Oligonucleotide mediated inhibition of hepatitis B virus and hepatitis C virus replication

Information

  • Patent Application
  • 20040127446
  • Publication Number
    20040127446
  • Date Filed
    September 23, 2003
    20 years ago
  • Date Published
    July 01, 2004
    19 years ago
Abstract
The present invention relates to nucleic acid molecules, including antisense and enzymatic nucleic acid molecules, such as hammerhead ribozymes, DNAzymes, Inozymes, Zinzymes, Amberzymes, and G-cleaver ribozymes, which modulate the synthesis, expression and/or stability of an HCV or HBV RNA and methods for their use alone or in combination with other therapies. In addition, nucleic acid decoy molecules and aptamers that bind to HBV reverse transcriptase and/or HBV reverse transcriptase primer sequences and methods for their use alone or in combination with other therapies, are disclosed. Oligonucleotides that specifically bind the Enhancer I region of HBV DNA are further disclosed. The present invention further relates to the use of nucleic acids, such as decoy and aptamer molecules of the invention, to modulate the expression of Hepatitis B virus (HBV) genes and HBV viral replication. Furthermore, HBV animal models and methods of use are disclosed, including methods of screening for compounds and/or potential therapies directed against HBV. The present invention also relates to compounds, including enzymatic nucleic acid molecules, ribozymes, DNAzymes, nuclease activating compounds and chimeras such as 2′,5′-adenylates, that modulate the expression and/or replication of hepatitis C virus (HCV).
Description


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) and hepatitis C virus (HCV) infection, replication and gene expression. Specifically, the invention relates to nucleic acid molecules used to modulate expression of HBV and HCV. In addition, the instant invention relates to methods, models and systems for screening inhibitors of HBV and HCV replication and propagation.


[0003] The following is a discussion of relevant art pertaining to hepatitis B virus (HBV) and hepatitis C virus (HCV). 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] In 1989, the Hepatitis C Virus (HCV) was determined to be an RNA virus and was identified as the causative agent of most non-A non-B viral Hepatitis (Choo et al., Science. 1989; 244:359-362). Unlike retroviruses such as HIV, HCV does not go though a DNA replication phase and no integrated forms of the viral genome into the host chromosome have been detected (Houghton et al., Hepatology 1991;14:381-388). Rather, replication of the coding (plus) strand is mediated by the production of a replicative (minus) strand leading to the generation of several copies of plus strand HCV RNA. The genome consists of a single, large, open-reading frame that is translated into a polyprotein (Kato et al., FEBS Letters. 1991; 280: 325-328). This polyprotein subsequently undergoes post-translational cleavage, producing several viral proteins (Leinbach et al., Virology. 1994: 204:163-169).


[0005] Examination of the 9.5-kilobase genome of HCV has demonstrated that the viral nucleic acid can mutate at a high rate (Smith et al., Mol. Evol. 1997 45:238-246). This rate of mutation has led to the evolution of several distinct genotypes of HCV that share approximately 70% sequence identity (Simmonds et al., J. Gen. Virol. 1994;75 :1053-1061). It is important to note that these sequences are evolutionarily quite distant. For example, the genetic identity between humans and primates such as the chimpanzee is approximately 98%. In addition, it has been demonstrated that an HCV infection in an individual patient is composed of several distinct and evolving quasispecies that have 98% identity at the RNA level. Thus, the HCV genome is hypervariable and continuously changing. Although the HCV genome is hypervariable, there are 3 regions of the genome that are highly conserved. These conserved sequences occur in the 5′ and 3′ non-coding regions as well as the 5′-end of the core protein coding region and are thought to be vital for HCV RNA replication as well as translation of the HCV polyprotein. Thus, therapeutic agents that target these conserved HCV genomic regions can have a significant impact over a wide range of HCV genotypes. Moreover, it is unlikely that drug resistance will occur with enzymatic nucleic acids specific to conserved regions of the HCV genome. In contrast, therapeutic modalities that target inhibition of enzymes such as the viral proteases or helicase are likely to result in the selection for drug resistant strains since the RNA for these viral encoded enzymes is located in the hypervariable portion of the HCV genome.


[0006] After initial exposure to HCV, the patient experiences a transient rise in liver enzymes, which indicates the occurrence of inflammatory processes (Alter et al., IN: Seeff L B, Lewis J H, eds. Current Perspectives in Hepatology. New York: Plenum Medical Book Co; 1989:83-89). This elevation in liver enzymes will occur at least 4 weeks after the initial exposure and can last for up to two months (Farci et al., New England Journal of Medicine. 1991:325:98-104). Prior to the rise in liver enzymes, it is possible to detect HCV RNA in the patient's serum using RT-PCR analysis (Takahashi et al., American Journal of Gastroenterology. 1993:88:2:240-243). This stage of the disease is called the acute stage and usually goes undetected since 75% of patients with acute viral hepatitis from HCV infection are asymptomatic. The remaining 25% of these patients develop jaundice or other symptoms of hepatitis.


[0007] Acute HCV infection is a benign disease, however, and as many as 80% of acute HCV patients progress to chronic liver disease as evidenced by persistent elevation of serum alanine aminotransferase (ALT) levels and by continual presence of circulating HCV RNA (Sherlock, Lancet 1992; 339:802). The natural progression of chronic HCV infection over a 10 to 20 year period leads to cirrhosis in 20 to 50% of patients (Davis et al., Infectious Agents and Disease 1993;2:150:154) and progression of HCV infection to hepatocellular carcinoma has been well documented (Liang et al., Hepatology. 1993; 18:1326-1333; Tong et al., Western Journal of Medicine, 1994; Vol. 160, No. 2: 133-138). 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.


[0008] 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., American Journal of Gastroenterology. 1993:88:2:240-243). 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., Presse Medicine. 1994:23:831-833). Given the aggressive nature of primary hepatocellular carcinoma, the only viable treatment alternative to surgery is liver transplantation (Pichlmayr et al., Hepatology. 1994:20:33S-40S).


[0009] 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., Digestive Diseases and Sciences. 1986;31:5: 468-475). These clinical features can include: bleeding esophageal varices, ascites, jaundice, and encephalopathy (Zakim D, Boyer T D. 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.


[0010] 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.


[0011] 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.


[0012] 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).


[0013] Chronic Hepatitis C is a slowly progressing inflammatory disease of the liver, mediated by a virus (HCV) that can lead to cirrhosis, liver failure and/or hepatocellular carcinoma over a period of 10 to 20 years. In the US, it is estimated that infection with HCV accounts for 50,000 new cases of acute hepatitis in the United States each year (NIH Consensus Development Conference Statement on Management of Hepatitis C March 1997). The prevalence of HCV in the United States is estimated at 1.8% and the CDC places the number of chronically infected Americans at approximately 4.5 million people. The CDC also estimates that up to 10,000 deaths per year are caused by chronic HCV infection. The prevalence of HCV in the United States is estimated at 1.8% and the CDC places the number of chronically infected Americans at approximately 4.5 million people. The CDC also estimates that up to 10,000 deaths per year are caused by chronic HCV infection.


[0014] Numerous well controlled clinical trials using interferon (IFN-alpha) in the treatment of chronic HCV infection have demonstrated that treatment three times a week results in lowering of serum ALT values in approximately 50% (range 40% to 70%) of patients by the end of 6 months of therapy (Davis et al., New England Journal of Medicine 1989; 321:1501-1506; Marcellin et al., Hepatology. 1991; 13:393-397; Tong et al., Hepatology 1997:26:747-754; Tong et al., Hepatology 1997 26(6): 1640-1645). However, following cessation of interferon treatment, approximately 50% of the responding patients relapsed, resulting in a “durable” response rate as assessed by normalization of serum ALT concentrations of approximately 20 to 25%.


[0015] In recent years, direct measurement of the HCV RNA has become possible through use of either the branched-DNA or Reverse Transcriptase Polymerase Chain Reaction (RT-PCR) analysis. In general, the RT-PCR methodology is more sensitive and leads to more accurate assessment of the clinical course (Tong et al., supra). Studies that have examined six months of type 1 interferon therapy using changes in HCV RNA values as a clinical endpoint have demonstrated that up to 35% of patients will have a loss of HCV RNA by the end of therapy (Marcellin et al., supra). However, as with the ALT endpoint, about 50% of the patients relapse six months following cessation of therapy resulting in a durable virologic response of only 12% (Marcellin et al., supra). Studies that have examined 48 weeks of therapy have demonstrated that the sustained virological response is up to 25% (NIH consensus statement: 1997). Thus, standard of care for treatment of chronic HCV infection with type 1 interferon is now 48 weeks of therapy using changes in HCV RNA concentrations as the primary assessment of efficacy (Hoofnagle et al., New England Journal of Medicine 1997; 336(5) 347-356).


[0016] Side effects resulting from treatment with type 1 interferons can be divided into four general categories, which include 1. Influenza-like symptoms; 2. Neuropsychiatric; 3. Laboratory abnormalities; and, 4. Miscellaneous (Dusheiko et al., Journal of Viral Hepatitis. 1994:1:3-5). 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 (Dushieko et al., supra). Neuropsychiatric side effects include: irritability, apathy; mood changes; insomnia; cognitive changes and depression. The most important of these neuropsychiatric side effects is depression and patients who have a history of depression should not be given type 1 interferon. Laboratory abnormalities include; reduction in 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 (Dushieko et al., supra). In addition, increases in triglyceride concentrations and elevations in serum alanine 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).


[0017] Type 1 Interferon is a key constituent of many treatment programs for chronic HCV infection. Treatment with type 1 interferon induces a number of genes and results in an antiviral state within the cell. One of the genes induced is 2′,5′ oligoadenylate synthetase, an enzyme that synthesizes short 2′,5′ oligoadenylate (2-5A) molecules. Nascent 2-5A subsequently activates a latent RNase, RNase L, which in turn nonspecifically degrades viral RNA.


[0018] 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.


[0019] 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.


[0020] 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.


[0021] Hepatitis B virus (HBV) infects over 300 million people worldwide (Imperial, 1999, Gastroenterol. Hepatol., 14 (suppl), Si-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.


[0022] 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.


[0023] 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).


[0024] Upon progression to cirrhosis, patients with chronic HCV and HBV 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 T D. 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.


[0025] 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.


[0026] 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.


[0027] 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).


[0028] 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.


[0029] 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.


[0030] 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 that 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.


[0031] 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.


[0032] 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.


[0033] 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.


[0034] 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.


[0035] Since the pregenomic RNA is required as a template for DNA synthesis, this RNA is an excellent target for nucleic acid based therapeutics. Nucleoside analogues that have been documented to modulate HBV replication target the reverse transcriptase activity needed to convert the pregenomic RNA into DNA. Nucleic acid decoy and aptamer modulation of HBV reverse transcriptase would be expected to result in a similar modulation of HBV replication.


[0036] 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).


[0037] 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.


[0038] 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.


[0039] 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 alanine 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).


[0040] 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.


[0041] 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 that utilizes antiviral modulators that work by mechanisms other than those currently utilized in the treatment of both acute and chronic hepatitis B infections.


[0042] Welch et al., Gene Therapy 1996 3(11): 994-1001 describe in vitro an in vivo studies with two vector expressed hairpin ribozymes targeted against hepatitis C virus.


[0043] Sakamoto et al., J. Clinical Investigation 1996 98(12): 2720-2728 describe intracellular cleavage of hepatitis C virus RNA and inhibition of viral protein translation by certain vector expressed hammerhead ribozymes.


[0044] Lieber et al., J. Virology 1996 70(12): 8782-8791 describe elimination of hepatitis C virus RNA in infected human hepatocytes by adenovirus-mediated expression of certain hammerhead ribozymes.


[0045] Ohkawa et al., 1997, J. Hepatology, 27; 78-84, describe in vitro cleavage of HCV RNA and inhibition of viral protein translation using certain in vitro transcribed hammerhead ribozymes.


[0046] Barber et al., International PCT Publication No. WO 97/32018, describe the use of an adenovirus vector to express certain anti-hepatitis C virus hairpin ribozymes.


[0047] Kay et al., International PCT Publication No. WO 96/18419, describe certain recombinant adenovirus vectors to express anti-HCV hammerhead ribozymes.


[0048] Yamada et al., Japanese Patent Application No. JP 07231784 describe a specific poly-(L)-lysine conjugated hammerhead ribozyme targeted against HCV.


[0049] Draper, U.S. Pat. Nos. 5,610,054 and 5,869,253, describes enzymatic nucleic acid molecules capable of inhibiting replication of HCV.


[0050] Macejak et al., 2000, Hepatology, 31, 769-776, describe enzymatic nucleic acid molecules capable of inhibiting replication of HCV.


[0051] Weifeng and Torrence, 1997, Nucleosides and Nucleotides, 16, 7-9, describe the synthesis of 2-5A antisense chimeras with various non-nucleoside components.


[0052] Torrence et al., U.S. Pat. No. 5,583,032 describe targeted cleavage of RNA using an antisense oligonulceotide linked to a 2′,5′-oligoadenylate activator of RNase L.


[0053] Suhadolnik and Pfleiderer, U.S. Pat. Nos. 5,863,905; 5,700,785; 5,643,889; 5,556,840; 5,550,111; 5,405,939; 5,188,897; 4,924,624; and 4,859,768 describe specific internucleotide phosphorothioate 2′,5′-oligoadenlyates and 2′,5′-oligoadenlyate conjugates.


[0054] Budowsky et al., U.S. Pat. No. 5,962,431 describe a method of treating papillomavirus using specific 2′,5′-oligoadenylates.


[0055] Torrence et al., International PCT publication No. WO 00/14219, describe specific peptide nucleic acid 2′,5′-oligoadenylate chimeric molecules.


[0056] Stinchcomb et al., U.S. Pat. No. 5,817,796, describe C-myb ribozymes having 2′-5′-Linked Adenylate Residues.


[0057] Draper, U.S. Pat. No. 6,017,756, describes the use of ribozymes for the inhibition of Hepatitis B Virus.


[0058] 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, Jiefangiun 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.


[0059] Hunt et al., U.S. Pat. No. 5,859,226, describes specific non-naturally occurring oligonucleotide decoys intended to inhibit the expression of MHC-II genes through binding of the RF-X transcription factor, that can inhibit the expression of certain HBV and CMV viral proteins.


[0060] Kao et al., International PCT Publication No. WO 00/04141, describes linear single stranded nucleic acid molecules capable of specifically binding to viral polymerases and inhibiting the activity of the viral polymerase.


[0061] Lu, International PCT Publication No. WO 99/20641, describes specific triplex-forming oligonucleotides used in treating HBV infection.



SUMMARY OF THE INVENTION

[0062] This invention relates to enzymatic nucleic acid molecules that can disrupt the function of RNA species of hepatitis B virus (HBV), hepatitis C virus (HCV) and/or those RNA species encoded by HBV or HCV. In particular, applicant provides enzymatic nucleic acid molecules capable of specifically cleaving HBV RNA or HCV RNA and describes the selection and function thereof. Such enzymatic nucleic acid molecules can be used to treat diseases and disorders associated with HBV and HCV infection.


[0063] 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. 10887.


[0064] In another embodiment, the invention features a composition comprising an enzymatic nucleic acid molecule of the invention and a pharmaceutically acceptable carrier.


[0065] In another embodiment, the invention features a mammalian cell, for example a human cell, comprising an enzymatic nucleic acid molecule contemplated by the invention.


[0066] In one embodiment, the invention features a method for the treatment of cirrhosis, liver failure or hepatocellular carcinoma comprising administering to a patient an enzymatic nucleic acid molecule of the invention under conditions suitable for the treatment.


[0067] In another embodiment, the invention features a method for the treatment of a patient having a condition associated with HBV and/or HCV infection, comprising contacting cells of said patient with an enzymatic nucleic acid molecule of the invention.


[0068] In another embodiment, the invention features a method for the treatment of a patient having a condition associated with HBV and/or HCV 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.


[0069] In another embodiment, the invention features a method for inhibiting HBV and/or HCV replication in a mammalian cell comprising administering to the cell an enzymatic nucleic acid molecule of the invention under conditions suitable for the inhibition.


[0070] In yet another embodiment, the invention features a method of cleaving a separate HBV and/or HCV RNA comprising contacting an enzymatic nucleic acid molecule of the invention with the separate RNA under conditions suitable for the cleavage of the separate RNA.


[0071] 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+.


[0072] In another embodiment, the enzymatic nucleic acid molecule of the invention is chemically synthesized.


[0073] 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.


[0074] In one embodiment, the invention features a composition comprising type I interferon and an enzymatic nucleic acid molecule of the invention and a pharmaceutically acceptable carrier.


[0075] 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.


[0076] 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.


[0077] In another 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.


[0078] In another 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 HCV RNA and/or replication of HCV.


[0079] In one embodiment, the invention features the use of one or more of the enzymatic nucleic acid-based techniques to down-regulate or inhibit the expression of the genes encoding HBV and/or HCV viral proteins. Specifically, the invention features the use of enzymatic nucleic acid-based techniques to specifically down-regulate or inhibit the expression of the HBV and/or HCV viral genome.


[0080] In another embodiment, the invention features nucleic acid-based inhibitors (e.g., enzymatic nucleic acid molecules (ribozymes), antisense nucleic acids, triplex DNA, decoys, siRNA, aptamers, and 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 and/or HCV) capable of progression and/or maintenance of hepatitis, hepatocellular carcinoma, cirrhosis, and/or liver failure.


[0081] In one embodiment, nucleic acid molecules of the invention are used to treat HBV infected cells or an 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.


[0082] In yet another 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 and/or HCV RNA.


[0083] The enzymatic nucleic acid molecules described herein 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 and/or HCV 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 and/or HCV.


[0084] The enzymatic nucleic acid-based modulators of HBV and HCV expression are useful for the prevention of the diseases and conditions including HBV and HCV infection, hepatitis, cancer, cirrhosis, liver failure, and any other diseases or conditions that are related to the levels of HBV and/or HCV in a cell or tissue.


[0085] 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). Targeting 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.


[0086] Alternative regions outside of the 5′ most 1500 nucleotides of the pregenomic mRNA also make suitable targets for 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.


[0087] 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 ribozyme intervention.


[0088] 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 acids 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.


[0089] 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 RNA molecules. 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 an enzymatic nucleic acid molecule.


[0090] The enzymatic nucleic acid molecules 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 other conditions related to the level of HBV.


[0091] 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 can 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).


[0092] In preferred embodiments of the present invention, a nucleic acid molecule, e.g., an antisense molecule, a triplex DNA, or a ribozyme, is 13 to 100 nucleotides in length, e.g., in specific embodiments 35, 36, 37, or 38 nucleotides in length (e.g., for particular ribozymes 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.


[0093] Exemplary enzymatic nucleic acid molecules of the invention targeting HBV 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.


[0094] 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., ribozymes and antisense) can be expressed from DNA and/or RNA vectors that are delivered to specific cells.


[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] 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 HBV 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.


[0097] In yet another embodiment, the invention features antisense nucleic acid molecules including sequences complementary to the HBV 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 regions containing the DNA equivalent of a target sequence or a sequence complementary to the specified target (substrate) sequence. Typically, antisense molecules are complementary to a target sequence along a single contiguous sequence of the antisense molecule. However, in certain embodiments, an antisense molecule can bind to substrate such that the substrate molecule forms a loop, and/or an antisense molecule can bind such that the antisense molecule forms a loop. Thus, the antisense molecule can be complementary to two (or even more) non-contiguous substrate sequences or two (or even more) non-contiguous sequence portions of an antisense molecule can be complementary to a target sequence or both.


[0098] 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 loops, 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. 16201), 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.


[0099] 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 can 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 can be used that provide for transient expression of enzymatic nucleic acids or antisense. Such vectors can 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 acids or antisense expressing vectors can 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 allow for introduction into the desired target cell. Antisense DNA can be expressed via the use of a single stranded DNA intracellular expression vector.


[0100] In another embodiment, the invention features nucleic acid-based inhibitors (e.g., enzymatic nucleic acid molecules (ribozymes), antisense nucleic acids, triplex DNA, decoys, aptamers, siRNA, 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.


[0101] In another embodiment, the invention features nucleic acid-based techniques (e.g., enzymatic nucleic acid molecules (ribozymes), antisense nucleic acids, triplex DNA, decoys, aptamers, siRNA, antisense nucleic acids containing RNA cleaving chemical groups) and methods for their use to down regulate or inhibit the expression of HBV RNA expression.


[0102] In other 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.


[0103] 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 can be varied to achieve optimum results, a non-limiting example is described in Example 6.


[0104] 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.


[0105] This invention also relates to nucleic acid molecules directed to disrupt the function of HBV reverse transcriptase. In addition, the invention relates to nucleic acid molecules directed to disrupt the function of the Enhancer I core region of the HBV genomic DNA. In particular, the present invention describes the selection and function of nucleic acid molecules, such as decoys and aptamers, capable of specifically binding to the HBV reverse transcriptase (pol) primer and modulating reverse transcription of the HBV pregenomic RNA. In another embodiment, the present invention relates to nucleic acid molecules, such as decoys, antisense and aptamers, capable of specifically binding to the HBV reverse transcriptase (pol) and modulating reverse transcription of the HBV pregenomic RNA. In yet another embodiment, the present invention relates to nucleic acid molecules capable of specifically binding to the HBV Enhancer I core region and modulating transcription of the HBV genomic DNA. The invention further relates to allosteric enzymatic nucleic acid molecules or “allozymes” that are used to modulate HBV gene expression. Such allozymes are active in the presence of HBV-derived nucleic acids, peptides, and/or proteins such as HBV reverse transcriptase and/or a HBV reverse transcriptase primer sequence, thereby allowing the allozyme to selectively cleave a sequence of HBV DNA or RNA. Allozymes of the invention are also designed to be active in the presence of HBV Enhancer I sequences and/or mutant HBV Enhancer I sequences, thereby allowing the allozyme to selectively cleave a sequence of HBV DNA or RNA. These nucleic acid molecules can be used to treat diseases and disorders associated with HBV infection.


[0106] In one embodiment, the invention features a nucleic acid decoy molecule that specifically binds the hepatitis B virus (HBV) reverse transcriptase primer sequence. In another embodiment, the invention features a nucleic acid decoy molecule that specifically binds the hepatitis B virus (HBV) reverse transcriptase. In yet another embodiment, the invention features a nucleic acid decoy molecule that specifically binds to the HBV Enhancer I core sequence.


[0107] In one embodiment, the invention features a nucleic acid aptamer that specifically binds the hepatitis B virus (HBV) reverse transcriptase primer. In another embodiment, the invention features a nucleic acid aptamer that specifically binds the hepatitis B virus (HBV) reverse transcriptase. In yet another embodiment, the invention features a nucleic acid aptamer molecule that specifically binds to the HBV Enhancer I core sequence.


[0108] In one embodiment, the invention features an allozyme that specifically binds the hepatitis B virus (HBV) reverse transcriptase primer. In another embodiment, the invention features an allozyme that specifically binds the hepatitis B virus (HBV) reverse transcriptase. In yet another embodiment, the invention features an allozyme that specifically binds to the HBV Enhancer I core sequence.


[0109] In yet another embodiment, the invention features a nucleic acid molecule, for example a triplex forming nucleic acid molecule or antisense nucleic acid molecule, that binds the hepatitis B virus (HBV) reverse transcriptase primer. In another embodiment, the invention features a triplex forming nucleic acid molecule or antisense nucleic acid molecule that specifically binds the hepatitis B virus (HBV) reverse transcriptase. In yet another embodiment, the invention features a triplex forming nucleic acid molecule or antisense nucleic acid molecule that specifically binds to the HBV Enhancer I core sequence.


[0110] In another embodiment, a nucleic acid molecule of the invention binds to Hepatocyte Nuclear Factor 3 (HNF3) and/or Hepatocyte Nuclear Factor 4 (HNF4) binding sequence within the HBV Enhancer I region of HBV genomic DNA, for example the plus strand and/or minus strand DNA of the Enhancer I region, and blocks the binding of HNF3 and/or HNF4 to the Enhancer 1 region.


[0111] In another embodiment, the nucleic acid molecule of the invention comprises a sequence having (UUCA)n domain, where n is an integer from 1-10. In another embodiment, the nucleic acid molecules of the invention comprise the sequence of SEQ. ID NOs: 11216-11342.


[0112] In another embodiment, the invention features a composition comprising a nucleic acid molecule of the invention and a pharmaceutically acceptable carrier. In another embodiment, the invention features a mammalian cell, for example a human cell, including a nucleic acid molecule contemplated by the invention.


[0113] In one embodiment, the invention features a method for treatment of HBV infection, cirrhosis, liver failure, or hepatocellular carcinoma, comprising administering to a patient a nucleic acid molecule of the invention under conditions suitable for the treatment.


[0114] In another embodiment, the invention features a method for the treatment of a patient having a condition associated with HBV infection comprising contacting cells of said patient with a nucleic acid molecule of the invention under conditions suitable for such treatment. In another embodiment, the invention features a method for the treatment of a patient having a condition associated with HBV infection comprising contacting cells of said patient with a 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 nucleic acid molecule.


[0115] In another embodiment, the invention features a method for modulating HBV replication in a mammalian cell comprising administering to the cell a nucleic acid molecule of the invention under conditions suitable for the modulation.


[0116] In yet another embodiment, the invention features a method of modulating HBV reverse transcriptase activity comprising contacting a nucleic acid molecule of the invention, for example a decoy or aptamer, with HBV reverse transcriptase under conditions suitable for the modulating of the HBV reverse transcriptase activity.


[0117] In another embodiment, the invention features a method of modulating HBV transcription comprising contacting a nucleic molecule of the invention with a HBV Enhancer I sequence under conditions suitable for the modulation of HBV transcription.


[0118] In one embodiment, a nucleic acid molecule of the invention, for example a decoy or aptamer, is chemically synthesized. In another embodiment, the nucleic acid molecule of the invention comprises at least one nucleic acid sugar modification. In yet another embodiment, the nucleic acid molecule of the invention comprises at least one nucleic acid base modification. In another embodiment, the nucleic acid molecule of the invention comprises at least one nucleic acid backbone modification.


[0119] In another embodiment, the nucleic acid molecule of the invention comprises at least one 2′-O-alkyl, 2′-alkyl, 2′-alkoxylalkyl, 2′-alkylthioalkyl, 2′-amino, 2′-O-amino, or 2′-halo modification and/or any combination thereof with or without 2′-deoxy and/or 2′-ribo nucleotides. In yet another embodiment, the nucleic acid molecule of the invention comprises all 2′-O-alkyl nucleotides, for example, all 2′-O-allyl nucleotides.


[0120] In one embodiment, the nucleic acid molecule of the invention comprises a 5′-cap, 3′-cap, or 5′-3′ cap structure, for example an abasic or inverted abasic moiety.


[0121] In another embodiment, the nucleic acid molecule of the invention is a linear nucleic acid molecule. In another embodiment, the nucleic acid molecule of the invention is a linear nucleic acid molecule that can optionally form a hairpin, loop, stem-loop, or other secondary structure. In yet another embodiment, the nucleic acid molecule of the invention is a circular nucleic acid molecule.


[0122] In one embodiment, the nucleic acid molecule of the invention is a single stranded oligonucleotide. In another embodiment, the nucleic acid molecule of the invention is a double-stranded oligonucleotide.


[0123] In one embodiment, the nucleic acid molecule of the invention comprises an oligonucleotide having between about 3 and about 100 nucleotides. In another embodiment, the nucleic acid molecule of the invention comprises an oligonucleotide having between about 3 and about 24 nucleotides. In another embodiment, the nucleic acid molecule of the invention comprises an oligonucleotide having between about 4 and about 16 nucleotides.


[0124] The nucleic acid decoy molecules and/or aptamers that bind to a reverse transcriptase and/or reverse transcriptase primer and therefore inactivate the reverse transcriptase, represent a novel therapeutic approach to treat a variety of pathologic indications, including, viral infection such as HBV infection, hepatitis, hepatocellular carcinoma, tumorigenesis, cirrhosis, liver failure and others.


[0125] The nucleic acid molecules that bind to a HBV Enhancer I sequence and therefore inactivate HBV transcription, represent a novel therapeutic approach to treat a variety of pathologic indications, including viral infection such as HBV infection, hepatitis, hepatocellular carcinoma, tumorigenesis, cirrhosis, liver failure and others conditions associated with the level of HBV.


[0126] In one embodiment of the present invention, a decoy nucleic acid molecule of the invention is 4 to 50 nucleotides in length, in specific embodiments about 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, or 16 nucleotides in length. In another embodiment, a non-decoy nucleic acid molecule, e.g., an antisense molecule, a triplex DNA, or a ribozyme, is 13 to 100 nucleotides in length, e.g., in specific embodiments 35, 36, 37, or 38 nucleotides in length (e.g., for particular ribozymes 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.


[0127] Exemplary nucleic acid decoy molecules of the invention are shown in Table XIV. Exemplary synthetic nucleic acid molecules of the invention are shown in Table XV. For example, decoy molecules of the invention are between 4 and 40 nucleotides in length. Exemplary decoys of the invention are 4, 8, 12, or 16 nucleotides in length. In an additional 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 that the nucleic acid molecule is 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.


[0128] In one embodiment, the invention provides a method for producing a class of nucleic acid-based gene modulating agents, which exhibit a high degree of specificity for a viral reverse transcriptase such as HBV reverse transcriptase or reverse transcriptase primer such as a HBV reverse transcriptase primer. For example, the nucleic acid molecule is preferably targeted to a highly conserved nucleic acid binding region of the viral reverse transcriptase 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 can be expressed from DNA and/or RNA vectors that are delivered to specific cells.


[0129] In another embodiment, the invention provides a method for producing a class of nucleic acid-based gene modulating agents which exhibit a high degree of specificity for a viral enhancer regions such as the HBV Enhancer I core sequence. For example, the nucleic acid molecule is preferably targeted to a highly conserved transcription factor-binding region of the viral Enhancer I sequence 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 can be expressed from DNA and/or RNA vectors that are delivered to specific cells.


[0130] In a another embodiment the invention provides a method for producing a class of enzymatic cleaving agents which exhibit a high degree of specificity for the RNA of a desired target. The enzymatic nucleic acid molecule, nuclease activating compound or chimera is preferably targeted to a highly conserved sequence region of a target mRNAs encoding HCV or HBV proteins such that specific treatment of a disease or condition can be provided with either one or several enzymatic nucleic acids. Such nucleic acid molecules can be delivered exogenously to specific cells as required. Alternatively, the enzymatic nucleic acid molecules can be expressed from DNA/RNA vectors that are delivered to specific cells. DNAzymes can be synthesized chemically or expressed endogenously in vivo, by means of a single stranded DNA vector or equivalent thereof.


[0131] In another embodiment, the nucleic acid molecule of the invention binds irreversibly to the HBV reverse transcriptase target, for example by covalent attachment of the nucleic molecule to the reverse transcriptase primer sequence. The covalent attachment can be accomplished by introducing chemical modifications into the nucleic acid molecule's (for example, decoy or aptamer) sequence that are capable of forming covalent bonds to the reverse transcriptase primer sequence.


[0132] In another embodiment, the nucleic acid molecule of the invention binds irreversibly to the HBV Enhancer I sequence target, for example, by covalent attachment of the nucleic acid molecule to the HBV Enhancer I sequence. The covalent attachment can be accomplished by introducing chemical modifications into the nucleic acid molecule's sequence that are capable of forming covalent bonds to the reverse transcriptase primer sequence.


[0133] In another embodiment, the type I interferon contemplated by the invention is interferon alpha, interferon beta, consensus interferon, polyethylene glycol interferon, polyethylene glycol interferon alpha 2a, polyethylene glycol interferon alpha 2b, polyethylene glycol consensus interferon.


[0134] In one embodiment, the invention features a composition comprising type I interferon and a nucleic acid molecule of the invention and a pharmaceutically acceptable carrier.


[0135] In another embodiment, the invention features a method of administering to a cell, for example a mammalian cell or human cell, a 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 nucleic acid molecule under conditions suitable for the administration.


[0136] In yet another embodiment, the invention features a method of administering to a cell, for example a mammalian cell or human cell, a nucleic acid molecule of the invention independently or in conjunction with other therapeutic compounds such as enzymatic nucleic acid molecules, antisense molecules, triplex forming oligonucleotides, 2,5-A chimeras, and/or RNAi, comprising contacting the cell with the nucleic acid molecule of the invention under conditions suitable for the administration.


[0137] In another embodiment, administration of a nucleic acid molecule of the invention is administered to a cell or patient in the presence of a delivery reagent, for example a lipid, cationic lipid, phospholipid, or liposome.


[0138] In one embodiment, the invention features novel nucleic acid-based techniques such as nucleic acid decoy molecules and/or aptamers, used alone or in combination with enzymatic nucleic acid molecules, antisense molecules, and/or RNAi, and methods for use to down regulate or modulate the expression of HBV RNA and/or replication of HBV.


[0139] In another embodiment, the invention features the use of one or more of the nucleic acid-based techniques to modulate the expression of the genes encoding HBV viral proteins. Specifically, the invention features the use of nucleic acid-based techniques to specifically modulate the expression of the HBV viral genome.


[0140] In another embodiment, the invention features the use of one or more of the nucleic acid-based techniques to modulate the activity, expression, or level of cellular proteins required for HBV replication. For example, the invention features the use of nucleic acid-based techniques to specifically modulate the activity of cellular proteins required for HBV replication.


[0141] In another embodiment, the invention features nucleic acid-based modulators (e.g., nucleic acid decoy molecules, aptamers, 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 modulate reverse transcriptase activity and/or the expression of RNA (e.g., HBV) capable of progression and/or maintenance of HBV infection, hepatocellular carcinoma, liver disease and failure.


[0142] In another embodiment, the invention features nucleic acid-based techniques (e.g., nucleic acid decoy molecules, aptamers, enzymatic nuleic acid molecules (ribozymes), antisense nucleic acid molecules, triplex DNA, antisense nucleic acids containing RNA cleaving chemical groups) and methods for their use to down regulate or modulate reverse transcriptase activity and/or the expression of HBV RNA.


[0143] In another embodiment, the invention features nucleic acid-based modulators (e.g., nucleic acid decoy molecules, aptamers, enzymatic nucleic acid molecules (ribozymes), antisense nucleic acids, triplex DNA, siRNA, dsRNA, antisense nucleic acids containing RNA cleaving chemical groups) and methods for their use to down regulate or modulate Enhancer I mediated transcription activity and/or the expression of DNA (e.g., HBV) capable of progression and/or maintenance of HBV infection, hepatocellular carcinoma, liver disease and failure.


[0144] In another embodiment, the invention features nucleic acid-based techniques (e.g., nucleic acid decoy molecules, aptamers, enzymatic nucleic acid molecules, antisense nucleic acid molecules, triplex DNA, siRNA, antisense nucleic acids containing DNA cleaving chemical groups) and methods for their use to down regulate or modulate Enhancer I mediated transcription activity and/or the expression of HBV DNA.


[0145] In another embodiment, the invention features a nucleic acid sensor molecule having an enzymatic nucleic acid domain and a sensor domain that interacts with an HBV peptide, protein, or polynucleotide sequence, for example, HBV reverse transcriptase, HBV reverse transcriptase primer, or the Enhancer I element of the HBV pregenomic RNA, wherein such interaction results in modulation of the activity of the enzymatic nucleic acid domain of the nucleic acid sensor molecule. In another embodiment, the invention features HBV-specific nucleic acid sensor molecules or allozymes, and methods for their use to down regulate or modulate the expression of HBV RNA capable of progression and/or maintenance of hepatitis, hepatocellular carcinoma, cirrhosis, and/or liver failure. In yet another embodiment, the enzymatic nucleic acid domain of a nucleic acid sensor molecule of the invention is a Hammerhead, Inozyme, G-cleaver, DNAzyme, Zinzyme, Amberzyme, or Hairpin enzymatic nucleic acid molecule.


[0146] 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.


[0147] 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.


[0148] The invention also relates to in vitro and in vivo systems, including, e.g., mammalian systems for screening inhibitors of HBV. In one embodiment, the invention features a mouse, for example a male or female mouse, implanted with HepG2.2.15 cells, wherein the mouse is susceptible to HBV infection and capable of sustaining HBV DNA expression. One embodiment of the invention provides a mouse implanted with HepG2.2.15 cells, wherein said mouse sustains the propagation of HEPG2.2.15 cells and HBV production.


[0149] In another embodiment, a mouse of the invention has been infected with HBV for at least one week to at least eight weeks, including, for example at least 4 weeks.


[0150] In yet another embodiment, a mouse of the invention, for example a male or female mouse, is an immunocompromised mouse, for example a nu/nu mouse or a scid/scid mouse.


[0151] In one embodiment, the invention features a method of producing a mouse of the invention, comprising injecting, for example by subcutaneous injection, HepG2.2.15 (Sells, et al, 1987, Proc Natl Acad Sci USA., 84, 1005-1009) cells into the mouse under conditions suitable for the propagation of HepG2.2.15 cells in said mouse. HepG2.2.15 cells can be suspended in, for example, Delbecco's PBS solution including calcium and magnesium. In another embodiment, HepG2.2.15 cells are selected for antibiotic resistance and are then introduced into the mouse under conditions suitable for the propagation of HepG2.2.15 cells in said mouse. A non-limiting example of antibiotic resistant HepG2.2.15 cells include G418 antibiotic resistant HepG2.2.15 cells.


[0152] In another embodiment, the invention features a method of screening a compound for therapeutic activity against HBV, comprising administering the compound to a mouse of the invention and monitoring the the levels of HBV produced (e.g. by assaying for HBV DNA levels) in the mouse.


[0153] In one embodiment, a therapeutic compound or therapy contemplated by the invention is a lipid, steroid, peptide, protein, antibody, monoclonal antibody, humanized monoclonal antibody, small molecule, and/or isomers and analogs thereof, and/or a cell.


[0154] In one embodiment, a therapeutic compound or therapy contemplated by the invention is a nucleic acid molecule, for example a nucleic acid molecule, such as an enzymatic nucleic acid molecule, antisense nucleic acid molecule, allozyme, peptide nucleic acid, decoy, triplex oligonucleotide, dsRNA, ssRNA, RNAi, siRNA, aptamer, or 2,5-A chimera used alone or in combination with another therapy, for example antiviral therapy. Antiviral therapy can be, for example, treatment with 3TC® (Lamivudine) or interferon. Interferon can include, for example, consensus interferon or type I interferon. Type I interferon can include interferon alpha, interferon beta, consensus interferon, polyethylene glycol interferon, polyethylene glycol interferon alpha 2a, polyethylene glycol interferon alpha 2b, or polyethylene glycol consensus interferon.


[0155] In one embodiment, the invention features a non-human mammal implanted with HepG2.2.15 cells, wherein the non-human mammal is susceptible to HBV infection and capable of sustaining HBV DNA expression in the implanted HepG2.2.15 cells.


[0156] In another embodiment, a non-human mammal of the invention, for example a male or female non-human mammal, has been infected with HBV for at least one week to at least eight weeks, including for example at least four weeks.


[0157] In yet another embodiment, a non-human mammal of the invention is an immunocompromised mammal, for example a nu/nu mammal or a scid/scid mammal.


[0158] In one embodiment, the invention features a method of producing a non-human mammal comprising HepG2.2.15 cells comprising injecting, for example by subcutaneous injection, HepG2.2.15 cells into the non-human mammal under conditions suitable for the propagation of HepG2.2.15 cells in said non-human mammal.


[0159] In another embodiment, the invention features a method of screening a compound for therapeutic activity against HBV comprising administering the compound to a non-human mammal of the invention and monitoring the levels of HBV produced (e.g. by assaying for HBV DNA levels) in the non-human mammals.


[0160] In one embodiment, a therapeutic compound or therapy contemplated by the invention is a nucleic acid molecule, for example an enzymatic nucleic acid molecule, allozyme, antisense nucleic acid molecule, decoy, triplex oligonucleotide, dsRNA, ssRNA, RNAi, siRNA, or 2,5-A chimera used alone or in combination with another therapy, for example antiviral therapy.


[0161] Methods and chimeric immunocompromised heterologous non-human mammalian hosts, particularly mouse hosts, are provided for the expression of hepatitis B virus (“HBV”). In one embodiment, the chimeric hosts have transplanted viable, HepG2.2.15 cells in an immunocompromised host.


[0162] The non-human mammals contemplated by the invention are immunocompromised in normally inheriting the desired immune incapacity, or the desired immune incapacity can be created. For example, hosts with severe combined immunodeficiency, known as scid/scid hosts, are available. Rodentia, particularly mice, and equine, particularly horses, are presently available as scid/scid hosts, for example scid/scid mice and scid/scid rats. The scid/scid hosts lack functioning lymphocyte types, particularly B-cells and some T-cell types. In the scid/scid mouse hosts, the genetic defect appears to be a non-functioning recombinase, as the germline DNA is not rearranged to produce functioning surface immunoglobulin and T-cell receptors.


[0163] Any immunodeficient non-human mammals, e.g. mouse, can be used to generate the animal models described herein. The term “immunodeficient,” as used herein, refers to a genetic alteration that impairs the animal's ability to mount an effective immune response. In this regard, an “effective immune response” is one which is capable of destroying invading pathogens such as (but not limited to) viruses, bacteria, parasites, malignant cells, and/or a xenogeneic or allogeneic transplant. In one embodiment, the immunodeficient mouse is a severe immunodeficient (SCID) mouse, which lacks recombinase activity that is necessary for the generation of immunoglobulin and functional T cell antigen receptors, and thus does not produce functional B and T lymphocytes. In another embodiment, the immunodeficient mouse is a nude mouse, which contains a genetic defect that results in the absence of a functional thymus, leading to T-cell and B-cell deficiencies. However, mice containing other immunodeficiencies (such as rag-1 or rag-2 knockouts, as described in Chen et al., 1994, Curr. Opin. Immunol, 6, 313-319 and Guidas et al., 1995, J. Exp. Med., 181, 1187-1195, or beige-nude mice, which also lack natural killer cells, as described in Kollmann et al., 1993, J. Exp. Med., 177, 821-832) can also be employed.


[0164] The introduction of HepG2.2.15 cells occurs with a host at an age less than about 25% of its normal lifespan, usually to 20% of the normal lifespan with mice, and the age will generally be of an age of about 3 to 10 weeks, more usually from about 4 to 8 weeks. The mice can be of either sex, can be neutered, and can be otherwise normal, except for the immunocompromised state, or they can have one or more mutations, which can be naturally occurring or as a result of mutagenesis.


[0165] In another embodiment, the mouse model described herein is used to evaluate the effectiveness of the therapeutic compounds and methods. The terms “therapeutic compounds”, “therapeutic methods” and “therapy” as used herein, encompass exogenous factors, such as dietary or environmental conditions, as well as pharmaceutical compositions “drugs” and vaccines. In one embodiment, the therapeutic method is an immunotherapy, which can include the treatment of the HBV bearing animal with populations of HBV-reactive immune cells. The therapeutic method can also, or alternatively, be a gene therapy (i.e., a therapy that involves treatment of the HBV-bearing mouse with a cell population that has been manipulated to express one or more genes, the products of which can possess anti-viral activity), see for example The Development of Human Gene Therapy, Theodore Friedmann, Ed. Cold Spring Harbor Laboratory Press, Cold Spring Harbor, N.Y., 1999. Therapeutic compounds of the invention can comprise a drug or composition with pharmaceutical activity that can be used to treat illness or disease. A therapeutic method can comprise the use of a plurality of compounds in a mixture or a distinct entity. Examples of such compounds include nucleosides, nucleic acids, nucleic acid chimeras, RNA and DNA oligonucleotides, peptide nucleic acids, enzymatic nucleic acid molecules, antisense nucleic acid molecules, decoys, triplex oligonucleotides, ssDNA, dsRNA, ssRNA, siRNA, 2,5-A chimeras, lipids, steroids, peptides, proteins, antibodies, monoclonal antibodies (see for example Hall, 1995, Science, 270, 915-916), small molecules, and/or isomers and analogs thereof.


[0166] 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 that infect non-human animals where such infections are of veterinary importance.


[0167] Preferred binding sites of the nucleic acid molecules of the invention include, but are not limited, to the primer binding site on HBV reverse transcriptase, the primer binding sequences of the HBV RNA, and/or the HBV Enhancer I region of HBV DNA.


[0168] This invention further relates to nucleic acid molecules that target RNA species of hepatitis C virus (HCV) and/or encoded by the HCV. In one embodiment, applicant describes enzymatic nucleic acid molecules that specifically cleave HCV RNA and the selection and function thereof. The invention further relates to compounds and chimeric molecules comprising nuclease activating activity. The invention also relates to compositions and methods for the cleavage of RNA using these nuclease activating compounds and chimeras. Nucleic acid molecules, nuclease activating compounds and chimeras, and compostions and methods of the invention can be used to treat diseases associated with HCV infection.


[0169] Due to the high sequence variability of the HCV genome, selection of nucleic acid molecules and nuclease activating compounds and chimeras for broad therapeutic applications preferably involve the conserved regions of the HCV genome. Thus, in one embodiment the present invention describes nucleic acid molecules that cleave the conserved regions of the HCV genome. The invention further describes compounds and chimeric molecules that activate cellular nucleases that cleave HCV RNA, including concerved regions of the HCV genome. Examples of conserved regions of the HCV genome include but are not limited to the 5′-Non Coding Region (NCR), the 5′-end of the core protein coding region, and the 3′-NCR. HCV genomic RNA contains an internal ribosome entry site (IRES) in the 5′-NCR which mediates translation independently of a 5′-cap structure (Wang et al., 1993, J. Virol., 67, 3338-44). The full-length sequence of the HCV RNA genome is heterologous among clinically isolated subtypes, of which there are at least 15 (Simmonds, 1995, Hepatology, 21, 570-583), however, the 5′-NCR sequence of HCV is highly conserved across all known subtypes, most likely to preserve the shared IRES mechanism (Okamoto et al., 1991, J. General Virol., 72, 2697-2704). In general, enzymatic nucleic acid molecules and nuclease activating compounds, and chimeras that cleave sites located in the 5′ end of the HCV genome are expected to block translation while nucleic acid molecules and nuclease activating compounds, and chimeras that cleave sites located in the 3′ end of the genome are expected to block RNA replication. Therefore, one nucleic acid molecule, compound, or chimera can be designed to cleave all the different isolates of HCV. Enzymatic nucleic acid molecules and nuclease activating compounds, and chimeras designed against conserved regions of various HCV isolates enable efficient inhibition of HCV replication in diverse patient populations and ensure the effectiveness of the nucleic acid molecules and nuclease activating compounds, and chimeras against HCV quasi species which evolve due to mutations in the non-conserved regions of the HCV genome.


[0170] In one embodiment, the invention features an enzymatic nucleic acid molecule, preferably in the hammerhead, NCH (Inozyme), G-cleaver, amberzyme, zinzyme and/or DNAzyme motif, and the use thereof to down-regulate or inhibit the expression of HCV RNA.


[0171] In another embodiment, the invention features an enzymatic nucleic acid molecule, preferably in the hammerhead, Inozyme, G-cleaver, amberzyme, zinzyme and/or DNAzyme motif, and the use thereof to down-regulate or inhibit the expression of HCV minus strand RNA.


[0172] In yet another embodiment, the invention featues a nuclease activating compound and/or a chimera and the use thereof to down-regulate or inhibit the expression of HCV RNA.


[0173] In another embodiment, the invention featues the use of a nuclease activating compound and/or a chimera to inhibit the expression of HCV minus strand RNA.


[0174] In one embodiment, the invention features a compound having formula I:
1


[0175] wherein X1 is an integer selected from the group consisting of 1, 2, and 3; X2 is an integer greater than or equal to 1; R6 is independently selected from the group including H. OH, NH2, ONH2, alkyl, S-alkyl, O-alkyl, O-alkyl-S-alkyl, O-alkoxyalkyl, allyl, O-allyl, and fluoro; each R1 and R2 are independently selected from the group consisting of O and S; each R3 and R4 are independently selected from the group consisting of O, N, and S; and R5 is selected from the group consisting of alkyl, alkylamine, an oligonucleotide having any of SEQ ID NOS. 11343-16182, an oligonucleotide having a sequence complementary to a sequence selected from the group including SEQ ID NOS. 2594-7433, and abasic moiety.


[0176] In another embodiment, the abasic moiety of the instant invention is selected from the group consisting of:
2


[0177] wherein R3 is selected from the group consisting of O, N, and S, and R7 is independently selected from the group consisting of H, OH, NH2, O—NH2, alkyl, S-alkyl, O-alkyl, O-alkyl-S-alkyl, O-alkoxyalkyl, allyl, O-allyl, fluoro, oligonucleotide, alkyl, alkylamine and abasic moiety.


[0178] In another embodiment, the oligonucleotide R5 of Formula I having a sequence complementary to a sequence selected from the group consisting of SEQ ID NOS. 2594-7433 is an enzymatic nucleic acid molecule.


[0179] In yet another embodiment, the oligonucleotide R5 of Formula I having a sequence complementary to a sequence selected from the group consisting of SEQ ID NOS. 2594-7433 is an antisense nucleic acid molecule.


[0180] In another embodiment, the oligonucleotide R5 of Formula I having a sequence complementary to a sequence selected from the group consisting of SEQ ID NOS. 2594-7433 is an enzymatic nucleic acid molecule selected from the group consisting of Hammerhead, Inozyme, G-cleaver, DNAzyme, Amberzyme, and Zinzyme motifs.


[0181] In another embodiment, the Inozyme enzymatic nucleic acid molecule of the instant invention comprises a stem II region of length greater than or equal to 2 base pairs.


[0182] In one embodiment, the oligonucleotide R5 of Formula I having a sequence complementary to a sequence selected from the group consisting of SEQ ID NOS. 2594-7433 is an enzymatic nucleic acid comprising between 12 and 100 bases complementary to an RNA derived from HCV.


[0183] In another embodiment, the oligonucleotide R5 of Formula I having a sequence complementary to a sequence selected from the group consisting of SEQ ID NOS. 2594-7433 is an enzymatic nucleic acid comprising between 14 and 24 bases complementary to said RNA derived from HCV.


[0184] In one embodiment, the oligonucleotide R5 of Formula I having a sequence complementary to a sequence selected from the group consisting of SEQ ID NOS. 2594-7433 is an antisense nucleic acid comprising between 12 and 100 bases complementary to an RNA derived from HCV.


[0185] In another embodiment, the oligonucleotide R5 of Formula I having a sequence complementary to a sequence selected from the group consisting of SEQ ID NOS. 2594-7433 is an antisense nucleic acid comprising between 14 and 24 bases complementary to said RNA derived from HCV.


[0186] In another embodiment, the invention features a composition comprising a compound of Formula I, in a pharmaceutically acceptable carrier.


[0187] In yet another embodiment, the invention features a mammalian cell comprising a compound of Formula I. For example, the mammalian cell comprising a compound of Formula I can be a human cell.


[0188] In one embodiment, the invention features a method for the treatment of cirrhosis, liver failure, hepatocellular carcinoma, or a condition associated with HCV infection comprising the step of administering to a patient a compound of Formula I under conditions suitable for said treatment.


[0189] In another embodiment, the invention features a method of treatment of a patient having a condition associated with HCV infection comprising contacting cells of said patient with a compound having Formula I, and further comprising the use of one or more drug therapies under conditions suitable for said treatment. For example, the other therapies of the instant invention can be selected from the group consisting of type I interferon, interferon alpha, interferon beta, consensus interferon, polyethylene glycol interferon, polyethylene glycol interferon alpha 2a, polyethylene glycol interferon alpha 2b, polyethylene glycol consensus interferon, treatment with an enzymatic nucleic acid molecule, and treatment with an antisense molecule.


[0190] In another embodiment, the other therapies of the instant invention, for example type I interferon, interferon alpha, interferon beta, consensus interferon, polyethylene glycol interferon, polyethylene glycol interferon alpha 2a, polyethylene glycol interferon alpha 2b, polyethylene glycol consensus interferon, treatment with an enzymatic nucleic acid molecule, and treatment with an antisense nucleic acid molecule, and the compound having Formula I are administered separately in separate pharmaceutically acceptable carriers.


[0191] In yet another embodiment, the other therapies of the instant invention, for example type I interferon, interferon alpha, interferon beta, consensus interferon, polyethylene glycol interferon, polyethylene glycol interferon alpha 2a, polyethylene glycol interferon alpha 2b, polyethylene glycol consensus interferon, treatment with an enzymatic nucleic acid molecule, and treatment with an antisense nucleic acid molecule, and the compound having Formula I are administered simultaneously in a pharmaceutically acceptable carrier. The invention features a composition comprising a compound of Formula I and one or more of the above-listed compounds in a pharmaceutically acceptable carrier.


[0192] In yet another embodiment, the invention features a method for inhibiting HCV replication in a mammalian cell comprising the step of administering to said cell a compound having Formula I under conditions suitable for said inhibition.


[0193] In another embodiment, the invention features a method of cleaving a separate RNA molecule (i.e., HCV RNA or RNA necessary for HCV replication) comprising contacting a compound having Formula I with the separate RNA molecule under conditions suitable for the cleavage of the separate RNA molecule. In one example, the method of cleaving a separate RNA molecule is carried out in the presence of a divalent cation, for example Mg2+.


[0194] In yet another embodiment, the method of cleaving a separate RNA molecule of the invention is carried out in the presence of a protein nuclease, for example RNAse L.


[0195] In one embodiment, a compound having Formula I is chemically synthesized. In one embodiment, a compound having Formula I comprises at least one 2′-sugar modification, at least one nucleic acid base modification, and/or at least one phosphate modification.


[0196] The nucleic acid-based modulators 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 particular embodiments, the nucleic acid molecules of the invention comprise sequences shown in Tables IV-XI, XIV-XV and XVIII-XXIII. Examples of such nucleic acid molecules consist essentially of sequences defined in the tables.


[0197] The nucleic acid-based inhibitors, nuclease activating compounds and chimeras 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, and nuclease activating compounds or chimeras can be locally administered to relevant tissues ex vivo, or in vivo through injection or infusion pump, with or without their incorporation in biopolymers. In preferred embodiments, the enzymatic nucleic acid inhibitors, and nuclease activating compounds or chimeras comprise sequences, which are complementary to the substrate sequences in Tables XVIII, XIX, XX and XXIII. Examples of such enzymatic nucleic acid molecules also are shown in Tables XVIII, XIX, XX, XXI and XXIII. Examples of such enzymatic nucleic acid molecules consist essentially of sequences defined in these tables. In additional embodiments, the enzymatic nucleic acid inhibitors of the invention that comprise sequences which are complementary to the substrate sequences in Tables XVIII, XIX, XX and XXIII are covalently attached to nuclease activating compound or chimeras of the invention, for example a compound having Formula I.


[0198] In yet another embodiment, the invention features antisense nucleic acid molecules and 2-5A chimera including sequences complementary to the substrate sequences shown in Tables XVIII, XIX, XX and XXIII. Such nucleic acid molecules can include sequences as shown for the binding arms of the enzymatic nucleic acid molecules in Tables XVIII, XIX, XX, XXI and XXIII. 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 are complementary to a target sequence along a single contiguous sequence of the antisense molecule. However, in certain embodiments, an antisense molecule can bind to substrate such that the substrate molecule forms a loop, and/or an antisense molecule can bind such that the antisense molecule forms a loop. Thus, the antisense molecule can be complementary to two (or even more) non-contiguous substrate sequences or two (or even more) non-contiguous sequence portions of an antisense molecule can be complementary to a target sequence or both.


[0199] In one embodiment, the invention features nucleic acid molecules and nuclease activating compounds or chimeras that inhibit gene expression and/or viral replication. These chemically or enzymatically synthesized nucleic acid molecules can contain substrate binding domains that bind to accessible regions of their target mRNAs. The nucleic acid molecules also contain domains that catalyze the cleavage of RNA. The enzymatic nucleic acid molecules are preferably molecules of the hammerhead, Inozyme, DNAzyme, Zinzyme, Amberzyme, and/or G-cleaver motifs. Upon binding, the enzymatic nucleic acid molecules cleave the target mRNAs, preventing translation and protein accumulation. In the absence of the expression of the target gene, HCV gene expression and/or replication is inhibited.


[0200] 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 can independently be targeted to the same or different sites.


[0201] In one embodiment, nucleic acid decoys, aptamers, siRNA, enzymatic nucleic acids or antisense molecules that interact with target protein and/or RNA molecules and modulate HBV (specifically HBV reverse transcriptase, or transcription of HBV genomic DNA) activity are expressed from transcription units inserted into DNA or RNA vectors. The recombinant vectors are preferably DNA plasmids or viral vectors. Decoys, aptamers, enzymatic nucleic acid or antisense expressing viral vectors can be constructed based on, but not limited to, adeno-associated virus, retrovirus, adenovirus, or alphavirus. Preferably, the recombinant vectors capable of expressing the decoys, aptamers, enzymatic nucleic acids or antisense are delivered as described above, and persist in target cells. Alternatively, viral vectors can be used that provide for transient expression of decoys, aptamers, siRNA, enzymatic nucleic acids or antisense. Such vectors can be repeatedly administered as necessary. Once expressed, the decoys, aptamers, enzymatic nucleic acids or antisense bind to the target protein and/or RNA and modulate its function or expression. Delivery of decoy, aptamer, siRNA, enzymatic nucleic acid or antisense expressing vectors can 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. DNA based nucleic acid molecules of the invention can be expressed via the use of a single stranded DNA intracellular expression vector.


[0202] In one embodiment, nucleic acid molecules and nuclease activating compounds or chimeras are added directly, or can be complexed with cationic lipids, packaged within liposomes, or otherwise delivered to target cells. 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 another preferred embodiment, the nucleic acid molecule, nuclease activating compound or chimera is administered to the site of HBV or HCV activity (e.g., hepatocytes) in an appropriate liposomal vehicle.


[0203] In another embodiment, nucleic acid molecules that cleave target molecules and inhibit HCV activity are expressed from transcription units inserted into DNA or RNA vectors. The recombinant vectors are preferably DNA plasmids or viral vectors. Nucleic acid molecule expressing viral vectors can 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 can be used that provide for transient expression of nucleic acid molecules. Such vectors can be repeatedly administered as necessary. Once expressed, the nucleic acid molecules cleave the target mRNA. Delivery of enzymatic nucleic acid molecule expressing vectors can 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 and Stinchcomb, 1996, TIG., 12, 510). In another aspect of the invention, nucleic acid molecules that cleave target molecules and inhibit viral replication are expressed from transcription units inserted into DNA, RNA, or viral vectors. Preferably, the recombinant vectors capable of expressing the nucleic acid molecules are locally delivered as described above, and transiently persist in smooth muscle cells. However, other mammalian cell vectors that direct the expression of RNA can be used for this purpose.


[0204] The nucleic acid molecules of the instant invention, individually, or in combination or in conjunction with other drugs, and/or therapies can be used to treat diseases or conditions discussed herein. For example, to treat a disease or condition associated with the levels of HBV or HCV, the nucleic acid molecules can be administered to a patient or can be administered to other appropriate cells evident to those skilled in the art, individually or in combination with one or more drugs under conditions suitable for the treatment.


[0205] In a further embodiment, the described molecules, such as decoys, aptamers, antisense, enzymatic nucleic acids, or nuclease activating compounds and chimeras 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, HCV infection, hepatitis, hepatocellular carcinoma, cancer, cirrhosis, and liver failure. Such therapeutic agents can 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).


[0206] Nucleic acid molecules, nuclease activating compounds and chimeras of the 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 or HCV levels, the patient can be treated, or other appropriate cells can be treated, as is evident to those skilled in the art.


[0207] In a further embodiment, the described molecules can be used in combination with other known treatments to treat conditions or diseases discussed above. For example, the described molecules can be used in combination with one or more known therapeutic agents to treat liver failure, hepatocellular carcinoma, cirrhosis, and/or other disease states associated with HBV or HCV infection. Additional known therapeutic agents are those comprising antivirals, interferons, and/or antisense compounds.


[0208] The term “inhibit” or “down-regulate” as used herein refers to the expression of the gene, or level of RNAs or equivalent RNAs encoding one or more protein subunits or components, or activity of one or more protein subunits or components, such as HBV protein or proteins, is reduced below that observed in the absence of the therapies of the invention. In one embodiment, inhibition or down-regulation 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 or down-regulation 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 or down-regulation of HBV with the nucleic acid molecule of the instant invention is greater in the presence of the nucleic acid molecule than in its absence.


[0209] The term “up-regulate” as used herein refers to the expression of the gene, or level of RNAs or equivalent RNAs encoding one or more protein subunits or components, or activity of one or more protein subunits or components, such as HBV or HCV protein or proteins, is greater than that observed in the absence of the therapies of the invention. For example, the expression of a gene, such as HBV or HCV genes, can be increased in order to treat, prevent, ameliorate, or modulate a pathological condition caused or exacerbated by an absence or low level of gene expression.


[0210] The term “modulate” as used herein refers to the expression of the gene, or level of RNAs or equivalent RNAs encoding one or more protein subunits or components, or activity of one or more proteins is up-regulated or down-regulated, such that the expression, level, or activity is greater than or less than that observed in the absence of the therapies of the invention.


[0211] The term “decoy” as used herein refers to a nucleic acid molecule, for example RNA or DNA, or aptamer that is designed to preferentially bind to a predetermined ligand. Such binding can result in the inhibition or activation of a target molecule. A decoy or aptamer can compete with a naturally occurring binding target for the binding of a specific ligand. For example, it has been shown that over-expression of HIV trans-activation response (TAR) RNA can act as a “decoy” and efficiently binds HIV tat protein, thereby preventing it from binding to TAR sequences encoded in the HIV RNA (Sullenger et al., 1990, Cell, 63, 601-608). This is but a specific example and those in the art will recognize that other embodiments can be readily generated using techniques generally known in the art, see for example Gold et al., 1995, Annu. Rev. Biochem., 64, 763; Brody and Gold, 2000, J. Biotechnol., 74, 5; Sun, 2000, Curr. Opin. Mol. Ther., 2, 100; Kusser, 2000, J. Biotechnol., 74, 27; Hermann and Patel, 2000, Science, 287, 820; and Jayasena, 1999, Clinical Chemistry, 45, 1628. Similarly, a decoy can be designed to bind to HBV or HCV proteins and block the binding of HBV or HCV DNA or RNA or a decoy can be designed to bind to HBV or HCV proteins and prevent molecular interaction with the HBV or HCV proteins.


[0212] By “aptamer” or “nucleic acid aptamer” as used herein is meant a nucleic acid molecule that binds specifically to a target molecule wherein the nucleic acid molecule has sequence that is distinct from sequence recognized by the target molecule in its natural setting. Alternately, an aptamer can be a nucleic acid molecule that binds to a target molecule where the target molecule does not naturally bind to a nucleic acid. The target molecule can be any molecule of interest. For example, the aptamer can be used to bind to a ligand-binding domain of a protein, thereby preventing interaction of the naturally occurring ligand with the protein. This is a non-limiting example and those in the art will recognize that other embodiments can be readily generated using techniques generally known in the art, see for example Gold et al., 1995, Annu. Rev. Biochem., 64, 763; Brody and Gold, 2000, J. Biotechnol., 74, 5; Sun, 2000, Curr. Opin. Mol. Ther., 2, 100; Kusser, 2000, J. Biotechnol., 74, 27; Hermann and Patel, 2000, Science, 287, 820; and Jayasena, 1999, Clinical Chemistry, 45, 1628.


[0213] By “enzymatic nucleic acid molecule” is meant a nucleic acid molecule that has complementarity in a substrate binding region to a specified gene target, and also has an enzymatic activity which is active to specifically cleave a target RNA molecule. That is, the enzymatic nucleic acid molecule is able to intermolecularly cleave a RNA molecule and thereby inactivate a target RNA molecule. These complementary regions allow sufficient hybridization of the enzymatic nucleic acid molecule to a target RNA molecule 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 can 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 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 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).


[0214] By “nucleic acid molecule” as used herein is meant a molecule comprising nucleotides. The nucleic acid can be single, double, or multiple stranded and can comprise modified or unmodified nucleotides or non-nucleotides or various mixtures and combinations thereof.


[0215] 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).


[0216] By “substrate binding arm” or “substrate binding domain” is meant that portion/region of a ribozyme 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 a ribozyme which are intended to bring ribozyme and target RNA together through complementary base-pairing interactions. The ribozyme of the invention can have binding arms that are contiguous or non-contiguous and may 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).


[0217] By “nuclease activating compound” is meant a compound, for example a compound having Formula I, that activates the cleavage of an RNA by a nuclease. The nuclease can comprise RNAse L. By “nuclease activating chimera” or “chimera” is meant a nuclease activating compound, for example a compound having Formula I, that is attached to a nulceic acid molecule, for example a nucleic acid molecule that binds preferentially to a target RNA. These chimeric nucleic acid molecules can comprise a nuclease activating compound and an antisense nucleic acid molecule, for example a 2′,5′-oligoadenylate antisense chimera, or an enzymatic nucleic acid moleucle, for example a 2′,5′-oligoadenylate enzymatic nucleic acid chimera.


[0218] By “Inozyme” or “NCH” motif or configuration is meant, an enzymatic nucleic acid molecule comprising a motif as is generally described as NCH Rz in Ludwig et al., International PCT Publication No. WO 98/58058 and U.S. patent application Ser. No. 08/878,640. Inozymes possess endonuclease activity to cleave RNA substrates having a cleavage triplet NCH/, where N is a nucleotide, C is cytidine and H is adenosine, uridine or cytidine, and/represents the cleavage site. Inozymes can also possess endonuclease activity to cleave RNA substrates having a cleavage triplet NCN/, where N is a nucleotide, C is cytidine, and/represents the cleavage site.


[0219] By “G-cleaver” motif or configuration is meant, an enzymatic nucleic acid molecule comprising a motif as is generally described in Eckstein et al., U.S. Pat. No. 6,127,173 and in Kore et al., 1998, Nucleic Acids Research 26, 4116-4120. G-cleavers possess endonuclease activity to cleave RNA substrates having a cleavage triplet NYN/, where N is a nucleotide, Y is uridine or cytidine and/represents the cleavage site. G-cleavers can be chemically modified.


[0220] By “zinzyme” motif or configuration is meant, an enzymatic nucleic acid molecule comprising a motif as is generally described in Beigelman et al., International PCT publication No. WO 99/55857 and U.S. patent application Ser. No. 09/918,728. Zinzymes possess endonuclease activity to cleave RNA substrates having a cleavage triplet including but not limited to, YG/Y, where Y is uridine or cytidine, and G is guanosine and/represents the cleavage site. Zinzymes can be chemically modified to increase nuclease stability through various substitutions, including substituting 2′-O-methyl guanosine nucleotides for guanosine nucleotides. In addition, differing nucleotide and/or non-nucleotide linkers can be used to substitute the 5′-gaaa-2′ loop of the motif. Zinzymes represent a non-limiting example of an enzymatic nucleic acid molecule that does not require a ribonucleotide (2′-OH) group within its own nucleic acid sequence for activity.


[0221] By “amberzyme” motif or configuration is meant, an enzymatic nucleic acid molecule comprising a motif as is generally described in Beigelman et al., International PCT publication No. WO 99/55857 and U.S. patent application Ser. No. 09/476,387. Amberzymes possess endonuclease activity to cleave RNA substrates having a cleavage triplet NG/N, where N is a nucleotide, G is guanosine, and/represents the cleavage site. Amberzymes can be chemically modified to increase nuclease stability. In addition, differing nucleoside and/or non-nucleoside linkers can be used to substitute the 5′-gaaa-3′ loops of the motif. Amberzymes represent a non-limiting example of an enzymatic nucleic acid molecule that does not require a ribonucleotide (2′-OH) group within its own nucleic acid sequence for activity.


[0222] By ‘DNAzyme’ is meant, an enzymatic nucleic acid molecule that does not require the presence of a 2′-OH group within its own nucleic acid sequence for activity. In particular embodiments, the enzymatic nucleic acid molecule can have an attached linker or linkers or other attached or associated groups, moieties, or chains containing one or more nucleotides with 2′-OH groups. DNAzymes can be synthesized chemically or expressed endogenously in vivo, by means of a single stranded DNA vector or equivalent thereof. Non-limiting examples of DNAzymes are generally reviewed in Usman et al., U.S. Pat. No., 6,159,714; Chartrand et al., 1995, NAR 23, 4092; Breaker et al., 1995, Chem. Bio. 2, 655; Santoro et al., 1997, PNAS 94, 4262; Breaker, 1999, Nature Biotechnology, 17, 422-423; and Santoro et. al., 2000, J. Am. Chem. Soc., 122, 2433-39. The “10-23” DNAzyme motif is one particular type of DNAzyme that was evolved using in vitro selection as generally described in Joyce et al., U.S. Pat. No. 5,807,718 and Santoro et al., supra. Additional DNAzyme motifs can be selected for using techniques similar to those described in these references, and hence, are within the scope of the present invention.


[0223] By “nucleic acid sensor molecule” or “allozyme” as used herein is meant a nucleic acid molecule comprising an enzymatic domain and a sensor domain, where the enzymatic nucleic acid domain's ability to catalyze a chemical reaction is dependent on the interaction with a target signaling molecule, such as a nucleic acid, polynucleotide, oligonucleotide, peptide, polypeptide, or protein, for example HBV RT, HBV RT primer, or HBV Enhancer I sequence. The introduction of chemical modifications, additional functional groups, and/or linkers, to the nucleic acid sensor molecule can provide enhanced catalytic activity of the nucleic acid sensor molecule, increased binding affinity of the sensor domain to a target nucleic acid, and/or improved nuclease/chemical stability of the nucleic acid sensor molecule, and are hence within the scope of the present invention (see for example Usman et al., U.S. patent application Ser. No. 09/877,526, George et al., U.S. Pat. Nos. 5,834,186 and 5,741,679, Shih et al., U.S. Pat. No. 5,589,332, Nathan et al., U.S. Pat. No. 5,871,914, Nathan and Ellington, International PCT publication No. WO 00/24931, Breaker et al., International PCT Publication Nos. WO 00/26226 and 98/27104, and Sullenger et al., U.S. patent application Ser. No. 09/205,520).


[0224] By “sensor component” or “sensor domain” of the nucleic acid sensor molecule as used herein is meant, a nucleic acid sequence (e.g., RNA or DNA or analogs thereof) which interacts with a target signaling molecule, for example a nucleic acid sequence in one or more regions of a target nucleic acid molecule or more than one target nucleic acid molecule, and which interaction causes the enzymatic nucleic acid component of the nucleic acid sensor molecule to either catalyze a reaction or stop catalyzing a reaction. In the presence of target signaling molecule of the invention, such as HBV RT, HBV RT primer, or HBV Enhancer I sequence, the ability of the sensor component, for example, to modulate the catalytic activity of the nucleic acid sensor molecule, is altered or diminished in a manner that can be detected or measured. The sensor component can comprise recognition properties relating to chemical or physical signals capable of modulating the nucleic acid sensor molecule via chemical or physical changes to the structure of the nucleic acid sensor molecule. The sensor component can be derived from a naturally occurring nucleic acid binding sequence, for example, RNAs that bind to other nucleic acid sequences in vivo. Alternately, the sensor component can be derived from a nucleic acid molecule (aptamer), which is evolved to bind to a nucleic acid sequence within a target nucleic acid molecule. The sensor component can be covalently linked to the nucleic acid sensor molecule, or can be non-covalently associated. A person skilled in the art will recognize that all that is required is that the sensor component is able to selectively modulate the activity of the nucleic acid sensor molecule to catalyze a reaction.


[0225] By “target molecule” or “target signaling molecule” is meant a molecule capable of interacting with a nucleic acid sensor molecule, specifically a sensor domain of a nucleic acid sensor molecule, in a manner that causes the nucleic acid sensor molecule to be active or inactive. The interaction of the signaling agent with a nucleic acid sensor molecule can result in modification of the enzymatic nucleic acid component of the nucleic acid sensor molecule via chemical, physical, topological, or conformational changes to the structure of the molecule, such that the activity of the enzymatic nucleic acid component of the nucleic acid sensor molecule is modulated, for example is activated or inactivated. Signaling agents can comprise target signaling molecules such as macromolecules, ligands, small molecules, metals and ions, nucleic acid molecules including but not limited to RNA and DNA or analogs thereof, proteins, peptides, antibodies, polysaccharides, lipids, sugars, microbial or cellular metabolites, pharmaceuticals, and organic and inorganic molecules in a purified or unpurified form, for example HBV RT or HBV RT primer.


[0226] By “sufficient length” is meant a nucleic acid molecule long enough to provide the intended function under the expected condition. For example, a nucleic acid molecule of the invention needs to be of “sufficient length” to provide stable binding to a target site under the expected binding conditions and environment. In another non-limiting example, for the binding arms of an 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 reaction conditions and environment. The binding arms are not so long as to prevent useful turnover of the nucleic acid molecule. 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) that is sufficient for the intended purpose (e.g., cleavage of target RNA by an enzyme).


[0227] By “equivalent” RNA to HBV or HCV is meant to include those naturally occurring RNA molecules having homology (partial or complete) to HBV or HCV proteins or encoding for proteins with similar function as HBV or HCV 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.


[0228] The term “component” of HBV or HCV as used herein refers to a peptide or protein subunit expressed from a HBV or HCV gene.


[0229] By “homology” is meant the nucleotide sequence of two or more nucleic acid molecules is partially or completely identical.


[0230] 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 are complementary to a target sequence along a single contiguous sequence of the antisense molecule. However, in certain embodiments, an antisense molecule can bind to substrate such that the substrate molecule forms a loop, and/or an antisense molecule can bind such that the antisense molecule forms a loop. Thus, the antisense molecule can be complementary to two or more non-contiguous substrate sequences or two or more non-contiguous sequence portions of an antisense molecule can 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, 2000, Methods Enzymol., 313, 3-45; Crooke, 1998, Biotech. Genet. Eng. Rev., 15, 121-157, Crooke, 1997, Ad. Pharmacol., 40, 1-49. Antisense molecules of the instant invention can include 2-5A antisense chimera molecules. 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 that 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.


[0231] 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 (for example, 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.


[0232] By “2-5A antisense” or “2-5A antisense chimera” 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; Silverman et al., 2000, Methods Enzymol., 313, 522-533; Player and Torrence, 1998, Pharmacol. Ther., 78, 55-113).


[0233] By “triplex nucleic acid” or “triplex oligonucleotide” it is meant a polynucleotide or 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 modulate transcription of the targeted gene (Duval-Valentin et al., 1992, Proc. Natl. Acad. Sci. USA, 89, 504). Triplex nucleic acid molecules of the invention also include steric blocker nucleic acid molecules that bind to the Enhancer I region of HBV DNA (plus strand and/or minus strand) and prevent translation of HBV genomic DNA.


[0234] The term “single stranded RNA” (ssRNA) as used herein refers to a naturally occurring or synthetic ribonucleic acid molecule comprising a linear single strand, for example a ssRNA can be a messenger RNA (mRNA), transfer RNA (tRNA), ribosomal RNA (rRNA) etc. of a gene.


[0235] The term “single stranded DNA” (ssDNA) as used herein refers to a naturally occurring or synthetic deoxyribonucleic acid molecule comprising a linear single strand, for example, a ssDNA can be a sense or antisense gene sequence or EST (Expressed Sequence Tag).


[0236] The term “allozyme” as used herein refers to an allosteric enzymatic nucleic acid molecule, see for example George et al., U.S. Pat. Nos. 5,834,186 and 5,741,679, Shih et al., U.S. Pat. No. 5,589,332, Nathan et al., U.S. Pat. No. 5,871,914, Nathan and Ellington, International PCT publication No. WO 00/24931, Breaker et al., International PCT Publication Nos. WO 00/26226 and 98/27104, and Sullenger et al., International PCT publication No. WO 99/29842.


[0237] The term “2-5A chimera” as used herein refers to an 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; Silverman et al., 2000, Methods Enzymol., 313, 522-533; Player and Torrence, 1998, Pharmacol. Ther., 78, 55-113).


[0238] The term “double stranded RNA” or “dsRNA” as used herein refers to a double stranded RNA molecule capable of RNA interference “RNAi”, including short interfering RNA “siRNA” see for example Bass, 2001, Nature, 411, 428-429; Elbashir et al., 2001, Nature, 411, 494-498; and Kreutzer et al., International PCT Publication No. WO 00/44895; Zernicka-Goetz et al., International PCT Publication No. WO 01/36646; Fire, International PCT Publication No. WO 99/32619; Plaetinck et al., International PCT Publication No. WO 00/01846; Mello and Fire, International PCT Publication No. WO 01/29058; Deschamps-Depaillette, International PCT Publication No. WO 99/07409; and Li et al., International PCT Publication No. WO 00/44914.


[0239] By “gene” it is meant, a nucleic acid that encodes an RNA, for example, nucleic acid sequences including, but not limited to, structural genes encoding a polypeptide.


[0240] By “complementarity” is meant that a nucleic acid can form hydrogen bond(s) with another nucleic acid 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., ribozyme cleavage, antisense or triple helix modulation. 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 that 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.


[0241] As used 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 can be present in an organism, e.g., birds, plants and mammals such as humans, cows, sheep, apes, monkeys, swine, dogs, and cats. The cell can be prokaryotic (e.g., bacterial cell) or eukaryotic (e.g., mammalian or plant cell).


[0242] By “HBV proteins” or “HCV proteins” is meant, a protein or a mutant protein derivative thereof, comprising sequence expressed and/or encoded by the HBV genome.


[0243] 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.


[0244] By “highly conserved nucleic acid binding region” is meant an amino acid sequence of one or more regions in a target protein that does not vary significantly from one generation to the other or from one biological system to the other.


[0245] By “related to the levels of HBV” 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.


[0246] By “related to the levels of HCV” is meant that the reduction of HCV expression (specifically HCV 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.


