloxycarbonyl, isobutyloxycarbonyl, sec-butyloxycarbonyl, t-butyloxycarbonyl, 2-ethylhexyloxycarbonyl, cyclohexyloxycarbonyl, methyloxycarbonyl, and the like; alkoxyalkoxycarbonyl groups, such as methoxymethoxycarbonyl, ethoxymethoxycarbonyl, 2-methoxyethoxycarbonyl, 2-ethoxyethoxycarbonyl, 2-butoxyethoxycarbonyl, 2-methoxyethoxymethoxycarbonyl, allyloxycarbonyl, propargyloxycarbonyl, 2-butenoxycarbonyl, 3-methyl-2-butenoxycarbonyl, and the like; haloalkoxycarbonyls, such as 2-chloroethoxycarbonyl, 2-chloroethoxycarbonyl, 2,2,2-trichloroethoxycarbonyl, and the like; optionally substituted arylalkoxycarbonyl groups, such as benzyloxycarbonyl, p-methylbenzyloxycarbonyl, p-methoxybenzyloxycarbonyl, p-nitrobenzyloxycarbonyl, 2,4-dinitrobenzyloxycarbonyl, 3,5-dimethylbenzyloxycarbonyl, p-chlorobenzyloxycarbonyl, p-bromobenzyloxycarbonyl, fluorenylmethyloxycarbonyl, and the like; and optionally substituted aryloxycarbonyl groups, such as phenoxycarbonyl, p-nitrophenoxycarbonyl, o-nitrophenoxycarbonyl, 2,4-dinitrophenoxycarbonyl, p-methyl-phenoxycarbonyl, m-methylphenoxycarbonyl, o-bromophenoxycarbonyl, 3,5-dimethylphenoxycarbonyl, p-chlorophenoxycarbonyl, 2-chloro-4-nitrophenoxy-carbonyl, and the like); substituted alkyl, aryl, and alkaryl ethers (e.g., uityl; methylthiomethyl; methoxymethyl; benzyloxymethyl; siloxymethyl; 2,2,2,-trichloroethoxymethyl; tetrahydropyranyl; tetrahydrofuranyl; ethoxyethyl; 1-[2-(trimethylsilyl)ethoxy]ethyl; 2-trimethylsilylethyl; t-butyl ether; p-chlorophenyl, p-methoxyphenyl, p-nitrophenyl, benzyl, p-methoxybenzyl, and nitrobenzyl); silyl ethers (e.g., trimethylsilyl; triethylsilyl; triisopropylsilyl; dimethylisopropylsilyl; t-butyldimethylsilyl; t-butyldiphenylsilyl; tribenzylsilyl; triphenylsilyl; and diphenymethylsilyl); carbonates (e.g., methyl, methoxymethyl, 9-fluorenylmethyl; ethyl; 2,2,2-trichloroethyl; 2-(trimethylsilyl)ethyl; vinyl, allyl, nitrophenyl; benzyl; methoxybenzyl; 3,4-dimethoxybenzyl; and nitrobenzyl); carbonyl-protecting groups (e.g., acetal and ketal groups, such as dimethyl acetal, 1,3-dioxolane, and the like; acylal groups; and dithiane groups, such as 1,3-dithianes, 1,3-dithiolane, and the like); carboxylic acid-protecting groups (e.g., ester groups, such as methyl ester, benzyl ester, t-butyl ester, orthoesters, and the like; and oxazoline groups.

The term “oxo” as used herein, represents ═O.

The prefix “perfluoro,” as used herein, represents anyl group, as defined herein, where each hydrogen radical bound to the alkyl group has been replaced by a fluoride radical. For example, perfluoroalkyl groups are exemplified by trifluoromethyl, pentafluoroethyl, and the like.

The term “protected hydroxyl,” as used herein, refers to an oxygen atom bound to an O-protecting group.

The term “spirocyclyl,” as used herein, represents a C₂0.7 alkylene diradical, both ends of which are bonded to the same carbon atom of the parent group to form a spirocyclic group, and also a C_1-6heteroalkylene diradical, both ends of which are bonded to the same atom. The heteroalkylene radical forming the spirocyclyl group can containing one, two, three, or four heteroatoms independently selected from the group consisting of nitrogen, oxygen, and sulfur. In some embodiments, the spirocyclyl group includes one to seven carbons, excluding the carbon atom to which the diradical is attached. The spirocyclyl groups of the invention may be optionally substituted with 1, 2, 3, or 4 substituents provided herein as optional substituents for cycloalkyl and/or heterocyclyl groups.

The term “sulfonyl,” as used herein, represents an —S(O)₂—group.

The term “thiol,” as used herein represents an —SH group.

Chimera: As used herein, “chimera” is an entity having two or more incongruous or heterogeneous parts or regions.

Chimeric polynucleotide: As used herein, “chimeric polynucleotides” are those nucleic acid polymers having portions or regions which differ in size and/or chemical modification pattern, chemical modification position, chemical modification percent or chemical modification population and combinations of the foregoing.

Compound: As used herein, the term “compound,” is meant to include all stereoisomers, geometric isomers, tautomers, and isotopes of the structures depicted.

The compounds described herein can be asymmetric (e.g., having one or more stereocenters). All stereoisomers, such as enantiomers and diastereomers, are intended unless otherwise indicated. Compounds of the present disclosure that contain asymmetrically substituted carbon atoms can be isolated in optically active or racemic forms. Methods on how to prepare optically active forms from optically active starting materials are known in the art, such as by resolution of racemic mixtures or by stereoselective synthesis. Many geometric isomers of olefins, C=N double bonds, and the like can also be present in the compounds described herein, and all such stable isomers are contemplated in the present disclosure. Cis and trans geometric isomers of the compounds of the present disclosure are described and may be isolated as a mixture of isomers or as separated isomeric forms.

Compounds of the present disclosure also include tautomeric forms. Tautomeric forms result from the swapping of a single bond with an adjacent double bond and the concomitant migration of a proton. Tautomeric forms include prototropic tautomers which are isomeric protonation states having the same empirical formula and total charge. Examples prototropic tautomers include ketone—enol pairs, amide—imidic acid pairs, lactam—lactim pairs, amide—imidic acid pairs, enamine—imine pairs, and annular forms where a proton can occupy two or more positions of a heterocyclic system, such as, 1H- and 3H-imidazole, 1H-, 2H- and 4H-1,2,4-triazole, 1H- and 2H-isoindole, and 1H- and 2H-pyrazole. Tautomeric forms can be in equilibrium or sterically locked into one form by appropriate substitution.

Compounds of the present disclosure also include all of the isotopes of the atoms occurring in the intermediate or final compounds. “Isotopes” refers to atoms having the same atomic number but different mass numbers resulting from a different number of neutrons in the nuclei. For example, isotopes of hydrogen include tritium and deuterium.

The compounds and salts of the present disclosure can be prepared in combination with solvent or water molecules to form solvates and hydrates by routine methods.

Conserved: As used herein, the term “conserved” refers to nucleotides or amino acid residues of a polynucleotide sequence or polypeptide sequence, respectively, that are those that occur unaltered in the same position of two or more sequences being compared. Nucleotides or amino acids that are relatively conserved are those that are conserved amongst more related sequences than nucleotides or amino acids appearing elsewhere in the sequences.

In some embodiments, two or more sequences are said to be “completely conserved” if they are 100% identical to one another. In some embodiments, two or more sequences are said to be “highly conserved” if they are at least 70% identical, at least 80% identical, at least 90% identical, or at least 95% identical to one another. In some embodiments, two or more sequences are said to be “highly conserved” if they are about 70% identical, about 80% identical, about 90% identical, about 95%, about 98%, or about 99% identical to one another. In some embodiments, two or more sequences are said to be “conserved” if they are at least 30% identical, at least 40% identical, at least 50% identical, at least 60% identical, at least 70% identical, at least 80% identical, at least 90% identical, or at least 95% identical to one another. In some embodiments, two or more sequences are said to be “conserved” if they are about 30% identical, about 40% identical, about 50% identical, about 60% identical, about 70% identical, about 80% identical, about 90% identical, about 95% identical, about 98% identical, or about 99% identical to one another. Conservation of sequence may apply to the entire length of an polynucleotide or polypeptide or may apply to a portion, region or feature thereof.

Controlled Release: As used herein, the term “controlled release” refers to a pharmaceutical composition or compound release profile that conforms to a particular pattern of release to effect a therapeutic outcome.

Cyclic or Cyclized: As used herein, the term “cyclic” refers to the presence of a continuous loop. Cyclic molecules need not be circular, only joined to form an unbroken chain of subunits. Cyclic molecules such as the engineered RNA or mRNA of the present invention may be single units or multimers or comprise one or more components of a complex or higher order structure.

Cytostatic: As used herein, “cytostatic” refers to inhibiting, reducing, suppressing the growth, division, or multiplication of a cell (e.g., a mammalian cell (e.g., a human cell)), bacterium, virus, fungus, protozoan, parasite, prion, or a combination thereof.

Cytotoxic: As used herein, “cytotoxic” refers to killing or causing injurious, toxic, or deadly effect on a cell (e.g., a mammalian cell (e.g., a human cell)), bacterium, virus, fungus, protozoan, parasite, prion, or a combination thereof.

Delivery: As used herein, “delivery” refers to the act or manner of delivering a compound, substance, entity, moiety, cargo or payload.

Delivery Agent: As used herein, “delivery agent” refers to any substance which facilitates, at least in part, the in vivo delivery of a polynucleotide to targeted cells.

Destabilized: As used herein, the term “destable,” “destabilize,” or “destabilizing region” means a region or molecule that is less stable than a starting, wild-type or native form of the same region or molecule.

Detectable label: As used herein, “detectable label” refers to one or more markers, signals, or moieties which are attached, incorporated or associated with another entity that is readily detected by methods known in the art including radiography, fluorescence, chemiluminescence, enzymatic activity, absorbance and the like. Detectable labels include radioisotopes, fluorophores, chromophores, enzymes, dyes, metal ions, ligands such as biotin, avidin, streptavidin and haptens, quantum dots, and the like. Detectable labels may be located at any position in the peptides or proteins disclosed herein. They may be within the amino acids, the peptides, or proteins, or located at the N- or C—termini.

Diastereomer: As used herein, the term “diastereomer,” means stereoisomers that are not mirror images of one another and are non-superimposable on one another.

Digest: As used herein, the term “digest” means to break apart into smaller pieces or components. When referring to polypeptides or proteins, digestion results in the production of peptides.

Differentiated cell: As used herein, the term “differentiated cell” refers to any somatic cell that is not, in its native form, pluripotent. Differentiated cell also encompasses cells that are partially differentiated.

Differentiation: As used herein, the term “differentiation factor” refers to a developmental potential altering factor such as a protein, RNA or small molecule that can induce a cell to differentiate to a desired cell-type.

Differentiate: As used herein, “differentiate” refers to the process where an uncommitted or less committed cell acquires the features of a committed cell.

Distal: As used herein, the term “distal” means situated away from the center or away from a point or region of interest.

Dosing regimen: As used herein, a “dosing regimen” is a schedule of administration or physician determined regimen of treatment, prophylaxis, or palliative care.

Dose splitting factor (DSF)-ratio of PUD of dose split treatment divided by PUD of total daily dose or single unit dose. The value is derived from comparison of dosing regimens groups.

Enantiomer: As used herein, the term “enantiomer” means each individual optically active form of a compound of the invention, having an optical purity or enantiomeric excess (as determined by methods standard in the art) of at least 80% (i.e., at least 90% of one enantiomer and at most 10% of the other enantiomer), preferably at least 90% and more preferably at least 98%.

Encapsulate: As used herein, the term “encapsulate” means to enclose, surround or encase.

Encoded protein cleavage signal: As used herein, “encoded protein cleavage signal” refers to the nucleotide sequence which encodes a protein cleavage signal.

Engineered: As used herein, embodiments of the invention are “engineered” when they are designed to have a feature or property, whether structural or chemical, that varies from a starting point, wild type or native molecule.

Effective Amount: As used herein, the term “effective amount” of an agents that amount sufficient to effect beneficial or desired results, for example, clinical results, and, as such, an “effective amount” depends upon the context in which it is being applied. For example, in the context of administering an agent that treats cancer, an effective amount of an agent is, for example, an amount sufficient to achieve treatment, as defined herein, of cancer, as compared to the response obtained without administration of the agent.

Exosome: As used herein, “exosome” is a vesicle secreted by mammalian cells or a complex involved in RNA degradation.

Expression: As used herein, “expression” of a nucleic acid sequence refers to one or more of the following events: (1) production of an RNA template from a DNA sequence (e.g., by transcription); (2) processing of an RNA transcript (e.g., by splicing, editing, 5′ cap formation, and/or 3′ end processing); (3) translation of an RNA into a polypeptide or protein; and (4) post-translational modification of a polypeptide or protein.

Feature: As used herein, a “feature” refers to a characteristic, a property, or a distinctive element.

Formulation: As used herein, a “formulation” includes at least a polynucleotide of a NAV and a delivery agent.

Fragment: A “fragment,” as used herein, refers to a portion. For example, fragments of proteins may comprise polypeptides obtained by digesting full-length protein isolated from cultured cells.

Functional: As used herein, a “functional” biological molecule is a biological molecule in a form in which it exhibits a property and/or activity by which it is characterized.

Homology: As used herein, the term “homology” refers to the overall relatedness between polymeric molecules, e.g. between nucleic acid molecules (e.g. DNA molecules and/or RNA molecules) and/or between polypeptide molecules. In some embodiments, polymeric molecules are considered to be “homologous” to one another if their sequences are at least 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, or 99% identical or similar. The term “homologous” necessarily refers to a comparison between at least two sequences (polynucleotide or polypeptide sequences). In accordance with the invention, two polynucleotide sequences are considered to be homologous if the polypeptides they encode are at least about 50%, 60%, 70%, 80%, 90%, 95%, or even 99% for at least one stretch of at least about 20 amino acids. In some embodiments, homologous polynucleotide sequences are characterized by the ability to encode a stretch of at least 4-5 uniquely specified amino acids. For polynucleotide sequences less than 60 nucleotides in length, homology is determined by the ability to encode a stretch of at least 4-5 uniquely specified amino acids. In accordance with the invention, two protein sequences are considered to be homologous if the proteins are at least about 50%, 60%, 70%, 80%, or 90% identical for at least one stretch of at least about 20 amino acids.

Identity: As used herein, the term “identity” refers to the overall relatedness between polymeric molecules, e.g., between polynucleotide molecules (e.g. DNA molecules and/or RNA molecules) and/or between polypeptide molecules. Calculation of the percent identity of two polynucleotide sequences, for example, can be performed by aligning the two sequences for optimal comparison purposes (e.g., gaps can be introduced in one or both of a first and a second nucleic acid sequences for optimal alignment and non-identical sequences can be disregarded for comparison purposes). In certain embodiments, the length of a sequence aligned for comparison purposes is at least 30%, at least 40%, at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, at least 95%, or 100% of the length of the reference sequence. The nucleotides at corresponding nucleotide positions are then compared. When a position in the first sequence is occupied by the same nucleotide as the corresponding position in the second sequence, then the molecules are identical at that position. The percent identity between the two sequences is a function of the number of identical positions shared by the sequences, taking into account the number of gaps, and the length of each gap, which needs to be introduced for optimal alignment of the two sequences. The comparison of sequences and determination of percent identity between two sequences can be accomplished using a mathematical algorithm. For example, the percent identity between two nucleotide sequences can be determined using methods such as those described in Computational Molecular Biology, Lesk, A. M., ed., Oxford University Press, New York, 1988; Biocomputing: Informatics and Genome Projects, Smith, D. W., ed., Academic Press, New York, 1993; Sequence Analysis in Molecular Biology, von Heinje, G., Academic Press, 1987; Computer Analysis of Sequence Data, Part I, Griffin, A. M., and Griffin, H. G., eds., Humana Press, New Jersey, 1994; and Sequence Analysis Primer, Gribskov, M. and Devereux, J., eds., M Stockton Press, New York, 1991; each of which is incorporated herein by reference. For example, the percent identity between two nucleotide sequences can be determined using the algorithm of Meyers and Miller (CABIOS, 1989. 4:11-17), which has been incorporated into the ALIGN program (version 2.0) using a PAM120 weight residue table, a gap length penalty of 12 and a gap penalty of 4. The percent identity between two nucleotide sequences can, alternatively, be determined using the GAP program in the GCG software package using an NWSgapdna.CMP matrix. Methods commonly employed to determine percent identity between sequences include, but are not limited to those disclosed in Carillo, H., and Lipman, D., SIAM J Applied Math., 48:1073 (1988); incorporated herein by reference. Techniques for determining identity are codified in publicly available computer programs. Exemplary computer software to determine homology between two sequences include, but are not limited to, GCG program package, Devereux, J., et al., Nucleic Acids Research, 12(1), 387 (1984)), BLASTP, BLASTN, and FASTA Altschul, S. F. et al., J. Molec. Biol., 215, 403 (1990)).

Infectious Agent: As used herein, the phrase “infectious agent” means an agent capable of producing an infection in an organism, for example, in an animal. An infectious agent may refer to any microorganism, virus, infectious substance, or biological product that may be engineered as a result of biotechnology, or any naturally occurring or bioengineered component of any such microorganism, virus, infectious substance, or biological product, can cause emerging and contagious disease, death or other biological malfunction in a human, an animal, a plant or another living organism.

Inhibit expression of a gene: As used herein, the phrase “inhibit expression of a gene” means to cause a reduction in the amount of an expression product of the gene. The expression product can be an RNA transcribed from the gene (e.g., an mRNA) or a polypeptide translated from an mRNA transcribed from the gene. Typically a reduction in the level of an mRNA results in a reduction in the level of a polypeptide translated therefrom. The level of expression may be determined using standard techniques for measuring mRNA or protein.

Influenza: As used herein, “influenza” or “flu” is an infectious disease of birds and mammals caused by RNA viruses of the family Orthomyxoviridae, the influenza viruses.

Isomer: As used herein, the term “isomer” means any tautomer, stereoisomer, enantiomer, or diastereomer of any compound of the invention. It is recognized that the compounds of the invention can have one or more chiral centers and/or double bonds and, therefore, exist as stereoisomers, such as double-bond isomers (i.e., geometric E/Z isomers) or diastereomers (e.g., enantiomers (i.e., (+) or (−)) or cis/trans isomers). According to the invention, the chemical structures depicted herein, and therefore the compounds of the invention, encompass all of the corresponding stereoisomers, that is, both the stereomerically pure form (e.g., geometrically pure, enantiomerically pure, or diastereomerically pure) and enantiomeric and stereoisomeric mixtures, e.g., racemates. Enantiomeric and stereoisomeric mixtures of compounds of the invention can typically be resolved into their component enantiomers or stereoisomers by well-known methods, such as chiral-phase gas chromatography, chiral-phase high performance liquid chromatography, crystallizing the compound as a chiral salt complex, or crystallizing the compound in a chiral solvent. Enantiomers and stereoisomers can also be obtained from stereomerically or enantiomerically pure intermediates, reagents, and catalysts by well-known asymmetric synthetic methods.

In vitro: As used herein, the term “in vitro” refers to events that occur in an artificial environment, e.g., in a test tube or reaction vessel, in cell culture, in a Petri dish, etc., rather than within an organism (e.g., animal, plant, or microbe).

In vivo: As used herein, the term “in vivo” refers to events that occur within an organism (e.g., animal, plant, or microbe or cell or tissue thereof).

Isolated: As used herein, the term “isolated” refers to a substance or entity that has been separated from at least some of the components with which it was associated (whether in nature or in an experimental setting). Isolated substances may have varying levels of purity in reference to the substances from which they have been associated. Isolated substances and/or entities may be separated from at least about 10%, about 20%, about 30%, about 40%, about 50%, about 60%, about 70%, about 80%, about 90%, or more of the other components with which they were initially associated. In some embodiments, isolated agents are more than about 80%, about 85%, about 90%, about 91%, about 92%, about 93%, about 94%, about 95%, about 96%, about 97%, about 98%, about 99%, or more than about 99% pure. As used herein, a substance is “pure” if it is substantially free of other components. Substantially isolated: By “substantially isolated” is meant that the compound is substantially separated from the environment in which it was formed or detected. Partial separation can include, for example, a composition enriched in the compound of the present disclosure. Substantial separation can include compositions containing at least about 50%, at least about 60%, at least about 70%, at least about 80%, at least about 90%, at least about 95%, at least about 97%, or at least about 99% by weight of the compound of the present disclosure, or salt thereof. Methods for isolating compounds and their salts are routine in the art.

IVT Polynucleotide: As used herein, an “IVT polynucleotide” is a linear polynucleotide which may be made using in vitro transcription (IVT) enzymatic synthesis methods.

