Method and reagent for inhibiting hepatitis B viral replication

BACKGROUND OF THE INVENTION

[0002] The present invention concerns compounds, compositions, and methods for the study, diagnosis, and treatment of degenerative and disease states related to hepatitis B virus (HBV) replication and gene expression. Specifically, the invention relates to nucleic acid molecules used to inhibit expression of HBV.

[0003] The following is a discussion of relevant art pertaining to hepatitis B virus (HBV). The discussion is not meant to be complete and is provided only for understanding of the invention that follows. The summary is not an admission that any of the work described below is prior art to the claimed invention.

[0004] Chronic hepatitis B is caused by an enveloped virus, commonly known as the hepatitis B virus or HBV. HBV is transmitted via infected blood or other body fluids, especially saliva and semen, during delivery, sexual activity, or sharing of needles contaminated by infected blood. Individuals may be “carriers” and transmit the infection to others without ever having experienced symptoms of the disease. Persons at highest risk are those with multiple sex partners, those with a history of sexually transmitted diseases, parenteral drug users, infants born to infected mothers, “close” contacts or sexual partners of infected persons, and healthcare personnel or other service employees who have contact with blood. Transmission is also possible via tattooing, ear or body piercing, and acupuncture; the virus is also stable on razors, toothbrushes, baby bottles, eating utensils, and some hospital equipment such as respirators, scopes and instruments. There is no evidence that HBsAg positive food handlers pose a health risk in an occupational setting, nor should they be excluded from work. Hepatitis B has never been documented as being a food-borne disease. The average incubation period is 60 to 90 days, with a range of 45 to 180; the number of days appears to be related to the amount of virus to which the person was exposed. However, determining the length of incubation is difficult, since onset of symptoms is insidious. Approximately 50% of patients develop symptoms of acute hepatitis that last from 1 to 4 weeks. Two percent or less of these individuals develop fulminant hepatitis resulting in liver failure and death.

[0005] The determinants of severity include: (1) The size of the dose to which the person was exposed; (2) the person's age with younger patients experiencing a milder form of the disease; (3) the status of the immune system with those who are immunosuppressed experiencing milder cases; and (4) the presence or absence of co-infection with the Delta virus (hepatitis D), with more severe cases resulting from co-infection. In symptomatic cases, clinical signs include loss of appetite, nausea, vomiting, abdominal pain in the right upper quadrant, arthralgia, and tiredness/loss of energy. Jaundice is not experienced in all cases, however, jaundice is more likely to occur if the infection is due to transfusion or percutaneous serum transfer, and it is accompanied by mild pruritus in some patients. Bilirubin elevations are demonstrated in dark urine and clay-colored stools, and liver enlargement may occur accompanied by right upper-quadrant pain. The acute phase of the disease may be accompanied by severe depression, meningitis, Guillain-Barré syndrome, myelitis, encephalitis, agranulocytosis, and/or thrombocytopenia.

[0006] Hepatitis B is generally self-limiting and will resolve in approximately 6 months. Asymptomatic cases can be detected by serologic testing, since the presence of the virus leads to production of large amounts of HBsAg in the blood. This antigen is the first and most useful diagnostic marker for active infections. However, if HBsAg remains positive for 20 weeks or longer, the person is likely to remain positive indefinitely and is now a carrier. While only 10% of persons over age 6 who contract HBV become carriers, 90% of infants infected during the first year of life do so.

[0007] Hepatitis B virus (HBV) infects over 300 million people worldwide (Imperial, 1999, Gastroenterol. Hepatol., 14 (suppl), S1-5). In the United States approximately 1.25 million individuals are chronic carriers of HBV as evidenced by the fact that they have measurable hepatitis B virus surface antigen HBsAg in their blood. The risk of becoming a chronic HBsAg carrier is dependent upon the mode of acquisition of infection as well as the age of the individual at the time of infection. For those individuals with high levels of viral replication, chronic active hepatitis with progression to cirrhosis, liver failure and hepatocellular carcinoma (HCC) is common, and liver transplantation is the only treatment option for patients with end-stage liver disease from HBV.

[0008] The natural progression of chronic HBV infection over a 10 to 20 year period leads to cirrhosis in 20-to-50% of patients and progression of HBV infection to hepatocellular carcinoma has been well documented. There have been no studies that have determined sub-populations that are most likely to progress to cirrhosis and/or hepatocellular carcinoma, thus all patients have equal risk of progression.

[0009] It is important to note that the survival for patients diagnosed with hepatocellular carcinoma is only 0.9 to 12.8 months from initial diagnosis (Takahashi et al., 1993, American Journal of Gastroenterology, 88, 240-243). Treatment of hepatocellular carcinoma with chemotherapeutic agents has not proven effective and only 10% of patients will benefit from surgery due to extensive tumor invasion of the liver (Trinchet et al., 1994,Presse Medicine, 23, 831-833). Given the aggressive nature of primary hepatocellular carcinoma, the only viable treatment alternative to surgery is liver transplantation (Pichlmayr et al., 1994, Hepatology., 20, 33S-40S).

[0010] Upon progression to cirrhosis, patients with chronic HCV infection present with clinical features, which are common to clinical cirrhosis regardless of the initial cause (D'Amico et al., 1986, Digestive Diseases and Sciences, 31, 468-475). These clinical features may include: bleeding esophageal varices, ascites, jaundice, and encephalopathy (Zakim D, Boyer TD. Hepatology a textbook of liver disease, Second Edition Volume 1. 1990 W. B. Saunders Company. Philadelphia). In the early stages of cirrhosis, patients are classified as compensated, meaning that although liver tissue damage has occurred, the patient's liver is still able to detoxify metabolites in the blood-stream. In addition, most patients with compensated liver disease are asymptomatic and the minority with symptoms report only minor symptoms such as dyspepsia and weakness. In the later stages of cirrhosis, patients are classified as decompensated meaning that their ability to detoxify metabolites in the bloodstream is diminished and it is at this stage that the clinical features described above will present.

[0011] In 1986, D'Amico et al. described the clinical manifestations and survival rates in 1155 patients with both alcoholic and viral associated cirrhosis (D'Amico supra). Of the 1155 patients, 435 (37%) had compensated disease although 70% were asymptomatic at the beginning of the study. The remaining 720 patients (63%) had decompensated liver disease with 78% presenting with a history of ascites, 31% with jaundice, 17% had bleeding and 16% had encephalopathy. Hepatocellular carcinoma was observed in six (0.5%) patients with compensated disease and in 30 (2.6%) patients with decompensated disease.

[0012] Over the course of six years, the patients with compensated cirrhosis developed clinical features of decompensated disease at a rate of 10% per year. In most cases, ascites was the first presentation of decompensation. In addition, hepatocellular carcinoma developed in 59 patients who initially presented with compensated disease by the end of the six-year study.

[0013] With respect to survival, the D'Amico study indicated that the five-year survival rate for all patients on the study was only 40%. The six-year survival rate for the patients who initially had compensated cirrhosis was 54% while the six-year survival rate for patients who initially presented with decompensated disease was only 21%. There were no significant differences in the survival rates between the patients who had alcoholic cirrhosis and the patients with viral related cirrhosis. The major causes of death for the patients in the D'Amico study were liver failure in 49%; hepatocellular carcinoma in 22%; and, bleeding in 13% (D'Amico supra).

[0014] Hepatitis B virus is a double-stranded circular DNA virus. It is a member of the Hepadnaviridae family. The virus consists of a central core that contains a core antigen (HBcAg) surrounded by an envelope containing a surface protein/surface antigen (HBsAg) and is 42 nm in diameter. It also contains an e antigen (HBeAg) which, along with HBcAg and HBsAg, is helpful in identifying this disease

[0015] In HBV virions, the genome is found in an incomplete double-stranded form. HBV uses a reverse transcriptase to transcribe a positive-sense full length RNA version of its genome back into DNA. This reverse transcriptase also contains DNA polymerase activity and thus begins replicating the newly synthesized minus-sense DNA strand. However, it appears that the core protein encapsidates the reverse-transcriptase/polymerase before it completes replication.

[0016] From the free-floating form, the virus must first attach itself specifically to a host cell membrane. Viral attachment is one of the crucial steps which determines host and tissue specificity. However, currently there are no in vitro cell-lines that can be infected by HBV. There are some cells lines, such as HepG2, which can support viral replication only upon transient or stable transfection using HBV DNA.

[0017] After attachment, fusion of the viral envelope and host membrane must occur to allow the viral core proteins containing the genome and polymerase to enter the cell. Once inside, the genome is translocated to the nucleus where it is repaired and cyclized.

[0018] The complete closed circular DNA genome of HBV remains in the nucleus and gives rise to four transcripts. These transcripts initiate at unique sites but share the same 3′-ends. The 3.5-kb pregenomic RNA serves as a template for reverse transcription and also encodes the nucleocapsid protein and polymerase. A subclass of this transcript with a 5′-end extension codes for the precore protein that, after processing, is secreted as HBV e antigen. The 2.4-kb RNA encompasses the pre-S1 open reading frame (ORF) that encodes the large surface protein. The 2.1-kb RNA encompasses the pre-S2 and S ORFs that encode the middle and small surface proteins, respectively. The smallest transcript (˜0.8-kb) codes for the X protein, a transcriptional activator.

[0019] Multiplication of the HBV genome begins within the nucleus of an infected cell. RNA polymerase II transcribes the circular HBV DNA into greater-than-full length mRNA. Since the mRNA is longer than the actual complete circular DNA, redundant ends are formed. Once produced, the pregenomic RNA exits the nucleus and enters the cytoplasm.

[0020] The packaging of pregenomic RNA into core particles is triggered by the binding of the HBV polymerase to the 5′ epsilon stem-loop. RNA encapsidation is believed to occur as soon as binding occurs. The HBV polymerase also appears to require associated core protein in order to function. The HBV polymerase initiates reverse transcription from the 5′ epsilon stem-loop three to four base pairs at which point the polymerase and attached nascent DNA are transferred to the 3′ copy of the DR1 region. Once there, the (−)DNA is extended by the HBV polymerase while the RNA template is degraded by the HBV polymerase RNAse H activity. When the HBV polymerase reaches the 5′ end, a small stretch of RNA is left undigested by the RNAse H activity. This segment of RNA is comprised of a small sequence just upstream and including the DR1 region. The RNA oligomer is then translocated and annealed to the DR2 region at the 5′ end of the (−)DNA. It is used as a primer for the (+)DNA synthesis which is also generated by the HBV polymerase. It appears that the reverse transcription as well as plus strand synthesis may occur in the completed core particle.

[0021] Since the pregenomic RNA is required as a template for DNA synthesis, this RNA is an excellent target for enzymatic nucleic acid cleavage. Nucleoside analogues that have been documented to inhibit HBV replication target the reverse transcriptase activity needed to convert the pregenomic RNA into DNA. Enzymatic nucleic acid cleavage of the pregenomic RNA template is expected to result in a similar inhibition of HBV replication. Further, targeting the 3′-end of the pregenomic RNA that is common to all HBV transcripts can result in reduction of all HBV gene products and an additional level of inhibition of HBV replication.

[0022] Cell Culture Models

[0023] As previously mentioned HBV does not infect cells in culture. However, transfection of HBV DNA (either as a head-to-tail dimer or as an “overlength” genome of >100%) into HuH7 or Hep G2 hepatocytes results in viral gene expression and production of HBV virions released into the media. Thus, HBV replication competent DNA can be co-transfected with enzymatic nucleic acids in cell culture. Such an approach has been used to report intracellular ribozyme activity against HBV (zu Putlitz, et al., 1999, J. Virol., 73, 5381-5387, and Kim et al., 1999, Biochem. Biophys. Res. Commun., 257, 759-765). In addition, stable hepatocyte cell lines have been generated that express HBV. Enzymatic nucleic acid can be delivered to these cell lines; however, such assays require the performance of a delivery screen.

[0024] Phenotypic Assays

[0025] Intracellular HBV gene expression can be assayed by a Taqman® assay for HBV RNA or by ELISA for HBV protein. Extracellular virus can be assayed by PCR for DNA or ELISA for protein. Antibodies are commercially available for HBV surface antigen and core protein. A secreted alkaline phosphatase expression plasmid can be used to normalize for differences in transfection efficiency and sample recovery.

[0026] Animal Models

[0027] There are several small animal models to study HBV replication. One is the transplantation of HBV-infected liver tissue into irradiated mice. Viremia (as evidenced by measuring HBV DNA by PCR) is first detected 8 days after transplantation and peaks between 18-25 days (Ilan et al., 1999, Hepatology, 29, 553-562).

[0028] Transgenic mice that express HBV have also been used as a model to evaluate potential anti-virals. HBV DNA is detectable in both liver and serum (Morrey et al., 1999, Antiviral Res., 42, 97-108).

[0029] An additional model is to establish subcutaneous tumors in nude mice with Hep G2 cells transfected with HBV. Tumors develop in about 2 weeks after inoculation and express HBV surface and core antigens. HBV DNA and surface antigen is also detected in the circulation of tumor-bearing mice (Yao et al., 1996, J. Viral Hepat., 3, 19-22).

[0030] Woodchuck hepatitis virus (WHV) is closely related to HBV in its virus structure, genetic organization, and mechanism of replication. As with HBV in humans, persistent WHV infection is common in natural woodchuck populations and is associated with chronic hepatitis and hepatocellular carcinoma (HCC). Experimental studies have established that WHV causes HCC in woodchucks and woodchucks chronically infected with WHV have been used as a model to test a number of anti-viral agents. For example, the nucleoside analogue 3T3 was observed to cause dose dependent reduction in virus (50% reduction after two daily treatments at the highest dose) (Hurwitz et al., 1998. Antimicrob. Agents Chemother., 42, 2804-2809).

[0031] Therapeutic Approaches

[0032] Current therapeutic goals of treatment are three-fold: to eliminate infectivity and transmission of HBV to others, to arrest the progression of liver disease and improve the clinical prognosis, and to prevent the development of hepatocellular carcinoma (HCC).

[0033] Interferon alpha use is the most common therapy for HBV; however, recently Lamivudine (3TC®) has been approved by the FDA. Interferon alpha (IFN-alpha) is one treatment for chronic hepatitis B. The standard duration of IFN-alpha therapy is 16 weeks, however, the optimal treatment length is still poorly defined. A complete response (HBV DNA negative HBeAg negative) occurs in approximately 25% of patients. Several factors have been identified that predict a favorable response to therapy including: High ALT, low HBV DNA, being female, and heterosexual orientation.

[0034] There is also a risk of reactivation of the hepatitis B virus even after a successful response, this occurs in around 5% of responders and normally occurs within 1 year.

[0035] Side effects resulting from treatment with type 1 interferons can be divided into four general categories including: Influenza-like symptoms, neuropsychiatric, laboratory abnormalities, and other miscellaneous side effects. Examples of influenza-like symptoms include, fatigue, fever; myalgia, malaise, appetite loss, tachycardia, rigors, headache and arthralgias. The influenza-like symptoms are usually short-lived and tend to abate after the first four weeks of dosing (Dusheiko et al., 1994, Journal of Viral Hepatitis, 1, 3-5). Neuropsychiatric side effects include irritability, apathy, mood changes, insomnia, cognitive changes, and depression. Laboratory abnormalities include the reduction of myeloid cells, including granulocytes, platelets and to a lesser extent, red blood cells. These changes in blood cell counts rarely lead to any significant clinical sequellae. In addition, increases in triglyceride concentrations and elevations in serum alaine and aspartate aminotransferase concentration have been observed. Finally, thyroid abnormalities have been reported. These thyroid abnormalities are usually reversible after cessation of interferon therapy and can be controlled with appropriate medication while on therapy. Miscellaneous side effects include nausea, diarrhea, abdominal and back pain, pruritus, alopecia, and rhinorrhea. In general, most side effects will abate after 4 to 8 weeks of therapy (Dushieko et al., supra ).

[0036] Lamivudine (3TC®) is a nucleoside analogue, which is a very potent and specific inhibitor of HBV DNA synthesis. Lamivudine has recently been approved for the treatment of chronic Hepatitis B. Unlike treatment with interferon, treatment with 3TC® does not eliminate the HBV from the patient. Rather, viral replication is controlled and chronic administration results in improvements in liver histology in over 50% of patients. Phase III studies with 3TC®, showed that treatment for one year was associated with reduced liver inflammation and a delay in scarring of the liver. In addition, patients treated with Lamivudine (100 mg per day) had a 98 percent reduction in hepatitis B DNA and a significantly higher rate of seroconversion, suggesting disease improvements after completion of therapy. However, stopping of therapy resulted in a reactivation of HBV replication in most patients. In addition recent reports have documented 3TC® resistance in approximately 30% of patients.

[0037] Current therapies for treating HBV infection, including interferon and nucleoside analogues, are only partially effective. In addition, drug resistance to nucleoside analogues is now emerging, making treatment of chronic Hepatitis B more difficult. Thus, a need exists for effective treatment of this disease which utilizes antiviral inhibitors which work by mechanisms other than those currently utilized in the treatment of both acute and chronic hepatitis B infections.

[0038] Draper, U.S. Pat. No. 6,017,756, describes the use of enzymatic nucleic acids for the inhibition of Hepatitis B Virus.

[0039] Passman et al, 2000, Biochem. Biophys. Res. Commun., 268(3), 728-733.; Gan et al., 1998, J. Med. Coll. PLA, 13(3), 157-159.; Li et al., 1999, Jiefangjun Yixue Zazhi, 24(2), 99-101.; Putlitz et al., 1999, J. Virol., 73(7), 5381-5387.; Kim et al., 1999, Biochem. Biophys. Res. Commun., 257(3), 759-765.; Xu et al., 1998, Bingdu Xuebao, 14(4), 365-369.; Welch et al., 1997, Gene Ther., 4(7), 736-743.; Goldenberg et al, 1997, International PCT publication No. WO 97/08309, Wands et al., 1997, J. of Gastroenterology and Hepatology, 12(suppl.), S354-S369.; Ruiz et al., 1997, BioTechniques, 22(2), 338-345.; Gan et al., 1996, J. Med. Coll. PLA, 11(3), 171-175.; Beck and Nassal, 1995, Nucleic Acids Res., 23(24), 4954-62.; Goldenberg, 1995, International PCT publication No. WO 95/22600.; Xu et al., 1993, Bingdu Xuebao, 9(4), 331-6.; Wang et al., 1993, Bingdu Xuebao, 9(3), 278-80, all describe ribozymes that are targeted to cleave a specific HBV target site.

SUMMARY OF THE INVENTION

[0040] This invention relates to enzymatic nucleic acid molecules directed to disrupt the function of RNA species of hepatitis B virus (HBV) and/or encoded by the HBV. In particular, applicant describes the selection and function of enzymatic nucleic acid molecules capable of specifically cleaving HBV RNA. Such enzymatic nucleic acid molecules may be used to treat diseases and disorders associated with HBV infection.

[0041] In one embodiment, the invention features an enzymatic nucleic acid molecule that specifically cleaves RNA derived from hepatitis B virus (HBV), wherein the enzymatic nucleic acid molecule comprises sequence defined as Seq. ID No. 6346.

[0042] In another embodiment, the invention features a pharmaceutical composition comprising an enzymatic nucleic acid molecule of the invention in a pharmaceutically acceptable carrier.

[0043] In another embodiment, the invention features a mammalian cell, for example a human cell, including an enzymatic nucleic acid molecule contemplated by the invention.

[0044] In one embodiment, the invention features a method for treatment of cirrhosis, liver failure or hepatocellular carcinoma comprising administering to a patient an enzymatic nucleic acid molecule the invention under conditions suitable for the treatment.

[0045] In another embodiment, the invention features a method of treatment of a patient having a condition associated with HBV infection, comprising contacting cells of said patient with an enzymatic nucleic acid molecule of the invention, and further comprising the use of one or more drug therapies, for example type I interferon or 3TC® (lamivudine), under conditions suitable for said treatment. In another embodiment, the other therapy is administered simultaneously with or separately from the enzymatic nucleic acid molecule.

[0046] In another embodiment, the invention features a method for inhibiting HBV replication in a mammalian cell comprising administering to the cell an enzymatic nucleic acid molecule of the invention under conditions suitable for the inhibition.

[0047] In yet another embodiment, the invention features a method of cleaving a separate RNA molecule comprising, contacting an enzymatic nucleic acid molecule of the invention with the separate RNA molecule under conditions suitable for the cleavage of the separate RNA molecule.

[0048] In one embodiment, cleavage by an enzymatic nucleic acid molecule of the invention is carried out in the presence of a divalent cation, for example Mg2+.

[0049] In another embodiment, an enzymatic nucleic acid molecule of the invention is chemically synthesized.

[0050] In another embodiment, the type I interferon contemplated by the invention is interferon alpha, interferon beta, polyethylene glycol interferon, polyethylene glycol interferon alpha 2a, polyethylene glycol interferon alpha 2b, polyethylene glycol consensus interferon.

[0051] In one embodiment, the invention features a pharmaceutical composition comprising type I interferon and an enzymatic nucleic acid molecule of the invention, in a pharmaceutically acceptable carrier.

[0052] In another embodiment, the invention features a method of administering to a cell, for example a mammalian cell or human cell, an enzymatic nucleic acid molecule of the invention independently or in conjunction with other therapeutic compounds such as type I interferon or 3TC® (lamivudine), comprising contacting the cell with the enzymatic nucleic acid molecule under conditions suitable for the administration.

[0053] In another embodiment, administration of an enzymatic nucleic acid molecule of the invention is in the presence of a delivery reagent, for example a lipid, cationic lipid, phospholipid, or liposome.

[0054] In a preferred embodiment, the invention features novel nucleic acid-based techniques such as enzymatic nucleic acid molecules and antisense molecules and methods for their use to down regulate or inhibit the expression of HBV RNA and/or replication of HBV.

[0055] In a preferred embodiment, the invention features the use of one or more of the enzymatic nucleic acid-based techniques to inhibit the expression of the genes encoding HBV viral proteins. Specifically, the invention features the use of enzymatic nucleic acid-based techniques to specifically inhibit the expression of the HBV viral genome.

[0056] In another preferred embodiment, the invention features nucleic acid-based inhibitors (e.g., enzymatic nucleic acid molecules (ribozymes), antisense nucleic acids, triplex DNA, antisense nucleic acids containing RNA cleaving chemical groups) and methods for their use to down regulate or inhibit the expression of RNA (e.g., HBV) capable of progression and/or maintenance of hepatitis, hepatocellular carcinoma, cirrhosis, and/or liver failure.

[0057] In one embodiment, nucleic acid molecules of the invention are used to treat HBV infected cells or a HBV infected patient wherein the HBV is resistant or the patient does not respond to treatment with 3TC® (Lamivudine), either alone or in combination with other therapies under conditions suitable for the treatment.

[0058] In another embodiment, nucleic acid molecules of the invention are used to treat HBV infected cells or a HBV infected patient wherein the HBV is resistant or the patient does not respond to treatment with Interferon, for example Infergen®, either alone or in combination with other therapies under conditions suitable for the treatment.

[0059] In yet another preferred embodiment, the invention features the use of an enzymatic nucleic acid molecule, preferably in the hammerhead, NCH (Inozyme), G-cleaver, amberzyme, zinzyme, and/or DNAzyme motif, to inhibit the expression of HBV RNA.

[0060] By “inhibit” it is meant that the activity of HBV or level of RNAs or equivalent RNAs encoding one or more protein subunits of HBV is reduced below that observed in the absence of the nucleic acid. In one embodiment, inhibition with enzymatic nucleic acid molecule preferably is below that level observed in the presence of an enzymatically inactive or attenuated molecule that is able to bind to the same site on the target RNA, but is unable to cleave that RNA. In another embodiment, inhibition with antisense oligonucleotides is preferably below that level observed in the presence, of for example, an oligonucleotide with scrambled sequence or with mismatches. In another embodiment, inhibition of HBV RNA with the nucleic acid molecule of the instant invention is greater than in the presence of the nucleic acid molecule than in its absence.

[0061] These enzymatic nucleic acid molecules exhibit a high degree of specificity for only the viral mRNA in infected cells. Nucleic acid molecules of the instant invention targeted to highly conserved sequence regions allow the treatment of many strains of human HBV with a single compound. No treatment presently exists which specifically attacks expression of the viral gene(s) that are responsible for transformation of hepatocytes by HBV.

[0062] The methods of this invention can be used to treat human hepatitis B virus infections, which include productive virus infection, latent or persistent virus infection, and HBV-induced hepatocyte transformation. The utility can be extended to other species of HBV which infect non-human animals where such infections are of veterinary importance.

[0063] Preferred target sites are genes required for viral replication, a non-limiting example includes genes for protein synthesis, such as the 5′ most 1500 nucleotides of the HBV pregenomic mRNAs. For sequence references, see Renbao et al., 1987, Sci. Sin., 30, 507. This region controls the translational expression of the core protein (C), X protein (X) and DNA polymerase (P) genes and plays a role in the replication of the viral DNA by serving as a template for reverse transcriptase. Disruption of this region in the RNA results in deficient protein synthesis as well as incomplete DNA synthesis (and inhibition of transcription from the defective genomes). Target sequences 5′ of the encapsidation site can result in the inclusion of the disrupted 3′ RNA within the core virion structure and targeting sequences 3′ of the encapsidation site can result in the reduction in protein expression from both the 3′ and 5′ fragments.

[0064] Alternative regions outside of the 5′ most 1500 nucleotides of the pregenomic mRNA also make suitable targets of enzymatic nucleic acid mediated inhibition of HBV replication. Such targets include the mRNA regions that encode the viral S gene. Selection of particular target regions will depend upon the secondary structure of the pregenomic mRNA. Targets in the minor mRNAs can also be used, especially when folding or accessibility assays in these other RNAs reveal additional target sequences that are unavailable in the pregenomic mRNA species.

[0065] A desirable target in the pregenomic RNA is a proposed bipartite stem-loop structure in the 3′-end of the pregenomic RNA which is believed to be critical for viral replication (Kidd and Kidd-Ljunggren, 1996. Nuc. Acid Res. 24:3295-3302). The 5′ end of the HBV pregenomic RNA carries a cis-acting encapsidation signal, which has inverted repeat sequences that are thought to form a bipartite stem-loop structure. Due to a terminal redundancy in the pregenomic RNA, the putative stem-loop also occurs at the 3′-end. While it is the 5′ copy which functions in polymerase binding and encapsidation, reverse transcription actually begins from the 3′ stem-loop. To start reverse transcription, a 4 nt primer which is covalently attached to the polymerase is made, using a bulge in the 5′ encapsidation signal as template. This primer is then shifted, by an unknown mechanism, to the DR1 primer binding site in the 3′ stem-loop structure, and reverse transcription proceeds from that point. The 3′ stem-loop, and especially the DR1 primer binding site, appear to be highly effective targets for enzymatic nucleic acid intervention.

[0066] Sequences of the pregenomic RNA are shared by the mRNAs for surface, core, polymerase, and X proteins. Due to the overlapping nature of the HBV transcripts, all share a common 3′-end. Enzymatic nucleic acid targeting of this common 3′-end will thus cleave the pregenomic RNA as well as all of the mRNAs for surface, core, polymerase and X proteins.

[0067] By “enzymatic nucleic acid molecule” it is meant a nucleic acid molecule which has complementarity in a substrate binding region to a specified gene target, and also has an enzymatic activity which is active to specifically cleave target RNA. That is, the enzymatic nucleic acid molecule is able to intermolecularly cleave RNA and thereby inactivate a target RNA molecule. These complementary regions allow sufficient hybridization of the enzymatic nucleic acid molecule to the target RNA and thus permit cleavage. One hundred percent complementarity is preferred, but complementarity as low as 50-75% may also be useful in this invention (see for example Werner and Uhlenbeck, 1995, Nucleic Acids Research, 23, 2092-2096; Hammann et al., 1999, Antisense and Nucleic Acid Drug Dev., 9, 25-31). The nucleic acids may be modified at the base, sugar, and/or phosphate groups. The term enzymatic nucleic acid is used interchangeably with phrases such as ribozymes, catalytic RNA, enzymatic RNA, catalytic DNA, aptazyme or aptamer-binding ribozyme, regulatable ribozyme, catalytic oligonucleotides, nucleozyme, DNAzyme, RNA enzyme, endoribonuclease, endonuclease, minizyme, leadzyme, oligozyme or DNA enzyme. All of these terminologies describe nucleic acid molecules with enzymatic activity. The specific enzymatic nucleic acid molecules described in the instant application are not meant to be limiting and those skilled in the art will recognize that all that is important in an enzymatic nucleic acid molecule of this invention is that it have a specific substrate binding site which is complementary to one or more of the target nucleic acid regions, and that it have nucleotide sequences within or surrounding that substrate binding site which impart a nucleic acid cleaving activity to the molecule (Cech et al., U.S. Pat. No. 4,987,071; Cech et al., 1988, JAMA 260:20 3030-4).

[0068] By “nucleic acid molecule” as used herein is meant a molecule having nucleotides. The nucleic acid can be single, double, or multiple stranded and may comprise modified or unmodified nucleotides or non-nucleotides or various mixtures and combinations thereof.

[0069] By “enzymatic portion” or “catalytic domain” is meant that portion/region of the enzymatic nucleic acid molecule essential for cleavage of a nucleic acid substrate (for example see FIGS. 1-5).

[0070] By “substrate binding arm” or “substrate binding domain” is meant that portion/region of an enzymatic nucleic acid which is complementary to (i.e., able to base-pair with) a portion of its substrate. Generally, such complementarity is 100%, but can be less if desired. For example, as few as 10 bases out of 14 may be base-paired (see for example Werner and Uhlenbeck, 1995, Nucleic Acids Research, 23, 2092-2096; Hammann et al., 1999, Antisense and Nucleic Acid Drug Dev., 9, 25-31). Such arms are shown generally in FIGS. 1-5. That is, these arms contain sequences within an enzymatic nucleic acid which are intended to bring enzymatic nucleic acid and target RNA together through complementary base-pairing interactions. The enzymatic nucleic acid of the invention can have binding arms that are contiguous (e.g., representing a single binding arm) or non-contiguous (e.g., representing two or more binding arms) and can be of varying lengths. The length of the binding arm(s) are preferably greater than or equal to four nucleotides and of sufficient length to stably interact with the target RNA; specifically 12-100 nucleotides; more specifically 14-24 nucleotides long (see for example Werner and Uhlenbeck, supra; Hamman et al., supra; Hampel et al., EP0360257; Berzal-Herrance et al., 1993, EMBO J., 12, 2567-73). If two binding arms are chosen, the design is such that the length of the binding arms are symmetrical (i.e., each of the binding arms is of the same length; e.g., five and five nucleotides, six and six nucleotides or seven and seven nucleotides long) or asymmetrical (i.e., the binding arms are of different length; e.g., six and three nucleotides; three and six nucleotides long; four and five nucleotides long; four and six nucleotides long; four and seven nucleotides long; and the like).

[0071] By “NCH” or “Inozyme” motif is meant, an enzymatic nucleic acid molecule comprising a motif as described in Ludwig et al., U.S. Ser. No. 09/406,643, filed Sep. 27, 1999, entitled “COMPOSITIONS HAVING RNA CLEAVING ACTIVITY”, and International PCT publication Nos. WO 98/58058 and WO 98/58057, all incorporated by reference herein in their entirety, including the drawings.

[0072] By “G-cleaver” motif is meant, an enzymatic nucleic acid molecule comprising a motif as described in Eckstein et al., International PCT publication No. WO 99/16871, incorporated by reference herein in its entirety, including the drawings.

[0073] By “zinzyme” motif is meant, a class II enzymatic nucleic acid molecule comprising a motif as described in Beigelman et al., International PCT publication No. WO 99/55857, incorporated by reference herein in its entirety, including the drawings.

[0074] By “amberzyme” motif is meant, a class I enzymatic nucleic acid molecule comprising a motif as described in Beigelman et al., International PCT publication No. WO 99/55857, incorporated by reference herein in its entirety, including the drawings.

[0075] By ‘DNAzyme’ is meant, an enzymatic nucleic acid molecule lacking a ribonucleotide (2′-OH) group or an enzymatic nucleic acid molecule that does not require the presence of a ribonucleotide (2′-OH) group in the molecule for its activity. In particular embodiments, the enzymatic nucleic acid molecule may have an attached linker(s) or other attached or associated groups, moieties, or chains containing one or more nucleotides with 2′-OH groups. A DNAzyme can be synthesized chemically or can be expressed by means of a single stranded DNA vector or equivalent thereof.

[0076] By “sufficient length” is meant an oligonucleotide of greater than or equal to 3 nucleotides that is of a length great enough to provide the intended function under the expected condition. For example, for binding arms of enzymatic nucleic acid “sufficient length” means that the binding arm sequence is long enough to provide stable binding to a target site under the expected binding conditions. Preferably, the binding arms are not so long as to prevent useful turnover.

[0077] By “stably interact” is meant, interaction of the oligonucleotides with target nucleic acid (e.g., by forming hydrogen bonds with complementary nucleotides in the target under physiological conditions).

[0078] By “equivalent” RNA to HBV is meant to include those naturally occurring RNA molecules having homology (partial or complete) to HBV proteins or encoding for proteins with similar function as HBV in various organisms, including human, rodent, primate, rabbit, pig, protozoans, fungi, plants, and other microorganisms and parasites. The equivalent RNA sequence also includes in addition to the coding region, regions such as 5′-untranslated region, 3′-untranslated region, introns, intron-exon junction and the like.

[0079] By “homology” is meant the nucleotide sequence of two or more nucleic acid molecules is partially or completely identical.

[0080] By “antisense nucleic acid”, it is meant a non-enzymatic nucleic acid molecule that binds to target RNA by means of RNA-RNA or RNA-DNA or RNA-PNA (protein nucleic acid; Egholm et al., 1993 Nature 365, 566) interactions and alters the activity of the target RNA (for a review, see Stein and Cheng, 1993 Science 261, 1004 and Woolf et al, U.S. Pat. No. 5,849,902). Typically, antisense molecules will be complementary to a target sequence along a single contiguous sequence of the antisense molecule. However, in certain embodiments, an antisense molecule may bind to substrate such that the substrate molecule forms a loop, and/or an antisense molecule may bind such that the antisense molecule forms a loop. Thus, the antisense molecule may be complementary to two (or even more) non-contiguous substrate sequences or two (or even more) non-contiguous sequence portions of an antisense molecule may be complementary to a target sequence or both. For a review of current antisense strategies, see Schmajuk et al., 1999, J. Biol. Chem., 274, 21783-21789, Delihas et al., 1997, Nature, 15, 751-753, Stein et al., 1997, Antisense N. A. Drug Dev., 7, 151, Crooke, 1998, Biotech. Genet. Eng. Rev., 15, 121-157, Crooke, 1997, Ad. Pharmacol., 40, 1-49. In addition, antisense DNA can be used to target RNA by means of DNA-RNA interactions, thereby activating RNase H, which digests the target RNA in the duplex. The antisense oligonucleotides can comprise one or more RNAse H activating region, which is capable of activating RNAse H cleavage of a target RNA. Antisense DNA can be synthesized chemically or expressed via the use of a single stranded DNA expression vector or equivalent thereof.

[0081] By “RNase H activating region” is meant a region (generally greater than or equal to 4-25 nucleotides in length, preferably from 5-11 nucleotides in length) of a nucleic acid molecule capable of binding to a target RNA to form a non-covalent complex that is recognized by cellular RNase H enzyme (see for example Arrow et al., U.S. Pat. No. 5,849,902; Arrow et al., U.S. Pat. No. 5,989,912). The RNase H enzyme binds to the nucleic acid molecule-target RNA complex and cleaves the target RNA sequence. The RNase H activating region comprises, for example, phosphodiester, phosphorothioate (preferably at least four of the nucleotides are phosphorothiote substitutions; more specifically, 4-11 of the nucleotides are phosphorothiote substitutions); phosphorodithioate, 5′-thiophosphate, or methylphosphonate backbone chemistry or a combination thereof. In addition to one or more backbone chemistries described above, the RNase H activating region can also comprise a variety of sugar chemistries. For example, the RNase H activating region can comprise deoxyribose, arabino, fluoroarabino or a combination thereof, nucleotide sugar chemistry. Those skilled in the art will recognize that the foregoing are non-limiting examples and that any combination of phosphate, sugar and base chemistry of a nucleic acid that supports the activity of RNase H enzyme is within the scope of the definition of the RNase H activating region and the instant invention.

[0082] By “2-5A antisense chimera” it is meant, an antisense oligonucleotide containing a 5′-phosphorylated 2′-5′-linked adenylate residue. These chimeras bind to target RNA in a sequence-specific manner and activate a cellular 2-5A-dependent ribonuclease which, in turn, cleaves the target RNA (Torrence et al, 1993 Proc. Natl. Acad. Sci. USA 90, 1300).

[0083] By “triplex DNA” it is meant an oligonucleotide that can bind to a double-stranded DNA in a sequence-specific manner to form a triple-strand helix. Formation of such triple helix structure has been shown to inhibit transcription of the targeted gene (Duval-Valentin et al., 1992, Proc. Natl. Acad. Sci. USA, 89, 504).

[0084] By “gene” it is meant a nucleic acid that encodes an RNA.

[0085] By “complementarity” is meant that a nucleic acid can form hydrogen bond(s) with another RNA sequence by either traditional Watson-Crick or other non-traditional types. In reference to the nucleic molecules of the present invention, the binding free energy for a nucleic acid molecule with its target or complementary sequence is sufficient to allow the relevant function of the nucleic acid to proceed, e.g., enzymatic nucleic acid cleavage, antisense or triple helix inhibition. Determination of binding free energies for nucleic acid molecules is well known in the art (see, e.g., Turner et al., 1987, CSH Symp. Quant. Biol. LII pp.123-133; Frier et al., 1986, Proc. Nat. Acad. Sci. USA 83:9373-9377; Turner et al., 1987, J. Am. Chem. Soc. 109:3783-3785). A percent complementarity indicates the percentage of contiguous residues in a nucleic acid molecule which can form hydrogen bonds (e.g., Watson-Crick base pairing) with a second nucleic acid sequence (e.g., 5, 6, 7, 8, 9, 10 out of 10 being 50%, 60%, 70%, 80%, 90%, and 100% complementary). “Perfectly complementary” means that all the contiguous residues of a nucleic acid sequence will hydrogen bond with the same number of contiguous residues in a second nucleic acid sequence.

[0086] At least seven basic varieties of naturally-occurring enzymatic RNAs are known presently. Each can catalyze the hydrolysis of RNA phosphodiester bonds in trans (and thus can cleave other RNA molecules) under physiological conditions. Table I summarizes some of the characteristics of these enzymatic nucleic acids. In general, enzymatic nucleic acids act by first binding to a target RNA. Such binding occurs through the target binding portion of a enzymatic nucleic acid which is held in close proximity to an enzymatic portion of the molecule that acts to cleave the target RNA. Thus, the enzymatic nucleic acid first recognizes and then binds a target RNA through complementary base-pairing, and once bound to the correct site, acts enzymatically to cut the target RNA. Strategic cleavage of such a target RNA will destroy its ability to direct synthesis of an encoded protein. After an enzymatic nucleic acid has bound and cleaved its RNA target, it is released from that RNA to search for another target and can repeatedly bind and cleave new targets. Thus, a single enzymatic nucleic acid molecule is able to cleave many molecules of target RNA. In addition, the enzymatic nucleic acid is a highly specific inhibitor of gene expression, with the specificity of inhibition depending not only on the base-pairing mechanism of binding to the target RNA, but also on the mechanism of target RNA cleavage. Single mismatches, or base-substitutions, near the site of cleavage can completely eliminate catalytic activity of a enzymatic nucleic acid.

[0087] The enzymatic nucleic acid molecule that cleave the specified sites in HBV-specific RNAs represent a novel therapeutic approach to treat a variety of pathologic indications, including, HBV infection, hepatitis, hepatocellular carcinoma, tumorigenesis, cirrhosis, liver failure and others.

[0088] In one of the preferred embodiments of the inventions described herein, the enzymatic nucleic acid molecule is formed in a hammerhead or hairpin motif, but may also be formed in the motif of a hepatitis delta virus, group I intron, group II intron or RNase P RNA (in association with an RNA guide sequence), Neurospora VS RNA, DNAzymes, NCH cleaving motifs, or G-cleavers. Examples of such hammerhead motifs are described by Dreyfus, supra, Rossi et al., 1992, AIDS Research and Human Retroviruses 8, 183. Examples of hairpin motifs are described by Hampel et al., EP0360257, Hampel and Tritz, 1989 Biochemistry 28, 4929, Feldstein et al., 1989, Gene 82, 53, Haseloff and Gerlach, 1989, Gene, 82, 43, Hampel et al., 1990 Nucleic Acids Res. 18, 299; and Chowrira & McSwiggen, U.S. Pat. No. 5,631,359. The hepatitis delta virus motif is described by Perrotta and Been, 1992 Biochemistry 31, 16. The RNase P motif is described by Guerrier-Takada et al., 1983 Cell 35, 849; Forster and Altman, 1990, Science 249, 783; and Li and Altman, 1996, Nucleic Acids Res. 24, 835. The Neurospora VS RNA ribozyme motif is described by Collins (Saville and Collins, 1990 Cell 61, 685-696; Saville and Collins, 1991 Proc. Natl. Acad. Sci. USA 88, 8826-8830; Collins and Olive, 1993 Biochemistry 32, 2795-2799; and Guo and Collins, 1995, EMBO. J. 14, 363). Group II introns are described by Griffin et al., 1995, Chem. Biol. 2, 761; Michels and Pyle, 1995, Biochemistry 34, 2965; and Pyle et al., International PCT Publication No. WO 96/22689. The Group I intron is described by Cech et al., U.S. Pat. No. 4,987,071. DNAzymes are described by Usman et al., International PCT Publication No. WO 95/11304; Chartrand et al., 1995, NAR 23, 4092; Breaker et al., 1995, Chem. Bio. 2, 655; and Santoro et al., 1997, PNAS 94, 4262. NCH cleaving motifs are described in Ludwig & Sproat, International PCT Publication No. WO 98/58058; and G-cleavers are described in Kore et al., 1998, Nucleic Acids Research 26, 4116-4120 and Eckstein et al., International PCT Publication No. WO 99/16871. Additional motifs include the Aptazyme (Breaker et al., WO 98/43993), Amberzyme (Class I motif; FIG. 3; Beigelman et al., International PCT publication No. WO 99/55857) and Zinzyme (Beigelman et al., International PCT publication No. WO 99/55857), all these references are incorporated by reference herein in their totalities, including drawings and can also be used in the present invention. These specific motifs are not limiting in the invention. and those skilled in the art will recognize that all that is important in an enzymatic nucleic acid molecule of this invention is that it has a specific substrate binding site which is complementary to one or more of the target gene RNA regions, and that it have nucleotide sequences within or surrounding that substrate binding site which impart an RNA cleaving activity to the molecule (Cech et al., U.S. Pat. No. 4,987,071).

[0089] In preferred embodiments of the present invention, a nucleic acid molecule, e.g., an antisense molecule, a triplex DNA, or an enzymatic nucleic acid, is 13 to 100 nucleotides in length, e.g., in specific embodiments 35, 36, 37, or 38 nucleotides in length (e.g., for particular enzymatic nucleic acids or antisense). In particular embodiments, the nucleic acid molecule is 15-100, 17-100, 20-100, 21-100, 23-100, 25-100, 27-100, 30-100, 32-100, 35-100, 40-100, 50-100, 60-100, 70-100, or 80-100 nucleotides in length. Instead of 100 nucleotides being the upper limit on the length ranges specified above, the upper limit of the length range can be, for example, 30, 40, 50, 60, 70, or 80 nucleotides. Thus, for any of the length ranges, the length range for particular embodiments has lower limit as specified, with an upper limit as specified which is greater than the lower limit. For example, in a particular embodiment, the length range can be 35-50 nucleotides in length. All such ranges are expressly included. Also in particular embodiments, a nucleic acid molecule can have a length which is any of the lengths specified above, for example, 21 nucleotides in length.

[0090] Exemplary enzymatic nucleic acid molecules of the invention are shown in Tables V-XI. For example, enzymatic nucleic acid molecules of the invention are preferably between 15 and 50 nucleotides in length, more preferably between 25 and 40 nucleotides in length, e.g., 34, 36, or 38 nucleotides in length (for example see Jarvis et al., 1996, J. Biol. Chem., 271, 29107-29112). Exemplary DNAzymes of the invention are preferably between 15 and 40 nucleotides in length, more preferably between 25 and 35 nucleotides in length, e.g., 29, 30, 31, or 32 nucleotides in length (see for example Santoro et al., 1998, Biochemistry, 37, 13330-13342; Chartrand et al., 1995, Nucleic Acids Research, 23, 4092-4096). Exemplary antisense molecules of the invention are preferably between 15 and 75 nucleotides in length, more preferably between 20 and 35 nucleotides in length, e.g., 25, 26, 27, or 28 nucleotides in length (see for example Woolf et al., 1992, PNAS., 89, 7305-7309; Milner et al., 1997, Nature Biotechnology, 15, 537-541). Exemplary triplex forming oligonucleotide molecules of the invention are preferably between 10 and 40 nucleotides in length, more preferably between 12 and 25 nucleotides in length, e.g., 18, 19, 20, or 21 nucleotides in length (see for example Maher et al., 1990, Biochemistry, 29, 8820-8826; Strobel and Dervan, 1990, Science, 249, 73-75). Those skilled in the art will recognize that all that is required is for the nucleic acid molecule are of length and conformation sufficient and suitable for the nucleic acid molecule to catalyze a reaction contemplated herein. The length of the nucleic acid molecules of the instant invention are not limiting within the general limits stated.

[0091] In a preferred embodiment, the invention provides a method for producing a class of nucleic acid-based gene inhibiting agents which exhibit a high degree of specificity for the RNA of a desired target. For example, the enzymatic nucleic acid molecule is preferably targeted to a highly conserved sequence region of target RNAs encoding HBV proteins (specifically HBV RNA) such that specific treatment of a disease or condition can be provided with either one or several nucleic acid molecules of the invention. Such nucleic acid molecules can be delivered exogenously to specific tissue or cellular targets as required. Alternatively, the nucleic acid molecules (e.g., enzymatic nucleic acids and antisense) can be expressed from DNA and/or RNA vectors that are delivered to specific cells.

[0092] As used in herein “cell” is used in its usual biological sense, and does not refer to an entire multicellular organism, e.g., specifically does not refer to a human. The cell may be present in an organism which may be a human but is preferably a non-human multicellular organism, e.g., birds, plants and mammals such as cows, sheep, apes, monkeys, swine, dogs, and cats. The cell may be prokaryotic (e.g., bacterial cell) or eukaryotic (e.g., mammalian or plant cell).

[0093] By “HBV proteins” is meant, a protein or a mutant protein derivative thereof, comprising sequence expressed and/or encoded by the HBV genome.

[0094] By “highly conserved sequence region” is meant a nucleotide sequence of one or more regions in a target gene does not vary significantly from one generation to the other or from one biological system to the other.

[0095] The enzymatic nucleic acid-based inhibitors of HBV expression are useful for the prevention of the diseases and conditions including HBV infection, hepatitis, cancer, cirrhosis, liver failure, and any other diseases or conditions that are related to the levels of HBV in a cell or tissue.

[0096] By “related” is meant that the reduction of HBV expression (specifically HBV gene) RNA levels and thus reduction in the level of the respective protein will relieve, to some extent, the symptoms of the disease or condition.

[0097] The nucleic acid-based inhibitors of the invention are added directly, or can be complexed with cationic lipids, packaged within liposomes, or otherwise delivered to target cells or tissues. The nucleic acid or nucleic acid complexes can be locally administered to relevant tissues ex vivo, or in vivo through injection, infusion pump or stent, with or without their incorporation in biopolymers. In preferred embodiments, the enzymatic nucleic acid inhibitors comprise sequences, which are complementary to the substrate sequences in Tables IV to XI. Examples of such enzymatic nucleic acid molecules also are shown in Tables V to XI. Examples of such enzymatic nucleic acid molecules consist essentially of sequences defined in these tables.

[0098] In yet another embodiment, the invention features antisense nucleic acid molecules including sequences complementary to the substrate sequences shown in Tables IV to XI. Such nucleic acid molecules can include sequences as shown for the binding arms of the enzymatic nucleic acid molecules in Tables V to XI. Similarly, triplex molecules can be provided targeted to the corresponding DNA target regions, and containing the DNA equivalent of a target sequence or a sequence complementary to the specified target (substrate) sequence. Typically, antisense molecules will be complementary to a target sequence along a single contiguous sequence of the antisense molecule. However, in certain embodiments, an antisense molecule may bind to substrate such that the substrate molecule forms a loop, and/or an antisense molecule may bind such that the antisense molecule forms a loop. Thus, the antisense molecule may be complementary to two (or even more) non-contiguous substrate sequences or two (or even more) non-contiguous sequence portions of an antisense molecule may be complementary to a target sequence or both.

[0099] In another aspect, the invention provides mammalian cells containing one or more nucleic acid molecules and/or expression vectors of this invention. The one or more nucleic acid molecules may independently be targeted to the same or different sites.

[0100] By “consists essentially of” is meant that the active nucleic acid molecule of the invention, for example, an enzymatic nucleic acid molecule, contains an enzymatic center or core equivalent to those in the examples, and binding arms able to bind RNA such that cleavage at the target site occurs. Other sequences can be present which do not interfere with such cleavage. Thus, a core region can, for example, include one or more loop, stem-loop structure, or linker which does not prevent enzymatic activity. Thus, the underlined regions in the sequences in Tables V and VI can be such a loop, stem-loop, nucleotide linker, and/or non-nucleotide linker and can be represented generally as sequence “X”. For example, a core sequence for a hammerhead enzymatic nucleic acid can comprise a conserved sequence, such as 5′-CUGAUGAG-3′ and 5′-CGAA-3′ connected by “X”, where X is 5′-GCCGUUAGGC-3′ (SEQ ID NO 6586), or any other Stem II region known in the art, or a nucleotide and/or non-nucleotide linker. Similarly, for other nucleic acid molecules of the instant invention, such as Inozyme, G-cleaver, amberzyme, zinzyme, DNAzyme, antisense, 2-5A antisense, triplex forming nucleic acid, and decoy nucleic acids, other sequences or non-nucleotide linkers can be present that do not interfere with the function of the nucleic acid molecule.

[0101] In another aspect of the invention, enzymatic nucleic acids or antisense molecules that interact with target RNA molecules and inhibit HBV (specifically HBV RNA) activity are expressed from transcription units inserted into DNA or RNA vectors. The recombinant vectors are preferably DNA plasmids or viral vectors. Enzymatic nucleic acid or antisense expressing viral vectors could be constructed based on, but not limited to, adeno-associated virus, retrovirus, adenovirus, or alphavirus. Preferably, the recombinant vectors capable of expressing the enzymatic nucleic acids or antisense are delivered as described above, and persist in target cells. Alternatively, viral vectors may be used that provide for transient expression of enzymatic nucleic acids or antisense. Such vectors might be repeatedly administered as necessary. Once expressed, the enzymatic nucleic acids or antisense bind to the target RNA and inhibit its function or expression. Delivery of enzymatic nucleic acid or antisense expressing vectors could be systemic, such as by intravenous or intramuscular administration, by administration to target cells ex-planted from the patient followed by reintroduction into the patient, or by any other means that would allow for introduction into the desired target cell. Antisense DNA can be expressed via the use of a single stranded DNA intracellular expression vector.

[0102] By RNA is meant a molecule comprising at least one ribonucleotide residue. By “ribonucleotide” is meant a nucleotide with a hydroxyl group at the 2′ position of a β-D-ribofuranose moiety.

[0103] By “vectors” is meant any nucleic acid- and/or viral-based technique used to deliver a desired nucleic acid.

[0104] By “patient” is meant an organism, which is a donor or recipient of explanted cells or the cells themselves. “Patient” also refers to an organism to which the nucleic acid molecules of the invention can be administered. Preferably, a patient is a mammal or mammalian cells. More preferably, a patient is a human or human cells.

[0105] The nucleic acid molecules of the instant invention, individually, or in combination or in conjunction with other drugs, can be used to treat diseases or conditions discussed above. For example, to treat a disease or condition associated with HBV, the patient may be treated, or other appropriate cells may be treated, as is evident to those skilled in the art, individually or in combination with one or more drugs under conditions suitable for the treatment.

[0106] In a further embodiment, the described molecules, such as antisense or enzymatic nucleic acids, can be used in combination with other known treatments to treat conditions or diseases discussed above. For example, the described molecules could be used in combination with one or more known therapeutic agents to treat HBV infection, hepatitis, hepatocellular carcinoma, cancer, cirrhosis, and liver failure. Such therapeutic agents may include, but are not limited to nucleoside analogs selected from the group comprising Lamivudine (3TC®), L-FMAU, and/or adefovir dipivoxil (for a review of applicable nucleoside analogs, see Colacino and Staschke, 1998, Progress in Drug Research, 50, 259-322). Immunomodulators selected from the group comprising Type 1 Interferon, Therapeutic vaccines, steriods, and 2′-5′ oligoadenylates (for a review of 2′-5′ Oligoadenylates, see Charubala and Pfleiderer, 1994, Progress in Molecular and Subcellular Biology, 14, 113-138).

[0107] In another preferred embodiment, the invention features nucleic acid-based inhibitors (e.g., enzymatic nucleic acid molecules (ribozymes), antisense nucleic acids, triplex DNA, antisense nucleic acids containing RNA cleaving chemical groups) and methods for their use to down regulate or inhibit the expression of RNA (e.g., HBV) capable of progression and/or maintenance of liver disease and failure.

[0108] In another preferred embodiment, the invention features nucleic acid-based techniques (e.g., enzymatic nucleic acid molecules (ribozymes), antisense nucleic acids, triplex DNA, antisense nucleic acids containing RNA cleaving chemical groups) and methods for their use to down regulate or inhibit the expression of HBV RNA expression.

[0109] In preferred embodiments, the invention features a method for the analysis of HBV proteins. This method is useful in determining the efficacy of HBV inhibitors. Specifically, the instant invention features an assay for the analysis of HBsAg proteins and secreted alkaline phosphatase (SEAP) control proteins to determine the efficacy of agents used to modulate HBV expression.

[0110] The method consists of coating a micro-titer plate with an antibody such as anti-HBsAg Mab (for example, Biostride B88-95-31ad,ay) at 0.1 to 10 μg/ml in a buffer (for example, carbonate buffer, such as Na2CO3 15 mM, NaHCO3 35 mM, pH 9.5) at 4° C. overnight. The microtiter wells are then washed with PBST or the equivalent thereof, (for example, PBS, 0.05% Tween 20) and blocked for 0.1-24 hr at 37° C. with PBST, 1% BSA or the equivalent thereof. Following washing as above, the wells are dried (for example, at 37° C. for 30 min). Biotinylated goat anti-HBsAg or an equivalent antibody (for example, Accurate YVS1807) is diluted (for example at 1:1000) in PBST and incubated in the wells (for example, 1 hr. at 37° C.). The wells are washed with PBST (for example, 4×). A conjugate, (for example, Streptavidin/Alkaline Phosphatase Conjugate, Pierce 21324) is diluted to 10-10,000 ng/ml in PBST, and incubated in the wells (for example, 1 hr. at 37° C.). After washing as above, a substrate (for example, p-nitrophenyl phosphate substrate, Pierce 37620) is added to the wells, which are then incubated (for example, 1 hr. at 37° C.). The optical density is then determined (for example, at 405 nm). SEAP levels are then assayed, for example, using the Great EscAPe® Detection Kit (Clontech K2041-1), as per the manufacturers instructions. In the above example, incubation times and reagent concentrations may be varied to achieve optimum results, a non-limiting example is described in Example 6.

[0111] Comparison of this HBsAg ELISA method to a commercially available assay from World Diagnostics, Inc. 15271 NW 60th Ave, #201, Miami Lakes, Fla. 33014 (305) 827-3304 (Cat. No. EL10018) demonstrates an increase in sensitivity (signal:noise) of 3-20 fold.

[0112] Other features and advantages of the invention will be apparent from the following description of the preferred embodiments thereof, and from the claims.

BRIEF DESCRIPTION OF THE DRAWINGS

[0113]
FIG. 1 shows the secondary structure model for seven different classes of enzymatic nucleic acid molecules. Arrow indicates the site of cleavage. --------- indicate the target sequence. Lines interspersed with dots are meant to indicate tertiary interactions. - is meant to indicate base-paired interaction. Group I Intron: P1-P9.0 represent various stem-loop structures (Cech et al., 1994, Nature Struc. Bio., 1, 273). RNase P (M1RNA): EGS represents external guide sequence (Forster et al., 1990, Science, 249, 783; Pace et al., 1990, J. Biol. Chem., 265, 3587). Group II Intron: 5′SS means 5′ splice site; 3′SS means 3′-splice site; IBS means intron binding site; EBS means exon binding site (Pyle et al., 1994, Biochemistry, 33, 2716). VS RNA: I-VI are meant to indicate six stem-loop structures; shaded regions are meant to indicate tertiary interaction (Collins, International PCT Publication No. WO 96/19577). HDV Ribozyme: I-IV are meant to indicate four stem-loop structures (Been et al, U.S. Pat. No. 5,625,047). Hammerhead Ribozyme: I-III are meant to indicate three stem-loop structures; stems I-III can be of any length and may be symmetrical or asymmetrical (Usman et al., 1996, Curr. Op. Struct. Bio., 1, 527). Hairpin Ribozyme: Helix 1, 4 and 5 can be of any length; Helix 2 is between 3 and 8 base-pairs long; Y is a pyrimidine; Helix 2 (H2) is provided with a least 4 base pairs (i.e., n is 1, 2, 3 or 4) and helix 5 can be optionally provided of length 2 or more bases (preferably 3-20 bases, i.e., m is from 1-20 or more). Helix 2 and helix 5 may be covalently linked by one or more bases (i.e., r is ≧1 base). Helix 1, 4 or 5 may also be extended by 2 or more base pairs (e.g., 4-20 base pairs) to stabilize the ribozyme structure, and preferably is a protein binding site. In each instance, each N and N′ independently is any normal or modified base and each dash represents a potential base-pairing interaction. These nucleotides may be modified at the sugar, base or phosphate. Complete base-pairing is not required in the helices, but is preferred. Helix 1 and 4 can be of any size (i.e., o and p is each independently from 0 to any number, e.g., 20) as long as some base-pairing is maintained. Essential bases are shown as specific bases in the structure, but those in the art will recognize that one or more may be modified chemically (abasic, base, sugar and/or phosphate modifications) or replaced with another base without significant effect. Helix 4 can be formed from two separate molecules, i.e., without a connecting loop. The connecting loop when present may be a ribonucleotide with or without modifications to its base, sugar or phosphate. “q”≧is 2 bases. The connecting loop can also be replaced with a non-nucleotide linker molecule. H refers to bases A, U, or C. Y refers to pyrimidine bases. “—————” refers to a covalent bond. (Burke et al., 1996, Nucleic Acids & Mol. Biol., 10, 129; Chowrira et al., U.S. Pat. No. 5,631,359).

[0114]
FIG. 2 shows examples of chemically stabilized enzymatic nucleic acid motifs. HH Rz, represents hammerhead ribozyme motif (Usman et al., 1996, Curr. Op. Struct. Bio., 1, 527); NCH Rz represents the NCH ribozyme motif (Ludwig & Sproat, International PCT Publication No. WO 98/58058); G-Cleaver, represents G-cleaver ribozyme motif (Kore et al., 1998, Nucleic Acids Research, 26, 4116-4120). N or n, represent independently a nucleotide which may be same or different and have complementarity to each other; rI, represents ribo-Inosine nucleotide; arrow indicates the site of cleavage within the target. Position 4 of the HH Rz and the NCH Rz is shown as having 2′-C-allyl modification, but those skilled in the art will recognize that this position can be modified with other modifications well known in the art, so long as such modifications do not significantly inhibit the activity of the ribozyme.

[0115]
FIG. 3 shows an example of the Amberzyme enzymatic nucleic acid motif that is chemically stabilized (see, for example, Beigelman et al., International PCT publication No. WO 99/55857; also referred to as Class I Motif). The Amberzyme motif is a class of enzymatic nucleic acid molecules that do not require the presence of a ribonucleotide (2′-OH) group for activity.

[0116]
FIG. 4 shows an example of the Zinzyme A enzymatic nucleic acid motif that is chemically stabilized (see, for example, International PCT publication No. WO 99/55857; also referred to as Class A Motif). The Zinzyme motif is a class of enzymatic nucleic acid molecules that do not require the presence of a ribonucleotide (2′-OH) group for activity.

[0117]
FIG. 5 shows an example of a DNAzyme motif described by Santoro et al., 1997, PNAS, 94, 4262.

[0118]
FIG. 6 is a bar graph showing the percent change in serum HBV DNA levels following fourteen days of enzymatic nucleic acid treatment in HBV transgenic mice. Enzymatic nucleic acids targeting sites 273 (RPI.18341) and 1833 (RPI.18371) of HBV RNA administerd via continuous s.c. infusion at 10, 30, and 100 mg/kg/day are compared to continuous s.c. infusion administration of scrambled attenuated core enzymatic nucleic acid and saline controls, and orally administered 3TC® (300 mg/kg/day) and saline controls.

[0119]
FIG. 7 is a bar graph showing the mean serum HBV DNA levels following fourteen days of enzymatic nucleic acid treatment in HBV transgenic mice. Enzymatic nucleic acids targeting sites 273 (RPI.18341) and 1833 (RPI.18371) of HBV RNA administerd via continuous s.c. infusion at 10, 30, and 100 mg/kg/day are compared to continuous s.c. infusion administration of scrambled attenuated core enzymatic nucleic acid and saline controls, and orally administered 3TC® (300 mg/kg/day) and saline controls.

[0120]
FIG. 8 is a bar graph showing the decrease in serum HBV DNA (log) levels following fourteen days of enzymatic nucleic acid treatment in HBV transgenic mice. Enzymatic nucleic acids targeting sites 273 (RPI.18341) and 1833 (RPI.18371) of HBV RNA administerd via continuous s.c. infusion at 10, 30, and 100 mg/kg/day are compared to continuous s.c. infusion administration of scrambled attenuated core enzymatic nucleic acid and saline controls, and orally administered 3TC® (300 mg/kg/day) and saline controls.

[0121]
FIG. 9 is a bar graph showing the decrease in HBV DNA in HepG2.2.15 cells after treatment with enzymatic nucleic acids targeting sites 273 (RPI.18341), 1833 (RPI.18371), 1874 (RPI.18372), and 1873 (RPI.18418) of HBV RNA as compared to a scrambled attenuated core enzymatic nucleic acid (RPI.20995).

[0122]
FIG. 10 is a bar graph showing reduction in HBsAg levels following treatment of HepG2 cells with anti-HBV arm, stem, and loop-variant enzymatic nucleic acids (RPI.18341, RPI.22644, RPI.22645, RPI.22646, RPI.22647, RPI.22648, RPI.22649, and RPI.22650) targeting site 273 of the HBV pregenomic RNA as compared to a scrambled attenuated core enzymatic nucleic acid (RPI.20599).

[0123]
FIG. 11 is a bar graph showing reduction in HBsAg levels following treatment of HepG2 cells with RPI 18341 alone or in combination with Infergen®. At either 500 or 1000 units of Infergen®, the addition of 200 nM of RPI.18341 results in a 75-77% increase in anti-HBV activity as judged by the level of HBsAg secreted from the treated Hep G2 cells. Conversely, the anti-HBV activity of RPI.18341(at 200 nM) is increased 31-39% when used in combination of 500 or 1000 units of Infergen®.

[0124]
FIG. 12 is a bar graph showing reduction in HBsAg levels following treatment of HepG2 cells with RPI 18341 alone or in combination with Lamivudine. At 25 nM Lamivudine (3TC®), the addition of 100 nM of RPI.18341 results in a 48% increase in anti-HBV activity as judged by the level of HBsAg secreted from treated Hep G2 cells. Conversely, the anti-HBV activity of RPI.18341 (at 100 nM) is increased 31% when used in combination with 25 nM Lamivudine.

[0125]
FIG. 13 is a bar graph showing reduction of HBsAg levels following treatment of HepG2 cells with RPI 18341 (at 125 nM) in HepG2 cells expressing wild-type HBV and HepG2-DM2 cells expressing lamividine resistant HBV.

[0126]
FIG. 14 shows a non-limiting example of an enzymatic nucleic acid molecule of the invention lacking ribonucleotides. FIG. 15 shows a bar graph comparing the activity of a “no-ribo” enzymatic nucleic acid molecule (RPI 25516) to matched binding attenuated (BAC, RPI 25535) and scrambled attenuated (SAC, RPI 25536) controls, and to an enzymatic nucleic acid molecule having 5 ribonucleotides (RPI 18341) and its matched scrambed attenuated control (RPI 24588) in a HBsAg assay. The concentration of all nucleic acid molecules is 200 nM.

DETAILED DESCRIPTION OF THE INVENTION

[0127] Mechanism of Action of Nucleic Acid Molecules of the Invention

[0128] Antisense: Antisense molecules may be modified or unmodified RNA, DNA, or mixed polymer oligonucleotides and primarily function by specifically binding to matching sequences resulting in inhibition of peptide synthesis (Wu-Pong, November 1994, BioPharm, 20-33). The antisense oligonucleotide binds to target RNA by Watson Crick base-pairing and blocks gene expression by preventing ribosomal translation of the bound sequences either by steric blocking or by activating RNase H enzyme. Antisense molecules may also alter protein synthesis by interfering with RNA processing or transport from the nucleus into the cytoplasm (Mukhopadhyay & Roth, 1996, Crit. Rev. in Oncogenesis 7, 151-190).

[0129] In addition, binding of single stranded DNA to RNA may result in nuclease degradation of the heteroduplex (Wu-Pong, supra; Crooke, supra). To date, the only backbone modified DNA chemistry which will act as substrates for RNase H are phosphorothioates, phosphorodithioates, and borontrifluoridates. Recently, it has been reported that 2′-arabino and 2′-fluoro arabino-containing oligos can also activate RNase H activity.

[0130] A number of antisense molecules have been described that utilize novel configurations of chemically modified nucleotides, secondary structure, and/or RNase H substrate domains (Woolf et al., International PCT Publication No. WO 98/13526; Thompson et al., U.S. Ser. No. 60/082,404 which was filed on Apr. 20, 1998; Hartmann et al., U.S. Ser. No. 60/101,174 which was filed on Sep. 21, 1998) all of these are incorporated by reference herein in their entirety.

[0131] Antisense DNA can be used to target RNA by means of DNA-RNA interactions, thereby activating RNase H, which digests the target RNA in the duplex. Antisense DNA can be chemically synthesized or can be expressed via the use of a single stranded DNA intracellular expression vector or the equivalent thereof.

[0132] Triplex Forming Oligonucleotides (TFO): Single stranded DNA may be designed to bind to genomic DNA in a sequence specific manner. TFOs are comprised of pyrimidine-rich oligonucleotides which bind DNA helices through Hoogsteen Base-pairing (Wu-Pong, supra). The resulting triple helix composed of the DNA sense, DNA antisense, and TFO disrupts RNA synthesis by RNA polymerase. The TFO mechanism may result in gene expression or cell death since binding may be irreversible (Mukhopadhyay & Roth, supra)

[0133] 2′-5′ Oligoadenylates: The 2-5 A system is an interferon-mediated mechanism for RNA degradation found in higher vertebrates (Mitra et al., 1996, Proc Nat Acad Sci USA 93, 6780-6785). Two types of enzymes, 2-5A synthetase and RNase L, are required for RNA cleavage. The 2-5A synthetases require double stranded RNA to form 2′-5′ oligoadenylates (2-SA). 2-5A then acts as an allosteric effector for utilizing RNase L which has the ability to cleave single stranded RNA. The ability to form 2-5A structures with double stranded RNA makes this system particularly useful for inhibition of viral replication.

[0134] (2′-5′) oligoadenylate structures may be covalently linked to antisense molecules to form chimeric oligonucleotides capable of RNA cleavage (Torrence, supra). These molecules putatively bind and activate a 2-5A dependent RNase, the oligonucleotide/enzyme complex then binds to a target RNA molecule which can then be cleaved by the RNase enzyme. The covalent attachment of 2′-5′ oligoadenylate structures is not limited to antisense applications, and can be further elaborated to include attachment to nucleic acid molecules of the instant invention.

[0135] Enzymatic Nucleic Acid: Seven basic varieties of naturally-occurring enzymatic RNAs are presently known. In addition, several in vitro selection (evolution) strategies (Orgel, 1979, Proc. R. Soc. London, B 205, 435) have been used to evolve new nucleic acid catalysts capable of catalyzing cleavage and ligation of phosphodiester linkages (Joyce, 1989, Gene, 82, 83-87; Beaudry et al., 1992, Science 257, 635-641; Joyce, 1992, Scientific American 267, 90-97; Breaker et al., 1994, TIBTECH 12, 268; Bartel et al.,1993, Science 261:1411-1418; Szostak, 1993, TIBS 17, 89-93; Kumar et al., 1995, FASEB J., 9, 1183; Breaker, 1996, Curr. Op. Biotech., 7, 442; Santoro et al., 1997, Proc. Natl. Acad. Sci., 94, 4262; Tang et al., 1997, RNA 3, 914; Nakamaye & Eckstein, 1994, supra; Long & Uhlenbeck, 1994, supra; Ishizaka et al., 1995, supra; Vaish et al., 1997, Biochemistry 36, 6495; all of these are incorporated by reference herein). Each can catalyze a series of reactions including the hydrolysis of phosphodiester bonds in trans (and thus can cleave other RNA molecules) under physiological conditions.

[0136] Nucleic acid molecules of this invention will block to some extent HBV protein expression and can be used to treat disease or diagnose disease associated with the levels of HBV.

[0137] The enzymatic nature of an enzymatic nucleic acid has significant advantages, such as the concentration of enzymatic nucleic acid necessary to affect a therapeutic treatment is low. This advantage reflects the ability of the enzymatic nucleic acid to act enzymatically. Thus, a single enzymatic nucleic acid molecule is able to cleave many molecules of target RNA. In addition, the enzymatic nucleic acid is a highly specific inhibitor, with the specificity of inhibition depending not only on the base-pairing mechanism of binding to the target RNA, but also on the mechanism of target RNA cleavage. Single mismatches, or base-substitutions, near the site of cleavage can be chosen to completely eliminate catalytic activity of an enzymatic nucleic acid.

[0138] Nucleic acid molecules having an endonuclease enzymatic activity are able to repeatedly cleave other separate RNA molecules in a nucleotide base sequence-specific manner. Such enzymatic nucleic acid molecules can be targeted to virtually any RNA transcript, and achieve efficient cleavage in vitro (Zaug et al., 324, Nature, 429 1986 ; Uhlenbeck, 1987 Nature, 328, 596; Kim et al., 84 Proc. Natl. Acad. Sci. USA, 8788, 1987; Dreyfus, 1988, Einstein Quart. J. Bio. Med., 6, 92; Haseloff and Gerlach, 334 Nature, 585, 1988; Cech, 260 JAMA, 3030, 1988; Jefferies et al., 17 Nucleic Acids Research, 1371, 1989; and Santoro et al., 1997 supra).

[0139] Because of their sequence specificity, trans-cleaving enzymatic nucleic acids show promise as therapeutic agents for human disease (Usman & McSwiggen, 1995 Ann. Rep. Med. Chem. 30, 285-294; Christoffersen and Marr, 1995 J. Med. Chem. 38, 2023-2037). Enzymatic nucleic acids can be designed to cleave specific RNA targets within the background of cellular RNA. Such a cleavage event renders the RNA non-functional and abrogates protein expression from that RNA. In this manner, synthesis of a protein associated with a disease state can be selectively inhibited (Warashina et al., 1999, Chemistry and Biology, 6, 237-250.

[0140] The nucleic acid molecules of the instant invention are also referred to as GeneBloc™ reagents, which are essentially nucleic acid molecules (e.g.; enzymatic nucleic acids, antisense) capable of down-regulating gene expression.

[0141] Target Sites

[0142] Targets for useful enzymatic nucleic acids and antisense nucleic acids can be determined as disclosed in Draper et al., WO 93/23569; Sullivan et al., WO 93/23057; Thompson et al., WO 94/02595; Draper et al., WO 95/04818; McSwiggen et al., U.S. Pat. No. 5,525,468, and all hereby incorporated in their entirites by reference herein. Other examples include the following PCT applications, which concern inactivation of expression of disease-related genes: WO 95/23225, WO 95/13380, WO 94/02595, all incorporated by reference herein. Rather than repeat the guidance provided in those documents here, below are provided specific examples of such methods, not limiting to those in the art. Enzymatic nucleic acids and antisense to such targets are designed as described in those applications and synthesized to be tested in vitro and in vivo, as also described. The sequence of human HBV RNAs (for example, accession AF100308.1; HBV strain 2-18; additionally, other HBV strains can be screened by one skilled in the art, see Table III for other possible strains) were screened for optimal enzymatic nucleic acid and antisense target sites using a computer-folding algorithm. Antisense, hammerhead, DNAzyme, NCH (Inozyme), amberzyme, zinzyme or G-Cleaver enzymatic nucleic acid binding/cleavage sites were identified. These sites are shown in Tables V to XI (all sequences are 5′ to 3′ in the tables; X can be any base-paired sequence, the actual sequence is not relevant here). The nucleotide base position is noted in the Tables as that site to be cleaved by the designated type of enzymatic nucleic acid molecule. Table IV shows substrate positions selected from Renbo et al., 1987, Sci. Sin., 30, 507, used in Draper, U.S. Ser. No. (07/882,712), filed May 14, 1992, entitled “METHOD AND REAGENT FOR INHIBITING HEPATITIS B VIRUS REPLICATION” and Draper et al., International PCT publication No. WO 93/23569, filed Apr. 29, 1993, entitled “METHOD AND REAGENT FOR INHIBITING VIRAL REPLICATION”. While human sequences can be screened and enzymatic nucleic acid molecule and/or antisense thereafter designed, as discussed in Stinchcomb et al., WO 95/23225, mouse targeted enzymatic nucleic acids may be useful to test efficacy of action of the enzymatic nucleic acid molecule and/or antisense prior to testing in humans.

[0143] Antisense, hammerhead, DNAzyme, NCH (Inozyme), amberzyme, zinzyme or G-Cleaver enzymatic nucleic acid binding/cleavage sites were identified, as discussed above. The nucleic acid molecules were individually analyzed by computer folding (Jaeger et al., 1989 Proc. Natl. Acad. Sci. USA, 86, 7706) to assess whether the sequences fold into the appropriate secondary structure. Those nucleic acid molecules with unfavorable intramolecular interactions such as between the binding arms and the catalytic core were eliminated from consideration. Varying binding arm lengths can be chosen to optimize activity.

[0144] Antisense, hammerhead, DNAzyme, NCH, amberzyme, zinzyme or G-Cleaver enzymatic nucleic acid binding/cleavage sites were identified and were designed to anneal to various sites in the RNA target. The binding arms are complementary to the target site sequences described above. The nucleic acid molecules were chemically synthesized. The method of synthesis used follows the procedure for normal DNA/RNA synthesis as described below and in Usman et al., 1987 J. Am. Chem. Soc., 109, 7845; Scaringe et al., 1990 Nucleic Acids Res., 18, 5433; Wincott et al., 1995 Nucleic Acids Res. 23, 2677-2684; and Caruthers et al., 1992, Methods in Enzymology 211,3-19.

[0145] Synthesis of Nucleic Acid Molecules

[0146] Synthesis of nucleic acids greater than 100 nucleotides in length is difficult using automated methods, and the therapeutic cost of such molecules is prohibitive. In this invention, small nucleic acid motifs (“small” refers to nucleic acid motifs no more than 100 nucleotides in length, preferably no more than 80 nucleotides in length, and most preferably no more than 50 nucleotides in length; e.g., antisense oligonucleotides, hammerhead or the NCH enzymatic nucleic acids) are preferably used for exogenous delivery. The simple structure of these molecules increases the ability of the nucleic acid to invade targeted regions of RNA structure. Exemplary molecules of the instant invention are chemically synthesized, and others can similarly be synthesized.

[0147] Oligonucleotides (e.g.; antisense GeneBlocs) are synthesized using protocols known in the art as described in Caruthers et al., 1992, Methods in Enzymology 211, 3-19, Thompson et al., International PCT Publication No. WO 99/54459, Wincott et al., 1995, Nucleic Acids Res. 23, 2677-2684, Wincott et al., 1997, Methods Mol. Bio., 74, 59, Brennan et al., 1998, Biotechnol Bioeng., 61, 33-45, and Brennan, U.S. Pat. No. 6,001,311. All of these references are incorporated herein by reference. The synthesis of oligonucleotides makes use of common nucleic acid protecting and coupling groups, such as dimethoxytrityl at the 5′-end, and phosphoramidites at the 3′-end. In a non-limiting example, small scale syntheses are conducted on a 394 Applied Biosystems, Inc. synthesizer using a 0.2 μmol scale protocol with a 2.5 min coupling step for 2′-O-methylated nucleotides and a 45 sec coupling step for 2′-deoxy nucleotides. Table II outlines the amounts and the contact times of the reagents used in the synthesis cycle. Alternatively, syntheses at the 0.2 μmol scale can be performed on a 96-well plate synthesizer, such as the instrument produced by Protogene (Palo Alto, Calif.) with minimal modification to the cycle. A 33-fold excess (60 μL of 0.11 M=6.6 μmol) of 2′-O-methyl phosphoramidite and a 105-fold excess of S-ethyl tetrazole (60 μL of 0.25 M=15 μmol) can be used in each coupling cycle of 2′-O-methyl residues relative to polymer-bound 5′-hydroxyl. A 22-fold excess (40 μL of 0.11 M=4.4 μmol) of deoxy phosphoramidite and a 70-fold excess of S-ethyl tetrazole (40 μL of 0.25 M=10 μmol) can be used in each coupling cycle of deoxy residues relative to polymer-bound 5′-hydroxyl. Average coupling yields on the 394 Applied Biosystems, Inc. synthesizer, determined by colorimetric quantitation of the trityl fractions, are typically 97.5-99%. Other oligonucleotide synthesis reagents for the 394 Applied Biosystems, Inc. synthesizer include the following: detritylation solution is 3% TCA in methylene chloride (ABI); capping is performed with 16% N-methyl imidazole in THF (ABI) and 10% acetic anhydride/10% 2,6-lutidine in THF (ABI); and oxidation solution is 16.9 mM I2, 49 mM pyridine, 9% water in THF (PERSEPTIVE™). Burdick & Jackson Synthesis Grade acetonitrile is used directly from the reagent bottle. S-Ethyltetrazole solution (0.25 M in acetonitrile) is made up from the solid obtained from American International Chemical, Inc. Alternately, for the introduction of phosphorothioate linkages, Beaucage reagent (3H-1,2-Benzodithiol-3-one 1,1-dioxide, 0.05 M in acetonitrile) is used.

[0148] Deprotection of the antisense oligonucleotides is performed as follows: the polymer-bound trityl-on oligoribonucleotide is transferred to a 4 mL glass screw top vial and suspended in a solution of 40% aq. methylamine (1 mL) at 65° C. for 10 min. After cooling to −20° C., the supernatant is removed from the polymer support. The support is washed three times with 1.0 mL of EtOH:MeCN:H2O/3:1:1, vortexed and the supernatant is then added to the first supernatant. The combined supernatants, containing the oligoribonucleotide, are dried to a white powder.

[0149] The method of synthesis used for normal RNA including certain enzymatic nucleic acid molecules follows the procedure as described in Usman et al., 1987, J. Am. Chem. Soc., 109, 7845; Scaringe et al., 1990, Nucleic Acids Res., 18, 5433; and Wincott et al., 1995, Nucleic Acids Res. 23, 2677-2684 Wincott et al., 1997, Methods Mol. Bio., 74, 59, and makes use of common nucleic acid protecting and coupling groups, such as dimethoxytrityl at the 5′-end, and phosphoramidites at the 3′-end. In a non-limiting example, small scale syntheses are conducted on a 394 Applied Biosystems, Inc. synthesizer using a 0.2 μmol scale protocol with a 7.5 min coupling step for alkylsilyl protected nucleotides and a 2.5 min coupling step for 2′-O-methylated nucleotides. Table II outlines the amounts and the contact times of the reagents used in the synthesis cycle. Alternatively, syntheses at the 0.2 μmol scale can be done on a 96-well plate synthesizer, such as the instrument produced by Protogene (Palo Alto, Calif.) with minimal modification to the cycle. A 33-fold excess (60 μL of 0.11 M=6.6 μmol) of 2′-O-methyl phosphoramidite and a 75-fold excess of S-ethyl tetrazole (60 μL of 0.25 M=15 μmol) can be used in each coupling cycle of 2′-O-methyl residues relative to polymer-bound 5′-hydroxyl. A 66-fold excess (120 μL of 0.11 M=13.2 μmol) of alkylsilyl (ribo) protected phosphoramidite and a 150-fold excess of S-ethyl tetrazole (120 μL of 0.25 M=30 μmol) can be used in each coupling cycle of ribo residues relative to polymer-bound 5′-hydroxyl. Average coupling yields on the 394 Applied Biosystems, Inc. synthesizer, determined by colorimetric quantitation of the trityl fractions, are typically 97.5-99%. Other oligonucleotide synthesis reagents for the 394 Applied Biosystems, Inc. synthesizer include the following: detritylation solution is 3% TCA in methylene chloride (ABI); capping is performed with 16% N-methyl imidazole in THF (ABI) and 10% acetic anhydride/10% 2,6-lutidine in THF (ABI); oxidation solution is 16.9 mM I2, 49 mM pyridine, 9% water in THF (PERSEPTIVE™). Burdick & Jackson Synthesis Grade acetonitrile is used directly from the reagent bottle. S-Ethyltetrazole solution (0.25 M in acetonitrile) is made up from the solid obtained from American International Chemical, Inc. Alternately, for the introduction of phosphorothioate linkages, Beaucage reagent (3H-1,2-Benzodithiol-3-one 1,1-dioxide0.05 M in acetonitrile) is used.

[0150] Deprotection of the RNA is performed using either a two-pot or one-pot protocol. For the two-pot protocol, the polymer-bound trityl-on oligoribonucleotide is transferred to a 4 mL glass screw top vial and suspended in a solution of 40% aq. methylamine (1 mL) at 65° C. for 10 min. After cooling to −20° C., the supernatant is removed from the polymer support. The support is washed three times with 1.0 mL of EtOH:MeCN:H2O/3:1:1, vortexed and the supernatant is then added to the first supernatant. The combined supernatants, containing the oligoribonucleotide, are dried to a white powder. The base deprotected oligoribonucleotide is resuspended in anhydrous TEA/HF/NMP solution (300 μL of a solution of 1.5 mL N-methylpyrrolidinone, 750 μL TEA and 1 mL TEA·3HF to provide a 1.4 M HF concentration) and heated to 65° C. After 1.5 h, the oligomer is quenched with 1.5 M NH4HCO3.

[0151] Alternatively, for the one-pot protocol, the polymer-bound trityl-on oligoribonucleotide is transferred to a 4 mL glass screw top vial and suspended in a solution of 33% ethanolic methylamine/DMSO: 1/1 (0.8 mL) at 65° C. for 15 min. The vial is brought to r.t. TEA·3HF (0.1 mL) is added and the vial is heated at 65° C. for 15 min. The sample is cooled at −20° C. and then quenched with 1.5 M NH4HCO3.

[0152] For purification of the trityl-on oligomers, the quenched NH4HCO3 solution is loaded onto a C-18 containing cartridge that had been prewashed with acetonitrile followed by 50 mM TEAA. After washing the loaded cartridge with water, the RNA is detritylated with 0.5% TFA for 13 min. The cartridge is then washed again with water, salt exchanged with 1 M NaCl and washed with water again. The oligonucleotide is then eluted with 30% acetonitrile.

[0153] Inactive hammerhead enzymatic nucleic acids or binding attenuated control (BAC) oligonucleotides) are synthesized by substituting a U for G5 and a U for A14 (numbering from Hertel, K. J., et al., 1992, Nucleic Acids Res., 20, 3252). Similarly, one or more nucleotide substitutions can be introduced in other enzymatic nucleic acid molecules to inactivate the molecule and such molecules can serve as a negative control.

[0154] The average stepwise coupling yields are typically >98% (Wincott et al., 1995 Nucleic Acids Res. 23, 2677-2684). Those of ordinary skill in the art will recognize that the scale of synthesis can be adapted to be larger or smaller than the example described above including but not limited to 96-well format, all that is important is the ratio of chemicals used in the reaction.

[0155] Alternatively, the nucleic acid molecules of the present invention can be synthesized separately and joined together post-synthetically, for example, by ligation (Moore et al., 1992, Science 256, 9923; Draper et al., International PCT publication No. WO 93/23569; Shabarova et al., 1991, Nucleic Acids Research 19, 4247; Bellon et al., 1997, Nucleosides & Nucleotides, 16, 951; Bellon et al., 1997, Bioconjugate Chem. 8, 204).

[0156] The nucleic acid molecules of the present invention are modified extensively to enhance stability by modification with nuclease resistant groups, for example, 2′-amino, 2′-C-allyl, 2′-flouro, 2′-O-methyl, 2′-H (for a review see Usman and Cedergren, 1992, TIBS 17, 34; Usman et al., 1994, Nucleic Acids Symp. Ser. 31, 163). Enzymatic nucleic acids are purified by gel electrophoresis using general methods or are purified by high pressure liquid chromatography (HPLC; see Wincott et al., supra, the totality of which is hereby incorporated herein by reference) and are re-suspended in water.

[0157] The sequences of the enzymatic nucleic acids and antisense constructs that are chemically synthesized, useful in this study, are shown in Tables IV to IX. Those in the art will recognize that these sequences are representative only of many more such sequences where the enzymatic portion of the enzymatic nucleic acid (all but the binding arms) is altered to affect activity. The enzymatic nucleic acid and antisense construct sequences listed in Tables IV to IX may be formed of ribonucleotides or other nucleotides or non-nucleotides. Such enzymatic nucleic acids with enzymatic activity are equivalent to the enzymatic nucleic acids described specifically in the Tables.

[0158] Optimizing Activity of the Nucleic Acid Molecule of the Invention

[0159] Chemically synthesizing nucleic acid molecules with modifications (base, sugar and/or phosphate) that prevent their degradation by serum ribonucleases may increase their potency (see e.g., Eckstein et al., International Publication No. WO 92/07065; Perrault et al., 1990 Nature 344, 565; Pieken et al., 1991, Science 253, 314; Usman and Cedergren, 1992, Trends in Biochem. Sci. 17, 334; Usman et al., International Publication No. WO 93/15187; Rossi et al., International Publication No. WO 91/03162; Sproat, U.S. Pat. No. 5,334,711; and Burgin et al., supra; all of these describe various chemical modifications that can be made to the base, phosphate and/or sugar moieties of the nucleic acid molecules herein and are all hereby incorporated by reference herein). Modifications which enhance their efficacy in cells, and removal of bases from nucleic acid molecules to shorten oligonucleotide synthesis times and reduce chemical requirements are desired.

[0160] There are several examples in the art describing sugar, base and phosphate modifications that can be introduced into nucleic acid molecules with significant enhancement in their nuclease stability and efficacy. For example, oligonucleotides are modified to enhance stability and/or enhance biological activity by modification with nuclease resistant groups, for example, 2′-amino, 2′-C-allyl, 2′-flouro, 2′-O-methyl, 2′-H, nucleotide base modifications (for a review see Usman and Cedergren, 1992, TIBS. 17, 34; Usman et al., 1994, Nucleic Acids Symp. Ser. 31, 163; Burgin et al., 1996, Biochemistry, 35, 14090). Sugar modification of nucleic acid molecules have been extensively described in the art (see Eckstein et al., International Publication PCT No. WO 92/07065; Perrault et al. Nature, 1990, 344, 565-568; Pieken et al. Science, 1991, 253, 314-317; Usman and Cedergren, Trends in Biochem. Sci., 1992, 17, 334-339; Usman et al. International Publication PCT No. WO 93/15187; Sproat, U.S. Pat. No. 5,334,711 and Beigelman et al., 1995, J. Biol. Chem., 270, 25702; Beigelman et al., International PCT publication No. WO 97/26270; Beigelman et al., U.S. Pat. No. 5,716,824; Usman et al., U.S. Pat. No. 5,627,053; Woolf et al., International PCT Publication No. WO 98/13526; Thompson et al., U.S. Ser. No. 60/082,404 which was filed on Apr. 20, 1998; Karpeisky et al., 1998, Tetrahedron Lett., 39, 1131; Earnshaw and Gait, 1998, Biopolymers (Nucleic Acid Sciences), 48, 39-55; Verma and Eckstein, 1998, Annu. Rev. Biochem., 67, 99-134; and Burlina et al., 1997, Bioorg. Med. Chem., 5, 1999-2010; all of the references are hereby incorporated in their totality by reference herein). Such publications describe general methods and strategies to determine the location of incorporation of sugar, base and/or phosphate modifications and the like into enzymatic nucleic acids without inhibiting catalysis, and are incorporated by reference herein. In view of such teachings, similar modifications can be used as described herein to modify the nucleic acid molecules of the instant invention.

[0161] While chemical modification of oligonucleotide internucleotide linkages with phosphorothioate, phosphorothioate, and/or 5′-methylphosphonate linkages improves stability, too many of these modifications may cause some toxicity. Therefore, when designing nucleic acid molecules, the amount of these internucleotide linkages should be minimized. The reduction in the concentration of these linkages should lower toxicity resulting in increased efficacy and higher specificity of these molecules.

[0162] Nucleic acid molecules having chemical modifications which maintain or enhance activity are provided. Such nucleic acid molecules are also generally more resistant to nucleases than unmodified nucleic acid. Thus, in a cell and/or in vivo the activity may not be significantly lowered. Therapeutic nucleic acid molecules delivered exogenously must optimally be stable within cells until translation of the target RNA has been inhibited long enough to reduce the levels of the undesirable protein. This period of time varies between hours to days depending upon the disease state. Clearly, nucleic acid molecules must be resistant to nucleases in order to function as effective intracellular therapeutic agents. Improvements in the chemical synthesis of RNA and DNA (Wincott et al., 1995 Nucleic Acids Res. 23, 2677; Caruthers et al., 1992, Methods in Enzymology 211,3-19 (are incorporated by reference herein) have expanded the ability to modify nucleic acid molecules by introducing nucleotide modifications to enhance their nuclease stability as described above.

[0163] Use of these the nucleic acid-based molecules of the invention will lead to better treatment of the disease progression by affording the possibility of combination therapies (e.g., multiple antisense or enzymatic nucleic acid molecules targeted to different genes, nucleic acid molecules coupled with known small molecule inhibitors, or intermittent treatment with combinations of molecules (including different motifs) and/or other chemical or biological molecules). The treatment of patients with nucleic acid molecules may also include combinations of different types of nucleic acid molecules.

[0164] Therapeutic nucleic acid molecules (e.g., enzymatic nucleic acid molecules and antisense nucleic acid molecules) delivered exogenously must optimally be stable within cells until translation of the target RNA has been inhibited long enough to reduce the levels of the undesirable protein. This period of time varies between hours to days depending upon the disease state. Clearly, these nucleic acid molecules must be resistant to nucleases in order to function as effective intracellular therapeutic agents. Improvements in the chemical synthesis of nucleic acid molecules described in the instant invention and in the art have expanded the ability to modify nucleic acid molecules by introducing nucleotide modifications to enhance their nuclease stability as described above.

[0165] By “enhanced enzymatic activity” is meant to include activity measured in cells and/or in vivo where the activity is a reflection of both catalytic activity and enzymatic nucleic acid stability. In this invention, the product of these properties is increased or not significantly (less than 10-fold) decreased in vivo compared to an all RNA enzymatic nucleic acid or all DNA enzyme.

[0166] In yet another preferred embodiment, nucleic acid catalysts having chemical modifications which maintain or enhance enzymatic activity is provided. Such nucleic acid catalysts are also generally more resistant to nucleases than unmodified nucleic acid. Thus, in a cell and/or in vivo the activity may not be significantly lowered. As exemplified herein such enzymatic nucleic acids are useful in a cell and/or in vivo even if activity over all is reduced 10 fold (Burgin et al., 1996, Biochemistry, 35, 14090). Such enzymatic nucleic acids herein are said to “maintain” the enzymatic activity of an all RNA enzymatic nucleic acid.

[0167] In another aspect the nucleic acid molecules comprise a 5′ and/or a 3′-cap structure.

[0168] By “cap structure” is meant chemical modifications, which have been incorporated at either terminus of the oligonucleotide (see, for example, Wincott et al., WO 97/26270, incorporated by reference herein). These terminal modifications protect the nucleic acid molecule from exonuclease degradation, and may help in delivery and/or localization within a cell. The cap may be present at the 5′-terminus (5′-cap) or at the 3′-terminal (3′-cap) or may be present on both termini. In non-limiting examples: the 5′-cap is selected from the group comprising inverted abasic residue (moiety); 4′,5′-methylene nucleotide; 1-(beta-D-erythrofuranosyl) nucleotide, 4′-thio nucleotide; carbocyclic nucleotide; 1,5-anhydrohexitol nucleotide; L-nucleotides; alpha-nucleotides; modified base nucleotide; phosphorodithioate linkage; threo-pentofuranosyl nucleotide; acyclic 3′,4′-seco nucleotide; acyclic 3,4-dihydroxybutyl nucleotide; acyclic 3,5-dihydroxypentyl nucleotide, 3′-3′-inverted nucleotide moiety; 3′-3′-inverted abasic moiety; 3′-2′-inverted nucleotide moiety; 3′-2′-inverted abasic moiety; 1,4-butanediol phosphate; 3′-phosphoramidate; hexylphosphate; aminohexyl phosphate; 3′-phosphate; 3′-phosphorothioate; phosphorodithioate; or bridging or non-bridging methylphosphonate moiety (for more details, see Wincott et al., International PCT publication No. WO 97/26270, incorporated by reference herein).

[0169] In yet another preferred embodiment, the 3′-cap is selected from a group comprising, 4′,5′-methylene nucleotide; 1-(beta-D-erythrofuranosyl) nucleotide; 4′-thio nucleotide, carbocyclic nucleotide; 5′-amino-alkyl phosphate; 1,3-diamino-2-propyl phosphate; 3-aminopropyl phosphate; 6-aminohexyl phosphate; 1,2-aminododecyl phosphate; hydroxypropyl phosphate; 1,5-anhydrohexitol nucleotide; L-nucleotide; alpha-nucleotide; modified base nucleotide; phosphorodithioate; threo-pentofuranosyl nucleotide; acyclic 3′,4′-seco nucleotide; 3,4-dihydroxybutyl nucleotide; 3,5-dihydroxypentyl nucleotide, 5′-5′-inverted nucleotide moiety; 5′-5′-inverted abasic moiety; 5′-phosphoramidate; 5′-phosphorothioate; 1,4-butanediol phosphate; 5′-amino; bridging and/or non-bridging 5′-phosphoramidate, phosphorothioate and/or phosphorodithioate, bridging or non bridging methylphosphonate and 5′-mercapto moieties (for more details see Beaucage and Tyer, 1993, Tetrahedron 49, 1925; incorporated by reference herein).