[0247] 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-ribo-furanose moiety.


[0248] By “vector” is meant any nucleic acid- and/or viral-based technique used to express and/or deliver a desired nucleic acid.


[0249] 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. In one embodiment, a patient is a mammal or mammalian cells. In another embodiment, a patient is a human or human cells.


[0250] Other features and advantages of the invention will be apparent from the following description of the preferred embodiments thereof, and from the claims.



DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0251] First the drawings will be described briefly.







DRAWINGS

[0252]
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).


[0253]
FIG. 2 shows examples of chemically stabilized ribozyme 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.


[0254]
FIG. 3 shows an example of the Amberzyme ribozyme 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.


[0255]
FIG. 4 shows an example of the Zinzyme A ribozyme 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.


[0256]
FIG. 5 shows an example of a DNAzyme motif described by Santoro et al., 1997, PNAS, 94, 4262.


[0257]
FIG. 6 is a bar graph showing the percent change in serum HBV DNA levels following fourteen days of ribozyme treatment in HBV transgenic mice. Ribozymes 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 ribozyme and saline controls, and orally administered 3TC® (300 mg/kg/day) and saline controls.


[0258]
FIG. 7 is a bar graph showing the mean serum HBV DNA levels following fourteen days of ribozyme treatment in HBV transgenic mice. Ribozymes 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 ribozyme and saline controls, and orally administered 3TC® (300 mg/kg/day) and saline controls.


[0259]
FIG. 8 is a bar graph showing the decrease in serum HBV DNA (log) levels following fourteen days of ribozyme treatment in HBV transgenic mice. Ribozymes 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 ribozyme and saline controls, and orally administered 3TC® (300 mg/kg/day) and saline controls.


[0260]
FIG. 9 is a bar graph showing the decrease in HBV DNA in HepG2.2.15 cells after treatment with ribozymes 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 ribozyme (RPI.20995).


[0261]
FIG. 10 is a bar graph showing reduction in HBsAg levels following treatment of HepG2 cells with anti-HBV arm, stem, and loop-variant ribozymes (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 ribozyme (RPI.20599).


[0262]
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®.


[0263]
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 mM Lamivudine.


[0264]
FIG. 13 shows a scheme which outlines the steps involved in HBV reverse transcription. The HBV polymerase/reverse transcriptase binds to the 5′-stem-loop of the HBV pregenomic RNA and synthesizes a primer from the UUCA template. The reverse transcriptase and tetramer primer are translocated to the 3′-DR1 site. The RT primer binds to the UUCA sequence in the DR1 element and minus strand synthesis begins.


[0265]
FIG. 14 shows a non-limiting example of inhibition of HBV reverse transcription. A decoy molecule binds to the HBV RT primer, thereby preventing translocation of the RT to the 3′-DR1 site and preventing minus strand synthesis.


[0266]
FIG. 15 shows data of a HBV nucleic acid screen of 2′-O-allyl modified nucleic acid molecules. The levels of HbsAg were determined by ELISA. Inhibition of HBV is correlated to HBsAg antigen levels.


[0267]
FIG. 16 shows data of a HBV nucleic acid screen of 2′-O-methyl modified nucleic acid molecules. The levels of HbsAg were determined by ELISA. Inhibition of HBV is correlated to HBsAg antigen levels.


[0268]
FIG. 17 shows dose response data of 2′-O-methyl modified nucleic acid molecules targeting the HBV reverse transcriptase primer compared to levels of HBsAg.


[0269]
FIG. 18 shows data of nucleic acid screen of nucleic acid molecules (200 nM) targeting the HBV Enhancer I core region compared to levels of HBsAg.


[0270]
FIG. 19 shows data of nucleic acid screen of nucleic acid molecules (400 nM) targeting the HBV Enhancer I core region compared to levels of HBsAg.


[0271]
FIG. 20 shows dose response data of nucleic acid molecules targeting the HBV Enhancer I core region compared to levels of HBsAg.


[0272]
FIG. 21 shows a graph depicting HepG2.2.15 tumor growth in athymic nu/nu female mice as tumor volume (mm3) vs time (days).


[0273]
FIG. 22 shows a graph depicting HepG2.2.15 tumor growth in athymic nu/nu female mice as tumor volume (mm3) vs time (days). Inoculated HepG2.2.15 cells were selected for antibiotic resistance to G418 before introduction into the mouse.


[0274]
FIG. 23 is a schematic representation of the Dual Reporter System utilized to demonstrate enzymatic nucleic acid mediated reduction of luciferase activity in cell culture.


[0275]
FIG. 24 shows a schematic view of the secondary structure of the HCV 5′UTR (Brown et al., 1992, Nucleic Acids Res., 20, 5041-45; Honda et al., 1999, J. Virol., 73, 1165-74). Major structural domains are indicated in bold. Enzymatic nucleic acid cleavage sites are indicated by arrows. Solid arrows denote sites amenable to amino-modified enzymatic nucleic acid inhibition. Lead cleavage sites (195 and 330) are indicated with oversized solid arrows.


[0276]
FIG. 25 shows a non-limiting example of a nuclease resistant enzymatic nucleic acid molecule. Binding arms are indicated as stem I and stem III. Nucleotide modifications are indicated as follows: 2′-O-methyl nucleotides, lowercase; ribonucleotides, uppercase G, A; 2′-amino-uridine, u; inverted 3′-3′ deoxyabasic, B. The positions of phosphorothioate linkages at the 5′-end of each enzymatic nucleic acid are indicated by subscript “s”. H indicates A, C or U ribonucleotide, N′ indicates A, C G or U ribonucleotide in substrate, n indicates base complementary to the N′. The U4 and U7 positions in the catalytic core are indicated.


[0277]
FIG. 26 is a set of bar graphs showing enzymatic nucleic acid mediated inhibition of HCV-luciferase expression in OST7 cells. OST7 cells were transfected with complexes containing reporter plasmids (2 μg/mL), enzymatic nucleic acids (100 nM) and lipid. The ratio of HCV-firefly luciferase luminescence/Renilla luciferase luminescence was determined for each enzymatic nucleic acid tested and was compared to treatment with the ICR, an irrelevant control enzymatic nucleic acid lacking specificity to the HCV 5′UTR (adjusted to 1). Results are reported as the mean of triplicate samples ±SD. In FIG. 26A, OST7 cells were treated with enzymatic nucleic acids (100 nM) targeting conserved sites (indicated by cleavage site) within the HCV 5′UTR. In FIG. 26B, OST7 cells were treated with a subset of enzymatic nucleic acids to lead HCV sites (indicated by cleavage site) and corresponding attenuated core (AC) controls. Percent decrease in firefly/Renilla luciferase ratio after treatment with active enzymatic nucleic acids as compared to treatment with corresponding ACs is shown when the decrease is ≧50% and statistically significant. Similar results were obtained with 50 nM enzymatic nucleic acid.


[0278]
FIG. 27 is a series of line graphs showing the dose-dependent inhibition of HCV/luciferase expression following enzymatic nucleic acid treatment. Active enzymatic nucleic acid was mixed with corresponding AC to maintain a 100 nM total oligonucleotide concentration and the same lipid charge ratio. The concentration of active enzymatic nucleic acid for each point is shown. FIGS. 27A-E shows enzymatic nucleic acids targeting sites 79, 81, 142, 195, or 330, respectively. Results are reported as the mean of triplicate samples ±SD.


[0279]
FIG. 28 is a set of bar graphs showing reduction of HCV/luciferase RNA and inhibition of HCV-luciferase expression in OST7 cells. OST7 cells were transfected with complexes containing reporter plasmids (2 μg/ml), enzymatic nucleic acids, BACs or SACs (50 mM) and lipid. Results are reported as the mean of triplicate samples ±SD. In FIG. 28A the ratio of HCV-firefly luciferase RNA/Renilla luciferase RNA is shown for each enzymatic nucleic acid or control tested. As compared to paired BAC controls (adjusted to 1), luciferase RNA levels were reduced by 40% and 25% for the site 195 or 330 enzymatic nucleic acids, respectively. In FIG. 28B the ratio of HCV-firefly luciferase luminescence/Renilla luciferase luminescence is shown after treatment with site 195 or 330 enzymatic nucleic acids or paired controls. As compared to paired BAC controls (adjusted to 1), inhibition of protein expression was 70% and 40% for the site 195 or 330 enzymatic nucleic acids, respectively P<0.01.


[0280]
FIG. 29 is a set a bar graphs showing interferon (IFN) alpha 2a and 2b dose response in combination with site 195 anti-HCV enzymatic nucleic acid treatment. FIG. 29A shows data for IFN alfa 2a treatment. FIG. 29B shows data for IFN alfa 2b treatment. Viral yield is reported from HeLa cells pretreated with IFN in units/ml (U/ml) as indicated for 4 h prior to infection and then treated with either 200 nM control (SAC) or site 195 anti-HCV enzymatic nucleic acid (195 RZ) for 24 h after infection. Cells were infected with a MOI=0.1 for 30 min and collected at 24 h post infection. Error bars represent the S.D. of the mean of triplicate determinations.


[0281]
FIG. 30 is a line graph showing site 195 anti-HCV enzymatic nucleic acid dose response in combination with interferon (IFN) alpha 2a and 2b pretreatment. Viral yield is reported from HeLa cells pretreated for 4 h with or without IFN and treated with doses of site 195 anti-HCV enzymatic nucleic acid (195 RZ) as indicated for 24 h after infection. Anti-HCV enzymatic nucleic acid was mixed with control oligonucleotide (SAC) to maintain a constant 200 nM total dose of nucleic acid for delivery. Cells were infected with a MOI=0.1 for 30 min and collected at 24 h post infection. Error bars represent the S.D. of the mean of triplicate determinations.


[0282]
FIG. 31 is a set of bar graphs showing data from consensus interferon (CIFN)/enzymatic nucleic acid combination treatment. FIG. 31A shows CIFN dose response with site 195 anti-HCV enzymatic nucleic acid treatment. Viral yield is reported from cells pretreated with CIFN in units/ml (U/ml) as indicated and treated with either 200 nM control (SAC) or site 195 anti-HCV enzymatic nucleic acid (195 RZ). FIG. 31B shows site 195 anti-HCV enzymatic nucleic acid dose response with CIFN pretreatment. Viral yield is reported from cells pretreated with or without CIFN and treated with concentrations of site 195 anti-HCV enzymatic nucleic acid (195 RZ) as indicated. Anti-HCV enzymatic nucleic acid was mixed with control oligonucleotide (SAC) to maintain a constant 200 nM total dose of nucleic acid for delivery. Cells were infected with a MOI=0.1 for 30 min. and collected at 24 h post infection. Error bars represent the S.D. of the mean of triplicate determinations.


[0283]
FIG. 32 is a bar graph showing enzymatic nucleic acid activity and enhanced antiviral effect of an anti-HCV enzymatic nucleic acid targeting site 195 used in combination with consensus interferon (CIFN). Viral yield is reported from cells treated as indicated. BAC, cells were treated with 200 nM BAC (binding attenuated control) for 24 h after infection; CIFN+BAC, cells were treated with 12.5 U/ml CIFN for 4 h prior to infection and with 200 nM BAC for 24 h after infection; 195 RZ, cells were treated with 200 nM site 195 anti-HCV enzymatic nucleic acid for 24 h after infection; CIFN+195 RZ, cells were treated with 12.5 U/ml CIFN for 4 h prior to infection and with 200 nM site 195 anti-HCV enzymatic nucleic acid for 24 h after infection. Cells were infected with a MOI=0.1 for 30 min. Error bars represent the S.D. of the mean of triplicate determinations.


[0284]
FIG. 33 is a bar graph showing inhibition of a HCV-PV chimera replication by treatment with zinzyme enzymatic nucleic acid molecules targeting different sites within the HCV 5′-UTR compared to a scrambled attenuated core control (SAC) zinzyme.


[0285]
FIG. 34 is a bar graph showing inhibition of a HCV-PV chimera replication by antisense nucleic acid molecules targeting conserved regions of the HCV 5′-UTR compared to scrambled antisense controls.


[0286]
FIG. 35 shows the structure of compounds (2-5A) utilized in the study. “X” denotes the position of oxygen (O) in analog I or sulfur (S) in thiophosphate (P═S) analog II. The 2-5A compounds were synthesized, deprotected and purified as described herein utilizing CPG support with 3′-inverted abasic nucleotide. For chain extension 5′-O-(4,4′-dimetoxytrityl)-3′-O-(tert-butyldimethylsilyl)-N-6-benzoyladenosine-2-cyanoethyl-N,N-diisopropyl-phosphoramidite (Chem. Genes Corp., Waltham, Mass.) was employed. Introduction of a 5′-terminal phosphate (analog I) or thiophosphate (analog II) group was performed with “Chemical Phosphorylation Reagent” (Glen Research, Sterling, Va.). Structures of the final compounds were confirmed by MALDI-TOF analysis.


[0287]
FIG. 36 is a bar graph showing ribozyme activity and enhanced antiviral effect. (A) Interferon/ribozyme combination treatment. (B) 2-5A/ribozyme combination treatment. HeLa cells seeded in 96-well plates (10,000 cells per well) were pretreated as indicated for 4 hours. For pretreatment, SAC (RPI 17894), RZ (RPI 13919), and 2-5A analog I (RPI 21096) (200 nM) were complexed with lipid cytofectin. Cells were then infected with HCV-PV at a multiplicity of infection of 0.1. Virus inoculum was replaced after 30 minutes with media containing 5% serum and 100 nM RZ or SAC as indicated, complexed with cytofectin RPI.9778. After 20 hours, cells were lysed by 3 freeze/thaw cycles and virus was quantified by plaque assay. Plaque forming units (PFU)/ml are shown as the mean of triplicate samples +SEM. The absolute amount of viral yield in treated cells varied from day to day, presumably due to day to day variations in cell plating and transfection complexation. None, normal media; IFN, 10 U/ml consensus interferon; SAC, scrambled arm attenuated core control (RPI 17894); RZ, anti-HCV ribozyme (RPI 13919); 2-5A, (RPI 21096).


[0288]
FIG. 37 is a graph showing the inhibition of viral replication with anti-HCV ribozyme (RPI 13919) or 2-5A (RPI 21096) treatment. HeLa cells were treated as described in FIG. 36 except that there was no pretreatment and 200 nM oligonucleotide was used for treatment. 2-5A P═S contains a 5′-terminal thiophosphate (RPI21095) (see FIG. 35).


[0289]
FIG. 38 is a bar graph showing anti-HCV ribozyme in combination with 2-5A treatment. HeLa cells were treated as described in FIG. 37 except concentrations were co-varied as shown to maintain a constant 200 nM total oligonucleotide dose for transfection. Cells treated with 50 nM anti-HCV ribozyme (RPI 13919) (middle bars) were also treated with 150 nM SAC (RPI 17894) or 2-5A (RPI 21096); likewise, cells treated with 100 nM anti-HCV ribozyme (bars at right) were also treated with 100 nM SAC or 2-5A.







MECHANISM OF ACTION OF NUCLEIC ACID MOLECULES OF THE INVENTION

[0290] Decoy: Nucleic acid decoy molecules are mimetics of naturally occurring nucleic acid molecules or portions of naturally occurring nucleic acid molecules that can be used to modulate the function of a specific protein or a nucleic acid whose activity is dependant on interaction with the naturally occurring nucleic acid molecule. Decoys modulate the function of a target protein or nucleic acid by competing with authentic nucleic acid binding to the ligand of interest. Often, the nucleic acid decoy is a truncated version of a nucleic acid sequence that is recognized, for example by a particular protein, such as a transcription factor or polymerase. Decoys can be chemically modified to increase binding affinity to the target ligand as well as to increase the enzymatic and chemical stability of the decoy. In addition, bridging and non-bridging linkers can be introduced into the decoy sequence to provide additional binding affinity to the target ligand. Decoy molecules of the invention that bind to an HCV or HBV target, such as HBV reverse transcriptase or HBV reverse transcriptase primer, or an enhancer region of the HBV pregenomic RNA, for example the Enhancer I element, modulate the transcription of RNA to DNA and therefore modulate expression of the pregenomic RNA of the virus (see FIGS. 13 and 14).


[0291] Aptamer: Nucleic acid aptamers can be selected to specifically bind to a particular ligand of interest (see for example Gold et al., U.S. Pat. No. 5,567,588 and U.S. Pat. No. 5,475,096, Gold et al., 1995, Annu. Rev. Biochem., 64, 763; Brody and Gold, 2000, J. Biotechnol., 74, 5; Sun, 2000, Curr. Opin. Mol. Ther., 2, 100; Kusser, 2000, J. Biotechnol., 74, 27; Hermann and Patel, 2000, Science, 287, 820; and Jayasena, 1999, Clinical Chemistry, 45, 1628). For example, the use of in vitro selection can be applied to evolve nucleic acid aptamers with binding specificity for HBV RT and/or HBV RT primer. Nucleic acid aptamers can include chemical modifications and linkers as described herein. Aptamer molecules of the invention that bind to a reverse transcriptase or reverse transcriptase primer, such as HBV reverse transcriptase or HBV reverse transcriptase primer, modulate the transcription of RNA to DNA and therefore modulate expression of the pregenomic RNA of the virus.


[0292] Antisense: Antisense molecules can be modified or unmodified RNA, DNA, or mixed polymer oligonucleotides and primarily function by specifically binding to matching sequences resulting in modulation 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 can 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).


[0293] 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.


[0294] 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. S No. 60/082,404 which was filed on Apr. 20, 1998; Hartmann et al., U.S. S No. 60/101,174 which was filed on Sep. 21, 1998) all of these are incorporated by reference herein in their entirety.


[0295] 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.


[0296] Triplex Forming Oligonucleotides (TFO): Single stranded oligonucleotide can be designed to bind to genomic DNA in a sequence specific manner. TFOs can be comprised of pyrimidine-rich oligonucleotides which bind DNA helices through Hoogsteen Base-pairing (Wu-Pong, supra). In addition, TFOs can be chemically modified to increase binding affinity to target DNA sequences. The resulting triple helix composed of the DNA sense, DNA antisense, and TFO disrupts RNA synthesis by RNA polymerase. The TFO mechanism can result in gene expression or cell death since binding may be irreversible (Mukhopadhyay & Roth, supra) 2′-5′ Oligoadenylates: The 2-5A 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 (2-5A). 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 modulation of viral replication.


[0297] (2′-5′) oligoadenylate structures can 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.


[0298] RNA interference (RNAi): RNA interference refers to the process of sequence specific post transcriptional gene silencing in animals mediated by short interfering RNAs (siRNA) (Fire et al., 1998, Nature, 391, 806). The corresponding process in plants is commonly referred to as post transcriptional gene silencing or RNA silencing and is also referred to as quelling in fungi. The process of post transcriptional gene silencing is thought to be an evolutionarily conserved cellular defense mechanism used to prevent the expression of foreign genes which is commonly shared by diverse flora and phyla (Fire et al., 1999, Trends Genet., 15, 358). Such protection from foreign gene expression may have evolved in response to the production of double stranded RNAs (dsRNA) derived from viral infection or the random integration of transposon elements into a host genome via a cellular response that specifically destroys homologous single stranded RNA or viral genomic RNA. The presence of dsRNA in cells triggers the RNAi response though a mechanism that has yet to be fully characterized. This mechanism appears to be different from the interferon response that results from dsRNA mediated activation of protein kinase PKR and 2′,5′-oligoadenylate synthetase resulting in non-specific cleavage of mRNA by ribonuclease L.


[0299] The presence of long dsRNAs in cells stimulates the activity of a ribonuclease III enzyme referred to as dicer. Dicer is involved in the processing of the dsRNA into short pieces of dsRNA known as short interfering RNAs (siRNA) (Berstein et al., 2001, Nature, 409, 363). Short interfering RNAs derived from dicer activity are typically about 21-23 nucleotides in length and comprise about 19 base pair duplexes. Dicer has also been implicated in the excision of 21 and 22 nucleotide small temporal RNAs (stRNA) from precursor RNA of conserved structure that are implicated in translational control (Hutvagner et al., 2001, Science, 293, 834). The RNAi response also features an endonuclease complex containing a siRNA, commonly referred to as an RNA-induced silencing complex (RISC), which mediates cleavage of single stranded RNA having sequence homologous to the siRNA. Cleavage of the target RNA takes place in the middle of the region complementary to the guide sequence of the siRNA duplex (Elbashir et al., 2001, Genes Dev., 15, 188).


[0300] Short interfering RNA mediated RNAi has been studied in a variety of systems. Fire et al., 1998, Nature, 391, 806, were the first to observe RNAi in C. Elegans. Wianny and Goetz, 1999, Nature Cell Biol., 2, 70, describes RNAi mediated by dsRNA in mouse embryos. Hammond et al., 2000, Nature, 404, 293, describe RNAi in Drosophila cells transfected with dsRNA. Elbashir et al., 2001, Nature, 411, 494, describe RNAi induced by introduction of duplexes of synthetic 21-nucleotide RNAs in cultured mammalian cells including human embryonic kidney and HeLa cells. Recent work in Drosophila embryonic lysates has revealed certain requirements for siRNA length, structure, chemical composition, and sequence that are essential to mediate efficient RNAi activity. These studies have shown that 21 nucleotide siRNA duplexes are most active when containing two nucleotide 3′-overhangs. Furthermore, substitution of one or both siRNA strands with 2′-deoxy or 2′-O-methyl nucleotides abolishes RNAi activity, whereas substitution of 3′-terminal siRNA nucleotides with deoxy nucleotides was shown to be tolerated. Mismatch sequences in the center of the siRNA duplex were also shown to abolish RNAi activity. In addition, these studies also indicate that the position of the cleavage site in the target RNA is defined by the 5′-end of the siRNA guide sequence rather than the 3′-end (Elbashir et al., 2001, EMBO J., 20, 6877). Other studies have indicated that a 5′-phosphate on the target-complementary strand of a siRNA duplex is required for siRNA activity and that ATP is utilized to maintain the 5′-phosphate moiety on the siRNA (Nykanen et al., 2001, Cell, 107, 309), however siRNA molecules lacking a 5′-phosphate are active when introduced exogenously, suggesting that 5′-phosphorylation of siRNA constructs may occur in vivo.


[0301] Enzymatic Nucleic Acid: Several varieties of naturally occurring enzymatic RNAs are presently known (Doherty and Doudna, 2001, Annu. Rev. Biophys. Biomol. Struct., 30, 457-475; Symons, 1994, Curr. Opin. Struct. Biol., 4, 322-30). 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). 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.


[0302] Nucleic acid molecules of this invention can block HBV or HCV protein expression and can be used to treat disease or diagnose disease associated with the levels of HBV or HCV.


[0303] The enzymatic nature of an enzymatic nucleic acid has significant advantages, such as the concentration of nucleic acid necessary to affect a therapeutic treatment is low. This advantage reflects the ability of the enzymatic nucleic acid molecule 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 molecule is a highly specific modulator, with the specificity of modulation 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 molecule.


[0304] Nucleic acid molecules having an endonuclease enzymatic activity are able to repeatedly cleave other separate RNA molecules in a nucleotide base sequence-specific manner. With proper design and construction, such enzymatic nucleic acid molecules can be targeted to any RNA transcript, and efficient cleavage achieved 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; and Jefferies et al., 17 Nucleic Acids Research 1371, 1989; Chartrand et al., 1995, Nucleic Acids Research 23, 4092; Santoro et al., 1997, PNAS 94, 4262).


[0305] Because of their sequence specificity, trans-cleaving enzymatic nucleic acid molecules 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 acid molecule 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 modulated (Warashina et al., 1999, Chemistry and Biology, 6, 237-250.


[0306] The present invention also features nucleic acid sensor molecules or allozymes having sensor domains comprising nucleic acid decoys and/or aptamers of the invention. Interaction of the nucleic acid sensor molecule's sensor domain with a molecular target, such as HCV or HBV target, e.g., HBV RT and/or HBV RT primer, can activate or inactivate the enzymatic nucleic acid domain of the nucleic acid sensor molecule, such that the activity of the nucleic acid sensor molecule is modulated in the presence of the target-signaling molecule. The nucleic acid sensor molecule can be designed to be active in the presence of the target molecule or alternately, can be designed to be inactive in the presence of the molecular target. For example, a nucleic acid sensor molecule is designed with a sensor domain having the sequence (UUCA)n, where n is an integer from 1-10. In a non-limiting example, interaction of the HBV RT primer with the sensor domain of the nucleic acid sensor molecule can activate the enzymatic nucleic acid domain of the nucleic acid sensor molecule such that the sensor molecule catalyzes a reaction, for example cleavage of HBV RNA. In this example, the nucleic acid sensor molecule is activated in the presence of HBV RT or HBV RT primer, and can be used as a therapeutic to treat HBV infection. Alternately, the reaction can comprise cleavage or ligation of a labeled nucleic acid reporter molecule, providing a useful diagnostic reagent to detect the presence of HBV in a system.


[0307] HCV Target Sites


[0308] Targets for useful nucleic acid molecules and nuclease activating compounds or chimeras 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. 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. Nucleic acid molecules and nuclease activating compounds or chimeras to such targets are designed as described in those applications and synthesized to be tested in vitro and in vivo, as also described. Such nucleic acid molecules and nuclease activating compounds or chimeras can also be optimized and delivered as described therein.


[0309] The sequence of HCV RNAs were screened for optimal enzymatic nucleic acid molecule target sites using a computer folding algorithm. Enzymatic nucleic acid cleavage sites were identified. These sites are shown in Tables XVIII, XIX, XX and XXIII (All sequences are 5′ to 3′ in the tables). The nucleotide base position is noted in the tables as that site to be cleaved by the designated type of enzymatic nucleic acid molecule. The nucleotide base position is noted in the tables as that site to be cleaved by the designated type of enzymatic nucleic acid molecule.


[0310] Because HCV RNAs are highly homologous in certain regions, some enzymatic nucleic acid molecule target sites are also homologous. In this case, a single enzymatic nucleic acid molecule will target different classes of HCV RNA. The advantage of one enzymatic nucleic acid molecule that targets several classes of HCV RNA is clear, especially in cases where one or more of these RNAs can contribute to the disease state.


[0311] Enzymatic nucleic acid molecules were designed that could bind and were individually analyzed by computer folding (Jaeger et al., 1989 Proc. Natl. Acad. Sci. USA, 86, 7706) to assess whether the enzymatic nucleic acid molecule sequences fold into the appropriate secondary structure. Those enzymatic nucleic acid molecules with unfavorable intramolecular interactions between the binding arms and the catalytic core are eliminated from consideration. 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. Enzymatic nucleic acid molecules were designed to anneal to various sites in the mRNA message. The binding arms are complementary to the target site sequences described above.


[0312] HBV Target Sites


[0313] Targets for useful ribozymes and antisense nucleic acids targeting HBV 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. 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. 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. Ribozymes 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 ribozyme 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, USSN (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 ribozymes can be useful to test efficacy of action of the enzymatic nucleic acid molecule and/or antisense prior to testing in humans.


[0314] Antisense, hammerhead, DNAzyme, NCH (Inozyme), amberzyme, zinzyme or G-Cleaver ribozyme 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.


[0315] Antisense, hammerhead, DNAzyme, NCH, amberzyme, zinzyme or G-Cleaver ribozyme 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.


[0316] Synthesis of Nucleic acid Molecules


[0317] 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., decoy nucleic acid molecules, aptamer nucleic acid molecules antisense nucleic acid molecules, enzymatic nucleic acid molecules) are preferably used for exogenous delivery. The simple structure of these molecules increases the ability of the nucleic acid to invade targeted regions of protein and/or RNA structure. Exemplary molecules of the instant invention are chemically synthesized, and others can similarly be synthesized.


[0318] Oligonucleotides (e.g., DNA oligonucleotides) are synthesized using protocols known in the art, for example 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. 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 12, 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.


[0319] Deprotection of the DNA-based 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.


[0320] The method of synthesis used for normal RNA including certain decoy nucleic acid molecules and 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 12, 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.


[0321] 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.


[0322] 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.


[0323] 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.


[0324] Inactive hammerhead ribozymes 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 nucleic acid decoy molecules to inactivate the molecule and such molecules can serve as a negative control.


[0325] 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.


[0326] 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).


[0327] The nucleic acid molecules of the present invention can be 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). Ribozymes can be purified by gel electrophoresis using general methods or can be purified by high pressure liquid chromatography (HPLC; see Wincott et al., supra, the totality of which is hereby incorporated herein by reference) and re-suspended in water.


[0328] The sequences of the nucleic acid molecules that are chemically synthesized, useful in this study, are shown in Tables XI, XV, XX, XXI, XXII and XXIII. The nucleic acid sequences listed in Tables IV-XI, XIV-XV and XVIII-XXIII can be formed of ribonucleotides or other nucleotides or non-nucleotides. Such nucleic acid sequences are equivalent to the sequences described specifically in the Tables.


[0329] Optimizing Activity of the Nucleic Acid Molecule of the Invention


[0330] Chemically synthesizing nucleic acid molecules with modifications (base, sugar and/or phosphate) can prevent their degradation by serum ribonucleases, which can 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; and Rossi et al., International Publication No. WO 91/03162; Sproat, U.S. Pat. No. 5,334,711; Gold et al., U.S. Pat. No. 6,300,074; and Burgin et al., supra; all of which are incorporated by reference herein). All of the above references describe various chemical modifications that can be made to the base, phosphate and/or sugar moieties of the nucleic acid molecules described herein. Modifications that enhance their efficacy in cells, and removal of bases from nucleic acid molecules to shorten oligonucleotide synthesis times and reduce chemical requirements are desired.


[0331] 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. S 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 ribozymes without modulating 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.


[0332] While chemical modification of oligonucleotide internucleotide linkages with phosphorothioate, phosphorothioate, and/or 5′-methylphosphonate linkages improves stability, excessive modifications can 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.


[0333] Nucleic acid molecules having chemical modifications that maintain or enhance activity are provided. Such a nucleic acid is also generally more resistant to nucleases than an unmodified nucleic acid. Accordingly, the in vitro and/or in vivo activity should not be significantly lowered. In cases in which modulation is the goal, therapeutic nucleic acid molecules delivered exogenously should optimally be stable within cells until translation of the target RNA has been modulated long enough to reduce the levels of the undesirable protein. This period of time varies between hours to days depending upon the disease state. 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 (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.


[0334] In one embodiment, nucleic acid molecules of the invention include one or more G-clamp nucleotides. A G-clamp nucleotide is a modified cytosine analog wherein the modifications confer the ability to hydrogen bond both Watson-Crick and Hoogsteen faces of a complementary guanine within a duplex, see for example Lin and Matteucci, 1998, J. Am. Chem. Soc., 120, 8531-8532. A single G-clamp analog substation within an oligonucleotide can result in substantially enhanced helical thermal stability and mismatch discrimination when hybridized to complementary oligonucleotides. The inclusion of such nucleotides in nucleic acid molecules of the invention results in both enhanced affinity and specificity to nucleic acid targets. In another embodiment, nucleic acid molecules of the invention include one or more LNA “locked nucleic acid” nucleotides such as a 2′,4′-C methylene bicyclo nucleotide (see for example Wengel et al., International PCT Publication No. WO 00/66604 and WO 99/14226).


[0335] In another embodiment, the invention features conjugates and/or complexes of nucleic acid molecules targeting HBV or HCV. Such conjugates and/or complexes can be used to facilitate delivery of molecules into a biological system, such as a cell. The conjugates and complexes provided by the instant invention can impart therapeutic activity by transferring therapeutic compounds across cellular membranes, altering the pharmacokinetics, and/or modulating the localization of nucleic acid molecules of the invention. The present invention encompasses the design and synthesis of novel conjugates and complexes for the delivery of molecules, including, but not limited to, small molecules, lipids, phospholipids, nucleosides, nucleotides, nucleic acids, antibodies, toxins, negatively charged polymers and other polymers, for example proteins, peptides, hormones, carbohydrates, polyethylene glycols, or polyamines, across cellular membranes. In general, the transporters described are designed to be used either individually or as part of a multi-component system, with or without degradable linkers. These compounds are expected to improve delivery and/or localization of nucleic acid molecules of the invention into a number of cell types originating from different tissues, in the presence or absence of serum (see Sullenger and Cech, U.S. Pat. No. 5,854,038). Conjugates of the molecules described herein can be attached to biologically active molecules via linkers that are biodegradable, such as biodegradable nucleic acid linker molecules.


[0336] The term “biodegradable nucleic acid linker molecule” as used herein, refers to a nucleic acid molecule that is designed as a biodegradable linker to connect one molecule to another molecule, for example, a biologically active molecule. The stability of the biodegradable nucleic acid linker molecule can be modulated by using various combinations of ribonucleotides, deoxyribonucleotides, and chemically modified nucleotides, for example, 2′-O-methyl, 2′-fluoro, 2′-amino, 2′-O-amino, 2′-C-allyl, 2′-O-allyl, and other 2′-modified or base modified nucleotides. The biodegradable nucleic acid linker molecule can be a dimer, trimer, tetramer or longer nucleic acid molecule, for example, an oligonucleotide of about 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20 nucleotides in length, or can comprise a single nucleotide with a phosphorus-based linkage, for example, a phosphoramidate or phosphodiester linkage. The biodegradable nucleic acid linker molecule can also comprise nucleic acid backbone, nucleic acid sugar, or nucleic acid base modifications.


[0337] The term “biodegradable” as used herein, refers to degradation in a biological system, for example enzymatic degradation or chemical degradation.


[0338] The term “biologically active molecule” as used herein, refers to compounds or molecules that are capable of eliciting or modifying a biological response in a system. Non-limiting examples of biologically active molecules contemplated by the instant invention include therapeutically active molecules such as antibodies, hormones, antivirals, peptides, proteins, chemotherapeutics, small molecules, vitamins, co-factors, nucleosides, nucleotides, oligonucleotides, enzymatic nucleic acids, antisense nucleic acids, triplex forming oligonucleotides, 2,5-A chimeras, siRNA, dsRNA, allozymes, aptamers, decoys and analogs thereof. Biologically active molecules of the invention also include molecules capable of modulating the pharmacokinetics and/or pharmacodynamics of other biologically active molecules, for example, lipids and polymers such as polyamines, polyamides, polyethylene glycol and other polyethers.


[0339] The term “phospholipid” as used herein, refers to a hydrophobic molecule comprising at least one phosphorus group. For example, a phospholipid can comprise a phosphorus-containing group and saturated or unsaturated alkyl group, optionally substituted with OH, COOH, oxo, amine, or substituted or unsubstituted aryl groups.


[0340] Therapeutic nucleic acid molecules (e.g., decoy nucleic acid molecules) delivered exogenously optimally are stable within cells until reverse trascription of the pregenomic RNA has been modulated long enough to reduce the levels of HBV or HCV DNA. The nucleic acid molecules are 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.


[0341] In yet another embodiment, nucleic acid molecules having chemical modifications that maintain or enhance enzymatic activity are provided. Such nucleic acids are also generally more resistant to nucleases than unmodified nucleic acids. Thus, in vitro and/or in vivo the activity should not be significantly lowered. As exemplified herein, such nucleic acid molecules are useful in vitro and/or in vivo even if activity over all is reduced 10 fold (Burgin et al., 1996, Biochemistry, 35, 14090).


[0342] Use of 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, nucleic acid decoy, or nucleic acid aptamer molecules targeted to different genes; nucleic acid molecules coupled with known small molecule modulators ors; 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.


[0343] In another aspect the nucleic acid molecules comprise a 5′ and/or a 3′-cap structure.


[0344] 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).


[0345] 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 Iyer, 1993, Tetrahedron 49, 1925; incorporated by reference herein).


[0346] 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.


[0347] The term “alkyl” as used herein refers to a saturated aliphatic hydrocarbon, including straight-chain, branched-chain “isoalkyl”, and cyclic alkyl groups. The term “alkyl” also comprises alkoxy, alkyl-thio, alkyl-thio-alkyl, alkoxyalkyl, alkylamino, alkenyl, alkynyl, alkoxy, cycloalkenyl, cycloalkyl, cycloalkylalkyl, heterocycloalkyl, heteroaryl, C1-C6 hydrocarbyl, aryl or substituted aryl groups. Preferably, the alkyl group has 1 to 12 carbons. More preferably it is a lower alkyl of from about 1 to 7 carbons, more preferably about 1 to 4 carbons. The alkyl group can be substituted or unsubstituted. When substituted the substituted group(s) preferably comprise hydroxy, oxy, thio, amino, nitro, cyano, alkoxy, alkyl-thio, alkyl-thio-alkyl, alkoxyalkyl, alkylamino, silyl, alkenyl, alkynyl, alkoxy, cycloalkenyl, cycloalkyl, cycloalkylalkyl, heterocycloalkyl, heteroaryl, C1-C6 hydrocarbyl, aryl or substituted aryl groups. The term “alkyl” also includes alkenyl groups containing at least one carbon-carbon double bond, including straight-chain, branched-chain, and cyclic groups. Preferably, the alkenyl group has about 2 to 12 carbons. More preferably it is a lower alkenyl of from about 2 to 7 carbons, more preferably about 2 to 4 carbons. The alkenyl group can be substituted or unsubstituted. When substituted the substituted group(s) preferably comprise hydroxy, oxy, thio, amino, nitro, cyano, alkoxy, alkyl-thio, alkyl-thio-alkyl, alkoxyalkyl, alkylamino, silyl, alkenyl, alkynyl, alkoxy, cycloalkenyl, cycloalkyl, cycloalkylalkyl, heterocycloalkyl, heteroaryl, C1-C6 hydrocarbyl, aryl or substituted aryl groups. The term “alkyl” also includes alkynyl groups containing at least one carbon-carbon triple bond, including straight-chain, branched-chain, and cyclic groups. Preferably, the alkynyl group has about 2 to 12 carbons. More preferably it is a lower alkynyl of from about 2 to 7 carbons, more preferably about 2 to 4 carbons. The alkynyl group can be substituted or unsubstituted. When substituted the substituted group(s) preferably comprise hydroxy, oxy, thio, amino, nitro, cyano, alkoxy, alkyl-thio, alkyl-thio-alkyl, alkoxyalkyl, alkylamino, silyl, alkenyl, alkynyl, alkoxy, cycloalkenyl, cycloalkyl, cycloalkylalkyl, heterocycloalkyl, heteroaryl, C1-C6 hydrocarbyl, aryl or substituted aryl groups. Alkyl groups or moieties of the invention can also include aryl, alkylaryl, carbocyclic aryl, heterocyclic aryl, amide and ester groups. 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 about 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.


[0348] The term “alkoxyalkyl” as used herein refers to an alkyl-O-alkyl ether, for example methoxyethyl or ethoxymethyl.


[0349] The term “alkyl-thio-alkyl” as used herein refers to an alkyl-S-alkyl thioether, for example methylthiomethyl or methylthioethyl.


[0350] The term “amination” as used herein refers to a process in which an amino group or substituted amine is introduced into an organic molecule.


[0351] The term “exocyclic amine protecting moiety” as used herein refers to a nucleobase amino protecting group compatible with oligonucleotide synthesis, for example an acyl or amide group.


[0352] The term “alkenyl” as used herein refers to a straight or branched hydrocarbon of a designed number of carbon atoms containing at least one carbon-carbon double bond. Examples of “alkenyl” include vinyl, allyl, and 2-methyl-3-heptene.


[0353] The term “alkoxy” as used herein refers to an alkyl group of indicated number of carbon atoms attached to the parent molecular moiety through an oxygen bridge. Examples of alkoxy groups include, for example, methoxy, ethoxy, propoxy and isopropoxy.


[0354] The term “alkynyl” as used herein refers to a straight or branched hydrocarbon of a designed number of carbon atoms containing at least one carbon-carbon triple bond. Examples of “alkynyl” include propargyl, propyne, and 3-hexyne.


[0355] The term “aryl” as used herein refers to an aromatic hydrocarbon ring system containing at least one aromatic ring. The aromatic ring can optionally be fused or otherwise attached to other aromatic hydrocarbon rings or non-aromatic hydrocarbon rings. Examples of aryl groups include, for example, phenyl, naphthyl, 1,2,3,4-tetrahydronaphthalene and biphenyl. Preferred examples of aryl groups include phenyl and naphthyl.


[0356] The term “cycloalkenyl” as used herein refers to a C3-C8 cyclic hydrocarbon containing at least one carbon-carbon double bond. Examples of cycloalkenyl include cyclopropenyl, cyclobutenyl, cyclopentenyl, cyclopentadiene, cyclohexenyl, 1,3-cyclohexadiene, cycloheptenyl, cycloheptatrienyl, and cyclooctenyl.


[0357] The term “cycloalkyl” as used herein refers to a C3-C8 cyclic hydrocarbon. Examples of cycloalkyl include cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl and cyclooctyl.


[0358] The term “cycloalkylalkyl,” as used herein, refers to a C3-C7 cycloalkyl group attached to the parent molecular moiety through an alkyl group, as defined above. Examples of cycloalkylalkyl groups include cyclopropylmethyl and cyclopentylethyl.


[0359] The terms “halogen” or “halo” as used herein refers to indicate fluorine, chlorine, bromine, and iodine.


[0360] The term “heterocycloalkyl,” as used herein refers to a non-aromatic ring system containing at least one heteroatom selected from nitrogen, oxygen, and sulfur. The heterocycloalkyl ring can be optionally fused to or otherwise attached to other heterocycloalkyl rings and/or non-aromatic hydrocarbon rings. Preferred heterocycloalkyl groups have from 3 to 7 members. Examples of heterocycloalkyl groups include, for example, piperazine, morpholine, piperidine, tetrahydrofuran, pyrrolidine, and pyrazole. Preferred heterocycloalkyl groups include piperidinyl, piperazinyl, morpholinyl, and pyrolidinyl.


[0361] The term “heteroaryl” as used herein refers to an aromatic ring system containing at least one heteroatom selected from nitrogen, oxygen, and sulfur. The heteroaryl ring can be fused or otherwise attached to one or more heteroaryl rings, aromatic or non-aromatic hydrocarbon rings or heterocycloalkyl rings. Examples of heteroaryl groups include, for example, pyridine, furan, thiophene, 5,6,7,8-tetrahydroisoquinoline and pyrimidine. Preferred examples of heteroaryl groups include thienyl, benzothienyl, pyridyl, quinolyl, pyrazinyl, pyrimidyl, imidazolyl, benzimidazolyl, furanyl, benzofuranyl, thiazolyl, benzothiazolyl, isoxazolyl, oxadiazolyl, isothiazolyl, benzisothiazolyl, triazolyl, tetrazolyl, pyrrolyl, indolyl, pyrazolyl, and benzopyrazolyl.


[0362] The term “C1-C6 hydrocarbyl” as used herein refers to straight, branched, or cyclic alkyl groups having 1-6 carbon atoms, optionally containing one or more carbon-carbon double or triple bonds. Examples of hydrocarbyl groups include, for example, methyl, ethyl, propyl, isopropyl, n-butyl, sec-butyl, tert-butyl, pentyl, 2-pentyl, isopentyl, neopentyl, hexyl, 2-hexyl, 3-hexyl, 3-methylpentyl, vinyl, 2-pentene, cyclopropylmethyl, cyclopropyl, cyclohexylmethyl, cyclohexyl and propargyl. When reference is made herein to C1-C6 hydrocarbyl containing one or two double or triple bonds it is understood that at least two carbons are present in the alkyl for one double or triple bond, and at least four carbons for two double or triple bonds.


[0363] The term “nucleotide” as used herein refers to a heterocyclic nitrogenous base in N-glycosidic linkage with a phosphorylated sugar. Nucleotides are 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, non-natural 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 chemically modified and other natural nucleic acid bases that can be introduced into nucleic acids include, for example, 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, quesosine, 2-thiouridine, 4-thiouridine, wybutosine, wybutoxosine, 4-acetylcytidine, 5-(carboxyhydroxymethyl)uridine, 5′-carboxymethylaminomethyl-2-thiouridine, 5-carboxymethylaminomethyluridine, beta-D-galactosylqueosine, 1-methyladenosine, 1-methylinosine, 2,2-dimethylguanosine, 3-methylcytidine, 2-methyladenosine, 2-methylguanosine, N6-methyladenosine, 7-methylguanosine, 5-methoxyaminomethyl-2-thiouridine, 5-methylaminomethyluridine, 5-methylcarbonylmethyluridine, 5-methyloxyuridine, 5-methyl-2-thiouridine, 2-methylthio-N-6-isopentenyladenosine, beta-D-mannosylqueosine, uridine-5-oxyacetic acid, 2-thiocytidine, threonine derivatives 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 can 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.


[0364] The term “nucleoside” as used herein refers to a heterocyclic nitrogenous base in N-glycosidic linkage with a sugar. Nucleosides are 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 nucleoside sugar moiety. Nucleosides generally comprise a base and sugar group. The nucleosides can be unmodified or modified at the sugar, and/or base moiety (also referred to interchangeably as nucleoside analogs, modified nucleosides, non-natural nucleosides, non-standard nucleosides 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 chemically modified and other natural nucleic acid bases that can be introduced into nucleic acids 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, quesosine, 2-thiouridine, 4-thiouridine, wybutosine, wybutoxosine, 4-acetylcytidine, 5-(carboxyhydroxymethyl)uridine, 5′-carboxymethylaminomethyl-2-thiouridine, 5-carboxymethylaminomethyluridine, beta-D-galactosylqueosine, 1-methyladenosine, 1-methylinosine, 2,2-dimethylguanosine, 3-methylcytidine, 2-methyladenosine, 2-methylguanosine, N6-methyladenosine, 7-methylguanosine, 5-methoxyaminomethyl-2-thiouridine, 5-methylaminomethyluridine, 5-methylcarbonylmethyluridine, 5-methyloxyuridine, 5-methyl-2-thiouridine, 2-methylthio-N-6-isopentenyladenosine, beta-D-mannosylqueosine, uridine-5-oxyacetic acid, 2-thiocytidine, threonine derivatives and others (Burgin et al., 1996, Biochemistry, 35, 14090; Uhlman & Peyman, supra). By “modified bases” in this aspect is meant nucleoside bases other than adenine, guanine, cytosine and uracil at 1′ position or their equivalents; such bases can 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.


[0365] In one embodiment, the invention features modified nucleic acid molecules with phosphate backbone modifications comprising one or more phosphorothioate, phosphorodithioate, methylphosphonate, morpholino, amidate carbamate, carboxymethyl, acetamidate, polyamide, sulfonate, sulfonamide, sulfamate, formacetal, thioformacetal, 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.


[0366] The term “abasic” as used herein refers to sugar moieties lacking a base or having other chemical groups in place of a base at the 1′ position, for example a 3′,3′-linked or 5′,5′-linked deoxyabasic ribose derivative (for more details see Wincott et al., International PCT publication No. WO 97/26270).


[0367] The term “unmodified nucleoside” as used herein refers to one of the bases adenine, cytosine, guanine, thymine, uracil joined to the 1′ carbon of β-D-ribo-furanose.


[0368] The term “modified nucleoside” as used herein refers to any nucleotide base which contains a modification in the chemical structure of an unmodified nucleotide base, sugar and/or phosphate.


[0369] In connection with 2′-modified nucleotides as described for the present invention, by “amino” is meant 2′-NH2 or 2′-O—NH2, which can 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, respectively, which are both incorporated by reference in their entireties.


[0370] Various modifications to nucleic acid (e.g., enzymatic nucleic acid, antisense, decoy, aptamer, siRNA, triplex oligonucleotides, 2,5-A oligonucleotides and other nucleic acid molecules) structure can be made to enhance the utility of these molecules. For example, such modifications can enhance shelf life, half-life in vitro, stability, and ease of introduction of such oligonucleotides to the target site, including e.g., enhancing penetration of cellular membranes and conferring the ability to recognize and bind to targeted cells.


[0371] Use of these molecules can lead to better treatment of the disease progression by affording the possibility of combination therapies (e.g., multiple nucleic acid molecules targeted to different genes, nucleic acid molecules coupled with known small molecule inhibitors, or intermittent treatment with combinations of nucleic acid molecules (including different nucleic acid molecule motifs) and/or other chemical or biological molecules). The treatment of patients with nucleic acid molecules can also include combinations of different types of nucleic acid molecules. Therapies can be devised which include a mixture of enzymatic nucleic acid molecules (including different enzymatic nucleic acid molecule motifs), antisense, decoy, aptamer and/or 2-5A chimera molecules to one or more targets to alleviate symptoms of a disease.


[0372] Administration of Nucleic Acid Molecules


[0373] Methods for the delivery of nucleic acid molecules are described in Akhtar et al., 1992, Trends Cell Bio., 2, 139; Delivery Strategies for Antisense Oligonucleotide Therapeutics, ed. Akhtar, 1995, Maurer et al., 1999, Mol. Membr. Biol., 16, 129-140; Hofland and Huang, 1999, Handb. Exp. Pharmacol., 137, 165-192; and Lee et al., 2000, ACS Symp. Ser., 752, 184-192, Sullivan et al., PCT WO 94/02595, further describes the general methods for delivery of enzymatic nucleic acid molecules. These protocols can be utilized for the delivery of virtually any nucleic acid molecule. Nucleic acid molecules can be administered to cells by a variety of methods known to those of skill in 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, or by proteinaceous vectors (O'Hare and Normand, International PCT Publication No. WO 00/53722). Alternatively, the nucleic acid/vehicle combination is locally delivered by direct injection or by use of an infusion pump. Direct injection of the nucleic acid molecules of the invention, whether subcutaneous, intramuscular, or intradermal, can take place using standard needle and syringe methodologies, or by needle-free technologies such as those described in Conry et al., 1999, Clin. Cancer Res., 5, 2330-2337 and Barry et al., International PCT Publication No. WO 99/31262. The molecules of the instant invention can be used as pharmaceutical agents. Pharmaceutical agents prevent, modulate the occurrence, or treat (alleviate a symptom to some extent, preferably all of the symptoms) of a disease state in a patient.


[0374] Thus, the invention features a pharmaceutical composition comprising one or more nucleic acid(s) of the invention in an acceptable carrier, such as a stabilizer, buffer, and the like. 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.


[0375] 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.


[0376] 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, including for example 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 nucleic acid is desirable for delivery). 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 that prevent the composition or formulation from exerting its effect.


[0377] 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 limitation: 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 that 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.


[0378] 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, D F 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.


[0379] 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). 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.


[0380] 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.


[0381] A pharmaceutically effective dose is that dose required to prevent, inhibit the occurrence of, or treat (alleviate a symptom to some extent, preferably all of the symptoms) 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 that 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.


[0382] The present invention also includes compositions prepared for storage or administration that 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 can be provided. These include sodium benzoate, sorbic acid and esters of p-hydroxybenzoic acid. In addition, antioxidants and suspending agents can be used.


[0383] 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 that 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.


[0384] The nucleic acid molecules of the invention and formulations thereof can be administered orally, topically, parenterally, by inhalation or spray, or rectally in dosage unit formulations containing conventional non-toxic pharmaceutically acceptable carriers, adjuvants and/or vehicles. The term parenteral as used herein includes percutaneous, subcutaneous, intravascular (e.g., intravenous), intramuscular, or intrathecal injection or infusion techniques and the like. In addition, there is provided a pharmaceutical formulation comprising a nucleic acid molecule of the invention and a pharmaceutically acceptable carrier. One or more nucleic acid molecules of the invention can be present in association with one or more non-toxic pharmaceutically acceptable carriers and/or diluents and/or adjuvants, and if desired other active ingredients. The pharmaceutical compositions containing nucleic acid molecules of the invention can be in a form suitable for oral use, for example, as tablets, troches, lozenges, aqueous or oily suspensions, dispersible powders or granules, emulsion, hard or soft capsules, or syrups or elixirs.


[0385] Compositions intended for oral use can be prepared according to any method known to the art for the manufacture of pharmaceutical compositions and such compositions can contain one or more such sweetening agents, flavoring agents, coloring agents or preservative agents in order to provide pharmaceutically elegant and palatable preparations. Tablets contain the active ingredient in admixture with non-toxic pharmaceutically acceptable excipients that are suitable for the manufacture of tablets. These excipients can be, for example, inert diluents; such as calcium carbonate, sodium carbonate, lactose, calcium phosphate or sodium phosphate; granulating and disintegrating agents, for example, corn starch, or alginic acid; binding agents, for example starch, gelatin or acacia; and lubricating agents, for example magnesium stearate, stearic acid or talc. The tablets can be uncoated or they can be coated by known techniques. In some cases such coatings can be prepared by known techniques to delay disintegration and absorption in the gastrointestinal tract and thereby provide a sustained action over a longer period. For example, a time delay material such as glyceryl monosterate or glyceryl distearate can be employed.


[0386] Formulations for oral use can also be presented as hard gelatin capsules wherein the active ingredient is mixed with an inert solid diluent, for example, calcium carbonate, calcium phosphate or kaolin, or as soft gelatin capsules wherein the active ingredient is mixed with water or an oil medium, for example peanut oil, liquid paraffin or olive oil.


[0387] Aqueous suspensions contain the active materials in admixture with excipients suitable for the manufacture of aqueous suspensions. Such excipients are suspending agents, for example sodium carboxymethylcellulose, methylcellulose, hydropropyl-methylcellulose, sodium alginate, polyvinylpyrrolidone, gum tragacanth and gum acacia; dispersing or wetting agents can be a naturally-occurring phosphatide, for example, lecithin, or condensation products of an alkylene oxide with fatty acids, for example polyoxyethylene stearate, or condensation products of ethylene oxide with long chain aliphatic alcohols, for example heptadecaethyleneoxycetanol, or condensation products of ethylene oxide with partial esters derived from fatty acids and a hexitol such as polyoxyethylene sorbitol monooleate, or condensation products of ethylene oxide with partial esters derived from fatty acids and hexitol anhydrides, for example polyethylene sorbitan monooleate. The aqueous suspensions can also contain one or more preservatives, for example ethyl, or n-propyl p-hydroxybenzoate, one or more coloring agents, one or more flavoring agents, and one or more sweetening agents, such as sucrose or saccharin.


[0388] Oily suspensions can be formulated by suspending the active ingredients in a vegetable oil, for example arachis oil, olive oil, sesame oil or coconut oil, or in a mineral oil such as liquid paraffin. The oily suspensions can contain a thickening agent, for example beeswax, hard paraffin or cetyl alcohol. Sweetening agents and flavoring agents can be added to provide palatable oral preparations. These compositions can be preserved by the addition of an anti-oxidant such as ascorbic acid.


[0389] Dispersible powders and granules suitable for preparation of an aqueous suspension by the addition of water provide the active ingredient in admixture with a dispersing or wetting agent, suspending agent and one or more preservatives. Suitable dispersing or wetting agents or suspending agents are exemplified by those already mentioned above. Additional excipients, for example sweetening, flavoring and coloring agents, can also be present.


[0390] Pharmaceutical compositions of the invention can also be in the form of oil-in-water emulsions. The oily phase can be a vegetable oil or a mineral oil or mixtures of these. Suitable emulsifying agents can be naturally-occurring gums, for example gum acacia or gum tragacanth, naturally-occurring phosphatides, for example soy bean, lecithin, and esters or partial esters derived from fatty acids and hexitol, anhydrides, for example sorbitan monooleate, and condensation products of the said partial esters with ethylene oxide, for example polyoxyethylene sorbitan monooleate. The emulsions can also contain sweetening and flavoring agents.


[0391] Syrups and elixirs can be formulated with sweetening agents, for example glycerol, propylene glycol, sorbitol, glucose or sucrose. Such formulations can also contain a demulcent, a preservative and flavoring and coloring agents. The pharmaceutical compositions can be in the form of a sterile injectable aqueous or oleaginous suspension. This suspension can be formulated according to the known art using those suitable dispersing or wetting agents and suspending agents that have been mentioned above. The sterile injectable preparation can also be a sterile injectable solution or suspension in a non-toxic parentally acceptable diluent or solvent, for example as a solution in 1,3-butanediol. Among the acceptable vehicles and solvents that can be employed are water, Ringer's solution and isotonic sodium chloride solution. In addition, sterile, fixed oils are conventionally employed as a solvent or suspending medium. For this purpose, any bland fixed oil can be employed including synthetic mono-or diglycerides. In addition, fatty acids such as oleic acid find use in the preparation of injectables.


[0392] The nucleic acid molecules of the invention can also be administered in the form of suppositories, e.g., for rectal administration of the drug. These compositions can be prepared by mixing the drug with a suitable non-irritating excipient that is solid at ordinary temperatures but liquid at the rectal temperature and will therefore melt in the rectum to release the drug. Such materials include cocoa butter and polyethylene glycols.


[0393] Nucleic acid molecules of the invention can be administered parenterally in a sterile medium. The drug, depending on the vehicle and concentration used, can either be suspended or dissolved in the vehicle. Advantageously, adjuvants such as local anesthetics, preservatives and buffering agents can be dissolved in the vehicle.


[0394] Dosage levels of the order of from about 0.1 mg to about 140 mg per kilogram of body weight per day are useful in the treatment of the above-indicated conditions (about 0.5 mg to about 7 g per patient per day). The amount of active ingredient that can be combined with the carrier materials to produce a single dosage form varies depending upon the host treated and the particular mode of administration. Dosage unit forms generally contain between from about 1 mg to about 500 mg of an active ingredient.


[0395] It is understood that the specific dose level for any particular patient depends upon a variety of factors including the activity of the specific compound employed, the age, body weight, general health, sex, diet, time of administration, route of administration, and rate of excretion, drug combination and the severity of the particular disease undergoing therapy.


[0396] For administration to non-human animals, the composition can also be added to the animal feed or drinking water. It can be convenient to formulate the animal feed and drinking water compositions so that the animal takes in a therapeutically appropriate quantity of the composition along with its diet. It can also be convenient to present the composition as a premix for addition to the feed or drinking water.


[0397] 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.


[0398] In one embodiment, the invention compositions suitable for administering nucleic acid molecules of the invention to specific cell types, such as hepatocytes. For example, the asialoglycoprotein receptor (ASGPr) (Wu and Wu, 1987, J. Biol. Chem. 262, 4429-4432) is unique to hepatocytes and binds branched galactose-terminal glycoproteins, such as asialoorosomucoid (ASOR). Binding of such glycoproteins or synthetic glycoconjugates to the receptor takes place with an affinity that strongly depends on the degree of branching of the oligosaccharide chain, for example, triatennary structures are bound with greater affinity than biatenarry or monoatennary chains (Baenziger and Fiete, 1980, Cell, 22, 611-620; Connolly et al., 1982, J. Biol. Chem., 257, 939-945). Lee and Lee, 1987, Glycoconjugate J., 4, 317-328, obtained this high specificity through the use of N-acetyl-D-galactosamine as the carbohydrate moiety, which has higher affinity for the receptor, compared to galactose. This “clustering effect” has also been described for the binding and uptake of mannosyl-terminating glycoproteins or glycoconjugates (Ponpipom et al., 1981, J. Med. Chem., 24, 1388-1395). The use of galactose and galactosamine based conjugates to transport exogenous compounds across cell membranes can provide a targeted delivery approach to the treatment of liver disease such as HBV infection or hepatocellular carcinoma. The use of bioconjugates can also provide a reduction in the required dose of therapeutic compounds required for treatment. Furthermore, therapeutic bioavialability, pharmacodynamics, and pharmacokinetic parameters can be modulated through the use of nucleic acid bioconjugates of the invention.


[0399] 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 totalities 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).


[0400] 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. Ribozyme 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 intra-muscular 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).


[0401] 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.


[0402] 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).


[0403] 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 ribozymes 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 ribozymes 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 ribozyme 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).


[0404] 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 that 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 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.


[0405] Interferons


[0406] Type I interferons (IFN) are a class of natural cytokines that includes a family of greater than 25 IFN-α (Pesta, 1986, Methods Enzymol. 119, 3-14) as well as IFN-β, and IFN-ω. Although evolutionarily derived from the same gene (Diaz et al., 1994, Genomics 22, 540-552), there are many differences in the primary sequence of these molecules, implying an evolutionary divergence in biologic activity. All type I IFN share a common pattern of biologic effects that begin with binding of the IFN to the cell surface receptor (Pfeffer & Strulovici, 1992, Transmembrane secondary messengers for IFN-α/p. In: Interferon. Principles and Medical Applications., S. Baron, D. H. Coopenhaver, F. Dianzani, W. R. Fleischmann Jr., T. K. Hughes Jr., G. R. Kimpel, D. W. Niesel, G. J. Stanton, and S. K. Tyring, eds. 151-160). Binding is followed by activation of tyrosine kinases, including the Janus tyrosine kinases and the STAT proteins, which leads to the production of several IFN-stimulated gene products (Johnson et al., 1994, Sci. Am. 270, 68-75). The IFN-stimulated gene products are responsible for the pleotropic biologic effects of type I IFN, including antiviral, antiproliferative, and immunomodulatory effects, cytokine induction, and HLA class I and class II regulation (Pestka et al., 1987, Annu. Rev. Biochem 56, 727). Examples of IFN-stimulated gene products include 2-5-oligoadenylate synthetase (2-5 OAS), β2-microglobulin, neopterin, p68 kinases, and the Mx protein (Chebath & Revel, 1992 The 2-5 A system: 2-5 A synthetase, isospecies and functions. In: Interferon. Principles and Medical Applications. S. Baron, D. H. Coopenhaver, F. Dianzani, W. R. Jr. Fleischmann, T. K. Jr Hughes, G. R. Kimpel, D. W. Niesel, G. J. Stanton, and S. K. Tyring, eds., pp. 225-236; Samuel, 1992, The RNA-dependent P1/eIF-2α protein kinase. In: Interferon. Principles and Medical Applications. S. Baron, D. H. Coopenhaver, F. Dianzani, W. R. Fleischmann Jr., T. K. Hughes Jr., G. R. Kimpel, D. W. Niesel, G. H. Stanton, and S. K. Tyring, eds. 237-250; Horisberger, 1992, MX protein: function and Mechanism of Action. In: Interferon. Principles and Medical Applications. S. Baron, D. H. Coopenhaver, F. Dianzani, W. R. Fleischmann Jr., T. K. Hughes Jr., G. R. Kimpel, D. W. Niesel, G. H. Stanton, and S. K. Tyring, eds. 215-224). Although all type I IFN have similar biologic effects, not all the activities are shared by each type I IFN, and, in many cases, the extent of activity varies quite substantially for each IFN subtype (Fish et al, 1989, J. Interferon Res. 9, 97-114; Ozes et al., 1992, J. Interferon Res. 12, 55-59). More specifically, investigations into the properties of different subtypes of IFN-α and molecular hybrids of IFN-α have shown differences in pharmacologic properties (Rubinstein, 1987, J. Interferon Res. 7, 545-551). These pharmacologic differences can arise from as few as three amino acid residue changes (Lee et al., 1982, Cancer Res. 42, 1312-1316).


[0407] Eighty-five to 166 amino acids are conserved in the known IFN-α subtypes. Excluding the IFN-α pseudogenes, there are approximately 25 known distinct IFN-α subtypes. Pairwise comparisons of these nonallelic subtypes show primary sequence differences ranging from 2% to 23%. In addition to the naturally occurring IFNs, a non-natural recombinant type I interferon known as consensus interferon (CIFN) has been synthesized as a therapeutic compound (Tong et al., 1997, Hepatology 26, 747-754).


[0408] Interferon is currently in use for at least 12 different indications including infectious and autoimmune diseases and cancer (Borden, 1992, N. Engl. J. Med. 326, 1491-1492). For autoimmune diseases IFN has been utilized for treatment of rheumatoid arthritis, multiple sclerosis, and Crohn's disease. For treatment of cancer IFN has been used alone or in combination with a number of different compounds. Specific types of cancers for which IFN has been used include squamous cell carcinomas, melanomas, hypernephromas, hemangiomas, hairy cell leukemia, and Kaposi's sarcoma. In the treatment of infectious diseases, IFNs increase the phagocytic activity of macrophages and cytotoxicity of lymphocytes and inhibits the propagation of cellular pathogens. Specific indications for which IFN has been used as treatment include: hepatitis B, human papillomavirus types 6 and 11 (i.e. genital warts) (Leventhal et al., 1991, N Engl J Med 325, 613-617), chronic granulomatous disease, and hepatitis C virus.


[0409] Numerous well controlled clinical trials using IFN-alpha in the treatment of chronic HCV infection have demonstrated that treatment three times a week results in lowering of serum ALT values in approximately 50% (range 40% to 70%) of patients by the end of 6 months of therapy (Davis et al., 1989, The new England Journal of Medicine 321, 1501-1506; Marcellin et al., 1991, Hepatology 13, 393-397; Tong et al., 1997, Hepatology 26, 747-754; Tong et al., Hepatology 26, 1640-1645). However, following cessation of interferon treatment, approximately 50% of the responding patients relapsed, resulting in a “durable” response rate as assessed by normalization of serum ALT concentrations of approximately 20 to 25%. In addition, studies that have examined six months of type 1 interferon therapy using changes in HCV RNA values as a clinical endpoint have demonstrated that up to 35% of patients will have a loss of HCV RNA by the end of therapy (Tong et al., 1997, supra). However, as with the ALT endpoint, about 50% of the patients relapse six months following cessation of therapy resulting in a durable virologic response of only 12% (23). Studies that have examined 48 weeks of therapy have demonstrated that the sustained virological response is up to 25%.


[0410] Pegylated interferons, ie. interferons conjugated with polyethylene glycol (PEG), have demonstrated improved characteristics over interferon. Advantages incurred by PEG conjugation can include an improved pharmacokinetic profile compared to interferons lacking PEG, thus imparting more convenient dosing regimes, improved tolerance, and improved antiviral efficacy. Such improvements have been demonstrated in clinical studies of both polyethylene glycol interferon alfa-2a (PEGASYS, Roche) and polyethylene glycol interferon alfa-2b (VIRAFERON PEG, PEG-INTRON, Enzon/Schering Plough).


[0411] Enzymatic nucleic acid molecules in combination with interferons and polyethylene glycol interferons have the potential to improve the effectiveness of treatment of HCV or any of the other indications discussed above. Enzymatic nucleic acid molecules targeting RNAs associated with diseases such as infectious diseases, autoimmune diseases, and cancer, can be used individually or in combination with other therapies such as interferons and polyethylene glycol interferons and to achieve enhanced efficacy.



EXAMPLES

[0412] The following are non-limiting examples showing the selection, isolation, synthesis and activity of nucleic acids of the instant invention. These examples demonstrate the selection and design of Antisense, Hammerhead, DNAzyme, NCH, Amberzyme, Zinzyme or G-Cleaver ribozyme molecules and binding/cleavage sites within HBV and HCV RNA. The following examples also demonstrate the selection and design of nucleic acid decoy molecules that target HBV reverse transcriptase. The following examples also demonstrate the use of enzymatic nucleic acid molecules that cleave HCV RNA. The methods described herein represent a scheme by which nucleic acid molecules can be derived that cleave other RNA targets required for HCV replication.



Example 1


Identification of Potential Target Sites in Human HBV RNA

[0413] 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 ribozyme 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

[0414] Ribozyme target sites were chosen by analyzing sequences of Human HBV (accession number: AF100308.1) and prioritizing the sites on the basis of folding. Ribozymes 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 ribozyme sequences fold into the appropriate secondary structure. Those ribozymes 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 Ribozymes and Antisense for Efficient Cleavage and/or Blocking of HBV RNA

[0415] Ribozymes and antisense constructs were designed to anneal to various sites in the RNA message. The binding arms of the ribozymes are complementary to the target site sequences described above, while the antisense constructs are fully complementary to the target site sequences described above. The ribozymes 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%.


[0416] Ribozymes and antisense constructs were also synthesized from DNA templates using bacteriophage T7 RNA polymerase (Milligan and Uhlenbeck, 1989, Methods Enzymol. 180, 51). Ribozymes 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 ribozymes used in this study are shown below in Table XI.



Example 4


Ribozyme Cleavage of HBV RNA Target In Vitro

[0417] Ribozymes targeted to the human HBV RNA are designed and synthesized as described above. These ribozymes 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.


[0418] Cleavage Reactions: Full-length or partially full-length, internally-labeled target RNA for ribozyme 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 ribozyme in ribozyme 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× ribozyme 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 ribozyme, i.e., ribozyme 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 ribozyme 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 Ribozymes

[0419] 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.


[0420] 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/ribozyme 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 ribozyme (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.


[0421] 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 ribozymes for the treatment of chronic HBV infection, a series of ribozymes that target the 3′ terminus of the HBV genome have been synthesized. Ribozymes 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 ribozymes, 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 ribozymes was determined by comparing the ratio of HBsAg:SEAP and/or HBeAg:SEAP to that of a scrambled attenuated control (SAC) ribozyme. Twenty-five ribozymes (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 ribozyme. In addition, loop variant anti-HBV ribozymes targeting site 273 were tested using this system, the results of this study are summarized in FIG. 10. As indicated in the figure, the ribozymes tested demonstrate significant reduction in HepG2 HBsAg levels as compared to a scrambled attenuated core ribozyme control, with RPI 22650 and RPI 22649 showing the greatest decrease in HBsAg levels.



Example 6


Analysis of HBsAg and SEAP Levels Following Ribozyme Treatment

[0422] Immulon 4 (Dynax) microtiter wells were coated overnight at 4° C. with anti-HBsAg Mab (Biostride B88-95-31 ad,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

[0423] The effect of ribozyme 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/ribozyme 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 ribozyme (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.


[0424] The HBV X protein is a transactivator of a number of viral and cellular genes. Ribozymes 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 ribozymes was determined by comparing the ratio of firefly luciferase: Renilla luciferase to that of a scrambled attenuated control (SAC) ribozyme. Eleven ribozymes (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 ribozyme.



Example 8


HBV Transgenic Mouse Study A

[0425] 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 ribozymes (RPI.18341, RPI.18371, RPI.18372, and RPI.18418) of the instant invention. This model is predictive in screening for anti-HBV agents. Ribozyme 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 (ie., 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.


[0426] Results


[0427] 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 ribozymes (100 mg/kg/day) as a continuous SC infusion. After 14 days, animals treated with a ribozyme 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 ribozyme (RPI.18341) resulted in a 60% decrease in serum HBV DNA concentrations. Ribozymes 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

[0428] 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 ribozymes (RPI.18341 and RPI.18371) of the instant invention. This model is predictive in screening for anti-HBV agents. Ribozyme 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 (ie., 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.


[0429] Results


[0430] 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 ribozymes (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, Ribozymes directed against sites 273 (RPI.18341) and 1833 (RPI.18371) demonstrate reduction in the serum HBV DNA levels following 14 days of ribozyme treatment in HBV transgenic mice, as compared to scrambled attenuated core (SAC) ribozyme and saline controls. Furthermore, these ribozymes 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

[0431] Ribozyme treatment of HepG2.2.15 cells was performed in a 96-well plate format, with 12 wells for each different ribozyme 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®

[0432] 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.


[0433] Hep G2 cells were plated (2×104 cells/well) in 96-well microtiter plates and incubated overnight. A cationic lipid/DNA/ribozyme complex was formed containing (at final concentrations) lipid (11-15 μg/mL), re-ligated psHBV-1 (4.5 μg/mL) and ribozyme (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 ribozyme-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.


[0434] Results


[0435] 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).


[0436] 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 13


Modulation of HBV Reverse Transcriptase

[0437] The HBV reverse transcriptase (pol) binds to the 5′ stem-loop structure in the HBV pregenomic RNA and synthesizes a four-nucleotide primer from the template UUCA. The reverse transcriptase then translocates to the 3′ end of the pregenomic RNA where the primer binds to the UUCA sequence within the DR1 element and begins first-strand synthesis of HBV DNA. A number of short oligos, ranging in size from 4 to 16-mers, were designed to act as competitive inhibitors of the HBV reverse transcriptase primer, either by blocking the primer binding sites on the HBV RNA or by acting as a decoy.


[0438] The oligonucleotides and controls were synthesized in all 2′-O-methyl and 2′-O-allyl versions (Table XV). The inverse sequence of all oligos were generated to serve as controls. Primary screening of the competitive inhibitors was completed in the HBsAg transfection/ELISA system, in which the oligo is co-transfeceted with a HBV cDNA vector into Hep G2 cells. Following 4 days of incubation, the levels of HBsAg secreted into the cell culture media were determined by ELISA. Screening of the 2′-O-allyl versions revealed that two of the decoy oligos (RPI.24944 and RPI.24945), consisting of 3× or 4× repeats of the RT primer binding site UUCA, along with the matched inverse controls, displayed considerable activity by decreasing HBsAg levels (FIG. 15). This dramatic decrease in HBsAg levels is not due to cellular toxicity, because a MTS assay showed no difference in proliferation between any of the treated cells. A follow up experiment with a 5× UUCA repeat, the inverse sequence control, and a matched scrambled control, showed that all three oligos decreased HBsAg levels without cellular toxicity. Screening of the 2′-O-methyl versions of the oligos showed no activity from the 3× and 4× UUCA repeat (FIG. 16), also suggesting that the anti-HBV effect is perhaps related to the 2′-O-allyl chemistry rather than to sequence specificity.


[0439] Screening of the 2′-O-methyl oligos did show that the 2′-O-methyl 2× UUCA repeat, RPI.24986, displayed activity in decreasing HBsAg levels as compared to the inverse control, RPI.24950. A dose response experiment showed that at the lower concentrations of 100 and 200 nM, RPI.24986 showed greater activity in decreasing HbsAg levels as compared to the inverse control RPI.24950 (FIG. 17).



Example 14


Modulation of HBV Transcription via Oligonucleotides Targeting the Enchancer I Core Region of HBV DNA

[0440] In an effort to block HBV replication, oligonucleotides were designed to bind to two liver-specific factor binding sites in the Enhancer I core region of HBV genomic DNA. Hepatocyte Nuclear Factor 3 (HNF3) and Hepatocyte Nuclear Factor 4 (HNF4) bind to sites in the core region, with the HNF3 site being 5′ to the HNF4 site. The HNF3 and HNF4 sites overlap or are adjacent to binding sites for a number of more ubiquitous factors, and are termed nuclear receptor response elements (NRRE). These elements are critical in regulating HBV transcription and replication in infected hepatocytes, with mutations in the HNF3 and HNF4 binding sites having been demonstrated to greatly reduce the levels of HBV replication (Bock et al., 2000, J. Virology, 74, 2193)


[0441] Oligonucleotides (Table XV) were designed to bind to either the positive or negative strands of the HNF3 or HNF4 binding sites. Scrambled controls were made to match each oligo. Each oligo was synthesized in all 2′-O-methyl/all phosphorothioate, or all 2′-O-allyl/all phosphorothioate chemistries. The initial screening of the oligos was done in the HBsAg transfection/ELISA system in Hep G2 cells. RPI.25654, which targets the negative strand of the HNF4 binding site, shows greater activity in reducing HBsAg levels as compared to RPI.25655, which targets the HNF4 site positive strand, and the scrambled control RPI.25656. This result was observed at both 200 and 400 nM (FIGS. 18 and 19). In a follow-up study, RPI.25654 reduced HBsAg levels in a dose-dependent manner, from 50-200 nM (FIG. 20).



Example 15


Transfection of HepG2 Cells with psHBV-1 and Nucleic Acid

[0442] 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 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. One skilled in the art would realize that other methods can be used to generate a replication competent cDNA 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/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 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.


[0443] 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.



Example 16


Analysis of HBsAg and SEAP Levels Following Nucleic Acid Treatment

[0444] 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 anti-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 17


Analysis of HBV DNA Expression a HepG2.2.15 Murine Model

[0445] The development of new antiviral agents for the treatment of chronic Hepatitis B has been aided by the use of animal models that are permissive to replication of related Hepadnaviridae such as Woodchuck Hepatitis Virus (WHV) and Duck Hepatitis Virus (DHV). In addition, the use of transgenic mice has also been employed. The human hepatoblastoma cell line, HepG2.2.15, implanted as a subcutaneous (SC) tumor, can be used to produce Hepatitis B viremia in mice. This model is useful for evaluating new HBV therapies. Mice bearing HepG2.2.15 SC tumors show HBV viremia. HBV DNA can be detected in serum beginning on Day 35. Maximum serum viral levels reach 1.9×105 copies/mL by day 49. A study also determined that the minimum tumor volume associated with viremia was 300 mm3. Therefore, the HepG2.2.15 cell line grown as a SC tumor produces a useful model of HBV viremia in mice. This new model can be suitable for evaluating new therapeutic regimens for chronic Hepatitis B.


[0446] HepG2.2.15 tumor cells contain a slightly truncated version of viral HBV DNA and sheds HBV particles. The purpose of this study was to identify what time period viral particles are shed from the tumor. Serum was analyzed for presence of HBV DNA over a time course after HepG2.2.15 tumor inoculation in Athymic Ncr nu/nu mice. HepG2.2.15 cells were carried and expanded in DMEM/10% FBS/2.4% HEPES/1% NEAA/1% Glutamine/1% Sodium Pyruvate media. Cells were resuspended in Delbecco's PBS with calcium/magnesium for injection. One hundred microliters of the tumor cell suspension (at a concentration of 1×108 cells/mL) were injected subcutaneously in the flank of NCR nu/nu female mice with a 23 gl needle and 1 cc syringe, thereby giving each mouse 1×107 cells. Tumors were allowed to grow for a period of up to 49 days post tumor cell inoculation. Serum was sampled for analysis on days 1, 7, 14, 35, 42 and 49 post tumor inoculation. Length and width measurements from each tumor were obtained three times per week using a Jamison microcaliper. Tumor volumes were calculated from tumor length/width measurements (tumor volume=0.5[a(b)2] where a=longest axis of the tumor and b=shortest axis of the tumor). Serum was analyzed for the presence of HBV DNA by the Roche Amplicor HBV moniter TM DNA assay.