Linker: As used herein, a “linker” refers to a group of atoms, e.g., 10-1,000 atoms, and can be comprised of the atoms or groups such as, but not limited to, carbon, amino, alkylamino, oxygen, sulfur, sulfoxide, sulfonyl, carbonyl, and imine. The linker can be attached to a modified nucleoside or nucleotide on the nucleobase or sugar moiety at a first end, and to a payload, e.g., a detectable or therapeutic agent, at a second end. The linker may be of sufficient length as to not interfere with incorporation into a nucleic acid sequence. The linker can be used for any useful purpose, such as to form polynucleotide multimers (e.g., through linkage of two or more chimeric polynucleotides molecules or IVT polynucleotides) or polynucleotides conjugates, as well as to administer a payload, as described herein. Examples of chemical groups that can be incorporated into the linker include, but are not limited to, alkyl, alkenyl, alkynyl, amido, amino, ether, thioether, ester, alkylene, heteroalkylene, aryl, or heterocyclyl, each of which can be optionally substituted, as described herein. Examples of linkers include, but are not limited to, unsaturated alkanes, polyethylene glycols (e.g., ethylene or propylene glycol monomeric units. e.g., diethylene glycol, dipropylene glycol, triethylene glycol, tripropylene glycol, tetraethylene glycol, or tetraethylene glycol), and dextran polymers and derivatives thereof. Other examples include, but are not limited to, cleavable moieties within the linker, such as, for example, a disulfide bond (—S—S—) or an azo bond (—N═N—), which can be cleaved using a reducing agent or photolysis. Non-limiting examples of a selectively cleavable bond include an amido bond can be cleaved for example by the use of tris(2-carboxyethyl)phosphine (TCEP), or other reducing agents, and/or photolysis, as well as an ester bond can be cleaved for example by acidic or basic hydrolysis.

MicroRNA (miRNA) binding site: As used herein, a microRNA (miRNA) binding site represents a nucleotide location or region of a nucleic acid transcript to which at least the “seed” region of a miRNA binds.

Modified: As used herein “modified” refers to a changed state or structure of a molecule of the invention. Molecules may be modified in many ways including chemically, structurally, and functionally. In one embodiment, the polynucleotide molecules of the present invention are modified by the introduction of non-natural nucleosides and/or nucleotides, e.g., as it relates to the natural ribonucleotides A, U, G, and C. Noncanonical nucleotides such as the cap structures are not considered “modified” although they differ from the chemical structure of the A, C, G, U ribonucleotides.

Mucus: As used herein, “mucus” refers to the natural substance that is viscous and comprises mucin glycoproteins.

Naturally occurring: As used herein, “naturally occurring” means existing in nature without artificial aid.

Neutralizing antibody: As used herein, a “neutralizing antibody” refers to an antibody which binds to its antigen and defends a cell from an antigen or infectious agent by neutralizing or abolishing any biological activity it has.

Non-human vertebrate: As used herein, a “non human vertebrate” includes all vertebrates except Homo sapiens, including wild and domesticated species. Examples of non-human vertebrates include, but are not limited to, mammals, such as alpaca, banteng, bison, camel, cat, cattle, deer, dog, donkey, gayal, goat, guinea pig, horse, llama, mule, pig, rabbit, reindeer, sheep water buffalo, and yak.

Nucleic Acid Vaccine: As used herein, “nucleic acid vaccine” or “NAV” or “NAV composition” refers to a vaccine or vaccine composition which includes a nucleic acid or nucleic acid molecule (e.g., a polynucleotide) encoding an antigen (e.g., an antigenic protein or polypeptide.) in exemplary embodiments, a nucleic acid vaccine or NAV includes a ribonucleic (“RNA”) polynucleotide, ribonucleic acid (“RNA”) or ribonucleic acid (“RNA”) molecule. Such embodiments can be referred to as ribonucleic acid (“RNA”) vaccines (RNAVs). In preferred embodiments, a nucleic acid vaccine or NAV includes a messenger RNA (“mRNA”) polynucleotide, messenger RNA (“mRNA”) or messenger RNA (“mRNA”) molecule as described in detail herein. Such embodiments can be referred to as messenger RNA (“mRNA”) vaccines (mRNAVs).

Off-target: As used herein, “off target” refers to any unintended effect on any one or more target, gene, or cellular transcript.

Open reading frame: As used herein, the term “open reading frame” or “ORF” refers to a continuous polynucleotide sequence, for example, a DNA sequence or RNA sequence (e.g., an mRNA sequence), comprising a start codon, a subsequent region comprising a plurality of amino acid-encoding codons, and a terminal stop codon, wherein the region comprising the plurality of amino acid-encoding codons contains no stop codons.

Operably linked: As used herein, the phrase “operably linked” refers to a functional connection between two or more molecules, constructs, transcripts, entities, moieties or the like.

Optionally substituted: Herein a phrase of the form “optionally substituted X” (e.g., optionally substituted alkyl) is intended to be equivalent to “X, wherein X is optionally substituted” (e.g., “alkyl, wherein said alkyl is optionally substituted”). It is not intended to mean that the feature “X” (e.g. alkyl) per se is optional.

Part: As used herein, a “part” or “region” of a polynucleotide is defined as any portion of the polynucleotide which is less than the entire length of the polynucleotide.

Peptide: As used herein, “peptide” is less than or equal to 50 amino acids long, e.g., about 5, 10, 15, 20, 25, 30, 35, 40, 45, or 50 amino acids long.

Paratope: As used herein, a “paratope” refers to the antigen-binding site of an antibody.

Patient: As used herein, “patient” refers to a subject who may seek or be in need of treatment, requires treatment, is receiving treatment, will receive treatment, or a subject who is under care by a trained professional for a particular disease or condition.

Pharmaceutically acceptable: The phrase “pharmaceutically acceptable” is employed herein to refer to those compounds, materials, compositions, and/or dosage forms which are, within the scope of sound medical judgment, suitable for use in contact with the tissues of human beings and animals without excessive toxicity, irritation, allergic response, or other problem or complication, commensurate with a reasonable benefit/risk ratio.

Pharmaceutically acceptable excipients: The phrase “pharmaceutically acceptable excipient,” as used herein, refers any ingredient other than the compounds described herein (for example, a vehicle capable of suspending or dissolving the active compound) and having the properties of being substantially nontoxic and non-inflammatory in a patient. Excipients may include, for example: antiadherents, antioxidants, binders, coatings, compression aids, disintegrants, dyes (colors), emollients, emulsifiers, fillers (diluents), film formers or coatings, flavors, fragrances, glidants (flow enhancers), lubricants, preservatives, printing inks, sorbents, suspensing or dispersing agents, sweeteners, and waters of hydration. Exemplary excipients include, but are not limited to: butylated hydroxytoluene (BHT), calcium carbonate, calcium phosphate (dibasic), calcium stearate, croscarmellose, crosslinked polyvinyl pyrrolidone, citric acid, crospovidone, cysteine, ethylcellulose, gelatin, hydroxypropyl cellulose, hydroxypropyl methylcellulose, lactose, magnesium stearate, maltitol, mannitol, methionine, methylcellulose, methyl paraben, microcrystalline cellulose, polyethylene glycol, polyvinyl pyrrolidone, povidone, pregelatinized starch, propyl paraben, retinyl palmitate, shellac, silicon dioxide, sodium carboxymethyl cellulose, sodium citrate, sodium starch glycolate, sorbitol, starch (corn), stearic acid, sucrose, talc, titanium dioxide, vitamin A, vitamin E, vitamin C, and xylitol.

Pharmaceutically acceptable salts: The present disclosure also includes pharmaceutically acceptable salts of the compounds described herein. As used herein, “pharmaceutically acceptable salts” refers to derivatives of the disclosed compounds wherein the parent compound is modified by converting an existing acid or base moiety to its salt form (e.g., by reacting the free base group with a suitable organic acid). Examples of pharmaceutically acceptable salts include, but are not limited to, mineral or organic acid salts of basic residues such as amines; alkali or organic salts of acidic residues such as carboxylic acids; and the like. Representative acid addition salts include acetate, acetic acid, adipate, alginate, ascorbate, aspartate, benzenesulfonate, benzene sulfonic acid, benzoate, bisulfate, borate, butyrate, camphorate, camphorsulfonate, citrate, cyclopentanepropionate, digluconate, dodecylsulfate, ethanesulfonate, fumarate, glucoheptonate, glycerophosphate, hemisulfate, heptonate, hexanoate, hydrobromide, hydrochloride, hydroiodide, 2-hydroxy-ethanesulfonate, lactobionate, lactate, laurate, lauryl sulfate, malate, maleate, malonate, methanesulfonate, 2-naphthalenesulfonate, nicotinate, nitrate, oleate, oxalate, palmitate, pamoate, pectinate, persulfate, 3-phenylpropionate, phosphate, picrate, pivalate, propionate, stearate, succinate, sulfate, tartrate, thiocyanate, toluenesulfonate, undecanoate, valerate salts, and the like. Representative alkali or alkaline earth metal salts include sodium, lithium, potassium, calcium, magnesium, and the like, as well as nontoxic ammonium, quaternary ammonium, and amine cations, including, but not limited to ammonium, tetramethylammonium, tetraethylammonium, methylamine, dimethylamine, trimethylamine, triethylamine, ethylamine, and the like. The pharmaceutically acceptable salts of the present disclosure include the conventional non-toxic salts of the parent compound formed, for example, from non-toxic inorganic or organic acids. The pharmaceutically acceptable salts of the present disclosure can be synthesized from the parent compound which contains a basic or acidic moiety by conventional chemical methods. Generally, such salts can be prepared by reacting the free acid or base forms of these compounds with a stoichiometric amount of the appropriate base or acid in water or in an organic solvent, or in a mixture of the two: generally, nonaqueous media like ether, ethyl acetate, ethanol, isopropanol, or acetonitrile are preferred. Lists of suitable salts are found in Remington's Pharmaceutical Sciences, 17^thed., Mack Publishing Company, Easton, Pa., 1985, p. 1418, Pharmaceutical Salts: Properties, Selection, and Use, P. H. Stahl and C. G. Wermuth (eds.), Wiley-VCH, 2008, and Berge et al., Journal of Pharmaceutical Science, 66, 1-19 (1977), each of which is incorporated herein by reference in its entirety.

Pharmaceutically acceptable solvate: The term “pharmaceutically acceptable solvate,” as used herein, means a compound of the invention wherein molecules of a suitable solvent are incorporated in the crystal lattice. A suitable solvent is physiologically tolerable at the dosage administered. For example, solvates may be prepared by crystallization, recrystallization, or precipitation from a solution that includes organic solvents, water, or a mixture thereof. Examples of suitable solvents are ethanol, water (for example, mono-, di-, and tri-hydrates), N-methylpyrrolidinone (NMP), dimethyl sulfoxide (DMSO), N,N′-dimethylformamide (DMF), N,N′-dimethylacetamide (DMAC), 1,3-dimethyl-2-imidazolidinone (DMEU), 1,3-dimethyl-3,4,5,6-tetrahydro-2-(1H)-pyrimidinone (DMPU), acetonitrile (ACN), propylene glycol, ethyl acetate, benzyl alcohol, 2-pyrrolidone, benzyl benzoate, and the like. When water is the solvent, the solvate is referred to as a “hydrate.”

Pharmacokinetic: As used herein, “pharmacokinetic” refers to any one or more properties of a molecule or compound as it relates to the determination of the fate of substances administered to a living organism. Pharmacokinetics is divided into several areas including the extent and rate of absorption, distribution, metabolism and excretion. This is commonly referred to as ADME where: (A) Absorption is the process of a substance entering the blood circulation; (D) Distribution is the dispersion or dissemination of substances throughout the fluids and tissues of the body; (M) Metabolism (or Biotransformation) is the irreversible transformation of parent compounds into daughter metabolites; and (E) Excretion (or Elimination) refers to the elimination of the substances from the body. In rare cases, some drugs irreversibly accumulate in body tissue.

Physicochemical: As used herein, “physicochemical” means of or relating to a physical and/or chemical property.

Polypeptide per unit drug (PUD): As used herein, a PUD or product per unit drug, is defined as a subdivided portion of total daily dose, usually 1 mg, pg, kg, etc., of a product (such as a polypeptide) as measured in body fluid or tissue, usually defined in concentration such as pmol/mL, mmol/mL, etc divided by the measure in the body fluid.

Preventing: As used herein, the term “preventing” refers to partially or completely delaying onset of an infection, disease, disorder and/or condition; partially or completely delaying onset of one or more symptoms, features, or clinical manifestations of a particular infection, disease, disorder, and/or condition; partially or completely delaying onset of one or more symptoms, features, or manifestations of a particular infection, disease, disorder, and/or condition; partially or completely delaying progression from an infection, a particular disease, disorder and/or condition; and/or decreasing the risk of developing pathology associated with the infection, the disease, disorder, and/or condition.

Prodrug: The present disclosure also includes prodrugs of the compounds described herein. As used herein, “prodrugs” refer to any substance, molecule or entity which is in a form predicate for that substance, molecule or entity to act as a therapeutic upon chemical or physical alteration. Prodrugs may by covalently bonded or sequestered in some way and which release or are converted into the active drug moiety prior to, upon or after administered to a mammalian subject. Prodrugs can be prepared by modifying functional groups present in the compounds in such a way that the modifications are cleaved, either in routine manipulation or in vivo, to the parent compounds. Prodrugs include compounds wherein hydroxyl, amino, sulfhydryl, or carboxyl groups are bonded to any group that, when administered to a mammalian subject, cleaves to form a free hydroxyl, amino, sulfhydryl, or carboxyl group respectively. Preparation and use of prodrugs is discussed in T. Higuchi and V. Stella, “Pro-drugs as Novel Delivery Systems,” Vol. 14 of the A.C.S. Symposium Series, and in Bioreversible Carriers in Drug Design, ed. Edward B. Roche, American Pharmaceutical Association and Pergamon Press, 1987, both of which are hereby incorporated by reference in their entirety.

Proliferate: As used herein, the term “proliferate” means to grow, expand or increase or cause to grow, expand or increase rapidly. “Proliferative” means having the ability to proliferate. “Anti-proliferative” means having properties counter to or inapposite to proliferative properties.

Prophylactic: As used herein, “prophylactic” refers to a therapeutic or course of action used to prevent the spread of disease.

Prophylaxis: As used herein, a “prophylaxis” refers to a measure taken to maintain health and prevent the spread of disease. An “immune prophylaxis” refers to a measure to produce active or passive immunity to prevent the spread of disease.

Protein cleavage site: As used herein, “protein cleavage site” refers to a site where controlled cleavage of the amino acid chain can be accomplished by chemical, enzymatic or photochemical means.

Protein cleavage signal: As used herein “protein cleavage signal” refers to at least one amino acid that flags or marks a polypeptide for cleavage.

Protein of interest: As used herein, the terms “proteins of interest” or “desired proteins” include those provided herein and fragments, mutants, variants, and alterations thereof.

Proximal: As used herein, the term “proximal” means situated nearer to the center or to a point or region of interest.

Pseudouridine: As used herein, pseudouridine refers to the C-glycoside isomer of the nucleoside uridine. A “pseudouridine analog” is any modification, variant, isoform or derivative of pseudouridine. For example, pseudouridine analogs include but are not limited to 1-carboxymethyl-pseudouridine, 1-propynyl-pseudouridine, 1-taurinomethyl-pseudouridine, 1-taurinomethyl-4-thio-pseudouridine, 1-methylpseudouridine (m¹ψ), 1-methyl-4-thio-pseudouridine (m¹s⁴ψ), 4-thio-1-methyl-pseudouridine, 3-methyl-pseudouridine (m³ψ), 2-thio-1-methyl-pseudouridine, 1-methyl-1-deaza-pseudouridine, 2-thio-1-methyl-1-deaza-pseudouridine, dihydropseudouridine, 2-thio-dihydropseudouridine, 2-methoxyuridine, 2-methoxy-4-thio-uridine, 4-methoxy-pseudouridine, 4-methoxy-2-thio-pseudouridine, N1-methyl-pseudouridine, 1-methyl-3-(3-amino-3-carboxypropyl)pseudouridine (acp³ψ), and 2′-O-methyl-pseudouridine (Wm).

Purified: As used herein, “purify,” “purified,” “purification” means to make substantially pure or clear from unwanted components, material defilement, admixture or imperfection.

Repeated transfection: As used herein, the term “repeated transfection” refers to transfection of the same cell culture with a polynucleotide a plurality of times. The cell culture can be transfected at least twice, at least 3 times, at least 4 times, at least 5 times, at least 6 times, at least 7 times, at least 8 times, at least 9 times, at least 10 times, at least 11 times, at least 12 times, at least 13 times, at least 14 times, at least 15 times, at least 16 times, at least 17 times at least 18 times, at least 19 times, at least 20 times, at least 25 times, at least 30 times, at least 35 times, at least 40 times, at least 45 times, at least 50 times or more.

Sample: As used herein, the term “sample” or “biological sample” refers to a subset of its tissues, cells or component parts (e.g. body fluids, including but not limited to blood, mucus, lymphatic fluid, synovial fluid, cerebrospinal fluid, saliva, amniotic fluid, amniotic cord blood, urine, vaginal fluid and semen). A sample further may include a homogenate, lysate or extract prepared from a whole organism or a subset of its tissues, cells or component parts, or a fraction or portion thereof, including but not limited to, for example, plasma, serum, spinal fluid, lymph fluid, the external sections of the skin, respiratory, intestinal, and genitourinary tracts, tears, saliva, milk, blood cells, tumors, organs. A sample further refers to a medium, such as a nutrient broth or gel, which may contain cellular components, such as proteins or nucleic acid molecule.

Signal Sequences: As used herein, the phrase “signal sequences” refers to a sequence which can direct the transport or localization of a protein.

Single unit dose: As used herein, a “single unit dose” is a dose of any therapeutic administered in one dose/at one time/single route/single point of contact, i.e., single administration event.

Similarity: As used herein, the term “similarity” refers to the overall relatedness between polymeric molecules, e.g. between polynucleotide molecules (e.g. DNA molecules and/or RNA molecules) and/or between polypeptide molecules. Calculation of percent similarity of polymeric molecules to one another can be performed in the same manner as a calculation of percent identity, except that calculation of percent similarity takes into account conservative substitutions as is understood in the art.

Split dose: As used herein, a “split dose” is the division of single unit dose or total daily dose into two or more doses.

Stable: As used herein “stable” refers to a compound that is sufficiently robust to survive isolation to a useful degree of purity from a reaction mixture, and preferably capable of formulation into an efficacious therapeutic agent.

Stabilized: As used herein, the term “stabilize”, “stabilized,” “stabilized region” means to make or become stable.

Stereoisomer: As used herein, the term “stereoisomer” refers to all possible different isomeric as well as conformational forms which a compound may possess (e.g., a compound of any formula described herein), in particular all possible stereochemically and conformationally isomeric forms, all diastereomers, enantiomers and/or conformers of the basic molecular structure. Some compounds of the present invention may exist in different tautomeric forms, all of the latter being included within the scope of the present invention.

Subject: As used herein, the term “subject” or “patient” refers to any organism to which a composition in accordance with the invention may be administered, e.g., for experimental, diagnostic, prophylactic, and/or therapeutic purposes. Typical subjects include animals (e.g., mammals such as mice, rats, rabbits, non-human primates, and humans) and/or plants.

Substantially: As used herein, the term “substantially” refers to the qualitative condition of exhibiting total or near-total extent or degree of a characteristic or property of interest. One of ordinary skill in the biological arts will understand that biological and chemical phenomena rarely, if ever, go to completion and/or proceed to completeness or achieve or avoid an absolute result. The term “substantially” is therefore used herein to capture the potential lack of completeness inherent in many biological and chemical phenomena.

Substantially equal: As used herein as it relates to time differences between doses, the term means plus/minus 2%.

Substantially simultaneously: As used herein and as it relates to plurality of doses, the term means within 2 seconds.

Suffering from: An individual who is “suffering from” a disease, disorder, and/or condition has been diagnosed with or displays one or more symptoms of a disease, disorder, and/or condition.

Susceptible to: An individual who is “susceptible to” a disease, disorder, and/or condition has not been diagnosed with and/or may not exhibit symptoms of the disease, disorder, and/or condition but harbors a propensity to develop a disease or its symptoms. In some embodiments, an individual who is susceptible to a disease, disorder, and/or condition (for example, cancer) may be characterized by one or more of the following: (1) a genetic mutation associated with development of the disease, disorder, and/or condition; (2) a genetic polymorphism associated with development of the disease, disorder, and/or condition; (3) increased and/or decreased expression and/or activity of a protein and/or nucleic acid associated with the disease, disorder, and/or condition; (4) habits and/or lifestyles associated with development of the disease, disorder, and/or condition; (5) a family history of the disease, disorder, and/or condition; and (6) exposure to and/or infection with a microbe associated with development of the disease, disorder, and/or condition. In some embodiments, an individual who is susceptible to a disease, disorder, and/or condition will develop the disease, disorder, and/or condition. In some embodiments, an individual who is susceptible to a disease, disorder, and/or condition will not develop the disease, disorder, and/or condition.