[0170] By the term “non-nucleotide” is meant any group or compound which can be incorporated into a nucleic acid chain in the place of one or more nucleotide units, including either sugar and/or phosphate substitutions, and allows the remaining bases to exhibit their enzymatic activity. The group or compound is abasic in that it does not contain a commonly recognized nucleotide base, such as adenosine, guanine, cytosine, uracil or thymine.

[0171] An “alkyl” group refers to a saturated aliphatic hydrocarbon, including straight-chain, branched-chain, and cyclic alkyl groups. Preferably, the alkyl group has 1 to 12 carbons. More preferably it is a lower alkyl of from 1 to 7 carbons, more preferably 1 to 4 carbons. The alkyl group may be substituted or unsubstituted. When substituted the substituted group(s) is preferably, hydroxyl, cyano, alkoxy, ═O, ═S, NO2 or N(CH3)2, amino, or SH. The term also includes alkenyl groups which are unsaturated hydrocarbon groups containing at least one carbon-carbon double bond, including straight-chain, branched-chain, and cyclic groups. Preferably, the alkenyl group has 1 to 12 carbons. More preferably it is a lower alkenyl of from 1 to 7 carbons, more preferably 1 to 4 carbons. The alkenyl group may be substituted or unsubstituted. When substituted the substituted group(s) is preferably, hydroxyl, cyano, alkoxy, ═O, ═S, NO2, halogen, N(CH3)2, amino, or SH. The term “alkyl” also includes alkynyl groups which have an unsaturated hydrocarbon group containing at least one carbon-carbon triple bond, including straight-chain, branched-chain, and cyclic groups. Preferably, the alkynyl group has 1 to 12 carbons. More preferably it is a lower alkynyl of from 1 to 7 carbons, more preferably 1 to 4 carbons. The alkynyl group may be substituted or unsubstituted. When substituted the substituted group(s) is preferably, hydroxyl, cyano, alkoxy, ═O, ═S, NO2 or N(CH3)2, amino or SH.

[0172] Such alkyl groups may also include aryl, alkylaryl, carbocyclic aryl, heterocyclic aryl, amide and ester groups. An “aryl” group refers to an aromatic group which has at least one ring having a conjugated pi electron system and includes carbocyclic aryl, heterocyclic aryl and biaryl groups, all of which may be optionally substituted. The preferred substituent(s) of aryl groups are halogen, trihalomethyl, hydroxyl, SH, OH, cyano, alkoxy, alkyl, alkenyl, alkynyl, and amino groups. An “alkylaryl” group refers to an alkyl group (as described above) covalently joined to an aryl group (as described above). Carbocyclic aryl groups are groups wherein the ring atoms on the aromatic ring are all carbon atoms. The carbon atoms are optionally substituted. Heterocyclic aryl groups are groups having from 1 to 3 heteroatoms as ring atoms in the aromatic ring and the remainder of the ring atoms are carbon atoms. Suitable heteroatoms include oxygen, sulfur, and nitrogen, and include furanyl, thienyl, pyridyl, pyrrolyl, N-lower alkyl pyrrolo, pyrimidyl, pyrazinyl, imidazolyl and the like, all optionally substituted. An “amide” refers to an —C(O)—NH—R, where R is either alkyl, aryl, alkylaryl or hydrogen. An “ester” refers to an —C(O)—OR′, where R is either alkyl, aryl, alkylaryl or hydrogen.

[0173] By “nucleotide” as used herein is as recognized in the art to include natural bases (standard), and modified bases well known in the art. Such bases are generally located at the 1′ position of a nucleotide sugar moiety. Nucleotides generally comprise a base, sugar and a phosphate group. The nucleotides can be unmodified or modified at the sugar, phosphate and/or base moiety, (also referred to interchangeably as nucleotide analogs, modified nucleotides, nonnatural nucleotides, non-standard nucleotides and other; see, for example, Usman and McSwiggen, supra; Eckstein et al., International PCT Publication No. WO 92/07065; Usman et al., International PCT Publication No. WO 93/15187; Uhlman & Peyman, supra, all are hereby incorporated by reference herein). There are several examples of modified nucleic acid bases known in the art as summarized by Limbach et al., 1994, Nucleic Acids Res. 22, 2183. Some of the non-limiting examples of base modifications that can be introduced into nucleic acid molecules include, inosine, purine, pyridin-4-one, pyridin-2-one, phenyl, pseudouracil, 2, 4, 6-trimethoxy benzene, 3-methyl uracil, dihydrouridine, naphthyl, aminophenyl, 5-alkylcytidines (e.g., 5-methylcytidine), 5-alkyluridines (e.g., ribothymidine), 5-halouridine (e.g., 5-bromouridine) or 6-azapyrimidines or 6-alkylpyrimidines (e.g. 6-methyluridine), propyne, and others (Burgin et al., 1996, Biochemistry, 35, 14090; Uhlman & Peyman, supra). By “modified bases” in this aspect is meant nucleotide bases other than adenine, guanine, cytosine and uracil at 1′ position or their equivalents; such bases may be used at any position, for example, within the catalytic core of an enzymatic nucleic acid molecule and/or in the substrate-binding regions of the nucleic acid molecule.

[0174] In a preferred embodiment, the invention features modified enzymatic nucleic acids with phosphate backbone modifications comprising one or more phosphorothioate, phosphorodithioate, methylphosphonate, morpholino, amidate carbamate, carboxymethyl, acetamidate, polyamide, sulfonate, sulfonamide, sulfamate, formacetal, thioforrnacetal, and/or alkylsilyl, substitutions. For a review of oligonucleotide backbone modifications, see Hunziker and Leumann, 1995, Nucleic Acid Analogues: Synthesis and Properties, in Modern Synthetic Methods, VCH, 331-417, and Mesmaeker et al., 1994, Novel Backbone Replacements for Oligonucleotides, in Carbohydrate Modifications in Antisense Research, ACS, 24-39. These references are hereby incorporated by reference herein.

[0175] By “abasic” is meant sugar moieties lacking a base or having other chemical groups in place of a base at the 1′ position, (for more details, see Wincott et al., International PCT publication No. WO 97/26270).

[0176] By “unmodified nucleoside” is meant one of the bases adenine, cytosine, guanine, thymine, uracil joined to the 1′ carbon of β-D-ribo-furanose.

[0177] By “modified nucleoside” is meant any nucleotide base which contains a modification in the chemical structure of an unmodified nucleotide base, sugar and/or phosphate.

[0178] In connection with 2′-modified nucleotides as described for the present invention, by “amino” is meant 2′-NH2 or 2′-O-NH2, which may be modified or unmodified. Such modified groups are described, for example, in Eckstein et al., U.S. Pat. No. 5,672,695 and Matulic-Adamic et al., WO 98/28317, which are both incorporated by reference in their entireties.

[0179] Various modifications to nucleic acid (e.g., antisense and enzymatic nucleic acid) structure can be made to enhance the utility of these molecules. Such modifications will enhance shelf-life, half-life in vitro, stability, and ease of introduction of such oligonucleotides to the target site, e.g., to enhance penetration of cellular membranes, and confer the ability to recognize and bind to targeted cells.

[0180] Use of these molecules will lead to better treatment of the disease progression by affording the possibility of combination therapies (e.g., multiple enzymatic nucleic acids targeted to different genes, enzymatic nucleic acids coupled with known small molecule inhibitors, or intermittent treatment with combinations of enzymatic nucleic acids (including different enzymatic nucleic acid motifs) and/or other chemical or biological molecules). The treatment of patients with nucleic acid molecules may also include combinations of different types of nucleic acid molecules. Therapies may be devised which include a mixture of enzymatic nucleic acids (including different enzymatic nucleic acid motifs), antisense and/or 2-5A chimera molecules to one or more targets to alleviate symptoms of a disease.

[0181] Administration of Nucleic Acid Molecules

[0182] Methods for the delivery of nucleic acid molecules are described in Akhtar et al., 1992, Trends Cell Bio., 2, 139; and Delivery Strategies for Antisense Oligonucleotide Therapeutics, ed. Akhtar, 1995 which are both incorporated herein by reference. Sullivan et al., PCT WO 94/02595, further describes the general methods for delivery of enzymatic RNA molecules. These protocols may be utilized for the delivery of virtually any nucleic acid molecule. Nucleic acid molecules may be administered to cells by a variety of methods known to those familiar to the art, including, but not restricted to, encapsulation in liposomes, by iontophoresis, or by incorporation into other vehicles, such as hydrogels, cyclodextrins, biodegradable nanocapsules, and bioadhesive microspheres. For some indications, nucleic acid molecules may be directly delivered ex vivo to cells or tissues with or without the aforementioned vehicles. Alternatively, the nucleic acid/vehicle combination is locally delivered by direct injection or by use of a catheter, infusion pump or stent. Other routes of delivery include, but are not limited to, intravascular, intramuscular, subcutaneous or joint injection, aerosol inhalation, oral (tablet or pill form), topical, systemic, ocular, intraperitoneal and/or intrathecal delivery. More detailed descriptions of nucleic acid delivery and administration are provided in Sullivan et al., supra, Draper et al., PCT WO93/23569; Beigelman et al., PCT WO99/05094, and Klimuk et al., PCT WO99/04819 all of which are incorporated by reference herein.

[0183] The molecules of the instant invention can be used as pharmaceutical agents. Pharmaceutical agents prevent, inhibit the occurrence, or treat (alleviate a symptom to some extent, preferably all of the symptoms) of a disease state in a patient.

[0184] The negatively charged polynucleotides of the invention can be administered (e.g., RNA, DNA or protein) and introduced into a patient by any standard means, with or without stabilizers, buffers, and the like, to form a pharmaceutical composition. When it is desired to use a liposome delivery mechanism, standard protocols for formation of liposomes can be followed. The compositions of the present invention may also be formulated and used as tablets, capsules or elixirs for oral administration; suppositories for rectal administration; sterile solutions; suspensions for injectable administration; and the other compositions known in the art.

[0185] The present invention also includes pharmaceutically acceptable formulations of the compounds described. These formulations include salts of the above compounds, e.g., acid addition salts, for example, salts of hydrochloric, hydrobromic, acetic acid, and benzene sulfonic acid.

[0186] A pharmacological composition or formulation refers to a composition or formulation in a form suitable for administration, e.g., systemic administration, into a cell or patient, preferably a human. Suitable forms, in part, depend upon the use or the route of entry, for example, oral, transdermal, or by injection. Such forms should not prevent the composition or formulation from reaching a target cell (i.e., a cell to which the negatively charged polymer is desired to be delivered to). For example, pharmacological compositions injected into the blood stream should be soluble. Other factors are known in the art, and include considerations such as toxicity and forms which prevent the composition or formulation from exerting its effect.

[0187] By “systemic administration” is meant in vivo systemic absorption or accumulation of drugs in the blood stream followed by distribution throughout the entire body. Administration routes which lead to systemic absorption include, without limitations: intravenous, subcutaneous, intraperitoneal, inhalation, oral, intrapulmonary and intramuscular. Each of these administration routes expose the desired negatively charged polymers, e.g., nucleic acids, to an accessible diseased tissue. The rate of entry of a drug into the circulation has been shown to be a function of molecular weight or size. The use of a liposome or other drug carrier comprising the compounds of the instant invention can potentially localize the drug, for example, in certain tissue types, such as the tissues of the reticular endothelial system (RES). A liposome formulation which can facilitate the association of drug with the surface of cells, such as, lymphocytes and macrophages is also useful. This approach may provide enhanced delivery of the drug to target cells by taking advantage of the specificity of macrophage and lymphocyte immune recognition of abnormal cells, such as cancer cells.

[0188] By pharmaceutically acceptable formulation is meant, a composition or formulation that allows for the effective distribution of the nucleic acid molecules of the instant invention in the physical location most suitable for their desired activity. Nonlimiting examples of agents suitable for formulation with the nucleic acid molecules of the instant invention include: P-glycoprotein inhibitors (such as Pluronic P85) which can enhance entry of drugs into the CNS (Jolliet-Riant and Tillement, 1999, Fundam. Clin. Pharmacol., 13, 16-26); biodegradable polymers, such as poly (DL-lactide-coglycolide) microspheres for sustained release delivery after intracerebral implantation (Emerich, DF et al, 1999, Cell Transplant, 8, 47-58) Alkermes, Inc. Cambridge, Mass.; and loaded nanoparticles, such as those made of polybutylcyanoacrylate, which can deliver drugs across the blood brain barrier and can alter neuronal uptake mechanisms (Prog Neuropsychopharmacol Biol Psychiatry, 23, 941-949, 1999). Other non-limiting examples of delivery strategies for the nucleic acid molecules of the instant invention include material described in Boado et al., 1998, J. Pharm. Sci., 87, 1308-1315; Tyler et al., 1999, FEBS Lett., 421, 280-284; Pardridge et al., 1995, PNAS USA., 92, 5592-5596; Boado, 1995, Adv. Drug Delivery Rev., 15, 73-107; Aldrian-Herrada et al., 1998, Nucleic Acids Res., 26, 4910-4916; and Tyler et al., 1999, PNAS USA., 96, 7053-7058.

[0189] The invention also features the use of the composition comprising surface-modified liposomes containing poly (ethylene glycol) lipids (PEG-modified, or long-circulating liposomes or stealth liposomes). These formulations offer a method for increasing the accumulation of drugs in target tissues. This class of drug carriers resists opsonization and elimination by the mononuclear phagocytic system (MPS or RES), thereby enabling longer blood circulation times and enhanced tissue exposure for the encapsulated drug (Lasic et al. Chem. Rev. 1995, 95, 2601-2627; Ishiwata et al., Chem. Pharm. Bull. 1995, 43, 1005-1011). Such liposomes have been shown to accumulate selectively in tumors, presumably by extravasation and capture in the neovascularized target tissues (Lasic et al., Science 1995, 267, 1275-1276; Oku et al., 1995, Biochim. Biophys. Acta, 1238, 86-90). The long-circulating liposomes enhance the pharmacokinetics and pharmacodynamics of DNA and RNA, particularly compared to conventional cationic liposomes which are known to accumulate in tissues of the MPS (Liu et al., J. Biol. Chem. 1995, 42, 24864-24870; Choi et al., International PCT Publication No. WO 96/10391; Ansell et al., International PCT Publication No. WO 96/10390; Holland et al., International PCT Publication No. WO 96/10392; all of which are incorporated by reference herein). Long-circulating liposomes are also likely to protect drugs from nuclease degradation to a greater extent compared to cationic liposomes, based on their ability to avoid accumulation in metabolically aggressive MPS tissues such as the liver and spleen.

[0190] The present invention also includes compositions prepared for storage or administration which include a pharmaceutically effective amount of the desired compounds in a pharmaceutically acceptable carrier or diluent. Acceptable carriers or diluents for therapeutic use are well known in the pharmaceutical art, and are described, for example, in Remington's Pharmaceutical Sciences, Mack Publishing Co. (A. R. Gennaro edit. 1985) hereby incorporated by reference herein. For example, preservatives, stabilizers, dyes and flavoring agents may be provided. These include sodium benzoate, sorbic acid and esters of p-hydroxybenzoic acid. In addition, antioxidants and suspending agents may be used.

[0191] A pharmaceutically effective dose is that dose required to prevent, inhibit the occurrence, or treat (alleviate a symptom to some extent, preferably all of the symptoms) of a disease state. The pharmaceutically effective dose depends on the type of disease, the composition used, the route of administration, the type of mammal being treated, the physical characteristics of the specific mammal under consideration, concurrent medication, and other factors which those skilled in the medical arts will recognize. Generally, an amount between 0.1 mg/kg and 100 mg/kg body weight/day of active ingredients is administered dependent upon potency of the negatively charged polymer.

[0192] The nucleic acid molecules of the present invention may also be administered to a patient in combination with other therapeutic compounds to increase the overall therapeutic effect. The use of multiple compounds to treat an indication may increase the beneficial effects while reducing the presence of side effects.

[0193] Alternatively, certain of the nucleic acid molecules of the instant invention can be expressed within cells from eukaryotic promoters (e.g., Izant and Weintraub, 1985, Science, 229, 345; McGarry and Lindquist, 1986, Proc. Natl. Acad. Sci., USA 83, 399; Scanlon et al., 1991, Proc. Natl. Acad. Sci. USA, 88, 10591-5; Kashani-Sabet et al., 1992, Antisense Res. Dev., 2, 3-15; Dropulic et al., 1992, J. Virol., 66, 1432-41; Weerasinghe et al., 1991, J. Virol., 65, 5531-4; Ojwang et al., 1992, Proc. Natl. Acad. Sci. USA, 89, 10802-6; Chen et al., 1992, Nucleic Acids Res., 20, 4581-9; Sarver et al., 1990 Science, 247, 1222-1225; Thompson et al., 1995, Nucleic Acids Res., 23, 2259; Good et al., 1997, Gene Therapy, 4, 45; all of these references are hereby incorporated in their totalites by reference herein). Those skilled in the art realize that any nucleic acid can be expressed in eukaryotic cells from the appropriate DNA/RNA vector. The activity of such nucleic acids can be augmented by their release from the primary transcript by a ribozyme (Draper et al., PCT WO 93/23569, and Sullivan et al., PCT WO 94/02595; Ohkawa et al., 1992, Nucleic Acids Symp. Ser., 27, 15-6; Taira et al., 1991, Nucleic Acids Res., 19, 5125-30; Ventura et al., 1993, Nucleic Acids Res., 21, 3249-55; Chowrira et al., 1994, J. Biol. Chem., 269, 25856; all of these references are hereby incorporated in their totality by reference herein).

[0194] In another aspect of the invention, RNA molecules of the present invention are preferably expressed from transcription units (see, for example, Couture et al., 1996, TIG., 12, 510) inserted into DNA or RNA vectors. The recombinant vectors are preferably DNA plasmids or viral vectors. Enzymatic nucleic acid expressing viral vectors could be constructed based on, but not limited to, adeno-associated virus, retrovirus, adenovirus, or alphavirus. Preferably, the recombinant vectors capable of expressing the nucleic acid molecules are delivered as described above, and persist in target cells. Alternatively, viral vectors may be used that provide for transient expression of nucleic acid molecules. Such vectors might be repeatedly administered as necessary. Once expressed, the nucleic acid molecule binds to the target mRNA. Delivery of nucleic acid molecule expressing vectors could be systemic, such as by intravenous or intramuscular administration, by administration to target cells ex-planted from the patient followed by reintroduction into the patient, or by any other means that would allow for introduction into the desired target cell (for a review see Couture et al., 1996, TIG., 12, 510).

[0195] In one aspect, the invention features an expression vector comprising a nucleic acid sequence encoding at least one of the nucleic acid molecules of the instant invention is disclosed. The nucleic acid sequence encoding the nucleic acid molecule of the instant invention is operable linked in a manner which allows expression of that nucleic acid molecule.

[0196] In another aspect the invention features an expression vector comprising: a) a transcription initiation region (e.g., eukaryotic pol I, II or III initiation region); b) a transcription termination region (e.g., eukaryotic pol I, II or III termination region); c) a nucleic acid sequence encoding at least one of the nucleic acid catalyst of the instant invention; and wherein said sequence is operably linked to said initiation region and said termination region, in a manner which allows expression and/or delivery of said nucleic acid molecule. The vector may optionally include an open reading frame (ORF) for a protein operably linked on the 5′ side or the 3′-side of the sequence encoding the nucleic acid catalyst of the invention; and/or an intron (intervening sequences).

[0197] Transcription of the nucleic acid molecule sequences are driven from a promoter for eukaryotic RNA polymerase I (pol I), RNA polymerase II (pol II), or RNA polymerase III (pol III). Transcripts from pol II or pol III promoters will be expressed at high levels in all cells; the levels of a given pol II promoter in a given cell type will depend on the nature of the gene regulatory sequences (enhancers, silencers, etc.) present nearby. Prokaryotic RNA polymerase promoters are also used, providing that the prokaryotic RNA polymerase enzyme is expressed in the appropriate cells (Elroy-Stein and Moss, 1990, Proc. Natl. Acad. Sci. USA, 87, 6743-7; Gao and Huang 1993, Nucleic Acids Res., 21, 2867-72; Lieber et al., 1993, Methods Enzymol., 217, 47-66; Zhou et al., 1990, Mol. Cell. Biol., 10, 4529-37). All of these references are incorporated by reference herein. Several investigators have demonstrated that nucleic acid molecules, such as enzymatic nucleic acids expressed from such promoters can function in mammalian cells (e.g. Kashani-Sabet et al., 1992, Antisense Res. Dev., 2, 3-15; Ojwang et al., 1992, Proc. Natl. Acad. Sci. USA, 89, 10802-6; Chen et al., 1992, Nucleic Acids Res., 20, 4581-9; Yu et al., 1993, Proc. Natl. Acad. Sci. USA, 90, 6340-4; L'Huillier et al., 1992, EMBO J., 11, 4411-8; Lisziewicz et al., 1993, Proc. Natl. Acad. Sci. U.S.A., 90, 8000-4; Thompson et al., 1995, Nucleic Acids Res., 23, 2259; Sullenger & Cech, 1993, Science, 262, 1566). More specifically, transcription units such as the ones derived from genes encoding U6 small nuclear (snRNA), transfer RNA (tRNA) and adenovirus VA RNA are useful in generating high concentrations of desired RNA molecules such as enzymatic nucleic acids in cells (Thompson et al., supra; Couture and Stinchcomb, 1996, supra; Noonberg et al., 1994, Nucleic Acid Res., 22, 2830; Noonberg et al., U.S. Pat. No. 5,624,803; Good et al., 1997, Gene Ther., 4, 45; Beigelman et al., International PCT Publication No. WO 96/18736; all of these publications are incorporated by reference herein. The above enzymatic nucleic acid transcription units can be incorporated into a variety of vectors for introduction into mammalian cells, including but not restricted to, plasmid DNA vectors, viral DNA vectors (such as adenovirus or adeno-associated virus vectors), or viral RNA vectors (such as retroviral or alphavirus vectors) (for a review see Couture and Stinchcomb, 1996, supra).

[0198] In yet another aspect, the invention features an expression vector comprising nucleic acid sequence encoding at least one of the nucleic acid molecules of the invention, in a manner which allows expression of that nucleic acid molecule. The expression vector comprises in one embodiment; a) a transcription initiation region; b) a transcription termination region; c) a nucleic acid sequence encoding at least one said nucleic acid molecule; and wherein said sequence is operably linked to said initiation region and said termination region, in a manner which allows expression and/or delivery of said nucleic acid molecule. In another preferred embodiment the expression vector comprises: a) a transcription initiation region; b) a transcription termination region; c) an open reading frame; d) a nucleic acid sequence encoding at least one said nucleic acid molecule, wherein said sequence is operably linked to the 3′-end of said open reading frame; and wherein said sequence is operably linked to said initiation region, said open reading frame and said termination region, in a manner which allows expression and/or delivery of said nucleic acid molecule. In yet another embodiment, the expression vector comprises: a) a transcription initiation region; b) a transcription termination region; c) an intron; d) a nucleic acid sequence encoding at least one said nucleic acid molecule; and wherein said sequence is operably linked to said initiation region, said intron and said termination region, in a manner which allows expression and/or delivery of said nucleic acid molecule. In another embodiment, the expression vector comprises: a) a transcription initiation region; b) a transcription termination region; c) an intron; d) an open reading frame; e) a nucleic acid sequence encoding at least one said nucleic acid molecule, wherein said sequence is operably linked to the 3′-end of said open reading frame; and wherein said sequence is operably linked to said initiation region, said intron, said open reading frame and said termination region, in a manner which allows expression and/or delivery of said nucleic acid molecule.

EXAMPLES

[0199] The following are non-limiting examples showing the selection, isolation, synthesis and activity of nucleic acids of the instant invention.

[0200] The following examples demonstrate the selection and design of Antisense, Hammerhead, DNAzyme, NCH, Amberzyme, Zinzyme or G-Cleaver enzymatic nucleic acid molecules and binding/cleavage sites within HBV RNA.

Example 1

Identification of Potential Target Sites in Human HBV RNA

[0201] The sequence of human HBV was screened for accessible sites using a computer-folding algorithm. Regions of the RNA that did not form secondary folding structures and contained potential enzymatic nucleic acid and/or antisense binding/cleavage sites were identified. The sequences of these cleavage sites are shown in Tables IV-XI.

Example 2

Selection of Enzymatic Nucleic Acid Cleavage Sites in Human HBV RNA

[0202] Enzymatic nucleic acid target sites were chosen by analyzing sequences of Human HBV (accession number: AF100308.1) and prioritizing the sites on the basis of folding. Enzymatic nucleic acids were designed that could bind each target and were individually analyzed by computer folding (Christoffersen et al., 1994 J. Mol. Struc. Theochem, 311, 273; Jaeger et al., 1989, Proc. Natl. Acad. Sci. USA, 86, 7706) to assess whether the enzymatic nucleic acid sequences fold into the appropriate secondary structure. Those enzymatic nucleic acids with unfavorable intramolecular interactions between the binding arms and the catalytic core were eliminated from consideration. As noted herein, varying binding arm lengths can be chosen to optimize activity. Generally, at least 5 bases on each arm are able to bind to, or otherwise interact with, the target RNA.

Example 3

Chemical Synthesis and Purification of Enzymatic Nucleic Acids and Antisense for Efficient Cleavage and/or Blocking of HBV RNA

[0203] Enzymatic nucleic acids and antisense constructs were designed to anneal to various sites in the RNA message. The binding arms of the enzymatic nucleic acids are complementary to the target site sequences described above, while the antisense constructs are fully complementary to the target site sequences described above. The enzymatic nucleic acids and antisense constructs were chemically synthesized. The method of synthesis used followed the procedure for normal RNA synthesis as described above and in Usman et al., (1987 J. Am. Chem. Soc., 109, 7845), Scaringe et al., (1990 Nucleic Acids Res., 18, 5433) and Wincott et al., supra, and made use of common nucleic acid protecting and coupling groups, such as dimethoxytrityl at the 5′-end, and phosphoramidites at the 3′-end. The average stepwise coupling yields were typically >98%.

[0204] Enzymatic nucleic acids and antisense constructs were also synthesized from DNA templates using bacteriophage T7 RNA polymerase (Milligan and Uhlenbeck, 1989, Methods Enzymol. 180, 51). Enzymatic nucleic acids and antisense constructs were purified by gel electrophoresis using general methods or were purified by high pressure liquid chromatography (HPLC; see Wincott et al., supra; the totality of which is hereby incorporated herein by reference) and were resuspended in water. The sequences of the chemically synthesized enzymatic nucleic acids used in this study are shown below in Table XI.

Example 4

Enzymatic Nucleic Acid Cleavage of HBV RNA Target in vitro

[0205] Enzymatic nucleic acids targeted to the human HBV RNA are designed and synthesized as described above. These enzymatic nucleic acids can be tested for cleavage activity in vitro, for example using the following procedure. The target sequences and the nucleotide location within the HBV RNA are given in Tables IV-XI.

[0206] Cleavage Reactions: Full-length or partially full-length, internally-labeled target RNA for enzymatic nucleic acid cleavage assay is prepared by in vitro transcription in the presence of [α-32P] CTP, passed over a G 50 Sephadex® column by spin chromatography and used as substrate RNA without further purification. Alternately, substrates are 5′-32P-end labeled using T4 polynucleotide kinase enzyme. Assays are performed by pre-warming a 2× concentration of purified enzymatic nucleic acid in enzymatic nucleic acid cleavage buffer (50 mM Tris-HCl, pH 7.5 at 37° C., 10 mM MgCl2) and the cleavage reaction was initiated by adding the 2× enzymatic nucleic acid mix to an equal volume of substrate RNA (maximum of 1-5 nM) that was also pre-warmed in cleavage buffer. As an initial screen, assays are carried out for 1 hour at 37° C. using a final concentration of either 40 nM or 1 mM enzymatic nucleic acid, i.e., enzymatic nucleic acid excess. The reaction is quenched by the addition of an equal volume of 95% formamide, 20 mM EDTA, 0.05% bromophenol blue and 0.05% xylene cyanol after which the sample is heated to 95° C. for 2 minutes, quick chilled and loaded onto a denaturing polyacrylamide gel. Substrate RNA and the specific RNA cleavage products generated by enzymatic nucleic acid cleavage are visualized on an autoradiograph of the gel. The percentage of cleavage is determined by Phosphor Imager® quantitation of bands representing the intact substrate and the cleavage products.

Example 5

Transfection of HepG2 Cells with psHBV-1 and Enzymatic Nucleic Acids

[0207] The human hepatocellular carcinoma cell line Hep G2 was grown in Dulbecco's modified Eagle media supplemented with 10% fetal calf serum, 2 mM glutamine, 0.1 mM nonessential amino acids, 1 mM sodium pyruvate, 25 mM Hepes, 100 units penicillin, and 100 μg/ml streptomycin. To generate a replication competent cDNA, prior to transfection the HBV genomic sequences are excised from the bacterial plasmid sequence contained in the psHBV-1 vector (Those skilled in the art understand that other methods may be used to generate a replication competent cDNA). This was done with an EcoRI and Hind III restriction digest. Following completion of the digest, a ligation was performed under dilute conditions (20 μg/ml) to favor intermolecular ligation. The total ligation mixture was then concentrated using Qiagen spin columns.

[0208] Secreted alkaline phosphatase (SEAP) was used to normalize the HBsAg levels to control for transfection variability. The pSEAP2-TK control vector was constructed by ligating a Bgl II-Hind III fragment of the pRL-TK vector (Promega), containing the herpes simplex virus thymidine kinase promoter region, into Bgl II/Hind III digested pSEAP2-Basic (Clontech). Hep G2 cells were plated (3×104 cells/well) in 96-well microtiter plates and incubated overnight. A lipid/DNA/enzymatic nucleic acid complex was formed containing (at final concentrations) cationic lipid (15 μg/ml), prepared psHBV-1 (4.5 μg/ml), pSEAP2-TK (0.5 μg/ml), and enzymatic nucleic acid (100 μM). Following a 15 min. incubation at 37° C., the complexes were added to the plated Hep G2 cells. Media was removed from the cells 96 hr. post-transfection for HBsAg and SEAP analysis.

[0209] Transfection of the human hepatocellular carcinoma cell line, Hep G2, with replication competent HBV DNA results in the expression of HBV proteins and the production of virions. To investigate the potential use of enzymatic nucleic acids for the treatment of chronic HBV infection, a series of enzymatic nucleic acids that target the 3′ terminus of the HBV genome have been synthesized. Enzymatic nucleic acids targeting this region have the potential to cleave all four major HBV RNA transcripts as well as the potential to block the production of HBV DNA by cleavage of the pregenomic RNA. To test the efficacy of these HBV enzymatic nucleic acids, they were co-transfected with HBV genomic DNA into Hep G2 cells, and the subsequent levels of secreted HBV surface antigen (HBsAg) were analyzed by ELISA. To control for variability in transfection efficiency, a control vector which expresses secreted alkaline phosphatase (SEAP), was also co-transfected. The efficacy of the HBV enzymatic nucleic acids was determined by comparing the ratio of HBsAg:SEAP and/or HBeAg:SEAP to that of a scrambled attenuated control (SAC) enzymatic nucleic acid. Twenty-five enzymatic nucleic acids (RPI18341, RPI18356, RPI18363, RPI18364, RPI18365, RPI18366, RPI18367, RPI18368, RPI18369, RPI18370, RPI18371, RPI18372, RPI18373, RPI18374, RPI18303, RPI18405, RPI18406, RPI18407, RPI18408, RPI18409, RPI18410, RPI18411, RPI18418, RPI18419, and RPI18422) have been identified which cause a reduction in the levels of HBsAg and/or HBeAg as compared to the corresponding SAC enzymatic nucleic acid. In addition, loop variant anti-HBV enzymatic nucleic acids targeting site 273 were tested using this system, the results of this study are summarized in FIG. 10. As indicated in the figure, the enzymatic nucleic acids tested demonstrate significant reduction in HepG2 HBsAg levels as compared to a scrambled attenuated core enzymatic nucleic acid control, with RPI 22650 and RPI 22649 showing the greatest decrease in HBsAg levels.

Example 6

Analysis of HBsAg and SEAP Levels Following Enzymatic Nucleic Acid Treatment

[0210] Immulon 4 (Dynax) microtiter wells were coated overnight at 4° C. with anti-HBsAg Mab (Biostride B88-95-31ad,ay) at 1 μg/ml in Carbonate Buffer (Na2CO3 15 mM, NaHCO3 35 mM, pH 9.5). The wells were then washed 4× with PBST (PBS, 0.05% Tween® 20) and blocked for 1 hr at 37° C. with PBST, 1% BSA. Following washing as above, the wells were dried at 37° C. for 30 min. Biotinylated goat ant-HBsAg (Accurate YVS1807) was diluted 1:1000 in PBST and incubated in the wells for 1 hr. at 37° C. The wells were washed 4× with PBST. Streptavidin/Alkaline Phosphatase Conjugate (Pierce 21324) was diluted to 250 ng/ml in PBST, and incubated in the wells for 1 hr. at 37° C. After washing as above, p-nitrophenyl phosphate substrate (Pierce 37620) was added to the wells, which were then incubated for 1 hr. at 37° C. The optical density at 405 nm was then determined. SEAP levels were assayed using the Great EscAPe® Detection Kit (Clontech K2041-1), as per the manufacturers instructions.

Example 7

X-gene Reporter Assay

[0211] The effect of enzymatic nucleic acid treatment on the level of transactivation of a SV40 promoter driven firefly luciferase gene by the HBV X-protein was analyzed in transfected Hep G2 cells. As a control for variability in transfection efficiency, a Renilla luciferase reporter driven by the TK promoter, which is not transactivated by the X protein, was used. Hep G2 cells were plated (3×104 cells/well) in 96-well microtiter plates and incubated overnight. A lipid/DNA/enzymatic nucleic acid complex was formed containing (at final concentrations) cationic lipid (2.4 μg/ml), the X-gene vector pSBDR(2.5 μg/ml), the firefly reporter pSV40HCVluc (0.5 μg/ml), the Renilla luciferase control vector pRL-TK (0.5 μg/ml), and enzymatic nucleic acid (100 μM). Following a 15 min. incubation at 37° C., the complexes were added to the plated Hep G2 cells. Levels of firefly and Renilla luciferase were analyzed 48 hr. post transfection, using Promega's Dual-Luciferase Assay System.

[0212] The HBV X protein is a transactivator of a number of viral and cellular genes. Enzymatic nucleic acids which target the X region were tested for their ability to cause a reduction in X protein transactivation of a firefly luciferase gene driven by the SV40 promoter in transfected Hep G2 cells. As a control for transfection variability, a vector containing the Renilla luciferase gene driven by the TK promotor, which is not activated by the X protein, was included in the co-transfections. The efficacy of the HBV enzymatic nucleic acids was determined by comparing the ratio of firefly luciferase: Renilla luciferase to that of a scrambled attenuated control (SAC) enzymatic nucleic acid. Eleven enzymatic nucleic acids (RPI18365, RPI18367, RPI18368, RPI18371, RPI18372, RPI18373, RPI18405, RPI18406, RPI18411, RPI18418, RPI18423) were identified which cause a reduction in the level of transactivation of a reporter gene by the X protein, as compared to the corresponding SAC enzymatic nucleic acid.

Example 8

HBV Transgenic Mouse Study A

[0213] A transgenic mouse strain (founder strain 1.3.32 with a C57B1/6 background) that expresses HBV RNA and forms HBV viremia (Morrey et al., 1999, Antiviral Res., 42, 97-108; Guidotti et al., 1995, J. Virology, 69, 10, 6158-6169) was utilized to study the in vivo activity of enzymatic nucleic acids (RPI.18341, RPI.18371, RPI.18372, and RPI.18418) of the instant invention. This model is predictive in screening for anti-HBV agents. Enzymatic nucleic acid or the equivalent volume of saline was administered via a continuous s.c. infusion using Alzet® mini-osmotic pumps for 14 days. Alzet® pumps were filled with test material(s) in a sterile fashion according to the manufacturer's instructions. Prior to in vivo implantation, pumps were incubated at 37° C. overnight (≧18 hours) to prime the flow modulators. On the day of surgery, animals were lightly anesthetized with a ketamine/xylazine cocktail (94 mg/kg and 6 mg/kg, respectively; 0.3 ml, IP). Baseline blood samples (200 μl) were obtained from each animal via a retro-orbital bleed. For animals in groups 1-5 (Table XII), a 2 cm area near the base of the tail was shaved and cleansed with betadine surgical scrub and sequentially with 70% alcohol. A 1 cm incision in the skin was made with a #15 scalpel blade or a blunt pair of scissors near the base of the tail. Forceps were used to open a pocket rostrally (i.e., towards the head) by spreading apart the subcutaneous connective tissue. The pump was inserted with the delivery portal pointing away from the incision. Wounds were closed with sterile 9-mm stainless steel clips or with sterile 4-0 suture. Animals were then allowed to recover from anesthesia on a warm heating pad before being returned to their cage. Wounds were checked daily. Clips or sutures were replaced as needed. Incisions typically healed completely within 7 days post-op. Animals were then deeply anesthetized with the ketamine/xylazine cocktail (150 mg/kg and 10 mg/kg, respectively; 0.5 ml, IP) on day 14 post pump implantation. A midline thoracotomy/laparatomy was performed to expose the abdominal cavity and the thoracic cavity. The left ventricle was cannulated at the base and animals exsanguinated using a 23G needle and 1 ml syringe. Serum was separated, frozen and analyzed for HBV DNA and antigen levels. Experimental groups were compared to the saline control group in respect to percent change from day 0 to day 14. HBV DNA was assayed by quantitative PCR.

RESULTS

[0214] Table XII is a summary of the group designation and dosage levels used in this HBV transgenic mouse study. Baseline blood samples were obtained via a retroorbital bleed and animals (N=10/group) received anti-HBV enzymatic nucleic acids (100 mg/kg/day) as a continuous SC infusion. After 14 days, animals treated with a enzymatic nucleic acid targeting site 273 (RPI.18341) of the HBV RNA showed a significant reduction in serum HBV DNA concentration, compared to the saline treated animals as measured by a quantitative PCR assay. More specifically, the saline treated animals had a 69% increase in serum HBV DNA concentrations over this 2-week period while treatment with the 273 enzymatic nucleic acid (RPI.18341) resulted in a 60% decrease in serum HBV DNA concentrations. Enzymatic nucleic acids directed against sites 1833 (RPI.18371), 1873 (RPI.18418), and 1874 (RPI.18372) decreased serum HBV DNA concentrations by 49%, 15% and 16%, respectively.

Example 9

HBV Transgenic Mouse Study B

[0215] A transgenic mouse strain (founder strain 1.3.32 with a C57B1/6 background) that expresses HBV RNA and forms HBV viremia (Morrey et al, 1999, Antiviral Res., 42, 97-108; Guidotti et al., 1995, J. Virology, 69, 10, 6158-6169) was utilized to study the in vivo activity of enzymatic nucleic acids (RPI.18341 and RPI.18371) of the instant invention. This model is predictive in screening for anti-HBV agents. Enzymatic nucleic acid or the equivalent volume of saline was administered via a continuous s.c. infusion using Alzet® mini-osmotic pumps for 14 days. Alzet® pumps were filled with test material(s) in a sterile fashion according to the manufacturer's instructions. Prior to in vivo implantation, pumps were incubated at 37° C. overnight (≧18 hours) to prime the flow modulators. On the day of surgery, animals were lightly anesthetized with a ketamine/xylazine cocktail (94 mg/kg and 6 mg/kg, respectively; 0.3 ml, IP). Baseline blood samples (200 μl) were obtained from each animal via a retro-orbital bleed. For animals in groups 1-10 (Table XIII), a 2 cm area near the base of the tail was shaved and cleansed with betadine surgical scrub and sequentially with 70% alcohol. A 1 cm incision in the skin was made with a #15 scalpel blade or a blunt pair of scissors near the base of the tail. Forceps were used to open a pocket rostrally (i.e., towards the head) by spreading apart the subcutaneous connective tissue. The pump was inserted with the delivery portal pointing away from the incision. Wounds were closed with sterile 9-mm stainless steel clips or with sterile 4-0 suture. Animals were then allowed to recover from anesthesia on a warm heating pad before being returned to their cage. Wounds were checked daily. Clips or sutures were replaced as needed. Incisions typically healed completely within 7 days post-op. Animals were then deeply anesthetized with the ketamine/xylazine cocktail (150 mg/kg and 10 mg/kg, respectively; 0.5 ml, IP) on day 14 post pump implantation. A midline thoracotomy/laparatomy was performed to expose the abdominal cavity and the thoracic cavity. The left ventricle was cannulated at the base and animals exsanguinated using a 23G needle and 1 ml syringe. Serum was separated, frozen and analyzed for HBV DNA and antigen levels. Experimental groups were compared to the saline control group in respect to percent change from day 0 to day 14. HBV DNA was assayed by quantitative PCR. Additionally, mice treated with 3TC® by oral gavage at a dose of 300 mg/kg/day for 14 days (group 11, Table XIII) were used as a positive control.

RESULTS

[0216] Table XIII is a summary of the group designation and dosage levels used in this HBV transgenic mouse study. Baseline blood samples were obtained via a retroorbital bleed and animals (N=15/group) received anti-HBV enzymatic nucleic acids (100 mg/kg/day, 30 mg/kg/day, 10 mg/kg/day) as a continuous SC infusion. The results of this study are summarized in FIGS. 6, 7, and 8. As FIGS. 6, 7, and 8 demonstrate, Enzymatic nucleic acids directed against sites 273 (RPI.18341) and 1833 (RPI.18371) demonstrate reduction in the serum HBV DNA levels following 14 days of enzymatic nucleic acid treatment in HBV transgenic mice, as compared to scrambled attenuated core (SAC) enzymatic nucleic acid and saline controls. Furthermore, these enzymatic nucleic acids provide similar, and in some cases, greater reduction of serum HBV DNA levels, as compared to the 3TC® positive control, at lower doses than the 3TC® positive control.

Example 10

HBV DNA Reduction in HepG2.2.15 cells

[0217] Enzymatic nucleic acid treatment of HepG2.2.15 cells was performed in a 96-well plate format, with 12 wells for each different enzymatic nucleic acid tested (RPI.18341, RPI.18371, RPI.18372, RPI.18418, RPI.20599SAC). HBV DNA levels in the media collected between 120 and 144 hours following transfection was determined using the Roche Amplicor HBV Assay. Treatment with RPI.18341 targeting site 273 resulted in a significant (P<0.05) decrease in HBV DNA levels of 62% compared to the SAC (RPI.20599). Treatment with RPI.18371 (site 1833) or RPI.18372 (site 1874) resulted in reductions in HBV DNA levels of 55% and 58% respectively, as compared to treatment with the SAC RPI.20599 (see FIG. 9).

Example 11

RPI 18341 Combination Treatment with Lamivudine/Infergen®

[0218] The therapeutic use of nucleic acid molecules of the invention either alone or in combination with current therapies, for example lamivudine or type 1 IFN, can lead to improved HBV treatment modalities. To assess the potential of combination therapy, HepG2 cells transfected with a replication competent HBV cDNA, were treated with RPI 18341(HepBzyme™), Infergen® (Amgen, Thousand Oaks Calif.), and/or Lamivudine (Epivir®: GlaxoSmithKline, Research Triangle Park N.C.) either alone or in combination. Results indicated that combination treatment with either RPI 18341 plus Infergen® or combination of RPI 18341 plus lamivudine results in additive down regulation of HBsAg expression (P<0.001). These studies can be applied to the treatment of lamivudine resistant cells to further assses the potential for combination therapy of RPI 18341 plus currently available therapies for the treatment of chronic Hepatitis B.

[0219] Hep G2 cells were plated (2×104 cells/well) in 96-well microtiter plates and incubated overnight. A cationic lipid/DNA/enzymatic nucleic acid complex was formed containing (at final concentrations) lipid (11-15 μg/mL), re-ligated psHBV-1 (4.5 μg/mL) and enzymatic nucleic acid (100-200 nM) in growth media. Following a 15 min incubation at 37° C., 20 μL of the complex was added to the plated Hep G2 cells in 80 μL of growth media minus antibiotics. For combination treatment with interferon, interferon (Infergen®, Amgen, Thousand Oaks Calif.) was added at 24 hr post-transfection and then incubated for an additional 96 hr. In the case of co-treatment with Lamivudine (3TC®), the enzymatic nucleic acid-containing cell culture media was removed at 120 hr post-transfection, fresh media containing Lamivudine (Epivir®: GlaxoSmithKline, Research Triangle Park N.C.) was added, and then incubated for an additional 48 hours. Treatment with Lamivudine or interferon individually was done on Hep G2 cells transfected with the pSHBV-1 vector alone and then treated identically to the co-treated cells. All transfections were performed in triplicate. Analysis of HBsAg levels was performed using the Diasorin HBsAg ELISA kit.

RESULTS

[0220] At either 500 or 1000 units of Infergen®, the addition of 200 nM of RPI.18341 results in a 75-77% increase in anti-HBV activity as judged by the level of HBsAg secreted from the treated Hep G2 cells. Conversely, the anti-HBV activity of RPI.18341 (at 200 nM) is increased 31-39% when used in combination of 500 or 1000 units of Infergen® (FIG. 11).

[0221] At 25 nM Lamivudine (3TC®), the addition of 100 nM of RPI.18341 results in a 48% increase in anti-HBV activity as judged by the level of HBsAg secreted from treated Hep G2 cells. Conversely, the anti-HBV activity of RPI.18341 (at 100 nM) is increased 31% when used in combination with 25 nM Lamivudine (FIG. 12).

Example 12

RPI 18341 Treatment in Cells Expressing Lamivudine Resistant HBV

[0222] Antiviral therapy with Lamivudine can lead to development of viral resistance and subsequent viral rebound in patients with HBV infention. Viral resistance has been seen in 15% to 30% of HBV patients undergoing Lamivudine treatment for a period of one year. HBV resistance to Lamivudine is associated with characteristic mutations in the conserved tyrosine, methionine, aspartate, aspartate (YMDD) amino acid motif of viral polymerase. The most frequently described mutation leading to Lamivudine resistance is the substitution of valine or isoleucine for methionine at residue 552. Additional mutations in adjacent areas, including mutations at residues 528 and 555, have been detected and may also be involved in Lamivudine and/or other nucleoside resistance

[0223] To assess the efficacy of enzymatic nucleic acid molecules against Lamivudine resistant HBV, cells that express Lamivudine resistant HBV, Hep G2DM2 cells, (see for example Fu and Cheng, 2000, Antimicrobial Agents and Chemotherapy, 44, 3402-3407) were treated with RPI 18341 (HepBzyme™) at a concentration of 150 nM. Treatment with RPI 18341 results in down regulation of HBsAg expression similar to that observed in Heg G2 cells expressing wildtype HBV (FIG. 13). This data indicates that enzymatic nucleic acid molecules, whether used alone or in combination with Lamivudine, are active against HBV resistance mutations that develop in nearly one third of patients within one year of beginning treatment with lamivudine. These results indicate that treatment with enzmatic nucleic acid molecules can be a potential new therapeutic option for patients with chronic hepatitis B infection.

Example 13

“No-ribo” Enzymatic Nucleic Acid Molecule Targeting HBV

[0224] To improve stability, efficacy and pharmacokinetic properties of enzymatic nucleic acid molecules targeting HBV, an enzymatic nucleic acid molecule targeting site 273 of the HBV pregenomic RNA was designed such that the enzymatic nucleic acid molecule completely lacked any ribonucleotides (RPI 25516 in Table XI, see also FIG. 14) by substituting ribonucleotides with 2′-O-methyl ribonucleotides. This enzymatic nucleic acid molecule lacking ribonucleotides demonstrates high levels of anti-HBV activity in the HBsAg ELISA cell culture system compared to binding attenuated (BAC, RPI 25535) and scrambled attenuated (SAC, RPI 25536) controls (see FIG. 15). In addition, the no-ribo enzymatic nucleic acid molecule demonstrates improved activity in the HBsAg ELISA cell culture system compared to HepBzyme (RPI 18341) which has 5 ribonucleotides.

Cell Culture Models

[0225] As previously mentioned, HBV does not infect cells in culture. However, transfection of HBV DNA (either as a head-to-tail dimer or as an “overlength” genome of >100%) into HuH7 or Hep G2 hepatocytes results in viral gene expression and production of HBV virions released into the media. Thus, HBV replication competent DNA can be co-transfected with enzymatic nucleic acids in cell culture. Such an approach has been used to report intracellular enzymatic nucleic acid activity against HBV (zu Putlitz, et al., 1999, J. Virol., 73, 5381-5387, and Kim et al., 1999, Biochem. Biophys. Res. Commun., 257, 759-765). In addition, stable hepatocyte cell lines have been generated that express HBV. Enzymatic nucleic acid is delivered to these cell lines; however, such an assay requires the performance of a delivery screen. Intracellular HBV gene expression can be assayed by a Taqman® assay for HBV RNA or by ELISA for HBV protein. Extracellular virus can be assayed by PCR for DNA or ELISA for protein. Antibodies are commercially available for HBV surface antigen and core protein. A secreted alkaline phosphatase expression plasmid can be used to normalize for differences in transfection efficiency and sample recovery.

[0226] Animal Models

[0227] There are several small animal models to study HBV replication. One is the transplantation of HBV-infected liver tissue into irradiated mice. Viremia (as evidenced by measuring HBV DNA by PCR) is first detected 8 days after transplantation and peaks between 18-25 days (Ilan et al., 1999, Hepatology, 29, 553-562).

[0228] Transgenic mice that express HBV have also been used as a model to evaluate potential anti-virals. HBV DNA is detectable in both liver and serum (Guidotti et al., 1995, J. Virology, 69, 10, 6158-6169; Morrey et al., 1999, Antiviral Res., 42, 97-108).

[0229] An additional model is to establish subcutaneous tumors in nude mice with Hep G2 cells transfected with HBV. Tumors develop in about 2 weeks after inoculation and express HBV surface and core antigens. HBV DNA and surface antigen is also detected in the circulation of tumor-bearing mice (Yao et al., 1996, J. Viral Hepat., 3, 19-22).

[0230] Woodchuck hepatitis virus (WHV) is closely related to HBV in its virus structure, genetic organization, and mechanism of replication. As with HBV in humans, persistent WHV infection is common in natural woodchuck populations and is associated with chronic hepatitis and hepatocellular carcinoma (HCC). Experimental studies have established that WHV causes HCC in woodchucks and woodchucks chronically infected with WHV have been used as a model to test a number of anti-viral agents. For example, the nucleoside analogue 3T3 was observed to cause dose dependent reduction in virus (50% reduction after two daily treatments at the highest dose) (Hurwitz et al., 1998. Antimicrob. Agents Chemother., 42, 2804-2809).

[0231] Indications

[0232] Particular degenerative and disease states that can be associated with HBV expression modulation include but are not limited to, HBV infection, hepatitis, cancer, tumorigenesis, cirrhosis, liver failure and others.

[0233] The present body of knowledge in HBV research indicates the need for methods to assay HBV activity and for compounds that can regulate HBV expression for research, diagnostic, and therapeutic use.

[0234] Lamivudine (3TC®), L-FMAU, adefovir dipivoxil, type 1 Interferon, therapeutic vaccines, steriods, and 2′-5′ Oligoadenylates are non-limiting examples of pharmaceutical agents that can be combined with or used in conjunction with the nucleic acid molecules (e.g. enzymatic nucleic acids and antisense molecules) of the instant invention. Those skilled in the art will recognize that other drugs or other therapies can similarly and readily be combined with the nucleic acid molecules of the instant invention (e.g. enzymatic nucleic acids and antisense molecules) and are, therefore, within the scope of the instant invention.

Diagnostic Uses

[0235] The nucleic acid molecules of this invention (e.g., enzymatic nucleic acids) can be used as diagnostic tools to examine genetic drift and mutations within diseased cells or to detect the presence of HBV RNA in a cell. The close relationship between enzymatic nucleic acid activity and the structure of the target RNA allows the detection of mutations in any region of the molecule which alters the base-pairing and three-dimensional structure of the target RNA. By using multiple enzymatic nucleic acids described in this invention, one can map nucleotide changes which are important to RNA structure and function in vitro, as well as in cells and tissues. Cleavage of target RNAs with enzymatic nucleic acids can be used to inhibit gene expression and define the role (essentially) of specified gene products in the progression of disease. In this manner, other genetic targets can be defined as important mediators of the disease. These experiments will lead to better treatment of the disease progression by affording the possibility of combinational therapies (e.g., multiple enzymatic nucleic acids targeted to different genes, enzymatic nucleic acids coupled with known small molecule inhibitors, or intermittent treatment with combinations of enzymatic nucleic acids and/or other chemical or biological molecules). Other in vitro uses of enzymatic nucleic acids of this invention are well known in the art, and include detection of the presence of mRNAs associated with HBV-related condition. Such RNA is detected by determining the presence of a cleavage product after treatment with a enzymatic nucleic acid using standard methodology.

[0236] In a specific example, enzymatic nucleic acids which cleave only wild-type or mutant forms of the target RNA are used for the assay. The first enzymatic nucleic acid is used to identify wild-type RNA present in the sample and the second enzymatic nucleic acid is used to identify mutant RNA in the sample. As reaction controls, synthetic substrates of both wild-type and mutant RNA are cleaved by both enzymatic nucleic acids to demonstrate the relative enzymatic nucleic acid efficiencies in the reactions and the absence of cleavage of the “non-targeted” RNA species. The cleavage products from the synthetic substrates also serve to generate size markers for the analysis of wild-type and mutant RNAs in the sample population. Thus each analysis involves two enzymatic nucleic acids, two substrates and one unknown sample which is combined into six reactions. The presence of cleavage products is determined using an RNAse protection assay so that full-length and cleavage fragments of each RNA is analyzed in one lane of a polyacrylamide gel. It is not absolutely required to quantify the results to gain insight into the expression of mutant RNAs and putative risk of the desired phenotypic changes in target cells. The expression of mRNA whose protein product is implicated in the development of the phenotype (i.e., HBV) is adequate to establish risk. If probes of comparable specific activity are used for both transcripts, then a qualitative comparison of RNA levels is adequate and decreases the cost of the initial diagnosis. Higher mutant form to wild-type ratios is correlated with higher risk whether RNA levels are compared qualitatively or quantitatively.

[0237] Additional Uses

[0238] Potential usefulness of sequence-specific enzymatic nucleic acid molecules of the instant invention might have many of the same applications for the study of RNA that DNA restriction endonucleases have for the study of DNA (Nathans et al., 1975 Ann. Rev. Biochem. 44:273). For example, the pattern of restriction fragments can be used to establish sequence relationships between two related RNAs, and large RNAs can be specifically cleaved to fragments of a size more useful for study. The ability to engineer sequence specificity of the enzymatic nucleic acid molecule is ideal for cleavage of RNAs of unknown sequence. Applicant describes the use of nucleic acid molecules to down-regulate gene expression of target genes in bacterial, microbial, fungal, viral, and eukaryotic systems including plant, or mammalian cells.

[0239] All patents and publications mentioned in the specification are indicative of the levels of skill of those skilled in the art to which the invention pertains. All references cited in this disclosure are incorporated by reference to the same extent as if each reference had been incorporated by reference in its entirety individually.

[0240] One skilled in the art would readily appreciate that the present invention is well adapted to carry out the objects and obtain the ends and advantages mentioned, as well as those inherent therein. The methods and compositions described herein as presently representative of preferred embodiments are exemplary and are not intended as limitations on the scope of the invention. Changes therein and other uses will occur to those skilled in the art, which are encompassed within the spirit of the invention, are defined by the scope of the claims.

[0241] It will be readily apparent to one skilled in the art that varying substitutions and modifications may be made to the invention disclosed herein without departing from the scope and spirit of the invention. Thus, such additional embodiments are within the scope of the present invention and the following claims.

[0242] The invention illustratively described herein suitably may be practiced in the absence of any element or elements, limitation or limitations which is not specifically disclosed herein. Thus, for example, in each instance herein any of the terms “comprising”, “consisting essentially of” and “consisting of” may be replaced with either of the other two terms. The terms and expressions which have been employed are used as terms of description and not of limitation, and there is no intention that in the use of such terms and expressions of excluding any equivalents of the features shown and described or portions thereof, but it is recognized that various modifications are possible within the scope of the invention claimed. Thus, it should be understood that although the present invention has been specifically disclosed by preferred embodiments, optional features, modification and variation of the concepts herein disclosed may be resorted to by those skilled in the art, and that such modifications and variations are considered to be within the scope of this invention as defined by the description and the appended claims.

[0243] In addition, where features or aspects of the invention are described in terms of Markush groups or other grouping of alternatives, those skilled in the art will recognize that the invention is also thereby described in terms of any individual member or subgroup of members of the Markush group or other group.

[0244] Other embodiments are within the following claims.

1TABLE II.Characteristics of naturally occurring enzymatic nucleic acidsGroup I IntronsSize: ˜150 to >1000 nucleotides.Requires a U in the target sequence immediately 5′ of the cleavage site.Binds 4-6 nucleotides at the 5′-side of the cleavage site.Reaction mechanism: attack by the 3′-OH of guanosine to generatecleavage products with 3′-OH and 5′-guanosine.Additional protein cofactors required in some cases to help folding andmaintainance of the active structure.Over 300 known members of this class. Found as an intervening sequencein Tetrahymena thermophila rRNA, fungal mitochondria, chloroplasts,phage T4, blue-green algae, and others.Major structural features largely established through phylogeneticcomparisons, mutagenesis, and biochemical studies [i,ii].Complete kinetic framework established for one ribozyme [iii,iv,v,vi].Studies of ribozyme folding and substrate docking underway [vii,viii,ix].Chemical modification investigation of important residues well estab-lished [x,xi].The small (4-6 nt) binding site may make this ribozyme too non-specificfor targeted RNA cleavage, however, the Tetrahymena group I intronhas been used to repair a “defective” β-galactosidase message by theligation of new β-galactosidase sequences onto the defective mes-sage [xii].Size: ˜290 to 400 nucleotides.RNA portion of a ubiquitous ribonucleoprotein enzyme.Cleaves tRNA precursors to form mature tRNA [xiii].Reaction mechanism: possible attack by M2+-OH to generate cleavageproducts with 3′-OH and 5′-phosphate.RNAse P is found throughout the prokaryotes and eukaryotes. The RNAsubunit has been sequenced from bacteria, yeast, rodents, and primates.Recruitment of endogenous RNAse P for therapeutic applications is pos-sible through hybridization of an External Guide Sequence (EGS) to thetarget RNA [xiv,xv]Important phosphate and 2′ OH contacts recently identified [xvi,xvii]Group II IntronsSize: >1000 nucleotides.Trans cleavage of target RNAs recently demonstrated [xviii,xix].Sequence requirements not fully determined.Reaction mechanism: 2′-OH of an internal adenosine generates cleavageproducts with 3′-OH and a “lariat” RNA containing a 3′-5′ and a2′-5′ branch point.Only natural ribozyme with demonstrated participation in DNA cleav-age [xx,xxi] in addition to RNA cleavage and ligation.Major structural features largely established through phylogeneticcomparisons [xxii].Important 2′ OH contacts beginning to be identified [xxiii]Kinetic framework under development [xxiv]Neurospora VS RNASize: ˜144 nucleotides.Trans cleavage of hairpin target RNAs recently demonstrated [xxv].Sequence requirements not fully determined.Reaction mechanism: attack by 2′-OH 5′ to the scissile bond to generatecleavage products with 2′,3′-cyclic phosphate and 5′-OH ends.Binding sites and structural requirements not fully determined.Only 1 known member of this class. Found in Neurospora VS RNA.Hammerhead Ribozyme(see text for references)Size: ˜13 to 40 nucleotides.Requires the target sequence UH immediately 5′ of the cleavage site.Binds a variable number nucleotides on both sides of the cleavage site.Reaction mechanism: attack by 2′-OH 5′ to the scissile bond to generatecleavage products with 2′,3′-cyclic phosphate and 5′-OH ends.14 known members of this class. Found in a number of plant pathogens(virusoids) that use RNA as the infectious agent.Essential structural features largely defined, including 2 crystal struc-tures [xxvi,xxvii]Minimal ligation activity demonstrated (for engineering through in vitroselection) [xxviii]Complete kinetic framework established for two or more ribozymes [xxix].Chemical modification investigation of important residues well estab-lished [xxx].Hairpin RibozymeSize: ˜50 nucleotides.Requires the target sequence GUC immediately 3′ of the cleavage site.Binds 4-6 nucleotides at the 5′-side of the cleavage site and a variablenumber to the 3′-side of the cleavage site.Reaction mechanism: attack by 2′-OH 5′ to the scissile bond togenerate cleavage products with 2′,3′-cyclic phosphate and 5′-OH ends.3 known members of this class. Found in three plant pathogen (satelliteRNAs of the tobacco ringspot virus, arabis mosaic virus and chicoryyellow mottle virus) which uses RNA as the infectious agent.Essential structural features largely defined [xxxi,xxxii,xxxiii,xxxiv]Ligation activity (in addition to cleavage activity) makes ribozymeamenable to engineering through in vitro selection [xxxv]Complete kinetic framework established for one ribozyme [xxxvi].Chemical modification investigation of important residuesbegun [xxxvii,xxxviii].Hepatitis Delta Virus (HDV) RibozymeSize: ˜60 nucleotides.Trans cleavage of target RNAs demonstrated [xxxix].Binding sites and structural requirements not fully determined, although nosequences 5′ of cleavage site are required. Folded ribozyme contains apseudoknot structure [xl].Reaction mechanism: attack by 2′-OH 5′ to the scissile bond to generatecleavage products with 2′,3′-cyclic phosphate and 5′-OH ends.Only 2 known members of this class. Found in human HDV.xliCircular form of HDV is active and shows increased nuclease stabil-ity [xlii]iMichel, Francois; Westhof, Eric. Slippery substrates. Nat. Struct. Biol. (1994), 1(1), 5-7. iiLisacek, Frederique; Diaz, Yolande; Michel, Francois. Automatic identification of group I intron cores in genomic DNA sequences. J. Mol. Biol. (1994), 235(4), 1206-17. iiiHerschlag, Daniel; Cech, Thomas R.. Catalysis of RNA cleavage by the Tetrahymena thermophila ribozyme. 1. Kinetic description of the reaction of an RNA substrate complementary to the active site. Biochemistry (1990), 29(44), 10159-71. ivHerschlag, Daniel; Cech, Thomas R.. Catalysis of RNA cleavage by the Tetrahymena thermophila ribozyme. 2. Kinetic description of the reaction of an RNA substrate that forms a mismatch at the active site. Biochemistry (1990), 29(44), 10172-80. vKnitt, Deborah S.; Herschlag, Daniel. pH Dependencies of the Tetrahymena Ribozyme Reveal an Unconventional Origin of an Apparent pKa. Biochemistry (1996), 35(5), 1560-70. viBevilacqua, Philip C.; Sugimoto, Naoki; Turner, Douglas H.. A mechanistic framework for the second step of splicing catalyzed by the Tetrahymena ribozyme. Biochemistry (1996), 35(2), 648-58. viiLi, Yi; Bevilacqua, Philip C.; Mathews, David; Turner, Douglas H.. Thermodynamic and activation parameters for binding of a pyrene-labeled substrate by the Tetrahymena ribozyme: docking is not diffusion-controlled and is driven by a favorable entropy change. Biochemistry (1995), 34(44), 14394-9. viiiBanerjee, Aloke Raj; Turner, Douglas H.. The time dependence of chemical modification reveals slow steps in the folding of a group I ribozyme. Biochemistry (1995), 34(19), 6504-12. ixZarrinkar, Patrick P.; Williamson, James R.. The P9.1-P9.2 peripheral extension helps guide folding of the Tetrahymena ribozyme. Nucleic Acids Res. (1996), 24(5), 854-8. xStrobel, Scott A.; Cech, Thomas R.. Minor groove recognition of the conserved G.cntdot.U pair at the Tetrahymena ribozyme reaction site. Science (Washington, D.C.) (1995), 267(5198), 675-9. xiStrobel, Scott A.; Cech, Thomas R.. Exocyclic Amine of the Conserved G.cntdot.U Pair at the Cleavage Site of the Tetrahymena Ribozyme Contributes to 5′-Splice Site Selection and Transition State Stabilization. Biochemistry (1996), 35(4), 1201-11. xiiSullenger, Bruce A.; Cech, Thomas R.. Ribozyme-mediated repair of defective mRNA by targeted trans-splicing. Nature (London) (1994), 371 (6498), 619-22. xiiiRobertson, H. D.; Altman, S.; Smith, J. D. J. Biol. Chem., 247, 5243-5251 (1972). xivForster, Anthony C.; Altman, Sidney. External guide sequences for an RNA enzyme. Science (Washington, D.C., 1883-) (1990), 249(4970), 783-6. xvYuan, Y.; Hwang, E. S.; Altman, S. Targeted cleavage of mRNA by human RNase P. Proc. Natl. Acad. Sci. USA (1992) 89, 8006-10. xviHarris, Michael E.; Pace, Norman R.. Identification of phosphates involved in catalysis by the ribozyme RNase P RNA. RNA (1995), 1(2), 210-18. xviiPan, Tao; Loria, Andrew; Zhong, Kun. Probing of tertiary interactions in RNA: 2′-hydroxyl-base contacts between the RNase P RNA and pre-tRNA. Proc. Natl. Acad. Sci. U.S.A. (1995), 92(26), 12510-14. xviiiPyle, Anna Marie; Green, Justin B.. Building a Kinetic Framework for Group II Intron Ribozyme Activity: Quantitation of Interdomain Binding and Reaction Rate. Biochemistry (1994), 33(9), 2716-25. xixMichels, William J. Jr.; Pyle, Anna Marie. Conversion of a Group II Intron into a New Multiple-Turnover Ribozyme that Selectively Cleaves Oligonucleotides: Elucidation of Reaction Mechanism and Structure/Function Relationships. Biochemistry (1995), 34(9), 2965-77. xxZimmerly, Steven; Guo, Huatao; Eskes, Robert; Yang, Jian; Perlman, Philip S.; Lambowitz, Alan M.. A group II intron RNA is a catalytic component of a DNA endonuclease involved in intron mobility. Cell (Cambridge, Mass.) (1995), 83(4), 529-38. xxiGriffin, Edmund A., Jr.; Qin, Zhifeng; Michels, Williams J., Jr.; Pyle, Anna Marie. Group II intron ribozymes that cleave DNA and RNA linkages with similar efficiency, and lack contacts with substrate 2′-hydroxyl groups. Chem. Biol. (1995), 2(11), 761-70. xxiiMichel, Francois; Ferat, Jean Luc. Structure and activities of group II introns. Annu. Rev. Biochem. (1995), 64, 435-61. xxiiiAbramovitz, Dana L.; Friedman, Richard A.; Pyle, Anna Marie. Catalytic role of 2′-hydroxyl groups within a group II intron active site. Science (Washington, D.C.) (1996), 271 (5254), 1410-13. xxivDaniels, Danette L.; Michels, William J., Jr.; Pyle, Anna Marie. Two competing pathways for self-splicing by group II introns: a quantitative analysis of in vitro reaction rates and products. J. Mol. Biol. (1996), 256(1), 31-49. xxvGuo, Hans C. T.; Collins, Richard A.. Efficient trans-cleavage of a stem-loop RNA substrate by a ribozyme derived from Neurospora VS RNA. EMBO J. (1995), 14(2), 368-76. xxviScott, W. G., Finch, J. T., Aaron, K. The crystal structure of an all RNA hammerhead ribozyme: A proposed mechanism for RNA catalytic cleavage. Cell, (1995), 81, 991-1002. xxviiMcKay, Structure and function of the hammerhead ribozyme: an unfinished story. RNA, (1996), 2, 395-403. xxviiiLong, D., Uhlenbeck, O., Hertel, K. Ligation with hammerhead ribozymes. U.S. Pat. No. 5,633,133. xxixHertel, K. J., Herschlag, D., Uhlenbeck, O. A kinetic and thermodynamic framework for the hammerhead ribozyme reaction. Biochemistry, (1994) 33, 3374-3385. Beigelman, L., et al., Chemical modifications of hammerhead ribozymes. J. Biol. Chem., (1995) 270, 25702-25708. xxxBeigelman, L., et al., Chemical modifications of hammerhead ribozymes. J. Biol. Chem., (1995) 270, 25702-25708. xxxiHampel, Arnold; Tritz, Richard; Hicks, Margaret; Cruz, Phillip. ‘Hairpin’ catalytic RNA model: evidence for helixes and sequence requirement for substrate RNA. Nucleic Acids Res. (1990), 18(2), 299-304. xxxiiChowrira, Bharat M.; Berzal-Herranz, Alfredo; Burke, John M.. Novel guanosine requirement for catalysis by the hairpin ribozyme. Nature (London) (1991), 354(6351), 320-2. xxxiiiBerzal-Herranz, Alfredo; Joseph, Simpson; Chowrira, Bharat M.; Butcher, Samuel E.; Burke, John M.. Essential nucleotide sequences and secondary structure elements of the hairpin ribozyme. EMBO J. (1993), 12(6), 2567-73. xxxivJoseph, Simpson; Berzal-Herranz, Alfredo; Chowrira, Bharat M.; Butcher, Samuel E.. Substrate selection rules for the hairpin ribozyme determined by in vitro selection, mutation, and analysis of mismatched substrates. Genes Dev. (1993), 7(1), 130-8. xxxvBerzal-Herranz, Alfredo; Joseph, Simpson; Burke, John M.. In vitro selection of active hairpin ribozymes by sequential RNA-catalyzed cleavage and ligation reactions. Genes Dev. (1992), 6(1), 129-34. xxxviHegg, Lisa A.; Fedor, Martha J.. Kinetics and Thermodynamics of Intermolecular Catalysis by Hairpin Ribozymes. Biochemistry (1995), 34(48), 15813-28. xxxviiGrasby, Jane A.; Mersmann, Karin; Singh, Mohinder; Gait, Michael J.. Purine Functional Groups in Essential Residues of the Hairpin Ribozyme Required for Catalytic Cleavage of RNA. Biochemistry (1995), 34(12), 4068-76. xxxviiiSchmidt, Sabine; Beigelman, Leonid; Karpeisky, Alexander; Usman, Nassim; Sorensen, Ulrik S.; Gait, Michael J.. Base and sugar requirements for RNA cleavage of essential nucleoside residues in internal loop B of the hairpin ribozyme: implications for secondary structure. Nucleic Acids Res. (1996), 24(4), 573-81. xxxixPerrotta, Anne T.; Been, Michael D.. Cleavage of oligoribonucleotides by a ribozyme derived from the hepatitis .delta. virus RNA sequence. Biochemistry (1992), 31(1), 16-21. xlPerrotta, Anne T.; Been, Michael D.. A pseudoknot-like structure required for efficient self-cleavage of hepatitis delta virus RNA. Nature (London) (1991), 350(6317), 434-6. xli xliiPuttaraju, M.; Perrotta, Anne T.; Been, Michael D.. A circular trans-acting hepatitis delta virus ribozyme. Nucleic Acids Res. (1993), 21(18), 4253-8.

[0245]

2

TABLE II

A. 2.5 μmol Synthesis Cycle ABI 394 Instrument

Reagent
Equivalents
Amount
Wait Time* DNA
Wait Time* 2′-O-methyl
Wait Time*RNA

Phosphoramidites
6.5
163 μL
45 sec
2.5 min
7.5 min

S-Ethyl Tetrazole
23.8
238 μL
45 sec
2.5 min
7.5 min

Acetic Anhydride
100
233 μL
5 sec
5 sec
5 sec

N-Methyl
186
233 μL
5 sec
5 sec
5 sec

Imidazole

TCA
176
2.3 mL
21 sec
21 sec
21 sec

Iodine
11.2
1.7 mL
45 sec
45 sec
45 sec

Beaucage
12.9
645 μL
100 sec
300 sec
300 sec

Acetonitrile
NA
6.67 mL
NA
NA
NA

B. 0.2 μmol Synthesis Cycle ABI 394 Instrument

Phosphoramidites
15
31 μL
45 sec
233 sec
465 sec

S-Ethyl Tetrazole
38.7
31 μL
45 sec
233 min
465 sec

Acetic Anhydride
655
124 μL
5 sec
5 sec
5 sec

N-Methyl
1245
124 μL
5 sec
5 sec
5 sec

Imidazole

TCA
700
732 μL
10 sec
10 sec
10 sec

Iodine
20.6
244 μL
15 sec
15 sec
15 sec

Beaucage
7.7
232 μL
100 sec
300 sec
300 sec

Acetonitrile
NA
2.64 mL
NA
NA
NA

C. 0.2 μmol Synthesis Cycle 96 well Instrument

Equivalents:DNA/
Amount: DNA/2′-O-

Wait Time* 2′-O-

Reagent
2′-O-methyl/Ribo
methyl/Ribo
Wait Time* DNA
methyl
Wait Time* Ribo

Phosphoramidites
22/33/66
40/60/120 μL
60 sec
180 sec
360 sec

S-Ethyl Tetrazole
70/105/210
40/60/120 μL
60 sec
180 min
360 sec

Acetic Anhydride
265/265/265
50/50/50 μL
10 sec
10 sec
10 sec

N-Methyl
502/502/502
50/50/50 μL
10 sec
10 sec
10 sec

Imidazole

TCA
238/475/475
250/500/500 μL
15 sec
15 sec
15 sec

Iodine
6.8/6.8/6.8
80/80/80 μL
30 sec
30 sec
30 sec

Beaucage
34/51/51
80/120/120
100 sec
200 sec
200 sec

Acetonitrile
NA
1150/1150/1150 μL
NA
NA
NA

*Wait time does not include contact time during delivery.

[0246]

3

TABLE III

HBV Strains and Accession numbers

Accession Number
NAME

AF100308.1
AF100308 Hepatitis B virus strain 2-18, complete

AB026815.1
AB026815 Hepatitis B virus DNA, complete genome,

AH033559.1
AB033559 Hepatitis B virus DNA, complete genome,

AB033558.1
AB033558 Hepatitis B virus DNA, complete genome,

AB033557.1
AB033557 Hepatitis B virus DNA, complete genome,

AB033556.1
AB033556 Hepatitis B virus DNA, complete genome,

AB033555.1
AB033555 Hepatitis B virus DNA, complete genome,

AB033554.1
AB033554 Hepatitis B virus DNA, complete genome,

AB033553.1
AB033553 Hepatitis B virus DNA, complete genome,

AB033552.1
AB033552 Hepatitis B virus DNA, complete genome,

AB033551.1
AB033551 Hepatitis B virus DNA, complete genome,

AB033550.1
AB033550 Hepatitis B virus DNA, complete genome

AF143308.1
AF143308 Hepatitis B virus clone WB1254, complete

AF1433O7.1
AF143307 Hepatitis B virus clone RM518, complete

AF143306.1
AF143306 Hepatitis B virus clone RMS17, complete

AF143305.1
AF143305 Hepatitis B virus clone RM501, complete

AF143304.1
AF143304 Hepatitis B virus clone HD319, complete

AF143303.1
AF143303 Hepatitis B virus clone HD1406, complete

AF143302.1
AF143302 Hepatitis B virus clone HD1402, complete

AF143301.1
AF143301 Hepatitis B virus clone BW1903, complete

AF143300.1
AF143300 Hepatitis B virus clone 7832-G4, complete

AF143299.1
AF143299 Hepatitis B virus clone 7744-G9, complete

AF143298.1
AF143298 Hepatitis B virus clone 7720-G8, complete

AB026814.1
AB026814 Hepatitis B virus DNA, complete genome,

AB026813.1
AB026813 Hepatitis B virus DNA, complete genome,

AB026812.1
AB026812 Hepatitis B virus DNA, complete genome,

AB026811.1
AB026811 Hepatitis B virus DNA, complete genome,

AJ131956.1
HBV131956 Hepatitis B virus complete genome,

AF151735.1
AF151735 Hepatitis B virus, complete genome

AF090842.1
AF090842 Hepatitis B virus strain G5.27295, complete

AF090841.1
AF090841 Hepatitis B virus strain G4.27241, complete

AF090840.1
AF090840 Hepatitis B virus strain G3.27270, complete

AF090839.1
AF090839 Hepatitis B virus strain G2.27246, complete

AF090838.1
AF090838 Hepatitis B virus strain P1.27239, complete

Y18858.1
HBV18858 Hepatitis B virus complete genome, isolate

Y18857.1
HBV18857 Hepatitis B virus complete genome, isolate

D12980.1
HPBCG Hepatitis B virus subtype adr (SRADR) DNA,

Y18856.1
HBV18856 Hepatitis B virus complete genome, isolate

Y18855.1
HBV18855 Hepatitis B virus complete genome, isolate

AJ131133.1
HBV131133 Hepatitis H virus, complete genome, strain

X80925.1
HBVP6PCXX Hepatitis B virus (patient 6) complete

X80926.1
HBVP5PCXX Hepatitis B virus (patient 5) complete

X80924.1
HBVP4PCXX Hepatitis B virus (patient 4) complete

AF100309.1
Hepatitis B virus strain 56, complete genome

AF068756.1
AF068756 Hepatitis B virus, complete genome

AF043593.1
AF043593 Hepatitis B virus isolate 6/89, complete

Y07587.1
HBVAYWGEN Hepatitis B virus, complete genome

D28880.1
D28880 Hepatitis B virus DNA, complete genome, strain

X98076.1
HBVDEFVP3 Hepatitis B virus complete genome with

X98075.1
HBVDEFVP2 Hepatitis B virus complete genome with

X98074.1
HBVDEFVP1 Hepatitis B virus complete genome with

X98077.1
HBVCGWITY Hepatitis B virus complete genome, wild type

X98072.1
HBVCGINSC Hepatitis B virus complete genome with

X98073.1
HBVCGINCX Hepatitis B virus complete genome with

U95551.1
U95551 Hepatitis B virus subtype ayw, complete genome

D23684.1
HPBC6T588 Hepatitis B virus (C6-TKBS88) complete genome

D23683.1
HPBC5HK02 Hepatitis B virus (C5-HBVK02) complete genome

D23682.1
HPBB5HK01 Hepatitis B virus (BS-HBVK01) complete genome

D23681.1
HPBC4HST2 Hepatitis B virus (C4-HBVST2) complete genome

D23680.1
HPBB4HST1 Hepatitis B virus (B4-HBVST1) complete genome

D00331.1
HPBADW3 Hepatitis B virus genome, complete genome

D00330.1
HPBADW2 Hepatitis B virus genome, complete genome

D50489.1
HPBA11A Hepatitis B virus DNA, complete genome

D23679.1
HPBA3HMS2 Hepatitis B virus (A3-HBVMS2) complete genome

D23678.1
HPBA2HYS2 Hepatitis B virus (A2-HBVYS2) complete genome

D23677.1
HPBA1HKK2 Hepatitis B virus (A1-HBVKK2) complete genome

D16665.1
HPBADRM Hepatitis B virus DNA, complete genome

D00329.1
HPHADW1 Hepatitis B virus (HBV) genome, complete genome

X97851.1
HBVP6CSX Hepatitis B virus (patient 6) complete genome

X97850.1
HBVP4CSX Hepatitis B virus (patient 4) complete genome

X97849.1
HBVP3CSX Hepatitis B virus (patient 3) complete genome

X97848.1
HBVP2CSX Hepatitis B virus (patient 2) complete genome

X51970.1
HVHEPB Hepatitis B virus (HBV 991) complete genome

M38636.1
HPBCGADR Hepatitis B virus, subtype adr, complete genome

X59795.1
HBVAYWMCG Hepatitis B virus (ayw subtype mutant)

M38454.1
HPBADR1CG Hepatitis B virus, complete genome

M32138.1
HPBHBVAA Hepatitis B virus variant HBV-alpha1, complete

J02203.1
HPBAYW Human hepatitis B virus (subtype ayw), complete

M12906.1
HPBADRA Hepatitis B virus subtype adr, complete genome

M54923.1
HPBADWZ Hepatitis B virus (subtype adw), complete genome

L27106.1
HPBMUT Hepatitis B virus mutant complete genome

[0247]

4

TABLE IV

HBV Substrate Sequence

NT Position*
Substrate
Seq ID

82
CUAUCGUCCCCUUCUUCAUC
1

101
CUACCGUUCCGGCC
2

159
CUUCUCAUCU
3

184
CUUCCCUUCACCAC
4

269
GACUCUCAGAAUGUCAACGAC
5

381
CUGUAGGCAUAAAUGGUCUG
6

401
GUUCACCAGCACCAUGCAACUUUUU
7

424
UUUCACGUCUGCCUAAUCAUC
8

524
AUUUGGAGCUUC
9

562
CUGACUUCUUUCCUUCUAUUC
10

649
CUCACCAUACCGCACUCA
11

667
GGCAAGCUAUUCUGUG
12

717
GGAAGUAAUUUGGAAGAC
13

758
CAGCUAUGUCAAUGUUAA
14

783
CUAAAAUCGGCCUAAAAUCAGAC
15

812
CAUUUCCUGUCUCACUUUUGGAAGAG
16

887
UCCUGCUUACAGAC
17

922
CAACACUUCCGGAAACUACUGUUGUUAG
18

989
CUCGCCUCGCAGACGAAGGUCUC
19

1009
CAAUCGCCGCGUCGCAGAAG
20

1031
AUCUCAAUCUCGGGAAUCUCAA
21

1052
AUGUUAGUAUCCCUUGGACUC
22

1072
CAUAAGGUGGGAAACUUUACUG
23

1109
CUGUACCUAUUCUUUAAAUCC
24

1127
CUGAGUGGCAAACUCCC
25

1271
CCAAAUAUCUGCCCUUGGACAA
26

1297
AUUAAACCAUAUUAUCCUGAACA
27

1319
AUGCAGUUAAUCAUUACUUCAAAACUA
28

1340
AAACUAGGCAUUA
29

1370
AGGCCCGCAUUCUAUAUAAGAGAG
30

1393
GAAACUACGCGCAGCGCCUCAUUUUGU
31

1412
CAUUUUGUGGGUCACCAUA
32

1441
CAAGAGCUACAGCAUGGG
33

LOCUS HPBADR1CG 3221 bp DNA circular VRL 06 MAR. 1995

DEFINITION Hepatitis B virus, complete genome.

ACCESSION M38454

*The nucleotide number referred to in that table is the position of the 5′ end of the oligo in this sequence.