[0447] Experiment 1


[0448] HepG2.2.15 cells were carried and expanded in DMEM/10% FBS/2.4% HEPES/1% NEAA/1% Glutamine/1% Sodium Pyruvate media. Cells were resuspended in Delbecco's PBS with calcium/magnesium for injection. One hundred microliters of the tumor cell suspension (at a concentration of 1×108 cells/mL) were injected subcutaneously in the flank of NCR nu/nu female mice with a 23 gl needle and 1 cc syringe, thereby giving each mouse 1×107 cells. Tumors were allowed to grow for a period of up to 49 days post tumor cell inoculation. Serum was sampled for analysis on days 1, 7, 14, 35, 42 and 49 post tumor inoculation. Length and width measurements from each tumor were obtained three times per week using a Jamison microcaliper. Tumor volumes were calculated from tumor length/width measurements (tumor volume=0.5[a(b)2] where a=longest axis of the tumor and b=shortest axis of the tumor). Serum was analyzed for the presence of HBV DNA by the Roche Amplicor HBV moniter TM DNA assay.


[0449] Results


[0450] When athymic nu/nu female mice are subcutaneously injected with HepG2.2.15 cells and form tumors, HBV DNA is detected in serum (peak serum level was 1.9×105 copies/mL). There is a positive correlation (rs=0.7, p<0.01) between tumor weight (milligrams) and HB viral copies/mL serum. FIG. 21 shows a plot of HepG2.2.15 tumors in nu/nu female mice as tumor volume vs time. Table XVI shows the concentration of HBV DNA in relation to tumor size in the HepG2.2.15 implanted nu/nu female mice used in the study.


[0451] Experiment 2


[0452] HepG2.2.15 cells were carried and expanded in DMEM/10% FBS/2.4% HEPES/1% NEAA/1% Glutamine/1% Sodium Pyruvate media containing 400 μg/ml G418 antibiotic. G418-resistant cells were resuspended in Dulbecco's PBS with calcium/magnesium for injection. One hundred microliters of the tumor cell suspension (at a concentration of 1×108 cells/mL) were injected subcutaneously in the flank of NCR nu/nu female mice with a 23 gl needle and 1 cc syringe, thereby giving each mouse 1×107 cells. Tumors were allowed to grow for a period of up to 49 days post tumor cell inoculation. Serum was sampled for analysis on day 37 post tumor inoculation. Length and width measurements from each tumor were obtained three times per week using a Jamison microcaliper. Tumor volumes were calculated from tumor length/width measurements (tumor volume=0.5[a(b)2] where a=longest axis of the tumor and b=shortest axis of the tumor). Serum was analyzed for the presence of HBV DNA by the Roche Amplicor HBV moniter TM DNA assay.


[0453] Results


[0454] When athymic nu/nu female mice are subcutaneously injected with G418 antibiotic resistant HepG2.2.15 cells and form tumors, HBV DNA is detected in serum (peak serum level was 4.0×105 copies/mL). There is a positive correlation (rs=0.7, p<0.01) between tumor weight (milligrams) and HB viral copies/mL serum. FIG. 22 shows a plot of HepG2.2.15 tumors in nu/nu female mice as tumor volume vs time. Table XVII shows the concentration of HBV DNA in relation to tumor size in the G418 antibiotic resistant HepG2.2.15 implanted nu/nu female mice used in the study.



Example 18


Identification of Potential Enzymatic Nucleic Acid Molecules Cleavage Sites in HCV RNA

[0455] The sequence of HCV RNA was screened for accessible sites using a computer folding algorithm. Regions of the mRNA that did not form secondary folding structures and contained potential enzymatic nucleic acid cleavage sites were identified. The sequences of these cleavage sites are shown in Tables XVIII, XIX, XX and XXIII.



Example 19


Selection of Enzymatic Nucleic Acid Molecules Cleavage Sites in HCV RNA

[0456] Enzymatic nucleic acid target sites were chosen by analyzing sequences of Human HCV (Genbank accession Nos: D11168, D50483.1, L38318 and S82227) and prioritizing the sites on the basis of folding. Enzymatic nucleic acid molecules are designed that could bind each target and are 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 molecules sequences fold into the appropriate secondary structure. Those enzymatic nucleic acid molecules with unfavorable intramolecular interactions between the binding arms and the catalytic core can be eliminated from consideration. As noted below, varying binding arm lengths can be chosen to optimize activity. Generally, at least 4 bases on each arm are able to bind to, or otherwise interact with, the target RNA.



Example 20


Chemical Synthesis and Purification of Enzymatic Nucleic Acids

[0457] Enzymatic nucleic acid molecules can be designed to anneal to various sites in the RNA message. The binding arms of the enzymatic nucleic acid molecules are complementary to the target site sequences described above. The enzymatic nucleic acid molecules can be chemically synthesized using, for example, RNA syntheses such as those described above and those 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., supra. Such methods make 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 are typically >98%. Enzymatic nucleic acid molecules can be modified 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).


[0458] Enzymatic nucleic acid molecules can also be synthesized from DNA templates using bacteriophage T7 RNA polymerase (Milligan and Uhlenbeck, 1989, Methods Enzymol. 180, 51). Enzymatic nucleic acid molecules can be purified by gel electrophoresis using known methods, or can be purified by high pressure liquid chromatography (HPLC; See Wincott et al., supra; the totality of which is hereby incorporated herein by reference), and are resuspended in water. The sequences of chemically synthesized enzymatic nucleic acid constructs are shown below in Tables XX, XXI and XXIII. The antisense nucleic acid molecules shown in Table XXII were chemically synthesized.


[0459] Inactive enzymatic nucleic acid molecules, for example inactive hammerhead enzymatic nucleic acids, can be synthesized by substituting the order of G5A6 and substituting a U for A14 (numbering from Hertel et al., 1992 Nucleic Acids Res., 20, 3252).



Example 21


Enzymatic Nucleic Acid Cleavage of HCV RNA Target In Vitro

[0460] Enzymatic nucleic acid molecules targeted to the HCV are designed and synthesized as described above. These enzymatic nucleic acid molecules can be tested for cleavage activity in vitro, for example using the following procedure. The target sequences and the nucleotide location within the HCV are given in Tables XVIII, XIX, XX and XXIII.


[0461] Cleavage Reactions: Full-length or partially full-length, internally-labeled target RNA for enzymatic nucleic acid molecule 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 molecule in enzymatic nucleic acid molecule 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 molecule 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 molecule, i.e., enzymatic nucleic acid molecule 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 molecule 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.


[0462] Alternatively, enzymatic nucleic acid molecules and substrates were synthesized in 96-well format using 0.2 μmol scale. Substrates were 5′-32P labeled and gel purified using 7.5% polyacrylamide gels, and eluting into water. Assays were done by combining trace substrate with 500 nM enzymatic nucleic acid or greater, and initiated by adding final concentrations of 40 mM Mg+2, and 50 mM Tris-Cl pH 8.0. For each enzymatic nucleic acid/substrate combination a control reaction was done to ensure cleavage was not the result of non-specific substrate degradation. A single three hour time point was taken and run on a 15% polyacrylamide gel to asses cleavage activity. Gels were dried and scanned using a Molecular Dynamics Phosphorimager and quantified using Molecular Dynamics ImageQuant software. Percent cleaved was determined by dividing values for cleaved substrate bands by full-length (uncleaved) values plus cleaved values and multiplying by 100 (% cleaved=[C/(U+C)]*100). In vitro cleavage data of enzymatic nucleic acid molecules targeting plus and minus strand HCV RNA is shown in Table XXIII.



Example 22


Inhibition of Luciferase Activity Using HCV Targeting Enzymatic Nucleic Acids in OST7 Cells

[0463] The capability of enzymatic nucleic acids to inhibit HCV RNA intracellularly was tested using a dual reporter system that utilizes both firefly and Renilla luciferase (FIG. 23). The enzymatic nucleic acids targeted to the 5′ HCV UTR region, which when cleaved, would prevent the translation of the transcript into luciferase.


[0464] Synthesis of Stabilized Enzymatic Nucleic Acids


[0465] Enzymatic nucleic acids were designed to target 15 sites within the 5′UTR of the HCV RNA (FIG. 24) and synthesized as previously described, except that all enzymatic nucleic acids contain two 2′-amino uridines. Enzymatic nucleic acid and paired control sequences for targeted sites used in various examples herein are shown in Table XXI.


[0466] Reporter Plasmids


[0467] The T7/HCV/firefly luciferase plasmid (HCVT7C1-341, genotype 1a) was graciously provided by Aleem Siddiqui (University of Colorado Health Sciences Center, Denver, Colo.). The T7/HCV/firefly luciferase plasmid contains a T7 bacteriophage promoter upstream of the HCV 5′UTR (nucleotides 1-341)/firefly luciferase fusion DNA. The Renilla luciferase control plasmid (pRLSV40) was purchased from PROMEGA.


[0468] Luciferase Assay


[0469] Dual luciferase assays were carried out according to the manufacturer's instructions (PROMEGA) at 4 hours after co-transfection of reporter plasmids and enzymatic nucleic acids. All data is shown as the average ratio of HCV/firefly luciferase luminescence over Renilla luciferase luminescence as determined by triplicate samples ±SD.


[0470] Cell Culture and Transfections


[0471] OST7 cells were maintained in Dulbecco's modified Eagle's medium (GIBCO BRL) supplemented with 10% fetal calf serum, L-glutamine (2 mM) and penicillin/streptomycin. For transfections, OST7 cells were seeded in black-walled 96-well plates (Packard) at a density of 12,500 cells/well and incubated at 37° C. under 5% CO2 for 24 hours. Co-transfection of target reporter HCVT7C (0.8 μg/mL), control reporter pRLSV40, (1.2 μg/mL) and enzymatic nucleic acid, (50-200 nM) was achieved by the following method: a 5× mixture of HCVT7C (4 μg/mL), pRLSV40 (6 μg/mL) enzymatic nucleic acid (250-1000 nM) and cationic lipid (28.5 μg/mL) was made in 150 μL of OPTI-MEM (GIBCO BRL) minus serum. Reporter/enzymatic nucleic acid/lipid complexes were allowed to form for 20 min at 37° C. under 5% CO2. Medium was aspirated from OST7 cells and replaced with 120 μL of OPTI-MEM (GIBCO BRL) minus serum, immediately followed by the addition of 30 μL of 5× reporter/enzymatic nucleic acid/lipid complexes. Cells were incubated with complexes for 4 hours at 37° C. under 5% CO2.


[0472] IC50 Determinations for Dose Response Curves


[0473] Apparent IC50 values were calculated by linear interpolation. The apparent IC50 is 1/2 the maximal response between the two consecutive points in which approximately 50% inhibition of HCV/luciferase expression is observed on the dose curve.


[0474] Quantitation of RNA Samples


[0475] Total RNA from transfected cells was purified using the Qiagen RNeasy 96 procedure including a DNase I treatment according to the manufacturer's instructions. Real time RT-PCR (Taqman assay) was performed on purified RNA samples using separate primer/probe sets specific for either firefly or Renilla luciferase RNA. Firefly luciferase primers and probe were upper (5′-CGGTCGGTAAAGTTGTTCCATT-3′) (SEQ ID NO. 16202), lower (5′-CCTCTGACACATAATTCGCCTCT-3′) (SEQ ID NO. 16203), and probe (5′-FAM-TGAAGCGAAGGTTGTGGATCTGGATACC-TAMRA-3′) (SEQ ID NO 16204), and Renilla luciferase primers and probe were upper (5′-GTTTATTGAATCGGACCCAGGAT-3′) (SEQ ID NO. 16205), lower (5′-AGGTGCATCTTCTTGCGAAAA-3′) (SEQ ID NO. 16206), and probe (5′-FAM-CTTTTCCAATGCTATTGTTGAAGGTGCCAA-3′) (SEQ ID NO. 16207)-TAMRA, both sets of primers and probes were purchased from Integrated DNA Technologies. RNA levels were determined from a standard curve of amplified RNA purified from a large-scale transfection. RT minus controls established that RNA signals were generated from RNA and not residual plasmid DNA. RT-PCR conditions were: 30 min at 48° C., 10 min at 95° C., followed by 40 cycles of 15 sec at 95° C. and 1 min at 60° C. Reactions were performed on an ABI Prism 7700 sequence detector. Levels of firefly luciferase RNA were normalized to the level of Renilla luciferase RNA present in the same sample. Results are shown as the average of triplicate treatments ±SD.



Example 23


Inhibition of HCV 5′UTR-Luciferase Expression by Synthetic Stabilized Enzymatic Nucleic Acids

[0476] The primary sequence of the HCV 5′UTR and characteristic secondary structure (FIG. 24) is highly conserved across all HCV genotypes, thus making it a very attractive target for enzymatic nucleic acid-mediated cleavage. Enzymatic hammerhead nucleic acids, as a generally shown in FIG. 25 and Table XXI (RPI 12249-12254, 12257-12265) were designed and synthesized to target 15 of the most highly conserved sites in the 5′UTR of HCV RNA. These synthetic enzymatic nucleic acids were stabilized against nuclease degradation by the addition of modifications such as 2′-O-methyl nucleotides, 2′-amino-uridines at U4 and U7 core positions, phosphorothioate linkages, and a 3′-inverted abasic cap.


[0477] In order to mimic cytoplasmic transcription of the HCV genome, OST7 cells were transfected with a target reporter plasmid containing a T7 bacteriophage promoter upstream of a HCV 5′UTR/firefly luciferase fusion gene. Cytoplasmic expression of the target reporter is facilitated by high levels of T7 polymerase expressed in the cytoplasm of OST7 cells. Co-transfection of target reporter HCVT7C1-341 (firefly luciferase), control reporter pRLSV40 (Renilla luciferase) and enzymatic nucleic acid was carried out in the presence of cationic lipid. To determine the background level of luciferase activity, applicant used a control enzymatic nucleic acid that targets an irrelevant, non-HCV sequence. Transfection of reporter plasmids in the presence of this irrelevant control enzymatic nucleic acid (ICR) resulted in a slight decrease of reporter expression when compared to transfection of reporter plasmids alone. Therefore, the ICR was used to control for non-specific effects on reporter expression during treatment with HCV specific enzymatic nucleic acids. Renilla luciferase expression from the pRLSV40 reporter was used to normalize for transfection efficiency and sample recovery.


[0478] Of the 15 amino-modified hammerhead enzymatic nucleic acids tested, 12 significantly inhibited HCV/luciferase expression (>45%, P<0.05) as compared to the ICR (FIG. 26A). These data suggest that most of the HCV 5′UTR sites targeted here are accessible to enzymatic nucleic acid binding and subsequent RNA cleavage. To investigate further the enzymatic nucleic acid-dependent inhibition of HCV/luciferase activity, hammerhead enzymatic nucleic acids designed to cleave after sites 79, 81, 142, 192, 195, 282 or 330 of the HCV 5′UTR were selected for continued study because their anti-HCV activity was the most efficacious over several experiments. A corresponding attenuated core (AC) control was synthesized for each of the 7 active enzymatic nucleic acids (Table XX). Each paired AC control contains similar nucleotide composition to that of its corresponding active enzymatic nucleic acid however, due to scrambled binding arms and changes to the catalytic core, lacks the ability to bind or catalyze the cleavage of HCV RNA. Treatment of OST7 cells with enzymatic nucleic acids designed to cleave after sites 79, 81, 142, 195 or 330 resulted in significant inhibition of HCV/luciferase expression (65%, 50%, 50%, 80% and 80%, respectively) when compared to HCV/luciferase expression in cells treated with corresponding ACs, P<0.05 (FIG. 26B). It should be noted that treatment with either the ICR or ACs for sites 79, 81, 142 or 192 caused a greater reduction of HCV/luciferase expression than treatment with ACs for sites 195, 282 or 330. The observed differences in HCV/luciferase expression after treatment with ACs most likely represents the range of activity due to non-specific effects of oligonucleotide treatment and/or differences in base composition. Regardless of differences in HCV/luciferase expression levels observed as a result of treatment with ACs, active enzymatic nucleic acids designed to cleave after sites 79, 81, 142, 195, or 330 demonstrated similar and potent anti-HCV activity (FIG. 26B).



Example 24


Synthetic Stabilized Enzymatic Nucleic Acids Inhibit HCV/Luciferase Expression in a Concentration-Dependent Manner

[0479] In order to characterize enzymatic nucleic acid efficacy in greater detail, these same 5 lead hammerhead enzymatic nucleic acids were tested for their ability to inhibit HCV/luciferase expression over a range of enzymatic nucleic acid concentrations (0 nM-100 nM). For constant transfection conditions, the total concentration of nucleic acid was maintained at 100 nM for all samples by mixing the active enzymatic nucleic acid with its corresponding AC. Moreover, mixing of active enzymatic nucleic acid and AC maintains the lipid to nucleic acid charge ratio. A concentration-dependent inhibition of HCV/luciferase expression was observed after treatment with each of the 5 enzymatic nucleic acids (FIGS. 27A-E). By linear interpolation, the enzymatic nucleic acid concentration resulting in 50% inhibition (apparent IC50) of HCV/luciferase expression ranged from 40-215 nM. The two most efficacious enzymatic nucleic acids were those designed to cleave after sites 195 or 330 with apparent IC50 values of 46 nM and 40 nM, respectively (FIGS. 27D and E).



Example 25


An Enzymatic Nucleic Acid Mechanism is Required for the Observed Inhibition of HCV/Luciferase Expression

[0480] To confirm that an enzymatic nucleic acid mechanism of action was responsible for the observed inhibition of HCV/luciferase expression, paired binding-arm attenuated core (BAC) controls (RPI 15291 and 15294) were synthesized for direct comparison to enzymatic nucleic acids targeting sites 195 (RPI 12252) and 330 (RPI 12254). Paired BACs can specifically bind HCV RNA but are unable to promote RNA cleavage because of changes in the catalytic core and, thus, can be used to assess inhibition due to binding alone. Also included in this comparison were paired SAC controls (RPI 15292 and 15295) that contain scrambled binding arms and attenuated catalytic cores, and so lack the ability to bind the target RNA or to catalyze target RNA cleavage.


[0481] Enzymatic nucleic acid cleavage of target RNA should result in both a lower level of HCV/luciferase RNA and a subsequent decrease in HCV/luciferase expression. In order to analyze target RNA levels, a reverse transcriptase/polymerase chain reaction (RT-PCR) assay was employed to quantify HCV/luciferase RNA levels. Primers were designed to amplify the luciferase coding region of the HCV 5′UTR/luciferase RNA. This region was chosen because HCV-targeted enzymatic nucleic acids that might co-purify with cellular RNA would not interfere with RT-PCR amplification of the luciferase RNA region. Primers were also designed to amplify the Renilla luciferase RNA so that Renilla RNA levels could be used to control for transfection efficiency and sample recovery.


[0482] OST7 cells were treated with active enzymatic nucleic acids designed to cleave after sites 195 or 330, paired SACs, or paired BACs. Treatment with enzymatic nucleic acids targeting site 195 or 330 resulted in a significant reduction of HCV/luciferase RNA when compared to their paired SAC controls (P<0.01). In this experiment the site 195 enzymatic nucleic acid was more efficacious than the site 330 enzymatic nucleic acid (FIG. 28A). Treatment with paired BACs that target site 195 or 330 did not reduce HCV/luciferase RNA when compared to the corresponding SACs, thus confirming that the ability to bind alone does not result in a reduction of HCV/luciferase RNA.


[0483] To confirm that enzymatic nucleic acid-mediated cleavage of target RNA is necessary for inhibition of HCV/luciferase expression, HCV/luciferase activity was determined in the same experiment. As expected, significant inhibition of HCV/luciferase expression was observed after treatment with active enzymatic nucleic acids when compared to paired SACs (FIG. 28B). Importantly, treatment with paired BACs did not inhibit HCV/luciferase expression, thus confirming that the ability to bind alone is also not sufficient to inhibit translation. As observed in the RNA assay, the site 195 enzymatic nucleic acid was more efficacious than the site 330 enzymatic nucleic acid in this experiment. However, a correlation between enzymatic nucleic acid-mediated HCV RNA reduction and inhibition of HCV/luciferase translation was observed for enzymatic nucleic acids to both sites. The reduction in target RNA and the necessity for an active enzymatic nucleic acid catalytic core confirm that a enzymatic nucleic acid mechanism is required for the observed reduction in HCV/luciferase protein activity in cells treated with site 195 or site 330 enzymatic nucleic acids.



Example 26


Zinzyme Inhibition of Chimeric HCV/Poliovirus Replication

[0484] During HCV infection, viral RNA is present as a potential target for enzymatic nucleic acid cleavage at several processes: un-coating, translation, RNA replication and packaging. Target RNA can be more or less accessible to enzymatic nucleic acid cleavage at any one of these steps. Although the association between the HCV initial ribosome entry site (IRES) and the translation apparatus is mimicked in the HCV 5′UTR/luciferase reporter system, these other viral processes are not represented in the OST7 system. The resulting RNA/protein complexes associated with the target viral RNA are also absent. Moreover, these processes can be coupled in an HCV-infected cell which could further impact target RNA accessibility. Therefore, applicant tested whether enzymatic nucleic acids designed to cleave the HCV 5′UTR could effect a replicating viral system.


[0485] Recently, Lu and Wimmer characterized a HCV-poliovirus chimera in which the poliovirus IRES was replaced by the IRES from HCV (Lu & Wimmer, 1996, Proc. Natl. Acad. Sci. USA. 93, 1412-1417). Poliovirus (PV) is a positive strand RNA virus like HCV, but unlike HCV is non-enveloped and replicates efficiently in cell culture. The HCV-PV chimera expresses a stable, small plaque phenotype relative to wild type PV.


[0486] The following enzymatic nucleic acid molecules (zinzymes) were synthesized and tested for replicative inhibition of an HCV/Poliovirus chimera: RPI 18763, RPI 18812, RPI 18749, RPI 18765, RPI 18792, and RPI 18814 (Table XX). A scrambled attenuated core enzymatic nucleic acid, RPI 18743, was used as a control.


[0487] HeLa cells were infected with the HCV-PV chimera for 30 minutes and immediately treated with enzymatic nucleic acid. HeLa cells were seeded in U-bottom 96-well plates at a density of 9000-10,000 cells/well and incubated at 37° C. under 5% CO2 for 24 h. Transfection of nucleic acid (200 nM) was achieved by mixing of 10× nucleic acid (2000 nM) and 10× of a cationic lipid (80 μg/ml) in DMEM (Gibco BRL) with 5% fetal bovine serum (FBS). Nucleic acid/lipid complexes were allowed to incubate for 15 minutes at 37° C. under 5% CO2. Medium was aspirated from cells and replaced with 80 μl of DMEM (Gibco BRL) with 5% FBS serum, followed by the addition of 20 μls of 10× complexes. Cells were incubated with complexes for 24 hours at 37° C. under 5% CO2.


[0488] The yield of HCV-PV from treated cells was quantified by plaque assay. The plaque assays were performed by diluting virus samples in serum-free DMEM (Gibco BRL) and applying 100 μl to HeLa cell monolayers (˜80% confluent) in 6-well plates for 30 minutes. Infected monolayers were overlayed with 3 ml 1.2% agar (Sigma) and incubated at 37° C. under 5% CO2. Two or three days later the overlay was removed, monolayers were stained with 1.2% crystal violet, and plaque forming units were counted. The results for the zinzyme inhibition of HCV-PV replication are shown in FIG. 33.



Example 27


Antisense Inhibition of Chimeric HCV/Poliovirus Replication

[0489] Antisense nucleic acid molecules (RPI 17501 and RPI 17498, Table XXII) were tested for replicative inhibition of an HCV/Poliovirus chimera compared to scrambled controls. An antisense nucleic acid molecule is 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 are complementary to a target sequence along a single contiguous sequence of the antisense molecule. However, in certain embodiments, an antisense molecule can bind to substrate such that the substrate molecule forms a loop, and/or an antisense molecule can bind such that the antisense molecule forms a loop. Thus, the antisense molecule can be complementary to two (or even more) non-contiguous substrate sequences or two (or even more) non-contiguous sequence portions of an antisense molecule can 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, 2000, Methods Enzymol., 313, 3-45; 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. Additionally, antisense molecules can be used in combination with the enzymatic nucleic acid molecules of the instant invention.


[0490] A RNase H activating region is 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.


[0491] HeLa cells were infected with the HCV-PV chimera for 30 minutes and immediately treated with antisense nucleic acid. HeLa cells were seeded in U-bottom 96-well plates at a density of 9000-10,000 cells/well and incubated at 37° C. under 5% CO2 for 24 h. Transfection of nucleic acid (200 nM) was achieved by mixing of 10× nucleic acid (2000 nM) and 10× of a cationic lipid (80 μg/ml) in DMEM (Gibco BRL) with 5% fetal bovine serum (FBS). Nucleic acid/lipid complexes were allowed to incubate for 15 minutes at 37° C. under 5% CO2. Medium was aspirated from cells and replaced with 80 μl of DMEM (Gibco BRL) with 5% FBS serum, followed by the addition of 20 μls of 10× complexes. Cells were incubated with complexes for 24 hours at 37° C. under 5% CO2.


[0492] The yield of HCV-PV from treated cells was quantified by plaque assay. The plaque assays were performed by diluting virus samples in serum-free DMEM (Gibco BRL) and applying 100 μl to HeLa cell monolayers (˜80% confluent) in 6-well plates for 30 minutes. Infected monolayers were overlayed with 3 ml 1.2% agar (Sigma) and incubated at 37° C. under 5% CO2. Two or three days later the overlay was removed, monolayers were stained with 1.2% crystal violet, and plaque forming units were counted. The results for the antisense inhibition of HCV-PV are shown in FIG. 34.



Example 28


Nucleic Acid Inhibition of Chimeric HCV/PV in Combination with Interferon

[0493] One of the limiting factors in interferon (IFN) therapy for chronic HCV are the toxic side effects associated with IFN. Applicant has reasoned that lowering the dose of IFN needed can reduce these side effects. Applicant has previously shown that enzymatic nucleic acid molecules targeting HCV RNA have a potent antiviral effect against replication of an HCV-poliovirus (PV) chimera (Macejak et al., 2000, Hepatology, 31, 769-776). In order to determine if the antiviral effect of type 1 IFN could be improved by the addition of anti-HCV enzymatic nucleic acid treatment, a dose response (0 U/ml to 100 U/ml) with IFN alfa 2a or IFN alfa 2b was performed in HeLa cells in combination with 200 nM site 195 anti-HCV enzymatic nucleic acid (RPI 13919) or enzymatic nucleic acid control (SAC) treatment. The SAC control (RPI 17894) is a scrambled binding arm, attenuated core version of the site 195 enzymatic nucleic acid (RPI 13919). IFN dose responses were performed with different pretreatment regimes to find the dynamic range of inhibition in this system. In these studies, HeLa cells were used instead of HepG2 because of more efficient enzymatic nucleic acid delivery (Macejak et al., 2000, Hepatology, 31, 769-776).


[0494] Cells and Virus


[0495] HeLa cells were maintained in DMEM (BioWhittaker, Walkersville, Md.) supplemented with 5% fetal bovine serum. A cloned DNA copy of the HCV-PV chimeric virus was a gift of Dr. Eckard Wimmer (NYU, Stony Brook, N.Y.). An RNA version was generated by in vitro transcription and transfected into HeLa cells to produce infectious virus (Lu and Wimmer, 1996, PNAS USA., 93, 1412-1417).


[0496] Enzymatic Nucleic Acid Synthesis


[0497] Nuclease resistant enzymatic nucleic acids and control oligonucleotides containing 2′-O-methyl-nucleotides, 2′-deoxy-2′-C-allyl uridine, a 3′-inverted abasic cap, and phosphorothioate linkages were chemically synthesized. The anti-HCV enzymatic nucleic acid (RPI 13919) targeting cleavage after nucleotide 195 of the 5′ UTR of HCV is shown in Table XX. Attenuated core controls have nucleotide changes in the core sequence that greatly diminished the enzymatic nucleic acid's cleavage activity. The attenuated controls either contain scrambled binding arms (referred to as SAC, RPI 18743) or maintain binding arms (BAC, RPI 17894) capable of binding to the HCV RNA target.


[0498] Enzymatic Nucleic Acid Delivery


[0499] A cationic lipid was used as a cytofectin agent. HeLa cells were seeded in 96-well plates at a density of 9000-10,000 cells/well and incubated at 37° C. under 5% CO2 for 24 h. Transfection of enzymatic nucleic acid or control oligonucleotides (200 nM) was achieved by mixing 10× enzymatic nucleic acid or control oligonucleotides (2000 nM) with 10× RPI.9778 (80 μg/ml) in DMEM containing 5% fetal bovine serum (FBS) in U-bottom 96-well plates to make 5× complexes. Enzymatic nucleic acid/lipid complexes were allowed to incubate for 15 min at 37° C. under 5% CO2. Medium was aspirated from cells and replaced with 80 μl of DMEM (Gibco BRL) containing 5% FBS serum, followed by the addition of 20 μl of 5× complexes. Cells were incubated with complexes for 24 h at 37° C. under 5% CO2.


[0500] Interferon/Enzymatic Nucleic Acid Combination Treatment


[0501] Interferon alfa 2a (Roferon®) was purchased from Roche Bioscience (Palo Alto, Calif.). Interferon alfa 2b (Intron A®) was purchased from Schering-Plough Corporation (Madison, N.J.). Consensus interferon (interferon-alfa-con 1) was a generous gift of Amgen, Inc. (Thousand Oaks, Calif.). For the basis of comparison, the manufacturers' specified units were used in the studies reported here; however, the manufacturers' unit definitions of these three IFN preparations are not necessarily the same. Nevertheless, since clinical dosing is based on the manufacturers' specified units, a direct comparison based on these units has relevance to clinical therapeutic indices. HeLa cells were seeded (10,000 cells per well) and incubated at 37° C. under 5% CO2 for 24 h. Cells were then pre-treated with interferon in complete media (DMEM+5% FBS) for 4 h and then infected with HCV-PV at a multiplicity of infection (MOI)=0.1 for 30 min. The viral inoculum was then removed and enzymatic nucleic acid or attenuated control (SAC or BAC) was delivered with the cytofectin formulation (8 μg/ml) in complete media for 24 h as described above. Where indicated for enzymatic nucleic acid dose response studies, active enzymatic nucleic acid was mixed with SAC to maintain a 200 nM total oligonucleotide concentration and the same lipid charge ratio. After 24 h, cells were lysed to release virus by three cycles of freeze/thaw. Virus was quantified by plaque assay and viral yield is reported as mean plaque forming units per ml (pfu/ml)+SD. All experiments were repeated at least twice and the trends in the results reported were reproducible. Significance levels (P values) were determined by the Student's test.


[0502] Plaque Assay


[0503] Virus samples were diluted in serum-free DMEM and 100 μl applied to Vero cell monolayers (˜80% confluent) in 6-well plates for 30 min. Infected monolayers were overlaid with 3 ml 1.2% agar (Sigma Chemical Company, St. Louis, Mo.) and incubated at 37° C. under 5% CO2. When plaques were visible (after two to three days) the overlay was removed, monolayers were stained with 1.2% crystal violet, and plaque forming units were counted.


[0504] Results


[0505] As shown in FIGS. 29A and 29B, treatment with the site 195 (RPI 13919) anti-HCV hammerhead enzymatic nucleic acid alone (0 U/ml IFN) resulted in viral replication that was dramatically reduced compared to SAC-treated cells (85%, P<0.01). For both IFN alfa 2a (FIG. 29A) or IFN alfa 2b (FIG. 29B), treatment with 25 U/ml resulted in a ˜90% inhibition of HCV-PV replication in SAC-treated cells as compared to cells treated with SAC alone (p<0.01 for both observations). The maximal level of inhibition in SAC-treated cells (94%) was achieved by treatment with >50 U/ml of either IFN alfa 2a or IFN alfa 2b (p<0.01 for both observations versus SAC alone). Maximal inhibition could however, be achieved by a 5-fold lower dose of IFN alfa 2a (10 U/ml) if enzymatic nucleic acid targeting site 195 in the 5′ UTR of HCV RNA was given in combination (FIG. 29A, p<0.01). While the additional effect of enzymatic nucleic acid treatment on IFN alfa 2b-treated cells at 10 U/ml was very slight, the combined effect with 25 U/ml IFN alfa 2b was greater in magnitude (FIG. 29B). For both interferons tested, pretreatment with 25 U/ml in combination with 200 nM site 195 anti-HCV enzymatic nucleic acid resulted in an even greater level of inhibition of viral replication (>98%) compared to replication in cells treated with 200 nM SAC alone (P<0.01).


[0506] A dose response of the site 195 anti-HCV enzymatic nucleic acid was also performed in HeLa cells, either with or without 12.5 U/ml IFN alfa 2a or IFN alfa 2b pretreatment. As shown in FIG. 30, enzymatic nucleic acid-mediated inhibition was dose-dependent and a significant inhibition of HCV-PV replication (>75% versus 0 nM enzymatic nucleic acid, P<0.01) could be achieved by treatment with >150 nM anti-HCV enzymatic nucleic acid alone (no IFN). However, in IFN-pretreated cells, the dose of anti-HCV enzymatic nucleic acid needed to achieve this level of inhibition was decreased 3-fold to 50 nM (P<0.01 versus 0 nM enzymatic nucleic acid). In comparison, treatment with the site 195 anti-HCV enzymatic nucleic acid alone at 50 nM resulted in only 40% inhibition of virus replication. Pretreatment with IFN enhanced the antiviral effect of site 195 enzymatic nucleic acid at all enzymatic nucleic acid doses, compared to no IFN pretreatment.


[0507] Interferon-alfacon1, consensus IFN (CIFN), is another type 1 IFN that is used to treat chronic HCV. To determine if a similar enhancement can occur in CIFN-treated cells, a dose response with CIFN was performed in HeLa cells using 0 U/ml to 12.5 U/ml CIFN in combination with 200 nM site 195 anti-HCV enzymatic nucleic acid or SAC treatment (FIG. 31A). Again, in the presence of the site 195 anti-HCV enzymatic nucleic acid alone, viral replication was dramatically reduced compared to SAC-treated cells. As shown in FIG. 31A, treatment with 200 mM anti-HCV enzymatic nucleic acid alone significantly inhibited HCV-PV replication (90% versus SAC treatment, P<0.01). However, pretreatment with concentrations of CIFN from 1 U/ml to 12.5 U/ml in combination with 200 nM anti-HCV enzymatic nucleic acid resulted in even greater inhibition of viral replication (>98%) compared to replication in cells treated with 200 nM SAC alone (P<0.01). It is important to note that pretreatment with 1 U/ml CIFN in SAC-treated cells did not have a significant effect on HCV-poliovirus replication, but in the presence of enzymatic nucleic acid a significant inhibition of replication was observed (>98%, P<0.01). Thus, the dose of CIFN needed to achieve a >98% inhibition could be lowered to 1 U/ml in cells also treated with 200 nM site 195 anti-HCV enzymatic nucleic acid.


[0508] A dose response of site 195 anti-HCV enzymatic nucleic acid was then performed in HeLa cells, either with or without 12.5 U/ml CIFN pretreatment. As shown in FIG. 31B, a significant inhibition of HCV-PV replication (>95% versus 0 mM enzymatic nucleic acid, P<0.01) could be achieved by treatment with ≧150 nM anti-HCV enzymatic nucleic acid alone. However, in CIFN-pretreated cells, the dose of anti-HCV enzymatic nucleic acid needed to achieve this level of inhibition was only 50 nM (P<0.01). In comparison, treatment with the site 195 anti-HCV enzymatic nucleic acid alone at 50 nM resulted in ˜50% inhibition of virus replication. Thus, as was seen with IFN alfa 2a and IFN alfa 2b, the dose of enzymatic nucleic acid could be reduced 3-fold in the presence of CIFN pretreatment to achieve a similar antiviral effect as enzymatic nucleic acid-treatment alone.


[0509] To further explore the combination of lower enzymatic nucleic acid concentration and CIFN, a dose response with 0 U/ml to 12.5 U/ml CIFN was subsequently performed in HeLa cells in combination with 50 nM site 195 anti-HCV enzymatic nucleic acid treatment. In multiple experiments, treatment with 50 nM anti-HCV enzymatic nucleic acid alone inhibited HCV-PV replication 50%-81% compared to viral replication in SAC-treated cells. As for the experiment shown in FIG. 31A, treatment with CIFN alone at 5 U/ml resulted in ˜50% inhibition of viral replication. However, a four hour pretreatment with 5 U/ml CIFN followed by 50 nM anti-HCV enzymatic nucleic acid treatment resulted in 95%-97% inhibition compared to SAC-treated cells (P<0.01).


[0510] To demonstrate that the enhanced antiviral effect of CIFN and enzymatic nucleic acid combination treatment was dependent upon enzymatic nucleic acid cleavage activity, the effect of CIFN in combination with site 195 anti-HCV enzymatic nucleic acid versus the effect of CIFN in combination with a binding competent, attenuated core, control (BAC) was then compared. The BAC can still bind to its specific RNA target, but is greatly diminished in cleavage activity. Pretreatment with 12.5 U/ml CIFN reduced the viral yield −90% (7-fold) in cells treated with BAC (compare CIFN versus BAC in FIG. 32). Cells treated with 200 nM site 195 anti-HCV enzymatic nucleic acid alone produced −95% (17-fold) less virus than BAC-treated cells (195 RZ BAC in FIG. 32). The combination of CIFN pretreatment and 200 nM site 195 anti-HCV enzymatic nucleic acid results in an augmented >98% (300-fold) reduction in viral yield (CIFN+RZ versus control in FIG. 32).


[0511] 2′-5′-Oligoadenylate Inhibition of HCV


[0512] Type 1 Interferon is a key constituent of many effective treatment programs for chronic HCV infection. Treatment with type 1 interferon induces a number of genes and results in an antiviral state within the cell. One of the genes induced is 2′,5′ oligoadenylate synthetase, an enzyme that synthesizes short 2′,5′ oligoadenylate (2-5A) molecules. Nascent 2-5A subsequently activates a latent RNase, RNase L, which in turn nonspecifically degrades viral RNA. As described herein, ribozymes targeting HCV RNA that inhibit the replication of an HCV-poliovirus (HCV-PV) chimera in cell culture and have shown that this antiviral effect is augmented if ribozyme is given in combination with type 1 interferon. In addtion, the 2-5A component of the interferon response can also inhibit replication of the HCV-PV chimera.


[0513] The antiviral effect of anti-HCV ribozyme treatment is enhanced if type 1 interferon is given in combination. Interferon induces a number of gene products including 2′,5′ oligoadenylate (2-5A) synthetase, double-stranded RNA-activated protein kinase (PKR), and the Mx proteins. Mx proteins appear to interfere with nuclear transport of viral complexes and are not thought to play an inhibitory role in HCV infection. On the other hand, the additional 2-5A-mediated RNA degradation (via RNase L) and/or the inhibition of viral translation by PKR in interferon-treated cells can augment the ribozyme-mediated inhibition of HCV-PV replication.


[0514] To investigate the potential role of the 2-5A/RNase L pathway in this enhancement phenomenon, HCV-PV replication was analyzed in HeLa cells treated exogenously with chemically-synthesized analogs of 2-5A (FIG. 35), alone and in combination with the anti-HCV ribozyme (RPI 13919). These results were compared to replication in cells treated with interferon and/or anti-HCV ribozyme. Anti-HCV ribozyme was transfected into cells with a cationic lipid. To control for nonspecific effects due to lipid-mediated transfection, a scrambled arm, attenuated core, oligonucleotide (SAC) (RPI 17894) was transfected for comparison. The SAC is the same base composition as the ribozyme but is greatly attenuated in catalytic activity due to changes in the core sequence and cannot bind specifically to the HCV sequence.


[0515] As shown in FIG. 36A, HeLa cells pretreated with 10 U/ml consensus interferon for 4 hours prior to HCV-PV infection resulted in ˜70% reduction of viral replication in SAC-treated cells. Similarly, HeLa cells treated with 100 nM anti-HCV ribozyme for 20 hours after infection resulted in an ˜80% reduction in viral yield. This antiviral effect was enhanced to ˜98% inhibition in HeLa cells pretreated with interferon for 4 hours before infection and then treated with anti-HCV ribozyme for 20 hours after infection. In parallel, a 2-5A compound (analog I, FIG. 35) that was protected from nuclease digestion at the 3′-end with an inverted abasic moiety was tested. As shown in FIG. 36B, treatment with 200 nM 2-5A analog I for 4 hours prior to HCV-PV infection only slightly inhibited HCV-PV replication (˜20%) in SAC-treated cells. Moreover, the inhibition due to a 20 hour anti-HCV ribozyme treatment was not augmented with a 4 hour pretreatment of 2-5A in combination (compare third bar to fourth bar in FIG. 36B).


[0516] There are several possible possible explanations why the chemically synthesized 2-5A analog was not able to completely activate RNase L. It is possible that the 2-5A analog was not sufficiently stable or that in this experiment the 4 hour pretreatment period was too short for RNase L activation. To test these possibilities, a 2-5A compound containing a 5′-terminal thiophosphate (P═S) for added nuclease resistance, in addition to the 3′-abasic, was also included (analog II, FIG. 35). In addition, a longer 2-5A treatment was used. In this experiment (FIG. 37), HeLa cells were treated with 2-5A or 2-5A (P═S) for 20 hours after HCV-PV infection. Again, anti-HCV ribozyme treatment resulted in >80% inhibition. In contrast to the 20% inhibition of viral replication seen with a 4 hour 2-5A pretreatment, viral replication in cells treated with 2-5A analog I for 20 hours after HCV-PV infection was inhibited by ˜70%. The P═S version (analog II) inhibited HCV-PV replication by −35%. Thus, both 2-5A analogs used here are able to generate an antiviral effect, presumably through RNase L activation. The P═S version, although more resistant to 5′ dephosphorylation, did not yield as great an anti-viral effect. It is possible that combination of the 5′-terminal thiophosphate together with the presence of a 3′-inverted abasic moiety can interfere with RNase L activation. Nevertheless, these results demonstrate potent anti-HCV activity by a nuclease-stabilized 2-5A analog.


[0517] The level of reduction in HCV-PV replication in cells treated with 2-5A analog I for 20 hours was similar to that in cells pretreated with consensus interferon for 4 hours. To determine if this expanded 2-5A treatment regimen would enhance anti-HCV ribozyme efficacy to the same degree as does the interferon pretreatment, HeLa cells infected with HCV-PV were treated with a combination of 2-5A and anti-HCV ribozyme for 20 hours after infection. In this experiment, a 200 mM treatment with anti-HCV ribozyme or 2-5A treatment alone inhibited viral replication by 88% or ˜60%, respectively, compared to SAC treatment (FIG. 38, left three bars). To maintain consistent transfection conditions but vary the concentration of anti-HCV ribozyme or 2-5A, anti-HCV ribozyme was mixed with the SAC to maintain a total dose of 200 nM. A 50 mM treatment with anti-HCV ribozyme inhibited HCV-PV replication by ˜70% (solid middle bar). However, the amount of HCV-PV replication was not further reduced in cells treated with a combination of 50 nM anti-HCV ribozyme and 150 nM 2-5A (striped middle bar). Likewise, cells treated with 100 nM anti-HCV ribozyme inhibited HCV-PV replication by ˜80% whether they were also treated with 100 mM of 2-5A or SAC (right two bars). In contrast, antiviral activity increased from 80% to 98% when 100 nM anti-HCV ribozyme was given in combination with interferon (FIG. 36A). The reasons for the lack of additive or synergistic effects for the ribozyme/2-5A combination therapy is unclear at this time but can be due to that fact that both compounds have a similar mechanism of action (degradation of RNA). Further study is warranted to examine this possibility.


[0518] As a monotherapy, 2-5A treatment generates a similar inhibitory effect on HCV-poliovirus replication as does interferon treatment. If these results are maintained in HCV patients, treatment with 2-5A can not only be efficacious but can also generate less side effects than those observed with interferon if the plethora of interferon-induced genes were not activated.


[0519] HBV Cell Culture Models


[0520] 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 are co-transfected with ribozymes 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. In these cells, only ribozyme need be delivered; however, performance of a delivery screen is required. 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.


[0521] HBV Animal Models


[0522] 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).


[0523] 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).


[0524] 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).


[0525] In one embodiment, the invention features a mouse, for example a male or female mouse, implanted with HepG2.2.15 cells, wherein the mouse is susceptible to HBV infection and capable of sustaining HBV DNA expression. One embodiment of the invention provides a mouse implanted with HepG2.2.15 cells, wherein said mouse sustains the propagation of HEPG2.2.15 cells and HBV production (see Macejak, U.S. Provisional Patent Application No. 60/296,876).


[0526] 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).


[0527] HCV Cell Culture Models


[0528] Although there have been reports of replication of HCV in cell culture (see below), these systems are difficult to replicate and have proven unreliable. Therefore, as was the case for development of other anti-HCV therapeutics such as interferon and ribavirin, after demonstration of safety in animal studies applicant can proceed directly into a clinical feasibility study.


[0529] Several recent reports have documented in vitro growth of HCV in human cell lines (Mizutani et al, Biochem Biophys Res Commun 1996 227(3):822-826; Tagawa et al., Journal of Gasteroenterology and Hepatology 1995 10(5):523-527; Cribier et al., Journal of General Virology 76(10):2485-2491; Seipp et al., Journal of General Virology 1997 78(10)2467-2478; lacovacci et al., Research Virology 1997 148(2):147-151; locavacci et al., Hepatology 1997 26(5) 1328-1337; Ito et al., Journal of General Virology 1996 77(5):1043-1054; Nakajima et al., Journal of Virology 1996 70(5):3325-3329; Mizutani et al., Journal of Virology 1996 70(10):7219-7223; Valli et al., Res Virol 1995 146(4): 285-288; Kato et al., Biochem Biophys Res Comm 1995 206(3):863-869). Replication of HCV has been demonstrated in both T and B cell lines as well as cell lines derived from human hepatocytes. Demonstration of replication was documented using either RT-PCR based assays or the b-DNA assay. It is important to note that the most recent publications regarding HCV cell cultures document replication for up to 6-months.


[0530] Additionally, another recent study has identified more robust strains of hepatitis C virus having adaptive mutations that allow the strains to replicate more vigorously in human cell cult. The mutations that confer this enhanced ability to replicate are located in a specific region of a protein identified as NS5A. Studies performed at Rockefeller University have shown that in certain cell culture systems, infection with the robust strains produces a 10,000-fold increase in the number of infected cells. The greatly increased availability of HCV-infected cells in culture can be used to develop high-throughput screening assays, in which a large number of compounds, such as enzymatic nucleic acid molecules, can be tested to determine their effectiveness.


[0531] In addition to cell lines that can be infected with HCV, several groups have reported the successful transformation of cell lines with cDNA clones of full-length or partial HCV genomes (Harada et al., Journal of General Virology 1995 76(5)1215-1221; Haramatsu et al., Journal of Viral Hepatitis 1997 4S(1):61-67; Dash et al., American Journal of Pathology 1997 151(2):363-373; Mizuno et al., Gasteroenterology 1995 109(6):1933-40; Yoo et al., Journal Of Virology 1995 69(1):32-38).


[0532] HCV Animal Models


[0533] The best characterized animal system for HCV infection is the chimpanzee. Moreover, the chronic hepatitis that results from HCV infection in chimpanzees and humans is very similar. Although clinically relevant, the chimpanzee model suffers from several practical impediments that make use of this model difficult. These include; high cost, long incubation requirements and lack of sufficient quantities of animals. Due to these factors, a number of groups have attempted to develop rodent models of chronic hepatitis C infection. While direct infection has not been possible several groups have reported on the stable transfection of either portions or entire HCV genomes into rodents (Yamamoto et al., Hepatology 1995 22(3): 847-855; Galun et al., Journal of Infectious Disease 1995 172(1):25-30; Koike et al., Journal of general Virology 1995 76(12)3031-3038; Pasquinelli et al., Hepatology 1997 25(3): 719-727; Hayashi et al., Princess Takamatsu Symp 1995 25:1430149; Mariya K, Yotsuyanagi H, Shintani Y, Fujie H, Ishibashi K, Matsuura Y, Miyamura T, Koike K. Hepatitis C virus core protein induces hepatic steatosis in transgenic mice. Journal of General Virology 1997 78(7) 1527-1531; Takehara et al., Hepatology 1995 21(3):746-751; Kawamura et al., Hepatology 1997 25(4): 1014-1021). In addition, transplantation of HCV infected human liver into immunocompromised mice results in prolonged detection of HCV RNA in the animal's blood.


[0534] Vierling, International PCT Publication No. WO 99/16307, describes a method for expressing hepatitis C virus in an in vivo animal model. Viable, HCV infected human hepatocytes are transplanted into a liver parenchyma of a scid/scid mouse host. The scid/scid mouse host is then maintained in a viable state, whereby viable, morphologically intact human hepatocytes persist in the donor tissue and hepatitis C virus is replicated in the persisting human hepatocytes. This model provides an effective means for the study of HCV inhibition by enzymatic nucleic acids in vivo.


[0535] Indications


[0536] 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 other conditions related to the level of HBV.


[0537] Particular degenerative and disease states that can be associated with HCV expression modulation include, but are not limited to, HCV infection, hepatitis, cancer, tumorigenesis, cirrhosis, liver failure and other conditions related to the level of HCV.


[0538] The present body of knowledge in HBV and HCV research indicates the need for methods to assay HBV or HCV activity and for compounds that can regulate HBV and HCV expression for research, diagnostic, and therapeutic use.


[0539] Lamivudine (3TC®), L-FMAU, adefovir dipivoxil, type 1 Interferon (e.g, interferon alpha, interferon beta, consensus interferon, polyethylene glycol interferon, polyethylene glycol interferon alpha 2a, polyethylene glycol interferon 2b, and polyethylene glycol consensus 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. ribozymes 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. ribozymes and antisense molecules) and are, therefore, within the scope of the instant invention.


[0540] Diagnostic Uses


[0541] The nucleic acid molecules of this invention can be used as diagnostic tools to examine genetic drift and mutations within diseased cells or to detect the presence of HBV or HCV RNA in a cell. For example, 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 can lead to better treatment of the disease progression by affording the possibility of combinational therapies (e.g., multiple enzymatic nucleic acid molecules targeted to different genes, enzymatic nucleic acid molecules coupled with known small molecule inhibitors, or intermittent treatment with combinations of enzymatic nucleic acid molecules and/or other chemical or biological molecules). Other in vitro uses of enzymatic nucleic acid molecules of this invention are well known in the art, and include detection of the presence of mRNAs associated with HBV or HCV-related condition. Such RNA is detected by determining the presence of a cleavage product after treatment with an enzymatic nucleic acid using standard methodology.


[0542] In a specific example, enzymatic nucleic acid molecules which can 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 can be cleaved by both enzymatic nucleic acid molecules to demonstrate the relative ribozyme efficiencies in the reactions and the absence of cleavage of the “non-targeted” RNA species. The cleavage products from the synthetic substrates can 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 acid molecules, 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 can be 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 or HCV) 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 will decrease the cost of the initial diagnosis. Higher mutant form to wild-type ratios are correlated with higher risk whether RNA levels are compared qualitatively or quantitatively.


[0543] Additional Uses


[0544] Potential usefulness of sequence-specific enzymatic nucleic acid molecules of the instant invention 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.


[0545] 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.


[0546] 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.


[0547] 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.


[0548] The invention illustratively described herein suitably can be practiced in the absence of any element or elements, limitation or limitations that are 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.


[0549] 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.
1TABLE ICharacteristics of naturally occurring ribozymesGroup 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: aftack by the 3′-OH of guanosine to generate cleavageproducts with 3′-OH and 5′-guanosine.Additional protein cofactors required in some cases to help folding andmaintenance of the active structure.Over 300 known members of this class. Found as an intervening sequence inTetrahymena thermophila rRNA, fungal mitochondria, chloroplasts, phage T4,blue-green algae, and others.Major structural features largely established through phylogenetic comparisons,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 established [xxi].The small (4-6 nt) binding site may make this ribozyme too non-specific fortargeted RNA cleavage, however, the Tetrahymena group I intron has been used to repaira “defective” β-galactosidase message by the ligation of newβ-galactosidase sequences onto the defective message [xii]RNAse P RNA (M1 RNA)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 cleavage productswith 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 possiblethrough hybridization of an External Guide Sequence (EGS) to the target 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,xvix].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 a 2′-5′ branch point.Only natural ribozyme with demonstrated participation in DNA cleavage [xx,xxi]in addition to RNA cleavage and ligation.Major structural features largely established through phylogenetic comparisons[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 structures[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 established [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 variable number tothe 3′-side 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.3 known members of this class. Found in three plant pathogen (satellite RNAsof the tobacco ringspot virus, arabis mosaic virus and chicory yellow mottlevirus) which uses RNA as the infectious agent.Essential structural features largely defined [xxxi,xxxii,xxiii,xxxiv]Ligation activity (in addition to cleavage activity) makes ribozyme amenable toengineering through in vitro selection [xxxv]Complete kinetic framework established for one ribozyme [xxxvi]Chemical modification investigation of important residues begun [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 [x1].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.Circular form of HDV is active and shows increased nuclease stability [x1i]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), 3149. 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: Aproposed 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.Beigehnan, 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, Philip. ‘Hairpin’ catalytic RNA model: evidence for helixes and sequence requirement for substrate RNA. Nucleic Acids Res. (1990), 18 (2), 299-304. xxxiiChowrira, Bliarat M.; Berzal-Herranz, Aifredo; 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, Aifredo; 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, Aifredo; 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. x1Perrotta, 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. x1iPuttaraju, M.; Perrotta, Anne T.; Been, Michael D.. A circular trans-acting hepatitis delta virus ribozyme. Nucleic Acids Res. (1993), 21 (18), 4253-8.


[0550]

2










TABLE II














Wait Time*



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










A. 2.5 μmol Synthesis Cycle ABI 394 Instrument















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
















Equivalents:
Amount:

Wait Time*




DNA/2′-O-
DNA/2′-O-
Wait Time*
2′-O-
Wait Time*


Reagent
methyl/Ribo
methyl/Ribo
DNA
methyl
Ribo










C. 0.2 μmol Synthesis Cycle 96 well Instrument














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.








[0551]

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,


AB033559.1
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


AF143307.1
AF143307 Hepatitis B virus clone RM518, complete


AF143306.1
AF143306 Hepatitis B virus clone RM517, 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 B 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-TKB588) complete



genome


D23683.1
HPBC5HKO2 Hepatitis B virus (C5-HBVKO2) complete



genome


D23682.1
HPBB5HKO1 Hepatitis B virus (B5-HBVKO1) 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
HPBADW1 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










[0552]

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
AAACUAGGCAUEJA
29.


1370
AGGCGGGCAUUCUAUAUAAGAGAG
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.








[0553]