Sustained release: As used herein, the term “sustained release” refers to a pharmaceutical composition or compound release profile that conforms to a release rate over a specific period of time.

Synthetic: The term “synthetic” means produced, prepared, and/or manufactured by the hand of man. Synthesis of polynucleotides or polypeptides or other molecules of the present invention may be chemical or enzymatic.

Vaccine: As used herein, a vaccine is a compound or composition which comprises at least one polynucleotide encoding at least one antigen.

Targeted Cells: As used herein, “targeted cells” refers to any one or more cells of interest. The cells may be found in vitro, in vivo, in situ or in the tissue or organ of an organism. The organism may be an animal, preferably a mammal, more preferably a human and most preferably a patient.

Therapeutic Agent: The term “therapeutic agent” refers to any agent that, when administered to a subject, has a therapeutic, diagnostic, and/or prophylactic effect and/or elicits a desired biological and/or pharmacological effect.

Therapeutically effective amount: As used herein, the term “therapeutically effective amount” means an amount of an agent to be delivered (e.g., nucleic acid, drug, therapeutic agent, diagnostic agent, prophylactic agent, etc.) that is sufficient, when administered to a subject suffering from or susceptible to an infection, disease, disorder, and/or condition, to treat, improve symptoms of, diagnose, prevent, and/or delay the onset of the infection, disease, disorder, and/or condition.

Therapeutically effective outcome: As used herein, the term “therapeutically effective outcome” means an outcome that is sufficient in a subject suffering from or susceptible to an infection, disease, disorder, and/or condition, to treat, improve symptoms of, diagnose, prevent, and/or delay the onset of the infection, disease, disorder, and/or condition.

Total daily dose: As used herein, a “total daily dose” is an amount given or prescribed in 24 hr period. It may be administered as a single unit dose.

Transcription factor: As used herein, the term “transcription factor” refers to a DNA-binding protein that regulates transcription of DNA into RNA, for example, by activation or repression of transcription. Some transcription factors effect regulation of transcription alone, while others act in concert with other proteins. Some transcription factor can both activate and repress transcription under certain conditions. In general, transcription factors bind a specific target sequence or sequences highly similar to a specific consensus sequence in a regulatory region of a target gene. Transcription factors may regulate transcription of a target gene alone or in a complex with other molecules.

Transfection: As used herein, the term “transfection” refers to methods to introduce exogenous nucleic acids into a cell. Methods of transfection include, but are not limited to, chemical methods, physical treatments and cationic lipids or mixtures.

Translation: As used herein “translation” is the process by which a polynucleotide molecule is processed by a ribosome or ribosomal-like machinery, e.g., cellular or artificial, to produce a peptide or polypeptide.

Transcription: As used herein “transcription” is the process by which a polynucleotide molecule is processed by a polymerase or other enzyme to produce a polynucleotide, e.g., an RNA polynucleotide.

Treating: As used herein, the term “treating” refers to partially or completely alleviating, ameliorating, improving, relieving, delaying onset of, inhibiting progression of, reducing severity of, and/or reducing incidence of one or more symptoms or features of a particular infection, disease, disorder, and/or condition. Treatment may be administered to a subject who does not exhibit signs of a disease, infection, disorder, and/or condition and/or to a subject who exhibits only early signs of a disease, infection, disorder, and/or condition for the purpose of decreasing the risk of developing pathology associated with the disease, infection, disorder, and/or condition.

Unmodified: As used herein, “unmodified” refers to any substance, compound or molecule prior to being changed in any way. Unmodified may, but does not always, refer to the wild type or native form of a biomolecule. Molecules may undergo a series of modifications whereby each modified molecule may serve as the “unmodified” starting molecule for a subsequent modification.

Vaccine: As used herein, the phrase “vaccine” refers to a biological preparation that improves immunity in the context of a particular disease, disorder or condition.

Viral protein: As used herein, the pharse “viral protein” means any protein originating from a virus.

EQUIVALENTS AND SCOPE

Those skilled in the art will recognize, or be able to ascertain using no more than routine experimentation, many equivalents to the specific embodiments in accordance with the invention described herein. The scope of the present invention is not intended to be limited to the above Description, but rather is as set forth in the appended claims.

In the claims, articles such as “a,” “an,” and “the” may mean one or more than one unless indicated to the contrary or otherwise evident from the context. Claims or descriptions that include “or” between one or more members of a group are considered satisfied if one, more than one, or all of the group members are present in, employed in, or otherwise relevant to a given product or process unless indicated to the contrary or otherwise evident from the context. The invention includes embodiments in which exactly one member of the group is present in, employed in, or otherwise relevant to a given product or process. The invention includes embodiments in which more than one, or all of the group members are present in, employed in, or otherwise relevant to a given product or process.

It is also noted that the term “comprising” is intended to be open and permits but does not require the inclusion of additional elements or steps. When the term “comprising” is used herein, the term “consisting of” is thus also encompassed and disclosed.

Where ranges are given, endpoints are included. Furthermore, it is to be understood that unless otherwise indicated or otherwise evident from the context and understanding of one of ordinary skill in the art, values that are expressed as ranges can assume any specific value or subrange within the stated ranges in different embodiments of the invention, to the tenth of the unit of the lower limit of the range, unless the context clearly dictates otherwise.

In addition, it is to be understood that any particular embodiment of the present invention that falls within the prior art may be explicitly excluded from any one or more of the claims. Since such embodiments are deemed to be known to one of ordinary skill in the art, they may be excluded even if the exclusion is not set forth explicitly herein. Any particular embodiment of the compositions of the invention (e.g., any nucleic acid or protein encoded thereby; any method of production; any method of use; etc.) can be excluded from any one or more claims, for any reason, whether or not related to the existence of prior art.

All cited sources, for example, references, publications, databases, database entries, and art cited herein, are incorporated into this application by reference, even if not expressly stated in the citation. In case of conflicting statements of a cited source and the instant application, the statement in the instant application shall control.

Section and table headings are not intended to be limiting.

EXAMPLES
Example 1. Manufacture of Polynucleotides

According to the present invention, the manufacture of polynucleotides and or parts or regions thereof may be accomplished utilizing the methods taught in U.S. Ser. No. 61/800,049 filed Mar. 15, 2013 entitled “Manufacturing Methods for Production of RNA Transcripts” (Attorney Docket number M500), the contents of which is incorporated herein by reference in its entirety.

Purification methods may include those taught in U.S. Provisional Patent Application No. 61/799,872, U.S. Provisional Patent Application No. 61/794,842, U.S. Provisional Patent Application 61/800,326, each of which is incorporated herein by reference in its entirety.

Detection and characterization methods of the polynucleotides may be performed as taught in US Provisional Patent Application No. 61n99,780 and U.S. Provisional Patent Application No. 61/798,945, each of which is incorporated herein by reference in its entirety.

Characterization of the polynucleotides of the invention may be accomplished using a procedure selected from the group consisting of polynucleotide mapping, reverse transcriptase sequencing, charge distribution analysis, and detection of RNA impurities, wherein characterizing comprises determining the RNA transcript sequence, determining the purity of the RNA transcript, or determining the charge heterogeneity of the RNA transcript. Such methods are taught in, for example, U.S. Provisional Patent Application No. 61/799,905 and US Provisional Patent Application No. 61/800,110, the contents of each of which is incorporated herein by reference in its entirety.

Example 2. Chimeric Polynucleotide Synthesis
Introduction

According to the present invention, two regions or parts of a chimeric polynucleotide may be joined or ligated using triphosphate chemistry.

According to this method, a first region or part of 100 nucleotides or less is chemically synthesized with a 5′ monophosphate and terminal 3′desOH or blocked OH. If the region is longer than 80 nucleotides, it may be synthesized as two strands for ligation.

If the first region or part is synthesized as a non-positionally modified region or part using in vitro transcription (IVT), conversion the 5′monophosphate with subsequent capping of the 3′ terminus may follow.

Monophosphate protecting groups may be selected from any of those known in the art.

The second region or part of the chimeric polynucleotide may be synthesized using either chemical synthesis or IVT methods. IVT methods may include an RNA polymerase that can utilize a primer with a modified cap. Alternatively, a cap of up to 130 nucleotides may be chemically synthesized and coupled to the IVT region or part.

It is noted that for ligation methods, ligation with DNA T4 ligase, followed by treatment with DNAse should readily avoid concatenation.

The entire chimeric polynucleotide need not be manufactured with a phosphate-sugar backbone. If one of the regions or parts encodes a polypeptide, then it is preferable that such region or part comprise a phosphate-sugar backbone.

Ligation is then performed using any known click chemistry, orthoclick chemistry, solulink, or other bioconjugate chemistries known to those in the art.

Synthetic Route

The chimeric polynucleotide is made using a series of starting segments. Such segments include:

- (a) Capped and protected 5′ segment comprising a normal 3′OH (SEG. 1)
- (b) 5′ triphosphate segment which may include the coding region of a polypeptide and comprising a normal 3′OH (SEG. 2)
- (c) 5′ monophosphate segment for the 3′ end of the chimeric polynucleotide (e.g., the tail) comprising cordycepin or no 3′OH (SEG. 3)

After synthesis (chemical or IVT), segment 3 (SEG. 3) is treated with cordycepin and then with pyrophosphatase to create the 5′monophosphate.

Segment 2 (SEG. 2) is then ligated to SEG. 3 using RNA ligase. The ligated polynucleotide is then purified and treated with pyrophosphatase to cleave the diphosphate. The treated SEG.2-SEG. 3 construct is then purified and SEG. 1 is ligated to the 5′ terminus. A further purification step of the chimeric polynucleotide may be performed.

Where the chimeric polynucleotide encodes a polypeptide, the ligated or joined segments may be represented as: 5′UTR (SEG. 1), open reading frame or ORF (SEG. 2) and 3′UTR+PolyA (SEG. 3).

The yields of each step may be as much as 90-95%.

Example 3: PCR for cDNA Production

PCR procedures for the preparation of cDNA are performed using 2×KAPA HIFI™ HotStart ReadyMix by Kapa Biosystems (Woburn, MA). This system includes 2×KAPA ReadyMix12.5 μl; Forward Primer (10 uM) 0.75 μl; Reverse Primer (10 uM) 0.75 μl; Template cDNA −100 ng; and dH₂0 diluted to 25.0 μl. The reaction conditions are at 95° C. for 5 min. and 25 cycles of 98° C. for 20 sec, then 58° C. for 15 sec, then 72° C. for 45 sec, then 72° C. for 5 min. then 4° C. to termination.

The reverse primer of the instant invention incorporates a poly-T₁₂₀for a poly-A₁₂₀in the mRNA. Other reverse primers with longer or shorter poly(T) tracts can be used to adjust the length of the poly(A) tail in the polynucleotide mRNA.

The reaction is cleaned up using Invitrogen's PURELINK™ PCR Micro Kit (Carlsbad, CA) per manufacturer's instructions (up to 5 μg). Larger reactions will require a cleanup using a product with a larger capacity. Following the cleanup, the cDNA is quantified using the NANODROP™ and analyzed by agarose gel electrophoresis to confirm the cDNA is the expected size. The cDNA is then submitted for sequencing analysis before proceeding to the in vitro transcription reaction.

Example 4. In Vitro Transcription (IVT)

The in vitro transcription reaction generates polynucleotides containing uniformly modified polynucleotides. Such uniformly modified polynucleotides may comprise a region or part of the polynucleotides of the invention. The input nucleotide triphosphate (NTP) mix is made in-house using natural and un-natural NTPs.

A typical in vitro transcription reaction includes the following:

1
Template cDNA
1.0
μg

2
10× transcription buffer (400 mM Tris-
2.0
μl

HCl pH 8.0, 190 mM MgCl₂, 50

mM DTT, 10 mM Spermidine)

3
Custom NTPs (25 mM each)
7.2
μl

4
RNase Inhibitor
20
U

5
T7 RNA polymerase
3000
U

6
dH₂0
Up to 20.0 μl. and

7
Incubation at 37° C. for 3 hr-5 hrs.

The crude IVT mix may be stored at 4° C. overnight for cleanup the next day. 1 U of RNase-free DNase is then used to digest the original template. After 15 minutes of incubation at 37° C., the mRNA is purified using Ambion's MEGACLEAR™ Kit (Austin, TX) following the manufacturer's instructions. This kit can purify up to 500 μg of RNA. Following the cleanup, the RNA is quantified using the NanoDrop and analyzed by agarose gel electrophoresis to confirm the RNA is the proper size and that no degradation of the RNA has occurred.

Example 5. Enzymatic Capping

Capping of a polynucleotide is performed as follows where the mixture includes: IVT RNA 60 μg-180 μg and dH₂0 up to 72 μl. The mixture is incubated at 65° C. for 5 minutes to denature RNA, and then is transferred immediately to ice.

The protocol then involves the mixing of 10× Capping Buffer (0.5 M Tris-HCl (pH 8.0), 60 mM KCl, 12.5 mM MgCl₂) (10.0 μl); 20 mM GTP (5.0 μl); 20 mM S-Adenosyl Methionine (2.5 μl); RNase Inhibitor (100 U); 2′-O-Methyltransferase (400 U); Vaccinia capping enzyme (Guanylyl transferase) (40 U); dH₂0 (Up to 28 μl); and incubation at 37° C. for 30 minutes for 60 μg RNA or up to 2 hours for 180 μg of RNA.

The polynucleotide is then purified using Ambion's MEGACLEAR™ Kit (Austin, TX) following the manufacturer's instructions. Following the cleanup, the RNA is quantified using the NANODROI™ (ThermoFisher, Waltham, MA) and analyzed by agarose gel electrophoresis to confirm the RNA is the proper size and that no degradation of the RNA has occurred. The RNA product may also be sequenced by running a reverse-transcription-PCR to generate the cDNA for sequencing.

Example 6. PolyA Tailing Reaction

Without a poly-T in the cDNA, a poly-A tailing reaction must be performed before cleaning the final product. This is done by mixing Capped IVT RNA (100 μl); RNase Inhibitor (20 U); 10× Tailing Buffer (0.5 M Tris-HCl (pH 8.0), 2.5 M NaCl, 100 mM MgCl₂)(12.0 μl); 20 mM ATP (6.0 μl); Poly-A Polymerase (20 U); dH₂0 up to 123.5 μl and incubation at 37° C. for 30 min. If the poly-A tail is already in the transcript, then the tailing reaction may be skipped and proceed directly to cleanup with Ambion's MEGACLEAR™ kit (Austin, TX) (up to 500 μg). Poly-A Polymerase is preferably a recombinant enzyme expressed in yeast.

It should be understood that the processivity or integrity of the polyA tailing reaction may not always result in an exact size polyA tail. Hence polyA tails of approximately between 40-200 nucleotides, e.g, about 40, 50, 60, 70, 80, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105, 106, 107, 108, 109, 110, 150-165, 155, 156, 157, 158, 159, 160, 161, 162, 163, 164 or 165 are within the scope of the invention.

Example 7. Natural 5′ Caps and 5′ Cap Analogues

5′-capping of polynucleotides may be completed concomitantly during the in vitro-transcription reaction using the following chemical RNA cap analogs to generate the 5′-guanosine cap structure according to manufacturer protocols: 3′-O-Me-m7G(5′)ppp(5′) G [the ARCA cap];G(5′)ppp(5′)A; G(5′)ppp(5′)G; m7G(5′)ppp(5′)A; m7G(5′)ppp(5′)G (New England BioLabs. Ipswich, MA). 5′-capping of modified RNA may be completed post-transcriptionally using a Vaccinia Virus Capping Enzyme to generate the “Cap 0” structure: m7G(5′)ppp(5′)G (New England BioLabs, Ipswich, MA). Cap 1 structure may be generated using both Vaccinia Virus Capping Enzyme and a 2′-O methyl-transferase to generate: m7G(5′)ppp(5′)G-2′-O-methyl. Cap 2 structure may be generated from the Cap 1 structure followed by the 2′-O-methylation of the 5′-antepenultimate nucleotide using a 2′-0 methyl-transferase. Cap 3 structure may be generated from the Cap 2 structure followed by the 2′-O-methylation of the 5′-preantepenultimate nucleotide using a 2′-O methyl-transferase. Enzymes are preferably derived from a recombinant source.

When transfected into mammalian cells, the modified mRNAs have a stability of between 12-18 hours or more than 18 hours, e.g., 24, 36, 48, 60, 72 or greater than 72 hours.

Example 8. Capping Assays
A. Protein Expression Assay

Polynucleotides encoding a polypeptide, containing any of the caps taught herein can be transfected into cells at equal concentrations. 6, 12, 24 and 36 hours post-transfection the amount of protein secreted into the culture medium can be assayed by ELISA. Synthetic polynucleotides that secrete higher levels of protein into the medium would correspond to a synthetic polynucleotide with a higher translationally-competent Cap structure.

B. Purity Analysis Synthesis

Polynucleotides encoding a polypeptide, containing any of the caps taught herein can be compared for purity using denaturing Agarose-Urea gel electrophoresis or HPLC analysis. Polynucleotides with a single, consolidated band by electrophoresis correspond to the higher purity product compared to polynucleotides with multiple bands or streaking bands. Synthetic polynucleotides with a single HPLC peak would also correspond to a higher purity product. The capping reaction with a higher efficiency would provide a more pure polynucleotide population.

C. Cytokine Analysis

Polynucleotides encoding a polypeptide, containing any of the caps taught herein can be transfected into cells at multiple concentrations. 6, 12, 24 and 36 hours post-transfection the amount of pro-inflammatory cytokines such as TNF-alpha and IFN-beta secreted into the culture medium can be assayed by ELISA. Polynucleotides resulting in the secretion of higher levels of pro-inflammatory cytokines into the medium would correspond to a polynucleotides containing an immune-activating cap structure.

D. Capping Reaction Efficiency

Polynucleotides encoding a polypeptide, containing any of the caps taught herein can be analyzed for capping reaction efficiency by LC-MS after nuclease treatment. Nuclease treatment of capped polynucleotides would yield a mixture of free nucleotides and the capped 5′-5-triphosphate cap structure detectable by LC-MS. The amount of capped product on the LC-MS spectra can be expressed as a percent of total polynucleotide from the reaction and would correspond to capping reaction efficiency. The cap structure with higher capping reaction efficiency would have a higher amount of capped product by LC-MS.

Example 9. Agarose Gel Electrophoresis of Modified RNA or RT PCR Products

Individual polynucleotides (200-400 ng in a 20 μl volume) or reverse transcribed PCR products (200-400 ng) are loaded into a well on a non-denaturing 1.2% Agarose E-Gel (Invitrogen, Carlsbad, CA) and run for 12-15 minutes according to the manufacturer protocol.

Example 10. Nanodrop Modified RNA Quantification and UV Spectral Data

Modified polynucleotides in TE buffer (1 μl) are used for Nanodrop UV absorbance readings to quantitate the yield of each polynucleotide from an chemical synthesis or in vitro transcription reaction.

Example 11. Formulation of Modified mRNA Using Lipidoids

Polynucleotides are formulated for in vitro experiments by mixing the polynucleotides with the lipidoid at a set ratio prior to addition to cells. In vivo formulation may require the addition of extra ingredients to facilitate circulation throughout the body. To test the ability of these lipidoids to form particles suitable for in vivo work, a standard formulation process used for siRNA-lipidoid formulations may used as a starting point. After formation of the particle, polynucleotide is added and allowed to integrate with the complex. The encapsulation efficiency is determined using a standard dye exclusion assays.

Example 12. Method of Screening for Protein Expression
A. Electrospray Ionization

A biological sample which may contain proteins encoded by a polynucleotide administered to the subject is prepared and analyzed according to the manufacturer protocol for electrospray ionization (ESI) using 1, 2, 3 or 4 mass analyzers. A biologic sample may also be analyzed using a tandem ESI mass spectrometry system.

Patterns of protein fragments, or whole proteins, are compared to known controls for a given protein and identity is determined by comparison.

B. Matrix-Assisted Laser Desorption/Ionization

A biological sample which may contain proteins encoded by one or more polynucleotides administered to the subject is prepared and analyzed according to the manufacturer protocol for matrix-assisted laser desorption/ionization (MALDI).

Patterns of protein fragments, or whole proteins, are compared to known controls for a given protein and identity is determined by comparison.