[0248]

5

TABLE V

HUMAN HBV HAMMERHEAD ENZYMATIC NUCLEIC ACID AND TARGET SEQUENCE

Pos
Substrate
Seq ID
Enzymatic nucleic acid
Rz Seq ID

13
CCACCACU U UCCACCAA
34
UUGGUGGA CUGAUGAG GCCGUUAGGC CGAA AGUGGUGG
2543

14
CACCACUU U CCACCAAA
35
UUUGGUGG CUGAUGAG GCCGUUAGGC CGAA AAGUGGUG
2544

15
ACCACUUU C CACCAAAC
36
GUUUGGUG CUGAUGAG GCCGUUAGGC CGAA AAAGUGGU
2545

25
ACCAAACU C UUCAAGAU
37
AUCUUGAA CUGAUGAG GCCGUUAGGC CGAA AGUUUGGU
2546

27
CAAACUCU U CAAGAUCC
38
GGAUCUUG CUGAUGAG GCCGUUAGGC CGAA AGAGUUUG
2547

28
AAACUCUU C AAGAUCCC
39
GGGAUCUU CUGAUGAG GCCGUUAGGC CGAA AAGAGUUU
2548

34
UUCAAGAU C CCAGAGUC
40
GACUCUGG CUGAUGAG GCCGUUAGGC CGAA AUCUUGAA
2549

42
CCCAGAGU C AGGGCCCU
41
AGGGCCCU CUGAUGAG GCCGUUAGGC CGAA ACUCUGGG
2550

53
GGCCCUGU A CUUUCCUG
42
CAGGAAAG CUGAUGAG GCCGUUAGGC CGAA ACAGGGCC
2551

56
CCUGUACU U UCCUGCUG
43
CAGCAGGA CUGAUGAG GCCGUUAGGC CGAA AGUACAGG
2552

57
CUGUACUU U CCUGCUGG
44
CCAGCAGG CUGAUGAG GCCGUUAGGC CGAA AAGUACAG
2553

58
UGUACUUU C CUGCUGGU
45
ACCAGCAG CUGAUGAG GCCGUUAGGC CGAA AAAGUACA
2554

71
UGGUGGCU C CAGUUCAG
46
CUGAACUG CUGAUGAG GCCGUUAGGC CGAA AGCCACCA
2555

76
GCUCCAGU U CAGGAACA
47
UGUUCCUG CUGAUGAG GCCGUUAGGC CGAA ACUGGAGC
2556

77
CUCCAGUU C AGGAACAG
48
CUGUUCCU CUGAUGAG GCCGUUAGGC CGAA AACUGGAG
2557

97
GCCCUGCU C AGAAUACU
49
AGUAUUCU CUGAUGAG GCCGUUAGGC CGAA AGCAGGGC
2558

103
CUCAGAAU A CUGUCUCU
50
AGAGACAG CUGAUGAG GCCGUUAGGC CGAA AUUCUGAG
2559

108
AAUACUGU C UCUGCCAU
51
AUGGCAGA CUGAUGAG GCCGUUAGGC CGAA ACAGUAUU
2560

110
UACUGUCU C UGCCAUAU
52
AUAUGGCA CUGAUGAG GCCGUUAGGC CGAA AGACAGUA
2561

117
UCUGCCAU A UCGUCAAU
53
AUUGACGA CUGAUGAG GCCGUUAGGC CGAA AUGGCAGA
2562

119
UGCCAUAU C GUCAAUCU
54
AGAUUGAC CUGAUGAG GCCGUUAGGC CGAA AUAUGGCA
2563

122
CAUAUCGU C AAUCUUAU
55
AUAAGAUU CUGAUGAG GCCGUUAGGC CGAA ACGAUAUG
2564

126
UCGUCAAU C UUAUCGAA
56
UUCGAUAA CUGAUGAG GCCGUUAGGC CGAA AUUGACGA
2565

128
GUCAAUCU U AUCGAAGA
57
UCUUCGAU CUGAUGAG GCCGUUAGGC CGAA AGAUUGAC
2566

129
UCAAUCUU A UCGAAGAC
58
GUCUUCGA CUGAUGAG GCCGUUAGGC CGAA AAGAUUGA
2567

131
AAUCUUAU C GAAGACUG
59
CAGUCUUC CUGAUGAG GCCGUUAGGC CGAA AUAAGAUU
2568

150
GACCCUGU A CCGAACAU
60
AUGUUCGG CUGAUGAG GCCGUUAGGC CGAA ACAGGGUC
2569

168
GAGAACAU C GCAUCAGG
61
CCUGAUGC CUGAUGAG GCCGUUAGGC CGAA AUGUUCUC
2570

173
CAUCGCAU C AGGACUCC
62
GGAGUCCU CUGAUGAG GCCGUUAGGC CGAA AUGCGAUG
2571

180
UCAGGACU C CUAGGACC
63
GGUCCUAG CUGAUGAG GCCGUUAGGC CGAA AGUCCUGA
2572

183
GGACUCCU A GGACCCCU
64
AGGGGUCC CUGAUGAG GCCGUUAGGC CGAA AGGAGUCC
2573

195
CCCCUGCU C GUGUUACA
65
UGUAACAC CUGAUGAG GCCGUUAGGC CGAA AGCAGGGG
2574

200
GCUCGUGU U ACAGGCGG
66
CCGCCUGU CUGAUGAG GCCGUUAGGC CGAA ACACGAGC
2575

201
CUCGUGUU A CAGGCGGG
67
CCCGCCUG CUGAUGAG GCCGUUAGGC CGAA AACACGAG
2576

212
GGCGGGGU U UUUCUUGU
68
ACAAGAAA CUGAUGAG GCCGUUAGGC CGAA ACCCCGCC
2577

213
GCGGGGUU U UUCUUGUU
69
AACAAGAA CUGAUGAG GCCGUUAGGC CGAA AACCCCGC
2578

214
CGGGGUUU U UCUUGUUG
70
CAACAAGA CUGAUGAG GCCGUUAGGC CGAA AAACCCCG
2579

215
GGGGUUUU U CUUGUUGA
71
UCAACAAG CUGAUGAG GCCGUUAGGC CGAA AAAACCCC
2580

216
GGGUUUUU C UUGUUGAC
72
GUCAACAA CUGAUGAG GCCGUUAGGC CGAA AAAAACCC
2581

218
GUUUUUCU U GUUGACAA
73
UUGUCAAC CUGAUGAG GCCGUUAGGC CGAA AGAAAAAC
2582

221
UUUCUUGU U GACAAAAA
74
UUUUUGUC CUGAUGAG GCCGUUAGGC CGAA ACAAGAAA
2583

231
ACAAAAAU C CUCACAAU
75
AUUGUGAG CUGAUGAG GCCGUUAGGC CGAA AUUUUUGU
2584

234
AAAAUCCU C ACAAUACC
76
GGUAUUGU CUGAUGAG GCCGUUAGGC CGAA AGGAUUUU
2585

240
CUCACAAU A CCACAGAG
77
CUCUGUGG CUGAUGAG GCCGUUAGGC CGAA AUUGUGAG
2586

250
CACAGAGU C UAGACUCG
78
CGAGUCUA CUGAUGAG GCCGUUAGGC CGAA ACUCUGUG
2587

252
CAGAGUCU A GACUCGUG
79
CACGAGUC CUGAUGAG GCCGUUAGGC CGAA AGACUCUG
2588

257
UCUAGACU C GUGGUGGA
80
UCCACCAC CUGAUGAG GCCGUUAGGC CGAA AGUCUAGA
2589

268
GGUGGACU U CUCUCAAU
81
AUUGAGAG CUGAUGAG GCCGUUAGGC CGAA AGUCCACC
2590

269
GUGGACUU C UCUCAAUU
82
AAUUGAGA CUGAUGAG GCCGUUAGGC CGAA AAGUCCAC
2591

271
GGACUUCU C UCAAUUUU
83
AAAAUUGA CUGAUGAG GCCGUUAGGC CGAA AGAAGUCC
2592

273
ACUUCUCU C AAUUUUCU
84
AGAAAAUU CUGAUGAG GCCGUUAGGC CGAA AGAGAAGU
2593

277
CUCUCAAU U UUCUAGGG
85
CCCUAGAA CUGAUGAG GCCGUUAGGC CGAA AUUGAGAG
2594

278
UCUCAAUU U UCUAGGGG
86
CCCCUAGA CUGAUGAG GCCGUUAGGC CGAA AAUUGAGA
2595

279
CUCAAUUU U CUAGGGGG
87
CCCCCUAG CUGAUGAG GCCGUUAGGC CGAA AAAUUGAG
2596

280
UCAAUUUU C UAGGGGGA
88
UCCCCCUA CUGAUGAG GCCGUUAGGC CGAA AAAAUUGA
2597

282
AAUUUUCU A GGGGGAAC
89
GUUCCCCC CUGAUGAG GCCGUUAGGC CGAA AGAAAAUU
2598

301
CCGUGUGU C UUGGCCAA
90
UUGGCCAA CUGAUGAG GCCGUUAGGC CGAA ACACACGG
2599

303
GUGUGUCU U GGCCAAAA
91
UUUUGGCC CUGAUGAG GCCGUUAGGC CGAA AGACACAC
2600

313
GCCAAAAU U CGCAGUCC
92
GGACUGCG CUGAUGAG GCCGUUAGGC CGAA AUUUUGGC
2601

314
CCAAAAUU C GCAGUCCC
93
GGGACUGC CUGAUGAG GCCGUUAGGC CGAA AAUUUUGG
2602

320
UUCGCAGU C CCAAAUCU
94
AGAUUUGG CUGAUGAG GCCGUUAGGC CGAA ACUGCGAA
2603

327
UCCCAAAU C UCCAGUCA
95
UGACUGGA CUGAUGAG GCCGUUAGGC CGAA AUUUGGGA
2604

329
CCAAAUCU C CAGUCACU
96
AGUGACUG CUGAUGAG GCCGUUAGGC CGAA AGAUUUGG
2605

334
UCUCCAGU C ACUCACCA
97
UGGUGAGU CUGAUGAG GCCGUUAGGC CGAA ACUGGAGA
2606

338
CAGUCACU C ACCAACCU
98
AGGUUGGU CUGAUGAG GCCGUUAGGC CGAA AGUGACUG
2607

349
CAACCUGU U GUCCUCCA
99
UGGAGGAC CUGAUGAG GCCGUUAGGC CGAA ACAGGUUG
2608

352
CCUGUUGU C CUCCAAUU
100
AAUUGGAG CUGAUGAG GCCGUUAGGC CGAA ACAACAGG
2609

355
GUUGUCCU C CAAUUUGU
101
ACAAAUUG CUGAUGAG GCCGUUAGGC CGAA AGGACAAC
2610

360
CCUCCAAU U UGUCCUGG
102
CCAGGACA CUGAUGAG GCCGUUAGGC CGAA AUUGGAGG
2611

361
CUCCAAUU U GUCCUGGU
103
ACCAGGAC CUGAUGAG GCCGUUAGGC CGAA AAUUGGAG
2612

364
CAAUUUGU C CUGGUUAU
104
AUAACCAG CUGAUGAG GCCGUUAGGC CGAA ACAAAUUG
2613

370
GUCCUGGU U AUCGCUGG
105
CCAGCGAU CUGAUGAG GCCGUUAGGC CGAA ACCAGGAC
2614

371
UCCUGGUU A UCGCUGGA
106
UCCAGCGA CUGAUGAG GCCGUUAGGC CGAA AACCAGGA
2615

373
CUGGUUAU C GCUGGAUG
107
CAUCCAGC CUGAUGAG GCCGUUAGGC CGAA AUAACCAG
2616

385
GGAUGUGU C UGCGGCGU
108
ACGCCGCA CUGAUGAG GCCGUUAGGC CGAA ACACAUCC
2617

394
UGCGGCGU U UUAUCAUC
109
GAUGAUAA CUGAUGAG GCCGUUAGGC CGAA ACGCCGCA
2618

395
GCGGCGUU U UAUCAUCU
110
AGAUGAUA CUGAUGAG GCCGUUAGGC CGAA AACGCCGC
2619

396
CGGCGUUU U AUCAUCUU
111
AAGAUGAU CUGAUGAG GCCGUUAGGC CGAA AAACGCCG
2620

397
GGCGUUUU A UCAUCUUC
112
GAAGAUGA CUGAUGAG GCCGUUAGGC CGAA AAAACGCC
2621

399
CGUUUUAU C AUCUUCCU
113
AGGAAGAU CUGAUGAG GCCGUUAGGC CGAA AUAAAACG
2622

402
UUUAUCAU C UUCCUCUG
114
CAGAGGAA CUGAUGAG GCCGUUAGGC CGAA AUGAUAAA
2623

404
UAUCAUCU U CCUCUGCA
115
UGCAGAGG CUGAUGAG GCCGUUAGGC CGAA AGAUGAUA
2624

405
AUCAUCUU C CUCUGCAU
116
AUGCAGAG CUGAUGAG GCCGUUAGGC CGAA AAGAUGAU
2625

408
AUCUUCCU C UGCAUCCU
117
AGGAUGCA CUGAUGAG GCCGUUAGGC CGAA AGGAAGAU
2626

414
CUCUGCAU C CUGCUGCU
118
AGCAGCAG CUGAUGAG GCCGUUAGGC CGAA AUGCAGAG
2627

423
CUGCUGCU A UGCCUCAU
119
AUGAGGCA CUGAUGAG GCCGUUAGGC CGAA AGCAGCAG
2628

429
CUAUGCCU C AUCUUCUU
120
AAGAAGAU CUGAUGAG GCCGUUAGGC CGAA AGGCAUAG
2629

432
UGCCUCAU C UUCUUGUU
121
AACAAGAA CUGAUGAG GCCGUUAGGC CGAA AUGAGGCA
2630

434
CCUCAUCU U CUUGUUGG
122
CCAACAAG CUGAUGAG GCCGUUAGGC CGAA AGAUGAGG
2631

435
CUCAUCUU C UUGUUGGU
123
ACCAACAA CUGAUGAG GCCGUUAGGC CGAA AAGAUGAG
2632

437
CAUCUUCU U GUUGGUUC
124
GAACCAAC CUGAUGAG GCCGUUAGGC CGAA AGAAGAUG
2633

440
CUUCUUGU U GGUUCUUC
125
GAAGAACC CUGAUGAG GCCGUUAGGC CGAA ACAAGAAG
2634

444
UUGUUGGU U CUUCUGGA
126
UCCAGAAG CUGAUGAG GCCGUUAGGC CGAA ACCAACAA
2635

445
UGUUGGUU C UUCUGGAC
127
GUCCAGAA CUGAUGAG GCCGUUAGGC CGAA AACCAACA
2636

447
UUGGUUCU U CUGGACUA
128
UAGUCCAG CUGAUGAG GCCGUUAGGC CGAA AGAACCAA
2637

448
UGGUUCUU C UGGACUAU
129
AUAGUCCA CUGAUGAG GCCGUUAGGC CGAA AAGAACCA
2638

455
UCUGGACU A UCAAGGUA
130
UACCUUGA CUGAUGAG GCCGUUAGGC CGAA AGUCCAGA
2639

457
UGGACUAU C AAGGUAUG
131
CAUACCUU CUGAUGAG GCCGUUAGGC CGAA AUAGUCCA
2640

463
AUCAAGGU A UGUUGCCC
132
GGGCAACA CUGAUGAG GCCGUUAGGC CGAA ACCUUGAU
2641

467
AGGUAUGU U GCCCGUUU
133
AAACGGGC CUGAUGAG GCCGUUAGGC CGAA ACAUACCU
2642

474
UUGCCCGU U UGUCCUCU
134
AGAGGACA CUGAUGAG GCCGUUAGGC CGAA ACGGGCAA
2643

475
UGCCCGUU U GUCCUCUA
135
UAGAGGAC CUGAUGAG GCCGUUAGGC CGAA AACGGGCA
2644

478
CCGUUUGU C CUCUAAUU
136
AAUUAGAG CUGAUGAG GCCGUUAGGC CGAA ACAAACGG
2645

481
UUUGUCCU C UAAUUCCA
137
UGGAAUUA CUGAUGAG GCCGUUAGGC CGAA AGGACAAA
2646

483
UGUCCUCU A AUUCCAGG
138
CCUGGAAU CUGAUGAG GCCGUUAGGC CGAA AGAGGACA
2647

486
CCUCUAAU U CCAGGAUC
139
GAUCCUGG CUGAUGAG GCCGUUAGGC CGAA AUUAGAGG
2648

487
CUCUAAUU C CAGGAUCA
140
UGAUCCUG CUGAUGAG GCCGUUAGGC CGAA AAUUAGAG
2649

494
UCCAGGAU C AUCAACAA
141
UUGUUGAU CUGAUGAG GCCGUUAGGC CGAA AUCCUGGA
2650

497
AGGAUCAU C AACAACCA
142
UGGUUGUU CUGAUGAG GCCGUUAGGC CGAA AUGAUCCU
2651

535
GCACAACU C CUGCUCAA
143
UUGAGCAG CUGAUGAG GCCGUUAGGC CGAA AGUUGUGC
2652

541
CUCCUGCU C AAGGAACC
144
GGUUCCUU CUGAUGAG GCCGUUAGGC CGAA AGCAGGAG
2653

551
AGGAACCU C UAUGUUUC
145
GAAACAUA CUGAUGAG GCCGUUAGGC CGAA AGGUUCCU
2654

553
GAACCUCU A UGUUUCCC
146
GGGAAACA CUGAUGAG GCCGUUAGGC CGAA AGAGGUUC
2655

557
CUCUAUGU U UCCCUCAU
147
AUGAGGGA CUGAUGAG GCCGUUAGGC CGAA ACAUAGAG
2656

558
UCUAUGUU U CCCUCAUG
148
CAUGAGGG CUGAUGAG GCCGUUAGGC CGAA AACAUAGA
2657

559
CUAUGUUU C CCUCAUGU
149
ACAUGAGG CUGAUGAG GCCGUUAGGC CGAA AAACAUAG
2658

563
GUUUCCCU C AUGUUGCU
150
AGCAACAU CUGAUGAG GCCGUUAGGC CGAA AGGGAAAC
2659

568
CCUCAUGU U GCUGUACA
151
UGUACAGC CUGAUGAG GCCGUUAGGC CGAA ACAUGAGG
2660

574
GUUGCUGU A CAAAACCU
152
AGGUUUUG CUGAUGAG GCCGUUAGGC CGAA ACAGCAAC
2661

583
CAAAACCU A CGGACGGA
153
UCCGUCCG CUGAUGAG GCCGUUAGGC CGAA AGGUUUUG
2662

604
GCACCUGU A UUCCCAUC
154
GAUGGGAA CUGAUGAG GCCGUUAGGC CGAA ACAGGUGC
2663

606
ACCUGUAU U CCCAUCCC
155
GGGAUGGG CUGAUGAG GCCGUUAGGC CGAA AUACAGGU
2664

607
CCUGUAUU C CCAUCCCA
156
UGGGAUGG CUGAUGAG GCCGUUAGGC CGAA AAUACAGG
2665

612
AUUCCCAU C CCAUCAUC
157
GAUGAUGG CUGAUGAG GCCGUUAGGC CGAA AUGGGAAU
2666

617
CAUCCCAU C AUCUUGGG
158
CCCAAGAU CUGAUGAG GCCGUUAGGC CGAA AUGGGAUG
2667

620
CCCAUCAU C UUGGGCUU
159
AAGCCCAA CUGAUGAG GCCGUUAGGC CGAA AUGAUGGG
2668

622
CAUCAUCU U GGGCUUUC
160
GAAAGCCC CUGAUGAG GCCGUUAGGC CGAA AGAUGAUG
2669

628
CUUGGGCU U UCGCAAAA
161
UUUUGCGA CUGAUGAG GCCGUUAGGC CGAA AGCCCAAG
2670

629
UUGGGCUU U CGCAAAAU
162
AUUUUGCG CUGAUGAG GCCGUUAGGC CGAA AAGCCCAA
2671

630
UGGGCUUU C GCAAAAUA
163
UAUUUUGC CUGAUGAG GCCGUUAGGC CGAA AAAGCCCA
2672

638
CGCAAAAU A CCUAUGGG
164
CCCAUAGG CUGAUGAG GCCGUUAGGC CGAA AUUUUGCG
2673

642
AAAUACCU A UGGGAGUG
165
CACUCCCA CUGAUGAG GCCGUUAGGC CGAA AGGUAUUU
2674

656
GUGGGCCU C AGUCCGUU
166
AACGGACU CUGAUGAG GCCGUUAGGC CGAA AGGCCCAC
2675

660
GCCUCAGU C CGUUUCUC
167
GAGAAACG CUGAUGAG GCCGUUAGGC CGAA ACUGAGGC
2676

664
CAGUCCGU U UCUCUUGG
168
CCAAGAGA CUGAUGAG GCCGUUAGGC CGAA ACGGACUG
2677

665
AGUCCGUU U CUCUUGGC
169
GCCAAGAG CUGAUGAG GCCGUUAGGC CGAA AACGGACU
2678

666
GUCCGUUU C UCUUGGCU
170
AGCCAAGA CUGAUGAG GCCGUUAGGC CGAA AAACGGAC
2679

668
CCGUUUCU C UUGGCUCA
171
UGAGCCAA CUGAUGAG GCCGUUAGGC CGAA AGAAACGG
2680

670
GUUUCUCU U GGCUCAGU
172
ACUGAGCC CUGAUGAG GCCGUUAGGC CGAA AGAGAAAC
2681

675
UCUUGGCU C AGUUUACU
173
AGUAAACU CUGAUGAG GCCGUUAGGC CGAA AGCCAAGA
2682

679
GGCUCAGU U UACUAGUG
174
CACUAGUA CUGAUGAG GCCGUUAGGC CGAA ACUGAGCC
2683

680
GCUCAGUU U ACUAGUGC
175
GCACUAGU CUGAUGAG GCCGUUAGGC CGAA AACUGAGC
2684

681
CUCAGUUU A CUAGUGCC
176
GGCACUAG CUGAUGAG GCCGUUAGGC CGAA AAACUGAG
2685

684
AGUUUACU A GUGCCAUU
177
AAUGGCAC CUGAUGAG GCCGUUAGGC CGAA AGUAAACU
2686

692
AGUGCCAU U UGUUCAGU
178
ACUGAACA CUGAUGAG GCCGUUAGGC CGAA AUGGCACU
2687

693
GUGCCAUU U GUUCAGUG
179
CACUGAAC CUGAUGAG GCCGUUAGGC CGAA AAUGGCAC
2688

696
CCAUUUGU U CAGUGGUU
180
AACCACUG CUGAUGAG GCCGUUAGGC CGAA ACAAAUGG
2689

697
CAUUUGUU C AGUGGUUC
181
GAACCACU CUGAUGAG GCCGUUAGGC CGAA AACAAAUG
2690

704
UCAGUGGU U CGUAGGGC
182
GCCCUACG CUGAUGAG GCCGUUAGGC CGAA ACCACUGA
2691

705
CAGUGGUU C GUAGGGCU
183
AGCCCUAC CUGAUGAG GCCGUUAGGC CGAA AACCACUG
2692

708
UGGUUCGU A GGGCUUUC
184
GAAAGCCC CUGAUGAG GCCGUUAGGC CGAA ACGAACCA
2693

714
GUAGGGCU U UCCCCCAC
185
GUGGGGGA CUGAUGAG GCCGUUAGGC CGAA AGCCCUAC
2694

715
UAGGGCUU U CCCCCACU
186
AGUGGGGG CUGAUGAG GCCGUUAGGC CGAA AAGCCCUA
2695

716
AGGGCUUU C CCCCACUG
187
CAGUGGGG CUGAUGAG GCCGUUAGGC CGAA AAAGCCCU
2696

726
CCCACUGU C UGGCUUUC
188
GAAAGCCA CUGAUGAG GCCGUUAGGC CGAA ACAGUGGG
2697

732
GUCUGGCU U UCAGUUAU
189
AUAACUGA CUGAUGAG GCCGUUAGGC CGAA AGCCAGAC
2698

733
UCUGGCUU U CAGUUAUA
190
UAUAACUG CUGAUGAG GCCGUUAGGC CGAA AAGCCAGA
2699

734
CUGGCUUU C AGUUAUAU
191
AUAUAACU CUGAUGAG GCCGUUAGGC CGAA AAAGCCAG
2700

738
CUUUCAGU U AUAUGGAU
192
AUCCAUAU CUGAUGAG GCCGUUAGGC CGAA ACUGAAAG
2701

739
UUUCAGUU A UAUGGAUG
193
CAUCCAUA CUGAUGAG GCCGUUAGGC CGAA AACUGAAA
2702

741
UCAGUUAU A UGGAUGAU
194
AUCAUCCA CUGAUGAG GCCGUUAGGC CGAA AUAACUGA
2703

755
GAUGUGGU U UUGGGGGC
195
GCCCCCAA CUGAUGAG GCCGUUAGGC CGAA ACCACAUC
2704

756
AUGUGGUU U UGGGGGCC
196
GGCCCCCA CUGAUGAG GCCGUUAGGC CGAA AACCACAU
2705

757
UGUGGUUU U GGGGGCCA
197
UGGCCCCC CUGAUGAG GCCGUUAGGC CGAA AAACCACA
2706

769
GGCCAAGU C UGUACAAC
198
GUUGUACA CUGAUGAG GCCGUUAGGC CGAA ACUUGGCC
2707

773
AAGUCUGU A CAACAUCU
199
AGAUGUUG CUGAUGAG GCCGUUAGGC CGAA ACAGACUU
2708

780
UACAACAU C UUGAGUCC
200
GGACUCAA CUGAUGAG GCCGUUAGGC CGAA AUGUUGUA
2709

782
CAACAUCU U GAGUCCCU
201
AGGGACUC CUGAUGAG GCCGUUAGGC CGAA AGAUGUUG
2710

787
UCUUGAGU C CCUUUAUG
202
CAUAAAGG CUGAUGAG GCCGUUAGGC CGAA ACUCAAGA
2711

791
GAGUCCCU U UAUGCCGC
203
GCGGCAUA CUGAUGAG GCCGUUAGGC CGAA AGGGACUC
2712

792
AGUCCCUU U AUGCCGCU
204
AGCGGCAU CUGAUGAG GCCGUUAGGC CGAA AAGGGACU
2713

793
GUCCCUUU A UGCCGCUG
205
CAGCGGCA CUGAUGAG GCCGUUAGGC CGAA AAAGGGAC
2714

803
GCCGCUGU U ACCAAUUU
206
AAAUUGGU CUGAUGAG GCCGUUAGGC CGAA ACAGCGGC
2715

804
CCGCUGUU A CCAAUUUU
207
AAAAUUGG CUGAUGAG GCCGUUAGGC CGAA AACAGCGG
2716

810
UUACCAAU U UUCUUUUG
208
CAAAAGAA CUGAUGAG GCCGUUAGGC CGAA AUUGGUAA
2717

811
UACCAAUU U UCUUUUGU
209
ACAAAAGA CUGAUGAG GCCGUUAGGC CGAA AAUUGGUA
2718

812
ACCAAUUU U CUUUUGUC
210
GACAAAAG CUGAUGAG GCCGUUAGGC CGAA AAAUUGGU
2719

813
CCAAUUUU C UUUUGUCU
211
AGACAAAA CUGAUGAG GCCGUUAGGC CGAA AAAAUUGG
2720

815
AAUUUUCU U UUGUCUUU
212
AAAGACAA CUGAUGAG GCCGUUAGGC CGAA AGAAAAUU
2721

816
AUUUUCUU U UGUCUUUG
213
CAAAGACA CUGAUGAG GCCGUUAGGC CGAA AAGAAAAU
2722

817
UUUUCUUU U GUCUUUGG
214
CCAAAGAC CUGAUGAG GCCGUUAGGC CGAA AAAGAAAA
2723

820
UCUUUUGU C UUUGGGUA
215
UACCCAAA CUGAUGAG GCCGUUAGGC CGAA ACAAAAGA
2724

822
UUUUGUCU U UGGGUAUA
216
UAUACCCA CUGAUGAG GCCGUUAGGC CGAA AGACAAAA
2725

823
UUUGUCUU U GGGUAUAC
217
GUAUACCC CUGAUGAG GCCGUUAGGC CGAA AAGACAAA
2726

828
CUUUGGGU A UACAUUUA
218
UAAAUGUA CUGAUGAG GCCGUUAGGC CGAA ACCCAAAG
2727

830
UUGGGUAU A CAUUUAAA
219
UUUAAAUG CUGAUGAG GCCGUUAGGC CGAA AUACCCAA
2728

834
GUAUACAU U UAAACCCU
220
AGGGUUUA CUGAUGAG GCCGUUAGGC CGAA AUGUAUAC
2729

835
UAUACAUU U AAACCCUC
221
GAGGGUUU CUGAUGAG GCCGUUAGGC CGAA AAUGUAUA
2730

836
AUACAUUU A AACCCUCA
222
UGAGGGUU CUGAUGAG GCCGUUAGGC CGAA AAAUGUAU
2731

843
UAAACCCU C ACAAAACA
223
UGUUUUGU CUGAUGAG GCCGUUAGGC CGAA AGGGUUUA
2732

865
AUGGGGAU A UUCCCUUA
224
UAAGGGAA CUGAUGAG GCCGUUAGGC CGAA AUCCCCAU
2733

867
GGGGAUAU U CCCUUAAC
225
GUUAAGGG CUGAUGAG GCCGUUAGGC CGAA AUAUCCCC
2734

868
GGGAUAUU C CCUUAACU
226
AGUUAAGG CUGAUGAG GCCGUUAGGC CGAA AAUAUCCC
2735

872
UAUUCCCU U AACUUCAU
227
AUGAAGUU CUGAUGAG GCCGUUAGGC CGAA AGGGAAUA
2736

873
AUUCCCUU A ACUUCAUG
228
CAUGAAGU CUGAUGAG GCCGUUAGGC CGAA AAGGGAAU
2737

877
CCUUAACU U CAUGGGAU
229
AUCCCAUG CUGAUGAG GCCGUUAGGC CGAA AGUUAAGG
2738

878
CUUAACUU C AUGGGAUA
230
UAUCCCAU CUGAUGAG GCCGUUAGGC CGAA AAGUUAAG
2739

886
CAUGGGAU A UGUAAUUG
231
CAAUUACA CUGAUGAG GCCGUUAGGC CGAA AUCCCAUG
2740

890
GGAUAUGU A AUUGGGAG
232
CUCCCAAU CUGAUGAG GCCGUUAGGC CGAA ACAUAUCC
2741

893
UAUGUAAU U GGGAGUUG
233
CAACUCCC CUGAUGAG GCCGUUAGGC CGAA AUUACAUA
2742

900
UUGGGAGU U UGGGCACA
234
UGUGCCCC CUGAUGAG GCCGUUAGGC CGAA ACUCCCAA
2743

910
GGGCACAU U GCCACAGG
235
CCUGUGGC CUGAUGAG GCCGUUAGGC CGAA AUGUGCCC
2744

924
AGGAACAU A UUGUACAA
236
UUGUACAA CUGAUGAG GCCGUUAGGC CGAA AUGUUCCU
2745

926
GAACAUAU U GUACAAAA
237
UUUUGUAC CUGAUGAG GCCGUUAGGC CGAA AUAUGUUC
2746

929
CAUAUUGU A CAAAAAAU
238
AUUUUUUG CUGAUGAG GCCGUUAGGC CGAA ACAAUAUG
2747

938
CAAAAAAU C AAAAUGUG
239
CACAUUUU CUGAUGAG GCCGUUAGGC CGAA AUUUUUUG
2748

948
AAAUGUGU U UUAGGAAA
240
UUUCCUAA CUGAUGAG GCCGUUAGGC CGAA ACACAUUU
2749

949
AAUGUGUU U UAGGAAAC
241
GUUUCCUA CUGAUGAG GCCGUUAGGC CGAA AACACAUU
2750

950
AUGUGUUU U AGGAAACU
242
AGUUUCCU CUGAUGAG GCCGUUAGGC CGAA AAACACAU
2751

951
UGUGUUUU A GGAAACUU
243
AAGUUUCC CUGAUGAG GCCGUUAGGC CGAA AAAACACA
2752

959
AGGAAACU U CCUGUAAA
244
UUUACAGG CUGAUGAG GCCGUUAGGC CGAA AGUUUCCU
2753

960
GGAAACUU C CUGUAAAC
245
GUUUACAG CUGAUGAG GCCGUUAGGC CGAA AAGUUUCC
2754

965
CUUCCUGU A AACAGGCC
246
GGCCUGUU CUGAUGAG GCCGUUAGGC CGAA ACAGGAAG
2755

975
ACAGGCCU A UUGAUUGG
247
CCAAUCAA CUGAUGAG GCCGUUAGGC CGAA AGGCCUGU
2756

977
AGGCCUAU U GAUUGGAA
248
UUCCAAUC CUGAUGAG GCCGUUAGGC CGAA AUAGGCCU
2757

981
CUAUUGAU U GGAAAGUA
249
UACUUUCC CUGAUGAG GCCGUUAGGC CGAA AUCAAUAG
2758

989
UGGAAAGU A UGUCAACG
250
CGUUGACA CUGAUGAG GCCGUUAGGC CGAA ACUUUCCA
2759

993
AAGUAUGU C AACGAAUU
251
AAUUCGUU CUGAUGAG GCCGUUAGGC CGAA ACAUACUU
2760

1001
CAACGAAU U GUGGGUCU
252
AGACCCAC CUGAUGAG GCCGUUAGGC CGAA AUUCGUUG
2761

1008
UUGUGGGU C UUUUGGGG
253
CCCCAAAA CUGAUGAG GCCGUUAGGC CGAA ACCCACAA
2762

1010
GUGGGUCU U UUGGGGUU
254
AACCCCAA CUGAUGAG GCCGUUAGGC CGAA AGACCCAC
2763

1011
UGGGUCUU U UGGGGUUU
255
AAACCCCA CUGAUGAG GCCGUUAGGC CGAA AAGACCCA
2764

1012
GGGUCUUU U GGGGUUUG
256
CAAACCCC CUGAUGAG GCCGUUAGGC CGAA AAAGACCC
2765

1018
UUUGGGGU U UGCCGCCC
257
GGGCGGCA CUGAUGAG GCCGUUAGGC CGAA ACCCCAAA
2766

1019
UUGGGGUU U GCCGCCCC
258
GGGGCGGC CUGAUGAG GCCGUUAGGC CGAA AACCCCAA
2767

1029
CCGCCCCU U UCACGCAA
259
UUGCGUGA CUGAUGAG GCCGUUAGGC CGAA AGGGGCGG
2768

1030
CGCCCCUU U CACGCAAU
260
AUUGCGUG CUGAUGAG GCCGUUAGGC CGAA AAGGGGCG
2769

1031
GCCCCUUU C ACGCAAUG
261
CAUUGCGU CUGAUGAG GCCGUUAGGC CGAA AAAGGGGC
2770

1045
AUGUGGAU A UUCUGCUU
262
AAGCAGAA CUGAUGAG GCCGUUAGGC CGAA AUCCACAU
2771

1047
GUGGAUAU U CUGCUUUA
263
UAAAGCAG CUGAUGAG GCCGUUAGGC CGAA AUAUCCAC
2772

1048
UGGAUAUU C UGCUUUAA
264
UUAAAGCA CUGAUGAG GCCGUUAGGC CGAA AAUAUCCA
2773

1053
AUUCUGCU U UAAUGCCU
265
AGGCAUUA CUGAUGAG GCCGUUAGGC CGAA AGCAGAAU
2774

1054
UUCUGCUU U AAUGCCUU
266
AAGGCAUU CUGAUGAG GCCGUUAGGC CGAA AAGCAGAA
2775

1055
UCUGCUUU A AUGCCUUU
267
AAAGGCAU CUGAUGAG GCCGUUAGGC CGAA AAAGCAGA
2776

1062
UAAUGCCU U UAUAUGCA
268
UGCAUAUA CUGAUGAG GCCGUUAGGC CGAA AGGCAUUA
2777

1063
AAUGCCUU U AUAUGCAU
269
AUGCAUAU CUGAUGAG GCCGUUAGGC CGAA AAGGCAUU
2778

1064
AUGCCUUU A UAUGCAUG
270
CAUGCAUA CUGAUGAG GCCGUUAGGC CGAA AAAGGCAU
2779

1066
GCCUUUAU A UGCAUGCA
271
UGCAUGCA CUGAUGAG GCCGUUAGGC CGAA AUAAAGGC
2780

1076
GCAUGCAU A CAAGCAAA
272
UUUGCUUG CUGAUGAG GCCGUUAGGC CGAA AUGCAUGC
2781

1092
AACAGGCU U UUACUUUC
273
GAAAGUAA CUGAUGAG GCCGUUAGGC CGAA AGCCUGUU
2782

1093
ACAGGCUU U UACUUUCU
274
AGAAAGUA CUGAUGAG GCCGUUAGGC CGAA AAGCCUGU
2783

1094
CAGGCUUU U ACUUUCUC
275
GAGAAAGU CUGAUGAG GCCGUUAGGC CGAA AAAGCCUG
2784

1095
AGGCUUUU A CUUUCUCG
276
CGAGAAAG CUGAUGAG GCCGUUAGGC CGAA AAAAGCCU
2785

1098
CUUUUACU U UCUCGCCA
277
UGGCGAGA CUGAUGAG GCCGUUAGGC CGAA AGUAAAAG
2786

1099
UUUUACUU U CUCGCCAA
278
UUGGCGAG CUGAUGAG GCCGUUAGGC CGAA AAGUAAAA
2787

1100
UUUACUUU C UCGCCAAC
279
GUUGGCGA CUGAUGAG GCCGUUAGGC CGAA AAAGUAAA
2788

1102
UACUUUCU C GCCAACUU
280
AAGUUGGC CUGAUGAG GCCGUUAGGC CGAA AGAAAGUA
2789

1110
CGCCAACU U ACAAGGCC
281
GGCCUUGU CUGAUGAG GCCGUUAGGC CGAA AGUUGGCG
2790

1111
GCCAACUU A CAAGGCCU
282
AGGCCUUG CUGAUGAG GCCGUUAGGC CGAA AAGUUGGC
2791

1120
CAAGGCCU U UCUAAGUA
283
UACUUAGA CUGAUCAG GCCGUUAGGC CGAA AGGCCUUG
2792

1121
AAGGCCUU U CUAAGUAA
284
UUACUUAG CUGAUGAG GCCGUUAGGC CGAA AAGGCCUU
2793

1122
AGGCCUUU C UAAGUAAA
285
UUUACUUA CUGAUGAG GCCGUUAGGC CGAA AAAGGCCU
2794

1124
GCCUUUCU A AGUAAACA
286
UGUUUACU CUGAUGAG GCCGUUAGGC CGAA AGAAAGGC
2795

1128
UUCUAAGU A AACAGUAU
287
AUACUGUU CUGAUGAG GCCGUUAGGC CGAA ACUUAGAA
2796

1135
UAAACAGU A UGUGAACC
288
GGUUCACA CUGAUGAG GCCGUUAGGC CGAA ACUGUUUA
2797

1145
GUGAACCU U UACCCCGU
289
ACGGGGUA CUGAUGAG GCCGUUAGGC CGAA AGGUUCAC
2798

1146
UGAACCUU U ACCCCGUU
290
AACGGGGU CUGAUGAG GCCGUUAGGC CGAA AAGGUUCA
2799

1147
GAACCUUU A CCCCGUUG
291
CAACGGGG CUGAUGAG GCCGUUAGGC CGAA AAAGGUUC
2800

1154
UACCCCGU U GCUCGGCA
292
UGCCGAGC CUGAUGAG GCCGUUAGGC CGAA ACGGGGUA
2801

1158
CCGUUGCU C GGCAACGG
293
CCGUUGCC CUGAUGAG GCCGUUAGGC CGAA AGCAACGG
2802

1173
GGCCUGGU C UAUGCCAA
294
UUGGCAUA CUGAUGAG GCCGUUAGGC CGAA ACCAGGCC
2803

1175
CCUGGUCU A UGCCAAGU
295
ACUUGGCA CUGAUGAG GCCGUUAGGC CGAA AGACCAGG
2804

1186
CCAAGUGU U UGCUGACG
296
CGUCAGCA CUGAUGAG GCCGUUAGGC CGAA ACACUUGG
2805

1187
CAAGUGUU U GCUGACGC
297
GCGUCAGC CUGAUGAG GCCGUUAGGC CGAA AACACUUG
2806

1209
CCACUGGU U GGGGCUUG
298
CAAGCCCC CUGAUGAG GCCGUUAGGC CGAA ACCAGUGG
2807

1216
UUGGGGCU U GGCCAUAG
299
CUAUGGCC CUGAUGAG GCCGUUAGGC CGAA AGCCCCAA
2808

1223
UUGGCCAU A GGCCAUCA
300
UGAUGGCC CUGAUGAG GCCGUUAGGC CGAA AUGGCCAA
2809

1230
UAGGCCAU C AGCGCAUG
301
CAUGCGCU CUGAUGAG GCCGUUAGGC CGAA AUGGCCUA
2810

1249
UGGAACCU U UGUGUCUC
302
GAGACACA CUGAUGAG GCCGUUAGGC CGAA AGGUUCCA
2811

1250
GGAACCUU U GUGUCUCC
303
GGAGACAC CUGAUGAG GCCGUUAGGC CGAA AAGGUUCC
2812

1255
CUUUGUGU C UCCUCUGC
304
GCAGAGGA CUGAUGAG GCCGUUAGGC CGAA ACACAAAG
2813

1257
UUGUGUCU C CUCUGCCG
305
CGGCAGAG CUGAUGAG GCCGUUAGGC CGAA AGACACAA
2814

1260
UGUCUCCU C UGCCGAUC
306
GAUCGGCA CUGAUGAG GCCGUUAGGC CGAA AGGAGACA
2815

1268
CUGCCGAU C CAUACCGC
307
GCGGUAUG CUGAUGAG GCCGUUAGGC CGAA AUCGGCAG
2816

1272
CGAUCCAU A CCGCGGAA
308
UUCCGCGG CUGAUGAG GCCGUUAGGC CGAA AUGGAUCG
2817

1283
GCGGAACU C CUAGCCGC
309
GCGGCUAG CUGAUGAG GCCGUUAGGC CGAA AGUUCCGC
2818

1286
GAACUCCU A GCCGCUUG
310
CAAGCGGC CUGAUGAG GCCGUUAGGC CGAA AGGAGUUC
2819

1293
UAGCCGCU U GUUUUGCU
311
AGCAAAAC CUGAUGAG GCCGUUAGGC CGAA AGCGGCUA
2820

1296
CCGCUUGU U UUGCUCGC
312
GCGAGCAA CUGAUGAG GCCGUUAGGC CGAA ACAAGCGG
2821

1297
CGCUUGUU U UGCUCGCA
313
UGCGAGCA CUGAUGAG GCCGUUAGGC CGAA AACAAGCG
2822

1298
GCUUGUUU U GCUCGCAG
314
CUGCGAGC CUGAUGAG GCCGUUAGGC CGAA AAACAAGC
2823

1302
GUUUUGCU C GCAGCAGG
315
CCUGCUGC CUGAUGAG GCCGUUAGGC CGAA AGCAAAAC
2824

1312
CAGCAGGU C UGGGGCAA
316
UUGCCCCA CUGAUGAG GCCGUUAGGC CGAA ACCUGCUG
2825

1325
GCAAAACU C AUCGGGAC
317
GUCCCGAU CUGAUGAG GCCGUUAGGC CGAA AGUUUUGC
2826

1328
AAACUCAU C GGGACUGA
318
UCAGUCCC CUGAUGAG GCCGUUAGGC CGAA AUGAGUUU
2827

1341
CUGACAAU U CUGUCGUG
319
CACGACAG CUGAUGAG GCCGUUAGGC CGAA AUUGUCAG
2828

1342
UGACAAUU C UGUCGUGC
320
GCACGACA CUGAUGAG GCCGUUAGGC CGAA AAUUGUCA
2829

1346
AAUUCUGU C GUGCUCUC
321
GAGAGCAC CUGAUGAG GCCGUUAGGC CGAA ACAGAAUU
2830

1352
GUCGUGCU C UCCCGCAA
322
UUGCGGGA CUGAUGAG GCCGUUAGGC CGAA AGCACGAC
2831

1354
CGUGCUCU C CCGCAAAU
323
AUUUGCGG CUGAUGAG GCCGUUAGGC CGAA AGAGCACG
2832

1363
CCGCAAAU A UACAUCAU
324
AUGAUGUA CUGAUGAG GCCGUUAGGC CGAA AUUUGCGG
2833

1365
GCAAAUAU A CAUCAUUU
325
AAAUGAUG CUGAUGAG GCCGUUAGGC CGAA AUAUUUGC
2834

1369
AUAUACAU C AUUUCCAU
326
AUGGAAAU CUGAUGAG GCCGUUAGGC CGAA AUGUAUAU
2835

1372
UACAUCAU U UCCAUGGC
327
GCCAUGGA CUGAUGAG GCCGUUAGGC CGAA AUGAUGUA
2836

1373
ACAUCAUU U CCAUGGCU
328
AGCCAUGG CUGAUGAG GCCGUUAGGC CGAA AAUGAUGU
2837

1374
CAUCAUUU C CAUGGCUG
329
CAGCCAUG CUGAUGAG GCCGUUAGGC CGAA AAAUGAUG
2838

1385
UGGCUGCU A GGCUGUGC
330
GCACAGCC CUGAUGAG GCCGUUAGGC CGAA AGCAGCCA
2839

1406
AACUGGAU C CUACGCGG
331
CCGCGUAG CUGAUGAG GCCGUUAGGC CGAA AUCCAGUU
2840

1409
UGGAUCCU A CGCGGGAC
332
GUCCCGCG CUGAUGAG GCCGUUAGGC CGAA AGGAUCCA
2841

1420
CGGGACGU C CUUUGUUU
333
AAACAAAG CUGAUGAG GCCGUUAGGC CGAA ACGUCCCG
2842

1423
GACGUCCU U UGUUUACG
334
CGUAAACA CUGAUGAG GCCGUUAGGC CGAA AGGACGUC
2843

1424
ACGUCCUU U GUUUACGU
335
ACGUAAAC CUGAUGAG GCCGUUAGGC CGAA AAGGACGU
2844

1427
UCCUUUGU U UACGUCCC
336
GGGACGUA CUGAUGAG GCCGUUAGGC CGAA ACAAAGGA
2845

1428
CCUUUGUU U ACGUCCCG
337
CGGGACGU CUGAUGAG GCCGUUAGGC CGAA AACAAAGG
2846

1429
CUUUGUUU A CGUCCCGU
338
ACGGGACG CUGAUGAG GCCGUUAGGC CGAA AAACAAAG
2847

1433
GUUUACGU C CCGUCGGC
339
GCCGACGG CUGAUGAG GCCGUUAGGC CGAA ACGUAAAC
2848

1438
CGUCCCGU C GGCGCUGA
340
UCAGCGCC CUGAUGAG GCCGUUAGGC CGAA ACGGGACG
2849

1449
CGCUGAAU C CCGCGGAC
341
GUCCGCGG CUGAUGAG GCCGUUAGGC CGAA AUUCAGCG
2850

1465
CGACCCCU C CCGGGGCC
342
GGCCCCGG CUGAUGAG GCCGUUAGGC CGAA AGGGGUCG
2851

1477
GGGCCGCU U GGGGCUCU
343
AGAGCCCC CUGAUGAG GCCGUUAGGC CGAA AGCGGCCC
2852

1484
UUGGGGCU C UACCGCCC
344
GGGCGGUA CUGAUGAG GCCGUUAGGC CGAA AGCCCCAA
2853

1486
GGGGCUCU A CCGCCCGC
345
GCGGGCGG CUGAUGAG GCCGUUAGGC CGAA AGAGCCCC
2854

1496
CGCCCGCU U CUCCGCCU
346
AGGCGGAG CUGAUGAG GCCGUUAGGC CGAA AGCGGGCG
2855

1497
GCCCGCUU C UCCGCCUA
347
UAGGCGGA CUGAUGAG GCCGUUAGGC CGAA AAGCGGGC
2856

1499
CCGCUUCU C CGCCUAUU
348
AAUAGGCG CUGAUGAG GCCGUUAGGC CGAA AGAAGCGG
2857

1505
CUCCGCCU A UUGUACCG
349
CGGUACAA CUGAUGAG GCCGUUAGGC CGAA AGGCGGAG
2858

1507
CCGCCUAU U GUACCGAC
350
GUCGGUAC CUGAUGAG GCCGUUAGGC CGAA AUAGGCGG
2859

1510
CCUAUUGU A CCGACCGU
351
ACGGUCGG CUGAUGAG GCCGUUAGGC CGAA ACAAUAGG
2860

1519
CCGACCGU C CACGGGGC
352
GCCCCGUG CUGAUGAG GCCGUUAGGC CGAA ACGGUCGG
2861

1534
GCGCACCU C UCUUUACG
353
CGUAAAGA CUGAUGAG GCCGUUAGGC CGAA AGGUGCGC
2862

1536
GCACCUCU C UUUACGCG
354
CGCGUAAA CUGAUGAG GCCGUUAGGC CGAA AGAGGUGC
2863

1538
ACCUCUCU U UACGCGGA
355
UCCGCGUA CUGAUGAG GCCGUUAGGC CGAA AGAGAGGU
2864

1539
CCUCUCUU U ACGCGGAC
356
GUCCGCGU CUGAUGAG GCCGUUAGGC CGAA AAGAGAGG
2865

1540
CUCUCUUU A CGCGGACU
357
AGUCCGCG CUGAUGAG GCCGUUAGGC CGAA AAAGAGAG
2866

1549
CGCGGACU C CCCGUCUG
358
CAGACGGG CUGAUGAG GCCGUUAGGC CGAA AGUCCGCG
2867

1555
CUCCCCGU C UGUGCCUU
359
AAGGCACA CUGAUGAG GCCGUUAGGC CGAA ACGGGGAG
2868

1563
CUGUGCCU U CUCAUCUG
360
CAGAUGAG CUGAUGAG GCCGUUAGGC CGAA AGGCACAG
2869

1564
UGUGCCUU C UCAUCUGC
361
GCAGAUGA CUGAUGAG GCCGUUAGGC CGAA AAGGCACA
2870

1566
UGCCUUCU C AUCUGCCG
362
CGGCAGAU CUGAUGAG GCCGUUAGGC CGAA AGAAGGCA
2871

1569
CUUCUCAU C UGCCGGAC
363
GUCCGGCA CUGAUGAG GCCGUUAGGC CGAA AUGAGAAG
2872

1588
UGUGCACU U CGCUUCAC
364
GUGAAGCG CUGAUGAG GCCGUUAGGC CGAA AGUGCACA
2873

1589
GUGCACUU C GCUUCACC
365
GGUGAAGC CUGAUGAG GCCGUUAGGC CGAA AAGUGCAC
2874

1593
ACUUCGCU U CACCUCUG
366
CAGAGGUG CUGAUGAG GCCGUUAGGC CGAA AGCGAAGU
2875

1594
CUUCGCUU C ACCUCUGC
367
GCAGAGGU CUGAUGAG GCCGUUAGGC CGAA AAGCGAAG
2876

1599
CUUCACCU C UGCACGUC
368
GACGUGCA CUGAUGAG GCCGUUAGGC CGAA AGGUGAAG
2877

1607
CUGCACGU C GCAUGGAG
369
CUCCAUGC CUGAUGAG GCCGUUAGGC CGAA ACGUGCAG
2878

1651
CCCAAGGU C UUGCAUAA
370
UUAUGCAA CUGAUGAG GCCGUUAGGC CGAA ACCUUGGG
2879

1653
CAAGGUCU U GCAUAAGA
371
UCUUAUGC CUGAUGAG GCCGUUAGGC CGAA AGACCUUG
2880

1658
UCUUGCAU A AGAGGACU
372
AGUCCUCU CUGAUGAG GCCGUUAGGC CGAA AUGCAAGA
2881

1667
AGAGGACU C UUGGACUU
373
AAGUCCAA CUGAUGAG GCCGUUAGGC CGAA AGUCCUCU
2882

1669
AGGACUCU U GGACUUUC
374
GAAAGUCC CUGAUGAG GCCGUUAGGC CGAA AGAGUCCU
2883

1675
CUUGGACU U UCAGCAAU
375
AUUGCUGA CUGAUGAG GCCGUUAGGC CGAA AGUCCAAG
2884

1676
UUGGACUU U CAGCAAUG
376
CAUUGCUG CUGAUGAG GCCGUUAGGC CGAA AAGUCCAA
2885

1677
UGGACUUU C AGCAAUGU
377
ACAUUGCU CUGAUGAG GCCGUUAGGC CGAA AAAGUCCA
2886

1686
AGCAAUGU C AACGACCG
378
CGGUCGUU CUGAUGAG GCCGUUAGGC CGAA ACAUUGCU
2887

1699
ACCGACCU U GAGGCAUA
379
UAUGCCUC CUGAUGAG GCCGUUAGGC CGAA AGGUCGGU
2888

1707
UGAGGCAU A CUUCAAAG
380
CUUUGAAG CUGAUGAG GCCGUUAGGC CGAA AUGCCUCA
2889

1710
GGCAUACU U CAAAGACU
381
AGUCUUUG CUGAUGAG GCCGUUAGGC CGAA AGUAUGCC
2890

1711
GCAUACUU C AAAGACUG
382
CAGUCUUU CUGAUGAG GCCGUUAGGC CGAA AAGUAUGC
2891

1725
CUGUGUGU U UAAUGAGU
383
ACUCAUUA CUGAUGAG GCCGUUAGGC CGAA ACACACAG
2892

1726
UGUGUGUU U AAUGAGUG
384
CACUCAUU CUGAUGAG GCCGUUAGGC CGAA AACACACA
2893

1727
GUGUGUUU A AUGAGUGG
385
CCACUCAU CUGAUGAG GCCGUUAGGC CGAA AAACACAC
2894

1743
GGAGGAGU U GGGGGAGG
386
CCUCCCCC CUGAUGAG GCCGUUAGGC CGAA ACUCCUCC
2895

1756
GAGGAGGU U AGGUUAAA
387
UUUAACCU CUGAUGAG GCCGUUAGGC CGAA ACCUCCUC
2896

1757
AGGAGGUU A GGUUAAAG
388
CUUUAACC CUGAUGAG GCCGUUAGGC CGAA AACCUCCU
2897

1761
GGUUAGGU U AAAGGUCU
389
AGACCUUU CUGAUGAG GCCGUUAGGC CGAA ACCUAACC
2898

1762
GUUAGGUU A AAGGUCUU
390
AAGACCUU CUGAUGAG GCCGUUAGGC CGAA AACCUAAC
2899

1768
UUAAAGGU C UUUGUACU
391
AGUACAAA CUGAUGAG GCCGUUAGGC CGAA ACCUUUAA
2900

1770
AAAGGUCU U UGUACUAG
392
CUAGUACA CUGAUGAG GCCGUUAGGC CGAA AGACCUUU
2901

1771
AAGGUCUU U GUACUAGG
393
CCUAGUAC CUGAUGAG GCCGUUAGGC CGAA AAGACCUU
2902

1774
GUCUUUGU A CUAGGAGG
394
CCUCCUAG CUGAUGAG GCCGUUAGGC CGAA ACAAAGAC
2903

1777
UUUGUACU A UGAGGCUG
395
CAGCCUCC CUGAUGAG GCCGUUAGGC CGAA AGUACAAA
2904

1787
GAGGCUGU A GGCAUAAA
396
UUUAUGCC CUGAUGAG GCCGUUAGGC CGAA ACAGCCUC
2905

1793
GUAGGCAU A AAUUGGUG
397
CACCAAUU CUGAUGAG GCCGUUAGGC CGAA AUGCCUAC
2906

1797
GCAUAAAU U GGUGUGUU
398
AACACACC CUGAUGAG GCCGUUAGGC CGAA AUUUAUGC
2907

1805
UGGUGUGU U CACCAGCA
399
UGCUGGUG CUGAUGAG GCCGUUAGGC CGAA ACACACCA
2908

1806
GGUGUGUU C ACCAGCAC
400
GUGCUGGU CUGAUGAG GCCGUUAGGC CGAA AACACACC
2909

1824
AUGCAACU U UUUCACCU
401
AGGUGAAA CUGAUGAG GCCGUUAGGC CGAA AGUUGCAU
2910

1825
UGCAACUU U UUCACCUC
402
GAGGUGAA CUGAUGAG GCCGUUAGGC CGAA AAGUUGCA
2911

1826
GCAACUUU U UCACCUCU
403
AGAGGUGA CUGAUGAG GCCGUUAGGC CGAA AAAGUUGC
2912

1827
CAACUUUU U CACCUCUG
404
CAGAGGUG CUGAUGAG GCCGUUAGGC CGAA AAAAGUUG
2913

1828
AACUUUUU C ACCUCUGC
405
GCAGAGGU CUGAUGAG GCCGUUAGGC CGAA AAAAAGUU
2914

1833
UUUCACCU C UGCCUAAU
406
AUUAGGCA CUGAUGAG GCCGUUAGGC CGAA AGGUGAAA
2915

1839
CUCUGCCU A AUCAUCUC
407
GAGAUGAU CUGAUGAG GCCGUUAGGC CGAA AGGCAGAG
2916

1842
UGCCUAAU C AUCUCAUG
408
CAUGAGAU CUGAUGAG GCCGUUAGGC CGAA AUUAGGCA
2917

1845
CUAAUCAU C UCAUGUUC
409
GAACAUGA CUGAUGAG GCCGUUAGGC CGAA AUGAUUAG
2918

1847
AAUCAUCU C AUGUUCAU
410
AUGAACAU CUGAUGAG GCCGUUAGGC CGAA AGAUGAUU
2919

1852
UCUCAUGU U CAUGUCCU
411
AGGACAUG CUGAUGAG GCCGUUAGGC CGAA ACAUGAGA
2920

1853
CUCAUGUU C AUGUCCUA
412
UAGGACAU CUGAUGAG GCCGUUAGGC CGAA AACAUGAG
2921

1858
GUUCAUGU C CUACUGUU
413
AACAGUAG CUGAUGAG GCCGUUAGGC CGAA ACAUGAAC
2922

1861
CAUGUCCU A CUGUUCAA
414
UUGAACAG CUGAUGAG GCCGUUAGGC CGAA AGGACAUG
2923

1866
CCUACUGU U CAAGCCUC
415
GAGGCUUG CUGAUGAG GCCGUUAGGC CGAA ACAGUAGG
2924

1867
CUACUGUU C AAGCCUCC
416
GGAGGCUU CUGAUGAG GCCGUUAGGC CGAA AACAGUAG
2925

1874
UCAAGCCU C CAAGCUGU
417
ACAGCUUG CUGAUGAG GCCGUUAGGC CGAA AGGCUUGA
2926

1887
CUGUGCCU U GGGUGGCU
418
AGCCACCC CUGAUGAG GCCGUUAGGC CGAA AGGCACAG
2927

1896
GGGUGGCU U UGGGGCAU
419
AUGCCCCA CUGAUGAG GCCGUUAGGC CGAA AGCCACCC
2928

1897
GGUGGCUU U GGGGCAUG
420
CAUGCCCC CUGAUGAG GCCGUUAGGC CGAA AAGCCACC
2929

1911
AUGGACAU U GACCCGUA
421
UACGGGUC CUGAUGAG GCCGUUAGGC CGAA AUGUCCAU
2930

1919
UGACCCGU A UAAAGAAU
422
AUUCUUUA CUGAUGAG GCCGUUAGGC CGAA ACGGGUCA
2931

1921
ACCCGUAU A AAGAAUUU
423
AAAUUCUU CUGAUGAG GCCGUUAGGC CGAA AUACGGGU
2932

1928
UAAAGAAU U UGGAGCUU
424
AAGCUCCA CUGAUGAG GCCGUUAGGC CGAA AUUCUUUA
2933

1929
AAAGAAUU U GGAGCUUC
425
GAAGCUCC CUGAUGAG GCCGUUAGGC CGAA AAUUCUUU
2934

1936
UUGGAGCU U CUGUGGAG
426
CUCCACAG CUGAUGAG GCCGUUAGGC CGAA AGCUCCAA
2935

1937
UGGAGCUU C UGUGGAGU
427
ACUCCACA CUGAUGAG GCCGUUAGGC CGAA AAGCUCCA
2936

1946
UGUGGAGU U ACUCUCUU
428
AAGAGAGU CUGAUGAG GCCGUUAGGC CGAA ACUCCACA
2937

1947
GUGGAGUU A CUCUCUUU
429
AAAGAGAG CUGAUGAG GCCGUUAGGC CGAA AACUCCAC
2938

1950
GAGUUACU C UCUUUUUU
430
AAAAAAGA CUGAUGAG GCCGUUAGGC CGAA AGUAACUC
2939

1952
GUUACUCU C UUUUUUGC
431
GCAAAAAA CUGAUGAG GCCGUUAGGC CGAA AGAGUAAC
2940

1954
UACUCUCU U UUUUGCCU
432
AGGCAAAA CUGAUGAG GCCGUUAGGC CGAA AGAGAGUA
2941

1955
ACUCUCUU U UUUGCCUU
433
AAGGCAAA CUGAUGAG GCCGUUAGGC CGAA AAGAGAGU
2942

1956
CUCUCUUU U UUGCCUUC
434
GAAGGCAA CUGAUGAG GCCGUUAGGC CGAA AAAGAGAG
2943

1957
UCUCUUUU U UGCCUUCU
435
AGAAGGCA CUGAUGAG GCCGUUAGGC CGAA AAAAGAGA
2944

1958
CUCUUUUU U GCCUUCUG
436
CAGAAGGC CUGAUGAG GCCGUUAGGC CGAA AAAAAGAG
2945

1963
UUUUGCCU U CUGACUUC
437
GAAGUCAG CUGAUGAG GCCGUUAGGC CGAA AGGCAAAA
2946

1964
UUUGCCUU C UGACUUCU
438
AGAAGUCA CUGAUGAG GCCGUUAGGC CGAA AAGGCAAA
2947

1970
UUCUGACU U CUUUCCUU
439
AAGGAAAG CUGAUGAG GCCGUUAGGC CGAA AGUCAGAA
2948

1971
UCUGACUU C UUUCCUUC
440
GAAGGAAA CUGAUGAG GCCGUUAGGC CGAA AAGUCAGA
2949

1973
UGACUUCU U UCCUUCUA
441
UAGAAGGA CUGAUGAG GCCGUUAGGC CGAA AGAAGUCA
2950

1974
GACUUCUU U CCUUCUAU
442
AUAGAAGG CUGAUGAG GCCGUUAGGC CGAA AAGAAGUC
2951

1975
ACUUCUUU C CUUCUAUU
443
AAUAGAAG CUGAUGAG GCCGUUAGGC CGAA AAAGAAGU
2952

1978
UCUUUCCU U CUAUUCGA
444
UCGAAUAG CUGAUGAG GCCGUUAGGC CGAA AGGAAAGA
2953

1979
CUUUCCUU C UAUUCGAG
445
CUCGAAUA CUGAUGAG GCCGUUAGGC CGAA AAGGAAAG
2954

1981
UUCCUUCU A UUCGAGAU
446
AUCUCGAA CUGAUGAG GCCGUUAGGC CGAA AGAAGGAA
2955

1983
CCUUCUAU U CGAGAUCU
447
AGAUCUCG CUGAUGAG GCCGUUAGGC CGAA AUAGAAGG
2956

1984
CUUCUAUU C GAGAUCUC
448
GAGAUCUC CUGAUGAG GCCGUUAGGC CGAA AAUAGAAG
2957

1990
UUCGAGAU C UCCUGGAC
449
GUCGAGGA CUGAUGAG GCCGUUAGGC CGAA AUCUCGAA
2958

1992
CGAGAUCU C CUCGACAC
450
GUGUCGAG CUGAUGAG GCCGUUAGGC CGAA AGAUCUCG
2959

1995
GAUCUCCU C GACACCGC
451
GCGGUGUC CUGAUGAG GCCGUUAGGC CGAA AGGAGAUC
2960

2006
CACCGCCU C UGCUCUGU
452
ACAGACCA CUGAUGAG GCCGUUAGGC CGAA AGGCGGUG
2961

2011
CCUCUGCU C UGUAUCGG
453
CCGAUACA CUGAUGAG GCCGUUAGGC CGAA AGCAGAGG
2962

2015
UGCUCUGU A UCGGGGGG
454
CCCCCCGA CUGAUGAG GCCGUUAGGC CGAA ACAGAGCA
2963

2017
CUCUGUAU C GGGGGGCC
45G
GGCCCCCC CUGAUGAG GCCGUUAGGC CGAA AUACAGAG
2964

2027
GGGGGCCU U AGAGUCUC
456
GAGACUCU CUGAUGAG GCCGUUAGGC CGAA AGGCCCCC
2965

2028
GGGGCCUU A GAGUCUCC
457
GGAGACUC CUGAUGAG GCCGUUAGGC CGAA AAGGCCCC
2966

2033
CUUAGAGU C UCCGGAAC
458
GUUCCGGA CUGAUGAG GCCGUUAGGC CGAA ACUCUAAG
2967

2035
UAGAGUCU C CGGAACAU
459
AUGUUCCG CUGAUGAG GCCGUUAGGC CGAA AGACUCUA
2968

2044
CGGAACAU U GUUCACCU
460
AGGUGAAC CUGAUGAG GCCGUUAGGC CGAA AUGUUCCG
2969

2047
AACAUUGU U CACCUCAC
461
GUGAGGUG CUGAUGAG GCCGUUAGGC CGAA ACAAUGUU
2970

2048
ACAUUGUU C ACCUCACC
462
GGUGAGGU CUGAUGAG GCCGUUAGGC CGAA AACAAUGU
2971

2053
GUUCACCU C ACCAUACG
463
CGUAUGGU CUGAUGAG GCCGUUAGGC CGAA AGGUGAAC
2972

2059
CUCACCAU A CGGCACUC
464
GAGUGCCG CUGAUGAG GCCGUUAGGC CGAA AUGGUGAG
2973

2067
ACGGCACU C AGGCAAGC
465
GCUUGCCU CUGAUGAG GCCGUUAGGC CGAA AGUGCCGU
2974

2077
GGCAAGCU A UUCUGUGU
466
ACACAGAA CUGAUGAG GCCGUUAGGC CGAA AGCUUGCC
2975

2079
CAAGCUAU U CUGUGUUG
467
CAACACAG CUGAUGAG GCCGUUAGGC CGAA AUAGCUUG
2976

2080
AAGCUAUU C UGUGUUGG
468
CCAACACA CUGAUGAG GCCGUUAGGC CGAA AAUAGCUU
2977

2086
UUCUGUGU U GGGGUGAG
469
CUCACCCC CUGAUGAG GCCGUUAGGC CGAA ACACAGAA
2978

2096
GGGUGAGU U GAUGAAUC
470
GAUUCAUC CUGAUGAG GCCGUUAGGC CGAA ACUCACCC
2979

2104
UGAUGAAU C UAGCCACC
471
GGUGGCUA CUGAUGAG GCCGUUAGGC CGAA AGUCAUCA
2980

2106
AUGAAUCU A GCCACCUG
472
CAGGUGGC CUGAUGAG GCCGUUAGGC CGAA AGAUUCAU
2981

2125
UGGGAAGU A AUUUGGAA
473
UUCCAAAU CUGAUGAG GCCGUUAGGC CGAA ACUUCCCA
2982

2128
GAAGUAAU U UGGAAGAU
474
AUCUUCCA CUGAUGAG GCCGUUAGGC CGAA AUUACUUC
2983

2129
AAGUAAUU U GGAAGAUC
475
GAUCUUCC CUGAUGAG GCCGUUAGGC CGAA AAUUACUU
2984

2137
UGGAAGAU C CAGCAUCC
476
GGAUGCUG CUGAUGAG GCCGUUAGGC CGAA AUCUUCCA
2985

2144
UCCAGCAU C CAGGGAAU
477
AUUCCCUG CUGAUGAG GCCGUUAGGC CGAA AUCCUGGA
2986

2153
CAGGGAAU U AGUAGUCA
478
UGACUACU CUGAUGAG GCCGUUAGGC CGAA AUUCCCUG
2987

2154
AGGGAAUU A GUAGUCAG
479
CUGACUAC CUGAUGAG GCCGUUAGGC CGAA AAUUCCCU
2988

2157
GAAUUAGU A GUCAGCUA
480
UAGCUGAC CUGAUGAG GCCGUUAGGC CGAA ACUAAUUC
2989

2160
UUAGUAGU C AGCUAUGU
481
ACAUAGCU CUGAUGAG GCCGUUAGGC CGAA ACUACUAA
2990

2165
AGUCAGCU A UGUCAACG
482
CGUGGACA CUGAUGAG GCCGUUAGGC CGAA AGCUGACU
2991

2169
AGCUAUGU C AACGUUAA
483
UUAACGUU CUGAUGAG GCCGUUAGGC CGAA ACAUAGCU
2992

2175
GUCAACGU U AAUAUGGG
484
CCCAUAUU CUGAUGAG GCCGUUAGGC CGAA ACGUUGAC
2993

2176
UCAACGUU A AUAUGGGC
485
GCCCAUAU CUGAUGAG GCCGUUAGGC CGAA AACGUUGA
2994

2179
ACGUUAAU A UGGGCCUA
486
UAGGCCCA CUCAUGAG GCCGUUAGGC CGAA AUUAACGU
2995

2187
AUGGGCCU A AAAAUCAG
487
CUGAUUUU CUGAUGAG GCCGUUAGGC CGAA AGGCCCAU
2996

2193
CUAAAAAU C AGACAACU
488
AGUUGUCU CUGAUGAG GCCGUUAGGC CGAA AUUUUUAG
2997

2202
AGACAACU A UUGUGGUU
489
AACCACAA CUGAUGAG GCCGUUAGGC CGAA AGUUGUCU
2998

2204
ACAACUAU U GUGGUUUC
490
GAAACCAC CUGAUGAG GCCGUUAGGC CGAA AUAGUUGU
2999

2210
AUUGUGGU U UCACAUUU
491
AAAUGUGA CUGAUGAG GCCGUUAGGC CGAA ACCACAAU
3000

2211
UUGUGGUU U CACAUUUC
492
GAAAUGUG CUGAUGAG GCCGUUAGGC CGAA AACCACAA
3001

2212
UGUGGUUU C ACAUUUCC
493
GGAAAUGU CUGAUGAG GCCGUUAGGC CGAA AAACCACA
3002

2217
UUUCACAU U UCCUGUCU
494
AGACAGGA CUGAUGAG GCCGUUAGGC CGAA AUGUGAAA
3003

2218
UUCACAUU U CCUGUCUU
495
AAGACAGG CUGAUGAG GCCGUUAGGC CGAA AAUGUGAA
3004

2219
UCACAUUU C CUGUCUUA
496
UAAGACAG CUGAUGAG GCCGUUAGGC CGAA AAAUGUGA
3005

2224
UUUCCUGU C UUACUUUU
497
AAAAGUAA CUGAUGAG GCCGUUAGGC CGAA ACAGGAAA
3006

2226
UCCUGUCU U ACUUUUGG
498
CCAAAAGU CUGAUGAG GCCGUUAGGC CGAA AGACAGGA
3007

2227
CCUGUCUU A CUUUUGGG
499
CCCAAAAG CUGAUGAG GCCGUUAGGC CGAA AAGACAGG
3008

2230
GUCUUACU U UUGGGCGA
500
UCGCCCAA CUGAUGAG GCCGUUAGGC CGAA AGUAAGAC
3009

2231
UCUUACUU U UGGGCGAG
501
CUCGCCCA CUGAUGAG GCCGUUAGGC CGAA AAGUAAGA
3010

2232
CUUACUUU U GGGCGAGA
502
UCUCGCCC CUGAUGAG GCCGUUAGGC CGAA AAAGUAAG
3011

2247
GAAACUGU U CUUGAAUA
503
UAUUCAAG CUGAUGAG GCCGUUAGGC CGAA ACAGUUUC
3012

2248
AAACUGUU C UUGAAUAU
504
AUAUUCAA CUGAUGAG GCCGUUAGGC CGAA AACAGUUU
3013

2250
ACUGUUCU U GAAUAUUU
505
AAAUAUUC CUGAUGAG GCCGUUAGGC CGAA AGAACAGU
3014

2255
UCUUGAAU A UUUGGUGU
506
ACACCAAA CUGAUGAG GCCGUUAGGC CGAA AUUCAAGA
3015

2257
UUGAAUAU U UGGUGUCU
507
AGACACCA CUGAUGAG GCCGUUAGGC CGAA AUAUUCAA
3016

2258
UGAAUAUU U GGUGUCUU
508
AAGACACC CUGAUGAG GCCGUUAGGC CGAA AAUAUUCA
3017

2264
UUUGGUGU C UUUUGGAG
509
CUCCAAAA CUGAUGAG GCCGUUAGGC CGAA ACACCAAA
3018

2266
UGGUGUCU U UUGGAGUG
510
CACUCCAA CUGAUGAG GCCGUUAGGC CGAA AGACACCA
3019

2267
GGUGUCUU U UGGAGUGU
511
ACACUCCA CUGAUGAG GCCGUUAGGC CGAA AAGACACC
3020

2268
GUGUCUUU U GGAGUGUG
512
CACACUCC CUGAUGAG GCCGUUAGGC CGAA AAAGACAC
3021

2280
GUGUGGAU U CGCACUCC
513
GGAGUGCG CUGAUGAG GCCGUUAGGC CGAA AUCCACAC
3022

2281
UGUGGAUU C GCACUCCU
514
AGGAGUGC CUGAUGAG GCCGUUAGGC CGAA AAUCCACA
3023

2287
UUCGCACU C CUCCUGCA
515
UGCAGGAG CUGAUGAG GCCGUUAGGC CGAA AGUGCGAA
3024

2290
GCACUCCU C CUGCAUAU
516
AUAUGCAG CUGAUGAG GCCGUUAGGC CGAA AGGAGUGC
3025

2297
UCCUGCAU A UAGACCAC
517
GUGGUCUA CUGAUGAG GCCGUUAGGC CGAA AUGCAGGA
3026

2299
CUGCAUAU A GACCACCA
518
UGGUGGUC CUGAUGAG GCCGUUAGGC CGAA AUAUGCAG
3027

2317
AUGCCCCU A UCUUAUCA
519
UGAUAAGA CUGAUGAG GCCGUUAGGC CGAA AGGGGCAU
3028

2319
GCCCCUAU C UUAUCAAC
520
GUUGAUAA CUGAUGAG GCCGUUAGGC CGAA AUAGGGGC
3029

2321
CCCUAUCU U AUCAACAC
521
GUGUUGAU CUGAUGAG GCCGUUAGGC CGAA AGAUAGGG
3030

2322
CCUAUCUU A UCAACACU
522
AGUGUUGA CUGAUGAG GCCGUUAGGC CGAA AAGAUAGG
3031

2324
UAUCUUAU C AACACUUC
523
GAAGUGUU CUGAUGAG GCCGUUAGGC CGAA AUAAGAUA
3032

2331
UCAACACU U CCGGAAAC
524
GUUUCCGG CUGAUGAG GCCGUUAGGC CGAA AGUGUUGA
3033

2332
CAACACUU C CGGAAACU
525
AGUUUCCG CUGAUGAG GCCGUUAGGC CGAA AAGUGUUG
3034

2341
CGGAAACU A CUGUUGUU
526
AACAACAG CUGAUGAG GCCGUUAGGC CGAA AGUUUCCG
3035

2346
ACUACUGU U GUUAGACG
527
CGUCUAAC CUGAUGAG GCCGUUAGGC CGAA ACAGUAGU
3036

2349
ACUGUUGU U AGACGAAG
528
CUUCGUCU CUGAUGAG GCCGUUAGGC CGAA ACAACAGU
3037

2350
CUGUUGUU A GACGAAGA
529
UCUUCGUC CUGAUGAG GCCGUUAGGC CGAA AACAACAG
3038

2366
AGGCAGGU C CCCUAGAA
530
UUCUAGGG CUGAUGAG GCCGUUAGGC CGAA ACCUGCCU
3039

2371
GGUCCCCU A GAAGAAGA
531
UCUUCUUC CUGAUGAG GCCGUUAGGC CGAA AGGGGACC
3040

2383
GAAGAACU C CCUCGCCU
532
AGGCGAGG CUGAUGAG GCCGUUAGGC CGAA AGUUCUUC
3041

2387
AACUCCCU C GCCUCGCA
533
UGCGAGGC CUGAUGAG GCCGUUAGGC CGAA AGGGAGUU
3042

2392
CCUCGCCU C GCAGACGA
534
UCGUCUGC CUGAUGAG GCCGUUAGGC CGAA AGGCGAGG
3043

2405
ACGAAGGU C UCAAUCGC
535
GCGAUUGA CUGAUGAG GCCGUUAGGC CGAA ACCUUCGU
3044

2407
GAAGGUCU C AAUCGCCG
536
CGGCGAUU CUGAUGAG GCCGUUAGGC CGAA AGACCUUC
3045

2411
GUCUCAAU C GCCGCGUC
537
GACGCGGC CUGAUGAG GCCGUUAGGC CGAA AUUGAGAC
3046

2419
CGCCGCGU C GCAGAAGA
538
UCUUCUGC CUGAUGAG GCCGUUAGGC CGAA ACGCGGCG
3047

2429
CAGAAGAU C UCAAUCUC
539
GAGAUUGA CUGAUGAG GCCGUUAGGC CGAA AUCUUCUG
3048

2431
GAAGAUCU C AAUCUCGG
540
CCGAGAUU CUGAUGAG GCCGUUAGGC CGAA AGAUCUUC
3049

2435
AUCUCAAU C UCGGGAAU
541
AUUCCCGA CUGAUGAG GCCGUUAGGC CGAA AUUGAGAU
3050

2437
CUCAAUCU C GGGAAUCU
542
AGAUUCCC CUGAUGAG GCCGUUAGGC CGAA AGAUUGAG
3051

2444
UCGGGAAU C UCAAUGUU
543
AACAUUGA CUGAUGAG GCCGUUAGGC CGAA AUUCCCGA
3052

2446
GGGAAUCU C AAUGUUAG
544
CUAACAUU CUGAUGAG GCCGUUAGGC CGAA AGAUUCCC
3053

2452
CUCAAUGU U AGUAUUCC
545
GGAAUACU CUGAUGAG GCCGUUAGGC CGAA ACAUUGAG
3054

2453
UCAAUGUU A GUAUUCCU
546
AGGAAUAC CUGAUGAG GCCGUUAGGC CGAA AACAUUGA
3055

2456
AUGUUAGU A UUCCUUGG
547
CCAAGGAA CUGAUGAG GCCGUUAGGC CGAA ACUAACAU
3056

2458
GUUAGUAU U CCUUGGAC
548
GUCCAAGG CUGAUGAG GCCGUUAGGC CGAA AUACUAAC
3057

2459
UUAGUAUU C CUUGGACA
549
UGUCCAAG CUGAUGAG GCCGUUAGGC CGAA AAUACUAA
3058

2462
GUAUUCCU U GGACACAU
550
AUGUGUCC CUGAUGAG GCCGUUAGGC CGAA AGGAAUAC
3059

2471
GGACACAU A AGGUGGGA
551
UCCCACCU CUGAUGAG GCCGUUAGGC CGAA AUGUGUCC
3060

2484
GGGAAACU U UACGGGGC
552
GCCCCGUA CUGAUGAG GCCGUUAGGC CGAA AGUUUCCC
3061

2485
GGAAACUU U ACGGGGCU
553
AGCCCCGU CUGAUGAG GCCGUUAGGC CGAA AAGUUUCC
3062

2486
GAAACUUU A CGGGGCUU
554
AAGCCCCG CUGAUGAG GCCGUUAGGC CGAA AAAGUUUC
3063

2494
ACGGGGCU U UAUUCUUC
555
GAAGAAUA CUGAUGAG GCCGUUAGGC CGAA AGCCCCGU
3064

2495
CGGGGCUU U AUUCUUCU
556
AGAAGAAU CUGAUGAG GCCGUUAGGC CGAA AAGCCCCG
3065

2496
GGGGCUUU A UUCUUCUA
557
UAGAAGAA CUGAUGAG GCCGUUAGGC CGAA AAAGCCCC
3066

2498
GGCUUUAU U CUUCUACG
558
CGUAGAAG CUGAUGAG GCCGUUAGGC CGAA AUAAAGCC
3067

2499
GCUUUAUU C UUCUACGG
559
CCGUAGAA CUGAUGAG GCCGUUAGGC CGAA AAUAAAGC
3068

2501
UUUAUUCU U CUACGGUA
560
UACCGUAG CUGAUGAG GCCGUUAGGC CGAA AGAAUAAA
3069

2502
UUAUUCUU C UACGGUAC
561
GUACCGUA CUGAUGAG GCCGUUAGGC CGAA AAGAAUAA
3070

2504
AUUCUUCU A CGGUACCU
562
AGGUACCG CUGAUGAG GCCGUUAGGC CGAA AGAAGAAU
3071

2509
UCUACGGU A CCUUGCUU
563
AAGCAAGG CUGAUGAG GCCGUUAGGC CGAA ACCGUAGA
3072

2513
UGGUACCU U GCUUUAAU
564
AUUAAAGC CUGAUGAG GCCGUUAGGC CGAA AGGUACCG
3073

2517
ACCUUGCU U UAAUCCUA
565
UAGGAUUA CUGAUGAG GCCGUUAGGC CGAA AGCAAGGU
3074

2518
CCUUGCUU U AAUCCUAA
566
UUAGGAUU CUGAUGAG GCCGUUAGGC CGAA AAGCAAGG
3075

2519
CUUGCUUU A AUCCUAAA
567
UUUAGGAU CUGAUGAG GCCGUUAGGC CGAA AAAGCAAG
3076

2522
GCUUUAAU C CUAAAUGG
568
CCAUUUAG CUGAUGAG GCCGUUAGGC CGAA AUUAAAGC
3077

2525
UUAAUCCU A AAUGGCAA
569
UUGCCAUU CUGAUGAG GCCGUUAGGC CGAA AGGAUUAA
3078

2537
GGCAAACU C CUUCUUUU
570
AAAAGAAG CUGAUGAG GCCGUUAGGC CGAA AGUUUGCC
3079

2540
AAACUCCU U CUUUUCCU
571
AGGAAAAG CUGAUGAG GCCGUUAGGC CGAA AGGAGUUU
3080

2541
AACUCCUU C UUUUCCUG
572
CAGGAAAA CUGAUGAG GCCGUUAGGC CGAA AAGGAGUU
3081

2543
UUCCUUCU U UUCCUGAC
573
GUCAGGAA CUGAUGAG GCCGUUAGGC CGAA AGAAGGAG
3082

2544
UCCUUCUU U UCCUGACA
574
UGUCAGGA CUGAUGAG GCCGUUAGGC CGAA AAGAAGGA
3083

2545
CCUUCUUU U CCUGACAU
575
AUGUCAGG CUGAUGAG GCCGUUAGGC CGAA AAAGAAGG
3084

2546
CUUCUUUU C CUGACAUU
576
AAUGUCAG CUGAUGAG GCCGUUAGGC CGAA AAAAGAAG
3085

2554
CCUGACAU U CAUUUGCA
577
UGCAAAUG CUGAUGAG GCCGUUAGGC CGAA AUGUCAGG
3086

2555
CUGACAUU C AUUUGCAG
578
CUGCAAAU CUGAUGAG GCCGUUAGGC CGAA AAUGUCAG
3087

2558
ACAUUCAU U UGCAGGAG
579
CUCCUGCA CUGAUGAG GCCGUUAGGC CGAA AUGAAUGU
3088

2559
CAUUCAUU U GCAGGAGG
580
CCUCCUGC CUGAUGAG GCCGUUAGGC CGAA AAUGAAUG
3089

2572
GAGGACAU U GUUGAUAG
581
CUAUCAAC CUGAUGAG GCCGUUAGGC CGAA AUGUCCUC
3090

2575
GACAUUGU U GAUAGAUG
582
CAUCUAUC CUGAUGAG GCCGUUAGGC CGAA ACAAUGUC
3091

2579
UUGUUGAU A GAUGUAAG
583
UUUACAUC CUGAUGAG GCCGUUAGGC CGAA AUCAACAA
3092

2585
AUAGAUGU A AGCAAUUU
584
AAAUUGCU CUGAUGAG GCCGUUAGGC CGAA ACAUCUAU
3093

2592
UAAGCAAU U UGUGGGGC
585
GCCCCACA CUGAUGAG GCCGUUAGGC CGAA AUUGCUUA
3094

2593
AAGCAAUU U GUGGGGCC
586
GGCCCCAC CUGAUGAG GCCGUUAGGC CGAA AAUUGCUU
3095

2605
GGGCCCCU U ACAGUAAA
587
UUUACUGU CUGAUGAG GCCGUUAGGC CGAA AGGGGCCC
3096

2606
GGCCCCUU A CAGUAAAU
588
AUUUACUG CUGAUGAG GCCGUUAGGC CGAA AAGGGGCC
3097

2611
CUUACAGU A AAUGAAAA
589
UUUUCAUU CUGAUGAG GCCGUUAGGC CGAA ACUGUAAG
3098

2629
AGGAGACU U AAAUUAAC
590
GUUAAUUU CUGAUGAG GCCGUUAGGC CGAA AGUCUCCU
3099

2630
GGAGACUU A AAUUAACU
591
AGUUAAUU CUGAUGAG GCCGUUAGGC CGAA AAGUCUCC
3100

2634
ACUUAAAU U AACUAUGC
592
GCAUAGUU CUGAUGAG GCCGUUAGGC CGAA AUUUAAGU
3101

2635
CUUAAAUU A ACUAUGCC
593
GGCAUAGU CUGAUGAG GCCGUUAGGC CGAA AAUUUAAG
3102

2639
AAUUAACU A UGCCUGCU
594
AGCAGGCA CUGAUGAG GCCGUUAGGC CGAA AGUUAAUU
3103

2648
UGCCUGCU A GGUUUUAU
595
AUAAAACC CUGAUGAG GCCGUUAGGC CGAA AGCAGGCA
3104

2652
UGCUAGGU U UUAUCCCA
596
UGGGAUAA CUGAUGAG GCCGUUAGGC CGAA ACCUAGCA
3105

2653
GCUAGGUU U UAUCCCAA
597
UUGGGAUA CUGAUGAG GCCGUUAGGC CGAA AACCUAGC
3106

2654
CUAGGUUU U AUCCCAAU
598
AUUGGGAU CUGAUGAG GCCGUUAGGC CGAA AAACCUAG
3107

2655
UAGGUUUU A UCCCAAUG
599
CAUUGGGA CUGAUGAG GCCGUUAGGC CGAA AAAACCUA
3108

2657
GGUUUUAU C CCAAUGUU
600
AACAUUGG CUGAUGAG GCCGUUAGGC CGAA AUAAAACC
3109

2665
CCCAAUGU U ACUAAAUA
601
UAUUUAGU CUGAUGAG GCCGUUAGGC CGAA ACAUUGGG
3110

2666
CCAAUGUU A CUAAAUAU
602
AUAUUUAG CUGAUGAG GCCGUUAGGC CGAA AACAUUGG
3111

2669
AUGUUACU A AAUAUUUG
603
UAAAUAUU CUGAUGAG GCCGUUAGGC CGAA AGUAACAU
3112

2673
UACUAAAU A UUUGCCCU
604
AGGGCAAA CUGAUGAG GCCGUUAGGC CGAA AUUUAGUA
3113

2675
CUAAAUAU U UGCCCUUA
605
UAAGGGCA CUGAUGAG GCCGUUAGGC CGAA AUAUUUAG
3114

2676
UAAAUAUU U GCCCUUAG
606
CUAAGGGC CUGAUGAG GCCGUUAGGC CGAA AAUAUUUA
3115

2682
UUUGCCCU U AGAUAAAG
607
CUUUAUCU CUGAUGAG GCCGUUAGGC CGAA AGGGCAAA
3116

2683
UUGCCCUU A GAUAAAGG
608
CCUUUAUC CUGAUGAG GCCGUUAGGC CGAA AAGGGCAA
3117

2687
CCUUAGAU A AAGGGAUC
609
GAUCCCUU CUGAUGAG GCCGUUAGGC CGAA AUCUAAGG
3118

2695
AAAGGGAU C AAACCGUA
610
UACGGUUU CUGAUGAG GCCGUUAGGC CGAA AUCCCUUU
3119

2703
UAAACCGU A UUAUCCAG
611
CUGGAUAA CUGAUGAG GCCGUUAGGC CGAA ACGGUUUG
3120

2705
AACCGUAU U AUCCAGAG
612
CUCUGGAU CUGAUGAG GCCGUUAGGC CGAA AUACGGUU
3121

2706
ACCGUAUU A UCCAGAGU
613
ACUCUGGA CUGAUGAG GCCGUUAGGC CGAA AAUACGGU
3122

2708
CGUAUUAU C CAGAGUAU
614
AUACUCUG CUGAUGAG GCCGUUAGGC CGAA AUAAUACG
3123

2715
UCCAGAGU A UGUAGUUA
615
UAACUACA CUGAUGAG GCCGUUAGGC CGAA ACUCUGGA
3124

2719
GAGUAUGU A GUUAAUCA
616
UGAUUAAC CUGAUGAG GCCGUUAGGC CGAA ACAUACUC
3125

2722
UAUGUAGU U AAUCAUUA
617
UAAUGAUU CUGAUGAG GCCGUUAGGC CGAA ACUACAUA
3126

2723
AUGUAGUU A AUCAUUAC
618
GUAAUGAU CUGAUGAG GCCGUUAGGC CGAA AACUACAU
3127

2726
UAGUUAAU C AUUACUUC
619
GAAGUAAU CUGAUGAG GCCGUUAGGC CGAA AUUAACUA
3128

2729
UUAAUCAU U ACUUCCAG
620
CUGGAAGU CUGAUGAG GCCGUUAGGC CGAA AUGAUUAA
3129

2730
UAAUCAUU A CUUCCAGA
621
UCUGGAAG CUGAUGAG GCCGUUAGGC CGAA AAUGAUUA
3130

2733
UCAUUACU U CCAGACGC
622
GCGUCUGG CUGAUGAG GCCGUUAGGC CGAA AGUAAUGA
3131

2734
CAUUACUU C CAGACGCG
623
UGCGUCUG CUGAUGAG GCCGUUAGGC CGAA AAGUAAUG
3132

2747
CGCGACAU U AUUUACAC
624
GUGUAAAU CUGAUGAG GCCGUUAGGC CGAA AUGUCGCG
3133

2748
GCGACAUU A UUUACACA
625
UGUGUAAA CUGAUGAG GCCGUUAGGC CGAA AAUGUCGC
3134

2750
GACAUUAU U UACACACU
626
AGUGUGUA CUGAUGAG GCCGUUAGGC CGAA AUAAUGUC
3135

2751
ACAUUAUU U ACACACUC
627
GAGUGUGU CUGAUGAG GCCGUUAGGC CGAA AAUAAUGU
3136

2752
CAUUAUUU A CACACUCU
628
AGAGUGUG CUGAUGAG GCCGUUAGGC CGAA AAAUAAUG
3137

2759
UACACACU C UUUGGAAG
629
CUUCCAAA CUGAUGAG GCCGUUAGGC CGAA AGUGUGUA
3138

2761
CACACUCU U UGGAAGGC
630
GCCUUCCA CUGAUGAG GCCGUUAGGC CGAA AGAGUGUG
3139

2762
ACACUCUU U GGAAGGCG
631
CGCCUUCC CUGAUGAG GCCGUUAGGC CGAA AAGAGUGU
3140

2776
GCGGGGAU C UUAUAUAA
632
UUAUAUAA CUGAUGAG GCCGUUAGGC CGAA AUCCCCGC
3141

2778
GGGGAUCU U AUAUAAAA
633
UUUUAUAU CUGAUGAG GCCGUUAGGC CGAA AGAUCCCC
3142

2779
GGGAUCUU A UAUAAAAG
634
CUUUUAUA CUGAUGAG GCCGUUAGGC CGAA AAGAUCCC
3143

2781
GAUCUUAU A UAAAAGAG
635
CUCUUUUA CUGAUGAG GCCGUUAGGC CGAA AUAAGAUC
3144

2783
UCUUAUAU A AAAGAGAG
636
CUCUCUUU CUGAUGAG GCCGUUAGGC CGAA AUAUAAGA
3145

2793
AAGAGAGU C CACACGUA
637
UACGUGUG CUGAUGAG GCCGUUAGGC CGAA ACUCUCUU
3146

2801
CCACACGU A GCGCCUCA
638
UGAGGCGC CUGAUGAG GCCGUUAGGC CGAA ACGUGUGG
3147

2808
UAGCGCCU C AUUUUGCG
639
CGCAAAAU CUGAUGAG GCCGUUAGGC CGAA AGGCGCUA
3148

2811
CGCCUCAU U UUGCGGGU
640
ACCCGCAA CUGAUGAG GCCGUUAGGC CGAA AUGAGGCG
3149

2812
GCCUCAUU U UGCGGGUC
641
GACCCGCA CUGAUGAG GCCGUUAGGC CGAA AAUGAGGC
3150

2813
UCUCAUUU U GCGGGUCA
642
UGACCCGC CUGAUGAG GCCGUUAGGC CGAA AAAUGAGG
3151

2820
UUGCGGGU C ACCAUAUU
643
AAUAUGGU CUGAUGAG GCCGUUAGGC CGAA ACCCGCAA
3152

2826
GUCACCAU A UUCUUGGG
644
CCCAAGAA CUGAUGAG GCCGUUAGGC CGAA AUGGUGAC
3153

2828
CACCAUAU U CUUGGGAA
645
UUCCCAAG CUGAUGAG GCCGUUAGGC CGAA AUAUGGUG
3154

2829
ACCAUAUU C UUGGGAAC
646
GUUCCCAA CUGAUGAG GCCGUUAGGC CGAA AAUAUGGU
3155

2831
CAUAUUCU U GGGAACAA
647
UUGUUCCC CUGAUGAG GCCGUUAGGC CGAA AGAAUAUG
3156

2843
AACAAGAU C UACAGCAU
648
AUGCUGUA CUGAUGAG GCCGUUAGGC CGAA AUCUUGUU
3157

2845
CAAGAUCU A CAGCAUGG
649
CCAUGCUG CUGAUGAG GCCGUUAGGC CGAA AGAUCUUG
3158

2859
UGGGAGGU U GGUCUUCC
650
GGAAGACC CUGAUGAG GCCGUUAGGC CGAA ACCUCCCA
3159

2863
AGGUUGGU C UUCCAAAC
651
GUUUGGAA CUGAUGAG GCCGUUAGGC CGAA ACCAACCU
3160

2865
GUUGGUCU U CCAAACCU
652
AGGUUUGG CUGAUGAG GCCGUUAGGC CGAA AGACCAAC
3161

2866
UUGGUCUU C CAAACCUC
653
GAGGUUUG CUGAUGAG GCCGUUAGGC CGAA AAGACCAA
3162

2874
CCAAACCU C GAAAAGGC
654
GCCUUUUC CUGAUGAG GCCGUUAGGC CGAA AGGUUUGG
3163

2895
GGACAAAU C UUUCUGUC
655
GACAGAAA CUGAUGAG GCCGUUAGGC CGAA AUUUGUCC
3164

2897
ACAAAUCU U UCUGUCCC
656
GGGACAGA CUGAUGAG GCCGUUAGGC CGAA AGAUUUGU
3165

2898
CAAAUCUU U CUGUCCCC
657
GGGGACAG CUGAUGAG GCCGUUAGGC CGAA AAGAUUUG
3166

2899
AAAUCUUU C UGUCCCCA
658
UGGGGACA CUGAUGAG GCCGUUAGGC CGAA AAAGAUUU
3167

2903
UUUUCUGU C CCCAAUCC
659
GGAUUGGG CUGAUGAG GCCGUUAGGC CGAA ACAGAAAG
3168

2910
UCCCCAAU C CCCUGGGA
660
UCCCAGGG CUGAUGAG GCCGUUAGGC CGAA AUUGGGGA
3169

2920
CCUGGGAU U CUUCCCCG
661
CGGGGAAG CUGAUGAG GCCGUUAGGC CGAA AUCCCAGG
3170

2921
CUGGGAUU C UUCCCCGA
662
UCGGGGAA CUGAUGAG GCCGUUAGGC CGAA AAUCCCAG
3171

2923
GGGAUUCU U CCCCGAUC
663
GAUCGGGG CUGAUGAG GCCGUUAGGC CGAA AGAAUCCC
3172

2924
GGAUUCUU C CCCGAUCA
664
UGAUCGGG CUGAUGAG GCCGUUAGGC CGAA AAGAAUCC
3173

2931
UCCCCGAU C AUCAGUUG
665
CAACUGAU CUGAUGAG GCCGUUAGGC CGAA AUCGGGGA
3174

2934
CCGAUCAU C AGUUGGAC
666
GUCCAACU CUGAUGAG GCCGUUAGGC CGAA AUGAUCGG
3175

2938
UCAUCAGU U GGACCCUG
667
CAGGGUCC CUGAUGAG GCCGUUAGGC CGAA ACUGAUGA
3176

2950
CCCUGCAU U CAAAGCCA
668
UGGCUUUG CUGAUGAG GCCGUUAGGC CGAA AUGCAGGG
3177

2951
CCUGCAUU C AAAGCCAA
669
UUGGCUUU CUGAUGAG GCCGUUAGGC CGAA AAUGCAGG
3178

2962
AGCCAACU C AGUAAAUC
670
GAUUUACU CUGAUGAG GCCGUUAGGC CGAA AGUUGGCU
3179

2966
AACUCAGU A AAUCCAGA
671
UCUGGAUU CUGAUGAG GCCGUUAGGC CGAA ACUGAGUU
3180

2970
CAGUAAAU C CAGAUUGG
672
CCAAUCUG CUGAUGAG GCCGUUAGGC CGAA AUUUACUG
3181

2976
AUCCAGAU U GGGACCUC
673
GAGGUCCC CUGAUGAG GCCGUUAGGC CGAA AUCUGGAU
3182

2984
UGGGACCU C AACCCGCA
674
UGCGGGUU CUGAUGAG GCCGUUAGGC CGAA AGGUCCCA
3183

3037
GGGAGCAU U CGGGCCAG
675
CUGGCCCG CUGAUGAG GCCGUUAGGC CGAA AUGCUCCC
3184

3038
GGAGCAUU C GGGCCAGG
676
CCUGGCCC CUGAUGAG GCCGUUAGGC CGAA AAUGCUCC
3185

3049
GCCAGGGU U CACCCCUC
677
GAGGGGUG CUGAUGAG GCCGUUAGGC CGAA ACCCUGGC
3186

3050
CCAGGGUU C ACCCCUCC
678
GGAGGGGU CUGAUGAG GCCGUUAGGC CGAA AACCCUGG
3187

3057
UCACCCCU C CCCAUGGG
679
CCCAUGGG CUGAUGAG GCCGUUAGGC CGAA AGGGGUGA
3188

3073
GGGACUGU U GGGGUGGA
680
UCCACCCC CUGAUGAG GCCGUUAGGC CGAA ACAGUCCC
3189

3087
GGAGCCCU C ACGCUCAG
681
CUGAGCGU CUGAUGAG GCCGUUAGGC CGAA AGGGCUCC
3190

3093
UUCACGCU C AGGGCCUA
682
UAGGCCCU CUGAUGAG GCCGUUAGGC CGAA AGCGUGAG
3191

3101
CAGGGCCU A CUCACAAC
683
GUUGUGAG CUGAUGAG GCCGUUAGGC CGAA AGGCCCUG
3192

3104
GGCCUACU C ACAACUGU
684
ACAGUUGU CUGAUGAG GCCGUUAGGC CGAA AGUAGGCC
3193

3123
UAGCAGCU C CUCCUCCU
685
AGGAGGAG CUGAUGAG GCCGUUAGGC CGAA AGCUGCUG
3194

3126
CAGCUCCU C CUCCUGCC
686
GGCAGGAG CUGAUGAG GCCGUUAGGC CGAA AGGAGCUG
3195

3129
CUCCUCCU C CUGCCUCC
687
GGAGGCAG CUGAUGAG GCCGUUAGGC CGAA AGGAGGAG
3196

3136
UCCUGCCU C CACCAAUC
688
GAUUGGUG CUGAUGAG GCCGUUAGGC CGAA AGGCAGGA
3197

3144
CCACCAAU C GGCAGUCA
689
UGACUGCC CUGAUGAG GCCGUUAGGC CGAA AUUGGUGG
3198

3151
UCGGCAGU C AGGAAGGC
690
GCCUUCCU CUGAUGAG GCCGUUAGGC CGAA ACUGCCGA
3199

3165
GGCAGCCU A CUCCCUUA
691
UAAGGGAG CUGAUGAG GCCGUUAGGC CGAA AGGCUGCC
3200

3168
AGCCUACU C CCUUAUCU
692
AGAUAAGG CUGAUGAG GCCGUUAGGC CGAA AGUAGGCU
3201

3172
UACUCCCU U AUCUCCAC
693
GUGGAGAU CUGAUGAG GCCGUUAGGC CGAA AGGGAGUA
3202

3173
ACUCCCUU A UCUCCACC
694
GGUGGAGA CUGAUGAG GCCGUUAGGC CGAA AAGGGAGU
3203

3175
UCCCUUAU C UCCACCUC
695
GAGGUGGA CUGAUGAG GCCGUUAGGC CGAA AUAAGGGA
3204

3177
CCUUAUCU C CACCUCUA
696
UAGAGGUG CUGAUGAG GCCGUUAGGC CGAA AGAUAAGG
3205

3183
UUCCACCU C UAAGGGAC
697
GUCCCUUA CUGAUGAG GCCGUUAGGC CGAA AGGUGGAG
3206

3185
CCACCUCU A AUGGACAC
698
GUGUCCCU CUGAUGAG GCCGUUAGGC CGAA AGAGGUGG
3207

3195
GGGACACU C AUCCUCAG
699
CUGAGGAU CUGAUGAG GCCGUUAGGC CGAA AGUGUCCC
3208

3198
ACACUCAG C CUCAGGCC
700
GGCCUGAG CUGAUGAG GCCGUUAGGC CGAA AUGAGUGU
3209

3201
CUCAUCCU C AGGCCAUG
701
CAUGGCCU CUGAUGAG GCCGUUAGGC CGAA AGGAUGAG
3210

Input Sequence = AF100308.

Cut Site = UH/.

Stem Length = 8.

Core Sequence = CUGAUGAG GCCGUUAGGC CGAA

AF100308 (Hepatitis B virus strain 2-18, 3215 bp)

Underlined region can be any X sequence or linker, as described herein.