5






TABLE V










HUMAN HBV HAMMERHEAD RIBOZYME AND TARGET SEQUENCE















Seq

Seq



Pos
Substrate
ID
Hammerhead
ID















13
CCACCACU U UCCACCAA
34
UUGGUGGA CUGAUGAG GCCGUUAGGC CGAA AGUGGUGG
7434



14
CACCACUU U CCACCAAA
34
UUUGGUGG CUGAUGAG GCCGUUAGGC CGAA AAGUGGUG
7435


15
ACCACUUU C CACCAAAC
36
GUUUGGUG CUGAUGAG GCCGUUAGGC CGAA AAAGUGGU
7436


25
ACCAAACU C UUCAAGAU
37
AUCUUGAA CUGAUGAG GCCGUUAGGC CGAA AGUUUGGU
7437


27
CAAACUCU U CAAGAUCC
38
GGAUCUUG CUGAUGAG GCCGUUAGGC CGAA AGAGUUUG
7438


28
AAACUCUU C AAGAUCCC
39
GGGAUCUU CUGAUGAG GCCGUUAGGC CGAA AAGAGUUU
7439


34
UUCAAGAU C CCAGAGUC
40
GACUCUGG CUGAUGAG GCCGUUAGGC CGAA AUCUUGAA
7440


42
CCCAGAGU C AGGGCCCU
41
AGGGCCCU CUGAUGAG GCCGUUAGGC CGAA ACUCUGGG
7441


53
GGCCCUGU A CUUUCCUG
42
CAGGAAAG CUGAUGAG GCCGUUAGGC CGAA ACAGGGCC
7442


56
CCUGUACU U UCCUGCUG
43
CAGCAGGA CUGAUGAG GCCGUUAGGC CGAA AGUACAGG
7443


57
CUGUACUU U CCUGCUGG
44
CCAGCAGG CUGAUGAG GCCGUUAGGC CGAA AAGUACAG
7444


58
UGUACUUU C CUGCUGGU
45
ACCAGCAG CUGAUGAG GCCGUUAGGC CGAA AAAGUACA
7445


71
UGGUGGCU C CAGUUCAG
46
CUGAACUG CUGAUGAG GCCGUUAGGC CGAA AGCCACCA
7446


76
GCUCCAGU U CAGGAACA
47
UGUUCCUG CUGAUGAG GCCGUUAGGC CGAA ACUGGAGC
7447


77
CUCCAGUU C AGGAACAG
48
CUGUUCCU CUGAUGAG GCCGUUAGGC CGAA AACUGGAG
7448


97
GCCCUGCU C AGAAUACU
49
AGUAUUCU CUGAUGAG GCCGUUAGGC CGAA AGCAGGGC
7449


103
CUCAGAAU A CUGUCUCU
50
AGAGACAG CUGAUGAG GCCGUUAGGC CGAA AUUCUGAG
7450


108
AAUACUGU C UCUGCCAU
51
AUGGCAGA CUGAUGAG GCCGUUAGGC CGAA ACAGUAUU
7451


110
UACUGUCU C UGCCAUAU
52
AUAUGGCA CUGAUGAG GCCGUUAGGC CGAA AGACAGUA
7452


117
UCUGCCAU A UCGUCAAU
53
AUUGACGA CUGAUGAG GCCGUUAGGC CGAA AUGGCAGA
7453


119
UGCCAUAU C GUCAAUCU
54
AGAUUGAC CUGAUGAG GCCGUUAGGC CGAA AUAUGGCA
7454


122
CAUAUCGU C AAUCUUAU
55
AUAAGAUU CUGAUGAG GCCGUUAGGC CGAA ACGAUAUG
7455


126
UCGUCAAU C UUAUCGAA
56
UUCGAUAA CUGAUGAG GCCGUUAGGC CGAA AUUGACGA
7456


128
GUCAAUCU U AUCGAAGA
57
UCUUCGAU CUGAUGAG GCCGUUAGGC CGAA AGAUUGAC
7457


129
UCAAUCUU A UCGAAGAC
58
GUCUUCGA CUGAUGAG GCCGUUAGGC CGAA AAGAUUGA
7458


131
AAUCUUAU C GAAGACUG
59
CAGUCUUC CUGAUGAG GCCGUUAGGC CGAA AUAAGAUU
7459


150
GACCCUGU A CCGAACAU
60
AUGUUCGG CUGAUGAG GCCGUUAGGC CGAA ACAGGGUC
7460


168
GAGAACAU C GCAUCAGG
61
CCUGAUGC CUGAUGAG GCCGUUAGGC CGAA AUGUUCUC
7461


173
CAUCGCAU C AGGACUCC
62
GGAGUCCU CUGAUGAG GCCGUUAGGC CGAA AUGCGAUG
7462


180
UCAGGACU C CUAGGACC
63
GGUCCUAG CUGAUGAG GCCGUUAGGC CGAA AGUCCUGA
7463


183
GGACUCCU A GGACCCCU
64
AGGGGUCC CUGAUGAG GCCGUUAGGC CGAA AGGAGUCC
7464


195
CCCCUGCU C GUGUUACA
65
UGUAACAC CUGAUGAG GCCGUUAGGC CGAA AGCAGGGG
7465


200
GCUCGUGU U ACAGGCGG
66
CCGCCUGU CUGAUGAG GCCGUUAGGC CGAA ACACGAGC
7466


201
CUCGUGUU A CAGGCGGG
67
CCCGCCUG CUGAUGAG GCCGUUAGGC CGAA AACACGAG
7467


212
GGCGGGGU U UUUCUUGU
68
ACAAGAAA CUGAUGAG GCCGUUAGGC CGAA ACCCCGCC
7468


213
GCGGGGUU U UUCUUGUU
69
AACAAGAA CUGAUGAG GCCGUUAGGC CGAA AACCCCGC
7469


214
CGGGGUUU U UCUUGUUG
70
CAACAAGA CUGAUGAG GCCGUUAGGC CGAA AAACCCCG
7470


215
GGGGUUUU U CUUGUUGA
71
UCAACAAG CUGAUGAG GCCGUUAGGC CGAA AAAACCCC
7471


216
GGGUUUUU C UUGUUGAC
72
GUCAACAA CUGAUGAG GCCGUUAGGC CGAA AAAAACCC
7472


218
GUUUUUCU U GUUGACAA
73
UUGUCAAC CUGAUGAG GCCGUUAGGC CGAA AGAAAAAC
7473


221
UUUCUUGU U GACAAAAA
74
UUUUUGUC CUGAUGAG GCCGUUAGGC CGAA ACAAGAAA
7474


231
ACAAAAAU C CUCACAAU
75
AUUGUGAG CUGAUGAG GCCGUUAGGC CGAA AUUUUUGU
7475


234
AAAAUCCU C ACAAUACC
76
GGUAUUGU CUGAUGAG GCCGUUAGGC CGAA AGGAUUUU
7476


240
CUCACAAU A CCACAGAG
77
CUCUGUGG CUGAUGAG GCCGUUAGGC CGAA AUUGUGAG
7477


250
CACAGAGU C UAGACUCG
78
CGAGUCUA CUGAUGAG GCCGUUAGGC CGAA ACUCUGUG
7478


252
CAGAGUCU A GACUCGUG
79
CACGAGUC CUGAUGAG GCCGUUAGGC CGAA AGACUCUG
7479


257
UCUAGACU C GUGGUGGA
80
UCCACCAC CUGAUGAG GCCGUUAGGC CGAA AGUCUAGA
7480


268
GGUGGACU U CUCUCAAU
81
AUUGAGAG CUGAUGAG GCCGUUAGGC CGAA AGUCCACC
7481


269
GUGGACUU C UCUCAAUU
82
AAUUGAGA CUGAUGAG GCCGUUAGGC CGAA AAGUCCAC
7482


271
GGACUUCU C UCAAUUUU
83
AAAAUUGA CUGAUGAG GCCGUUAGGC CGAA AGAAGUCC
7483


273
ACUUCUCU C AAUUUUCU
84
AGAAAAUU CUGAUGAG GCCGUUAGGC CGAA AGAGAAGU
7484


277
CUCUCAAU U UUCUAGGG
85
CCCUAGAA CUGAUGAG GCCGUUAGGC CGAA AUUGAGAG
7485


278
UCUCAAUU U UCUAGGGG
86
CCCCUAGA CUGAUGAG GCCGUUAGGC CGAA AAUUGAGA
7486


279
CUCAAUUU U CUAGGGGG
87
CCCCCUAG CUGAUGAG GCCGUUAGGC CGAA AAAUUGAG
7487


280
UCAAUUUU C UAGGGGGA
88
UCCCCCUA CUGAUGAG GCCGUUAGGC CGAA AAAAUUGA
7488


282
AAUUUUCU A GGGGGAAC
89
GUUCCCCC CUGAUGAG GCCGUUAGGC CGAA AGAAAAUU
7489


301
CCGUGUGU C UUGGCCAA
90
UUGGCCAA CUGAUGAG GCCGUUAGGC CGAA ACACACGG
7490


303
GUGUGUCU U GGCCAAAA
91
UUUUGGCC CUGAUGAG GCCGUUAGGC CGAA AGACACAC
7491


313
GCCAAAAU U CGCAGUCC
92
GGACUGCG CUGAUGAG GCCGUUAGGC CGAA AUUUUGGC
7492


314
CCAAAAUU C GCAGUCCC
93
GGGACUGC CUGAUGAG GCCGUUAGGC CGAA AAUUUUGG
7493


320
UUCGCAGU C CCAAAUCU
94
AGAUUUGG CUGAUGAG GCCGUUAGGC CGAA ACUGCGAA
7494


327
UCCCAAAU C UCCAGUCA
95
UGACUGGA CUGAUGAG GCCGUUAGGC CGAA AUUUGGGA
7495


329
CCAAAUCU C CAGUCACU
96
AGUGACUG CUGAUGAG GCCGUUAGGC CGAA AGAUUUGG
7496


334
UCUCCAGU C ACUCACCA
97
UGGUGAGU CUGAUGAG GCCGUUAGGC CGAA ACUGGAGA
7497


338
CAGUCACU C ACCAACCU
98
AGGUUGGU CUGAUGAG GCCGUUAGGC CGAA AGUGACUG
7498


349
CAACCUGU U GUCCUCCA
99
UGGAGGAC CUGAUGAG GCCGUUAGGC CGAA ACAGGUUG
7499


352
CCUGUUGU C CUCCAAUU
100
AAUUGGAG CUGAUGAG GCCGUUAGGC CGAA ACAACAGG
7500


355
GUUGUCCU C CAAUUUGU
101
ACAAAUUG CUGAUGAG GCCGUUAGGC CGAA AGGACAAC
7501


360
CCUCCAAU U UGUCCUGG
102
CCAGGACA CUGAUGAG GCCGUUAGGC CGAA AUUGGAGG
7502


361
CUCCAAUU U GUCCUGGU
103
ACCAGGAC CUGAUGAG GCCGUUAGGC CGAA AAUUGGAG
7503


364
CAAUUUGU C CUGGUUAU
104
AUAACCAG CUGAUGAG GCCGUUAGGC CGAA ACAAAUUG
7504


370
GUCCUGGU U AUCGCUGG
105
CCAGCGAU CUGAUGAG GCCGUUAGGC CGAA ACCAGGAC
7505


371
UCCUGGUU A UCGCUGGA
106
UCCAGCGA CUGAUGAG GCCGUUAGGC CGAA AACCAGGA
7506


373
CUGGUUAU C GCUGGAUG
107
CAUCCAGC CUGAUGAG GCCGUUAGGC CGAA AUAACCAG
7507


385
GGAUGUGU C UGCGGCGU
108
ACGCCGCA CUGAUGAG GCCGUUAGGC CGAA ACACAUCC
7508


394
UGCGGCGU U UUAUCAUC
109
GAUGAUAA CUGAUGAG GCCGUUAGGC CGAA ACGCCGCA
7509


395
GCGGCGUU U UAUCAUCU
110
AGAUGAUA CUGAUGAG GCCGUUAGGC CGAA AACGCCGC
7510


396
CGGCGUUU U AUCAUCUU
111
AAGAUGAU CUGAUGAG GCCGUUAGGC CGAA AAACGCCG
7511


397
GGCGUUUU A UCAUCUUC
112
GAAGAUGA CUGAUGAG GCCGUUAGGC CGAA AAAACGCC
7512


399
CGUUUUAU C AUCUUCCU
113
AGGAAGAU CUGAUGAG GCCGUUAGGC CGAA AUAAAACG
7513


402
UUUAUCAU C UUCCUCUG
114
CAGAGGAA CUGAUGAG GCCGUUAGGC CGAA AUGAUAAA
7514


404
UAUCAUCU U CCUCUGCA
115
UGCAGAGG CUGAUGAG GCCGUUAGGC CGAA AGAUGAUA
7515


405
AUCAUCUU C CUCUGCAU
116
AUGCAGAG CUGAUGAG GCCGUUAGGC CGAA AAGAUGAU
7516


408
AUCUUCCU C UGCAUCCU
117
AGGAUGCA CUGAUGAG GCCGUUAGGC CGAA AGGAAGAU
7517


414
CUCUGCAU C CUGCUGCU
118
AGCAGCAG CUGAUGAG GCCGUUAGGC CGAA AUGCAGAG
7518


423
CUGCUGCU A UGCCUCAU
119
AUGAGGCA CUGAUGAG GCCGUUAGGC CGAA AGCAGCAG
7519


429
CUAUGCCU C AUCUUCUU
120
AAGAAGAU CUGAUGAG GCCGUUAGGC CGAA AGGCAUAG
7520


432
UGCCUCAU C UUCUUGUU
121
AACAAGAA CUGAUGAG GCCGUUAGGC CGAA AUGAGGCA
7521


434
CCUCAUCU U CUUGUUGG
122
CCAACAAG CUGAUGAG GCCGUUAGGC CGAA AGAUGAGG
7522


435
CUCAUCUU C UUGUUGGU
123
ACCAACAA CUGAUGAG GCCGUUAGGC CGAA AAGAUGAG
7523


437
CAUCUUCU U GUUGGUUC
124
GAACCAAC CUGAUGAG GCCGUUAGGC CGAA AGAAGAUG
7524


440
CUUCUUGU U GGUUCUUC
125
GAAGAACC CUGAUGAG GCCGUUAGGC CGAA ACAAGAAG
7525


444
UUGUUGGU U CUUCUGGA
126
UCCAGAAG CUGAUGAG GCCGUUAGGC CGAA ACCAACAA
7526


445
UGUUGGUU C UUCUGGAC
127
GUCCAGAA CUGAUGAG GCCGUUAGGC CGAA AACCAACA
7527


447
UUGGUUCU U CUGGACUA
128
UAGUCCAG CUGAUGAG GCCGUUAGGC CGAA AGAACCAA
7528


448
UGGUUCUU C UGGACUAU
129
AUAGUCCA CUGAUGAG GCCGUUAGGC CGAA AAGAACCA
7529


455
UCUGGACU A UCAAGGUA
130
UACCUUGA CUGAUGAG GCCGUUAGGC CGAA AGUCCAGA
7530


457
UGGACUAU C AAGGUAUG
131
CAUACCUU CUGAUGAG GCCGUUAGGC CGAA AUAGUCCA
7531


463
AUCAAGGU A UGUUGCCC
132
GGGCAACA CUGAUGAG GCCGUUAGGC CGAA ACCUUGAU
7532


467
AGGUAUGU U GCCCGUUU
133
AAACGGGC CUGAUGAG GCCGUUAGGC CGAA ACAUACCU
7533


474
UUGCCCGU U UGUCCUCU
134
AGAGGACA CUGAUGAG GCCGUUAGGC CGAA ACGGGCAA
7534


475
UGCCCGUU U GUCCUCUA
135
UAGAGGAC CUGAUGAG GCCGUUAGGC CGAA AACGGGCA
7535


478
CCGUUUGU C CUCUAAUU
136
AAUUAGAG CUGAUGAG GCCGUUAGGC CGAA ACAAACGG
7536


481
UUUGUCCU C UAAUUCCA
137
UGGAAUUA CUGAUGAG GCCGUUAGGC CGAA AGGACAAA
7537


483
UGUCCUCU A AUUCCAGG
138
CCUGGAAU CUGAUGAG GCCGUUAGGC CGAA AGAGGACA
7538


486
CCUCUAAU U CCAGGAUC
139
GAUCCUGG CUGAUGAG GCCGUUAGGC CGAA AUUAGAGG
7539


487
CUCUAAUU C CAGGAUCA
140
UGAUCCUG CUGAUGAG GCCGUUAGGC CGAA AAUUAGAG
7540


494
UCCAGGAU C AUCAACAA
141
UUGUUGAU CUGAUGAG GCCGUUAGGC CGAA AUCCUGGA
7541


497
AGGAUCAU C AACAACCA
142
UGGUUGUU CUGAUGAG GCCGUUAGGC CGAA AUGAUCCU
7542


535
GCACAACU C CUGCUCAA
143
UUGAGCAG CUGAUGAG GCCGUUAGGC CGAA AGUUGUGC
7543


541
CUCCUGCU C AAGGAACC
144
GGUUCCUU CUGAUGAG GCCGUUAGGC CGAA AGCAGGAG
7544


551
AGGAACCU C UAUGUUUC
145
GAAACAUA CUGAUGAG GCCGUUAGGC CGAA AGGUUCCU
7545


553
GAACCUCU A UGUUUCCC
146
GGGAAACA CUGAUGAG GCCGUUAGGC CGAA AGAGGUUC
7546


557
CUCUAUGU U UCCCUCAU
147
AUGAGGGA CUGAUGAG GCCGUUAGGC CGAA ACAUAGAG
7547


558
UCUAUGUU U CCCUCAUG
148
CAUGAGGG CUGAUGAG GCCGUUAGGC CGAA AACAUAGA
7548


559
CUAUGUUU C CCUCAUGU
149
ACAUGAGG CUGAUGAG GCCGUUAGGC CGAA AAACAUAG
7549


563
GUUUCCCU C AUGUUGCU
150
AGCAACAU CUGAUGAG GCCGUUAGGC CGAA AGGGAAAC
7550


568
CCUCAUGU U GCUGUACA
151
UGUACAGC CUGAUGAG GCCGUUAGGC CGAA ACAUGAGG
7551


574
GUUGCUGU A CAAAACCU
152
AGGUUUUG CUGAUGAG GCCGUUAGGC CGAA ACAGCAAC
7552


583
CAAAACCU A CGGACGGA
153
UCCGUCCG CUGAUGAG GCCGUUAGGC CGAA AGGUUUUG
7553


604
GCACCUGU A UUCCCAUC
154
GAUGGGAA CUGAUGAG GCCGUUAGGC CGAA ACAGGUGC
7554


606
ACCUGUAU U CCCAUCCC
155
GGGAUGGG CUGAUGAG GCCGUUAGGC CGAA AUACAGGU
7555


607
CCUGUAUU C CCAUCCCA
156
UGGGAUGG CUGAUGAG GCCGUUAGGC CGAA AAUACAGG
7556


612
AUUCCCAU C CCAUCAUC
157
GAUGAUGG CUGAUGAG GCCGUUAGGC CGAA AUGGGAAU
7557


617
CAUCCCAU C AUCUUGGG
158
CCCAAGAU CUGAUGAG GCCGUUAGGC CGAA AUGGGAUG
7558


620
CCCAUCAU C UUGGGCUU
159
AAGCCCAA CUGAUGAG GCCGUUAGGC CGAA AUGAUGGG
7559


622
CAUCAUCU U GGGCUUUC
160
GAAAGCCC CUGAUGAG GCCGUUAGGC CGAA AGAUGAUG
7560


628
CUUGGGCU U UCGCAAAA
161
UUUUGCGA CUGAUGAG GCCGUUAGGC CGAA AGCCCAAG
7561


629
UUGGGCUU U CGCAAAAU
162
AUUUUGCG CUGAUGAG GCCGUUAGGC CGAA AAGCCCAA
7562


630
UGGGCUUU C GCAAAAUA
163
UAUUUUGC CUGAUGAG GCCGUUAGGC CGAA AAAGCCCA
7563


638
CGCAAAAU A CCUAUGGG
164
CCCAUAGG CUGAUGAG GCCGUUAGGC CGAA AUUUUGCG
7564


642
AAAUACCU A UGGGAGUG
165
CACUCCCA CUGAUGAG GCCGUUAGGC CGAA AGGUAUUU
7565


656
GUGGGCCU C AGUCCGUU
166
AACGGACU CUGAUGAG GCCGUUAGGC CGAA AGGCCCAC
7566


660
GCCUCAGU C CGUUUCUC
167
GAGAAACG CUGAUGAG GCCGUUAGGC CGAA ACUGAGGC
7567


664
CAGUCCGU U UCUCUUGG
168
CCAAGAGA CUGAUGAG GCCGUUAGGC CGAA ACGGACUG
7568


665
AGUCCGUU U CUCUUGGC
169
GCCAAGAG CUGAUGAG GCCGUUAGGC CGAA AACGGACU
7569


666
GUCCGUUU C UCUUGGCU
170
AGCCAAGA CUGAUGAG GCCGUUAGGC CGAA AAACGGAC
7570


668
CCGUUUCU C UUGGCUCA
171
UGAGCCAA CUGAUGAG GCCGUUAGGC CGAA AGAAACGG
7571


670
GUUUCUCU U GGCUCAGU
172
ACUGAGCC CUGAUGAG GCCGUUAGGC CGAA AGAGAAAC
7572


675
UCUUGGCU C AGUUUACU
173
AGUAAACU CUGAUGAG GCCGUUAGGC CGAA AGCCAAGA
7573


679
GGCUCAGU U UACUAGUG
174
CACUAGUA CUGAUGAG GCCGUUAGGC CGAA ACUGAGCC
7574


680
GCUCAGUU U ACUAGUGC
175
GCACUAGU CUGAUGAG GCCGUUAGGC CGAA AACUGAGC
7575


681
CUCAGUUU A CUAGUGCC
176
GGCACUAG CUGAUGAG GCCGUUAGGC CGAA AAACUGAG
7576


684
AGUUUACU A GUGCCAUU
177
AAUGGCAC CUGAUGAG GCCGUUAGGC CGAA AGUAAACU
7577


692
AGUGCCAU U UGUUCAGU
178
ACUGAACA CUGAUGAG GCCGUUAGGC CGAA AUGGCACU
7578


693
GUGCCAUU U GUUCAGUG
179
CACUGAAC CUGAUGAG GCCGUUAGGC CGAA AAUGGCAC
7579


696
CCAUUUGU U CAGUGGUU
180
AACCACUG CUGAUGAG GCCGUUAGGC CGAA ACAAAUGG
7580


697
CAUUUGUU C AGUGGUUC
181
GAACCACU CUGAUGAG GCCGUUAGGC CGAA AACAAAUG
7581


704
UCAGUGGU U CGUAGGGC
182
GCCCUACG CUGAUGAG GCCGUUAGGC CGAA ACCACUGA
7582


705
CAGUGGUU C GUAGGGCU
183
AGCCCUAC CUGAUGAG GCCGUUAGGC CGAA AACCACUG
7583


708
UGGUUCGU A GGGCUUUC
184
GAAAGCCC CUGAUGAG GCCGUUAGGC CGAA ACGAACCA
7584


714
GUAGGGCU U UCCCCCAC
185
GUGGGGGA CUGAUGAG GCCGUUAGGC CGAA AGCCCUAC
7585


715
UAGGGCUU U CCCCCACU
186
AGUGGGGG CUGAUGAG GCCGUUAGGC CGAA AAGCCCUA
7586


716
AGGGCUUU C CCCCACUG
187
CAGUGGGG CUGAUGAG GCCGUUAGGC CGAA AAAGCCCU
7587


726
CCCACUGU C UGGCUUUC
188
GAAAGCCA CUGAUGAG GCCGUUAGGC CGAA ACAGUGGG
7588


732
GUCUGGCU U UCAGUUAU
189
AUAACUGA CUGAUGAG GCCGUUAGGC CGAA AGCCAGAC
7589


733
UCUGGCUU U CAGUUAUA
190
UAUAACUG CUGAUGAG GCCGUUAGGC CGAA AAGCCAGA
7590


734
CUGGCUUU C AGUUAUAU
191
AUAUAACU CUGAUGAG GCCGUUAGGC CGAA AAAGCCAG
7591


738
CUUUCAGU U AUAUGGAU
192
AUCCAUAU CUGAUGAG GCCGUUAGGC CGAA ACUGAAAG
7592


739
UUUCAGUU A UAUGGAUG
193
CAUCCAUA CUGAUGAG GCCGUUAGGC CGAA AACUGAAA
7593


741
UCAGUUAU A UGGAUGAU
194
AUCAUCCA CUGAUGAG GCCGUUAGGC CGAA AUAACUGA
7594


755
GAUGUGGU U UUGGGGGC
195
GCCCCCAA CUGAUGAG GCCGUUAGGC CGAA ACCACAUC
7595


756
AUGUGGUU U UGGGGGCC
196
GGCCCCCA CUGAUGAG GCCGUUAGGC CGAA AACCACAU
7596


757
UGUGGUUU U GGGGGCCA
197
UGGCCCCC CUGAUGAG GCCGUUAGGC CGAA AAACCACA
7597


769
GGCCAAGU C UGUACAAC
198
GUUGUACA CUGAUGAG GCCGUUAGGC CGAA ACUUGGCC
7598


773
AAGUCUGU A CAACAUCU
199
AGAUGUUG CUGAUGAG GCCGUUAGGC CGAA ACAGACUU
7599


780
UACAACAU C UUGAGUCC
200
GGACUCAA CUGAUGAG GCCGUUAGGC CGAA AUGUUGUA
7600


782
CAACAUCU U GAGUCCCU
201
AGGGACUC CUGAUGAG GCCGUUAGGC CGAA AGAUGUUG
7601


787
UCUUGAGU C CCUUUAUG
202
CAUAAAGG CUGAUGAG GCCGUUAGGC CGAA ACUCAAGA
7602


791
GAGUCCCU U UAUGCCGC
203
GCGGCAUA CUGAUGAG GCCGUUAGGC CGAA AGGGACUC
7603


792
AGUCCCUU U AUGCCGCU
204
AGCGGCAU CUGAUGAG GCCGUUAGGC CGAA AAGGGACU
7604


793
GUCCCUUU A UGCCGCUG
205
CAGCGGCA CUGAUGAG GCCGUUAGGC CGAA AAAGGGAC
7605


803
GCCGCUGU U ACCAAUUU
206
AAAUUGGU CUGAUGAG GCCGUUAGGC CGAA ACAGCGGC
7606


804
CCGCUGUU A CCAAUUUU
207
AAAAUUGG CUGAUGAG GCCGUUAGGC CGAA AACAGCGG
7607


810
UUACCAAU U UUCUUUUG
208
CAAAAGAA CUGAUGAG GCCGUUAGGC CGAA AUUGGUAA
7608


811
UACCAAUU U UCUUUUGU
209
ACAAAAGA CUGAUGAG GCCGUUAGGC CGAA AAUUGGUA
7609


812
ACCAAUUU U CUUUUGUC
210
GACAAAAG CUGAUGAG GCCGUUAGGC CGAA AAAUUGGU
7610


813
CCAAUUUU C UUUUGUCU
211
AGACAAAA CUGAUGAG GCCGUUAGGC CGAA AAAAUUGG
7611


815
AAUUUUCU U UUGUCUUU
212
AAAGACAA CUGAUGAG GCCGUUAGGC CGAA AGAAAAUU
7612


816
AUUUUCUU U UGUCUUUG
213
CAAAGACA CUGAUGAG GCCGUUAGGC CGAA AAGAAAAU
7613


817
UUUUCUUU U GUCUUUGG
214
CCAAAGAC CUGAUGAG GCCGUUAGGC CGAA AAAGAAAA
7614


820
UCUUUUGU C UUUGGGUA
215
UACCCAAA CUGAUGAG GCCGUUAGGC CGAA ACAAAAGA
7615


822
UUUUGUCU U UGGGUAUA
216
UAUACCCA CUGAUGAG GCCGUUAGGC CGAA AGACAAAA
7616


823
UUUGUCUU U GGGUAUAC
217
GUAUACCC CUGAUGAG GCCGUUAGGC CGAA AAGACAAA
7617


828
CUUUGGGU A UACAUUUA
218
UAAAUGUA CUGAUGAG GCCGUUAGGC CGAA ACCCAAAG
7618


830
UUGGGUAU A CAUUUAAA
219
UUUAAAUG CUGAUGAG GCCGUUAGGC CGAA AUACCCAA
7619


834
GUAUACAU U UAAACCCU
220
AGGGUUUA CUGAUGAG GCCGUUAGGC CGAA AUGUAUAC
7620


835
UAUACAUU U AAACCCUC
221
GAGGGUUU CUGAUGAG GCCGUUAGGC CGAA AAUGUAUA
7621


836
AUACAUUU A AACCCUCA
222
UGAGGGUU CUGAUGAG GCCGUUAGGC CGAA AAAUGUAU
7622


843
UAAACCCU C ACAAAACA
223
UGUUUUGU CUGAUGAG GCCGUUAGGC CGAA AGGGUUUA
7623


865
AUGGGGAU A UUCCCUUA
224
UAAGGGAA CUGAUGAG GCCGUUAGGC CGAA AUCCCCAU
7624


867
GGGGAUAU U CCCUUAAC
225
GUUAAGGG CUGAUGAG GCCGUUAGGC CGAA AUAUCCCC
7625


868
GGGAUAUU C CCUUAACU
226
AGUUAAGG CUGAUGAG GCCGUUAGGC CGAA AAUAUCCC
7626


872
UAUUCCCU U AACUUCAU
227
AUGAAGUU CUGAUGAG GCCGUUAGGC CGAA AGGGAAUA
7627


873
AUUCCCUU A ACUUCAUG
228
CAUGAAGU CUGAUGAG GCCGUUAGGC CGAA AAGGGAAU
7628


877
CCUUAACU U CAUGGGAU
229
AUCCCAUG CUGAUGAG GCCGUUAGGC CGAA AGUUAAGG
7629


878
CUUAACUU C AUGGGAUA
230
UAUCCCAU CUGAUGAG GCCGUUAGGC CGAA AAGUUAAG
7630


886
CAUGGGAU A UGUAAUUG
231
CAAUUACA CUGAUGAG GCCGUUAGGC CGAA AUCCCAUG
7631


890
GGAUAUGU A AUUGGGAG
232
CUCCCAAU CUGAUGAG GCCGUUAGGC CGAA ACAUAUCC
7632


893
UAUGUAAU U GGGAGUUG
233
CAACUCCC CUGAUGAG GCCGUUAGGC CGAA AUUACAUA
7633


900
UUGGGAGU U GGGGCACA
234
UGUGCCCC CUGAUGAG GCCGUUAGGC CGAA ACUCCCAA
7634


910
GGGCACAU U GCCACAGG
235
CCUGUGGC CUGAUGAG GCCGUUAGGC CGAA AUGUGCCC
7635


924
AGGAACAU A UUGUACAA
236
UUGUACAA CUGAUGAG GCCGUUAGGC CGAA AUGUUCCU
7636


926
GAACAUAU U GUACAAAA
237
UUUUGUAC CUGAUGAG GCCGUUAGGC CGAA AUAUGUUC
7637


929
CAUAUUGU A CAAAAAAU
238
AUUUUUUG CUGAUGAG GCCGUUAGGC CGAA ACAAUAUG
7638


938
CAAAAAAU C AAAAUGUG
239
CACAUUUU CUGAUGAG GCCGUUAGGC CGAA AUUUUUUG
7639


948
AAAUGUGU U UUAGGAAA
240
UUUCCUAA CUGAUGAG GCCGUUAGGC CGAA ACACAUUU
7640


949
AAUGUGUU U UAGGAAAC
241
GUUUCCUA CUGAUGAG GCCGUUAGGC CGAA AACACAUU
7641


950
AUGUGUUU U AGGAAACU
242
AGUUUCCU CUGAUGAG GCCGUUAGGC CGAA AAACACAU
7642


951
UGUGUUUU A GGAAACUU
243
AAGUUUCC CUGAUGAG GCCGUUAGGC CGAA AAAACACA
7643


959
AGGAAACU U CCUGUAAA
244
UUUACAGG CUGAUGAG GCCGUUAGGC CGAA AGUUUCCU
7644


960
GGAAACUU C CUGUAAAC
245
GUUUACAG CUGAUGAG GCCGUUAGGC CGAA AAGUUUCC
7645


965
CUUCCUGU A AACAGGCC
246
GGCCUGUU CUGAUGAG GCCGUUAGGC CGAA ACAGGAAG
7646


975
ACAGGCCU A UUGAUUGG
247
CCAAUCAA CUGAUGAG GCCGUUAGGC CGAA AGGCCUGU
7647


977
AGGCCUAU U GAUUGGAA
248
UUCCAAUC CUGAUGAG GCCGUUAGGC CGAA AUAGGCCU
7648


981
CUAUUGAU U GGAAAGUA
249
UACUUUCC CUGAUGAG GCCGUUAGGC CGAA AUCAAUAG
7649


989
UGGAAAGU A UGUCAACG
250
CGUUGACA CUGAUGAG GCCGUUAGGC CGAA ACUUUCCA
7650


993
AAGUAUGU C AACGAAUU
251
AAUUCGUU CUGAUGAG GCCGUUAGGC CGAA ACAUACUU
7651


1001
CAACGAAU U GUGGGUCU
252
AGACCCAC CUGAUGAG GCCGUUAGGC CGAA AUUCGUUG
7652


1008
UUGUGGGU C UUUUGGGG
253
CCCCAAAA CUGAUGAG GCCGUUAGGC CGAA ACCCACAA
7653


1010
GUGGGUCU U UUGGGGUU
254
AACCCCAA CUGAUGAG GCCGUUAGGC CGAA AGACCCAC
7654


1011
UGGGUCUU U UGGGGUUU
255
AAACCCCA CUGAUGAG GCCGUUAGGC CGAA AAGACCCA
7655


1012
GGGUCUUU U GGGGUUUG
256
CAAACCCC CUGAUGAG GCCGUUAGGC CGAA AAAGACCC
7656


1018
UUUGGGGU U UGCCGCCC
257
GGGCGGCA CUGAUGAG GCCGUUAGGC CGAA ACCCCAAA
7657


1019
UUGGGGUU U GCCGCCCC
258
GGGGCGGC CUGAUGAG GCCGUUAGGC CGAA AACCCCAA
7658


1029
CCGCCCCU U UCACGCAA
259
UUGCGUGA CUGAUGAG GCCGUUAGGC CGAA AGGGGCGG
7659


1030
CGCCCCUU U CACGCAAU
260
AUUGCGUG CUGAUGAG GCCGUUAGGC CGAA AAGGGGCG
7660


1031
GCCCCUUU C ACGCAAUG
261
CAUUGCGU CUGAUGAG GCCGUUAGGC CGAA AAAGGGGC
7661


1045
AUGUGGAU A UUCUGCUU
262
AAGCAGAA CUGAUGAG GCCGUUAGGC CGAA AUCCACAU
7662


1047
GUGGAUAU U CUGCUUUA
263
UAAAGCAG CUGAUGAG GCCGUUAGGC CGAA AUAUCCAC
7663


1048
UGGAUAUU C UGCUUUAA
264
UUAAAGCA CUGAUGAG GCCGUUAGGC CGAA AAUAUCCA
7664


1053
AUUCUGCU U UAAUGCCU
265
AGGCAUUA CUGAUGAG GCCGUUAGGC CGAA AGCAGAAU
7665


1054
UUCUGCUU U AAUGCCUU
266
AAGGCAUU CUGAUGAG GCCGUUAGGC CGAA AAGCAGAA
7666


1055
UCUGCUUU A AUGCCUUU
267
AAAGGCAU CUGAUGAG GCCGUUAGGC CGAA AAAGCAGA
7667


1062
UAAUGCCU U UAUAUGCA
268
UGCAUAUA CUGAUGAG GCCGUUAGGC CGAA AGGCAUUA
7668


1063
AAUGCCUU U AUAUGCAU
269
AUGCAUAU CUGAUGAG GCCGUUAGGC CGAA AAGGCAUU
7669


1064
AUGCCUUU A UAUGCAUG
270
CAUGCAUA CUGAUGAG GCCGUUAGGC CGAA AAAGGCAU
7670


1066
GCCUUUAU A UGCAUGCA
271
UGCAUGCA CUGAUGAG GCCGUUAGGC CGAA AUAAAGGC
7671


1076
GCAUGCAU A CAAGCAAA
272
UUUGCUUG CUGAUGAG GCCGUUAGGC CGAA AUGCAUGC
7672


1092
AACAGGCU U UUACUUUC
273
GAAAGUAA CUGAUGAG GCCGUUAGGC CGAA AGCCUGUU
7673


1093
ACAGGCUU U UACUUUCU
274
AGAAAGUA CUGAUGAG GCCGUUAGGC CGAA AAGCCUGU
7674


1094
CAGGCUUU U ACUUUCUC
275
GAGAAAGU CUGAUGAG GCCGUUAGGC CGAA AAAGCCUG
7675


1095
AGGCUUUU A CUUUCUCG
276
CGAGAAAG CUGAUGAG GCCGUUAGGC CGAA AAAAGCCU
7676


1098
CUUUUACU U UCUCGCCA
277
UGGCGAGA CUGAUGAG GCCGUUAGGC CGAA AGUAAAAG
7677


1099
UUUUACUU U CUCGCCAA
278
UUGGCGAG CUGAUGAG GCCGUUAGGC CGAA AAGUAAAA
7678


1100
UUUACUUU C UCGCCAAC
279
GUUGGCGA CUGAUGAG GCCGUUAGGC CGAA AAAGUAAA
7679


1102
UACUUUCU C GCCAACUU
280
AAGUUGGC CUGAUGAG GCCGUUAGGC CGAA AGAAAGUA
7680


1110
CGCCAACU U ACAAGGCC
281
GGCCUUGU CUGAUGAG GCCGUUAGGC CGAA AGUUGGCG
7681


1111
GCCAACUU A CAAGGCCU
282
AGGCCUUG CUGAUGAG GCCGUUAGGC CGAA AAGUUGGC
7682


1120
CAAGGCCU U UCUAAGUA
283
UACUUAGA CUGAUGAG GCCGUUAGGC CGAA AGGCCUUG
7683


1121
AAGGCCUU U CUAAGUAA
284
UUACUUAG CUGAUGAG GCCGUUAGGC CGAA AAGGCCUU
7684


1122
AGGCCUUU C UAAGUAAA
285
UUUACUUA CUGAUGAG GCCGUUAGGC CGAA AAAGGCCU
7685


1124
GCCUUUCU A AGUAAACA
286
UGUUUACU CUGAUGAG GCCGUUAGGC CGAA AGAAAGGC
7686


1128
UUCUAAGU A AACAGUAU
287
AUACUGUU CUGAUGAG GCCGUUAGGC CGAA ACUUAGAA
7687


1135
UAAACAGU A UGUGAACC
288
GGUUCACA CUGAUGAG GCCGUUAGGC CGAA ACUGUUUA
7688


1145
GUGAACCU U UACCCCGU
289
ACGGGGUA CUGAUGAG GCCGUUAGGC CGAA AGGUUCAC
7689


1146
UGAACCUU U ACCCCGUU
290
AACGGGGU CUGAUGAG GCCGUUAGGC CGAA AAGGUUCA
7690


1147
GAACCUUU A CCCCGUUG
291
CAACGGGG CUGAUGAG GCCGUUAGGC CGAA AAAGGUUC
7691


1154
UACCCCGU U GCUCGGCA
292
UGCCGAGC CUGAUGAG GCCGUUAGGC CGAA ACGGGGUA
7692


1158
CCGUUGCU C GGCAACGG
293
CCGUUGCC CUGAUGAG GCCGUUAGGC CGAA AGCAACGG
7693


1173
GGCCUGGU C UAUGCCAA
294
UUGGCAUA CUGAUGAG GCCGUUAGGC CGAA ACCAGGCC
7694


1175
CCUGGUCU A UGCCAAGU
295
ACUUGGCA CUGAUGAG GCCGUUAGGC CGAA AGACCAGG
7695


1186
CCAAGUGU U UGCUGACG
296
CGUCAGCA CUGAUGAG GCCGUUAGGC CGAA ACACUUGG
7696


1187
CAAGUGUU U GCUGACGC
297
GCGUCAGC CUGAUGAG GCCGUUAGGC CGAA AACACUUG
7697


1209
CCACUGGU U GGGGCUUG
298
CAAGCCCC CUGAUGAG GCCGUUAGGC CGAA ACCAGUGG
7698


1216
UUGGGGCU U GGCCAUAG
299
CUAUGGCC CUGAUGAG GCCGUUAGGC CGAA AGCCCCAA
7699


1223
UUGGCCAU A GGCCAUCA
300
UGAUGGCC CUGAUGAG GCCGUUAGGC CGAA AUGGCCAA
7700


1230
UAGGCCAU C AGCGCAUG
301
CAUGCGCU CUGAUGAG GCCGUUAGGC CGAA AUGGCCUA
7701


1249
UGGAACCU U UGUGUCUC
302
GAGACACA CUGAUGAG GCCGUUAGGC CGAA AGGUUCCA
7702


1250
GGAACCUU U GUGUCUCC
303
GGAGACAC CUGAUGAG GCCGUUAGGC CGAA AAGGUUCC
7703


1255
CUUUGUGU C UCCUCUGC
304
GCAGAGGA CUGAUGAG GCCGUUAGGC CGAA ACACAAAG
7704


1257
UUGUGUCU C CUCUGCCG
305
CGGCAGAG CUGAUGAG GCCGUUAGGC CGAA AGACACAA
7705


1260
UGUCUCCU C UGCCGAUC
306
GAUCGGCA CUGAUGAG GCCGUUAGGC CGAA AGGAGACA
7706


1268
CUGCCGAU C CAUACCGC
307
GCGGUAUG CUGAUGAG GCCGUUAGGC CGAA AUCGGCAG
7707


1272
CGAUCCAU A CCGCGGAA
308
UUCCGCGG CUGAUGAG GCCGUUAGGC CGAA AUGGAUCG
7708


1283
GCGGAACU C CUAGCCGC
309
GCGGCUAG CUGAUGAG GCCGUUAGGC CGAA AGUUCCGC
7709


1286
GAACUCCU A GCCGCUUG
310
CAAGCGGC CUGAUGAG GCCGUUAGGC CGAA AGGAGUUC
7710


1293
UAGCCGCU U GUUUUGCU
311
AGCAAAAC CUGAUGAG GCCGUUAGGC CGAA AGCGGCUA
7711


1296
CCGCUUGU U UUGCUCGC
312
GCGAGCAA CUGAUGAG GCCGUUAGGC CGAA ACAAGCGG
7712


1297
CGCUUGUU U UGCUCGCA
313
UGCGAGCA CUGAUGAG GCCGUUAGGC CGAA AACAAGCG
7713


1298
GCUUGUUU U GCUCGCAG
314
CUGCGAGC CUGAUGAG GCCGUUAGGC CGAA AAACAAGC
7714


1302
GUUUUGCU C GCAGCAGG
315
CCUGCUGC CUGAUGAG GCCGUUAGGC CGAA AGCAAAAC
7715


1312
CAGCAGGU C UGGGGCAA
316
UUGCCCCA CUGAUGAG GCCGUUAGGC CGAA ACCUGCUG
7716


1325
GCAAAACU C AUCGGGAC
317
GUCCCGAU CUGAUGAG GCCGUUAGGC CGAA AGUUUUGC
7717


1328
AAACUCAU C GGGACUGA
318
UCAGUCCC CUGAUGAG GCCGUUAGGC CGAA AUGAGUUU
7718


1341
CUGACAAU U CUGUCGUG
319
CACGACAG CUGAUGAG GCCGUUAGGC CGAA AUUGUCAG
7719


1342
UGACAAUU C UGUCGUGC
320
GCACGACA CUGAUGAG GCCGUUAGGC CGAA AAUUGUCA
7720


1346
AAUUCUGU C GUGCUCUC
321
GAGAGCAC CUGAUGAG GCCGUUAGGC CGAA ACAGAAUU
7721


1352
GUCGUGCU C UCCCGCAA
322
UUGCGGGA CUGAUGAG GCCGUUAGGC CGAA AGCACGAC
7722


1354
CGUGCUCU C CCGCAAAU
323
AUUUGCGG CUGAUGAG GCCGUUAGGC CGAA AGAGCACG
7723


1363
CCGCAAAU A UACAUCAU
324
AUGAUGUA CUGAUGAG GCCGUUAGGC CGAA AUUUGCGG
7724


1365
GCAAAUAU A CAUCAUUU
325
AAAUGAUG CUGAUGAG GCCGUUAGGC CGAA AUAUUUGC
7725


1369
AUAUACAU C AUUUCCAU
326
AUGGAAAU CUGAUGAG GCCGUUAGGC CGAA AUGUAUAU
7726


1372
UACAUCAU U UCCAUGGC
327
GCCAUGGA CUGAUGAG GCCGUUAGGC CGAA AUGAUGUA
7727


1373
ACAUCAUU U CCAUGGCU
328
AGCCAUGG CUGAUGAG GCCGUUAGGC CGAA AAUGAUGU
7728


1374
CAUCAUUU C CAUGGCUG
329
CAGCCAUG CUGAUGAG GCCGUUAGGC CGAA AAAUGAUG
7729


1385
UGGCUGCU A GGCUGUGC
330
GCACAGCC CUGAUGAG GCCGUUAGGC CGAA AGCAGCCA
7730


1406
AACUGGAU C CUACGCGG
331
CCGCGUAG CUGAUGAG GCCGUUAGGC CGAA AUCCAGUU
7731


1409
UGGAUCCU A CGCGGGAC
332
GUCCCGCG CUGAUGAG GCCGUUAGGC CGAA AGGAUCCA
7732


1420
CGGGACGU C CUUUGUUU
333
AAACAAAG CUGAUGAG GCCGUUAGGC CGAA ACGUCCCG
7733


1423
GACGUCCU U UGUUUACG
334
CGUAAACA CUGAUGAG GCCGUUAGGC CGAA AGGACGUC
7734


1424
ACGUCCUU U GUUUACGU
335
ACGUAAAC CUCAUGAG GCCGUUAGGC CGAA AAGGACGU
7735


1427
UCCUUUGU U UACGUCCC
336
GGGACGUA CUGAUGAG GCCGUUAGGC CGAA ACAAAGGA
7736


1428
CCUUUGUU U ACGUCCCG
337
CGGGACGU CUGAUGAG GCCGUUAGGC CGAA AACAAAGG
7737


1429
CUUUGUUU A CGUCCCGU
338
ACGGGACG CUGAUGAG GCCGUUAGGC CGAA AAACAAAG
7738


1433
GUUUACGU C CCGUCGGC
339
GCCGACGG CUGAUGAG GCCGUUAGGC CGAA ACGUAAAC
7739


1438
CGUCCCGU C GGCGCUGA
340
UCAGCGCC CUGAUGAG GCCGUUAGGC CGAA ACGGGACG
7740


1449
CGCUGAAU C CCGCGGAC
341
GUCCGCGG CUGAUGAG GCCGUUAGGC CGAA AUUCAGCG
7741


1465
CGACCCCU C CCGGGGCC
342
GGCCCCGG CUGAUGAG GCCGUUAGGC CGAA AGGGGUCG
7742


1477
GGGCCGCU U GGGGCUCU
343
AGAGCCCC CUGAUGAG GCCGUUAGGC CGAA AGCGGCCC
7743


1484
UUGGGGCU C UACCGCCC
344
GGGCGGUA CUGAUGAG GCCGUUAGGC CGAA AGCCCCAA
7744


1486
GGGGCUCU A CCGCCCGC
345
GCGGGCGG CUGAUGAG GCCGUUAGGC CGAA AGAGCCCC
7745


1496
CGCCCGCU U CUCCGCCU
346
AGGCGGAG CUGAUGAG GCCGUUAGGC CGAA AGCGGGCG
7746


1497
GCCCGCUU C UCCGCCUA
347
UAGGCGGA CUGAUGAG GCCGUUAGGC CGAA AAGCGGGC
7747


1499
CCGCUUCU C CGCCUAUU
348
AAUAGGCG CUGAUGAG GCCGUUAGGC CGAA AGAAGCGG
7748


1505
CUCCGCCU A UUGUACCG
349
CGGUACAA CUGAUGAG GCCGUUAGGC CGAA AGGCGGAG
7749


1507
CCGCCUAU U GUACCGAC
350
GUCGGUAC CUGAUGAG GCCGUUAGGC CGAA AUAGGCGG
7750


1510
CCUAUUGU A CCGACCGU
351
ACGGUCGG CUGAUGAG GCCGUUAGGC CGAA ACAAUAGG
7751


1519
CCGACCGU C CACGGGGC
352
GCCCCGUG CUGAUGAG GCCGUUAGGC CGAA ACGGUCGG
7752


1534
GCGCACCU C UCUUUACG
353
CGUAAAGA CUGAUGAG GCCGUUAGGC CGAA AGGUGCGC
7753


1536
GCACCUCU C UUUACGCG
354
CGCGUAAA CUGAUGAG GCCGUUAGGC CGAA AGAGGUGC
7754


1538
ACCUCUCU U UACGCGGA
355
UCCGCGUA CUGAUGAG GCCGUUAGGC CGAA AGAGAGGU
7755


1539
CCUCUCUU U ACGCGGAC
356
GUCCGCGU CUGAUGAG GCCGUUAGGC CGAA AAGAGAGG
7756


1540
CUCUCUUU A CGCGGACU
357
AGUCCGCG CUGAUGAG GCCGUUAGGC CGAA AAAGAGAG
7757


1549
CGCGGACU C CCCGUCUG
358
CAGACGGG CUGAUGAG GCCGUUAGGC CGAA AGUCCGCG
7758


1555
CUCCCCGU C UGUGCCUU
359
AAGGCACA CUGAUGAG GCCGUUAGGC CGAA ACGGGGAG
7759


1563
CUGUGCCU U CUCAUCUG
360
CAGAUGAG CUGAUGAG GCCGUUAGGC CGAA AGGCACAG
7760


1564
UGUGCCUU C UCAUCUGC
361
GCAGAUGA CUGAUGAG GCCGUUAGGC CGAA AAGGCACA
7761


1566
UGCCUUCU C AUCUGCCG
362
CGGCAGAU CUGAUGAG GCCGUUAGGC CGAA AGAAGGCA
7762


1569
CUUCUCAU C UGCCGGAC
363
GUCCGGCA CUGAUGAG GCCGUUAGGC CGAA AUGAGAAG
7763


1588
UGUGCACU U CGCUUCAC
364
GUGAAGCG CUGAUGAG GCCGUUAGGC CGAA AGUGCACA
7764


1589
GUGCACUU C GCUUCACC
365
GGUGAAGC CUGAUGAG GCCGUUAGGC CGAA AAGUGCAC
7765


1593
ACUUCGCU U CACCUCUG
366
CAGAGGUG CUGAUGAG GCCGUUAGGC CGAA AGCGAAGU
7766


1594
CUUCGCUU C ACCUCUGC
367
GCAGAGGU CUGAUGAG GCCGUUAGGC CGAA AAGCGAAG
7767


1599
CUUCACCU C UGCACGUC
368
GACGUGCA CUGAUGAG GCCGUUAGGC CGAA AGGUGAAG
7768


1607
CUGCACGU C GCAUGGAG
369
CUCCAUGC CUGAUGAG GCCGUUAGGC CGAA ACGUGCAG
7769


1651
CCCAAGGU C UUGCAUAA
370
UUAUGCAA CUGAUGAG GCCGUUAGGC CGAA ACCUUGGG
7770


1653
CAAGGUCU U GCAUAAGA
371
UCUUAUGC CUGAUGAG GCCGUUAGGC CGAA AGACCUUG
7771


1658
UCUUGCAU A AGAGGACU
372
AGUCCUCU CUGAUGAG GCCGUUAGGC CGAA AUGCAAGA
7772


1667
AGAGGACU C UUGGACUU
373
AAGUCCAA CUGAUGAG GCCGUUAGGC CGAA AGUCCUCU
7773


1669
AGGACUCU U GGACUUUC
374
GAAAGUCC CUGAUGAG GCCGUUAGGC CGAA AGAGUCCU
7774


1675
CUUGGACU U UCAGCAAU
375
AUUGCUGA CUGAUGAG GCCGUUAGGC CGAA AGUCCAAG
7775


1676
UUGGACUU U CAGCAAUG
376
CAUUGCUG CUGAUGAG GCCGUUAGGC CGAA AAGUCCAA
7776


1677
UGGACUUU C AGCAAUGU
377
ACAUUGCU CUGAUGAG GCCGUUAGGC CGAA AAAGUCCA
7777


1686
AGCAAUGU C AACGACCG
378
CGGUCGUU CUGAUGAG GCCGUUAGGC CGAA ACAUUGCU
7778


1699
ACCGACCU U GAGGCAUA
379
UAUGCCUC CUGAUGAG GCCGUUAGGC CGAA AGGUCGGU
7779


1707
UGAGGCAU A CUUCAAAG
380
CUUUGAAG CUGAUGAG GCCGUUAGGC CGAA AUGCCUCA
7780


1710
GGCAUACU U CAAAGACU
381
AGUCUUUG CUGAUGAG GCCGUUAGGC CGAA AGUAUGCC
7781


1711
GCAUACUU C AAAGACUG
382
CAGUCUUU CUGAUGAG GCCGUUAGGC CGAA AAGUAUGC
7782


1725
CUGUGUGU U UAAUGAGU
383
ACUCAUUA CUGAUGAG GCCGUUAGGC CGAA ACACACAG
7783


1726
UGUGUGUU U AAUGAGUG
384
CACUCAUU CUGAUGAG GCCGUUAGGC CGAA AACACACA
7784


1727
GUGUGUUU A AUGAGUGG
385
CCACUCAU CUGAUGAG GCCGUUAGGC CGAA AAACACAC
7785


1743
GGAGGAGU U GGGGGAGG
386
CCUCCCCC CUGAUGAG GCCGUUAGGC CGAA ACUCCUCC
7786


1756
GAGGAGGU U AGGUUAAA
387
UUUAACCU CUGAUGAG GCCGUUAGGC CGAA ACCUCCUC
7787


1757
AGGAGGUU A GGUUAAAG
388
CUUUAACC CUGAUGAG GCCGUUAGGC CGAA AACCUCCU
7788


1761
GGUUAGGU U AAAGGUCU
389
AGACCUUU CUGAUGAG GCCGUUAGGC CGAA ACCUAACC
7789


1762
GUUAGGUU A AAGGUCUU
390
AAGACCUU CUGAUGAG GCCGUUAGGC CGAA AACCUAAC
7790


1768
UUAAAGGU C UUUGUACU
391
AGUACAAA CUGAUGAG GCCGUUAGGC CGAA ACCUUUAA
7791


1770
AAAGGUCU U UGUACUAG
392
CUAGUACA CUGAUGAG GCCGUUAGGC CGAA AGACCUUU
7792


1771
AAGGUCUU U GUACUAGG
393
CCUAGUAC CUGAUGAG GCCGUUAGGC CGAA AAGACCUU
7793


1774
GUCUUUGU A CUAGGAGG
394
CCUCCUAG CUGAUGAG GCCGUUAGGC CGAA ACAAAGAC
7794


1777
UUUGUACU A GGAGGCUG
395
CAGCCUCC CUGAUGAG GCCGUUAGGC CGAA AGUACAAA
7795


1787
GAGGCUGU A GGCAUAAA
396
UUUAUGCC CUGAUGAG GCCGUUAGGC CGAA ACAGCCUC
7796


1793
GUAGGCAU A AAUUGGUG
397
CACCAAUU CUGAUGAG GCCGUUAGGC CGAA AUGCCUAC
7797


1797
GCAUAAAU U GGUGUGUU
398
AACACACC CUGAUGAG GCCGUUAGGC CGAA AUUUAUGC
7798


1805
UGGUGUGU U CACCAGCA
399
UGCUGGUG CUGAUGAG GCCGUUAGGC CGAA ACACACCA
7799


1806
GGUGUGUU C ACCAGCAC
400
GUGCUGGU CUGAUGAG GCCGUUAGGC CGAA AACACACC
7800


1824
AUGCAACU U UUUCACCU
401
AGGUGAAA CUGAUGAG GCCGUUAGGC CGAA AGUUGCAU
7801


1825
UGCAACUU U UUCACCUC
402
GAGGUGAA CUGAUGAG GCCGUUAGGC CGAA AAGUUGCA
7802


1826
GCAACUUU U UCACCUCU
403
AGAGGUGA CUGAUGAG GCCGUuAGGC CGAA AAAGUUGC
7803


1827
CAACUUUU U CACCUCUG
404
CAGAGGUG CUGAUGAG GCCGUUAGGC CGAA AAAAGUUG
7804


1828
AACUUUUU C ACCUCUGC
405
GCAGAGGU CUGAUGAG GCCGUUAGGC CGAA AAAAAGUU
7805


1833
UUUCACCU C UGCCUAAU
406
AUUAGGCA CUGAUGAG GCCGUUAGGC CGAA AGGUGAAA
7806


1839
CUCUGCCU A AUCAUCUC
407
GAGAUGAU CUGAUGAG GCCGUUAGGC CGAA AGGCAGAG
7807


1842
UGCCUAAU C AUCUCAUG
408
CAUGAGAU CUGAUGAG GCCGUUAGGC CGAA AUUAGGCA
7808


1845
CUAAUCAU C UCAUGUUC
409
GAACAUGA CUGAUGAG GCCGUUAGGC CGAA AUGAUUAG
7809


1847
AAUCAUCU C AUGUUCAU
410
AUGAACAU CUGAUGAG GCCGUUAGGC CGAA AGAUGAUU
7810


1852
UCUCAUGU U CAUGUCCU
411
AGGACAUG CUGAUGAG GCCGUUAGGC CGAA ACAUGAGA
7811


1853
CUCAUGUU C AUGUCCUA
412
UAGGACAU CUGAUGAG GCCGUUAGGC CGAA AACAUGAG
7812


1858
GUUCAUGU C CUACUGUU
413
AACAGUAG CUGAUGAG GCCGUUAGGC CGAA ACAUGAAC
7813


1861
CAUGUCCU A CUGUUCAA
414
UUGAACAG CUGAUGAG GCCGUUAGGC CGAA AGGACAUG
7814


1866
CCUACUGU U CAAGCCUC
415
GAGGCUUG CUGAUGAG GCCGUUAGGC CGAA ACAGUAGG
7815


1867
CUACUGUU C AAGCCUCC
416
GGAGGCUU CUGAUGAG GCCGUUAGGC CGAA AACAGUAG
7816


1874
UCAAGCCU C CAAGCUGU
417
ACAGCUUG CUGAUGAG GCCGUUAGGC CGAA AGGCUUGA
7817


1887
CUGUGCCU U GGGUGGCU
418
AGCCACCC CUGAUGAG GCCGUUAGGC CGAA AGGCACAG
7818


1896
GGGUGGCU U UGGGGCAU
419
AUGCCCCA CUGAUGAG GCCGUUAGGC CGAA AGCCACCC
7819


1897
GGUGGCUU U GGGGCAUG
420
CAUGCCCC CUGAUGAG GCCGUUAGGC CGAA AAGCCACC
7820


1911
AUGGACAU U GACCCGUA
421
UACGGGUC CUGAUGAG GCCGUUAGGC CGAA AUGUCCAU
7821


1919
UGACCCGU A UAAAGAAU
422
AUUCUUUA CUGAUGAG GCCGUUAGGC CGAA ACGGGUCA
7822


1921
ACCCGUAU A AAGAAUUU
423
AAAUUCUU CUGAUGAG GCCGUUAGGC CGAA AUACGGGU
7823


1928
UAAAGAAU U UGGAGCUU
424
AAGCUCCA CUGAUGAG GCCGUUAGGC CGAA AUUCUUUA
7824


1929
AAAGAAUU U GGAGCUUC
425
GAAGCUCC CUGAUGAG GCCGUUAGGC CGAA AAUUCUUU
7825


1936
UUGGAGCU U CUGUGGAG
426
CUCCACAG CUGAUGAG GCCGUUAGGC CGAA AGCUCCAA
7826


1937
UGGAGCUU C UGUGGAGU
427
ACUCCACA CUGAUGAG GCCGUUAGGC CGAA AAGCUCCA
7827


1946
UGUGGAGU U ACUCUCUU
428
AAGAGAGU CUGAUGAG GCCGUUAGGC CGAA ACUCCACA
7828


1947
GUGGAGUU A CUCUCUUU
429
AAAGAGAG CUGAUGAG GCCGUUAGGC CGAA AACUCCAC
7829


1950
GAGUUACU C UCUUUUUU
430
AAAAAAGA CUGAUGAG GCCGUUAGGC CGAA AGUAACUC
7830


1952
GUUACUCU C UUUUUUGC
431
GCAAAAAA CUGAUGAG GCCGUUAGGC CGAA AGAGUAAC
7831


1954
UACUCUCU U UUUUGCCU
432
AGGCAAUU CUGAUGAG GCCGUUAGGC CGAA AGAGAGUA
7832


1955
ACUCUCUU U UUUGCCUU
433
AAGGCAAA CUGAUGAG GCCGUUAGGC CGAA AAGAGAGU
7833


1956
CUCUCUUU U UUGCCUUC
434
GAAGGCAA CUGAUGAG GCCGUUAGGC CGAA AAAGAGAG
7834


1957
UCUCUUUU U UGCCUUCU
435
AGAAGGCA CUGAUGAG GCCGUUAGGC CGAA AAAAGAGA
7835


1958
CUCUUUUU U GCCUUCUG
436
CAGAAGGC CUGAUGAG GCCGUUAGGC CGAA AAAAAGAG
7836


1963
UUUUGCCU U CUGACUUC
437
GAACUCAG CUGAUGAG GCCGUUAGGC CGAA AGGCAAAA
7837


1964
UUUGCCUU C UGACUUCU
438
AGAAGUCA CUGAUGAG GCCGUUAGGC CGAA AAGGCAAA
7838


1970
UUCUGACU U CUUUCCUU
439
AAGGAAAG CUGAUGAG GCCGUUAGGC CGAA AGUCAGAA
7839


1971
UCUGACUU C UUUCCUUC
440
GAAGGAAA CUGAUGAG GCCGUUAGGC CGAA AAGUCAGA
7840


1973
UGACUUCU U UCCUUCUA
441
UAGAAGGA CUGAUGAG GCCGUUAGGC CGAA AGAAGUCA
7841


1974
GACUUCUU U CCUUCUAU
442
AUAGAAGG CUGAUGAG GCCGUUAGGC CGAA AAGAAGUC
7842


1975
ACUUCUUU C CUUCUAUU
443
AAUAGAAG CUGAUGAG GCCGUUAGGC CGAA AAAGAAGU
7843


1978
UCUUUCCU U CUAUUCGA
444
UCGAAUAG CUGAUGAG GCCGUUAGGC CGAA AGGAAAGA
7844


1979
CUUUCCUU C UAUUCGAG
445
CUCGAAUA CUGAUGAG GCCGUUAGGC CGAA AAGGAAAG
7845


1981
UUCCUUCU A UUCGAGAU
446
AUCUCGAA CUGAUGAG GCCGUUAGGC CGAA AGAAGGAA
7846


1983
CCUUCUAU U CGAGAUCU
447
AGAUCUCG CUGAUGAG GCCGUUAGGC CGAA AUAGAAGG
7847


1984
CUUCUAUU C GAGAUCUC
448
GAGAUCUC CUGAUGAG GCCGUUAGGC CGAA AAUAGAAG
7848


1990
UUCGAGAU C UCCUCGAC
449
GUCGAGGA CUGAUGAG GCCGUUAGGC CGAA AUCUCGAA
7849


1992
CGAGAUCU C CUCGACAC
450
GUGUCGAG CUGAUGAG GCCGUUAGGC CGAA AGAUCUCG
7850


1995
GAUCUCCU C GACACCGC
451
GCGGUGUC CUGAUGAG GCCGUUAGGC CGAA AGGAGAUC
7851


2006
CACCGCCU C UGCUCUGU
452
ACAGAGCA CUGAUGAG GCCGUUAGGC CGAA AGGCGGUG
7852


2011
CCUCUGCU C UGUAUCGG
453
CCGAUACA CUGAUGAG GCCGUUAGGC CGAA AGCAGAGG
7853


2015
UGCUCUGU A UCGGGGGG
454
CCCCCCGA CUGAUGAG GCCGUUAGGC CGAA ACAGAGCA
7854


2017
CUCUGUAU C GGGGGGCC
455
GGCCCCCC CUGAUGAG GCCGUUAGGC CGAA AUACAGAG
7855


2027
GGGGGCCU U AGAGUCUC
456
GAGACUCU CUGAUGAG GCCGUUAGGC CGAA AGGCCCCC
7856


2028
GGGGCCUU A GAGUCUCC
457
GGAGACUC CUGAUGAG GCCGUUAGGC CGAA AAGGCCCC
7857


2033
CUUAGAGU C UCCGGAAC
458
GUUCCGGA CUGAUGAG GCCGUUAGGC CGAA ACUCUAAG
7858


2035
UAGAGUCU C CGGAACAU
459
AUGUUCCG CUGAUGAG GCCGUUAGGC CGAA AGACUCUA
7859


2044
CGGAACAU U GUUCACCU
460
AGGUGAAC CUGAUGAG GCCGUUAGGC CGAA AUGUUCCG
7860


2047
AACAUUGU U CACCUCAC
461
GUGAGGUG CUGAUGAG GCCGUUAGGC CGAA ACAAUGUU
7861


2048
ACAUUGUU C ACCUCACC
462
GGUGAGGU CUGAUGAG GCCGUUAGGC CGAA AACAAUGU
7862


2053
GUUCACCU C ACCAUACG
463
CGUAUGGU CUGAUGAG GCCGUUAGGC CGAA AGGUGAAC
7863


2059
CUCACCAU A CGGCACUC
464
GAGUGCCG CUGAUGAG GCCGUUAGGC CGAA AUGGUGAG
7864


2067
ACGGCACU C AGGCAAGC
465
GCUUGCCU CUGAUGAG GCCGUUAGGC CGAA AGUGCCGU
7865


2077
GGCAAGCU A UUCUGUGU
466
ACACAGAA CUGAUGAG GCCGUUAGGC CGAA AGCUUGCC
7866


2079
CAAGCUAU U CUGUGUUG
467
CAACACAG CUGAUGAG GCCGUUAGGC CGAA AUAGCUUG
7867


2080
AAGCUAUU C UGUGUUGG
468
CCAACACA CUGAUGAG GCCGUUAGGC CGAA AAUAGCUU
7868


2086
UUCUGUGU U GGGGUGAG
469
CUCACCCC CUGAUGAG GCCGUUAGGC CGAA UCACAGAA
7869


2096
GGGUGAGU U GAUGAAUC
470
GAUUCAUC CUGAUGAG GCCGUUAGGC CGAA ACUCACCC
7870


2104
UGAUGAAU C UAGCCACC
471
GGUGGCUA CUGAUGAG GCCGUUAGGC CGAA AUUCAUCA
7871


2106
AUGAAUCU A GCCACCUG
472
CAGGUGGC CUGAUGAG GCCGUUAGGC CGAA AGAUUCAU
7872


2125
UGGGAAGU A AUUUGGAA
473
UUCCAAAU CUGAUGAG GCCGUUAGGC CGAA ACUUCCCA
7873


2128
GAAGUAAU U UGGAAGAU
474
AUCUUCCA CUGAUGAG GCCGUUAGGC CGAA AUUACUUC
7874


2129
AAGUAAUU U GGAAGAUC
475
GAUCUUCC CUGAUGAG GCCGUUAGGC CGAA AAUUACUU
7875


2137
UGGAAGAU C CAGCAUCC
476
GGAUGCUG CUGAUGAG GCCGUUAGGC CGAA AUCUUCCA
7876


2144
UCCAGCAU C CAGGGAAU
477
AUUCCCUG CUGAUGAG GCCGUUAGGC CGAA AUGCUGGA
7877


2153
CAGGGAAU U AGUAGUCA
478
UGACUACU CUGAUGAG GCCGUUAGGC CGAA AUUCCCUG
7878


2154
AGGGAAUU A GUAGUCAG
479
CUGACUAC CUGAUGAG GCCGUUAGGC CGAA AAUUCCCU
7879


2157
GAAUUAGU A GUCAGCUA
480
UAGCUGAC CUGAUGAG GCCGUUAGGC CGAA ACUAAUUC
7880


2160
UUAGUAGU C AGCUAUGU
481
ACAUAGCU CUGAUGAG GCCGUUAGGC CGAA ACUACUAA
7881


2165
AGUCAGCU A UGUCAACG
482
CGUUGACA CUGAUGAG GCCGUUAGGC CGAA AGCUGACU
7882


2169
AGCUAUGU C AACGUUAA
483
UUAACGUU CUGAUGAG GCCGUUAGGC CGAA ACAUAGCU
7883


2175
GUCAACGU U AAUAUGGG
484
CCCAUAUU CUGAUGAG GCCGUUAGGC CGAA ACGUUGAC
7884


2176
UCAACGUU A AUAUGGGC
485
GCCCAUAU CUGAUGAG GCCGUUAGGC CGAA AACGUUGA
7885


2179
ACGUUAAU A UGGGCCUA
486
UAGGCCCA CUGAUGAG GCCGUUAGGC CGAA AUUAACGU
7886


2187
AUGGGCCU A AAAAUCAG
487
CUGAUUUU CUGAUGAG GCCGUUAGGC CGAA AGGCCCAU
7887


2193
CUAAAAAU C AGACAACU
488
AGUUGUCU CUGAUGAG GCCGUUAGGC CGAA AUUUUUAG
7888


2202
AGACAACU A UUGUGGUU
489
AACCACAA CUGAUGAG GCCGUUAGGC CGAA AGUUGUCU
7889


2204
ACAACUAU U GUGGUUUC
490
GAAACCAC CUGAUGAG GCCGUUAGGC CGAA AUAGUUGU
7890


2210
AUUGUGGU U UCACAUUU
491
AAAUGUGA CUGAUGAG GCCGUUAGGC CGAA ACCACAAU
7891


2211
UUGUGGUU U CACAUUUC
492
GAAAUGUG CUGAUGAG GCCGUUAGGC CGAA AACCACAA
7892


2212
UGUGGUUU C ACAUUUCC
493
GGAAAUGU CUGAUGAG GCCGUUAGGC CGAA AAACCACA
7893


2217
UUUCACAU U UCCUGUCU
494
AGACAGGA CUGAUGAG GCCGUUAGGC CGAA AUGUGAAA
7894


2218
UUCACAUU U CCUGUCUU
495
AAGACAGG CUGAUGAG GCCGUUAGGC CGAA AAUGUGAA
7895


2219
UCACAUUU C CUGUCUUA
496
UAAGACAG CUGAUGAG GCCGUUAGGC CGAA AAAUGUGA
7896


2224
UUUCCUGU C UUACUUUU
497
AAAGUAAU CUGAUGAG GCCGUUAGGC CGAA ACAGGAAA
7897


2226
UCCUGUCU U ACUUUUGG
498
CCAAAAGU CUGAUGAG GCCGUUAGGC CGAA AGACAGGA
7898


2227
CCUGUCUU A CUUUUGGG
499
CCCAAAAG CUGAUGAG GCCGUUAGGC CGAA AAGACAGG
7899


2230
GUCUUACU U UUGGGCGA
500
UCGCCCAA CUGAUGAG GCCGUUAGGC CGAA AGUAAGAC
7900


2231
UCUUACUU U UGGGCGAG
501
CUCGCCCA CUGAUGAG GCCGUUAGGC CGAA AAGUAAGA
7901


2232
CUUACUUU U GGGCGAGA
502
UCUCGCCC CUGAUGAG GCCGUUAGGC CGAA AAAGUAAG
7902


2247
GAAACUGU U CUUGAAUA
503
UAUUCAAG CUGAUGAG GCCGUUAGGC CGAA ACAGUUUC
7903


2248
AAACUGUU C UUGAAUAU
504
AUAUUCAA CUGAUGAG GCCGUUAGGC CGAA AACAGUUU
7904


2250
ACUGUUCU U GAAUAUUU
505
AAAUAUUC CUGAUGAG GCCGUUAGGC CGAA AGAACAGU
7905


2255
UCUUGAAU A UUUGGUGU
506
ACACCAAA CUGAUGAG GCCGUUAGGC CGAA AUUCAAGA
7906


2257
UUGAAUAU U UGGUGUCU
507
AGACACCA CUGAUGAG GCCGUUAGGC CGAA AUAUUCAA
7907


2258
UGAAUAUU U GGUGUCUU
508
AAGACACC CUGAUGAG GCCGUUAGGC CGAA AAUAUUCA
7908


2264
UUUGGUGU C UUUUGGAG
509
CUCCAAAA CUGAUGAG GCCGUUAGGC CGAA ACACCAAA
7909


2266
UGGUGUCU U UUGGAGUG
510
CACUCCAA CUGAUGAG GCCGUUAGGC CGAA AGACACCA
7910


2267
GGUGUCUU U UGGAGUGU
511
ACACUCCA CUGAUGAG GCCGUUAGGC CGAA AAGACACC
7911


2268
GUGUCUUU U GGAGUGUG
512
CACACUCC CUGAUGAG GCCGUUAGGC CGAA AAAGACAC
7912


2280
GUGUGGAU U CGCACUCC
513
GGAGUGCG CUGAUGAG GCCGUUAGGC CGAA AUCCACAC
7913


2281
UGUGGAUU C GCACUCCU
514
AGGAGUGC CUGAUGAG GCCGUUAGGC CGAA AAUCCACA
7914


2287
UUCGCACU C CUCCUGCA
515
UCCAGGAG CUGAUGAG GCCGUUAGGC CGAA AGUGCGAA
7915


2290
GCACUCCU C CUGCAUAU
516
AUAUGCAG CUGAUGAG GCCGUUAGGC CGAA AGGAGUGC
7916


2297
UCCUGCAU A UAGACCAC
517
GUGGUCUA CUGAUGAG GCCGUUAGGC CGAA AUGCAGGA
7917


2299
CUGCAUAU A GACCACCA
518
UGGUGGUC CUGAUGAG GCCGUUAGGC CGAA AUAUGCAG
7918


2317
AUGCCCCU A UCUUAUCA
519
UGAUAAGA CUGAUGAG GCCGUUAGGC CGAA AGGGGCAU
7919


2319
GCCCCUAU C UUAUCAAC
520
GUUGAUAA CUGAUGAG GCCGUUAGGC CGAA AUAGGGGC
7920


2321
CCCUAUCU U AUCAACAC
521
GUGUUGAU CUGAUGAG GCCGUUAGGC CGAA AGAUAGGG
7921


2322
CCUAUCUU A UCAACACU
522
AGUGUUGA CUGAUGAG GCCGUUAGGC CGAA AAGAUAGG
7922


2324
UAUCUUAU C AACACUUC
523
GAAGUGUU CUGAUGAG GCCGUUAGGC CGAA AUAAGAUA
7923


2331
UCAACACU U CCGGAAAC
524
GUUUCCGG CUGAUGAG GCCGUUAGGC CGAA AGUGUUGA
7924


2332
CAACACUU C CGGAAACU
525
AGUUUCCG CUGAUGAG GCCGUUAGGC CGAA AAGUGUUG
7925


2341
CGGAAACU A CUGUUGUU
526
AACAACAG CUGAUGAG GCCGUUAGGC CGAA AGUUUCCG
7926


2346
ACUACUGU U GUUAGACG
527
CGUCUAAC CUGAUGAG GCCGUUAGGC CGAA ACAGUAGU
7927


2349
ACUGUUGU U AGACGAAG
528
CUUCGUCU CUGAUGAG GCCGUUAGGC CGAA ACAACAGU
7928


2350
CUGUUGUU A GACGAAGA
529
UCUUCGUC CUGAUGAG GCCGUUAGGC CGAA AACAACAG
7929


2366
AGGCAGGU C CCCUAGAA
530
UUCUAGGG CUGAUGAG GCCGUUAGGC CGAA ACCUGCCU
7930


2371
GGUCCCCU A GAAGAAGA
531
UCUUCUUC CUGAUGAG GCCGUUAGGC CGAA AGGGGACC
7931


2383
GAAGAACU C CCUCGCCU
532
AGGCGAGG CUGAUGAG GCCGUUAGGC CGAA AGUUCUUC
7932


2387
AACUCCCU C GCCUCGCA
533
UGCGAGGC CUGAUGAG GCCGUUAGGC CGAA AGGGAGUU
7933


2392
CCUCGCCU C GCAGACGA
534
UCGUCUGC CUGAUGAG GCCGUUAGGC CGAA AGGCGAGG
7934


2405
ACGAAGGU C UCAAUCGC
535
GCGAUUGA CUGAUGAG GCCGUUAGGC CGAA ACCUUCGU
7935


2407
GAAGGUCU C AAUCGCCG
536
CGGCGAUU CUGAUGAG GCCGUUAGGC CGAA AGACCUUC
7936


2411
GUCUCAAU C GCCGCGUC
537
GACGCGGC CUGAUGAG GCCGUUAGGC CGAA AUUGAGAC
7937


2419
CGCCGCGU C GCAGAAGA
538
UCUUCUGC CUGAUGAG GCCGUUAGGC CGAA ACGCGGCG
7938


2429
CAGAAGAU C UCAAUCUC
539
GAGAUUGA CUGAUGAG GCCGUUAGGC CGAA AUCUUCUG
7939


2431
GAAGAUCU C AAUCUCGG
540
CCGAGAUU CUGAUGAG GCCGUUAGGC CGAA AGAUCUUC
7940


2435
AUCUCAAU C UCGGGAAU
541
AUUCCCGA CUGAUGAG GCCGUUAGGC CGAA AUUGAGAU
7941


2437
CUCAAUCU C GGGAAUCU
542
AGAUUCCC CUGAUGAG GCCGUUAGGC CGAA AGAUUGAG
7942


2444
UCGGGAAU C UCAAUGUU
543
AACAUUGA CUGAUGAG GCCGUUAGGC CGAA AUUCCCGA
7943


2446
GGGAAUCU C AAUGUUAG
544
CUAACAUU CUGAUGAG GCCGUUAGGC CGAA AGAUUCCC
7944


2452
CUCAAUGU U AGUAUUCC
545
GGAAUACU CUGAUGAG GCCGUUAGGC CGAA ACAUUGAG
7945


2453
UCAAUGUU A GUAUUCCU
546
AGGAAUAC CUGAUGAG GCCGUUAGGC CGAA AACAUUGA
7946


2456
AUGUUAGU A UUCCUUGG
547
CCAAGGAA CUGAUGAG GCCGUUAGGC CGAA ACUAACAU
7947


2458
GUUAGUAU U CCUUGGAC
548
GUCCAAGG CUGAUGAG GCCGUUAGGC CGAA AUACUAAC
7948


2459
UUAGUAUU C CUUGGACA
549
UGUCCAAG CUGAUGAG GCCGUUAGGC CGAA AAUACUAA
7949


2462
GUAUUCCU U GGACACAU
550
AUGUGUCC CUGAUGAG GCCGUUAGGC CGAA AGGAAUAC
7950


2471
GGACACAU A AGGUGGGA
551
UCCCACCU CUGAUGAG GCCGUUAGGC CGAA AUGUGUCC
7951


2484
GGGAAACU U UACGGGGC
552
GCCCCGUA CUGAUGAG GCCGUUAGGC CGAA AGUUUCCC
7952


2485
GGAAACUU U ACGGGGCU
553
AGCCCCGU CUGAUGAG GCCGUUAGGC CGAA AAGUUUCC
7953


2486
GAAACUUU A CGGGGCUU
554
AAGCCCCG CUGAUGAG GCCGUUAGGC CGAA AAAGUUUC
7954


2494
ACGGGGCU U UAUUCUUC
555
GAAGAAUA CUGAUGAG GCCGUUAGGC CGAA AGCCCCGU
7955


2495
CGGGGCUU U AUUCUUCU
556
AGAAGAAU CUGAUGAG GCCGUUAGGC CGAA AAGCCCCG
7956


2496
GGGGCUUU A UUCUUCUA
557
UAGAAGAA CUGAUGAG GCCGUUAGGC CGAA AAAGCCCC
7957


2498
GGCUUUAU U CUUCUACG
558
CGUAGAAG CUGAUGAG GCCGUUAGGC CGAA AUAAAGCC
7958


2499
GCUUUAUU C UUCUACGG
559
CCGUAGAA CUGAUGAG GCCGUUAGGC CGAA AAUAAAGC
7959


2501
UUUAUUCU U CUACGGUA
560
UACCGUAG CUGAUGAG GCCGUUAGGC CGAA AGAAUAAA
7960


2502
UUAUUCUU C UACGGUAC
561
GUACCGUA CUGAUGAG GCCGUUAGGC CGAA AAGAAUAA
7961


2504
AUUCUUCU A CGGUACCU
562
AGGUACCG CUGAUGAG GCCGUUAGGC CGAA AGAAGAAU
7962


2509
UCUACGGU A CCUUGCUU
563
AAGCAAGG CUGAUGAG GCCGUUAGGC CGAA ACCGUAGA
7963


2513
CGGUACCU U GCUUUAAU
564
AUUAAAGC CUGAUGAG GCCGUUAGGC CGAA AGGUACCG
7964


2517
ACCUUGCU U UAAUCCUA
565
UAGGAUUA CUGAUGAG GCCGUUAGGC CGAA AGCAAGGU
7965


2518
CCUUGCUU U AAUCCUAA
566
UUAGGAUU CUGAUGAG GCCGUUAGGC CGAA AAGCAAGG
7966


2519
CUUGCUUU A AUCCUAAA
567
UUUAGGAU CUGAUGAG GCCGUUAGGC CGAA AAAGCAAG
7967


2522
GCUUUAAU C CUAAAUGG
568
CCAUUUAG CUGAUGAG GCCGUUAGGC CGAA AUUAAAGC
7968


2525
UUAAUCCU A AAUGGCAA
569
UUGCCAUU CUGAUGAG GCCGUUAGGC CGAA AGGAUUAA
7969


2537
GGCAAACU C CUUCUUUU
570
AAAAGAAG CUGAUGAG GCCGUUAGGC CGAA AGUUUGCC
7970


2540
AAACUCCU U CUUUUCCU
571
AGGAAAAG CUGAUGAG GCCGUUAGGC CGAA AGGAGUUU
7971


2541
AACUCCUU C UUUUCCUG
572
CAGGAAAA CUGAUGAG GCCGUUAGGC CGAA AAGGAGUU
7972


2543
CUCCUUCU U UUCCUGAC
573
GUCAGGAA CUGAUGAG GCCGUUAGGC CGAA AGAAGGAG
7973


2544
UCCUUCUU U UCCUGACA
574
UGUCAGGA CUGAUGAG GCCGUUAGGC CGAA AAGAAGGA
7974


2545
CCUUCUUU U CCUGACAU
575
AUGUCAGG CUGAUGAG GCCGUUAGGC CGAA AAAGAAGG
7975


2546
CUUCUUUU C CUGACAUU
576
AAUGUCAG CUGAUGAG GCCGUUAGGC CGAA AAAAGAAG
7976


2554
CCUGACAU U CAUUUGCA
577
UGCAAAUG CUGAUGAG GCCGUUAGGC CGAA AUGUCAGG
7977


2555
CUGACAUU C AUUUGCAG
578
CUGCAAAU CUGAUGAG GCCGUUAGGC CGAA AAUGUCAG
7978


2558
ACAUUCAU U UGCAGGAG
579
CUCCUGCA CUGAUGAG GCCGUUAGGC CGAA AUGAAUGU
7979


2559
CAUUCAUU U GCAGGAGG
580
CCUCCUGC CUGAUGAG GCCGUUAGGC CGAA AAUGAAUG
7980


2572
GAGGACAU U GUUGAUAG
581
CUAUCAAC CUGAUGAG GCCGUUAGGC CGAA AUGUCCUC
7981


2575
GACAUUGU U GAUAGAUG
582
CAUCUAUC CUGAUGAG GCCGUUAGGC CGAA ACAAUGUC
7982


2579
UUGUUGAU A GAUGUAAG
583
CUUACAUC CUGAUGAG GCCGUUAGGC CGAA AUCAACAA
7983


2585
AUAGAUGU A AGCAAUUU
584
AAAUUGCU CUGAUGAG GCCGUUAGGC CGAA ACAUCUAU
7984


2592
UAAGCAAU U UGUGGGGC
585
GCCCCACA CUGAUGAG GCCGUUAGGC CGAA AUUGCUUA
7985


2593
AAGCAAUU U GUGGGGCC
586
GGCCCCAC CUGAUGAG GCCGUUAGGC CGAA AAUUGCUU
7986


2605
GGGCCCCU U ACAGUAAA
587
UUUACUGU CUGAUGAG GCCGUUAGGC CGAA AGGGGCCC
7987


2606
GGCCCCUU A CAGUAAAU
588
AUUUACUG CUGAUGAG GCCGUUAGGC CGAA AAGGGGCC
7988


2611
CUUACAGU A AAUGAAAA
589
UUUUCAUU CUGAUGAG GCCGUUAGGC CGAA ACUGUAAG
7989


2629
AGGAGACU U AAAUUAAC
590
GUUAAUUU CUGAUGAG GCCGUUAGGC CGAA AGUCUCCU
7990


2630
GGAGACUU A AAUUAACU
591
AGUUAAUU CUGAUGAG GCCGUUAGGC CGAA AAGUCUCC
7991


2634
ACUUAAAU U AACUAUGC
592
GCAUAGUU CUGAUGAG GCCGUUAGGC CGAA AUUUAAGU
7992


2635
CUUAAAUU A ACUAUGCC
593
GGCAUAGU CUGAUGAG GCCGUUAGGC CGAA AAUUUAAG
7993


2639
AAUUAACU A UGCCUGCU
594
AGCAGGCA CUGAUGAG GCCGUUAGGC CGAA AGUUAAUU
7994


2648
UGCCUGCU A GGUUUUAU
595
AUAAAACC CUGAUGAG GCCGUUAGGC CGAA AGCAGGCA
7995


2652
UGCUAGGU U UUAUCCCA
596
UGGGAUAA CUGAUGAG GCCGUUAGGC CGAA ACCUAGCA
7996


2653
GCUAGGUU U UAUCCCAA
597
UUGGGAUA CUGAUGAG GCCGUUAGGC CGAA AACCUAGC
7997


2654
CUAGGUUU U AUCCCAAU
598
AUUGGGAU CUGAUGAG GCCGUUAGGC CGAA AAACCUAG
7998


2655
UAGGUUUU A UCCCAAUG
599
CAUUGGGA CUGAUGAG GCCGUUAGGC CGAA AAAACCUA
7999


2657
GGUUUUAU C CCAAUGUU
600
AACAUUGG CUGAUGAG GCCGUUAGGC CGAA AUAAAACC
8000


2665
CCCAAUGU U ACUAAAUA
601
UAUUUAGU CUGAUGAG GCCGUUAGGC CGAA ACAUUGGG
8001


2666
CCAAUGUU A CUAAAUAU
602
AUAUUUAG CUGAUGAG GCCGUUAGGC CGAA AACAUUGG
8002


2669
AUGUUACU A AAUAUUUG
603
CAAAUAUU CUGAUGAG GCCGUUAGGC CGAA AGUAACAU
8003


2673
UACUAAAU A UUUGCCCU
604
AGGGCAAA CUGAUGAG GCCGUUAGGC CGAA AUUUAGUA
8004


2675
CUAAAUAU U UGCCCUUA
605
UAAGGGCA CUGAUGAG GCCGUUAGGC CGAA AUAUUUAG
8005


2676
UAAAUAUU U GCCCUUAG
606
CUAAGGGC CUGAUGAG GCCGUUAGGC CGAA AAUAUUUA
8006


2682
UUUGCCCU U AGAUAAAG
607
CUUUAUCU CUGAUGAG GCCGUUAGGC CGAA AGGGCAAA
8007


2683
UUGCCCUU A GAUAAAGG
608
CCUUUAUC CUGAUGAG GCCGUUAGGC CGAA AAGGGCAA
8008


2687
CCUUAGAU A AAGGGAUC
609
GAUCCCUU CUGAUGAG GCCGUUAGGC CGAA AUCUAAGG
8009


2695
AAAGGGAU C AAACCGUA
610
UACGGUUU CUGAUGAG GCCGUUAGGC CGAA AUCCCUUU
8010


2703
CAAACCGU A UUAUCCAG
611
CUGGAUAA CUGAUGAG GCCGUUAGGC CGAA ACGGUUUG
8011


2705
AACCGUAU U AUCCAGAG
612
CUCUGGAU CUGAUGAG GCCGUUAGGC CGAA AUACGGUU
8012


2706
ACCGUAUU A UCCAGAGU
613
ACUCUGGA CUGAUGAG GCCGUUAGGC CGAA AAUACGGU
8013


2708
CGUAUUAU C CAGAGUAU
614
AUACUCUG CUGAUGAG GCCGUUAGGC CGAA AUAAUACG
8014


2715
UCCAGAGU A UGUAGUUA
615
UAACUACA CUGAUGAG GCCGUUAGGC CGAA ACUCUGGA
8015


2719
GAGUAUGU A GUUAAUCA
616
UGAUUAAC CUGAUGAG GCCGUUAGGC CGAA ACAUACUC
8016


2722
UAUGUAGU U AAUCAUUA
617
UAAUGAUU CUGAUGAG GCCGUUAGGC CGAA ACUACAUA
8017


2723
AUGUAGUU A AUCAUUAC
618
GUAAUGAU CUGAUGAG GCCGUUAGGC CGAA AACUACAU
8018


2726
UAGUUAAU C AUUACUUC
619
GAAGUAAU CUGAUGAG GCCGUUAGGC CGAA AUUAACUA
8019


2729
UUAAUCAU U ACUUCCAG
620
CUGGAAGU CUGAUGAG GCCGUUAGGC CGAA AUGAUUAA
8020


2730
UAAUCAUU A CUUCCAGA
621
UCUGGAAG CUGAUGAG GCCGUUAGGC CGAA AAUGAUUA
8021


2733
UCAUUACU U CCAGACGC
622
GCGUCUGG CUGAUGAG GCCGUUAGGC CGAA AGUAAUGA
8022


2734
CAUUACUU C CAGACGCG
623
CGCGUCUG CUGAUGAG GCCGUUAGGC CGAA AAGUAAUG
8023


2747
CGCGACAU U AUUUACAC
624
GUGUAAAU CUGAUGAG GCCGUUAGGC CGAA AUGUCGCG
8024


2748
GCGACAUU A UUUACACA
625
UGUGUAAA CUGAUGAG GCCGUUAGGC CGAA AAUGUCGC
8025


2750
GACAUUAU U UACACACU
626
AGUGUGUA CUGAUGAG GCCGUUAGGC CGAA AUAAUGUC
8026


2751
ACAUUAUU U ACACACUC
627
GAGUGUGU CUGAUGAG GCCGUUAGGC CGAA AAUAAUGU
8027


2752
CAUUAUUU A CACACUCU
628
AGAGUGUG CUGAUGAG GCCGUUAGGC CGAA AAAUAAUG
8028


2759
UACACACU C UUUGGAAG
629
CUUCCAAA CUGAUGAG GCCGUUAGGC CGAA AGUGUGUA
8029


2761
CACACUCU U UGGAAGGC
630
GCCUUCCA CUGAUGAG GCCGUUAGGC CGAA AGAGUGUG
8030


2762
ACACUCUU U GGAAGGCG
631
CGCCUUCC CUGAUGAG GCCGUUAGGC CGAA AAGAGUGU
8031


2776
GCGGGGAU C UUAUAUAA
632
UUAUAUAA CUGAUGAG GCCGUUAGGC CGAA AUCCCCGC
8032


2778
GGGGAUCU U AUAUAAAA
633
UUUUAUAU CUGAUGAG GCCGUUAGGC CGAA AGAUCCCC
8033


2779
GGGAUCUU A UAUAAAAG
634
CUUUUAUA CUGAUGAG GCCGUUAGGC CGAA AAGAUCCC
8034


2781
GAUCUUAU A UAAAAGAG
635
CUCUUUUA CUGAUGAG GCCGUUAGGC CGAA AUAAGAUC
8035


2783
UCUUAUAU A AAAGAGAG
636
CUCUCUUU CUGAUGAG GCCGUUAGGC CGAA AUAUAAGA
8036


2793
AAGAGAGU C CACACGUA
637
UACGUGUG CUGAUGAG GCCGUUAGGC CGAA ACUCUCUU
8037


2801
CCACACGU A GCGCCUCA
638
UGAGGCGC CUGAUGAG GCCGUUAGGC CGAA ACGUGUGG
8038


2808
UAGCGCCU C AUUUUGCG
639
CGCAAAAU CUGAUGAG GCCGUUAGGC CGAA AGGCGCUA
8039


2811
CGCCUCAU U UUGCGGGU
640
ACCCGCAA CUGAUGAG GCCGUUAGGC CGAA AUGAGGCG
8040


2812
GCCUCAUU U UGCGGGUC
641
GACCCGCA CUGAUGAG GCCGUUAGGC CGAA AAUGAGGC
8041


2813
CCUCAUUU U GCGGGUCA
642
UGACCCGC CUGAUGAG GCCGUUAGGC CGAA AAAUGAGG
8042


2820
UUGCGGGU C ACCAUAUU
643
AAUAUGGU CUGAUGAG GCCGUUAGGC CGAA ACCCGCAA
8043


2826
GUCACCAU A UUCUUGGG
644
CCCAAGAA CUGAUGAG GCCGUUAGGC CGAA AUGGUGAC
8044


2828
CACCAUAU U CUUGGGAA
645
UUCCCAAG CUGAUGAG GCCGUUAGGC CGAA AUAUGGUG
8045


2829
ACCAUAUU C UUGGGAAC
646
GUUCCCAA CUGAUGAG GCCGUUAGGC CGAA AAUAUGGU
8046


2831
CAUAUUCU U GGGAACAA
647
UUGUUCCC CUGAUGAG GCCGUUAGGC CGAA AGAAUAUG
8047


2843
AACAAGAU C UACAGCAU
648
AUGCUGUA CUGAUGAG GCCGUUAGGC CGAA AUCUUGUU
8048


2845
CAAGAUCU A CAGCAUGG
649
CCAUGCUG CUGAUGAG GCCGUUAGGC CGAA AGAUCUUG
8049


2859
UGGGAGGU U GGUCUUCC
650
GGAAGACC CUGAUGAG GCCGUUAGGC CGAA ACCUCCCA
8050


2863
AGGUUGGU C UUCCAAAC
651
GUUUGGAA CUGAUGAG GCCGUUAGGC CGAA ACCAACCU
8051


2865
GUUGGUCU U CCAAACCU
652
AGGUUUGG CUGAUGAG GCCGUUAGGC CGAA AGACCAAC
8052


2866
UUGGUCUU C CAAACCUC
653
GAGGUUUG CUGAUGAG GCCGUUAGGC CGAA AAGACCAA
8053


2874
CCAAACCU C GAAAAGGC
654
GCCUUUUC CUGAUGAG GCCGUUAGGC CGAA AGGUUUGG
8054


2895
GGACAAAU C UUUCUGUC
655
GACAGAAA CUGAUGAG GCCGUUAGGC CGAA AUUUGUCC
8055


2897
ACAAAUCU U UCUGUCCC
656
GGGACAGA CUGAUGAG GCCGUUAGGC CGAA AGAUUUGU
8056


2898
CAAAUCUU U CUGUCCCC
657
GGGGACAG CUGAUGAG GCCGUUAGGC CGAA AAGAUUUG
8057


2899
AAAUCUUU C UGUCCCCA
658
UGGGGACA CUGAUGAG GCCGUUAGGC CGAA AAAGAUUU
8058


2903
CUUUCUGU C CCCAAUCC
659
GGAUUGGG CUGAUGAG GCCGUUAGGC CGAA ACAGAAAG
8059


2910
UCCCCAAU C CCCUGGGA
660
UCCCAGGG CUGAUGAG GCCGUUAGGC CGAA AUUGGGGA
8060


2920
CCUGGGAU U CUUCCCCG
661
CGGGGAAG CUGAUGAG GCCGUUAGGC CGAA AUCCCAGG
8061


2921
CUGGGAUU C UUCCCCGA
662
UCGGGGAA CUGAUGAG GCCGUUAGGC CGAA AAUCCCAG
8062


2923
GGGAUUCU U CCCCGAUC
663
GAUCGGGG CUGAUGAG GCCGUUAGGC CGAA AGAAUCCC
8063


2924
GGAUUCUU C CCCGAUCA
664
UGAUCGGG CUGAUGAG GCCGUUAGGC CGAA AAGAAUCC
8064


2931
UCCCCGAU C AUCAGUUG
665
CAACUGAU CUGAUGAG GCCGUUAGGC CGAA AUCGGGGA
8065


2934
CCGAUCAU C AGUUGGAC
666
GUCCAACU CUGAUGAG GCCGUUAGGC CGAA AUGAUCGG
8066


2938
UCAUCAGU U GGACCCUG
667
CAGGGUCC CUGAUGAG GCCGUUAGGC CGAA ACUGAUGA
8067


2950
CCCUGCAU U CAAAGCCA
668
UGGCUUUG CUGAUGAG GCCGUUAGGC CGAA AUGCAGGG
8068


2951
CCUGCAUU C AAAGCCAA
669
UUGGCUUU CUGAUGAG GCCGUUAGGC CGAA AAUGCAGG
8069


2962
AGCCAACU C AGUAAAUC
670
GAUUUACU CUGAUGAG GCCGUUAGGC CGAA AGUUGGCU
8070


2966
AACUCAGU A AAUCCAGA
671
UCUGGAUU CUGAUGAG GCCGUUAGGC CGAA ACUGAGUU
8071


2970
CAGUAAAU C CAGAUUGG
672
CCAAUCUG CUGAUGAG GCCGUUAGGC CGAA AUUUACUG
8072


2976
AUCCAGAU U GGGACCUC
673
GAGGUCCC CUGAUGAG GCCGUUAGGC CGAA AUCUGGAU
8073


2984
UGGGACCU C AACCCGCA
674
UGCGGGUU CUGAUGAG GCCGUUAGGC CGAA AGGUCCCA
8074


3037
GGGAGCAU U CGGGCCAG
675
CUGGCCCG CUGAUGAG GCCGUUAGGC CGAA AUGCUCCC
8075


3038
GGAGCAUU C GGGCCAGG
676
CCUGGCCC CUGAUGAG GCCGUUAGGC CGAA AAUGCUCC
8076


3049
GCCAGGGU U CACCCCUC
677
GAGGGGUG CUGAUGAG GCCGUUAGGC CGAA ACCCUGGC
8077


3050
CCAGGGUU C ACCCCUCC
678
GGAGGGGU CUGAUGAG GCCGUUAGGC CGAA AACCCUGG
8078


3057
UCACCCCU C CCCAUGGG
679
CCCAUGGG CUGAUGAG GCCGUUAGGC CGAA AGGGGUGA
8079


3073
GGGACUGU U GGGGUGGA
680
UCCACCCC CUGAUGAG GCCGUUAGGC CGAA ACAGUCCC
8080


3087
GGAGCCCU C ACGCUCAG
681
CUGAGCGU CUGAUGAG GCCGUUAGGC CGAA AGGGCUCC
8081


3093
CUCACGCU C AGGGCCUA
682
UAGGCCCU CUGAUGAG GCCGUUAGGC CGAA AGCGUGAG
8082


3101
CAGGGCCU A CUCACAAC
683
GUUGUGAG CUGAUGAG GCCGUUAGGC CGAA AGGCCCUG
8083


3104
GGCCUACU C ACAACUGU
684
ACAGUUGU CUGAUGAG GCCGUUAGGC CGAA AGUAGGCC
8084


3123
CAGCAGCU C CUCCUCCU
685
AGGAGGAG CUGAUGAG GCCGUUAGGC CGAA AGCUGCUG
8085


3126
CAGCUCCU C CUCCUGCC
686
GGCAGGAG CUGAUGAG GCCGUUAGGC CGAA AGGAGCUG
8086


3129
CUCCUCCU C CUGCCUCC
687
GGAGGCAG CUGAUGAG GCCGUUAGGC CGAA AGGAGGAG
8087


3136
UCCUGCCU C CACCAAUC
688
GAUUGGUG CUGAUGAG GCCGUUAGGC CGAA AGGCAGGA
8088


3144
CCACCAAU C GGCAGUCA
689
UGACUGCC CUGAUGAG GCCGUUAGGC CGAA AUUGGUGG
8089


3151
UCGGCAGU C AGGAAGGC
690
GCCUUCCU CUGAUGAG GCCGUUAGGC CGAA ACUGCCGA
8090


3165
GGCAGCCU A CUCCCUUA
691
UAAGGGAG CUGAUGAG GCCGUUAGGC CGAA AGGCUGCC
8091


3168
AGCCUACU C CCUUAUCU
692
AGAUAAGG CUGAUGAG GCCGUUAGGC CGAA AGUAGGCU
8092


3172
UACUCCCU U AUCUCCAC
693
GUGGAGAU CUGAUGAG GCCGUUAGGC CGAA AGGGAGUA
8093


3173
ACUCCCUU A UCUCCACC
694
GGUGGAGA CUGAUGAG GCCGUUAGGC CGAA AAGGGAGU
8094


3175
UCCCUUAU C UCCACCUC
695
GAGGUGGA CUGAUGAG GCCGUUAGGC CGAA AUAAGGGA
8095


3177
CCUUAUCU C CACCUCUA
696
UAGAGGUG CUGAUGAG GCCGUUAGGC CGAA AGAUAAGG
8096


3183
CUCCACCU C UAAGGGAC
697
GUCCCUUA CUGAUGAG GCCGUUAGGC CGAA AGGUGGAG
8097


3185
CCACCUCU A AGGGACAC
698
GUGUCCCU CUGAUGAG GCCGUUAGGC CGAA AGAGGUGG
8098


3195
GGGACACU C AUCCUCAG
699
CUGAGGAU CUGAUGAG GCCGUUAGGC CGAA AGUGUCCC
8099


3198
ACACUCAU C CUCAGGCC
700
GGCCUGAG CUGAUGAG GCCGUUAGGC CGAA AUGAGUGU
8100


3201
CUCAUCCU C AGGCCAUG
701
CAUGGCCU CUGAUGAG GCCGUUAGGC CGAA AGGAUGAG
8101






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.