C. Liquid Chromatography-Mass Spectrometry-Mass Spectrometry

A biological sample, which may contain proteins encoded by one or more polynucleotides, may be treated with a trypsin enzyme to digest the proteins contained within. The resulting peptides are analyzed by liquid chromatography-mass spectrometry-mass spectrometry (LC/MS/MS). The peptides are fragmented in the mass spectrometer to yield diagnostic patterns that can be matched to protein sequence databases via computer algorithms. The digested sample may be diluted to achieve 1 ng or less starting material for a given protein. Biological samples containing a simple buffer background (e.g. water or volatile salts) are amenable to direct in-solution digest; more complex backgrounds (e.g. detergent, non-volatile salts, glycerol) require an additional clean-up step to facilitate the sample analysis.

Patterns of protein fragments, or whole proteins, are compared to known controls for a given protein and identity is determined by comparison.

Example 13. Cyclization and/or Concatemerization

According to the present invention, a polynucleotide may be cyclized, or concatemerized, to generate a translation competent molecule to assist interactions between poly-A binding proteins and 5′-end binding proteins. The mechanism of cyclization or concatemerization may occur through at least 3 different routes: 1) chemical, 2) enzymatic, and 3) ribozyme catalyzed. The newly formed 5′-/3′-linkage may be intramolecular or intermolecular.

In the first route, the 5′-end and the 3′-end of the nucleic acid contain chemically reactive groups that, when close together, form a new covalent linkage between the 5′-end and the 3′-end of the molecule. The 5′-end may contain an NHS-ester reactive group and the 3′-end may contain a 3′-amino-terminated nucleotide such that in an organic solvent the 3′-amino-terminated nucleotide on the 3′-end of a synthetic mRNA molecule will undergo a nucleophilic attack on the 5′-NHS-ester moiety forming a new 5′-/3′-amide bond.

In the second route, T4 RNA ligase may be used to enzymatically link a 5′-phosphorylated nucleic acid molecule to the 3′-hydroxyl group of a nucleic acid forming a new phosphorodiester linkage. In an example reaction, 1 μg of a nucleic acid molecule is incubated at 37° C. for 1 hour with 1-10 units of T4 RNA ligase (New England Biolabs, Ipswich, MA) according to the manufacturer's protocol. The ligation reaction may occur in the presence of a split polynucleotide capable of base-pairing with both the 5′- and 3′-region in juxtaposition to assist the enzymatic ligation reaction.

In the third route, either the 5′- or 3′-end of the cDNA template encodes a ligase ribozyme sequence such that during in vitro transcription, the resultant nucleic acid molecule can contain an active ribozyme sequence capable of ligating the 5′-end of a nucleic acid molecule to the 3′-end of a nucleic acid molecule. The ligase ribozyme may be derived from the Group I Intron, Group I Intron, Hepatitis Delta Virus, Hairpin ribozyme or may be selected by SELEX (systematic evolution of ligands by exponential enrichment). The ribozyme ligase reaction may take 1 to 24 hours at temperatures between 0 and 37° C.

Example 14. Antigen Polynucleotides

Polynucleotides used in the studies herein which encode certain infectious agent antigens or variants thereof are shown in Table 28.

TABLE 28

Antigen polynucleotides (RNA vaccine)

Construct

Number
Gene ID
Description
Construct

1
120552
Flu PR8 HA
HAPR8_Ferritin_Hs3

ferritin

2
120553
flu 1999NC HA
HA1999NC_Ferritin_

ferritin
Hs3

3
125387
H5N1 HA antigen
H5N1_HA_NIBRG-

14

4
125388
H1N1 PR8 HA
CurevacPR8HA_

antigen with MT
MT5U_Hs3U

5U/3U

5
135929
Influenza HA
HA_A/Mallard/

antigen
Netherlands/12/2000_

H7N3_Hs3U

6
135930
Influenza HA
HA_A/Puerto

antigen
Rico/8/1934_H1N1_

Hs3U

7
135931
Influenza HA
HA_A/Viet

antigen
Nam/850/2009_

H1N1_Hs3U

8
135932
Influenza HA
HA_A/New

antigen
Calcedonia/20/99_H1N1_

Hs3U

9
135933
Influenza HA
HA_A/Vietnam/1203/

antigen
2004_H5N1_Hs3U

10
135934
Influenza HA
HA_A/Hong

antigen
Kong/1073/99_H9N2_

Hs3U

11
135935
Influenza HA
HA_A/Wisconsin/67/

antigen
2005_H3N2_Hs3U

12
135936
Influenza HA
HA_A/Hong

antigen
Kong/1/1968_H3N2_

Hs3U

13
136473
flu HA antigen
A/duck/Anhui/SC702/

2013(H7N9)_Hs3U

14
136754
C diff antigen
Cdiff_toxinA.truc_

nMyc.cFLAG_Hs3U

15
136755
C diff antigen
Cdiff_toxinB.truc_

nMyc.cFLAG_Hs3U

16
136756
C diff antigen
Cdiff_cdtA.truc_nMyc.

cFLAG_Hs3U

17
136757
C diff antigen
Cdiff_cdtB.truc_nMyc.

cFLAG_Hs3U

18
120554
Dengue strain 2
DEN2_DIII_Ferritin_

domain 3 ferritin
Hs3

19
120555
Dengue strain 3
DEN3_DIII_Ferritin_

domain 3 ferritin
Hs3

20
120556
Dengue strain 4
DEN4_DIII_Ferritin_

domain 3 ferritin
Hs3

21
120557
dengue strain 1-4
Dengue_TDIII_Hs3

Domain 3

22
121542
Dengue strain 1
DEN1_DIII_Ferritin_

domain 3 ferritin
Corr_Hs3

23
131502
Dengue 2,
DEN2_D2Y98P_

D2Y98P strain,
PrME_Hs3

PrME

transmembrane

antigen

24
131503
Dengue 2,
DEN2_D2Y98P_

D2Y98P strain,
PrME80_Hs3

PrME secreted

antigen

25
131507
Dengue 2,
DEN2_D2Y98P_

D2Y98P strain,
PrME80_ScFv.aDEC205.

PrME secreted
FLAG_Hs3

antigen with

dendritic targeting

ScFv against

mouse DEC205

26
136358

Staph aureus

SpA_sec.D. wt.nXpress.

antigen
cHA_VKsp_Hs3U

27
136359

Staph aureus

SpA_intra.D.kkaa.

antigen
nFLAG.cMyc_Hs3U

28
136360

Staph aureus

SpA_mem.D.kkaa.

antigen
nFLAG.cMyc_

CD28mem_Hs3U

29
136361

Staph aureus

SpA_sec.D.kkaa.

antigen
nFLAG.cMyc_VKsp_

Hs3U

30
136362

Staph aureus

SpA_intra.D.wt.nXpress.

antigen
cHA_Hs3U

31
136363

Staph aureus

SpA_mem.D.wt.

antigen
nXpress.cHA_CD28mem_

Hs3U

32
136364

Staph aureus

SpA_sec.D.wt_VKsp

antigen

33
136758
MRSA IsdA
MRSA_IsdA.truc_

antigen
nMyc.cFLAG_Hs3U

34
136759
MRSA IsdB
MRSA_IsdB.truc_

antigen
nMyc.cFLAG_Hs3U

35
136763
MRSA SDRD
MRSA_sdrd.truc_

antigen
nMyc.cFLAG_Hs3U

36
136764
MRSA SDRE
MRSA_sdre.truc

antigen
nMyc.cFLAG_Hs3U

37
136765
MRSA MECA
MRSA_mecA.truc_

antigen
nMyc.cFLAG_Hs3U

38
139325
MRSA SDRD
MRSA_sdrd.contig1._

antigen
FLAG_Hs3U

39
139326
MRSA SDRD
MRSA_sdrd.Contig2._

antigen
FLAG_Hs3U

40
139327
MRSA SDRE
MRSA_sdre.Contig1._

antigen
FLAG_Hs3U

41
139328
MRSA SDRE
MRSA_sdre.Contig2._

antigen
FLAG_Hs3U

42
140470
MRSA ISDA
MRSA_IsdA.fl_

antigen
FLAG_Hs3U

43
139277
MRSA MECA
MRSA_mecA.fl._

antigen
FLAG_Hs3U

44
136747
ETEC antigen
ETEC.eltA(S63K/

R192G/L211A)_nMyc.

cFLAG_Hs3U

45
136748
ETEC antigen
ETEC.eltB_nMyc.

cFLAG_Hs3U

46
136749
ETEC antigen
ETEC.Sta3(A14Q)_

nMyc.cFLAG_Hs3U

47
136750
ETEC antigen
ETEC.etpA._nMyc.

cFLAG_Hs3U

48
136751
ETEC antigen
ETEC.etpB._nMyc.

cFLAG_Hs3U

49
136752
ETEC antigen
ETEC.EatA_nMyc.

cFLAG_Hs3U

50
136753
ETEC antigen
ETEC_cssA_nMyc.

cFLAG_Hs3U

51
136747
ETEC antigen
ETEC.eltA(S63K/

R192G/L211A)_nMyc.

cFLAG_Hs3U

52
142544
ETEC antigen
ETEC.etpB.fl_FLAG_

Hs3U

53
136749
ETEC antigen
ETEC.Sta3(A14Q)_

nMyc.cFLAG_Hs3U

54
136753
ETEC CSSA
ETEC_cssA_nMyc.

antigen
cFLAG_Hs3U

55
139323
ETEC EATA
ETEC_EatA.contig1._

antigen
FLAG_Hs3U

56
139324
ETEC EATA
ETEC_EatA.contig2._

antigen
FLAG_Hs3U

57
139321
ETEC EPTA
ETEC_eptA.contig1._

antigen
FLAG_Hs3U

58
139322
ETEC ETPA
ETEC_etpA.contig2._

antigen
FLAG_Hs3U

59
136760
Tuberculosis
TB_Ag85A_nMyc.

antigen
cFLAG_Hs3U

60
136761
Tuberculosis
TB_Ag85B_nMyc.

antigen
cFLAG_Hs3U

61
136762
Tuberculosis
TB_TB10.4_nMyc.

antigen
cFLAG_Hs3U

62
136335
Cholera toxin B
CholeraToxB.H78A.

FLAG_VKsp_Hs3U

63
144097
vaccine Influenza
PR8HA.Stalk.

HA antigen
pscaffold_Hs3U

(nanoscaffold)

64
144094
vaccine Influenza
PR8HA.stalk.HbCore.

HA antigen
monoRNA_Hs3U

(splitcore)

65
144095
vaccine Influenza
PR8HA.stalk.HbCoreC.

HA antigen
RKR_Hs3U

(splitcore)

66
144096
vaccine Influenza
PR8HA.stalk.HbCoreN.

HA antigen
RKR_Hs3U

(splitcore)

67
144098
vaccine Influenza
PR8HA.headless.

HA antigen;
Stalk.ugly(N76D/N270D)_

aglycosylated
Hs3U

68
144099
vaccine Influenza
PR8HA.headless.

HA antigen;
Stalk.ugly(N27D/N28D/

aglycosylated
N40D/N76D/N270D)_

Hs3U

69
150088
Vaccine MERS
MERS-

CoV spike protein
CoV_ProteinS/EMC/

(V5 epitope
2012.V5_Hs3U

tagged)

70
139276
vaccine MRSA
MRSA_IsdB.fl._

IsdB antigen
FLAG_Hs3U

71
149385
MERS-CoV
DPPIV.Fc_HS3U

passive immunity

72
150092
Vaccine HEV71
HEV71.VP1.2.3.VP5_

(polycistronic
HS3U

antigen containing

VP1 VP2 & VP3)

each separated by

a furin cleavage

site RKR

73
144093
vaccine Influenza
PR8HA.Stalk_Hs3U

HA antigen

74

Vaccine Klebsiella
Beta-lactamase

pneumoniae:
SHV-2

cefotaxime,

ceftazidime and

other broad

spectrum

cephalosporins.

75

Vaccine PsaA SP
Pneumococcal

Streptococcus

surface adhesin A

pneumoniae

surface adhesin A

Fragment (22-

309)

76

Vaccine

Pseudomonas type 2

Pseudomonas

Cephalosporinase

aeruginosa ampC

beta-lactamase

77

Vaccine
Beta-lactamase class

Pseudomonas

B VIM-2

aeruginosa VIM-2,

a carbapenem-

hydrolyzing

metallo-beta-

lactamase

78

Vaccine
Beta-lactamase

Pseudomonas

LCR-1

aeruginosa, LCR-1

hydrolyzes

methicillin.

79

Vaccine Staph

Staph aureus

aureus Toxic
TSST1

shock syndrome

toxin-1

80

Vaccine Staph

Staph aureus PVL

aureus PVL toxin
toxin

81

vaccine
Pneumolysin toxoid

Streptococcus

pneumoniae

Pneumolysin

toxoid

82

Full length with

Streptococcus

mutations of

pneumoniae ppaC

W433F, D385N,

and C428G

Additional antigens including wild type and engineered antigens are taught in Tables 29 and 30.

Pan-Flu NAVs

In one embodiment the “HA head” region of one or more influenza virus strains is removed leaving only the stem or transmembrane region. This region or multiple regions if selected, is then used as the immunogen to screen for optimal response to a viral challenge. As such broad neutralization could be achieved against multiple strains or a multi-response to one strain. The resultant vaccine would represent a pan-influenza vaccine.

Further, a pan-influenza vaccine could also be combined with any immune potentiator disclosed herein.

Polynucleotides used in the studies herein which encode certain infectious agent antigens or variants thereof may be formulated in any of the formulations described herein including LNPs and may be administered intradermally (ID) or intramuscularly (IM) or by any suitable route.

Disclosed in Table 29 are the HA regions, transmembrane and cytoplasmic regions of several influenza strains to be used in the stem vaccination generation protocol just described.

TABLE 29

Wild type antigens encoded by NAV polynucleotides

Full length HA AA

Virus
Strain
Sequence
HA1
HA2
TM
CY

H1N1
A/PR8/34
(SEQ ID NO: 931)
(SEQ ID NO:
(SEQ ID NO:
(SEQ
(SEQ

MKANLLVLLCALAAA
932)
933)
ID
ID

DADTICIGYHANNSTD
MKANLLVLL
GLFGAIAG
NO:
NO:

TVDTVLEKNVTVTHS
CALAAADAD
FIEGGWTG
934)
935)

VNLLEDSHNGKLCRL
TICIGYHANN
MIDGWYG
ILAI
SFW

KGIAPLQLGKCNIAGW
STDTVDTVLE
YHHQNEQ
YST
MCSN

LLGNPECDPLLPVRSW
KNVTVTHSV
GSGYAADQ
VAS
GSLQ

SYIVETPNSENGICYPG
NLLEDSHNG
KSTQNAIN
SLVL
CRICI

DFIDYEELREQLSSVSS
KLCRLKGIAP
GITNKVNT
LVSL

PERFEIFPKESSWPNHN
LQLGKCNIAG
VIEKMNIQF
GAI

TNGVTAACSHEGKSSF
WLLGNPECD
TAVGKEFN

YRNLLWLTEKEGSYP
PLLPVRSWSY
KLEKRMEN

KLKNSYVNKKGKEVL
IVETPNSENGI
LNKKVDD

VLWGIHHPPNSKEQQ
CYPGDFIDYE
GFLDIWTY

NLYQNENAYVSVVTS
ELREQLSSVS
NAELLVLL

NYNRRFTPEIAERPKV
SFERFEIFPKE
ENERTLDF

RDQAGRMNYYWTLL
SSWPNHNTN
HDSNVKNL

KPGDTIIFEANGNLIAP
GVTAACSHE
YEKVKSQL

MYAFALSRGFGSGIITS
GKSSFYRNLL
KNNAKEIG

NASMHECNTKCQTPL
WLTEKEGSY
NGCFEFYH

GAINSSLPYQNIHPVTI
PKLKNSYVN
KCDNECME

GECPKYVRSAKLRMV
KKGKEVLVL
SVRNGTYD

TGLRNNPSIQSRGLFG
WGIHHPPNSK
YPKYSEES

AIAGFIEGGWTGMIDG
EQQNLYQNE
KLNREKVD

WYGYHHQNEQGSGY
NAYVSVVTS
GVKLESMG

AADQKSTQNAINGITN
NYNRRFTPEI
IYQ

KVNTVIEKMNIQFTAV
AERPKVRDQ

GKEFNKLEKRMENLN
AGRMNYYW

KKVDDGFLDIWTYNA
TLLKPGDTIIF

ELLVLLENERTLDFHD
EANGNLIAPM

SNVKNLYEKVKSQLK
YAFALSRGFG

NNAKEIGNGCFEFYHK
SGIITSNASM

CDNECMESVRNGTYD
HECNTKCQTP

YPKYSEESKLNREKVD
LGAINSSLPY

GVKLESMGIYQILAIYS
QNIHPVTIGE

TVASSLVLLVSLGAISF
CPKYVRSAK

WMCSNGSLQCRICI
LRMVTGLRN

NPSIQSR

H1N1
A/New
(SEQ ID NO: 936)
(SEQ ID NO:
(SEQ ID NO:
(SEQ
(SEQ

Caledonia/
MKAKLLVLLCTFTAT
937)
938)
ID
ID

20/1999
YADTICIGYHANNSTD
MKAKLLVLL
GLFGAIAG
NO:
NO:

TVDTVLEKNVTVTHS
CTFTATYADT
FIEGGWTG
939)
940)

VNLLEDSHNGKLCLL
ICIGYHANNS
MVDGWYG
ILAI
SFW

KGIAPLQLGNCSVAG
TDTVDTVLE
YHHQNEQ
YST
MCSN

WILGNPECELLISKES
KNVTVTHSV
GSGYAADQ
VAS
GSLQ

WSYIVETPNPENGTCY
NLLEDSHNG
KSTQNAIN
SLVL
CRICI

PGYFADYEELREQLSS
KLCLLKGIAP
GITNKVNS
LVSL

VSSFERFEIFPKESSWP
LQLGNCSVA
VIEKMNTQ
GAI

NHTVTGVSASCSHNG
GWILGNPECE
FTAVGKEF

KSSFYRNLLWLTGKN
LLISKESWSYI
NKLERRME

GLYPNLSKSYVNNKE
VETPNPENGT
NLNKKVD

KEVLVLWGVHHPPNI
CYPGYFADY
DGFLDIWT

GNQRALYHTENAYVS
EELREQLSSV
YNAELLVL

VVSSHYSRRFTPEIAK
SSFERFEIFPK
LENERTLD

RPKVRDQEGRINYYW
ESSWPNHTVT
FHDSNVKN

TLLEPGDTIIFEANGNL
GVSASCSHN
LYEKVKSQ

IAPWYAFALSRGFGSG
GKSSFYRNLL
LKNNAKEI

IITSNAPMDECDAKCQ
WLTGKNGLY
GNGCFEFY

TPQGAINSSLPFQNVH
PNLSKSYVNN
HKCNNEC

PVTIGECPKYVRSAKL
KEKEVLVLW
MESVKNGT

RMVTGLRNIPSIQSRG
GVHHPPNIGN
YDYPKYSE

LFGAIAGFIEGGWTGM
QRALYHTEN
ESKLNREKI

VDGWYGYHHQNEQG
AYVSVVSSH
DGVKLESM

SGYAADQKSTQNAIN
YSRRFTPEIA
GVYQ

GITNKVNSVIEKMNTQ
KRPKVRDQE

FTAVGKEFNKLERRM
GRINYYWTL

ENLNKKVDDGFLDIW
LEPGDTIIFEA

TYNAELLVLLENERTL
NGNLIAPWY

DFHDSNVKNLYEKVK
AFALSRGFGS

SQLKNNAKEIGNGCFE
GIITSNAPMD

FYHKCNNECMESVKN
ECDAKCQTP

GTYDYPKYSEESKLNR
QGAINSSLPF

EKIDGVKLESMGVYQI
QNVHPVTIGE

LAIYSTVASSLVLLVSL
CPKYVRSAK

GAISFWMCSNGSLQCR
LRMVTGLRNI

ICI
PSIQSR

H10N8
A/JX346/
(SEQ ID NO: 941)
(SEQ ID NO:
(SEQ ID NO:
(SEQ
(SEQ

2013
MYKIVVIIALLGAVKG
942)
943)
ID
ID

LDKICLGHHAVANGTI
MYKIVVIIAL
RGLFGAIA
NO:
NO:

VKTLTNEQEEVTNATE
LGAVKGLDKI
GFLENGWE
944)
945)