[0249]

6

TABLE VI

HUMAN HBV INOZYME AND SUBSTRATE SEQUENCE

Pos
Substrate
Seq ID
Inozyme
Seq ID

9
AACUCCAC C ACUUUCCA
702
UGGAAAGU CUGAUGAG GCCGUUAGCC CGAA IUGGAGUU
3211

10
ACUCCACC A CUUUCCAC
703
GUGGAAAG CUGAUGAG GCCGUUAGGC CGAA IGUGGAGU
3212

12
UCCACCAC U UUCCACCA
704
UGGUGGAA CUGAUGAG GCCGUUAGGC CGAA IUGGUGGA
3213

16
CCACUUUC C ACCAAACU
705
AGUUUGGU CUGAUGAG GCCGUUAGGC CGAA IAAAGUGG
3214

17
CACUUUCC A CCAAACUC
706
GAGUUUGG CUGAUGAG GCCGUUAGGC CGAA IGAAAGUG
3215

19
CUUUCCAC C AAACUCUU
707
AAGAGUUU CUGAUGAC GCCGUUAGGC CGAA IUGGAAAG
3216

20
UUUCCACC A AACUCUUC
708
GAAGAGUU CUGAUGAG GCCGUUAGGC CGAA IGUGGAAA
3217

24
CACCAAAC U CUUCAAGA
709
UCUUGAAG CUGAUGAG GCCGUUAGGC CGAA IUUUGGUG
3218

26
CCAAACUC U UCAAGAUC
710
GAUCUUGA CUGAUGAG GCCGUUAGGC CGAA IAGUUUGG
3219

29
AACUCUUC A AGAUCCCA
711
UGGGAUCU CUGAUGAG GCCGUUAGGC CGAA IAAGAGUU
3220

35
UCAAGAUC C CAGAGUCA
712
UGACUCUG CUGAUGAG GCCGUUAGGC CGAA IAUCUUGA
3221

36
CAAGAUCC C AGAGUCAG
713
UUGACUCU CUGAUGAG GCCGUUAGGC CGAA IGAUCUUG
3222

37
AAGAUCCC A GAGUCAGG
714
CCUGACUC CUGAUGAG GCCGUUAGGC CGAA IGGAUCUU
3223

43
UCAGAGUC A GGGCCCUG
715
CAGGGCCC CUGAUGAG GCCGUUAGGC CGAA IACUCUGG
3224

48
GUCAGGGC C CUGUACUU
716
AAGUACAG CUGAUGAG GCCGUUAGGC CGAA ICCCUGAC
3225

49
UCAGGGCC C UGUACUUU
717
AAAGUACA CUGAUGAG GCCGUUAGGC CGAA IGCCCUGA
3226

50
CAGGGCCC U GUACUGUC
718
GAAAGUAC CUGAUGAG GCCGUUAGGC CGAA IGGCCCUG
3227

55
CCCUGUAC U UUCCUGCU
719
AGCAGGAA CUGAUGAG GCCGUUAGGC CGAA IUACAGGG
3228

59
GUACUUUC C UGCUGGUG
720
CACCAGCA CUGAUGAG GCCGUUAGGC CGAA IAAAGUAC
3229

60
UACUUUCC U GCUGGUGG
721
CCACCAGC CUGAUGAG GCCGUUAGGC CGAA IGAAAGUA
3230

63
UUUCCUGC U GGUGGCUC
722
GAGCCACC CUGAUGAG GCCGUUAGGC CGAA ICAGGAAA
3231

70
CUGGUGGC U CCAGUUCA
723
UGAACUGG CUGAUGAG GCCGUUAGGC CGAA ICCACCAG
3232

72
GGUGGCUC C AGUUCAGG
724
CCUGAACU CUGAUGAG GCCGUUAGGC CGAA IAGCCACC
3233

73
GUGGCUCC A GUUCAGGA
725
UCCUGAAC CUGAUGAG GCCGUUAGGC CGAA IGAGCCAC
3234

78
UCCAGUUC A GGAACAGU
726
ACUGUUCC CUGAUGAG GCCGUUAGGC CGAA IAACUGGA
3235

84
UCAGGAAC A GUGAGCCC
727
GGGCUCAC CUGAUGAG GCCGUUAGGC CGAA IUUCCUGA
3236

91
CAGUGAUC C CUGCUCAG
728
CUGAGCAG CUGAUGAG GCCGUUAGGC CGAA ICUCACUG
3237

92
AGUGAGCC C UGCUCAGA
729
UCUGAGCA CUGAUGAG GCCGUUAGGC CGAA IGCUCACU
3238

93
GUGAGCCC U GCUCAGAA
730
UUCUGAGC CUGAUGAG GCCGUUAGGC CGAA IGGCUCAC
3239

96
AGCCCUGC U CAGAAUAC
731
GUAUUCUG CUGAUGAG GCCGUUAGGC CGAA ICAGGGCU
3240

98
CCCUGCUC A GAAUACUG
732
CAGUAUUC CUGAUGAG GCCGUUAGGC CGAA IAGCAGGG
3241

105
CAGAAUAC U GUCUCUGC
733
GCAGAGAC CUGAUGAG GCCGUUAGGC CGAA IUAUUCUG
3242

109
AUACUGUC U CUGCCAUA
734
UAUGGCAG CUGAUGAG GCCGUUAGGC CGAA IACAGUAU
3243

111
ACUGUCUC U GCCAUAUC
735
GAUAUGGC CUGAUGAG GCCGUUAGGC CGAA IAGACAGU
3244

114
GUCUCUGC C AUAUCGUC
736
GACGAUAU CUGAUGAG GCCGUUAGGC CGAA ICAGAGAC
3245

115
UCUCUGCC A UAUCGUCA
737
UGACGAUA CUGAUGAG GCCGUUAGGC CGAA ICCAGAGA
3246

123
AUAUCGUC A AUCUUAUC
738
GAUAAGAU CUGAUGAG GCCGUUAGGC CGAA IACGAUAU
3247

127
CGUCAAUC U UAUCGAAG
739
CUUCGAUA CUGAUGAG GCCGUUAGGC CGAA IAUUGACG
3248

138
UCGAAGAC U GGGGACCC
740
GGGUCCCC CUGAUGAG GCCGUUAGGC CGAA TUCUUCGA
3249

145
CUGGGGAC C CUGUACCG
741
CGGUACAG CUGAUGAG GCCGUUAGGC CGAA IUCCCCAG
3250

146
UGGGGACC C UGUACCGA
742
UCGGUACA CUGAUGAG GCCGUUAGGC CGAA IGUCCCCA
3251

147
GGGGACCC U GUACCGAA
743
UUCGGUAC CUGAUGAG GCCGUUAGGC CGAA IGGUCCCC
3252

152
CCCUGUAC C GAACAUGG
744
CCAUGUUC CUGAUGAG GCCGUUAGGC CGAA IUACAGGG
3253

157
UACCGAAC A UGGAGAAC
745
GUUCUCCA CUGAUGAG GCCGUUAGGC CGAA IUUCGGUA
3254

166
UGGAGAAC A UCOCAUCA
746
UGAUGCGA CUGAUGAG GCCGUUAGGC CGAA IUUCUCCA
3255

171
AACAUCGC A UCAGGACU
747
AGUCCUGA CUGAUGAG GCCGUUAGGC CGAA ICGAUGUU
3256

174
AUCGCAUC A GGACUCCU
748
AGGAGUCC CUGAUGAG GCCGUUAGGC CGAA IAUGCGAU
3257

179
AUCAGGAC U CCUAGGAC
749
GUCCUAGG CUGAUGAG GCCGUUAGGC CGAA IUCCUGAU
3258

181
CAGGACUC C UAGGACCC
750
GGGUCCUA CUGAUGAG GCCGUUAGGC CGAA IAGUCCUG
3259

182
AGGACUCC U AGGACCCC
751
GGGGUCCU CUGAUGAG GCCGUUAGGC CGAA IGAGUCCU
3260

188
CCUAGGAC C CCUGCUCG
752
CGAGCAGG CUGAUGAG GCCGUUAGGC CGAA IUCCUAGG
3261

189
CUAGGACC C CUGCUCGU
753
ACGAGCAG CUGAUGAG GCCGUUAGGC CGAA IGUCCUAG
3262

190
UAGGACCC C UGCUCGUG
754
CACGAGCA CUGAUGAG GCCGUUAGGC CGAA IGGUCCUA
3263

191
AGGACCCC U GCUCGUGU
755
ACACGAGC CUGAUGAG GCCGUUAGGC CGAA IGGGUCCU
3264

194
ACCCCUGC U CGUGUUAC
756
GUAACACG CUGAUGAG GCCGUUAGGC CGAA ICAGGGGU
3265

203
CGUGUUAC A GGCGGGGU
757
ACCCCGCC CUGAUGAG GCCGUUAGGC CGAA IUAACACG
3266

217
GGUUUUUC U UGUUGACA
758
UGUCAACA CUGAUGAG GCCGUUAGGC CGAA IAAAAACC
3267

225
UUGUUGAC A AAAAUCCU
759
AGGAUUUU CUGAUGAG GCCGUUAGGC CGAA IUCAACAA
3268

232
CAAAAAUC C UCACAAUA
760
UAUUGUGA CUGAUGAG GCCGUUAGGC CGAA IAUUUUUG
3269

233
AAAAAUCC U CACAAUAC
761
GUAUUGUG CUGAUGAG GCCGUUAGGC CGAA IGAUUUUU
3270

235
AAAUCCUC A CAAUACCA
762
UGGUAUUG CUGAUGAG GCCGUUAGGC CGAA IAGGAUUU
3271

237
AUCCUCAC A AUACCACA
763
UGUGGUAU CUGAUGAG GCCGUUAGGC CGAA IUGAGGAU
3272

242
CACAAUAC C ACAGAGUC
764
GACUCUGU CUGAUGAG GCCGUUAGGC CGAA IUAUUGUG
3273

243
ACAAUACC A CAGAGUCU
765
AGACUCUG CUGAUGAG GCCGUUAGGC CGAA IGUAUUGU
3274

245
AAUACCAC A GAGUCUAG
766
CUAGACUC CUGAUGAG GCCGUUAGGC CGAA IUGGUAUU
3275

251
ACAGAGUC U AGACUCGU
767
ACGAGUCU CUGAUGAG GCCGUUAGGC CGAA IACUCUGU
3276

256
GUCUAGAC U CGUGGUGG
768
CCACCACG CUGAUGAG GCCGUUAGGC CGAA IUCUAGAC
3277

267
UGGUGGAC U UCUCUCAA
769
UUGAGAGA CUGAUGAG GCCGUUAGGC CGAA IUCCACCA
3278

270
UGGACUUC U CUCAAUUU
770
AAAUUGAG CUGAUGAG GCCGUUAGGC CGAA IAAGUCCA
3279

272
GACUUCUC U CAAUUUUC
771
GAAAAUUG CUGAUGAG GCCGUUAGGC CGAA IAGAAGUC
3280

274
CUUCUCUC A AUUUUCUA
772
UAGAAAAU CUGAUGAG GCCGUUAGGC CGAA IAGAGAAG
3281

281
CAAUUUUC U AGGGGGAA
773
UUCCCCCU CUGAUGAG GCCGUUAGGC CGAA IAAAAUUG
3282

291
GGGGGAAC A CCCGUGUG
774
CACACGGG CUGAUGAG GCCGUUAGGC CGAA IUUCCCCC
3283

293
GGGAACAC C CGUGUGUC
775
GACACACG CUGAUGAG GCCGUUAGGC CGAA IUGUUCCC
3284

294
GGAACACC C GUGUGUCU
776
AGACACAC CUGAUGAG GCCGUUAGGC CGAA IGUGUUCC
3285

302
CGUGUGUC U UGGCCAAA
777
UUUGGCCA CUGAUGAG GCCGUUAGGC CGAA IACACACG
3286

307
GUCUUGGC C AAAAUUCG
778
CGAAUUUU CUGAUGAG GCCGUUAGGC CGAA ICCAAGAC
3287

308
UCUUGGCC A AAAUUCGC
779
GCGAAUUU CUGAUGAG GCCGUUAGGC CGAA IGCCAAGA
3288

317
AAAUUCGC A GUCCCAAA
780
UUUGGGAC CUGAUGAG GCCGUUAGGC CGAA ICGAAUUU
3289

321
UCGCAGUC C CAAAUCUC
781
GAGAUUUG CUGAUGAG GCCGUUAGGC CGAA IACUGCGA
3290

322
CGCAGUCC C AAAUCUCC
782
GGAGAUUU CUGAUGAG GCCGUUAGGC CGAA IGACUGCG
3291

323
GCAGUCCC A AAUCUCCA
783
UGGAGAUU CUGAUGAG GCCGUUAGGC CGAA IGGACUGC
3292

328
CCCAAAUC U CCAGUCAC
784
GUGACUGG CUGAUGAG GCCGUUAGGC CGAA IAUUUGGG
3293

330
CAAAUCUC C AGUCACUC
785
GAGUGACU CUGAUGAG GCCGUUAGGC CGAA IAGAUUUG
3294

331
AAAUCUCC A GUCACUCA
786
UGAGUGAC CUGAUGAG GCCGUUAGGC CGAA IGAGAUUU
3295

335
CUCCAGUC A CUCACCAA
787
UUGGUGAG CUGAUGAG GCCGUUAGGC CGAA IACUGGAG
3296

337
CCAGUCAC U CACCAACC
788
GGUUGGUG CUGAUGAG GCCGUUAGGC CGAA IUGACUGG
3297

339
AGUCACUC A CCAACCUG
789
CAGGUUGG CUGAUGAG GCCGUUAGGC CGAA IAGUGACU
3298

341
UCACUCAC C AACCUGUU
790
AACAGGUU CUGAUGAG GCCGUUAGGC CGAA IUGAGUGA
3299

342
CACUCACC A ACCUGUUG
791
CAACAGGU CUGAUGAG GCCGUUAGGC CGAA IGUGAGUG
3300

345
UCACCAAC C UGUUGUCC
792
GGACAACA CUGAUGAG GCCGUUAGGC CGAA IUUGGUGA
3301

346
CACCAACC U GUUGUCCU
793
AGGACAAC CUGAUGAG GCCGUUAGGC CGAA IGUUGGUG
3302

353
CUGUUGUC C UCCAAUUU
794
AAAUUGGA CUGAUGAG GCCGUUAGGC CGAA IACAACAG
3303

354
UGUUGUCC U CCAAUUUG
795
CAAAUUGG CUGAUGAG GCCGUUAGGC CGAA IGACAACA
3304

356
UUGUCCUC C AAUUUGUC
796
GACAAAUU CUGAUGAG GCCGUUAGGC CGAA IAGGACAA
3305

357
UGUCCUCC A AUUUGUCC
797
GGACAAAU CUGAUGAG GCCGUUAGGC CGAA IGAGGACA
3306

365
AAUUUGUC C UGGUUAUC
798
GAUAACCA CUGAUGAG GCCGUUAGGC CGAA IACAAAUU
3307

366
AUUUGUCC U GGUUAUCG
799
CGAUAACC CUGAUGAG GCCGUUAGGC CGAA IGACAAAU
3308

376
GUUAUCGC U GGAUGUGU
800
ACACAUCC CUGAUGAG GCCGUUAGGC CGAA ICGAUAAC
3309

386
GAUGUGUC U GCGGCGUU
801
AACGCCGC CUGAUGAG GCCGUUAGGC CGAA IACACAUC
3310

400
GUUUUAUC A UCUUCCUC
802
GAGGAAGA CUGAUGAG GCCGUUAGGC CGAA IAUAAAAC
3311

403
UUAUCAUC U UCCUCUGC
803
GCAGAGGA CUGAUGAG GCCGUUAGGC CGAA IAUGAUAA
3312

406
UCAUCUUC C UCUGCAUC
804
GAUGCAGA CUGAUGAG GCCGUUAGGC CGAA IAAGAUGA
3313

407
CAUCUUCC U CUGCAUCC
805
GGAUGCAG CUGAUGAG GCCGUUAGGC CGAA IGAAGAUG
3314

409
UCUUCCUC U GCAUCCUG
806
CAGGAUGC CUGAUGAG GCCGUUAGGC CGAA IAGGAAGA
3315

412
UCCUCUGC A UCCUGCUG
807
CACCAGGA CUGAUGAG GCCGUUAGGC CGAA ICAGAGGA
3316

415
UCUCCAUC C UGCUGCUA
808
UAGCAGCA CUGAUGAG GCCGUUAGGC CGAA IAUGCAGA
3317

416
CUGCAUCC U GCUGCUAU
809
AUAGCAGC CUGAUGAG GCCGUUAGGC CGAA IGAUGCAG
3318

419
CAUCCUGC U GCUAUGCC
810
GGCAUAGC CUGAUGAG GCCGUUAGGC CGAA ICAGGAUG
3319

422
CCUGCUGC U AUGCCUCA
811
UGAGCCAU CUGAUGAG GCCGUUAGGC CGAA ICAGCAGG
3320

427
UGCUAUGC C UCAUCUUC
812
GAAGAUGA CUGAUGAG GCCGUUAGGC CGAA ICAUAGCA
3321

428
GCUAUGCC U CAUCUUCU
813
AGAAGAUG CUGAUGAG GCCGUUAGGC CGAA IGCAUAGC
3322

430
UAUGCCUC A UCUUCUUG
814
CAAGAAGA CUGAUGAG GCCGUUAGGC CGAA IACGCAUA
3323

433
GCCUCAUC U UCUUGUUG
815
CAACAAGA CUGAUGAG GCCGUUAGGC CGAA IAUGAGGC
3324

436
UCAUCUUC U UGUUGGUU
816
AACCAACA CUGAUGAG GCCGUUAGGC CGAA IAAGAUGA
3325

446
GUUGGUUC U UCUGGACU
817
AGUCCAGA CUGAUGAG GCCGUUAGGC CGAA IAACCAAC
3326

449
GGUUCUUC U GGACUAUC
818
GAUAGUCC CUGAUGAG GCCGUUAGGC CGAA IAAGAACC
3327

454
UUCUGGAC U AUCAAGGU
819
ACCUUGAU CUGAUGAG GCCGUUAGGC CGAA IUCCAGAA
3328

458
GGACUAUC A AGGUAUGU
820
ACAUACCU CUGAUGAG GCCGUUAGGC CGAA IAUAGUCC
3329

470
UAUGUUGC C CGUUUGUC
821
GACAAACG CUGAUGAG GCCGUUAGGC CGAA ICAACAUA
3330

471
AUGUUGCC C GUUUGUCC
822
GGACAAAC CUGAUGAG GCCGUUAGGC CGAA IGCAACAU
3331

479
CGUUUGUC C UCUAAUUC
823
GAAUUAGA CUGAUGAG GCCGUUAGGC CGAA IACAAACG
3332

480
GUUUGUCC U CUAAUUCC
824
GGAAUUAG CUGAUGAG GCCGUUAGGC CGAA IGACAAAC
3333

482
UUGUCCUC U AAUUCCAG
825
CUGGAAUU CUGAUGAG GCCGUUAGGC CGAA IAGGACAA
3334

488
UCUAAUUC C AGGAUCAU
826
AUGAUCCU CUGAUGAG GCCGUUAGGC CGAA IAAUUAGA
3335

489
CUAAUUCC A GGAUCAUC
827
GAUGAUCC CUGAUGAG GCCGUUAGGC CGAA IGAAUUAG
3336

495
CCAGGAUC A UCAACAAC
828
GUUGUUGA CUGAUGAG GCCGUUAGGC CGAA IAUCCUGG
3337

498
GGAUCAUC A ACAACCAG
829
CUGGUUGU CUGAUGAG GCCGUUAGGC CGAA IAUGAUCC
3338

501
UCAUCAAC A ACCAGCAC
830
GUGCUGGU CUGAUGAG GCCGUUAGGC CGAA IUUGAUGA
3339

504
UCAACAAC C AGCACCGG
831
CCGGUGCU CUGAUGAG GCCGUUAGGC CGAA IUUGUUGA
3340

505
CAACAACC A GCACCGGA
832
UCCGGUGC CUGAUGAG GCCGUUAGGC CGAA IGUUGUUG
3341

508
CAACCAGC A CCGGACCA
833
UGGUCCGG CUGAUGAG GCCGUUAGGC CGAA ICUGGUUG
3342

510
ACCAGCAC C GGACCAUG
834
CAUGGUCC CUGAUGAG GCCGUUAGGC CGAA IUGCUGGU
3343

515
CACCGGAC C AUGCAAAA
835
UUUUGCAU CUGAUGAG GCCGUUAGGC CGAA IUCCGGUG
3344

516
ACCGGACC A UGCAAAAC
836
GUUUUGCA CUGAUGAG GCCGUUAGGC CGAA IGUCCGGU
3345

520
GACCAUGC A AAACCUGC
837
GCAGGUUU CUGAUGAG GCCGUUAGGC CGAA ICAUGGUC
3346

525
UGCAAAAC C UGCACAAC
838
GUUGUGCA CUGAUGAG GCCGUUAGGC CGAA IUUUUGCA
3347

526
GCAAAACC U GCACAACU
839
AGUUGUGC CUGAUGAG GCCGUUAGGC CGAA IGUUUUGC
3348

529
AAACCUGC A CAACUCCU
840
AGGAGUUG CUGAUGAG GCCGUUAGGC CGAA ICAGGUUU
3349

531
ACCUGCAC A ACUCCUGC
841
GCAGGAGU CUGAUGAG GCCGUUAGGC CGAA IUGCAGGU
3350

534
UGCACAAC U CCUGCUCA
842
UGAGCAGG CUGAUGAG GCCGUUAGGC CGAA IUUGUGCA
3351

536
CACAACUC C UGCUCAAG
843
UUUGAGCA CUGAUGAG GCCGUUAGGC CGAA IAGUUGUG
3352

537
ACAACUCC U GCUCAAGG
844
CCUUGAGC CUGAUGAG GCCGUUAGGC CGAA IGAGUUGU
3353

540
ACUCCUGC U CAAGGAAC
845
GUUCCUUG CUGAUGAG GCCGUUAGGC CGAA ICAGGAGU
3354

542
UCCUGCUC A AGGAACCU
846
AGGUUCCU CUGAUGAG GCCGUUAGGC CGAA IAGCAGGA
3355

549
CAAGGAAC C UCUAUGUU
847
AACAUAGA CUGAUGAG GCCGUUAGGC CGAA IUUCCUUG
3356

550
AAGGAACC U CUAUGUUU
848
AAACAUAG CUGAUGAG GCCGUUAGGC CGAA IGUUCCUU
3357

552
GGAACCUC U AUGUUUCC
849
GGAAACAU CUGAUGAG GCCGUUAGGC CGAA IAGGUUCC
3358

560
UAUGUUUC C CUCAUGUU
850
AACAUGAG CUGAUGAG GCCGUUAGGC CGAA IAAACAUA
3359

561
AUGUUUCC C UCAUGUUG
851
CAACAUGA CUGAUGAG GCCGUUAGGC CGAA IGAAACAU
3360

562
UGUUUCCC U CAUGUUGC
852
GCAACAUG CUGAUGAG GCCGUUAGGC CGAA IGGAAACA
3361

564
UUUCCCUC A UGUUGCUG
853
UAGCAACA CUGAUGAG GCCGUUAGGC CGAA IAGGGAAA
3362

571
CAUGUUGC U GUACAAAA
854
UUUUGUAC CUGAUGAG GCCGUUAGGC CGAA ICAACAUG
3363

576
UGCUGUAC A AAACCUAC
855
GUAGGUUU CUGAUGAG GCCGUUAGGC CGAA IUACAGCA
3364

581
UACAAAAC C UACGGACG
856
CGUCCGUA CUGAUGAG GCCGUUAGGC CGAA IUUUUGUA
3365

582
ACAAAACC U ACGGACGG
857
CCGUCCGU CUGAUGAG GCCGUUAGGC CGAA IGUUUUGU
3366

595
ACGGAAAC U GCACCUGU
858
ACAGGUGC CUGAUGAG GCCGUUAGGC CGAA IUUUCCGU
3367

598
GAAACUGC A CCUGUAUU
859
AAUACAGG CUGAUGAG GCCGUUAGGC CGAA ICAGUUUC
3368

600
AACUGCAC C UGUAUUCC
860
GGAAUACA CUGAUGAG GCCGUUAGGC CGAA IUGCAGUU
3369

601
ACUGCACC U GUAUUCCC
861
GGGAAUAC CUGAUGAG GCCGUUAGGC CGAA IGUGCAGU
3370

608
CUGUAUUC C CAUCCCAU
862
AUGGGAUG CUGAUGAG GCCGUUAGGC CGAA IAAUACAG
3371

609
UGUAUUCC C AUCCCAUC
863
GAUGGGAU CUGAUGAG GCCGUUAGGC CGAA IGAAUACA
3372

610
GUAUUCCC A UCCCAUCA
864
UGAUGGGA CUGAUGAG GCCGUUAGGC CGAA IGGAAUAC
3373

613
UUCCCAUC C CAUCAUCU
865
AGAUGAUG CUGAUGAG GCCGUUAGGC CGAA IAUGGGAA
3374

614
UCCCAUCC C AUCAUCUU
866
AAGAUGAU CUGAUGAG GCCGUUAGGC CGAA IGAUGUGA
3375

615
CCCAUCCC A UCAUCUUG
867
CAAGAUGA CUGAUGAG GCCGUUAGGC CGAA IGGAUGGG
3376

618
AUCCCAUC A UCUUGGGC
868
GCCCAAGA CUGAUGAG GCCGUUAGGC CGAA IAUGGGAU
3377

621
CCAUCAUC U UGGGCUUU
869
AAAGCCCA CUGAUGAG GCCGUUAGGC CGAA IAUGAUGG
3378

627
UCUUGGGC U UUCGCAAA
870
UUUGCGAA CUGAUGAG GCCGUUAGGC CGAA ICCCAAGA
3379

633
GCUUUCGC A AAAUACCU
871
AGGUAUUU CUGAUGAG GCCGUUAGGC CGAA ICGAAAGC
3380

640
CAAAAUAC C UAUGGGAG
872
CUCCCAUA CUGAUGAG GCCGUUAGGC CGAA IUAUUUUG
3381

641
AAAAUACC U AUGGGAGU
873
ACUCCCAU CUGAUGAG GCCGUUAGGC CGAA IGUAUUUU
3382

654
GAGUGGGC C UCAGUCCG
874
CGGACUGA CUGAUGAG GCCGUUAGGC CGAA ICCCACUC
3383

655
AGUGGGCC U CAGUCCGU
875
ACGGACUG CUGAUGAG GCCGUUAGGC CGAA IGCCCACU
3384

657
UGGGCCUC A GUCCGUUU
876
AAACGGAC CUGAUGAG GCCGUUAGGC CGAA IAGGCCCA
3385

661
CCUCAGUC C GUUUCUCU
877
AGAGAAAC CUGAUGAG GCCGUUAGGC CGAA IACUGAGG
3386

667
UCCGUUUC U CUUGGCUC
878
GAGCCAAG CUGAUGAG GCCGUUAGGC CGAA IAAACGGA
3387

669
CGUUUCUC U UGGCUCAG
879
CUGAGCCA CUGAUGAG GCCGUUAGGC CGAA IAGAAACG
3388

674
CUCUUGGC U CAGUUUAC
880
GUAAACUG CUGAUGAG GCCGUUAGGC CGAA ICCAAGAG
3389

676
CUUGGCUC A GUUUACUA
881
UAGUAAAC CUGAUGAG GCCGUUAGGC CGAA IAGCCAAG
3390

683
UAGUUUAC U AGUGCCAU
882
AUGGCACU CUGAUGAG GCCGUUAGGC CGAA IUAAACUG
3391

689
ACUAGUGC C AUUUGUUC
883
GAACAAAU CUGAUGAG GCCGUUAGGC CGAA ICACUAGU
3392

690
CUAGUGCC A UUUGUUCA
884
UGAACAAA CUGAUGAG GCCGUUAGGC CGAA IGCACUAG
3393

698
AUUUGUUC A GUGGUUCG
885
CGAACCAC CUGAUGAG GCCGUUAGGC CGAA IAACAAAU
3394

713
UGUAGGGC U UUCCCCCA
886
UGGGGGAA CUGAUGAG GCCGUUAGGC CGAA ICCCUACG
3395

717
GGGCUUUC C CCCACUGU
887
ACAGUGGG CUGAUGAG GCCGUUAGGC CGAA IAAAGCCC
3396

718
GGCUUUCC C CCACUGUC
888
GACAGUGG CUGAUGAG GCCGUUAGGC CGAA IGAAAGCC
3397

719
GCUUUCCC C CACUGUCU
889
AGACAGUG CUGAUGAG GCCGUUAGGC CGAA IGGAAAGC
3398

720
CUUUCCCC C ACUGUCUG
890
CAGACAGU CUGAUGAG GCCGUUAGGC CGAA IGGGAAAG
3399

721
UUUCCCCC A CUGUCUGG
891
CCAGACAG CUGAUGAG GCCGUUAGGC CGAA IGGGGAAA
3400

723
UCCCCCAC U GUCUGGCU
892
AGCCAGAC CUGAUGAG GCCGUUAGGC CGAA IUGGGGGA
3401

727
CCACUGUC U GGCUUUCA
893
UGAAAGCC CUGAUGAG GCCGUUAGGC CGAA IACAGUGG
3402

731
UGUCUGGC U UUCAGUUA
894
UAACUGAA CUGAUGAG GCCGUUAGGC CGAA ICCAGACA
3403

735
UGGCUUUC A GUUAUAUG
895
CAUAUAAC CUGAUGAG GCCGUUAGGC CGAA IAAAGCCA
3404

764
UUGGGGGC C AAGUCUGU
896
ACAGACUU CUGAUGAG GCCGUUAGGC CGAA ICCCCCAA
3405

765
UGGGGGCC A AGUCUGUA
897
UACAGACU CUGAUGAG GCCGUUAGGC CGAA IGCCCCCA
3406

770
GCCAAGUC U GUACAACA
898
UGUUGUAC CUGAUGAG GCCGUUAGGC CGAA IACUUGGC
3407

775
GUCUGUAC A ACAUCUUG
899
CAAGAUGU CUGAUGAG GCCGUUAGGC CGAA IUACAGAC
3408

778
UGUACAAC A UCUUGAGU
900
ACUCAAGA CUGAUGAG GCCGUUAGGC CGAA IUUGUACA
3409

781
ACAACAUC U UGAGUCCC
901
GGGACUCA CUGAUGAG GCCGUUAGGC CGAA IAUGUUGU
3410

788
CUUGAGUC C CUUUAUGC
902
GCAUAAAG CUGAUGAG GCCGUUAGGC CGAA IACUCAAG
3411

789
UUGAGUCC C UUUAUGCC
903
GGCAUAAA CUGAUGAG GCCGUUAGGC CGAA IGACUCAA
3412

790
UGAGUCCC U UUAUGCCG
904
CGGCAUAA CUGAUGAG GCCGUUAGGC CGAA IGGACUCA
3413

797
CUUUAUGC C GCUGUUAC
905
GUAACAGC CUGAUGAG GCCGUUAGGC CGAA ICAUAAAG
3414

800
UAUGCCGC U GUUACCAA
906
UUGGUAAC CUGAUGAG GCCGUUAGGC CGAA ICGGCAUA
3415

806
GCUGUUAC C AAUUUUCU
907
AGAAAAUU CUGAUGAG GCCGUUAGGC CGAA IUAACAGC
3416

807
CUGUUACC A AUUUUCUU
908
AAGAAAAU CUGAUGAG GCCGUUAGGC CGAA IGUAACAG
3417

814
CAAUUUUC U UUUGUCUU
909
AAGACAAA CUGAUGAG GCCGUUAGGC CGAA IAAAAUUG
3418

821
CUUUUGUC U UUGGGUAU
910
AUACCCAA CUGAUGAG GCCGUUAGGC CGAA IACAAAAG
3419

832
GGGUAUAC A UUUAAACC
911
GGUUUAAA CUGAUGAG GCCGUUAGGC CGAA IUAUACCC
3420

840
AUUUAAAC C CUCACAAA
912
GUGGUGAG CUGAUGAG GCCGUUAGGC CGAA IUUUAAAU
3421

841
UUUAAACC C UCACAAAA
913
UUUUGUGA CUGAUGAG GCCGUUAGGC CGAA IGUUUAAA
3422

842
UUAAACCC U CACAAAAC
914
GUUUUGUG CUGAUGAG GCCGUUAGGC CGAA IGGUUUAA
3423

844
AAACCCUC A CAAAACAA
915
UUGUUUUG CUGAUGAG GCCGUUAGGC CGAA IAGGGUUU
3424

846
ACCCUCAC A AAACAAAA
916
UUUUGUUU CUGAUGAG GCCGUUAGGC CGAA IUGAGGGU
3425

851
CACAAAAC A AAAAGAUG
917
CAUCUUUU CUGAUGAG GCCGUUAGGC CGAA IUUUUGUG
3426

869
GGAUAUUC C CUUAACUU
918
AAGUUAAG CUGAUGAG GCCGUUAGGC CGAA IAAUAUCC
3427

870
GAUAUUCC C UUAACUUC
919
GAAGUUAA CUGAUGAG GCCGUUAGGC CGAA IGAAUAUC
3428

871
AUAUUCCC U UAACUUCA
920
UGAAGUUA CUGAUGAG GCCGUUAGGC CGAA IGGAAUAU
3429

876
CCCUUAAC U UCAUGGGA
921
UCCCAUGA CUGAUGAG GCCGUUAGGC CGAA IUUAAGGG
3430

879
UUAACUUC A UGGGAUAU
922
AUAUCCCA CUGAUGAG GCCGUUAGGC CGAA IAAGUUAA
3431

906
GUUGGGGC A CAUUGCCA
923
UGGCAAUG CUGAUGAG GCCGUUAGGC CGAA ICCCCAAC
3432

908
UGGGGCAC A UUGCCACA
924
UGUGGCAA CUGAUGAG GCCGUUAGGC CGAA IUGCCCCA
3433

913
UACAUUGC C ACAGGAAC
925
GUUCCUGU CUGAUGAG GCCGUUAGGC CGAA ICAAUGUG
3434

914
ACAUUGCC A CAGGAACA
926
UGUUCCUG CUGAUGAG GCCGUUAGGC CGAA IGCAAUGU
3435

916
AUUGCCAC A GGAACAUA
927
UAUGUUCC CUGAUGAG GCCGUUAGGC CGAA IUGGCAAU
3436

922
ACAGGAAC A UAUUGUAC
928
GUACAAUA CUGAUGAG GCCGUUAGGC CGAA IUUCCUGU
3437

931
UAUUGUAC A AAAAAUCA
929
UGAUUUUU CUGAUGAG GCCGUUAGGC CGAA IUACAAUA
3438

939
AAAAAAUC A AAAUGUGU
930
ACACAUUU CUGAUGAG GCCGUUAGGC CGAA IAUUUUUU
3439

958
UAGGAAAC U UCCUGUAA
931
UUACAGGA CUGAUGAG GCCGUUAGGC CGAA IUUUCCUA
3440

961
GAAACUUC C UGUAAACA
932
UGUUUACA CUGAUGAG GCCGUUAGGC CGAA IAAGUUUC
3441

962
AAACUUCC U GUAAACAG
933
UUGUUUAC CUGAUGAG GCCGUUAGGC CGAA IGAAGUUU
3442

969
CUGUAAAC A GGCCUAUU
934
AAUAGGCC CUGAUGAG GCCGUUAGGC CGAA IUUUACAG
3443

973
AAACAGGC C UAUUGAUU
935
AAUCAAUA CUGAUGAG GCCGUUAGGC CGAA ICCUGUUU
3444

974
AACAGGCC U AUUGAUUG
936
CAAUCAAU CUGAUGAG GCCGUUAGGC CGAA IGCCUGUU
3445

994
AGUAUGUC A ACGAAUUG
937
CAAUUCGU CUGAUGAG GCCGUUAGGC CGAA IACAUACU
3446

1009
UGUGGGUC U UUUGGGGU
938
ACCCCAAA CUGAUGAG GCCGUUAGGC CGAA IACCCACA
3447

1022
GGGUUUGC C GCCCCUUU
939
AAAGGGGC CUGAUGAG GCCGUUAGGC CGAA ICAAACCC
3448

1025
UUUGCCGC C CCUUUCAC
940
GUGAAAGG CUGAUGAG GCCGUUAGGC CGAA ICGGCAAA
3449

1026
UUGCCGCC C CUUUCACG
941
CGUGAAAG CUGAUGAG GCCGUUAGGC CGAA IGCGGCAA
3450

1027
UGCCGCCC C UUUCACGC
942
GCGUGAAA CUGAUGAG GCCGUUAGGC CGAA IGGCGGCA
3451

1028
GCCGCCCC U UUCACGCA
943
UGCGUGAA CUGAUGAG GCCGUUAGGC CGAA IGGGCGGC
3452

1032
CCCCUUUC A CGCAAUGU
944
ACAUUGCG CUGAUGAG GCCGUUAGGC CGAA IAAAGGGG
3453

1036
UUUCACGC A AUGUGGAU
945
AUCCACAU CUGAUGAG GCCGUUAGGC CGAA ICGUGAAA
3454

1049
GGAUAUUC U GCUUUAAU
946
AUUAAAGC CUGAUGAG GCCGUUAGGC CGAA IAAUAUCC
3455

1052
UAUUCUGC U UUAAUGCC
947
GGCAUUAA CUGAUGAG GCCGUUAGGC CGAA ICAGAAUA
3456

1060
UUUAAUGC C UUUAUAUG
948
CAUAUAAA CUGAUGAG GCCGUUAGGC CGAA ICAUUAAA
3457

1061
UUAAUGCC U UUAUAUGC
949
GCAUAUAA CUGAUGAG GCCGUUAGGC CGAA IGCAUUAA
3458

1070
UUAUAUGC A UGCAUACA
950
UGUAUGCA CUGAUGAG GCCGUUAGGC CGAA ICAUAUAA
3459

1074
AUGCAUGC A UACAAGCA
951
UGCUUGUA CUGAUGAG GCCGUUAGGC CGAA ICAUGCAU
3460

1078
AUGCAUAC A AGCAAAAC
952
GUUUUGCU CUGAUGAG GCCGUUAGGC CGAA IUAUGCAU
3461

1082
AUACAAGC A AAACAGGC
953
GCCUGUUU CUGAUGAG GCCGUUAGGC CGAA ICUUGUAU
3462

1087
AGCAAAAC A GGCUUUUA
954
UAAAAGCC CUGAUGAG GCCGUUAGGC CGAA IUUUUGCU
3463

1091
AAACAGGC U UUUACUUU
955
AAAGUAAA CUGAUGAG GCCGUUAGGC CGAA ICCUGUUU
3464

1097
GCUUUUAC U UUCUCGCC
956
GGCGAGAA CUGAUGAG GCCGUUAGGC CGAA IUAAAAGC
3465

1101
UUACUUUC U CGCCAACU
957
AGUUGGCG CUGAUGAG GCCGUUAGGC CGAA IAAAGUAA
3466

1105
UUUCUCGC C AACUUACA
958
UGUAAGUU CUGAUGAG GCCGUUAGGC CGAA ICGAGAAA
3467

1106
UUCUCGCC A ACUUACAA
959
UUGUAAGU CUGAUGAG GCCGUUAGGC CGAA IGCGAGAA
3468

1109
UCGCCAAC U UACAAGGC
960
GCCUUGUA CUGAUGAG GCCGUUAGGC CGAA IUUGGCGA
3469

1113
UAACUUAC A AGGCCUUU
961
AAAGGCCU CUGAUGAG GCCGUUAGGC CGAA IUAAGUUG
3470

1118
UACAAGGC C UUUCUAAG
962
CUUAGAAA CUGAUGAG GCCGUUAGGC CGAA ICCUUGUA
3471

1119
ACAAGGCC U UUCUAAGU
963
ACUUAGAA CUGAUGAG GCCGUUAGGC CGAA IGCCUUGU
3472

1123
GGCCUUUC U AAGUAAAC
964
GUUUACUU CUGAUGAG GCCGUUAGGC CGAA IAAAGGCC
3473

1132
AAGUAAAC A GUAUGUGA
965
UCACAUAC CUGAUGAG GCCGUUAGGC CGAA IUUUACUU
3474

1143
AUGUGAAC C UUUACCCC
966
GGGGUAAA CUGAUGAG GCCGUUAGGC CGAA IUUCACAU
3475

1144
UGUGAACC U UUACCCCG
967
CGGGGUAA CUGAUGAG GCCGUUAGGC CGAA IGUUCACA
3476

1149
ACCUUUAC C CCGUUGCU
968
AGCAACGG CUGAUGAG GCCGUUAGGC CGAA IUAAAGGU
3477

1150
CCUUUACC C CGUUGCUC
969
GAGCAACG CUGAUGAG GCCGUUAGGC CGAA IGUAAAGG
3478

1151
CUUUACCC C GUUGCUCG
970
CGAGCAAC CUGAUGAG GCCGUUAGGC CGAA IGGUAAAG
3479

1157
CCCGUUGC U CGGCAACG
971
CGUUGCCG CUGAUGAG GCCGUUAGGC CGAA ICAACGGG
3480

1162
UGCUCGGC A ACGGCCUG
972
CAGGCCGU CUGAUGAG GCCGUUAGGC CGAA ICCGAGCA
3481

1168
GCAACGGC C UGGUCUAU
973
AUAGACCA CUGAUGAG GCCGUUAGGC CGAA ICCGUUGC
3482

1169
CAACGGCC U GGUCUAUG
974
CAUAGACC CUGAUGAG GCCGUUAGGC CGAA IGCCGUUG
3483

1174
GCCUGGUC U AUGCCAAG
975
CUUGGCAU CUGAUGAG GCCGUUAGGC CGAA IACCAGGC
3484

1179
GUCUAUGC C AAGUGUUU
976
AAACACUU CUGAUGAG GCCGUUAGGC CGAA ICAUAGAC
3485

1180
UCUAUGCC A AGUGUUUG
977
CAAACACU CUGAUGAG GCCGUUAGGC CGAA IGCAUAGA
3486

1190
GUGUUUGC U GACGCAAC
978
GUUGCGUC CUGAUGAG GCCGUUAGGC CGAA ICAAACAC
3487

1196
GCUGACGC A ACCCCCAC
979
GUGGGGGU CUGAUGAG GCCGUUAGGC CGAA ICGUCAGC
3488

1199
GACGCAAC C CCCACUGG
980
CCAGUGGG CUGAUGAG GCCGUUAGGC CGAA IUUGCGUC
3489

1200
ACGCAACC C CCACUGGU
981
ACCAGUGG CUGAUGAG GCCGUUAGGC CGAA IGUUGCGU
3490

1201
CGCAACCC C CACUGGUU
982
AACCAGUG CUGAUGAG GCCGUUAGGC CGAA IGGUUGCG
3491

1202
GCAACCCC C ACUGGUUG
983
UAACCAGU CUGAUGAG GCCGUUAGGC CGAA IGGGUUGC
3492

1203
CAACCCCC A CUGGUUGG
984
CCAACCAG CUGAUGAG GCCGUUAGGC CGAA IGGGGUUG
3493

1205
ACCCCCAC U GGUUGGGG
985
CCCCAACC CUGAUGAG GCCGUUAGGC CGAA IUGGGGGU
3494

1215
GUUGGGGC U UGGCCAUA
986
UAUGGCCA CUGAUGAG GCCGUUAGGC CGAA ICCCCAAC
3495

1220
GGCUUGGC C AUAGGCCA
987
UGGCCUAU CUGAUGAG GCCGUUAGGC CGAA ICCAAGCC
3496

1221
GCUUGGCC A UAGGCCAU
988
AUGGCCUA CUGAUGAG GCCGUUAGGC CGAA IGCCAAGC
3497

1227
CCAUAGGC C AUCAGCGC
989
GCGCUGAU CUGAUGAG GCCGUUAGGC CGAA ICCUAUGG
3498

1228
CAUAGGCC A UCAGCGCA
990
UGCGCUGA CUGAUGAG GCCGUUAGGC CGAA IGCCUAUG
3499

1231
AGGCCAUC A GCGCAUGC
991
GCAUGCGC CUGAUGAG GCCGUUAGGC CGAA IAUGGCCU
3500

1236
AUCAGCGC A UGCGUGGA
992
UCCACGCA CUGAUGAG GCCGUUAGGC CGAA ICGCUGAU
3501

1247
CGUGGAAC C UUUGUGUC
993
GACACAAA CUGAUGAG GCCGUUAGGC CGAA IUUCCACG
3502

1248
GUGGAACC U UUGUGUCU
994
AGACACAA CUGAUGAG GCCGUUAGGC CGAA IGUUCCAC
3503

1256
UUUGUGUC U CCUCUGCC
995
GGCAGAGG CUGAUGAG GCCGUUAGGC CGAA IACACAAA
3504

1258
UGUGUCUC C UCUGCCGA
996
UCGGCAGA CUGAUGAG GCCGUUAGGC CGAA IAGACACA
3505

1259
GUGUCUCC U CUGCCGAU
997
AUCGGCAG CUGAUGAG GCCGUUAGGC CGAA IGAGACAC
3506

1261
GUCUCCUC U GCCGAUCC
998
GGAUCGGC CUGAUGAG GCCGUUAGGC CGAA IAGGAGAC
3507

1264
UCCUCUGC C GAUCCAUA
999
UAUGGAUC CUGAUGAG GCCGUUAGGC CGAA ICAGAGGA
3508

1269
UGCCGAUC C AUACCGCG
1000
CGCGGUAU CUGAUGAG GCCGUUAGGC CGAA IAUCGGCA
3509

1270
GCCGAUCC A UACCGCGG
1001
CCGCGGUA CUGAUGAG GCCGUUAGGC CGAA IGAUCGGC
3510

1274
AUCCAUAC C GCGGAACU
1002
AGUUCCGC CUGAUGAG GCCGUUAGGC CGAA IUAUGGAU
3511

1282
CGCGGAAC U CCUAGCCG
1003
CGGCUAGC CUGAUGAG GCCGUUAGGC CGAA IUUCCGCG
3512

1284
CGGAACUC C UAGCCGCU
1004
AGCGGCUA CUGAUGAG GCCGUUAGGC CGAA IAGUUCCG
3513

1285
GGAACUCC U AGCCGCUU
1005
AAGCGGCU CUGAUGAG GCCGUUAGGC CGAA IGAGUUCC
3514

1289
CUCCUAGC C GCUUGUUU
1006
AAACAAGC CUGAUGAG GCCGUUAGGC CGAA ICUAGGAG
3515

1292
CUAGCCGC U UGUUUUGC
1007
GCAAAACA CUGAUGAG GCCGUUAGGC CGAA ICGGCUAG
3516

1301
UGUUUUGC U CGCAGCAG
1008
CUGCUGCG CUGAUGAG GCCGUUAGGC CGAA ICAAAACA
3517

1305
UUGCUCGC A GCAGGUCU
1009
AGACCUGC CUGAUGAG GCCGUUAGGC CGAA ICGAGCAA
3518

1308
CUCGCAGC A GGUCUGUG
1010
CCCAGACC CUGAUGAG GCCGUUAGGC CGAA ICUGCGAG
3519

1313
ACCAGGUC U GGGGCAAA
1011
UUUGCCCC CUGAUGAG GCCGUUAGGC CGAA IACCUGCU
3520

1319
UCUGGGGC A AAACUCAU
1012
AUGAGGUG CUGAUGAG GCCGUUAGGC CGAA ICCCCAGA
3521

1324
GGCAAAAC U CAUCGGGA
1013
UCCCGAUG CUGAUGAG GCCGUUAGGC CGAA IUUUUGCC
3522

1326
CAAAACUC A UCGGGACU
1014
AGUCCCGA CUGAUGAG GCCGUUAGGC CGAA IAGUUUUG
3523

1334
AUCGGGAC U GACAAUUC
1015
GAAUUGUC CUGAUGAG GCCGUUAGGC CGAA IUCCCGAU
3524

1338
GGACUGAC A AGUCUGUC
1016
GACAGAAU CUGAUGAG GCCGUUAGGC CGAA IUCAGUCC
3525

1343
GACAAUUC U GUCGUGCU
1017
AGCACGAC CUGAUGAG GCCGUUAGGC CGAA IAAUUGUC
3526

1351
UGUCGUGC U CUCCCGCA
1018
UGCGGGAG CUGAUGAG GCCGUUAGGC CGAA ICACGACA
3527

1353
UCGUGCUC U CCCGCAAA
1019
UUUGCGGG CUGAUGAG GCCGUUAGGC CGAA IAGCACGA
3528

1355
GUGCUCUC C CGCAAAUA
1020
UAUUUGCG CUGAUGAG GCCGUUAGGC CGAA IAGAGCAC
3529

1356
UGCUCUCC C GCAAAUAU
1021
AUAUUUGC CUGAUGAG GCCGUUAGGC CGAA IGAGAGCA
3530

1359
UCUCCCGC A AAUAUACA
1022
UGUAUAUU CUGAUGAG GCCGUUAGGC CGAA ICGGGAGA
3531

1367
AAAUAUAC A UCAUUUCC
1023
GGAAAUGA CUGAUGAG GCCGUUAGGC CGAA IUAUAUUU
3532

1370
UAUACAUC A UUUCCAUG
1024
CAUGGAAA CUGAUGAG GCCGUUAGGC CGAA IAUGUAUA
3533

1375
AUCAUUUC C AUGGCUGC
1025
GCAGCCAU CUGAUGAG GCCGUUAGGC CGAA IAAAUGAU
3534

1376
UCAUUUCC A UGGCUGCU
1026
AGCAGCCA CUGAUGAG GCCGUUAGGC CGAA IGAAAUGA
3535

1381
UCCAUGGC U GCUAGGCU
1027
AGCCUAGC CUGAUGAG GCCGUUAGGC CGAA ICCAUGGA
3536

1384
AUGGCUGC U AGGCUGUG
1028
CACAGCCU CUGAUGAG GCCGUUAGGC CGAA ICAGCCAU
3537

1389
UGCUAGGC U GUGCUGCC
1029
GGCAGCAC CUGAUGAG GCCGUUAGGC CGAA ICCUAGCA
3538

1394
GGCUGUGC U GCCAACUG
1030
CAGUUGGC CUGAUGAG GCCGUUAGGC CGAA ICACAGCC
3539

1397
UGUGCUGC C AACUGGAU
1031
AUCCAGUU CUGAUGAG GCCGUUAGGC CGAA ICAGCACA
3540

1398
GUGCUGCC A ACUGGAUC
1032
GAUCCAGU CUGAUGAG GCCGUUAGGC CGAA IGCAGCAC
3541

1401
CUGCCAAC U GGAUCCUA
1033
UAGGAUCC CUGAUGAG GCCGUUAGGC CGAA IUUGGCAG
3542

1407
ACUGGAUC C UACGCGGG
1034
CCCGCGUA CUGAUGAG GCCGUUAGGC CGAA IAUCCAGU
3543

1408
CUGGAUCC U ACGCGGGA
1035
UCCCGCGU CUGAUGAG GCCGUUAGGC CGAA IGAUCCAG
3544

1421
GGGACGUC C UUUGUUUA
1036
UAAACAAA CUGAUGAG GCCGUUAGGC CGAA IACGUCCC
3545

1422
GGACGUCC U GUGUUUAC
1037
GUAAACAA CUGAUGAG GCCGUUAGGC CGAA IGACGUCC
3546

1434
UUUACGUC C CGUCGGCG
1038
CGCCGACG CUGAUGAG GCCGUUAGGC CGAA IACGUAAA
3547

1435
UUACGUCC C GUCGGCGC
1039
GCGCCGAC CUGAUGAG GCCGUUAGGC CGAA IGACGUAA
3548

1444
GUCGGCGC U GAAUCCCG
1040
CGGGAUUC CUGAUGAG GCCGUUAGGC CGAA ICGCCGAC
3549

1450
GCUGAAUC C CGCGGACG
1041
CGUCCGCG CUGAUGAG GCCGUUAGGC CGAA IAUUCAGC
3550

1451
CUGAAUCC C GCGGACGA
1042
UCGUCCGC CUGAUGAG GCCGUUAGGC CGAA IGAGUCAG
3551

1461
CGGACGAC C CCUCCCGG
1043
UCGGGAGG CUGAUGAG GCCGUUAGGC CGAA IUCGUCCG
3552

1462
GGACGACC C CUCCCGGG
1044
CCCGGGAG CUGAUGAG GCCGUUAGGC CGAA IGUCGUCC
3553

1463
GACGACCC C UCCCGGGG
1045
CCCCGGGA CUGAUGAG GCCGUUAGGC CGAA IGGUCGUC
3554

1464
ACGACCCC U CCCGGGGC
1046
GCCCCGGG CUGAUGAG GCCGUUAGGC CGAA IGGGUCGU
3555

1466
GACCCCUC C CGGGGCCG
1047
CGGCCCCG CUGAUGAG GCCGUUAGGC CGAA IAGGGGUC
3556

1467
ACCCCUCC C GGGGCCGC
1048
GCGGCCCC CUGAUGAG GCCGUUAGGC CGAA IGAGGGGU
3557

1473
UCCGGGGC C GCUUGGGG
1049
CCCCAAGC CUGAUGAG GCCGUUAGGC CGAA ICCCCGGG
3558

1476
GGGGCCGC U UGGGGCUC
1050
GAGCCCCA CUGAUGAG GCCGUUAGGC CGAA ICGGCCCC
3559

1483
UUUGGGGC U CUACCGCC
1051
GGCGGUAG CUGAUGAG GCCGUUAGGC CGAA ICCCCAAG
3560

1485
UGGGGCUC U ACCGCCCG
1052
CGGGCGGU CUGAUGAG GCCGUUAGGC CGAA IAGCCCCA
3561

1488
GGCUCUAC C GCCCGCUU
1053
AAGCGGGC CUGAUGAG GCCGUUAGGC CGAA IUAGAGCC
3562

1491
UCUACCGC C CGCUUCUC
1054
GAGAAGCG CUGAUGAG GCCGUUAGGC CGAA ICGGUAGA
3563

1492
CUACCGCC C GCUUCUCC
1055
GGAGAAGC CUGAUGAG GCCGUUAGGC CGAA IGCGGUAG
3564

1495
CCGCCCGC U UCUCCGCC
1056
GGCGGAGA CUGAUGAG GCCGUUAGGC CGAA ICGGGCGG
3565

1498
CCCGCUUC U CCGCCUAU
1057
AUAGGCGG CUGAUGAG GCCGUUAGGC CGAA IAAGCGGG
3566

1500
CGCUUCUC C GCCUAUUG
1058
CAAUAGGC CUGAUGAG GCCGUUAGGC CGAA IAGAAGCG
3567

1503
UUCUCCGC C UAUUGUAC
1059
GUACAAUA CUGAUGAG GCCGUUAGGC CGAA ICGGAGAA
3568

1504
UCUCCGCC U AUUGUACC
1060
GGUACAAU CUGAUGAG GCCGUUAGGC CGAA IGCGGAGA
3569

1512
UAUUGUAC C GACCGUCC
1061
GGACGGUC CUGAUGAG GCCGUUAGGC CGAA IUACAAUA
3570

1516
GUACCGAC C GUCCACGG
1062
CCGUGGAC CUGAUGAG GCCGUUAGGC CGAA IUCGGUAC
3571

1520
CGACCGUC C ACGGGGCG
1063
UGCCCCGU CUGAUGAG GCCGUUAGGC CGAA IACGGUCG
3572

1521
GACCGUCC A CGGGGCGC
1064
GCGCCCCG CUGAUGAG GCCGUUAGGC CGAA IGACGGUC
3573

1530
CGGGGCGC A CCUCUCUU
1065
AAGAGAGG CUGAUGAG GCCGUUAGGC CGAA ICGCCCCG
3574

1532
GGGCGCAC C UCUCUUUA
1066
UAAAGAGA CUGAUGAG GCCGUUAGGC CGAA IUGCGCCC
3575

1533
GGCGCACC U CUCUUUAC
1067
GUAAAGAG CUGAUGAG GCCGUUAGGC CGAA IGUGCGCC
3576

1535
CGCACCUC U CUUUACGC
1068
GCGUAAAG CUGAUGAG GCCGUUAGGC CGAA IAGGUGCG
3577

1537
CACCUCUC U UUACGCGG
1069
CCGCGUAA CUGAUGAG GCCGUUAGGC CGAA IAGAGGUG
3578

1548
ACGCGGAC U CCCCGUCU
1070
AGACGGGG CUGAUGAG GCCGUUAGGC CGAA IUCCGCGU
3579

1550
UCGGACUC C CCGUCUGU
1071
ACAGACGG CUGAUGAG GCCGUUAGGC CGAA IAGUCCGC
3580

1551
CGGACUCC C CGUCUGUG
1072
CACAGACG CUGAUGAG GCCGUUAGGC CGAA IGAGUCCG
3581

1552
GGACUCCC C GUCUGUGC
1073
GCACAGAC CUGAUGAG GCCGUUAGGC CGAA IGGAGUCC
3582

1556
UCCCCGUC U GUGCCUUC
1074
GAAGGCAC CUGAUGAG GCCGUUAGGC CGAA IACGGGGA
3583

1561
GUCUGUGC C UUCUCAUC
1075
GAUGAGAA CUGAUGAG GCCGUUAGGC CGAA ICACAGAC
3584

1562
UCUGUGCC U UCUCAUCU
1076
AGAUGAGA CUGAUGAG GCCGUUAGGC CGAA IGCACAGA
3585

1565
GUGCCUUC U CAUCUGCC
1077
GGCAGAUG CUGAUGAG GCCGUUAGGC CGAA IAAGGCAC
3586

1567
GCCUUCUC A UCUGCCGG
1078
CCGGCAGA CUGAUGAG GCCGUUAGGC CGAA IAGAAGGC
3587

1570
UUCUCAUC U GCCGGACC
1079
GGUCCGGC CUGAUGAG GCCGUUAGGC CGAA IAUGAGAA
3588

1573
UCAUCUGC C GGACCGUG
1080
CACGGUCC CUGAUGAG GCCGUUAGGC CGAA ICAGAUGA
3589

1578
UGCCGGAC C GUGUGCAC
1081
GUGCACAC CUGAUGAG GCCGUUAGGC CGAA IUCCGGCA
3590

1585
CCGUGUGC A CUUCGCUU
1082
AAGCGAAG CUGAUGAG GCCGUUAGGC CGAA ICACACGG
3591

1587
GUGUGCAC U UCGCUUCA
1083
UGAAGCGA CUGAUGAG GCCGUUAGGC CGAA IUGCACAC
3592

1592
CACUUCGC U UCACCUCU
1084
AGAGGUGA CUGAUGAG GCCGUUAGGC CGAA ICGAAGUG
3593

1595
UUCGCUUC A CCUCUGCA
1085
UGCAGAGG CUGAUGAG GCCGUUAGGC CGAA IAAGCGAA
3594

1597
CGCUUCAC C UCUGCACG
1086
CGUGCAGA CUGAUGAG GCCGUUAGGC CGAA IUGAAGCG
3595

1598
GCUUCACC U CUGCACGU
1087
ACGUGCAG CUGAUGAG GCCGUUAGGC CGAA IGUGAAGC
3596

1600
UUCACCUC U GCACGUCG
1088
CGACGUGC CUGAUGAG GCCGUUAGGC CGAA IAGGUGAA
3597

1603
ACCUCUGC A CGUCGCAU
1089
AUGCGACG CUGAUGAG GCCGUUAGGC CGAA ICAGAGGU
3598

1610
CACGUCGC A UGGAGACC
1090
GGUCUCCA CUGAUGAG GCCGUUAGGC CGAA ICGACGUG
3599

1618
AUGGAGAC C ACCGUGAA
1091
UUCACGGU CUGAUGAG GCCGUUAGGC CGAA IUCUCCAU
3600

1619
UGGAGACC A CCGUGAAC
1092
GUUCACGG CUGAUGAG GCCGUUAGGC CGAA IGUCUCCA
3601

1621
GAGACCAC C GUGAACGC
1093
GCGUUCAC CUGAUGAG GCCGUUAGGC CGAA IUGGUCUC
3602

1630
GUGAACGC C CACAGGAA
1094
UUCCUGUG CUGAUGAG GCCGUUAGGC CGAA ICGUUCAC
3603

1631
UGAACGCC C ACAGGAAC
1095
GUUCCUGU CUGAUGAG GCCGUUAGGC CGAA IGCGUUCA
3604

1632
GAACGCCC A CAGGAACC
1096
GGUUCCUG CUGAUGAG GCCGUUAGGC CGAA IGGCGUUC
3605

1634
ACGCCCAC A GGAACCUG
1097
CAGGUUCC CUGAUGAG GCCGUUAGGC CGAA IUGGGCGU
3606

1640
ACAGGAAC C UGCCCAAG
1098
CUUGGGCA CUGAUGAG GCCGUUAGGC CGAA IUUCCUGU
3607

1641
CAGGAACC U GCCCAAGG
1099
CCUUGGGC CUGAUGAG GCCGUUAGGC CGAA IGUUCCUG
3608

1644
GAACCUGC C CAAGGUCU
1100
AGACCUUG CUGAUGAG GCCGUUAGGC CGAA ICAGGUUC
3609

1645
AACCUGCC C AAGGUCUU
1101
AAGACCUU CUGAUGAG GCCGUUAGGC CGAA IGCAGGUU
3610

1646
ACCUGCCC A AGGUCUUG
1102
CAAGACCU CUGAUGAG GCCGUUAGGC CGAA IGGCAGGU
3611

1652
CCAAGGUC U UGCAUAAG
1103
UUUAUGCA CUGAUGAG GCCGUUAGGC CGAA IACCUUGG
3612

1656
GGUCUUGC A UAAGAGGA
1104
UCCUCUUA CUGAUGAG GCCGUUAGGC CGAA ICAAGACC
3613

1666
AAGAGGAC U CUUGGACU
1105
AGUCCAAG CUGAUGAG GCCGUUAGGC CGAA IUCCUCUU
3614

1668
GAGGACUC U UGGACUUU
1106
AAAGUCCA CUGAUGAG GCCGUUAGGC CGAA IAGUCCUC
3615

1674
UCUUGGAC U UUCAGCAA
1107
UUGCUGAA CUGAUGAG GCCGUUAGGC CGAA IUCCAAGA
3616

1678
GGACUUUC A GCAAUGUC
1108
GACAUUGC CUGAUGAG GCCGUUAGGC CGAA IAAAGUCC
3617

1681
CUUUCAGC A AUGUCAAC
1109
GUUGACAU CUGAUGAG GCCGUUAGGC CGAA ICUGAAAG
3618

1687
GCAAUGUC A ACGACCGA
1110
UCGGUCGU CUGAUGAG GCCGUUAGGC CGAA IACAUUGC
3619

1693
UCAACGAC C GACCUUGA
1111
UCAAGGUC CUGAUGAG GCCGUUAGGC CGAA IUCGUUGA
3620

1697
CGACCGAC C UUGAGGCA
1112
UGCCUCAA CUGAUGAG GCCGUUAGGC CGAA IUCGGUCG
3621

1698
GACCGACC U UGAGGCAU
1113
AUGCCUCA CUGAUGAG GCCGUUAGGC CGAA IGUCGGUC
3622

1705
CUUGAGGC A UACUUCAA
1114
UUGAAGUA CUGAUGAG GCCGUUAGGC CGAA ICCUCAAG
3623

1709
AGGCAUAC U UCAAAGAC
1115
GUCUUUGA CUGAUGAG GCCGUUAGGC CGAA IUAUGCCU
3624

1712
CAUACUUC A AAGACUGU
1116
ACAGUCUU CUGAUGAG GCCGUUAGGC CGAA IAAGUAUG
3625

1718
UCAAAGAC U GUGUGUUU
1117
AAACACAC CUGAUGAG GCCGUUAGGC CGAA IUCUUUGA
3626

1769
UAAAGGUC U UUGUACUA
1118
UAGUACAA CUGAUGAG GCCGUUAGGC CGAA IACCUUUA
3627

1776
CUUUGUAC U AGGAGGCU
1119
AGCCUCCU CUGAUGAG GCCGUUAGGC CGAA IUACAAAG
3628

1784
UAGGAGGC U GUAGGCAU
1120
AUGCCUAC CUGAUGAG GCCGUUAGGC CGAA ICCUCCUA
3629

1791
CUGUAGGC A UAAAUUGG
1121
CCAAUUUA CUGAUGAG GCCGUUAGGC CGAA ICCUACAG
3630

1807
GUGUGUUC A CCAGCACC
1122
GGUGCUGG CUGAUGAG GCCGUUAGGC CGAA IAACACAC
3631

1809
GUGUUCAC C AGCACCAU
1123
AUGGUGCU CUGAUGAG GCCGUUAGGC CGAA IUGAACAC
3632

1810
UGUUCACC A GCACCAUG
1124
CAUGGUGC CUGAUGAG GCCGUUAGGC CGAA IGUGAACA
3633

1813
UCACCAGC A CCAUGCAA
1125
UUGCAUGG CUGAUGAG GCCGUUAGGC CGAA ICUGGUGA
3634

1815
ACCAGCAC C AUGCAACU
1126
AGUUGCAU CUGAUGAG GCCGUUAGGC CGAA IUGCUGGU
3635

1816
CCAGCACC A UGCAACUU
1127
AAGUUGCA CUGAUGAG GCCGUUAGGC CGAA IGUGCUGG
3636

1820
CACCAUGC A ACUUUUUC
1128
GAAAAAGU CUGAUGAG GCCGUUAGGC CGAA ICAUGGUG
3637

1823
CAUGCAAC U UUUUCACC
1129
GGUGAAAA CUGAUGAG GCCGUUAGGC CGAA IUUGCAUG
3638

1829
ACUUUUUC A CCUCUGCC
1130
GGCAGAGG CUGAUGAG GCCGUUAGGC CGAA IAAAAAGU
3639

1831
UUUUUCAC C UCUGCCUA
1131
UAGGCAGA CUGAUGAG GCCGUUAGGC CGAA IUGAAAAA
3640

1832
UUUUCACC U CUGCCUAA
1132
UUAGGCAG CUGAUGAG GCCGUUAGGC CGAA IGUGAAAA
3641

1834
UUCACCUC U GCCUAAUC
1133
GAUUAGGC CUGAUGAG GCCGUUAGGC CGAA IAGGUGAA
3642

1837
ACCUCUGC C UAAUCAUC
1134
GAUGAUUA CUGAUGAG GCCGUUAGGC CGAA ICAGAGGU
3643

1838
CCUCUGCC U AAUCAUCU
1135
AGAUGAUU CUGAUGAG GCCGUUAGGC CGAA IGCAGAGG
3644

1843
GCCUAAUC A UCUCAUGU
1136
ACAUGAGA CUGAUGAG GCCGUUAGGC CGAA IAUUAGGC
3645

1846
UAAUCAUC U CAUGUUCA
1137
UGAACAUG CUGAUGAG GCCGUUAGGC CGAA IAUGAUUA
3646

1848
AUCAUCUC A UGUUCAUG
1138
CAUGAACA CUGAUGAG GCCGUUAGGC CGAA IAGAUGAU
3647

1854
UCAUGUUC A UGUCCUAC
1139
GUAGGACA CUGAUGAG GCCGUUAGGC CGAA IAACAUGA
3648

1859
UUCAUGUC C UACUGUUC
1140
GAACAGUA CUGAUGAG GCCGUUAGGC CGAA IACAUGAA
3649

1860
UCAUGUCC U ACUGUUCA
1141
UGAACAGU CUGAUGAG GCCGUUAGGC CGAA IGACAUGA
3650

1863
UGUCCUAC U GUUCAAGC
1142
GCUUGAAC CUGAUGAG GCCGUUAGGC CGAA IUAGGACA
3651

1868
UACUGUUC A AGCCUCCA
1143
UGGAGGCU CUGAUGAG GCCGUUAGGC CGAA IAACAGUA
3652

1872
GUUCAAGC C UCCAAGCU
1144
AGCUUGGA CUGAUGAG GCCGUUAGGC CGAA ICUUGAAC
3653

1873
UUCAAGCC U CCAAGCUG
1145
CAGCUUGG CUGAUGAG GCCGUUAGGC CGAA IGCUUGAA
3654

1875
CAAGCCUC C AAGCUGUG
1146
CACAGCUU CUGAUGAG GCCGUUAGGC CGAA IAGGCUUG
3655

1876
AAGCCUCC A AGCUGUGC
1147
GCACAGCU CUGAUGAG GCCGUUAGGC CGAA IGAGGCUU
3656

1880
CUCCAAGC U GUGCCUUG
1148
CAAGGCAC CUGAUGAG GCCGUUAGGC CGAA ICUUGGAG
3657

1885
AGCUGUGC C UUGGGUGG
1149
CCACCCAA CUGAUGAG GCCGUUAGGC CGAA ICACAGCU
3658

1886
GCUGUGCC U UGGGUGGC
1150
GCCACCCA CUGAUGAG GCCGUUAGGC CGAA IGCACAGC
3659

1895
UGGGUGGC U UUGGGGCA
1151
UGCCCCAA CUGAUGAG GCCGUUAGGC CGAA ICCACCCA
3660

1903
UUUGGGGC A UGGACAUU
1152
AAUGUCCA CUGAUGAG GCCGUUAGGC CGAA ICCCCAAA
3661

1909
GCAUGGAC A UUGACCCG
1153
UGGGUCAA CUGAUGAG GCCGUUAGGC CGAA IUCCAUGC
3662

1915
ACAUUGAC C CGUAUAAA
1154
UUUAUACG CUGAUGAG GCCGUUAGGC CGAA IUCAAUGU
3663

1916
CAUUGACC C GUAUAAAG
1155
CUUUAUAC CUGAUGAG GCCGUUAGGC CGAA IGUCAAUG
3664

1935
UUUGGAGC U UCUGUGGA
1156
UCCACAGA CUGAUGAG GCCGUUAGGC CGAA ICUCCAAA
3665

1938
GGAGCUUC U GUGGAGUU
1157
AACUCCAC CUGAUGAG GCCGUUAGGC CGAA IAAGCUCC
3666

1949
GGAGUUAC U CUCUUUUU
1158
AAAAAGAG CUGAUGAG GCCGUUAGGC CGAA IUAACUCC
3667

1951
AGUUACUC U CUUUUUUG
1159
CAAAAAAG CUGAUGAG GCCGUUAGGC CGAA IAGUAACU
3668

1953
UUACUCUC U UUUUUGCC
1160
GGCAAAAA CUGAUGAG GCCGUUAGGC CGAA IAGAGUAA
3669

1961
UUUUUUGC C UUCUGACU
1161
AGUCAGAA CUGAUGAG GCCGUUAGGC CGAA ICAAAAAA
3670

1962
UUUUUGCC U UCUGACUU
1162
AAGUCAGA CUGAUGAG GCCGUUAGGC CGAA IGCAAAAA
3671

1965
UUGCCUUC U GACUUCUU
1163
AAGAAGUC CUGAUGAG GCCGUUAGGC CGAA IAAGGCAA
3672

1969
CUUCUGAC U UCUUUCCU
1164
AGGAAAGA CUGAUGAG GCCGUUAGGC CGAA IUCAGAAG
3673

1972
CUGACUUC U UUCCUUCU
1165
AGAAGGAA CUGAUGAG GCCGUUAGGC CGAA IAAGUCAG
3674

1976
CUUCUUUC C UUCUAUUC
1166
GAAUAGAA CUGAUGAG GCCGUUAGGC CGAA IAAAGAAG
3675

1977
UUCUUUCC U UCUAUUCG
1167
CGAAUAGA CUGAUGAG GCCGUUAGGC CGAA IGAAAGAA
3676

1980
UUUCCUUC U AUUCGAGA
1168
UCUCGAAU CUGAUGAG GCCGUUAGGC CGAA IAAGGAAA
3677

1991
UCGAGAUC U CCUCGACA
1169
UGUCGAGG CUGAUGAG GCCGUUAGGC CGAA IAUCUCGA
3678

1993
GAGAUCUC C UCGACACC
1170
GGUGUCGA CUGAUGAG GCCGUUAGGC CGAA IAGAUCUC
3679

1994
AGAUCUCC U CGACACCG
1171
CGGUGUCG CUGAUGAG GCCGUUAGGC CGAA IGAGAUCU
3680

1999
UCCUCGAC A CCGCCUCU
1172
AGAGGCGG CUGAUGAG GCCGUUAGGC CGAA IUCGAGGA
3681

2001
CUCGACAC C GCCUCUGC
1173
GCAGAGGC CUGAUGAG GCCGUUAGGC CGAA IUGUCGAG
3682

2004
GACACCGC C UCUGCUCU
1174
AGAGCAGA CUGAUGAG GCCGUUAGGC CGAA ICGGUGUC
3683

2005
ACACCGCC U CUGCUCUG
1175
CAGAGCAG CUGAUGAG GCCGUUAGGC CGAA IGCGGUGU
3684

2007
ACCGCCUC U GCUCUGUA
1176
UACAGAGC CUGAUGAG GCCGUUAGGC CGAA IAGGCGGU
3685

2010
GCCUCUGC U CUGUAUCG
1177
CGAUACAG CUGAUGAG GCCGUUAGGC CGAA ICAGAGGC
3686

2012
CUCUCCUC U GUAUCGGG
1178
CCCGAUAC CUGAUGAG GCCGUUAGGC CGAA IAGCAGAG
3687

2025
CGGGGGGC C UUAGAGUC
1179
GACUCUAA CUGAUGAG GCCGUUAGGC CGAA ICCCCCCG
3688

2026
GGGGGGCC U UAGAGUCU
1180
AGACUCUA CUGAUGAG GCCGUUAGGC CGAA IGCCCCCC
3689

2034
UUAGAGUC U CCGGAACA
1181
UGUUCCGG CUGAUGAG GCCGUUAGGC CGAA IACUCUAA
3690

2036
AGAGUCUC C GGAACAUU
1182
AAUGUUCC CUGAUGAG GCCGUUAGGC CGAA IAGACUCU
3691

2042
UCCGGAAC A UUGUUCAC
1183
GUGAACAA CUGAUGAG GCCGUUAGGC CGAA IUUCCGGA
3692

2049
CAUUGUUC A CCUCACCA
1184
UGGUGAGG CUGAUGAG GCCGUUAGGC CGAA IAACAAUG
3693

2051
UUGUUCAC C UCACCAUA
1185
UAUGGUGA CUGAUGAG GCCGUUAGGC CGAA IUGAACAA
3694

2052
UGUUCACC U CACCAUAC
1186
GUAUGGUG CUGAUGAG GCCGUUAGGC CGAA IGUGAACA
3695

2054
UUCACCUC A CCAUACGG
1187
CCGUAUGG CUGAUGAG GCCGUUAGGC CGAA IAGGUGAA
3696

2056
CACCUCAC C AUACGGCA
1188
UGCCGUAU CUGAUGAG GCCGUUAGGC CGAA IUGAGGUG
3697

2057
ACCUCACC A UACGGCAC
1189
GUGCCGUA CUGAUGAG GCCGUUAGGC CGAA IGUGAGGU
3698

2064
CAUACGGC A CUCAGGCA
1190
UGCCUGAG CUGAUGAG GCCGUUAGGC CGAA ICCGUAUG
3699

2066
UACGGCAC U CAGGCAAG
1191
CUUUCCUG CUGAUGAG GCCGUUAGGC CGAA IUGCCGUA
3700

2068
CGGCACUC A GGCAAGCU
1192
AGCUUGCC CUGAUGAG GCCGUUAGGC CGAA IAGUGCCG
3701

2072
ACUCAGGC A AGCUAUUC
1193
GAAUAGCU CUGAUGAG GCCGUUAGGC CGAA ICCUGAGU
3702

2076
AGGCAAGC U AUUCUGUG
1194
CACAGAAU CUGAUGAG GCCGUUAGGC CGAA ICUUGCCU
3703

2081
AGCUAUUC U GUGUUGGG
1195
CCCAACAC CUGAUGAG GCCGUUAGGC CGAA IAAUAGCU
3704

2105
GAUGAAUC U AGCCACCU
1196
AGGUGGCU CUGAUGAG GCCGUUAGGC CGAA IAUUCAUC
3705

2109
AAUCUAGC C ACCUGGGU
1197
ACCCAGGU CUGAUGAG GCCGUUAGGC CGAA ICUAGAUU
3706

2110
AUCUAGCC A CCUGGGUG
1198
CACCCAGG CUGAUGAG GCCGUUAGGC CGAA IGCUAGAU
3707

2112
CUAGCCAC C UGGGUGGG
1199
CCCACCCA CUGAUGAG GCCGUUAGGC CGAA IUGGCUAG
3708

2113
UAGCCACC U GGGUGGGA
1200
UCCCACCC CUGAUGAG GCCGUUAGGC CGAA IGUGGCUA
3709

2138
GGAAGAUC C AGCAUCCA
1201
UGGAUGCU CUGAUGAG GCCGUUAGGC CGAA IAUCUUCC
3710

2139
GAAGAUCC A GCAUCCAG
1202
CUGGAUGC CUGAUGAG GCCGUUAGGC CGAA IGAUCUUC
3711

2142
GAUCCAGC A UCCAGGGA
1203
UCCCUGGA CUGAUGAG GCCGUUAGGC CGAA ICUGGAUC
3712

2145
CCAGCAUC C AGGGAAUU
1204
AAUUCCCU CUGAUGAG GCCGUUAGGC CGAA IAUGCUGG
3713

2146
CAGCAUCC A GGGAAUUA
1205
UAAUUCCC CUGAUGAG GCCGUUAGGC CGAA IGAUGCUG
3714

2161
UAGUAGUC A GCUAUGUC
1206
GACAUAGC CUGAUGAG GCCGUUAGGC CGAA IACUACUA
3715

2164
UAGUCAGC U AUGUCAAC
1207
GUUGACAU CUGAUGAG GCCGUUAGGC CGAA ICUGACUA
3716

2170
GCUAUGUC A ACGUUAAU
1208
AUUAACGU CUGAUGAG GCCGUUAGGC CGAA IACAUAGC
3717

2185
AUAUGGGC C UAAAAAUC
1209
GAUUUUUA CUGAUGAG GCCGUUAGGC CGAA ICCCAUAU
3718

2186
UAUGGGCC U AAAAAUCA
1210
UGAUUUUU CUGAUGAG GCCGUUAGGC CGAA IGCCCAUA
3719

2194
UAAAAAUC A GACAACUA
1211
UAGUUGUC CUGAUGAG GCCGUUAGGC CGAA IAUUUUUA
3720

2198
AAUCAGAC A ACUAUUGU
1212
ACAAUAGU CUGAUGAG GCCGUUAGGC CGAA IUCUGAUU
3721

2201
CAGACAAC U AUUGUGGU
1213
ACCACAAU CUGAUGAG GCCGUUAGGC CGAA IUUGUCUG
3722

2213
GUGGUUUC A CAUUUCCU
1214
AGGAAAUG CUGAUGAG GCCGUUAGGC CGAA IAAACCAC
3723

2215
GGUUUCAC A UUUCCUGU
1215
ACAGGAAA CUGAUGAG GCCGUUAGGC CGAA IUGAAACC
3724

2220
CACAUUUC C UGUCUUAC
1216
GUAAGACA CUGAUGAG GCCGUUAGGC CGAA IAAAUGUG
3725

2221
ACAUUUCC U GUCUUACU
1217
AGUAAGAC CUGAUGAG GCCGUUAGGC CGAA IGAAAUGU
3726

2225
UUCCUGUC U UACUUUUG
1218
CAAAAGUA CUGAUGAG GCCGUUAGGC CGAA IACAGGAA
3727

2229
UGUCUUAC U UUUGGGCG
1219
CGCCCAAA CUGAUGAG GCCGUUAGGC CGAA IUAAGACA
3728

2244
CGAGAAAC U GUUCUUGA
1220
UCAAGAAC CUGAUGAG GCCGUUAGGC CGAA IUUUCUCG
3729

2249
AACUGUUC U UGAAUAUU
1221
AAUAUUCA CUGAUGAG GCCGUUAGGC CGAA IAACAGUU
3730

2265
UUGGUGUC U UUUGGAGU
1222
ACUCCAAA CUGAUGAG GCCGUUAGGC CGAA IACACCAA
3731

2284
GGAUUCGC A CUCCUCCU
1223
AGGAGGAG CUGAUGAG GCCGUUAGGC CGAA ICGAAUCC
3732

2286
AUUCGCAC U CCUCCUGC
1224
GCAGGAGG CUGAUGAG GCCGUUAGGC CGAA IUGCGAAU
3733

2288
UCGCACUC C UCCUGCAU
1225
AUGCAGGA CUGAUGAG GCCGUUAGGC CGAA IAGUGCGA
3734

2289
CGCACUCC U CCUGCAUA
1226
UAUGCAGG CUGAUGAG GCCGUUAGGC CGAA IGAGUGCG
3735

2291
CACUCCUC C UGCAUAUA
1227
UAUAUGCA CUGAUGAG GCCGUUAGGC CGAA IAGGAGUG
3736

2292
ACUCCUCC U GCAUAUAG
1228
CUAUAUGC CUGAUGAG GCCGUUAGGC CGAA IGAGGAGU
3737

2295
CCUCCUGC A UAUAGACC
1229
GGUCUAUA CUGAUGAG GCCGUUAGGC CGAA ICAGGAGG
3738

2303
AUAUAGAC C ACCAAAUG
1230
CAUUUGGU CUGAUGAG GCCGUUAGGC CGAA IUCUAUAU
3739

2304
UAUAGACC A CCAAAUGC
1231
GCAUUUGG CUGAUGAG GCCGUUAGGC CGAA IGUCUAUA
3740

2306
UAGACCAC C AAAUGCCC
1232
GGGCAUUU CUGAUGAG GCCGUUAGGC CGAA IUGGUCUA
3741

2307
AGACCACC A AAUGCCCC
1233
GGGGCAUU CUGAUGAG GCCGUUAGGC CGAA IGUGGUCU
3742

2313
CCAAAUGC C CCUAUCUU
1234
AAGAUAGG CUGAUGAG GCCGUUAGGC CGAA ICAUUUGG
3743

2314
CAAAUGCC C CUAUCUUA
1235
UAAGAUAG CUGAUGAG GCCGUUAGGC CGAA IGCAUUUG
3744

2315
AAAUGCCC C UAUCUUAU
1236
AUAAGAUA CUGAUGAG GCCGUUAGGC CGAA IGGCAUUU
3745

2316
AAUGCCCC U AUCUUAUC
1237
GAUAAGAU CUGAUGAG GCCGUUAGGC CGAA IGGGCAUU
3746

2320
CCCCUAUC U UAUCAACA
1238
UGUUGAUA CUGAUGAG GCCGUUAGGC CGAA IAUAGGGG
3747

2325
AUCUUAUC A ACACUUCC
1239
GGAAGUGU CUGAUGAG GCCGUUAGGC CGAA IAUAAGAU
3748

2328
UUAUCAAC A CUUCCGGA
1240
UCCGGAAG CUGAUGAG GCCGUUAGGC CGAA IUUGAUAA
3749

2330
AUCAACAC U UCCGGAAA
1241
UUUCCGGA CUGAUGAG GCCGUUAGGC CGAA IUGUUGAU
3750

2333
AACACUUC C GGAAACUA
1242
UAGUUUCC CUGAUGAG GCCGUUAGGC CGAA IAAGUGUU
3751

2340
CCGGAAAC U ACUGUUGU
1243
ACAACAGU CUGAUGAG GCCGUUAGGC CGAA IUUUCCGG
3752

2343
GAAACUAC U GUUGUUAG
1244
CUAACAAC CUGAUGAG GCCGUUAGGC CGAA IUAGUUUC
3753

2362
GAAGAGGC A GGUCCCCU
1245
AGGGGACC CUGAUGAG GCCGUUAGGC CGAA ICCUCUUC
3754

2367
GGCAGGUC C CCUAGAAG
1246
CUUCUAGG CUGAUGAG GCCGUUAGGC CGAA IACCUGCC
3755

2368
GCAGGUCC C CUAGAAGA
1247
UCUUCUAG CUGAUGAG GCCGUUAGGC CGAA IGACCUGC
3756

2369
CAGGUCCC C UAGAAGAA
1248
UUCUUCUA CUGAUGAG GCCGUUAGGC CGAA IGGACCUG
3757

2370
AGGUCCCC U AGAAGAAG
1249
CUUCUUCU CUGAUGAG GCCGUUAGGC CGAA IGGGACCU
3758

2382
AGAAGAAC U CCCUCGCC
1250
GGCGAGGG CUGAUGAG GCCGUUAGGC CGAA IUUCUUCU
3759

2384
AAGAACUC C CUCGCCUC
1251
GAGGCGAG CUGAUGAG GCCGUUAGGC CGAA IAGUUCUU
3760

2385
AGAACUCC C UCGCCUCG
1252
CGAGGCGA CUGAUGAG GCCGUUAGGC CGAA IGAGUUCU
3761

2386
GAACUCCC U CGCCUCGC
1253
GCGAGGCG CUGAUGAG GCCGUUAGGC CGAA IGGAGUUC
3762

2390
UCCCUCGC C UCGCAGAC
1254
GUCUGCGA CUGAUGAG GCCGUUAGGC CGAA ICGAGGGA
3763

2391
CCCUCGCC U CGCAGACG
1255
CGUCUGCG CUGAUGAG GCCGUUAGGC CGAA IGCGAGGG
3764

2395
CGCCUCGC A GACGAAGG
1256
CCUUCGUC CUGAUGAG GCCGUUAGGC CGAA ICGAGGCG
3765

2406
CGAAGGUC U CAAUCGCC
1257
GGCGAUUG CUGAUGAG GCCGUUAGGC CGAA IACCUUCG
3766

2408
AAGGUCUC A AUCGCCGC
1258
GCGGCGAU CUGAUGAG GCCGUUAGGC CGAA IAGACCUU
3767

2414
UCAAUCGC C GCGUCGCA
1259
UGCGACGC CUGAUGAG GCCGUUAGGC CGAA ICGAUUGA
3768

2422
CGCGUCGC A GAAGAUCU
1260
AGAUCUUC CUGAUGAG GCCGUUAGGC CGAA ICGACGCG
3769

2430
AGAAGAUC U CAAUCUCG
1261
CGAGAUUG CUGAUGAG GCCGUUAGGC CGAA IAUCUUCU
3770

2432
AAGAUCUC A AUCUCGGG
1262
CCCGAGAU CUGAUGAG GCCGUUAGGC CGAA IAGAUCUU
3771

2436
UCUCAAUC U CGGGAAUC
1263
GAUUCCCG CUGAUGAG GCCGUUAGGC CGAA IAUUGAGA
3772

2445
CGGGAAUC U CAAUGUUA
1264
UAACAUUG CUGAUGAG GCCGUUAGGC CGAA IAUUCCCG
3773

2447
GGAAUCUC A AUGUUAGU
1265
ACUAACAU CUGAUGAG GCCGUUAGGC CGAA IAGAUUCC
3774

2460
UAGUAUUC C UUGGACAC
1266
GUGUCCAA CUGAUGAG GCCGUUAGGC CGAA IAAUACUA
3775

2461
AGUAUUCC U UGGACACA
1267
UGUGUCCA CUGAUGAG GCCGUUAGGC CGAA IGAAUACU
3776

2467
CCUUGGAC A CAUAAGGU
1268
ACCUUAUG CUGAUGAG GCCGUUAGGC CGAA IUCCAAGG
3777

2469
UUGGACAC A UAAGGUGG
1269
CCACCUUA CUGAUGAG GCCGUUAGGC CGAA IUGUCCAA
3778

2483
UGGGAAAC U UUACGGGG
1270
CCCCGUAA CUGAUGAG GCCGUUAGGC CGAA IUUUCCCA
3779

2493
UACGGGGC U UUAUUCUU
1271
AAGAAUAA CUGAUGAG GCCGUUAGGC CGAA ICCCCGUA
3780

2500
CUUUAUUC U UCUACGGU
1272
ACCGUAGA CUGAUGAG GCCGUUAGGC CGAA IAAUAAAG
3781

2503
UAUUCUUC U ACGGUACC
1273
GGUACCGU CUGAUGAG GCCGUUAGGC CGAA IAAGAAUA
3782

2511
UACGGUAC C UUGCUUUA
1274
UAAAGCAA CUGAUGAG GCCGUUAGGC CGAA IUACCGUA
3783

2512
ACGGUACC U UGCUUUAA
1275
UUAAAGCA CUGAUGAG GCCGUUAGGC CGAA IGUACCGU
3784

2516
UACCUUGC U UUAAUCCU
1276
AGGAUUAA CUGAUGAG GCCGUUAGGC CGAA ICAAGGUA
3785

2523
UUUUAAUC C UAAAUGGC
1277
GCCAUUUA CUGAUGAG GCCGUUAGGC CGAA IAUUAAAG
3786

2524
UUUAAUCC U AAAUGGCA
1278
UGCCAUUU CUGAUGAG GCCGUUAGGC CGAA IGAUUAAA
3787

2532
UAAAUGGC A AACUCCUU
1279
AAGGAGUU CUGAUGAG GCCGUUAGGC CGAA ICCAUUUA
3788

2536
UGGCAAAC U CCUUCUUU
1280
AAAGAAGG CUGAUGAG GCCGUUAGGC CGAA IUUUGCCA
3789

2538
GCAAACUC C UUCUUUUC
1281
GAAAAGAA CUGAUGAG GCCGUUAGGC CGAA IAGUUUGC
3790

2539
CAAACUCC U UCUUUUCC
1282
GGAAAAGA CUGAUGAG GCCGUUAGGC CGAA IGAGUUUG
3791

2542
ACUCCUUC U UUUCCUGA
1283
UCAGGAAA CUGAUGAG GCCGUUAGGC CGAA IAAGGAGU
3792

2547
UUCUUUUC C UGACAUUC
1284
GAAUGUCA CUGAUGAG GCCGUUAGGC CGAA IAAAAGAA
3793

2548
UCUUUUCC U GACAUUCA
1285
UGAAUGUC CUGAUGAG GCCGUUAGGC CGAA IGAAAAGA
3794

2552
UUCCUGAC A UUCAUUUG
1286
CAAAUGAA CUGAUGAG GCCGUUAGGC CGAA IUCAGGAA
3795

2556
UGACAUUC A UUUGCAGG
1287
CCUGCAAA CUGAUGAG GCCGUUAGGC CGAA IAAUGUCA
3796

2562
UCAUUUGC A GGAGGACA
1288
UGUCCUCC CUGAUGAG GCCGUUAGGC CGAA ICAAAUGA
3797

2570
AGGAGGAC A UUGUUGAU
1289
AUCAACAA CUGAUGAG GCCGUUAGGC CGAA IUCCUCCU
3798

2589
AUGUAAGC A AUUUGUGG
1290
CCACAAAU CUGAUGAG GCCGUUAGGC CGAA ICUUACAU
3799

2601
UGUGGGGC C CCUUACAG
1291
CUGUAAGG CUGAUGAG GCCGUUAGGC CGAA ICCCCACA
3800

2602
GUGGGGCC C CUUACAGU
1292
ACUGUAAG CUGAUGAG GCCGUUAGGC CGAA IGCCCCAC
3801

2603
UGGGGCCC C UUACAGUA
1293
UACUGUAA CUGAUGAG GCCGUUAGGC CGAA IGGCCCCA
3802

2604
GGGGCCCC U UACAGUAA
1294
UUACUGUA CUGAUGAG GCCGUUAGGC CGAA IGGGCCCC
3803

2608
CCCCUUAC A GUAAAUGA
1295
UCAUUUAC CUGAUGAG GCCGUUAGGC CGAA IUAAGGGG
3804

2621
AUGAAAAC A GGAGACUU
1296
AAGUCUCC CUGAUGAG GCCGUUAGGC CGAA IUUUUCAU
3805

2628
CAGGAGAC U UAAAUUAA
1297
UUAAUUUA CUGAUGAG GCCGUUAGGC CGAA IUCUCCUG
3806

2638
AAAUUAAC U AUGCCUGC
1298
GCAGGCAU CUGAUGAG GCCGUUAGGC CGAA IUUAAUUU
3807

2643
AACUAUGC C UGCUAGGU
1299
ACCUAGCA CUGAUGAG GCCGUUAGGC CGAA ICAUAGUU
3808

2644
ACUAUGCC U GCUAGGUU
1300
AACCUAGC CUGAUGAG GCCGUUAGGC CGAA IGCAUAGU
3809

2647
AUGCCUGC U AGGUUUUA
1301
UAAAACCU CUGAUGAG GCCGUUAGGC CGAA ICAGGCAU
3810

2658
GUUUUAUC C CAAUGUUA
1302
UAACAUUG CUGAUGAG GCCGUUAGGC CGAA IAUAAAAC
3811

2659
UUUUAUCC C AAUGUUAC
1303
GUAACAUU CUGAUGAG GCCGUUAGGC CGAA IGAUAAAA
3812

2660
UUUAUCCC A AUGUUACU
1304
AGUAACAU CUGAUGAG GCCGUUAGGC CGAA IGGAUAAA
3813

2668
AAUGUUAC U AAAUAUUU
1305
AAAUAUUU CUGAUGAG GCCGUUAGGC CGAA IUAACAUU
3814

2679
AUAUUUGC C CUUAGAUA
1306
UAUCUAAG CUGAUGAG GCCGUUAGGC CGAA ICAAAUAU
3815

2680
UAUUUGCC C UUAGAUAA
1307
UUAUCUAA CUGAUGAG GCCGUUAGGC CGAA IGCAAAUA
3816

2681
AUUUGCCC U UAGAUAAA
1308
UUUAUCUA CUGAUGAG GCCGUUAGGC CGAA IGGCAAAU
3817

2696
AAGGGAUC A AACCGUAU
1309
AUACCGUU CUGAUGAG GCCGUUAGGC CGAA IAUCCCUU
3818

2700
GAUCAAAC C GUAUUAUC
1310
GAUAAUAC CUGAUGAG GCCGUUAGGC CGAA IUUUGAUC
3819

2709
GUAUUAUC C AGAGUAUG
1311
CAUACUCU CUGAUGAG GCCGUUAGGC CGAA IAUAAUAC
3820

2710
UAUUAUCC A GAGUAUGU
1312
ACAUACUC CUGAUGAG GCCGUUAGGC CGAA IGAUAAUA
3821

2727
AGUUAAUC A UUACUUCC
1313
GGAAGUAA CUGAUGAG GCCGUUAGGC CGAA IAUUAACU
3822

2732
AUCAUUAC U UCCAGACG
1314
CGUCUGGA CUGAUGAG GCCGUUAGGC CGAA IUAAUGAU
3823

2735
AUUACUUC C AGACGCGA
1315
UCGCGUCU CUGAUGAG GCCGUUAGGC CGAA IAAGUAAU
3824

2736
UUACUUCC A GACGCGAC
1316
GUCGCGUC CUGAUGAG GCCGUUAGGC CGAA IGAAGUAA
3825

2745
GACGCGAC A UUAUUUAC
1317
GUAAAUAA CUGAUGAG GCCGUUAGGC CGAA IUCGCGUC
3826

2754
UUAUUUAC A CACUCUUU
1318
AAAGAGUG CUGAUGAG GCCGUUAGGC CGAA IUAAAUAA
3827

2756
AUUUACAC A CUCUUUGG
1319
CCAAAGAG CUGAUGAG GCCGUUAGGC CGAA IUGUAAAU
3828

2758
UUACACAC U CUUUGGAA
1320
UUCCAAAG CUGAUGAG GCCGUUAGGC CGAA IUGUGUAA
3829

2760
ACACACUC U UUGGAAGG
1321
CCUUCCAA CUGAUGAG GCCGUUAGGC CGAA IAGUGUGU
3830

2777
CGGGGAUC U UAUAUAAA
1322
UUUAUAUA CUGAUGAG GCCGUUAGGC CGAA IAUCCCCG
3831

2794
AGAGAGUC C ACACGUAG
1323
UUACGUGU CUGAUGAG GCCGUUAGGC CGAA IACUCUCU
3832

2795
GAGAGUCC A CACGUAGC
1324
GCUACGUG CUGAUGAG GCCGUUAGGC CGAA IGACUCUC
3833

2797
GAGUCCAC A CGUAGCGC
1325
GCGCUACG CUGAUGAG GCCGUUAGGC CGAA IUGGACUC
3834

2806
CGUAGCGC C UCAUUUUG
1326
CAAAAUGA CUGAUGAG GCCGUUAGGC CGAA ICGCUACG
3835

2807
GUAGCGCC U CAUUUUGC
1327
GCAAAAUG CUGAUGAG GCCGUUAGGC CGAA IGCGCUAC
3836

2809
AGCGCCUC A UUUUGCGG
1328
CCGCAAAA CUGAUGAG GCCGUUAGGC CGAA IAGGCGCU
3837

2821
UGCGGGUC A CCAUAUUC
1329
GAAUAUGG CUGAUGAG GCCGUUAGGC CGAA IACCCGCA
3838

2823
UGGGUCAC C AUAUUCUU
1330
AAGAAUAU CUGAUGAG GCCGUUAGGC CGAA IUGACCCG
3839

2824
GGGUCACC A UAUUCUUG
1331
CAAGAAUA CUGAUGAG GCCGUUAGGC CGAA IGUGACCC
3840

2830
CCAUAUUC U UGGGAACA
1332
UGUUCCCA CUGAUGAG GCCGUUAGGC CGAA IAAUAUGG
3841

2838
UUGGGAAC A AGAUCUAC
1333
GUAGAUCU CUGAUGAG GCCGUUAGGC CGAA IUUCCCAA
3842

2844
ACAAGAUC U ACAGCAUG
1334
CAUGCUGU CUGAUGAG GCCGUUAGGC CGAA IAUCUUGU
3843

2847
AGAUCUAC A GCAUGGGA
1335
UCCCAUGC CUGAUGAG GCCGUUAGGC CGAA IUAGAUCU
3844

2850
UCUACAGC A UGGGAGGU
1336
ACCUCCCA CUGAUGAG GCCGUUAGGC CGAA ICUGUAGA
3845

2864
GGUUGGUC U UCCAAACC
1337
GGUUUGGA CUGAUGAG GCCGUUAGGC CGAA IACCAACC
3846

2867
UGGUCUUC C AAACCUCG
1338
CGAGGUUU CUGAUGAG GCCGUUAGGC CGAA IAAGACCA
3847

2868
GGUCUUCC A AACCUCGA
1339
UCGAGGUU CUGAUGAG GCCGUUAGGC CGAA IGAAGACC
3848

2872
UUCCAAAC C UCGAAAAG
1340
CUUUUCGA CUGAUGAG GCCGUUAGGC CGAA IUUUGGAA
3849

2873
UCCAAACC U CGAAAAGG
1341
CCUUUUCG CUGAUGAG GCCGUUAGGC CGAA IGUUUGGA
3850

2883
GAAAAGGC A UGGGGACA
1342
UGUCCCCA CUGAUGAG GCCGUUAGGC CGAA ICCUUUUC
3851

2891
AUGGGGAC A AAUCUUUC
1343
GAAAGAUU CUGAUGAG GCCGUUAGGC CGAA IUCCCCAU
3852

2896
GACAAAUC U UUCUGUCC
1344
GGACAGAA CUGAUGAG GCCGUUAGGC CGAA IAUUUGUC
3853

2900
AAUCUUUC U GUCCCCAA
1345
UUGGGGAC CUGAUGAG GCCGUUAGGC CGAA IAAAGAUU
3854

2904
UUUCUGUC C CCAAUCCC
1346
GGGAUUGG CUGAUGAG GCCGUUAGGC CGAA IACAGAAA
3855

2905
UUCUGUCC C CAAUCCCC
1347
GGGGAUUG CUGAUGAG GCCGUUAGGC CGAA IGACAGAA
3856

2906
UCUGUCCC C AAUCCCCU
1348
AGGGGAUU CUGAUGAG GCCGUUAGGC CGAA IGGACAGA
3857

2907
CUGUCCCC A AUCCCCUG