[0554]

6






TABLE VI










HUMAN HBV INOZYME AND SUBSTRATE SEQUENCE












Pos
Substrate
Seq ID
Inozyme
Seq ID















9
AACUCCAC C ACUUUCCA
702
UGGAAAGU CUGAUGAG GCCGUUAGGC CGAA IUGGAGUU
8102



10
ACUCCACC A CUUUCCAC
703
GUGGAAAG CUGAUGAG GCCGUUAGGC CGAA IGUGGAGU
8103


12
UCCACCAC U UUCCACCA
704
UGGUGGAA CUGAUGAG GCCGUUAGGC CGAA IUGGUGGA
8104


16
CCACUUUC C ACCAAACU
705
AGUUUGGU CUGAUGAG GCCGUUAGGC CGAA IAAAGUGG
8105


17
CACUUUCC A CCAAACUC
706
GAGUUUGG CUGAUGAG GCCGUUAGGC CGAA IGAAAGUG
8106


19
CUUUCCAC C AAACUCUU
707
AAGAGUUU CUGAUGAG GCCGUUAGGC CGAA IUGGAAAG
8107


20
UUUCCACC A AACUCUUC
708
GAAGAGUU CUGAUGAG GCCGUUAGGC CGAA IGUGGAAA
8108


24
CACCAAAC U CUUCAAGA
709
UCUUGAAG CUGAUGAG GCCGUUAGGC CGAA IUUUGGUG
8109


26
CCAAACUC U UCAAGAUC
710
GAUCUUGA CUGAUGAG GCCGUUAGGC CGAA IAGUUUGG
8110


29
AACUCUUC A AGAUCCCA
711
UGGGAUCU CUGAUGAG GCCGUUAGGC CGAA IAAGAGUU
8111


35
UCAAGAUC C CAGAGUCA
712
UGACUCUG CUGAUGAG GCCGUUAGGC CGAA IAUCUUGA
8112


36
CAAGAUCC C AGAGUCAG
713
CUGACUCU CUGAUGAG GCCGUUAGGC CGAA IGAUCUUG
8113


37
AAGAUCCC A GAGUCAGG
714
CCUGACUC CUGAUGAG GCCGUUAGGC CGAA IGGAUCUU
8114


43
CCAGAGUC A GGGCCCUG
715
CAGGGCCC CUGAUGAG GCCGUUAGGC CGAA IACUCUGG
8115


48
GUCAGGGC C CUGUACUU
716
AAGUACAG CUGAUGAG GCCGUUAGGC CGAA ICCCUGAC
8116


49
UCAGGGCC C UGUACUUU
717
AAAGUACA CUGAUGAG GCCGUUAGGC CGAA IGCCCUGA
8117


50
CAGGGCCC U GUACUUUC
718
GAAAGUAC CUGAUGAG GCCGUUAGGC CGAA IGGCCCUG
8118


55
CCCUGUAC U UUCCUGCU
719
AGCAGGAA CUGAUGAG GCCGUUAGGC CGAA IUACAGGG
8119


59
GUACUUUC C UGCUGGUG
720
CACCAGCA CUGAUGAG GCCGUUAGGC CGAA IAAAGUAC
8120


60
UACUUUCC U GCUGGUGG
721
CCACCAGC CUGAUGAG GCCGUUAGGC CGAA IGAAAGUA
8121


63
UUUCCUGC U GGUGGCUC
722
GAGCCACC CUGAUGAG GCCGUUAGGC CGAA ICAGGAAA
8122


70
CUGGUGGC U CCAGUUCA
723
UGAACUGG CUGAUGAG GCCGUUAGGC CGAA ICCACCAG
8123


72
GGUGGCUC C AGUUCAGG
724
CCUGAACU CUGAUGAG GCCGUUAGGC CGAA IAGCCACC
8124


73
GUGGCUCC A GUUCAGGA
725
UCCUGAAC CUGAUGAG GCCGUUAGGC CGAA IGAGCCAC
8125


78
UCCAGUUC A GGAACAGU
726
ACUGUUCC CUGAUGAG GCCGUUAGGC CGAA IAACUGGA
8126


84
UCAGGAAC A GUGAGCCC
727
GGGCUCAC CUGAUGAG GCCGUUAGGC CGAA IUUCCUGA
8127


91
CAGUGAGC C CUGCUCAG
728
CUGAGCAG CUGAUGAG GCCGUUAGGC CGAA ICUCACUG
8128


92
AGUGAGCC C UGCUCAGA
729
UCUGAGCA CUGAUGAG GCCGUUAGGC CGAA IGCUCACU
8129


93
GUGAGCCC U GCUCAGAA
730
UUCUGAGC CUGAUGAG GCCGUUAGGC CGAA IGGCUCAC
8130


96
AGCCCUGC U CAGAAUAC
731
GUAUUCUG CUGAUGAG GCCGUUAGGC CGAA ICAGGGCU
8131


98
CCCUGCUC A GAAUACUG
732
CAGUAUUC CUGAUGAG GCCGUUAGGC CGAA IAGCAGGG
8132


105
CAGAAUAC U GUCUCUGC
733
GCAGAGAC CUGAUGAG GCCGUUAGGC CGAA IUAUUCUG
8133


109
AUACUGUC U CUGCCAUA
734
UAUGGCAG CUGAUGAG GCCGUUAGGC CGAA IACAGUAU
8134


111
ACUGUCUC U GCCAUAUC
735
GAUAUGGC CUGAUGAG GCCGUUAGGC CGAA IAGACAGU
8135


114
GUCUCUGC C AUAUCGUC
736
GACGAUAU CUGAUGAG GCCGUUAGGC CGAA ICAGAGAC
8136


115
UCUCUGCC A UAUCGUCA
737
UGACGAUA CUGAUGAG GCCGUUAGGC CGAA IGCAGAGA
8137


123
AUAUCGUC A AUCUUAUC
738
GAUAAGAU CUGAUGAG GCCGUUAGGC CGAA IACGAUAU
8138


127
CGUCAAUC U UAUCGAAG
739
CUUCGAUA CUGAUGAG GCCGUUAGGC CGAA IAUUGACG
8139


138
UCGAAGAC U GGGGACCC
740
GGGUCCCC CUGAUGAG GCCGUUAGGC CGAA IUCUUCGA
8140


145
CUGGGGAC C CUGUACCG
741
CGGUACAG CUGAUGAG GCCGUUAGGC CGAA IUCCCCAG
8141


146
UGGGGACC C UGUACCGA
742
UCGGUACA CUGAUGAG GCCGUUAGGC CGAA IGUCCCCA
8142


147
GGGGACCC U GUACCGAA
743
UUCGGUAC CUGAUGAG GCCGUUAGGC CGAA IGGUCCCC
8143


152
CCCUGUAC C GAACAUGG
744
CCAUGUUC CUGAUGAG GCCGUUAGGC CGAA IUACAGGG
8144


157
UACCGAAC A UGGAGAAC
745
GUUCUCCA CUGAUGAG GCCGUUAGGC CGAA IUUCGGUA
8145


166
UGGAGAAC A UCGCAUCA
746
UGAUGCGA CUGAUGAG GCCGUUAGGC CGAA IUUCUCCA
8146


171
AACAUCGC A UCAGGACU
747
AGUCCUGA CUGAUGAG GCCGUUAGGC CGAA ICGAUGUU
8147


174
AUCGCAUC A GGACUCCU
748
AGGAGUCC CUGAUGAG GCCGUUAGGC CGAA IAUGCGAU
8148


179
AUCAGGAC U CCUAGGAC
749
GUCCUAGG CUGAUGAG GCCGUUAGGC CGAA IUCCUGAU
8149


181
CAGGACUC C UAGGACCC
750
GGGUCCUA CUGAUGAG GCCGUUAGGC CGAA IAGUCCUG
8150


182
AGGACUCC U AGGACCCC
751
GGGGUCCU CUGAUGAG GCCGUUAGGC CGAA IGAGUCCU
8151


188
CCUAGGAC C CCUGCUCG
752
CGAGCAGG CUGAUGAG GCCGUUAGGC CGAA IUCCUAGG
8152


189
CUAGGACC C CUGCUCGU
753
ACGAGCAG CUGAUGAG GCCGUUAGGC CGAA IGUCCUAG
8153


190
UAGGACCC C UGCUCGUG
754
CACGAGCA CUGAUGAG GCCGUUAGGC CGAA IGGUCCUA
8154


191
AGGACCCC U GCUCGUGU
755
ACACGAGC CUGAUGAG GCCGUUAGGC CGAA IGGGUCCU
8155


194
ACCCCUGC U CGUGUUAC
756
GUAACACG CUGAUGAG GCCGUUAGGC CGAA ICAGGGGU
8156


203
CGUGUUAC A GGCGGGGU
757
ACCCCGCC CUGAUGAG GCCGUUAGGC CGAA IUAACACG
8157


217
GGUUUUUC U UGUUGACA
758
UGUCAACA CUGAUGAG GCCGUUAGGC CGAA IAAAAACC
8158


225
UUGUUGAC A AAAAUCCU
759
AGGAUUUU CUGAUGAG GCCGUUAGGC CGAA IUCAACAA
8159


232
CAAAAAUC C UCACAAUA
760
UAUUGUGA CUGAUGAG GCCGUUAGGC CGAA IAUUUUUG
8160


233
AAAAAUCC U CACAAUAC
761
GUAUUGUG CUGAUGAG GCCGUUAGGC CGAA IGAUUUUU
8161


235
AAAUCCUC A CAAUACCA
762
UGGUAUUG CUGAUGAG GCCGUUAGGC CGAA IAGGAUUU
8162


237
AUCCUCAC A AUACCACA
763
UGUGGUAU CUGAUGAG GCCGUUAGGC CGAA IUGAGGAU
8163


242
CACAAUAC C ACAGAGUC
764
GACUCUGU CUGAUGAG GCCGUUAGGC CGAA IUAUUGUG
8164


243
ACAAUACC A CAGAGUCU
765
AGACUCUG CUGAUGAG GCCGUUAGGC CGAA IGUAUUGU
8165


245
AAUACCAC A GAGUCUAG
766
CUAGACUC CUGAUGAG GCCGUUAGGC CGAA IUGGUAUU
8166


251
ACAGAGUC U AGACUCGU
767
ACGAGUCU CUGAUGAG GCCGUUAGGC CGAA IACUCUGU
8167


256
GUCUAGAC U CGUGGUGG
768
CCACCACG CUGAUGAG GCCGUUAGGC CGAA IUCUAGAC
8168


267
UGGUGGAC U UCUCUCAA
769
UUGAGAGA CUGAUGAG GCCGUUAGGC CGAA IUCCACCA
8169


270
UGGACUUC U CUCAAUUU
770
AAAUUGAG CUGAUGAG GCCGUUAGGC CGAA IAAGUCCA
8170


272
GACUUCUC U CAAUUUUC
771
GAAAAUUG CUGAUGAG GCCGUUAGGC CGAA IAGAAGUC
8171


274
CUUCUCUC A AUUUUCUA
772
UAGAAAAU CUGAUGAG GCCGUUAGGC CGAA IAGAGAAG
8172


281
CAAUUUUC U AGGGGGAA
773
UUCCCCCU CUGAUGAG GCCGUUAGGC CGAA IAAAAUUG
8173


291
GGGGGAAC A CCCGUGUG
774
CACACGGG CUGAUGAG GCCGUUAGGC CGAA IUUCCCCC
8174


293
GGGAACAC C CGUGUGUC
775
GACACACG CUGAUGAG GCCGUUAGGC CGAA IUGUUCCC
8175


294
GGAACACC C GUGUGUCU
776
AGACACAC CUGAUGAG GCCGUUAGGC CGAA IGUGUUCC
8176


302
CGUGUGUC U UGGCCAAA
777
UUUGGCCA CUGAUGAG GCCGUUAGGC CGAA IACACACG
8177


307
GUCUUGGC C AAAAUUCG
778
CGAAUUUU CUGAUGAG GCCGUUAGGC CGAA ICCAAGAC
8178


308
UCUUGGCC A AAAUUCGC
779
GCGAAUUU CUGAUGAG GCCGUUAGGC CGAA IGCCAAGA
8179


317
AAAUUCGC A GUCCCAAA
780
UUUGGGAC CUGAUGAG GCCGUUAGGC CGAA ICGAAUUU
8180


321
UCGCAGUC C CAAAUCUC
781
GAGAUUUG CUGAUGAG GCCGUUAGGC CGAA IACUGCGA
8181


322
CGCAGUCC C AAAUCUCC
782
GGAGAUUU CUGAUGAG GCCGUUAGGC CGAA IGACUGCG
8182


323
GCAGUCCC A AAUCUCCA
783
UGGAGAUU CUGAUGAG GCCGUUAGGC CGAA IGGACUGC
8183


328
CCCAAAUC U CCAGUCAC
784
GUGACUGG CUGAUGAG GCCGUUAGGC CGAA IAUUUGGG
8184


330
CAAAUCUC C AGUCACUC
785
GAGUGACU CUGAUGAG GCCGUUAGGC CGAA IAGAUUUG
8185


331
AAAUCUCC A GUCACUCA
786
UGAGUGAC CUGAUGAG GCCGUUAGGC CGAA IGAGAUUU
8186


335
CUCCAGUC A CUCACCAA
787
UUGGUGAG CUGAUGAG GCCGUUAGGC CGAA IACUGGAG
8187


337
CCAGUCAC U CACCAACC
788
GGUUGGUG CUGAUGAG GCCGUUAGGC CGAA IUGACUGG
8188


339
AGUCACUC A CCAACCUG
789
CAGGUUGG CUGAUGAG GCCGUUAGGC CGAA IAGUGACU
8189


341
UCACUCAC C AACCUGUU
790
AACAGGUU CUGAUGAG GCCGUUAGGC CGAA IUGAGUGA
8190


342
CACUCACC A ACCUGUUG
791
CAACAGGU CUGAUGAG GCCGUUAGGC CGAA IGUGAGUG
8191


345
UCACCAAC C UGUUGUCC
792
GGACAACA CUGAUGAG GCCGUUAGGC CGAA IUUGGUGA
8192


346
CACCAACC U GUUGUCCU
793
AGGACAAC CUGAUGAG GCCGUUAGGC CGAA IGUUGGUG
8193


353
CUGUUGUC C UCCAAUUU
794
AAAUUGGA CUGAUGAG GCCGUUAGGC CGAA IACAACAG
8194


354
UGUUGUCC U CCAAUUUG
795
CAAAUUGG CUGAUGAG GCCGUUAGGC CGAA IGACAACA
8195


356
UUGUCCUC C AAUUUGUC
796
GACAAAUU CUGAUGAG GCCGUUAGGC CGAA IAGGACAA
8196


357
UGUCCUCC A AUUUGUCC
797
GGACAAAU CUGAUGAG GCCGUUAGGC CGAA IGAGGACA
8197


365
AAUUUGUC C UGGUUAUC
798
GAUAACCA CUGAUGAG GCCGUUAGGC CGAA IACAAAUU
8198


366
AUUUGUCC U GGUUAUCG
799
CGAUAACC CUGAUGAG GCCGUUAGGC CGAA IGACAAAU
8199


376
GUUAUCGC U GGAUGUGU
800
ACACAUCC CUGAUGAG GCCGUUAGGC CGAA ICGAUAAC
8200


386
GAUGUGUC U GCGGCGUU
801
AACGCCGC CUGAUGAG GCCGUUAGGC CGAA IACACAUC
8201


400
GUUUUAUC A UCUUCCUC
802
GAGGAAGA CUGAUGAG GCCGUUAGGC CGAA IAUAAAAC
8202


403
UUAUCAUC U UCCUCUGC
803
GCAGAGGA CUGAUGAG GCCGUUAGGC CGAA IAUGAUAA
8203


406
UCAUCUUC C UCUGCAUC
804
GAUGCAGA CUGAUGAG GCCGUUAGGC CGAA IAAGAUGA
8204


407
CAUCUUCC U CUGCAUCC
805
GGAUGCAG CUGAUGAG GCCGUUAGGC CGAA IGAAGAUG
8205


409
UCUUCCUC U GCAUCCUG
806
CAGGAUGC CUGAUGAG GCCGUUAGGC CGAA IAGGAAGA
8206


412
UCCUCUGC A UCCUGCUG
807
CAGCAGGA CUGAUGAG GCCGUUAGGC CGAA ICAGAGGA
8207


415
UCUGCAUC C UGCUGCUA
808
UAGCAGCA CUGAUGAG GCCGUUAGGC CGAA IAUGCAGA
8208


416
CUGCAUCC U GCUGCUAU
809
AUAGCAGC CUGAUGAG GCCGUUAGGC CGAA IGAUGCAG
8209


419
CAUCCUGC U GCUAUGCC
810
GGCAUAGC CUGAUGAG GCCGUUAGGC CGAA ICAGGAUG
8210


422
CCUGCUGC U AUGCCUCA
811
UGAGGCAU CUGAUGAG GCCGUUAGGC CGAA ICAGCAGG
8211


427
UGCUAUGC C UCAUCUUC
812
GAAGAUGA CUGAUGAG GCCGUUAGGC CGAA ICAUAGCA
8212


428
GCUAUGCC U CAUCUUCU
813
AGAAGAUG CUGAUGAG GCCGUUAGGC CGAA IGCAUAGC
8213


430
UAUGCCUC A UCUUCUUG
814
CAAGAAGA CUGAUGAG GCCGUUAGGC CGAA IAGGCAUA
8214


433
GCCUCAUC U UCUUGUUG
815
CAACAAGA CUGAUGAG GCCGUUAGGC CGAA IAUGAGGC
8215


436
UCAUCUUC U UGUUGGUU
816
AACCAACA CUGAUGAG GCCGUUAGGC CGAA IAAGAUGA
8216


446
GUUGGUUC U UCUGGACU
817
AGUCCAGA CUGAUGAG GCCGUUAGGC CGAA IAACCAAC
8217


449
GGUUCUUC U GGACUAUC
818
GAUAGUCC CUGAUGAG GCCGUUAGGC CGAA IAAGAACC
8218


454
UUCUGGAC U AUCAAGGU
819
ACCUUGAU CUGAUGAG GCCGUUAGGC CGAA IUCCAGAA
8219


458
GGACUAUC A AGGUAUGU
820
ACAUACCU CUGAUGAG GCCGUUAGGC CGAA IAUAGUCC
8220


470
UAUGUUGC C CGUUUGUC
821
GACAAACG CUGAUGAG GCCGUUAGGC CGAA ICAACAUA
8221


471
AUGUUGCC C GUUUGUCC
822
GGACAAAC CUGAUGAG GCCGUUAGGC CGAA IGCAACAU
8222


479
CGUUUGUC C UCUAAUUC
823
GAAUUAGA CUGAUGAG GCCGUUAGGC CGAA IACAAACG
8223


480
GUUUGUCC U CUAAUUCC
824
GGAAUUAG CUGAUGAG GCCGUUAGGC CGAA IGACAAAC
8224


482
UUGUCCUC U AAUUCCAG
825
CUGGAAUU CUGAUGAG GCCGUUAGGC CGAA IAGGACAA
8225


488
UCUAAUUC C AGGAUCAU
826
AUGAUCCU CUGAUGAG GCCGUUAGGC CGAA IAAUUAGA
8226


489
CUAAUUCC A GGAUCAUC
827
GAUGAUCC CUGAUGAG GCCGUUAGGC CGAA IGAAUUAG
8227


495
CCAGGAUC A UCAACAAC
828
GUUGUUGA CUGAUGAG GCCGUUAGGC CGAA IAUCCUGG
8228


498
GGAUCAUC A ACAACCAG
829
CUGGUUGU CUGAUGAG GCCGUUAGGC CGAA IAUGAUCC
8229


501
UCAUCAAC A ACCAGCAC
830
GUGCUGGU CUGAUGAG GCCGUUAGGC CGAA IUUGAUGA
8230


504
UCAACAAC C AGCACCGG
831
CCGGUGCU CUGAUGAG GCCGUUAGGC CGAA IUUGUUGA
8231


505
CAACAACC A GCACCGGA
832
UCCGGUGC CUGAUGAG GCCGUUAGGC CGAA IGUUGUUG
8232


508
CAACCAGC A CCGGACCA
833
UGGUCCGG CUGAUGAG GCCGUUAGGC CGAA ICUGGUUG
8233


510
ACCAGCAC C GGACCAUG
834
CAUGGUCC CUGAUGAG GCCGUUAGGC CGAA IUGCUGGU
8234


515
CACCGGAC C AUGCAAAA
835
UUUUGCAU CUGAUGAG GCCGUUAGGC CGAA IUCCGGUG
8235


516
ACCGGACC A UGCAAAAC
836
GUUUUGCA CUGAUGAG GCCGUUAGGC CGAA IGUCCGGU
8236


520
GACCAUGC A AAACCUGC
837
GCAGGUUU CUGAUGAG GCCGUUAGGC CGAA ICAUGGUC
8237


525
UGCAAAAC C UGCACAAC
838
GUUGUGCA CUGAUGAG GCCGUUAGGC CGAA IUUUUGCA
8238


526
GCAAAACC U GCACAACU
839
AGUUGUGC CUGAUGAG GCCGUUAGGC CGAA IGUUUUGC
8239


529
AAACCUGC A CAACUCCU
840
AGGAGUUG CUGAUGAG GCCGUUAGGC CGAA ICAGGUUU
8240


531
ACCUGCAC A ACUCCUGC
841
GCAGGAGU CUGAUGAG GCCGUUAGGC CGAA IUGCAGGU
8241


534
UGCACAAC U CCUGCUCA
842
UGAGCAGG CUGAUGAG GCCGUUAGGC CGAA IUUGUGCA
8242


536
CACAACUC C UGCUCAAG
843
CUUGAGCA CUGAUGAG GCCGUUAGGC CGAA IAGUUGUG
8243


537
ACAACUCC U GCUCAAGG
844
CCUUGAGC CUGAUGAG GCCGUUAGGC CGAA IGAGUUGU
8244


540
ACUCCUGC U CAAGGAAC
845
GUUCCUUG CUGAUGAG GCCGUUAGGC CGAA ICAGGAGU
8245


542
UCCUGCUC A AGGAACCU
846
AGGUUCCU CUGAUGAG GCCGUUAGGC CGAA IAGCAGGA
8246


549
CAAGGAAC C UCUAUGUU
847
AACAUAGA CUGAUGAG GCCGUUAGGC CGAA IUUCCUUG
8247


550
AAGGAACC U CUAUGUUU
848
AAACAUAG CUGAUGAG GCCGUUAGGC CGAA IGUUCCUU
8248


552
GGAACCUC U AUGUUUCC
849
GGAAACAU CUGAUGAG GCCGUUAGGC CGAA IAGGUUCC
8249


560
UAUGUUUC C CUCAUGUU
850
AACAUGAG CUGAUGAC GCCGUUAGGC CGAA IAAACAUA
8250


561
AUGUUUCC C UCAUGUUG
851
CAACAUGA CUGAUGAG GCCGUUAGGC CGAA IGAAACAU
8251


562
UGUUUCCC U CAUGUUGC
852
GCAACAUG CUGAUGAG GCCGUUAGGC CGAA IGGAAACA
8252


564
UUUCCCUC A UGUUGCUG
853
CAGCAACA CUGAUGAG GCCGUUAGGC CGAA IAGGGAAA
8253


571
CAUGUUGC U GUACAAAA
854
UUUUGUAC CUGAUGAG GCCGUUAGGC CGAA ICAACAUG
8254


576
UGCUGUAC A AAACCUAC
855
GUAGGUUU CUGAUGAG GCCGUUAGGC CGAA IUACAGCA
8255


581
UACAAAAC C UACGGACG
856
CGUCCGUA CUGAUGAG GCCGUUAGGC CGAA IUUUUGUA
8256


582
ACAAAACC U ACGGACGG
857
CCGUCCGU CUGAUGAG GCCGUUAGGC CGAA IGUUUUGU
8257


595
ACGGAAAC U GCACCUGU
858
ACAGGUGC CUGAUGAG GCCGUUAGGC CGAA IUUUCCGU
8258


598
GAAACUGC A CCUGUAUU
859
AAUACAGG CUGAUGAG GCCGUUAGGC CGAA ICAGUUUC
8259


600
AACUGCAC C UGUAUUCC
860
GGAAUACA CUGAUGAG GCCGUUAGGC CGAA IUGCAGUU
8260


601
ACUGCACC U GUAUUCCC
861
GGGAAUAC CUGAUGAG GCCGUUAGGC CGAA IGUGCAGU
8261


608
CUGUAUUC C CAUCCCAU
862
AUGGGAUG CUGAUGAG GCCGUUAGGC CGAA IAAUACAG
8262


609
UGUAUUCC C AUCCCAUC
863
GAUGGGAU CUGAUGAG GCCGUUAGGC CGAA IGAAUACA
8263


610
GUAUUCCC A UCCCAUCA
864
UGAUGGGA CUGAUGAG GCCGUUAGGC CGAA IGGAAUAC
8264


613
UUCCCAUC C CAUCAUCU
865
AGAUGAUG CUGAUGAG GCCGUUAGGC CGAA IAUGGGAA
8265


614
UCCCAUCC C AUCAUCUU
866
AAGAUGAU CUGAUGAG GCCGUUAGGC CGAA IGAUGGGA
8266


615
CCCAUCCC A UCAUCUUG
867
CAAGAUGA CUGAUGAG GCCGUUAGGC CGAA IGGAUGGG
8267


618
AUCCCAUC A UCUUGGGC
868
GCCCAAGA CUGAUGAG GCCGUUAGGC CGAA IAUGGGAU
8268


621
CCAUCAUC U UGGGCUUU
869
AAAGCCCA CUGAUGAG GCCGUUAGGC CGAA IAUGAUGG
8269


627
UCUUGGGC U UUCGCAAA
870
UUUGCGAA CUGAUGAG GCCGUUAGGC CGAA ICCCAAGA
8270


633
GCUUUCGC A AAAUACCU
871
AGGUAUUU CUGAUGAG GCCGUUAGGC CGAA ICGAAAGC
8271


640
CAAAAUAC C UAUGGGAG
872
CUCCCAUA CUGAUGAG GCCGUUAGGC CGAA IUAUUUUG
8272


641
AAAAUACC U AUGGGAGU
873
ACUCCCAU CUGAUGAG GCCGUUAGGC CGAA IGUAUUUU
8273


654
GAGUGGGC C UCAGUCCG
874
CGGACUGA CUGAUGAG GCCGUUAGGC CGAA ICCCACUC
8274


655
AGUGGGCC U CAGUCCGU
875
ACGGACUG CUGAUGAG GCCGUUAGGC CGAA IGCCCACU
8275


657
UGGGCCUC A GUCCGUUU
876
AAACGGAC CUGAUGAG GCCGUUAGGC CGAA IAGGCCCA
8276


661
CCUCAGUC C GUUUCUCU
877
AGAGAAAC CUGAUGAG GCCGUUAGGC CGAA IACUGAGG
8277


667
UCCGUUUC U CUUGGCUC
878
GAGCCAAG CUGAUGAG GCCGUUAGGC CGAA IAAACGGA
8278


669
CGUUUCUC U UGGCUCAG
879
CUGAGCCA CUGAUGAG GCCGUUAGGC CGAA IAGAAACG
8279


674
CUCUUGGC U CAGUUUAC
880
GUAAACUG CUGAUGAG GCCGUUAGGC CGAA ICCAAGAG
8280


676
CUUGGCUC A GUUUACUA
881
UAGUAAAC CUGAUGAG GCCGUUAGGC CGAA IAGCCAAG
8281


683
CAGUUUAC U AGUGCCAU
882
AUGGCACU CUGAUGAG GCCGUUAGGC CGAA IUAAACUG
8282


689
ACUAGUGC C AUUUGUUC
883
GAACAAAU CUGAUGAG GCCGUUAGGC CGAA ICACUAGU
8283


690
CUAGUGCC A UUUGUUCA
884
UGAACAAA CUGAUGAG GCCGUUAGGC CGAA IGCACUAG
8284


698
AUUUGUUC A GUGGUUCG
885
CGAACCAC CUGAUGAG GCCGUUAGGC CGAA IAACAAAU
8285


713
CGUAGGGC U UUCCCCCA
886
UGGGGGAA CUGAUGAG GCCGUUAGGC CGAA ICCCUACG
8286


717
GGGCUUUC C CCCACUGU
887
ACAGUGGG CUGAUGAG GCCGUUAGGC CGAA IAAAGCCC
8287


718
GGCUUUCC C CCACUGUC
888
GACAGUGG CUGAUGAG GCCGUUAGGC CGAA IGAAAGCC
8288


719
GCUUUCCC C CACUGUCU
889
AGACAGUG CUGAUGAG GCCGUUAGGC CGAA IGGAAAGC
8289


720
CUUUCCCC C ACUGUCUG
890
CAGACAGU CUGAUGAG GCCGUUAGGC CGAA IGGGAAAG
8290


721
UUUCCCCC A CUGUCUGG
891
CCAGACAG CUGAUGAG GCCGUUAGGC CGAA IGGGGAAA
8291


723
UCCCCCAC U GUCUGGCU
892
AGCCAGAC CUGAUGAG GCCGUUAGGC CGAA IUGGGGGA
8292


727
CCACUGUC U GGCUUUCA
893
UGAAAGCC CUGAUGAG GCCGUUAGGC CGAA IACAGUGG
8293


731
UGUCUGGC U UUCAGUUA
894
UAACUGAA CUGAUGAG GCCGUUAGGC CGAA ICCAGACA
8294


735
UGGCUUUC A GUUAUAUG
895
CAUAUAAC CUGAUGAG GCCGUUAGGC CGAA IAAAGCCA
8295


764
UUGGGGGC C AAGUCUGU
896
ACAGACUU CUGAUGAG GCCGUUAGGC CGAA ICCCCCAA
8296


765
UGGGGGCC A AGUCUGUA
897
UACAGACU CUGAUGAG GCCGUUAGGC CGAA IGCCCCCA
8297


770
GCCAAGUC U GUACAACA
898
UGUUGUAC CUGAUGAG GCCGUUAGGC CGAA IACUUGGC
8298


775
GUCUGUAC A ACAUCUUG
899
CAAGAUGU CUGAUGAG GCCGUUAGGC CGAA IUACAGAC
8299


778
UGUACAAC A UCUUGAGU
900
ACUCAAGA CUGAUGAG GCCGUUAGGC CGAA IUUGUACA
8300


781
ACAACAUC U UGAGUCCC
901
GGGACUCA CUGAUGAG GCCGUUAGGC CGAA IAUGUUGU
8301


788
CUUGAGUC C CUUUAUGC
902
GCAUAAAG CUGAUGAG GCCGUUAGGC CGAA IACUCAAG
8302


789
UUGAGUCC C UUUAUGCC
903
GGCAUAAA CUGAUGAG GCCGUUAGGC CGAA IGACUCAA
8303


790
UGAGUCCC U UUAUGCCG
904
CGGCAUAA CUGAUGAG GCCGUUAGGC CGAA IGGACUCA
8304


797
CUUUAUGC C GCUGUUAC
905
GUAACAGC CUGAUGAG GCCGUUAGGC CGAA ICAUAAAG
8305


800
UAUGCCGC U GUUACCAA
906
UUGGUAAC CUGAUGAG GCCGUUAGGC CGAA ICGGCAUA
8306


806
GCUGUUAC C AAUUUUCU
907
AGAAAAUU CUGAUGAG GCCGUUAGGC CGAA IUAACAGC
8307


807
CUGUUACC A AUUUUCUU
908
AAGAAAAU CUGAUGAG GCCGUUAGGC CGAA IGUAACAG
8308


814
CAAUUUUC U UUUGUCUU
909
AAGACAAA CUGAUGAG GCCGUUAGGC CGAA IAAAAUUG
8309


821
CUUUUGUC U UUGGGUAU
910
AUACCCAA CUGAUGAG GCCGUUAGGC CGAA IACAAAAG
8310


832
GGGUAUAC A UUUAAACC
911
GGUUUAAA CUGAUGAG GCCGUUAGGC CGAA IUAUACCC
8311


840
AUUUAAAC C CUCACAAA
912
UUUGUGAG CUGAUGAG GCCGUUAGGC CGAA IUUUAAAU
8312


841
UUUAAACC C UCACAAAA
913
UUUUGUGA CUGAUGAG GCCGUUAGGC CGAA IGUUUAAA
8313


842
UUAAACCC U CACAAAAC
914
GUUUUGUG CUGAUGAG GCCGUUAGGC CGAA IGGUUUAA
8314


844
AAACCCUC A CAAAACAA
915
UUGUUUUG CUGAUGAG GCCGUUAGGC CGAA IAGGGUUU
8315


846
ACCCUCAC A AAACAAAA
916
UUUUGUUU CUGAUGAG GCCGUUAGGC CGAA IUGAGGGU
8316


851
CACAAAAC A AAAAGAUG
917
CAUCUUUU CUGAUGAG GCCGUUAGGC CGAA IUUUUGUG
8317


869
GGAUAUUC C CUUAACUU
918
AAGUUAAG CUGAUGAG GCCGUUAGGC CGAA IAAUAUCC
8318


870
GAUAUUCC C UUAACUUC
919
GAAGUUAA CUGAUGAG GCCGUUAGGC CGAA IGAAUAUC
8319


871
AUAUUCCC U UAACUUCA
920
UGAAGUUA CUGAUGAG GCCGUUAGGC CGAA IGGAAUAU
8320


876
CCCUUAAC U UCAUGGGA
921
UCCCAUGA CUGAUGAG GCCGUUAGGC CGAA IUUAAGGG
8321


879
UUAACUUC A UGGGAUAU
922
AUAUCCCA CUGAUGAG GCCGUUAGGC CGAA IAAGUUAA
8322


906
GUUGGGGC A CAUUGCCA
923
UGGCAAUG CUGAUGAG GCCGUUAGGC CGAA ICCCCAAC
8323


908
UGGGGCAC A UUGCCACA
924
UGUGGCAA CUGAUGAG GCCGUUAGGC CGAA IUGCCCCA
8324


913
CACAUUGC C ACAGGAAC
925
GUUCCUGU CUGAUGAG GCCGUUAGGC CGAA ICAAUGUG
8325


914
ACAUUGCC A CAGGAACA
926
UGUUCCUG CUGAUGAG GCCGUUAGGC CGAA IGCAAUGU
8326


916
AUUGCCAC A GGAACAUA
927
UAUGUUCC CUGAUGAG GCCGUUAGGC CGAA IUGGCAAU
8327


922
ACAGGAAC A UAUUGUAC
928
GUACAAUA CUGAUGAG GCCGUUAGGC CGAA IUUCCUGU
8328


931
UAUUGUAC A AAAAAUCA
929
UGAUUUUU CUGAUGAG GCCGUUAGGC CGAA IUACAAUA
8329


939
AAAAAAUC A AAAUGUGU
930
ACACAUUU CUGAUGAG GCCGUUAGGC CGAA IAUUUUUU
8330


958
UAGGAAAC U UCCUGUAA
931
UUACAGGA CUGAUGAG GCCGUUAGGC CGAA IUUUCCUA
8331


961
GAAACUUC C UGUAAACA
932
UGUUUACA CUGAUGAG GCCGUUAGGC CGAA IAAGUUUC
8332


962
AAACUUCC U GUAAACAG
933
CUGUUUAC CUGAUGAG GCCGUUAGGC CGAA IGAAGUUU
8333


969
CUGUAAAC A GGCCUAUU
934
AAUAGGCC CUGAUGAG GCCGUUAGGC CGAA IUUUACAG
8334


973
AAACAGGC C UAUUGAUU
935
AAUCAAUA CUGAUGAG GCCGUUAGGC CGAA ICCUGUUU
8335


974
AACAGGCC U AUUGAUUG
936
CAAUCAAU CUGAUGAG GCCGUUAGGC CGAA IGCCUGUU
8336


994
AGUAUGUC A ACGAAUUG
937
CAAUUCGU CUGAUGAG GCCGUUAGGC CGAA IACAUACU
8337


1009
UGUGGGUC U UUUGGGGU
938
ACCCCAAA CUGAUGAG GCCGUUAGGC CGAA IACCCACA
8338


1022
GGGUUUGC C GCCCCUUU
939
AAAGGGGC CUGAUGAG GCCGUUAGGC CGAA ICAAACCC
8339


1025
UUUGCCGC C CCUUUCAC
940
GUGAAAGG CUGAUGAG GCCGUUAGGC CGAA ICGGCAAA
8340


1026
UUGCCGCC C CUUUCACG
941
CGUGAAAG CUGAUGAG GCCGUUAGGC CGAA IGCGGCAA
8341


1027
UGCCGCCC C UUUCACGC
942
GCGUGAAA CUGAUGAG GCCGUUAGGC CGAA IGGCGGCA
8342


1028
GCCGCCCC U UUCACGCA
943
UGCGUGAA CUGAUGAG GCCGUUAGGC CGAA IGGGCGGC
8343


1032
CCCCUUUC A CGCAAUGU
944
ACAUUGCG CUGAUGAG GCCGUUAGGC CGAA IAAAGGGG
8344


1036
UUUCACGC A AUGUGGAU
945
AUCCACAU CUGAUGAG GCCGUUAGGC CGAA ICGUGAAA
8345


1049
GGAUAUUC U GCUUUAAU
946
AUUAAAGC CUGAUGAG GCCGUUAGGC CGAA IAAUAUCC
8346


1052
UAUUCUGC U UUAAUGCC
947
GGCAUUAA CUGAUGAG GCCGUUAGGC CGAA ICAGAAUA
8347


1060
UUUAAUGC C UUUAUAUG
948
CAUAUAAA CUGAUGAG GCCGUUAGGC CGAA ICAUUAAA
8348


1061
UUAAUGCC U UUAUAUGC
949
GCAUAUAA CUGAUGAG GCCGUUAGGC CGAA IGCAUUAA
8349


1070
UUAUAUGC A UGCAUACA
950
UGUAUGCA CUGAUGAG GCCGUUAGGC CGAA ICAUAUAA
8350


1074
AUGCAUGC A UACAAGCA
951
UGCUUGUA CUGAUGAG GCCGUUAGGC CGAA ICAUGCAU
8351


1078
AUGCAUAC A AGCAAAAC
952
GUUUUGCU CUGAUCAG GCCGUUAGGC CGAA IUAUGCAU
8352


1082
AUACAAGC A AAACAGGC
953
GCCUGUUU CUGAUGAG GCCGUUAGGC CGAA ICUUGUAU
8353


1087
AGCAAAAC A GGCUUUUA
954
UAAAAGCC CUGAUGAG GCCGUUAGGC CGAA IUUUUGCU
8354


1091
AAACAGGC U UUUACUUU
955
AAAGUAAA CUGAUGAG GCCGUUAGGC CGAA ICCUGUUU
8355


1097
GCUUUUAC U UUCUCGCC
956
GGCGAGAA CUGAUGAG GCCGUUAGGC CGAA IUAAAAGC
8356


1101
UUACUUUC U CGCCAACU
957
AGUUGGCG CUGAUGAG GCCGUUAGGC CGAA IAAAGUAA
8357


1105
UUUCUCGC C AACUUACA
958
UGUAAGUU CUGAUGAG GCCGUUAGGC CGAA ICGAGAAA
8358


1106
UUCUCGCC A ACUUACAA
959
UUGUAAGU CUGAUGAG GCCGUUAGGC CGAA IGCGAGAA
8359


1109
UCGCCAAC U UACAAGGC
960
GCCUUGUA CUGAUGAG GCCGUUAGGC CGAA IUUGGCGA
8360


1113
CAACUUAC A AGGCCUUU
961
AAAGGCCU CUGAUGAG GCCGUUAGGC CGAA IUAAGUUG
8361


1118
UACAAGGC C UUUCUAAG
962
CUUAGAAA CUGAUGAG GCCGUUAGGC CGAA ICCUUGUA
8362


1119
ACAAGGCC U UUCUAAGU
963
ACUUAGAA CUGAUGAG GCCGUUAGGC CGAA IGCCUUGU
8363


1123
GGCCUUUC U AAGUAAAC
964
GUUUACUU CUGAUGAG GCCGUUAGGC CGAA IAAAGGCC
8364


1132
AAGUAAAC A GUAUGUGA
965
UCACAUAC CUGAUGAG GCCGUUAGGC CGAA IUUUACUU
8365


1143
AUGUGAAC C UUUACCCC
966
GGGGUAAA CUGAUGAG GCCGUUAGGC CGAA IUUCACAU
8366


1144
UGUGAACC U UUACCCCG
967
CGGGGUAA CUGAUGAG GCCGUUAGGC CGAA IGUUCACA
8367


1149
ACCUUUAC C CCGUUGCU
968
AGCAACGG CUGAUGAG GCCGUUAGGC CGAA IUAAAGGU
8368


1150
CCUUUACC C CGUUGCUC
969
GAGCAACG CUGAUGAG GCCGUUAGGC CGAA IGUAAAGG
8369


1151
CUUUACCC C GUUGCUCG
970
CGAGCAAC CUGAUGAG GCCGUUAGGC CGAA IGGUAAAG
8370


1157
CCCGUUGC U CGGCAACG
971
CGUUGCCG CUGAUGAG GCCGUUAGGC CGAA ICAACGGG
8371


1162
UGCUCGGC A ACGGCCUG
972
CAGGCCGU CUGAUGAG GCCGUUAGGC CGAA ICCGAGCA
8372


1168
GCAACGGC C UGGUCUAU
973
AUAGACCA CUGAUGAG GCCGUUAGGC CGAA ICCGUUGC
8373


1169
CAACGGCC U GGUCUAUG
974
CAUAGACC CUGAUGAG GCCGUUAGGC CGAA IGCCGUUG
8374


1174
GCCUGGUC U AUGCCAAG
975
CUUGGCAU CUGAUGAG GCCGUUAGGC CGAA IACCAGGC
8375


1179
GUCUAUGC C AAGUGUUU
976
AAACACUU CUGAUGAG GCCGUUAGGC CGAA ICAUAGAC
8376


1180
UCUAUGCC A AGUGUUUG
977
CAAACACU CUGAUGAG GCCGUUAGGC CGAA IGCAUAGA
8377


1190
GUGUUUGC U GACGCAAC
978
GUUGCGUC CUGAUGAG GCCGUUAGGC CGAA ICAAACAC
8378


1196
GCUGACGC A ACCCCCAC
979
GUGGGGGU CUGAUGAG GCCGUUAGGC CGAA ICGUCAGC
8379


1199
GACGCAAC C CCCACUGG
980
CCAGUGGG CUGAUGAG GCCGUUAGGC CGAA IUUGCGUC
8380


1200
ACGCAACC C CCACUGGU
981
ACCAGUGG CUGAUGAG GCCGUUAGGC CGAA IGUUGCGU
8381


1201
CGCAACCC C CACUGGUU
982
AACCAGUG CUGAUGAG GCCGUUAGGC CGAA IGGUUGCG
8382


1202
GCAACCCC C ACUGGUUG
983
CAACCAGU CUGAUGAG GCCGUUAGGC CGAA IGGGUUGC
8383


1203
CAACCCCC A CUGGUUGG
984
CCAACCAG CUGAUGAG GCCGUUAGGC CGAA IGGGGUUG
8384


1205
ACCCCCAC U GGUUGGGG
985
CCCCAACC CUGAUGAG GCCGUUAGGC CGAA IUGGGGGU
8385


1215
GUUGGGGC U UGGCCAUA
986
UAUGGCCA CUGAUGAG GCCGUUAGGC CGAA ICCCCAAC
8386


1220
GGCUUGGC C AUAGGCCA
987
UGGCCUAU CUGAUGAG GCCGUUAGGC CGAA ICCAAGCC
8387


1221
GCUUGGCC A UAGGCCAU
988
AUGGCCUA CUGAUGAG GCCGUUAGGC CGAA IGCCAAGC
8388


1227
CCAUAGGC C AUCAGCGC
989
GCGCUGAU CUGAUGAG GCCGUUAGGC CGAA ICCUAUGG
8389


1228
CAUAGGCC A UCAGCGCA
990
UGCGCUGA CUGAUGAG GCCGUUAGGC CGAA IGCCUAUG
8390


1231
AGGCCAUC A GCGCAUGC
991
GCAUGCGC CUGAUGAG GCCGUUAGGC CGAA IAUGGCCU
8391


1236
AUCAGCGC A UGCGUGGA
992
UCCACGCA CUGAUGAG GCCGUUAGGC CGAA ICGCUGAU
8392


1247
CGUGGAAC C UUUGUGUC
993
GACACAAA CUGAUGAG GCCGUUAGGC CGAA IUUCCACG
8393


1248
GUGGAACC U UUGUGUCU
994
AGACACAA CUGAUGAG GCCGUUAGGC CGAA IGUUCCAC
8394


1256
UUUGUGUC U CCUCUGCC
995
GGCAGAGG CUGAUGAG GCCGUUAGGC CGAA IACACAAA
8395


1258
UGUGUCUC C UCUGCCGA
996
UCGGCAGA CUGAUGAG GCCGUUAGGC CGAA IAGACACA
8396


1259
GUGUCUCC U CUGCCGAU
997
AUCGGCAG CUGAUGAG GCCGUUAGGC CGAA IGAGACAC
8397


1261
GUCUCCUC U GCCGAUCC
998
GGAUCGGC CUGAUGAG GCCGUUAGGC CGAA IAGGAGAC
8398


1264
UCCUCUGC C GAUCCAUA
999
UAUGGAUC CUGAUGAG GCCGUUAGGC CGAA ICAGAGGA
8399


1269
UGCCGAUC C AUACCGCG
1000
CGCGGUAU CUGAUGAG GCCGUUAGGC CGAA IAUCGGCA
8400


1270
GCCGAUCC A UACCGCGG
1001
CCGCGGUA CUGAUGAG GCCGUUAGGC CGAA IGAUCGGC
8401


1274
AUCCAUAC C GCGGAACU
1002
AGUUCCGC CUGAUGAG GCCGUUAGGC CGAA IUAUGGAU
8402


1282
CGCGGAAC U CCUAGCCG
1003
CGGCUAGG CUGAUGAG GCCGUUAGGC CGAA IUUCCGCG
8403


1284
CGGAACUC C UAGCCGCU
1004
AGCGGCUA CUGAUGAG GCCGUUAGGC CGAA IAGUUCCG
8404


1285
GGAACUCC U AGCCGCUU
1005
AAGCGGCU CUGAUGAG GCCGUUAGGC CGAA IGAGUUCC
8405


1289
CUCCUAGC C GCUUGUUU
1006
AAACAAGC CUGAUGAG GCCGUUAGGC CGAA ICUAGGAG
8406


1292
CUAGCCGC U UGUUUUGC
1007
GCAAAACA CUGAUGAG GCCGUUAGGC CGAA ICGGCUAG
8407


1301
UGUUUUGC U CGCAGCAG
1008
CUGCUGCG CUGAUGAG GCCGUUAGGC CGAA ICAAAACA
8408


1305
UUGCUCGC A GCAGGUCU
1009
AGACCUGC CUGAUGAG GCCGUUAGGC CGAA ICGAGCAA
8409


1308
CUCGCAGC A GGUCUGGG
1010
CCCAGACC CUGAUGAG GCCGUUAGGC CGAA ICUGCGAG
8410


1313
AGCAGGUC U GGGGCAAA
1011
UUUGCCCC CUGAUGAG GCCGUUAGGC CGAA IACCUGCU
8411


1319
UCUGGGGC A AAACUCAU
1012
AUGAGUUU CUGAUGAG GCCGUUAGGC CGAA ICCCCAGA
8412


1324
GGCAAAAC U CAUCGGGA
1013
UCCCGAUG CUGAUGAG GCCGUUAGGC CGAA IUUUUGCC
8413


1326
CAAAACUC A UCGGGACU
1014
AGUCCCGA CUGAUGAG GCCGUUAGGC CGAA IAGUUUUG
8414


1334
AUCGGGAC U GACAAUUC
1015
GAAUUGUC CUGAUGAG GCCGUUAGGC CGAA IUCCCGAU
8415


1338
GGACUGAC A AUUCUGUC
1016
GACAGAAU CUGAUGAG GCCGUUAGGC CGAA IUCAGUCC
8416


1343
GACAAUUC U GUCGUGCU
1017
AGCACGAC CUGAUGAG GCCGUUAGGC CGAA IAAUUGUC
8417


1351
UGUCGUGC U CUCCCGCA
1018
UGCGGGAG CUGAUGAG GCCGUUAGGC CGAA ICACGACA
8418


1353
UCGUGCUC U CCCGCAAA
1019
UUUGCGGG CUGAUGAG GCCGUUAGGC CGAA IAGCACGA
8419


1355
GUGCUCUC C CGCAAAUA
1020
UAUUUGCG CUGAUGAG GCCGUUAGGC CGAA IAGAGCAC
8420


1356
UGCUCUCC C GCAAAUAU
1021
AUAUUUGC CUGAUGAG GCCGUUAGGC CGAA IGAGAGCA
8421


1359
UCUCCCGC A AAUAUACA
1022
UGUAUAUU CUGAUGAG GCCGUUAGGC CGAA ICGGGAGA
8422


1367
AAAUAUAC A UCAUUUCC
1023
GGAAAUGA CUGAUGAG GCCGUUAGGC CGAA IUAUAUUU
8423


1370
UAUACAUC A UUUCCAUG
1024
CAUGGAAA CUGAUGAG GCCGUUAGGC CGAA IAUGUAUA
8424


1375
AUCAUUUC C AUGGCUGC
1025
GCAGCCAU CUGAUGAG GCCGUUAGGC CGAA IAAAUGAU
8425


1376
UCAUUUCC A UGGCUGCU
1026
AGCAGCCA CUGAUGAG GCCGUUAGGC CGAA IGAAAUGA
8426


1381
UCCAUGGC U GCUAGGCU
1027
AGCCUAGC CUGAUGAG GCCGUUAGGC CGAA ICCAUGGA
8427


1384
AUGGCUGC U AGGCUGUG
1028
CACAGCCU CUGAUGAG GCCGUUAGGC CGAA ICAGCCAU
8428


1389
UGCUAGGC U GUGCUGCC
1029
GGCAGCAC CUGAUGAG GCCGUUAGGC CGAA ICCUAGCA
8429


1394
GGCUGUGC U GCCAACUG
1030
CAGUUGGC CUGAUGAG GCCGUUAGGC CGAA ICACAGCC
8430


1397
UGUGCUGC C AACUGGAU
1031
AUCCAGUU CUGAUGAG GCCGUUAGGC CGAA ICAGCACA
8431


1398
GUGCUGCC A ACUGGAUC
1032
GAUCCAGU CUGAUGAG GCCGUUAGGC CGAA IGCAGCAC
8432


1401
CUGCCAAC U GGAUCCUA
1033
UAGGAUCC CUGAUGAG GCCGUUAGGC CGAA IUUGGCAG
8433


1407
ACUGGAUC C UACGCGGG
1034
CCCGCGUA CUGAUGAG GCCGUUAGGC CGAA IAUCCAGU
8434


1408
CUGGAUCC U ACGCGGGA
1035
UCCCGCGU CUGAUGAG GCCGUUAGGC CGAA IGAUCCAG
8435


1421
GGGACGUC C UUUGUUUA
1036
UAAACAAA CUGAUGAG GCCGUUAGGC CGAA IACGUCCC
8436


1422
GGACGUCC U UUGUUUAC
1037
GUAAACAA CUGAUGAG GCCGUUAGGC CGAA IGACGUCC
8437


1434
UUUACGUC C CGUCGGCG
1038
CGCCGACG CUGAUGAG GCCGUUAGGC CGAA IACGUAAA
8438


1435
UUACGUCC C GUCGGCGC
1039
GCGCCGAC CUGAUGAG GCCGUUAGGC CGAA IGACGUAA
8439


1444
GUCGGCGC U GAAUCCCG
1040
CGGGAUUC CUGAUGAG GCCGUUAGGC CGAA ICGCCGAC
8440


1450
GCUGAAUC C CGCGGACG
1041
CGUCCGCG CUGAUGAG GCCGUUAGGC CGAA IAUUCAGC
8441


1451
CUGAAUCC C GCGGACGA
1042
UCGUCCGC CUGAUGAG GCCGUUAGGC CGAA IGAUUCAG
8442


1461
CGGACGAC C CCUCCCGG
1043
CCGGGAGG CUGAUGAG GCCGUUAGGC CGAA IUCGUCCG
8443


1462
GGACGACC C CUCCCGGG
1044
CCCGGGAG CUGAUGAG GCCGUUAGGC CGAA IGUCGUCC
8444


1463
GACGACCC C UCCCGGGG
1045
CCCCGGGA CUGAUGAG GCCGUUAGGC CGAA IGGUCGUC
8445


1464
ACGACCCC U CCCGGGGC
1046
GCCCCGGG CUGAUGAG GCCGUUAGGC CGAA IGGGUCGU
8446


1466
GACCCCUC C CGGGGCCG
1047
CGGCCCCG CUGAUGAG GCCGUUAGGC CGAA IAGGGGUC
8447


1467
ACCCCUCC C GGGGCCGC
1048
GCGGCCCC CUGAUGAG GCCGUUAGGC CGAA IGAGGGGU
8448


1473
CCCGGGGC C GCUUGGGG
1049
CCCCAAGC CUGAUGAG GCCGUUAGGC CGAA ICCCCGGG
8449


1476
GGGGCCGC U UGGGGCUC
1050
GAGCCCCA CUGAUGAG GCCGUUAGGC CGAA ICGGCCCC
8450


1483
CUUGGGGC U CUACCGCC
1051
GGCGGUAG CUGAUGAG GCCGUUAGGC CGAA ICCCCAAG
8451


1485
UGGGGCUC U ACCGCCCG
1052
CGGGCGGU CUGAUGAG GCCGUUAGGC CGAA IAGCCCCA
8452


1488
GGCUCUAC C GCCCGCUU
1053
AAGCGGGC CUGAUGAG GCCGUUAGGC CGAA IUAGAGCC
8453


1491
UCUACCGC C CGCUUCUC
1054
GAGAAGCG CUGAUGAG GCCGUUAGGC CGAA ICGGUAGA
8454


1492
CUACCGCC C GCUUCUCC
1055
GGAGAAGC CUGAUGAG GCCGUUAGGC CGAA IGCGGUAG
8455


1495
CCGCCCGC U UCUCCGCC
1056
GGCGGAGA CUGAUGAG GCCGUUAGGC CGAA ICGGGCGG
8456


1498
CCCGCUUC U CCGCCUAU
1057
AUAGGCGG CUGAUGAG GCCGUUAGGC CGAA IAAGCGGG
8457


1500
CGCUUCUC C GCCUAUUG
1058
CAAUAGGC CUGAUGAG GCCGUUAGGC CGAA IAGAAGCG
8458


1503
UUCUCCGC C UAUUGUAC
1059
GUACAAUA CUGAUGAG GCCGUUAGGC CGAA ICGGAGAA
8459


1504
UCUCCGCC U AUUGUACC
1060
GGUACAAU CUGAUGAG GCCGUUAGGC CGAA IGCGGAGA
8460


1512
UAUUGUAC C GACCGUCC
1061
GGACGGUC CUGAUGAG GCCGUUAGGC CGAA IUACAAUA
8461


1516
GUACCGAC C GUCCACGG
1062
CCGUGGAC CUGAUGAG GCCGUUAGGC CGAA IUCGGUAC
8462


1520
CGACCGUC C ACGGGGCG
1063
CGCCCCGU CUGAUGAG GCCGUUAGGC CGAA IACGGUCG
8463


1521
GACCGUCC A CGGGGCGC
1064
GCGCCCCG CUGAUGAG GCCGUUAGGC CGAA IGACGGUC
8464


1530
CGGGGCGC A CCUCUCUU
1065
AAGAGAGG CUGAUGAG GCCGUUAGGC CGAA ICGCCCCG
8465


1532
GGGCGCAC C UCUCUUUA
1066
UAAAGAGA CUGAUGAG GCCGUUAGGC CGAA IUGCGCCC
8466


1533
GGCGCACC U CUCUUUAC
1067
GUAAAGAG CUGAUGAG GCCGUUAGGC CGAA IGUGCGCC
8467


1535
CGCACCUC U CUUUACGC
1068
GCGUAAAG CUGAUGAG GCCGUUAGGC CGAA IAGGUGCG
8468


1537
CACCUCUC U UUACGCGG
1069
CCGCGUAA CUGAUGAG GCCGUUAGGC CGAA IAGAGGUG
8469


1548
ACGCGGAC U CCCCGUCU
1070
AGACGGGG CUGAUGAG GCCGUUAGGC CGAA IUCCGCGU
8470


1550
GCGGACUC C CCGUCUGU
1071
ACAGACGG CUGAUGAG GCCGUUAGGC CGAA IAGUCCGC
8471


1551
CGGACUCC C CGUCUGUG
1072
CACAGACG CUGAUGAG GCCGUUAGGC CGAA IGAGUCCG
8472


1552
GGACUCCC C GUCUGUGC
1073
GCACAGAC CUGAUGAG GCCGUUAGGC CGAA IGGAGUCC
8473


1556
UCCCCGUC U GUGCCUUC
1074
GAAGGCAC CUGAUGAG GCCGUUAGGC CGAA IACGGGGA
8474


1561
GUCUGUGC C UUCUCAUC
1075
GAUGAGAA CUGAUGAG GCCGUUAGGC CGAA ICACAGAC
8475


1562
UCUGUGCC U UCUCAUCU
1076
AGAUGAGA CUGAUGAG GCCGUUAGGC CGAA IGCACAGA
8476


1565
GUGCCUUC U CAUCUGCC
1077
GGCAGAUG CUGAUGAG GCCGUUAGGC CGAA IAAGGCAC
8477


1567
GCCUUCUC A UCUGCCGG
1078
CCGGCAGA CUGAUGAG GCCGUUAGGC CGAA IAGAAGGC
8478


1570
UUCUCAUC U GCCGGACC
1079
GGUCCGGC CUGAUGAG GCCGUUAGGC CGAA IAUGAGAA
8479


1573
UCAUCUGC C GGACCGUG
1080
CACGGUCC CUGAUGAG GCCGUUAGGC CGAA ICAGAUGA
8480


1578
UGCCGGAC C GUGUCCAC
1081
GUGCACAC CUGAUGAG GCCGUUAGGC CGAA IUCCGGCA
8481


1585
CCGUGUGC A CUUCGCUU
1082
AAGCGAAG CUGAUGAG GCCGUUAGGC CGAA ICACACGG
8482


1587
GUGUGCAC U UCGCUUCA
1083
UGAAGCGA CUGAUGAG GCCGUUAGGC CGAA IUGCACAC
8483


1592
CACUUCGC U UCACCUCU
1084
AGAGGUGA CUGAUGAG GCCGUUAGGC CGAA ICGAAGUG
8484


1595
UUCGCUUC A CCUCUGCA
1085
UGCAGAGG CUGAUGAG GCCGUUAGGC CGAA IAAGCGAA
8485


1597
CGCUUCAC C UCUGCACG
1086
CGUGCAGA CUGAUGAG GCCGUUAGGC CGAA IUGAAGCG
8486


1598
GCUUCACC U CUGCACGU
1087
ACGUGCAG CUGAUGAG GCCGUUAGGC CGAA IGUGAAGC
8487


1600
UUCACCUC U GCACGUCG
1088
CGACGUGC CUGAUGAG GCCGUUAGGC CGAA IAGGUGAA
8488


1603
ACCUCUGC A CGUCGCAU
1089
AUGCGACG CUGAUGAG GCCGUUAGGC CGAA ICAGAGGU
8489


1610
CACGUCGC A UGGAGACC
1090
GGUCUCCA CUGAUGAG GCCGUUAGGC CGAA ICGACGUG
8490


1618
AUGGAGAC C ACCGUGAA
1091
UUCACGGU CUGAUGAG GCCGUUAGGC CGAA IUCUCCAU
8491


1619
UGGAGACC A CCGUGAAC
1092
GUUCACGG CUGAUGAG GCCGUUAGGC CGAA IGUCUCCA
8492


1621
GAGACCAC C GUGAACGC
1093
GCGUUCAC CUGAUGAG GCCGUUAGGC CGAA IUGGUCUC
8493


1630
GUGAACGC C CACAGGAA
1094
UUCCUGUG CUGAUGAG GCCGUUAGGC CGAA ICGUUCAC
8494


1631
UGAACGCC C ACAGGAAC
1095
GUUCCUGU CUGAUGAG GCCGUUAGGC CGAA IGCGUUCA
8495


1632
GAACGCCC A CAGGAACC
1096
GGUUCCUG CUGAUGAG GCCGUUAGGC CGAA IGGCGUUC
8496


1634
ACGCCCAC A GGAACCUG
1097
CAGGUUCC CUGAUGAG GCCGUUAGGC CGAA IUGGGCGU
8497


1640
ACAGGAAC C UGCCCAAG
1098
CUUGGGCA CUGAUGAG GCCGUUAGGC CGAA IUUCCUGU
8498


1641
CAGGAACC U GCCCAAGG
1099
CCUUGGGC CUGAUGAG GCCGUUAGGC CGAA IGUUCCUG
8499


1644
GAACCUGC C CAAGGUCU
1100
AGACCUUG CUGAUGAG GCCGUUAGGC CGAA ICAGGUUC
8500


1645
AACCUGCC C AAGGUCUU
1101
AAGACCUU CUGAUGAG GCCGUUAGGC CGAA IGCAGGUU
8501


1646
ACCUGCCC A AGGUCUUG
1102
CAAGACCU CUGAUGAG GCCGUUAGGC CGAA IGGCAGGU
8502


1652
CCAAGGUC U UGCAUAAG
1103
CUUAUGCA CUGAUGAG GCCGUUAGGC CGAA IACCUUGG
8503


1656
GGUCUUGC A UAAGAGGA
1104
UCCUCUUA CUGAUGAG GCCGUUAGGC CGAA ICAAGACC
8504


1666
AAGAGGAC U CUUGGACU
1105
AGUCCAAG CUGAUGAG GCCGUUAGGC CGAA IUCCUCUU
8505


1668
GAGGACUC U UGGACUUU
1106
AAAGUCCA CUGAUGAG GCCGUUAGGC CGAA IAGUCCUC
8506


1674
UCUUGGAC U UUCAGCAA
1107
UUGCUGAA CUGAUGAG GCCGUUAGGC CGAA IUCCAAGA
8507


1678
GGACUUUC A GCAAUGUC
1108
GACAUUGC CUGAUGAG GCCGUUAGGC CGAA IAAAGUCC
8508


1681
CUUUCAGC A AUGUCAAC
1109
GUUGACAU CUGAUGAG GCCGUUAGGC CGAA ICUGAAAG
8509


1687
GCAAUGUC A ACGACCGA
1110
UCGGUCGU CUGAUGAG GCCGUUAGGC CGAA IACAUUGC
8510


1693
UCAACGAC C GACCUUGA
1111
UCAAGGUC CUGAUGAG GCCGUUAGGC CGAA IUCGUUGA
8511


1697
CGACCGAC C UUGAGGCA
1112
UGCCUCAA CUGAUGAG GCCGUUAGGC CGAA IUCGGUCG
8512


1698
GACCGACC U UGAGGCAU
1113
AUGCCUCA CUGAUGAG GCCGUUAGGC CGAA IGUCGGUC
8513


1705
CUUGAGGC A UACUUCAA
1114
UUGAAGUA CUGAUGAG GCCGUUAGGC CGAA ICCUCAAG
8514


1709
AGGCAUAC U UCAAAGAC
1115
GUCUUUGA CUGAUGAG GCCGUUAGGC CGAA IUAUGCCU
8515


1712
CAUACUUC A AAGACUGU
1116
ACAGUCUU CUGAUGAG GCCGUUAGGC CGAA IAAGUAUG
8516


1718
UCAAAGAC U GUGUGUUU
1117
AAACACAC CUGAUGAG GCCGUUAGGC CGAA IUCUUUGA
8517


1769
UAAAGGUC U UUGUACUA
1118
UAGUACAA CUGAUGAG GCCGUUAGGC CGAA IACCUUUA
8518


1776
CUUUGUAC U AGGAGGCU
1119
AGCCUCCU CUGAUGAG GCCGUUAGGC CGAA IUACAAAG
8519


1784
UAGGAGGC U GUAGGCAU
1120
AUGCCUAC CUGAUGAG GCCGUUAGGC CGAA ICCUCCUA
8520


1791
CUGUAGGC A UAAAUUGG
1121
CCAAUUUA CUGAUGAG GCCGUUAGGC CGAA ICCUACAG
8521


1807
GUGUGUUC A CCAGCACC
1122
GGUGCUGG CUGAUGAG GCCGUUAGGC CGAA IAACACAC
8522


1809
GUGUUCAC C AGCACCAU
1123
AUGGUGCU CUGAUGAG GCCGUUAGGC CGAA IUGAACAC
8523


1810
UGUUCACC A GCACCAUG
1124
CAUGGUGC CUGAUGAG GCCGUUAGGC CGAA IGUGAACA
8524


1813
UCACCAGC A CCAUGCAA
1125
UUGCAUGG CUGAUGAG GCCGUUAGGC CGAA ICUGGUGA
8525


1815
ACCAGCAC C AUGCAACU
1126
AGUUGCAU CUGAUGAG GCCGUUAGGC CGAA IUGCUGGU
8526


1816
CCAGCACC A UGCAACUU
1127
AAGUUGCA CUGAUGAG GCCGUUAGGC CGAA IGUGCUGG
8527


1820
CACCAUGC A ACUUUUUC
1128
GAAAAAGU CUGAUGAG GCCGUUAGGC CGAA ICAUGGUG
8528


1823
CAUGCAAC U UUUUCACC
1129
GGUGAAAA CUGAUGAG GCCGUUAGGC CGAA IUUGCAUG
8529


1829
ACUUUUUC A CCUCUGCC
1130
GGCAGAGG CUGAUGAG GCCGUUAGGC CGAA IAAAAAGU
8530


1831
UUUUUCAC C UCUGCCUA
1131
UAGGCAGA CUGAUGAG GCCGUUAGGC CGAA IUGAAAAA
8531


1832
UUUUCACC U CUGCCUAA
1132
UUAGGCAG CUGAUGAG GCCGUUAGGC CGAA IGUGAAAA
8532


1834
UUCACCUC U GCCUAAUC
1133
GAUUAGGC CUGAUGAG GCCGUUAGGC CGAA IAGGUGAA
8533


1837
ACCUCUGC C UAAUCAUC
1134
GAUGAUUA CUGAUGAG GCCGUUAGGC CGAA ICAGAGGU
8534


1838
CCUCUGCC U AAUCAUCU
1135
AGAUGAUU CUGAUGAG GCCGUUAGGC CGAA IGCAGAGG
8535


1843
GCCUAAUC A UCUCAUGU
1136
ACAUGAGA CUGAUGAG GCCGUUAGGC CGAA IAUUAGGC
8536


1846
UAAUCAUC U CAUGUUCA
1137
UGAACAUG CUGAUGAG GCCGUUAGGC CGAA IAUGAUUA
8537


1848
AUCAUCUC A UGUUCAUG
1138
CAUGAACA CUGAUGAG GCCGUUAGGC CGAA IAGAUGAU
8538


1854
UCAUGUUC A UGUCCUAC
1139
GUAGGACA CUGAUGAG GCCGUUAGGC CGAA IAACAUGA
8539


1859
UUCAUGUC C UACUGUUC
1140
GAACAGUA CUGAUGAG GCCGUUAGGC CGAA IACAUGAA
8540


1860
UCAUGUCC U ACUGUUCA
1141
UGAACAGU CUGAUGAG GCCGUUAGGC CGAA IGACAUGA
8541


1863
UGUCCUAC U GUUCAAGC
1142
GCUUGAAC CUGAUGAG GCCGUUAGGC CGAA IUAGGACA
8542


1868
UACUGUUC A AGCCUCCA
1143
UGGAGGCU CUGAUGAG GCCGUUAGGC CGAA IAACAGUA
8543


1872
GUUCAAGC C UCCAAGCU
1144
AGCUUGGA CUGAUGAG GCCGUUAGGC CGAA ICUUGAAC
8544


1873
UUCAAGCC U CCAAGCUG
1145
CAGCUUGG CUGAUGAG GCCGUUAGGC CGAA IGCUUGAA
8545


1875
CAAGCCUC C AAGCUGUG
1146
CACAGCUU CUGAUGAG GCCGUUAGGC CGAA IAGGCUUG
8546


1876
AAGCCUCC A AGCUGUGC
1147
GCACAGCU CUGAUGAG GCCGUUAGGC CGAA IGAGGCUU
8547


1880
CUCCAAGC U GUGCCUUG
1148
CAAGGCAC CUGAUGAG GCCGUUAGGC CGAA ICUUGGAG
8548


1885
AGCUGUGC C UUGGGUGG
1149
CCACCCAA CUGAUGAG GCCGUUAGGC CGAA ICACAGCU
8549


1886
GCUGUGCC U UGGGUGGC
1150
GCCACCCA CUGAUGAG GCCGUUAGGC CGAA IGCACAGC
8550


1895
UGGGUGGC U UUGGGGCA
1151
UGCCCCAA CUGAUGAG GCCGUUAGGC CGAA ICCACCCA
8551


1903
UUUGGGGC A UGGACAUU
1152
AAUGUCCA CUGAUGAG GCCGUUAGGC CGAA ICCCCAAA
8552


1909
GCAUGGAC A UUGACCCG
1153
CGGGUCAA CUGAUGAG GCCGUUAGGC CGAA IUCCAUGC
8553


1915
ACAUUGAC C CGUAUAAA
1154
UUUAUACG CUGAUGAG GCCGUUAGGC CGAA IUCAAUGU
8554


1916
CAUUGACC C GUAUAAAG
1155
CUUUAUAC CUGAUGAG GCCGUUAGGC CGAA IGUCAAUG
8555


1935
UUUGGAGC U UCUGUGGA
1156
UCCACAGA CUGAUGAG GCCGUUAGGC CGAA ICUCCAAA
8556


1938
GGAGCUUC U GUGGAGUU
1157
AACUCCAC CUGAUGAG GCCGUUAGGC CGAA IAAGCUCC
8557


1949
GGAGUUAC U CUCUUUUU
1158
AAAAAGAG CUGAUGAG GCCGUUAGGC CGAA IUAACUCC
8558


1951
AGUUACUC U CUUUUUUG
1159
CAAAAAAG CUGAUGAG GCCGUUAGGC CGAA IAGUAACU
8559


1953
UUACUCUC U UUUUUGCC
1160
GGCAAAAA CUGAUGAG GCCGUUAGGC CGAA IAGAGUAA
8560


1961
UUUUUUGC C UUCUGACU
1161
AGUCAGAA CUGAUGAG GCCGUUAGGC CGAA ICAAAAAA
8561


1962
UUUUUGCC U UCUGACUU
1162
AAGUCAGA CUGAUGAG GCCGUUAGGC CGAA IGCAAAAA
8562


1965
UUGCCUUC U GACUUCUU
1163
AAGAAGUC CUGAUGAG GCCGUUAGGC CGAA IAAGGCAA
8563


1969
CUUCUGAC U UCUUUCCU
1164
AGGAAAGA CUGAUGAG GCCGUUAGGC CGAA IUCAGAAG
8564


1972
CUGACUUC U UUCCUUCU
1165
AGAAGGAA CUGAUGAG GCCGUUAGGC CGAA IAAGUCAG
8565


1976
CUUCUUUC C UUCUAUUC
1166
GAAUAGAA CUGAUGAG GCCGUUAGGC CGAA IAAAGAAG
8566


1977
UUCUUUCC U UCUAUUCG
1167
CGAAUAGA CUGAUGAG GCCGUUAGGC CGAA IGAAAGAA
8567


1980
UUUCCUUC U AUUCGAGA
1168
UCUCGAAU CUGAUGAG GCCGUUAGGC CGAA IAAGGAAA
8568


1991
UCGAGAUC U CCUCGACA
1169
UGUCGAGG CUGAUGAG GCCGUUAGGC CGAA IAUCUCGA
8569


1993
GAGAUCUC C UCGACACC
1170
GGUGUCGA CUGAUGAG GCCGUUAGGC CGAA IAGAUCUC
8570


1994
AGAUCUCC U CGACACCG
1171
CGGUGUCG CUGAUGAG GCCGUUAGGC CGAA IGAGAUCU
8571


1999
UCCUCGAC A CCGCCUCU
1172
AGAGGCGG CUGAUGAG GCCGUUAGGC CGAA IUCGAGGA
8572


2001
CUCGACAC C GCCUCUGC
1173
GCAGAGGC CUGAUGAG GCCGUUAGGC CGAA IUGUCGAG
8573


2004
GACACCGC C UCUGCUCU
1174
AGAGCAGA CUGAUGAG GCCGUUAGGC CGAA ICGGUGUC
8574


2005
ACACCGCC U CUGCUCUG
1175
CAGAGCAG CUGAUGAG GCCGUUAGGC CGAA IGCGGUGU
8575


2007
ACCGCCUC U GCUCUGUA
1176
UACAGAGC CUGAUGAG GCCGUUAGGC CGAA IAGGCGGU
8576


2010
GCCUCUGC U CUGUAUCG
1177
CGAUACAG CUGAUGAG GCCGUUAGGC CGAA ICAGAGGC
8577


2012
CUCUGCUC U GUAUCGGG
1178
CCCGAUAC CUGAUGAG GCCGUUAGGC CGAA IAGCAGAG
8578


2025
CGGGGGGC C UUAGAGUC
1179
GACUCUAA CUGAUGAG GCCGUUAGGC CGAA ICCCCCCG
8579


2026
GGGGGGCC U UAGAGUCU
1180
AGACUCUA CUGAUGAG GCCGUUAGGC CGAA IGCCCCCC
8580


2034
UUAGAGUC U CCGGAACA
1181
UGUUCCGG CUGAUGAG GCCGUUAGGC CGAA IACUCUAA
8581


2036
AGAGUCUC C GGAACAUU
1182
AAUGUUCC CUGAUGAG GCCGUUAGGC CGAA IAGACUCU
8582


2042
UCCGGAAC A UUGUUCAC
1183
GUGAACAA CUGAUGAG GCCGUUAGGC CGAA IUUCCGGA
8583


2049
CAUUGUUC A CCUCACCA
1184
UGGUGAGG CUGAUGAG GCCGUUAGGC CGAA IAACAAUG
8584


2051
UUGUUCAC C UCACCAUA
1185
UAUGGUGA CUGAUGAG GCCGUUAGGC CGAA IUGAACAA
8585


2052