TVESTGINRLCMKGRK
CLGHHAVAN
GMVDGWY
WFS
CLKN

HKDLGNCHPIGMLIGT
GTIVKTLTNE
GFRHQNAQ
FGA
GNM

PACDLHLTGMWDTLI
QEEVTNATET
GTGQAAD
SCFV
RCTIC

ERENAIAYCYPGATVN
VESTGINRLC
YKSTQAAI
LLA
I

VEALRQKIMESGGINK
MKGRKHKDL
DQITGKLN
VVM

ISTGFTYGSSINSAGTT
GNCHPIGMLI
RLVEKTNT
GLFF

RACMRNGGNSFYAEL
GTPACDLHLT
EFESIESEFS
F

KWLVSKSKGQNFPQT
GMWDTLIER
EIEHQIGNV

TNTYRNTDTAEHLIM
ENAIAYCYPG
INWTKDSIT

WGIHHPSSTQEKNDLY
ATVNVEALR
DIWTYQAE

GTQSLSISVGSSTYRN
QKIMESGGIN
LLVAMENQ

NFVPVVGARPQVNGQ
KISTGFTYGS
HTIDMADS

SGRIDFHWTLVQPGDN
SINSAGTTRA
EMLNLYER

ITFSHNGGLIAPSRVSK
CMRNGGNSF
VRKQLRQN

LIGRGLGIQSDAPIDNN
YAELKWLVS
AEEDGKGC

CESKCFWRGGSINTRL
KSKGQNFPQT
FEIYHACD

PFQNLSPRTVGQCPKY
TNTYRNTDT
DSCMESIR

VNRRSLMLATGMRNV
AEHLIMWGIH
NNTYDHSQ

PELIQGRGLFGAIAGFL
HPSSTQEKND
YREEALLN

ENGWEGMVDGWYGF
LYGTQSLSIS
RLNINPVTL

RHQNAQGTGQAADY
VGSSTYRNNF
SSGYKDIIL

KS TQAAIDQITGKLNR
VPVVGARPQ

LVEKTNTEFESIESEFS
VNGQSGRIDF

EIEHQIGNVINWTKDSI
HWTLVQPGD

TDIWTYQAELLVAME
NITFSHNGGLI

NQHTIDMADSEMLNL
APSRVSKLIG

YERVRKQLRQNAEED
RGLGIQSDAP

GKGCFEIYHACDDSC
IDNNCESKCF

MESIRNNTYDHSQYRE
WRGGSINTRL

EALLNRLNINPVTLSS
PFQNLSPRTV

GYKDIILWFSFGASCF
GQCPKYVNR

VLLAVVMGLFFFCLK
RSLMLATGM

NGNMRCTICI
RNVPELIQG

H7N9
A/Anhui/1/
(SEQ ID NO: 946)
(SEQ ID NO:
(SEQ ID NO:
(SEQ
(SEQ

2013
MNTQILVFALIAIIPTN
947)
948)
ID
ID

ADKICLGHHAVSNGT
MNTQILVFAL
RGLFGAIA
NO:
NO:

KVNTLTERGVEVVNA
IAIIPTNADKI
GFIENGWE
949)
950)

TETVERTNIPRICSKGK
CLGHHAVSN
GLIDGWYG
WFS
CVKN

KTVDLGQCGLLGTITG
GTKVNTLTER
FRHQNAQG
FGA
GNM

PPQCDQFLEFSADLIIE
GVEVVNATE
EGTAADYK
SCFI
RCTIC

RREGSDVCYPGKFVN
TVERTNIPRIC
STQSAIDQI
LLAI
I

EEALRQILRESGGIDKE
SKGKKTVDL
TGKLNRLIE
VMG

AMGFTYSGIRTNGATS
GQCGLLGTIT
KTNQQFELI
LVFI

ACRRSGSSFYAEMKW
GPPQCDQFLE
DNEFNEVE

LLSNTDNAAFPQMTKS
FSADLIIERRE
KQIGNVIN

YKNTRKSPALIVWGIH
GSDVCYPGK
WTRDSITE

HSVSTAEQTKLYGSGN
FVNEEALRQI
VWSYNAEL

KLVTVGSSNYQQSFVP
LRESGGIDKE
LVAMENQ

SPGARPQVNGQSGRID
AMGFTYSGIR
HTIDLADSE

FHWLMLNPNDTVTFS
TNGATSACR
MDKLYER

FNGAFIAPDRASFLRG
RSGSSFYAEM
VKRQLREN

KSMGIQSGVQVDANC
KWLLSNTDN
AEEDGTGC

EGDCYHSGGTIISNLPF
AAFPQMTKS
FEIFHKCDD

QNIDSRAVGKCPRYV
YKNTRKSPAL
DCMASIRN

KQRSLLLATGMKNVP
IVWGIHHSVS
NTYDHSKY

EIPKGRGLFGAIAGFIE
TAEQTKLYGS
REEAMQNR

NGWEGLIDGWYGFRH
GNKLVTVGS
IQIDPVKLS

QNAQGEGTAADYKST
SNYQQSFVPS
SGYKDVIL

QSAIDQITGKLNRLIEK
PGARPQVNG

TNQQFELIDNEFNEVE
QSGRIDFHWL

KQIGNVINWTRDSITE
MLNPNDTVT

VWSYNAELLVAMENQ
FSFNGAFIAP

HTIDLADSEMDKLYER
DRASFLRGKS

VKRQLRENAEEDGTG
MGIQSGVQV

CFEIFHKCDDDCMASI
DANCEGDCY

RNNTYDHSKYREEAM
HSGGTIISNLP

QNRIQIDPVKLSSGYK
FQNIDSRAVG

DVILWFSFGASCFILLA
KCPRYVKQR

IVMGLVFICVKNGNM
SLLLATGMK

RCTICI
NVPEIPKG

H7N9
.A/Jiangsu/
(SEQ ID NO: 951)
(SEQ ID NO:
(SEQ ID NO:
(SEQ
(SEQ

2/2013(H
MNTQILVFALIAIIPTN
952)
953)
ID
ID

242)
ADKICLGHHAVSNGT
MNTQILVFAL
RGLFGAIA
NO:
NO:

KVNTLTERGVEVVNA
IAIIPTNADKI
GFIENGWE
954)
955)

TETVERTNIPRICSKGK
CLGHHAVSN
GLIDGWYG
WFS
CVKN

MTVDLGQCGLLGTITG
GTKVNTLTER
FRHQNAQG
FGA
GNM

PPQCDQFLEFSADLIIE
GVEVVNATE
EGTAADYK
SCFI
RCTIC

RREGSDVCYPGKFVN
TVERTNIPRIC
STQSAIDQI
LLAI
I

EEALRQILRESGGIDKE
SKGKMTVDL
TGKLNRLIE
VMG

AMGFTYSGIRTNGATS
GQCGLLGTIT
KTNQQFELI
LVFI

ACRRSGSSFYAEMKW
GPPQCDQFLE
DNEFNEVE

LLSNTDNAAFPQMTKS
FSADLIIERRE
KQIGNVIN

YKNTRKSPALIVWGIH
GSDVCYPGK
WTRDSITE

HSVSTAEQTKLYGSGN
FVNEEALRQI
VWSYNAEL

KLVTVGSSNYQQSFVP
LRESGGIDKE
LVAMENQ

SPGARPQVNGLSGRID
AMGFTYSGIR
HTIDLADSE

FHWLMLNPNDTVTFS
TNGATSACR
MDKLYER

FNGAFIAPDRASFLRG
RSGSSFYAEM
VKRQLREN

KSMGIQSGVQVDANC
KWLLSNTDN
AEEDGTGC

EGDCYHSGGTIISNLPF
AAFPQMTKS
FEIFHKCDD

QNIDSRAVGKCPRYV
YKNTRKSPAL
DCMASIRN

KQRSLLLATGMKNVP
IVWGIHHSVS
NTYDHSKY

EIPKGRGLFGAIAGFIE
TAEQTKLYGS
ReEAMQNR

NGWEGLIDGWYGFRH
GNKLVTVGS
IQIDPVKLS

QNAQGEGTAADYKST
SNYQQSFVPS
SGYKDVIL

QSAIDQITGKLNRLIEK
PGARPQVNG

TNQQFELIDNEFNEVE
LSGRIDFHWL

KQIGNVINWTRDSITE
MLNPNDTVT

VWSYNAELLVAMENQ
FSFNGAFIAP

HTIDLADSEMDKLYER
DRASFLRGKS

VKRQLRENAEEDGTG
MGIQSGVQV

CFEIFHKCDDDCMASI
DANCEGDCY

RNNTYDHSKYReEAM
HSGGTIISNLP

QNRIQIDPVKLSSGYK
FQNIDSRAVG

DVILWFSFGASCFILLA
KCPRYVKQR

IVMGLVFICVKNGNM
SLLLATGMK

RCTICI
NVPEIPKG

In the Table, TM stands for transmembrane and CY stands for cytoplasmic.

Following the vaccine generation strategy above, engineered antigens may also be used to develop pan-flu vaccines. Such constructs are shown in Table 30.

TABLE 30

Engineered antigens encoded by NAV polynucleotides

Configur-
Protein

SEQ ID

Virus
Strain
ation
engineering
Full length Sequence
NO.

H1N1
PR8/34
HA(PR8)-
fusion protein
MKANLLVLLCALAAADADTICIGY
956

Ferritin
of HA
HANNSTDTVDTVLEKNVTVTHSV

antigen with
NLLEDSHNGKLCRLKGIAPLQLGK

ferritin (H
CNIAGWLLGNPECDPLLPVRSWSY

pylori) to
IVETPNSENGICYPGDFIDYEELRE

form
QLSSVSSFERFEIFPKESSWPNHNT

nanoscaffold,
NGVTAACSHEGKSSFYRNLLWLTE

secreted
KEGSYPKLKNSYVNKKGKEVLVL

WGIHHPPNSKEQQNLYQNENAYV

SVVTSNYNRRFTPEIAERPKVRDQ

AGRMNYYWTLLKPGDTIIFEANGN

LIAPMYAFALSRGFGSGIITSNASM

HECNTKCQTPLGAINSSLPYQNIHP

VTIGECPKYVRSAKLRMVTGLRNN

PSIQSRGLFGAIAGFIEGGWTGMID

GWYGYHHQNEQGSGYAADQKST

QNAINGITNKVNTVIEKMNIQFTA

VGKEFNKLEKRMENLNKKVDDGF

LDIWTYNAELLVLLENERTLDFHD

SNVKNLYEKVKSQLKNNAKEIGN

GCFEFYHKCDNECMESVRNGTYD

YPKYSEESKLNREKVDSGGDIIKLL

NEQVNKEMQSSNLYMSMSSWCYT

HSLDGAGLFLFDHAAEEYEHAKK

LIIFLNENNVPVQLTSISAPEHKFEG

LTQIFQKAYEHEQHISESINNIVDH

AIKSKDHATFNFLQWYVAEQHEEE

VLFKDILDKIELIGNENHGLYLADQ

YVKGIAKSRKS

H1N1
A/New
HA(NC19
fusion protein
MKAKLLVLLCTFTATYADTICIGY
957

Caledonia/
99)-
of HA
HANNSTDTVDTVLEKNVTVTHSV

20/1999
Ferritin
antigen with
NLLEDSHNGKLCLLKGIAPLQLGN

(1999

ferritin (H
CSVAGWILGNPECELLISKESWSYI

NC)

pylori) to
VETPNPENGTCYPGYFADYEELRE

form
QLSSVSSFERFEIFPKESSWPNHTV

nanoscaffold,
TGVSASCSHNGKSSFYRNLLWLTG

secreted
KNGLYPNLSKSYVNNKEKEVLVL

WGVHHPPNIGNQRALYHTENAYV

SVVSSHYSRRFTPEIAKRPKVRDQE

GRINYYWTLLEPGDTIIFEANGNLI

APWYAFALSRGFGSGIITSNAPMD

ECDAKCQTPQGAINSSLPFQNVHP

VTIGECPKYVRSAKLRMVTGLRNI

PQRETRGLFGAIAGFIEGGWTGMV

DGWYGYHHQNEQGSGYAADQKS

TQNAINGITNKVNSVIEKMNTQFT

AVGKEFNKLERRMENLNKKVDDG

FLDIWTYNAELLVLLENERTLDFH

DSNVKNLYEKVKSQLKNNAKEIG

NGCFEFYHKCNNECMESVKNGTY

DYPKYSEESKLNREKIDSGGDIIKL

LNEQVNKEMQSSNLYMSMSSWCY

THSLDGAGLFLFDHAAEEYEHAK

KLIIFLNENNVPVQLTSISAPEHKFE

GLTQIFQKAYEHEQHISESINNIVD

HAIKSKDHATFNFLQWYVAEQHE

EEVLFKDILDKIELIGNENHGLYLA

DQYVKGIAKSRKSGS

H1N1
PR8/34
HA1(-)
Headless HA
MKANLLVLLCALAAADADTICIGY
958

stem only
antigen (Stem
HANNSTDTVDTVLEKNVTVTHSV

HA
only),
NLLEDSHNGKLCGGGGCNTKCQT

antigen
transmembrane,
PLGAINSSLPYQNIHPVTIGECPKY

VRSAKLRMVTGLRNIPSIQSRGLFG

AIAGFIEGGWTGMIDGWYGYHHQ

NEQGSGYAADQKSTQNAINGITNK

VNTVIEKMNIQFTAVGKEFNKLEK

RMENLNKKVDDGFLDIWTYNAEL

LVLLENERTLDFHDSNVKNLYEKV

KSQLKNNAKEIGNGCFEFYHKCDN

ECMESVRNGTYDYPKYSEESKLNR

EKVDGVKLESMGIYQILAIYSTVAS

SLVLLVSLGAISFWMCSNGSLQCRI

CI

H1N1
PR8/34
Mono-
Headless HA
MKANLLVLLCALAAADADTICIGY
959

glycosyl-
antigen (Stem
HANNSTDTVDTVLEKNVTVTHSV

ated
only),
NLLEDSHNGKLCGGGGCNTKCQT

HA 1(-)
transmembrane,
PLGAIDSSLPYQNIHPVTIGECPKY

stem only
mongly-
VRSAKLRMVTGLRNIPSIQSRGLFG

HA
cosylated
AIAGFIEGGWTGMIDGWYGYHHQ

antigen
by N76D,
NEQGSGYAADQKSTQNAINGITNK

N270D
VNTVIEKMNIQFTAVGKEFNKLEK

RMENLNKKVDDGFLDIWTYNAEL

LVLLENERTLDFHDSNVKNLYEKV

KSQLKNNAKEIGNGCFEFYHKCDN

ECMESVRDGTYDYPKYSEESKLNR

EKVDGVKLESMGIYQILAIYSTVAS

SLVLLVSLGAISFWMCSNGSLQCRI

CI

H1N1
PR8/34
agly-
Headless HA
MKANLLVLLCALAAADADTICIGY
960

cosylated
antigen (Stem
HADDSTDTVDTVLEKDVTVTHSV

HA 1(-)
only),
NLLEDSHNGKLCGGGGCNTKCQT

Stem
transmembrane,
PLGAIDSSLPYQNIHPVTIGECPKY

only HA
agly-
VRSAKLRMVTGLRNIPSIQSRGLFG

antigen
cosylated
AIAGFIEGGWTGMIDGWYGYHHQ

by
NEQGSGYAADQKSTQNAINGITNK

N27D,N28D,
VNTVIEKMNIQFTAVGKEFNKLEK

N40D, N76D,
RMENLNKKVDDGFLDIWTYNAEL

N279D
LVLLENERTLDFHDSNVKNLYEKV

KSQLKNNAKEIGNGCFEFYHKCDN

ECMESVRDGTYDYPKYSEESKLNR

EKVDGVKLESMGIYQILAIYSTVAS

SLVLLVSLGAISFWMCSNGSLQCRI

CI

H1N1
PR8/34
HA1(-)
Headless HA
MKANLLVLLCALAAADADTICIGY
961

stem HA-
antigen (stem
HANNSTDTVDTVLEKNVTVTHSV

ferritin
only) fused to
NLLEDSHNGKLCGGGGCNTKCQT

ferritin
PLGAINSSLPYQNIHPVTIGECPKY

nanoscaffold,
VRSAKLRMVTGLRNIPSIQSRGLFG

secreted
AIAGFIEGGWTGMIDGWYGYHHQ

NEQGSGYAADQKSTQNAINGITNK

VNTVIEKMNIQFTAVGKEFNKLEK

RMENLNKKVDDGFLDIWTYNAEL

LVLLENERTLDFHDSNVKNLYEKV

KSQLKNNAKEIGNGCFEFYHKCDN

ECMESVRNGTYDYPKYSEESKLNR

EKVDSGGDIIKLLNEQVNKEMQSS

NLY

MSMSSWCYTHSLDGAGLFLFDHA

AEEYEHAKKLIIFLNENNVPVQLTS

ISAPEHKFEGLT

QIFQKAYEHEQHISESINNIVDHAIK

SKDHATFNFLQWYVAEQHEEEVL

FKDILDKIELI

GNENHGLYLADQYVKGIAKSRKS

GS

Example 15. Influenza Study—H1N1 Hemagglutinin (HA) Antigen

The instant study was designed in two phases, first to test the the immunogenicity of mRNA vaccines encoding HA from influenza A/PR/8 (HiNi1) in mice and second to test the efficacy of candidate influenza vaccines in mice against a lethal challenge with influenza (INFV) A/PR/8/34 (HIN1). The study design is outlined in Table 31. The NAV polynucleotide used in the study was construct 4 from Table 28.

In phase I of this study, mice were vaccinated on week 0 and 3 via intravenous (IV), intramuscular (IM), or intradermal (ID) routes. One group remained unvaccinated and one was administered inactivated PR8 antigen. Serum was collected from each mouse on weeks 1, 3 (pre-dose), and 5. Individual bleeds were tested for anti-HA activity via virus neutralization assay and HA inhibition (HAI) from all three time points and pooled samples from week 5 only were tested by Western blot using A/PR/8/34 (H1N1).

Phase II

Since the desired immune response was achieved (HAI titer >40), phase II of the study was performed. In phase II, mice were challenged with a lethal dose (10×LD₉₀; ˜100 plaque-forming units; PFU) of A/PR/8/34 (H1N1) via intranasal (IN) instillation. Mice were monitored for weights, health, and survival for 14 days.

This study tested the immunogenicity of mRNA vaccines encoding HA from Influenza A/PR/8 (H1N1) in mice. The study utilized 12 groups of five BALB/c female mice. Mice were vaccinated on week 0 and 3 via intranasal (positive control), intravenous, intramuscular, or intradermal routes. One group was unvaccinated and one administered inactivated PR8 antigen via intranasal vaccination.

This study tested whether candidate ribonucleic acid vaccines and formulations could protect mice from lethal influenza A/PR/8/34 (H1N1) infection. The mice used were 6-8 week old female BALB/c mice in groups of 10. Mice were vaccinated on weeks 0 and 3 via IM, ID, or IV route. Mouse serum was tested for microneutralization and HAI. Mice were then challenged with ˜1 LD₉₀of influenza A/PR/8/34 (H1N1) on week 7 administered intranasally (IN). Endpoint was day 13 post infection, death, or euthanasia. Animals displaying severe illness as determined by >30% weight loss, extreme lethargy, or paralysis were euthanized. Temperature and weights were taken daily.

The LNP formulation consisted of a cationic lipid, non-cationic lipid, PEG lipid and structural lipid in the ratios 50:10:1.5:38.5. The cationic lipid was DLin-KC2-DMA (50 mol %), the non-cationic lipid was DSPC (10 mol %), the PEG lipid was PEG-DOMG (1.5 mol %) and the structural lipid was cholesterol (38.5 mol %).

Serum was collected from each mouse on weeks 1, 3 (pre-dose), and 5. Individual bleeds were tested for anti-HA activity via virus neutralization assay and HA inhibition (HAI) from all three time points (individual animals) and pooled samples from week 5 only were tested by Western blot using inactivated Influenza A/PR/8 (H1N1).

Standard Protocol for Intranasal Infection of Mice

Female 6-8 week old BALB/c mice were housed in groups of 5 mice. Mice were quarantined at the study site (Noble Life Sciences, Gaithersburg, MD) for at least 3 days prior to the start of the study. Food and water was provided ad libitum.

The groups of mice challenged with INFV were infected via intranasal (IN) inoculation with ˜10×LD90 in 100 μL of INFV in PBS under light anesthesia (Isoflurane). After the infection, mice were placed back into their cages for observation and subsequent dosing.

Microneutralization

The microneutralization protocol was the standard protocol for microneutralization of influenza as published by the World Health Organization, 6 December, 2010 and outlined by the WHO Collaborating Center for Surveillance, Epidemiology and Control of Influenza, Centers for Disease Control and Prevention, Atlanta, USA, the contents of which are incorporated herein by reference in their entirety.

Serologic Diagnosis of Influenza Virus Infections by Hemagglutination Inhibition.