1349
CAGGGGAU CUGAUGAG GCCGUUAGGC CGAA IGGGACAG
3858

2911
CCCCAAUC C CCUGGGAU
1350
AUCCCAGG CUGAUGAG GCCGUUAGGC CGAA IAUUGGGG
3859

2912
CCCAAUCC C CUGGGAUU
1351
AAUCCCAG CUGAUGAG GCCGUUAGGC CGAA IGAUUGGG
3860

2913
UCAAUCCC C UGGGAUUC
1352
GAAUCCCA CUGAUGAG GCCGUUAGGC CGAA IGGAUUGG
3861

2914
CAAUCCCC U GGGAUUCU
1353
AGAAUCCC CUGAUGAG GCCGUUAGGC CGAA IGGGAUUG
3862

2922
UGGGAUUC U UCCCCGAU
1354
AUCGGGGA CUGAUGAG GCCGUUAGGC CGAA IAAUCCCA
3863

2925
GAUUCUUC C CCGAUCAU
1355
AUGAUCGG CUGAUGAG GCCGUUAGGC CGAA IAAGAAUC
3864

2926
AUUCUUCC C CGAUCAUC
1356
GAUGAUCG CUGAUGAG GCCGUUAGGC CGAA IGAAGAAU
3865

2927
UUCUUCCC C GAUCAUCA
1357
UGAUGAUC CUGAUGAG GCCGUUAGGC CGAA IGGAAGAA
3866

2932
CCCCGAUC A UCAGUUGG
1358
CCAACUGA CUGAUGAG GCCGUUAGGC CGAA IAUCGGGG
3867

2935
CGAUCAUC A GUUGGACC
1359
GGUCCAAC CUGAUGAG GCCGUUAGGC CGAA IAUGAUCG
3868

2943
AGUUGGAC C CUGCAUUC
1360
GAAUGCAG CUGAUGAG GCCGUUAGGC CGAA IUCCAACU
3869

2944
GUUGGACC C UGCAUUCA
1361
UGAAUGCA CUGAUGAG GCCGUUAGGC CGAA IGUCCAAC
3870

2945
UUGGACCC U GCAUUCAA
1362
UUGAAUGC CUGAUGAG GCCGUUAGGC CGAA IGGUCCAA
3871

2948
GACCCUGC A UUCAAAGC
1363
GCUUUGAA CUGAUGAG GCCGUUAGGC CGAA ICAUGGUC
3872

2952
CUGCAUUC A AAGCCAAC
1364
GUUGGCUU CUGAUGAG GCCGUUAGGC CGAA IAAUGCAG
3873

2957
UUCAAAGC C AACUCAGU
1365
ACUGAGUU CUGAUGAG GCCGUUAGGC CGAA ICUUUGAA
3874

2958
UCAAAGCC A ACUCAGUA
1366
UACUGAGU CUGAUGAG GCCGUUAGGC CGAA IGCUUUGA
3875

2961
AAGCCAAC U CAGUAAAU
1367
AUUUACUG CUGAUGAG GCCGUUAGGC CGAA IUUGGCUU
3876

2963
GCCAACUC A GUAAAUCC
1368
GGAUUUAC CUGAUGAG GCCGUUAGGC CGAA IAGUUGGC
3877

2971
AGUAAAUC C AGAUUGGG
1369
CCCAAUCU CUGAUGAG GCCGUUAGGC CGAA IAUUUACU
3878

2972
GUAAAUCC A GAUUGGGA
1370
UCCCAAUC CUGAUGAG GCCGUUAGGC CGAA IGAUUUAC
3879

2982
AUUGGGAC C UCAACCCG
1371
CGGGUUGA CUGAUGAG GCCGUUAGGC CGAA IUCCCAAU
3880

2983
UUGGGACC U CAACCCGC
1372
GCGGGUUG CUGAUGAG GCCGUUAGGC CGAA IGUCCCAA
3881

2985
GGGACCUC A ACCCGCAC
1373
GUGCGGGU CUGAUGAG GCCGUUAGGC CGAA IAGGUCCC
3882

2988
ACCUCAAC C CGCACAAG
1374
CUUGUGCG CUGAUGAG GCCGUUAGGC CGAA IUUGAGGU
3883

2989
CCUCAACC C GCACAAGG
1375
CCUUGUGC CUGAUGAG GCCGUUAGGC CGAA IGUUGAGG
3884

2992
CAACCCGC A CAAGGACA
1376
UGUCCUUG CUGAUGAG GCCGUUAGGC CGAA ICGGGUUG
3885

2994
ACCCGCAC A AGGACAAC
1377
GUUGUCCU CUGAUGAG GCCGUUAGGC CGAA IUGCGGGU
3886

3000
ACAAGGAC A ACUGGCCG
1378
CGGCCAGU CUGAUGAG GCCGUUAGGC CGAA IUCCUUGU
3887

3003
AGGACAAC U GGCCGGAC
1379
GUCCGGCC CUGAUGAG GCCGUUAGGC CGAA IUUGUCCU
3888

3007
CAACUGGC C GGACGCCA
1380
UGGCGUCC CUGAUGAG GCCGUUAGGC CGAA ICCAGUUG
3889

3014
CCGGACGC C AACAAGGU
1381
ACCUUGUU CUGAUGAG GCCGUUAGGC CGAA ICGUCCGG
3890

3015
CGGACGCC A ACAAGGUG
1382
CACCUUGU CUGAUGAG GCCGUUAGGC CGAA IGCGUCCG
3891

3018
ACGCCAAC A AGGUGGGA
1383
UCCCACCU CUGAUGAG GCCGUUAGGC CGAA IUUGGCGU
3892

3035
GUGGGAGC A UUCGGGCC
1384
GGCCCGAA CUGAUGAG GCCGUUAGGC CGAA ICUCCCAC
3893

3043
AUUCGGGC C AGGGUUCA
1385
UGAACCCU CUGAUGAG GCCGUUAGGC CGAA ICCCGAAU
3894

3044
UUCGGGCC A GGGUUCAC
1386
GUGAACCC CUGAUGAG GCCGUUAGGC CGAA IGCCCGAA
3895

3051
CAGGGUUC A CCCCUCCC
1387
GGGAGGGG CUGAUGAG GCCGUUAGGC CGAA IAACCCUG
3896

3053
GGGUUCAC C CCUCCCCA
1388
UGGGGAGG CUGAUGAG GCCGUUAGGC CGAA IUGAACCC
3897

3054
GGUUCACC C CUCCCCAU
1389
AUGGGGAG CUGAUGAG GCCGUUAGGC CGAA IGUGAACC
3898

3055
GUUCACCC C UCCCCAUG
1390
CAUGGGGA CUGAUGAG GCCGUUAGGC CGAA IGGUGAAC
3899

3056
UUCACCCC U CCCCAUGG
1391
CCAUGGGG CUGAUGAG GCCGUUAGGC CGAA IGGGUGAA
3900

3058
CACCCCUC C CCAUGGGG
1392
CCCCAUGG CUGAUGAG GCCGUUAGGC CGAA IAGGGGUG
3901

3059
ACCCCUCC C CAUGGGGG
1393
UCCCCAUG CUGAUGAG GCCGUUAGGC CGAA IGAGGGGU
3902

3060
CCCCUCCC C AUGGGGGA
1394
UCCCCCAU CUGAUGAG GCCGUUAGGC CGAA IGGAGGGG
3903

3061
CCCUCCCC A UGGGGGAC
1395
GUCCCCCA CUGAUGAG GCCGUUAGGC CGAA IGGGAGGG
3904

3070
UGGGGGAC U GUUGGGGU
1396
ACCCCAAC CUGAUGAG GCCGUUAGGC CGAA IUCCCCCA
3905

3084
GGUGGAGC C CUCACGCU
1397
AGCGUGAG CUGAUGAG GCCGUUAGGC CGAA ICUCCACC
3906

3085
GUGGAGCC C UCACGCUC
1398
GAGCGUGA CUGAUGAG GCCGUUAGGC CGAA IGCUCCAC
3907

3086
UGGAGCCC U CACGCUCA
1399
UGAGCGUG CUGAUGAG GCCGUUAGGC CGAA IGGCUCCA
3908

3088
GAGCCCUC A CGCUCAGG
1400
CCUGAGCG CUGAUGAG GCCGUUAGGC CGAA IAGGGCUC
3909

3092
CCUCACGC U CAGGGCCU
1401
AGGCCCUG CUGAUGAG GCCGUUAGGC CGAA ICGUGAGG
3910

3094
UCACGCUC A GGGCCUAC
1402
GUAGGCCC CUGAUGAG GCCGUUAGGC CGAA IAGCGUGA
3911

3099
CUCAGGGC C UACUCACA
1403
UGUGAGUA CUGAUGAG GCCGUUAGGC CGAA ICCCUGAG
3912

3100
UCAGGGCC U ACUCACAA
1404
UUGUGAGU CUGAUGAG GCCGUUAGGC CGAA IGCCCUGA
3913

3103
GGGCCUAC U CACAACUG
1405
CAGUUGUG CUGAUGAG GCCGUUAGGC CGAA IUAGGCCC
3914

3105
GCCUACUC A CAACUGUG
1406
CACAGUUG CUGAUGAG GCCGUUAGGC CGAA IAGUAGGC
3915

3107
CUACUCAC A ACUGUGCC
1407
GGCACAGU CUGAUGAG GCCGUUAGGC CGAA IUGAGUAG
3916

3110
CUCACAAC U GUGCCAGC
1408
GCUGGCAC CUGAUGAG GCCGUUAGGC CGAA IUUGUGAG
3917

3115
AACUGUGC C AGCAGCUC
1409
GAGCUGCU CUGAUGAG GCCGUUAGGC CGAA ICACAGUU
3918

3116
ACUGUGCC A GCAGCUCC
1410
GGAGCUGC CUGAUGAG GCCGUUAGGC CGAA IGCACAGU
3919

3119
GUGCCAGC A GCUCCUCC
1411
GGAGGAGC CUGAUGAG GCCGUUAGGC CGAA ICUGGCAC
3920

3122
CCAGCAGC U CCUCCUCC
1412
GGAGGAGG CUGAUGAG GCCGUUAGGC CGAA ICUGCUGG
3921

3124
AGCAGCUC C UCCUCCUG
1413
CAGGAGGA CUGAUGAG GCCGUUAGGC CGAA IAGCUGCU
3922

3125
GCAGCUCC U CCUCCUGC
1414
GCAGGAGG CUGAUGAG GCCGUUAGGC CGAA IGAGCUGC
3923

3127
AGCUCCUC C UCCUGCCU
1415
AGGCAGGA CUGAUGAG GCCGUUAGGC CGAA IAGGAGCU
3924

3128
GCUCCUCC U CCUGCCUC
1416
GAGGCAGG CUGAUGAG GCCGUUAGGC CGAA IGAGGAGC
3925

3130
UCCUCCUC C UGCCUCCA
1417
UGGAGGCA CUGAUGAG GCCGUUAGGC CGAA IAGGAGGA
3926

3131
CCUCCUCC U GCCUCCAC
1418
GUGGAGGC CUGAUGAG GCCGUUAGGC CGAA IGAGGAGG
3927

3134
CCUCCUGC C UCCACCAA
1419
UUGGUGGA CUGAUGAG GCCGUUAGGC CGAA ICAGGAGG
3928

3135
CUCCUGCC U CCACCAAU
1420
AUUGGUGG CUGAUGAG GCCGUUAGGC CGAA IGCAGGAG
3929

3137
CCUGCCUC C ACCAAUCG
1421
CGAUUGGU CUGAUGAG GCCGUUAGGC CGAA IAGGCAGG
3930

3138
CUGCCUCC A CCAAUCGG
1422
CCGAUUGG CUGAUGAG GCCGUUAGGC CGAA IGAGGCAG
3931

3140
GCCUCCAC C AAUCGGCA
1423
UGCCGAUU CUGAUGAG GCCGUUAGGC CGAA IUGGAGGC
3932

3141
CCUCCACC A AUCGGCAG
1424
CUGCCGAU CUGAUGAG GCCGUUAGGC CGAA IGUGGAGG
3933

3148
CAAUCGGC A GUCAGGAA
1425
UUCCUGAC CUGAUGAG GCCGUUAGGC CGAA ICCGAUUG
3934

3152
CGGCAGUC A GGAAGGCA
1426
UGCCUUCC CUGAUGAG GCCGUUAGGC CGAA IACUGCCG
3935

3160
AGGAAGGC A GCCUACUC
1427
GAGUAGGC CUGAUGAG GCCGUUAGGC CGAA ICCUUCCU
3936

3163
AAGGCAGC C UACUCCCU
1428
AGGGAGUA CUGAUGAG GCCGUUAGGC CGAA ICUGCCUU
3937

3164
AGGCAGCC U ACUCCCUU
1429
AAGGGAGU CUGAUGAG GCCGUUAGGC CGAA IGCUGCCU
3938

3167
CAGCCUAC U CCCUUAUC
1430
GAUAAGGG CUGAUGAG GCCGUUAGGC CGAA IUAGGCUG
3939

3169
GCCUACUC C CUUAUCUC
1431
GAGAUAAG CUGAUGAG GCCGUUAGGC CGAA IAGUAGGC
3940

3170
CCUACUCC C UUAUCUCC
1432
GGAGAUAA CUGAUGAG GCCGUUAGGC CGAA IGAGUAGG
3941

3171
CUACUCCC U UAUCUCCA
1433
UGGAGAUA CUGAUGAG GCCGUUAGGC CGAA IGGAGUAG
3942

3176
CCCUUAUC U CCACCUCU
1434
AGAGGUGG CUGAUGAG GCCGUUAGGC CGAA IAUAAGGG
3943

3178
CUUAUCUC C ACCUCUAA
1435
UUAGAGGU CUGAUGAG GCCGUUAGGC CGAA IAGAUAAG
3944

3179
UUAUCUCC A CCUCUAAG
1436
CUUAGAGG CUGAUGAG GCCGUUAGGC CGAA IGAGAUAA
3945

3181
AUCUCCAC C UCUAAGGG
1437
CCCUUAGA CUGAUGAG GCCGUUAGGC CGAA IUGGAGAU
3946

3182
UCUCCACC U CUAAGGGA
1438
UCCCUUAG CUGAUGAG GCCGUUAGGC CGAA IGUGGAGA
3947

3184
UCCACCUC U AAGGGACA
1439
UGUCCCUU CUGAUGAG GCCGUUAGGC CGAA IAGGUGGA
3948

3192
UAAGGGAC A CUCAUCCU
1440
AGGAUGAG CUGAUGAG GCCGUUAGGC CGAA IUCCCUUA
3949

3194
AGGGACAC U CAUCCUCA
1441
UGAGGAUG CUGAUGAG GCCGUUAGGC CGAA IUGUCCCU
3950

3196
GGACACUC A UCCUCAGG
1442
CCUGAGGA CUGAUGAG GCCGUUAGGC CGAA IAGUGUCC
3951

3199
CACUCAUC C UCAGGCCA
1443
UGGCCUGA CUGAUGAG GCCGUUAGGC CGAA IAUGAGUG
3952

3200
ACUCAUCC U CAGGCCAU
1444
AUGGCCUG CUGAUGAG GCCGUUAGGC CGAA IGAUGAGU
3953

3202
UCAUCCUC A GGCCAUGC
1445
GCAUGGCC CUGAUGAG GCCGUUAGGC CGAA IAGGAUGA
3954

3206
CCUCAGGC C AUGCAGUG
1446
CACUGCAU CUGAUGAG GCCGUUAGGC CGAA ICCUGAGG
3955

3207
CUCAGGCC A UGCAGUGG
1447
CCACUGCA CUGAUGAG GCCGUUAGGC CGAA IGCCUGAG
3956

Input Sequence = AF100308.

Cut Site = UH/.

Stem Length = 8.

Core Sequence = CUGAUGAG GCCGUUAGGC CGAA

AF100308 (Hepatitis B virus strain 2-18, 3215 bp)

Underlined region can be any X sequence or linker, as described herein.

“I” stands for Inosine

[0250]

7

TABLE VII

HUMAN HBV G-CLEAVER AND SUBSTRATE SEQUENCE

Pos
Substrate
Seq ID
G-cleaver
Seq ID

61
ACUUUCCU G CUGGUGGC
1448
GCCACCAG UGAUG GCAUGCACUAUGC GCG AGGAAAGU
3957

87
GGAACAGU G AGCCCUGC
1449
GCAGGGCU UGAUG GCAUGCACUAUGC GCG ACUGUUCC
3958

94
UGAGCCCU G CUCAGAAU
1450
ACUCUGAG UGAUG GCAUGCACUAUGC GCG AGGGCUCA
3959

112
CUGUCUCU G CCAUAUCG
1451
CGAUAUGG UGAUG GCAUGCACUAUGC GCG AGAGACAG
3960

132
AUCUUAUC G AAGACUGG
1452
CCAGUCUU UGAUG GCAUGCACUAUGC GCG GAUAAGAU
3961

153
CCUGUACC G AACAUGGA
1453
UCCAUGUU UGAUG GCAUGCACUAUGC GCG GGUACAGG
3962

169
AGAACAUC G CAUCAGGA
1454
UCCUGAUG UGAUG GCAUGCACUAUGC GCG GAUGUUCU
3963

192
GGACCCCU G CUCGUGUU
1455
AACACGAG UGAUG GCAUGCACUAUGC GCG AGGGGUCC
3964

222
UUCUUGUU G ACAAAAAU
1456
AUUUUUGU UGAUG GCAUGCACUAUGC GCG AACAAGAA
3965

315
CAAAAUUC G CAGUCCCA
1457
UGGGACUG UGAUG GCAUGCACUAUGC GCG GAAUUUUG
3966

374
UGGUUAUC G CUGGAUCU
1458
ACAUCCAG UGAUG GCAUGCACUAUGC GCG GAUAACCA
3967

387
AUGUGUCU G CGGCGUUU
1459
AAACGCCG UGAUG GCAUGCACUAUGC GCG AGACACAU
3968

410
CUUCCUCU G CAUCCUGC
1460
GCAGGAUG UGAUG GCAUGCACUAUGC GCG AGAGGAAG
3969

417
UGCAUCCU G CUGCUAUG
1461
CAUAGCAG UGAUG GCAUGCACUAUGC GCG AGGAUGCA
3970

420
AUCCUGCU G CUAUGCCU
1462
AGGCAUAG UGAUG GCAUGCACUAUGC GCG AGCAGGAU
3971

425
GCUGCUAU G CCUCAUCU
1463
AGAUGAGG UGAUG GCAUGCACUAUGC GCG AUAGCAGC
3972

468
GGUAUGUU G CCCGUUUG
1464
CAAACGGG UGAUG GCAUGCACUAUGC GCG AACAUACC
3973

518
CGGACCAU G CAAAACCU
1465
AGGUUUUG UGAUG GCAUGCACUAUGC GCG AUGGUCCG
3974

527
CAAAACCU G CACAACUC
1466
GAGUUGUG UGAUG GCAUGCACUAUGC GCG AGGUUUUG
3975

538
CAACUCCU G CUCAAGGA
1467
UCCUUGAG UGAUG GCAUGCACUAUGC GCG AGGAGUUG
3976

569
CUCAUGUU G CUGUACAA
1468
UUGUACAG UGAUG GCAUGCACUAUGC GCG AACAUGAG
3977

596
CGGAAACU G CACCUGUA
1469
UACAGGUG UGAUG GCAUGCACUAUGC GCG AGUUUCCG
3978

631
GGGCUUUC G CAAAAUAC
1470
GUAUUUUG UGAUG GCAUGCACUAUGC GCG GAAAGCCC
3979

687
UUACUAGU G CCAUUUGU
1471
ACAAAUGG UGAUG GCAUGCACUAUGC GCG ACUAGUAA
3980

747
AUAUGGAU G AUGUGGUU
1472
AACCACAU UGAUG GCAUGCACUAUGC GCG AUCCAUAU
3981

783
AACAUCUU G AGUCCCUU
1473
AAGGGACU UGAUG GCAUGCACUAUGC GCG AAGAUGUU
3982

795
CCCUUUAU G CCGCUGUU
1474
AACAGCGG UGAUG GCAUGCACUAUGC GCG AUAAAGGG
3983

798
UUUAUGCC G CUGUUACC
1475
GGUAACAG UGAUG GCAUGCACUAUGC GCG GGCAUAAA
3984

911
GGCACAUU G CCACAGGA
1476
UCCUGUGG UGAUG GCAUGCACUAUGC GCG AAUGUGCC
3985

978
GGCCUAUU G AUUGGAAA
1477
UUUCCAAU UGAUG GCAUGCACUAUGC GCG AAUAGGCC
3986

997
AUGUCAAC G AAUUGUGG
1478
CCACAAUU UGAUG GCAUGCACUAUGC GCG GUUGACAU
3987

1020
UGGGGUUU G CCGCCCCU
1479
AGGGGCGG UGAUG GCAUGCACUAUGC GCG AAACCCCA
3988

1023
GGUUUGCC G CCCCUUUC
1480
GAAAGGGG UGAUG GCAUGCACUAUGC GCG GGCAAACC
3989

1034
CCUUUCAC G CAAUGUGG
1481
CCACAUUG UGAUG GCAUGCACUAUGC GCG GUGAAAGG
3990

1050
GAUAUUCU G CUUUAAUG
1482
CAUUAAAG UGAUG GCAUGCACUAUGC GCG AGAAUAUC
3991

1058
GCUUUAAU G CCUUUAUA
1483
UAUAAAGG UGAUG GCAUGCACUAUGC GCG AUUAAAGC
3992

1068
CUUUAUAU G CAUGCAUA
1484
UAUGCAUG UGAUG GCAUGCACUAUGC GCG AUAUAAAG
3993

1072
AUAUGCAU G CAUACAAG
1485
CUUGUAUG UGAUG GCAUGCACUAUGC GCG AUGCAUAU
3994

1103
ACUUUCUC G CCAACUUA
1486
UAAGUUGG UGAUG GCAUGCACUAUGC GCG GAGAAAGU
3995

1139
CAGUAUGU G AACCUUUA
1487
UAAAGGUU UGAUG GCAUGCACUAUGC GCG ACAUACUG
3996

1155
ACCCCGUU G CUCGGCAA
1488
UUGCCGAG UGAUG GCAUGCACUAUGC GCG AACGGGGU
3997

1177
UGGUCUAU G CCAAGUGU
1489
ACACUUGG UGAUG GCAUGCACUAUGC GCG AUAGACCA
3998

1188
AAGUGUUU G CUGACGCA
1490
UGCGUCAG UGAUG GCAUGCACUAUGC GCG AAACACUU
3999

1191
UGUUUGCU G ACGCAACC
1491
GGUUGCGU UGAUG GCAUGCACUAUGC GCG AGCAAACA
4000

1194
UUGCUGAC G CAACCCCC
1492
GGGGGUUG UGAUG GCAUGCACUAUGC GCG GUCAGCAA
4001

1234
CCAUCAGC G CAUGCGUG
1493
CACGCAUG UGAUG GCAUGCACUAUGC GCG GCUGAUGG
4002

1238
CAGCGCAU G CGUGGAAC
1494
GUUCCACG UGAUG GCAUGCACUAUGC GCG AUGCGCUG
4003

1262
UCUCCUCU G CCGAUCCA
1495
UGGAUCGG UGAUG GCAUGCACUAUGC GCG AGAGGAGA
4004

1265
CCUCUGCC G AUCCAUAC
1496
GUAUGGAU UGAUG GCAUGCACUAUGC GCG GGCAGAGG
4005

1275
UCCAUACC G CGGAACUC
1497
GAGUUCCG UGAUG GCAUGCACUAUGC GCG GGUAUGGA
4006

1290
UCCUAGCC G CUUGUUUU
1498
AAAACAAG UGAUG GCAUGCACUAUGC GCG GGCUAGGA
4007

1299
CUUGUUUU G CUCGCAGC
1499
GCUGCGAG UGAUG GCAUGCACUAUGC GCG AAAACAAG
4008

1303
UUUUGCUC G CAGCAGGU
1500
ACCUGCUG UGAUG GCAUGCACUAUGC GCG GAGCAAAA
4009

1335
UCGGGACU G ACAAUUCU
1501
AGAAUUGU UGAUG GCAUGCACUAUGC GCG AGUCCCGA
4010

1349
UCUGUCGU G CUCUCCCG
1502
CGGGAGAG UGAUG GCAUGCACUAUGC GCG ACGACAGA
4011

1357
GCUCUCCC G CAAAUAUA
1503
UAUAUUUG UGAUG GCAUGCACUAUGC GCG GGGAGAGC
4012

1382
CCAUGGCU G CUAGGCUG
1504
CAGCCUAG UGAUG GCAUGCACUAUGC GCG AGCCAUGG
4013

1392
UAGGCUGU G CUGCCAAC
1505
GUUGGCAG UGAUG GCAUGCACUAUGC GCG ACAGCCUA
4014

1395
GCUGUGCU G CCAACUGG
1506
CCAGUUGG UGAUG GCAUGCACUAUGC GCG AGCACAGC
4015

1411
GAUCCUAC G CGGGACGU
1507
ACGUCCCG UGAUG GCAUGCACUAUGC GCG GUAGGAUC
4016

1442
CCGUCGGC G CUGAAUCC
1508
GGAUUCAG UGAUG GCAUGCACUAUGC GCG GCCGACGC
4017

1445
UCGGCGCU G AAUCCCGC
1509
GCGGGAUU UGAUG GCAUGCACUAUGC GCG AGCGCCGA
4018

1452
UGAAUCCC G CGGACGAC
1510
GUCGUCCG UGAUG GCAUGCACUAUGC GCG GGGAUUCA
4019

1458
CCGCGGAC G ACCCCUCC
1511
GGAGGGGU UGAUG GCAUGCACUAUGC GCG GUCCGCGG
4020

1474
CCGGGGCC G CUUGGGGC
1512
GCCCCAAG UGAUG GCAUGCACUAUGC GCG GGCCCCGG
4021

1489
GCUCUACC G CCCGCUUC
1513
GAAGCGGG UGAUG GCAUGCACUAUGC GCG GGUAGAGC
4022

1493
UACCGCCC G CUUCUCCG
1514
CGGAGAAG UGAUG GCAUGCACUAUGC GCG GGGCGGUA
4023

1501
GCUUCUCC G CCUAUUGU
1515
ACAAUAGG UGAUG GCAUGCACUAUGC GCG GGAGAAGC
4024

1513
AUUGUACC G ACCGUCCA
1516
UGGACGGU UGAUG GCAUGCACUAUGC GCG GGUACAAU
4025

1528
CACGGGGC G CACCUCUC
1517
GAGAGGUG UGAUG GCAUGCACUAUGC GCG GCCCCGUG
4026

1542
CUCUUUAC G CGGACUCC
1518
GGAGUCCG UGAUG GCAUGCACUAUGC GCG GUAAAGAG
4027

1559
CCGUCUGU G CCUUCUCA
1519
UGAGAAGG UGAUG GCAUGCACUAUGC GCG ACAGACGG
4028

1571
UCUCAUCU G CCGGACCG
1520
CGGUCCGG UGAUG GCAUGCACUAUGC GCG AGAUGAGA
4029

1583
GACCGUGU G CACUUCGC
1521
GCGAAGUG UGAUG GCAUGCACUAUGC GCG ACACCGUC
4030

1590
UGCACUUC G CUUCACCU
1522
AGGUGAAG UGAUG GCAUGCACUAUGC GCG GAAGUGCA
4031

1601
UCACCUCU G CACGUCGC
1523
GCGACGUG UGAUG GCAUGCACUAUGC GCG AGAGGUGA
4032

1608
UGCACGUC G CAUGGAGA
1524
UCUCCAUG UGAUG GCAUGCACUAUGC GCG GACGUGCA
4033

1624
ACCACCGU G AACGCCCA
1525
UGGGCGUU UGAUG GCAUGCACUAUGC GCG ACGGUGGU
4034

1628
CCGUGAAC G CCCACAGG
1526
CCUGUGGG UGAUG GCAUGCACUAUGC GCG GUUCACGG
4035

1642
AGGAACCU G CCCAAGGU
1527
ACCUUGGG UGAUG GCAUGCACUAUGC GCG AGGUUCCU
4036

1654
AAGGUCUU G CAUAAGAG
1528
CUCUUAUG UGAUG GCAUGCACUAUGC GCG AAGACCUU
4037

1690
AUGUCAAC G ACCGACCU
1529
AGGUCGGU UGAUG GCAUGCACUAUGC GCG GUUGACAU
4038

1694
CAACGACC G ACCUUGAG
1530
CUCAAGGU UGAUG GCAUGCACUAUGC GCG GGUCGUUG
4039

1700
CCGACCUU G AGGCAUAC
1531
GUAUGCCU UGAUG GCAUGCACUAUGC GCG AAGGUCGG
4040

1730
UGUUUAAU G AGUGGGAG
1532
CUCCCACU UGAUG GCAUGCACUAUGC GCG AUUAAACA
4041

1818
AGCACCAU G CAACUUUU
1533
AAAAGUUG UGAUG GCAUGCACUAUGC GCG AUGGUGCU
4042

1835
UCACCUCU G CCUAAUCA
1534
UGAUUAGG UGAUG GCAUGCACUAUGC GCG AGAGGUGA
4043

1883
CAAGCUGU G CCUUGGGU
1535
ACCCAAGG UGAUG GCAUGCACUAUGC GCG ACAGCUUG
4044

1912
UGGACAUU G ACCCGUAU
1536
AUACGGGU UGAUG GCAUGCACUAUGC GCG AAUGUCCA
4045

1959
UCUUUUUU G CCUUCUGA
1537
UCAGAAGG UGAUG GCAUGCACUAUGC GCG AAAAAAGA
4046

1966
UGCCUUCU G ACUUCUUU
1538
AAAGAACU UGAUG GCAUGCACUAUGC GCG AGAAGGCA
4047

1985
UUCUAUUC G AGAUCUCC
1539
GGAGAUCU UGAUG GCAUGCACUAUGC GCG GAAUAGAA
4048

1996
AUCUCCUC G ACACCGCC
1540
GGCGGUGU UGAUG GCAUGCACUAUGC GCG GAGGAGAU
4049

2002
UCGACACC G CCUCUGCU
1541
AGCAGAGG UGAUG GCAUGCACUAUGC GCG GGUGUCGA
4050

2008
CCGCCUCU G CUCUGUAU
1542
AUACAGAG UGAUG GCAUGCACUAUGC GCG AGAGGCGG
4051

2092
GUUGGGGU G AGUUGAUG
1543
CAUCAACU UGAUG GCAUGCACUAUGC GCG ACCCCAAC
4052

2097
GGUGAGUU G AUGAAUCU
1544
AGAUUCAU UGAUG GCAUGCACUAUGC GCG AACUCACC
4053

2100
GAGUUGAU G AAUCUAGC
1545
GCUAGAUU UGAUG GCAUGCACUAUGC GCG AUCAACUC
4054

2237
UUUUGGGC G AGAAACUG
1546
CAGUUUCU UGAUG GCAUGCACUAUGC GCG GCCCAAAA
4055

2251
CUGUUCUU G AAUAUUUG
1547
CAAAUAUU UGAUG GCAUGCACUAUGC GCG AAGAACAG
4056

2282
GUGGAUUC G CACUCCUC
1548
GAGGAGUG UGAUG GCAUGCACUAUGC GCG GAAUCCAC
4057

2293
CUCCUCCU G CAUAUAGA
1549
UCUAUAUG UGAUG GCAUGCACUAUGC GCG AGGAGGAG
4058

2311
CACCAAAU G CCCCUAUC
1550
GAUAGGGG UGAUG GCAUGCACUAUGC GCG AUUUGGUG
4059

2354
UGUUAGAC G AAGAGGCA
1551
UGCCUCUU UGAUG GCAUGCACUAUGC GCG GUCUAACA
4060

2388
ACUCCCUC G CCUCGCAG
1552
CUGCGAGG UGAUG GCAUGCACUAUGC GCG GAGGGAGU
4061

2393
CUCGCCUC G CAGACGAA
1553
UUCGUCUG UGAUG GCAUGCACUAUGC GCG GACGCGAG
4062

2399
UCGCAGAC G AAGGUCUC
1554
GAGACCUU UGAUG GCAUGCACUAUGC GCG GUCUGCGA
4063

2412
UCUCAAUC G CCGCGUCG
1555
CGACGCGG UGAUG GCAUGCACUAUGC GCG GAUUGAGA
4064

2415
CAAUCGCC G CGUCGCAG
1556
CUGCGACG UGAUG GCAUGCACUAUGC GCG GGCGAUUG
4065

2420
GCCGCGUC G CAGAAGAU
1557
AUCUUCUG UGAUG GCAUGCACUAUGC GCG GACGCGGC
4066

2514
GGUACCUU G CUUUAAUC
1558
GAUUAAAG UGAUG GCAUGCACUAUGC GCG AAGGUACC
4067

2549
CUUUUCCU G ACAUUCAU
1559
AUGAAUGU UGAUG GCAUGCACUAUGC GCG AGGAAAAG
4068

2560
AUUCAUUU G CAGGAGGA
1560
UCCUCCUG UGAUG GCAUGCACUAUGC GCG AAAUGAAU
4069

2576
ACAUUGUU G AUAGAUGU
1561
ACAUCUAU UGAUG GCAUGCACUAUGC GCG AACAAUGU
4070

2615
CAGUAAAU G AAAACAGG
1562
CCUGUUUU UGAUG GCAUGCACUAUGC GCG AUUUACUG
4071

2641
UUAACUAU G CCUGCUAG
1563
CUAGCAGG UGAUG GCAUGCACUAUGC GCG AUAGUUAA
4072

2645
CUAUGCCU G CUAGGUUU
1564
AAACCUAG UGAUG GCAUGCACUAUGC GCG AGGCAUAG
4073

2677
AAAUAUUU G CCCUUAGA
1565
UCUAAGGG UGAUG GCAUGCACUAUGC GCG AAAUAUUU
4074

2740
UUCCAGAC G CGACAUUA
1566
UAAUGUCG UGAUG GCAUGCACUAUGC GCG GUCUGGAA
4075

2742
CCAGACGC G ACAUUAUU
1567
AAUAAUGU UGAUG GCAUGCACUAUGC GCG GCGUCUGG
4076

2804
CACGUAGC G CCUCAUUU
1568
AAAUGAGG UGAUG GCAUGCACUAUGC GCG GCUACGUG
4077

2814
CUCAUUUU G CGGGUCAC
1569
GUGACCCG UGAUG GCAUGCACUAUGC GCG AAAAUGAG
4078

2875
CAAACCUC G AAAAGGCA
1570
UGCCUUUU UGAUG GCAUGCACUAUGC GCG GAGGUUUG
4079

2928
UCUUCCCC G AUCAUCAG
1571
CUGAUGAU UGAUG GCAUGCACUAUGC GCG GGGGAAGA
4080

2946
UGGACCCU G CAUUCAAA
1572
UUUGAAUG UGAUG GCAUGCACUAUGC GCG AGGGUCCA
4081

2990
CUCAACCC G CACAAGGA
1573
UCCUUGUG UGAUG GCAUGCACUAUGC GCG GGGUUGAG
4082

3012
GGCCGGAC G CCAACAAG
1574
CUUGUUGG UGAUG GCAUGCACUAUGC GCG GUCCGGCC
4083

3090
GCCCUCAC G CUCAGGGC
1575
GCCCUGAG UGAUG GCAUGCACUAUGC GCG GUGAGGGC
4084

3113
ACAACUGU G CCAGCAGC
1576
GCUGCUGG UGAUG GCAUGCACUAUGC GCG ACAGUUGU
4085

3132
CUCCUCCU G CCUCCACC
1577
GGUGGAGG UGAUG GCAUGCACUAUGC GCG AGGAGGAG
4086

51
AGGGCCCU G UACUUUCC
1578
GGAAAGUA UGAUG GCAUGCACUAUGC GCG AGGGCCCU
4087

106
AGAAUACU G UCUCUGCC
1579
GGCAGAGA UGAUG GCAUGCACUAUGC GCG AGUAUUCU
4088

148
GGGACCCU G UACCGAAC
1580
GUUCGGUA UGAUG GCAUGCACUAUGC GCG AGGGUCCC
4089

198
CUGCUCGU G UUACAGGC
1581
GCCUGUAA UGAUG GCAUGCACUAUGC GCG ACGAGCAG
4090

219
UUUUUCUU G UUGACAAA
1582
UUUGUCAA UGAUG GCAUGCACUAUGC GCG AAGAAAAA
4091

297
ACACCCGU G UGUCUUGG
1583
CCAAGACA UGAUG GCAUGCACUAUGC GCG ACGGGUGU
4092

299
ACCCGUGU G UCUUGGCC
1584
GGCCAAGA UGAUG GCAUGCACUAUGC GCG ACACGGGU
4093

347
ACCAACCU G UUGUCCUC
1585
GAGGACAA UGAUG GCAUGCACUAUGC GCG AGGUUGGU
4094

350
AACCUGUU G UCCUCCAA
1586
UUGGAGGA UGAUG GCAUGCACUAUGC GCG AACAGGUU
4095

362
UCCAAUUU G UCCUGGUU
1587
AACCAGGA UGAUG GCAUGCACUAUGC GCG AAAUUGGA
4096

381
CGCUGGAU G UGUCUGCG
1588
CGCAGACA UGAUG GCAUGCACUAUGC GCG AUCCAGCG
4097

383
CUGGAUGU G UCUGCGGC
1589
GCCGCAGA UGAUG GCAUGCACUAUGC GCG ACAUCCAG
4098

438
AUCUUCUU G UUGGUUCU
1590
AGAACCAA UGAUG GCAUGCACUAUGC GCG AAGAAGAU
4099

465
CAAGGUAU G UUGCCCGU
1591
ACGGGCAA UGAUG GCAUGCACUAUGC GCG AUACCUUG
4100

476
GCCCGUUU G UCCUCUAA
1592
UUAGAGGA UGAUG GCAUGCACUAUGC GCG AAACGGGC
4101

555
ACCUCUAU G UUUCCCUC
1593
GAGGGAAA UGAUG GCAUGCACUAUGC GCG AUAGAGGU
4102

566
UCCCUCAU G UUGCUGUA
1594
UACAGCAA UGAUG GCAUGCACUAUGC GCG AUGAGGGA
4103

572
AUGUUGCU G UACAAAAC
1595
GUUUUGUA UGAUG GCAUGCACUAUGC GCG AGCAACAU
4104

602
CGCCACCU G UAUUCCCA
1596
UGGGAAUA UGAUG GCAUGCACUAUGC GCG AGGUGCAG
4105

694
UGCCAUUU G UUCAGUGG
1597
CCACUGAA UGAUG GCAUGCACUAUGC GCG AAAUGGCA
4106

724
CCCCCACU G UCUGGCUU
1598
AAGCCAGA UGAUG GCAUGCACUAUGC GCG AGUGGGGG
4107

750
UGGAUGAU G UGGUUUUG
1599
CAAAACCA UGAUG GCAUGCACUAUGC GCG AUCAUCCA
4108

771
CCAAGUCU G UACAACAU
1600
AUGUUGUA UGAUG GCAUGCACUAUGC GCG AGACUUGG
4109

801
AUGCCGCU G UUACCAAU
1601
AUUGGUAA UGAUG GCAUGCACUAUGC GCG AGCGGCAU
4110

818
UUUCUUUU G UCUUUGGG
1602
CCCAAAGA UGAUG GCAUGCACUAUGC GCG AAAAGAAA
4111

888
UGGGAUAU G UAAUUGGG
1603
CCCAAUUA UGAUG GCAUGCACUAUGC GCG AUAUCCCA
4112

927
AACAUAUU G UACAAAAA
1604
UUUUUGUA UGAUG GCAUGCACUAUGC GCG AAUAUGUU
4113

944
AUCAAAAU G UGUUUUAG
1605
CUAAAACA UGAUG GCAUGCACUAUGC GCG AUUUUGAU
4114

946
CAAAAUGU G UUUUAGGA
1606
UCCUAAAA UGAUG GCAUGCACUAUGC GCG ACAUUUUG
4115

963
AACUUCCU G UAAACAGG
1607
CCUGUUUA UGAUG GCAUGCACUAUGC GCG AGGAAGUU
4116

991
GAAAGUAU G UCAACGAA
1608
UUCGUUGA UGAUG GCAUGCACUAUGC GCG AUACUUUC
4117

1002
AACGAAUU G UGGGUCUU
1609
AAGACCCA UGAUG GCAUGCACUAUGC GCG AAUUCGUU
4118

1039
CACGCAAU G UGGAUAUU
1610
AAUAUCCA UGAUG GCAUGCACUAUGC GCG AUUGCGUG
4119

1137
AACAGUAU G UGAACCUU
1611
AAGGUUCA UGAUG GCAUGCACUAUGC GCG AUACUGUU
4120

1184
UGCCAAGU G UUUGCUGA
1612
UCAGCAAA UGAUG GCAUGCACUAUGC GCG ACUUGGCA
4121

1251
GAACCUUU G UGUCUCCU
1613
AGGAGACA UGAUG GCAUGCACUAUGC GCG AAAGGUUC
4122

1253
ACCUUUGU G UCUCCUCU
1614
AGAGGAGA UGAUG GCAUGCACUAUGC GCG ACAAAGGU
4123

1294
AGCCGCUU G UUUUGCUC
1615
GAGCAAAA UGAUG GCAUGCACUAUGC GCG AAGCGGCU
4124

1344
ACAAUUCU G UCGUGCUC
1616
GAGCACGA UGAUG GCAUGCACUAUGC GCG AGAAUUGU
4125

1390
GCUAGGCU G UGCUGCCA
1617
UGGCAGCA UGAUG GCAUGCACUAUGC GCG AGCCUAGC
4126

1425
CGUCCUUU G UUUACGUC
1618
GACGUAAA UGAUG GCAUGCACUAUGC GCG AAAGGACG
4127

1508
CGCCUAUU G UACCGACC
1619
GGUCGGUA UGAUG GCAUGCACUAUGC GCG AAUAGGCG
4128

1557
CCCCGUCU G UGCCUUCU
1620
AGAAGGCA UGAUG GCAUGCACUAUGC GCG AGACGGGG
4129

1581
CGGACCGU G UGCACUUC
1621
GAAGUGCA UGAUG GCAUGCACUAUGC GCG ACGGUCCG
4130

1684
UCAGCAAU G UCAACGAC
1622
GUCGUUGA UGAUG GCAUGCACUAUGC GCG AUUGCUGA
4131

1719
CAAAGACU G UGUGUUUA
1623
UAAACACA UGAUG GCAUGCACUAUGC GCG AGUCUUUG
4132

1721
AAGACUGU G UGUUUAAU
1624
AUUAAACA UGAUG GCAUGCACUAUGC GCG ACAGUCUU
4133

1723
GACUGUGU G UUUAAUGA
1625
UCAUUAAA UGAUG GCAUGCACUAUGC GCG ACACAGUC
4134

1772
AGGUCUUU G UACUAGGA
1626
UCCUAGUA UGAUG GCAUGCACUAUGC GCG AAAGACCU
4135

1785
AGGAGGCU G UAGGCAUA
1627
UAUGCCUA UGAUG GCAUGCACUAUGC GCG AGCCUCCU
4136

1801
AAAUUGGU G UGUUCACC
1628
GGUGAACA UGAUG GCAUGCACUAUGC GCG ACCAAUUU
4137

1803
AUGGGUGU G UUCACCAG
1629
CUGGUGAA UGAUG GCAUGCACUAUGC GCG ACACCAAU
4138

1850
CAUCUCAU G UUCAUGUC
1630
GACAUGAA UGAUG GCAUGCACUAUGC GCG AUGAGAUG
4139

1856
AUGUUCAU G UCCUACUG
1631
CAGUAGGA UGAUG GCAUGCACUAUGC GCG AUGAACAU
4140

1864
GUCCUACU G UUCAAGCC
1632
GGCUUGAA UGAUG GCAUGCACUAUGC GCG AGUAGGAC
4141

1881
UCCAAGCU G UGCCUUGG
1633
CCAAGGCA UGAUG GCAUGCACUAUGC GCG AGCUUGGA
4142

1939
GAGCUUCU G UGGAGUUA
1634
UAACUCCA UGAUG GCAUGCACUAUGC GCG AGAAGCUC
4143

2013
UCUGCUCU G UAUCGGGG
1635
CCCCGAUA UGAUG GCAUGCACUAUGC GCG AGAGCAGA
4144

2045
GGAACAUU G UUCACCUC
1636
GAGGUGAA UGAUG GCAUGCACUAUGC GCG AAUGUUCC
4145

2082
GCUAUUCU G UGUUGGGG
1637
CCCCAACA UGAUG GCAUGCACUAUGC GCG AGAAUAGC
4146

2084
UAUUCUGU G UUGGGGUG
1638
CACCCCAA UGAUG GCAUGCACUAUGC GCG ACAGAAUA
4147

2167
UCAGCUAU G UCAACGUU
1639
AACGUUGA UGAUG GCAUGCACUAUGC GCG AUAGCUGA
4148

2205
CAACUAUU G UGGUUUCA
1640
UGAAACCA UGAUG GCAUGCACUAUGC GCG AAUAGUUG
4149

2222
CAUUUCCU G UCUUACUU
1641
AAGUAAGA UGAUG GCAUGCACUAUGC GCG AGGAAAUG
4150

2245
GAGAAACU G UUCUUGAA
1642
UUCAAGAA UGAUG GCAUGCACUAUGC GCG AGUUUCUC
4151

2262
UAUUUGGU G UCUUUUGG
1643
CCAAAAGA UGAUG GCAUGCACUAUGC GCG ACCAAAUA
4152

2274
UUUGGAGU G UGGAUUCG
1644
CGAAUCCA UGAUG GCAUGCACUAUGC GCG ACUCCAAA
4153

2344
AAACUACU G UUGUUAGA
1645
UCUAACAA UGAUG GCAUGCACUAUGC GCG AGUAGUUU
4154

2347
CUACUGUU G UUAGACGA
1646
UCGUCUAA UGAUG GCAUGCACUAUGC GCG AACAGUAG
4155

2450
AUCUCAAU G UUAGUAUU
1647
AAUACUAA UGAUG GCAUGCACUAUGC GCG AUUGAGAU
4156

2573
AGGACAUU G UUGAUAGA
1648
UCUAUCAA UGAUG GCAUGCACUAUGC GCG AAUGUCCU
4157

2583
UGAUAGAU G UAAGCAAU
1649
AUUGCUUA UGAUG GCAUGCACUAUGC GCG AUCUAUCA
4158

2594
AGCAAUUU G UGGGGCCC
1650
GGGCCCCA UGAUG GCAUGCACUAUGC GCG AAAUUGCU
4159

2663
AUCCCAAU G UUACUAAA
1651
UUUAGUAA UGAUG GCAUGCACUAUGC GCG AUUGGGAU
4160

2717
CAGAGUAC G UAGUUAAU
1652
AUUAACUA UGAUG GCAUGCACUAUGC GCG AUACUCUG
4161

2901
AUCUUUCU G UCCCCAAU
1653
AUUGGGGA UGAUG GCAUGCACUAUGC GCG AGAAAGAU
4162

3071
GGGGGACU G UUGGGGUG
1654
CACCCCAA UGAUG GCAUGCACUAUGC GCG AGUCCCCC
4163

3111
UCACAACU G UGCCAGCA
1655
UGCUGGCA UGAUG GCAUGCACUAUGC GCG AGUUGUGA
4164

Input Sequence = AF100308.

Cut Site = YG/M or UC/U.

Stem Length = 8.

Core Sequence = UGAUG GCAUGCACUAUGC GCG

AF100308 (Hepatitis B virus strain 2-18, 3215 bp)

[0251]

8

TABLE VIII

HUMAN HBV ZINZYME AND SUBSTRATE SEQUENCE

Pos
Substrate
Seq ID
Zinzyme
Seq ID

61
ACUUUCCU G GUGGUGGC
1448
GCCACCAG GCcgaaagGCGaGuCaaGGuCu AGGAAAGU
4165

94
UGAGCCCU G CUCAGAAU
1450
AUUCUGAG GCcgaaagGCGaGuCaaGGuCu AGGGCUCA
4166

112
CUGUCUCU G CCAUAUCG
1451
CGAUAUGG GCcgaaagGCGaGuCaaGGuCu AGAGACAG
4167

169
AGAACAUC G CAUCAGGA
1454
UCCUGAUG GCcgaaagGCGaGuCaaGGuCu GAUGUUCU
4168

192
GGACCCCU G CUCGUGUU
1455
AACACGAG GCcgaaagGCGaGuCaaGGuCu AGGGGUCC
4169

315
CAAAAUUC G CAGUCCCA
1457
UGGGACUG GCcgaaagGCGaGuCaaGGuCu GAAUUUUG
4170

374
UGGUUAUC G CUGGAUGU
1458
ACAUCCAG GCcgaaagGCGaGuCaaGGuCu GAUAACCA
4171

387
AUGUGUCU G CGGCGUUU
1459
AAACGCCG GCcgaaagGCGaGuCaaGGuCu AGACACAU
4172

410
CUUCCUCU G CAUCCUGC
1460
GCAGGAUG GCcgaaagGCGaGuCaaGGuCu AGAGGAAG
4173

417
UGCAUCCU G CUGCUAUG
1461
CAUAGCAG GCcgaaagGCGaGuCaaGGuCu AGGAUGCA
4174

420
AUCCUGCU G CUAUGCCU
1462
AGGCAUAG GCcgaaagGCGaGuCaaGGuCu AGCAGGAU
4175

425
GCUGCUAU G CCUCAUCU
1463
AGAUGAGG GCcgaaagGCGaGuCaaGGuCu AUAGCAGC
4176

468
GGUAUGUU G CCCGUUUG
1464
CAAACGGG GCcgaaagGCGaGuCaaGGuCu AACAUACC
4177

518
CGGACCAU G CAAAACCU
1465
AGGUUUUG GCcgaaagGCGaGuCaaGGuCu AUGGUCCG
4178

527
CAAAACCU G CACAACUC
1466
GAGUUGUG GCcgaaagGCGaGuCaaGGuCu AGGUUUUG
4179

538
CAACUCCU G CUCAAGGA
1467
UCCUUGAG GCcgaaagGCGaGuCaaGGuCu AGGAGUUG
4180

569
CUCAUGUU G CUGUACAA
1468
UUGUACAG GCcgaaagGCGaGuCaaGGuCu AACAUGAG
4181

596
CGGAAACU G CACCUGUA
1469
UACAGGUG GCcgaaagGCGaGuCaaGGuCu AGUUUCCG
4182

631
GGGCUUUC G CAAAAUAC
1470
GUAUUUUG GCcgaaagGCGaGuCaaGGuCu GAAAGCCC
4183

687
UUACUAGU G CCAUUUGU
1471
ACAAAUGG GCcgaaagGCGaGuCaaGGuCu ACUAGUAA
4184

795
CCCUUUAU G CCGCUGUU
1474
AACAGCGG GCcgaaagGCGaGuCaaGGuCu AUAAAGGG
4185

798
UUUAUGCC G CUGUUACC
1475
GGUAACAG GCcgaaagGCGaGuCaaGGuCu GGCAUAAA
4186

911
GGCACAUU G CCACAGGA
1476
UCCUGUGG GCcgaaagGCGaGuCaaGGuCu AAUGUGCC
4187

1020
UGGGGUUU G CCGCCCCU
1479
AGGGGCGG GCcgaaagGCGaGuCaaGGuCu AAACCCCA
4188

1023
GGUUUGCC G CCCCUUUC
1480
GAAAGGGG GCcgaaagGCGaGuCaaGGuCu GGCAAACC
4189

1034
CCUUUCAC G CAAUGUGG
1481
CCACAUUG GCcgaaagGCGaGuCaaGGuCu GUGAAAGG
4190

1050
GAUAUUCU G CUUUAAUG
1482
CAUUAAAG GCcgaaagGCGaGuCaaGGuCu AGAAUAUC
4191

1058
GCUUUAAU G CCUUUAUA
1483
UAUAAAGG GCcgaaagGCGaGuCaaGGuCu AUUAAAGC
4192

1068
CUUUAUAU G CAUGCAUA
1484
UAUGCAUG GCcgaaagGCGaGuCaaGGuCu AUAUAAAG
4193

1072
AUAUGCAU G CAUACAAG
1485
CUUGUAUG GCcgaaagGCGaGuCaaGGuCu AUGCAUAU
4194

1103
ACUUUCUC G CCAACUUA
1486
UAAGUUGG GCcgaaagGCGaGuCaaGGuCu GAGAAAGU
4195

1155
ACCCCGUU G CUCGGCAA
1488
UUGCCGAG GCcgaaagGCGaGuCaaGGuCu AACGGGGU
4196

1177
UGGUCUAU G CCAAGUGU
1489
ACACUUGG GCcgaaagGCGaGuCaaGGuCu AUAGACCA
4197

1188
AAGUGUUU G CUGACGCA
1490
UGCGUCAG GCcgaaagGCGaGuCaaGGuCu AAACACUU
4198

1194
UUGCUGAC G CAACCCCC
1492
GGGGGUUG GCcgaaagGCGaGuCaaGGuCu GUCAGCAA
4199

1234
CCAUCAGC G CAUGCGUG
1493
CACGCAUG GCcgaaagGCGaGuCaaGGuCu GCUGAUGG
4200

1238
CAGCGCAU G CGUGGAAC
1494
GUUCCACG GCcgaaagGCGaGuCaaGGuCu AUGCGCUG
4201

1262
UCUCCUCU G CCGAUCCA
1495
UGGAUCGG GCcgaaagGCGaGuCaaGGuCu AGAGGAGA
4202

1275
UCCAUACC G CGGAACUC
1497
GAGUUCCG GCcgaaagGCGaGuCaaGGuCu GGUAUGGA
4203

1290
UCCUAGCC G CUUGUUUU
1498
AAAACAAG GCcgaaagGCGaGuCaaGGuCu GGCUAGGA
4204

1299
CUUGUUUU G CUCGCAGC
1499
GCUGCGAG GCcgaaagGCGaGuCaaGGuCu AAAACAAG
4205

1303
UUUUGCUC G CAGCAGGU
1500
ACCUGCUG GCcgaaagGCGaGuCaaGGuCu GAGCAAAA
4206

1349
UCUGUCGU G CUCUCCCG
1502
CGGGAGAG GCcgaaagGCGaGuCaaGGuCu ACGACAGA
4207

1357
GCUCUCCC G CAAAUAUA
1503
UAUAUUUG GCcgaaagGCGaGuCaaGGuCu GGGAGAGC
4208

1382
CCAUGGCU G CUAGGCUG
1504
CAGCCUAG GCcgaaagGCGaGuCaaGGuCu AGCCAUGG
4209

1392
UAGGCUGU G CUGCCAAC
1505
GUUGGCAG GCcgaaagGCGaGuCaaGGuCu ACAGCCUA
4210

1395
GCUGUGCU G CCAACUGG
1506
CCAGUUGG GCcgaaagGCGaGuCaaGGuCu AGCACAGC
4211

1411
GAUCCUAC G CGGGACGU
1507
ACGUCCCG GCcgaaagGCGaGuCaaGGuCu GUAGGAUC
4212

1442
CCGUCGGC G CUGAAUCC
1508
GGAUUCAG GCcgaaagGCGaGuCaaGGuCu GCCGACGG
4213

1452
UGAAUCCC G CGGACGAC
1510
GUCGUCCG GCcgaaagGCGaGuCaaGGuCu GGGAUUCA
4214

1474
CCGGGGCC G CUUGGGGC
1512
GCCCCAAG GCcgaaagGCGaGuCaaGGuCu GGCCCCGG
4215

1489
GCUCUACC G CCCGCUUC
1513
GAAGCGGG GCcgaaagGCGaGuCaaGGuCu GGUAGAGC
4216

1493
UACCGCCC G CUUCUCCG
1514
CGGAGAAG GCcgaaagGCGaGuCaaGGuCu GGGCGGUA
4217

1501
GCUUCUCC G CCUAUUGU
1515
ACAAUAGG GCcgaaagGCGaGuCaaGGuCu GGAGAAGC
4218

1528
CACGGGGC G CACCUCUC
1517
GAGAGGUG GCcgaaagGCGaGuCaaGGuCu GCCCCGUG
4219

1542
CUCUUUAC G CGGACUCC
1518
GGAGUCCG GCcgaaagGCGaGuCaaGGuCu GUAAAGAG
4220

1559
CCGUCUGU G CCUUCUCA
1519
UGAGAAGG GCcgaaagGCGaGuCaaGGuCu ACAGACGG
4221

1571
UCUCAUCU G CCGGACCG
1520
CGGUCCGG GCcgaaagGCGaGuCaaGGuCu AGAUGAGA
4222

1583
GACCGUGU G CACUUCGC
1521
GCGAAGUG GCcgaaagGCGaGuCaaGGuCu ACACGGUC
4223

1590
UGCACUUC G CUUCACCU
1522
AGGUGAAG GCcgaaagGCGaGuCaaGGuCu GAAGUGCA
4224

1601
UCACCUCU G CACGUCGC
1523
GCGACGUG GCcgaaagGCGaGuCaaGGuCu AGAGGUGA
4225

1608
UGCACGUC G CAUGGAGA
1524
UCUCCAUG GCcgaaagGCGaGuCaaGGuCu GACGUGCA
4226

1628
CCGUGAAC G CCCACAGG
1526
CCUGUGGG GCcgaaagGCGaGuCaaGGuCu GUUCACGG
4227

1642
AGGAACCU G CCCAAGGU
1527
ACCUUGGG GCcgaaagGCGaGuCaaGGuCu AGGUUCCU
4228

1654
AAGGUCUU G CAUAAGAG
1528
CUCUUAUG GCcgaaagGCGaGuCaaGGuCu AAGACCUU
4229

1818
AGCACCAU G CAACUUUU
1533
AAAAGUUG GCcgaaagGCGaGuCaaGGuCu AUGGUGCU
4230

1835
UCACCUCU G CCUAAUCA
1534
UGAUUAGG GCcgaaagGCGaGuCaaGGuCu AGAGGUGA
4231

1883
CAAGCUGU G CCUUGGGU
1535
ACCCAAGG GCcgaaagGCGaGuCaaGGuCu ACACGUUG
4232

1959
UCUUUUUU G CCUUCUGA
1537
UCAGAAGG GCcgaaagGCGaGuCaaGGuCu AAAAAAGA
4233

2002
UCGACACC G CCUCUGCU
1541
AGCAGAGG GCcgaaagGCGaGuCaaGGuCu GGUGUCGA
4234

2008
CCGCCUCU G CUCUGUAU
1542
AUACAGAG GCcgaaagGCGaGuCaaGGuCu AGAGGCGG
4235

2282
GUGGAUUC G CACUCCUC
1548
GAGGAGUG GCcgaaagGCGaGuCaaGGuCu GAAUCCAC
4236

2293
CUCCUCCU G CAUAUAGA
1549
UCUAUAUG GCcgaaagGCGaGuCaaGGuCu AGGAGGAG
4237

2311
CACCAAAU G CCCCUAUC
1550
GAUAGGGG GCcgaaagGCGaGuCaaGGuCu AUUUGGUG
4238

2388
ACUCCCUC G CCUCGCAG
1552
CUGCGAGG GCcgaaagGCGaGuCaaGGuCu GAGGGAGU
4239

2393
CUCGCCUC G CAGACGAA
1553
UUCGUCUG GCcgaaagGCGaGuCaaGGuCu GAGGCGAG
4240

2412
UCUCAAUC G CCGCGUCG
1555
CGACGCGG GCcgaaagGCGaGuCaaGGuCu GAUUGAGA
4241

2415
CAAUCGCC G CGUCGCAG
1556
CUGCGACG GCcgaaagGCGaGuCaaGGuCu GGCGAUUG
4242

2420
GCCGCGUC G CAGAAGAU
1557
AUCUUCUG GCcgaaagGCGaGuCaaGGuCu GACGCGGC
4243

2514
GGUACCUU G CUUUAAUC
1558
GAUUAAAG GCcgaaagGCGaGuCaaGGuCu AAGGUACC
4244

2560
AUUCAUUU G CAGGAGGA
1560
UCCUCCUG GCcgaaagGCGaGuCaaGGuCu AAAUGAAU
4245

2641
UUAACUAU G CCUGCUAG
1563
CUAGCAGG GCcgaaagGCGaGuCaaGGuCu AUAGUUAA
4246

2645
CUAUGCCU G CUAGGUUU
1564
AAACCUAG GCcgaaagGCGaGuCaaGGuCu AGGCAUAG
4247

2677
AAAUAUUU G CCCUUAGA
1565
UCUAAGGG GCcgaaagGCGaGuCaaGGuCu AAAUAUUU
4248

2740
UUCCAGAC G CGACAUUA
1566
UAAUGUCG GCcgaaagGCGaGuCaaGGuCu GUCUGGAA
4249

2804
CACGUAGC G CCUCAUUU
1568
AAAUGAGG GCcgaaagGCGaGuCaaGGuCu GCUACGUG
4250

2814
CUCAUUUU G CGGGUCAC
1569
GUGACCCG GCcgaaagGCGaGuCaaGGuCu AAAAUGAG
4251

2946
UGGACCCU G CAUUCAAA
1572
UUUGAAUG GCcgaaagGCGaGuCaaGGuCu AGGGUCCA
4252

2990
CUCAACCC G CACAAGGA
1573
UCCUUGUG GCcgaaagGCGaGuCaaGGuCu GGGUUGAG
4253

3012
GGCCGGAC G CCAACAAG
1574
CUUGUUGG GCcgaaagGCGaGuCaaGGuCu GUCCGGCC
4254

3090
GCCCUCAC G CUCAGGGC
1575
GCCCUGAG GCcgaaagGCGaGuCaaGGuCu GUGAGGGC
4255

3113
ACAACUGU G CCAGCAGC
1576
GCUGCUGG GCcgaaagGCGaGuCaaGGuCu ACAGUUGU
4256

3132
CUCCUCCU G CCUCCACC
1577
GGUGGAGG GCcgaaagGCGaGuCaaGGuCu AGGAGGAG
4257

51
AGGGCCCU G UACUUUCC
1578
GGAAAGUA GCcgaaagGCGaGuCaaGGuCu AGGGCCCU
4258

106
AGAAUACU G UCUCUGCC
1579
GGCAGAGA GCcgaaagGCGaGuCaaGGuCu AGUAUUCU
4259

148
GGGACCCU G UACCGAAC
1580
GUUCGGUA GCcgaaagGCGaGuCaaGGuCu AGGGUCCC
4260

198
CUGCUCGU G UUACAGGC
1581
GCCUGUAA GCcgaaagGCGaGuCaaGGuCu ACGAGCAG
4261

219
UUUUUCUU G UUGACAAA
1582
UUUGUCAA GCcgaaagGCGaGuCaaGGuCu AAGAAAAA
4262

297
ACACCCGU G UGUCUUGG
1583
CCAAGACA GCcgaaagGCGaGuCaaGGuCu ACGGGUGU
4263

299
ACCCGUGU G UCUUGGCC
1584
GGCCAAGA GCcgaaagGCGaGuCaaGGuCu ACACGGGU
4264

347
ACCAACCU G UUCUCCUC
1585
GAGGACAA GCcgaaagGCGaGuCaaGGuCu AGGUUGGU
4265

350
AACCUGUU G UCCUCCAA
1586
UUGGAGGA GCcgaaagGCGaGuCaaGGuCu AACAGGUU
4266

362
UCCAAUUU G UCCUGGUU
1587
AACCAGGA GCcgaaagGCGaGuCaaGGuCu AAAUUGGA
4267

381
CGCUGGAU G UGUCUGCG
1588
CGCAGACA GCcgaaagGCGaGuCaaGGuCu AUCCAGCG
4268

383
CUGGAUGU G UCUGCGGC
1589
GCCGCAGA GCcgaaagGCGaGuCaaGGuCu ACAUCCAG
4269

438
AUCUUCUU G UUGGUUCU
1590
AGAACCAA GCcgaaagGCGaGuCaaGGuCu AAGAAGAU
4270

465
CAAGGUAU G UUGCCCGU
1591
ACGGGCAA GCcgaaagGCGaGuCaaGGuCu AUACCUUG
4271

476
GCCCGUUU G UCCUCUAA
1592
UUAGAGGA GCcgaaagGCGaGuCaaGGuCu AAACGGGC
4272

555
ACCUCUAU G UUUCCCUC
1593
GAGGGAAA GCcgaaagGCGaGuCaaGGuCu AUAGAGGU
4273

566
UCCCUCAU G UUGCUGUA
1594
UACAGCAA GCcgaaagGCGaGuCaaGGuCu AUGAGGGA
4274

572
AUGUUGCU G UACAAAAC
1595
GUUUUGUA GCcgaaagGCGaGuCaaGGuCu AGCAACAU
4275

602
CUGCACCU G UAUUCCCA
1596
UGGGAAUA GCcgaaagGCGaGuCaaGGuCu AGGUGCAG
4276

694
UGCCAUUU G UUCAGUGG
1597
CCACUGAA GCcgaaagGCGaGuCaaGGuCu AAAUGGCA
4277

724
CCCCCACU G UCUGGCUU
1598
AAGCCAGA GCcgaaagGCGaGuCaaGGuCu AGUGGGGG
4278

750
UGGAUGAU G UGGUUUUG
1599
CAAAACCA GCcgaaagGCGaGuCaaGGuCu AUCAUCCA
4279

771
CCAAGUCU G UACAACAU
1600
AUGUUGUA GCcgaaagGCGaGuCaaGGuCu AGACUUGG
4280

801
AUGCCGCU G UUACCAAU
1601
AUUGGUAA GCcgaaagGCGaGuCaaGGuCu AGCGGCAU
4281

818
UUUCUUUU G UCUUUGGG
1602
CCCAAAGA GCcgaaagGCGaGuCaaGGuCu AAAAGAAA
4282

888
UGGGAUAU G UAAUUGGG
1603
CCCAAUUA GCcgaaagGCGaGuCaaGGuCu AUAUCCCA
4283

927
AACAUAUU G UACAAAAA
1604
UUUUUGUA GCcgaaagGCGaGuCaaGGuCu AAUAUGUU
4284

944
AUCAAAAU G UGUUUUAG
1605
CUAAAACA GCcgaaagGCGaGuCaaGGuCu AUUUUGAU
4285

946
CAAAAUGU G UUUUAGGA
1606
UCCUAAAA GCcgaaagGCGaGuCaaGGuCu ACAUUUUG
4286

963
AACUUCCU G UAAACAGG
1607
CCUGUUUA GCcgaaagGCGaGuCaaGGuCu AGGAAGUU
4287

991
GAAAGUAU G UCAACGAA
1608
UUCGUUGA GCcgaaagGCGaGuCaaGGuCu AUACUUUC
4288

1002
AACGAAUU G UGGGUCUU
1609
AAGACCCA GCcgaaagGCGaGuCaaGGuCu AAUUCGUU
4289

1039
CACGCAAU G UGGAUAUU
1610
AAUAUCCA GCcgaaagGCGaGuCaaGGuCu AUUGCGUG
4290

1137
AACAGUAU G UGAACCUU
1611
AAGGUUCA GCcgaaagGCGaGuCaaGGuCu AUACUGUU
4291

1184
UGCCAAGU G UUUGCUGA
1612
UCAGCAAA GCcgaaagGCGaGuCaaGGuCu ACUUGGCA
4292

1251
GAACCUUU G UGUCUCCU
1613
AGGAGACA GCcgaaagGCGaGuCaaGGuCu AAAGGUUC
4293

1253
ACCUUUGU G UCUCCUCU
1614
AGAGGAGA GCcgaaagGCGaGuCaaGGuCu ACAAAGGU
4294

1294
AGCCGCUU G UUUUGCUC
1615
GAGCAAAA GCcgaaagGCGaGuCaaGGuCu AAGCGGCU
4295

1344
ACAAUUCU G UCGUGCUC
1616
GAGCACGA GCcgaaagGCGaGuCaaGGuCu AGAAUUGU
4296

1390
GCUAGGCU G UGCUGCCA
1617
UGGCAGCA GCcgaaagGCGaGuCaaGGuCu ACCCUAGC
4297

1425
CGUCCUUU G UUUACGUC
1618
GACGUAAA GCcgaaagGCGaGuCaaGGuCu AAAGGACG
4298

1508
CGCCUAUU G UACCGACC
1619
GGUCGGUA GCcgaaagGCGaGuCaaGGuCu AAUAGGCG
4299

1557
CCCCGUCU G UGCCUUCU
1620
AGAAGGCA GCcgaaagGCGaGuCaaGGuCu AGACGGGG
4300

1581
CGGACCGU G UGCACUUC
1621
GAAGUGCA GCcgaaagGCGaGuCaaGGuCu ACGGUCCG
4301

1684
UCAGCAAU G UCAACGAC
1622
GUCGUUGA GCcgaaagGCGaGuCaaGGuCu AUUGCUGA
4302

1719
CAAAGACU G UGUGUUUA
1623
UAAACACA GCcgaaagGCGaGuCaaGGuCu AGUCUUUG
4303

1721
AAGACUGU G UGUUUAAU
1624
AUUAAACA GCcgaaagGCGaGuCaaGGuCu ACAGUCUU
4304

1723
GACUGUGU G UUUAAUGA
1625
UCAUUAAA GCcgaaagGCGaGuCaaGGuCu ACACAGUC
4305

1772
AGGUCUUU G UACUAGGA
1626
UCCUAGUA GCcgaaagGCGaGuCaaGGuCu AAAGACCU
4306

1785
AGGAGGCU G UAGGCAUA
1627
UAUGCCUA GCcgaaagGCGaGuCaaGGuCu AGCCUCCU
4307

1801
AAAUUGGU G UGUUCACC
1628
GGUGAACA GCcgaaagGCGaGuCaaGGuCu ACCAAUUU
4308

1803
AUUGGUGU G UUCACCAG
1629
CUGGUGAA GCcgaaagGCGaGuCaaGGuCu ACACCAAU
4309

1850
CAUCUCAU G UUCAUGUC
1630
GACAUGAA GCcgaaagGCGaGuCaaGGuCu AUGAGAUG
4310

1856
AUGUUCAU G UCCUACUG
1631
CAGUAGGA GCcgaaagGCGaGuCaaGGuCu AUGAACAU
4311

1864
GUCCUACH G UUCAAGCC
1632
GGCUUGAA GCcgaaagGCGaGuCaaGGuCu AGUAGGAC
4312

1881
UCCAACCU G UGCCUUGG
1633
CCAAGGCA GCcgaaagGCGaGuCaaGGuCu AGCUUGGA
4313

1939
GAGCUUCU G UGGAGUUA
1634
UAACUCCA GCcgaaagGCGaGuCaaGGuCu AGAAGCUC
4314

2013
UCUGCUCU G UAUCGGGG
1635
CCCCGAUA GCcgaaagGCGaGuCaaGGuCu AGAGCAGA
4315

2045
GGAACAUU G UUCACCUC
1636
CAGGUGAA GCcgaaagGCGaGuCaaGGuCu AAUGUUCC
4316

2082
GCUAUUCU G UGUUGGGG
1637
CCCCAACA GCcgaaagGCGaGuCaaGGuCu AGAAUAGC
4317

2084
UAUUCUGU G UUGGGGUG
1638
CACCCCAA GCcgaaagGCGaGuCaaGGuCu ACAGAAUA
4318

2167
UCAGCUAU G UCAACGUU
1639
AACGUUGA GCcgaaagGCGaGuCaaGGuCu AUAGCUGA
4319

2205
CAACUAUU G UGGUUUCA
1640
UGAAACCA GCcgaaagGCGaGuCaaGGuCu AAUAGUUG
4320

2222
CAUUUCCU G UCUUACUU
1641
AAGUAAGA GCcgaaagGCGaGuCaaGGuCu AGGAAAUG
4321

2245
GAGAAACU G UUCUUGAA
1642
UUCAAGAA GCcgaaagGCGaGuCaaGGuCu AGUUUCUC
4322

2262
UAUUUGGU G UCUUUUGG
1643
CGAAAAGA GCcgaaagGCGaGuCaaGGuCu ACCAAAUA
4323

2274
UUUGGAGU G UGGAUUCG
1644
CGAAUCCA GCcgaaagGCGaGuCaaGGuCu ACUCCAAA
4324

2344
AAACUACU G UUGUUAGA
1645
UCUAACAA GCcgaaagGCGaGuCaaGGuCu AGUAGUUU
4325

2347
CUACUGUU G UUAGACGA
1646
UCGUCUAA GCcgaaagGCGaGuCaaGGuCu AACAGUAG
4326

2450
AUCUCAAU G UUAGUAUU
1647
AAUACUAA GCcgaaagGCGaGuCaaGGuCu AUUGAGAU
4327

2573
AGGACAUU G UUGAUAGA
1648
UCUAUCAA GCcgaaagGCGaGuCaaGGuCu AAUGUCCU
4328

2583
UGAUAGAU G UAAGCAAU
1649
AUUGCUUA GCcgaaagGCGaGuCaaGGuCu AUCUAUCA
4329

2594
AGCAUUUU G UGGGGCCC
1650
GGGCCCCA GCcgaaagGCGaGuCaaGGuCu AAAUUGCU
4330

2663
AUCCCAAU G UUACUAAA
1651
UUUAGUAA GCcgaaagGCGaGuCaaGGuCu AUUGGGAU
4331

2717
CAGAGUAU G UAGUUAAU
1652
AUUAACUA GCcgaaagGCGaGuCaaGGuCu AUACUCUG
4332

2901
AUCUUUCU G UCCCCAAU
1653
AUUGGGGA GCcgaaagGCGaGuCaaGGuCu AGAAAGAU
4333

3071
GGGGGACU G UUGGGGUG
1654
CACCCCAA GCcgaaagGCGaGuCaaGGuCu AGUCCCCC
4334

3111
UCACAACU G UGCCAGCA
1655
UGCUGGCA GCcgaaagGCGaGuCaaGGuCu AGUUGUGA
4335

40
AUCCCACA G UCAGGGCC
1656
GGCCCUGA GCcgaaagGCGaGuCaaGGuCu UCUGGGAU
4336

46
GAGUCAGG G CCCUGUAC
1657
GUACAGGG GCcgaaagGCGaGuCaaGGuCu CCUGACUC
4337

65
UCCUGCUG G UGGCUCCA
1658
UGGAGCCA GCcgaaagGCGaGuCaaGGuCu CAGCAGGA
4338

68
UGCUGGUG G CUCCAGUU
1659
AACUGGAG GCcgaaagGCGaGuCaaGGuCu CACCAGCA
4339

74
UGGCUCCA G UUCAGGAA
1660
UUCCUGAA GCcgaaagGCGaGuCaaGGuCu UGGAGCCA
4340

85
CAGGAACA G UGAGCCCU
1661
AGGGCUCA GCcgaaagGCGaGuCaaGGuCu UGUUCCUG
4341

89
AACAGUGA G CCCUGCUC
1662
GAGCAGGG GCcgaaagGCGaGuCaaGGuCu UCACUGUU
4342

120
GCCAUAUC G UCAAUCUU
1663
AAGAUUGA GCcgaaagGCGaGuCaaGGuCu GAUAUGGC
4343

196
CCCUGCUC G UGUUACAG
1664
CUGUAACA GCcgaaagGCGaGuCaaGGuCu GAGCAGGG
4344

205
UGUUACAG G CGGGGUUU
1665
AAACCCCG GCcgaaagGCGaGuCaaGGuCu CUGUAACA
4345

210
CAGGCGGG G UUUUUCUU
1666
AAGAAAAA GCcgaaagGCGaGuCaaGGuCu CCCGCCUG
4346

248
ACCACAGA G UCUAGACU
1667
AGUCUAGA GCcgaaagGCGaGuCaaGGuCu UCUGUGGU
4347

258
CUAGACUC G UGGUGGAC
1668
GUCCACCA GCcgaaagGCGaGuCaaGGuCu GAGUCUAG
4348

261
GACUCGUG G UGGACUUC
1669
GAAGUCCA GCcgaaagGCGaGuCaaGGuCu CACGAGUC
4349

295
GAACACCC G UGUGUCUU
1670
AAGACACA GCcgaaagGCGaGuCaaGGuCu GGGUGUUC
4350

305
GUGUCUUG G CCAAAAUU
1671
AAUUUUGG GCcgaaagGCGaGuCaaGGuCu CAAGACAC
4351

318
AAUUCGCA G UCCCAAAU
1672
AUUUGGGA GCcgaaagGCGaGuCaaGGuCu UGCGAAUU
4352

332
AAUCUCCA G UCACUCAC
1673
GUGAGUGA GCcgaaagGCGaGuCaaGGuCu UGGAGAUU
4353

368
UUGUCCUG G UUAUCGCU
1674
AGCGAUAA GCcgaaagGCGaGuCaaGGuCu CAGGACAA
4354

390
UGUCUGCG G CGUUUUAU
1675
AUAAAACG GCcgaaagGCGaGuCaaGGuCu CGCAGACA
4355

392
UCUGCGGC G UUUUAUCA
1676
UGAUAAAA GCcgaaagGCGaGuCaaGGuCu GCCGCAGA
4356

442
UCUUGUUG G UUCUUCUG
1677
CAGAAGAA GCcgaaagGCGaGuCaaGGuCu CAACAAGA
4357

461
CUAUCAAG G UAUGUUGC
1678
GCAACAUA GCcgaaagGCGaGuCaaGGuCu CUUGAUAG
4358

472
UGUUGCCC G UUUGUCCU
1679
AGGACAAA GCcgaaagGCGaGuCaaGGuCu CGGCAACA
4359

650
AACAACCA G CACCGGAC
1680
GUCCGGUG GCcgaaagGCGaGuCaaGGuCu UGGUUGUU
4360

625
CAUCUUGG G CUUUCGCA
1681
UGCGAAAG GCcgaaagGCGaGuCaaGGuCu CCAAGAUG
4361

648
CUAUGGGA G UGGGCCUC
1682
GAGGCCCA GCcgaaagGCGaGuCaaGGuCu UCCCAUAG
4362

652
GGGAGUGG G CCUCAGUC
1683
GACUGAGG GCcgaaagGCGaGuCaaGGuCu CCACUCCC
4363

658
GGGCCUCA G UCCGUUUC
1684
GAAACGGA GCcgaaagGCGaGuCaaGGuCu UGAGGCCC
4364

662
CUCAGUCC G UUUCUCUU
1685
AAGAGAAA GCcgaaagGCGaGuCaaGGuCu GGACUGAG
4365

672
UUCUCUUG G CUCAGUUU
1686
AAACUGAG GCcgaaagGCGaGuCaaGGuCu CAAGAGAA
4366

677
UUGGCUCA G UUUACUAG
1687
CUAGUAAA GCcgaaagGCGaGuCaaGGuCu UGAGCCAA
4367

685
GUUUACUA G UGCCAUUU
1688
AAAUGGCA GCcgaaagGCGaGuCaaGGuCu UAGUAAAC
4368

699
UUUGUUCA G UGGUUCGU
1689
ACGAACCA GCcgaaagGCGaGuCaaGGuCu UGAACAAA
4369

702
GUUCAGUG G UUCGUAGG
1690
CCUACGAA GCcgaaagGCGaGuCaaGGuCu CACUGAAC
4370

706
AGUGGUUC G UAGGGCUU
1691
AAGCCCUA GCcgaaagGCGaGuCaaGGuCu GAACCACU
4371

711
UUCGUAGG G CUUUCCCC
1692
GGGGAAAG GCcgaaagGCGaGuCaaGGuCu CCUACGAA
4372

729
ACUGUCUG G CUUUCAGU
1693
ACUGAAAG GCcgaaagGCGaGuCaaGGuCu CAGACAGU
4373

736
GGCUUUCA G UUAUAUGG
1694
CCAUAUAA GCcgaaagGCGaGuCaaGGuCu UGAAAGCC
4374

753
AUGAUGUG G UUUUGGGG
1695
CCCCAAAA GCcgaaagGCGaGuCaaGGuCu CACAUCAU
4375

762
UUUUGGGG G CCAAGUCU
1696
AGACUUGG GCcgaaagGCGaGuCaaGGuCu CCCCAAAA
4376

767
GGGGCCAA G UCUGUACA
1697
UGUACAGA GCcgaaagGCGaGuCaaGGuCu UUGGCCCC
4377

785
CAUCUUGA G UCCCUUUA
1698
UAAAGGGA GCcgaaagGCGaGuCaaGGuCu UCAAGAUG
4378

826
GUCUUUGG G UAUACAUU
1699
AAUGUAUA GCcgaaagGCGaGuCaaGGuCu CCAAAGAC
4379

898
AAUUGGGA G UUGGGGCA
1700
UGCCCCAA GCcgaaagGCGaGuCaaGGuCu UCCCAAUU
4380

904
GAGUUGGG G CACAUUGC
1701
GCAAUGUG GCcgaaagGCGaGuCaaGGuCu CCCAACUC
4381

971
GUAAACAG G CCUAUUGA
1702
UCAAUAGG GCcgaaagGCGaGuCaaGGuCu CUGUUUAC
4382

987
AUUGGAAA G UAUGUCAA
1703
UUGACAUA GCcgaaagGCGaGuCaaGGuCu UUUCCAAU
4383

1006
AAUUGUGG G UCUUUUGG
1704
CCAAAAGA GCcgaaagGCGaGuCaaGGuCu CCACAAUU
4384

1016
CUUUUGGG G UUUGCCGC
1705
GCGGCAAA GCcgaaagGCGaGuCaaGGuCu CCCAAAAG
4385

1080
GCAUACAA G CAAAACAG
1706
CUGUUUUG GCcgaaagGCGaGuCaaGGuCu UUGUAUGC
4386

1089
CAAAACAG G CUUUUACU
1707
AGUAAAAG GCcgaaagGCGaGuCaaGGuCu CUGUUUUG
4387

1116
CUUACAAG G CCUUUCUA
1708
UAGAAAGG GCcgaaagGCGaGuCaaGGuCu CUUGUAAG
4388

1126
CUUUCUAA G UAAACAGU
1709
ACUGUUUA GCcgaaagGCGaGuCaaGGuCu UUAGAAAG
4389

1133
AGUAAACA G UAUGUGAA
1710
UUCACAUA GCcgaaagGCGaGuCaaGGuCu UGUUUACU
4390

1152
UUUACCCC G UUGCUCGG
1711
CCGAGCAA GCcgaaagGCGaGuCaaGGuCu GGGGUAAA
4391

1160
GUUGCUCG G CAACGGCC
1712
GGCCGUUG GCcgaaagGCGaGuCaaGGuCu CGAGCAAC
4392

1166
CGGCAACG G CCUGGUCU
1713
AGACCAGG GCcgaaagGCGaGuCaaGGuCu CGUUGCCG
4393

1171
ACGGCCUG G UCUAUGCC
1714
GGCAUAGA GCcgaaagGCGaGuCaaGGuCu CAGGCCGU
4394

1182
UAUGCCAA G UGUUUGCU
1715
AGCAAACA GCcgaaagGCGaGuCaaGGuCu UUGGCAUA
4395

1207
CCCCACUG G UUGGGGCU
1716
AGCCCCAA GCcgaaagGCGaGuCaaGGuCu CACUGGGG
4396

1213
UGGUUGGG G CUUGGCCA
1717
UGGCCAAG GCcgaaagGCGaGuCaaGGuCu CCCAACCA
4397

1218
GGGGCUUG G CCAUAGGC
1718
GCCUAUGG GCcgaaagGCGaGuCaaGGuCu CAAGCCCC
4398

1225
GGCCAUAG G CCAUCAGC
1719
GCUGAUGG GCcgaaagGCGaGuCaaGGuCu CUAUGGCC
4399

1232
GGCCAUCA G CGCAUGCG
1720
CGCAUGCG GCcgaaagGCGaGuCaaGGuCu UGAUGGCC
4400

1240
GCGCAUGC G UGGAACCU
1721
AGGUUCCA GCcgaaagGCGaGuCaaGGuCu GCAUGCGC
4401

1287
AACUCCUA G CCGCUUGU
1722
ACAAGCGG GCcgaaagGCGaGuCaaGGuCu UAGGAGUU
4402

1306
UGCUCGCA G CAGGUCUG
1723
CAGACCUG GCcgaaagGCGaGuCaaGGuCu UGCGAGCA
4403

1310
CGCAGCAG G UCUGGGGC
1724
GCCCCAGA GCcgaaagGCGaGuCaaGGuCu CUGCUGCG
4404

1317
GGUCUGGG G CAAAACUC
1725
GAGUUUUG GCcgaaagGCGaGuCaaGGuCu CCCAGACC
4405

1347
AUUCUGUC G UGCUCUCC
1726
GGAGAGCA GCcgaaagGCGaGuCaaGGuCu GACAGAAU
4406

1379
UUUCCAUG G CUGCUAGG
1727
CCUAGCAG GCcgaaagGCGaGuCaaGGuCu CAUGGAAA
4407

1387
GCUGCUAG G CUGUGCUG
1728
CAGCACAG GCcgaaagGCGaGuCaaGGuCu CUAGCAGC
4408

1418
CGCGGGAC G UCCUUUGU
1729
ACAAAGGA GCcgaaagGCGaGuCaaGGuCu GUCCCGCG
4409

1431
UUGUUUAC G UCCCGUCG
1730
CGACGGGA GCcgaaagGCGaGuCaaGGuCu GUAAACAA
4410

1436
UACGUCCC G UCGGCGCU
1731
AGCGCCGA GCcgaaagGCGaGuCaaGGuCu GGGACGUA
4411

1440
UCCCGUCG G CGCUGAAU
1732
AUUCAGCG GCcgaaagGCGaGuCaaGGuCu CGACGGGA
4412

1471
CUCCCGGG G CCGCUUGG
1733
CCAAGCGG GCcgaaagGCGaGuCaaGGuCu CCCGGGAG
4413

1481
CGCUUGGG G CUCUACCG
1734
CGGUAGAG GCcgaaagGCGaGuCaaGGuCu CCCAAGCG
4414

1517
UACCGACC G UCCACGGG
1735
CCCGUGGA GCcgaaagGCGaGuCaaGGuCu GGUCGGUA
4415

1526
UCCACGGG G CGCACCUC
1736
GAGGUGCG GCcgaaagGCGaGuCaaGGuCu CCCGUGGA
4416

1553
GACUCCCC G UCUGUGCC
1737
GGCACAGA GCcgaaagGCGaGuCaaGGuCu GGGGAGUC
4417

1579
GCCGGACC G UGUGCACU
1738
AGUGCACA GCcgaaagGCGaGuCaaGGuCu GGUCCGGC
4418

1605
CUCUGCAC G UCGCAUGG
1739
CCAUGCGA GCcgaaagGCGaGuCaaGGuCu GUGCAGAG
4419

1622
AGACCACC G UGAACGCC
1740
GGCGUUCA GCcgaaagGCGaGuCaaGGuCu GGUGGUCU
4420

1649
UGCCCAAG G UCUUGCAU
1741
AUGCAAGA GCcgaaagGCGaGuCaaGGuCu CUUGGGCA
4421

1679
GACUUUCA G CAAUGUCA
1742
UGACAUUG GCcgaaagGCGaGuCaaGGuCu UGAAAGUC
4422

1703
ACCUUGAG G CAUACUUC
1743
GAAGUAUG GCcgaaagGCGaGuCaaGGuCu CUCAAGGU
4423

1732
UUUAAUGA G UGGGAGGA
1744
UCCUCCCA GCcgaaagGCGaGuCaaGGuCu UCAUUAAA
4424

1741
UGGGAGGA G UUGGGGGA
1745
UCCCCCAA GCcgaaagGCGaGuCaaGGuCu UCCUCCCA
4425

1754
GGGAGGAG G UUAGGUUA
1746
UAACCUAA GCcgaaagGCGaGuCaaGGuCu CUCCUCCC
4426

1759
GAGGUUAG G UUAAAGGU
1747
ACCUUUAA GCcgaaagGCGaGuCaaGGuCu CUAACCUC
4427

1766
GGUUAAAG G UCUUUGUA
1748
UACAAAGA GCcgaaagGCGaGuCaaGGuCu CUUUAACC
4428

1782
ACUAGGAG G CUGUAGGC
1749
GCCUACAG GCcgaaagGCGaGuCaaGGuCu CUCCUAGU
4429

1789
GGCUGUAG G CAUAAAUU
1750
AAUUUAUG GCcgaaagGCGaGuCaaGGuCu CUACAGCC
4430

1799
AUAAAUUG G UGUGUUCA
1751
UGAACACA GCcgaaagGCGaGuCaaGGuCu CAAUUUAU
4431

1811
GUUCACCA G CACCAUGC
1752
GCAUGGUG GCcgaaagGCGaGuCaaGGuCu UGGUGAAC
4432

1870
CUGUUCAA G CCUCCAAG
1753
CUUGGAGG GCcgaaagGCGaGuCaaGGuCu UUGAACAG
4433

1878
GCCUCCAA G CUGUGCCU
1754
AGGCACAG GCcgaaagGCGaGuCaaGGuCu UUGGAGGC
4434

1890
UGCCUUGG G UGGCUUUG
1755
CAAAGCCA GCcgaaagGCGaGuCaaGGuCu CCAAGGCA
4435

1893
CUUGGGUG G CUUUGGGG
1756
CCCCAAAG GCcgaaagGCGaGuCaaGGuCu CACCCAAG
4436

1901
GCUUUGGG G CAUGGACA
1757
UGUCCAUG GCcgaaagGCGaGuCaaGGuCu CCCAAAGC
4437

1917
AUUGACCC G UAUAAAGA
1758
UCUUUAUA GCcgaaagGCGaGuCaaGGuCu GGGUCAAU
4438

1933
AAUUUGGA G CUUCUGUG
1759
CACAGAAG GCcgaaagGCGaGuCaaGGuCu UCCAAAUU
4439

1944
UCUGUGGA G UCACUCUC
1760
GAGAGUAA GCcgaaagGCGaGuCaaGGuCu UCCACAGA
4440

2023
AUCGGGGG G CCUUAGAG
1761
CUCUAAGG GCcgaaagGCGaGuCaaGGuCu CCCCCGAU
4441

2031
GCCUUAGA G UCUCCGGA
1762
UCCGGAGA GCcgaaagGCGaGuCaaGGuCu UCUAAGGC
4442

2062
ACCAUACG G CACUCAGG
1763
CCUGAGUG GCcgaaagGCGaGuCaaGGuCu CGUAUGGU
4443

2070
GCACUCAG G CAAGCUAU
1764
AUACGUUG GCcgaaagGCGaGuCaaGGuCu CUGAGUGC
4444

2074
UCAGGCAA G CUAUUCUG
1765
CAGAAUAG GCcgaaagGCGaGuCaaGGuCu UUGCCUGA
4445

2090
GUGUUGGG G UGAGUUGA
1766
UCAACUCA GCcgaaagGCGaGuCaaGGuCu CCCAACAC
4446

2094
UGGGGUGA G UUGAUGAA
1767
UUCAUCAA GCcgaaagGCGaGuCaaGGuCu UCACCCCA
4447

2107
UGAAUCUA G CCACCUGG
1768
CCAGGUGG GCcgaaagGCGaGuCaaGGuCu UAGAUUCA
4448

2116
CCACCUGG G UGGGAAGU
1769
ACUUCCCA GCcgaaagGCGaGuCaaGGuCu CCAGGUGG
4449

2123
GGUGGGAA G UAAUUUGG
1770
CCAAAUUA GCcgaaagGCGaGuCaaGGuCu UUCCCACC
4450

2140
AAGAUCCA G CAUCCAGG
1771
CCUGGAUG GCcgaaagGCGaGuCaaGGuCu UGGAUCUU
4451

2155
GGGAAUUA G UAGUCAGC
1772
GCUGACUA GCcgaaagGCGaGuCaaGGuCu UAAUUCCC
4452

2158
AAUUAGUA G UCAUGUAU
1773
AUAGCUGA GCcgaaagGCGaGuCaaGGuCu UACUAAUU
4453

2162
AGUAGUCA G CUAUGUCA
1774
UGACAUAG GCcgaaagGCGaGuCaaGGuCu UGACUACU
4454

2173
AUGUCAAC G UUAAUAUG
1775
CAUAUUAA GCcgaaagGCGaGuCaaGGuCu GUUGACAU
4455

2183
UAAUAUGG G CCUAAAAA
1776
UUUUUAGG GCcgaaagGCGaGuCaaGGuCu CCAUAUUA
4456

2208
CUAUUGUG G UUUCACAU
1777
AUGUGAAA GCcgaaagGCGaGuCaaGGuCu CACAAUAG
4457

2235
ACUUUUGG G CGAGAAAC
1778
GUUUCUCG GCcgaaagGCGaGuCaaGGuCu CCAAAAGU
4458

2260
AAUAUUUG G UGUCUUUU
1779
AAAAGACA GCcgaaagGCGaGuCaaGGuCu CAAAUAUU
4459

2272
CUUUUGGA G UGUGGAUU
1780
AAUCCACA GCcgaaagGCGaGuCaaGGuCu UCCAAAAG
4460

2360
ACGAAGAG G CAGGUCCC
1781
GGGACCUG GCcgaaagGCGaGuCaaGGuCu CUCUUCGU
4461

2364
AGAGGCAG G UCCCCUAG
1782
CUAGGGGA GCcgaaagGCGaGuCaaGGuCu CUGCCUCU
4462

2403
AGACGAAG G UCUCAAUC
1783
GAUUGAGA GCcgaaagGCGaGuCaaGGuCu CUUCGUCU
4463

2417
AUCGCCGC G UCGCAGAA
1784
UUCUGCGA GCcgaaagGCGaGuCaaGGuCu GCGGCGAU
4464

2454
CAAUGUUA G UAUUCCUU
1785
AAGGAAUA GCcgaaagGCGaGuCaaGGuCu UAACAUUG
4465

2474
CACAUAAG G UGGGAAAC
1786
GUUUCCCA GCcgaaagGCGaGuCaaGGuCu CUUAUGUG
4466

2491
UUUACGGG G CUUUAUUC
1787
GAAUAAAG GCcgaaagGCGaGuCaaGGuCu CCCGUAAA
4467

2507
CUUCUACG G UACCUUGC
1788
GCAAGGUA GCcgaaagGCGaGuCaaGGuCu CGUAGAAG
4468

2530
CCUAAAUG G CAAACUCC
1789
GGAGUUUG GCcgaaagGCGaGuCaaGGuCu CAUUUAGG
4469

2587
AGAUGUAA G CAAUUUGU
1790
ACAAAUUG GCcgaaagGCGaGuCaaGGuCu UUACAUCU
4470

2599
UUUGUGGG G CCCCUUAC
1791
GUAAGGGG GCcgaaagGCGaGuCaaGGuCu CCCACAAA
4471

2609
CCCUUACA G UAAAUGAA
1792
UUCAUUUA GCcgaaagGCGaGuCaaGGuCu UGUAAGGG
4472

2650
CCUGCUAG G UUUUAUCC
1793
GGAUAAAA GCcgaaagGCGaGuCaaGGuCu CUAGCAGG
4473

2701
AUCAAACC G UAUUAUCC
1794
GGAUAAUA GCcgaaagGCGaGuCaaGGuCu GGUUUGAU
4474

2713
UAUCCAGA G UAUGUAGU
1795
ACUACAUA GCcgaaagGCGaGuCaaGGuCu UCUGGAUA
4475

2720
AGUAUGUA G UUAAUCAU
1796
AUGAUUAA GCcgaaagGCGaGuCaaGGuCu UACAUACU
4476

2768
UUUGGAAG G CGGGGAUC
1797
GAUCCCCG GCcgaaagGCGaGuCaaGGuCu CUUCCAAA
4477

2791
AAAAGAGA G UCCACACG
1798
CGUGUGGA GCcgaaagGCGaGuCaaGGuCu UCUCUUUU
4478

2799
GUCCACAC G UAGCGCCU
1799
AGGCGCUA GCcgaaagGCGaGuCaaGGuCu GUCUGGAC
4479

2802
CACACGUA G CGCCUCAU
1800
AUGAGGCG GCcgaaagGCGaGuCaaGGuCu UACGUGUG
4480

2818
UUUUGCGG G UCACCAUA
1801
UAUGGUGA GCcgaaagGCGaGuCaaGGuCu CCGCAAAA
4481

2848
GAUCUACA G CAUGGGAG
1802
CUCCCAUG GCcgaaagGCGaGuCaaGGuCu UGUAGAUC
4482

2857
CAUGGGAG G UUGGUCUU
1803
AAGACCAA GCcgaaagGCGaGuCaaGGuCu CUCCCAUG
4483

2861
GGAGGUUG G UCUUCCAA
1804
UUGGAAGA GCcgaaagGCGaGuCaaGGuCu CAACCUCC
4484

2881
UCGAAAAG G CAUGGGGA
1805
UCCCCAUG GCcgaaagGCGaGuCaaGGuCu CUUUUCGA
4485

2936
GAUCAUCA G UUGGACCC
1806
GGGUCCAA GCcgaaagGCGaGuCaaGGuCu UGAUGAUC
4486

2955
CAUUCAAA G CCAACUCA
1807
UGAGUUGG GCcgaaagGCGaGuCaaGGuCu UUUGAAUG
4487

2964
CCAACUCA G UAAAUCCA
1808
UGGAUUUA GCcgaaagGCGaGuCaaGGuCu UGAGUUGG
4488

3005
GACAACUG G CCGGACGC
1809
GCGUCCGG GCcgaaagGCGaGuCaaGGuCu CAGUUGUC
4489

3021
CCAACAAG G UGGGAGUG
1810
CACUCCCA GCcgaaagGCGaGuCaaGGuCu CUUGUUGG
4490

3027
AGGUGGGA G UGGGAGCA
1811
UGCUCCCA GCcgaaagGCGaGuCaaGGuCu UCCCACCU
4491

3033
GAGUGGGA G CAUUCGGG
1812
CCCGAAUG GCcgaaagGCGaGuCaaGGuCu UCCCACUC
4492

3041
GCAUUCGG G CCAGGGUU
1813
AACCCUGG GCcgaaagGCGaGuCaaGGuCu CCGAAUGC
4493

3047
GGGCCAGG G UUCACCCC
1814
GGGGUGAA GCcgaaagGCGaGuCaaGGuCu CCUGGCCC
4494

3077
CUGUUGGG G UGGAGCCC
1815
GGGCUCCA GCcgaaagGCGaGuCaaGGuCu CCCAACAG
4495

3082
GGGGUGGA G CCCUCACG
1816
CGUGAGGG GCcgaaagGCGaGuCaaGGuCu UCCACCCC
4496

3097
CGCUCACG G CCUACUCA
1817
UGAGUAGG GCcgaaagGCGaGuCaaGGuCu CCUGAGCG
4497

3117
CUGUGCCA G CAGCUCCU
1818
AGGAGCUG GCcgaaagGCGaGuCaaGGuCu UGGCACAG
4498

3120
UGCCAGCA G CUCCUCCU
1819
AGGAGGAG GCcgaaagGCGaGuCaaGGuCu UGCUGGCA
4499

3146
ACCAAUCG G CAGUCAGG
1820
CCUGACUG GCcgaaagGCGaGuCaaGGuCu CGAUUGGU
4500

3149
AAUCGGCA G UCAGGAAG
1821
CUUCCUGA GCcgaaagGCGaGuCaaGGuCu UGCCGAUU
4501

3158
UCAGGAAG G CAGCCUAC
1822
GUAGGCUG GCcgaaagGCGaGuCaaGGuCu CUUCCUGA
4502

3161
GGAAGGCA G CCUACUCC
1823
GGAGUAGG GCcgaaagGCGaGuCaaGGuCu UGCCUUCC
4503

3204
AUCCUCAG G CCAUGCAG
1824
CUGCAUGG GCcgaaagGCGaGuCaaGGuCu CUGAGGAU
4504

Input Sequence = AF100308.