UGUUCACC U CACCAUAC
1186
GUAUGGUG CUGAUGAG GCCGUUAGGC CGAA IGUGAACA
8586


2054
UUCACCUC A CCAUACGG
1187
CCGUAUGG CUGAUGAG GCCGUUAGGC CGAA IAGGUGAA
8587


2056
CACCUCAC C AUACGGCA
1188
UGCCGUAU CUGAUGAG GCCGUUAGGC CGAA IUGAGGUG
8588


2057
ACCUCACC A UACGGCAC
1189
GUGCCGUA CUGAUGAG GCCGUUAGGC CGAA IGUGAGGU
8589


2064
CAUACGGC A CUCAGGCA
1190
UGCCUGAG CUGAUGAG GCCGUUAGGC CGAA ICCGUAUG
8590


2066
UACGGCAC U CAGGCAAG
1191
CUUGCCUG CUGAUGAG GCCGUUAGGC CGAA IUGCCGUA
8591


2068
CGGCACUC A GGCAAGCU
1192
AGCUUGCC CUGAUGAG GCCGUUAGGC CGAA IAGUGCCG
8592


2072
ACUCAGGC A AGCUAUUC
1193
GAAUAGCU CUGAUGAG GCCGUUAGGC CGAA ICCUGAGU
8593


2076
AGGCAAGC U AUUCUGUG
1194
CACAGAAU CUGAUGAG GCCGUUAGGC CGAA ICUUGCCU
8594


2081
AGCUAUUC U GUGUUGGG
1195
CCCAACAC CUGAUGAG GCCGUUAGGC CGAA IAAUAGCU
8595


2105
GAUGAAUC U AGCCACCU
1196
AGGUGGCU CUGAUGAG GCCGUUAGGC CGAA IAUUCAUC
8596


2109
AAUCUAGC C ACCUGGGU
1197
ACCCAGGU CUGAUGAG GCCGUUAGGC CGAA ICUAGAUU
8597


2110
AUCUAGCC A CCUGGGUG
1198
CACCCAGG CUGAUGAG GCCGUUAGGC CGAA IGCUAGAU
8598


2112
CUAGCCAC C UGGGUGGG
1199
CCCACCCA CUGAUGAG GCCGUUAGGC CGAA IUGGCUAG
8599


2113
UAGCCACC U GGGUGGGA
1200
UCCCACCC CUGAUGAG GCCGUUAGGC CGAA IGUGGCUA
8600


2138
GGAAGAUC C AGCAUCCA
1201
UGGAUGCU CUGAUGAG GCCGUUAGGC CGAA IAUCUUCC
8601


2139
GAAGAUCC A GCAUCCAG
1202
CUGGAUGC CUGAUGAG GCCGUUAGGC CGAA IGAUCUUC
8602


2142
GAUCCAGC A UCCAGGGA
1203
UCCCUGGA CUGAUGAG GCCGUUAGGC CGAA ICUGGAUC
8603


2145
CCAGCAUC C AGGGAAUU
1204
AAUUCCCU CUGAUGAG GCCGUUAGGC CGAA IAUGCUGG
8604


2146
CAGCAUCC A GGGAAUUA
1205
UAAUUCCC CUGAUGAG GCCGUUAGGC CGAA IGAUGCUG
8605


2161
UAGUAGUC A GCUAUGUC
1206
GACAUAGC CUGAUGAG GCCGUUAGGC CGAA IACUACUA
8606


2164
UAGUCAGC U AUGUCAAC
1207
GUUGACAU CUGAUGAG GCCGUUAGGC CGAA ICUGACUA
8607


2170
GCUAUGUC A ACGUUAAU
1208
AUUAACGU CUGAUGAG GCCGUUAGGC CGAA IACAUAGC
8608


2185
AUAUGGGC C UAAAAAUC
1209
GAUUUUUA CUGAUGAG GCCGUUAGGC CGAA ICCCAUAU
8609


2186
UAUGGGCC U AAAAAUCA
1210
UGAUUUUU CUGAUGAG GCCGUUAGGC CGAA IGCCCAUA
8610


2194
UAAAAAUC A GACAACUA
1211
UAGUUGUC CUGAUGAG GCCGUUAGGC CGAA IAUUUUUA
8611


2198
AAUCAGAC A ACUAUUGU
1212
ACAAUAGU CUGAUGAG GCCGUUAGGC CGAA IUCUGAUU
8612


2201
CAGACAAC U AUUGUGGU
1213
ACCACAAU CUGAUGAG GCCGUUAGGC CGAA IUUGUCUG
8613


2213
GUGGUUUC A CAUUUCCU
1214
AGGAAAUG CUGAUGAG GCCGUUAGGC CGAA IAAACCAC
8614


2215
GGUUUCAC A UUUCCUGU
1215
ACAGGAAA CUGAUGAG GCCGUUAGGC CGAA IUGAAACC
8615


2220
CACAUUUC C UGUCUUAC
1216
GUAAGACA CUGAUGAG GCCGUUAGGC CGAA IAAAUGUG
8616


2221
ACAUUUCC U GUCUUACU
1217
AGUAAGAC CUGAUGAG GCCGUUAGGC CGAA IGAAAUGU
8617


2225
UUCCUGUC U UACUUUUG
1218
CAAAAGUA CUGAUGAG GCCGUUAGGC CGAA IACAGGAA
8618


2229
UGUCUUAC U UUUGGGCG
1219
CGCCCAAA CUGAUGAG GCCGUUAGGC CGAA IUAAGACA
8619


2244
CGAGAAAC U GUUCUUGA
1220
UCAAGAAC CUGAUGAG GCCGUUAGGC CGAA IUUUCUCG
8620


2249
AACUGUUC U UGAAUAUU
1221
AAUAUUCA CUGAUGAG GCCGUUAGGC CGAA IAACAGUU
8621


2265
UUGGUGUC U UUUGGAGU
1222
ACUCCAAA CUGAUGAG GCCGUUAGGC CGAA IACACCAA
8622


2284
GGAUUCGC A CUCCUCCU
1223
AGGAGGAG CUGAUGAG GCCGUUAGGC CGAA ICGAAUCC
8623


2286
AUUCGCAC U CCUCCUGC
1224
GCAGGAGG CUGAUGAG GCCGUUAGGC CGAA IUGCGAAU
8624


2288
UCGCACUC C UCCUGCAU
1225
AUGCAGGA CUGAUGAG GCCGUUAGGC CGAA IAGUGCGA
8625


2289
CGCACUCC U CCUGCAUA
1226
UAUGCAGG CUGAUGAG GCCGUUAGGC CGAA IGAGUGCG
8626


2291
CACUCCUC C UGCAUAUA
1227
UAUAUGCA CUGAUGAG GCCGUUAGGC CGAA IAGGAGUG
8627


2292
ACUCCUCC U GCAUAUAG
1228
CUAUAUGC CUGAUGAG GCCGUUAGGC CGAA IGAGGAGU
8628


2295
CCUCCUGC A UAUAGACC
1229
GGUCUAUA CUGAUGAG GCCGUUAGGC CGAA ICAGGAGG
8629


2303
AUAUAGAC C ACCAAAUG
1230
CAUUUGGU CUGAUGAG GCCGUUAGGC CGAA IUCUAUAU
8630


2304
UAUAGACC A CCAAAUGC
1231
GCAUUUGG CUGAUGAG GCCGUUAGGC CGAA IGUCUAUA
8631


2306
UAGACCAC C AAAUGCCC
1232
GGGCAUUU CUGAUGAG GCCGUUAGGC CGAA IUGGUCUA
8632


2307
AGACCACC A AAUGCCCC
1233
GGGGCAUU CUGAUGAG GCCGUUAGGC CGAA IGUGGUCU
8633


2313
CCAAAUGC C CCUAUCUU
1234
AAGAUAGG CUGAUGAG GCCGUUAGGC CGAA ICAUUUGG
8634


2314
CAAAUGCC C CUAUCUUA
1235
UAAGAUAG CUGAUGAG GCCGUUAGGC CGAA IGCAUUUG
8635


2315
AAAUGCCC C UAUCUUAU
1236
AUAAGAUA CUGAUGAG GCCGUUAGGC CGAA IGGCAUUU
8636


2316
AAUGCCCC U AUCUUAUC
1237
GAUAAGAU CUGAUGAG GCCGUUAGGC CGAA IGGGCAUU
8637


2320
CCCCUAUC U UAUCAACA
1238
UGUUGAUA CUGAUGAG GCCGUUAGGC CGAA IAUAGGGG
8638


2325
AUCUUAUC A ACACUUCC
1239
GGAAGUGU CUGAUGAG GCCGUUAGGC CGAA IAUAAGAU
8639


2328
UUAUCAAC A CUUCCGGA
1240
UCCGGAAG CUGAUGAG GCCGUUAGGC CGAA IUUGAUAA
8640


2330
AUCAACAC U UCCGGAAA
1241
UUUCCGGA CUGAUGAG GCCGUUAGGC CGAA IUGUUGAU
8641


2333
AACACUUC C GGAAACUA
1242
UAGUUUCC CUGAUGAG GCCGUUAGGC CGAA IAAGUGUU
8642


2340
CCGGAAAC U ACUGUUGU
1243
ACAACAGU CUGAUGAG GCCGUUAGGC CGAA IUUUCCGG
8643


2343
GAAACUAC U GUUGUUAG
1244
CUAACAAC CUGAUGAG GCCGUUAGGC CGAA IUAGUUUC
8644


2362
GAAGAGGC A GGUCCCCU
1245
AGGGGACC CUGAUGAG GCCGUUAGGC CGAA ICCUCUUC
8645


2367
GGCAGGUC C CCUAGAAG
1246
CUUCUAGG CUGAUGAG GCCGUUAGGC CGAA IACCUGCC
8646


2368
GCAGGUCC C CUAGAAGA
1247
UCUUCUAG CUGAUGAG GCCGUUAGGC CGAA IGACCUGC
8647


2369
CAGGUCCC C UAGAAGAA
1248
UUCUUCUA CUGAUGAG GCCGUUAGGC CGAA IGGACCUG
8648


2370
AGGUCCCC U AGAAGAAG
1249
CUUCUUCU CUGAUGAG GCCGUUAGGC CGAA IGGGACCU
8649


2382
AGAAGAAC U CCCUCGCC
1250
GGCGAGGG CUGAUGAG GCCGUUAGGC CGAA IUUCUUCU
8650


2384
AAGAACUC C CUCGCCUC
1251
GAGGCGAG CUGAUGAG GCCGUUAGGC CGAA IAGUUCUU
8651


2385
AGAACUCC C UCGCCUCG
1252
CGAGGCGA CUGAUGAG GCCGUUAGGC CGAA IGAGUUCU
8652


2386
GAACUCCC U CGCCUCGC
1253
GCGAGGCG CUGAUGAG GCCGUUAGGC CGAA IGGAGUUC
8653


2390
UCCCUCGC C UCGCAGAC
1254
GUCUGCGA CUGAUGAG GCCGUUAGGC CGAA ICGAGGGA
8654


2391
CCCUCGCC U CGCAGACG
1255
CGUCUGCG CUGAUGAG GCCGUUAGGC CGAA IGCGAGGG
8655


2395
CGCCUCGC A GACGAAGG
1256
CCUUCGUC CUGAUGAG GCCGUUAGGC CGAA ICGAGGCG
8656


2406
CGAAGGUC U CAAUCGCC
1257
GGCGAUUG CUGAUGAG GCCGUUAGGC CGAA IACCUUCG
8657


2408
AAGGUCUC A AUCGCCGC
1258
GCGGCGAU CUGAUGAG GCCGUUAGGC CGAA IAGACCUU
8658


2414
UCAAUCGC C GCGUCGCA
1259
UGCGACGC CUGAUGAG GCCGUUAGGC CGAA ICGAUUGA
8659


2422
CGCGUCGC A GAAGAUCU
1260
AGAUCUUC CUGAUGAG GCCGUUAGGC CGAA ICGACGCG
8660


2430
AGAAGAUC U CAAUCUCG
1261
CGAGAUUG CUGAUGAG GCCGUUAGGC CGAA IAUCUUCU
8661


2432
AAGAUCUC A AUCUCGGG
1262
CCCGAGAU CUGAUGAG GCCGUUAGGC CGAA IAGAUCUU
8662


2436
UCUCAAUC U CGGGAAUC
1263
GAUUCCCG CUGAUGAG GCCGUUAGGC CGAA IAUUGAGA
8663


2445
CGGGAAUC U CAAUGUUA
1264
UAACAUUG CUGAUGAG GCCGUUAGGC CGAA IAUUCCCG
8664


2447
GGAAUCUC A AUGUUAGU
1265
ACUAACAU CUGAUGAG GCCGUUAGGC CGAA IAGAUUCC
8665


2460
UAGUAUUC C UUGGACAC
1266
GUGUCCAA CUGAUGAG GCCGUUAGGC CGAA IAAUACUA
8666


2461
AGUAUUCC U UGGACACA
1267
UGUGUCCA CUGAUGAG GCCGUUAGGC CGAA IGAAUACU
8667


2467
CCUUGGAC A CAUAAGGU
1268
ACCUUAUG CUGAUGAG GCCGUUAGGC CGAA IUCCAAGG
8668


2469
UUGGACAC A UAAGGUGG
1269
CCACCUUA CUGAUGAG GCCGUUAGGC CGAA IUGUCCAA
8669


2483
UGGGAAAC U UUACGGGG
1270
CCCCGUAA CUGAUGAG GCCGUUAGGC CGAA IUUUCCCA
8670


2493
UACGGGGC U UUAUUCUU
1271
AAGAAUAA CUGAUGAG GCCGUUAGGC CGAA ICCCCGUA
8671


2500
CUUUAUUC U UCUACGGU
1272
ACCGUAGA CUGAUGAG GCCGUUAGGC CGAA IAAUAAAG
8672


2503
UAUUCUUC U ACGGUACC
1273
GGUACCGU CUGAUGAG GCCGUUAGGC CGAA IAAGAAUA
8673


2511
UACGGUAC C UUGCUUUA
1274
UAAAGCAA CUGAUGAG GCCGUUAGGC CGAA IUACCGUA
8674


2512
ACGGUACC U UGCUUUAA
1275
UUAAAGCA CUGAUGAG GCCGUUAGGC CGAA IGUACCGU
8675


2516
UACCUUGC U UUAAUCCU
1276
AGGAUUAA CUGAUGAG GCCGUUAGGC CGAA ICAAGGUA
8676


2523
CUUUAAUC C UAAAUGGC
1277
GCCAUUUA CUGAUGAG GCCGUUAGGC CGAA IAUUAAAG
8677


2524
UUUAAUCC U AAAUGGCA
1278
UGCCAUUU CUGAUGAG GCCGUUAGGC CGAA IGAUUAAA
8678


2532
UAAAUGGC A AACUCCUU
1279
AAGGAGUU CUGAUGAG GCCGUUAGGC CGAA ICCAUUUA
8679


2536
UGGCAAAC U CCUUCUUU
1280
AAAGAAGG CUGAUGAG GCCGUUAGGC CGAA IUUUGCCA
8680


2538
GCAAACUC C UUCUUUUC
1281
GAAAAGAA CUGAUGAG GCCGUUAGGC CGAA IAGUUUGC
8681


2539
CAAACUCC U UCUUUUCC
1282
GGAAAAGA CUGAUGAG GCCGUUAGGC CGAA IGAGUUUG
8682


2542
ACUCCUUC U UUUCCUGA
1283
UCAGGAAA CUGAUGAG GCCGUUAGGC CGAA IAAGGAGU
8683


2547
UUCUUUUC C UGACAUUC
1284
GAAUGUCA CUGAUGAG GCCGUUAGGC CGAA IAAAAGAA
8684


2548
UCUUUUCC U GACAUUCA
1285
UGAAUGUC CUGAUGAG GCCGUUAGGC CGAA IGAAAAGA
8685


2552
UUCCUGAC A UUCAUUUG
1286
CAAAUGAA CUGAUGAG GCCGUUAGGC CGAA IUCAGGAA
8686


2556
UGACAUUC A UUUGCAGG
1287
CCUGCAAA CUGAUGAG GCCGUUAGGC CGAA IAAUGUCA
8687


2562
UCAUUUGC A GGAGGACA
1288
UGUCCUCC CUGAUGAG GCCGUUAGGC CGAA ICAAAUGA
8688


2570
AGGAGGAC A UUGUUGAU
1289
AUCAACAA CUGAUGAG GCCGUUAGGC CGAA IUCCUCCU
8689


2589
AUGUAAGC A AUUUGUGG
1290
CCACAAAU CUGAUGAG GCCGUUAGGC CGAA ICUUACAU
8690


2601
UGUGGGGC C CCUUACAG
1291
CUGUAAGG CUGAUGAG GCCGUUAGGC CGAA ICCCCACA
8691


2602
GUGGGGCC C CUUACAGU
1292
ACUGUAAG CUGAUGAG GCCGUUAGGC CGAA IGCCCCAC
8692


2603
UGGGGCCC C UUACAGUA
1293
UACUGUAA CUGAUGAG GCCGUUAGGC CGAA IGGCCCCA
8693


2604
GGGGCCCC U UACAGUAA
1294
UUACUGUA CUGAUGAG GCCGUUAGGC CGAA IGGGCCCC
8694


2608
CCCCUUAC A GUAAAUGA
1295
UCAUUUAC CUGAUGAG GCCGUUAGGC CGAA IUAAGGGG
8695


2621
AUGAAAAC A GGAGACUU
1296
AAGUCUCC CUGAUGAG GCCGUUAGGC CGAA IUUUUCAU
8696


2628
CAGGAGAC U UAAAUUAA
1297
UUAAUUUA CUGAUGAG GCCGUUAGGC CGAA IUCUCCUG
8697


2638
AAAUUAAC U AUGCCUGC
1298
GCAGGCAU CUGAUGAG GCCGUUAGGC CGAA IUUAAUUU
8698


2643
AACUAUGC C UGCUAGGU
1299
ACCUAGCA CUGAUGAG GCCGUUAGGC CGAA ICAUAGUU
8699


2644
ACUAUGCC U GCUAGGUU
1300
AACCUAGC CUGAUGAG GCCGUUAGGC CGAA IGCAUAGU
8700


2647
AUGCCUGC U AGGUUUUA
1301
UAAAACCU CUGAUGAG GCCGUUAGGC CGAA ICAGGCAU
8701


2658
GUUUUAUC C CAAUGUUA
1302
UAACAUUG CUGAUGAG GCCGUUAGGC CGAA IAUAAAAC
8702


2659
UUUUAUCC C AAUGUUAC
1303
GUAACAUU CUGAUGAG GCCGUUAGGC CGAA IGAUAAAA
8703


2660
UUUAUCCC A AUGUUACU
1304
AGUAACAU CUGAUGAG GCCGUUAGGC CGAA IGGAUAAA
8704


2668
AAUGUUAC U AAAUAUUU
1305
AAAUAUUU CUGAUGAG GCCGUUAGGC CGAA IUAACAUU
8705


2679
AUAUUUGC C CUUAGAUA
1306
UAUCUAAG CUGAUGAG GCCGUUAGGC CGAA ICAAAUAU
8706


2680
UAUUUGCC C UUAGAUAA
1307
UUAUCUAA CUGAUGAG GCCGUUAGGC CGAA IGCAAAUA
8707


2681
AUUUGCCC U UAGAUAAA
1308
UUUAUCUA CUGAUGAG GCCGUUAGGC CGAA IGGCAAAU
8708


2696
AAGGGAUC A AACCGUAU
1309
AUACGGUU CUGAUGAG GCCGUUAGGC CGAA IAUCCCUU
8709


2700
GAUCAAAC C GUAUUAUC
1310
GAUAAUAC CUGAUGAG GCCGUUAGGC CGAA IUUUGAUC
8710


2709
GUAUUAUC C AGAGUAUG
1311
CAUACUCU CUGAUGAG GCCGUUAGGC CGAA IAUAAUAC
8711


2710
UAUUAUCC A GAGUAUGU
1312
ACAUACUC CUGAUGAG GCCGUUAGGC CGAA IGAUAAUA
8712


2727
AGUUAAUC A UUACUUCC
1313
GGAAGUAA CUGAUGAG GCCGUUAGGC CGAA IAUUAACU
8713


2732
AUCAUUAC U UCCAGACG
1314
CGUCUGGA CUGAUGAG GCCGUUAGGC CGAA IUAAUGAU
8714


2735
AUUACUUC C AGACGCGA
1315
UCGCGUCU CUGAUGAG GCCGUUAGGC CGAA IAAGUAAU
8715


2736
UUACUUCC A GACGCGAC
1316
GUCGCGUC CUGAUGAG GCCGUUAGGC CGAA IGAAGUAA
8716


2745
GACGCGAC A UUAUUUAC
1317
GUAAAUAA CUGAUGAG GCCGUUAGGC CGAA IUCGCGUC
8717


2754
UUAUUUAC A CACUCUUU
1318
AAAGAGUG CUGAUGAG GCCGUUAGGC CGAA IUAAAUAA
8718


2756
AUUUACAC A CUCUUUGG
1319
CCAAAGAG CUGAUGAG GCCGUUAGGC CGAA IUGUAAAU
8719


2758
UUACACAC U CUUUGGAA
1320
UUCCAAAG CUGAUGAG GCCGUUAGGC CGAA IUGUGUAA
8720


2760
ACACACUC U UUGGAAGG
1321
CCUUCCAA CUGAUGAG GCCGUUAGGC CGAA IAGUGUGU
8721


2777
CGGGGAUC U UAUAUAAA
1322
UUUAUAUA CUGAUGAG GCCGUUAGGC CGAA IAUCCCCG
8722


2794
AGAGAGUC C ACACGUAG
1323
CUACGUGU CUGAUGAG GCCGUUAGGC CGAA IACUCUCU
8723


2795
GAGAGUCC A CACGUAGC
1324
GCUACGUG CUGAUGAG GCCGUUAGGC CGAA IGACUCUC
8724


2797
GAGUCCAC A CGUAGCGC
1325
GCGCUACG CUGAUGAG GCCGUUAGGC CGAA IUGGACUC
8725


2806
CGUAGCGC C UCAUUUUG
1326
CAAAAUGA CUGAUGAG GCCGUUAGGC CGAA ICGCUACG
8726


2807
GUAGCGCC U CAUUUUGC
1327
GCAAAAUG CUGAUGAG GCCGUUAGGC CGAA IGCGCUAC
8727


2809
AGCGCCUC A UUUUGCGG
1328
CCGCAAAA CUGAUGAG GCCGUUAGGC CGAA IAGGCGCU
8728


2821
UGCGGGUC A CCAUAUUC
1329
GAAUAUGG CUGAUGAG GCCGUUAGGC CGAA IACCCGCA
8729


2823
CGGGUCAC C AUAUUCUU
1330
AAGAAUAU CUGAUGAG GCCGUUAGGC CGAA IUGACCCG
8730


2824
GGGUCACC A UAUUCUUG
1331
CAAGAAUA CUGAUGAG GCCGUUAGGC CGAA IGUGACCC
8731


2830
CCAUAUUC U UGGGAACA
1332
UGUUCCCA CUGAUGAG GCCGUUAGGC CGAA IAAUAUGG
8732


2838
UUGGGAAC A AGAUCUAC
1333
GUAGAUCU CUGAUGAG GCCGUUAGGC CGAA IUUCCCAA
8733


2844
ACAAGAUC U ACAGCAUG
1334
CAUGCUGU CUGAUGAG GCCGUUAGGC CGAA IAUCUUGU
8734


2847
AGAUCUAC A GCAUGGGA
1335
UCCCAUGC CUGAUGAG GCCGUUAGGC CGAA IUAGAUCU
8735


2850
UCUACAGC A UGGGAGGU
1336
ACCUCCCA CUGAUGAG GCCGUUAGGC CGAA ICUGUAGA
8736


2864
GGUUGGUC U UCCAAACC
1337
GGUUUGGA CUGAUGAG GCCGUUAGGC CGAA IACCAACC
8737


2867
UGGUCUUC C AAACCUCG
1338
CGAGGUUU CUGAUGAG GCCGUUAGGC CGAA IAAGACCA
8738


2868
GGUCUUCC A AACCUCGA
1339
UCGAGGUU CUGAUGAG GCCGUUAGGC CGAA IGAAGACC
8739


2872
UUCCAAAC C UCGAAAAG
1340
CUUUUCGA CUGAUGAG GCCGUUAGGC CGAA IUUUGGAA
8740


2873
UCCAAACC U CGAAAAGG
1341
CCUUUUCG CUGAUGAG GCCGUUAGGC CGAA IGUUUGGA
8741


2883
GAAAAGGC A UGGGGACA
1342
UGUCCCCA CUGAUGAG GCCGUUAGGC CGAA ICCUUUUC
8742


2891
AUGGGGAC A AAUCUUUC
1343
GAAAGAUU CUGAUGAG GCCGUUAGGC CGAA IUCCCCAU
8743


2896
GACAAAUC U UUCUGUCC
1344
GGACAGAA CUGAUGAG GCCGUUAGGC CGAA IAUUUGUC
8744


2900
AAUCUUUC U GUCCCCAA
1345
UUGGGGAC CUGAUGAG GCCGUUAGGC CGAA IAAAGAUU
8745


2904
UUUCUGUC C CCAAUCCC
1346
GGGAUUGG CUGAUGAG GCCGUUAGGC CGAA IACAGAAA
8746


2905
UUCUGUCC C CAAUCCCC
1347
GGGGAUUG CUGAUGAG GCCGUUAGGC CGAA IGACAGAA
8747


2906
UCUGUCCC C AAUCCCCU
1348
AGGGGAUU CUGAUGAG GCCGUUAGGC CGAA IGGACAGA
8748


2907
CUGUCCCC A AUCCCCUG
1349
CAGGGGAU CUGAUGAG GCCGUUAGGC CGAA IGGGACAG
8749


2911
CCCCAAUC C CCUGGGAU
1350
AUCCCAGG CUGAUGAG GCCGUUAGGC CGAA IAUUGGGG
8750


2912
CCCAAUCC C CUGGGAUU
1351
AAUCCCAG CUGAUGAG GCCGUUAGGC CGAA IGAUUGGG
8751


2913
CCAAUCCC C UGGGAUUC
1352
GAAUCCCA CUGAUGAG GCCGUUAGGC CGAA IGGAUUGG
8752


2914
CAAUCCCC U GGGAUUCU
1353
AGAAUCCC CUGAUGAG GCCGUUAGGC CGAA IGGGAUUG
8753


2922
UGGGAUUC U UCCCCGAU
1354
AUCGGGGA CUGAUGAG GCCGUUAGGC CGAA IAAUCCCA
8754


2925
GAUUCUUC C CCGAUCAU
1355
AUGAUCGG CUGAUGAG GCCGUUAGGC CGAA IAAGAAUC
8755


2926
AUUCUUCC C CGAUCAUC
1356
GAUGAUCG CUGAUGAG GCCGUUAGGC CGAA IGAAGAAU
8756


2927
UUCUUCCC C GAUCAUCA
1357
UGAUGAUC CUGAUGAG GCCGUUAGGC CGAA IGGAAGAA
8757


2932
CCCCGAUC A UCAGUUGG
1358
CCAACUGA CUGAUGAG GCCGUUAGGC CGAA IAUCGGGG
8758


2935
CGAUCAUC A GUUGGACC
1359
GGUCCAAC CUGAUGAG GCCGUUAGGC CGAA IAUGAUCG
8759


2943
AGUUGGAC C CUGCAUUC
1360
GAAUGCAG CUGAUCAG GCCGUUAGGC CGAA IUCCAACU
8760


2944
GUUGGACC C UGCAUUCA
1361
UGAAUGCA CUGAUGAG GCCGUUAGGC CGAA IGUCCAAC
8762


2945
UUGGACCC U GCAUUCAA
1362
UUGAAUGC CUGAUGAG GCCGUUAGGC CGAA IGGUCCAA
8762


2948
GACCCUGC A UUCAAAGC
1363
GCUUUGAA CUGAUGAG GCCGUUAGGC CGAA ICAGGGUC
8763


2952
CUGCAUUC A AAGCCAAC
1364
GUUGGCUU CUGAUGAG GCCGUUAGGC CGAA IAAUGCAG
8764


2957
UUCAAAGC C AACUCAGU
1365
ACUGAGUU CUGAUGAG GCCGUUAGGC CGAA ICUUUGAA
8765


2958
UCAAAGCC A ACUCAGUA
1366
UACUGAGU CUGAUGAG GCCGUUAGGC CGAA IGCUUUGA
8766


2961
AAGCCAAC U CAGUAAAU
1367
AUUUACUG CUGAUGAG GCCGUUAGGC CGAA IUUGGCUU
8767


2963
GCCAACUC A GUAAAUCC
1368
GGAUUUAC CUGAUGAG GCCGUUAGGC CGAA IAGUUGGC
8768


2971
AGUAAAUC C AGAUUGGG
1369
CCCAAUCU CUGAUGAG GCCGUUAGGC CGAA IAUUUACU
8769


2972
GUAAAUCC A GAUUGGGA
1370
UCCCAAUC CUGAUGAG GCCGUUAGGC CGAA IGAUUUAC
8770


2982
AUUGGGAC C UCAACCCG
1371
CGGGUUGA CUGAUGAG GCCGUUAGGC CGAA IUCCCAAU
8771


2983
UUGGGACC U CAACCCGC
1372
GCGGGUUG CUGAUGAG GCCGUUAGGC CGAA IGUCCCAA
8772


2985
GGGACCUC A ACCCGCAC
1373
GUGCGGGU CUGAUGAG GCCGUUAGGC CGAA IAGGUCCC
8773


2988
ACCUCAAC C CGCACAAG
1374
CUUGUGCG CUGAUGAG GCCGUUAGGC CGAA IUUGAGGU
8774


2989
CCUCAACC C GCACAAGG
1375
CCUUGUGC CUGAUGAG GCCGUUAGGC CGAA IGUUGAGG
8775


2992
CAACCCGC A CAAGGACA
1376
UGUCCUUG CUGAUGAG GCCGUUAGGC CGAA ICGGGUUG
8776


2994
ACCCGCAC A AGGACAAC
1377
GUUGUCCU CUGAUGAG GCCGUUAGGC CGAA IUGCGGGU
8777


3000
ACAAGGAC A ACUGGCCG
1378
CGGCCAGU CUGAUGAG GCCGUUAGGC CGAA IUCCUUGU
8778


3003
AGGACAAC U GGCCGGAC
1379
GUCCGGCC CUGAUGAG GCCGUUAGGC CGAA IUUGUCCU
8779


3007
CAACUGGC C GGACGCCA
1380
UGGCGUCC CUGAUGAG GCCGUUAGGC CGAA ICCAGUUG
8780


3014
CCGGACGC C AACAAGGU
1381
ACCUUGUU CUGAUGAG GCCGUUAGGC CGAA ICGUCCGG
8781


3015
CGGACGCC A ACAAGGUG
1382
CACCUUGU CUGAUGAG GCCGUUAGGC CGAA IGCGUCCG
8782


3018
ACGCCAAC A AGGUGGGA
1383
UCCCACCU CUGAUGAG GCCGUUAGGC CGAA IUUGGCGU
8783


3035
GUGGGAGC A UUCGGGCC
1384
GGCCCGAA CUGAUGAG GCCGUUAGGC CGAA ICUCCCAC
8784


3043
AUUCGGGC C AGGGUUCA
1385
UGAACCCU CUGAUGAG GCCGUUAGGC CGAA ICCCGAAU
8785


3044
UUCGGGCC A GGGUUCAC
1386
GUGAACCC CUGAUGAG GCCGUUAGGC CGAA IGCCCGAA
8786


3051
CAGGGUUC A CCCCUCCC
1387
GGGAGGGG CUGAUGAG GCCGUUAGGC CGAA IAACCCUG
8787


3053
GGGUUCAC C CCUCCCCA
1388
UGGGGAGG CUGAUGAG GCCGUUAGGC CGAA IUGAACCC
8788


3054
GGUUCACC C CUCCCCAU
1389
AUGGGGAG CUGAUGAG GCCGUUAGGC CGAA IGUGAACC
8789


3055
GUUCACCC C UCCCCAUG
1390
CAUGGGGA CUGAUGAG GCCGUUAGGC CGAA IGGUGAAC
8790


3056
UUCACCCC U CCCCAUGG
1391
CCAUGGGG CUGAUGAG GCCGUUAGGC CGAA IGGGUGAA
8791


3058
CACCCCUC C CCAUGGGG
1392
CCCCAUGG CUGAUGAG GCCGUUAGGC CGAA IAGGGGUG
8792


3059
ACCCCUCC C CAUGGGGG
1393
CCCCCAUG CUGAUGAG GCCGUUAGGC CGAA IGAGGGGU
8793


3060
CCCCUCCC C AUGGGGGA
1394
UCCCCCAU CUGAUGAG GCCGUUAGGC CGAA IGGAGGGG
8794


3061
CCCUCCCC A UGGGGGAC
1395
GUCCCCCA CUGAUGAG GCCGUUAGGC CGAA IGGGAGGG
8795


3070
UGGGGGAC U GUUGGGGU
1396
ACCCCAAC CUGAUGAG GCCGUUAGGC CGAA IUCCCCCA
8796


3084
GGUGGAGC C CUCACGCU
1397
AGCGUGAG CUGAUGAG GCCGUUAGGC CGAA ICUCCACC
8797


3085
GUGGAGCC C UCACGCUC
1398
GAGCGUGA CUGAUGAG GCCGUUAGGC CGAA IGCUCCAC
8798


3086
UGGAGCCC U CACGCUCA
1399
UGAGCGUG CUGAUGAG GCCGUUAGGC CGAA IGGCUCCA
8799


3088
GAGCCCUC A CGCUCAGG
1400
CCUGAGCG CUGAUGAG GCCGUUAGGC CGAA IAGGGCUC
8800


3092
CCUCACGC U CAGGGCCU
1401
AGGCCCUG CUGAUGAG GCCGUUAGGC CGAA ICGUGAGG
8801


3094
UCACGCUC A GGGCCUAC
1402
GUAGGCCC CUGAUGAG GCCGUUAGGC CGAA IAGCGUGA
8802


3099
CUCAGGGC C UACUCACA
1403
UGUGAGUA CUGAUGAG GCCGUUAGGC CGAA ICCCUGAG
8803


3100
UCAGGGCC U ACUCACAA
1404
UUGUGAGU CUGAUGAG GCCGUUAGGC CGAA IGCCCUGA
8804


3103
GGGCCUAC U CACAACUG
1405
CAGUUGUG CUGAUGAG GCCGUUAGGC CGAA IUAGGCCC
8805


3105
GCCUACUC A CAACUGUG
1406
CACAGUUG CUGAUGAG GCCGUUAGGC CGAA IAGUAGGC
8806


3107
CUACUCAC A ACUGUGCC
1407
GGCACAGU CUGAUGAG GCCGUUAGGC CGAA IUGAGUAG
8807


3110
CUCACAAC U GUGCCAGC
1408
GCUGGCAC CUGAUGAG GCCGUUAGGC CGAA IUUGUGAG
8808


3115
AACUGUGC C AGCAGCUC
1409
GAGCUGCU CUGAUGAG GCCGUUAGGC CGAA ICACAGUU
8809


3116
ACUGUGCC A GCAGCUCC
1410
GGAGCUGC CUGAUGAG GCCGUUAGGC CGAA IGCACAGU
8810


3119
GUGCCAGC A GCUCCUCC
1411
GCAGGAGC CUGAUQAG GCCGUUAGGC CGAA ICUGGCAC
8811


3122
CCAGCAGC U CCUCCUCC
1412
GGAGGAGG CUGAUGAG GCCGUUAGGC CGAA ICUGCUGG
8812


3124
AGCAGCUC C UCCUCCUG
1413
CAGGAGGA CUGAUGAG GCCGUUAGGC CGAA IAGCUGCU
8813


3125
GCAGCUCC U CCUCCUGC
1414
GCAGGAGG CUGAUGAG GCCGUUAGGC CGAA IGAGCUGC
8814


3127
AGCUCCUC C UCCUGCCU
1415
AGGCAGGA CUGAUGAG GCCGUUAGGC CGAA IAGGAGCU
8815


3128
GCUCCUCC U CCUGCCUC
1416
GAGGCAGG CUGAUGAG GCCGUUAGGC CGAA IGAGGAGC
8816


3130
UCCUCCUC C UGCCUCCA
1417
UGGAGGCA CUGAUGAG GCCGUUAGGC CGAA IAGGAGGA
8817


3131
CCUCCUCC U GCCUCCAC
1418
GUGGAGGC CUGAUGAG GCCGUUAGGC CGAA IGAGGAGG
8818


3134
CCUCCUGC C UCCACCAA
1419
UUGGUGGA CUGAUGAG GCCGUUAGGC CGAA ICAGGAGG
8819


3135
CUCCUGCC U CCACCAAU
1420
AUUGGUGO CUGAUGAG GCCGUUAGGC CGAA IGCAGGAG
8820


3137
CCUGCCUC C ACCAAUCG
1421
CGAUUGGU CUGAUGAG GCCGUUAGGC CGAA IAGGCAGG
8821


3138
CUGCCUCC A CCAAUCGG
1422
CCGAUUGG CUGAUGAG GCCGUUAGGC CGAA IGAGGCAG
8822


3140
GCCUCCAC C AAUCGGCA
1423
UGCCGAUU CUGAUGAG GCCGUUAGGC CGAA IUGGAGGC
8823


3141
CCUCCACC A AUCGGCAG
1424
CUGCCGAU CUGAUGAG GCCGUUAGGC CGAA IGUGGAGG
8824


3148
CAAUCGGC A GUCAGGAA
1425
UUCCUGAC CUGAUGAG GCCGUUAGGC CGAA ICCGAUUG
8825


3152
CGGCAGUC A GGAAGGCA
1426
UGCCUUCC CUGAUGAG GCCGUUAGGC CGAA IACUGCCG
8826


3160
AGGAAGGC A GCCUACUC
1427
GAGUAGGC CUGAUGAG GCCGUUAGGC CGAA ICCUUCCU
8827


3163
AAGGCAGC C UACUCCCU
1428
AGGGAGUA CUGAUGAG GCCGUUAGGC CGAA ICUGCCUU
8828


3164
AGGCAGCC U ACUCCCUU
1429
AAGGGAGU CUGAUGAG GCCGUUAGGC CGAA IGCUGCCU
8829


3167
CAGCCUAC U CCCUUAUC
1430
GAUAAGGG CUGAUGAG GCCGUUAGGC CGAA IUAGGCUG
8830


3169
GCCUACUC C CUUAUCUC
1431
GAGAUAAG CUGAUGAG GCCGUUAGGC CGAA IAGUAGGC
8831


3170
CCUACUCC C UUAUCUCC
1432
GGAGAUAA CUGAUGAG GCCGUUAGGC CGAA IGAGUAGG
8832


3171
CUACUCCC U UAUCUCCA
1433
UGGAGAUA CUGAUGAG GCCGUUAGGC CGAA IGGAGUAG
8833


3176
CCCUUAUC U CCACCUCU
1434
AGAGGUGG CUGAUGAG GCCGUUAGGC CGAA IAUAAGGG
8834


3178
CUUAUCUC C ACCUCUAA
1435
UUAGAGGU CUGAUGAG GCCGUUAGGC CGAA IAGAUAAG
8835


3179
UUAUCUCC A CCUCUAAG
1436
CUUAGAGG CUGAUGAG GCCGUUAGGC CGAA IGAGAUAA
8836


3181
AUCUCCAC C UCUAAGGG
1437
CCCUUAGA CUGAUGAG GCCGUUAGGC CGAA IUGGAGAU
8837


3182
UCUCCACC U CUAAGGGA
1438
UCCCUUAG CUGAUGAG GCCGUUAGGC CGAA IGUGGAGA
8838


3184
UCCACCUC U AAGGGACA
1439
UGUCCCUU CUGAUGAG GCCGUUAGGC CGAA IAGGUGGA
8839


3192
UAAGGGAC A CUCAUCCU
1440
AGGAUGAG CUGAUGAG GCCGUUAGGC CGAA IUCCCUUA
8840


3194
AGGGACAC U CAUCCUCA
1441
UGAGGAUG CUGAUGAG GCCGUUAGGC CGAA IUGUCCCU
8841


3196
GGACACUC A UCCUCAGG
1442
CCUGAGGA CUGAUGAG GCCGUUAGGC CGAA IAGUGUCC
8842


3199
CACUCAUC C UCAGGCCA
1443
UGGCCUGA CUGAUGAG GCCGUUAGGC CGAA IAUGAGUG
8843


3200
ACUCAUCC U CAGGCCAU
1444
AUGGCCUG CUGAUGAG GCCGUUAGGC CGAA IGAUGAGU
8844


3202
UCAUCCUC A GGCCAUGC
1445
GCAUGGCC CUGAUGAG GCCGUUAGGC CGAA IAGGAUGA
8845


3206
CCUCAGGC C AUGCAGUG
1446
CACUGCAU CUGAUGAG GCCGUUAGGC CGAA ICCUGAGG
8846


3207
CUCAGGCC A UGCAGUGG
1447
CCACUGCA CUGAUGAG GCCGUUAGGC CGAA IGCCUGAG
8847






Input Sequence = AF100308.




Cut Site = CH/.




Stem Length = 8.




Core Sequence = CUGAUGAG X CGAA (X = GCCGUUAGGC or other stem II)




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




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




“I” stands for Inosime








[0555]

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
8848






87
GGAACAGU G AGCCCUGC
1449
GCAGGGCU UGAUG GCAUGCACUAUGC GCG ACUGUUCC
8849





94
UGAGCCCU G CUCAGAAU
1450
AUUCUGAG UGAUG GCAUGCACUAUGC GCG AGGGCUCA
8850





112
CUGUCUCU G CCAUAUCG
1451
CGAUAUGG UGAUG GCAUGCACUAUGC GCG AGAGACAG
8851





132
AUCUUAUC G AAGACUGG
1452
CCAGUCUU UGAUG GCAUGCACUAUGC GCG GAUAAGAU
8852





153
CCUGUACC G AACAUGGA
1453
UCCAUGUU UGAUG GCAUGCACUAUGC GCG GGUACAGG
8853





169
AGAACAUC G CAUCAGGA
1454
UCCUGAUG UGAUG GCAUGCACUAUGC GCG GAUGUUCU
8854





192
GGACCCCU G CUCGUGUU
1455
AACACGAG UGAUG GCAUGCACUAUGC GCG AGGGGUCC
8855





222
UUCUUGUU G ACAAAAAU
1456
AUUUUUGU UGAUG GCAUGCACUAUGC GCG AACAAGAA
8856





315
CAAAAUUC G CAGUCCCA
1457
UGGGACUG UGAUG GCAUGCACUAUGC GCG GAAUUUUG
8857





374
UGGUUAUC G CUGGAUGU
1458
ACAUCCAG UGAUG GCAUGCACUAUGC GCG GAUAACCA
8858





387
AUGUGUCU G CGGCGUUU
1459
AAACGCCG UGAUG GCAUGCACUAUGC GCG AGACACAU
8859





410
CUUCCUCU G CAUCCUGC
1460
GCAGGAUG UGAUG GCAUGCACUAUGC GCG AGAGGAAG
8860





417
UGCAUCCU G CUGCUAUG
1461
CAUAGCAG UGAUG GCAUGCACUAUGC GCG AGGAUGCA
8861





420
AUCCUGCU G CUAUGCCU
1462
AGGCAUAG UGAUG GCAUGCACUAUGC GCG AGCAGGAU
8862





425
GCUGCUAU G CCUCAUCU
1463
AGAUGAGG UGAUG GCAUGCACUAUGC GCG AUAGCAGC
8863





468
GGUAUGUU G CCCGUUUG
1464
CAAACGGG UGAUG GCAUGCACUAUGC GCG AACAUACC
8864





518
CGGACCAU G CAAAACCU
1465
AGGUUUUG UGAUG GCAUGCACUAUGC GCG AUGGUCCG
8865





527
CAAAACCU G CACAACUC
1466
GAGUUGUG UGAUG GCAUGCACUAUGC GCG AGGUUUUG
8866





538
CAACUCCU G CUCAAGGA
1467
UCCUUGAG UGAUG GCAUGCACUAUGC GCG AGGAGUUG
8867





569
CUCAUGUU G CUGUACAA
1468
UUGUACAG UGAUG GCAUGCACUAUGC GCG AACAUGAG
8868





596
CGGAAACU G CACCUGUA
1469
UACAGGUG UGAUG GCAUGCACUAUGC GCG AGUUUCCG
8869





631
GGGCUUUC G CAAAAUAC
1470
GUAUUUUG UGAUG GCAUGCACUAUGC GCG GAAAGCCC
8870





687
UUACUAGU G CCAUUUGU
1471
ACAAAUGG UGAUG GCAUGCACUAUGC GCG ACUAGUAA
8871





747
AUAUGGAU G AUGUGGUU
1472
AACCACAU UGAUG GCAUGCACUAUGC GCG AUCCAUAU
8872





783
AACAUCUU G AGUCCCUU
1473
AAGGGACU UGAUG GCAUGCACUAUGC GCG AAGAUGUU
8873





795
CCCUUUAU G CCGCUGUU
1474
AACAGCGG UGAUG GCAUGCACUAUGC GCG AUAAAGGG
8874





798
UUUAUGCC G CUGUUACC
1475
GGUAACAG UGAUG GCAUGCACUAUGC GCG GGCAUAAA
8875





911
GGCACAUU G CCACAGGA
1476
UCCUGUGG UGAUG GCAUGCACUAUGC GCG AAUGUGCC
8876





978
GGCCUAUU G AUUGGAAA
1477
UUUCCAAU UGAUG GCAUGCACUAUGC GCG AAUAGGCC
8877





997
AUGUCAAC G AAUUGUGG
1478
CCACAAUU UGAUG GCAUGCACUAUGC GCG GUUGACAU
8878





1020
UGGGGUUU G CCGCCCCU
1479
AGGGGCGG UGAUG GCAUGCACUAUGC GCG AAACCCCA
8879





1023
GGUUUGCC G CCCCUUUC
1480
GAAAGGGG UGAUG GCAUGCACUAUGC GCG GGCAAACC
8880





1034
CCUUUCAC G CAAUGUGG
1481
CCACAUUG UGAUG GCAUGCACUAUGC GCG GUGAAAGG
8881





1050
GAUAUUCU G CUUUAAUG
1482
CAUUAAAG UGAUG GCAUGCACUAUGC GCG AGAAUAUC
8882





1058
GCUUUAAU G CCUUUAUA
1483
UAUAAAGG UGAUG GCAUGCACUAUGC GCG AUUAAAGC
8883





1068
CUUUAUAU G CAUGCAUA
1484
UAUGCAUG UGAUG GCAUGCACUAUGC GCG AUAUAAAG
8884





1072
AUAUGCAU G CAUACAAG
1485
CUUGUAUG UGAUG GCAUGCACUAUGC GCG AUGCAUAU
8885





1103
ACUUUCUC G CCAACUUA
1486
UAAGUUGG UGAUG GCAUGCACUAUGC GCG GAGAAAGU
8886





1139
CAGUAUGU G AACCUUUA
1487
UAAAGGUU UGAUG GCAUGCACUAUGC GCG ACAUACUG
8887





1155
ACCCCGUU G CUCGGCAA
1488
UUGCCGAG UGAUG GCAUGCACUAUGC GCG AACGGGGU
8888





1177
UGGUCUAU G CCAAGUGU
1489
ACACUUGG UGAUG GCAUGCACUAUGC GCG AUAGACCA
8889





1188
AAGUGUUU G CUGACGCA
1490
UGCGUCAG UGAUG GCAUGCACUAUGC GCG AAACACUU
8890





1191
UGUUUGCU G ACGCAACC
1491
GGUUGCGU UGAUG GCAUGCACUAUGC GCG AGCAAACA
8891





1194
UUGCUGAC G CAACCCCC
1492
GGGGGUUG UGAUG GCAUGCACUAUGC GCG GUCAGCAA
8892





1234
CCAUCAGC G CAUGCGUG
1493
CACGCAUG UGAUG GCAUGCACUAUGC GCG GCUGAUGG
8893





1238
CAGCGCAU G CGUGGAAC
1494
GUUCCACG UGAUG GCAUGCACUAUGC GCG AUGCGCUG
8894





1262
UCUCCUCU G CCGAUCCA
1495
UGGAUCGG UGAUG GCAUGCACUAUGC GCG AGAGGAGA
8895





1265
CCUCUGCC G AUCCAUAC
1496
GUAUGGAU UGAUG GCAUGCACUAUGC GCG GGCAGAGG
8896





1275
UCCAUACC G CGGAACUC
1497
GAGUUCCG UGAUG GCAUGCACUAUGC GCG GGUAUGGA
8897





1290
UCCUAGCC G CUUGUUUU
1498
AAAACAAG UGAUG GCAUGCACUAUGC GCG GGCUAGGA
8898





1299
CUUGUUUU G CUCGCAGC
1499
GCUGCGAG UGAUG GCAUGCACUAUGC GCG AAAACAAG
8899





1303
UUUUGCUC G CAGCAGGU
1500
ACCUGCUG UGAUG GCAUGCACUAUGC GCG GAGCAAAA
8900





1335
UCGGGACU G ACAAUUCU
1501
AGAAUUGU UGAUG GCAUGCACUAUGC GCG AGUCCCGA
8901





1349
UCUGUCGU G CUCUCCCG
1502
CGGGAGAG UGAUG GCAUGCACUAUGC GCG ACGACAGA
8902





1357
GCUCUCCC G CAAAUAUA
1503
UAUAUUUG UGAUG GCAUGCACUAUGC GCG GGGAGAGC
8903





1382
CCAUGGCU G CUAGGCUG
1504
CAGCCUAG UGAUG GCAUGCACUAUGC GCG AGCCAUGG
8904





1392
UAGGCUGU G CUGCCAAC
1505
GUUGGCAG UGAUG GCAUGCACUAUGC GCG ACAGCCUA
8905





1395
GCUGUGCU G CCAACUGG
1506
CCAGUUGG UGAUG GCAUGCACUAUGC GCG AGCACAGC
8906





1411
GAUCCUAC G CGGGACGU
1507
ACGUCCCG UGAUG GCAUGCACUAUGC GCG GUAGGAUC
8907





1442
CCGUCGGC G CUGAAUCC
1508
GGAUUCAG UGAUG GCAUGCACUAUGC GCG GCCGACGG
8908





1445
UCGGCGCU G AAUCCCGC
1509
GCGGGAUU UGAUG GCAUGCACUAUGC GCG AGCGCCGA
8909





1452
UGAAUCCC G CGGACGAC
1510
GUCGUCCG UGAUG GCAUGCACUAUGC GCG GGGAUUCA
8910





1458
CCGCGGAC G ACCCCUCC
1511
GGAGGGGU UGAUG GCAUGCACUAUGC GCG GUCCGCGG
8911





1474
CCGGGGCC G CUUGGGGC
1512
GCCCCAAG UGAUG GCAUGCACUAUGC GCG GGCCCCGG
8912





1489
GCUCUACC G CCCGCUUC
1513
GAAGCGGG UGAUG GCAUGCACUAUGC GCG GGUAGAGC
8913





1493
UACCGCCC G CUUCUCCG
1514
CGGAGAAG UGAUG GCAUGCACUAUGC GCG GGGCGGUA
8914





1501
GCUUCUCC G CCUAUUGU
1515
ACAAUAGG UGAUG GCAUGCACUAUGC GCG GGAGAAGC
8915





1513
AUUGUACC G ACCGUCCA
1516
UGGACGGU UGAUG GCAUGCACUAUGC GCG GGUACAAU
8916





1528
CACGGGGC G CACCUCUC
1517
GAGAGGUG UGAUG GCAUGCACUAUGC GCG GCCCCGUG
8917





1542
CUCUUUAC G CGGACUCC
1518
GGAGUCCG UGAUG GCAUGCACUAUGC GCG GUAAAGAG
8918





1559
CCGUCUGU G CCUUCUCA
1519
UGAGAAGG UGAUG GCAUGCACUAUGC GCG ACAGACGG
8919





1571
UCUCAUCU G CCGGACCG
1520
CGGUCCGG UGAUG GCAUGCACUAUGC GCG AGAUGAGA
8920





1583
GACCGUGU G CACUUCGC
1521
GCGAAGUG UGAUG GCAUGCACUAUGC GCG ACACGGUC
8921





1590
UGCACUUC G CUUCACCU
1522
AGGUGAAG UGAUG GCAUGCACUAUGC GCG GAAGUGCA
8922





1601
UCACCUCU G CACGUCGC
1523
GCGACGUG UGAUG GCAUGCACUAUGC GCG AGAGGUGA
8923





1608
UGCACGUC G CAUGGAGA
1524
UCUCCAUG UGAUG GCAUGCACUAUGC GCG GACGUGCA
8924





1624
ACCACCGU G AACGCCCA
1525
UGGGCGUU UGAUG GCAUGCACUAUGC GCG ACGGUGGU
8925





1628
CCGUGAAC G CCCACAGG
1526
CCUGUGGG UGAUG GCAUGCACUAUGC GCG GUUCACGG
8926





1642
AGGAACCU G CCCAAGGU
1527
ACCUUGGG UGAUG GCAUGCACUAUGC GCG AGGUUCCU
8927





1654
AAGGUCUU G CAUAAGAG
1528
CUCUUAUG UGAUG GCAUGCACUAUGC GCG AAGACCUU
8928





1690
AUGUCAAC G ACCGACCU
1529
AGGUCGGU UGAUG GCAUGCACUAUGC GCG GUUGACAU
8929





1694
CAACGACC G ACCUUGAG
1530
CUCAAGGU UGAUG GCAUGCACUAUGC GCG GGUCGUUG
8930





1700
CCGACCUU G AGGCAUAC
1531
GUAUGCCU UGAUG GCAUGCACUAUGC GCG AAGGUCGG
8931





1730
UGUUUAAU G AGUGGGAG
1532
CUCCCACU UGAUG GCAUGCACUAUGC GCG AUUAAACA
8932





1818
AGCACCAU G CAACUUUU
1533
AAAAGUUG UGAUG GCAUGCACUAUGC GCG AUGGUGCU
8933





1835
UCACCUCU G CCUAAUCA
1534
UGAUUAGG UGAUG GCAUGCACUAUGC GCG AGAGGUGA
8934





1883
CAAGCUGU G CCUUGGGU
1535
ACCCAAGG UGAUG GCAUGCACUAUGC GCG ACAGCUUG
8935





1912
UGGACAUU G ACCCGUAU
1536
AUACGGGU UGAUG GCAUGCACUAUGC GCG AAUGUCCA
8936





1959
UCUUUUUU G CCUUCUGA
1537
UCAGAAGG UGAUG GCAUGCACUAUGC GCG AAAAAAGA
8937





1966
UGCCUUCU G ACUUCUUU
1538
AAAGAAGU UGAUG GCAUGCACUAUGC GCG AGAAGGCA
8938





1985
UUCUAUUC G AGAUCUCC
1539
GGAGAUCU UGAUG GCAUGCACUAUGC GCG GAAUAGAA
8939





1996
AUCUCCUC G ACACCGCC
1540
GGCGGUGU UGAUG GCAUGCACUAUGC GCG GAGGAGAU
8940





2002
UCGACACC G CCUCUGCU
1541
AGCAGAGG UGAUG GCAUGCACUAUGC GCG GGUGUCGA
8941





2008
CCGCCUCU G CUCUGUAU
1542
AUACAGAG UGAUG GCAUGCACUAUGC GCG AGAGGCGG
8942





2092
GUUGGGGU G AGUUGAUG
1543
CAUCAACU UGAUG GCAUGCACUAUGC GCG ACCCCAAC
8943





2097
GGUGAGUU G AUGAAUCU
1544
AGAUUCAU UGAUG GCAUGCACUAUGC GCG AACUCACC
8944





2100
GAGUUGAU G AAUCUAGC
1545
GCUAGAUU UGAUG GCAUGCACUAUGC GCG AUCAACUC
8945





2237
UUUUGGGC G AGAAACUG
1546
CAGUUUCU UGAUG GCAUGCACUAUGC GCG GCCCAAAA
8946





2251
CUGUUCUU G AAUAUUUG
1547
CAAAUAUU UGAUG GCAUGCACUAUGC GCG AAGAACAG
8947





2282
GUGGAUUC G CACUCCUC
1548
GAGGAGUG UGAUG GCAUGCACUAUGC GCG GAAUCCAC
8948





2293
CUCCUCCU G CAUAUAGA
1549
UCUAUAUG UGAUG GCAUGCACUAUGC GCG AGGAGGAG
8949





2311
CACCAAAU G CCCCUAUC
1550
GAUAGGGG UGAUG GCAUGCACUAUGC GCG AUUUGGUG
8950





2354
UGUUAGAC G AAGAGGCA
1551
UGCCUCUU UGAUG GCAUGCACUAUGC GCG GUCUAACA
8951





2388
ACUCCCUC G CCUCGCAG
1552
CUGCGAGG UGAUG GCAUGCACUAUGC GCG GAGGGAGU
8952





2393
CUCGCCUC G CAGACGAA
1553
UUCGUCUG UGAUG GCAUGCACUAUGC GCG GAGGCGAG
8953





2399
UCGCAGAC G AAGGUCUC
1554
GAGACCUU UGAUG GCAUGCACUAUGC GCG GUCUGCGA
8954





2412
UCUCAAUC G CCGCGUCG
1555
CGACGCGG UGAUG GCAUGCACUAUGC GCG GAUUGAGA
8955





2415
CAAUCGCC G CGUCGCAG
1556
CUGCGACG UGAUG GCAUGCACUAUGC GCG GGCGAUUG
8956





2420
GCCGCGUC G CAGAAGAU
1557
AUCUUCUG UGAUG GCAUGCACUAUGC GCG GACGCGGC
8957





2514
GGUACCUU G CUUUAAUC
1558
GAUUAAAG UGAUG GCAUGCACUAUGC GCG AAGGUACC
8958





2549
CUUUUCCU G ACAUUCAU
1559
AUGAAUGU UGAUG GCAUGCACUAUGC GCG AGGAAAAG
8959





2560
AUUCAUUU G CAGGAGGA
1560
UCCUCCUG UGAUG GCAUGCACUAUGC GCG AAAUGAAU
8960





2576
ACAUUGUU G AUAGAUGU
1561
ACAUCUAU UGAUG GCAUGCACUAUGC GCG AACAAUGU
8961





2615
CAGUAAAU G AAAACAGG
1562
CCUGUUUU UGAUG GCAUGCACUAUGC GCG AUUUACUG
8962





2641
UUAACUAU G CCUGCUAG
1563
CUAGCAGG UGAUG GCAUGCACUAUGC GCG AUAGUUAA
8963





2645
CUAUGCCU G CUAGGUUU
1564
AAACCUAG UGAUG GCAUGCACUAUGC GCG AGGCAUAG
8964





2677
AAAUAUUU G CCCUUAGA
1565
UCUAAGGG UGAUG GCAUGCACUAUGC GCG AAAUAUUU
8965





2740
UUCCAGAC G CGACAUUA
1566
UAAUGUCG UGAUG GCAUGCACUAUGC GCG GUCUGGAA
8966





2742
CCAGACGC G ACAUUAUU
1567
AAUAAUGU UGAUG GCAUGCACUAUGC GCG GCGUCUGG
8967





2804
CACGUAGC G CCUCAUUU
1568
AAAUGAGG UGAUG GCAUGCACUAUGC GCG GCUACGUG
8968





2814
CUCAUUUU G CGGGUCAC
1569
GUGACCCG UGAUG GCAUGCACUAUGC GCG AAAAUGAG
8969





2875
CAAACCUC G AAAAGGCA
1570
UGCCUUUU UGAUG GCAUGCACUAUGC GCG GAGGUUUG
8970





2928
UCUUCCCC G AUCAUCAG
1571
CUGAUGAU UGAUG GCAUGCACUAUGC GCG GGGGAAGA
8971





2946
UGGACCCU G CAUUCAAA
1572
UUUGAAUG UGAUG GCAUGCACUAUGC GCG AGGGUCCA
8972





2990
CUCAACCC G CACAAGGA
1573
UCCUUGUG UGAUG GCAUGCACUAUGC GCG GGGUUGAG
8973





3012
GGCCGGAC G CCAACAAG
1574
CUUGUUGG UGAUG GCAUGCACUAUGC GCG GUCCGGCC
8974





3090
GCCCUCAC G CUCAGGGC
1575
GCCCUGAG UGAUG GCAUGCACUAUGC GCG GUGAGGGC
8975





3113
ACAACUGU G CCAGCAGC
1576
GCUGCUGG UGAUG GCAUGCACUAUGC GCG ACAGUUGU
8976





3132
CUCCUCCU G CCUCCACC
1577
GGUGGAGG UGAUG GCAUGCACUAUGC GCG AGGAGGAG
8977





51
AGGGCCCU G UACUUUCC
1578
GGAAAGUA UGAUG GCAUGCACUAUGC GCG AGGGCCCU
8978





106
AGAAUACU G UCUCUGCC
1579
GGCAGAGA UGAUG GCAUGCACUAUGC GCG AGUAUUCU
8979





148
GGGACCCU G UACCGAAC
1580
GUUCGGUA UGAUG GCAUGCACUAUGC GCG AGGGUCCC
8980





198
CUGCUCGU G UUACAGGC
1581
GCCUGUAA UGAUG GCAUGCACUAUGC GCG ACGAGCAG
8981





219
UUUUUCUU G UUGACAAA
1582
UUUGUCAA UGAUG GCAUGCACUAUGC GCG AAGAAAAA
8982





297
ACACCCGU G UGUCUUGG
1583
CCAAGACA UGAUG GCAUGCACUAUGC GCG ACGGGUGU
8983





299
ACCCGUGU G UCUUGGCC
1584
GGCCAAGA UGAUG GCAUGCACUAUGC GCG ACACGGGU
8984





347
ACCAACCU G UUGUCCUC
1585
GAGGACAA UGAUG GCAUGCACUAUGC GCG AGGUUGGU
8985





350
AACCUGUU G UCCUCCAA
1586
UUGGAGGA UGAUG GCAUGCACUAUGC GCG AACAGGUU
8986





362
UCCAAUUU G UCCUGGUU
1587
AACCAGGA UGAUG GCAUGCACUAUGC GCG AAAUUGGA
8987





381
CGCUGGAU G UGUCUGCG
1588
CGCAGACA UGAUG GCAUGCACUAUGC GCG AUCCAGCG
8988





383
CUGGAUGU G UCUGCGGC
1589
GCCGCAGA UGAUG GCAUGCACUAUGC GCG ACAUCCAG
8989





438
AUCUUCUU G UUGGUUCU
1590
AGAACCAA UGAUG GCAUGCACUAUGC GCG AAGAAGAU
8990





465
CAAGGUAU G UUGCCCGU
1591
ACGGGCAA UGAUG GCAUGCACUAUGC GCG AUACCUUG
8991





476
GCCCGUUU G UCCUCUAA
1592
UUAGAGGA UGAUG GCAUGCACUAUGC GCG AAACGGGC
8992





555
ACCUCUAU G UUUCCCUC
1593
GAGGGAAA UGAUG GCAUGCACUAUGC GCG AUAGAGGU
8993





566
UCCCUCAU G UUGCUGUA
1594
UACAGCAA UGAUG GCAUGCACUAUGC GCG AUGAGGGA
8994





572
AUGUUGCU G UACAAAAC
1595
GUUUUGUA UGAUG GCAUGCACUAUGC GCG AGCAACAU
8995





602
CUGCACCU G UAUUCCCA
1596
UGGGAAUA UGAUG GCAUGCACUAUGC GCG AGGUGCAG
8996





694
UGCCAUUU G UUCAGUGG
1597
CCACUGAA UGAUG GCAUGCACUAUGC GCG AAAUGGCA
8997





724
CCCCCACU G UCUGGCUU
1598
AAGCCAGA UGAUG GCAUGCACUAUGC GCG AGUGGGGG
8998





750
UGGAUGAU G UGGUUUUG
1599
CAAAACCA UGAUG GCAUGCACUAUGC GCG AUCAUCCA
8999





771
CCAAGUCU G UACAACAU
1600
AUGUUGUA UGAUG GCAUGCACUAUGC GCG AGACUUGG
9000





801
AUGCCGCU G UUACCAAU
1601
AUUGGUAA UGAUG GCAUGCACUAUGC GCG AGCGGCAU
9001





818
UUUCUUUU G UCUUUGGG
1602
CCCAAAGA UGAUG GCAUGCACUAUGC GCG AAAAGAAA
9002





888
UGGGAUAU G UAAUUGGG
1603
CCCAAUUA UGAUG GCAUGCACUAUGC GCG AUAUCCCA
9003





927
AACAUAUU G UACAAAAA
1604
UUUUUGUA UGAUG GCAUGCACUAUGC GCG AAUAUGUU
9004





944
AUCAAAAU G UGUUUUAG
1605
CUAAAACA UGAUG GCAUGCACUAUGC GCG AUUUUGAU
9005





946
CAAAAUGU G UUUUAGGA
1606
UCCUAAAA UGAUG GCAUGCACUAUGC GCG ACAUUUUG
9006





963
AACUUCCU G UAAACAGG
1607
CCUGUUUA UGAUG GCAUGCACUAUGC GCG AGGAAGUU
9007





991
GAAAGUAU G UCAACGAA
1608
UUCGUUGA UGAUG GCAUGCACUAUGC GCG AUACUUUC
9008





1002
AACGAAUU G UGGGUCUU
1609
AAGACCCA UGAUG GCAUGCACUAUGC GCG AAUUCGUU
9009





1039
CACGCAAU G UGGAUAUU
1610
AAUAUCCA UGAUG GCAUGCACUAUGC GCG AUUGCGUG
9010





1137
AACAGUAU G UGAACCUU
1611
AAGGUUCA UGAUG GCAUGCACUAUGC GCG AUACUGUU
9011





1184
UGCCAAGU G UUUGCUGA
1612
UCAGCAAA UGAUG GCAUGCACUAUGC GCG ACUUGGCA
9012





1251
GAACCUUU G UGUCUCCU
1613
AGGAGACA UGAUG GCAUGCACUAUGC GCG AAAGGUUC
9013





1253
ACCUUUGU G UCUCCUCU
1614
AGAGGAGA UGAUG GCAUGCACUAUGC GCG ACAAAGGU
9014





1294
AGCCGCUU G UUUUGCUC
1615
GAGCAAAA UGAUG GCAUGCACUAUGC GCG AAGCGCCU
9015





1344
ACAAUUCU G UCGUGCUC
1616
GAGCACGA UGAUG GCAUGCACUAUGC GCG AGAAUUGU
9016





1390
GCUAGGCU G UGCUGCCA
1617
UGGCAGCA UGAUG GCAUGCACUAUGC GCG AGCCUAGC
9017





1425
CGUCCUUU G UUUACGUC
1618
GACGUAAA UGAUG GCAUGCACUAUGC GCG AAAGGACG
9018





1508
CGCCUAUU G UACCGACC
1619
GGUCGGUA UGAUG GCAUGCACUAUGC GCG AAUAGGCG
9019





1557
CCCCGUCU G UGCCUUCU
1620
AGAAGGCA UGAUG GCAUGCACUAUGC GCG AGACGGGG
9020





1581
CGGACCGU G UGCACUUC
1621
GAAGUGCA UGAUG GCAUGCACUAUGC GCG ACGGUCCG
9021





1684
UCAGCAAU G UCAACGAC
1622
GUCGUUGA UGAUG GCAUGCACUAUGC GCG AUUGCUGA
9022





1719
CAAAGACU G UGUGUUUA
1623
UAAACACA UGAUG GCAUGCACUAUGC GCG AGUCUUUG
9023





1721
AAGACUGU G UGUUUAAU
1624
AUUAAACA UGAUG GCAUGCACUAUGC GCG ACAGUCUU
9024





1723
GACUGUGU G UUUAAUGA
1625
UCAUUAAA UGAUG GCAUGCACUAUGC GCG ACACAGUC
9025





1772
AGGUCUUU G UACUAGGA
1626
UCCUAGUA UGAUG GCAUGCACUAUGC GCG AAAGACCU
9026





1785
AGGAGGCU G UAGGCAUA
1627
UAUGCCUA UGAUG GCAUGCACUAUGC GCG AGCCUCCU
9027





1801
AAAUUGGU G UGUUCACC
1628
GGUGAACA UGAUG GCAUGCACUAUGC GCG ACCAAUUU
9028





1803
AUUGGUGU G UUCACCAG
1629
CUGGUGAA UGAUG GCAUGCACUAUGC GCG ACACCAAU
9029





1850
CAUCUCAU G UUCAUGUC
1630
GACAUGAA UGAUG GCAUGCACUAUGC GCG AUGAGAUG
9030





1856
AUGUUCAU G UCCUACUG
1631
CAGUAGGA UGAUG GCAUGCACUAUGC GCG AUGAACAU
9031





1864
GUCCUACU G UUCAAGCC
1632
GGCUUGAA UGAUG GCAUGCACUAUGC GCG AGUAGGAC
9032





1881
UCCAAGCU G UGCCUUGG
1633
CCAAGGCA UGAUG GCAUGCACUAUGC GCG AGCUUGGA
9033





1939
GAGCUUCU G UGGAGUUA
1634
UAACUCCA UGAUG GCAUGCACUAUGC GCG AGAAGCUC
9034





2013
UCUGCUCU G UAUCGGGG
1635
CCCCGAUA UGAUG GCAUGCACUAUGC GCG AGAGCAGA
9035





2045
GGAACAUU G UUCACCUC
1636
GAGGUGAA UGAUG GCAUGCACUAUGC GCG AAUGUUCC
9036





2082
GCUAUUCU G UGUUGGGG
1637
CCCCAACA UGAUG GCAUGCACUAUGC GCG AGAAUAGC
9037





2084
UAUUCUGU G UUGGGGUG
1638
CACCCCAA UGAUG GCAUGCACUAUGC GCG ACAGAAUA
9038





2167
UCAGCUAU G UCAACGUU
1639
AACGUUGA UGAUG GCAUGCACUAUGC GCG AUAGCUGA
9039





2205
CAACUAUU G UGGUUUCA
1640
UGAAACCA UGAUG GCAUGCACUAUGC GCG AAUAGUUG
9040





2222
CAUUUCCU G UCUUACUU
1641
AAGUAAGA UGAUG GCAUGCACUAUGC GCG AGGAAAUG
9041





2245
GAGAAACU G UUCUUGAA
1642
UUCAAGAA UGAUG GCAUGCACUAUGC GCG AGUUUCUC
9042





2262
UAUUUGGU G UCUUUUGG
1643
CCAAAAGA UGAUG GCAUGCACUAUGC GCG ACCAAAUA
9043





2274
UUUGGAGU G UGGAUUCG
1644
CGAAUCCA UGAUG GCAUGCACUAUGC GCG ACUCCAAA
9044





2344
AAACUACU G UUGUUAGA
1645
UCUAACAA UGAUG GCAUGCACUAUGC GCG AGUAGUUU
9045





2347
CUACUGUU G UUAGACGA
1646
UCGUCUAA UGAUG GCAUGCACUAUGC GCG AACAGUAG
9046





2450
AUCUCAAU G UUAGUAUU
1647
AAUACUAA UGAUG GCAUGCACUAUGC GCG AUUGAGAU
9047





2573
AGGACAUU G UUGAUAGA
1648
UCUAUCAA UGAUG GCAUGCACUAUGC GCG AAUGUCCU
9048





2583
UGAUAGAU G UAAGCAAU
1649
AUUGCUUA UGAUG GCAUGCACUAUGC GCG AUCUAUCA
9049





2594
AGCAAUUU G UGGGGCCC
1650
GGGCCCCA UGAUG GCAUGCACUAUGC GCG AAAUUGCU
9050





2663
AUCCCAAU G UUACUAAA
1651
UUUAGUAA UGAUG GCAUGCACUAUGC GCG AUUGGGAU
9051





2717
CAGAGUAU G UAGUUAAU
1652
AUUAACUA UGAUG GCAUGCACUAUGC GCG AUACUCUG
9052





2901
AUCUUUCU G UCCCCAAU
1653
AUUGGGGA UGAUG GCAUGCACUAUGC GCG AGAAAGAU
9053





3071
GGGGGACU G UUGGGGUG
1654
CACCCCAA UGAUG GCAUGCACUAUGC GCG AGUCCCCC
9054





3111
UCACAACU G UGCCAGCA
1655
UGCUGGCA UGAUG GCAUGCACUAUGC GCG AGUUGUGA
9055






Input Sequence = AF100308.




Cut Site = YG/M or UG/U.




Stem Length = 8.