The standard protocol for inhibition of hemagglutination can be found in publication WHO Influenza Manual, WHO/CDS/CSR/NCS/2002.5 Rev. 1, at page 37, the contents of which are incorporated by reference in their entirety.

Briefly, the protocol is as follows.

Procedure
I. Treatment of Sera

- 1. Identification of Influenza Isolates by Hemagglutination.
- 2. Adsorb sera to remove nonspecific agglutinins as described above.

II. Standardization of RBCs

Standardize RBCs according to the procedure in art recognized procedures.

III. HA Titration of Control Antigens

Following the procedure for titration of the control antigens given above. IV. Preparation of standardized antigens for HAT test and “Back Titration” Each control antigen must be standardized to contain 4 HA units/25 μl, 8 HA units/50 μl.

Note: Four HA units are added to the test in 25 μl because the HA unit calculations are based on a volume of 50 μl.

V. HAI Test for Serologic Diagnosis

- 1. Label appropriate microtiter plates.
- 2. Add 25 μl of PBS to wells B through H (B1-H12) of each numbered column.
- 3. Add 50 μl of each treated serum (1:10) to the appropriate first well (A1-A 12) of the numbered column.
- 4. Prepare serial twofold dilutions of the treated sera by transferring 25 μl from the first well of the numbered columns 1-12 to successive wells.

Discard the final 25 μl after row H.

- 5. Add 25 μl of standardized antigen to all wells (A 1-H12) in a set of treated sera.
- 6. Add 25 μl of PBS instead of antigen to the set of treated sera for serum controls (A1-H12).
- 7. Mix the contents of the plates by shaking on a mechanical vibrator for 10 sec or by agitating the plates manually.
- 8. Cover the plates and incubate at room temperature (22 to 25° C.) for 30-45 min.
- 9. Add 50 μl of standardized RBCs to all wells. Mix as before.
- 10. Cover the plates and allow the RBCs to settle at room temperature (22 to 25C) for the appropriate time according to RBCs being used.
- 11. Record the HAI titers.

The positive control antigens and corresponding antisera should give consistent results when compared with previous tests. A fourfold titer increase between the acute and convalescent serum is considered diagnostically positive for that influenza type/subtype.

Western Blots

Serum from bleeds performed on vaccinated mice on week 5 was pooled and diluted 1:1000 for analysis in Western blots. Inactivated PR8 antigen was separated via SDS-PAGE and probed with the pooled sera. Positive signals were observed in groups 2-7 and 12, with the highest signals observed in groups 4-7 and 12.

500 ng per lane of inactivated PR8 antigen was separated via SDS- on 10% bis-tris gels. Protein was transferred to Polyvinylidene Difluoride (PVDF) membranes and membranes were blocked with milk and probed with a 1:1000 dilution of pooled sera from each group from week 5 bleeds.

Antibody was detected with 1:3000 dilution of goat anti-mouse alkaline phosphatase (AP)

Observation of Mice

Mice were observed through 13 days post infection (14 days total, 0-13 days post infection).

Mice were weighed daily on an Ohause scale and the weights were recorded.

All animals had chips implanted at least 3 days prior to virus challenge that monitored the body temperature. The temperatures were recorded daily.

Survival and health of each mouse was evaluated once Lime a day.

TABLE 31

Study Design

Vaccine (n = 5

mice/group)

Mouse
Delivered

Group
Strain
week 0, 3
Dosage/Route
Readouts

1
Female
N/A
N/A
Animals displaying

2
BALB/
Unmodified
LNP IV,
severe illness will

3
c, 6-8
N1-methyl
0.4 mg/kg
be euthanized.

weeks
pseudouridine/5-

Serum samples

of age
methyl cytosine

collected on weeks

4

Unmodified
IM, LNP
1, 3, and 5.

5

N1-methyl
0.4 mg/kg
Serum analyzed via

pseudouridine/5-

Western blot (week

methyl cytosine

5 pooled samples),

6

Unmodified
ID, LNP
virus neutralization

7

N1-methyl
0.4 mg/kg
assay (all

pseudouridine/5-

individuals), and

methyl cytosine

HAI (all

8

Unmodified
ID, 80 ug w/
individuals).

9

N1-methyl
lipoplex

pseudouridine/5-
(Lipofectamine

methyl cytosine
2000)

10

Unmodified
ID, 80 ug

11

N1-methyl
naked mRNA

pseudouridine/5-

methyl cytosine

12

Control
IN, Inactivated

PR8 virus

In the Table the following abbreviations apply; IM, intramuscular; ID, intradermal; IN, intranasal; IV, intravenous; LNP, lipid nanoparticle

TABLE 32

Mean HAI Titers

Sample ID
Week 1
Week 3
Week 5

Naïve
8
7
7

Unmodified; LNP IV, 0.4 mg/kg
8
28
635

N1-methyl pseudouridine/5-methyl
25
139
2004

cytosine; LNP IV, 0.4 mg/kg

Unmodified; LNP IM, 0.4 mg/kg
22
63
2560

N1-methyl pseudouridine/5-methyl
60
482
2803

cytosine; LNP IM, 0.4 mg/kg

Unmodified; LNP ID, 0.4 mg/kg
39
279
3796

N1-methyl pseudouridine/5-methyl
114
965
10152

cytosine; LNP ID, 0.4 mg/kg

Unmodified; 80 ug w/lipoplex
7
17
197

(Lipofectamine 2000)

N1-methyl pseudouridine/5-methyl
7
20
28

cytosine; 80 ug w/lipoplex

(Lipofectamine 2000)

Unmodified; ID, 80 ug naked mRNA
7
7
61

N1-methyl pseudouridine/5-methyl
7
16
133

cytosine; ID, 80 ug naked mRNA

Control PR8 Antigen
14
14
441

Inhibition of Hemagglutination

Inhibition of hemagglutination (HAI) was measured in mouse sera samples on weeks 1, 3, and 5 post-vaccination. After week 1, both groups 5 and 7 displayed HAI titers over 40, at 60 and 114, respectively. On week 3, groups 3-7 displayed HAI activity over 40, with the highest being group 7 at 965. On week 5, all groups except 1 (naïve) and 9 displayed HAI activity over 40, with group 7>10,000.

It is noted that 1:40 is predictive of efficacy. An HAI titer of >40 is deemed necessary to protect from a lethal challenge of influenza.

The data showed that there was 100% rescue from lethal influenza challenge with rapid onset of protective antibody titers after 1 week and high antibody titers, i.e., 50 fold over unmodified mRNA and 20 fold over the protein vaccine. Furthermore, it was shown that for ribonucleic acid vaccines of the invention a much lower effective mRNA dose is required, i.e., ten fold less than unmodified mRNA. (FIG. 10).

Microneutralization

Two-fold dilutions of mouse sera were added to 100 TCID50/ml of virus in 96-well plates. After 24-hours of incubation, 1.5×104 Madin-Darby Canine-Kidney cells were added to each well. After a −20 hour incubation at 37° C., virus was detected and scored with an anti-NP antibody and read at 490 nm. No neutralization activity was detected with week 1 samples (signal <50; lower limit of detection). By week 3, mice in groups 5 and 7 displayed neutralizing activity between 79 and 250 (group 5) and 250 (group 7). Neither of the other groups displayed any neutralizing activity. On week 5, groups 2-4 showed high neutralizing activity between 789 and 2493, with group 7 displaying neutralizing activity 2494 and ˜25,000. The control group of mice, vaccinated with inactivated PR8, displayed neutralizing activity in 3 of 5 mice and ranged between 79 and 250. The data are shown in Tables 33-35.

TABLE 33

Week 1 Microneutralization

Mouse
Mouse
Mouse
Mouse
Mouse

Sample ID
1
2
3
4
5

Naïve
<50*
<50
<50
<50
<50

Unmodified; LNP IV,
<50
<50
<50
<50
<50

0.4 mg/kg

N1-methyl
<50
<50
<50
<50
<50

pseudouridine/5-

methyl cytosine; LNP

IV, 0.4 mg/kg

Unmodified; LNP IM,
<50
<50
<50
<50
<50

0.4 mg/kg

N1-methyl
<50
<50
<50
<50
<50

pseudouridine/5-

methyl cytosine; LNP

IM, 0.4 mg/kg

Unmodified; LNP ID,
<50
<50
<50
<50
<50

0.4 mg/kg

N1-methyl
<50
<50
<50
<50
<50

pseudouridine/5-

methyl cytosine; LNP

ID, 0.4 mg/kg

Unmodified; 80 ug w/
<50
<50
<50
<50
<50

lipoplex

(Lipofectamine 2000)

N1-methyl
<50
<50
<50
<50
<50

pseudouridine/5-

methyl cytosine; 80 ug

w/lipoplex

(Lipofectamine 2000)

Unmodified; ID, 80 ug
<50
<50
<50
<50
<50

naked mRNA

N1-methyl
<50
<50
<50
<50
<50

pseudouridine/5-

methyl cytosine; ID,

80 ug naked mRNA

Control PR8 Antigen
<50
<50
<50
<50
<50

*Titers of ‘<50’ indicate titers below Limit of detection (1:50)

TABLE 34

Week 3 Microneutralization

Mouse
Mouse
Mouse
Mouse
Mouse

Sample ID
1
2
3
4
5

Naïve
<50*
<50
<50
<50
<50

Unmodified; LNP IV,
<50
<50
<50
<50
<50

0.4 mg/kg

N1-methyl
<50
<50
<50
<50
<50

pseudouridine/5-

methyl cytosine; LNP

IV, 0.4 mg/kg

Unmodified; LNP IM,
<50
<50
<50
<50
<50

0.4 mg/kg

N1-methyl
79
79
79
250
250

pseudouridine/5-

methyl cytosine; LNP

IM, 0.4 mg/kg

Unmodified; LNP ID,
<50
<50
<50
<50
<50

0.4 mg/kg

N1-methyl
250
250
250
250
250

pseudouridine/5-

methyl cytosine; LNP

ID, 0.4 mg/kg

Unmodified; 80 ug w/
<50
<50
<50
<50
<50

lipoplex

(Lipofectamine 2000)

N1-methyl
<50
<50
<50
<50
<50

pseudouridine/5-

methyl cytosine; 80 ug

w/lipoplex

(Lipofectamine 2000)

Unmodified; ID, 80 ug
<50
<50
<50
<50
<50

naked mRNA

N1-methyl
<50
<50
<50
<50
<50

pseudouridine/5-

methyl cytosine; ID,

80 ug naked mRNA

Control PR8 Antigen
<50
<50
<50
<50
<50

*Titers of ‘<50’ indicate titers below Limit of detection (1:50)

TABLE 35

Week 5 Microneutralization

Mouse
Mouse
Mouse
Mouse
Mouse

Sample ID
1
2
3
4
5

Naïve
<50*
<50
<50
<50
<50

Unmodified; LNP IV, 0.4
2493
789
789
<50
250

mg/kg

N1-methyl pseudouridine/5-
789
789
2493
789
2493

methyl cytosine; LNP IV,

0.4 mg/kg

Unmodified; LNP IM, 0.4
789
789
2493
789
2493

mg/kg

N1-methyl pseudouridine/5-
789
2493
2493
789
789

methyl cytosine; LNP IM,

0.4 mg/kg

Unmodified; LNP ID, 0.4
<50
<50
<50
<50
<50

mg/kg

N1-methyl pseudouridine/5-
7877
7877
24892
2493
7877

methyl cytosine; LNP ID,

0.4 mg/kg

Unmodified; 80 ug w/
<50
<50
<50
<50
79

lipoplex (Lipofectamine

2000)

N1-methyl pseudouridine/5-
<50
<50
<50
<50
<50

methyl cytosine; 80 ug w/

lipoplex (Lipofectamine

2000)

Unmodified; ID, 80 ug
<50
79
<50
<50
<50

naked mRNA

N1-methyl pseudouridine/5-
<50
<50
<50
<50
<50

methyl cytosine; ID, 80 ug

naked mRNA

Control PR8 Antigen
250
79
<50
<50
250

*Titers of ‘<50’ indicate titers below Limit of detection (1:50)

Survival

All mice were challenged with a lethal dose (10×LD90) of INFV A/PR/8/34 on week 7 post-vaccination. Mice were observed for morbidity and mortality for up to 14 days. All vaccinated mice displayed 100% survival, compared to the naïve group (group 1), which was not vaccinated. 12 groups of 5 mice were challenged via IN instillation with ˜100 PFU of INFV A/PR/8/34 (H1N1). Mice were observed daily for 14 days for health, morbidity, and mortality. All animals except for unvaccinated, which died at approximately day 7, survived the 14 day study.

Weight Loss Data

Weight loss and health of mice challenged with A/PR/8/34. 12 groups of 5 mice were challenged via IN instillation with ˜100 PFU of INFV A/PR/8/34 (H1N1). Mice were observed daily for 14 days for health, morbidity, and mortality.

All vaccinated mice displayed 100% survival, although some groups displayed weight loss. The unvaccinated group displayed 0% survival and died on days 6 and 7, post-infection. While differences in weight-loss were observed in challenged vaccinated mice, no conclusion can be drawn as to its significance. The group vaccinated with NAVs having N1 methylpseudouridine/5-methyl cytosine with naked mRNA displayed health scores of ‘2’ on days 2 and 3 post-infection, but made a recovery to ‘healthy’ for the rest of the study. The groups vaccinated with NAVs having N1 methylpseudouridine/5-methyl cytosine ID 80 ug w/ lipofecatmine 2000 (LF2000) and N1 methylpseudouridine and 5-methylcytosine LNP ID both displayed health scores of ‘2’ on days 5 and 6 post-infection which continued through the duration of the study. The LNP formulation consisted of a cationic lipid, non-cationic lipid, PEG lipid and structural lipid in the ratios 50:10:1.5:38.5. The cationic lipid was DLin-KC2-DMA (50 mol %), the non-cationic lipid was DSPC (10 mol %), the PEG lipid was PEG-DOMG (1.5 mol %) and the structural lipid was cholesterol (38.5 mol %).

All groups generally maintained weight between 90-110% of original weight with the exception of the unvaccinated group. These animals were at approximately 70% of their original weight by day 6. Health scoring was per Table 36.

TABLE 36

Health score chart

Score
Initial
Description
Appearance
Mobility
Attitude

1
H
Healthy
Smooth coat, bright eyes
Active, scurrying,
Alert

burrowing

2
SR
Slighly
Slightly ruffled coat
Active, scurrying,
Alert

Ruffled
(usually only around heand
burrowing

and neck

3
R
Ruffled
Ruffled coat throughout
Active, scurrying,
Alert

body. A “wet” appearance
burrowing

4
S
Sick
Verr ruffled coat. Slightly
Walking, but not
Mildly

closed, inset eyes
scurrying
lethargic

5
VS
Very Sick
Very ruffled coat, closed,
Slow to no movement;
Extremely

(euthanized)
inset eyes
will return upright
lethargic

position if put on side

6
E
Euthanize
Very ruffled coat, closed
No movement or
Completely

inset eyes; moribund
uncontrollable; spastic
unaware or

requires human euthenasia
movement. Will not
in noticeable

return to upright
distress

7
D
Deceased
—
—
—

Example 16. MRSA Study

Antigens of MRSA which may be encoded by the ribonucleic acid vaccines include, SpA, SpAKKAA, IsdA, IsdB, SDRD, SDRE, TSST-1, PVL, a-HL, NMD-1 and SCCmec. The study design is shown in Table 37. In these studies, construct number 27 from Table 28 was used.

A. Test for Efficacy of Modified Ribonucleic Acid Vaccines in Staph. Aureus Pneumonia Challenge Model in Mice

This study will test the efficacy of ribonucleic acid vaccine encoding MRSA Ag808 in BALB/c mice. The study utilizes 15 groups of 15 BALB/c female mice (225 total. Mice are vaccinated on week 0 and 3 via intradermal (ID) or intramuscular (IM) route with either an LNP Formulation comprising DLin-KC2-DMA (“KC2”) or DLin-MC3-DMA (“MC3”). The KC2 LNP formulation consisted of a cationic lipid (DLin-KC2-DMA, 50 mol %), non-cationic lipid (DSPC, 10 mol %), PEG lipid (PEG-DOMO 1.5 mol %) and a structural lipid (cholesterol, 38.5 mol %). The MC3 LNP formulation consisted of a cationic lipid (DLin-MC3-DMA, 50 mol %), non-cationic lipid (DSPC, 10 mol %), PEG lipid (PEG-DOMG 1.5 mol %) and a structural lipid (cholesterol, 38.5 mol %). One group is unvaccinated and one administered a positive control antigen. Prior to challenge, mice will be bled by tail vein on weeks 1, 3 and 5 and serum samples will be retained for later analysis. The mice will be challenged with MRSA (strain Newman) at ˜1×LD90 via intranasal (IN) inoculation on week 5. Mice will be monitored for morbidity using a health score assigned based on a standard scoring system, weight loss, and mortality and the endpoint is day 14 post infection, death, or euthanasia. Animals displaying severe illness as determined by >30% weight loss, extreme lethargy, or paralysis will be euthanized. Mice will be held until week 7, to perform additional work with the animals (ex. further vaccinations, bleed or infectious challenge).

B. Test for Efficacy of N1-Methylpseudouridine Modified Ribonucleic Acid

Vaccines in Staphylococcus aureus Peritonitis Challenge This study tested the efficacy of a ribonucleic acid vaccine encoding MRSA Ag808 in BALB/c mice. The study utilized 15 groups of 15 BALB/c female mice (270 total. Mice were vaccinated on week 0 and 3 via intradermal (ID) or intramuscular (IM) route with either an LNP Formulation comprising DLin-KC2-DMA (“KC2”) or DLin-MC3-DMA (“MC3”). The KC2 LNP formulation consisted of a cationic lipid (DLin-KC2-DMA, 50 mol %), non-cationic lipid (DSPC, 10 mol %), PEG lipid (PEG-DOMG 1.5 mol %) and a structural lipid (cholesterol, 38.5 mol %). The MC3 LNP formulation consisted of a cationic lipid (DLin-MC3-DMA, 50 mol %), non-cationic lipid (DSPC, 10 mol %), PEG lipid (PEG-DOMG 1.5 mol %) and a structural lipid (cholesterol, 38.5 mol %). One group was unvaccinated and one administered a positive control antigen. Prior to challenge, mice were bled by tail vein on weeks 1, 3 and 5 and serum samples were retained for later analysis. The mice that were challenged via intranasal instillation received a predicted challenge dose of 2e8 CFU/mouse (actual upon back-titration was 3.3e8/mouse) and the mice that were challenged via IP infection received a predicted 1e7 CFU/mouse (actual upon back-titration 6.7e6 CFU/mouse). Mice were monitored for morbidity using a heahh score assigned based on a standard scoring system, weight loss, and mortality and the endpoint is day 14 post infection, death, or euthanasia. Animals displaying severe illness as determined by >30% weight loss, extreme lethargy, or paralysis were euthanized.

TABLE 37

Study Design

Group

(n = 15)
Antigen
Dosage
Route
Chemistry
Formulation
Administration
Samples

1
N/A
N/A
N/A
N/A
NaCl
Vaccination on
Bled by

2
MRSA
0.4 mg/kg
ID
N1methyl-
LNP; KC2
weeks 0 and 3
tail vein

3
Ag808
0.08 mg/kg

pseudoruridine

on weeks

4

0.016 mg/kg

1, 3, and 5;

5

0.4 mg/kg
IM

retained

6

0.08 mg/kg

for future

7

0.016 mg/kg

analysis

8

0.4 mg/kg
ID

LNP; MC3

9

0.08 mg/kg

10

0.016 mg/kg

11

0.4 mg/kg
IM

12

0.08 mg/kg

13

0.016 mg/kg

14
Inactivated
TBD
TBD
N/A
TBD

bacteria

15
Inactivated
TBD
TBD
N/A
TBD

bacteria

Mice that were vaccinated and challenged via IP route with 3% hog mucin all displayed 0% survival within 24 hours of challenge. Mice that were vaccinated and challenged via IN instillation displayed between 6 and 33% survival and median survival times between 2 and 3 days. Efficacy was not shown with either the tested RNA vaccine construct or the controls (inactivated bacteria and protein control) in either challenge model, suggesting that the model was not adequate for testing the constructs. The vehicle-vaccinated group displayed 20% survival and a median survival time of 3 days. Without being bound in theory, is is believed that the severity of the MRSA infection model precluded detection of vaccine efficacy. Other models can be tested to determine efficacy.