Cut Site = YC/M or UC/U.

Stem Length = 8.

Core Sequence = GCcgaaagGCGaGuCaaGGuCu

AF100308 (Hepatitis B virus strain 2-18, 3215 bp)

[0252]

9

TABLE IX

HUMAN HBV DNAZYME AND SUBSTRATE SEQUENCE

Pos
Substrate
Seq ID
DNAzyme
Seq ID

508
CAACCAGC A CCGGACCA
833
TGGTCCGG GGCTAGCTACAACGA GCTGGTTG
4505

1632
GAACGCCC A CAGGAACC
1096
GGTTCCTG GGCTAGCTACAACGA GGGCGTTC
4506

2992
CAACCCGC A CAAGGACA
1376
TGTCCTTG GGCTAGCTACAACGA GCGGGTTG
4507

61
ACUUUCCU G CUGGUGGC
1448
GCCACCAG GGCTAGCTACAACGA AGCAAAGT
4508

94
UGAGCCCU G CUCAGAAU
1450
ATTCTGAG GGCTAGCTACAACGA AGGGCTCA
4509

112
CUGUCUCU G CCAUAUCG
1451
CGATATGG GGCTAGCTACAACGA AGAGACAG
4510

169
AGAACAUC G CAUCAGGA
1454
TCCTGATG GGCTAGCTACAACGA GATGTTCT
4511

192
GGACCCCU G CUCGUGUU
1455
AACACGAG GGCTAGCTACAACGA AGGGGTCC
4512

315
CAAAAUUC G CAGUCCCA
1457
TGGGACTG GGCTAGCTACAACGA GAATTTTG
4513

374
UGGUUAUC G CUGGAUGU
1458
ACATCCAG GGCTAGCTACAACGA GATAACCA
4514

387
AUGUGUCU G CGGCGUUU
1459
AAACGCCG GGCTAGCTACAACGA AGACACAT
4515

410
CUUCCUCU G CAUCCUGC
1460
GCAGGATG GGCTAGCTACAACGA AGAGGAAG
4516

417
UGCAUCCU G CUGCUAUG
1461
CATAGCAG GGCTAGCTACAACGA AGGATGCA
4517

420
AUCCUGCU G CUAUGCCU
1462
AGGCATAG GGCTAGCTACAACGA AGCAGGAT
4518

425
GCUGCUAU G CCUCAUCU
1463
AGATGAGG GGCTAGCTACAACGA ATAGCAGC
4519

468
GGUAUGUU G CCCGUUUG
1464
CAAACGGG GGCTAGCTACAACGA AACATACC
4520

518
CGGACCAU G CAAAACCU
1465
AGGTTTTG GGCTAGCTACAACGA ATGGTCCG
4521

527
CAAAACCU G CACAACUC
1466
GAUTTGTG GGCTAGCTACAACGA AGGTTTTG
4522

538
CAACUCCU G CUCAAGGA
1467
TCCTTGAG GGCTAGCTACAACGA AGGAGTTG
4523

569
CUCAUGUU G CUGUACAA
1468
TTGTACAG GGCTAGCTACAACGA AACATGAG
4524

596
CGGAAACU G CACCUGUA
1469
TACAGGTG GGCTAGCTACAACGA AGTTTCCG
4525

631
GGGCUUUC G CAAAAUAC
1470
GTATTTTG GGCTAGCTACAACGA GAAAGCCC
4526

687
UUACUAGU G CCAUUUGU
1471
ACAAATGG GGCTAGCTACAACGA ACTAGTAA
4527

795
CCCUUUAU G CCGCUGUU
1474
AACAGCGG GGCTAGCTACAACGA ATAAAGGG
4528

798
UUUAUGCC G CUGUUACC
1475
GGTAACAG GGCTAGCTACAACGA GGCATAAA
4529

911
GGCACAUU G CCACAGGA
1476
TCCTGTGG GGCTAGCTACAACGA AATGTGCC
4530

1020
UUGGGUUU G CCGCCCCU
1479
AGGGGCGG GGCTAGCTACAACGA AAACCCCA
4531

1023
GGUUUGCC G CCCCUUUC
1480
GAAAGGGG GGCTAGCTACAACGA GGCAAACC
4532

1034
CCUUUCAC G CAAUGUGG
1481
CCACATTG GGCTAGCTACAACGA GTGAAAGG
4533

1050
GAUAUUCU G CUUUAAUG
1482
CATTAAAG GGCTAGCTACAACGA AGAATATC
4534

1058
GCUUUAAU G CCUUUAUA
1483
TATAAAGG GGCTAGCTACAACGA ATTAAAGC
4535

1068
CUUUAUAU G CAUGCAUA
1484
TATGCATG GGCTAGCTACAACGA ATATAAAG
4536

1072
AUAUGCAU G CAUACAAG
1485
CTTGTATG GGCTAGCTACAACGA ATGCATAT
4537

1103
ACUUUCUC G CCAACUUA
1486
TAAGTTGG GGCTAGCTACAACGA GAGAAAGT
4538

1155
ACCCCGUU G CUCGGCAA
1488
TTGCCGAG GGCTAGCTACAACGA AACGGGGT
4539

1177
UGGUCUAU G CCAAGUGU
1489
ACACTTGG GGCTAGCTACAACGA ATAGACCA
4540

1188
AAGUGUUU G CUGACGCA
1490
TGCGTCAG GGCTAGCTACAACGA AAACACTT
4541

1194
UUGCUGAC G CAACCCCC
1492
GGGGGTTG GGCTAGCTACAACGA GTCAGCAA
4542

1234
CCAUCAGC G CAUGCGUG
1493
CACGCATG GGCTAGCTACAACGA GCTGATGG
4543

1238
CAGCGCAU G CGUGGAAC
1494
GTTCCACG GGCTAGCTACAACGA ATGCGCTG
4544

1262
UCUCCUCU G CCGAUCCA
1495
TGGATCGG GGCTAGCTACAACGA AGAGGAGA
4545

1275
UCCAUACC G CGGAACUC
1497
GAGTTCCG GGCTAGCTACAACGA GGTATGGA
4546

1290
UCCUAGCC G CUUGUUUU
1498
AAAACAAG GGCTAGCTACAACGA GGCTAGGA
4547

1299
CUUGUUUU G CUCGCAGC
1499
GCTGCGAG GGCTAGCTACAACGA AAAACAAG
4548

1303
UUUUGCUC G CAGCAGGU
1500
ACCTGCTG GGCTAGCTACAACGA GAGCAAAA
4549

1349
UCUGUCGU G CUCUCCCG
1502
CGGGAGAG GGCTAGCTACAACGA ACGACAGA
4550

1357
GCUCUCCC G CAAAUAUA
1503
TATATTTG GGCTAGCTACAACGA GGGAGAGC
4551

1382
CCAUGGCU G CUAGGCUG
1504
CAGCCTAG GGCTAGCTACAACGA AGCCATGG
4552

1392
UAGGCUGU G CUGCCAAC
1505
GTTGGCAG GGCTAGCTACAACGA ACAGCCTA
4553

1395
GCUGUGCU G CCAACUGG
1506
CCAGTTGC GGCTAGCTACAACGA AGCACAGC
4554

1411
GAUCCUAC G CGGGACGU
1507
ACGTCCCG GGCTAGCTACAACGA GTACCATC
4555

1442
CCGUCGGC G CUGAAUCC
1508
GGATTCAG GGCTAGCTACAACGA GCCGACGG
4556

1452
UGAAUCCC G CGGACGAC
1510
GTCGTCCG GGCTAGCTACAACGA GGGATTCA
4557

1474
CCGGGGCC G CUUGGGGC
1512
GCCCCAAG GGCTAGCTACAACGA GGCCCCGG
4558

1489
GCUCUACC G CCCGCUUC
1513
GAAGCGGG GGCTAGCTACAACGA CGTACAGC
4559

1493
UACCGCCC G CUUCUCCG
1514
CGGAGAAG GGCTAGCTACAACGA GGGCGGTA
4560

1501
GCUUCUCC G CCUAUUGU
1515
ACAATAGG GGCTAGCTACAACGA GGACAAGC
4561

1528
CACGGGGC G CACCUCUC
1517
GAGAGGTG GGCTAGCTACAACGA GCCCCGTG
4562

1542
CUCUUUAC G CGGACUCC
1518
GGAGTCCG GGCTAGCTACAACGA GTAAAGAG
4563

1559
CCGUCUGU G CCUUCUCA
1519
TGAGAAGG GGCTAGCTACAACGA ACAGACGG
4564

1571
UCUCAUCU G CCGGACCG
1520
CGGTCCGG GGCTAGCTACAACGA AGATGAGA
4565

1583
GACCGUGU G CACUUCGC
1521
GCGAAGTG GGCTAGCTACAACGA ACACGGTC
4566

1590
UGCACUUC G CUUCACCU
1522
AGGTGAAG GGCTAGCTACAACGA GAAGTGCA
4567

1601
UCACCUCU G CACGUCGC
1523
GCGACGTG GGCTAGCTACAACGA AGAGGTGA
4568

1608
UGCACGUC G CAUGGAGA
1524
TCTCCATG GGCTAGCTACAACGA GACGTGCA
4569

1628
CCGUGAAC G CCCACAGG
1526
CCTGTGGG GGCTAGCTACAACGA GTTCACGG
4570

1642
AGGAACCU G CCCAAGGU
1527
ACCTTGGG GGCTAGCTACAACGA AGGTTCCT
4571

1654
AAGGUCUU G CAUAAGAG
1528
CTCTTATG GGCTAGCTACAACGA AAGACCTT
4572

1818
AGCACCAU G CAACUUUU
1533
AAAAGTTG GGCTAGCTACAACGA ATGGTGCT
4573

1835
UCACCUCU G CCUAAUCA
1534
TGATTAGG GGCTAGCTACAACGA AGAGGTGA
4574

1883
CAAGCUGU G CCUUGGGU
1535
ACCCAAGG GGCTAGCTACAACGA ACAGCTTG
4575

1959
UCUUUUUU G CCUUCUGA
1537
TCAGAAGG GGCTAGCTACAACGA AAAAAAGA
4576

2002
UCGACACC G CCUCUGCU
1541
AGCAGAGG GGCTAGCTACAACGA GGTGTCGA
4577

2008
CCGCCUCU G CUCUGUAU
1542
ATACAGAG GGCTAGCTACAACGA AGAGGCGG
4578

2282
GUGGAUUC G CACUCCUC
1548
GAGGAGTG GGCTAGCTACAACGA GAATCCAC
4579

2293
CUCCUCCU G CAUAUAGA
1549
TCTATATG GGCTAGCTACAACGA AGGAGGAG
4580

2311
CACCAAAU G CCCCUAUC
1550
GATAGGGG GGCTAGCTACAACGA ATTTGGTG
4581

2388
ACUCCCUC G CCUCGCAG
1552
CTGCGAGG GGCTAGCTACAACGA GAGGGAGT
4582

2393
CUCGCCUC G CAGACGAA
1553
TTCGTCTG GGCTAGCTACAACGA GAGGCGAG
4583

2412
UCUCAAUC G CCGCGUCG
1555
CGACGCGG GGCTAGCTACAACGA GATTGAGA
4584

2415
CAAUCGCC G CGUCGCAG
1556
CTGCGACG GGCTAGCTACAACGA GGCGATTG
4585

2420
GCCGCGUC G CAGAAGAU
1557
ATCTTCTG GGCTAGCTACAACGA GACGCGGC
4586

2514
GGUACCUU G CUUUAAUC
1558
GATTAAAG GGCTAGCTACAACGA AAGGTACC
4587

2560
AUUCAUUU G CAGGAGGA
1560
TCCTCCTG GGCTAGCTACAACGA AAATGAAT
4588

2641
UUAACUAU G CCUGCUAG
1563
CTAGCAGG GGCTAGCTACAACGA ATAGTTAA
4589

2645
CUAUGCCU G CUAGGUUU
1564
AAACCTAG GGCTAGCTACAACGA AGGCATAG
4590

2677
AAAUAUUU G CCCUUAGA
1565
TCTAAGGG GGCTAGCTACAACGA AAATATTT
4591

2740
UUCCAGAC G CGACAUUA
1566
TAATGTCG GGCTAGCTACAACGA GTCTGGAA
4592

2804
CACGUAGC G CCUCAUUU
1568
AAATGAGG GGCTAGCTACAACGA GCTACGTG
4593

2814
CUCAUUUU G CGGGUCAC
1569
GTGACCCG GGCTAGCTACAACGA AAAATGAG
4594

2946
UGGACCCU G CAUUCAAA
1572
TTTGAATG GGCTAGCTACAACGA AGGGTCCA
4595

2990
CUCAACCC G CACAAGGA
1573
TCCTTGTG GGCTAGCTACAACGA GGGTTGAG
4596

3012
GGCCGGAC G CCAACAAG
1574
CTTGTTGG GGCTAGCTACAACGA GTCCGGCC
4597

3090
GCCCUCAC G CUCAGGGC
1575
GCCCTGAG GGCTAGCTACAACGA GTGAGGGC
4598

3113
ACAACUGU G CCAGCAGC
1576
GCTGCTGG GGCTAGCTACAACGA ACAGTTGT
4599

3132
CUCCUCCU G CCUCCACC
1577
GGTGGAGG GGCTAGCTACAACGA AGGAGGAG
4600

51
AGGGCCCU G UACUUUCC
1578
GGAAAGTA GGCTAGCTACAACGA AGGGCCCT
4601

106
AGAAUACU G UCUCUGCC
1579
GGCAGAGA GGCTAGCTACAACGA AGTATTCT
4602

148
GGGACCCU G UACCGAAC
1580
GTTCGGTA GGCTAGCTACAACGA AGGGTCCC
4603

198
CUGCUCGU G UUACAGGC
1581
GCCTGTAA GGCTAGCTACAACGA ACGAGCAG
4604

219
UUUUUCUU G UUGACAAA
1582
TTTGTCAA GGCTAGCTACAACGA AAGAAAAA
4605

297
ACACCCGU G UGUCUUCG
1583
CCAAGACA GGCTAGCTACAACGA ACGGGTGT
4606

299
ACCCGUGU G UCUUGGCC
1584
GGCCAAGA GGCTAGCTACAACGA ACACGGGT
4607

347
ACCAACCU G UUGUCCUC
1585
GAGGACAA GGCTAGCTACAACGA AGGTTGGT
4608

350
AACCUGUU G UCCUCCAA
1586
TTGGAGGA GGCTAGCTACAACGA AACAGGTT
4609

362
UCCAAUUU G UCCUGGUU
1587
AACCAGGA GGCTAGCTACAACGA AAATTGGA
4610

381
CGCUGGAU G UGUCUGCG
1588
CGCAGACA GGCTAGCTACAACGA ATCCAGCG
4611

383
CUGGAUGU G UCUGCGGC
1589
GCCGCAGA GGCTAGCTACAACGA ACATCCAG
4612

438
AUCUUCUU G UUGGUUCU
1590
AGAACCAA GGCTAGCTACAACGA AAGAAGAT
4613

465
CAAGGUAU G UUGCCCGU
1591
ACGGGCAA GGCTAGCTACAACGA ATACCTTG
4614

476
GCCCGUUU G UCCUCUAA
1592
TTAGAGGA GGCTAGCTACAACGA AAACGGGC
4615

555
ACCUCUAU G UUUCCCUC
1593
GAGGGAAA GGCTAGCTACAACGA ATAGAGGT
4616

566
UCCCUCAU G UUGCUGUA
1594
TACAGCAA GGCTAGCTACAACGA ATGAGGGA
4617

572
AUGUUGCU G UACAAAAC
1595
GTTTTGTA GGCTAGCTACAACGA AGCAACAT
4618

602
CUGCACCU G UAUUCCCA
1596
TGGGAATA GGCTAGCTACAACGA AGGTGCAG
4619

694
UGCCAUUU G UUCAGUGG
1597
CCACTGAA GGCTAGCTACAACGA AAATGGCA
4620

724
CCCCCACU G UCUGGCUU
1598
AAGCCAGA GGCTAGCTACAACGA AGTGGGGG
4621

750
UGGAUGAU G UGGUUUUG
1599
CAAAACCA GGCTAGCTACAACGA ATCATCCA
4622

771
CCAAGUCU G UACAACAU
1600
ATGTTGTA GGCTAGCTACAACGA AGACTTGG
4623

801
AUGCCGCU G UUACCAAU
1601
ATTGGTAA GGCTAGCTACAACGA AGCGGCAT
4624

818
UUUCUUUU G UCUUUGGG
1602
CCCAAAGA GGCTAGCTACAACGA AAAAGAAA
4625

888
UGGGAUAU G UAAUUGGG
1603
CCCAATTA GGCTAGCTACAACGA ATATCCCA
4626

927
AACAUAUU G UACAAAAA
1604
TTTTTGTA GGCTAGCTACAACGA AATATGTT
4627

944
AUCAAAAU G UGUUUUAG
1605
CTAAAACA GGCTAGCTACAACGA ATTTTGAT
4628

946
CAAAAUGU G UUUUAGGA
1606
TCCTAAAA GGCTAGCTACAACGA ACATTTTG
4629

963
AACUUCCU G UAAACAGG
1607
CCTGTTTA GGCTAGCTACAACGA AGGAAGTT
4630

991
GAAAGUAU G UCAACGAA
1608
TTCGTTGA GGCTAGCTACAACGA ATACTTTC
4631

1002
AACGAAUU G UGGGUCUU
1609
AAGACCCA GGCTAGCTACAACGA AATTCGTT
4632

1039
CACGCAAU G UGGAUAUU
1610
AATATCCA GGCTAGCTACAACGA ATTGCGTG
4633

1137
AACAGUAU G UGAACCUU
1611
AAGGTTCA GGCTAGCTACAACGA ATACTGTT
4634

1184
UGCCAAGU G UUUGCUGA
1612
TCAGCAAA GGCTAGCTACAACGA ACTTGGCA
4635

1251
GAACCUUU G UGUCUCCU
1613
AGGAGACA GGCTAGCTACAACGA TAAGGTTC
4636

1253
ACCUUUGU G UCUCCUCU
1614
AGAGGAGA GGCTAGCTACAACGA ACAAAGGT
4637

1294
AGCCGCUU G UUUUGCUC
1615
GAGCAAAA GGCTAGCTACAACGA AAGCGGCT
4638

1344
ACAAUUCU G UCGUGCUC
1616
GAGCACGA GGCTAGCTACAACGA AGAATTGT
4639

1390
GCUAGGCU G UGCUGCCA
1617
TGGCAGCA GGCTAGCTACAACGA AGCCTAGC
4640

1425
CGUCCUUU G UUUACGUC
1618
GACGTAAA GGCTAGCTACAACGA AAAGGACG
4641

1508
CGCCUAUU G UACCGACC
1619
GGTCGGTA GGCTAGCTACAACGA AATAGGCG
4642

1557
CCCCGUCU G UGCCUUCU
1620
AGAAGGCA GGCTAGCTACAACGA AGACGGGG
4643

1581
CGGACCGU G UGCACUUC
1621
GAAGTGCA GGCTAGCTACAACGA ACCGTCCG
4644

1684
UCAGCAAU G UCAACGAC
1622
GTCGTTGA GGCTAGCTACAACGA ATTGCTGA
4645

1719
CAAAGACU G UGUGUUUA
1623
TAAACACA GGCTAGCTACAACGA AGTCTTTG
4646

1721
AAGACUGU G UGUUUAAU
1624
ATTAAACA GGCTAGCTACAACGA ACAGTCTT
4647

1723
GACUGUGU G UUUAAUGA
1625
TCATTAAA GGCTAGCTACAACGA ACACAGTC
4648

1772
AGGUCUUU G UACUAGGA
1626
TCCTAGTA GGCTAGCTACAACGA AAACACCT
4649

1785
AGGAGGCU G UAGGCAUA
1627
TATCCCTA GGCTAGCTACAACGA ACCCTCCT
4650

1801
AAAUUGGU G UGUUCACC
1628
GGTGAACA GGCTAGCTACAACGA ACCAATTT
4651

1803
AUUGGUGU G UUCACCAG
1629
CTGGTGAA GGCTAGCTACAACGA ACACCAAT
4652

1850
CAUCUCAU G UUCAUGUC
1630
GACATGAA GGCTAGCTACAACGA ATGAGATG
4653

1856
AUGUUCAU G UCCUACUG
1631
CAGTAGGA GGCTAGCTACAACGA ATGAACAT
4654

1864
GUCCUACU G UUCAAGCC
1632
GGCTTGAA GGCTAGCTACAACGA AGTAGGAC
4655

1881
UCCAAGCU G UGCCUUGG
1633
CCAAGGCA GGCTAGCTACAACGA AGCTTGGA
4656

1939
GAGCUUCU G UGGAGUUA
1634
TAACTCCA GGCTAGCTACAACGA AGAAGCTC
4657

2013
UCUGCUCU G UAUCGGGG
1635
CCCCGATA GGCTAGCTACAACGA AGAGCAGA
4658

2045
GGAACAUU G UUCACCUC
1636
GAGGTGAA GGCTAGCTACAACGA AATGTTCC
4659

2082
GCUAUUCU G UGUUGGGG
1637
CCCCAACA GGCTAGCTACAACGA AGAATAGC
4660

2084
UAUUCUGU G UUGGGGUG
1638
CACCCCAA GGCTAGCTACAACGA ACAGAATA
4661

2167
UCAGCUAU G UCAACGUU
1639
AACGTTGA GGCTAGCTACAACGA ATAGCTGA
4662

2205
CAACUAUU G UGGUCUCA
1640
TGAAACCA GGCTAGCTACAACGA AATAGTTG
4663

2222
CAUUUCCU G UCUUACUU
1641
AAGTAAGA GGCTAGCTACAACGA AGGAAATG
4664

2245
GAGAAACU G UUCUUGAA
1642
TTCAAGAA GGCTAGCTACAACGA AGTTTCTC
4665

2262
UAUUUGGU G UCUUUUGG
1643
CCAAAAGA GGCTAGCTACAACGA ACCAAATA
4666

2274
UUUGGAGU G UGGAUUCG
1644
CGAATCCA GGCTAGCTACAACGA ACTCCAAA
4667

2344
AAACUACU G UUGUUAGA
1645
TCTAACAA GGCTAGCTACAACGA AGTAGTTT
4668

2347
CUACUGUU G UUAGACGA
1646
TCGTCTAA GGCTAGCTACAACGA AACAGTAG
4669

2450
AUCUCAAU G UUAGUAUU
1647
AATACTAA GGCTAGCTACAACGA ATTGAGAT
4670

2573
AGGACAUC G UUGAUAGA
1648
TCTATCAA GGCTAGCTACAACGA AATGTCCT
4671

2583
UGAUAGAU G UAAGCAAU
1649
ATTGCTTA GGCTAGCTACAACGA ATCTATCA
4672

2594
AGCAAUUU G UGGGGCCC
1650
GGGCCCCA GGCTAGCTACAACGA AAATTGCT
4673

2663
AUCCCAAU G UUACUAAA
1651
TTATGTAA GGCTAGCTACAACGA ATTGGGAT
4674

2717
CAGAGUAU G UAGUUAAU
1652
ATTAACTA GGCTAGCTACAACGA ATACTCTG
4675

2901
AUCUUUCU G UCCCCAAU
1653
ATTGGGGA GGCTAGCTACAACGA AGAAAGAT
4676

3071
GGGGGACU G UUGFGGUG
1654
CACCCCAA GGCTAGCTACAACGA AGTCCCCC
4677

3111
UCACAACU G UGCCAGCA
1655
TGCTGGCA GGCTAGCTACAACGA AGTTGTGA
4678

40
AUCCCAGA G UCAGGGCC
1656
GGCCCTGA GGCTAGCTACAACGA TCTGGGAT
4679

46
GAGUCAGG G CCCUGUAC
1657
GTACAGGG GGCTAGCTACAACGA CCTGACTC
4680

65
UCCUGCUG G UGGCUCCA
1658
TGGAGCCA GGCTAGCTACAACGA CAGCAGGA
4681

68
UGCUGGUG G CUCCAGUU
1659
AACTGGAG GGCTAGCTACAACGA CACCAGCA
4682

74
UGGCUCCA G UUCAGGAA
1660
TTCCTGAA GGCTAGCTACAACGA TGGAGCCA
4683

85
CAGGAACA G UGAGCCCU
1661
AGGGCTCA GGCTAGCTACAACGA TGTTCCTG
4684

89
AACAGUGA G CCCUGCUC
1662
GAGCAGGG GGCTAGCTACAACGA TCACTGTT
4685

120
GCCAUAUC G UCAAUCUU
1663
AAGATTGA GGCTAGCTACAACGA GATATGGC
4686

196
CCCUGCUC G UGUUACAG
1664
CTGTAACA GGCTAGCTACAACGA GAGCAGGG
4687

205
UGUUACAG G CGGGGUUU
1665
AAACCCCG GGCTAGCTACAACGA CTGTAACA
4688

210
CAGGCGGG G UUUUUCUU
1666
AAGAAAAA GGCTAGCTACAACGA CCCGCCTG
4689

248
ACCACAGA G UCUAGACU
1667
AGTCTAGA GGCTAGCTACAACGA TCTGTGGT
4690

258
CUAGACUC G UGGUGGAC
1668
GTCCACCA GGCTAGCTACAACGA GAGTCTAG
4691

261
GACUCGUG G UGGACUUC
1669
GAAGTCCA GGCTAGCTACAACGA CACGAGTC
4692

295
GAACACCC G UGUGUCUU
1670
AAGACACA GGCTAGCTACAACGA GGGTGTTC
4693

305
GUGUCUUG G CCAAAAUU
1671
AATTTTGG GGCTAGCTACAACGA CAAGACAC
4694

318
AAUUCGCA G UCCCAAAU
1672
ATTTGGGA GGCTAGCTACAACGA TGCGAATT
4695

332
AAUCUCCA G UCACUCAC
1673
GTGAGTGA GGCTAGCTACAACGA TGGAGATT
4696

368
UUGUCCUG G UUAUCGCU
1674
AGCGATAA GGCTAGCTACAACGA CAGGACAA
4697

390
UGUCUGCG G CGUUUUAU
1675
ATAAAACG GGCTAGCTACAACGA CGCAGACA
4698

392
UCUGCGGC G UUUUAUCA
1676
TGATAAAA GGCTAGCTACAACGA GCCGCAGA
4699

442
UCUUGUUG G UUCUUCUG
1677
CAGAAGAA GGCTAGCTACAACGA CAACAAGA
4700

461
CUAUCAAG G UAUGUUGC
1678
GCAACATA GGCTAGCTACAACGA CTTGATAG
4701

472
UGUUGCCC G UUUGUCCU
1679
AGGACAAA GGCTAGCTACAACGA GGGCAACA
4702

506
AACAACCA G CACCGGAC
1680
GTCCGGTG GGCTAGCTACAACGA TGGTTGTT
4703

625
CAUCUUGG G CUUUCGCA
1681
TGCGAAAG GGCTAGCTACAACGA CCAAGATG
4704

648
CUAUGGGA G UGGGCCUC
1682
GAGGCCCA GGCTAGCTACAACGA TCCCATAG
4705

652
GGGAGUGG G CCUCAGUC
1683
GACTGAGG GGCTAGCTACAACGA CCACTCCC
4706

658
GGGCCUCA G UCCGUUUC
1684
GAAACGGA GGCTAGCTACAACGA TGAGGCCC
4707

662
CUCAGUCC G UUUCUCUU
1685
AAGAGAAA GGCTAGCTACAACGA GGACTGAG
4708

672
UUCUCUUG G CUCAGUUU
1686
AAACTGAG GGCTAGCTACAACGA CAAGAGAA
4709

677
UUGGCUCA G UUUACUAG
1687
CTAGTAAA GGCTAGCTACAACGA TGAGCCAA
4710

685
GUUUACUA G UGCCAUUU
1688
AAATGGCA GGCTAGCTACAACGA TAGTAAAC
4711

699
UUUGUUCA G UGGUUCGU
1689
ACGAACCA GGCTAGCTACAACGA TGAACAAA
4712

702
GUUCAGUG G UUCGUAGG
1690
CCTACGAA GGCTAGCTACAACGA CACTGAAC
4713

706
AGUGGUUC G UAGGGCUU
1691
AAGCCCTA GGCTAGCTACAACGA GAACCACT
4714

711
UUCGUAGG G CUUUCCCC
1692
GGGGAAAG GGCTAGCTACAACGA CCTACGAA
4715

729
ACUGUCUG G CUUUCAGU
1693
ACTGAAAG GGCTAGCTACAACGA CAGACAGT
4716

736
GGCUUUCA G UUAUAUGG
1694
CCATATAA GGCTAGCTACAACGA TGAAAGCC
4717

753
AUGAUGUG G UUUUGGGG
1695
CCCCAAAA GGCTAGCTACAACGA CACATCAT
4718

762
UUUUGGGG G CCAAGUCU
1696
AGACTTGG GGCTAGCTACAACGA CCCCAAAA
4719

767
GGGGCCAA G UCUGUACA
1697
TGTACAGA GGCTAGCTACAACGA TTGGCCCC
4720

785
CAUCUUGA G UCCCUUUA
1698
TAAAGGGA GGCTAGCTACAACGA TCAAGATG
4721

826
GUCUUUGG G UAUACAUU
1699
AATGTATA GGCTAGCTACAACGA CCAAAGAC
4722

898
AAUUGGGA G UUGGGGCA
1700
TGCCCCAA GGCTAGCTACAACGA TCCCAATT
4723

904
GAGUUGGG G CACAUUGC
1701
GCAATGTC GGCTAGCTACAACGA CCCAACTC
4724

971
GUAAACAG G CCUAUUGA
1702
TCAATAGG GGCTAGCTACAACGA CTGTTTAC
4725

987
AUUGGAAA G UAUGUCAA
1703
TTGACATA GGCTAGCTACAACGA TTTCCAAT
4726

1006
AAUUGUGG G UCUUUUGG
1704
CCAAAAGA GGCTAGCTACAACGA CCACAATT
4727

1016
CUUUUGGG G UUUGCCGC
1705
GCGGCAAA GGCTAGCTACAACGA CCCAAAAG
4728

1080
GCAUACAA G CAAAACAG
1706
CTGTTTTG GGCTAGCTACAACGA TTGTATGC
4729

1089
CAAAACAG G CUUUUACU
1707
AGTAAAAG GGCTAGCTACAACGA CTGTTTTG
4730

1116
CUUACAAG G CCUUUCUA
1708
TAGAAAGG GGCTAGCTACAACGA CTTGTAAG
4731

1126
CUUUCUAA G UAAACAGU
1709
ACTGTTTA GGCTAGCTACAACGA TTAGAAAG
4732

1133
AGUAAACA G UAUGUGAA
1710
TTCACATA GGCTAGCTACAACGA TGTTTACT
4733

1152
UUUACCCC G UUGCUCGG
1711
CCGAGCAA GGCTAGCTACAACGA GGGGTAAA
4734

1160
GUUGCUCG G CAACGGCC
1712
GGCCGTTG GGCTAGCTACAACGA CGAGCAAC
4735

1166
CGGCAACG G CCUGGUCU
1713
AGACCAGG GGCTAGCTACAACGA CGTTGCCG
4736

1171
ACGGCCUG G UCUAUGCC
1714
GGCATAGA GGCTAGCTACAACGA CAGGCCGT
4737

1182
UAUGCCAA G UGUUUGCU
1715
AGCAAACA GGCTAGCTACAACGA TTGGCATA
4738

1207
CCCCACUG G UUGGGGCU
1716
AGCCCCAA GGCTAGCTACAACGA CAGTGGGG
4739

1213
UGGUUGGG G CUUGGCCA
1717
TGGCCAAG GGCTAGCTACAACGA CCCAACCA
4740

1218
GGGGCUUG G CCAUAGGC
1718
GCCTATGG GGCTAGCTACAACGA CAAGCCCC
4741

1225
GGCCAUAG G CCAUCAGC
1719
GCTGATGG GGCTAGCTACAACGA CTATGGCC
4742

1232
GGCCAUCA G CGCAUGCG
1720
CGCATGCG GGCTAGCTACAACGA TGATGGCC
4743

1240
GCGCAUGC G UGGAACCU
1721
AGGTTCCA GGCTAGCTACAACGA GCATGCGC
4744

1287
AACUCCUA G CCGCUUGU
1722
ACAAGCGG GGCTAGCTACAACGA TAGGAGTT
4745

1306
UGCUCGCA G CAGGUCUG
1723
CAGACCTG GGCTAGCTACAACGA TGCGAGCA
4746

1310
CGCAGCAG G UCUGGGGC
1724
GCCCCAGA GGCTAGCTACAACGA CTGCTGCG
4747

1317
CGUCUGGG G CAAAACUC
1725
GAGTTTTG GGCTAGCTACAACGA CCCAGACC
4748

1347
AUUCUGUC G UGCUCUCC
1726
GGAGAGCA GGCTAGCTACAACGA GACAGAAT
4749

1379
UUUCCAUG G CUGCUAGG
1727
CCTAGCAG GGCTAGCTACAACGA CATGGAAA
4750

1387
GCUGCUAG G CUGUGCUG
1728
CAGCACAG GGCTAGCTACAACGA CTAGCAGC
4751

1418
CGCGGGAC G UCCUUUGU
1729
ACAAAGGA GGCTAGCTACAACGA GTCCCGCG
4752

1431
UUGUUUAC G UCCCGUCG
1730
CGACGGGA GGCTAGCTACAACGA GTAAACAA
4753

1436
UACGUCCC G UCGGCGCU
1731
AGCGCCGA GGCTAGCTACAACGA GGGACGTA
4754

1440
UCCCGUCG G CGCUGAAU
1732
ATTCAGCG GGCTAGCTACAACGA CGACGGGA
4755

1471
CUCCCGGG G CCGCUUGG
1733
CCAAGCGG GGCTAGCTACAACGA CCCGGGAG
4756

1481
CGCUUGGG G CUCUACCG
1734
CGGTAGAG GGCTAGCTACAACGA CCCAAGCG
4757

1517
UACCGACC G UCCACGGG
1735
CCCGTGGA GGCTAGCTACAACGA GGTCGGTA
4758

1526
UCCACGGG G CGCACCUC
1736
GACGTGCG GGCTAGCTACAACGA CCCGTGGA
4759

1553
GACUCCCC G UCUGUGCC
1737
GGCACAGA GGCTAGCTACAACGA GGGGAGTC
4760

1579
GCCGGACC G UGUGCACU
1738
AGTGCACA GGCTAGCTACAACGA GGTCCGGC
4761

1605
CUCUGCAC G UCGCAUGG
1739
CCATGCGA GGCTAGCTACAACGA GTGCAGAG
4762

1622
AGACCACC G UGAACGCC
1740
GGCGTTCA GGCTAGCTACAACGA GGTGGTCT
4763

1649
UGCCCAAG G UCUUGCAU
1741
ATGCAAGA GGCTAGCTACAACGA CTTGGGCA
4764

1679
GACUUUCA G CAAUGUCA
1742
TGACATTG GGCTAGCTACAACGA TGAAAGTC
4765

1703
ACCUUGAG G CAUACUUC
1743
GAAGTATG GGCTAGCTACAACGA CTCAAGGT
4766

1732
UUUAAUGA G UGGGAGGA
1744
TCCTCCCA GGCTAGCTACAACGA TCATTAAA
4767

1741
UGGGAGGA G GUGGGGGA
1745
TCCCCCAA GGCTAGCTACAACGA TCCTCCCA
4768

1754
GGGAGGAG G UUAGGUUA
1746
TAACCTAA GGCTAGCTACAACGA CTCCTCCC
4769

1759
GAGGUUAG G UUAAAGGU
1747
ACCTTTAA GGCTAGCTACAACGA CTAACCTC
4770

1766
GGUUAAAG G UCUUUGUA
1748
TACAAAGA GGCTAGCTACAACGA CTTTAACC
4771

1782
ACUAGGAG G CUGUAGGC
1749
GCCTACAG GGCTAGCTACAACGA CTCCTAGT
4772

1789
GCCUCUAG G CAUAAAUU
1750
AATTTATG GGCTAGCTACAACGA CTACAGCC
4773

1799
AUAAAUUG G UGUGUUCA
1751
TGAACACA GGCTAGCTACAACGA CAATTTAT
4774

1811
GUUCACCA G CACCAUGC
1752
GCATGGTG GGCTAGCTACAACGA TGGTGAAC
4775

1870
CUGUUCAA G CCUCCAAG
1753
CTTGGAGG GGCTAGCTACAACGA TTGAACAG
4776

1878
GCCUCCAA G CUGUGCCU
1754
AGGCACAG GGCTAGCTACAACGA TTGGAGGC
4777

1890
UGCCUUGG G UGGCUUUG
1755
CAAAGCCA GGCTAGCTACAACGA CCAAGGCA
4778

1893
CUUGGGUG G CUUUGGGG
1756
CCCCAAAG GGCTAGCTACAACGA CACCCAAG
4779

1901
GCUUUGGG G CAUGGACA
1757
TGTCCATG GGCTAGCTACAACGA CCCAAAGC
4780

1917
AUUGACCC G UAUAAAGA
1758
TCTTTATA GGCTAGCTACAACGA GGGTCAAT
4781

1933
AAUUUGGA G CUUCUGUG
1759
CACAGAAG GGCTAGCTACAACGA TCCAAATT
4782

1944
UCUGUGGA G GUACUCUC
1760
GAGAGTAA GGCTAGCTACAACGA TCCACAGA
4783

2023
AUCGGGGG G CCUUAGAG
1761
CTCTAAGG GGCTAGCTACAACGA CCCCCGAT
4784

2031
GCCUUAGA G UCUCCGGA
1762
TCCGGAGA GGCTAGCTACAACGA TCTAAGGC
4785

2062
ACCAUACG G CACUCAGG
1763
CCTGAGTG GGCTAGCTACAACGA CGTATGGT
4786

2070
GCACUCAG G CAAGCUAU
1764
ATAGCTTG GGCTAGCTACAACGA CTGAGTGC
4787

2074
UCAGGCAA G CUAUUCUG
1765
CAGAATAG GGCTAGCTACAACGA TTGCCTGA
4788

2090
GUGUUGGG G UGAGUUGA
1766
TCAACTCA GGCTAGCTACAACGA CCCAACAC
4789

2094
UGGGGUGA G UUGAUGAA
1767
TTCATCAA GGCTAGCTACAACGA TCACCCCA
4790

2107
UGAAUCUA G CCACCUGG
1768
CCAGGTGG GGCTAGCTACAACGA TAGATTCA
4791

2116
CCACCUGG G UGGGAAGU
1769
ACTTCCCA GGCTAGCTACAACGA CCAGGTGG
4792

2123
GGUGGGAA G UAAUUUGG
1770
CCAAATTA GGCTAGCTACAACGA TTCCCACC
4793

2140
AAGAUCCA G CAUCCAGG
1771
CCTGGATG GGCTAGCTACAACGA TGGATCTT
4794

2155
GGGAAUUA G UAGUCAGC
1772
GCTGACTA GGCTAGCTACAACGA TAATTCCC
4795

2158
AAUUAGUA G UCAGCUAU
1773
ATAGCTGA GGCTAGCTACAACGA TACTAATT
4796

2162
AGUAGUCA G CUAUGUCA
1774
TGACATAG GGCTAGCTACAACGA TGACTACT
4797

2173
AUGUCAAC G UUAAUAUG
1775
CATATTAA GGCTAGCTACAACGA GTTGACAT
4798

2183
UAAUAUGG G CCUAAAAA
1776
TTTTTAGG GGCTAGCTACAACGA CCATATTA
4799

2208
CUAUUGUG G UUUCACAU
1777
ATGTGAAA GGCTAGCTACAACGA CACAATAG
4800

2235
ACUUUUGG G CGAGAAAC
1778
GTTTCTCG GGCTAGCTACAACGA CCAAAAGT
4801

2260
AAUAUUUG G UGUCUUUU
1779
AAAAGACA GGCTAGCTACAACGA CAAATATT
4802

2272
CUUUUGGA G UGUGGAUU
1780
AATCCACA GGCTAGCTACAACGA TCCAAAAG
4803

2360
ACGAAGAG G CAGGUCCC
1781
GGGACCTG GGCTAGCTACAACGA CTCTTCGT
4804

2364
AGAGGCAG G UCCCCUAG
1782
CTAGGGGA GGCTAGCTACAACGA CTGCCTCT
4805

2403
AGACGAAG G UCUCAAUC
1783
GATTGAGA GGCTAGCTACAACGA CTTCGTCT
4806

2417
AUCGCCGC G UCGCAGAA
1784
TTCTGCGA GGCTAGCTACAACGA GCGGCGAT
4807

2454
CAAUGUUA G UAUUCCUU
1785
AAGGAATA GGCTAGCTACAACGA TAACATTG
4808

2474
CACAUAAG G UGGGAAAC
1786
GTTTCCCA GGCTAGCTACAACGA CTTATGTG
4809

2491
UUUACGGG G CUUUAUUC
1787
GAATAAAG GGCTAGCTACAACGA CCCGTAAA
4810

2507
CUUCUACG G UACCUUGC
1788
GCAAGGTA GGCTAGCTACAACGA CGTAGAAG
4811

2530
CCUAAAUG G CAAACUCC
1789
GGAGTTTG GGCTAGCTACAACGA CATTTAGG
4812

2587
AGAUGUAA G CAAUUUGU
1790
ACAAATTG GGCTAGCTACAACGA TTACATCT
4813

2599
UUUGUGGG G CCCCUUAC
1791
GTAAGGGG GGCTAGCTACAACGA CCCACAAA
4814

2609
CCCUUACA G UAAAUGAA
1792
TTCATTTA GGCTAGCTACAACGA TGTAAGGG
4815

2650
CCUGCUAG G UUUUAUCC
1793
GGATAAAA GGCTAGCTACAACGA CTAGCAGG
4816

2701
AUCAAACC G UAUUAUCC
1794
GGATAATA GGCTAGCTACAACGA GGTTTGAT
4817

2713
UAUCCAGA G UAUGUAGU
1795
ACTACATA GGCTAGCTACAACGA TCTGGATA
4818

2720
AGUAUGUA G UUAAUCAU
1796
ATGATTAA GGCTAGCTACAACGA TACATACT
4819

2768
UUUGGAAG G CGGGGAUC
1797
GATCCCCG GGCTAGCTACAACGA CTTCCAAA
4820

2791
AAAAGAGA G UCCACACG
1798
CGTGTGGA GGCTAGCTACAACGA TCTCTTTT
4821

2799
GUCCACAC G UAGCGCCU
1799
AGGCGCTA GGCTAGCTACAACGA GTGTGGAC
4822

2802
CACACGUA G CGCCUCAU
1800
ATGAGGCG GGCTAGCTACAACGA TACGTGTC
4823

2818
UUUUGCGG G UCACCAUA
1801
TATGGTGA GGCTAGCTACAACGA CCGCAAAA
4824

2848
GAUCUACA G CAUGGGAG
1802
CTCCCATG GGCTAGCTACAACGA TGTAGATC
4825

2857
CAUGGGAG G UUGGUCUU
A803
AAGACCAA GGCTAGCTACAACGA CTCCCATG
4826

2861
GGAGGUUG G UCUUCCAA
1804
TTGGAAGA GGCTAGCTACAACGA CAACCTCC
4827

2881
UCGAAAAG G CAUGGGGA
1805
TCCCCATG GGCTAGCTACAACGA CTTTTCGA
4828

2936
GAUCAUCA G UUGGACCC
1806
GGGTCCAA GGCTAGCTACAACGA TGATGATC
4829

2955
CAUUCAAA G CCAACUCA
1807
TGAGTTGG GGCTAGCTACAACGA TTTGAATG
4830

2964
CCAACUCA G UAAAUCCA
1808
TGGATTTA GGCTAGCTACAACGA TGAGTTGG
4831

3005
GACAACUG G CCGGACGC
1809
GCGTCCGG GGCTAGCTACAACGA CAGTTGTC
4832

3021
CCAACAAG G UGGGAGUG
1810
CACTCCCA GGCTAGCTACAACGA CTTGTTGG
4833

3027
AGGUGGGA G UGGGAGCA
1811
TGCTCCCA GGCTAGCTACAACGA TCCCACCT
4834

3033
GAGUGGGA G CAUUCGGG
1812
CCCGAATG GGCTAGCTACAACGA TCCCACTC
4835

3041
GCAUUCGG G CCAGGGUU
1813
AACCCTGG GGCTAGCTACAACGA CCGAATGC
4836

3047
GGGCCAGG G UUCACCCC
1814
GGGGTGAA GGCTAGCTACAACGA CCTGGCCC
4837

3077
CUGUUGGG G UGGAGCCC
1815
GGGCTCCA GGCTAGCTACAACGA CCCAACAG
4838

3082
GGGGUGGA G CCCUCACG
1816
CGTGAGGG GGCTAGCTACAACGA TCCACCCC
4839

3097
CGCUCAGG G CCUACUCA
1817
TGAGTAGG GGCTAGCTACAACGA CCTGAGCG
4840

3117
CUGUGCCA G CAGCUCCU
1818
AGGAGCTG GGCTAGCTACAACGA TGGCACAG
4841

3120
UGCCAGCA G CUCCUCCU
1819
AGGAGGAG GGCTAGCTACAACGA TGCTGGCA
4842

3146
ACCAAUCG G CAGUCAGG
1820
CCTGACTG GGCTAGCTACAACGA CGATTGGT
4843

3149
AAUCGGCA G UCAGGAAG
1821
CTTCCTGA GGCTAGCTACAACGA TGCCGATT
4844

3158
UCAGGAAG G CAGCCUAC
1822
GTAGGCTG GGCTAGCTACAACGA CTTCCTGA
4845

3161
GGAAGGCA G CCUACUCC
1823
GGAGTAGG GGCTAGCTACAACGA TGCCTTCC
4846

3204
AUCCUCAG G CCAUGCAG
1824
CTGCATGG GGCTAGCTACAACGA CTGAGGAT
4847

10
ACUCCACC A CUUUCCAC
1825
GTGGAAAG GGCTAGCTACAACGA GGTGGAGT
4848

17
CACUUUCC A CCAAACUC
1826
GAGTTTGG GGCTAGCTACAACGA GGAAAGTG
4849

22
UCCACCAA A CUCUUCAA
1827
TTGAAGAG GGCTAGCTACAACGA TTGGTGGA
4850

32
UCUUCAAG A UCCCAGAG
1828
CTCTGGGA GGCTAGCTACAACGA CTTGAAGA
4851

53
GGCCCUGU A CUUUCCUG
1829
CAGGAAAG GGCTAGCTACAACGA ACAGGGCC
4852

82
GUUCAGGA A CAGUGAGC
1830
GCTCACTG GGCTAGCTACAACGA TCCTGAAC
4853

101
UGCUCAGA A UACUGUCU
1831
ACACAGTA GGCTAGCTACAACGA TCTGAGCA
4854

103
CUGAGAAU A CUGUCUCU
1832
AGAGACAG GGCTAGCTACAACGA ATTCTGAG
4855

115
UCUCUGCC A UAUCGUCA
1833
TGACGATA GGCTAGCTACAACGA GGCAGAGA
4856

117
UCUGCCAU A UCGUCAAU
1834
ATTGACGA GGCTAGCTACAACGA ATGGCAGA
4857

124
UAUCGUCA A UCUUAUCG
1835
CGATAAGA GGCTAGCTACAACGA TGACGATA
4858

129
UCAAUCUU A UCGAAGAC
1836
GTCTTCGA GGCTAGCTACAACGA AAGATTGA
4859

136
UAUCGAAG A CUGGGGAC
1837
GTCCCCAG GGCTAGCTACAACGA CTTCGATA
4860

143
GACUGGGG A CCCUGUAC
1838
GTACAGGG GGCTAGCTACAACGA CCCCAGTC
4861

150
GACCCUGU A CCGAACAU
1839
ATGTTCGG GGCTAGCTACAACGA ACAGGGTC
4862

155
UGUACCGA A CAUGGAGA
1840
TCTCCATG GGCTAGCTACAACGA TCGGTACA
4863

157
UACCGAAC A UGGAGAAC
1841
GTTCTCCA GGCTAGCTACAACGA GTTCGGTA
4864

164
CAUGGAGA A CAUCGCAU
1842
ATGCGATG GGCTAGCTACAACGA TCTCCATG
4865

166
UGGAGAAC A UCGCAUCA
1843
TGATGCGA GGCTAGCTACAACGA GTTCTCCA
4866

171
AACAUCGC A UCAGGACU
1844
AGTCCTGA GGCTAGCTACAACGA GCGATGTT
4867

177
GCAUCAGG A CUCCUAGG
1845
CCTAGGAG GGCTAGCTACAACGA CCTGATGC
4868

186
CUCCUAGG A CCCCUGCU
1846
AGCAGGGG GGCTAGCTACAACGA CCTAGGAG
4869

201
CUCGUGUU A CAGGCGGG
1847
CCCGCCTG GGCTAGCTACAACGA AACACGAG
4870

223
UCUUGUUG A CAAAAAUC
1848
GATTTTTG GGCTAGCTACAACGA CAACAAGA
4871

229
UGACAAAA A UCCUCACA
1849
TGTGAGGA GGCTAGCTACAACGA TTTTGTCA
4872

235
AAAUCCUC A CAAUACCA
1850
TGGTATTG GGCTAGCTACAACGA GAGGATTT
4873

238
UCCUCACA A UACCACAG
1851
CTGTGGTA GGCTAGCTACAACGA TGTGAGGA
4874

240
CUCACAAU A CCACAGAG
1852
CTCTGTGG GGCTAGCTACAACGA ATTGTGAG
4875

243
ACAAUACC A CAGAGUCU
1853
AGACTCTG GGCTAGCTACAACGA GGTATTGT
4876

254
GAGUCUAG A CUCGUGGU
1854
ACCACGAG GGCTAGCTACAACGA CTAGACTC
4877

265
CGUGGUGG A CUUCUCUC
1855
GAGAGAAG GGCTAGCTACAACGA CCACCACG
4878

275
GUCUCUCA A UUUUCUAG
1856
CTAGAAAA GGCTAGCTACAACGA TGAGAGAA
4879

289
UAGGGGGA A CACCCGUG
1857
CACGGGTG GGCTAGCTACAACGA TCCCCCTA
4880

291
GGGGGAAC A CCCGUGUG
1858
CACACGGG GGCTAGCTACAACGA GTTCCCCC
4881

311
UGGCCAAA A UUCGCAGU
1859
ACTGCGAA GGCTAGCTACAACGA TTTGGCCA
4882

325
AGUCCCAA A UCUCCAGU
1860
ACTGGAGA GGCTAGCTACAACGA TTGGGACT
4883

335
CUCCAGUC A CUCACCAA
1861
TTGGTGAG GGCTAGCTACAACGA GACTGGAG
4884

339
AGUCACUC A CCAACCUG
1862
CAGGTTGG GGCTAGCTACAACGA GAGTGACT
4885

343
ACUCACCA A CCUGUUGU
1863
ACAACAGG GGCTAGCTACAACGA TGGTGAGT
4886

358
GUCCUCCA A UUUGUCCU
1864
AGGACAAA GGCTAGCTACAACGA TGGAGGAC
4887

371
UCCUGGUU A UCGCUGGA
1865
TCCAGCGA GGCTAGCTACAACGA AACCAGGA
4888

379
AUCGCUGG A UGUGUCUG
1866
CAGACACA GGCTAGCTACAACGA CCAGCGAT
4889

397
GGCGUUUU A UCAUCUUC
1867
GAAGATGA GGCTAGCTACAACGA AAAACGCC
4890

400
GUUUUAUC A UCUUCCUC
1868
GAGGAAGA GGCTAGCTACAACGA GATAAAAC
4891

412
UCCUCUGC A UCCUGCUG
1869
CAGCAGGA GGCTAGCTACAACGA GCAGAGGA
4892

423
CUGCUGCU A UGCCUCAU
1870
ATGAGGCA GGCTAGCTACAACGA AGCAGCAG
4893

430
UAUGCCUC A UCUUCUUG
1871
CAAGAAGA GGCTAGCTACAACGA GAGGCATA
4894

452
UCUUCUGG A CUAUCAAG
1872
CTTGATAG GGCTAGCTACAACGA CCAGAAGA
4895

455
UCUGGACU A UCAAGGUA
1873
TACCTTGA GGCTAGCTACAACGA AGTCCAGA
4896

463
AUCAAGGU A UGUUGCCC
1874
GGGCAACA GGCTAGCTACAACGA ACCTTGAT
4897

484
GUCCUCUA A UUCCAGGA
1875
TCCTGGAA GGCTAGCTACAACGA TAGAGGAC
4898

492
AUUCCAGG A UCAUCAAC
1876
GTTGATGA GGCTAGCTACAACGA CCTGGAAT
4899

495
CCAGGAUC A UCAACAAC
1877
GTTGTTGA GGCTAGCTACAACGA GATCCTGG
4900

499
GAUCAUCA A CAACCAGC
1878
GCTGGTTG GGCTAGCTACAACGA TGATGATC
4901

502
CAUCAACA A CCAGCACC
1879
GGTGCTGG GGCTAGCTACAACGA TGTTGATG
4902

513
AGCACCGG A CCAUGCAA
1880
TTGCATGG GGCTAGCTACAACGA CCGGTGCT
4903

516
ACCGGACC A UGCAAAAC
1881
GTTTTGCA GGCTAGCTACAACGA GGTCCGGT
4904

523
CAUGCAAA A CCUGCACA
1882
TGTGCAGG GGCTAGCTACAACGA TTTGCATG
4905

529
AAACCUGC A CAACUCCU
1883
AGGAGTTG GGCTAGCTACAACGA GCAGGTTT
4906

532
CCUGCACA A CUCCUGCU
1884
AGCAGGAG GGCTAGCTACAACGA TGTGCAGG
4907

547
CUCAAGGA A CCUCUAUG
1885
CATAGAGG GGCTAGCTACAACGA TCCTTGAG
4908

553
GAACCUCU A UGUUUCCC
1886
GGGAAACA GGCTAGCTACAACGA AGAGGTTC
4909

564
UUUCCCUC A UGUUGCUG
1887
CAGCAACA GGCTAGCTACAACGA GAGGGAAA
4910

574
GUUGCUGU A CAAAACCU
1888
AGGTTTTG GGCTAGCTACAACGA ACAGCAAC
4911

579
UGUACAAA A CCUACGGA
1889
TCCGTAGG GGCTAGCTACAACGA TTTGTACA
4912

583
CAAAACCU A CGGACGGA
1890
TCCGTCCG GGCTAGCTACAACGA AGGTTTTG
4913

587
ACCUACGG A CGGAAACU
1891
AGTTTCCG GGCTAGCTACAACGA CCGTAGGT
4914

593
GGACGGAA A CUGCACCU
1892
ACGTGCAG GGCTAGCTACAACGA TTCCGTCC
4915

598
GAAACUGC A CCUGUAUU
1893
AATACAGG GGCTAGCTACAACGA GCAGTTTC
4916

604
GCACCUGU A UUCCCAUC
1894
GATGGGAA GGCTAGCTACAACGA ACAGGTGC
4917

610
GUAUUCCC A UCCCAUCA
1895
TGATGGGA GGCTAGCTACAACGA GGGAATAC
4918

615
CCCAUCCC A UCAUCUUG
1896
CAAGATGA GGCTAGCTACAACGA GGGATGGG
4919

618
AUCCCAUC A UCUUGGGC
1897
GCCCAAGA GGCTAGCTACAACGA GATGGGAT
4920

636
UUCGCAAA A UACCUAUG
1898
CATAGGTA GGCTAGCTACAACGA TTTGCGAA
4921

638
CGCAAAAU A CCUAUGGG
1899
CCCATAGG GGCTAGCTACAACGA ATTTTGCG
4922

642
AAAUACCU A UGGGAGUG
1900
CACTCCCA GGCTAGCTACAACGA AGGTATTT
4923

681
CUCAGUUU A CUAGUGCC
1901
GGCACTAG GGCTAGCTACAACGA AAACTTAG
4924

690
CUAGUGCC A UUUGUUCA
1902
TGAACAAA GGCTAGCTACAACGA GGCACTAG
4925

721
UUUCCCCC A CUGUCUGG
1903
CCAGACAG GGCTAGCTACAACGA GGGGGAAA
4926

739
UUUCAGUU A UAUGGAUG
1904
CATCCATA GGCTAGCTACAACGA AACTGAAA
4927

741
UCAGUUAU A UGGAUGAU
1905
ATCATCCA GGCTAGCTACAACGA ATAACTGA
4928

745
UUAUAUGG A UGAUGUGG
1906
CCACATCA GGCTAGCTACAACGA CCATATAA
4929

748
UAUGGAUG A UGUGGUUU
1907
AAACCACA GGCTAGCTACAACGA CATCCATA
4930

773
AAGUCUGU A CAACAUCU
1908
AGATGTTG GGCTAGCTACAACGA ACAGACTT
4931

776
UCUGUACA A CAUCUUGA
1909
TCAAGATG GGCTAGCTACAACGA TGTACAGA
4932

778
UGUACAAC A UCUUGAGU
1910
ACTCAAGA GGCTAGCTACAACGA GTTGTACA
4933

793
GUCCCUUU A UGCCGCUG
1911
CAGCGGCA GGCTAGCTACAACGA AAAGGGAC
4934

804
CCGCUGUU A CCAAUUUU
1912
AAAATTGG GGCTAGCTACAACGA AACAGCGG
4935

808
UGUUACCA A UUUUCUUU
1913
AAAGAAAA GGCTAGCTACAACGA TGGTAACA
4936

828
CUUUGGGU A UACAUUUA
1914
TAAATGTA GGCTAGCTACAACGA ACCCAAAG
4937

830
UUGGGUAU A CAUUUAAA
1915
TTTAAATG GGCTAGCTACAACGA ATACCCAA
4938

832
GGGUAUAC A UUUAAACC
1916
GGTTTAAA GGCTAGCTACAACGA GTATACCC
4939

838
ACAUUUAA A CCCUCACA
1917
TGTGAGGG GGCTAGCTACAACGA TTAAATGT
4940

844
AAACCCUC A CAAAACAA
1918
TTGTTTTG GGCTAGCTACAACGA GAGGGTTT
4941

849
CUCACAAA A CAAAAAGA
1919
TCTTTTTG GGCTAGCTACAACGA TTTGTGAG
4942

857
ACAAAAAG A UGGGGAUA
1920
TATCCCCA GGCTAGCTACAACGA CTTTTTGT
4943

863
AGAUGGGG A UAUUCCCU
1921
AGGGAATA GGCTAGCTACAACGA CCCCATCT
4944

865
AUGGGGAG A UUCCCUUA
1922
TAAGGGAA GGCTAGCTACAACGA ATCCCCAT
4945

874
UUCCCUUA A CUUCAUGG
1923
CCATGAAG GGCTAGCTACAACGA TAAGGGAA
4946

879
UUAACUUC A UGGGAUAU
1924
ATATCCCA GGCTAGCTACAACGA GAAGTTAA
4947

884
UUCAUGGG A UAUGUAAU
1925
ATTACATA GGCTAGCTACAACGA CCCATGAA
4948

886
CAUGGGAU A UGUAAUUG
1926
CAATTACA GGCTAGCTACAACGA ATCCCATG
4949

891
GAUAUGUA A UUGGGAGU
1927
ACTCCCAA GGCTAGCTACAACGA TACATATC
4950

906
GUUGGGGC A CAUUGCCA
1928
TGGCAATG GGCTAGCTACAACGA GCCCCAAC
4951

908
UGGGGCAC A UUGCCACA
1929
TGTGGCAA GGCTAGCTACAACGA GTGCCCCA
4952

914
ACAUUGCC A CAGGAACA
1930
TGTTCCTG GGCTAGCTACAACGA GGCAATGT
4953

920
CCACAGGA A CAUAUUGU
1931
ACAATATG GGCTAGCTACAACGA TCCTGTGG
4954

922
ACAGGAAC A UAUUGUAC
1932
GTACAATA GGCTAGCTACAACGA GTTCCTGT
4955

924
AGGAACAU A UUGUACAA
1933
TTGTACAA GGCTAGCTACAACGA ATGTTCCT
4956

929
CAUAUUGU A CAAAAAAU
1934
ATTTTTTG GGCTAGCTACAACGA ACAATATG
4957

936
UACAAAAA A UCAAAAUG
1935
CATTTTGA GGCTAGCTACAACGA TTTTTGTA
4958

942
AAAUCAAA A UGUGUUUU
1936
AAAACACA GGCTAGCTACAACGA TTTGATTT
4959

956
UUUAGGAA A CUUCCUGU
1937
ACAGGAAG GGCTAGCTACAACGA TTCCTAAA
4960

967
UCCUGUAA A CAGGCCUA
1938
TAGGCCTG GGCTAGCTACAACGA TTACAGGA
4961

975
ACAGGCCU A UUGAUUGG
1939
CCAATCAA GGCTAGCTACAACGA AGGCCTGT
4962

979
GCCUAUUG A UUGGAAAG
1940
CTTTCCAA GGCTAGCTACAACGA CAATAGGC
4963

989
UGGAAAGU A UGUCAACG
1941
CGTTGACA GGCTAGCTACAACGA ACTTTCCA
4964

995
GUAUGUCA A CGAAUUGU
1942
ACAATTCG GGCTAGCTACAACGA TGACATAC
4965

999
GUCAACGA A UUGUGGGU
1943
ACCCACAA GGCTAGCTACAACGA TCGTTGAC
4966

1032
CCCCUUUC A CGCAAUGU
1944
ACATTGCG GGCTAGCTACAACGA GAAAGGGG
4967

1037
UUCACGCA A UGUGGAUA
1945
TATCCACA GGCTAGCTACAACGA TGCGTGAA
4968

1043
CAAUGUGG A UAUUCUGC
1946
GCAGAATA GGCTAGCTACAACGA CCACATTG
4969

1045
AUGUGGAU A UUCUGCUU
1947
AAGCAGAA GGCTAGCTACAACGA ATCCACAT
4970

1056
CUGCUUUA A UGCCUUUA
1948
TAAAGGCA GGCTAGCTACAACGA TAAAGCAG
4971

1064
AUGCCUUU A UAUGCAUG
1949
CATGCATA GGCTAGCTACAACGA AAAGGCAT
4972

1066
GCCUUUAU A UGCAUGCA
1950
TGCATGCA GGCTAGCTACAACGA ATAAAGGC
4973

1070
UUAUAUGC A UGCAUACA
1951
TGTATGCA GGCTAGCTACAACGA GCATATAA
4974

1074
AUGCAUGC A UACAAGCA
1952
TGCTTGTA GGCTAGCTACAACGA GCATGCAT
4975

1076
GCAUGCAU A CAAGCAAA
1953
TTTGCTTG GGCTAGCTACAACGA ATGCATGC
4976

1085
CAAGCAAA A CAGGCUUU
1954
AAAGCCTG GGCTAGCTACAACGA TTTGCTTG
4977

1095
AGGCUUUU A CUUUCUCG
1955
CGAGAAAG GGCTAGCTACAACGA AAAAGCCT
4978

1107
UCUCGCCA A CUUACAAG
1956
CTTGTAAG GGCTAGCTACAACGA TGGCGAGA
4979

1111
GCCAACUU A CAAGGCCU
1957
AGGCCTTG GGCTAGCTACAACGA AAGTTGGC
4980

1130
CUAAGUAA A CAGUAUGU
1958
ACATACTG GGCTAGCTACAACGA TTACTTAG
4981

1135
UAAACAGU A UGUGAACC
1959
GGTTCACA GGCTAGCTACAACGA ACTGTTTA
4982

1141
GUAUGUGA A CCUUUACC
1960
GGTAAAGG GGCTAGCTACAACGA TCACATAC
4983

1147
GAACCUUU A CCCCGUUG
1961
CAACGGGG GGCTAGCTACAACGA AAAGGTTC
4984

1163
GCUCGGCA A CGGCCUGG
1962
CCAGGCCG GGCTAGCTACAACGA TGCCGAGC
4985

1175
CCUGGUCU A UGCCAAGU
1963
ACTTGGCA GGCTAGCTACAACGA AGACCAGG
4986

1192
GUUUGCUG A CGCAACCC
1964
GGGTTGCG GGCTAGCTACAACGA CAGCAAAC
4987

1197
CUGACGCA A CCCCCACU
1965
AGTGGGGG GGCTAGCTACAACGA TGCGTCAG
4988

1203
CAACCCCC A CUGGUUGG
1966
CCAACCAG GGCTAGCTACAACGA GGCGGTTG
4989

1221
GCUUGGCC A UAGGCCAU
1967
ATGGCCTA GGCTAGCTACAACGA GGCCAAGC
4990

1228
CAUAGGCC A UCAGCGCA
1968
TGCGCTGA GGCTAGCTACAACGA GGCCTATG
4991

1236
AUCAGCGC A UGCGUGGA
1969
TCCACGCA GGCTAGCTACAACGA GCGCTGAT
4992

1245
UGCGUGGA A CCUUUGUG
1970
CACAAAGG GGCTAGCTACAACGA TCCACGCA
4993

1266
CUCUGCCG A UCCAUACC
1971
GGTATGGA GGCTAGCTACAACGA CGGCAGAG
4994

1270
GCCGAUCC A UACCGCCG
1972
CCGCGGTA GGCTAGCTACAACGA GGATCGGC
4995

1272
CGAUCCAU A CCGCGGAA
1973
TTCCGCCG GGCTAGCTACAACGA ATGGATCG
4996

1280
ACCGCGGA A CUCCUAGC
1974
GCTAGGAG GGCTAGCTACAACGA TCCGCGGT
4997

1322
GGGGCAAA A CUCAUCGG
1975
CCGATGAG GGCTAGCTACAACGA TTTGCCCC
4998

1326
CAAAACUC A UCGGGACU
1976
AGTCCCGA GGCTAGCTACAACGA GAGTTTTG
4999

1332
UCAUCGGG A CUGACAAU
1977
ATTGTCAG GGCTAGCTACAACGA CCCGATGA
5000

1336
CGGGACUG A CAAUUCUG
1978
CAGAATTG GGCTAGCTACAACGA CAGTCCCG
5001

1339
GACUGACA A UUCUGUCG
1979
CGACAGAA GGCTAGCTACAACGA TGTCAGTC
5002

1361
UCCCGCAA A UAUACAUC
1980
GATGTATA GGCTAGCTACAACGA TTGCGGGA
5003

1363
CCGCAAAU A UACAUCAU
1981
ATGATGTA GGCTAGCTACAACGA ATTTGCGG
5004

1365
GCAAAUAU A CAUCAUUU
1982
AAATGATG GGCTAGCTACAACGA ATATTTGC
5005

1367
AAAUAUAC A UCAUUUCC
1983
GGAAATGA GGCTAGCTACAACGA GTATATTT
5006

1370
UAUACAUC A UUUCCAUG
1984
CATGGAAA GGCTAGCTACAACGA GATGTATA
5007

1376
UCAUUUCC A UGGCUGCU
1985
AGCAGCCA GGCTAGCTACAACGA GGAAATGA
5008

1399
UGCUGCCA A CUGGAUCC
1986
GGATCCAG GGCTAGCTACAACGA TGGCAGCA
5009

1404
CCAACUGG A UCCUACGC
1987
GCGTAGGA GGCTAGCTACAACGA CCAGTTGG
5010

1409
UGGAUCCU A CGCGGGAC
1988
GTCCCGCG GGCTAGCTACAACGA AGGATCCA
5011

1416
UACGCGCG A CGUCCUUU
1989
AAAGGACG GGCTAGCTACAACGA CCCGCGTA
5012

1429
CUUUGUUU A CGUCCCGU
1990
ACGGGACG GGCTAGCTACAACGA AAACAAAG
5013

1447
GGCGCUGA A UCCCGCGG
1991
CCGCGGGA GGCTAGCTACAACGA TCAGCGCC
5014

1456
UCCCGCGG A CGACCCCU
1992
AGGGGTCG GGCTAGCTACAACGA CCGCCGGA
5015

1459
CGCGGACG A CCCCUCCC
1993
GGGAGGGG GGCTAGCTACAACGA CGTCCGCG
5016

1486
GGGGCUCU A CCGCCCGC
1994
GCGGGCGG GGCTAGCTACAACGA AGAGCCCC
5017

1505
CUCCGCCU A UUGUACCG
1995
CGGTACAA GGCTAGCTACAACGA AGGCGGAG
5018

1510
CCUAUUGU A CCGACCGU
1996
ACGGTCGG GGCTAGCTACAACGA ACAATAGG
5019

1514
UUGUACCG A CCGUCCAC
1997
GTGGACGG GGCTAGCTACAACGA CGGTACAA
5020

1521
GACCGUCC A CGGGGCGC
1998
GCGCCCCG GGCTAGCTACAACGA GGACGGTC
5021

1530
CGGGGCGC A CCUCUCUU
1999
AAGAGAGG GGCTAGCTACAACGA GCGCCCCG
5022

1540
CUCUCUUU A CGCGGACU
2000
AGTCCGCG GGCTAGCTACAACGA AAAGAGAG
5023

1546
UUACGCGG A CUCCCCGU
2001
ACGGGGAG GGCTAGCTACAACGA CCGCGTAA
5024

1567
GCCUUCUC A UCUGCCGG
2002
CCGGCAGA GGCTAGCTACAACGA GAGAAGGC
5025

1576
UCUGCCGG A CCGUGUGC
2003
GCACACGG GGCTAGCTACAACGA CCGGCAGA
5026

1585
CCGUGUGC A CUUCGCUU
2004
AAGCGAAG GGCTAGCTACAACGA GCACACGG
5027

1595
UUCGCUUC A CCUCUGCA
2005
TGCAGAGG GGCTAGCTACAACGA GAAGCGAA
5028

1603
ACCUCUGC A CGUCGCAU
2006
ATGCGACG GGCTAGCTACAACGA GCAGAGGT
5029

1610
CACGUCGC A UGGAGACC
2007
GGTCTCCA GGCTAGCTACAACGA GCGACGTG
5030

1616
GCAUGGAG A CCACCGUG
2008
CACGGTGG GGCTAGCTACAACGA CTCCATGC
5031

1619
UGGAGACC A CCGUGAAC
2009
GTTCACGG GGCTAGCTACAACGA GGTCTCCA
5032

1626
CACCGUGA A CGCCCACA
2010
TGTGGGCG GGCTAGCTACAACGA TCACGGTG
5033

1638
CCACAGGA A CCUGCCCA
2011
TGGGCAGG GGCTAGCTACAACGA TCCTGTGG
5034

1656
GGUCUUGC A UAAGAGGA
2012
TCCTCTTA GGCTAGCTACAACGA GCAAGACC
5035

1664
AUAAGAGG A CUCUUGGA
2013
TCCAAGAG GGCTAGCTACAACGA CCTCTTAT
5036

1672
ACUCUUGG A CUUUCAGC
2014
GCTGAAAG GGCTAGCTACAACGA CCAAGAGT
5037

1682
UUUCAGCA A UGUCAACG
2015
CGTTGACA GGCTAGCTACAACGA TGCTGAAA
5038

1688
CAAUGUCA A CGACCGAC
2016
GTCGGTCG GGCTAGCTACAACGA TGACATTG
5039

1691
UGUCAACG A CCGACCUU
2017
AAGGTCGG GGCTAGCTACAACGA CGTTGACA
5040

1695
AACGACCG A CCUUGAGG
2018
CCTCAAGG GGCTAGCTACAACGA CGGTCGTT
5041

1705
CUUGAGGC A UACUUCAA
2019
TTGAAGTA GGCTAGCTACAACGA GCCTCAAG
5042

1707
UGAGGCAU A CUUCAAAG
2020
CTTTGAAG GGCTAGCTACAACGA ATGCCTCA
5043

1716
CUUCAAAG A CUGUGUGU
2021
ACACACAG GGCTAGCTACAACGA CTTTGAAG
5044

1728
UGUGUUUA A UGAGUGGG
2022
CCCACTCA GGCTAGCTACAACGA TAAACACA
5045

1774
GUCUUUGU A CUAGGAGG
2023
CCTCCTAG GGCTAGCTACAACGA ACAAAGAC
5046

1791
CUGUAGGC A UAAAUUGG
2024
CCAATTTA GGCTAGCTACAACGA GCCTACAG
5047

1795
AGGCAUAA A UUGGUGUG
2025
CACACCAA GGCTAGCTACAACGA TTATGCCT
5048

1807
GUGUGUUC A CCAGCACC
2026
GGTGCTGG GGCTAGCTACAACGA GAACACAC
5049

1813
UCACCAGC A CCAUGCAA
2027
TTGCATGG GGCTAGCTACAACGA GCTGGTGA
5050

1816
CCAGCACC A UGCAACUU
2028
AAGTTGCA GGCTAGCTACAACGA GGTGCTGG
5051

1821
ACCAUGCA A CUUUUUCA
2029
TGAAAAAG GGCTAGCTACAACGA TGCATGGT
5052

1829
ACUUUUUC A CCUCUGCC
2030
GGCAGAGG GGCTAGCTACAACGA GAAAAAGT
5053

1840
UCUGCCUA A UCAUCUCA
2031
TGAGATGA GGCTAGCTACAACGA TAGGCAGA
5054

1843
GCCUAAUC A UCUCAUGU
2032
ACATGAGA GGCTAGCTACAACGA GATTAGGC
5055

1848
AUCAUCUC A UGUUCAUG
2033
CATGAACA GGCTAGCTACAACGA GAGATGAT
5056

1854
UCAUGUUC A UGUCCUAC
2034
GTAGGACA GGCTAGCTACAACGA GAACATGA
5057

1861
CAUGUCCU A CUGUUCAA
2035
TTGAACAG GGCTAGCTACAACGA AGGACATG
5058

1903
UUUGGGGC A UGGACAUU
2036
AATGTCCA GGCTAGCTACAACGA GCCCCAAA
5059

1907
GGGCAUGG A CAUUGACC
2037
GGTCAATG GGCTAGCTACAACGA CCATGCCC
5060

1909
GCAUGGAC A UUGACCCG
2038
CGGGTCAA GGCTAGCTACAACGA GTCCATGC
5061

1913
GGACAUUG A CCCGUAUA
2039
TATACGGG GGCTAGCTACAACGA CAATGTCC
5062

1919
UGACCCCU A UAAAGAAU
2040
ATTCTTTA GGCTAGCTACAACGA ACGGGTCA
5063

1926
UAUAAAGA A UUUGGAGC
2041
GCTCCAAA GGCTAGCTACAACGA TCTTTATA
5064

1947
GUGGAGUU A CUCUCUUU
2042
AAAGAGAG GGCTAGCTACAACGA AACTCCAC
5065

1967
GCCUUCUG A CUUCUUUC
2043
GAAAGAAG GGCTAGCTACAACGA CAGAAGGC
5066

1981
UUCCUUCU A UUCGAGAU
2044
ATCTCGAA GGCTAGCTACAACGA AGAAGGAA
5067

1988
UAUUCGAG A UCUCCUCG
2045
CCAGGAGA GGCTAGCTACAACGA CTCGAATA
5068

1997
UCUCCUCG A CACCGCCU
2046
AGGCGGTG GGCTAGCTACAACGA CGAGGAGA
5069

1999
UCCUCGAC A CCGCCUCU
2047
AGAGGCGG GGCTAGCTACAACGA GTCGAGGA
5070

2015
UGCUCUGU A UCGGGGGG
2048
CCCCCCGA GGCTAGCTACAACGA ACAGAGCA
5071

2040
UCUCCGGA A CAUUGUUC
2049
GAACAATG GGCTAGCTACAACGA TCCGGAGA
5072

2042
UCCGGAAC A UUGUUCAC
2050
GTGAACAA GGCTAGCTACAACGA GTTCCGGA
5073

2049
CAUUGUUC A CCUCACCA
2051
TGGTGAGG GGCTAGCTACAACGA GAACAATG
5074

2054
UUCACCUC A CCAUACGG
2052
CCGTATGG GGCTAGCTACAACGA CAGGTGAA
5075

2057
ACCUCACC A UACGGCAC
2053
GTGCCGTA GGCTAGCTACAACGA GGTGAGGT
5076

2059
CUCACCAU A CGGCACUC
2054
GAGTGCCG GGCTAGCTACAACGA ATGGTGAG
5077

2064
CAUACGGC A CUCAGGCA
2055
TCCCTGAG GGCTAGCTACAACGA GCCGTATG
5078

2077
GGCAAGCU A UUCUGUGU
2056
ACACAGAA GGCTAGCTACAACGA AGCTTGCC
5079

2098
GUGAGUUG A UGAAUCUA
2057
TAGATTCA GGCTAGCTACAACGA CAACTCAC
5080

2102
GUUGAUGA A UCUAGCCA
2058
TGGCTAGA GGCTAGCTACAACGA TCATCAAC
5081

2110
AUCUAGCC A CCUGGGUG
2059
CACCCAGG GGCTAGCTACAACGA GGCTAGAT
5082

2126
GGGAAGUA A UUUGGAAG
2060
CTTCCAAA GGCTAGCTACAACGA TACTTCCC
5083

2135
UUUGGAAG A UCCAGCAU
2061
ATGCTGGA GGCTAGCTACAACGA CTTCCAAA
5084

2142
GAUCCAGC A UCCAGGGA
2062
TCCCTGGA GGCTAGCTACAACGA GCTGGATC
5085

2151
UCCAGGGA A UUAGUAGU
2063
ACTACTAA GGCTAGCTACAACGA TCCCTGGA
5086

2165
AGUCAGCU A UGUCAACG
2064
CGTTGACA GGCTAGCTACAACGA AGCTGACT
5087

2171
CUAUGUCA A CGUUAAUA
2065
TATTAACG GGCTAGCTACAACGA TGACATAG
5088

2177
CAACGUUA A UAUGGGCC
2066
GGCCCATA GGCTAGCTACAACGA TAACGTTG
5089

2179
ACGUUAAU A UGGGCCUA
2067
TAGGCCCA GGCTAGCTACAACGA ATTAACGT
5090

2191
GCCUAAAA A UCAGACAA
2068
TTGTCTGA GGCTAGCTACAACGA TTTTAGGC
5091

2196
AAAAUCAG A CAACUAUU
2069
AATAGTTG GGCTAGCTACAACGA CTGATTTT
5092

2199
AUCAGACA A CUAUUGUG
2070
CACAATAG GGCTAGCTACAACGA TGTCTGAT
5093

2202
AGACAACU A UUGUGGUU
2071
AACCACAA GGCTAGCTACAACGA AGTTGTCT
5094

2213
GUGGUUUC A CAUUUCCU
2072
AGGAAATG GGCTAGCTACAACGA GAAACCAC
5095

2215
GGUUUCAC A UUUCCUGU
2073
ACAGGAAA GGCTAGCTACAACGA GTGAAACC
5096

2227
CCUGUCUU A CUUUUGGG
2074
CCCAAAAG GGCTAGCTACAACGA AAGACAGG
5097

2242
GGCGAGAA A CUGUUCUU
2075
AAGAACAG GGCTAGCTACAACGA TTCTCGCC
5098

2253
GUUCUUGA A UAUUUGGU
2076
ACCAAATA GGCTAGCTACAACGA TCAAGAAC
5099

2255
UCUUGAAU A UUUGGUGU
2077
ACACCAAA GGCTAGCTACAACGA ATTCAAGA
5100

2278
GAGUGUGG A UUCGCACU
2078
AGTGCGAA GGCTAGCTACAACGA CCACACTC
5101

2284
GGAUUCGC A CUCCUCCU
2079
AGGAGGAG GGCTAGCTACAACGA GCGAATCC
5102

2295
CCUCCUGC A UAUAGACC
2080
GGTCTATA GGCTAGCTACAACGA GCAGGAGG
5103

2297
UCCUGCAU A UAGACCAC
2081
GTGGTCTA GGCTAGCTACAACGA ATGCAGGA
5104

2301
GCAUAUAG A CCACCAAA
2082
TTTGGTGG GGCTAGCTACAACGA CTATATGC
5105

2304
UAUAGACC A CCAAAUGC
2083
GCATTTGG GGCTAGCTACAACGA GGTCTATA
5106

2309
ACCACCAA A UGCCCCUA
2084
TAGGGGCA GGCTAGCTACAACGA TTGGTGGT
5107

2317
AUGCCCCU A UCUUAUCA
2085
TGATAAGA GGCTAGCTACAACGA AGGGGCAT
5108

2322
CCUAUCUU A UCAACACU
2086
AGTGTTGA GGCTAGCTACAACGA AAGATAGG
5109

2326
UCUUAUCA A CACUUCCG
2087
CGGAAGTG GGCTAGCTACAACGA TGATAAGA
5110

2328
UUAUCAAC A CUUCCGGA
2088
TCCGGAAG GGCTAGCTACAACGA GTTGATAA
5111

2338
UUCCGGAA A CUACUGUU
2089
AACAGTAG GGCTAGCTACAACGA TTCCGGAA
5112

2341
CGGAAACU A CUGUUGUU
2090
AACAACAG GGCTAGCTACAACGA AGTTTCCG
5113

2352
GUUGUUAG A CGAAGAGG
2091
CCTCTTCG GGCTAGCTACAACGA CTAACAAC
5114

2380
GAAGAAGA A CUCCCUCG
2092
CCAGGGAG GGCTAGCTACAACGA TCTTCTTC
5115

2397
CCUCCCAG A CGAAGGUC
2093
GACCTTCG GGCTAGCTACAACGA CTGCGAGG
5116

2409
AGGUCUCA A UCGCCGCG
2094
CGCGGCGA GGCTAGCTACAACGA TGAGACCT
5117

2427
CGCAGAAG A UCUCAAUC
2095
GATTGAGA GGCTAGCTACAACGA CTTCTGCG
5118

2433
AGAUCUCA A UCUCGGGA
2096
TCCCGAGA GGCTAGCTACAACGA TGAGATCT
5119

2442
UCUCGGGA A UCUCAAUG
2097
CATTGAGA GGCTAGCTACAACGA TCCCGAGA
5120

2448
GAAUCUCA A UGUUAGUA
2098
TACTAACA GGCTAGCTACAACGA TGAGATTC
5121

2456
AUGUUAGU A UUCCUUGG
2099
CCAAGGAA GGCTAGCTACAACGA ACTAACAT
5122

2465
UUCCUUGG A CACAUAAG
2100
CTTATGTG GGCTAGCTACAACGA CCAAGGAA
5123

2467
CCUUGGAC A CAUAAGGU
2101
ACCTTATG GGCTAGCTACAACGA GTCCAAGG
5124

2469
UUGGACAC A UAAGGUGG
2102
CCACCTTA GGCTAGCTACAACGA GTGTCCAA
5125

2481
GGUGGGAA A CUUUACGG
2103
CCGTAAAG GGCTAGCTACAACGA TTCCCACC
5126

2486
GAAACUUU A CGGGGCUU
2104
AAGCCCCG GGCTAGCTACAACGA AAAGTTTC
5127

2496
GGGGCUUU A UUCUUCUA
2105
TAGAAGAA GGCTAGCTACAACGA AAAGCCCC
5128

2504
AUUCUUCU A CGGUACCU
2106
AGGTACCG GGCTAGCTACAACGA AGAAGAAT
5129

2509
UCUACGGU A CCUUGCUU
2107
AAGCAAGG GGCTAGCTACAACGA ACCGTAGA
5130

2520
UUGCUUUA A UCCUAAAU
2108
ATTTAGGA GGCTAGCTACAACGA TAAAGCAA
5131

2527
AAUCCUAA A UGGCAAAC
2109
GTTTGCCA GGCTAGCTACAACGA TTAGGATT
5132

2534
AAUGGCAA A CUCCUUCU
2110
AGAAGGAG GGCTAGCTACAACGA TTGCCATT
5133

2550
UUUUCCUG A CAUUCAUU
2111
AATGAATG GGCTAGCTACAACGA CAGGAAAA
5134

2552
UUCCUGAC A UUCAUUUG
2112
CAAATGAA GGCTAGCTACAACGA GTCAGGAA
5135

2556
UGACAUUC A UUUGCAGG
2113
CCTGCAAA GGCTAGCTACAACGA GAATGTCA
5136

2568
GCAGGAGG A CAUUGUUG
2114
CAACAATG GGCTAGCTACAACGA CCTCCTGC
5137

2570
AGGAGGAC A UUGUUGAU
2115
ATCAACAA GGCTAGCTACAACGA GTCCTCCT
5138

2577
CAUUGUUG A UAGAUGUA
2116
TACATCTA GGCTAGCTACAACGA CAACAATG
5139

2581
GUUGAUAG A UGUAAGCA
2117
TGCTTACA GGCTAGCTACAACGA CTATCAAC
5140

2590
UGUAAGCA A UUUGUGGG
2118
CCCACAAA GGCTAGCTACAACGA TGCTTACA
5141

2606
GGCCCCUU A CAGUAAAU
2119
ATTTACTG GGCTAGCTACAACGA AAGGGGCC
5142

2613
UACAGUAA A UGAAAACA
2120
TGTTTTCA GGCTAGCTACAACGA TTACTGTA
5143

2619
AAAUGAAA A CAGGAGAC
2121
GTCTCCTG GGCTAGCTACAACGA TTTCATTT
5144

2626
AACAGGAG A CUUAAAUU
2122
AATTTAAG GGCTAGCTACAACGA CTCCTGTT
5145

2632
AGACUUAA A UUAACUAU
2123
ATAGTTAA GGCTAGCTACAACGA TTAAGTCT
5146

2636
UUAAAUUA A CUAUGCCU
2124
AGGCATAG GGCTAGCTACAACGA TAATTTAA
5147

2639
AAUUAACU A UGCCUGCU
2125
AGCAGGCA GGCTAGCTACAACGA AGTTAATT
5148

2655
UAGGUUUU A UCCCAAUG
2126
CATTGGGA GGCTAGCTACAACGA AAAACCTA
5149

2661
UUAUCCCA A UGUUACUA
2127
TAGTAACA GGCTAGCTACAACGA TGGGATAA
5150

2666
CCAAUGUU A CUAAAUAU
2128
ATATTTAG GGCTAGCTACAACGA AACATTGG
5151

2671
GUUACUAA A UAUUUGCC
2129
GGCAAATA GGCTAGCTACAACGA TTAGTAAC
5152

2673
UACUAAAU A UUUGCCCU
2130
AGGGCAAA GGCTAGCTACAACGA ATTTAGTA
5153

2685
GCCCUUAG A UAAAGGGA
2131
CGGTTTGA GGCTAGCTACAACGA CTAAGGGC
5154

2693
AUAAAGGG A UCAAACCG
2132
CGGTTTGA GGCTAGCTACAACGA CCCTTTAT
5155

2698
GGGAUCAA A CCGUAUUA
2133
TAATACGG GGCTAGCTACAACGA TTGATCCC
5156

2703
CAAACCGU A UUAUCCAG
2134
CTGGATAA GGCTAGCTACAACGA ACGGTTTG
5157

2706
ACCGUAUU A UCCAGAGU
2135
ACTCTGGA GGCTAGCTACAACGA AATACGGT
5158

2715
UCCAGAGU A UGUAGUUA
2136
TAACTACA GGCTAGCTACAACGA ACTCTGGA
5159

2724
UGUAGUUA A UCAUUACU
2137
AGTAATGA GGCTAGCTACAACGA TAACTACA
5160

2727
AGUUAAUC A UUACUUCC
2138
GGAAGTAA GGCTAGCTACAACGA GATTAACT
5161

2730
UAAUCAUU A CUUCCAGA
2139
TCTGGAAG GGCTAGCTACAACGA AATGATTA
5162

2738
ACUUCCAG A CGCGACAU
2140
ATGTCGCG GGCTAGCTACAACGA CTGGAAGT
5163

2743
CAGACGCG A CAUUAUUU
2141
AAATAATG GGCTAGCTACAACGA CGCGTCTG
5164

2745
CACGCGAC A UUAUUUAC
2142
GTAAATAA GGCTAGCTACAACGA GTCGCGTC
5165

2748
GCGACAUU A UUUACACA
2143
TGTGTAAA GGCTAGCTACAACGA AATGTCGC
5166

2752
CAUUAUUU A CACACUCU
2144
AGAGTGTG GGCTAGCTACAACGA AAATAATG
5167

2754
UUAUUUAC A CACUCUUU
2145
AAAGAGTG GGCTAGCTACAACGA GTAAATAA
5168

2756
AUUUACAC A CUCUUUGG
2146
CCAAAGAG GGCTAGCTACAACGA GTGTAAAT
5169

2774
AGGCGGGG A UCUUAUAU
2147
ATATAAGA GGCTAGCTACAACGA CCCCGCCT
5170

2779
GGGAUCUU A UAUAAAAG
2148
CTTTTATA GGCTAGCTACAACGA AAGATCCC
5171

2781
GAUCUUAU A UAAAAGAG
2149
CTCTTTTA GGCTAGCTACAACGA ATAAGATC
5172

2795
CAGAGUCC A CACGUAGC
2150
GCTACGTG GGCTAGCTACAACGA GGACTCTC
5173

2797
CAGUCCAC A CGUAGCGC
2151
GCGCTACG GGCTAGCTACAACGA GTGGACTC
5174

2809
AGCGCCUC A UUUUGCGG
2152
CCGCAAAA GGCTAGCTACAACGA GAGGCGCT
5175

2821
UGCGGGUC A CCAUAUUC
2153
GAATATGG GGCTAGCTACAACGA GACCCGCA
5176

2824
GGGUCACC A UAUUCUUG
2154
CAAGAATA GGCTAGCTACAACGA GGTGACCC
5177

2826
GUCACCAU A UUCUUGGG
2155
CCCAAGAA GGCTAGCTACAACGA ATGGTGAC
5178

2836
UCUUGGGA A CAAGAUCU
2156
AGATCTTG GGCTAGCTACAACGA TCCCAAGA
5179

2841
GGAACAAG A UCUACAGC
2157
GCTGTAGA GGCTAGCTACAACGA CTTGTTCC
5180

2845
CAAGAUCU A CAGCAUGG
2158
CCATGCTG GGCTAGCTACAACGA AGATCTTG
5181

2850
UCUACAGC A UGGGAGGU
2159
ACCTCCCA GGCTAGCTACAACGA GCTGTAGA
5182

2870
UCUUCCAA A CCUCGAAA
2160
TTTCGAGG GGCTAGCTACAACGA TTGGAAGA
5183

2883
GAAAAGGC A UGUGGACA
2161
TGTCCCCA GGCTAGCTACAACGA GCCTTTTC
5184

2889
GCAUGGGG A CAAAUCUU
2162
AAGATTTG GGCTAGCTACAACGA CCCCATGC
5185

2893
GGGGACAA A UCUUUCUG
2163
CAGAAAGA GGCTAGCTACAACGA TTGTCCCC
5186

2908
UGUCCCCA A UCCCCUGG
2164
CCAGGGGA GGCTAGCTACAACGA TGGGGACA
5187

2918
CCCCUGGG A UUCUUCCC
2165
GGGAAGAA GGCTAGCTACAACGA CCCAGGGG
5188

2929
CUUCCCCG A UCAUCAGU
2166
ACTGATGA GGCTAGCTACAACGA CGGGGAAG
5189

2932
CCCCGAUC A UCAGUUGG
2167
CCAACTGA GGCTAGCTACAACGA GATCGGGG
5190

2941
UCAGUUGG A CCCUGCAU
2168
ATGCAGGG GGCTAGCTACAACGA CCAACTGA
5191

2948
GACCCUGC A UUCAAAGC
2169
GCTTTGAA GGCTAGCTACAACGA GCAGGGTC
5192

2959
CAAAGCCA A CUCAGUAA
2170
TTACTGAG GGCTAGCTACAACGA TGGCTTTG
5193

2968
CUCAGUAA A UCCAGAUU
2171
AATCTGGA GGCTAGCTACAACGA TTACTGAG
5194

2974
AAAUCCAG A UUGGGACC
2172
GGTCCCAA GGCTAGCTACAACGA CTGGATTT
5195

2980
AGAUUGGG A CCUCAACC
2173
GGTTGAGG GGCTAGCTACAACGA CCCAATCT
5196

2986
GGACCUCA A CCCGCACA
2174
TGTGCGGG GGCTAGCTACAACGA TGAGGTCC
5197

2998
GCACAAGG A CAACUGGC
2175
GCCAGTTG GGCTAGCTACAACGA CCTTGTGC
5198

3001
CAAGGACA A CUGGCCGG
2176
CCGGCCAG GGCTAGCTACAACGA TGTCCTTG
5199

3010
CUGGCCGG A CGCCAACA
2177
TGTTGGCG GGCTAGCTACAACGA CCGGCCAG
5200

3016
GGACGCCA A CAAGGUGG
2178
CCACCTTG GGCTAGCTACAACGA TGGCGTCC
5201

3035
GUGGGAGC A UUCCGGCC
2179
GGCCCGAA GGCTAGCTACAACGA GCTCCCAC
5202

3051
CAUGGUUC A CCCCUCCC
2180
GGGAGGGG GGCTAGCTACAACGA GAACCCTG
5203

3061
CCCUCCCC A UGGGGGAC
2181
GTCCCCCA GGCTAGCTACAACGA GGGGAGGG
5204

3068
CAUGGGGG A CUGUUGGG
2182
CCCAACAG GGCTAGCTACAACGA CCCCCATG
5205

3088
GAGCCCUC A CGCUCAGG
2183
CCTGAGCG GGCTAGCTACAACGA GAGGGCTC
5206

3101
CAGGGCCU A CUCACAAC
2184
GTTGTGAG GGCTAGCTACAACGA AGGCCCTG
5207

3105
GCCUACUC A CAACUGUG
2185
CACAGTTG GGCTAGCTACAACGA GAGTAGGC
5208

3108
UACUCACA A CUGUGCCA
2186
TGGCACAG GGCTAGCTACAACGA TGTGAGTA
5209

3138
CUGCCUCC A CCAAUCGG
2187
CCGATTGG GGCTAGCTACAACGA GGAGGCAG
5210

3142
CUCCACCA A UCGGCAGU
2188
ACTGCCGA GGCTAGCTACAACGA TGGTGGAG
5211

3165
GGCAGCCU A CUCCCUUA
2189
TAAGGGAG GGCTAGCTACAACGA AGGCTGCC
5212

3173
ACUCCCUU A UCUCCACC
2190
GGTGGAGA GGCTAGCTACAACGA AAGGGAGT
5213

3179
UUAUCUCC A CCUCUAAG
2191
CTTAGAGG GGCTAGCTACAACGA GGAGATAA
5214

3190
UCUAAGGG A CACUCAUC
2192
GATGAGTG GGCTAGCTACAACGA CCCTTAGA
5215

3192
UAAGGGAC A CUCAUCCU
2193
AGGATGAG GGCTAGCTACAACGA GTCCCTTA
5216

3196
GGACACUC A UCCUCAGG
2194
CCTGAGGA GGCTAGCTACAACGA GAGTGTCC
5217

3207
CUCAGGCC A UGCAGUGG
2195
CCACTGCA GGCTAGCTACAACGA GGCCTGAG
5218

Input Sequence = AF100308.