Core Sequence = UGAUG GCAUGCACUAUGC GCG




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








[0556]

8






TABLE VIII










HUMAN HBV ZINZYME AND SUBSTRATE SEQUENCE












Pos
Substrate
Seq ID
Zinzyme
Seq ID















61
ACUUUCCU G CUGGUGGC
1448
GCCACCAG GCcgaaagGCGaGuCaaGGuCu AGGAAAGU
9056






94
UGAGCCCU G CUCAGAAU
1450
AUUCUGAG GCcgaaagGCGaGuCaaGGuCu AGGGCUCA
9057





112
CUGUCUCU G CCAUAUCG
1451
CGAUAUGG GCcgaaagGCGaGuCaaGGuCu AGAGACAG
9058





169
AGAACAUC G CAUCAGGA
1454
UCCUGAUG GCcgaaagGCGaGuCaaGGuCu GAUGUUCU
9059





192
GGACCCCU G CUCGUGUU
1455
AACACGAG GCcgaaagGCGaGuCaaGGuCu AGGGGUCC
9060





315
CAAAAUUC G CAGUCCCA
1457
UGGGACUG GCcgaaagGCGaGuCaaGGuCu GAAUUUUG
9061





374
UGGUUAUC G CUGGAUGU
1458
ACAUCCAG GCcgaaagGCGaGuCaaGGuCu GAUAACCA
9062





387
AUGUGUCU G CGGCGUUU
1459
AAACGCCG GCcgaaagGCGaGuCaaGGuCu AGACACAU
9063





410
CUUCCUCU G CAUCCUGC
1460
GCAGGAUG GCcgaaagGCGaGuCaaGGuCu AGAGGAAG
9064





417
UGCAUCCU G CUGCUAUG
1461
CAUAGCAG GCcgaaagGCGaGuCaaGGuCu AGGAUGCA
9065





420
AUCCUGCU G CUAUGCCU
1462
AGGCAUAG GCcgaaagGCGaGuCaaGGuCu AGCAGGAU
9066





425
GCUGCUAU G CCUCAUCU
1463
AGAUGAGG GCcgaaagGCGaGuCaaGGuCu AUAGCAGC
9067





468
GGUAUGUU G CCCGUUUG
1464
CAAACGGG GCcgaaagGCGaGuCaaGGuCu AACAUACC
9068





518
CGGACCAU G CAAAACCU
1465
AGGUUUUG GCcgaaagGCGaGuCaaGGuCu AUGGUCCG
9069





527
CAAAACCU G CACAACUC
1466
GAGUUGUG GCcgaaagGCGaGuCaaGGuCu AGGUUUUG
9070





538
CAACUCCU G CUCAAGGA
1467
UCCUUGAG GCcgaaagGCGaGuCaaGGuCu AGGAGUUG
9071





569
CUCAUGUU G CUGUACAA
1468
UUGUACAG GCcgaaagGCGaGuCaaGGuCu AACAUGAG
9072





596
CGGAAACU G CACCUGUA
1469
UACAGGUG GCcgaaagGCGaGuCaaGGuCu AGUUUCCG
9073





631
GGGCUUUC G CAAAAUAC
1470
GUAUUUUG GCcgaaagGCGaGuCaaGGuCu GAAAGCCC
9074





687
UUACUAGU G CCAUUUGU
1471
ACAAAUGG GCcgaaagGCGaGuCaaGGuCu ACUAGUAA
9075





795
CCCUUUAU G CCGCUGUU
1474
AACAGCGG GCcgaaagGCGaGuCaaGGuCu AUAAAGGG
9076





798
UUUAUGCC G CUGUUACC
1475
GGUAACAG GCcgaaagGCGaGuCaaGGuCu GGCAUAAA
9077





911
GGCACAUU G CCACAGGA
1476
UCCUGUGG GCcgaaagGCGaGuCaaGGuCu AAUGUGCC
9078





1020
UGGGGUUU G CCGCCCCU
1479
AGGGGCGG GCcgaaagGCGaGuCaaGGuCu AAACCCCA
9079





1023
GGUUUGCC G CCCCUUUC
1480
GAAAGGGG GCcgaaagGCGaGuCaaGGuCu GGCAAACC
9080





1034
CCUUUCAC G CAAUGUGG
1481
CCACAUUG GCcgaaagGCGaGuCaaGGuCu GUGAAAGG
9081





1050
GAUAUUCU G CUUUAAUG
1482
CAUUAAAG GCcgaaagGCGaGuCaaGGuCu AGAAUAUC
9082





1058
GCUUUAAU G CCUUUAUA
1483
UAUAAAGG GCcgaaagGCGaGuCaaGGuCu AUUAAAGC
9083





1068
CUUUAUAU G CAUGCAUA
1484
UAUGCAUG GCcgaaagGCGaGuCaaGGuCu AUAUAAAG
9084





1072
AUAUGCAU G CAUACAAG
1485
CUUGUAUG GCcgaaagGCGaGuCaaGGuCu AUGCAUAU
9085





1103
ACUUUCUC G CCAACUUA
1486
UAAGUUGG GCcgaaagGCGaGuCaaGGuCu GAGAAAGU
9086





1155
ACCCCGUU G CUCGGCAA
1488
UUGCCGAG GCcgaaagGCGaGuCaaGGuCu AACGGGGU
9087





1177
UGGUCUAU G CCAAGUGU
1489
ACACUUGG GCcgaaagGCGaGuCaaGGuCu AUAGACCA
9088





1188
AAGUGUUU G CUGACGCA
1490
UGCGUCAG GCcgaaagGCGaGuCaaGGuCu AAACACUU
9089





1194
UUGCUGAC G CAACCCCC
1492
GGGGGUUG GCcgaaagGCGaGuCaaGGuCu GUCAGCAA
9090





1234
CCAUCAGC G CAUGCGUG
1493
CACGCAUG GCcgaaagGCGaGuCaaGGuCu GCUGAUGG
9091





1238
CAGCGCAU G CGUGGAAC
1494
GUUCCACG GCcgaaagGCGaGuCaaGGuCu AUGCGCUG
9092





1262
UCUCCUCU G CCGAUCCA
1495
UGGAUCGG GCcgaaagGCGaGuCaaGGuCu AGAGGAGA
9093





1275
UCCAUACC G CGGAACUC
1497
GAGUUCCG GCcgaaagGCGaGuCaaGGuCu GGUAUGGA
9094





1290
UCCUAGCC G CUUGUUUU
1498
AAAACAAG GCcgaaagGCGaGuCaaGGuCu GGCUAGGA
9095





1299
CUUGUUUU G CUCGCAGC
1499
GCUGCGAG GCcgaaagGCGaGuCaaGGuCu AAAACAAG
9096





1303
UUUUGCUC G CAGCAGGU
1500
ACCUGCUG GCcgaaagGCGaGuCaaGGuCu GAGCAAAA
9097





1349
UCUGUCGU G CUCUCCCG
1502
CGGGAGAG GCcgaaagGCGaGuCaaGGuCu ACGACAGA
9098





1357
GCUCUCCC G CAAAUAUA
1503
UAUAUUUG GCcgaaagGCGaGuCaaGGuCu GGGAGAGC
9099





1382
CCAUGGCU G CUAGGCUG
1504
CAGCCUAG GCcgaaagGCGaGuCaaGGuCu AGCCAUGG
9100





1392
UAGGCUGU G CUGCCAAC
1505
GUUGGCAG GCcgaaagGCGaGuCaaGGuCu ACAGCCUA
9101





1395
GCUGUGCU G CCAACUGG
1506
CCAGUUGG GCcgaaagGCGaGuCaaGGuCu AGCACAGC
9102





1411
GAUCCUAC G CGGGACGU
1507
ACGUCCCG GCcgaaagGCGaGuCaaGGuCu GUAGGAUC
9103





1442
CCGUCGGC G CUGAAUCC
1508
GGAUUCAG GCcgaaagGCGaGuCaaGGuCu GCCGACGG
9104





1452
UGAAUCCC G CGGACGAC
1510
GUCGUCCG GCcgaaagGCGaGuCaaGGuCu GGGAUUCA
9105





1474
CCGGGGCC G CUUGGGGC
1512
GCCCCAAG GCcgaaagGCGaGuCaaGGuCu GGCCCCGG
9106





1489
GCUCUACC G CCCGCUUC
1513
GAAGCGGG GCcgaaagGCGaGuCaaGGuCu GGUAGAGC
9107





1493
UACCGCCC G CUUCUCCG
1514
CGGAGAAG GCcgaaagGCGaGuCaaGGuCu GGGCGGUA
9108





1501
GCUUCUCC G CCUAUUGU
1515
ACAAUAGG GCcgaaagGCGaGuCaaGGuCu GGAGAAGC
9109





1528
CACGGGGC G CACCUCUC
1517
GAGAGGUG GCcgaaagGCGaGuCaaGGuCu GCCCCGUG
9110





1542
CUCUUUAC G CGGACUCC
1518
GGAGUCCG GCcgaaagGCGaGuCaaGGuCu GUAAAGAG
9111





1559
CCGUCUGU G CCUUCUCA
1519
UGAGAAGG GCcgaaagGCGaGuCaaGGuCu ACAGACGG
9112





1571
UCUCAUCU G CCGGACCG
1520
CGGUCCGG GCcgaaagGCGaGuCaaGGuCu AGAUGAGA
9113





1583
GACCGUGU G CACUUCGC
1521
GCGAAGUG GCcgaaagGCGaGuCaaGGuCu ACACGGUC
9114





1590
UGCACUUC G CUUCACCU
1522
AGGUGAAG GCcgaaagGCGaGuCaaGGuCu GAAGUGCA
9115





1601
UCACCUCU G CACGUCGC
1523
GCGACGUG GCcgaaagGCGaGuCaaGGuCu AGAGGUGA
9116





1608
UGCACGUC G CAUGGAGA
1524
UCUCCAUG GCcgaaagGCGaGuCaaGGuCu GACGUGCA
9117





1628
CCGUGAAC G CCCACAGG
1526
CCUGUGGG GCcgaaagGCGaGuCaaGGuCu GUUCACGG
9118





1642
AGGAACCU G CCCAAGGU
1527
ACCUUGGG GCcgaaagGCGaGuCaaGGuCu AGGUUCCU
9119





1654
AAGGUCUU G CAUAAGAG
1528
CUCUUAUG GCcgaaagGCGaGuCaaGGuCu AAGACCUU
9120





1818
AGCACCAU G CAACUUUU
1533
AAAAGUUG GCcgaaagGCGaGuCaaGGuCu AUGGUGCU
9121





1835
UCACCUCU G CCUAAUCA
1534
UGAUUAGG GCcgaaagGCGaGuCaaGGuCu AGAGGUGA
9122





1883
CAAGCUGU G CCUUGGGU
1535
ACCCAAGG GCcgaaagGCGaGuCaaGGuCu ACAGCUUG
9123





1959
UCUUUUUU G CCUUCUGA
1537
UCAGAAGG GCcgaaagGCGaGuCaaGGuCu AAAAAACA
9124





2002
UCGACACC G CCUCUGCU
1541
AGCAGAGG GCcgaaagGCGaGuCaaGGuCu GGUGUCGA
9125





2008
CCGCCUCU G CUCUGUAU
1542
AUACAGAG GCcgaaagGCGaGuCaaGGuCu AGAGGCGG
9126





2282
GUGGAUUC G CACUCCUC
1548
GAGGAGUG GCcgaaagGCGaGuCaaGGuCu GAAUCCAC
9127





2293
CUCCUCCU G CAUAUAGA
1549
UCUAUAUG GCcgaaagGCGaGuCaaGGuCu AGGAGGAG
9128





2311
CACCAAAU G CCCCUAUC
1550
GAUAGGGG GCcgaaagGCGaGuCaaGGuCu AUUUGGUG
9129





2388
ACUCCCUC G CCUCGCAG
1552
CUGCGAGG GCcgaaagGCGaGuCaaGGuCu GAGGGAGU
9130





2393
CUCGCCUC G CAGACGAA
1553
UUCGUCUG GCcgaaagGCGaGuCaaGGuCu GAGGCGAG
9131





2412
UCUCAAUC G CCGCGUCG
1555
CGACGCGG GCcgaaagGCGaGuCaaGGuCu GAUUGAGA
9132





2415
CAAUCGCC G CGUCGCAG
1556
CUGCGACG GCcgaaagGCGaGuCaaGGuCu GGCGAUUG
9133





2420
GCCGCGUC G CAGAAGAU
1557
AUCUUCUG GCcgaaagGCGaGuCaaGGuCu GACGCGGC
9134





2514
GGUACCUU G CUUUAAUC
1558
GAUUAAAG GCcgaaagGCGaGuCaaGGuCu AAGGUACC
9135





2560
AUUCAUUU G CAGGAGGA
1560
UCCUCCUG GCcgaaagGCGaGuCaaGGuCu AAAUGAAU
9136





2641
UUAACUAU G CCUGCUAG
1563
CUAGCAGG GCcgaaagGCGaGuCaaGGuCu AUAGUUAA
9137





2645
CUAUGCCU G CUAGGUUU
1564
AAACCUAG GCcgaaagGCGaGuCaaGGuCu AGGCAUAG
9138





2677
AAAUAUUU G CCCUUAGA
1565
UCUAAGGG GCcgaaagGCGaGuCaaGGuCu AAAUAUUU
9139





2740
UUCCAGAC G CGACAUUA
1566
UAAUGUCG GCcgaaagGCGaGuCaaGGuCu GUCUGGAA
9140





2804
CACGUAGC G CCUCAUUU
1568
AAAUGAGG GCcgaaagGCGaGuCaaGGuCu GCUACGUC
9141





2814
CUCAUUUU G CGGGUCAC
1569
GUGACCCG GCcgaaagGCGaGuCaaGGuCu AAAAUGAG
9142





2946
UGGACCCU G CAUUCAAA
1572
UUUGAAUG GCcgaaagGCGaGuCaaGGuCu AGGGUCCA
9143





2990
CUCAACCC G CACAAGGA
1573
UCCUUGUG GCcgaaagGCGaGuCaaGGuCu GGGUUGAG
9144





3012
GGCCGGAC G CCAACAAG
1574
CUUGUUGG GCcgaaagGCGaGuCaaGGuCu GUCCGGCC
9145





3090
GCCCUCAC G CUCAGGGC
1575
GCCCUGAG GCcgaaagGCGaGuCaaGGuCu GUGAGGGC
9146





3113
ACAACUGU G CCAGCAGC
1576
GCUGCUGG GCcgaaagGCGaGuCaaGGuCu ACAGUUGU
9147





3132
CUCCUCCU G CCUCCACC
1577
GGUGGAGG GCcgaaagGCGaGuCaaGGuCu AGGAGGAG
9148





51
AGGGCCCU G UACUUUCC
1578
GGAAAGUA GCcgaaagGCGaGuCaaGGuCu AGGGCCCU
9149





106
AGAAUACU G UCUCUGCC
1579
GGCAGAGA GCcgaaagGCGaGuCaaGGuCu AGUAUUCU
9150





148
GGGACCCU G UACCGAAC
1580
GUUCGGUA GCcgaaagGCGaGuCaaGGuCu AGGGUCCC
9151





198
CUGCUCGU G UUACAGGC
1581
GCCUGUAA GCcgaaagGCGaGuCaaGGuCu ACGAGCAG
9152





219
UUUUUCUU G UUGACAAA
1582
UUUGUCAA GCcgaaagGCGaGuCaaGGuCu AAGAAAAA
9153





297
ACACCCGU G UGUCUUGG
1583
CCAAGACA GCcgaaagGCGaGuCaaGGuCu ACGGGUGU
9154





299
ACCCGUGU G UCUUGGCC
1584
GGCCAAGA GCcgaaagGCGaGuCaaGGuCu ACACGGGU
9155





347
ACCAACCU G UUGUCCUC
1585
GAGGACAA GCcgaaagGCGaGuCaaGGuCu AGGUUGGU
9156





350
AACCUGUU G UCCUCCAA
1586
UUGGAGGA GCcgaaagGCGaGuCaaGGuCu AACAGGUU
9157





362
UCCAAUUU G UCCUGGUU
1587
AACCAGGA GCcgaaagGCGaGuCaaGGuCu AAAUUGGA
9158





381
CGCUGGAU G UGUCUGCG
1588
CGCAGACA GCcgaaagGCGaGuCaaGGuCu AUCCAGCG
9159





383
CUGGAUGU G UCUGCGGC
1589
GCCGCAGA GCcgaaagGCGaGuCaaGGuCu ACAUCCAG
9160





438
AUCUUCUU G UUGGUUCU
1590
AGAACCAA GCcgaaagGCGaGuCaaGGuCu AAGAAGAU
9161





465
CAAGGUAU G UUGCCCGU
1591
ACGGGCAA GCcgaaagGCGaGuCaaGGuCu AUACCUUG
9162





476
GCCCGUUU G UCCUCUAA
1592
UUAGAGGA GCcgaaagGCGaGuCaaGGuCu AAACGGGC
9163





555
ACCUCUAU G UUUCCCUC
1593
GAGGGAAA GCcgaaagGCGaGuCaaGGuCu AUAGAGGU
9164





566
UCCCUCAU G UUGCUGUA
1594
UACAGCAA GCcgaaagGCGaGuCaaGGuCu AUGAGGGA
9165





572
AUGUUGCU G UACAAAAC
1595
GUUUUGUA GCcgaaagGCGaGuCaaGGuCu AGCAACAU
9166





602
CUGCACCU G UAUUCCCA
1596
UGGGAAUA GCcgaaagGCGaGuCaaGGuCu AGGUGCAG
9167





694
UGCCAUUU G UUCAGUGG
1597
CCACUGAA GCcgaaagGCGaGuCaaGGuCu AAAUGGCA
9168





724
CCCCCACU G UCUGGCUU
1598
AAGCCAGA GCcgaaagGCGaGuCaaGGuCu AGUGGGGG
9169





750
UGGAUGAU G UGGUUUUG
1599
CAAAACCA GCcgaaagGCGaGuCaaGGuCu AUCAUCCA
9170





771
CCAAGUCU G UACAACAU
1600
AUGUUGUA GCcgaaagGCGaGuCaaGGuCu AGACUUGG
9171





801
AUGCCGCU G UUACCAAU
1601
AUUGGUAA GCcgaaagGCGaGuCaaGGuCu AGCGGCAU
9172





818
UUUCUUUU G UCUUUGGG
1602
CCCAAAGA GCcgaaagGCGaGuCaaGGuCu AAAAGAAA
9173





888
UGGGAUAU G UAAUUGGG
1603
CCCAAUUA GCcgaaagGCGaGuCaaGGuCu AUAUCCCA
9174





927
AACAUAUU G UACAAAAA
1604
UUUUUGUA GCcgaaagGCGaGuCaaGGuCu AAUAUGUU
9175





944
AUCAAAAU G UGUUUUAG
1605
CUAAAACA GCcgaaagGCGaGuCaaGGuCu AUUUUGAU
9176





946
CAAAAUGU G UUUUAGGA
1606
UCCUAAAA GCcgaaagGCGaGuCaaGGuCu ACAUUUUG
9177





963
AACUUCCU G UAAACAGG
1607
CCUGUUUA GCcgaaagGCGaGuCaaGGuCu AGGAAGUU
9178





991
GAAAGUAU G UCAACGAA
1608
UUCGUUGA GCcgaaagGCGaGuCaaGGuCu AUACUUUC
9179





1002
AACGAAUU G UGGGUCUU
1609
AAGACCCA GCcgaaagGCGaGuCaaGGuCu AAUUCGUU
9180





1039
CACGCAAU G UGGAUAUU
1610
AAUAUCCA GCcgaaagGCGaGuCaaGGuCu AUUGCGUG
9181





1137
AACAGUAU G UGAACCUU
1611
AAGGUUCA GCcgaaagGCGaGuCaaGGuCu AUACUGUU
9182





1184
UGCCAAGU G UUUGCUGA
1612
UCAGCAAA GCcgaaagGCGaGuCaaGGuCu ACUUGGCA
9183





1251
GAACCUUU G UGUCUCCU
1613
AGGAGACA GCcgaaagGCGaGuCaaGGuCu AAAGGUUC
9184





1253
ACCUUUGU G UCUCCUCU
1614
AGAGGAGA GCcgaaagGCGaGuCaaGGuCu ACAAAGGU
9185





1294
AGCCGCUU G UUUUGCUC
1615
GAGCAAAA GCcgaaagGCGaGuCaaGGuCu AAGCGGCU
9186





1344
ACAAUUCU G UCGUGCUC
1616
GAGCACGA GCcgaaagGCGaGuCaaGGuCu AGAAUUGU
9187





1390
GCUAGGCU G UGCUGCCA
1617
UGGCAGCA GCcgaaagGCGaGuCaaGGuCu AGCCUAGC
9188





1425
CGUCCUUU G UUUACGUC
1618
GACGUAAA GCcgaaagGCGaGuCaaGGuCu AAAGGACG
9189





1508
CGCCUAUU G UACCGACC
1619
GGUCGGUA GCcgaaagGCGaGuCaaGGuCu AAUAGGCG
9190





1557
CCCCGUCU G UGCCUUCU
1620
AGAAGGCA GCcgaaagGCGaGuCaaGGuCu AGACGGGG
9191





1581
CGGACCGU G UGCACUUC
1621
GAAGUGCA GCcgaaagGCGaGuCaaGGuCu ACGGUCCG
9192





1684
UCAGCAAU G UCAACGAC
1622
GUCGUUGA GCcgaaagGCGaGuCaaGGuCu AUUGCUGA
9193





1719
CAAAGACU G UGUGUUUA
1623
UAAACACA GCcgaaagGCGaGuCaaGGuCu AGUCUUUG
9194





1721
AAGACUGU G UGUUUAAU
1624
AUUAAACA GCcgaaagGCGaGuCaaGGuCu ACAGUCUU
9195





1723
GACUGUGU G UUUAAUGA
1625
UCAUUAAA GCcgaaagGCGaGuCaaGGuCu ACACAGUC
9196





1772
AGGUCUUU G UACUAGGA
1626
UCCUAGUA GCcgaaagGCGaGuCaaGGuCu AAAGACCU
9197





1785
AGGAGGCU G UAGGCAUA
1627
UAUGCCUA GCcgaaagGCGaGuCaaGGuCu AGCCUCCU
9198





1801
AAAUUGGU G UGUUCACC
1628
GGUGAACA GCcgaaagGCGaGuCaaGGuCu ACCAAUUU
9199





1803
AUUGGUGU G UUCACCAG
1629
CUGGUGAA GCcgaaagGCGaGuCaaGGuCu ACACCAAU
9200





1850
CAUCUCAU G UUCAUGUC
1630
GACAUGAA GCcgaaagGCGaGuCaaGGuCu AUGAGAUG
9201





1856
AUGUUCAU G UCCUACUG
1631
CAGUAGGA GCcgaaagGCGaGuCaaGGuCu AUGAACAU
9202





1864
GUCCUACU G UUCAAGCC
1632
GGCUUGAA GCcgaaagGCGaGuCaaGGuCu AGUAGGAC
9203





1881
UCCAAGCU G UGCCUUGG
1633
CCAAGGCA GCcgaaagGCGaGuCaaGGuCu AGCUUGGA
9204





1939
GAGCUUCU G UGGAGUUA
1634
UAACUCCA GCcgaaagGCGaGuCaaGGuCu AGAAGCUC
9205





2013
UCUGCUCU G UAUCGGGG
1635
CCCCGAUA GCcgaaagGCGaGuCaaGGuCu AGAGCAGA
9206





2045
GGAACAUU G UUCACCUC
1636
GAGGUGAA GCcgaaagGCGaGuCaaGGuCu AAUGUUCC
9207





2082
GCUAUUCU G UGUUGGGG
1637
CCCCAACA GCcgaaagGCGaGuCaaGGuCu AGAAUAGC
9208





2084
UAUUCUGU G UUGGGGUG
1638
CACCCCAA GCcgaaagGCGaGuCaaGGuCu ACAGAAUA
9209





2167
UCAGCUAU G UCAACGUU
1639
AACGUUGA GCcgaaagGCGaGuCaaGGuCu AUAGCUGA
9210





2205
CAACUAUU G UGGUUUCA
1640
UGAAACCA GCcgaaagGCGaGuCaaGGuCu AAUAGUUG
9211





2222
CAUUUCCU G UCUUACUU
1641
AAGUAAGA GCcgaaagGCGaGuCaaGGuCu AGGAAAUG
9212





2245
GAGAAACU G UUCUUGAA
1642
UUCAAGAA GCcgaaagGCGaGuCaaGGuCu AGUUUCUC
9213





2262
UAUUUGGU G UCUUUUGG
1643
CCAAAAGA GCcgaaagGCGaGuCaaGGuCu ACCAAAUA
9214





2274
UUUGGAGU G UGGAUUCG
1644
CGAAUCCA GCcgaaagGCGaGuCaaGGuCu ACUCCAAA
9215





2344
AAACUACU G UUGUUAGA
1645
UCUAACAA GCcgaaagGCGaGuCaaGGuCu AGUAGUUU
9216





2347
CUACUGUU G UUAGACGA
1646
UCGUCUAA GCcgaaagGCGaGuCaaGGuCu AACAGUAG
9217





2450
AUCUCAAU G UUAGUAUU
1647
AAUACUAA GCcgaaagGCGaGuCaaGGuCu AUUGAGAU
9218





2573
AGGACAUU G UUGAUAGA
1648
UCUAUCAA GCcgaaagGCGaGuCaaGGuCu AAUGUCCU
9219





2583
UGAUAGAU G UAAGCAAU
1649
AUUGCUUA GCcgaaagGCGaGuCaaGGuCu AUCUAUCA
9220





2594
AGCAAUUU G UGGGGCCC
1650
GGGCCCCA GCcgaaagGCGaGuCaaGGuCu AAAUUGCU
9221





2663
AUCCCAAU G UUACUAAA
1651
UUUAGUAA GCcgaaagGCGaGuCaaGGuCu AUUGGGAU
9222





2717
CAGAGUAU G UAGUUAAU
1652
AUUAACUA GCcgaaagGCGaGuCaaGGuCu AUACUCUG
9223





2901
AUCUUUCU G UCCCCAAU
1653
AUUGGGGA GCcgaaagGCGaGuCaaGGuCu AGAAAGAU
9224





3071
GGGGGACU G UUGGGGUG
1654
CACCCCAA GCcgaaagGCGaGuCaaGGuCu AGUCCCCC
9225





3111
UCACAACU G UGCCAGCA
1655
UGCUGGCA GCcgaaagGCGaGuCaaGGuCu AGUUGUGA
9226





40
AUCCCAGA G UCAGGGCC
1656
GGCCCUGA GCcgaaagGCGaGuCaaGGuCu UCUGGGAU
9227





46
GAGUCAGG G CCCUGUAC
1657
GUACAGGG GCcgaaagGCGaGuCaaGGuCu CCUGACUC
9228





65
UCCUGCUG G UGGCUCCA
1658
UGGAGCCA GCcgaaagGCGaGuCaaGGuCu CAGCAGGA
9229





68
UGCUGGUG G CUCCAGUU
1659
AACUGGAG GCcgaaagGCGaGuCaaGGuCu CACCAGCA
9230





74
UGGCUCCA G UUCAGGAA
1660
UUCCUGAA GCcgaaagGCGaGuCaaGGuCu UGGAGCCA
9231





85
CAGGAACA G UGAGCCCU
1661
AGGGCUCA GCcgaaagGCGaGuCaaGGuCu UGUUCCUG
9232





89
AACAGUGA G CCCUGCUC
1662
GAGCAGGG GCcgaaagGCGaGuCaaGGuCu UCACUGUU
9233





120
GCCAUAUC G UCAAUCUU
1663
AAGAUUGA GCcgaaagGCGaGuCaaGGuCu GAUAUGGC
9234





196
CCCUGCUC G UGUUACAG
1664
CUGUAACA GCcgaaagGCGaGuCaaGGuCu GAGCAGGG
9235





205
UGUUACAG G CGGGGUUU
1665
AAACCCCG GCcgaaagGCGaGuCaaGGuCu CUGUAACA
9236





210
CAGGCGGG G UUUUUCUU
1666
AAGAAAAA GCcgaaagGCGaGuCaaGGuCu CCCGCCUG
9237





248
ACCACAGA G UCUAGACU
1667
AGUCUAGA GCcgaaagGCGaGuCaaGGuCu UCUGUGGU
9238





258
CUAGACUC G UGGUGGAC
1668
GUCCACCA GCcgaaagGCGaGuCaaGGuCu GAGUCUAG
9239





261
GACUCGUG G UGGACUUC
1669
GAAGUCCA GCcgaaagGCGaGuCaaGGuCu CACGAGUC
9240





295
GAACACCC G UGUGUCUU
1670
AAGACACA GCcgaaagGCGaGuCaaGGuCu GGGUGUUC
9241





305
GUGUCUUG G CCAAAAUU
1671
AAUUUUGG GCcgaaagGCGaGuCaaGGuCu CAAGACAC
9242





318
AAUUCGCA G UCCCAAAU
1672
AUUUGGGA GCcgaaagGCGaGuCaaGGuCu UGCGAAUU
9243





332
AAUCUCCA G UCACUCAC
1673
GUGAGUGA GCcgaaagGCGaGuCaaGGuCu UGGAGAUU
9244





368
UUGUCCUG G UUAUCGCU
1674
AGCGAUAA GCcgaaagGCGaGuCaaGGuCu CAGGACAA
9245





390
UGUCUGCG G CGUUUUAU
1675
AUAAAACG GCcgaaagGCGaGuCaaGGuCu CGCAGACA
9246





392
UCUGCGGC G UUUUAUCA
1676
UGAUAAAA GCcgaaagGCGaGuCaaGGuCu GCCGCAGA
9247





442
UCUUGUUG G UUCUUCUG
1677
CAGAAGAA GCcgaaagGCGaGuCaaGGuCu CAACAAGA
9248





461
CUAUCAAG G UAUGUUGC
1678
GCAACAUA GCcgaaagGCGaGuCaaGGuCu CUUGAUAG
9249





472
UGUUGCCC G UUUGUCCU
1679
AGGACAAA GCcgaaagGCGaGuCaaGGuCu GGGCAACA
9250





506
AACAACCA G CACCGGAC
1680
GUCCGGUG GCcgaaagGCGaGuCaaGGuCu UGGUUGUU
9251





625
CAUCUUGG G CUUUCGCA
1681
UGCGAAAG GCcgaaagGCGaGuCaaGGuCu CCAAGAUG
9252





648
CUAUGGGA G UGGGCCUC
1682
GAGGCCCA GCcgaaagGCGaGuCaaGGuCu UCCCAUAG
9253





652
GGGAGUGG G CCUCAGUC
1683
GACUGAGG GCcgaaagGCGaGuCaaGGuCu CCACUCCC
9254





658
GGGCCUCA G UCCGUUUC
1684
GAAACGGA GCcgaaagGCGaGuCaaGGuCu UGAGGCCC
9255





662
CUCAGUCC G UUUCUCUU
1685
AAGAGAAA GCcgaaagGCGaGuCaaGGuCu GGACUGAG
9256





672
UUCUCUUG G CUCAGUUU
1686
AAACUGAG GCcgaaagGCGaGuCaaGGuCu CAAGAGAA
9257





677
UUGGCUCA G UUUACUAG
1687
CUAGUAAA GCcgaaagGCGaGuCaaGGuCu UGAGCCAA
9258





685
GUUUACUA G UGCCAUUU
1688
AAAUGGCA GCcgaaagGCGaGuCaaGGuCu UAGUAAAC
9259





699
UUUGUUCA G UGGUUCGU
1689
ACGAACCA GCcgaaagGCGaGuCaaGGuCu UGAACAAA
9260





702
GUUCAGUG G UUCGUAGG
1690
CCUACGAA GCcgaaagGCGaGuCaaGGuCu CACUGAAC
9261





706
AGUGGUUC G UAGGGCUU
1691
AAGCCCUA GCcgaaagGCGaGuCaaGGuCu GAACCACU
9262





711
UUCGUAGG G CUUUCCCC
1692
GGGGAAAG GCcgaaagGCGaGuCaaGGuCu CCUACGAA
9263





729
ACUGUCUG G CUUUCAGU
1693
ACUGAAAG GCcgaaagGCGaGuCaaGGuCu CAGACAGU
9264





736
GGCUUUCA G UUAUAUGG
1694
CCAUAUAA GCcgaaagGCGaGuCaaGGuCu UGAAAGCC
9265





753
AUGAUGUG G UUUUGGGG
1695
CCCCAAAA GCcgaaagGCGaGuCaaGGuCu CACAUCAU
9266





762
UUUUGGGG G CCAAGUCU
1696
AGACUUGG GCcgaaagGCGaGuCaaGGuCu CCCCAAAA
9267





767
GGGGCCAA G UCUGUACA
1697
UGUACAGA GCcgaaagGCGaGuCaaGGuCu UUGGCCCC
9268





785
CAUCUUGA G UCCCUUUA
1698
UAAAGGGA GCcgaaagGCGaGuCaaGGuCu UCAAGAUG
9269





826
GUCUUUGG G UAUACAUU
1699
AAUGUAUA GCcgaaagGCGaGuCaaGGuCu CCAAAGAC
9270





898
AAUUGGGA G UUGGGGCA
1700
UGCCCCAA GCcgaaagGCGaGuCaaGGuCu UCCCAAUU
9271





904
GAGUUGGG G CACAUUGC
1701
GCAAUGUG GCcgaaagGCGaGuCaaGGuCu CCCAACUC
9272





971
GUAAACAG G CCUAUUGA
1702
UCAAUAGG GCcgaaagGCGaGuCaaGGuCu CUGUUUAC
9273





987
AUUGGAAA G UAUGUCAA
1703
UUGACAUA GCcgaaagGCGaGuCaaGGuCu UUUCCAAU
9274





1006
AAUUGUGG G UCUUUUGG
1704
CCAAAAGA GCcgaaagGCGaGuCaaGGuCu CCACAAUU
9275





1016
CUUUUGGG G UUUGCCGC
1705
GCGGCAAA GCcgaaagGCGaGuCaaGGuCu CCCAAAAG
9276





1080
GCAUACAA G CAAAACAG
1706
CUGUUUUG GCcgaaagGCGaGuCaaGGuCu UUGUAUGC
9277





1089
CAAAACAG G CUUUUACU
1707
AGUAAAAG GCcgaaagGCGaGuCaaGGuCu CUGUUUUG
9278





1116
CUUACAAG G CCUUUCUA
1708
UAGAAAGG GCcgaaagGCGaGuCaaGGuCu CUUGUAAG
9279





1126
CUUUCUAA G UAAACAGU
1709
ACUGUUUA GCcgaaagGCGaGuCaaGGuCu UUAGAAAG
9280





1133
AGUAAACA G UAUGUGAA
1710
UUCACAUA GCcgaaagGCGaGuCaaGGuCu UGUUUACU
9281





1152
UUUACCCC G UUGCUCGG
1711
CCGAGCAA GCcgaaagGCGaGuCaaGGuCu GGGGUAAA
9282





1160
GUUGCUCG G CAACGGCC
1712
GGCCGUUG GCcgaaagGCGaGuCaaGGuCu CGAGCAAC
9283





1166
CGGCAACG G CCUGGUCU
1713
AGACCAGG GCcgaaagGCGaGuCaaGGuCu CGUUGCCG
9284





1171
ACGGCCUG G UCUAUGCC
1714
GGCAUAGA GCcgaaagGCGaGuCaaGGuCu CAGGCCGU
9285





1182
UAUGCCAA G UGUUUGCU
1715
AGCAAACA GCcgaaagGCGaGuCaaGGuCu UUGGCAUA
9286





1207
CCCCACUG G UUGGGGCU
1716
AGCCCCAA GCcgaaagGCGaGuCaaGGuCu CAGUGGGG
9287





1213
UGGUUGGG G CUUGGCCA
1717
UGGCCAAG GCcgaaagGCGaGuCaaGGuCu CCCAACCA
9288





1218
GGGGCUUG G CCAUAGGC
1718
GCCUAUGG GCcgaaagGCGaGuCaaGGuCu CAAGCCCC
9289





1225
CCCCAUAG G CCAUCAGC
1719
GCUGAUGG GCcgaaagGCGaGuCaaGGuCu CUAUGGCC
9290





1232
GGCCAUCA G CGCAUGCG
1720
CGCAUGCG GCcgaaagGCGaGuCaaGGuCu UGAUGGCC
9291





1240
GCGCAUGC G UGGAACCU
1721
AGGUUCCA GCcgaaagGCGaGuCaaGGuCu GCAUGCGC
9292





1287
AACUCCUA G CCGCUUGU
1722
ACAAGCGG GCcgaaagGCGaGuCaaGGuCu UAGGAGUU
9293





1306
UGCUCGCA G CAGGUCUG
1723
CAGACCUG GCcgaaagGCGaGuCaaGGuCu UGCGAGCA
9294





1310
CGCAGCAG G UCUGGGGC
1724
GCCCCAGA GCcgaaagGCGaGuCaaGGuCu CUGCUGCG
9295





1317
GGUCUGGG G CAAAACUC
1725
GAGUUUUG GCcgaaagGCGaGuCaaGGuCu CCCAGACC
9296





1347
AUUCUGUC G UGCUCUCC
1726
GGAGAGCA GCcgaaagGCGaGuCaaGGuCu GACAGAAU
9297





1379
UUUCCAUG G CUGCUAGG
1727
CCUAGCAG GCcgaaagGCGaGuCaaGGuCu CAUGGAAA
9298





1387
GCUGCUAG G CUGUGCUG
1728
CAGCACAG GCcgaaagGCGaGuCaaGGuCu CUAGCAGC
9299





1418
CGCGGGAC G UCCUUUGU
1729
ACAAAGGA GCcgaaagGCGaGuCaaGGuCu GUCCCGCG
9300





1431
UUGUUUAC G UCCCGUCG
1730
CGACGGGA GCcgaaagGCGaGuCaaGGuCu GUAAACAA
9301





1436
UACGUCCC G UCGGCGCU
1731
AGCGCCGA GCcgaaagGCGaGuCaaGGuCu GGGACGUA
9302





1440
UCCCGUCG G CGCUGAAU
1732
AUUCAGCG GCcgaaagGCGaGuCaaGGuCu CGACGGGA
9303





1471
CUCCCGGG G CCGCUUGG
1733
CCAAGCGG GCcgaaagGCGaGuCaaGGuCu CCCGGGAG
9304





1481
CGCUUGGG G CUCUACCG
1734
CGGUAGAG GCcgaaagGCGaGuCaaGGuCu CCCAAGCG
9305





1517
UACCGACC G UCCACGGG
1735
CCCGUGGA GCcgaaagGCGaGuCaaGGuCu GGUCGGUA
9306





1526
UCCACGGG G CGCACCUC
1736
GAGGUGCG GCcgaaagGCGaGuCaaGGuCu CCCGUGGA
9307





1553
GACUCCCC G UCUGUGCC
1737
GGCACAGA GCcgaaagGCGaGuCaaGGuCu GGGGAGUC
9308





1579
GCCGGACC G UGUGCACU
1738
AGUGCACA GCcgaaagGCGaGuCaaGGuCu GGUCCGGC
9309





1605
CUCUGCAC G UCGCAUGG
1739
CCAUGCGA GCcgaaagGCGaGuCaaGGuCu GUGCAGAG
9310





1622
AGACCACC G UGAACGCC
1740
GGCGUUCA GCcgaaagGCGaGuCaaGGuCu GGUGGUCU
9311





1649
UGCCCAAG G UCUUGCAU
1741
AUGCAAGA GCcgaaagGCGaGuCaaGGuCu CUUGGGCA
9312





1679
GACUUUCA G CAAUGUCA
1742
UGACAUUG GCcgaaagGCGaGuCaaGGuCu UGAAAGUC
9313





1703
ACCUUGAG G CAUACUUC
1743
GAAGUAUG GCcgaaagGCGaGuCaaGGuCu CUCAAGGU
9314





1732
UUUAAUGA G UGGGAGGA
1744
UCCUCCCA GCcgaaagGCGaGuCaaGGuCu UCAUUAAA
9315





1741
UGGGAGGA G UUGGGGGA
1745
UCCCCCAA GCcgaaagGCGaGuCaaGGuCu UCCUCCCA
9316





1754
GGGAGGAG G UUAGGUUA
1746
UAACCUAA GCcgaaagGCGaGuCaaGGuCu CUCCUCCC
9317





1759
GAGGUUAG G UUAAAGGU
1747
ACCUUUAA GCcgaaagGCGaGuCaaGGuCu CUAACCUC
9318





1766
GGUUAAAG G UCUUUGUA
1748
UACAAAGA GCcgaaagGCGaGuCaaGGuCu CUUUAACC
9319





1782
ACUAGGAG G CUGUAGGC
1749
GCCUACAG GCcgaaagGCGaGuCaaGGuCu CUCCUAGU
9320





1789
GGCUGUAG G CAUAAAUU
1750
AAUUUAUG GCcgaaagGCGaGuCaaGGuCu CUACAGCC
9321





1799
AUAAAUUG G UGUGUUCA
1751
UGAACACA GCcgaaagGCGaGuCaaGGuCu CAAUUUAU
9322





1811
GUUCACCA G CACCAUGC
1752
GCAUGGUG GCcgaaagGCGaGuCaaGGuCu UGGUGAAC
9323





1870
CUGUUCAA G CCUCCAAG
1753
CUUGGAGG GCcgaaagGCGaGuCaaGGuCu UUGAACAG
9324





1878
GCCUCCAA G CUGUGCCU
1754
AGGCACAG GCcgaaagGCGaGuCaaGGuCu UUGGAGGC
9325





1890
UGCCUUGG G UGGCUUUG
1755
CAAAGCCA GCcgaaagGCGaGuCaaGGuCu CCAAGGCA
9326





1893
CUUGGGUG G CUUUGGGG
1756
CCCCAAAG GCcgaaagGCGaGuCaaGGuCu CACCCAAG
9327





1901
GCUUUGGG G CAUGGACA
1757
UGUCCAUG GCcgaaagGCGaGuCaaGGuCu CCCAAAGC
9328





1917
AUUGACCC G UAUAAAGA
1758
UCUUUAUA GCcgaaagGCGaGuCaaGGuCu GGGUCAAU
9329





1933
AAUUUGGA G CUUCUGUG
1759
CACAGAAG GCcgaaagGCGaGuCaaGGuCu UCCAAAUU
9330





1944
UCUGUGGA G UUACUCUC
1760
GAGAGUAA GCcgaaagGCGaGuCaaGGuCu UCCACAGA
9331





2023
AUCGGGGG G CCUUAGAG
1761
CUCUAAGG GCcgaaagGCGaGuCaaGGuCu CCCCCGAU
9332





2031
GCCUUAGA G UCUCCGGA
1762
UCCGGAGA GCcgaaagGCGaGuCaaGGuCu UCUAAGGC
9333





2062
ACCAUACG G CACUCAGG
1763
CCUGAGUG GCcgaaagGCGaGuCaaGGuCu CGUAUGGU
9334





2070
GCACUCAG G CAAGCUAU
1764
AUAGCUUG GCcgaaagGCGaGuCaaGGuCu CUGAGUGC
9335





2074
UCAGGCAA G CUAUUCUG
1765
CAGAAUAG GCcgaaagGCGaGuCaaGGuCu UUGCCUGA
9336





2090
GUGUUGGG G UGAGUUGA
1766
UCAACUCA GCcgaaagGCGaGuCaaGGuCu CCCAACAC
9337





2094
UGGGGUGA G UUGAUGAA
1767
UUCAUCAA GCcgaaagGCGaGuCaaGGuCu UCACCCCA
9338





2107
UGAAUCUA G CCACCUGG
1768
CCAGGUGG GCcgaaagGCGaGuCaaGGuCu UAGAUUCA
9339





2116
CCACCUGG G UGGGAAGU
1769
ACUUCCCA GCcgaaagGCGaGuCaaGGuCu CCAGGUGG
9340





2123
GGUGGGAA G UAAUUUGG
1770
CCAAAUUA GCcgaaagGCGaGuCaaGGuCu UUCCCACC
9341





2140
AAGAUCCA G CAUCCAGG
1771
CCUGGAUG GCcgaaagGCGaGuCaaGGuCu UGGAUCUU
9342





2155
GGGAAUUA G UAGUCAGC
1772
GCUGACUA GCcgaaagGCGaGuCaaGGuCu UAAUUCCC
9343





2158
AAUUAGUA G UCAGCUAU
1773
AUAGCUGA GCcgaaagGCGaGuCaaGGuCu UACUAAUU
9344





2162
AGUAGUCA G CUAUGUCA
1774
UGACAUAG GCcgaaagGCGaGuCaaGGuCu UGACUACU
9345





2173
AUGUCAAC G UUAAUAUG
1775
CAUAUUAA GCcgaaagGCGaGuCaaGGuCu GUUGACAU
9346





2183
UAAUAUGG G CCUAAAAA
1776
UUUUUAGG GCcgaaagGCGaGuCaaGGuCu CCAUAUUA
9347





2208
CUAUUGUG G UUUCACAU
1777
AUGUGAAA GCcgaaagGCGaGuCaaGGuCu CACAAUAG
9348





2235
ACUUUUGG G CGAGAAAC
1778
GUUUCUCG GCcgaaagGCGaGuCaaGGuCu CCAAAAGU
9349





2260
AAUAUUUG G UGUCUUUU
1779
AAAAGACA GCcgaaagGCGaGuCaaGGuCu CAAAUAUU
9350





2272
CUUUUGGA G UGUGGAUU
1780
AAUCCACA GCcgaaagGCGaGuCaaGGuCu UCCAAAAG
9351





2360
ACGAAGAG G CAGGUCCC
1781
GGGACCUG GCcgaaagGCGaGuCaaGGuCu CUCUUCGU
9352





2364
AGAGGCAG G UCCCCUAG
1782
CUAGGGGA GCcgaaagGCGaGuCaaGGuCu CUGCCUCU
9353





2403
AGACGAAG G UCUCAAUC
1783
GAUUGAGA GCcgaaagGCGaGuCaaGGuCu CUUCGUCU
9354





2417
AUCGCCGC G UCGCAGAA
1784
UUCUGCGA GCcgaaagGCGaGuCaaGGuCu GCGGCGAU
9355





2454
CAAUGUUA G UAUUCCUU
1785
AAGGAAUA GCcgaaagGCGaGuCaaGGuCu UAACAUUG
9356





2474
CACAUAAG G UGGGAAAC
1786
GUUUCCCA GCcgaaagGCGaGuCaaGGuCu CUUAUGUG
9357





2491
UUUACGGG G CUUUAUUC
1787
GAAUAAAG GCcgaaagGCGaGuCaaGGuCu CCCGUAAA
9358





2507
CUUCUACG G UACCUUGC
1788
GCAAGGUA GCcgaaagGCGaGuCaaGGuCu CGUAGAAG
9359





2530
CCUAAAUG G CAAACUCC
1789
GGAGUUUG GCcgaaagGCGaGuCaaGGuCu CAUUUAGG
9360





2587
AGAUGUAA G CAAUUUGU
1790
ACAAAUUG GCcgaaagGCGaGuCaaGGuCu UUACAUCU
9361





2599
UUUGUGGG G CCCCUUAC
1791
GUAAGGGG GCcgaaagGCGaGuCaaGGuCu CCCACAAA
9362





2609
CCCUUACA G UAAAUGAA
1792
UUCAUUUA GCcgaaagGCGaGuCaaGGuCu UGUAAGGG
9363





2650
CCUGCUAG G UUUUAUCC
1793
GGAUAAAA GCcgaaagGCGaGuCaaGGuCu CUAGCAGG
9364





2701
AUCAAACC G UAUUAUCC
1794
GGAUAAUA GCcgaaagGCGaGuCaaGGuCu GGUUUGAU
9365





2713
UAUCCAGA G UAUGUAGU
1795
ACUACAUA GCcgaaagGCGaGuCaaGGuCu UCUGGAUA
9366





2720
AGUAUGUA G UUAAUCAU
1796
AUGAUUAA GCcgaaagGCGaGuCaaGGuCu UACAUACU
9367





2768
UUUGGAAG G CGGGGAUC
1797
GAUCCCCG GCcgaaagGCGaGuCaaGGuCu CUUCCAAA
9368





2791
AAAAGAGA G UCCACACG
1798
CGUGUGGA GCcgaaagGCGaGuCaaGGuCu UCUCUUUU
9369





2799
GUCCACAC G UAGCGCCU
1799
AGGCGCUA GCcgaaagGCGaGuCaaGGuCu GUGUGGAC
9370





2802
CACACGUA G CGCCUCAU
1800
AUGAGGCG GCcgaaagGCGaGuCaaGGuCu UACGUGUG
9371





2818
UUUUGCGG G UCACCAUA
1801
UAUGGUGA GCcgaaagGCGaGuCaaGGuCu CCGCAAAA
9372





2848
GAUCUACA G CAUGGGAG
1802
CUCCCAUG GCcgaaagGCGaGuCaaGGuCu UGUAGAUC
9373





2857
CAUGGGAG G UUGGUCUU
1803
AAGACCAA GCcgaaagGCGaGuCaaGGuCu CUCCCAUG
9374





2861
GGAGGUUG G UCUUCCAA
1804
UUGGAAGA GCcgaaagGCGaGuCaaGGuCu CAACCUCC
9375





2881
UCGAAAAG G CAUGGGGA
1805
UCCCCAUG GCcgaaagGCGaGuCaaGGuCu CUUUUCGA
9376





2936
GAUCAUCA G UUGGACCC
1806
GGGUCCAA GCcgaaagGCGaGuCaaGGuCu UGAUGAUC
9377





2955
CAUUCAAA G CCAACUCA
1807
UGAGUUGG GCcgaaagGCGaGuCaaGGuCu UUUGAAUG
9378





2964
CCAACUCA G UAAAUCCA
1808
UGGAUUUA GCcgaaagGCGaGuCaaGGuCu UGAGUUGG
9379





3005
GACAACUG G CCGGACGC
1809
GCGUCCGG GCcgaaagGCGaGuCaaGGuCu CAGUUGUC
9380





3021
CCAACAAG G UGGGAGUG
1810
CACUCCCA GCcgaaagGCGaGuCaaGGuCu CUUGUUGG
9381





3027
AGGUGGGA G UGGGAGCA
1811
UGCUCCCA GCcgaaagGCGaGuCaaGGuCu UCCCACCU
9382





3033
GAGUGGGA G CAUUCGGG
1812
CCCGAAUG GCcgaaagGCGaGuCaaGGuCu UCCCACUC
9383





3041
GCAUUCGG G CCAGGGUU
1813
AACCCUGG GCcgaaagGCGaGuCaaGGuCu CCGAAUGC
9384





3047
GGGCCAGG G UUCACCCC
1814
GGGGUGAA GCcgaaagGCGaGuCaaGGuCu CCUGGCCC
9385





3077
CUGUUGGG G UGGAGCCC
1815
GGGCUCCA GCcgaaagGCGaGuCaaGGuCu CCCAACAG
9386





3082
GGGGUGGA G CCCUCACG
1816
CGUGAGGG GCcgaaagGCGaGuCaaGGuCu UCCACCCC
9387





3097
CGCUCAGG G CCUACUCA
1817
UGAGUAGG GCcgaaagGCGaGuCaaGGuCu CCUGAGCG
9388





3117
CUGUGCCA G CAGCUCCU
1818
AGGAGCUG GCcgaaagGCGaGuCaaGGuCu UGGCACAG
9389





3120
UGCCAGCA G CUCCUCCU
1819
AGGAGGAG GCcgaaagGCGaGuCaaGGuCu UGCUGGCA
9390





3146
ACCAAUCG G CAGUCAGG
1820
CCUGACUG GCcgaaagGCGaGuCaaGGuCu CGAUUGGU
9391





3149
AAUCGGCA G UCAGGAAG
1821
CUUCCUGA GCcgaaagGCGaGuCaaGGuCu UGCCGAUU
9392





3158
UCAGGAAG G CAGCCUAC
1822
GUAGGCUG GCcgaaagGCGaGuCaaGGuCu CUUCCUGA
9393





3161
GGAAGGCA G CCUACUCC
1823
GGAGUAGG GCcgaaagGCGaGuCaaGGuCu UGCCUUCC
9394





3204
AUCCUCAG G CCAUGCAG
1824
CUGCAUGG GCcgaaagGCGaGuCaaGGuCu CUGAGGAU
9395






Input Sequence = AF100308.




Cut Site = YG/M or UG/U.




Stem Length = 8.




Core Sequence = GCcgaaagGCGaGuCaaGGuCu




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








[0557]