Example 17. Dengue Study: Dengue Virus RNA Vaccine Immunogenicity in Mice

This study provides a preliminary analysis of the immunogenicity of a nucleic acid mRNA vaccine using a dengue virus (DENV) serotype 2 antigen in BALB/c mice. The study utilizes 44 groups of 10 BALB/c female (5) and male (5) mice (440 total, 6-8 weeks of age at study initiation, see Table 38 for design summary). In this study, construct numbers used are referenced and found in Table 28.

Mice were vaccinated on weeks 0 and 3 via intramuscular (M) or intradermal (ID) routes. One group remained unvaccinated and one was administered 10⁵plaque-forming units (PFU) live DENV2, D2Y98P isolate via intravenous ( ) injection as a positive control. Serum was collected from each mouse on weeks 1, 3, and 5; bleeds on weeks 1 and 3 were in-life samples (tail vein or submandibular bleeds) and week 5 will be a terminal (intracardiac) bleed. Individual serum samples were stored at −80° C. until analysis by neutralization or microneutralization assay. Pooled samples from each group at the week 5 time points were tested by Western blot for reactivity with viral lysate.

TABLE 38

Detailed experimental design (treatment, readouts)

Vaccine

(n = 10,

female)

mice/group)

Delivered

Mouse
week 0

Formulation/

Group
Strain
and 3
Chemistry
Route
Dose
Readouts

1
Female
N/A

N/A
N/A
Serum samples

2
BALB/c,
DEN2Y98—PrME
N1-methylpseudouridine/
ID
0.4 mg/kg
collected on

3
6-8 weeks
(construct 23 from
5-methyl cytosine
IM
in LNP
weeks 1, 3, and

4
of age
Table 28)

ID
0.08 mg/kg
5. Serum

5

IM
in LNP
analyzed via

6

ID
0.016 mg/kg
Western blot

7

IM
in LNP

8

N1-methylpseudouridine
ID
0.4 mg/kg

9

IM
in LNP

10

ID
0.08 mg/kg

11

IM
in LNP

11

ID
0.016 mg/kg

12

IM
in LNP

13

DEN2Y98—PrME80
N1-methylpseudouridine/
ID
0.4 mg/kg

14

(construct 24 from
5-methyl cytosine
IM
in LNP

15

Table 28)

ID
0.08 mg/kg

16

IM
in LNP

17

ID
0.016 mg/kg

18

IM
in LNP

19

N1-methylpseudouridine
ID
0.4 mg/kg

20

IM
in LNP

21

ID
0.08 mg/kg

22

IM
in LNP

23

ID
0.016 mg/kg

24

IM
in LNP

25

DEN2Y98—PrME80-
N1-methylpseudouridine/
ID
0.4 mg/kg

26

DC (construct 25
5-methyl cytosine
IM
in LNP

27

from Table 28)

ID
0.08 mg/kg

28

IM
in LNP

29

ID
0.016 mg/kg

30

IM
in LNP

31

N1-methylpseudouridine
ID
0.4 mg/kg

32

IM
in LNP

33

ID
0.08 mg/kg

34

IM
in LNP

35

ID
0.016 mg/kg

36

IM
in LNP

37

DEN2-DIII-Ferritin
N1-methylpseudouridine
ID
0.4 mg/kg in

38

(construct 18 from

IM
LNP

39

Table 28)

ID
0.08 mg/kg

40

IM
in LNP

41

ID
0.016 mg/kg

42

IM
in LNP

43

Control,
—
IV
10⁵PFU

D2Y98P

live virus

Signal was detected in groups 5, 15, 39, and 44 (live virus control) by a band that appeared between 50 and 60 kDa in the Western blot data. The data suggests that a mRNA vaccine to a single dengue viral antigen can produce antibody in preliminary studies.

Example 18. Tuberculosis Ribonucleic Acid Vaccine: Combinatorial Approach of Adjuvants and Antigens

The objective of the study is to identify a multi-valent, multi-adjuvant vaccine effective in different diseases stages of tuberculosis. Initial experiment assesses 12 antigens with 8 cytokine adjuvants in three disease stage models. The antigens encoded by the polynucleotides of the invention include Ag85A (Rv3804c), Ag85B (Rv1886c), TB10.4 (Rv0288), ESAT6 (Rv3785), Rv2660L, Rv3619, Rv1813c, Rv3620c, Rv2608. Rv1196, Rv0125 and/or MT401. Target cytokine adjuvants include GM-CSF, TL-17, IFNg, IL-15, IL-2, IL-21, Anti-PD1/2 and/or Lactoferrin.

Example 19. Human Enterovirus (HEV68 and HEV71) Study

Several key antigens for use in generating vaccines have been identified. These include: (i) VP1 BC/DE loop of all three HEV68 lineages and (ii) VP1+VP2 of HEV71. The RNAV polynucleotide for use in generating vaccines from the HEV71 antigen is construct 72 from Table 28).

Example 20. MERS-CoV Study

As MERS-CoV binds cells via DPP4Fc, treatment for MERS-CoV can include an mRNA encoding DPP4-Fc with or without MERS-CoA binding site and mutant binding sites for diabetes signaling and truncated receptor binding domain of MERS-CoV Spike protein. See PLoS One. 2013; 8(12): e81587). This vaccine would act as a decoy for the virus as it will attract the MERS-CoV.

Another key vaccine for MERS-CoV is identified as an mRNA encoding MERS-CoV Spike Glucoprotein as an antigen. The protein sequence is given here (SEQ ID NO: 962).

SEQ ID NO. 962:

mihsvfllmflltptesyvdvgpdsiksacievdiqqtffdktwprpid

vskadgiiypqgrtysnitityqglfpyqgdhgdmyvysaghatgttpq

klfvanysqdvkqfangfvvrigaaanstgtviispstsatirkiypaf

mlgssvgnfsdgkmgrffnhtlvllpdgcgtllrafycileprsgnhcp

agnsytsfatyhtpatdcsdgnynrnaslnsfkeyfnlrnctfmytyni

tedeilewfgitqtaqgvhlfssryvdlyggnmfqfatlpvydtikyys

iiphsirsiqsdrkawaafyvyklqpltflldfsvdgyirraidcgfnd

lsqlhcsyesfdvesgvysyssfeakpsgsvveqaegvecdfspllsgt

ppqvynfkrlvftncnynltkllslfsvndftcsqispaaiasncyssl

ildyfsyplsmksdlsyssagpisqfnykqsfsnptclilatvphnltt

itkplkysyinkcsrllsddrtevpqlvnanqyspcvsivpstvwedgd

yyrkqlsplegggwlvasgstvamteqlqmgfgitvqygtdtnsvcpkl

efandtkiasqlgncveyslygvsgrgvfqnctavgvrqqrfvydayqn

lvgyysddgnyyclracvsvpvsviydketkthatlfgsvacehisstm

sqysrstrsmlkrrdstygplqtpvgcvlglynsslfvedcklplgqsl

calpdtpstltprsvrsvpgemrlasiafnhpiqvdqlnssyfklsipt

nfsfgvtqeyiqttiqkvtvdckqyvcngfqkceqllreygqfcskinq

alhganlrqddsvrnlfasvkssqsspiipgfggdfnitllepvsistg

srsarsaiedllfdkvtiadpgymqgyddcmqqgpasardlicaqyvag

ykvlpplmdvnmeaaytssllgsiagvgwtaglssfaaipfaqsifyri

ngvgitqqvlsenqkliankfnqalgamqtgftttneafhkvqdavnnn

agalsklaselsntfgaisasigdiiqrldvleqdaqidrlingrlttl

nafvaqqlvrsesaalsaqlakdkvnecvkaqskrsgfcgqgthivsfv

vnapnglyfmhvgyypsnhievvsayglcdaanptnciapvngyfiktn

ntrivdewsytgssfyapepitslntkyvapqvtyqnistnlpppllgn

stgidfqdeldeffknvstsipnfgsltqinttlldltyemlslqqvvk

alnesyidlkelgnytyynkwpwyiwlgfiaglvalalcvffilcctgc

gtncmgklkcnrccdryeeydlephkvhvh

Example 21: H10N8 In Vitro Studies

In vitro studies on the translatability of H10 hemagglutinin mRNA were performed in HeLa cells.

Western blot analysis revealed that HA is expressed in HeLa cells following transfection with the mRNA NAV encoding the HA protein of the H10N8 strain of influenza virus.

Example 22: Influenza Study—Dosing and Formulations

A mRNA vaccine encoding the HA protein of the H1N1 strain of influenza virus was tested at various doses and in various formulations for the ability ti illicit an immune response in mice.

The efficacy of different doses and formulations were evaluated in mice. HAI titers of mice determined on Day 35 after vaccination on Day 0 and Day 21 with mRNA encoding HA of the H1N1 virus are shown in FIG. 11. Titers were highest at doses of 10 μg mRNA/mouse (400 μg mRNA/kg) with both the KC2 and MC3 formulations administered ID or IM (Table 39).

TABLE 39

Hemagglutinin inhibition titers in mice following vaccination with

different doses and formulations of mRNA encoding the

hemagglutinin protein of the H1N1 virus vaccine

Group No.
Route of

(n = 10
Vaccination

Dose

per
on days 0

Formula-
(μg/
Mean HAI

group)
and 21
Vaccine
tion
mouse)
titer ± SD

1
N/A
None
PBS
0
0

2
ID
H1N1/C1
KC2
10
1792 ± 661

3

2
1088 ± 309

4

0.4
272 ± 152

5

0.08
52 ± 44

6
ID
H1N1/C0
KC2
10
992 ± 648

7

2
692 ± 743

8

0.4
140 ± 78

9

0.08
35 ± 31

10
ID
H1N1/C0
MC3
10
1600 ± 867

11

2
1152 ± 588

12

0.4
290 ± 254

13

0.08
37 ± 25

14
IM
H1N1/C0
MC3
10
1664 ± 1422

15

2
1056 ± 641

16

0.4
800 ± 346

17

0.08
180 ± 105

18
IN
Inactivated
PBS
20 μL
96 ± 47

PR8 virus

19
ID
H1N1/
PBS
50
11 ± 3

G2/C1

G0 = generation 0, i.e. canonical unmodified nucleotides;

G2 = Generation 2 of the modified nucleotides;

G5 = Generation 5 of the modified nucleotides (intended for clinical development).

C0 = CAP0;

C1 = CAP1 (intended for clinical development)

N/A: Not applicable.

IN: intranasal:

ID: intradermal;

IM: intramuscular

Example 23: Influenza Study—Onset of Immunity—Survival and HAI

This study evaluated the efficacy of an mRNA vaccine encoding influenza A/PR/8 (H1 N1) in female BALB/c mice following lethal challenge with influenza A/PR/8 virus. Groups of animals were vaccinated and challenged after week 1, 2, 3, or 4. Serum was collected from each mouse one day prior to challenge. Individual bleeds were tested for hemagglutination inhibition using Influenza A/PR/8 (H1N1). Control groups included unvaccinated mice and mice vaccinated with inactivated PR8 virus as a positive control. These animals were challenged in parallel with groups that were vaccinated with the mRNA vaccine. Challenge was performed with a lethal dose (100 PFU) of A/PR/8/34 (H1N1) via intranasal instillation. Animals were monitored for morbidity using a health score assigned based on a standard scoring system, weight loss and mortality. All mice receiving the mRNA vaccine showed 100% survival and minimal body weight loss (FIG. 12A-12D). At week 1 post vaccination, hemagglutination inhibition titers of mice receiving the mRNA vaccine and mice receiving the positive control vaccine were similar. However, at weeks 2, 3 and 4 post vaccination, mice receiving the mRNA vaccine showed higher mean titers compared with mice receiving the positive control vaccine (FIG. 13).

Groups of 15 female BALB/c mice (6-8 weeks of age) were vaccinated in week 0 with: mRNA encapsulated in LNP at a dose of 0.4 mg/kg by ID injection; inactivated PR8 virus given IN: or vehicle.

In weeks 1, 2, 3 and 4 after vaccination, animals were inoculated with influenza A/PR/8/34 virus under light anesthesia. The animals received 100 μL of the virus diluted in PBS to a final concentration of 1×103 PFU/mL via IN instillation.

Health assessments were performed and weights were recorded daily for 14 days (days 0-13 post infection). Survival and health was evaluated using the scoring system shown in Table 36.

All animals had chips implanted at least 3 days prior to virus challenge that monitored the body temperature. The temperatures were recorded daily. One day prior to each challenge, serum samples were collected and the serum was analyzed in an HAI assay.

Survival curves are presented in FIG. 15. The animals were monitored for survival for 14 days. Log-rank analysis was performed in GraphPad Prism v6.

Mice vaccinated with mRNA vaccine or inactivated PR8 all displayed 100% survival, while mice that were unvaccinated displayed between 0 and 40% survival (Table 40.) No significant decreases in body weight of treated mice were detected.

TABLE 40

Percent and mean survival of mice after vaccination and challenge

with influenza A/PR/8/34 virus

Significance to

Mean
Relative Vehicle

Survival
Control (p

Group (n = 15 per group)
% Survival
(Days)
values)

Vehicle
Week 1
10
8
N/A

Week 2
40
10
N/A

Week 3
0
9
N/A

Week 4
6.67
9
N/A

Inactivated PR8
Week 1
100
Undefined
<0.0001

virus
Week 2
100
Undefined
0.0004

Week 3
100
Undefined
<0.0001

Week 4
100
Undefined
<0.0001

mRNA vaccine
Week 1
100
Undefined
<0.0001

encapsulated in
Week 2
100
Undefined
0.0004

LNP
Week 3
100
Undefined
<0.0001

Week 4
100
Undefined
<0.0001

Mean HA titers are shown in FIG. 13 and Table 41.

TABLE 41

Mean hemaglutination inhibition (±SD) titers of mice

after vaccination and challenge with influenza A/PR/8/34 virus

Vaccination
Challenge with influenza A/PR/8/34 virus

in week 0
Week 1
Week 2
Week 3
Week 4

Vehicle
0
0
0
0

Inactivated PR8 virus
25 ± 47
19 ± 26
37 ± 39
43 ± 30

mRNA vaccine
25 ± 17
203 ± 138
379 ± 178
363 ± 154

Values are mean ± SD (standard deviation)

These data demonstrate that mice vaccinated with mRNA vaccine at a dose of 0.4 mg/kg ID or inactivated PR8 virus showed 100% survival after challenge with influenza A/PR/8/34 virus in weeks 1, 2, 3, or 4 indicating that the vaccine conveyed protection against infection with influenza A/PR/8/34 virus under the conditions of this study. HAT activity remained low in weeks 1 through 4 for animals vaccinated with inactivated PR8 virus. Mice vaccinated with mRNA showed low mean HAI titers in week 1 after challenge, but increased titers in weeks 2, 3 and 4, respectively.

Example 24: Evaluation of H1 and H7-Specific T Cell Responses in Influenza Vaccine

Mice were immunized ID at week 0 and 3 with mRNA vaccine encoding the HA protein of influenza H1N1 or H7N9 virus and splenocytes were collected in week 5. T cells were stimulated for 16-18 hours with an HA peptide library (15mers of a full length protein)

that reproduce the H1 or H7 sequence. Non-specific stimulation of T cells was performed using PMA+ionomycin. IFNγ ELISpot was used to identify staining for IFNγ. B cells were stimulated with either a peptide library (15mers of a full length protein) that reproduce the H1 or H7 sequence. Polyclonal B cell stimulation was performed using R848+rIL-2. B cell ELISpot was used to identify staining for antigen-specific IgG.

IFNγ ELISpot results demonstrated increased IFNγ secretion by T cells after stimulation with H1 or H7 peptides (FIGS. 14A and 14B). No increased IFNγ secretion was observed in T cells stimulated with PMA+ionomycin (FIG. 14C). The results demonstrated that T cell responses are antigen specific.

B cell ELISpot results demonstrated IgG secretion upon stimulation of B cells with full antigen, but not with H1/H7 peptides (FIGS. 15A-15D). The lack of stimulation with the peptide library was to be expected because an IgG response is stimulated via MHCII antigens, which tend to be longer than MHCI antigen needed for stimulation of a T cell response.

Example 25: Evaluation of H1, H7, and H10-Specific T and B Cell Response Against Influenza Vaccines in Mouse Splenocytes

Influenza-specific T and B cell responses were evaluated following administration of mRNA vaccines (NAVs) encoding the H1, H10, and H7 hemagglutinin proteins. Briefly, 36 groups of 5 female 6-8 week old BALB/c mice were vaccinated with various doses via the intradermal route (ID) on day 0. Seven-week post vaccination, animals were sacrificed and spleens were harvested. The splenocytes were assessed by IFNγ ELISpot; Intracellular Cytokine Staining (ICS) for CD3, CD4, CD8, CD45, CCR7, CD44, CD25. IL-2 IFNγ, and TNFα markers; and by B-cell ELISpot.

IFNγ ELISpot Analyses

Splenocytes from groups of mice that had been administered H10N8/N1-methyl pseudouridine /C0 were assessed for H1, H7 and H10-specific IFNγ production by IFNγ ELISpot. Naïve mice did not yield measurable IFNγ cytokine response, whereas H10 peptide-specific IFNγ ELISpot responses were detected in mice vaccinated intradermally with H10N8/N1-methyl pseudouridine /C0. The magnitude of these responses was found to be dependent on the dose of the vaccine administered. Peptide-stimulated splenocytes did not yield detectable H1- or H7-specific IFNγ ELISpot responses. All groups produced IFNγ ELISpot responses following stimulation with PMA+ionomycin (positive control).

H1 peptide-specific IFNγ ELISpot responses were detected from splenocytes isolated from mice that had been administered H1N1/G2/C1, H1N1/G2/C0 (MC3 formulation), or H1N1/G2/C0 (KC2 formulation) intradermally, as well as from splenocytes from mice that had been administered H1N1/G2/C0 (MC3 formulation) intramuscularly.

H7 peptide-specific IFNγ ELISpot responses were detected from splenocytes isolated from mice that had been administered H7N9/G2/C0 either intradermally or intramuscularly.

Splenocytes from control mice that had received H1N1/G2/C1/PBS showed no response to peptide stimulation.

B Cell ELISpot Analyses

Briefly, H1-specific IgG and IgM responses were detected in several groups of mice vaccinated with different H1 vaccine formulations. H7- and H10-specific IgG and IgM responses were also elicited in the H7N9/N1-methyl pseudouridine /C0- and H10N8/N1-methyl pseudouridine /C0-vaccinated mice, respectively.

Intracellular Cytokine Staining Results

Intracellular Cytokine Staining and flow cytometric analysis indicated that H1-specific Th1 (IFNγ, TNFα, IL-2) cytokine responses were induced at both 16-18 hrs and 48 hrs in CD4+ T cells and CD8+ T cells following stimulation of splenocytes from H1-vaccinated mice with corresponding peptide or protein.

Additionally, H7- and H-10 peptide and protein-specific Th1 (IFNγ, TNFα, IL-2) responses were also detected in CD4+ and CD8+ T cells. H7-specific responses were noted in groups vaccinated with H7 vaccine formulations, and H10-specific responses were seen in groups vaccinated with H10 vaccine formulations.

Example 26: Evaluation of H7- and H10-Specific T and B Cell Response Against Influenza Vaccines in Mouse Splenocytes—Time Course

Influenza-specific T and B cell responses were evaluated following administration of mRNA vaccines (NAVs) encoding the H10 and H7 hemagglutinin proteins. Briefly, 27 groups of 5 female 6-8 week old BALB/c mice (135 mice total) were vaccinated with various doses via the intradermal route (ID) on day 0 shown in Table 42. On days 7, 21, and 84 groups of 5 animals were sacrificed and blood samples and spleens were harvested.

The mouse spleens were analyzed using IFNγ ELISPOT, IgG ELISPOT (for B cell responses), and Intracellular Cytokine Staining (ICS). Serum samples were analyzed for inhibition of hemagglutinin (HAI) by first treating with Receptor Destroying Enzyme (RDE) to inactivate non-specific inhibitors of hemagglutination (false positives) present in the sera. Next, RDE-treated sera were adsorbed using red blood cells (RBCs) to remove non-specific agglutinin (false negatives). Serially-diluted treated sera (2-fold dilutions) were pre-incubated with a standardized quantity of recombinant influenza antigen before RBCs were added to the mixture. Inhibition of hemagglutination indicates the presence of HA-specific antibodies. Pooled anti-H10 mouse serum was used as a positive control and showed HAI titers within range of previously-observed data.

After receiving a single dose of the mRNA NAVs on day 0, HAI titers were not detected at day 7 (Table 42) but were detected at day 21 (Table 43) and continued to increase through day 84 (Table 44). Day 84 titers were 2-fold to 15-fold higher than those from day 21 (FIGS. 15 and 16).