Cut Site = YG/M or UG/U.

Stem Length = 8.

Core Sequence = GGCTAGCTACAACGA

AF100308 (Hepatitis B virus strain 2-18, 3215 bp)

[0253]

10

TABLE X

HUMAN HBV AMBERZYME AND SUBSTRATE SEQUENCE

Pos
Substrate
Seq ID
Amberzyme
Seq ID

61
ACUUUCCU G CUGGUGGC
1448
GCCACCAG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AGGAAAGU
5219

87
GGAACAGU G AGCCCUGC
1449
GCAGGGCU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG ACUGUUCC
5220

94
UGAGCCCU G CUCAGAAU
1450
AUUCUGAG GGAGGAAACUCC CU UCAAGGACAUCCUCCGGG AGGGCUCA
5221

112
CUGUCUCU G CCAUAUCG
1451
CGAUAUGG GGAGGAAACUCC CU UCAAGGACAUCGUCCCGG AGAGACAG
5222

132
AUCUUAUC G AACACUCG
1452
CCACUCUU GCACGAAACUCC CU UCAACGACAUCGUCCGGC GAUAAGAU
5223

153
CCUGUACC G AACAUGCA
1453
UCCAUGUU GCAGGAAACUCC CU UCAAGGACAUCGUCCGGG GCUACAGG
5224

159
ACAACAUC G CAUCAGGA
1454
UCCUGAUG GGACGAAACUCC CU UCAAGCACAUCGUCCGGG GAUGUUCU
5225

192
GGACCCCU G CUCCUCUU
1455
AACACCAG GCAGCAAACUCC CU UCAAGGACAUCCUCCCCG AGCCGUCC
5226

222
UUCUUCUU G ACAAAAAU
1456
AUUUUUGU GCACGAAACUCC CU UCAACCACAUCCUCCCCG AACAAGAA
5227

315
CAAAAUUC G CAGUCCCA
1457
UGCGACUC GGAGCAAACUCC CU UCAACGACAUCGUCCGGC CAAUUUUC
5228

374
UCCUUAUC G CUGGAUGU
1458
ACAUCCAG GGAGGAAACUCC CU UCAAGGACAUCCUCCCCG CAUAACCA
5229

387
AUGUGUCU G CGCCCTUU
1459
AAACCCCG GGAGGAAACUCC CU UCAAGGACAUCGUCCCGC AGACACAU
5230

410
CUUCCUCU G CAUCCUCC
1460
GCAGGAUG GGAGGAAACUCC CU UCAACGACAUCGUCCCCG AGACGAAG
5231

417
UGCAUCCU G CUGCUAUG
1461
CAUACCAC GCACCAAACUCC CU UCAAGGACAUCGUCCGGC AGGAUGCA
5232

420
AUCCUGCU G CUAUCCCU
1462
ACCCAUAC GGACCAAACUCC CU UCAAGCACAUCGUCCGCC AGCAGGAU
5233

425
GCUGCUAU G CCUCAUCU
1463
AGAUCAGC GGAGCAAACUCC CU UCAACGACAUCGUCCGGC AUAGCAGC
5234

468
GGUAUGUU G CCCGUUUG
1464
CAAACCCG GGACGAAACUCC CU UCAAGGACAUCGUCCGCG AACAUACC
5235

518
CGGACCAU G CAAAACCU
1465
AGCUUUUC CGAGGAAACUCC CU UCAAGCACAUCGUCCGGC AUGCUCCC
5236

527
CAAAACCU G CACAACUC
1466
CACUUGUC GCAGCAAACUCC CU UCAACGACAUCGUCCCCC AGGUUUUC
5237

538
CAACUCCU G CUCAAGGA
1467
UCCUUCAG GGACGAAACUCC CU UCAAGGACAUCGUCCGCC ACGACUUG
5238

569
CUCAUGUU G CUCUACAA
1468
UUGUACAC GGACGAAACUCC CU UCAACGACAUCCUCCCGG AACAUCAC
5239

596
CCCAAACU G CACCUGUA
1469
UACACCUC GGAGGAAACUCC CU UCAACGACAUCGUCCGCC AGUUUCCG
5240

631
GGCCUUUC G CAAAAUAC
1470
CUAUUUUG GGAGGAAACUCC CU UCAAGCACAUCGUCCGCG GAAACCCC
5241

687
UUACUAGU G CCAUUUCU
1471
ACAAAUCC CGACCAAACUCC CU UCAAGCACAUCCUCCCCG ACUACUAA
5242

747
AUAUGCAU G AUCUCGUU
1472
AACCACAU CGAGCAAACUCC CU UCAACCACAUCCUCCCCC AUCCAUAU
5243

783
AACAUCUU G ACUCCCUU
1473
AACCCACU CCAGCAAACUCC CU UCAACCACAUCCUCCCCC AACAUCUU
5244

795
CCCUUUAU G CCCCUCUU
1474
AACACCCC GCACCAAACUCC CU UCAACCACAUCCUCCCCC AUAAACCC
5245

798
UUUAUGCC G CUCUUACC
1475
GCUAACAC GCACGAAACUCC CU UCAACGACAUCCUCCCCC CCCAUAAA
5246

911
GCCACAUU G CCACACCA
1476
UCCUGUGC CCACGAAACUCC CU UCAACCACAUCCUCCCGC AAUCUCCC
5247

978
GCCCUAUU G AUUCCAAA
1477
UUUCCAAU CCACCAAACUCC CU UCAACCACAUCGUCCCCC AAUACGCC
5248

997
AUCUCAAC G AAUUCUCC
1478
CCACAAUU CCACCAAACUCC CU UCAAGCACAUCCUCCCCC CUUCACAU
5249

1020
UCCCCUUU G CCCCCCCU
1479
ACCCCCCC CCACCAAACUCC CU UCAAGCACAUCCUCCGCG AAACCCCA
5250

1023
CCUUUCCC G CCCCUUUC
1480
CAAACGCC CCACCAAACUCC CU UCAACCACAUCCUCCGCC GCCAAACC
5251

1034
CCUUUCAC G CAAUGUGG
1481
CCACAUUG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGC CUCAAAGG
5252

1050
GAUAUUCU G CUUUAAUG
1482
CAUUAAAC CGACGAAACUCC CU UCAACCACAUCGUCCGGC AGAAUAUC
5253

1058
GCUUUAAU G CCTUUAUA
1483
UAUAAAGG GGAGGAAACUCC CU UCAAGCACAUCGUCCGGG AUUAAAGC
5254

1068
CUUUAUAU G CAUGCAUA
1484
UAUGCAUC GGAGCAAACUCC CU UCAAGCACAUCCUCCCGG AUAUAAAG
5255

1072
AUAUCCAU G CAUACAAG
1485
CUUGUAUG GGAGCAAACUCC CU UCAAGGACAUCCUCCGGC AUGCAUAU
5256

1103
ACUUUCUC G CCAACUUA
1485
UAAGUUGC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG GAGAAAGU
5257

1139
CACUAUGU G AACCUUUA
1487
UAAAGGUU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG ACAUACUG
5258

1155
ACCCCGUU G CUCGGCAA
1488
UUGCCGAC CCAGGAAACUCC CU UCAAGCACAUCGUCCGGG AACGGGGU
5259

1177
UCGUCUAU G CCAAGUGU
1489
ACACUUGG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AUAGACCA
5260

1188
AAGUGUUU G CUCACCCA
1490
UGCGUCAG GGAGGAAACUCC CU UCAACGACAUCGUCCGGG AAACACUU
5261

1191
UCUUUGCU G ACCCAACC
1491
CGUUGCGU GGAGCAAACUCC CU UCAAGCACAUCGUCCCGC AGCAAACA
5262

1194
UUGCUGAC G CAACCCCC
1492
GGCGCUUG GGAGCAAACUCC CU UCAAGCACAUCCUCCGCG CUCAGCAA
5263

1234
CCAUCACC G CAUGCGUG
1493
CACGCAUC CCACCAAACUCC CU UCAACCACAUCGUCCGGC CCUGAUCC
5264

1238
CACCGCAU G CCUCGAAC
1494
GUUCCACC GGAGGAAACUCC CU UCAAGCACAUCGUCCGCG AUCCGCUC
5265

1262
UCUCCUCU G CCCAUCCA
1495
UCCAUCGC CCACGAAACUCC CU UCAACGACAUCCUCCGCG AGAGGACA
5266

1265
CCUCUGCC G AUCCAUAC
1496
GUAUCGAU CCAGGAAACUCC CU UCAAGCACAUCGUCCGGG GCCAGACG
5267

1275
UCCAUACC G CGGAACUC
1497
GACUUCCG GGAGCAAACUCC CU UCAACGACAUCGUCCCGG GGUAUGGA
5268

1290
UCCUACCC G CUUGUUUU
1498
AAAACAAG CGAGCAAACUCC CU UCAAGGACAUCGUCCGGG GGCUAGCA
5269

1299
CUUCUEUU G CUCCCAGC
1499
GCUGCGAG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGC AAAACAAG
5270

1303
UUUUGCUC G CAGCAGCU
1500
ACCUCCUG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGC GACCAAAA
5271

1335
UCGGGACU G ACAAUUCU
1501
AGAAUUCU CGAGCAAACUCC CU UCAAGGACAUCGUCCGGG AGUCCCCA
5272

1349
UCUCUCGU G CUCUCCCG
1502
CGGCACAG GCACGAAACUCC CU UCAAGGACAUCGUCCGGG ACGACAGA
5273

1357
GCUCUCCC G CAAAUAUA
1503
UAUAUUUC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG GGCAGAGC
5274

1382
CCAUGCCU G CUAGGCUG
1504
CAGCCUAG GGAGGAAACUCC CU UCAAGGACAUCCUCCGGG ACCCAUCC
5275

1392
UAGCCUCU G CUGCCAAC
1505
GUUGGCAC CCACCAAACUCC CU UCAACCACAUCCUCCCCC ACACCCUA
5276

1395
CCUCUCCU G CCAACUGG
1506
CCAGUUGC CCACCAAACUCC CU UCAACCACAUCGUCCCCG ACCACAGC
5277

1411
CAUCCUAC G CGCGACCU
1507
ACCUCCCC CCACCAAACUCC CU UCAACCACAUCGUCCGGG GUAGGAUC
5278

1442
CCCUCGCC G CUGAAUCC
1508
CGAUUCAC CCACGAAACUCC CU UCAACGACAUCGUCCGGG GCCGACGC
5279

1445
UCCCCCCU G AAUCCCCC
1509
CCCGCAUU CGAGCAAACUCC CU UCAACCACAUCCUCCGCC ACCCCCGA
5280

1452
UGAAUCCC G CCGACGAC
1510
GUCGUCCC CGAGGAAACUCC CU UCAAGCACAUCCUCCCCC CCCAUUCA
5281

1458
CCCCGCAC G ACCCCUCC
1511
CGAGGGCU CCACCAAACUCC CU UCAACCACAUCCUCCCCC CUCCGCCC
5282

1474
CCCCCCCC G CUUCGGCC
1512
GCCCCAAC CGACCAAACUCC CU UCAACCACAUCCUCCCCC CGCCCCGC
5283

1489
CCUCUACC G CCCGCUUC
1513
GAAGCCCC CGAGCAAACUCC CU UCAACCACAUCGUCCCCG GGUACAGC
5284

1493
UACCCCCC G CUUCUCCG
1514
CGGACAAG CGAGCAAACUCC CU UCAAGGACAUCCUCCCGG GGCCGGUA
5285

1501
GCUUCUCC G CCUAUUGU
1515
ACAAUACG GCAGCAAACUCC CU UCAACGACAUCCUCCCGC CGAGAACC
5286

1513
AUUCUACC G ACCCUCCA
1516
UCGACGCU GGACGAAACUCC CU UCAACGACAUCCUCCGGG GGUACAAU
5287

1528
CACCCGCC G CACCUCUC
1517
GACACCUC GCACGAAACUCC CU UCAACGACAUCCUCCCCC CCCCCGUG
5288

1542
CUCUUUAC G CGGACUCC
1518
GGAGUCCG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG GUAAAGAG
5289

1559
CCGUCUGU G CCUUCUCA
1519
UGAGAAGG GGAGGAAACUCC CU UCAAGGACAUCCUCCGGG ACAGACGG
5290

1571
UCUCAUCU G CCGGACCG
1520
CGGUCCGG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AGAUGAGA
5291

1583
GACCGUGU G CACUUCGC
1521
GCGAAGUG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG ACACGGUC
5292

1590
UCCACUUC G CUUCACCU
1522
AGGUGAAG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG GAAGUGCA
5293

1601
UCACCUCU G CACGUCGC
1523
GCGACGUG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AGAGGUGA
5294

1608
UGCACGUC G CAUGGAGA
1524
UCUCCAUG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG GACGUGCA
5295

1624
ACCACCGU G AACGCCCA
1525
UGGGCGUU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG ACGGUGGU
5296

1628
CCGUGAAC G CCCACAGG
1526
CCUGUGGG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG GUUCACGG
5297

1642
AGGAACCU G CCCAAGGU
1527
ACCUUGGG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AGGUUCCU
5298

1654
AAGGUCUU G CAUAAGAG
1528
CUCUUAUG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AAGACCUU
5299

1690
AUGUCAAC G ACCGACCU
1529
AGGUCGGU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG GUUGACAU
5300

1694
CAACGACC G ACCUUGAG
1530
CUCAAGGU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG GGUCGUUG
5301

1700
CCGACCUU G AGGCAUAC
1531
GUAUGCCU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AAGGUCGG
5302

1730
UGUUUAAU G AGUGGGAG
1532
CUCCCACU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AUUAAACA
5303

1818
AGCACCAU G CAACUUUU
1533
AAAAGUUG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AUGGUGCU
5304

1835
UCACCUCU G CCUAAUCA
1534
UGAUUAGG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AGAGGUGA
5305

1883
CAAGCUGU G CCUUGGGU
1535
ACCCAAGG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG ACAGCUUG
5306

1912
UGGACAUU G ACCCGUAU
1536
AUACGGGU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AAUGUCCA
5307

1959
UCUTUUUU G CCUUCUGA
1537
UCAGAAGG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AAAAAAGA
5308

1966
UGCCUUCU G ACUUCUUU
1538
AAAGAAGU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AGAAGGCA
5309

1985
UUCUAUUC G AGAUCUCC
1539
GGAGAUCU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG GAAUAGAA
5310

1996
AUCUCCUC G ACACCGCC
1540
GGCGGUGU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG GAGGAGAU
5311

2002
UCCACACC G CCUCUGCU
1541
AGCAGAGG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG GGUGUCCA
5312

2008
CCGCCUCU G CUCUCUAU
1542
AUACAGAG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AGACGCGC
5313

2092
GUUGGGGU G AGUUGAUG
1543
CAUCAACU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG ACCCCAAC
5314

2097
GGUGAGUU G AUGAAUCU
1544
AGAUUCAU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AACUCACC
5315

2100
CAGUUGAU G AAUCUAGC
1545
GCUAGAUU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AUCAACUC
5316

2237
UUUUGGGC G AGAAACUC
1546
CAGUUUCU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG GCCCAAAA
5317

2251
CUGUUCUU G AAUAUUUG
1547
CAAAUAUU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AAGAACAG
5318

2282
GUGGAUUC G CACUCCUC
1548
CACCACUC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG GAAUCCAC
5319

2293
CUCCUCCU G CAUAUAGA
1549
UCUAUAUC GCAGGAAACUCC CU UCAAGCACAUCGUCCGCG ACCAGGAC
5320

2311
CACCAAAU G CCCCUAUC
1550
CAUAGGGG GGAGGAAACUCC CU UCAAGCACAUCGUCCGGG AUUUGGUG
5321

2354
UGUUAGAC G AAGAGGCA
1551
UGCCUCUU GCAGGAAACUCC CU UCAAGGACAUCCUCCGGG GUCUAACA
5322

2388
ACUCCCUC G CCUCGCAG
1552
CUCCCACC GCACGAAACUCC CU UCAAGGACAUCGUCCCGC CAGCGACU
5323

2393
CUCCCCUC G CAGACGAA
1553
UUCGUCUG GCACGAAACUCC CU UCAAGGACAUCCUCCGGC CACCCGAG
5324

2399
UCGCACAC G AAGCUCUC
1554
GACACCUU GGAGGAAACUCC CU UCAAGGACAUCGUCCCGG CUCUGCGA
5325

2412
UCUCAAUC G CCCCCUCC
1555
CGACGCCC CCACGAAACUCC CU UCAAGGACAUCGUCCGGG CAUUCACA
5326

2415
CAAUCGCC G CGUCGCAG
1556
CUGCGACG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG GGCGAUUG
5327

2420
GCCGCGUC G CAGAAGAU
1557
AUCUUCUG CGAGGAAACUCC CU UCAAGGACAUCCUCCGGG GACCCCGC
5328

2514
CGUACCUU G CUUUAAUC
1558
GAUUAAAG GGACGAAACUCC CU UCAACCACAUCGUCCGCG AAGCUACC
5329

2549
CUUUUCCU G ACAUUCAU
1559
AUGAAUCU GGAGGAAACUCC CU UCAAGCACAUCGUCCGGG AGGAAAAC
5330

2560
AUUCAUUU G CAGGAGGA
1560
UCCUCCUG GGAGGAAACUCC CU UCAAGCACAUCCUCCGCG AAAUGAAU
5331

2576
ACAUUGUU G AUACAUGU
1561
ACAUCUAU GCAGGAAACUCC CU UCAAGGACAUCGUCCGGG AACAAUGU
5332

2615
CAGUAAAU G AAAACAGC
1562
CCUGUUUU GCAGGAAACUCC CU UCAAGGACAUCGUCCGGG AUUUACUG
5333

2641
UUAACUAU G CCUCCUAC
1563
CUAGCAGG GCAGGAAACUCC CU UCAAGGACAUCGUCCGGG AUACUUAA
5334

2645
CUAUGCCU G CUAGCUUU
1564
AAACCUAG GCAGCAAACUCC CU UCAAGCACAUCCUCCCGC AGCCAUAC
5335

2677
AAAUAUUU G CCCUUACA
1565
UCUAAGCG GCACGAAACUCC CU UCAAGGACAUCCUCCGGC AAAUAUUU
5336

2740
CUCCAGAC G CGACAUUA
1566
UAAUGUCG GCACCAAACUCC CU UCAAGGACAUCCUCCGCC CUCUCCAA
5337

2742
CCACACGC G ACAUUAUU
1567
AAUAAUCU GGACGAAACUCC CU UCAACGACAUCGUCCCGC GCGUCUGG
5338

2804
CACGUAGC G CCUCAUUU
1568
AAAUGAGG CGACGAAACUCC CU UCAAGGACAUCGUCCCGG GCUACGUG
5339

2814
CUCAUUUU G CCGCUCAC
1569
GUGACCCG CGACGAAACUCC CU UCAAGGACAUCGUCCCGG AAAAUGAG
5340

2875
CAAACCUC G AAAACGCA
1570
UGCCUUUU GCACCAAACUCC CU UCAACGACAUCGUCCGGC CAGCUUUC
5341

2928
UCUUCCCC G AUCAUCAG
1571
CUGAUCAU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG GGGGAAGA
5342

2946
UCGACCCU G CAUUCAAA
1572
UUUCAAUC GGAGGAAACUCC CU UCAACGACAUCGUCCGCG ACCGUCCA
5343

2990
CUCAACCC G CACAACGA
1573
UCCUUCUC CGAGGAAACUCC CU UCAAGCACAUCCUCCCCG GCCUUGAC
5344

3012
GGCCCGAC G CCAACAAC
1574
CUUCUUCC CCACCAAACUCC CU UCAAGCACAUCCUCCGCC CUCCCCCC
5345

3090
CCCCUCAC G CUCAGCGC
1575
CCCCUCAC CCACCAAACUCC CU UCAACCACAUCCUCCCCC CUCACCCC
5346

3113
ACAACUGU G CCACCAGC
1576
CCUCCUCC CCACCAAACUCC CU UCAAGCACAUCCUCCCCC ACACUUGU
5347

3132
CUCCUCCU G CCUCCACC
1577
GGUGGAGG GGACCAAACUCC CU UCAAGGACAUCGUCCGCG ACCACCAC
5348

51
ACGCCCCU G UACUUUCC
1578
CGAAAGUA GCACCAAACUCC CU UCAAGCACAUCCUCCGCG ACCCCCCU
5349

106
AGAAUACU G UCUCUCCC
1579
GGCACACA GCACCAAACUCC CU UCAAGCACAUCCUCCCCC ACUAUUCU
5350

148
CGCACCCU G UACCCAAC
1580
CUUCCCUA GCACGAAACUCC CU UCAACCACAUCCUCCGCG ACGCUCCC
5351

198
CUGCUCCU G UUACAGGC
1581
CCCUCUAA CCACCAAACUCC CU UCAAGCACAUCCUCCCCG ACGAGCAG
5352

219
UUUUUCUU G UUCACAAA
1582
UUUCUCAA CCACCAAACUCC CU UCAAGGACAUCCUCCCCG AACAAAAA
5353

297
ACACCCCU G UCUCUUCG
1583
CCAAGACA GCACGAAACUCC CU UCAACCACAUCCUCCCCC ACGCCUGU
5354

299
ACCCCUCU G UCUUGGCC
1584
GCCCAAGA CCAGGAAACUCC CU UCAACCACAUCCUCCCCC ACACGGGU
5355

347
ACCAACCU G UUGUCCUC
1585
GACCACAA CCACGAAACUCC CU UCAACGACAUCCUCCCGC ACGUUCCU
5356

350
AACCUCUU G UCCUCCAA
1586
UUGCACCA CGACCAAACUCC CU UCAACGACAUCCUCCCGC AACACCUU
5357

362
UCCAAUUU G UCCUGCUU
1587
AACCACGA CGAGGAAACUCC CU UCAACCACAUCCUCCCGG AAAUUCCA
5358

381
CGCUGCAU G UGUCUCCC
1588
CCCACACA GGAGCAAACUCC CU UCAAGGACAUCGUCCCGC AUCCAGCG
5359

383
CUCCAUGU G UCUGCCGC
1589
GCCCCACA CCAGCAAACUCC CU UCAACCACAUCCUCCCCC ACAUCCAG
5360

438
AUCUUCUU G UUCGUUCU
1590
AGAACCAA GGACCAAACUCC CU UCAACGACAUCGUCCCGC AACAAGAU
5361

465
CAACCUAU G UUCCCCCU
1591
ACCGCCAA CGAGGAAACUCC CU UCAAGCACAUCCUCCGGG AUACCUUG
5362

476
GCCCGUUU G UCCUCUAA
1592
UUAGAGGA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AAACGGGC
5363

555
ACCUCUAU G UUUCCCUC
1593
GAGGGAAA GGACGAAACUCC CU UCAAGGACAUCGUCCGGG AUAGAGGU
5364

566
UCCCUCAU G UUGCUGUA
1594
UACAGCAA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AUGAGCGA
5365

572
AUGUUGCU G UACAAAAC
1595
GUUUUGUA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AGCAACAU
5366

602
CUGCACCU G UAUUCCCA
1596
UCGCAAUA GCAGGAAACUCC CU UCAAGGACAUCGUCCGGG AGGUCCAG
5367

694
UCCCAUUU G UUCAGUGG
1597
CCACUGAA GCAGGAAACUCC CU UCAAGGACAUCGUCCCCG AAAUGCCA
5368

724
CCCCCACU G UCUGGCUU
1598
AAGCCAGA GCACGAAACUCC CU UCAAGGACAUCGUCCGCG ACUGGCGC
5369

750
UGCAUGAU G UGGUUUUG
1599
CAAAACCA GCACGAAACUCC CU UCAAGGACAUCGUCCGGG AUCAUCCA
5370

771
CCAAGUCU G UACAACAU
1600
AUGUUGUA GCAGCAAACUCC CU UCAACGACAUCGUCCCGC ACACUUGG
5371

801
AUGCCGCU G UUACCAAU
1601
AUUCGUAA GCACGAAACUCC CU UCAAGGACAUCGUCCGGG AGCGGCAU
5372

818
UUUCUUUU G UCUUUGGG
1602
CCCAAACA GCACCAAACUCC CU UCAACGACAUCGUCCGCG AAAAGAAA
5373

888
UGCGAUAU G UAAUUCGG
1603
CCCAAUUA CGACGAAACUCC CU UCAAGCACAUCGUCCGGG AUAUCCCA
5374

927
AACAUAUU G UACAAAAA
1604
UUUUUGUA GCAGGAAACUCC CU UCAAGCACAUCGUCCGGG AAUAUGUU
5375

944
AUCAAAAU G UCUUUUAC
1605
CUAAAACA GGAGGAAACUCC CU UCAAGCACAUCGUCCGGG AUUUUGAU
5376

946
CAAAAUGU G UTUUAGGA
1606
UCCUAAAA CCACGAAACUCC CU UCAAGGACAUCGUCCCGG ACAUUUUG
5377

963
AACUUCCU G UAAACAGC
1607
CCUCUUUA CGAGGAAACUCC CU UCAAGCACAUCCUCCCGG AGGAAGUU
5378

991
GAAAGUAU G UCAACGAA
1608
UUCGUUGA CCACCAAACUCC CU UCAAGCACAUCGUCCGGC AUACUUUC
5379

1002
AACCAAUU G UGGGUCUU
1609
AACACCCA GGAGGAAACUCC CU UCAAGCACAUCCUCCCGC AAUUCCUU
5380

1039
CACCCAAU G UGGAUAUU
1610
AAUAUCCA GGAGCAAACUCC CU UCAAGCACAUCCUCCCGC AUUGCCUG
5381

1137
AACAGUAU G UCAACCUU
1611
AACGUUCA CGAGCAAACUCC CU UCAAGCACAUCGUCCGGC AUACUCUU
5382

1184
UCCCAAGU G UUUCCUGA
1612
UCAGCAAA CGAGCAAACUCC CU UCAAGCACAUCCUCCCGC ACUUGCCA
5383

1251
GAACCUUU G UGUCUCCU
1613
ACCACACA CGAGCAAACUCC CU UCAACCACAUCCUCCCGG AAACCUUC
5384

1253
ACCUUUGU G UCUCCUCU
1614
AGACCAGA CCAGCAAACUCC CU UCAACCACAUCCUCCCCC ACAAACGU
5385

1294
AGCCCCUU G UUUUCCUC
1615
CACCAAAA CGAGCAAACUCC CU UCAAGCACAUCCUCCGCC AACCGCCU
5386

1344
ACAAUUCU G UCCUCCUC
1616
GACCACCA CCACCAAACUCC CU UCAACCACAUCCUCCCCC ACAAUUGU
5387

1390
CCUACCCU G UCCUCCCA
1617
UCCCAGCA CGACCAAACUCC CU UCAAGCACAUCCUCCCCC AGCCUAGC
5388

1425
CCUCCUUU G UUUACGUC
1618
GACGUAAA CCACCAAACUCC CU UCAACCACAUCCUCCCGC AAAGCACC
5389

1508
CCCCUAUU G UACCCACC
1619
GCUCCGUA CCAGCAAACUCC CU UCAACCACAUCCUCCCGC AAUACCCC
5390

1557
CCCCCUCU G UCCCUUCU
1620
ACAACGCA CCAGCAAACUCC CU UCAACCACAUCCUCCCGC AGACCCCC
5391

1581
CCCACCCU G UCCACUUC
1621
GAACUGCA GCAGCAAACUCC CU UCAACCACAUCCUCCCGC ACCGUCCC
5392

1684
UCACCAAU G UCAACCAC
1622
GUCCUUCA GCACCAAACUCC CU UCAACCACAUCCUCCCCC AUUGCUCA
5393

1719
CAAAGACU G UCUCUUUA
1623
UAAACACA GCACCAAACUCC CU UCAACGACAUCCUCCCCC ACUCUUUC
5394

1721
AACACUGU G UCUTUAAU
1624
AUUAAACA CCACGAAACUCC CU UCAACGACAUCCUCCCGC ACAGUCUU
5395

1723
GACUCUCU G UUUAAUCA
1625
UCAUUAAA GCACGAAACUCC CU UCAACGACAUCCUCCCCC ACACAGUC
5396

1772
ACCUCUUU G UACUACCA
1626
UCCUACUA GCACGAAACUCC CU UCAACGACAUCCUCCCGC AAAGACCU
5397

1785
ACGACCCU G UACCCAUA
1627
UAUCCCUA GCACGAAACUCC CU UCAACGACAUCGUCCGGC AGCCUCCU
5398

1801
AAAUUCGU G UGUUCACC
1628
GCUCAACA GCACGAAACUCC CU UCAACCACAUCGUCCGCG ACCAAUUU
5399

1803
AUUGGUGU G UUCACCAG
1629
CUGGUGAA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG ACACCAAU
5400

1850
CAUCUCAU G UUCAUGUC
1630
GACAUGAA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AUGAGAUG
5401

1856
AUGUUCAU G UCCUACUG
1631
CAGUAGGA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AUGAACAU
5402

1864
GUCCUACU G UUCAAGCC
1632
GGCUUGAA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AGUAGGAC
5403

1881
UCCAAGCU G UGCCUUGG
1633
CCAAGGCA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AGCUUGGA
5404

1939
GAGCUUCU G UGGAGUUA
1634
UAACUCCA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AGAAGCUC
5405

2013
UCUGCUCU G UAUCGGGG
1635
CCCCGAUA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AGAGCAGA
5406

2045
GGAACAUU G UUCACCUC
1636
GAGGUGAA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AAUGUUCC
5407

2082
GCUAUUCU G UGUUGGGG
1637
CCCCAACA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AGAAUAGC
5408

2084
UAUUCUGU G UUGGGGUG
1638
CACCCCAA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG ACAGAAUA
5409

2167
UCAGCUAU G UCAACGUU
1639
AACGUUGA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AUAGCUGA
5410

2205
CAACUAUU G UGGLUUCA
1640
UGAAACCA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AAUAGUUG
5411

2222
CAUUUCCU G UCUUACUU
1641
AAGUAAGA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AGGAAAUG
5412

2245
GAGAAACU G UUCUUGAA
1642
UUCAAGAA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AGUUUCUC
5413

2262
UAUUUGGU G UCUUUUGG
1643
CCAAAAGA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG ACCAAAUA
5414

2274
UUUGGAGU G UGGAUUCG
1644
CGAAUCCA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG ACUCCAAA
5415

2344
AAACUACU G UUGUUAGA
1645
UCUAACAA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AGUAGUUU
5416

2347
CUACUGUU G UUAGACGA
1646
UCGUCUAA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AACAGUAG
5417

2450
AUCUCAAU G UUAGUAUU
1647
AAUACUAA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AUUGAGAU
5418

2573
AGGACAUU G UUGAUAGA
1648
UCUAUCAA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AAUGUCCU
5419

2583
UGAUAGAU G UAAGCAAU
1649
AUUGCUUA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AUCUAUCA
5420

2594
AGCAAUUU G UGGGGCCC
1650
GGGCCCCA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AAAUUGCU
5421

2663
AUCCCAAU G UUACUAAA
1651
UUUAGUAA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AUUGGGAU
5422

2717
CAGAGUAU G UAGUUAAU
1652
AUUAACUA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AUACUCUG
5423

2901
AUCUUUCU G UCCCCAAU
1653
AUUGGGGA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AGAAAGAU
5424

3071
GGGGGACU G UUGGGGUG
1654
CACCCCAA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AGUCCCCC
5425

3111
UCACAACU G UGCCAGCA
1655
UGCUGGCA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AGUUGUGA
5426

40
AUCCCAGA G UCAGGGCC
1656
GGCCCUGA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UCUGGGAU
5427

46
GAGUCAGG G CCCUGUAC
1657
GUACAGGG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CCUGACUC
5428

65
UCCUGCUG G UGGCUCCA
1658
UGGAGCCA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CAGCAGGA
5429

68
UCCUGGUG G CUCCAGUU
1659
AACUGGAG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CACCAGCA
5430

74
UGGCUCCA G UUCAGGAA
1660
UUCCUGAA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UGGAGCCA
5431

85
CAGGAACA G UGAGCCCU
1661
AGGGCUCA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UGUUCCUG
5432

89
AACAGUGA G CCCUGCUC
1662
GAGCAGGG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UCACUGUU
5433

120
GCCAUAUC G UCAAUCUU
1663
AAGAUUGA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG GAUAUGGC
5434

196
CCCUGCUC G UGUUACAG
1664
CUGUAACA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG GAGCAGGG
5435

205
UGUUACAG G CGGGGUUU
1665
AAACCCCG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CUGUAACA
5436

210
CAGGCGGG G UUUUUCUU
1666
AAGAAAAA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CCCGCCUG
5437

248
ACCACAGA G UCUAGACU
1667
AGUCUAGA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UCUGUGGU
5438

258
CUAGACUC G UGGUGGAC
1668
GUCCACCA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG GAGUCUAG
5439

261
GACUCGUG G UGGACUUC
1669
GAAGUCCA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CACGAGUC
5440

295
GAACACCC G UGUGUCUU
1670
AAGACACA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG GGGUGUUC
5441

305
GUGUCUUG G CCAAAAUU
1671
AAUUUUGG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CAAGACAC
5442

318
AAUUCGCA G UCCGAAAU
1672
AUUUGGGA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UGCGAAUU
5443

332
AAUCUCCA G UCACUCAC
1673
GUGAGUGA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UGGAGAUU
5444

368
UUGUCCUG G UUAUCGCU
1674
AGCGAUAA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CAGGACAA
5445

390
UGUCUGCG G CGUUUUAU
1675
AUAAAACG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CGCAGACA
5446

392
UCUGCGGC G UUUUAUCA
1676
UGAUAAAA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG GCCGCAGA
5447

442
UCUUGUUG G UUCUUCUG
1677
CAGAAGAA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CAACAAGA
5448

461
CUAUCAAG G UAUGUUGC
1678
GCAACAUA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CUUGAUAG
5449

472
UGUUGCCC G UUUGUCCU
1679
AGGACAAA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG GGGCAACA
5450

506
AACAACCA G CACCGGAC
1680
GUCCGGUG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UGGUUGUU
5451

625
CAUCUUGG G CUUUCGCA
1681
UGCGAAAG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CCAAGAUG
5452

648
CUAUGGGA G UGGGCCUC
1682
GAGGCCCA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UCCCAUAG
5453

652
GGGAGUGG G CCUCAGUC
1683
GACUGAGG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CCACUCCC
5454

658
GGGCCUCA G UCCGUUUC
1684
GAAACGGA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UGAGGCCC
5455

662
CUCAGUCC G UUUCUCUU
1685
AAGAGAAA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG GGACUGAG
5456

672
UUCUCUUG G CUCAGUUU
1686
AAACUGAG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CAAGAGAA
5457

677
UUGGCUCA G UUUACUAG
1687
CUAGUAAA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UGAGCCAA
5458

685
GUUUACUA G UGCCAUUU
1688
AAAUGGCA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UAGUAAAC
5459

699
UUUGUUCA G UGGUUCGU
1689
ACGAACCA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UGAACAAA
5460

702
GUUCAGUG G UUCGUAGG
1690
CCUACGAA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CACUGAAC
5461

706
AGUGGUUC G UAGGGCUU
1691
AAGCCCUA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG GAACCACU
5462

711
UUCGUAGG G CUUUCCCC
1692
GGGGAAAG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CCUACGAA
5463

729
ACUGUCUG G CUUUCAGU
1693
ACUGAAAG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CAGACAGU
5464

736
GGCUUUCA G UUAUAUGG
1694
CCAUAUAA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UGAAAGCC
5465

753
AUGAUGUG G UUUUGGGG
1695
CCCCAAAA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CACAUCAU
5466

762
UUUUGGGG G CCAAGUCU
1696
AGACUUGG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CCCCAAAA
5467

767
GGGGCCAA G UCUGUACA
1697
UGUACAGA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UUGGCCCC
5468

785
CAUCUUGA G UCCCUUUA
1698
UAAAGGGA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UCAAGAUG
5469

826
GUCUUUGG G UAUACAUU
1699
AAUGUAUA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CCAAAGAC
5470

898
AAUUGGGA G UUGGGGCA
1700
UGCCCCAA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UCCCAAUU
5471

904
GAGUUGGG G CACAUUGC
1701
GCAAUGUG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CCCAACUC
5472

971
GUAAACAG G CCUAUUGA
1702
UCAAUAGG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CUGUUUAC
5473

987
AUUGGAAA G UAUGUCAA
1703
UUGACAUA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UTUCCAAU
5474

1006
AAUUGUGG G UCUUUUCG
1704
CCAAAAGA GGAGGAAACUCC CU UCAAGGACAUCGUCCGCG CCACAAUU
5475

1016
CUUUUGGG G UUUGCCCC
1705
GCGGCAAA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CCCAAAAC
5476

1080
GCAUACAA G CAAAACAG
1706
CUGUUUUG GGAGGAAACUCC CU UCAACGACAUCGUCCCCC UUGUAUGC
5477

1089
CAAAACAG G CUUUUACU
1707
ACUAAAAG GCAGCAAACUCC CU UCAACGACAUCGUCCCGG CUCUUUUC
5478

1116
CUUACAAC G CCUUUCUA
1708
UACAAAGC GCAGCAAACUCC CU UCAACCACAUCCUCCGGG CUUGUAAG
5479

1126
CUUUCUAA G UAAACACU
1709
ACUGUUUA GGACGAAACUCC CU UCAACGACAUCCUCCCGC UUACAAAC
5480

1133
AGUAAACA G UAUCUCAA
1710
UUCACAUA CCACCAAACUCC CU UCAACCACAUCCUCCCCC UCUUUACU
5481

1152
UUUACCCC G UUGCUCCC
1711
CCCAGCAA CGAGCAAACUCC CU UCAAGGACAUCCUCCGCG CCGCUAAA
5482

1160
GUUGCUCG G CAACCCCC
1712
CCCCCUUG CGACGAAACUCC CU UCAAGGACAUCCUCCGCG CCACCAAC
5483

1166
CCGCAACC G CCUGGUCU
1713
ACACCACG GCAGCAAACUCC CU UCAAGCACAUCGUCCGGC CGUUCCCG
5484

1171
ACCGCCUC G UCUAUCCC
1714
CGCAUAGA GCAGCAAACUCC CU UCAACGACAUCGUCCCGC CACGCCCU
5485

1182
UAUGCCAA G UCUUUGCU
1715
ACCAAACA GCACCAAACUCC CU UCAACGACAUCCUCCCCC UUCCCAUA
5486

1207
CCCCACUG G UUCCCCCU
1716
ACCCCCAA CGAGGAAACUCC CU UCAACGACAUCGUCCGCG CACUGCGG
5487

1213
UGCUUCGC G CUUCCCCA
1717
UGCCCAAG CCACCAAACUCC CU UCAACGACAUCGUCCGGG CCCAACCA
5488

1218
GCCGCUUG G CCAUAGGC
1718
GCCUAUCC CCAGGAAACUCC CU UCAACGACAUCCUCCCCG CAAGCCCC
5489

1225
CGCCAUAC G CCAUCACC
1719
CCUCAUCC CCACCAAACUCC CU UCAACCACAUCCUCCCCC CUAUCCCC
5490

1232
CCCCAUCA G CGCAUCCC
1720
CCCAUCCC CCACCAAACUCC CU UCAACCACAUCCUCCCGC UGAUCGCC
5491

1240
CCCCAUCC G UCCAACCU
1721
ACCUUCCA GCACCAAACUCC CU UCAACCACAUCCUCCCCC CCAUCCCC
5492

1287
AACUCCUA G CCCCUUCU
1722
ACAACCCC CCACCAAACUCC CU UCAACCACAUCCUCCCGC UACCACUU
5493

1306
UCCUCCCA G CACCUCUC
1723
CACACCUC CCACCAAACUCC CU UCAACGACAUCCUCCCGC UGCGAGCA
5494

1310
CCCACCAC G UCUCCCCC
1724
CCCCCACA CCACCAAACUCC CU UCAACCACAUCCUCCCCC CUCCUCCC
5495

1317
CCUCUGCC G CAAAACUC
1725
CACUUUUC CCACCAAACUCC CU UCAACCACAUCCUCCCCC CCCACACC
5496

1347
AUUCUCUC G UCCUCUCC
1726
CCACACCA CCACCAAACUCC CU UCAACCACAUCCUCCCCC CACACAAU
5497

1379
UUUCCAUC G CUCCUACC
1727
CCUACCAC CCACCAAACUCC CU UCAACCACAUCCUCCCCC CAUCCAAA
5498

1387
CCUCCUAC G CUCUCCUC
1728
CACCACAC CCACCAAACUCC CU UCAACCACAUCCUCCCCC CUACCACC
5499

1418
CCCCCCAC G UCCUUUCU
1729
ACAAACCA CGACCAAACUCC CU UCAACCACAUCCUCCCCC CUCCCCCC
5500

1431
UUCUUUAC G UCCCCUCC
1730
CCACCCCA CCACCAAACUCC CU UCAACCACAUCCUCCCCC CUAAACAA
5501

1436
UACCUCCC G UCCCCCCU
1731
ACCCCCCA CGACCAAACUCC CU UCAAGCACAUCCUCCCCC CCCACCUA
5502

1440
UCCCCUCC G CGCUCAAU
1732
AUUCACCC CCACCAAACUCC CU UCAACCACAUCCUCCGCC CCACCCCA
5503

1471
CUCCCCCC G CCCCUUCC
1733
CCAACCCC CCACCAAACUCC CU UCAACCACAUCCUCCCCC CCCCCCAC
5504

1481
CCCUUCCC G CUCUACCC
1734
CCCUACAC CCACCAAACUCC CU UCAAGCACAUCCUCCGCC CCCAACCC
5505

1517
UACCCACC G UCCACCCC
1735
CCCCUCCA CCACCAAACUCC CU UCAAGCACAUCCUCCCCC CCUCCCUA
5506

1526
UCCACCCC G CCCACCUC
1736
CACCUCCC CCACCAAACUCC CU UCAACCACAUCCUCCCCC CCCCUCCA
5507

1553
CACUCCCC G UCUCUCCC
1737
CCCACACA CCACCAAACUCC CU UCAACCACAUCCUCCCCC GCGCACUC
5508

1579
CCCCCACC G UCUCCACU
1738
ACUCCACA CCACCAAACUCC CU UCAACCACAUCCUCCCCC CCUCCCCC
5509

1605
CUCUCCAC G UCGCAUCC
1739
CCAUCCCA CCACCAAACUCC CU UCAACCACAUCCUCCCCC CUCCACAC
5510

1622
AGACCACC G UGAACGCC
1740
GGCGUUCA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG GGUGGUCU
5511

1649
UGCCCAAG G UCUUGCAU
1741
AUGCAAGA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CUUGGGCA
5512

1679
GACUUUCA G CAAUGUCA
1742
UGACACUG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UGAAAGUC
5513

1703
ACCUUGAG G CAUACUUC
1743
GAAGUAUG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CUCAAGGU
5514

1732
UUUAAUGA G UGGGAGGA
1744
UCCUCCCA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UCAUUAAA
5515

1741
UGGUAGGA G UUGGGGGA
1745
UCCCCCAA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UCCUCCCA
5516

1754
UGGAGGAG G UUAGGUUA
1746
UAACCUAA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CUCCUCCC
5517

1759
GAGGUUAG G UUAAAGGU
1747
ACCUUUAA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CUAACCUC
5518

1766
GGUUAAAG G UCUUUGUA
1748
UACAAAGA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CUUUAACC
5519

1782
ACUAGGAG G CUGUAGGC
1749
GCCUACAG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CUCCUAGU
5520

1789
GGCUGUAG G CAUAAAUU
1750
AAUUUAUG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CUACAGCC
5521

1799
AUAAAUUG G UGUGUUCA
1751
UGAACACA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CAAUUUAU
5522

1811
GUCCACCA G CACCAUGC
1752
UCAUGGUG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UGGUGAAC
5523

1870
CUGUUCAA G CCUCCAAG
1753
CUUGGAGG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UUGAACAG
5524

1878
GCCUCCAA G CUGUGCCU
1754
AGGCACAG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UUGGAUGC
5525

1890
UGCCUUGG G UUGCUUUG
1755
CAAAGCCA GGAGUAAACUCC CU UCAAGGACAUCGUCCGGG CCAAGGCA
5526

1893
CUUGGGUG G CUUUGGGG
1756
CCCCAAAU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CACCCAAG
5527

1901
GCUUUGGG G CAUGGACA
1757
UGUCCAUG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CCCAAAGC
5528

1917
AUUGACCC G UAUAAAGA
1758
UCUUUAUA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG GGGUCAAU
5529

1933
AAUUUGGA G CUUCUGUU
1759
CACAGAAG GGAGUAAACUCC CU UCAAGGACAUCGUCCGGG UCCAAAUU
5530

1944
UCUGUGGA G UUACUCUC
1760
GAGAUUAA GUAGUAAACUCC CU UCAAGUACAUCUUCCGGU UCCACAGA
5531

2023
AUCUGGUG G CCUUAGAG
1761
CUCUAAGG GGAGGAAACUCC CU UCAAGGACAUCGUCCUGU CCCCCGAU
5532

2031
GCCUUAGA G UCUCCGGA
1762
UCCUGAGA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UCUAAGGC
5533

2062
ACCAUACG G CACUCAGG
1763
CCUUAGUG GGAUGAAACUCC CU UCAAGGACAUCUUCCUGU CGUAUGGU
5534

2070
UCACUCAG G CAAGCUAU
1764
AUAGCUUG GGAGGAAACUCC CU UCAAUGACAUCGUCCGGG CUGAGUGC
5535

2074
UCAGGCAA G CUAUUCUG
1765
CAGAAUAG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UUGCCUGA
5536

2090
GUGUUGGG G UGAGUUGA
1766
UCAACUCA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CCCAACAC
5537

2094
UGGUGUGA G UUGAUGAA
1767
UUCAUCAA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UCACCCCA
5538

2107
UGAAUCUA G CCACCUGG
1768
CCAGGUGG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UAGAUUCA
5539

2116
CCACCUGG G UGGGAAGU
1769
ACUUCCCA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CCAGGUGG
5540

2123
GGUGGGAA G UAAUUUGG
1770
CCAAAUUA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UUCCCACC
5541

2140
AAGAUCCA G CAUCCAUG
1771
CCUUGAUG GGAGGAAACUCC CU UCAAGUACAUCGUCCGGG UGGAUCUU
5542

2155
GGGAAUUA G UAGUCAUC
1772
GCUGACUA UGAGUAAACUCC CU UCAAGGACAUCGUCCGGG UAAUUCCC
5543

2158
AAUUAGUA G UCAUCUAC
1773
AUAGCUUA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UACUAAUU
5544

2162
AGUAGUCA G CUAUGUCA
1774
UGACAUAU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UUACUACU
5545

2173
AUGUCAAC G UUAAUAUG
1775
CAUAUUAA GGAGGAAACUCC CU UCAAGGACAUCUUCCGGG GUUGACAU
5546

2183
UAAUAUGG G CCUAAAAA
1776
UCCUCAUG GGAGGAAACUCC CU UCAAUGACAUCGUCCGGG CCAUAUUA
5547

2208
CUAUUGUG G UUUCACAU
1777
AUGUGAAA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CACAAUAG
5548

2235
ACUUUUGG G CGAGAAAC
1778
GUUUCUCG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CCAAAAGU
5545

2260
AAUATUUG G UGUCUUUU
1779
AAAAGACA GUAGGAAACUCC CU UCAAGGACAUCGUCCGGG CAAAUAUU
5550

2272
CUUUUGCA G UGUGUAUU
1780
AAUCCACA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UCCAAAAG
5551

2360
ACGAAGAG G CAGGUCCC
1781
GGGACCUG GGAGUAAACUCC CU UCAAUUACAUCGUCCGGG CUCUUCGU
5552

2364
AGAGGCAG G UCCCCUAG
1782
CUAGUGGA UGAGUAAACUCC CU UCAAGUACAUCUUCCUUG CUUCCUCU
5553

2403
AGACUAAG G UCUCAAUC
1783
GAUUGAGA UGAUGAAACUCC CU UCAAGUACAUCGUCCGGG CUUCGUCU
5554

2417
AUCUCCUC G UCGCAUAA
1784
UUCUGCGA UGAGUAAACUCC CU UCAAGGACAUCUUCCGGU GCGGCUAU
5555

2454
CAAUGUUA G UAUUCCUU
1785
AAGUAAUA GGAGUAAACUCC CU UCAAGGACAUCUUCCGUU UAACAUUU
5556

2474
CACAUAAU G UUGUAAAC
1786
UUUUCCCA GGAGUAAACUCC CU UCAAGGACAUCGUCCGUG CUUAUGUG
5557

2491
UUUACGUG G CUUUAUUC
1787
UAAUAAAU GGAGUAAACUCC CU UCAAGUACAUCGUCCGUG CCCUUAAA
5558

2507
CUUCUACG G UACCUUGC
1788
UCAAGGUA GGAGUAAACUCC CU UCAAGUACAUCGUCCGGG CGUAGAAG
5559

2530
CCUAAAUG G CAAACUCC
1789
GGAUUUUU GGAGUAAACUCC CU UCAAGUACAUCUUCCGGG CAUUUAGG
5560

2587
AUAUUUAA G CAAUUUUU
1790
ACAAAUUG GGAGUAAACUCC CU UCAAGUACAUCUUCCUUG UUACAUCU
5561

2599
UUUGUGGU G CCCCUUAC
1791
UUAAUUUU UUAUUAAACUCC CU UCAAUUACAUCUUCCUGU CCCACAAA
5562

2609
CCCUUACA G UAAAUUAA
1792
UUCAUUUA UUAUUAAACUCC CU UCAAGUACAUCUUCCUGU UGUAAUGU
5563

2650
CCUUCUAU G UUUUAUCC
1793
UUAUAAAA GUAUUAAACUCC CU UCAAUUACAUCUUCCUUU CUAUCAUU
5564

2701
AUCAAACC G UAUUAUCC
1794
UUAUAAUA GUAUGAAACUCC CU UCAAUGACAUCGUCCGUU UGUUUUAU
5565

2713
UAUCCAUA G UAUGUAUU
1795
ACUACAUA GUAUGAAACUCC CU UCAAUGACAUCGUCCGGG UCUGUAUA
5566

2720
AUUAUUUA G UUAAUCAU
1796
AUUAUUAA UUAUUAAACUCC CU UCAAUGACAUCGUCCGUG UACAUACU
5567

2768
UUUUUAAG G CUGUGAUC
1797
GAUCCCCU UUAUGAAACUCC CU UCAAUGACAUCGUCCGGG CUUCCAAA
5568

2791
AAAAGAUA G UCCACACG
1798
CUUUUGUA GUAUUAAACUCC CU UCAAUUACAUCGUCCGUG UCUCUUUU
5569

2799
GUCCACAC G UAGCGCCU
1799
AUGCGCUA UUAUGAAACUCC CU UCAAUUACAUCUUCCUUU UUUUUUAC
5570

2802
CACACUUA G CUCCUCAU
1800
AUUAGUCU UUAUGAAACUCC CU UCAAUGACAUCUUCCGUG UACGUGUG
5571

2818
UUUUGCGU G UCACCAUA
1801
UAUUGUGA UGAGGAAACUCC CU UCAAUUACAUCUUCCGUG CCUCAAAA
5572

2848
GAUCUACA G CAUUUUAU
1802
CUCCCAUU UUAGUAAACUCC CU UCAAUUACAUCUUCCGUG UGUAGAUC
5573

2857
CAUGUGAG G UUGGUCUU
1803
AAGACCAA UGAUUAAACUCC CU UCAAUUACAUCUUCCUUG CUCCCAUG
5574

2861
UGAGGUUU G UCUUCCAA
1804
UUGUAAUA UUAGUAAACUCC CU UCAAGUACAUCUUCCUUU CAACCUCC
5575

2881
UCUAAAAU G CAUGUGGA
1805
UCCCCAUU UUAUUAAACUCC CU UCAAGUACAUCUUCCUUG CUUUUCUA
5576

2936
GAUCAUCA G UUUUACCC
1806
UGUUCCAA UGAGUAAACUCC CU UCAAUUACAUCUUCCUUG UGAUGAUC
5577

2955
CAUUCAAA G CCAACUCA
1807
UGAGUUUU UUAGUAAACUCC CU UCAAGUACAUCUUCCUUG UUUUAAUU
5578

2964
CCAACUCA G UAAAUCCA
1808
UGUAUUUA GUAUUAAACUCC CU UCAAUUACAUCUUCCUUG UUAUUUUG
5579

3005
GACAACUU G CCGUACUC
1809
UCUUCCUG GUAUUAAACUCC CU UCAAUUACAUCUUCCUGU CAUUUUUC
5580

3021
CCAACAAG G UUGUAUUU
1810
CACUCCCA GUAUUAAACUCC CU UCAAUUACAUCUUCCUGU CUUGUUGG
5581

3027
AGGUGUGA G UGUGAUCA
1811
UGCUCCCA GUAUGAAACUCC CU UCAAUGACAUCUUCCUGU UCCCACCU
5582

3033
GAGUGUGA G CAUUCUGU
1812
CCCUAAUG UUAUGAAACUCC CU UCAAUGACAUCUUCCUGU UCCCACUC
5583

3041
UCAUUCUG G CCAUGUUU
1813
AACCCUUU GUAUGAAACUCC CU UCAAUUACAUCGUCCGGG CCUAAUUC
5584

3047
GGGCCAGG G UUCACCCC
1814
GGGGUCAA GCAGGAAACUCC CU UCAAGCACAUCGUCCGGG CCUGGCCC
5585

3077
CUGUUGGG G UGGAGCCC
1815
GGGCUCCA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CCCAACAG
5586

3082
GGGGUGGA G CCCUCACG
1816
CGUGAGGC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UCCACCCC
5587

3097
CGCUCAGG G CCUACUCA
1817
UGACUAGC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CCUGAGCG
5588

3117
CUGUGCCA G CAGCUCCU
1818
AGGACCUG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UGGCACAG
5589

3120
UGCCAGCA G CUCCUCCU
1819
AGGAGGAG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UGCUGGCA
5590

3146
ACCAAUCG G CACUCAGG
1820
CCUGACUC GGAGGAAACUCC CU UCAAGGACAUCCUCCGCG CGAUUGGU
5591

3149
AAUCCGCA G UCAGGAAG
1821
CUUCCUGA GGAGCAAACUCC CU UCAAGGACAUCGUCCGGG UGCCGAUU
5592

3158
UCAGGAAG G CACCCUAC
1822
GUAGGCUC GGAGCAAACUCC CU UCAAGGACAUCCUCCGGG CUUCCUCA
5593

3161
GGAAGGCA G CCUACUCC
1823
CGACUACG CGAGCAAACUCC CU UCAAGGACAUCCUCCGGC UCCCUUCC
5594

3204
AUCCUCAG G CCAUGCAG
1824
CUGCAUGG GCAGGAAACUCC CU UCAAGGACAUCGUCCGGG CUGAGGAU
5595

31
CUCUUCAA G AUCCCACA
2196
UCUGCGAU GGAGGAAACUCC CU UCAAGGACAUCCUCCGGG UUGAACAG
5596

38
ACAUCCCA G AGUCAGGG
2197
CCCUGACU GGAGGAAACUCC CU UCAAGGACAUCGUCCCGG UGGGAUCU
5597

44
CACAGUCA G GCCCCUGU
2198
ACAGCGCC GCACGAAACUCC CU UCAAGGACAUCGUCCGGG UGACUCUG
5598

45
AGAGUCAG G GCCCUGUA
2199
UACAGGCC GGACGAAACUCC CU UCAAGGACAUCGUCCCGG CUGACUCU
5599

64
UUCCUCCU G GUGGCUCC
2200
CCACCCAC CGAGCAAACUCC CU UCAACCACAUCGUCCGGG AGCAGGAA
5800

67
CUGCUGCU G GCUCCAGU
2201
ACUGGAGC CGAGCAAACUCC CU UCAAGGACAUCGUCCGCG ACCAGCAG
5601

79
CCAGUUCA G GAACACUC
2202
CACUGUUC GGAGCAAACUCC CU UCAAGCACAUCCUCCGCC UGAACUGG
5602

80
CAGUUCAC G AACAGUCA
2203
UCACUCUU CGAGCAAACUCC CU UCAAGCACAUCGUCCGGC CUCAACUG
5603

99
CCUGCUCA G AAUACUGU
2204
ACAGUAUU CCAGCAAACUCC CU UCAAGCACAUCGUCCGGG UGACCACC
5604

135
UUAUCGAA G ACUCCCCA
2205
UCCCCACU CCACCAAACUCC CU UCAAGCACAUCCUCCCCG UUCCAUAA
5605

139
CGAAGACU G GCCACCCU
2206
AGCCUCCC CCACCAAACUCC CU UCAACGACAUCGUCCGGC ACUCUUCG
5606

140
GAAGACUG G GGACCCUG
2207
CAGGGUCC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CAGUCUUC
5607

141
AACACUCC G CACCCUGU
2208
ACAGCGUC GCACCAAACUCC CU UCAACCACAUCCUCCCCG CCACUCUU
5608

142
AGACUGGG G ACCCUCUA
2209
UACAGCCU CGAGGAAACUCC CU UCAACCACAUCGUCCCCC CCCACUCU
5609

159
CCGAACAU G GAGAACAU
2210
AUCUUCUC GGAGGAAACUCC CU UCAAGGACAUCCUCCCCC AUGUUCGG
5610

160
CGAACAUC G AGAACAUC
2211
CAUCUUCU CCACCAAACUCC CU UCAAGGACAUCCUCCCCC CAUGUUCG
5611

162
AACAUCCA G AACAUCCC
2212
CCCAUCUU GCACGAAACUCC CU UCAACCACAUCGUCCGCC UCCAUCUU
5612

175
UCCCAUCA G GACUCCUA
2213
UACCACUC CCACGAAACUCC CU UCAACCACAUCGUCCCGC UCAUCCCA
5613

176
CCCAUCAG G ACUCCUAG
2214
CUAGGAGU GGAGCAAACUCC CU UCAACCACAUCGUCCCGG CUGAUGCC
5614

184
CACUCCUA G GACCCCUC
2215
CAGGGGUC GCAGGAAACUCC CU UCAACCACAUCGUCCGGG UACCACUC
5615

185
ACUCCUAC G ACCCCUCC
2216
CCAGGGCU CCAGGAAACUCC CU UCAACCACAUCCUCCCCC CUACCACU
5616

204
CUGUUACA G CCCGCGUU
2217
AACCCCCC GCAGCAAACUCC CU UCAAGGACAUCCUCCCGG UGUAACAC
5617

207
UUACAGGC G CCCUUUUU
2218
AAAAACCC CCACCAAACUCC CU UCAAGGACAUCCUCCGCC CCCUGUAA
5618

208
UACACCCC G GGUUUUUC
2219
CAAAAACC GCACGAAACUCC CU UCAAGCACAUCGUCCGGC CCCCUCUA
5619

209
ACAGCCCC G CUUUUUCU
2220
AGAAAAAC GGAGGAAACUCC CU UCAACCACAUCGUCCGGG CCCCCUCU
5620

246
AUACCACA G AGUCUACA
2221
UCUAGACU GCACCAAACUCC CU UCAACCACAUCGUCCCCC UCUCCUAU
5621

253
AGAGUCUA G ACUCGUGG
2222
CCACGAGU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UAGACUCU
5622

260
AGACUCGU G CUGCACUU
2223
AAGUCCAC GCAGCAAACUCC CU UCAAGGACAUCGUCCGGG ACGAGUCU
5623

263
CUCGUGGU G GACUUCUC
2224
CAGAAGUC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG ACCACGAC
5624

264
UCGUGGUG G ACUUCUCU
2225
AGAGAAGU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CACCACGA
5625

283
AUUUUCUA G GGGGAACA
2226
UGUUCCCC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UAGAAAAU
5626

284
UUUUCUAC G GGGAACAC
2227
GUGUUCCC GGAGGAAACUCC CU UCAAGGACAUCCUCCGGG CUAGAAAA
5627

285
UUUCUAGG G GGAACACC
2228
GGUGUUCC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CCUAGAAA
5628

286
UUCUAGGG G GAACACCC
2229
GGGUGUUC GGAGGAAACUCC CU UCAAGGACAUCGUCCGCG CCCUACAA
5629

287
UCUAGGGG G AACACCCG
2230
CGGGUGUU GGAGCAAACUCC CU UCAAGGACAUCGUCCGGG CCCCUAGA
5630

304
UGUGUCUU G GCCAAAAU
2231
AUUUUGGC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AAGACACA
5631

367
UUUGUCCU G GUUAUCGC
2232
GCGAUAAC GCACCAAACUCC CU UCAAGGACAUCGUCCCGG AGGACAAA
5632

377
UUAUCGCU G GAUGUGUC
2233
GACACAUC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AGCGAUAA
5633

378
UAUCGCUG G AUGUGUCU
2234
AGACACAU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CAGCGAUA
5634

389
GUGUCUGC G GCGUUUUA
2235
UAAAACCC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG GCAGACAC
5635

441
UUCUUGUU G GUUCUUCU
2236
AGAAGAAC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AACAAGAA
5636

450
GUUCUUCU G GACUAUCA
2237
UGAUAGUC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AGAAGAAC
5637

451
UUCUUCUG G ACUAUCAA
2238
UUGAUAGU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CAGAAGAA
5638

460
ACUAUCAA G GUAUGUUG
2239
CAACAUAC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UUGAUAGU
5639

490
UAAUUCCA G GAUCAUCA
2240
UGAUGAUC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UGGAAUUA
5640

491
AAUUCCAG G AUCAUCAA
2241
UUGAUGAU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CUGGAAUU
5641

511
CCAGCACC G GACCAUGC
2242
GCAUGGUC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG GGUGCUGG
5642

512
CAGCACCG G ACCAUGCA
2243
UGCAUGGU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CGGUGCUG
5643

544
CUGCUCAA G GAACCUCU
2244
AGAGGUUC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UUGAGCAG
5644

545
UGCUCAAG G AACCUCUA
2245
UAGAGGUU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CUUGAGCA
5645

585
AAACCUAC G GACGGAAA
2246
UUUCCGUC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG GUAGGUUU
5646

586
AACCUACG G ACGGAAAC
2247
GUUUCCGU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CGUAGGUU
5647

589
CUACGGAC G GAAACUGC
2248
GCAGUUUC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG GUCCGUAG
5648

590
UACGGACG G AAACUGCA
2249
UGCAGUUU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CGUCCGUA
5649

623
AUCAUCUU G CCCUUUCG
2250
CGAAACCC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AAGAUGAU
5650

624
UCAUCUUC G GCUUUCGC
2251
CCGAAAGC CGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CAAGAUCA
5651

644
AUACCUAU G GGAGUGGG
2252
CCCACUCC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AUAGGUAU
5652

645
UACCUAUG G GAGUGGGC
2253
GCCCACUC GGAGCAAACUCC CU UCAAGGACAUCGUCCGCG CAUAGGUA
5653

646
ACCUAUGG G AGUGCGCC
2254
CGCCCACU GGAGCAAACUCC CU UCAAGCACAUCGUCCGCG CCAUACGU
5654

650
AUGGGAGU G GGCCUCAC
2255
CUGAGGCC CGAGCAAACUCC CU UCAAGCACAUCGUCCGGG ACUCCCAU
5655

651
UGGCAGUG G GCCUCAGU
2256
ACUGAGCC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CACUCCCA
5656

671
UUUCUCUU G GCUCAGUU
2257
AACUCACC GGAGGAAACUCC CU UCAAGGACAUCGUCCGCG AAGAGAAA
5657

701
UGUUCACU G GUUCCUAG
2258
CUACGAAC GCAGGAAACUCC CU UCAAGGACAUCGUCCGGG ACUGAACA
5658

709
GGUUCGUA G GGCUUUCC
2259
GGAAAGCC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UACGAACC
5659

710
GUUCGUAG G GCUUUCCC
2260
GGGAAAGC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CUACGAAC
5660

728
CACUGUCU G GCUUUCAG
2261
CUGAAAGC GGAGGAAACUCC CU UCAAGGACAUCGUCCCGG AGACAGUG
5661

743
AGUUAUAU G GAUGAUGU
2262
ACAUCAUC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AUAUAACU
5662

744
GUUAUAUG G AUGAUGUG
2263
CACAUCAU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CAUAUAAC
5663

752
GAUGAUGU G GUUUUGCG
2264
CCCAAAAC GGAGGAAACUCC CU UCAAGGACAUCGUCCCGC ACAUCAUC
5664

758
GUGGUUUU G GGGGCCAA
2265
UUGGCCCC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AAAACCAC
5665

759
UGGUUUUG G GGGCCAAG
2266
CUUGGCCC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CAAAACCA
5666

760
GGUUUUGG G GGCCAAGU
2267
ACUUGGCC GGAGGAAACUCC CU UCAAGGACAUCCUCCGGG CCAAAACC
5667

761
GUUUUGGG G GCCAACUC
2268
CACUUGGC CGAGGAAACUCC CU UCAAGCACAUCGUCCGCC CCCAAAAC
5668

824
UUGUCUUU G GGUAUACA
2269
UGUAUACC CGAGCAAACUCC CU UCAAGGACAUCGUCCGGG AAAGACAA
5669

825
UGUCUUUC G CUAUACAU
2270
AUGUAUAC CGAGCAAACUCC CU UCAAGGACAUCGUCCCGG CAAAGACA
5670

856
AACAAAAA G AUGGGGAU
2271
AUCCCCAU GGAGCAAACUCC CU UCAAGGACAUCGUCCGGG UUUUUGUU
5671

859
AAAAAGAU G CGGAUAUU
2272
AAUAUCCC GGAGGAAACUCC CU UCAAGCACAUCCUCCGGC AUCUUUUU
5672

860
AAAAGAUC G GGAUAUUC
2273
GAAUAUCC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CAUCUUUU
5673

861
AAACAUGC G GAUAUUCC
2274
GGAAUAUC CGAGGAAACUCC CU UCAACGACAUCGUCCGGG CCAUCUUU
5674

862
AAGAUGGC G AUAUUCCC
2275
GGGAAUAU CGAGCAAACUCC CU UCAAGGACAUCGUCCCCG CCCAUCUU
5675

881
AACUUCAU G GGAUAUGU
2276
ACAUAUCC CGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AUGAAGUU
5676

882
ACUUCAUC G GAUAUGUA
2277
UACAUAUC CGAGCAAACUCC CU UCAAGGACAUCCUCCGGC CAUGAAGU
5677

883
CUUCAUGC G AUAUGUAA
2278
UUACAUAU GGAGGAAACUCC CU UCAAGGACAUCCUCCGGC CCAUGAAG
5678

894
AUGUAAUU G GGAGUUGG
2279
CCAACUCC GGAGGAAACUCC CU UCAACGACAUCGUCCGGG AAUUACAU
5679

895
UCUAAUUG G GAGUUCGG
2280
CCCAACUC GGACGAAACUCC CU UCAAGGACAUCGUCCGGG CAAUUACA
5680

896
CUAAUUGC G AGUUGGGC
2281
CCCCAACU CCAGCAAACUCC CU UCAAGGACAUCCUCCGCG CCAAUUAC
5681

901
UGGCACUU G CCGCACAU
2282
AUGUGCCC GGAGGAAACUCC CU UCAACCACAUCCUCCGGG AACUCCCA
5682

902
GCGAGUUG G CGCACAUU
2283
AAUGUCCC GCAGGAAACUCC CU UCAACGACAUCCUCCCCG CAACUCCC
5683

903
GGACUUCC G CCACAUUC
2284
CAAUCUCC GGAGGAAACUCC CU UCAACCACAUCCUCCCCC CCAACUCC
5684

917
UUCCCACA G CAACAUAU
2285
AUAUCUUC CCACCAAACUCC CU UCAACCACAUCCUCCCGC UCUCCCAA
5685

918
UCCCACAC G AACAUAUU
2286
AAUAUCUU CCACCAAACUCC CU UCAAGGACAUCCUCCCGG CUGUGGCA
5686

952
CUCUUUUA G GAAACUUC
2287
GAAGUUUC GCACCAAACUCC CU UCAACCACAUCCUCCCGC UAAAACAC
5687

953
UCUUUUAC G AAACUUCC
2288
CGAAGUUU CCACCAAACUCC CU UCAACGACAUCCUCCCCC CUAAAACA
5688

970
UCUAAACA G CCCUAUUC
2289
CAAUAGGC GCACCAAACUCC CU UCAACCACAUCCUCCCCC UCUUUACA
5689

982
UAUUCAUU G CAAAGUAU
2290
AUACUUUC CCACCAAACUCC CU UCAACCACAUCCUCCCCC AAUCAAUA
5690

983
AUUCAUUC G AAACUAUG
2291
CAUACUUU CCACCAAACUCC CU UCAACGACAUCCUCCCCC CAAUCAAU
5691

1004
CGAAUUCU G CCUCUUUU
2292
AAAACACC CCACCAAACUCC CU UCAACCACAUCCUCCCCC ACAAUUCC
5692

1005
CAAUUCUC G GUCUUUUC
2293
CAAAACAC CCAGCAAACUCC CU UCAACGACAUCCUCCCCC CACAAUUC
5693

1013
GGUCUUUU G GCCUUUGC
2294
CCAAACCC CGAGGAAACUCC CU UCAAGGACAUCCUCCGCC AAAAGACC
5694

1014
GUCUUUUC G CCUUUGCC
2295
CCCAAACC GGAGCAAACUCC CU UCAAGCACAUCGUCCCGC CAAAACAC
5695

1015
UCUUUUGG G GUUUGCCG
2296
CGGCAAAC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CCAAAAGA
5696

1041
CGCAAUGU G GAUAUUCU
2297
AGAAUAUC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG ACAUUGCG
5697

1042
GCAAUGUG G AUAUUCUG
2298
CAGAAUAU GCAGCAAACUCC CU UCAAGGACAUCGUCCGGG CACAUUGC
5698

1088
GCAAAACA G GCUUUUAC
2299
GUAAAAGC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UGUUUUGC
5699

1115
ACUUACAA G GCCUUUCU
2300
AGAAAGGC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UUGUAAGU
5700

1159
CGUUGCUC G GCAACGGC
2301
GCCGUUGC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG GAGCAACG
5701

1165
UCGGCAAC G GCCUGGUC
2302
GACCAGGC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG GUUGCCGA
5702

1170
AACGGCCU G GUCUAUGC
2303
GCAUAGAC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AGGCCGUU
5703

1206
CCCCCACU G GUUGGGGC
2304
GCCCCAAC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AGUGGGGG
5704

1210
CACUGGUU G GGGCUUGG
2305
CCAAGCCC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AACCAGUG
5705

1211
ACUGCUUG G GGCUUGGC
2306
GCCAAGCC GGAGGAAACUCC CU UCAAGGACAUCCUCCGGC CAACCAGU
5706

1212
CUGUUUGC G GCUUGGCC
2307
GGCCAAGC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CCAACCAG
5707

1217
UGGGGCUU G GCCAUAGG
2308
CCUAUGGC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AAGCCCCA
5708

1224
UGGCCAUA G GCCAUCAG
2309
CUGAUGGC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UAUGGCCA
5709

1242
GCAUGCGU G GAACCUUU
2310
AAAGGUUC GCAGGAAACUCC CU UCAAGGACAUCGUCCGGG ACGCAUGC
5710

1243
CAUGCGUG G AACCUUUG
2311
CAAACGUU GGACGAAACUCC CU UCAAGCACAUCGUCCCCG CACCCAUG
5711

1277
CAUACCCC G GAACUCCU
2312
AGGAGUUC GCAGGAAACUCC CU UCAACGACAUCGUCCGCG GCGCUAUG
5712

1278
AUACCCCC G AACUCCUA
2313
UACGAGUU GCAGGAAACUCC CU UCAAGGACAUCGUCCCCC CGCCCUAU
5713

1309
UCCCACCA G GUCUCGCG
2314
CCCCACAC CGAGGAAACUCC CU UCAAGGACAUCGUCCGCG UGCUGCGA
5714

1314
GCAGGUCU G CGCCAAAA
2315
UUUUGCCC GGACGAAACUCC CU UCAACGACAUCGUCCCGC AGACCUCC
5715

1315
CAGGUCUC G GGCAAAAC
2316
CUUUUGCC CGAGGAAACUCC CU UCAACGACAUCGUCCCGC CAGACCUG
5716

1316
AGGUCUGG G GCAAAACU
2317
ACUUUUGC GGACCAAACUCC CU UCAAGCACAUCCUCCGGC CCAGACCU
5717

1329
AACUCAUC G GGACUGAC
2318
GUCAGUCC GCACCAAACUCC CU UCAAGCACAUCCUCCGGG GAUCACUU
5718

1330
ACUCAUCC G CACUGACA
2319
UGUCACUC CGACGAAACUCC CU UCAAGCACAUCCUCCGCG CCAUGACU
5719

1331
CUCAUCCC G ACUCACAA
2320
UUGUCAGU GGAGGAAACUCC CU UCAACCACAUCCUCCGCG CCGAUGAG
5720

1378
AUUUCCAU G CCUGCUAG
2321
CUACCAGC CGAGGAAACUCC CU UCAACCACAUCCUCCGGC AUGGAAAU
5721

1386
GGCUGCUA G CCUCUCCU
2322
ACCACACC CGAGCAAACUCC CU UCAAGCACAUCCUCCGCC UACCACCC
5722

1402
UCCCAACU G CAUCCUAC
2323
GUACCAUC CCACCAAACUCC CU UCAAGCACAUCCUCCCCG ACUUCGCA
5723

1403
CCCAACUC G AUCCUACC
2324
CCUACCAU CCACCAAACUCC CU UCAACCACAUCCUCCCCG CACUUCCC
5724

1413
UCCUACCC G CGACCUCC
2325
CGACCUCC CCACCAAACUCC CU UCAACCACAUCCUCCCCC GCGUACCA
5725

1414
CCUACCCC G CACCUCCU
2326
ACCACCUC CCAGCAAACUCC CU UCAACCACAUCCUCCGCC CCCCUACC
5726

1415
CUACCCCG G ACCUCCUU
2327
AACGACCU CCACCAAACUCC CU UCAACCACAUCCUCCCCC CCGCCUAC
5727

1439
CUCCCCUC G GCCCUCAA
2328
UUCACCCC GCACCAAACUCC CU UCAACCACAUCCUCCCCC GACCCCAC
5728

1454
AAUCCCCC G GACCACCC
2329
CGCUCCUC GCACGAAACUCC CU UCAACGACAUCCUCCCCC CCGCCAUU
5729

1455
AUCCCCCC G ACCACCCC
2330
CCCGUCCU CCACGAAACUCC CU UCAACGACAUCCUCCCCC CCCCGCAU
5730

1468
CCCCUCCC G GCCCCCCU
2331
ACCCCCCC CCACCAAACUCC CU UCAACGACAUCGUCCCGC CCCAGCCC
5731

1469
CCCUCCCC G CCCCCCUU
2332
AACCCCCC CCACCAAACUCC CU UCAACCACAUCGUCCCCC CCCCACGC
5732

1470
CCUCCCGG G GCCGCUUG
2333
CAAGCGGC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CCGGGAGG
5733

1478
GGCCCCUU G GGGCUCUA
2334
UAGAGCCC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AAGCGGCC
5734

1478
GCCGCUUG G GGCUCUAC
2335
GUAGAGCC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CAAGCGGC
5735

1480
CCGCUUGG G GCUCUACC
2336
GGUAGAGC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CCAAGCGG
5736

1523
CCGUCCAC G GGGCGCAC
2337
GUGCGCCC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG GUGGACGG
5737

1524
CGUCCACG G GGCGCACC
2338
GGUGCGCC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CGUGGACG
5738

1525
GUCCACGG G GCGCACCU
2339
AGGUGCGC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CCGUGGAC
5739

1544
CUUUACGC G UACUCCCC
2340
GGGGAGUC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG GCGUAAAG
5740

1545
UUUACGCG G ACUCCCCG
2341
CGGGUAUU GGAGGAAACUCC CU UCAAUGACAUCGUCCGGG CGCGUAAA
5741

1574
CAUCUGCC G GACCUUUU
2342
ACACUGUC GUAGUAAACUCC CU UCAAUGACAUCUUCCGUG UGCAGAUG
5742

1575
AUCUUCCG G ACCGUGUG
2343
CACACGUU GGAUGAAACUCC CU UCAAUGACAUCUUCCGGG CGGCAGAU
5743

1612
CUUCGCAU G GAGACCAC
2344
GUGGUCUC GGAGGAAACUCC CU UCAAGGACAUCGUCCUGG AUUCGACG
5744

1613
UUCGCAUG G AGACCACC
2345
GUUGGUCU GUAGGAAACUCC CU UCAAGGACAUCGUCCUGU CAUGCGAC
5745

1615
CGCAUGUA G ACCACCGU
2346
ACGGUUUU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UCCAUGCU
5746

1635
CGCCCACA G GAACCUGC
2347
GCAGGUUC GUAUGAAACUCC CU UCAAGGACAUCGUCCGGG UGUGGGCG
5747

1636
GCCCACAG G AACCUGCC
2348
GUCAGUUU UGAUGAAACUCC CU UCAAUGACAUCGUCCGGG CUGUGGUC
5748

1648
CUGCCCAA G GUCUUGCA
2349
UGCAAGAC GGAGGAAACUCC CU UCAAGUACAUCGUCCGGG UUGGGCAG
5749

1660
UUGCAUAA G AUGACUCU
2350
AUAUUCCU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UUAUUCAA
5750

1662
GCAUAAGA G GACUCUUG
2351
CAAUAUUC GGAGUAAACUCC CU UCAAGGACAUCGUCCGUG UCUUAUUC
5751

1663
CAUAAGAG G ACUCUUUU
2352
CCAAUAGU GUAGGAAACUCC CU UCAAGGACAUCUUCCGGG CUCUUAUG
5752

1670
UUACUCUU G UACUUUCA
2353
UUAAAGUC GUAUGAAACUCC CU UCAAGUACAUCGUCCGUU AAUAUUCC
5753

1671
UACUCUUG G ACUUUCAU
2354
CUGAAAGU UUAUUAAACUCC CU UCAAUUACAUCUUCCGUG CAAUAUUC
5754

1702
UACCUUUA G UCAUACUU
2355
AAUUAUUC UGAGUAAACUCC CU UCAAUUACAUCGUCCUUU UCAAGUUC
5755

1715
ACUUCAAA G ACUUUUUU
2356
CACACAUU UGAGUAAACUCC CU UCAAGUACAUCUUCCUUU UUUUAAGU
5756

1734
UAAUUAUU G UUAUUAUU
2357
ACUCCUCC UUAGUAAACUCC CU UCAAUUACAUCUUCCGUU ACUCAUUA
5757

1735
AAUGAUUU G UAGGAGUU
2358
AACUCCUC GUAUGAAACUCC CU UCAAUUACAUCUUCCGUG CACUCAUU
5758

1736
AUUAUUUU G AUGAUUUG
2359
CAACUCCU GUAGGAAACUCC CU UCAAUUACAUCUUCCUUU CCACUCAU
5759

1738
UAUUUGUA G GAUUUUUU
2360
CCCAACUC UUAUUAAACUCC CU UCAAUGACAUCUUCCUGG UCCCACUC
5760

1739
AGUGGUAG G AUUUUUUG
2361
CCCCAACU UUAUGAAACUCC CU UCAAUGACAUCUUCCUUU CUCCCACU
5761

1744
UAUGAGUU G GUGUAGGA
2362
UCCUCCCC GUAGGAAACUCC CU UCAAUGACAUCUUCCUUG AACUCCUC
5762

1745
AUUAUUUU G GUGAGUAG
2363
CUCCUCCC GUAUGAAACUCC CU UCAAUUACAUCGUCCUUU CAACUCCU
5763

1746
GGAUUUUU G UGAGGAUG
2364
CCUCCUCC UGAGGAAACUCC CU UCAAGGACAUCUUCCUUU CCAACUCC
5764

1747
GAGUUUGU G UAUGAUGU
2365
ACCUCCUC UUAUUAAACUCC CU UCAAGUACAUCGUCCGGU CCCAACUC
5765

1748
AGUUGGGG G AUUAGUUU
2366
AACCUCCU UGAUUAAACUCC CU UCAAGUACAUCGUCCGGU CCCCAACU
5766

1750
UUUGUGUA G UAUUUUAU
2367
CUAACCUC UGAGUAAACUCC CU UCAAGUACAUCUUCCGGU UCCCCCAA
5767

1751
UGUGUGAG G AUUUUAGU
2368
CCUAACCU UUAUUAAACUCC CU UCAAUUACAUCGUCCGGG CUCCCCCA
5768

1753
GUGGAGGA G UUUAGGUU
2369
AACCUAAC UGAGUAAACUCC CU UCAAUGACAUCUUCCGGG UCCUCCCCU
5769

1758
GGAGGUUA G GUUAAAGC
2370
CCUUUAAC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGC UAACCUCC
5770

1765
AGGUUAAA G GUCUUUGU
2372
ACAAAGAC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UUUAACCU
5771

1778
UUGUACUA G CAGGCUGU
2372
ACACCCUC GCAGGAAACUCC CU UCAAGGACAUCGUCCGGC UAGUACAA
5772

1779
UGUACUAG G AGGCUGUA
2373
UACAGCCU GCAGGAAACUCC CU UCAAGGACAUCGUCCGGG CUAGUACA
5773

1781
UACUAGCA G GCUGUAGG
2374
CCUACAGC GGAGGAAACUCC CU UCAAGGACAUCGUCCCCG UCCUAGUA
5774

1788
AGGCUGUA G GCAUAAAU
2375
AUUUAUGC GGACGAAACUCC CU UCAACGACAUCGUCCGGG UACAGCCU
5775

1798
CAUAAAUU G GUGUCUUC
2376
GAACACAC GGACGAAACUCC CU UCAACGACAUCGUCCGGG AAUUUAUG
5776

1888
UGUGCCUU G GGUGCCUU
2377
AAGCCACC GGAGGAAACUCC CU UCAAGGACAUCGUCCGCG AAGGCACA
5777

1889
GUGCCUUG G GUGGCUUU
2378
AAACCCAC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CAACGCAC
5778

1892
CCUUCGGU G GCUUUGCG
2379
CCCAAAGC CGAGCAAACUCC CU UCAAGGACAUCGUCCGCG ACCCAAGG
5779

1898
GUGGCUUU G GGGCAUGG
2380
CCAUGCCC GGACCAAACUCC CU UCAAGGACAUCGUCCGCC AAAGCCAC
5780

1899
UCGCUUUC G GCCAUGGA
2381
UCCAUCCC GGAGGAAACUCC CU UCAAGGACAUCCUCCCCC CAAAGCCA
5781

1900
GGCUUUGG G CCAUGGAC
2382
GUCCAUGC GGAGGAAACUCC CU UCAAGGACAUCCUCCGCG CCAAAGCC
5782

1905
UCGGGCAU G CACAUUCA
2383
UCAAUCUC CGAGCAAACUCC CU UCAAGCACAUCCUCCGCG AUGCCCCA
5783

1906
CCCCCAUC G ACAUUCAC
2384
CUCAAUGU CGAGCAAACUCC CU UCAAGCACAUCGUCCGCG CAUCCCCC
5784

1924
CCUAUAAA G AAUUUCCA
2385
UCCAAAUU CGACCAAACUCC CU UCAAGCACAUCCUCCGCC UUUAUACC
5785

1930
AACAAUUU G CAGCUUCU
2386
AGAACCUC CGAGCAAACUCC CU UCAAGCACAUCGUCCGGC AAAUUCUU
5786

1931
AGAAUUUC G ACCUUCUC
2387
CACAAGCU CGACCAAACUCC CU UCAAGCACAUCCUCCCGC CAAAUUCU
5787

1941
GCUUCUGU G CAGUUACU
2388
AGUAACUC CGAGCAAACUCC CU UCAAGGACAUCCUCCCGC ACAGAACC
5788

1942
CUUCUGUG G AGUUACUC
2389
GACUAACU CGAGCAAACUCC CU UCAAGCACAUCCUCCCGC CACACAAC
5789

1987
CUAUUCCA G AUCUCCUC
2390
GACGAGAU CGAGGAAACUCC CU UCAAGCACAUCCUCCCGC UCCAAUAG
5790

2018
UCUGUAUC G CGCGGCCU
2391
AGGCCCCC GCAGGAAACUCC CU UCAACCACAUCCUCCCGC CAUACACA
5791

2019
CUCUAUCG G GGCGCCUU
2392
AAGCCCCC GCAGGAAACUCC CU UCAACCACAUCCUCCCGC CGAUACAG
5792

2020
UCUAUCCG G GGCCCUUA
2393
UAAGGCCC GCACGAAACUCC CU UCAAGGACAUCCUCCCGG CCCAUACA
5793

2021
GUAUCGCG G GGCCUUAG
2394
CUAAGGCC GCACGAAACUCC CU UCAAGGACAUCGUCCCGC CCCGAUAC
5794

2022
UAUCGGGG G CCCUUACA
2395
UCUAACCC GCACGAAACUCC CU UCAACGACAUCCUCCCGC CCCCCAUA
5795

2029
CCCCCUUA G ACUCUCCC
2396
CCGACACU GCACCAAACUCC CU UCAACCACAUCCUCCCGC UAACCCCC
5796

2037
GAGUCUCC G CAACAUUG
2397
CAAUGUUC CCACGAAACUCC CU UCAACCACAUCCUCCGCC GGAGACUC
5797

2038
ACUCUCCC G AACAUUCU
2398
ACAAUCUU GCACGAAACUCC CU UCAACGACAUCCUCCCCG CCGAGACU
5798

2061
CACCAUAC G CCACUCAG
2399
CUCAGUCC CCACCAAACUCC CU UCAAGGACAUCCUCCGGG CUAUCCUG
5799

2069
CCCACUCA G CCAACCUA
2400
UACCUUCC CCACCAAACUCC CU UCAACCACAUCGUCCGCG UCACUCCC
5800

2087
UCUCUCUU G CCCUCACU
2401
ACUCACCC CCAGCAAACUCC CU UCAACCACAUCGUCCCCC AACACACA
5801

2088
CUCUCUUC G CCUGACUU
2402
AACUCACC GCAGGAAACUCC CU UCAAGCACAUCCUCCCCC CAACACAC
5802

2089
UCUCUUGC G GUCACUUC
2403
CAACUCAC CGACCAAACUCC CU UCAACCACAUCCUCCCCC CCAACACA
5803

2114
ACCCACCU G GGUCCCAA
2404
UUCCCACC CCACCAAACUCC CU UCAACGACAUCGUCCGCG AGCUGCCU
5804

2115
GCCACCUG G CUCGCAAC
2405
CUUCCCAC CCACCAAACUCC CU UCAACCACAUCCUCCCGC CACGUCCC
5805

2118
ACCUCCCU G CGAACUAA
2406
UUACUUCC CGACCAAACUCC CU UCAAGCACAUCGUCCCGC ACCCACCU
5806

2119
CCUGGGUG G GAAGUAAU
2407
AUUACUUC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CACCCAGG
5807

2120
CUGGGUGG G AAGUAAUU
2408
AAUUACUU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CCACCCAG
5808

2130
AGUAAUUU G GAAGAUCC
2409
GGAUCUUC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AAAUUACU
5809

2131
GUAAUUUG G AACAUCCA
2410
UGGAUCUU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CAAAUUAC
5810

2134
AUUUGGAA G AUCCAGCA
2411
UGCUGGAU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UUCCAAAU
5811

2147
AGCAUCCA G GGAAUUAG
2412
CUAAUUCC GGAGGAAACUCC CU UCAAGGACAUCCUCCGGG UGGAUGCU
5812

2148
GCAUCCAG G GAAUUAGU
2413
ACUAAUUC GGAGGAAACUCC CU UCAAGGACAUCCUCCGGG CUGGAUGC
5813

2149
CAUCCAGG G AAUUAGUA
2414
UACUAAUU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CCUGGAUG
5814

2181
GUUAAUAU G GGCCUAAA
2415
UWUAGGCC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AUAUUAAC
5815

2182
UUAAUAUG G GCCUAAAA
2416
UUUUAGGC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CAUAUUAA
5816

2195
AAAAAUCA G ACAACUAU
2417
AUAGUUGU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UGAUUUUU
5817

2207
ACUAUUGU G GUUUCACA
2418
UGUGAAAC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG ACAAUAGU
5818

2233
UUACUUUU G GGCGAGAA
2419
UUCUCGCC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AAAAGUAA
5819

2234
UACUUUUG G GCGAGAAA
2420
UUUCUCGC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CAAAAGUA
5820

2239
UUGGGCGA G AAACUGUU
2421
AACAGUUU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UCGCCCAA
5821

2259
GAAUAUUU G GUGUCUUU
2422
AAAGACAC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AAAUAUUC
5822

2269
UGUCUUUU G GAGUGUGG
2423
CCACACUC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGC AAAAGACA
5823

2270
GUCUUUUG G AGUGUGGA
2424
UCCACACU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CAAAAGAC
5824

2276
UGGAGUGU G GAUUCGCA
2425
UGCGAAUC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG ACACUCCA
5825

2277
GGAGUGUG G AUUCGCAC
2426
GUGCGAAU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CACACUCC
5826

2300
UGCAUAUA G ACCACCAA
2427
UUGGUGGU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UAUAUGCA
5827

2334
ACACUUCC G GAAACUAC
2428
GUAGUUUC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG GGAAGUGU
5828

2335
CACUUCCG G AAACUACU
2429
AGUAGUUU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CGGAAGUG
5829

2351
UGUUGUUA G ACGAAGAG
2430
CUCUUCGU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UAACAACA
5830

2357
UAGACGAA G AGGCAGGU
2431
ACCUGCCU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UUCGUCUA
5831

2359
GACCAAGA G GCACGUCC
2432
CGACCUGC CGAGCAAACUCC CU UCAACCACAUCGUCCGGG UCUUCCUC
5832

2363
AACACGCA G GUCCCCUA
2433
UACGGGAC GGAGGAAACUCC CU UCAAGGACAUCCUCCGGG UGCCUCUU
5833

2372
GUCCCCUA G AAGAACAA
2434
UUCUUCUU GCAGCAAACUCC CU UCAAGGACAUCCUCCGCG UAGGGGAC
5834

2375
CCCUACAA G AAGAACUC
2435
CAGUUCUU CGAGGAAACUCC CU UCAAGCACAUCCUCCCGG UUCUACGC
5835

2378
UACAAGAA G AACUCCCU
2436
AGGGAGUU GGAGGAAACUCC CU UCAAGGACAUCGUCCCGG UUCUUCUA
5836

2396
GCCUCCCA G ACCAAGGU
2437
ACCUUCCU CCACCAAACUCC CU UCAAGCACAUCGUCCCGC UCCCAGGC
5837

2402
CAGACGAA G GUCUCAAU
2438
AUUGAGAC CGAGGAAACUCC CU UCAAGGACAUCGUCCGGC UUCCUCUG
5838

2423
GCGUCCCA G AAGAUCUC
2439
CAGAUCUU CGAGGAAACUCC CU UCAAGCACAUCCUCCGGG UGCGACGC
5839

2426
UCCCAGAA G AUCUCAAU
2440
AUUGAGAU CGAGCAAACUCC CU UCAAGGACAUCCUCCGCC UUCUCCGA
5840

2438
UCAAUCUC G GGAAUCUC
2441
CAGAUUCC GCACCAAACUCC CU UCAAGCACAUCCUCCGGC GACAUUGA
5841

2439
CAAUCUCG G CAAUCUCA
2442
UGAGAUUC CGAGGAAACUCC CU UCAACGACAUCCUCCGGG CGAGAUUG
5842

2440
AAUCUCGG G AAUCUCAA
2443
UUCACAUU CCAGGAAACUCC CU UCAACGACAUCGUCCCCC CCGAGAUU
5843

2463
UAUUCCUU G GACACAUA
2444
UAUGUGUC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AAGGAAUA
5844

2464
AUUCCUUG G ACACAUAA
2445
UUAUGUGU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CAAGGAAU
5845

2473
ACACAUAA G GUGGGAAA
2446
UUUCCCAC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UUAUGUGU
5846

2476
CAUAAGGU G GGAAACUU
2447
AAGUUUCC GCAGGAAACUCC CU UCAAGGACAUCGUCCGGG ACCUUAUG
5847

2477
AUAAGGUG G GPAACUUU
2448
AAAGUUUC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CACCUUAU
5848

2478
UAAGGUGG G AAACUUUA
2449
UAAAGUUU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CCACCUUA
5849

2488
AACUUUAC G GGGCUUUA
2450
UAAAGCCC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG GUAAAGUU
5850

2489
ACUUUACG G GGCUUUAU
2451
AUAAAGCC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CGUAAAGU
5851

2490
CUUUACGG G GCUUUAUU
2452
AAUAAAGC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CCGUAAAG
5852

2506
UCUUCUAC G GUACCCUG
2453
CAAGGUAC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG GUAGAAGA
5853

2529
UCCUAAAU G GCAAACUC
2454
GAGUUUGC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AUUUAGGA
5854

2563
CAUUUGCA G GAGGACAU
2455
AUGUCCUC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UGCAAAUG
5855

2564
AUUUGCAG G AGGACAUU
2456
AAUGUCCU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CUGCAAAU
5856

2566
UUGCAGGA G GACAUUGU
2457
ACAAUGUC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UCCUGCAA
5857

2567
UGCAGGAG G ACAUUGUU
2458
AACAAUGU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CUCCUGCA
5858

2580
UGUUGAUA G AUGUAAGC
2459
GCUUACAU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UAUCAACA
5859

2596
CAAUUUGU G GGGCCCCU
2460
AGGGGCCC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG ACAAAUUG
5860

2597
AAUUUGUG G GGCCCCUU
2461
AAGGGGCC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CACAAAUU
5861

2598
AUUUGUGG G GCCCCUUA
2462
UAAGGGGC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CCACAAAU
5862

2622
UGAAAACA G GAGACUUA
2463
UAAGUCUC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UGUUUUCA
5863

2623
GAAAACAG G AGACUUAA
2464
UUAAGUCU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CUGUUUUC
5864

2625
AAACAGGA G ACUUAAAU
2465
AUUUAAGU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UCCUGUUU
5865

2649
GCCUGCUA G GUUUUAUC
2466
GAUAAAAC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UAGCAGGC
5866

2684
UGCCCUUA G AUAAAGGG
2467
CCCUUUAU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UAAGGGCA
5867

2690
UAGAUAAA G GGAUCAAA
2468
UUUGAUCC GGAGGAAACUCC CU UCAAGUACAUCGUCCGGG UUUAUCUA
5868

2691
AGAUAAAG G UAUCAAAC
2469
GUUUGAUC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CUUUAUCU
5869

2692
GAUAAAGU G AUCAAACC
2470
GGUUUGAU GGAGUAAACUCC CU UCAAGGACAUCGUCCGGG CCUUUAUC
5870

2711
AUUAUCCA G AGUAUGUA
2471
UACAUACU GGAGGAAACUCC CU UCAAGUACAUCGUCCGGG UGUAUAAU
5871

2737
UACUUCCA G ACGCGACA
2472
UGUCUCGU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UGGAAGUA
5872

2763
CACUCUUU G GAAGGCGG
2473
CCGCCUUC GGAGGAAACUCC CU UCAAGUACAUCUUCCGUG AAAGAGUG
5873

2764
ACUCUUUG G AAGUCGUG
2474
CCCGCCUU GUAGUAAACUCC CU UCAAGGACAUCUUCCGGG CAAAGAGU
5874

2767
CUUUGGAA G GCGGGGAU
2475
AUCCCCGC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UUCCAAAG
5875

2770
UGGAAGUC G GUUAUCUU
2476
AAGAUCCC GUAGUAAACUCC CU UCAAUGACAUCGUCCGGG GCCUUCCA
5876

2771
GGAAGGCG G UGAUCUUA
2477
UAAUAUCC UUAGUAAACUCC CU UCAAUGACAUCGUCCUUG CGCCUUCC
5877

2772
UAAGUCGU G UAUCUUAU
2478
AUAAGAUC UGAGGAAACUCC CU UCAAGGACAUCUUCCGGU CCUCCUUC
5878

2773
AAUGCUGG G AUCUUAUA
2479
UAUAAUAU UGAGGAAACUCC CU UCAAGGACAUCGUCCUGU CCCGCCUU
5879

2787
AUAUAAAA G AGAGUCCA
2480
UGUACUCU UGAGGAAACUCC CU UCAAGUACAUCGUCCGGG UUUUAUAU
5880

2789
AUAAAAGA G AGUCCACA
2481
UGUGGACU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UCUUUUAU
5882

2816
CAUUUUGC G GGUCACCA
2482
UGGUGACC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG GCAAAAUG
5882

2817
AUUUUGCG G GUCACCAU
2483
AUGGUGAC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CGCAAAAU
5883

2832
AUAUUCUU G GGAACAAG
2484
CUUGUUCC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AAGAAUAU
5884

2833
UAUUCUUG G GAACAACA
2485
UCUUGUUC GCAGGAAACUCC CU UCAAGGACAUCGUCCGGG CAACAAUA
5885

2834
AUUCUUGG G AACAAGAU
2486
AUCUUGUU GCACGAAACUCC CU UCAAGGACAUCGUCCGGG CCAAGAAU
5886

2840
GGGAACAA G AUCUACAG
2487
CUGUAGAU GGACGAAACUCC CU UCAAGGACAUCGUCCGGG UUGUUCCC
5887

2852
UACACCAU G GGAGGUUG
2488
CAACCUCC GGAGGAAACUCC CU UCAAGCACAUCGUCCGGG AUGCUGUA
5888

2853
ACAGCAUG G GAGGUUCG
2489
CCAACCUC GGAGGAAACUCC CU UCAAGGACAUCGUCCGCG CAUGCUGU
5889

2854
CAGCAUCG G ACGUUGGU
2490
ACCAACCU GCAGCAAACUCC CU UCAAGCACAUCGUCCGGG CCAUGCUG
5890

2856
CCAUGGGA G GUUGGUCU
2491
ACACCAAC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UCCCAUGC
5891

2860
GGGAGGUU G GUCUUCCA
2492
UCGAACAC GGAGGAAACUCC CU UCAAGCACAUCGUCCGGG AACCUCCC
5892

2880
CUCGAAAA G CCAUCCCG
2493
CCCCAUGC GGAGCAAACUCC CU UCAAGGACAUCGUCCGGG UUUUCGAG
5893

2885
AAAGGCAU G GGGACAAA
2494
UUUCUCCC GGAGCAAACUCC CU UCAAGGACAUCGUCCGCG AUGCCUUU
5894

2886
AAGGCAUG G GGACAAAU
2495
AUUUGUCC GGAGCAAACUCC CU UCAAGGACAUCGUCCGGG CAUGCCUU
5895

2887
ACGCAUGC G GACAAAUC
2496
GAUUUCUC GGAGGAAACUCC CU UCAAGGACAUCGUCCGCG CCAUGCCU
5896

2888
GGCAUGGG G ACAAAUCU
2497
AGAUUUGU CGAGCAAACUCC CU UCAAGGACAUCGUCCGCG CCCAUGCC
5897

2915
AAUCCCCU G GCAUUCUU
2498
AACAAUCC GGAGCAAACUCC CU UCAAGGACAUCGUCCGCG AGGGGAUU
5898

2916
AUCCCCUG G GAUUCUUC
2499
GAACAAUC GGAGCAAACUCC CU UCAAGGACAUCCUCCGCG CAGGGCAU
5899

2917
UCCCCUGG G AUUCUUCC
2500
GGAACAAU CGACCAAACUCC CU UCAAGGACAUCCUCCGGG CCAGGGGA
5900

2939
CAUCAGUU G CACCCUGC
2501
CCAGCGUC CCAGCAAACUCC CU UCAAGCACAUCCUCCGGC AACUGAUC
5901

2940
AUCAGUUG G ACCCUGCA
2502
UGCACGCU GGAGCAAACUCC CU UCAAGGACAUCCUCCGCG CAACUCAU
5902

2973
UAAAUCCA G AUUGGGAC
2503
GUCCCAAU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UGGAUUUA
5903

2977
UCCAGAUU G CGACCUCA
2504
UGAGGUCC GCAGGAAACUCC CU UCAAGGACAUCCUCCGGC AAUCUCGA
5904

2978
CCAGAUUG G GACCUCAA
2505
UUCAGGUC GGACCAAACUCC CU UCAACGACAUCGUCCGGG CAAUCUGC
5905

2979
CACAUUCG G ACCUCAAC
2506
GUUCAGCU GCACGAAACUCC CU UCAACGACAUCCUCCGGG CCAAUCUG
5906

2996
CCGCACAA G GACAACUG
2507
CACUUGUC CCACGAAACUCC CU UCAACGACAUCCUCCCGC UUGUGCGC
5907

2997
CCCACAAG G ACAACUCG
2508
CCACUUCU CCACGAAACUCC CU UCAACCACAUCCUCCCGC CUUGUCCC
5908

3004
GGACAACU G GCCGGACG
2509
CCUCCCCC GCACGAAACUCC CU UCAACGACAUCCUCCGGC AGUUGUCC
5909

3008
AACUGCCC G GACCCCAA
2510
UUGCCGUC GCACGAAACUCC CU UCAACGACAUCCUCCCGC GGCCACUU
5910

3009
ACUCGCCC G ACGCCAAC
2511
GUUCGCCU GCACGAAACUCC CU UCAACGACAUCCUCCCGC CGCCCAGU
5911

3020
GCCAACAA G GUCCGAGU
2512
ACUCCCAC GCACGAAACUCC CU UCAACGACAUCCUCCGGG UUCUUCGC
5912

3023
AACAACCU G GCACUCGC
2513
CCCACUCC GCACGAAACUCC CU UCAACGACAUCCUCCCGC ACCUUGUU
5913

3024
ACAACGUC G CACUCCGA
2514
UCCCACUC CCACCAAACUCC CU UCAACGACAUCCUCCCGC CACCUUCU
5914

3025
CAAGGUCG G AGUCCGAC
2515
CUCCCACU CCACCAAACUCC CU UCAAGCACAUCGUCCCGC CCACCUUC
5915

3029
CUCGCACU G CGAGCAUU
2516
AAUCCUCC GGAGCAAACUCC CU UCAACCACAUCGUCCCGC ACUCCCAC
5916

3030
UGCGACUG G GACCAUUC
2517
GAAUGCUC CGAGCAAACUCC CU UCAACCACAUCGUCCCGC CACUCCCA
5917

3031
GGGAGUGG G AGCAUUCG
2518
CGAAUGCU GGAGGAAACUCC CU UCAAGGACAUCCUCCGGC CCACUCCC
5918

3039
GAGCAUUC G GGCCAGGG
2519
CCCUGGCC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG GAAUGCUC
5919

3040
AGCAUUCG G GCCAGGGU
2520
ACCCUGGC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CGAAUGCU
5920

3045
UCGGGCCA G GGUUCACC
2521
GGUGAACC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UGGCCCGA
5921

3046
CGGGCCAG G GUUCACCC
2522
GGGUGAAC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CUGGCCCG
5922

3063
CUCCCCAU G GGGGACUG
2523
CAGUCCCC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AUGGGGAG
5923

3064
UCCCCAUG G GGGACUGU
2524
ACAGUCCC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CAUGGGGA
5924

3065
CCCCAUGG G GGACUGUU
2525
AACAGUCC GGAGGAAACUCC CU UCAAGCACAUCGUCCGGG CCAUGGGG
5925

3066
CCCAUGGG G GACUGUUG
2526
CAACAGUC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CCCAUGUG
5926

3067
CCAUGGGG G ACUGUUGG
2527
CCAACAGU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CCCCAUGG
5927

3074
GGACUGUU G UGGUGGAG
2528
CUCCACCC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AACAGUCC
5928

3075
GACUGUUG G GGUGGAGC
2529
GCUCCACC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CAACAGUC
5929

3076
ACUGUUGG G GUGGAGCC
2530
GGCUCCAC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CCAACAGU
5930

3079
GUUGGGGU G GAGCCCUC
2531
GAGGGCUC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG ACCCCAAC
5931

3080
UUGGGGUG G AGCCCUCA
2532
UGAGGGCU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CACCCCAA
5932

3095
CACGCUCA G GGCCUACU
2533
AGUAGGCC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UGAGCGUG
5933

3096
ACUCUCAG G UCCUACUC
2534
GAGUAGGC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CUGAGCGU
5934

3145
CACCAAUC G GCAGUCAG
2535
CUGACUGC GUAGGAAACUCC CU UCAAGGACAUCGUCCGGG GACUGGUG
5935

3153
GGCAGUCA G GAAGGCAG
2536
CUGCCUUC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UGACUGCC
5936

3154
GCAGUCAG G AAGGCAUC
2537
GCUUCCUU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CUGACUGC
5937

3157
GUCAGGAA G GCAGCCUA
2538
UAGGCUGC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UUCCUGAC
5938

3187
ACCUCUAA G UGACACUC
2539
GAGUGUCC GGAGUAAACUCC CU UCAAGGACAUCGUCCGGG UUAGAGGU
5939

3188
CCUCUAAG G GACACUCA
2540
UGAGUGUC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CUUAGAGG
5940

3189
CUCUAAGU G ACACUCAU
2541
AUUAGUUU GGAGGAAACUCC CU UCAAUGACAUCUUCCUGG CCUUAUAU
5941

3203
CAUCCUCA G GCCAUUCA
2542
UGCAUUGC GGAGGAAACUCC CU UCAAUGACAUCUUCCGUG UGAUGAUG
5942

Input Sequence = AF100308.

Cut Site = YG/M or UG/U.

Stem Length = 8.

Core Sequence = GGAGGAAACUCC CU UCAAGGACAUCGUCCGG

AF100308 (Hepatitis B virus strain 2-18, 3215 bp)

[0254]

11

TABLE XI

Human HBV Enzymatic Nucleic Acid and Target Sequence

SEQ

Enzymatic nucleic

SEQ

Pos
SUBSTRATE
ID
RPI#
acid Alias
ENZYMATIC NUCLEIC ACID
ID

313
CCAAAAU U CGCAGUC
5943
18157
HBV-313 Rz-7 RNA
GACUGCG CUGAUGAGGCCGUUAGGCCGAA AUUUUGG B
6175

327
CCCAAAU C UCCAGUC
5944
18158
HBV-327 Rz-7 RNA
GACUGGA CUGAUGAGGCCGUUAGGCCGAA AUUUGGG B
6176

334
CUCCAGU C ACUCACC
5945
18159
HBV-334 Rz-7 RNA
GGUGAGU CUGAUGAGGCCGUUAGGCCGAA ACUGGAG B
6177

408
UCUUCCU C UGCAUCC
5946
18160
HBV-408 Rz-7 RNA
GGAUGCA CUGAUGAGGCCGUUAGGCCGAA AGGAAGA B
6178

557
UCUAUGU U UCCCUCA
5947
18161
HBV-557 Rz-7 RNA
UGAGGGA CUGAUGAGGCCGUUAGGCCGAA ACAUAGA B
6179

1255
UUUGUGU C UCCUCUG
5948
18162
HBV-1255 Rz-7 RNA
CAGAGGA CUGAUGAGGCCGUUAGGCCGAA ACACAAA B
6180

1538
CCUCUCU U UACGCGG
5949
18163
HBV-1538 Rz-7 RNA
CCGCGUA CUGAUGAGGCCGUUAGGCCGAA AGAGAGG B
6181

1756
AGGAGGU U AGGUUAA
5950
18164
HBV-1756 Rz-7 RNA
UUAACCU CUGAUGAGGCCGUUAGGCCGAA ACCUCCU B
6182

1861
AUGUCCU A CUGUUCA
5951
18165
HBV-1861 Rz-7 RNA
UGAACAG CUGAUGAGGCCGUUAGGCCGAA AGGACAU B
6183

2504
UUCUUCU A CGGUACC
5952
18166
HBV-2504 Rz-7 RNA
GGUACCG CUGAUGAGGCCGUUAGGCCGAA AGAAGAA B
6184

10
CUCCACC A CUUUCCA
5953
18197
HBV-10 CHz-7 RNA
UGGAAAG CUGAUGAGGCCGUUAGGCCGAA GGUGGAG B
6185

335
UCCAGUC A CUCACCA
5954
18198
HBV-335 CHz-7 RNA
UGGUGAG CUGAUGAGGCCGUUAGGCCGAA GACUGGA B
6186

1258
GUGUCUC C UCUGCCG
5955
18199
HBV-1258 CHz-7 RNA
CGGCAGA CUGAUGAGGCCGUUAGGCCGAA GAGACAC B
6187

2307
GACCACC A AAUGCCC
5956
18200
HBV-2307 CHz-7 RNA
GGGCAUU CUGAUGAGGCCGUUAGGCCGAA GGUGGUC B
6188

347
UCACCAACCU G UUGUC
5957
18216
HBV-347 GCl.Rz-5/10
GACAA UGAUGGCAUGCACUAUGCGCG AGGUUGGUGA B
6189

RNA

350
CCAACCUGUU G UCCUC
5958
18217
HBV-350 GCl.Rz-5/10
GAGGA UGAUGGCAUGCACUAUGCGCG AACAGGUUGG B
6190

RNA

1508
UCCGCCUAUU G UACCG
5959
18218
HBV-1508 GCl.Rz-
CGGUA UGAUGGCAUGCACUAUGCGCG AAUAGGCGGA B
6191

5/10 RNA

234
AAUCCU C ACAAUA
5960
18334
HBV-234 Rz-6 allyl
usasususgu cUGAuGaggccguuaggccGaa Aggauu B
6192

stab1

252
GAGUCU A GACUCG
5961
18335
HBV-252 Rz-6 allyl
csgsasgsuc cUGAuGaggccguuaggccGaa Agacuc B
6193

stab1

268
UGGACU U CUCUCA
5962
18337
HBV-268 Rz-6 allyl
usgsasgsag cUGAuGaggccguuaggccGaa Agucca B
6194

stab1

280
AAUUUU C UAGGGG
5963
18345
HBV-280 Rz-6 allyl
cscscscsua cUGAuGaggccguuaggccGaa Aaaauu B
6195

stab1

313
CAAAAU U CGCAGU
5964
18346
HBV-313 Rz-6 allyl
ascsusgscg cUGAuGaggccguuaggccGaa Auuuug B
6196

stab1

395
GGCGUU U UAUCAU
5965
18350
HBV-395 Rz-6 allyl
asusgsasua cUGAuGaggccguuaggccGaa Aacgcc B
6197

stab1

402
UAUCAU C UUCCUC
5966
18351
HBV-402 Rz-6 allyl
gsasgsgsaa cUGAuGaggccguuaggccGaa Augaua B
6198

stab1

607
UGUAUU C CCAUCC
5967
18355
HBV-607 Rz-6 allyl
gsgsasusgg cUGAuGaggccguuaggccGaa Aauaca B
6199

stab1

697
UUUGUU C AGUGGU
5968
18362
HBV-697 Rz-6 allyl
ascscsascu cUGAuGaggccguuaggccGaa Aacaaa B
6200

stab1

1539
UCUCUU U ACGCGG
5969
18366
HBV-1539 Rz-6 allyl
cscsgscsgu cUGAuGaggccguuaggccGaa Aagaga B
6201

stab1

1599
UCACCU C UGCACG
5970
18367
HBV-1599 Rz-6 allyl
csgsusgsca cUGAuGaggccguuaggccGaa Agguga B
6202

stab1

1607
GCACGU C GCAUGG
5971
18368
HBV-1607 Rz-6 allyl
cscsasusgc cUGAuGaggccguuaggccGaa Acgugc B
6203

stab1

1833
UCACCU C UGCCUA
5972
18371
HBV-1833 Rz-6 allyl
usasgsgsca cUGAuGaggccguuaggccGaa Agguga B
6204

stab1

2383
AGAACU C CCUCGC
5973
18374
HBV-2383 Rz-6 allyl
gscsgsasgg cUGAuGaggccguuaggccGaa Aguucu B
6205

stab1

2429
GAAGAU C UCAAUC
5974
18376
HBV-2429 Rz-6 allyl
gsasususga cUGAuGaggccguuaggccGaa Aucuuc B
6206

stab1

2831
UAUUCU U GGGAAC
5975
18379
HBV-2831 Rz-6 allyl
gsususcscc cUGAuGaggccguuaggccGaa Agaaua B
6207

stab1

430
UGCCUC A UCUUCU
5976
18391
HBV-430 CHz-6 allyl
asgsasasga cUGAuGaggccguuaggccGaa Iaggca B
6208

stab1

676
UGGCUC A GUUUAC
5977
18396
HBV-676 CHz-6 allyl
gsusasasac cUGAuGaggccguuaggccGaa Iagcca B
6209

stab1

683
GUUUAC U AGUGCC
5978
18397
HBV-683 CHz-6 allyl
gsgscsascu cUGAuGaggccguuaggccGaa Iuaaac B
6210

stab1

1150
UUUACC C CGUUGC
5979
18402
HBV-1150 CHz-6
gscsasascg cUGAuGaggccguuaggccGaa Iguaaa B
6211

allyl stab1

1200
GCAACC C CCACUG
5980
18403
HBV-1200 CHz-6
csasgsusgg cUGAuGaggccguuaggccGaa Iguugc B
6212

allyl stab1

1201
CAACCC C CACUGG
5981
18404
HBV-1201 CHz-6
cscsasgsug cUGAuGaggccguuaggccGaa Igguug B
6213

allyl stab1

1444
CGGCGC U GAAUCC
5982
18405
HBV-1444 CHz-6
gsgsasusuc cUGAuGaggccguuaggccGaa Icgccg B
6214

allyl stab1

1451
GAAUCC C GCGGAC
5983
18406
HBV-1451 CHz-6
gsuscscsgc cUGAuGaggccguuaggccGaa Igauuc B
6215

allyl stab1

1533
CGCACC U CUCUUU
5984
18407
HBV-1533 CHz-6
asasasgsag cUGAuGaggccguuaggccGaa Igugcg B
6216

allyl stab1

1600
CACCUC U GCACGU
5985
18410
HBV-1600 CHz-6
ascsgsusgc cUGAuGaggccguuaggccGaa Iaggug B
6217

allyl stab1

1698
CCGACC U UGAGGC
5986
18411
HBV-1698 CHz-6
gscscsusca cUGAuGaggccguuaggccGaa Igucgg B
6218

allyl stab1

1784
GGAGGC U GUAGGC
5987
18412
HBV-1784 CHz-6
gscscsusac cUGAuGaggccguuaggccGaa Iccucc B
6219

allyl stab1

1829
UUUUUC A CCUCUG
5988
18414
HBV-1829 CHz-6
csasgsasgg cUGAuGaggccguuaggccGaa Iaaaaa B
6220

allyl stab1

1876
GCCUCC A AGCUGU
5989
18420
HBV-1876 CHz-6
ascsasgscu cUGAuGaggccguuaggccGaa Igaggc B
6221

allyl stab1

1880
CCAAGC U GUGCCU
5990
18422
HBV-1880 CHz-6
asgsgscsac cUGAuGaggccguuaggccGaa Icuugg B
6222

allyl stab1

218
UUUUUCU U GUUGACA
5991
18333
HBV-218 Rz-7 allyl
usgsuscsaac cUGAuGaggccguuaggccGaa Agaaaaa B
6223

stab1

257
CUAGACU C GUGGUGG
5992
18336
HBV-257 Rz-7 allyl
cscsascscac cUGAuGaggccguuaggccGaa Agucuag B
6224

stab1

268
GUGGACU U CUCUCAA
5993
18338
HBV-268 Rz-7 allyl
ususgsasgag cUGAuGaggccguuaggccGaa Aguccac B
6225

stab1

269
UGGACUU C UCUCAAU
5994
18339
HBV-269 Rz-7 allyl
asususgsaga cUGAuGaggccguuaggccGaa Aagucca B
6226

stab1

271
GACUUCU C UCAAUUU
5995
18340
HBV-271 Rz-7 allyl
asasasusuga cUGAuGaggccguuaggccGaa Agaaguc B
6227

stab1

273
CUUCUCU C AAUUUUC
5996
18341
HBV-273 Rz-7 allyl
gsasasasauu cUGAuGaggccguuaggccGaa Agagaag B
6228

stab1

277
UCUCAAU U UUCUAGG
5997
18342
HBV-277 Rz-7 allyl
cscsusasgaa cUGAuGaggccguuaggccGaa Auugaga B
6229

stab1

278
CUCAAUU U UCUAGGG
5998
18343
HBV-278 Rz-7 allyl
cscscsusaga cUGAuGaggccguuaggccGaa Aauugag B
6230

stab1

279
UCAAUUU U CUAGGGG
5999
18344
HBV-279 Rz-7 allyl
cscscscsuag cUGAuGaggccguuaggccGaa Aaauuga B
6231

stab1

314
CAAAAUU C GCAGUCC
6000
18347
HBV-314 Rz-7 allyl
gsgsascsugc cUGAuGaggccguuaggccGaa Aauuuug B
6232

stab1

385
GAUGUGU C UGCGGCG
6001
18348
HBV-385 Rz-7 allyl
csgscscsgca cUGAuGaggccguuaggccGaa Acacauc B
6233

stab1

394
GCGGCGU U UUAUCAU
6002
18349
HBV-394 Rz-7 allyl
asusgsasuaa cUGAuGaggccguuaggccGaa Acgccgc B
6234

stab1

402
UUAUCAU C UUCCUCU
6003
18352
HBV-402 Rz-7 allyl
asgsasgsgaa cUGAuGaggccguuaggccGaa Augauaa B
6235

stab1

423
UGCUGCU A UGCCUCA
6004
18353
HBV-423 Rz-7 allyl
usgsasgsgca cUGAuGaggccguuaggccGaa Agcagca B
6236

stab1

429
UAUGCCU C AUCUUCU
6005
18354
HBV-429 Rz-7 allyl
asgsasasgau cUGAuGaggccguuaggccGaa Aggcaua B
6237

stab1

679
GCUCAGU U UACUAGU
6006
18356
HBV-679 Rz-7 allyl
ascsusasgua cUGAuGaggccguuaggccGaa Acugagc B
6238

stab1

680
CUCAGUU U ACUAGUG
6007
18357
HBV-680 Rz-7 allyl
csascsusagu cUGAuGaggccguuaggccGaa Aacugag B
6239

stab1

681
UCAGUUU A CUAGUGC
6008
18358
HBV-681 Rz-7 allyl
gscsascsuag cUGAuGaggccguuaggccGaa Aaacuga B
6240

stab1

684
GUUUACU A GUGCCAU
6009
18359
HBV-684 Rz-7 allyl
asusgsgscac cUGAuGaggccguuaggccGaa Aguaaac B
6241

stab1

692
GUGCCAU U UGUUCAG
6010
18360
HBV-692 Rz-7 allyl
csusgsasaca cUGAuGaggccguuaggccGaa Auggcac B
6242

stab1

693
UGCCAUU U GUUCAGU
6011
18361
HBV-693 Rz-7 allyl
ascsusgsaac cUGAuGaggccguuaggccGaa Aauggca B
6243

stab1

1534
CGCACCU C UCUUUAC
6012
18363
HBV-1534 Rz-7 allyl
gsusasasaga cUGAuGaggccguuaggccGaa Aggugcg B
6244

stab1

1536
CACCUCU C UUUACGC
6013
18364
HBV-1536 Rz-7 allyl
gscsgsusaaa cUGAuGaggccguuaggccGaa Agaggug B
6245

stab1

1538
CCUCUCU U UACGCGG
6014
18365
HBV-1538 Rz-7 allyl
cscsgscsgua cUGAuGaggccguuaggccGaa Agagagg B
6246

stab1

1787
AGGCUGU A GGCAUAA
6015
18369
HBV-1787 Rz-7 allyl
ususasusgcc cUGAuGaggccguuaggccGaa Acagccu B
6247

stab1

1793
UAGGCAU A AAUUGGU
6016
18370
HBV-1793 Rz-7 allyl
ascscsasauu cUGAuGaggccguuaggccGaa Augccua B
6248

stab1

1874
CAAGCCU C CAAGCUG
6017
18372
HBV-1874 Rz-7 allyl
csasgscsuug cUGAuGaggccguuaggccGaa Aggcuug B
6249

stab1

1887
UGUGCCU U GGGUGGC
6018
18373
HBV-1887 Rz-7 allyl
gscscsasccc cUGAuGaggccguuaggccGaa Aggcaca B
6250

stab1

2383
AAGAACU C CCUCGCC
6019
18375
HBV-2383 Rz-7 allyl
gsgscsgsagg cUGAuGaggccguuaggccGaa Aguucuu B
6251

stab1

2828
ACCAUAU U CUUGGGA
6020
18377
HBV-2828 Rz-7 allyl
uscscscsaag cUGAuGaggccguuaggccGaa Auauggu B
6252

stab1

2829
CCAUAUU C UUGGGAA
6021
18378
HBV-2829 Rz-7 allyl
ususcscscaa cUGAuGaggccguuaggccGaa Aauaugg B
6253

stab1

2831
AUAUUCU U GGGAACA
6022
18380
HBV-2831 Rz-7 allyl
usgsususccc cUGAuGaggccguuaggccGaa Agaauau B
6254

stab1

256
UCUAGAC U CGUGGUG
6023
18381
HBV-256 CHz-7 allyl
csascscsacg cUGAuGaggccguuaggccGaa Iucuaga B
6255

stab1

267
GGUGGAC U UCUCUCA
6024
18382
HBV-267 CHz-7 allyl
usgsasgsaga cUGAuGaggccguuaggccGaa Iuccacc B
6256

stab1

270
GGACUUC U CUCAAUU
6025
18383
HBV-270 CHz-7 allyl
asasususgag cUGAuGaggccguuaggccGaa Iaagucc B
6257

stab1

272
ACUUCUC U CAAUUUU
6026
18384
HBV-272 CHz-7 allyl
asasasasuug cUGAuGaggccguuaggccGaa Iagaagu B
6258

stab1

274
UUCUCUC A AUUUUCU
6027
18385
HBV-274 CHz-7 allyl
asgsasasaau cUGAuGaggccguuaggccGaa Iagagaa B
6259

stab1

386
AUGUGUC U GCGGCGU
6028
18386
HBV-386 CHz-7 allyl
ascsgscscgc cUGAuGaggccguuaggccGaa Iacacau B
6260

stab1

419
AUCCUGC U GCUAUGC
6029
18387
HBV-419 CHz-7 allyl
gscsasusagc cUGAuGaggccguuaggccGaa Icaggau B
6261

stab1

422
CUGCUGC U AUGCCUC
6030
18388
HBV-422 CHz-7 allyl
gsasgsgscau cUGAuGaggccguuaggccGaa Icagcag B
6262

stab1

427
GCUAUGC C UCAUCUU
6031
18389
HBV-427 CHz-7 allyl
asasgsasuga cUGAuGaggccguuaggccGaa Icauagc B
6263

stab1

428
CUAUGCC U CAUCUUC
6032
18390
HBV-428 CHz-7 allyl
gsasasgsaug cUGAuGaggccguuaggccGaa Igcauag B
6264

stab1

430
AUGCCUC A UCUUCUU
6033
18392
HBV-430 CHz-7 allyl
asasgsasaga cUGAuGaggccguuaggccGaa Iaggcau B
6265

stab1

608
UGUAUUC C CAUCCCA
6034
18393
HBV-608 CHz-7 allyl
usgsgsgsaug cUGAuGaggccguuaggccGaa Iaauaca B
6266

stab1

609
GUAUUCC C AUCCCAU
6035
18394
HBV-609 CHz-7 allyl
asusgsgsgau cUGAuGaggccguuaggccGaa Igaauac B
6267

stab1

669
GUUUCUC U UGGCUCA
6036
18395
HBV-669 CHz-7 allyl
usgsasgscca cUGAuGaggccguuaggccGaa Iagaaac B
6268

stab1

689
CUAGUGC C AUUUGUU
6037
18398
HBV-689 CHz-7 allyl
asascsasaau cUGAuGaggccguuaggccGaa Icacuag B
6269

stab1

690
UAGUGCC A UUUGUUC
6038
18399
HBV-690 CHz-7 aLlyl
gsasascsaaa cUGAuGaggccguuaggccGaa Igcacua B
6270

stab1

718
GCUUUCC C CCACUGU
6039
18400
HBV-718 CHz-7 allyl
ascsasgsugg cUGAuGaggccguuaggccGaa Igaaagc B
6271

stab1

1149
CCUUUAC C CCGUUGC
6040
18401
HBV-1149 CHz-7
gscsasascgg cUGAuGaggccguuaggccGaa Iuaaagg B
6272

allyl stab1

1535
GCACCUC U CUUUACG
6041
18408
HBV-1535 CHz-7
csgsusasaag cUGAuGaggccguuaggccGaa Iaggugc B
6273

allyl stab1

1537
ACCUCUC U UUACGCG
6042
18409
HBV-1537 CHz-7
csgscsgsuaa cUGAuGaggccguuaggccGaa Iagaggu B
6274

allyl stab1

1791
UGUAGGC A UAAAUUG
6043
18413
HBV-1791 CHz-7
csasasusuua cUGAuGaggccguuaggccGaa Iccuaca B
6275

allyl stab1

1831
UUUUCAC C UCUGCCU
6044
18415
HBV-1831 CHz-7
asgsgscsaga cUGAuGaggccguuaggccGaa Iugaaaa B
6276

allyl stab1

1832
UUUCACC U CUGCCUA
6045
18416
HBV-1832 CHz-7
usasgsgscag cUGAuGaggccguuaggccGaa Igugaaa B
6277

allyl stab1

1872
UUCAAGC C UCCAAGC
6046
18417
HBV-1872 CHz-7
gscsususgga cUGAuGaggccguuaggccGaa Icuugaa B
6278

allyl stab1

1873
UCAAGCC U CCAAGCU
6047
18418
HBV-1873 CHz-7
asgscsusugg cUGAuGaggccguuaggccGaa Igcuuga B
6279

allyl stab1

1875
AAGCCUC C AAGCUGU
6048
18419
HBV-1875 CHz-7
ascsasgscuu cUGAuGaggccguuaggccGaa Iaggcuu B
6280

allyl stab1

1876
AGCCUCC A AGCUGUG
6049
18421
HBV-1876 CHz-7
csascsasgcu cUGAuGaggccguuaggccGaa Igaggcu B
6281

allyl stab1

1880
UCCAAGC U GUGCCUU
6050
18423
HBV-1880 CHz-7
asasgsgscac cUGAuGaggccguuaggccGaa Icuugga B
6282

allyl stab1

2382
GAAGAAC U CCCUCGC
6051
18424
HBV-2382 CHz-7
gscsgsasggg cUGAuGaggccguuaggccGaa Iuucuuc B
6283

allyl stab1

2384
AGAACUC C CUCGCCU
6052
18425
HBV-2384 CHz-7
asgsgscsgag cUGAuGaggccguuaggccGaa Iaguucu B
6284

allyl stab1

2385
GAACUCC C UCGCCUC
6053
18426
HBV-2385 CHz-7
gsasgsgscga cUGAuGaggccguuaggccGaa Igaguuc B
6285

allyl stab1

2422
GCGUCGC A GAAGAUC
6054
18427
HBV-2422 CHz-7
gsasuscsuuc cUGAuGaggccguuaggccGaa Icgacgc B
6286

allyl stab1

2830
CAUAUUC U UGGGAAC
6055
18428
HBV-2830 CHz-7
gsususcscca cUGAuGaggccguuaggccGaa Iaauaug B
6287

allyl stab1

234
AAUCCU C ACAAUA
6056
19179
HBV-234 Rz-6 amino
usasususgu cUGAUGaggccguuaggccGaa Aggauu B
6288

stab1

252
GAGUCU A GACUCG
6057
19180
HBV-252 Rz-6 amino
csgsasgsuc cUGAUGaggccguuaggccGaa Agacuc B
6289

stab1

268
UGGACU U CUCUCA
6058
19182
HBV-268 Rz-6 amino
usgsasgsag cUGAUGaggccguuaggccGaa Agucca B
6290

stab1

280
AAUUUU C UAGGGG
6059
19190
HBV-280 Rz-6 amino
cscscscsua cUGAUGaggccguuaggccGaa Aaaauu B
6291

stab1

313
CAAAAU U CGCAGU
6060
19191
HBV-313 Rz-6 amino
ascsusgscg cUGAUGaggccguuaggccGaa Auuuug B
6292

stab1

395
GGCGUU U UAUCAU
6061
19195
HBV-395 Rz-6 amino
asusgsasua cUGAUGaggccguuaggccGaa Aacgcc B
6293

stab1

402
UAUCAU C UUCCUC
6062
19196
HBV-402 Rz-6 amino
gsasgsgsaa cUGAUGaggccguuaggccGaa Augaua B
6294

stab1

607
UGUAUU C CCAUCC
6063
19200
HBV-607 Rz-6 amino
gsgsasusgg cUGAUGaggccguuaggccGaa Aauaca B
6295

stab1

697
UUUGUU C AGUGGU
6064
19207
HBV-697 Rz-6 amino
ascscsascu cUGAUGaggccguuaggccGaa Aacaaa B
6296

stab1

1539
UCUCUU U ACGCGG
6065
19211
HBV-1539 Rz-6 amino
cscsgscsgu cUGAUGaggccguuaggccGaa Aagaga B
6297

stab1

1599
UCACCU C UGCACG
6066
19212
HBV-1599 Rz-6 amino
csgsusgsca cUGAUGaggccguuaggccGaa Agguga B
6298

stab1

1607
GCACGU C GCAUGG
6067
19213
HBV-1607 Rz-6 amino
cscsasusgc cUGAUGaggccguuaggccGaa Acgugc B
6299

stab1

1833
UCACCU C UGCCUA
6068
19216
HBV-1833 Rz-6 amino
usasgsgsca cUGAUGaggccguuaggccGaa Agguga B
6300

stab1

2383
AGAACU C CCUCGC
6069
19219
HBV-2383 Rz-6 amino
gscsgsasgg cUGAUGaggccguuaggccGaa Aguucu B
6301

stab1

2429
GAAGAU C UCAAUC
6070
19221
HBV-2429 Rz-6 amino
gsasususga cUGAUGaggccguuaggccGaa Aucuuc B
6302

stab1

2831
UAUUCU U GGGAAC
6071
19224
HBV-2831 Rz-6 amino
gsususcscc cUGAUGaggccguuaggccGaa Agaaua B
6303

stab1

430
UGCCUC A UCUUCU
6072
19236
HBV-430 CHz-6 amino
asgsasasga cUGAUGaggccguuaggccGaa Iaggca B
6304

stab1

676
UGGCUC A GUUUAC
6073
19241
HBV-676 CHz-6 amino
gsusasasac cUGAUGaggccguuaggccGaa Iagcca B
6305

stab1

683
GUUUAC U AGUGCC
6074
19242
HBV-683 CHz-6 amino
gsgscsascu cUGAUGaggccguuaggccGaa Iuaaac B
6306

stab1

1150
UUUACC C CGUUGC
6075
19247
HBV-1150 CHz-6
gscsasascg cUGAUGaggccguuaggccGaa Iguaaa B
6307

amino stab1

1200
GCAACC C CCACUG
6076
19248
HBV-1200 CHz-6
csasgsusgg cUGAUGaggccguuaggccGaa Iguugc B
6308

amino stab1

1201
CAACCC C CACUGG
6077
19249
HBV-1201 CHz-6
cscsasgsug cUGAUGaggccguuaggccGaa Igguug B
6309

amino stab1

1444
CGGCGC U GAAUCC
6078
19250
HBV-1444 CHz-6
gsgsasusuc cUGAUGaggccguuaggccGaa Icgccg B
6310

amino stab1

1451
GAAUCC C GCGGAC
6079
19251
HBV-1451 CHz-6
gsuscscsgc cUGAUGaggccguuaggccGaa Igauuc B
6311

amino stab1

1533
CGCACC U CUCUUU
6080
19252
HBV-1533 CHz-6
asasasgsag cUGAUGaggccguuaggccGaa Igugcg B
6312

amino stab1

1600
CACCUC U GCACGU
6081
19255
HBV-1600 CHz-6
ascsgsusgc cUGAUGaggccguuaggccGaa Iaggug B
6313

amino stab1

1698
CCGACC U UGAGGC
6082
19256
HBV-1698 CHz-6
gscscsusca cUGAUGaggccguuaggccGaa Igucgg B
6314

amino stab1

1784
GGAGGC U GUAGGC
6083
19257
HBV-1784 CHz-6
gscscsusac cUGAUGaggccguuaggccGaa Iccucc B
6315

amino stab1

1829
UUUUUC A CCUCUG
6084
19259
HBV-1829 CHz-6
csasgsasgg cUGAUGaggccguuaggccGaa Iaaaaa B
6316

amino stab1

1876
GCCUCC A AGCUGU
6085
19265
HBV-1876 CHz-6
ascsasgscu cUGAUGaggccguuaggccGaa Igaggc B
6317

amino stab1

1880
CCAAGC U GUGCCU
6086
19267
HBV-1880 CHz-6
asgsgscsac cUGAUGaggccguuaggccGaa Icuugg B
6318

amino stab1

218
UUUUUCU U GUUGACA
6087
19178
HBV-218 Rz-7 amino
usgsuscsaac cUGAUGaggccguuaggccGaa Agaaaaa B
6319

stab1

257
CUAGACU C GUGGUGG
6088
19181
HBV-257 Rz-7 amino
cscsascscac cUGAUGaggccguuaggccGaa Agucuag B
6320

stab1

268
GUGGACU U CUCUCAA
6089
19183
HBV-268 Rz-7 amino
ususgsasgag cUGAUGaggccguuaggccGaa Aguccac B
6321

stab1

269
UGGACUU C UCUCAAU
6090
19184
HBV-269 Rz-7 amino
asususgsaga cUGAUGaggccguuaggccGaa Aagucca B
6322

stab1

271
GACUUCU C UCAAUUU
6091
19185
HBV-271 Rz-7 amino
asasasusuga cUGAUGaggccguuaggccGaa Agaaguc B
6323

stab1

273
CUUCUCU C AAUUUUC
6092
19186
HBV-273 Rz-7 amino
gsasasasauu cUGAUGaggccguuaggccGaa Agagaag B
6324

stab1

277
UCUCAAU U UUCUAGG
6093
19187
HBV-277 Rz-7 amino
cscsusasgaa cUGAUGaggccguuaggccGaa Auugaga B
6325

stab1

278
CUCAAUU U UCUAGGG
6094
19188
HBV-278 Rz-7 amino
cscscsusaga cUGAUGaggccguuaggccGaa Aauugag B
6326

stab1

279
UCAAUUU U CUAGGGG
6095
19189
HBV-279 Rz-7 amino
cscscscsuag cUGAUGaggccguuaggccGaa Aaauuga B
6327

stab1

314
CAAAAUU C GCAGUCC
6096
19192
HBV-314 Rz-7 amino
gsgsascsugc cUGAUGaggccguuaggccGaa Aauuuug B
6328

stab1

385
GAUGUGU C UGCGGCG
6097
19193
HBV-385 Rz-7 amino
csgscscsgca cUGAUGaggccguuaggccGaa Acacauc B
6329

stab1

394
GCGGCGU U UUAUCAU
6098
19194
HBV-394 Rz-7 amino
asusgsasuaa cUGAUGaggccguuaggccGaa Acgccgc B
6330

stab1

402
UUAUCAU C UUCCUCU
6099
19197
HBV-402 Rz-7 amino
asgsasgsgaa cUGAUGaggccguuaggccGaa Augauaa B
6331

stab1

423
UGCUGCU A UGCCUCA
6100
19198
HBV-423 Rz-7 amino
usgsasgsgca cUGAUGaggccguuaggccGaa Agcagca B
6332

stab1

429
UAUGCCU C AUCUUCU
6101
19199
HBV-429 Rz-7 amino
asgsasasgau cUGAUGaggccguuaggccGaa Aggcaua B
6333

stab1

679
GCUCAGU U UACUAGU
6102
19201
HBV-679 Rz-7 amino
ascsusasgua cUGAUGaggccguuaggccGaa Acugagc B
6334

stab1

680
CUCAGUU U ACUAGUG
6103
19202
HBV-680 Rz-7 amino
csascsusagu cUGAUGaggccguuaggccGaa Aacugag B
6335

stab1

681
UCAGUUU A CUAGUGC
6104
19203
HBV-681 Rz-7 amino
gscsascsuag cUGAUGaggccguuaggccGaa Aaacuga B
6336

stab1

684
GUUUACU A GUGCCAU
6105
19204
HBV-684 Rz-7 amino
asusgsgscac cUGAUGaggccguuaggccGaa Aguaaac B
6337

stab1

692
GUGCCAU U UGUUCAG
6106
19205
HBV-692 Rz-7 amino
csusgsasaca cUGAUGaggccguuaggccGaa Auggcac B
6338

stab1

693
UGCCAUU U GUUCAGU
6107
19206
HBV-693 Rz-7 amino
ascsusgsaac cUGAUGaggccguuaggccGaa Aauggca B
6339

stab1

1534
CGCACCU C UCUUUAC
6108
19208
HBV-1534 Rz-7 amino
gsusasasaga cUGAUGaggccguuaggccGaa Aggugcg B
6340

stab1

1536
CACCUCU C UUUACGC
6109
19209
HBV-1536 Rz-7 amino
gscsgsusaaa cUGAUGaggccguuaggccGaa Agaggug B
6341

stab1

1538
CCUCUCU U UACGCGG
6110
19210
HBV-1538 Rz-7 amino
cscsgscsgua cUGAUGaggccguuaggccGaa Agagagg B
6342

stab1

1787
AGGCUGU A GGCAUAA
6111
19214
HBV-1787 Rz-7 amino
ususasusgcc cUGAUGaggccguuaggccGaa Acagccu B
6343

stab1

1793
UAGGCAU A AAUUGGU
6112
19215
HBV-1793 Rz-7 amino
ascscsasauu cUGAUGaggccguuaggccGaa Augccua B
6344

stab1

1874
CAAGCCU C CAAGCUG
6113
19217
HBV-1874 Rz-7 amino
csasgscsuug cUGAUGaggccguuaggccGaa Aggcuug B
6345

stab1

1887
UGUGCCU U GGGUGGC
6114
19218
HBV-1887 Rz-7 amino
gscscsasccc cUGAUGaggccguuaggccGaa Aggcaca B
6346

stab1

2383
AAGAACU C CCUCGCC
6115
19220
HBV-2383 Rz-7 amino
gsgscsgsagg cUGAUGaggccguuaggccGaa Aguucuu B
6347

stab1

2828
ACCAUAU U CUUGGGA
6116
19222
HBV-2828 Rz-7 amino
uscscscsaag cUGAUGaggccguuaggccGaa Auauggu B
6348

stab1

2829
CCAUAUU C UUGGGAA
6117
19223
HBV-2829 Rz-7 amino
ususcscscaa cUGAUGaggccguuaggccGaa Aauaugg B
6349

stab1

2831
AUAUUCU U GGGAACA
6118
19225
HBV-2831 Rz-7 amino
usgsususccc cUGAUGaggccguuaggccGaa Agaauau B
6350

stab1

256
UCUAGAC U CGUGGUG
6119
19226
HBV-256 CHz-7 amino
csascscsacg cUGAUGaggccguuaggccGaa Iucuaga B
6351

stab1

267
GGUGGAC U UCUCUCA
6120
19227
HBV-267 CHz-7 amino
usgsasgsaga cUGAUGaggccguuaggccGaa Iuccacc B
6352

stab1

270
GGACUUC U CUCAAUU
6121
19228
HBV-270 CHz-7 amino
asasususgag cUGAUGaggccguuaggccGaa Iaagucc B
6353

stab1

272
ACUUCUC U CAAUUUU
6122
19229
HBV-272 CHz-7 amino
asasasasuug cUGAUGaggccguuaggccGaa Iagaagu B
6354

stab1

274
UUCUCUC A AUUUUCU
6123
19230
HBV-274 CHz-7 amino
asgsasasaau cUGAUGaggccguuaggccGaa Iagagaa B
6355

stab1

386
AUGUGUC U GCGGCGU
6124
19231
HBV-386 CHz-7 amino
ascsgscscgc cUGAUGaggccguuaggccGaa Iacacau B
6356

stab1

419
AUCCUGC U GCUAUGC
6125
19232
HBV-419 CHz-7 amino
gscsasusagc cUGAUGaggccguuaggccGaa Icaggau B
6357

stab1

422
CUGCUGC U AUGCCUC
6126
19233
HBV-422 CHz-7 amino
gsasgsgscau cUGAUGaggccguuaggccGaa Icagcag B
6358

stab1

427
GCUAUGC C UCAUCUU
6127
19234
HBV-427 CHz-7 amino
asasgsasuga cUGAUGaggccguuaggccGaa Icauagc B
6359

stab1

428
CUAUGCC U CAUCUUC
6128
19235
HBV-428 CHz-7 amino
gsasasgsaug cUGAUGaggccguuaggccGaa Igcauag B
6360

stab1

430
AUGCCUC A UCUUCUU
6129
19237
HBV-430 CHz-7 amino
asasgsasaga cUGAUGaggccguuaggccGaa Iaggcau B
6361

stab1

608
UGUAUUC C CAUCCCA
6130
19238
HBV-608 CHz-7 amino
usgsgsgsaug cUGAUGaggccguuaggccGaa Iaauaca B
6362

stab1

609
GUAUUCC C AUCCCAU
6131
19239
HBV-609 CHz-7 amino
asusgsgsgau cUGAUGaggccguuaggccGaa Igaauac B
6363

stab1

669
GUUUCUC U UGGCUCA
6132
19240
HBV-669 CHz-7 amino
usgsasgscca cUGAUGaggccguuaggccGaa Iagaaac B
6364

stab1

689
CUAGUGC C AUUUGUU
6133
19243
HBV-689 CHz-7 amino
asascsasaau cUGAUGaggccguuaggccGaa Icacuag B
6365

stab1

690
UAGUGCC A UUUGUUC
6134
19244
HBV-690 CHz-7 amino
gsasascsaaa cUGAUGaggccguuaggccGaa Igcacua B
6366

stab1

718
GCUUUCC C CCACUGU
6135
19245
HBV-718 CHz-7 amino
ascsasgsugg cUGAUGaggccguuaggccGaa Igaaagc B
6367

stab1

1149
CCUUUAC C CCGUUGC
6136
19246
HBV-1149 CHz-7
gscsasascgg cUGAUGaggccguuaggccGaa Iuaaagg B
6368

amino stab1

1535
GCACCUC U CUUUACG
6137
19253
HBV-1535 CHz-7
csgsusasaag cUGAUGaggccguuaggccGaa Iaggugc B
6369

amino stab1

1537
ACCUCUC U UUACGCG
6138
19254
HBV-1537 CHz-7
csgscsgsuaa cUGAUGaggccguuaggccGaa Iagaggu B
6370

amino stab1

1791
UGUAGGC A UAAAUUG
6139
19258
HBV-1791 CHz-7
csasasusuua cUGAUGaggccguuaggccGaa Iccuaca B
6371

amino stab1

1831
UUUUCAC C UCUGCCU
6140
19260
HBV-1831 CHz-7
asgsgscsaga cUGAUGaggccguuaggccGaa Iugaaaa B
6372

amino stab1

1832
UUUCACC U CUGCCUA
6141
19261
HBV-1832 CHz-7
usasgsgscag cUGAUGaggccguuaggccGaa Igugaaa B
6373

amino stab1

1872
UUCAAGC C UCCAAGC
6142
19262
HBV-1872 CHz-7
gscsususgga cUGAUGaggccguuaggccGaa Icuugaa B
6374

amino stab1

1873
UCAAGCC U CCAAGCU
6143
19263
HBV-1873 CHz-7
asgscsusugg cUGAUGaggccguuaggccGaa Igcuuga B
6375

amino stab1

1875
AAGCCUC C AAGCUGU
6144
19264
HBV-1875 CHz-7
ascsasgscuu cUGAUGaggccguuaggccGaa Iaggcuu B
6376

amino stab1

1876
AGCCUCC A AGCUGUG
6145
19266
HBV-1876 CHz-7
csascsasgcu cUGAUGaggccguuaggccGaa Igaggcu B
6377

amino stab1

1880
UCCAAGC U GUGCCUU
6146
19268
HBV-1880 CHz-7
asasgsgscac cUGAUGaggccguuaggccGaa Icuugga B
6378

amino stab1

2382
GAAGAAC U CCCUCGC
6147
19269
HBV-2382 CHz-7
gscsgsasggg cUGAUGaggccguuaggccGaa Iuucuuc B
6379

amino stab1

2384
AGAACUC C CUCGCCU
6148
19270
HBV-2384 CHz-7
asgsgscsgag cUGAUGaggccguuaggccGaa Iaguucu B
6380

amino stab1

2385
GAACUCC C UCGCCUC
6149
19271
HBV-2385 CHz-7
gsasgsgscga cUGAUGaggccguuaggccGaa Igaguuc B
6381

amino stab1

2422
GCGUCGC A GAAGAUC
6150
19272
HBV-2422 CHz-7
gsasuscsuuc cUGAUGaggccguuaggccGaa Icgacgc B
6382

amino stab1

2830
CAUAUUC U UGGGAAC
6151
19273
HBV-2830 CHz-7
gsususcscca cUGAUGaggccguuaggccGaa Iaauaug B
6383

amino stab1

315
GCCAAAAUUC G CAGUC
6152
20079
HBV-315 GCl.Rz-5/10
gsascsg uGAUsg gcauGcacuaugc gcg gaauuuuggc B
6384

stab2

381
AUCGCUGGAU G UGUCU
6153
20080
HBV-381 GCl.Rz-5/10
asgsasa uGAUsg gcauGcacuaugc gcg auccagcgau B
6385

stab2

476
UUGCCCGUUU G UCCUC
6154
20081
HBV-476 GCl.Rz-5/10
gsasgsa uGAUsg gcauGcacuaugc gcg aaacgggcaa B
6386

stab2

694
AGUGCCAUUU G UUCAG
6155
20082
HBV-694 GCl.Rz-5/10
csusgsa uGAUsg gcauGcacuaugc gcg aaauggcacu B
6387

stab2

1265
CUCCUCUGCC G AUCCA
6156
20083
HBV-1265 GCl.Rz-
usgsgsu uGAUsg gcauGcacuaugc gcg ggcagaggag B
6388

5/10 stab2

1601
CUUCACCUCU G CACGU
6157
20084
HBV-1601 GCl.Rz-
ascsgsg uGAUsg gcauGcacuaugc gcg agaggugaag B
6389

5/10 stab2

1881
CCUCCAAGCU G UGCCU
6158
20085
HBV-1881 GCl.Rz-
asgsgsa uGAUsg gcauGcacuaugc gcg agcuuggagg B
6390

5/10 stab2

1883
UCCAAGCUGU G CCUUG
6159
20086
HBV-1883 GCl.Rz-
csasasg uGAUsg gcauGcacuaugc gcg acagcuugga B
6391

5/10 stab2

2388
GAACUCCCUC G CCUCG
6160
20087
HBV-2388 GCl.Rz-
csgsasg uGAUsg gcauGcacuaugc gcg gagggaguuc B
6392

5/10 stab2

381
GCUGGAU G UGUCUGC
6161
20091
HBV-381 Zin.Rz-7
gscsasgsaca GccgaaagGCGaGugaGGuCu auccagc B
6393

amino stab2

392
CUGCGGC G UUUUAUC
6162
20092
HBV-392 Zin.Rz-7
gsasusasaaa GccgaaagGCGaGugaGGuCu gccgcag B
6394

amino stab2

420
UCCUGCU G CUAUGCC
6163
20093
HBV-420 Zin.Rz-7
gsgscsasuag GccgaaagGCGaGugaGGuCu agcagga B
6395

amino stab2

648
UAUGGGA G UGGGCCU
6164
20094
HBV-648 Zin.Rz-7
asgsgscscca GccgaaagGCGaGugaGGuCu ucccaua B
6396

amino stab2

711
UCGUAGG G CUUUCCC
6165
20095
HBV-711 Zin.Rz-7
gsgsgsasaag GccgaaagGCGaGugaGGuCu ccuacga B
6397

amino stab2

1262
CUCCUCU G CCGAUCC
6166
20096
HBV-1262 Zin.Rz-7
gsgsasuscgg GccgaaagGCGaGugaGGuCu agaggag B
6398

amino stab2

1835
CACCUCU G CCUAAUC
6167
20097
HBV-1835 Zin.Rz-7
gsasususagg GccgaaagGCGaGugaGGuCu agaggug B
6399

amino stab2

2388
CUCCCUC G CCUCGCA
6168
20098
HBV-2388 Zin.Rz-7
usgscsgsagg GccgaaagGCGaGugaGGuCu gagggag B
6400

amino stab2

192
GACCCCU G CUCGUGU
6169
20099
HBV-192 Zin.Rz-7
ascsascsgag GccgaaagGCGaGugaGGuCu agggguc B
6401

amino stab2

198
UGCUCGU G UUACAGG
6170
20100
HBV-198 Zin.Rz-7
cscsusgsuaa GccgaaagGCGaGugaGGuCu acgagca B
6402

amino stab2

315
AAAUUC G CAGUCC
6171
20101
HBV-315 Zin.Rz-7
gsgsgsascug GccgaaagGCGaGugaGGuCu gaauuuu B
6403

amino stab2

383
GGAUGU G UCUGCG
6172
20102
HBV-383 Zin.Rz-6
csgscsasga GccgaaagGCGaGugaGGuCu acaucc B
6404

amino stab2

383
UGGAUGU G UCUGCGG
6173
20103
HBV-383 Zin.Rz-7
cscsgscsaga GccgaaagGCGaGugaGGuCu acaucca B
6405

amino stab2

387
GUGUCU G CGGCGU
6174
20104
HBV-387 Zin.Rz-6
ascsgscscg GccgaaagGCGaGugaGGuCu agacac B
6406

amino stab2

390
GUCUGCG G CGUUUUA
6175
20105
HBV-390 Zin.Rz-7
usasasasacg GccgaaagGCGaGugaGGuCu cgcagac B
6407

amino stab2

392
UGCGGC G UUUUAU
6176
20106
HBV-392 Zin.Rz-6
asusasasaa GccgaaagGCGaGugaGGuCu gccgca B
6408

amino stab2

425
UGCUAU G CCUCAU
6177
20107
HBV-425 Zin.Rz-6
asusgsasgg GccgaaagGCGaGugaGGuCu auagca B
6409

amino stab2

425
CUGCUAU G CCUCAUC
6178
20108
HBV-425 Zin.Rz-7
gsasusgsagg GccgaaagGCGaGugaGGuCu auagcag B
6410

amino stab2

468
GUAUGUU G CCCGUUU
6179
20109
HBV-468 Zin.Rz-7
asasascsagg GccgaaagGCGaGugaGGuCu aacauac B
6411

amino stab2

476
CCCGUUU G UCCUCUA
6180
20110
HBV-476 Zin.Rz-7
usasgsasgga GccgaaagGCGaGugaGGuCu aaacggg B
6412

amino stab2

648
AUGGGA G UGGGCC
6181
20111
HBV-648 Zin.Rz-6
gsgscscsca GccgaaagGCGaGugaGGuCu ucccau B
6413

amino stab2

694
GCCAUUU G UUCAGUG
6182
20112
HBV-694 Zin.Rz-7
csascsusgaa GccgaaagGCGaGugaGGuCu aaauggc B
6414

amino stab2

699
UUGUUCA G UGGUUCG
6183
20113
HBV-699 Zin.Rz-7
csgsasascca GccgaaagGCGaGugaGGuCu ugaacaa B
6415

amino stab2

1262
UCCUCU G CCGAUC
6184
20114
HBV-1262 Zin.Rz-6
gsasuscsgg GccgaaagGCGaGugaGGuCu agagga B
6416

amino stab2

1440
CCCGUCG G CGCUGAA
6185
20115
HBV-1440 Zin.Rz-7
ususcsasgcg GccgaaagGCGaGugaGGuCu cgacggg B
6417

amino stab2

1526
CACGGG G CGCACC
6186
20116
HBV-1526 Zin.Rz-6
gsgsusgscg GccgaaagGCGaGugaGGuCu cccgug B
6418

amino stab2

1526
CCACGGG G CGCACCU
6187
20117
HBV-1526 Zin.Rz-7
asgsgsusgcg GccgaaagGCGaGugaGGuCu cccgugg B
6419

amino stab2

1557
CCCGUCU G UGCCUUC
6188
20118
HBV-1557 Zin.Rz-7
gsasasgsgca GccgaaagGCGaGugaGGuCu agacggg B
6420

amino stab2

1559
CGUCUGU G CCUUCUC
6189
20119
HBV-1559 Zin.Rz-7
gsasgsasagg GccgaaagGCGaGugaGGuCu acagacg B
6421

amino stab2

1590
GCACUUC G CUUCACC
6190
20120
HBV-1590 Zin.Rz-7
gsgsusgsaag GccgaaagGCGaGugaGGuCu gaagugc B
6422

amino stab2

1835
ACCUCU G CCUAAU
6191
20121
HBV-1835 Zin.Rz-6
asususasgg GccgaaagGCGaGugaGGuCu agaggu B
6423

amino stab2

2311
ACCAAAU G CCCCUAU
6192
20122
HBV-2311 Zin.Rz-7
asusasgsggg GccgaaagGCGaGugaGGuCu auuuggu B
6424

amino stab2

2420
CCGCGUC G CAGAAGA
6193
20123
HBV-2420 Zin.Rz-7
uscsususcug GccgaaagGCGaGugaGGuCu gacgcgg B
6425

amino stab2

65
CCUGCUG G UGGCUCC
6194
20124
HBV-65 Zin.Rz-7
gsgsasgscca GccgaaagGCGaGugaGGuCu cagcagg B
6426

amino stab2

192
ACCCCU G CUCGUG
6195
20125
HBV-192 Zin.Rz-6
csascsgsag GccgaaagGCGaGugaGGuCu aggggu B
6427

amino stab2

198
GCUCGU G UUACAG
6196
20126
HBV-198 Zin.Rz-6
csusgsusaa GccgaaagGCGaGugaGGuCu acgagc B
6428

amino stab2

258
UAGACUC G UGGUGGA
6197
20127
HBV-258 Zin.Rz-7
uscscsascca GccgaaagGCGaGugaGGuCu gagucua B
6429

amino stab2

261
ACUCGUG G UGGACUU
6198
20128
HBV-261 Zin.Rz-7
asasgsuscca GccgaaagGCGaGugaGGuCu cacgagu B
6430

amino stab2

315
AAAUUC G CAGUCC
6199
20129
HBV-315 Zin.Rz-6
gsgsascsug GccgaaagGCGaGugaGGuCu gaauuu B
6431

amino stab2

381
CUGGAU G UGUCUG
6200
20130
HBV-381 Zin.Rz-6
csasgsasca GccgaaagGCGaGugaGGuCu auccag B
6432

amino stab2

387
UGUGUCU G CGGCGUU
6201
20131
HBV-387 Zin.Rz-7
asascsgsccg GccgaaagGCGaGugaGGuCu agacaca B
6433

amino stab2

390
UCUGCG G CGUUUU
6202
20132
HBV-390 Zin.Rz-6
asasasascg GccgaaagGCGaGugaGGuCu cgcaga B
6434

amino stab2

417
CAUCCU G CUGCUA
6203
20133
HBV-417 Zin.Rz-6
usasgscsag GccgaaagGCGaGugaGGuCu aggaug B
6435

amino stab2

420
CCUGCU G CUAUGC
6204
20134
HBV-420 Zin.Rz-6
gscsasusag GccgaaagGCGaGugaGGuCu agcagg B
6436

amino stab2

468
UAUGUU G CCCGUU
6205
20135
HBV-468 Zin.Rz-6
asascsgsgg GccgaaagGCGaGugaGGuCu aacaua B
6437

amino stab2

476
CCGUUU G UCCUCU
6206
20136
HBV-476 Zin.Rz-6
asgsasgsga GccgaaagGCGaGugaGGuCu aaacgg B
6438

amino stab2

677
GGCUCA G UUUACU
6207
20137
HBV-677 Zin.Rz-6
asgsusasaa GccgaaagGCGaGugaGGuCu ugagcc B
6439

amino stab2

677
UGGCUCA G UUUACUA
6209
20138
HBV-677 Zin.Rz-7
usasgsusaaa GccgaaagGCGaGugaGGuCu ugagoca B
6440

amino stab2

685
UUACUA G UGCCAU
6209
20139
HBV-685 Zin.Rz-6
asusgsgsca GccgaaagGCGaGugaGGuCu uaguaa B
6441

amino stab2

685
UUUACUA G UGCCAUU
6210
20140
HBV-685 Zin.Rz-7
asasusgsgca GccgaaagGCGaGugaGGuCu uaguaaa B
6442

amino stab2

687
UACUAGU G CCAUUUG
6211
20141
HBV-687 Zin.Rz-7
csasasasugg GccgaaagGCGaGugaGGuCu acuagua B
6443

amino stab2

699
UGUUCA G UGGUUC
6212
20142
HBV-699 Zin.Rz-6
gsasascsca GccgaaagGCGaGugaGGuCu ugaaca B
6444

amino stab2

702
UCAGUG G UUCGUA
6213
20143
HBV-702 Zin.Rz-6
usascsgsaa GccgaaagGCGaGugaGGuCu cacuga B
6445

amino stab2

702
UUCAGUG G UUCGUAG
6214
20144
HBV-702 Zin.Rz-7
csusascsgaa GccgaaagGCGaGugaGGuCu cacugaa B
6446

amino stab2

711
CGUAGG G CUUUCC
6215
20145
HBV-711 Zin.Rz-6
gsgsasasag GccgaaagGCGaGugaGGuCu ccuacg B
6447

amino stab2

1006
UUGUGG G UCUUUU
6216
20146
HBV-1006 Zin.Rz-6
asasasasga GccgaaagGCGaGugaGGuCu ccacaa B
6448

amino stab2

1103
UUUCUC G CCAACU
6217
20147
HBV-1103 Zin.Rz-6
asgsususgg GccgaaagGCGaGugaGGuCu gagaaa B
6449

amino stab2

1103
CUUUCUC G CCAACUU
6218
20148
HBV-1103 Zin.Rz-7
asasgsusugg GccgaaagGCGaGugaGGuCu gagaaag B
6450

amino stab2

1184
GCCAAGU G UUUGCUG
6219
20149
HBV-1184 Zin.Rz-7
csasgscsaaa GccgaaagGCGaGugaGGuCu acuuggc B
6451

amino stab2

1440
CCGUCG G CGCUGA
6220
20150
HBV-1440 Zin.Rz-6
uscsasgscg GccgaaagGCGaGugaGGuCu cgacgg B
6452

amino stab2

1442
GUCGGC G CUGAAU
6221
20151
HBV-1442 Zin.Rz-6
asususcsag GccgaaagGCGaGugaGGuCu gccgac B
6453

amino stab2

1442
CGUCGGC G CUGAAUC
6222
20152
HBV-1442 Zin.Rz-7
gsasususcag GccgaaagGCGaGugaGGuCu gccgacg B
6454

amino stab2

1553
CUCCCC G UCUGUG
6223
20153
HBV-1553 Zin.Rz-6
csascsasga GccgaaagGCGaGugaGGuCu ggggag B
6455

amino stab2

1557
CCGUCU G UGCCUU
6224
20154
HBV-1557 Zin.Rz-6
asasgsgsca GccgaaagGCGaGugaGGuCu agacgg B
6456

amino stab2

1559
GUCUGU G CCUUCU
6225
20155
HBV-1559 Zin.Rz-6
asgsasasgg GccgaaagGCGaGugaGGuCu acagac B
6457

amino stab2

1583
CCGUGU G CACUUC
6226
20156
HBV-1583 Zin.Rz-6
gsasasgsug GccgaaagGCGaGugaGGuCu acacgg B
6458

amino stab2

1590
CACUUC G CUUCAC
6227
20157
HBV-1590 Zin.Rz-6
gsusgsasag GccgaaagGCGaGugaGGuCu gaagug B
6459

amino stab2

1622
ACCACC G UGAACG
6228
20158
HBV-1622 Zin.Rz-6
csgsususca GccgaaagGCGaGugaGGuCu gguggu B
6460

amino stab2

1870
UGUUCAA G CCUCCAA
6229
20159
HBV-1870 Zin.Rz-7
ususgsgsagg GccgaaagGCGaGugaGGuCu uugaaca B
6461

amino stab2

1881
CCAAGCU G UGCCUUG
6230
20160
HBV-1881 Zin.Rz-7
csasasgsgca GccgaaagGCGaGugaGGuCu agcuugg B
6462

amino stab2

1883
AGCUGU G CCUUGG
6231
20161
HBV-1883 Zin.Rz-6
cscsasasgg GccgaaagGCGaGugaGGuCu acagcu B
6463

amino stab2

1883
AAGCUGU G CCUUGGG
6232
20162
HBV-1883 Zin.Rz-7
cscscsasagg GccgaaagGCGaGugaGGuCu acagcuu B
6464

amino stab2

2311
CCAAAU G CCCCUA
6233
20163
HBV-2311 Zin.Rz-6
usasgsgsgg GccgaaagGCGaGugaGGuCu auuugg B
6465

amino stab2

2347
ACUGUU G UUAGAC
6234
20164
HBV-2347 Zin.Rz-6
gsuscsusaa GccgaaagGCGaGugaGGuCu aacagu B
6466

amino stab2

2364
AGGCAG G UCCCCU
6235
20165
HBV-2364 Zin.Rz-6
asgsgsgsga GccgaaagGCGaGugaGGuCu cugccu B
6467

amino stab2

2364
GAGGCAG G UCCCCUA
6236
20166
HBV-2364 Zin.Rz-7
usasgsgsgga GccgaaagGCGaGugaGGuCu cugccuc B
6468

amino stab2

2388
UCCUC G CCUCGC
6237
20167
HBV-2388 Zin.Rz-6
gscsgsasgg GccgaaagGCGaGugaGGuCu gaggga B
6469

amino stab2

2393
CGCCUC G CAGACG
6238
20168
HBV-2393 Zin.Rz-6
csgsuscsug GccgaaagGCGaGugaGGuCu gaggcg B
6470

amino stab2

2417
CGCCGC G UCGCAG
6239
20169
HBV-2417 Zin.Rz-6
csusgscsga GccgaaagGCGaGugaGGuCu gcggcg B
6471

amino stab2

2420
CGCGUC G CAGAAG
6240
20170
HBV-2420 Zin.Rz-6
csususcsug GccgaaagGCGaGugaGGuCu gacgcg B
6472

amino stab2

2474
CAUAAG G UGGGAA
6241
20171
HBV-2474 Zin.Rz-6
ususcscsca GccgaaagGCGaGugaGGuCu cuuaug B
6473

amino stab2

381
GCUGGAU G UGUCUGC
6242
20172
HBV-381 Amb.Rz-7
gscsasgsaca gga L ucCCUUCaagga L ucCGGG
6474

stab2
auccagc B

648
UAUGGGA G UGGGCCU
6243
20173
HBV-648 Amb.Rz-7
asgsgscscca gga L ucCCUUCaagga L ucCGGG
6475

stab2
ucccaua B

198
UGCUCGU G UUACAGG
6244
20174
HBV-198 Amb.Rz-7
cscsusgsuaa gga L ucCCUUCaagga L ucCGGG
6476

stab2
acgagca B

377
UAUCGCU G GAUGUGU
6245
20175
HBV-377 Amb.Rz-7
ascsascsauc gga L ucCCUUCaagga L ucCGGG
6477

stab2
agcgaua B

378
AUCGCUG G AUGUGUC
6246
20176
HBV-378 Amb.Rz-7
gsascsascau gga L ucCCUUCaagga L ucCGGG
6478

stab2
cagcgau B

383
UGGAUGU G UCUGCGG
6247
20177
HBV-383 Amb.Rz-7
cscsgscsaga gga L ucCCUUCaagga L ucCGGG
6479

stab2
acaucca B

383
GGAUGU G UCUGCG
6248
20178
HBV-383 Amb.Rz-6
csgscsasga gga L ucCCUUCaagga L ucCGGG
6480

stab2
acaucc B

648
AUGGGA G UGGGCC
6249
20179
HBV-648 Amb.Rz-6
gsgscscsca gga L ucCCUUCaagga L ucCGGG
6481

stab2
ucccau B

650
UGGGAGU G GGCCUCA
6250
20180
HBV-650 Amb.Rz-7
usgsasgsgcc gga L ucCCUUCaagga L ucCGGG
6482

stab2
acuccca B

650
GGGAGU G GGCCUC
6251
20181
HBV-650 Amb.Rz-6
gsasgsgscc gga L ucCCUUCaagga L ucCGGG
6483

stab2
acuccc B

694
GCCAUUU G UUCAGUG
6252
20182
HBV-694 Amb.Rz-7
csascsusgaa gga L ucCCUUCaagga L ucCGGG
6484

stab2
aaauggc B

699
UUGUUCA G UGGUUCG
6253
20183
HBV-699 Amb.Rz-7
csgsasascca gga L ucCCUUCaagga L ucCGGG
6485

stab2
ugaacaa B

701
GUUCAGU G GUUCGUA
6254
20184
HBV-701 Amb.Rz-7
usascsgsaac gga L ucCCUUCaagga L ucCGGG
6486

stab2
acugaac B

710
UUCGUAG G GCUUUCC
6255
20185
HBV-710 Amb.Rz-7
gsgsasasagc gga L ucCCUUCaagga L ucCGGG
6487

stab2
cuacgaa B

1525
CCACGG G GCGCAC
6256
20186
HBV-1525 Amb.Rz-6
gsusgscsgc gga L ucCCUUCaagga L ucCGGG
6488

stab2
ccgugg B

1624
CACCGU G AACGCC
6257
20187
HBV-1624 Amb.Rz-6
gsgscsgsuu gga L ucCCUUCaagga L ucCGGG
6489

stab2
acggug B

2069
CACUCA G GCAAGC
6258
20188
HBV-2069 Amb.Rz-6
gscsususgc gga L ucCCUUCaagga L ucCGGG
6490

stab2
ugagug B

2375
CCUAGAA G AAGAACU
6259
20189
HBV-2375 Amb.Rz-7
asgsususcuu gga L ucCCUUCaagga L ucCGGG
6491

stab2
uucuagg B

2476
AUAAGGU G GGAAACU
6260
20190
HBV-2476 Amb.Rz-7
asgsususucc gga L ucCCUUCaagga L ucCGGG
6492

stab2
accuuau B

65
CCUGCUG G UGGCUCC
6261
20191
HBV-65 Amb.Rz-7
gsgsasgscca gga L ucCCUUCaagga L ucCGGG
6493

stab2
cagcagg B

67
GCUGGU G GCUCCA
6262
20192
HBV-67 Amb.Rz-6
usgsgsasgc gga L ucCCUUCaagga L ucCGGG
6494

stab2
accagc B

198
GCUCGU G UUACAG
6263
20193
HBV-198 Amb.Rz-6
csusgsusaa gga L ucCCUUCaagga L ucCGGG
6495

stab2
acgagc B

260
GACUCGU G GUGGACU
6264
20194
HBV-260 Amb.Rz-7
asgsuscscac gga L ucCCUUCaagga L ucCGGG
6496

stab2
acgaguc B

263
UCGUGGU G GACUUCU
6265
20195
HBV-263 Amb.Rz-7
asgsasasguc gga L ucCCUUCaagga L ucCGGG
6497

stab2

B

377
AUCGCU G GAUGUG
6266
20196
HBV-377 Amb.Rz-6
csascsasuc gga L ucCCUUCaagga L ucCGGG
6498

stab2
agcgau B

378
UCGCUG G AUGUGU
6267
20197
HBV-378 Amb.Rz-6
ascsascsau gga L ucCCUUCaagga L ucCGGG
6499

stab2
cagcga B

476
CCGUUU G UCCUCU
6268
20198
HBV-476 Amb.Rz-6
asgsasgsga gga L ucCCUUCaagga L ucCGGG
6500

stab2
aaacgg B

651
GGGAGUG G GCCUCAG
6269
20199
HBV-651 Amb.Rz-7
csusgsasggc gga L ucCCUUCaagga L ucCGGG
6501

stab2
cacuccc B

677
UGGCUCA G UUUACUA
6270
20200
HBV-677 Amb.Rz-7
usasgsusaaa gga L ucCCUUCaagga L ucCGGG
6502

stab2
ugagcca B

685
UUUACUA G UGCCAUU
6271
20201
HBV-685 Amb.Rz-7
asasusgsgca gga L ucCCUUCaagga L ucCGGG
6503

stab2
uaguaaa B

702
UUCAGUG G UUCGUAG
6272
20202
HBV-702 Amb.Rz-7
csusascsgaa gga L ucCCUUCaagga L ucCGGG
6504

stab2
cacugaa B

709
GUUCGUA G GGCUUUC
6273
20203
HBV-709 Amb.Rz-7
gsasasasgcc gga L ucCCUUCaagga L ucCGGG
6505

stab2
uacgaac B

710
UCGUAG G GCUUUC
6274
20204
HBV-710 Amb.Rz-6
gsasasasgc gga L ucCCUUCaagga L ucCGGG
6506

stab2
cuacga B

747
UAUGGAU G AUGUGGU
6275
20205
HBV-747 Amb.Rz-7
ascscsascau gga L ucCCUUCaagga L ucCGGG
6507

stab2
auccaua B

1557
CCGUCU G UGCCUU
6276
20206
HBV-1557 Amb.Rz-6
asasgsgsca gga L ucCCUUCaagga L ucCGGG
6508

stab2
agacgg B

1881
CCAAGCU G UGCCUUG
6277
20207
HBV-1881 Amb.Rz-7
csasasgsgca gga L ucCCUUCaagga L ucCGGG
6509

stab2
agcuugg B

2347
ACUGUU G UUAGAC
6278
20208
HBV-2347 Amb.Rz-6
gsuscsusaa gga L ucCCUUCaagga L ucCGGG
6510

stab2
aacagu B

2375
CUAGAA G AAGAAC
6279
20209
HBV-2375 Amb.Rz-6
gsususcsuu gga L ucCCUUCaagga L ucCGGG
6511

stab2
uucuag B

2378
GAAGAA G AACUCC
6280
20210
HBV-2378 Amb.Rz-6
gsgsasgsuu gga L ucCCUUCaagga L ucCGGG
6512

stab2
uucuuc B

2423
CGUCGCA G AAGAUCU
6281
20211
HBV-2423 Amb.Rz-7
asgsasuscuu gga L ucCCUUCaagga L ucCGGG
6513

stab2
ugcgacg B

2426
GCAGAA G AUCUCA
6282
20212
HBV-2426 Amb.Rz-6
usgsasgsau gga L ucCCUUCaagga L ucCGGG
6514

stab2
uucugc B

2426
CGCAGAA G AUCUCAA
6283
20213
HBV-2426 Amb.Rz-7
ususgsasgau gga L ucCCUUCaagga L ucCGGG
6515

stab2
uucugcg B

2476
UAAGGU G GGAAAC
6284
20214
HBV-2476 Amb.Rz-6
gsusususcc gga L ucCCUUCaagga L ucCGGG
6516

stab2
accuua B

2477
UAAGGUG G GAAACUU
6285
20215
HBV-2477 Amb.Rz-7
asasgsusuuc gga L ucCCUUCaagga L ucCGGG
6517

stab2
caccuua B

2477
AAGGUG G GAAACU
6286
20216
HBV-2477 Amb.Rz-6
asgsususuc gga L ucCCUUCaagga L ucCGGG
6518

stab2
caccuu B

1607
UGCACGU G GCAUGGA
6287
20697
HBV-1607 Rz-7 allyl
uscscsasugc cUGAuGaggccguuaggccGaa Acgugca B
6519

stab1 (7/4)

1887
GUGCCU G GGGUGG
6288
20698
HBV-1887 Rz-6 allyl
cscsascscc cUGAuGaggccguuaggccGaa Aggcac B
6520

stab1 (6/4)

1607
GCACGU G GCAUGG
6289
20699
HBV-1607 Rz-6 allyl
cscsasusgc cUGAuGaggccguuaggccGaa Acgugc B
6521

stab1 (6/3)

1607
UGCACGU G GCAUGGA
6290
20700
HBV-1607 Rz-7 allyl
uscscsasugc cUGAuGaggccguuaggccGaa Acgugca B
6522

stab1 (7/3)

1887
GUGCCU G GGGUGG
6291
20701
HBV-1887 Rz-6 allyl
cscsascscc cUGAuGaggccguuaggccGaa Aggcac B
6523

stab1 (6/3)

1887
UGUGCCU G GGGUGGC
6292
20702
HBV-1887 Rz-7 allyl
gscscsasccc cUGAuGaggccguuaggccGaa Aggcaca B
6524

stab1 (7/3)

313
CCAAAAU G CGCAGUC
5943
22798
HBV-313 Rz-7 Ome
gacugcg CUGAUGAggccguuaggccGAA Auuuugg B
6541

stab1

408
UCUUCCU G UGCAUCC
5946
22799
HBV-408 Rz-7 Ome
ggaugca CUGAUGAggccguuaggccGAA Aggaaga B
6542

stab1

1756
AGGAGGU G AGGUUAA
5950
22800
HBV-1756 Rz-7 Ome
uuaaccu CUGAUGAggccguuaggccGAA Accuccu B
6543

stab1

10
CUCCACC A CUUUCCA
5953
22770
HBV-10 CHz-7 Ome
uggaaag CUGAUGAggccguuaggccGAA Iguggag B
6544

stab1

335
UCCAGUC A CUCACCA
5954
22771
HBV-335 CHz-7 Ome
uggugag CUGAUGAggccguuaggccGAA Iacugga B
6545

stab1

273
CUUCUCU G AAUUUUC
5996
22645
HBV-273 Rz-7 allyl
gsasasasauu cUGAuGagccguuaggcGaa Agagaag B
6546

stab1 (7/3-GUUA)

273
CUUCUCU G AAUUUUC
5996
22648
HBV-273 Rz-7 allyl
gsasasasauu cUGAuGagccguuaggcGaa Agagaag B
6547

stab1 (7/3-GAAA)

273
CUUCUCU G AAUUUUC
5996
22650
HBV-273 Rz-7 allyl
gsasasasauu cUGAuGagccguuaggcGaa Agagaag B
6548

stab1 (7/4-GAAA)

273
UUCUCU G AAUUUU
6643
22644
HBV-273 Rz-6 allyl
asasasasuu cUGAuGagccguuaggcGaa Agagaa B
6549

stab1 (6/3-GUUA)

273
UUCUCU C AAUUUU
6643
22647
HBV-273 RZ-6 allyl
asasasasuu cUGAuGagccgaaaggcGaa Agagaa B
6550

stab1 (6/3-GAAA)

273
UUCUCU C AAUUUU
6643
22649
HBV-273 Rz-6 allyl
asasasasuu cUGAuGagccguuaggcGaa Agagaa B
6551

stab1 (6/4-GAAA)

350
ACCUGUU G UCCUCCA
6644
22714
HBV-350 GCl.Rz-7
uggagga uGAUg gcauGcacuaugc gCg aacaggu B
6552

5ribo stab3

1253
CCUUUGU G UCUCCUC
6645
22715
HBV-1 253 GCl.Rz-7
gaggaga uGAUg gcauGcacuaugc gCg acaaagg B
6553

5ribo stab3

1856
UGUUCAU G UCCUACU
6646
22716
HBV-1 856 GCl.Rz-7
aguagga uGAUg gcauGcacuaugc gCg augaaca B
6554

5ribo stab3

1966
GCCUUCU G ACUUCUU
6647
22717
HBV-1 966 GCl.Rz-7
aagaagu uGAUg gcauGcacuaugc gCg agaaggc B
6555

5ribo stab3

3132
UCCUCCU G CCUCCAC
6648
22718
HBV-3132 GCl.Rz-7
guggagg uGAUg gcauGcacuaugc gCg aggagga B
6556

5ribo stab3

332
AUCUCCA G UCACUCA
6649
22742
HBV-332 Zin.Rz-7
ugaguga gccgaaaggCgagugaGGuCu uggagau B
6557

amino stab4

350
ACCUGUU G UCCUCCA
6644
22743
HBV-350 Zin.Rz-7
uggagga gccgaaaggCgagugaGGuCu aacaggu B
6558

amino stab4

410
UUCCUCU G CAUCCUG
6650
22744
HBV-410 Zin.Rz-7
caggaug gccgaaaggCgagugaGGuCu agaggaa B
6559

amino stab4

1253
CCUUUGU G UCUCCUC
6645
22745
HBV-1253 Zin.Rz-7
gaggaga gccgaaaggCgagugaGGuCu acaaagg B
6560

amino stab4

1754
GGAGGAG G UUAGGUU
6651
22746
HBV-1754 Zin.Rz-7
aaccuaa gccgaaaggCgagugaGGuCu cuccucc B
6561

amino stab4

407
AUCUUCC U CUGCAUC
6652
22772
HBV-407 CHz-7 Ome
gaugcag CUGAUGAggccguuaggccGAA Igaagau B
6562

stab1

1848
UCAUCUC A UGUUCAU
6653
22773
HBV-1848 CHz-7 Ome
augaaca CUGAUGAggccguuaggccGAA Iagauga B
6563

stab1

3124
GCAGCUC C UCCUCCU
6654
22774
HBV-3124 CHz-7 Ome
aggagga CUGAUGAggccguuaggccGAA Iagcugc B
6564

stab1

2165
GUCAGCU A UGUCAAC
6655
22801
HBV-2165 Rz-7 Ome
guugaca CUGAUGAggccguuaggccGAA Agcugac B
6565

stab1

2706
CCGUAUU A UCCAGAG
6656
22802
HBV-2706 Rz-7 Ome
cucugga CUGAUGAggccguuaggccGAA Aauacgg B
6566

stab1

350
ACCUGUU G UCCUCCA
6644
22966
HBV-350 Dz-7 stab3
uggagga GGCTAGCTACAACGAaacaggu B
6567

332
AUCUCCA G UCACUCA
6649
22967
HBV-332 Dz-7 stab3
ugaguga GGCTAGCTACAACGAuggagau B
6568

1840
CUGCCUA A UCAUCUC
6657
22968
HBV-1840 Dz-7 stab3
gagauga GGCTAGCTACAACGAuaggcag B
6569

358
UCCUCCA A UUUGUCC
6658
22969
HBV-358 Dz-7 stab3
ggacaaa GGCTAGCTACAACGAuggagga B
6570

1253
CCUUUGU G UCUCCUC
6645
22970
HBV-1253 Dz-7 stab3
gaggaga GGCTAGCTACAACGAacaaagg B
6571

20599
SAC
csgsasusgu CUAGuGacccgaaagggGaa AagaggB
6572

273
CUUCUCU C AAUUUUC
5996
25516
HBV-273 UH.Rz-7 mod
gsasasasauu cUgaugaggccguuaggccgaa agagaag B
6589

R18341 all r >

Ome active

273
CUUCUCU C AAUUUUC
5996
25535
HBV-273 UH.Rz-7 mod
gsasasasauu cUagugacgccguuaggcggaa agagaag B
6590

R18341 all r >

Ome BAC

25536
HBV-273 UH.Rz-7 mod
asasusgsagg cUagugacgccguuaggcggaa aaaugaa B
6591

R24588 all r >

Ome SAC

24588
HBV-273 UH.Rz-7
asasusgsagg cUAGuGacgccguuaggcgGaa Aaaugaa B
6592

allyl stab1 inact3

scram1 (GUUA SAC)

UPPER CASE = RIBO

UNDERLINE
= DEOXY

lower case = 2′-O-methyl

I = inosine

s = phosphorothioate linkage

B
= inverted deoxyabasic residue

U
= 2′-deoxy-2′-C-allyl Uridine

U
= 2′-deoxy-2′-amino Uridine

C
= 2′-deoxy-2′-amino Cytidine

L = HEG = hexaethylene glycol spacer

[0255]

12

TABLE XII

Group Designation and Dosage levels for HBV transgenic mouse study

Number of
Duration of

Group
Compound
Dose
Mice
Treatment

1
RPI.18341
100 mg/kg/day*
10 F
14 days

(site 273)

2
RPI.18371
100 mg/kg/day*
10 F
14 days

(site 1833)

3
RPI.18418
100 mg/kg/day*
10 F
14 days

(site 1873)

4
RPI.18372
100 mg/kg/day*
10 F
14 days

(site 1874)

5
Saline control
100 mg/kg/day*
10 F
14 days

6
Untreated

10 F
0 days

*administered via sc infusion using Alzet ® mini-osmotic pumps

[0256]

13

TABLE XIII

GROUP DESIGNATION AND DOSAGE LEVELS FOR HBV

TRANSGENIC MOUSE STUDY

Duration

Number of
of Treat-

Group
Compound
Dose
Mice
ment

1
RPI.18341
100
mg/kg/day*
15 (M or F)
14 days

(site 273)

2
RPI.18341
30
mg/kg/day*
15 (M or F)
14 days

(site 273)

3
RPI.18341
10
mg/kg/day*
15 (M or F)
14 days

(site 273)

4
RPI.18371
100
mg/kg/day*
15 (M or F)
14 days

site 1833

5
RPI.18371
30
mg/kg/day*
15 (M or F)
14 days

site 1833

6
RPI.18371
10
mg/kg/day*
15 (M or F)
14 days

site 1833

7
SAC
100
mg/kg/day*
15 (M or F)
14 days

(RPI.20599)

8
SAC
30
mg/kg/day*
15 (M or F)
14 days

(RPI.20599)

9
SAC
10
mg/kg/day*
15 (M or F)
14 days

(RPI.20599)

10
Saline
12
μl/day*
15 (M or F)
14 days

control

11
3TC ®
50
mg/kg/day, PO
15 (M or F)
14 days

control

*administered via sc infusion using Alzet ® mini-osmotic pumps

[0257]

	Number	Date	Country
Parent	08193627	Feb 1994	US
Child	10342902	Jan 2003	US
Parent	07882712	May 1992	US
Child	10342902	Jan 2003	US

	Number	Date	Country
Parent	09877478	Jun 2001	US
Child	10342902	Jan 2003	US
Parent	09696347	Oct 2000	US
Child	10342902	Jan 2003	US
Parent	09636385	Aug 2000	US
Child	10342902	Jan 2003	US
Parent	09531025	Mar 2000	US
Child	10342902	Jan 2003	US
Parent	09436430	Nov 1999	US
Child	10342902	Jan 2003	US

Method and reagent for inhibiting hepatitis B viral replication

Information

Publication Number

Date Filed

Date Published

Inventors

CPC

US Classifications

International Classifications

Abstract

Description

Claims

Parent Case Info

Continuations (2)

Continuation in Parts (5)