Administration of the H10N8/N1-methyl pseudouridine /C1 formulation MC3 resulted in higher HAI titers as compared to the HAI titers induced by the H10N8/N1-methyl pseudouridine/C0 formulation MC3 (FIG. 17). The MC3 LNP formulation consisted of a cationic lipid (DLin-MC3-DMA, 50 mol %), non-cationic lipid (DSPC, 10 mol %), PEG lipid (PEG-DOMG 1.5 mol %) and a structural lipid (cholesterol, 38.5 mol %).

Administration of the H10N8/N1-methyl pseudouridine/C1 formulation MC3 at 10 μg/dose achieved the highest HAI titers, whereas the HAI titers following administration of the 2.0 μg/dose and 0.4 μg/dose are similar to each other (FIG. 16).

TABLE 42

HAI Titers against H10 and H7 at Day 7

Dose

HAI titers of mouse sera

mRNA vaccine
per

Day 0 (Nov. 10, 2014) = vaccination day 0

once at day 0
mouse
Group
Day 7 (Nov. 17, 2014) = terminal bleeds groups 1-9

via ID injection
(μg)
(N = 5)
M1
M2
M3
M4
M5
Mean
Stdev

H10N8/N1-methyl
10
1
<10
<10
<10
<10
<10
<
10
N/A
HAI titers

pseudouridine/C1,
2
2
<10
<10
<10
<10
<10
<
10
N/A
against H10

formulation MC3
0.4
3
<10
<10
<10
<10
<10
<
10
N/A
protein

H10N8/N1-methyl
10
4
<10
<10
<10
<10
<10
<
10
N/A

pseudouridine/C0,
2
5
<10
<10
<10
<10
<10
<
10
N/A

formulation MC3
0.4
6
<10
<10
<10
<10
<10
<
10
N/A

PBS
0
7
<10
<10
<10
<10
<10
<
10
N/A

PBS
0
7
<10
<10
<10
<10
<10
<
10
N/A
HAI titers

H7N9/C0
10
8
<10
<10
<10
<10
<10
<
10
N/A
against H7

H7N9/C1
10
9
<10
<10
<10
<10
<10
<
10
N/A
protein

TABLE 43

HAI Titers against H10 and H7 at Day 21

Dose

HAI titers of mouse sera

mRNAna vaccine
per

Day 0 (Nov. 10, 2014) = vaccination day 0

once at day 0 via
mouse
Group
Day 21 (Dec. 1, 2014) = terminal bleeds group 10-18

ID injection
(μg)
(N = 5)
M1
M2
M3
M4
M5
Mean
Stdev

H10N8/N1-methyl
10
10
160
320
640
80
160

272
223
HAI

pseudouridine/C1,
2
11
40
80
40
80
160

80
49
titers

formulation MC3
0.4
12
80
160
40
80
80

88
44
against

H10N8/N1-methyl
10
13
160
40
80
20
40

68
56
H10

pseudouridine/C0,
2
14
20
20
10
10
20

16
5
protein

formulation MC3
0.4
15
20
10
40
20
80

34
28

PBS
0
16
<10
<10
<10
<10
<10
<
10
N/A

PBS
0
16
<10
<10
<10
<10
<10
<
10
0
HAI

H7N9/C0
10
17
40
10
10
20
20

26
13
titers

H7N9C1
10
18
160
160
160
320
80

176
88
against

H7

protein

TABLE 44

HAI Titers against H10 and H7 at Day 84

Dose

HAI titers of mouse sera

mRNA vaccine
per

Day 0 Nov. 10, 2014) = vaccination day 0

once at day 0
mouse
Group
Day 84 (Feb. 2, 2015) = terminal bleeds groups 19-27

via ID injection
(μg)
(N = 5)
M1
M2
M3
M4
M5
Mean
Stdev

H10N8/N1-methyl
10
19
160
320
320
1280
640

544
447
HAI titers

pseudouridine/C1,
2
20
320
320
640
160
320

352
175
against

formulation MC3
0.4
21
640
320
160
320
640

416
215
H10

H10N8/N1-methyl
10
22
160
320
320
320
320

288
72
protein

pseudouridine/C0,
2
23
320
320
160
80
320

240
113

formulation MC3
0.4
24
40
320
320
320
80

216
143

PBS
0
25
<10
<10
<10
<10
<10
<
10
N/A

PBS
0
25
<10
<10
<10
<10
<10
<
10
N/A
HAI titers

H7N9/C0
10
26
20
40
80
20
<10
5
40
28
against H7

H7N9/C1
10
27
640
320
320
160
80

304
215
protein

Example 27: Anti-H10 Hemagglutinin Analysis in Non-Human Primates—Dose Range Study

Groups of cynomolgus monkeys were vaccinated with various doses of NAV encoding H10 HA/LNP formulations (50 μg/dose, 200 μg/dose, 400 μg/dose), NAV encoding H10 HA/LNP delivered with 3M device, or control NAV encoding H10 HA/PBS. Serum samples were taken from the monkeys weekly and evaluated for inhibition of hemagglutinin (Table 45, FIG. 19).

TABLE 45

HAI titers against H10 protein

HAI titers against H10 protein (A/Jiangxi-Donghu/346/2013)

Cynomolgus
Pre-
Week
Week
Week
Week
Week
Week
Week

monkey ID
treatment
1
2
3
4
5
6
9

Group 1
1001
10
40
20
20
320
1280
1280
5120

(50 μg)
1002
20
20
40
40
640
2560
2560
10240

1003
<10
<10
40
80
640
2560
2560
10240

Mean
<13
<23
33
47
533
2133
2133
8533

Group 2
2001
<10
<10
10
40
640
5120
2560
10240

(200 μg)
2002
20
20
20
40
640
2560
2560
10240

2003
<10
40
20
40
320
5120
5120
10240

Mean
<13
<23
17
40
533
4267
3413
10240

Group 3
3001
20
<10
40
80
1280
5120
10240
20480

(400 μg)
3002
<10
40
40
160
640
5120
5120
20480

3003
<10
20
80
160
1280
10240
20480
40960

Mean
<13
<23
53
133
1067
6827
11947
27307

Group 4
4001
<10
40
<10
20
40
80
80
160

(vaccine
4002
<10
40
<10
<10
40
160
160
160

device)
4003
20
40
<10
10
40
80
80
160

Mean
<13
40
<10
<13
40
107
107
160

Group 5
5001
<10
20
80
320
1280
5120
5120
10240

(PBS)
5002
<10
20
40
160
1280
5120
5120
10240

5003
<10
40
40
80
1280
5120
5120
20480

Mean
<10
27
53
187
1280
5120
5120
13653

Assay Positive Control: Anti-H10
Assay Positive Control: Anti H-10

Pool of 9 mouse sera
Pool of 9 mouse sera

M1, M2, M3, of Group 1, N1-methyl
M1, M2, M3 of Group 1, N1-

pseudouridine (m¹Ψ) and 5-methyl
methyl pseudouridine (m¹Ψ) and

cytidine, Group 3 of
5-methyl cytidine, Group 3 of

study day 14
study day 14

HAI titer = 160
HAI titer = 80

Example 28: Determination of Time to Onset of Immunity Using an H7N9 Vaccine in a Ferret Model

The time to onset of immunity (as measured by antibody titers and reduction in viral titers following challenge) of an influenza A/Anhui/l/2013 (H7N9) vaccine was evaluated in a ferrets model of influenza infection. Briefly, twenty groups of 8 ferrets each were vaccinated on day 0 with the H7N9 mRNA NAV vaccine at a dose of 10H/g, 50 μg, or 200 μg, a vH7N9 vaccine lacking the 14 kDa cap at a dose of 200 μg or PBS control via the intradermal route. Five of the 20 groups received a second vaccination (a booster) to determine if a second dose increased protection. The animals were then exposed to influenza A/Anhui/1/2013 (H7N9) virus via the intranasal route. The study design is shown in Table 45:

TABLE 45

Study Design

Group

Day of
No. of
Day of
Day of Blood

No.
Vaccine Dose
Vaccination
Animals
Challenge
Draws

1
H7N9/N1-methyl pseudouridine/
0
8
7
0, 7

C1/MC3, 200 μg

2
H7N9/N1-methyl pseudouridine/
0
8
7
0, 7

C1/MC3, 50 μg

3
H7N9/N1-methyl pseudouridine/
0
8
7
0, 7

C1/MC3, 10 μg

4
PBS
0
8
7
0, 7

5
H7N9/MC3 (−14 kDa Cap) 200 μg
0
8
7
0, 7

6
H7N9/N1-methyl pseudouridine/
0
8
21
0, 21

C1/MC3, 200 μg

7
H7N9/N1-methyl pseudouridine/
0
8
21
0, 21

C1/MC3, 50 μg

8
H7N9/N1-methyl pseudouridine/
0
8
21
0, 21

C1/MC3, 10 μg

9
PBS
0
8
21
0, 21

10
H7N9/MC3 (−14 kDa Cap) 200 μg
0
8
21
0, 21

11
H7N9/N1-methyl pseudouridine/
0
8
49
0, 49

C1/MC3, 200 μg

12
H7N9/N1-methyl pseudouridine/
0
8
49
0, 49

C1/MC3, 50 μg

13
H7N9/N1-methyl pseudouridine/
0
8
49
0, 49

C1/MC3, 10 μg

14
PBS
0
8
49
0, 49

15
H7N9/MC3 (−14 kDa Cap) 200 μg
0
8
49
0, 49

16
H7N9/N1-methyl pseudouridine/
4, 25
8
53
4, 25, 53

C1/MC3, 200 μg

17
H7N9/N1-methyl pseudouridine/
4, 25
8
53
4, 25, 53

C1/MC3, 50 μg

18
H7N9/N1-methyl pseudouridine/
4, 25
8
53
4, 25, 53

C1/MC3, 10 μg

19
PBS
4, 25
8
53
4, 25, 53

20
H7N9/MC3 (−14 kDa Cap) 200 μg
4, 25
8
53
4, 25, 53

Because H7N9 does not induce a lethal disease in ferrets, the primary endpoint was viral burden in tissues (primarily lung) 3 days post-challenge, as determined by TCID50 (50% tissue culture infective dose). In addition to viral titers, blood was collected prior to vaccination and immediately prior to challenge to determine influenza-specific antibody titers, as determined by hemagglutination inhibition (HAI) and microneutralization (MN) assays.

The lung homogenate data show that a single vaccination at any concentration resulted in a reduction in viral titers, with a time to onset of immunity before 7 days post vaccination (Table 46). There was a 1 log reduction in all vaccine groups challenged 7 days post vaccination. This improved for groups challenged 21 days post vaccination in a dose-dependent fashion to 3, 2, and 1 log reduction for the 200-, 50-, and 10-μg groups, respectively (FIG. 20). This further improved for groups challenged 49 days post vaccination to 4, 2, and 3 log reduction for the 200, 50-, and 10-μg groups, respectively. A statistically significant difference was observed relative to PBS control group at 7 days post vaccination in the 10- and 200-μg groups (p<0.05). The 50-μg dose group also tended towards reduced lung viral titers, but only had statistically significant differences from the PBS group when a boost was administered. This was likely due to the occasional outlying high viral titer sample, which increased the variability in this group.

TABLE 46

Virus Burden (TCID50 Group Geographic Means)

Nasal Wash
Lung Homogenate

Day 7
Day 21
Day 49
Day 7
Day 21
Day 49

H7N9/N1-methyl pseudouridine/
3.7 × 10³
3.1 × 10³
3.3 × 10⁴
3.0 × 10³
4.6 × 10¹
8.0 × 10⁰

C1/MC3 200 μg

H7N9/N1-methyl pseudouridine/
2.4 × 10³
1.6 × 10⁴
6.7 × 10⁴
2.0 × 10³
5.9 × 10²
9.7 × 10²

C1/MC3 50 μg

H7N9/N1-methyl pseudouridine/
3.7 × 10³
8.1 × 10²
1.0 × 10⁵
2.3 × 10³
2.9 × 10³
6.2 × 10¹

C1/MC3 10 μg

PBS
6.0 × 10³
2.9 × 10³
1.7 × 10⁵
3.8 × 10⁴
3.2 × 10⁴
2.1 × 10⁴

H7N9/MC3 (−14 kDa Cap) 200 μg
1.4 × 10⁴
1.5 × 10³
3.6 × 10⁵
7.9 × 10³
1.6 × 10³
4.8 × 10²

^† 158 is the lower limit of detection o the nasal wash TCID₅₀assay. All below LLOQ values were assigned a value of 79 for producing the geomean values for nasal wash. 15.8 is the lower limit of detection of the lung homogenate TCID₅₀assay. All below LLOQ values were assigned a value of 8 for producing the geomean values for nasal wash.

There was no statistical benefit observed from the boosting vaccination compared to a single vaccination, but this is likely due to the 2-4 log reduction in viral lung titers by 49 days seen in both the single vaccination and 2 (boost) vaccination groups (Table 47).

TABLE 47

Lung Virus Burden (TCID50 Group Geographic Means)-

Boosted vs. Unboosted

Day 49 with the

Day 49 Unboosted
Day 21 Boost

200 μg Vaccine
8.0 × 10⁰
8.0 × 10⁰

50 μg Vaccine
9.7 × 10²
8.0 × 10⁰

10 μg Vaccine
6.2 × 10¹
1.1 × 10²

PBS
2.1 × 10⁴
2.2 × 10⁴

Empty Vaccine Vector
4.8 × 10²
8.0 × 10⁰

^†15.8 is the lower limit of detection of the lung homogenate TCID₅₀assay. All below LLOQ values were assigned a value of 8 for producing the geomean values for nasal wash.

Serum was collected from each animal immediately before vaccination and challenge and analyzed by HAI assay. As seen from Table 48, a dose dependent increase was visible 7 days post vaccination, and titers increased over time. The 200-μg to 14-kDa cap vaccine did provide some titer above background, between the 10-μg vaccine and PBS response. The groups receiving a second vaccination showed a dose-dependent, 3 8 fold increase in antibody titers following the second vaccination. The 200-μg to 14-kDa cap vaccine also showed an approximately 2-fold increase in antibody titers following the second vaccination. In all cases, a statistically significant increase relative to the pre-vaccination blood sample was first observed 21 days post-vaccination (p<0.05).

TABLE 48

HAI Antibody Titer Results

Geomean

Cohort
Treatment
Day 0
Day 7
Day 21
Day 49

1
200 μg Vaccine
5.00^†
5.45
N/A^‡
N/A

1
50 μg Vaccine
5.00
6.48
N/A
N/A

1
10 μg Vaccine
5.00
5.94
N/A
N/A

1
PBS
5.00
5.00
N/A
N/A

1
Empty Vaccine Vector
5.00
5.45
N/A
N/A

2
200 μg Vaccine
5.00
N/A
43.62
N/A

2
50 μg Vaccine
5.00
N/A
25.94
N/A

2
10 μg Vaccine
5.00
N/A
25.94
N/A

2
PBS
5.00
N/A
5.00
N/A

2
Empty Vaccine Vector
5.00
N/A
9.35
N/A

3
200 μg Vaccine
5.00
N/A
N/A
61.69

3
50 μg Vaccine
5.00
N/A
N/A
33.64

3
10 μg Vaccine
5.00
N/A
N/A
25.94

3
PBS
5.00
N/A
N/A
5.00

3
Empty Vaccine Vector
5.00
N/A
N/A
18.34

4
200 μg Vaccine
5.00
N/A
59.93
480.67

4
50 μg Vaccine
5.00
N/A
29.97
195.85

4
10 μg Vaccine
5.00
N/A
40.00
97.92

4
PBS
5.00
N/A
5.00
5.45

4
Empty Vaccine Vector
5.94
N/A
5.96
36.68

^†Ten is the lower limit of detection of the HAI assay. All <10 were assigned a value of 5 for producing the geomean values.

^‡NA = Not applicable.

Serum samples were also analyzed by MN assay. As shown in Table 49, increases in MN titer was observed as early as 7 days post vaccination and continued to increase through 49 days post vaccination. The titers were highest in the 200-μg vaccine group, and were similar in the 50- and 10-μg groups. For the 50- and 200-μg vaccine dose groups, a statistically significant increase was observed by 7 days post-vaccination (p<0.05). For the 10-μg vaccine dose groups, the significant increase was not observed until 21 days post-vaccination (p<0.05). The 200-μg to 14-kDa cap vaccine did provide some titer above background, which was statistically significant by 49 days post vaccination (p<0.05) and were lower than the titers for the 50- and 10-μg groups. The groups receiving a second vaccination experienced a 3.0-4.5 fold increase in titers following the second vaccination. The 200-μg to 14-kDa cap vaccine also showed an approximately 1.5-fold increase in titers following the second vaccination.

TABLE 49

MN Antibody Titer Results

Geomean^†

Co-

Day
Day
Day
Day

hort
Treatment
0
7
21
49

1
H7N9/N1-methyl pseudouridine/
15.00
33.67
N/A^‡
N/A

C1/MC3 200 μg Vaccine

1
H7N9/N1-methyl pseudouridine/
17.38
42.29
N/A
N/A

C1/MC3 50 μg Vaccine

1
H7N9/N1-methyl pseudouridine/
21.21
25.94
N/A
N/A

C1/MC3 10 μg Vaccine

1
PBS
19.58
18.47
N/A
N/A

1
H7N9/MC3 (−14 kDa Cap)
17.43
20.03
N/A
N/A

200 μg

2
H7N9/N1-methyl pseudouridine/
14.69
N/A
92.41
N/A

C1/MC3 200 μg Vaccine

2
H7N9/N1-methyl pseudouridine/
17.49
N/A
42.50
N/A

C1/MC3 50 μg Vaccine

2
H7N9/N1-methyl pseudouridine/
15.07
N/A
43.48
N/A

C1/MC3 10 μg Vaccine

2
PBS
17.89
N/A
13.60
N/A

2
H7N9/MC3 (−14 kDa Cap)
18.52
N/A
17.43
N/A

200 μg

3
H7N9/N1-methyl pseudouridine/
15.51
N/A
N/A
160.08

C1/MC3 200 μg Vaccine

3
H7N9/N1-methyl pseudouridine/
13.16
N/A
N/A
89.80

C1/MC3 50 μg Vaccine

3
H7N9/N1-methyl pseudouridine/
13.12
N/A
N/A
77.51

C1/MC3 10 μg Vaccine

3
PBS
12.70
N/A
N/A
10.68

3
H7N9/MC3 (−14 kDa Cap)
10.33
N/A
N/A
46.21

200 μg

4
H7N9/N1-methyl pseudouridine/
10.33
N/A
63.44
697.88

C1/MC3 200 μg Vaccine

4
H7N9/N1-methyl pseudouridine/
10.68
N/A
29.99
273.04

C1/MC3 50 μg Vaccine

4
H7N9/N1-methyl pseudouridine/
10.68
N/A
31.97
232.65

C1/MC3 10 μg Vaccine

4
PBS
12.01
N/A
11.03
10.68

4
H7N9/MC3 (−14 kDa Cap)
11.78
N/A
16.47
69.06

200 μg

^†20 is the lower limit of detection of the MN assay. All <20 were assigned a value of 10 for producing the geomean values.

^‡N/A = Not applicable.

Quite surprisingly, the vaccine constructs of the invention reduced viral titers in the lungs when exposed to virus just 7 days following vaccination. Statistically significant increases in antibody titer as measured by HAI and MN were detected as early as 7 days following vaccination. A second vaccination (i.e., booster) did increase antibody Liters, but did not statistically reduce the viral titer, as a single vaccination eliminated all virus in most animals. The −14 kDa cap vaccine at 200 μg/animal provided less protection than 10-μg full vaccine, but did reduce viral burden in the lung and increased antibody titers, both relative to PBS control.

While the present invention has been described at some length and with some particularity with respect to the several described embodiments, it is not intended that it should be limited to any such particulars or embodiments or any particular embodiment, but it is to be construed with references to the appended claims so as to provide the broadest possible interpretation of such claims in view of the prior art and, therefore, to effectively encompass the intended scope of the invention.

All publications, patent applications, patents, and other references mentioned herein are incorporated by reference in their entirety. In case of conflict, the present specification, including definitions, will control. In addition, section headings, the materials, methods, and examples are illustrative only and not intended to be limiting.

It is to be understood that the words which have been used are words of description rather than limitation, and that changes may be made within the purview of the appended claims without departing from the true scope and spirit of the invention in its broader aspects.

	Number	Date	Country
	62088994	Dec 2014	US
	61983250	Apr 2014	US

	Number	Date	Country
Parent	17683171	Feb 2022	US
Child	18801174		US
Parent	16144394	Sep 2018	US
Child	17683171		US
Parent	16036318	Jul 2018	US
Child	16144394		US
Parent	15089050	Apr 2016	US
Child	16036318		US
Parent	PCT/US2015/027400	Apr 2015	WO
Child	15089050		US

NUCLEIC ACID VACCINES

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