9






TABLE IX










HUMAN HBV DNAZYME AND SUBSTRATE SEQUENCE












Pos
Substrate
Seq ID
DNAzyme
Seq ID















508
CAACCAGC A CCGGACCA
833
TGGTCCGG GGCTAGCTACAACGA GCTGGTTG
9396






1632
GAACGCCC A CAGGAACC
1096
GGTTCCTG GGCTAGCTACAACGA GGGCGTTC
9397





2992
CAACCCGC A CAAGGACA
1376
TGTCCTTG GGCTAGCTACAACGA GCGGGTTG
9398





61
ACUUUCCU G CUGGUGGC
1448
GCCACCAG GGCTAGCTACAACGA AGGAAAGT
9399





94
UGAGCCCU G CUCAGAAU
1450
ATTCTGAG GGCTAGCTACAACGA AGGGCTCA
9400





112
CUGUCUCU G CCAUAUCG
1451
CGATATGG GGCTAGCTACAACGA AGAGACAG
9401





169
AGAACAUC G CAUCAGGA
1454
TCCTGATG GGCTAGCTACAACGA GATGTTCT
9402





192
GGACCCCU G CUCGUGUU
1455
AACACGAG GGCTAGCTACAACGA AGGGGTCC
9403





315
CAAAAUUC G CAGUCCCA
1457
TGGGACTG GGCTAGCTACAACGA GAATTTTG
9404





374
UGGUUAUC G CUGGAUGU
1458
ACATCCAG GGCTAGCTACAACGA GATAACCA
9405





387
AUGUGUCU G CGGCGUUU
1459
AAACGCCG GGCTAGCTACAACGA AGACACAT
9406





410
CUUCCUCU G CAUCCUGC
1460
GCAGGATG GGCTAGCTACAACGA AGAGGAAG
9407





417
UGCAUCCU G CUGCUAUG
1461
CATAGCAG GGCTAGCTACAACGA AGGATGCA
9408





420
AUCCUGCU G CUAUGCCU
1462
AGGCATAG GGCTAGCTACAACGA AGCAGGAT
9409





425
GCUGCUAU G CCUCAUCU
1463
AGATGAGG GGCTAGCTACAACGA ATAGCAGC
9410





468
GGUAUGUU G CCCGUUUG
1464
CAAACGGG GGCTAGCTACAACGA AACATACC
9411





518
CGGACCAU G CAAAACCU
1465
AGGTTTTG GGCTAGCTACAACGA ATGGTCCG
9412





527
CAAAACCU G CACAACUC
1466
GAGTTGTG GGCTAGCTACAACGA AGGTTTTG
9413





538
CAACUCCU G CUCAAGGA
1467
TCCTTGAG GGCTAGCTACAACGA AGGAGTTG
9414





569
CUCAUGUU G CUGUACAA
1468
TTGTACAG GGCTAGCTACAACGA AACATGAG
9415





596
CGGAAACU G CACCUGUA
1469
TACAGGTG GGCTAGCTACAACGA AGTTTCCG
9416





631
GGGCUUUC G CAAAAUAC
1470
GTATTTTG GGCTAGCTACAACGA GAAAGCCC
9417





687
UUACUAGU G CCAUUUGU
1471
ACAAATGG GGCTAGCTACAACGA ACTAGTAA
9418





795
CCCUUUAU G CCGCUGUU
1474
AACAGCGG GGCTAGCTACAACGA ATAAAGGG
9419





798
UUUAUGCC G CUGUUACC
1475
GGTAACAG GGCTAGCTACAACGA GGCATAAA
9420





911
GGCACAUU G CCACAGGA
1476
TCCTGTGG GGCTAGCTACAACGA AATGTGCC
9421





1020
UGGGGUUU G CCGCCCCU
1479
AGGGGCGG GGCTAGCTACAACGA AAACCCCA
9422





1023
GGUUUGCC G CCCCUUUC
1480
GAAAGGGG GGCTAGCTACAACGA GGCAAACC
9423





1034
CCUUUCAC G CAAUGUGG
1481
CCACATTG GGCTAGCTACAACGA GTGAAAGG
9424





1050
GAUAUUCU G CUUUAAUG
1482
CATTAAAG GGCTAGCTACAACGA AGAATATC
9425





1058
GCUUUAAU G CCUUUAUA
1483
TATAAAGG GGCTAGCTACAACGA ATTAAAGC
9426





1068
CUUUAUAU G CAUGCAUA
1484
TATGCATG GGCTAGCTACAACGA ATATAAAG
9427





1072
AUAUGCAU G CAUACAAG
1485
CTTGTATG GGCTAGCTACAACGA ATGCATAT
9428





1103
ACUUUCUC G CCAACUUA
1486
TAAGTTGG GGCTAGCTACAACGA GAGAAAGT
9429





1155
ACCCCGUU G CUCGGCAA
1488
TTGCCGAG GGCTAGCTACAACGA AACGGGGT
9430





1177
UGGUCUAU G CCAAGUGU
1489
ACACTTGG GGCTAGCTACAACGA ATAGACCA
9431





1188
AAGUGUUU G CUGACGCA
1490
TGCGTCAG GGCTAGCTACAACGA AAACACTT
9432





1194
UUGCUGAC G CAACCCCC
1492
GGGGGTTG GGCTAGCTACAACGA GTCAGCAA
9433





1234
CCAUCAGC G CAUGCGUG
1493
CACGCATG GGCTAGCTACAACGA GCTGATGG
9434





1238
CAGCGCAU G CGUGGAAC
1494
GTTCCACG GGCTAGCTACAACGA ATGCGCTG
9435





1262
UCUCCUCU G CCGAUCCA
1495
TGGATCGG GGCTAGCTACAACGA AGAGGAGA
9436





1275
UCCAUACC G CGGAACUC
1497
GAGTTCCG GGCTAGCTACAACGA GGTATGGA
9437





1290
UCCUAGCC G CUUGUUUU
1498
AAAACAAG GGCTAGCTACAACGA GGCTAGGA
9438





1299
CUUGUUUU G CUCGCAGC
1499
GCTGCGAG GGCTAGCTACAACGA AAAACAAG
9439





1303
UUUUGCUC G CAGCAGGU
1500
ACCTGCTG GGCTAGCTACAACGA GAGCAAAA
9440





1349
UCUGUCGU G CUCUCCCG
1502
CGGGAGAG GGCTAGCTACAACGA ACGACAGA
9441





1357
GCUCUCCC G CAAAUAUA
1503
TATATTTG GGCTAGCTACAACGA GGGAGAGC
9442





1382
CCAUGGCU G CUAGGCUG
1504
CAGCCTAG GGCTAGCTACAACGA AGCCATGG
9443





1392
UAGGCUGU G CUGCCAAC
1505
GTTGGCAG GGCTAGCTACAACGA ACAGCCTA
9444





1395
GCUGUGCU G CCAACUGG
1506
CCAGTTGG GGCTAGCTACAACGA AGCACAGC
9445





1411
GAUCCUAC G CGGGACGU
1507
ACGTCCCG GGCTAGCTACAACGA GTAGGATC
9446





1442
CCGUCGGC G CUGAAUCC
1508
GGATTCAG GGCTAGCTACAACGA GCCGACGG
9447





1452
UGAAUCCC G CGGACGAC
1510
GTCGTCCG GGCTAGCTACAACGA GGGATTCA
9448





1474
CCGGGGCC G CUUGGGGC
1512
GCCCCAAG GGCTAGCTACAACGA GGCCCCGG
9449





1489
GCUCUACC G CCCGCUUC
1513
GAAGCGGG GGCTAGCTACAACGA GGTAGAGC
9450





1493
UACCGCCC G CUUCUCCG
1514
CGGAGAAG GGCTAGCTACAACGA GGGCGGTA
9451





1501
GCUUCUCC G CCUAUUGU
1515
ACAATAGG GGCTAGCTACAACGA GGAGAAGC
9452





1528
CACGGGGC G CACCUCUC
1517
CAGAGGTG GGCTAGCTACAACGA GCCCCGTG
9453





1542
CUCUUUAC G CGGACUCC
1518
GGACTCCG GGCTAGCTACAACGA GTAAAGAG
9454





1559
CCGUCUGU G CCUUCUCA
1519
TGAGAAGG GGCTAGCTACAACGA ACAGACGG
9455





1571
UCUCAUCU G CCGGACCG
1520
CGGTCCGG GGCTAGCTACAACGA AGATGAGA
9456





1583
GACCGUGU G CACUUCGC
1521
GCGAAGTG GGCTAGCTACAACGA ACACGGTC
9457





1590
UGCACUUC G CUUCACCU
1522
AGGTGAAG GGCTAGCTACAACGA GAAGTGCA
9458





1601
UCACCUCU G CACGUCGC
1523
GCGACGTG GGCTAGCTACAACGA AGAGGTGA
9459





1608
UGCACGUC G CAUGGAGA
1524
TCTCCATG GGCTAGCTACAACGA GACGTGCA
9460





1628
CCGUGAAC G CCCACAGG
1526
CCTGTGGG GGCTAGCTACAACGA GTTCACGG
9461





1642
AGGAACCU G CCCAAGGU
1527
ACCTTGGG GGCTAGCTACAACGA AGGTTCCT
9462





1654
AAGGUCUU G CAUAAGAG
1528
CTCTTATG GGCTAGCTACAACGA AAGACCTT
9463





1818
AGCACCAU G CAACUUUU
1533
AAAAGTTG GGCTAGCTACAACGA ATGGTGCT
9464





1835
UCACCUCU G CCUAAUCA
1534
TGATTAGG GGCTAGCTACAACGA AGAGGTGA
9465





1883
CAAGCUGU G CCUUGGGU
1535
ACCCAAGG GGCTAGCTACAACGA ACAGCTTG
9466





1959
UCUUUUUU G CCUUCUGA
1537
TCAGAAGG GGCTAGCTACAACGA AAAAAAGA
9467





2002
UCGACACC G CCUCUGCU
1541
AGCAGAGG GGCTAGCTACAACGA GGTGTCGA
9468





2008
CCGCCUCU G CUCUGUAU
1542
ATACAGAG GGCTAGCTACAACGA AGAGGCGG
9469





2282
GUGGAUUC G CACUCCUC
1548
GAGGAGTG GGCTAGCTACAACGA GAATCCAC
9470





2293
CUCCUCCU G CAUAUAGA
1549
TCTATATG GGCTAGCTACAACGA AGGAGGAG
9471





2311
CACCAAAU G CCCCUAUC
1550
GATAGGGG GGCTAGCTACAACGA ATTTGGTG
9472





2388
ACUCCCUC G CCUCGCAG
1552
CTGCGAGG GGCTAGCTACAACGA GAGGGAGT
9473





2393
CUCGCCUC G CAGACGAA
1553
TTCGTCTG GGCTAGCTACAACGA GAGGCGAG
9474





2412
UCUCAAUC G CCGCGUCG
1555
CGACGCGG GGCTAGCTACAACGA GATTGAGA
9475





2415
CAAUCGCC G CGUCGCAG
1556
CTGCGACG GGCTAGCTACAACGA GGCGATTG
9476





2420
GCCGCGUC G CAGAAGAU
1557
ATCTTCTG GGCTAGCTACAACGA GACGCGGC
9477





2514
GGUACCUU G CUUUAAUC
1558
GATTAAAG GGCTAGCTACAACGA AAGGTACC
9478





2560
AUUCAUUU G CAGGAGGA
1560
TCCTCCTG GGCTAGCTACAACGA AAATGAAT
9479





2641
UUAACUAU G CCUGCUAG
1563
CTAGCAGG GGCTAGCTACAACGA ATAGTTAA
9480





2645
CUAUGCCU G CUAGGUUU
1564
AAACCTAG GGCTAGCTACAACGA AGGCATAG
9481





2677
AAAUAUUU G CCCUUAGA
1565
TCTAAGGG GGCTAGCTACAACGA AAATATTT
9482





2740
UUCCAGAC G CGACAUUA
1566
TAATGTCG GGCTAGCTACAACGA GTCTGGAA
9483





2804
CACGUAGC G CCUCAUUU
1568
AAATGAGG GGCTAGCTACAACGA GCTACGTG
9484





2814
CUCAUUUU G CGGGUCAC
1569
GTGACCCG GGCTAGCTACAACGA AAAATGAG
9485





2946
UGGACCCU G CAUUCAAA
1572
TTTGAATG GGCTAGCTACAACGA AGGGTCCA
9486





2990
CUCAACCC G CACAAGGA
1573
TCCTTGTG GGCTAGCTACAACGA GGGTTGAG
9487





3012
GGCCGGAC G CCAACAAG
1574
CTTGTTGG GGCTAGCTACAACGA GTCCGGCC
9488





3090
GCCCUCAC G CUCAGGGC
1575
GCCCTGAG GGCTAGCTACAACGA GTGAGGGC
9489





3113
ACAACUGU G CCAGCAGC
1576
GCTGCTGG GGCTAGCTACAACGA ACAGTTGT
9490





3132
CUCCUCCU G CCUCCACC
1577
GGTGGAGG GGCTAGCTACAACGA AGGAGGAG
9491





51
AGGGCCCU G UACUUUCC
1578
GGAAAGTA GGCTAGCTACAACGA AGGGCCCT
9492





106
AGAAUACU G UCUCUGCC
1579
GGCAGAGA GGCTAGCTACAACGA AGTATTCT
9493





148
GGGACCCU G UACCGAAC
1580
GTTCGGTA GGCTAGCTACAACGA AGGGTCCC
9494





198
CUGCUCGU G UUACAGGC
1581
GCCTGTAA GGCTAGCTACAACGA ACGAGCAG
9495





219
UUUUUCUU G UUGACAAA
1582
TTTGTCAA GGCTAGCTACAACGA AAGAAAAA
9496





297
ACACCCGU G UGUCUUGG
1583
CCAAGACA GGCTAGCTACAACGA ACGGGTGT
9497





299
ACCCGUGU G UCUUGGCC
1584
GGCCAAGA GGCTAGCTACAACGA ACACGGGT
9498





347
ACCAACCU G UUGUCCUC
1585
GAGGACAA GGCTAGCTACAACGA AGGTTGGT
9499





350
AACCUGUU G UCCUCCAA
1586
TTGGAGGA GGCTAGCTACAACGA AACAGGTT
9500





362
UCCAAUUU G UCCUGGUU
1587
AACCAGGA GGCTAGCTACAACGA AAATTGGA
9501





381
CGCUGGAU G UGUCUGCG
1588
CGCAGACA GGCTAGCTACAACGA ATCCAGCG
9502





383
CUGGAUGU G UCUGCGGC
1589
GCCGCAGA GGCTAGCTACAACGA ACATCCAG
9503





438
AUCUUCUU G UUGGUUCU
1590
AGAACCAA GGCTAGCTACAACGA AAGAAGAT
9504





465
CAAGGUAU G UUGCCCGU
1591
ACGGGCAA GGCTAGCTACAACGA ATACCTTG
9505





476
GCCCGUUU G UCCUCUAA
1592
TTAGAGGA GGCTAGCTACAACGA AAACGGGC
9506





555
ACCUCUAU G UUUCCCUC
1593
GAGGGAAA GGCTAGCTACAACGA ATAGAGGT
9507





566
UCCCUCAU G UUGCUGUA
1594
TACAGCAA GGCTAGCTACAACGA ATGAGGGA
9508





572
AUGUUGCU G UACAAAAC
1595
GTTTTGTA GGCTAGCTACAACGA AGCAACAT
9509





602
CUGCACCU G UAUUCCCA
1596
TGGGAATA GGCTAGCTACAACGA AGGTGCAG
9510





694
UGCCAUUU G UUCAGUGG
1597
CCACTGAA GGCTAGCTACAACGA AAATGGCA
9511





724
CCCCCACU G UCUGGCUU
1598
AAGCCAGA GGCTAGCTACAACGA AGTGGGGG
9512





750
UGGAUGAU G UGGUUUUG
1599
CAAAACCA GGCTAGCTACAACGA ATCATCCA
9513





771
CCAAGUCU G UACAACAU
1600
ATGTTGTA GGCTAGCTACAACGA AGACTTGG
9514





801
AUGCCGCU G UUACCAAU
1601
ATTGGTAA GGCTAGCTACAACGA AGCGGCAT
9515





818
UUUCUUUU G UCUUUGGG
1602
CCCAAAGA GGCTAGCTACAACGA AAAACAAA
9516





888
UGGGAUAU G UAAUUGGG
1603
CCCAATTA GGCTAGCTACAACGA ATATCCCA
9517





927
AACAUAUU G UACAAAAA
1604
TTTTTGTA GGCTAGCTACAACGA AATATGTT
9518





944
AUCAAAAU G UGUUUUAG
1605
CTAAAACA GGCTAGCTACAACGA ATTTTGAT
9519





946
CAAAAUGU G UUUUAGGA
1606
TCCTAAAA GGCTAGCTACAACGA ACATTTTG
9520





963
AACUUCCU G UAAACAGG
1607
CCTGTTTA GGCTAGCTACAACGA AGGAAGTT
9521





991
GAAAGUAU G UCAACGAA
1608
TTCGTTGA GGCTAGCTACAACGA ATACTTTC
9522





1002
AACGAAUU G UGGGUCUU
1609
AAGACCCA GGCTAGCTACAACGA AATTCGTT
9523





1039
CACGCAAU G UGGAUAUU
1610
AATATCCA GGCTAGCTACAACGA ATTGCGTG
9524





1137
AACAGUAU G UGAACCUU
1611
AAGGTTCA GGCTAGCTACAACGA ATACTGTT
9525





1184
UGCCAAGU G UUUGCUGA
1612
TCAGCAAA GGCTAGCTACAACGA ACTTGGCA
9526





1251
GAACCUUU G UGUCUCCU
1613
AGGAGACA GGCTAGCTACAACGA AAAGGTTC
9527





1253
ACCUUUGU G UCUCCUCU
1614
AGAGGAGA GGCTAGCTACAACGA ACAAAGGT
9528





1294
AGCCGCUU G UUUUGCUC
1615
GAGCAAAA GGCTAGCTACAACGA AAGCGGCT
9529





1344
ACAAUUCU G UCGUGCUC
1616
GAGCACGA GGCTAGCTACAACGA AGAATTGT
9530





1390
GCUAGGCU G UGCUGCCA
1617
TGGCAGCA GGCTAGCTACAACGA AGCCTAGC
9531





1425
CGUCCUUU G UUUACGUC
1618
GACGTAAA GGCTAGCTACAACGA AAAGGACG
9532





1508
CGCCUAUU G UACCGACC
1619
GGTCGGTA GGCTAGCTACAACGA AATAGGCG
9533





1557
CCCCGUCU G UGCCUUCU
1620
AGAAGGCA GGCTAGCTACAACGA AGACGGGG
9534





1581
CGGACCGU G UGCACUUC
1621
GAAGTGCA GGCTAGCTACAACGA ACGGTCCG
9535





1684
UCAGCAAU G UCAACGAC
1622
GTCGTTGA GGCTAGCTACAACGA ATTGCTGA
9536





1719
CAAAGACU G UGUGUUUA
1623
TAAACACA GGCTAGCTACAACGA AGTCTTTG
9537





1721
AAGACUGU G UGUUUAAU
1624
ATTAAACA GGCTAGCTACAACGA ACAGTCTT
9538





1723
GACUGUGU G UUUAAUGA
1625
TCATTAAA GGCTAGCTACAACGA ACACAGTC
9539





1772
AGGUCUUU G UACUAGGA
1626
TCCTAGTA GGCTAGCTACAACGA AAAGACCT
9540





1785
AGGAGGCU G UAGGCAUA
1627
TATGCCTA GGCTAGCTACAACGA AGCCTCCT
9541





1801
AAAUUGGU G UGUUCACC
1628
GGTGAACA GGCTAGCTACAACGA ACCAATTT
9542





1803
AUUGGUGU G UUCACCAG
1629
CTGGTGAA GGCTAGCTACAACGA ACACCAAT
9543





1850
CAUCUCAU G UUCAUGUC
1630
GACATGAA GGCTAGCTACAACGA ATGAGATG
9544





1856
AUGUUCAU G UCCUACUG
1631
CAGTAGGA GGCTAGCTACAACGA ATGAACAT
9545





1864
GUCCUACU G UUCAAGCC
1632
GGCTTGAA GGCTAGCTACAACGA AGTAGGAC
9546





1881
UCCAAGCU G UGCCUUGG
1633
CCAAGGCA GGCTAGCTACAACGA AGCTTGGA
9547





1939
GAGCUUCU G UGGAGUUA
1634
TAACTCCA GGCTAGCTACAACGA AGAAGCTC
9548





2013
UCUGCUCU G UAUCGGGG
1635
CCCCGATA GGCTAGCTACAACGA AGAGCAGA
9549





2045
GGAACAUU G UUCACCUC
1636
GAGGTGAA GGCTAGCTACAACGA AATGTTCC
9550





2082
GCUAUUCU G UGUUGGGG
1637
CCCCAACA GGCTAGCTACAACGA AGAATAGC
9551





2084
UAUUCUGU G UUGGGGUG
1638
CACCCCAA GGCTAGCTACAACGA ACAGAATA
9552





2167
UCAGCUAU G UCAACGUU
1639
AACGTTGA GGCTAGCTACAACGA ATAGCTGA
9553





2205
CAACUAUU G UGGUUUCA
1640
TGAAACCA GGCTAGCTACAACGA AATAGTTG
9554





2222
CAUUUCCU G UCUUACUU
1641
AAGTAAGA GGCTAGCTACAACGA AGGAAATG
9555





2245
GAGAAACU G UUCUUGAA
1642
TTCAAGAA GGCTAGCTACAACGA AGTTTCTC
9556





2262
UAUUUGGU G UCUUUUGG
1643
CCAAAAGA GGCTAGCTACAACGA ACCAAATA
9557





2274
UUUGGAGU G UGGAUUCG
1644
CGAATCCA GGCTAGCTACAACGA ACTCCAAA
9558





2344
AAACUACU G UUGUUAGA
1645
TCTAACAA GGCTAGCTACAACGA AGTAGTTT
9559





2347
CUACUGUU G UUAGACGA
1646
TCGTCTAA GGCTAGCTACAACGA AACAGTAG
9560





2450
AUCUCAAU G UUAGUAUU
1647
AATACTAA GGCTAGCTACAACGA ATTGAGAT
9561





2573
AGGACAUU G UUGAUAGA
1648
TCTATCAA GGCTAGCTACAACGA AATGTCCT
9562





2583
UGAUAGAU G UAAGCAAU
1649
ATTGCTTA GGCTAGCTACAACGA ATCTATCA
9563





2594
AGCAAUUU G UGGGGCCC
1650
GGGCCCCA GGCTAGCTACAACGA AAATTGCT
9564





2663
AUCCCAAU G UUACUAAA
1651
TTTAGTAA GGCTAGCTACAACGA ATTGGGAT
9565





2717
CAGAGUAU G UAGUUAAU
1652
ATTAACTA GGCTAGCTACAACGA ATACTCTG
9566





2901
AUCUUUCU G UCCCCAAU
1653
ATTGGGGA GGCTAGCTACAACGA AGAAAGAT
9567





3071
GGGGGACU G UUGGGGUG
1654
CACCCCAA GGCTAGCTACAACGA AGTCCCCC
9568





3111
UCACAACU G UGCCAGCA
1655
TGCTGGCA GGCTAGCTACAACGA AGTTGTGA
9569





40
AUCCCAGA G UCAGGGCC
1656
GGCCCTGA GGCTAGCTACAACGA TCTGGGAT
9570





46
GAGUCAGG G CCCUGUAC
1657
GTACAGGG GGCTAGCTACAACGA CCTGACTC
9571





65
UCCUGCUG G UGGCUCCA
1658
TGGAGCCA GGCTAGCTACAACGA CAGCAGGA
9572





68
UGCUGGUG G CUCCAGUU
1659
AACTGGAG GGCTAGCTACAACGA CACCAGCA
9573





74
UGGCUCCA G UUCAGGAA
1660
TTCCTGAA GGCTAGCTACAACGA TGGAGCCA
9574





85
CAGGAACA G UGAGCCCU
1661
AGGGCTCA GGCTAGCTACAACGA TGTTCCTG
9575





89
AACAGUGA G CCCUGCUC
1662
GAGCAGGG GGCTAGCTACAACGA TCACTGTT
9576





120
GCCAUAUC G UCAAUCUU
1663
AAGATTGA GGCTAGCTACAACGA GATATGGC
9577





196
CCCUGCUC G UGUUACAG
1664
CTGTAACA GGCTAGCTACAACGA GAGCAGGG
9578





205
UGUUACAG G CGGGGUUU
1665
AAACCCCG GGCTAGCTACAACGA CTGTAACA
9579





210
CAGGCGGG G UUUUUCUU
1666
AAGAAAAA GGCTAGCTACAACGA CCCGCCTG
9580





248
ACCACAGA G UCUAGACU
1667
AGTCTAGA GGCTAGCTACAACGA TCTGTGGT
9581





258
CUAGACUC G UGGUGGAC
1668
GTCCACCA GGCTAGCTACAACGA GAGTCTAG
9582





261
GACUCGUG G UGGACUUC
1669
GAAGTCCA GGCTAGCTACAACGA CACGAGTC
9583





295
GAACACCC G UGUGUCUU
1670
AAGACACA GGCTAGCTACAACGA GGGTGTTC
9584





305
GUGUCUUG G CCAAAAUU
1671
AATTTTGG GGCTAGCTACAACGA CAAGACAC
9585





318
AAUUCGCA G UCCCAAAU
1672
ATTTGGGA GGCTAGCTACAACGA TGCGAATT
9586





332
AAUCUCCA G UCACUCAC
1673
GTGAGTGA GGCTAGCTACAACGA TGGAGATT
9587





368
UUGUCCUG G UUAUCGCU
1674
AGCGATAA GGCTAGCTACAACGA CAGGACAA
9588





390
UGUCUGCG G CGUUUUAU
1675
ATAAAACG GGCTAGCTACAACGA CGCAGACA
9589





392
UCUGCGGC G UUUUAUCA
1676
TGATAAAA GGCTAGCTACAACGA GCCGCAGA
9590





442
UCUUGUUG G UUCUUCUG
1677
CAGAAGAA GGCTAGCTACAACGA CAACAAGA
9591





461
CUAUCAAG G UAUGUUGC
1678
GCAACATA GGCTAGCTACAACGA CTTGATAG
9592





472
UGUUGCCC G UUUGUCCU
1679
AGGACAAA GGCTAGCTACAACGA GGGCAACA
9593





506
AACAACCA G CACCGGAC
1680
GTCCGGTG GGCTAGCTACAACGA TGGTTGTT
9594





625
CAUCUUGG G CUUUCGCA
1681
TGCGAAAG GGCTAGCTACAACGA CCAAGATG
9595





648
CUAUGGGA G UGGGCCUC
1682
GAGGCCCA GGCTAGCTACAACGA TCCCATAG
9596





652
GGGAGUGG G CCUCAGUC
1683
GACTGAGG GGCTAGCTACAACGA CCACTCCC
9597





658
GGGCCUCA G UCCGUUUC
1684
GAAACGGA GGCTAGCTACAACGA TGAGGCCC
9598





662
CUCAGUCC G UUUCUCUU
1685
AAGAGAAA GGCTAGCTACAACGA GGACTGAG
9599





672
UUCUCUUG G CUCAGUUU
1686
AAACTGAG GGCTAGCTACAACGA CAAGAGAA
9600





677
UUGGCUCA G UUUACUAG
1687
CTAGTAAA GGCTAGCTACAACGA TGAGCCAA
9601





685
GUUUACUA G UGCCAUUU
1688
AAATGGCA GGCTAGCTACAACGA TAGTAAAC
9602





699
UUUGUUCA G UGGUUCGU
1689
ACGAACCA GGCTAGCTACAACGA TGAACAAA
9603





702
GUUCAGUG G UUCGUAGG
1690
CCTACGAA GGCTAGCTACAACGA CACTGAAC
9604





706
AGUGGUUC G UAGGGCUU
1691
AAGCCCTA GGCTAGCTACAACGA GAACCACT
9605





711
UUCGUAGG G CUUUCCCC
1692
GGGGAAAG GGCTAGCTACAACGA CCTACGAA
9606





729
ACUGUCUG G CUUUCAGU
1693
ACTGAAAG GGCTAGCTACAACGA CAGACAGT
9607





736
GGCUUUCA G UUAUAUGG
1694
CCATATAA GGCTAGCTACAACGA TGAAAGCC
9608





753
AUGAUGUG G UUUUGGGG
1695
CCCCAAAA GGCTAGCTACAACGA CACATCAT
9609





762
UUUUGGGG G CCAAGUCU
1696
AGACTTGG GGCTAGCTACAACGA CCCCAAAA
9610





767
GGGGCCAA G UCUGUACA
1697
TGTACAGA GGCTAGCTACAACGA TTGGCCCC
9611





785
CAUCUUGA G UCCCUUUA
1698
TAAAGGGA GGCTAGCTACAACGA TCAAGATG
9612





826
GUCUUUGG G UAUACAUU
1699
AATGTATA GGCTAGCTACAACGA CCAAAGAC
9613





898
AAUUGGGA G UUGGGGCA
1700
TGCCCCAA GGCTAGCTACAACGA TCCCAATT
9614





904
GAGUUGGG G CACAUUGC
1701
GCAATGTG GGCTAGCTACAACGA CCCAACTC
9615





971
GUAAACAG G CCUAUUGA
1702
TCAATAGG GGCTAGCTACAACGA CTGTTTAC
9616





987
AUUGGAAA G UAUGUCAA
1703
TTGACATA GGCTAGCTACAACGA TTTCCAAT
9617





1006
AAUUGUGG G UCUUUUGG
1704
CCAAAAGA GGCTAGCTACAACGA CCACAATT
9618





1016
CUUUUGGG G UUUGCCGC
1705
GCGGCAAA GGCTAGCTACAACGA CCCAAAAG
9619





1080
GCAUACAA G CAAAACAG
1706
CTGTTTTG GGCTAGCTACAACGA TTGTATGC
9620





1089
CAAAACAG G CUUUUACU
1707
AGTAAAAG GGCTAGCTACAACGA CTGTTTTG
9621





1116
CUUACAAG G CCUUUCUA
1708
TAGAAAGG GGCTAGCTACAACGA CTTGTAAG
9622





1126
CUUUCUAA G UAAACAGU
1709
ACTGTTTA GGCTAGCTACAACGA TTAGAAAG
9623





1133
AGUAAACA G UAUGUGAA
1710
TTCACATA GGCTAGCTACAACGA TGTTTACT
9624





1152
UUUACCCC G UUGCUCGG
1711
CCGAGCAA GGCTAGCTACAACGA GGGGTAAA
9625





1160
GUUGCUCG G CAACGGCC
1712
GGCCGTTG GGCTAGCTACAACGA CGAGCAAC
9626





1166
CGGCAACG G CCUGGUCU
1713
AGACCAGG GGCTAGCTACAACGA CGTTGCCG
9627





1171
ACGGCCUG G UCUAUGCC
1714
GGCATAGA GGCTAGCTACAACGA CAGGCCGT
9628





1182
UAUGCCAA G UGUUUGCU
1715
AGCAAACA GGCTAGCTACAACGA TTGGCATA
9629





1207
CCCCACUG G UUGGGGCU
1716
AGCCCCAA GGCTAGCTACAACGA CAGTGGGG
9630





1213
UGGUUGGG G CUUGGCCA
1717
TGGCCAAG GGCTAGCTACAACGA CCCAACCA
9631





1218
GGGGCUUG G CCAUAGGC
1718
GCCTATGG GGCTAGCTACAACGA CAAGCCCC
9632





1225
GGCCAUAG G CCAUCAGC
1719
GCTGATGG GGCTAGCTACAACGA CTATGGCC
9633





1232
GGCCAUCA G CGCAUGCG
1720
CGCATGCG GGCTAGCTACAACGA TGATGGCC
9634





1240
GCGCAUGC G UGGAACCU
1721
AGGTTCCA GGCTAGCTACAACGA GCATGCGC
9635





1287
AACUCCUA G CCGCUUGU
1722
ACAAGCGG GGCTAGCTACAACGA TAGGAGTT
9636





1306
UGCUCGCA G CAGGUCUG
1723
CAGACCTG GGCTAGCTACAACGA TGCGAGCA
9637





1310
CGCAGCAG G UCUGGGGC
1724
GCCCCAGA GGCTAGCTACAACGA CTGCTGCG
9638





1317
GGUCUGGG G CAAAACUC
1725
GAGTTTTG GGCTAGCTACAACGA CCCAGACC
9639





1347
AUUCUGUC G UGCUCUCC
1726
GGAGAGCA GGCTAGCTACAACGA GACAGAAT
9640





1379
UUUCCAUG G CUGCUAGG
1727
CCTAGCAG GGCTAGCTACAACGA CATGGAAA
9641





1387
GCUGCUAG G CUGUGCUG
1728
CAGCACAG GGCTAGCTACAACGA CTAGCAGC
9642





1418
CGCGGGAC G UCCUUUGU
1729
ACAAAGGA GGCTAGCTACAACGA GTCCCGCG
9643





1431
UUGUUUAC G UCCCGUCG
1730
CGACGGGA GGCTAGCTACAACGA GTAAACAA
9644





1436
UACGUCCC G UCGGCGCU
1731
AGCGCCGA GGCTAGCTACAACGA GGGACGTA
9645





1440
UCCCGUCG G CGCUGAAU
1732
ATTCAGCG GGCTAGCTACAACGA CGACGGGA
9646





1471
CUCCCGGG G CCGCUUGG
1733
CCAAGCGG GGCTAGCTACAACGA CCCGGGAG
9647





1481
CGCUUGGG G CUCUACCG
1734
CGGTAGAG GGCTAGCTACAACGA CCCAAGCG
9648





1517
UACCGACC G UCCACGGG
1735
CCCGTGGA GGCTAGCTACAACGA GGTCGGTA
9649





1526
UCCACGGG G CGCACCUC
1736
GAGGTGCG GGCTAGCTACAACGA CCCGTGGA
9650





1553
GACUCCCC G UCUGUGCC
1737
GGCACAGA GGCTAGCTACAACGA GGGGAGTC
9651





1579
GCCGGACC G UGUGCACU
1738
AGTGCACA GGCTAGCTACAACGA GGTCCGGC
9652





1605
CUCUGCAC G UCGCAUGG
1739
CCATGCGA GGCTAGCTACAACGA GTGCAGAG
9653





1622
AGACCACC G UGAACGCC
1740
GGCGTTCA GGCTAGCTACAACGA GGTGGTCT
9654





1649
UGCCCAAG G UCUUGCAU
1741
ATGCAAGA GGCTAGCTACAACGA CTTGGGCA
9655





1679
GACUUUCA G CAAUGUCA
1742
TGACATTG GGCTAGCTACAACGA TGAAAGTC
9656





1703
ACCUUGAG G CAUACUUC
1743
GAAGTATG GGCTAGCTACAACGA CTCAAGGT
9657





1732
UUUAAUGA G UGGGAGGA
1744
TCCTCCCA GGCTAGCTACAACGA TCATTAAA
9658





1741
UGGGAGGA G UUGGGGGA
1745
TCCCCCAA GGCTAGCTACAACGA TCCTCCCA
9659





1754
GGGAGGAG G UUAGGUUA
1746
TAACCTAA GGCTAGCTACAACGA CTCCTCCC
9660





1759
GAGGUUAG G UUAAAGGU
1747
ACCTTTAA GGCTAGCTACAACGA CTAACCTC
9661





1766
GGUUAAAG G UCUUUGUA
1748
TACAAAGA GGCTAGCTACAACGA CTTTAACC
9662





1782
ACUAGGAG G CUGUAGGC
1749
GCCTACAG GGCTAGCTACAACGA CTCCTAGT
9663





1789
GGCUGUAG G CAUAAAUU
1750
AATTTATG GGCTAGCTACAACGA CTACAGCC
9664





1799
AUAAAUUG G UGUGUUCA
1751
TGAACACA GGCTAGCTACAACGA CAATTTAT
9665





1811
GUUCACCA G CACCAUGC
1752
GCATGGTG GGCTAGCTACAACGA TGGTGAAC
9666





1870
CUGUUCAA G CCUCCAAG
1753
CTTGGAGG GGCTAGCTACAACGA TTGAACAG
9667





1878
GCCUCCAA G CUGUGCCU
1754
AGGCACAG GGCTAGCTACAACGA TTGGAGGC
9668





1890
UGCCUUGG G UGGCUUUG
1755
CAAAGCCA GGCTAGCTACAACGA CCAAGGCA
9669





1893
CUIGGGUG G CUUUGGGG
1756
CCCCAAAG GGCTAGCTACAACGA CACCCAAG
9670





1901
GCUUUGGG G CAUGGACA
1757
TGTCCATG GGCTAGCTACAACGA CCCAAAGC
9671





1917
AUUGACCC G UAUAAAGA
1758
TCTTTATA GGCTAGCTACAACGA GGGTCAAT
9672





1933
AAUUUGGA G CUUCUGUG
1759
CACAGAAG GGCTAGCTACAACGA TCCAAATT
9673





1944
UCUGUGGA G UUACUCUC
1760
GAGAGTAA GGCTAGCTACAACGA TCCACAGA
9674





2023
AUCGGGGG G CCUUAGAG
1761
CTCTAAGG GGCTAGCTACAACGA CCCCCGAT
9675





2031
GCCUUAGA G UCUCCGGA
1762
TCCGGAGA GGCTAGCTACAACGA TCTAAGGC
9676





2062
ACCAUACG G CACUCAGG
1763
CCTGAGTG GGCTAGCTACAACGA CGTATGGT
9677





2070
GCACUCAG G CAAGCUAU
1764
ATAGCTTG GGCTAGCTACAACGA CTGAGTGC
9678





2074
UCAGGCAA G CUAUUCUG
1765
CAGAATAG GGCTAGCTACAACGA TTGCCTGA
9679





2090
GUGUUGGG G UGAGUUGA
1766
TCAACTCA GGCTAGCTACAACGA CCCAACAC
9680





2094
UGGGGUGA G UUGAUGAA
1767
TTCATCAA GGCTAGCTACAACGA TCACCCCA
9681





2107
UGAAUCUA G CCACCUGG
1768
CCAGGTGG GGCTAGCTACAACGA TAGATTCA
9682





2116
CCACCUGG G UGGGAAGU
1769
ACTTCCCA GGCTAGCTACAACGA CCAGGTGG
9683





2123
GGUGGGAA G UAAUUUGG
1770
CCAAATTA GGCTAGCTACAACGA TTCCCACC
9684





2140
AAGAUCCA G CAUCCAGG
1771
CCTGGATG GGCTAGCTACAACGA TGGATCTT
9685





2155
GGGAAUUA G UAGUCAGC
1772
GCTGACTA GGCTAGCTACAACGA TAATTCCC
9686





2158
AAUUAGUA G UCAGCUAU
1773
ATAGCTGA GGCTAGCTACAACGA TACTAATT
9687





2162
AGUAGUCA G CUAUGUCA
1774
TGACATAG GGCTAGCTACAACGA TGACTACT
9688





2173
AUGUCAAC G UUAAUAUG
1775
CATATTAA GGCTAGCTACAACGA GTTGACAT
9689





2183
UAAUAUGG G CCUAAAAA
1776
TTTTTAGG GGCTAGCTACAACGA CCATATTA
9690





2208
CUAUUGUG G UUUCACAU
1777
ATGTGAAA GGCTAGCTACAACGA CACAATAG
9691





2235
ACUUUUGG G CGAGAAAC
1778
GTTTCTCG GGCTAGCTACAACGA CCAAAAGT
9692





2260
AAUAUUUG G UGUCUUUU
1779
AAAAGACA GGCTAGCTACAACGA CAAATATT
9693





2272
CUUUUGGA G UGUGGAUU
1780
AATCCACA GGCTAGCTACAACGA TCCAAAAG
9694





2360
ACGAAGAG G CAGGUCCC
1781
GGGACCTG GGCTAGCTACAACGA CTCTTCGT
9695





2364
AGAGGCAG G UCCCCUAG
1782
CTAGGGGA GGCTAGCTACAACGA CTGCCTCT
9696





2403
AGACGAAG G UCUCAAUC
1783
GATTGAGA GGCTAGCTACAACGA CTTCGTCT
9697





2417
AUCGCCGC G UCGCAGAA
1784
TTCTGCGA GGCTAGCTACAACGA GCGGCGAT
9698





2454
CAAUGUUA G UAUUCCUU
1785
AAGGAATA GGCTAGCTACAACGA TAACATTG
9699





2474
CACAUAAG G UGGGAAAC
1786
GTTTCCCA GGCTAGCTACAACGA CTTATGTG
9700





2491
UUUACGGG G CUUUAUUC
1787
GAATAAAG GGCTAGCTACAACGA CCCGTAAA
9701





2507
CUUCUACG G UACCUUGC
1788
GCAAGGTA GGCTAGCTACAACGA CGTAGAAG
9702





2530
CCUAAAUG G CAAACUCC
1789
GGAGTTTG GGCTAGCTACAACGA CATTTAGG
9703





2587
AGAUGUAA G CAAUUUGU
1790
ACAAATTG GGCTAGCTACAACGA TTACATCT
9704





2599
UUUGUGGG G CCCCUUAC
1791
GTAAGGGG GGCTAGCTACAACGA CCCACAAA
9705





2609
CCCUUACA G UAAAUGAA
1792
TTCATTTA GGCTAGCTACAACGA TGTAAGGG
9706





2650
CCUGCUAG G UUUUAUCC
1793
GGATAAAA GGCTAGCTACAACGA CTAGCAGG
9707





2701
AUCAAACC G UAUUAUCC
1794
GGATAATA GGCTAGCTACAACGA GGTTTGAT
9708





2713
UAUCCAGA G UAUGUAGU
1795
ACTACATA GGCTAGCTACAACGA TCTGGATA
9709





2720
AGUAUGUA G UUAAUCAU
1796
ATGATTAA GGCTAGCTACAACGA TACATACT
9710





2768
UUUGGAAG G CGGGGAUC
1797
GATCCCCG GGCTAGCTACAACGA CTTCCAAA
9711





2791
AAAAGAGA G UCCACACG
1798
CGTGTGGA GGCTAGCTACAACGA TCTCTTTT
9712





2799
GUCCACAC G UAGCGCCU
1799
AGGCGCTA GGCTAGCTACAACGA GTGTGGAC
9713





2802
CACACGUA G CGCCUCAU
1800
ATGAGGCG GGCTAGCTACAACGA TACGTGTG
9714





2818
UUUUGCGG G UCACCAUA
1801
TATGGTGA GGCTAGCTACAACGA CCGCAAAA
9715





2848
GAUCUACA G CAUGGGAG
1802
CTCCCATG GGCTAGCTACAACGA TGTAGATC
9716





2857
CAUGGGAG G UUGGUCUU
1803
AAGACCAA GGCTAGCTACAACGA CTCCCATG
9717





2861
GGAGGUUG G UCUUCCAA
1804
TTGGAAGA GGCTAGCTACAACGA CAACCTCC
9718





2881
UCGAAAAG G CAUGGGGA
1805
TCCCCATG GGCTAGCTACAACGA CTTTTCGA
9719





2936
GAUCAUCA G UUGGACCC
1806
GGGTCCAA GGCTAGCTACAACGA TGATGATC
9720





2955
CAUUCAAA G CCAACUCA
1807
TGAGTTGG GGCTAGCTACAACGA TTTGAATG
9721





2964
CCAACUCA G UAAAUCCA
1808
TGGATTTA GGCTAGCTACAACGA TGAGTTGG
9722





3005
GACAACUG G CCGGACGC
1809
GCGTCCGG GGCTAGCTACAACGA CAGTTGTC
9723





3021
CCAACAAG G UGGGAGUG
1810
CACTCCCA GGCTAGCTACAACGA CTTGTTGG
9724





3027
AGGUGGGA G UGGGAGCA
1811
TGCTCCCA GGCTAGCTACAACGA TCCCACCT
9725





3033
GAGUGGGA G CAUUCGGG
1812
CCCGAATG GGCTAGCTACAACGA TCCCACTC
9726





3041
GCAUUCGG G CCAGGGUU
1813
AACCCTGG GGCTAGCTACAACGA CCGAATGC
9727





3047
GGGCCAGG G UUCACCCC
1814
GGGGTGAA GGCTAGCTACAACGA CCTGGCCC
9728





3077
CUGUUGGG G UGGAGCCC
1815
GGGCTCCA GGCTAGCTACAACGA CCCAACAG
9729





3082
GGGGUGGA G CCCUCACG
1816
CGTGAGGG GGCTAGCTACAACGA TCCACCCC
9730





3097
CGCUCAGG G CCUACUCA
1817
TGAGTAGG GGCTAGCTACAACGA CCTGAGCG
9731





3117
CUGUGCCA G CAGCUCCU
1818
AGGAGCTG GGCTAGCTACAACGA TGGCACAG
9732





3120
UGCCAGCA G CUCCUCCU
1819
AGGAGGAG GGCTAGCTACAACGA TGCTGGCA
9733





3146
ACCAAUCG G CAGUCAGG
1820
CCTGACTG GGCTAGCTACAACGA CGATTGGT
9734





3149
AAUCGGCA G UCAGGAAG
1821
CTTCCTGA GGCTAGCTACAACGA TGCCGATT
9735





3158
UCAGGAAG G CAGCCUAC
1822
GTAGGCTG GGCTAGCTACAACGA CTTCCTGA
9736





3161
GGAAGGCA G CCUACUCC
1823
GGAGTAGG GGCTAGCTACAACGA TGCCTTCC
9737





3204
AUCCUCAG G CCAUGCAG
1824
CTGCATGG GGCTAGCTACAACGA CTGAGGAT
9738





10
ACUCCACC A CUUUCCAC
703
GTGGAAAG GGCTAGCTACAACGA GGTGGAGT
9739





17
CACUUUCC A CCAAACUC
706
GAGTTTGG GGCTAGCTACAACGA GGAAAGTG
9740





22
UCCACCAA A CUCUUCAA
1825
TTGAAGAG GGCTAGCTACAACGA TTGGTGGA
9741





32
UCUUCAAG A UCCCAGAG
1826
CTCTGGGA GGCTAGCTACAACGA CTTGAAGA
9742





53
GGCCCUGU A CUUUCCUG
42
CAGGAAAG GGCTAGCTACAACGA ACAGGGCC
9743





82
GUUCAGGA A CAGUGAGC
1827
GCTCACTG GGCTAGCTACAACGA TCCTGAAC
9744





101
UGCUCAGA A UACUGUCU
1828
AGACAGTA GGCTAGCTACAACGA TCTGAGCA
9745





103
CUCAGAAU A CUGUCUCU
50
AGAGACAG GGCTAGCTACAACGA ATTCTGAG
9746





115
UCUCUGCC A UAUCGUCA
733
TGACGATA GGCTAGCTACAACGA GGCAGAGA
9747





117
UCUGCCAU A UCGUCAAU
53
ATTGACGA GGCTAGCTACAACGA ATGGCAGA
9748





124
UAUCGUCA A UCUUAUCG
1829
CGATAAGA GGCTAGCTACAACGA TGACGATA
9749





129
UCAAUCUU A UCGAAGAC
58
GTCTTCGA GGCTAGCTACAACGA AAGATTGA
9750





136
UAUCGAAG A CUGGGGAC
1830
GTCCCCAG GGCTAGCTACAACGA CTTCGATA
9751





143
GACUGGGG A CCCUGUAC
1831
GTACAGGG GGCTAGCTACAACGA CCCCAGTC
9752





150
CACCCUGU A CCGAACAU
60
ATGTTCGG GGCTAGCTACAACGA ACAGGGTC
9753





155
UGUACCGA A CAUGGAGA
1832
TCTCCATG GGCTAGCTACAACGA TCGGTACA
9754





157
UACCGAAC A UGGAGAAC
745
GTTCTCCA GGCTAGCTACAACGA GTTCGGTA
9755





164
CAUGGAGA A CAUCGCAU
1833
ATGCGATG GGCTAGCTACAACGA TCTCCATG
9756





166
UGGAGAAC A UCGCAUCA
746
TGATGCGA GGCTAGCTACAACGA GTTCTCCA
9757





171
AACAUCGC A UCAGGACU
747
AGTCCTGA GGCTAGCTACAACGA GCGATGTT
9758





177
GCAUCAGG A CUCCUAGG
1834
CCTAGGAG GGCTAGCTACAACGA CCTGATGC
9759





186
CUCCUAGG A CCCCUGCU
1835
AGCAGGGG GGCTAGCTACAACGA CCTAGGAG
9760





201
CUCGUGUU A CAGGCGGG
67
CCCGCCTG GGCTAGCTACAACGA AACACGAG
9761





223
UCUUGUUG A CAAAAAUC
1836
GATTTTTG GGCTAGCTACAACGA CAACAAGA
9762





229
UGACAAAA A UCCUCACA
1837
TGTGAGGA GGCTAGCTACAACGA TTTTGTCA
9763





235
AAAUCCUC A CAAUACCA
762
TGGTATTG GGCTAGCTACAACGA GAGGATTT
9764





238
UCCUCACA A UACCACAG
1838
CTGTGGTA GGCTAGCTACAACGA TGTGAGGA
9765





240
CUCACAAU A CCACAGAG
77
CTCTGTGG GGCTAGCTACAACGA ATTGTGAG
9766





243
ACAAUACC A CAGAGUCU
765
AGACTCTG GGCTAGCTACAACGA GGTATTGT
9767





254
GAGUCUAG A CUCGUGGU
1839
ACCACGAG GGCTAGCTACAACGA CTAGACTC
9768





265
CGUGGUGG A CUUCUCUC
1840
GAGAGAAG GGCTAGCTACAACGA CCACCACG
9769





275
UUCUCUCA A UUUUCUAG
1841
CTAGAAAA GGCTAGCTACAACGA TGAGAGAA
9770





289
UAGGGGGA A CACCCGUG
1842
CACGGGTG GGCTAGCTACAACGA TCCCCCTA
9771





291
GGGGGAAC A CCCGUGUG
774
CACACGGG GGCTAGCTACAACGA GTTCCCCC
9772





311
UGGCCAAA A UUCGCAGU
1843
ACTGCGAA GGCTAGCTACAACGA TTTGGCCA
9773





325
AGUCCCAA A UCUCCAGU
1844
ACTGGAGA GGCTAGCTACAACGA TTGGGACT
9774





335
CUCCAGUC A CUCACCAA
787
TTGGTGAG GGCTAGCTACAACGA GACTGGAG
9775





339
AGUCACUC A CCAACCUG
789
CAGGTTGG GGCTAGCTACAACGA GAGTGACT
9776





343
ACUCACCA A CCUGUUGU
1845
ACAACAGG GGCTAGCTACAACGA TGGTGAGT
9777





358
GUCCUCCA A UUUGUCCU
1846
AGGACAAA GGCTAGCTACAACGA TGGAGGAC
9778





371
UCCUGGUU A UCGCUGGA
106
TCCAGCGA GGCTAGCTACAACGA AACCAGGA
9779





379
AUCGCUGG A UGUGUCUG
1847
CAGACACA GGCTAGCTACAACGA CCAGCGAT
9780





397
GGCGUUUU A UCAUCUUC
112
GAAGATGA GGCTAGCTACAACGA AAAACGCC
9781





400
GUUUUAUC A UCUUCCUC
802
GAGGAAGA GGCTAGCTACAACGA GATAAAAC
9782





412
UCCUCUGC A UCCUGCUG
807
CAGCAGGA GGCTAGCTACAACGA GCAGAGGA
9783





423
CUGCUGCU A UGCCUCAU
119
ATGAGGCA GGCTAGCTACAACGA AGCAGCAG
9784





430
UAUGCCUC A UCUUCUUG
814
CAAGAAGA GGCTAGCTACAACGA GAGGCATA
9785





452
UCUUCUGG A CUAUCAAG
1848
CTTGATAG GGCTAGCTACAACGA CCAGAAGA
9786





455
UCUGGACU A UCAAGGUA
130
TACCTTGA GGCTAGCTACAACGA AGTCCAGA
9787





463
AUCAAGGU A UGUUGCCC
132
GGGCAACA GGCTAGCTACAACGA ACCTTGAT
9788





484
GUCCUCUA A UUCCAGGA
1849
TCCTGGAA GGCTAGCTACAACGA TAGAGGAC
9789





492
AUUCCAGG A UCAUCAAC
1850
GTTGATGA GGCTAGCTACAACGA CCTGGAAT
9790





495
CCAGGAUC A UCAACAAC
828
GTTGTTGA GGCTAGCTACAACGA GATCCTGG
9791





499
GAUCAUCA A CAACCAGC
1851
GCTGGTTG GGCTAGCTACAACGA TGATGATC
9792





502
CAUCAACA A CCAGCACC
1852
GGTGCTGG GGCTAGCTACAACGA TGTTGATG
9793





513
AGCACCGG A CCAUGCAA
1853
TTGCATGG GGCTAGCTACAACGA CCGGTGCT
9794





516
ACCGGACC A UGCAAAAC
836
GTTTTGCA GGCTAGCTACAACGA GGTCCGGT
9795





523
CAUGCAAA A CCUGCACA
1854
TGTGCAGG GGCTAGCTACAACGA TTTGCATG
9796





529
AAACCUGC A CAACUCCU
840
AGGAGTTG GGCTAGCTACAACGA GCAGGTTT
9797





532
CCUGCACA A CUCCUGCU
1855
AGCAGGAG GGCTAGCTACAACGA TGTGCAGG
9798





547
CUCAAGGA A CCUCUAUG
1856
CATAGAGG GGCTAGCTACAACGA TCCTTGAG
9799





553
GAACCUCU A UGUUUCCC
146
GGGAAACA GGCTAGCTACAACGA AGAGGTTC
9800





564
UUUCCCUC A UGUUGCUG
853
CAGCAACA GGCTAGCTACAACGA GAGGGAAA
9801





574
GUUGCUGU A CAAAACCU
152
AGGTTTTG GGCTAGCTACAACGA ACAGCAAC
9802





579
UGUACAAA A CCUACGGA
1857
TCCGTAGG GGCTAGCTACAACGA TTTGTACA
9803





583
CAAAACCU A CGGACGGA
153
TCCGTCCG GGCTAGCTACAACGA AGGTTTTG
9804





587
ACCUACGG A CGGAAACU
1858
AGTTTCCG GGCTAGCTACAACGA CCGTAGGT
9805





593
GGACGGAA A CUGCACCU
1859
AGGTGCAG GGCTAGCTACAACGA TTCCGTCC
9806





598
GAAACUGC A CCUGUAUU
859
AATACAGG GGCTAGCTACAACGA GCAGTTTC
9807





604
GCACCUGU A UUCCCAUC
154
GATGGGAA GGCTAGCTACAACGA ACAGGTGC
9808





610
GUAUUCCC A UCCCAUCA
864
TGATGGGA GGCTAGCTACAACGA GGGAATAC
9809





615
CCCAUCCC A UCAUCUUG
867
CAAGATGA GGCTAGCTACAACGA GGGATGGG
9810





618
AUCCCAUC A UCUUGGGC
868
GCCCAAGA GGCTAGCTACAACGA GATGGGAT
9811





636
UUCGCAAA A UACCUAUG
1860
CATAGGTA GGCTAGCTACAACGA TTTGCGAA
9812





638
CGCAAAAU A CCUAUGGG
164
CCCATAGG GGCTAGCTACAACGA ATTTTGCG
9813





642
AAAUACCU A UGGGAGUG
165
CACTCCCA GGCTAGCTACAACGA AGGTATTT
9814





681
CUCAGUUU A CUAGUGCC
176
GGCACTAG GGCTAGCTACAACGA AAACTGAG
9815





690
CUAGUGCC A UUUGUUCA
884
TGAACAAA GGCTAGCTACAACGA GGCACTAG
9816





721
UUUCCCCC A CUGUCUGG
891
CCAGACAG GGCTAGCTACAACGA GGGGGAAA
9817





739
UUUCAGUU A UAUGGAUG
193
CATCCATA GGCTAGCTACAACGA AACTGAAA
9818





741
UCAGUUAU A UGGAUGAU
194
ATCATCCA GGCTAGCTACAACGA ATAACTGA
9819





745
UUAUAUGG A UGAUGUGG
1861
CCACATCA GGCTAGCTACAACGA CCATATAA
9820





748
UAUGGAUG A UGUGGUUU
1862
AAACCACA GGCTAGCTACAACGA CATCCATA
9821





773
AAGUCUGU A CAACAUCU
199
AGATGTTG GGCTAGCTACAACGA ACAGACTT
9822





776
UCUGUACA A CAUCUUGA
1863
TCAAGATG GGCTAGCTACAACGA TGTACAGA
9823





778
UGUACAAC A UCUUGAGU
900
ACTCAAGA GGCTAGCTACAACGA GTTGTACA
9824





793
GUCCCUUU A UGCCGCUG
205
CAGCGGCA GGCTAGCTACAACGA AAAGGGAC
9825





804
CCGCUGUU A CCAAUUUU
207
AAAATTGG GGCTAGCTACAACGA AACAGCGG
9826





808
UGUUACCA A UUUUCUUU
1864
AAAGAAAA GGCTAGCTACAACGA TGGTAACA
9827





828
CUUUGGGU A UACAUUUA
218
TAAATGTA GGCTAGCTACAACGA ACCCAAAG
9828





830
UUGGGUAU A CAUUUAAA
219
TTTAAATG GGCTAGCTACAACGA ATACCCAA
9829





832
GGGUAUAC A UUUAAACC
911
GGTTTAAA GGCTAGCTACAACGA GTATACCC
9830





838
ACAUUUAA A CCCUCACA
1865
TGTGAGGG GGCTAGCTACAACGA TTAAATGT
9831





844
AAACCCUC A CAAAACAA
915
TTGTTTTG GGCTAGCTACAACGA GAGGGTTT
9832





849
CUCACAAA A CAAAAAGA
1866
TCTTTTTG GGCTAGCTACAACGA TTTGTGAG
9833





857
ACAAAAAG A UGGGGAUA
1867
TATCCCCA GGCTAGCTACAACGA CTTTTTGT
9834





863
AGAUGGGG A UAUUCCCU
1868
AGGGAATA GGCTAGCTACAACGA CCCCATCT
9835





865
AUGGGGAU A UUCCCUUA
224
TAAGGGAA GGCTAGCTACAACGA ATCCCCAT
9836





874
UUCCCUUA A CUUCAUGG
1869
CCATGAAG GGCTAGCTACAACGA TAAGGGAA
9837





879
UUAACUUC A UGGGAUAU
922
ATATCCCA GGCTAGCTACAACGA GAAGTTAA
9838





884
UUCAUGGG A UAUGUAAU
1870
ATTACATA GGCTAGCTACAACGA CCCATGAA
9839





886
CAUGGGAU A UGUAAUUG
231
CAATTACA GGCTAGCTACAACGA ATCCCATG
9840





891
GAUAUGUA A UUGGGAGU
1871
ACTCCCAA GGCTAGCTACAACGA TACATATC
9841





906
GUUGGGGC A CAUUGCCA
923
TGGCAATG GGCTAGCTACAACGA GCCCCAAC
9842





908
UGGGGCAC A UUGCCACA
924
TGTGGCAA GGCTAGCTACAACGA GTGCCCCA
9843





914
ACAUUGCC A CAGGAACA
926
TGTTCCTG GGCTAGCTACAACGA GGCAATGT
9844





920
CCACAGGA A CAUAUUGU
1872
ACAATATG GGCTAGCTACAACGA TCCTGTGG
9845





922
ACAGGAAC A UAUUGUAC
928
GTACAATA GGCTAGCTACAACGA GTTCCTGT
9846





924
AGGAACAU A UUGUACAA
236
TTGTACAA GGCTAGCTACAACGA ATGTTCCT
9847





929
CAUAUUGU A CAAAAAAU
238
ATTTTTTG GGCTAGCTACAACGA ACAATATG
9848





936
UACAAAAA A UCAAAAUG
1873
CATTTTGA GGCTAGCTACAACGA TTTTTGTA
9849





942
AAAUCAAA A UGUGUUUU
1874
AAAACACA GGCTAGCTACAACGA TTTGATTT
9850





956
UUUAGGAA A CUUCCUGU
1875
ACAGGAAG GGCTAGCTACAACGA TTCCTAAA
9851





967
UCCUGUAA A CAGGCCUA
1876
TAGGCCTG GGCTAGCTACAACGA TTACAGGA
9852





975
ACAGGCCU A UUGAUUGG
247
CCAATCAA GGCTAGCTACAACGA AGGCCTGT
9853





979
GCCUAUUG A UUGGAAAG
1877
CTTTCCAA GGCTAGCTACAACGA CAATAGGC
9854





989
UGGAAAGU A UGUCAACG
250
CGTTGACA GGCTAGCTACAACGA ACTTTCCA
9855





995
GUAUGUCA A CGAAUUGU
1878
ACAATTCG GGCTAGCTACAACGA TGACATAC
9856





999
GUCAACGA A UUGUGGGU
1879
ACCCACAA GGCTAGCTACAACGA TCGTTGAC
9857





1032
CCCCUUUC A CGCAAUGU
944
ACATTGCG GGCTAGCTACAACGA GAAAGGGG
9858





1037
UUCACGCA A UGUGGAUA
1880
TATCCACA GGCTAGCTACAACGA TGCGTGAA
9859





1043
CAAUGUGG A UAUUCUGC
1881
GCAGAATA GGCTAGCTACAACGA CCACATTG
9860





1045
AUGUGGAU A UUCUGCUU
262
AAGCAGAA GGCTAGCTACAACGA ATCCACAT
9861





1056
CUGCUUUA A UGCCUUUA
1882
TAAAGGCA GGCTAGCTACAACGA TAAAGCAG
9862





1064
AUGCCUUU A UAUGCAUG
270
CATGCATA GGCTAGCTACAACGA AAAGGCAT
9863





1066
GCCUUUAU A UGCAUGCA
271
TGCATGCA GGCTAGCTACAACGA ATAAAGGC
9864





1070
UUAUAUGC A UGCAUACA
950
TGTATGCA GGCTAGCTACAACGA GCATATAA
9865





1074
AUGCAUGC A UACAAGCA
951
TGCTTGTA GGCTAGCTACAACGA GCATGCAT
9866





1076
GCAUGCAU A CAAGCAAA
272
TTTGCTTG GGCTAGCTACAACGA ATGCATGC
9867





1085
CAAGCAAA A CAGGCUUU
1883
AAAGCCTG GGCTAGCTACAACGA TTTGCTTG
9868





1095
AGGCUUUU A CUUUCUCG
276
CGAGAAAG GGCTAGCTACAACGA AAAAGCCT
9869





1107
UCUCGCCA A CUUACAAG
1884
CTTGTAAG GGCTAGCTACAACGA TGGCGAGA
9870





1111
GCCAACUU A CAAGGCCU
282
AGGCCTTG GGCTAGCTACAACGA AAGTTGGC
9871





1130
CUAAGUAA A CAGUAUGU
1885
ACATACTG GGCTAGCTACAACGA TTACTTAG
9872





1135
UAAACAGU A UGUGAACC
288
GGTTCACA GGCTAGCTACAACGA ACTGTTTA
9873





1141
GUAUGUGA A CCUUUACC
1886
GGTAAAGG GGCTAGCTACAACGA TCACATAC
9874





1147
GAACCUUU A CCCCGUUG
291
CAACGGGG GGCTAGCTACAACGA AAAGGTTC
9875





1163
GCUCGGCA A CGGCCUGG
1887
CCAGGCCG GGCTAGCTACAACGA TGCCGAGC
9876





1175
CCUGGUCU A UGCCAAGU
295
ACTTGGCA GGCTAGCTACAACGA AGACCAGG
9877





1192
GUUUGCUG A CGCAACCC
1888
GGGTTGCG GGCTAGCTACAACGA CAGCAAAC
9878





1197
CUGACGCA A CCCCCACU
1889
AGTGGGGG GGCTAGCTACAACGA TGCGTCAG
9879





1203
CAACCCCC A CUGGUUGG
984
CCAACCAG GGCTAGCTACAACGA GGGGGTTG
9880





1221
GCUUGGCC A UAGGCCAU
988
ATGGCCTA GGCTAGCTACAACGA GGCCAAGC
9881





1228
CAUAGGCC A UCAGCGCA
990
TGCGCTGA GGCTAGCTACAACGA GGCCTATG
9882





1236
AUCAGCGC A UGCGUGGA
992
TCCACGCA GGCTAGCTACAACGA GCGCTGAT
9883





1245
UGCGUGGA A CCUUUGUG
1890
CACAAAGG GGCTAGCTACAACGA TCCACGCA
9884





1266
CUCUGCCG A UCCAUACC
1891
GGTATGGA GGCTAGCTACAACGA CGGCAGAG
9885





1270
GCCGAUCC A UACCGCGG
1001
CCGCGGTA GGCTAGCTACAACGA GGATCGGC
9886





1272
CGAUCCAU A CCGCGGAA
308
TTCCGCGG GGCTAGCTACAACGA ATGGATCG
9887





1280
ACCGCGGA A CUCCUAGC
1892
GCTAGGAG GGCTAGCTACAACGA TCCGCGGT
9888





1322
GGGGCAAA A CUCAUCGG
1893
CCGATGAG GGCTAGCTACAACGA TTTGCCCC
9889





1326
CAAAACUC A UCGGGACU
1014
AGTCCCGA GGCTAGCTACAACGA GAGTTTTG
9890





1332
UCAUCGGG A CUGACAAU
1894
ATTGTCAG GGCTAGCTACAACGA CCCGATGA
9891





1336
CGGGACUG A CAAUUCUG
1895
CAGAATTG GGCTAGCTACAACGA CAGTCCCG
9892





1339
GACUGACA A UUCUGUCG
1896
CGACAGAA GGCTAGCTACAACGA TGTCAGTC
9893





1361
UCCCGCAA A UAUACAUC
1897
GATGTATA GGCTAGCTACAACGA TTGCGGGA
9894





1363
CCGCAAAU A UACAUCAU
324
ATGATGTA GGCTAGCTACAACGA ATTTGCGG
9895





1365
GCAAAUAU A CAUCAUUU
325
AAATGATG GGCTAGCTACAACGA ATATTTGC
9896





1367
AAAUAUAC A UCAUUUCC
1023
GGAAATGA GGCTAGCTACAACGA GTATATTT
9897





1370
UAUACAUC A UUUCCAUG
1024
CATGGAAA GGCTAGCTACAACGA GATGTATA
9898





1376
UCAUUUCC A UGGCUGCU
1026
AGCAGCCA GGCTAGCTACAACGA GGAAATGA
9899





1399
UGCUGCCA A CUGGAUCC
1898
GGATCCAG GGCTAGCTACAACGA TGGCAGCA
9900





1404
CCAACUGG A UCCUACGC
1899
GCGTAGGA GGCTAGCTACAACGA CCAGTTGG
9901





1409
UGGAUCCU A CGCGGGAC
332
GTCCCGCG GGCTAGCTACAACGA AGGATCCA
9902





1416
UACGCGGG A CGUCCUUU
1900
AAAGGACG GGCTAGCTACAACGA CCCGCGTA
9903





1429
CUUUGUUU A CGUCCCGU
338
ACGGGACG GGCTAGCTACAACGA AAACAAAG
9904





1447
GGCGCUGA A UCCCGCGG
1901
CCGCGGGA GGCTAGCTACAACGA TCAGCGCC
9905





1456
UCCCGCGG A CGACCCCU
1902
AGGGGTCG GGCTAGCTACAACGA CCGCGGGA
9906





1459
CGCGGACG A CCCCUCCC
1903
GGGAGGGG GGCTAGCTACAACGA CGTCCGCG
9907





1486
GGGGCUCU A CCGCCCGC
345
GCGGGCGG GGCTAGCTACAACGA AGAGCCCC
9908





1505
CUCCGCCU A UUGUACCG
349
CGGTACAA GGCTAGCTACAACGA AGGCGGAG
9909





1510
CCUAUUGU A CCGACCGU
351
ACGGTCGG GGCTAGCTACAACGA ACAATAGG
9910





1514
UUGUACCG A CCGUCCAC
1904
GTGGACGG GGCTAGCTACAACGA CGGTACAA
9911





1521
GACCGUCC A CGGGGCGC
1064
GCGCCCCG GGCTAGCTACAACGA GGACGGTC
9912





1530
CGGGGCGC A CCUCUCUU
1065
AAGAGAGG GGCTAGCTACAACGA GCGCCCCG
9913





1540
CUCUCUUU A CGCGGACU
357
AGTCCGCG GGCTAGCTACAACGA AAAGAGAG
9914





1546
UUACGCGG A CUCCCCGU
1905
ACGGGGAG GGCTAGCTACAACGA CCGCGTAA
9915





1567
GCCUUCUC A UCUGCCGG
1078
CCGGCAGA GGCTAGCTACAACGA GAGAAGGC
9916





1576
UCUGCCGG A CCGUGUGC
1906
GCACACGG GGCTAGCTACAACGA CCGGCAGA
9917





1585
CCGUGUGC A CUUCGCUU
1082
AAGCGAAG GGCTAGCTACAACGA GCACACGG
9918





1595
UUCGCUUC A CCUCUGCA
1085
TGCAGAGG GGCTAGCTACAACGA GAAGCGAA
9919





1603
ACCUCUGC A CGUCGCAU
1089
ATGCGACG GGCTACCTACAACGA GCAGAGGT
9920





1610
CACGUCGC A UGGAGACC
1090
GGTCTCCA GGCTAGCTACAACGA GCGACGTG
9921





1616
GCAUGGAG A CCACCGUG
1907
CACGGTGG GGCTAGCTACAACGA CTCCATGC
9922





1619
UGGAGACC A CCGUGAAC
1092
GTTCACGG GGCTAGCTACAACGA GGTCTCCA
9923





1626
CACCGUGA A CGCCCACA
1908
TGTGGGCG GGCTAGCTACAACGA TCACGGTG
9924





1638
CCACAGGA A CCUGCCCA
1909
TGGGCAGG GGCTAGCTACAACGA TCCTGTGG
9925





1656
GGUCUUGC A UAAGAGGA
1104
TCCTCTTA GGCTAGCTACAACGA GCAAGACC
9926





1664
AUAAGAGG A CUCUUGGA
1910
TCCAAGAG GGCTAGCTACAACGA CCTCTTAT
9927





1672
ACUCUUGG A CUUUCAGC
1911
GCTGAAAG GGCTAGCTACAACGA CCAAGAGT
9928





1682
UUUCAGCA A UGUCAACG
1912
CGTTGACA GGCTAGCTACAACGA TGCTGAAA
9929





1688
CAAUGUCA A CGACCGAC
1913
GTCGGTCG GGCTAGCTACAACGA TGACATTG
9930





1691
UGUCAACG A CCGACCUU
1914
AAGGTCGG GGCTAGCTACAACGA CGTTGACA
9931





1695
AACGACCG A CCUUGAGG
1915
CCTCAAGG GGCTAGCTACAACGA CGGTCGTT
9932





1705
CUUGAGGC A UACUUCAA
1114
TTGAAGTA GGCTAGCTACAACGA GCCTCAAG
9933





1707
UGAGGCAU A CUUCAAAG
380
CTTTGAAG GGCTAGCTACAACGA ATGCCTCA
9934





1716
CUUCAAAG A CUGUGUGU
1916
ACACACAG GGCTAGCTACAACGA CTTTGAAG
9935





1728
UGUGUUUA A UGAGUGGG
1917
CCCACTCA GGCTAGCTACAACGA TAAACACA
9936





1774
GUCUUUGU A CUAGGAGG
394
CCTCCTAG GGCTAGCTACAACGA ACAAAGAC
9937





1791
CUGUAGGC A UAAAUUGG
1121
CCAATTTA GGCTAGCTACAACGA GCCTACAG
9938





1795
AGGCAUAA A UUGGUGUG
1918
CACACCAA GGCTAGCTACAACGA TTATGCCT
9939





1807
GUGUGUUC A CCAGCACC
1122
GGTGCTGG GGCTAGCTACAACGA GAACACAC
9940





1813
UCACCAGC A CCAUGCAA
1125
TTGCATGG GGCTAGCTACAACGA GCTGGTGA
9941





1816
CCAGCACC A UGCAACUU
1127
AAGTTGCA GGCTAGCTACAACGA GGTGCTGG
9942





1821
ACCAUGCA A CUUUUUCA
1919
TGAAAAAG GGCTAGCTACAACGA TGCATGGT
9943





1829
ACUUUUUC A CCUCUGCC
1130
GGCAGAGG GGCTAGCTACAACGA GAAAAAGT
9944





1840
UCUGCCUA A UCAUCUCA
1920
TGAGATGA GGCTAGCTACAACGA TAGGCAGA
9945





1843
GCCUAAUC A UCUCAUGU
1136
ACATGAGA GGCTAGCTACAACGA GATTAGGC
9946





1848
AUCAUCUC A UGUUCAUG
1138
CATGAACA GGCTAGCTACAACGA GAGATGAT
9947





1854
UCAUGUUC A UGUCCUAC
1139
GTAGGACA GGCTAGCTACAACGA GAACATGA
9948





1861
CAUGUCCU A CUGUUCAA
414
TTGAACAG GGCTAGCTACAACGA AGGACATG
9949





1903
UUUGGGGC A UGGACAUU
1152
AATGTCCA GGCTAGCTACAACGA GCCCCAAA
9950





1907
GGGCAUGG A CAUUGACC
1921
GGTCAATG GGCTAGCTACAACGA CCATGCCC
9951





1909
GCAUGGAC A UUGACCCG
1153
CGGGTCAA GGCTAGCTACAACGA GTCCATGC
9952





1913
GGACAUUG A CCCGUAUA
1922
TATACGGG GGCTAGCTACAACGA CAATGTCC
9953





1919
UGACCCGU A UAAAGAAU
422
ATTCTTTA GGCTAGCTACAACGA ACGGGTCA
9954





1926
UAUAAAGA A UUUGGAGC
1923
GCTCCAAA GGCTAGCTACAACGA TCTTTATA
9955





1947
GUGGAGUU A CUCUCUUU
429
AAAGAGAG GGCTAGCTACAACGA AACTCCAC
9956





1967
GCCUUCUG A CUUCUUUC
1924
GAAAGAAG GGCTAGCTACAACGA CAGAAGGC
9957





1981
UUCCUUCU A UUCGAGAU
446
ATCTCGAA GGCTAGCTACAACGA AGAAGGAA
9958





1988
UAUUCGAG A UCUCCUCG
1925
CGAGGAGA GGCTAGCTACAACGA CTCGAATA
9959





1997
UCUCCUCG A CACCGCCU
1926
AGGCGGTG GGCTAGCTACAACGA CGAGGAGA
9960





1999
UCCUCGAC A CCGCCUCU
1172
AGAGGCGG GGCTAGCTACAACGA GTCGAGGA
9961





2015
UGCUCUGU A UCGGGGGG
454
CCCCCCGA GGCTAGCTACAACGA ACAGAGCA
9962





2040
UCUCCGGA A CAUUGUUC
1927
GAACAATG GGCTAGCTACAACGA TCCGGAGA
9963





2042
UCCGGAAC A UUGUUCAC
1183
GTGAACAA GGCTAGCTACAACGA GTTCCGGA
9964





2049
CAUUGUUC A CCUCACCA
1184
TGGTGAGG GGCTAGCTACAACGA GAACAATG
9965





2054
UUCACCUC A CCAUACGG
1187
CCGTATGG GGCTAGCTACAACGA GAGGTGAA
9966





2057
ACCUCACC A UACGGCAC
1189
GTGCCGTA GGCTAGCTACAACGA GGTGAGGT
9967





2059
CUCACCAU A CGGCACUC
464
GAGTGCCG GGCTAGCTACAACGA ATGGTGAG
9968





2064
CAUACGGC A CUCAGGCA
1190
TGCCTGAC GGCTAGCTACAACGA GCCGTATG
9969





2077
GGCAAGCU A UUCUGUGU
466
ACACAGAA GGCTAGCTACAACGA AGCTTGCC
9970





2098
GUGAGUUG A UGAAUCUA
1928
TAGATTCA GGCTAGCTACAACGA CAACTCAC
9971





2102
GUUGAUGA A UCUAGCCA
1929
TGGCTAGA GGCTAGCTACAACGA TCATCAAC
9972





2110
AUCUAGCC A CCUGGGUG
1198
CACCCAGG GGCTAGCTACAACGA GGCTAGAT
9973





2126
GGGAAGUA A UUUGGAAG
1930
CTTCCAAA GGCTAGCTACAACGA TACTTCCC
9974





2135
UUUGGAAG A UCCAGCAU
1931
ATGCTGGA GGCTAGCTACAACGA CTTCCAAA
9975





2142
GAUCCAGC A UCCAGGGA
1203
TCCCTGGA GGCTAGCTACAACGA GCTGGATC
9976





2151
UCCAGGGA A UUAGUAGU
1932
ACTACTAA GGCTAGCTACAACGA TCCCTGGA
9977





2165
AGUCAGCU A UGUCAACG
482
CGTTGACA GGCTAGCTACAACGA AGCTGACT
9978





2171
CUAUGUCA A CGUUAAUA
1933
TATTAACG GGCTAGCTACAACGA TGACATAG
9979





2177
CAACGUUA A UAUGGGCC
1934
GGCCCATA GGCTAGCTACAACGA TAACGTTG
9980





2179
ACGUUAAU A UGGGCCUA
486
TAGGCCCA GGCTAGCTACAACGA ATTAACGT
9981





2191
GCCUAAAA A UCAGACAA
1935
TTGTCTGA GGCTAGCTACAACGA TTTTAGGC
9982





2196
AAAAUCAG A CAACUAUU
1936
AATAGTTG GGCTAGCTACAACGA CTGATTTT
9983





2199
AUCAGACA A CUAUUGUG
1937
CACAATAG GGCTAGCTACAACGA TGTCTGAT
9984





2202
AGACAACU A UUGUGGUU
489
AACCACAA GGCTAGCTACAACGA AGTTGTCT
9985





2213
GUGGUUUC A CAUUUCCU
1214
AGGAAATG GGCTAGCTACAACGA GAAACCAC
9986





2215
GGUUUCAC A UUUCCUGU
1215
ACAGGAAA GGCTAGCTACAACGA GTGAAACC
9987





2227
CCUGUCUU A CUUUUGGG
499
CCCAAAAG GGCTAGCTACAACGA AAGACAGG
9988





2242
GGCGAGAA A CUGUUCUU
1938
AAGAACAG GGCTAGCTACAACGA TTCTCGCC
9989





2253
GUUCUUGA A UAUUUGGU
1939
ACCAAATA GGCTAGCTACAACGA TCAAGAAC
9990





2255
UCUUGAAU A UUUGGUGU
506
ACACCAAA GGCTAGCTACAACGA ATTCAAGA
9991





2278
GAGUGUGG A UUCGCACU
1940
AGTGCGAA GGCTAGCTACAACGA CCACACTC
9992





2284
GGAUUCGC A CUCCUCCU
1223
AGGAGGAG GGCTAGCTACAACGA GCGAATCC
9993





2295
CCUCCUGC A UAUAGACC
1229
GGTCTATA GGCTAGCTACAACGA GCAGGAGG
9994





2297
UCCUGCAU A UAGACCAC
517
GTGGTCTA GGCTAGCTACAACGA ATGCAGGA
9995





2301
GCAUAUAG A CCACCAAA
1941
TTTGGTGG GGCTAGCTACAACGA CTATATGC
9996





2304
UAUAGACC A CCAAAUGC
1231
GCATTTGG GGCTAGCTACAACGA GGTCTATA
9997





2309
ACCACCAA A UGCCCCUA
1942
TAGGGGCA GGCTAGCTACAACGA TTGGTGGT
9998





2317
AUGCCCCU A UCUUAUCA
519
TGATAAGA GGCTAGCTACAACGA AGGGGCAT
9999





2322
CCUAUCUU A UCAACACU
522
AGTGTTGA GGCTAGCTACAACGA AAGATAGG
10000





2326
UCUUAUCA A CACUUCCG
1943
CGGAAGTG GGCTAGCTACAACGA TGATAAGA
10001





2328
UUAUCAAC A CUUCCGGA
1240
TCCGGAAG GGCTAGCTACAACGA GTTGATAA
10002





2338
UUCCGGAA A CUACUGUU
1944
AACAGTAG GGCTAGCTACAACGA TTCCGGAA
10003





2341
CGGAAACU A CUGUUGUU
526
AACAACAG GGCTAGCTACAACGA AGTTTCCG
10004





2352
GUUGUUAG A CGAAGAGG
1945
CCTCTTCG GGCTAGCTACAACGA CTAACAAC
10005





2380
GAAGAAGA A CUCCCUCG
1946
CGAGGGAG GGCTAGCTACAACGA TCTTCTTC
10006





2397
CCUCGCAG A CGAAGGUC
1947
GACCTTCG GGCTAGCTACAACGA CTGCGAGG
10007





2409
AGGUCUCA A UCGCCGCG
1948
CGCGGCGA GGCTAGCTACAACGA TGAGACCT
10008





2427
CGCAGAAG A UCUCAAUC
1949
GATTGAGA GGCTAGCTACAACGA CTTCTGCG
10009





2433
AGAUCUCA A UCUCGGGA
1950
TCCCGAGA GGCTAGCTACAACGA TGAGATCT
10010





2442
UCUCGGGA A UCUCAAUG
1951
CATTGAGA GGCTAGCTACAACGA TCCCGAGA
10011





2448
GAAUCUCA A UGUUAGUA
1952
TACTAACA GGCTAGCTACAACGA TGAGATTC
10012





2456
AUGUUAGU A UUCCUUGG
547
CCAAGGAA GGCTAGCTACAACGA ACTAACAT
10013





2465
UUCCUUGG A CACAUAAG
1953
CTTATGTG GGCTAGCTACAACGA CCAAGGAA
10014





2467
CCUUGGAC A CAUAAGGU
1268
ACCTTATG GGCTAGCTACAACGA GTCCAAGG
10015





2469
UUGGACAC A UAAGGUGG
1269
CCACCTTA GGCTAGCTACAACGA GTGTCCAA
10016





2481
GGUGGGAA A CUUUACGG
1954
CCGTAAAG GGCTAGCTACAACGA TTCCCACC
10017





2486
GAAACUUU A CGGGGCUU
554
AAGCCCCG GGCTAGCTACAACGA AAAGTTTC
10018





2496
GGGGCUUU A UUCUUCUA
557
TAGAAGAA GGCTAGCTACAACGA AAAGCCCC
10019





2504
AUUCUUCU A CGGUACCU
562
AGGTACCG GGCTAGCTACAACGA AGAAGAAT
10020





2509
UCUACGGU A CCUUGCUU
563
AAGCAAGG GGCTAGCTACAACGA ACCGTAGA
10021





2520
UUGCUUUA A UCCUAAAU
1955
ATTTAGGA GGCTAGCTACAACGA TAAAGCAA
10022





2527
AAUCCUAA A UGGCAAAC
1956
GTTTGCCA GGCTAGCTACAACGA TTAGGATT
10023





2534
AAUGGCAA A CUCCUUCU
1957
AGAAGGAG GGCTAGCTACAACGA TTGCCATT
10024





2550
UUUUCCUG A CAUUCAUU
1958
AATGAATG GGCTAGCTACAACGA CAGGAAAA
10025





2552
UUCCUGAC A UUCAUUUG
1286
CAAATGAA GGCTAGCTACAACGA GTCAGGAA
10026





2556
UGACAUUC A UUUGCAGG
1287
CCTGCAAA GGCTAGCTACAACGA GAATGTCA
10027





2568
GCAGGAGG A CAUUGUUG
1959
CAACAATG GGCTAGCTACAACGA CCTCCTGC
10028





2570
AGGAGGAC A UUGUUGAU
1289
ATCAACAA GGCTAGCTACAACGA GTCCTCCT
10029





2577
CAUUGUUG A UAGAUGUA
1960
TACATCTA GGCTAGCTACAACGA CAACAATG
10030





2581
GUUGAUAG A UGUAAGCA
1961
TGCTTACA GGCTAGCTACAACGA CTATCAAC
10031





2590
UGUAAGCA A UUUGUGGG
1962
CCCACAAA GGCTAGCTACAACGA TGCTTACA
10032





2606
GGCCCCUU A CAGUAAAU
588
ATTTACTG GGCTAGCTACAACGA AAGGGGCC
10033





2613
UACAGUAA A UGAAAACA
1963
TGTTTTCA GGCTAGCTACAACGA TTACTGTA
10034





2619
AAAUGAAA A CAGGAGAC
1964
GTCTCCTG GGCTAGCTACAACGA TTTCATTT
10035





2626
AACAGGAG A CUUAAAUU
1965
AATTTAAG GGCTAGCTACAACGA CTCCTGTT
10036





2632
AGACUUAA A UUAACUAU
1966
ATAGTTAA GGCTAGCTACAACGA TTAAGTCT
10037





2636
UUAAAUUA A CUAUGCCU
1967
AGGCATAG GGCTAGCTACAACGA TAATTTAA
10038





2639
AAUUAACU A UGCCUGCU
594
AGCAGGCA GGCTAGCTACAACGA AGTTAATT
10039





2655
UAGGUUUU A UCCCAAUG
599
CATTGGGA GGCTAGCTACAACGA AAAACCTA
10040





2661
UUAUCCCA A UGUUACUA
1968
TAGTAACA GGCTAGCTACAACGA TGGGATAA
10041





2666
CCAAUGUU A CUAAAUAU
602
ATATTTAG GGCTAGCTACAACGA AACATTGG
10042





2671
GUUACUAA A UAUUUGCC
1969
GGCAAATA GGCTAGCTACAACGA TTAGTAAC
10043





2673
UACUAAAU A UUUGCCCU
604
AGGGCAAA GGCTAGCTACAACGA ATTTAGTA
10044





2685
GCCCUUAG A UAAAGGGA
1970
TCCCTTTA GGCTAGCTACAACGA CTAAGGGC
10045





2693
AUAAAGGG A UCAAACCG
1971
CGGTTTGA GGCTAGCTACAACGA CCCTTTAT
10046





2698
GGGAUCAA A CCGUAUUA
1972
TAATACGG GGCTAGCTACAACGA TTGATCCC
10047





2703
CAAACCGU A UUAUCCAG
611
CTGGATAA GGCTAGCTACAACGA ACGGTTTG
10048





2706
ACCGUAUU A UCCAGAGU
613
ACTCTGGA GGCTAGCTACAACGA AATACGGT
10049





2715
UCCAGAGU A UGUAGUUA
615
TAACTACA GGCTAGCTACAACGA ACTCTGGA
10050





2724
UGUAGUUA A UCAUUACU
1973
AGTAATGA GGCTAGCTACAACGA TAACTACA
10051





2727
AGUUAAUC A UUACUUCC
1313
GGAAGTAA GGCTAGCTACAACGA GATTAACT
10052





2730
UAAUCAUU A CUUCCAGA
621
TCTGGAAG GGCTAGCTACAACGA AATGATTA
10053





2738
ACUUCCAG A CGCGACAU
1974
ATGTCGCG GGCTAGCTACAACGA CTGGAAGT
10054





2743
CAGACGCG A CAUUAUUU
1975
AAATAATG GGCTAGCTACAACGA CGCGTCTG
10055





2745
GACGCGAC A UUAUUUAC
1317
GTAAATAA GGCTAGCTACAACGA GTCGCGTC
10056





2748
GCGACAUU A UUUACACA
625
TGTGTAAA GGCTAGCTACAACGA AATGTCGC
10057





2752
CAUUAUUU A CACACUCU
628
AGAGTGTG GGCTAGCTACAACGA AAATAATG
10058





2754
UUAUUUAC A CACUCUUU
1318
AAAGAGTG GGCTAGCTACAACGA GTAAATAA
10059





2756
AUUUACAC A CUCUUUGG
1319
CCAAAGAG GGCTAGCTACAACGA GTGTAAAT
10060





2774
AGGCGGGG A UCUUAUAU
1976
ATATAAGA GGCTAGCTACAACGA CCCCGCCT
10061





2779
GGGAUCUU A UAUAAAAG
634
CTTTTATA GGCTAGCTACAACGA AAGATCCC
10062





2781
GAUCUUAU A UAAAAGAG
635
CTCTTTTA GGCTAGCTACAACGA ATAAGATC
10063





2795
GAGAGUCC A CACGUAGC
1324
GCTACGTG GGCTAGCTACAACGA GCACTCTC
10064





2797
CAGUCCAC A CGUAGCGC
1325
GCGCTACG GGCTAGCTACAACGA GTGGACTC
10065





2809
AGCGCCUC A UUUUGCGG
1328
CCGCAAAA GGCTAGCTACAACGA GAGGCGCT
10066





2821
UGCGGGUC A CCAUAUUC
1329
GAATATGG GGCTAGCTACAACGA GACCCGCA
10067





2824
GGGUCACC A UAUUCUUG
1331
CAAGAATA GGCTAGCTACAACGA GGTGACCC
10068





2826
GUCACCAU A UUCUUGGG
644
CCCAAGAA GGCTAGCTACAACGA ATGGTGAC
10069





2836
UCUUGGGA A CAAGAUCU
1977
AGATCTTG GGCTAGCTACAACGA TCCCAAGA
10070





2841
GGAACAAG A UCUACAGC
1978
GCTGTAGA GGCTAGCTACAACGA CTTGTTCC
10071





2845
CAAGAUCU A CAGCAUGG
649
CCATGCTG GGCTAGCTACAACGA AGATCTTG
10072





2850
UCUACAGC A UGGGAGGU
1336
ACCTCCCA GGCTAGCTACAACGA GCTGTAGA
10073





2870
UCUUCCAA A CCUCGAAA
1979
TTTCGAGG GGCTAGCTACAACGA TTGGAAGA
10074





2883
GAAAAGGC A UGGGGACA
1342
TGTCCCCA GGCTAGCTACAACGA GCCTTTTC
10075





2889
GCAUGGGG A CAAAUCUU
1980
AAGATTTG GGCTAGCTACAACGA CCCCATGC
10076





2893
GGGGACAA A UCUUUCUG
1981
CAGAAAGA GGCTAGCTACAACGA TTGTCCCC
10077





2908
UCUCCCCA A UCCCCUGG
1982
CCAGGGGA GGCTAGCTACAACGA TGGGGACA
10078





2918
CCCCUGGG A UUCUUCCC
1983
GGGAAGAA GGCTAGCTACAACGA CCCAGGGG
10079





2929
CUUCCCCG A UCAUCAGU
1984
ACTGATGA GGCTAGCTACAACGA CGGGGAAG
10080





2932
CCCCGAUC A UCAGUUGG
1358
CCAACTGA GGCTAGCTACAACGA GATCGGGG
10081





2941
UCAGUUGG A CCCUGCAU
1985
ATGCAGGG GGCTAGCTACAACGA CCAACTGA
10082





2948
GACCCUGC A UUCAAAGC
1363
GCTTTGAA GGCTAGCTACAACGA GCAGGGTC
10083





2959
CAAAGCCA A CUCAGUAA
1986
TTACTGAG GGCTAGCTACAACGA TGGCTTTG
10084





2968
CUCAGUAA A UCCAGAUU
1987
AATCTGGA GGCTAGCTACAACGA TTACTGAG
10085





2974
AAAUCCAG A UUGGGACC
1988
GGTCCCAA GGCTAGCTACAACGA CTGGATTT
10086





2980
AGAUUGGG A CCUCAACC
1989
GGTTGAGG GGCTAGCTACAACGA CCCAATCT
10087





2986
GGACCUCA A CCCGCACA
1990
TGTGCGGG GGCTAGCTACAACGA TGAGGTCC
10088





2998
GCACAAGG A CAACUGGC
1991
GCCAGTTG GGCTAGCTACAACGA CCTTGTGC
10089





3001
CAAGGACA A CUGGCCGG
1992
CCGGCCAG GGCTAGCTACAACGA TGTCCTTG
10090





3010
CUGGCCGG A CGCCAACA
1993
TGTTGGCG GGCTAGCTACAACGA CCGGCCAG
10091





3016
GGACGCCA A CAAGGUGG
1994
CCACCTTG GGCTAGCTACAACGA TGGCGTCC
10092





3035
GUGGGAGC A UUCGGGCC
1384
GGCCCGAA GGCTAGCTACAACGA GCTCCCAC
10093





3051
CAGGGUUC A CCCCUCCC
1387
GGGAGGGG GGCTAGCTACAACGA GAACCCTG
10094





3061
CCCUCCCC A UGGGGGAC
1395
GTCCCCCA GGCTAGCTACAACGA GGGGAGGG
10095





3068
CAUGGGGG A CUGUUGGG
1995
CCCAACAG GGCTAGCTACAACGA CCCCCATG
10096





3088
GAGCCCUC A CGCUCAGG
1400
CCTGAGCG GGCTAGCTACAACGA GAGGGCTC
10097





3101
CAGGGCCU A CUCACAAC
683
GTTGTGAG GGCTAGCTACAACGA AGGCCCTG
10098





3105
GCCUACUC A CAACUGUG
1406
CACAGTTG GGCTAGCTACAACGA GAGTAGGC
10099





3108
UACUCACA A CUGUGCCA
1996
TGGCACAG GGCTAGCTACAACGA TGTGAGTA
10100





3138
CUGCCUCC A CCAAUCGG
1422
CCGATTGG GGCTAGCTACAACGA GGAGGCAG
10101





3142
CUCCACCA A UCGGCAGU
1997
ACTGCCGA GGCTAGCTACAACGA TGGTGGAG
10102





3165
GGCAGCCU A CUCCCUUA
691
TAAGGGAG GGCTAGCTACAACGA AGGCTGCC
10103





3173
ACUCCCUU A UCUCCACC
694
GGTGGAGA GGCTAGCTACAACGA AAGGGAGT
10104





3179
UUAUCUCC A CCUCUAAG
1436
CTTAGAGG GGCTAGCTACAACGA GGAGATAA
10105





3190
UCUAAGGG A CACUCAUC
1998
GATGAGTG GGCTAGCTACAACGA CCCTTAGA
10106





3192
UAAGGGAC A CUCAUCCU
1440
AGGATGAG GGCTAGCTACAACGA GTCCCTTA
10107





3196
GGACACUC A UCCUCAGG
1442
CCTGAGGA GGCTAGCTACAACGA GAGTGTCC
10108





3207
CUCAGGCC A UGCAGUGG
1447
CCACTGCA GGCTAGCTACAACGA GGCCTGAG
10109






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)








[0558]

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
10110






87
GGAACAGU G AGCCCUGC
1449
GCAGGGCU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG ACUGUUCC
10111





94
UGAGCCCU G CUCAGAAU
1450
AUUCUGAG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AGGGCUCA
10112





112
CUGUCUCU G CCAUAUCG
1451
CGAUAUGG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AGAGACAG
10113





132
AUCUUAUC G AAGACUGG
1452
CCAGUCUU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG GAUAAGAU
10114





153
CCUGUACC G AACAUGGA
1453
UCCAUGUU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG GGUACAGG
10115





169
AGAACAUC G CAUCAGGA
1454
UCCUGAUG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG GAUGUUCU
10116





192
GGACCCCU G CUCGUGUU
1455
AACACGAG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AGGGGUCC
10117





222
UUCUUGUU G ACAAAAAU
1456
AUUUUUGU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AACAAGAA
10118





315
CAAAAUUC G CAGUCCCA
1457
UGGGACUG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG GAAUUUUG
10119





374
UGGUUAUC G CUGGAUGU
1458
ACAUCCAG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG GAUAACCA
10120





387
AUGUGUCU G CGGCGUUU
1459
AAACGCCG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AGACACAU
10121





410
CUUCCUCU G CAUCCUGC
1460
GCAGGAUG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AGAGGAAG
10122





417
UGCAUCCU G CUGCUAUG
1461
CAUAGCAG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AGGAUGCA
10123





420
AUCCUGCU G CUAUGCCU
1462
AGGCAUAG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AGCAGGAU
10124





425
GCUGCUAU G CCUCAUCU
1463
AGAUGAGG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AUAGCAGC
10125





468
GGUAUGUU G CCCGUUUG
1464
CAAACGGG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AACAUACC
10126





518
CGGACCAU G CAAAACCU
1465
AGGUUUUG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AUGGUCCG
10127





527
CAAAACCU G CACAACUC
1466
GAGUUGUG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AGGUUUUG
10128





538
CAACUCCU G CUCAAGGA
1467
UCCUUGAG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AGGAGUUG
10129





569
CUCAUGUU G CUGUACAA
1468
UUGUACAG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AACAUGAG
10130





596
CGGAAACU G CACCUGUA
1469
UACAGGUG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AGUUUCCG
10131





631
GGGCUUUC G CAAAAUAC
1470
GUAUUUUG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG GAAAGCCC
10132





687
UUACUAGU G CCAUUUGU
1471
ACAAAUGG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG ACUAGUAA
10133





747
AUAUGGAU G AUGUGGUU
1472
AACCACAU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AUCCAUAU
10134





783
AACAUCUU G AGUCCCUU
1473
AAGGGACU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AAGAUGUU
10135





795
CCCUUUAU G CCGCUGUU
1474
AACAGCGG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AUAAAGGG
10136





798
UUUAUGCC G CUGUUACC
1475
GGUAACAG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG GGCAUAAA
10137





911
GGCACAUU G CCACAGGA
1476
UCCUGUGG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AAUGUGCC
10138





978
GGCCUAUU G AUUGGAAA
1477
UUUCCAAU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AAUAGGCC
10139





997
AUGUCAAC G AAUUGUGG
1478
CCACAAUU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG GUUGACAU
10140





1020
UGGGGUUU G CCGCCCCU
1479
AGGGGCGG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AAACCCCA
10141





1023
GGUUUGCC G CCCCUUUC
1480
GAAAGGGG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG GGCAAACC
10142





1034
CCUUUCAC G CAAUGUGG
1481
CCACAUUG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG GUGAAAGG
10143





1050
GAUAUUCU G CUUUAAUG
1482
CAUUAAAG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AGAAUAUC
10144





1058
GCUUUAAU G CCUUUAUA
1483
UAUAAAGG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AUUAAAGC
10145





1068
CUUUAUAU G CAUGCAUA
1484
UAUGCAUG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AUAUAAAG
10146





1072
AUAUGCAU G CAUACAAG
1485
CUUGUAUG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AUGCAUAU
10147





1103
ACUUUCUC G CCAACUUA
1486
UAAGUUGG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG GAGAAAGU
10148





1139
CAGUAUGU G AACCUUUA
1487
UAAAGGUU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG ACAUACUG
10149





1155
ACCCCGUU G CUCGGCAA
1488
UUGCCGAG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AACGGGGU
10150





1177
UGGUCUAU G CCAAGUGU
1489
ACACUUGG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AUAGACCA
10151





1188
AAGUGUUU G CUGACGCA
1490
UGCGUCAG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AAACACUU
10152





1191
UGUUUGCU G ACGCAACC
1491
GGUUGCGU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AGCAAACA
10153





1194
UUGCUGAC G CAACCCCC
1492
GGGGGUUG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG GUCAGCAA
10154





1234
CCAUCAGC G CAUGCGUG
1493
CACGCAUG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG GCUGAUGG
10155





1238
CAGCGCAU G CGUGGAAC
1494
GUUCCACG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AUGCGCUG
10156





1262
UCUCCUCU G CCGAUCCA
1495
UGGAUCGG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AGAGGAGA
10157





1265
CCUCUGCC G AUCCAUAC
1496
GUAUGGAU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG GGCAGAGG
10158





1275
UCCAUACC G CGGAACUC
1497
GAGUUCCG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG GGUAUGGA
10159





1290
UCCUAGCC G CUUGUUUU
1498
AAAACAAG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG GGCUAGGA
10160





1299
CUUGUUUU G CUCGCAGC
1499
GCUGCGAG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AAAACAAG
10161





1303
UUUUGCUC G CAGCAGGU
1500
ACCUGCUG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG GAGCAAAA
10162





1335
UCGGGACU G ACAAUUCU
1501
AGAAUUGU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AGUCCCGA
10163





1349
UCUGUCGU G CUCUCCCG
1502
CGGGAGAG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG ACGACAGA
10164





1357
GCUCUCCC G CAAAUAUA
1503
UAUAUUUG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG GGGAGAGC
10165





1382
CCAUGGCU G CUAGGCUG
1504
CAGCCUAG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AGCCAUGG
10166





1392
UAGGCUGU G CUGCCAAC
1505
GUUGGCAG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG ACAGCCUA
10167





1395
GCUGUGCU G CCAACUGG
1506
CCAGUUGG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AGCACAGC
10168





1411
GAUCCUAC G CGGGACGU
1507
ACGUCCCG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG GUAGGAUC
10169





1442
CCGUCGGC G CUGAAUCC
1508
GGAUUCAG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG GCCGACGG
10170





1445
UCGGCGCU G AAUCCCGC
1509
GCGGGAUU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AGCGCCGA
10171





1452
UGAAUCCC G CGGACGAC
1510
GUCGUCCG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG GGGAUUCA
10172





1458
CCGCGGAC G ACCCCUCC
1511
GGAGGGGU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG GUCCGCGG
10173





1474
CCGGGGCC G CUUGGGGC
1512
GCCCCAAG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG GGCCCCGG
10174





1489
GCUCUACC G CCCGCUUC
1513
GAAGCGGG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG GGUAGAGC
10175





1493
UACCGCCC G CUUCUCCG
1514
CGGAGAAG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG GGGCGGUA
10176





1501
GCUUCUCC G CCUAUUGU
1515
ACAAUAGG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG GGAGAAGC
10177





1513
AUUGUACC G ACCGUCCA
1516
UGGACGGU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG GGUACAAU
10178





1528
CACGGGGC G CACCUCUC
1517
GAGAGGUG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG GCCCCGUG
10179





1542
CUCUUUAC G CGGACUCC
1518
GGAGUCCG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG GUAAAGAG
10180





1559
CCGUCUGU G CCUUCUCA
1519
UGAGAAGG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG ACAGACGG
10181





1571
UCUCAUCU G CCGGACCG
1520
CGGUCCGG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AGAUGAGA
10182





1583
GACCGUGU G CACUUCGC
1521
GCGAAGUG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG ACACGGUC
10183





1590
UGCACUUC G CUUCACCU
1522
AGGUGAAG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG GAAGUGCA
10184





1601
UCACCUCU G CACGUCGC
1523
GCGACGUG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AGAGGUGA
10185





1608
UGCACGUC G CAUGGAGA
1524
UCUCCAUG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG GACGUGCA
10186





1624
ACCACCGU G AACGCCCA
1525
UGGGCGUU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG ACGGUGGU
10187





1628
CCGUGAAC G CCCACAGG
1526
CCUGUGGG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG GUUCACGG
10188





1642
AGGAACCU G CCCAAGGU
1527
ACCUUGGG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AGGUUCCU
10189





1654
AAGGUCUU G CAUAAGAG
1528
CUCUUAUG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AAGACCUU
10190





1690
AUGUCAAC G ACCGACCU
1529
AGGUCGGU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG GUUGACAU
10191





1694
CAACGACC G ACCUUGAG
1530
CUCAAGGU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG GGUCGUUG
10192





1700
CCGACCUU G AGGCAUAC
1531
GUAUGCCU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AAGGUCGG
10193





1730
UCUUUAAU G AGUGGGAG
1532
CUCCCACU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AUUAAACA
10194





1818
AGCACCAU G CAACUUUU
1533
AAAAGUUG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AUGGUGCU
10195





1835
UCACCUCU G CCUAAUCA
1534
UGAUUAGG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AGAGGUGA
10196





1883
CAAGCUGU G CCUUGGGU
1535
ACCCAAGG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG ACAGCUUG
10197





1912
UGGACAUU G ACCCGUAU
1536
AUACGGGU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AAUGUCCA
10198





1959
UCUUUUUU G CCUUCUGA
1537
UCAGAAGG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AAAAAAGA
10199





1966
UGCCUUCU G ACUUCUUU
1538
AAAGAAGU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AGAAGGCA
10200





1985
UUCUAUUC G AGAUCUCC
1539
GGAGAUCU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG GAAUAGAA
10201





1996
AUCUCCUC G ACACCGCC
1540
GGCGGUGU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG GAGGAGAU
10202





2002
UCGACACC G CCUCUGCU
1541
AGCAGAGG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG GGUGUCGA
10203





2008
CCGCCUCU G CUCUGUAU
1542
AUACAGAG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AGAGGCGG
10204





2092
GUUGGGGU G AGUUGAUG
1543
CAUCAACU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG ACCCCAAC
10205





2097
GGUGAGUU G AUGAAUCU
1544
AGAUUCAU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AACUCACC
10206





2100
GAGUUGAU G AAUCUAGC
1545
GCUAGAUU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AUCAACUC
10207





2237
UUUUGGGC G AGAAACUG
1546
CAGUUUCU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG GCCCAAAA
10208





2251
CUGUUCUU G AAUAUUUG
1547
CAAAUAUU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AAGAACAG
10209





2282
GUGGAUUC G CACUCCUC
1548
GAGGAGUG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG GAAUCCAC
10210





2293
CUCCUCCU G CAUAUAGA
1549
UCUAUAUG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AGGAGGAG
10211





2311
CACCAAAU G CCCCUAUC
1550
GAUAGGGG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AUUUGGUG
10212





2354
UGUUAGAC G AAGAGGCA
1551
UGCCUCUU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG GUCUAACA
10213





2388
ACUCCCUC G CCUCGCAG
1552
CUGCGAGG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG GAGGGAGU
10214





2393
CUCGCCUC G CAGACGAA
1553
UUCGUCUG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG GAGGCGAG
10215





2399
UCGCAGAC G AAGGUCUC
1554
GAGACCUU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG GUCUGCGA
10216





2412
UCUCAAUC G CCGCGUCG
1555
CGACGCGG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG GAUUGAGA
10217





2415
CAAUCGCC G CGUCGCAG
1556
CUGCGACG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG GGCGAUUG
10218





2420
GCCGCGUC G CAGAAGAU
1557
AUCUUCUG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG GACGCGGC
10219





2514
GGUACCUU G CUUUAAUC
1558
GAUUAAAG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AAGGUACC
10220





2549
CUUUUCCU G ACAUUCAU
1559
AUGAAUGU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AGGAAAAG
10221





2560
AUUCAUUU G CAGGAGGA
1560
UCCUCCUG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AAAUGAAU
10222





2576
ACAUUGUU G AUAGAUGU
1561
ACAUCUAU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AACAAUGU
10223





2615
CAGUAAAU G AAAACAGG
1562
CCUGUUUU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AUUUACUG
10224





2641
UUAACUAU G CCUGCUAG
1563
CUAGCAGG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AUAGUUAA
10225





2645
CUAUGCCU G CUAGGUUU
1564
AAACCUAG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AGGCAUAG
10226





2677
AAAUAUUU G CCCUUAGA
1565
UCUAAGGG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AAAUAUUU
10227





2740
UUCCAGAC G CGACAUUA
1566
UAAUGUCG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG GUCUGGAA
10228





2742
CCAGACGC G ACAUUAUU
1567
AAUAAUGU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG GCGUCUGG
10229





2804
CACGUAGC G CCUCAUUU
1568
AAAUGAGG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG GCUACGUG
10230





2814
CUCAUUUU G CGGGUCAC
1569
GUGACCCG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AAAAUGAG
10231





2875
CAAACCUC G AAAAGGCA
1570
UGCCUUUU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG GAGGUUUG
10232





2928
UCUUCCCC G AUCAUCAG
1571
CUGAUGAU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG GGGGAAGA
10233





2946
UGGACCCU G CAUUCAAA
1572
UUUGAAUG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AGGGUCCA
10234





2990
CUCAACCC G CACAAGGA
1573
UCCUUGUG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG GGGUUGAG
10235





3012
GGCCGGAC G CCAACAAG
1574
CUUGUUGG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG GUCCGGCC
10236





3090
GCCCUCAC G CUCAGGGC
1575
GCCCUGAG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG GUGAGGGC
10237





3113
ACAACUGU G CCAGCAGC
1576
GCUGCUGG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG ACAGUUGU
10238





3132
CUCCUCCU G CCUCCACC
1577
GGUGGAGG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AGGAGGAG
10239





51
AGGGCCCU G UACUUUCC
1578
GGAAAGUA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AGGGCCCU
10240





106
AGAAUACU G UCUCUGCC
1579
GGCAGAGA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AGUAUUCU
10241





148
GGGACCCU G UACCGAAC
1580
GUUCGGUA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AGGGUCCC
10242





198
CUGCUCGU G UUACAGGC
1581
GCCUGUAA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG ACGAGCAG
10243





219
UUUUUCUU G UUUGUCAA
1582
UUUGUCAA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AAGAAAAA
10244





297
ACACCCGU G UGUCUUGG
1583
CCAAGACA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG ACGGGUGU
10245





299
ACCCGUGU G UCUUGGCC
1584
GGCCAAGA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG ACACGGGU
10246





347
ACCAACCU G UUGUCCUC
1585
GAGGACAA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AGGUUGGU
10247





350
AACCUGUU G UCCUCCAA
1586
UUGGAGGA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AACAGGUU
10248





362
UCCAAUUU G UCCUGGUU
1587
AACCAGGA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AAAUUGGA
10249





381
CGCUGGAU G UGUCUGCG
1588
CGCAGACA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AUCCAGCG
10250





383
CUGGAUGU G UCUGCGGC
1589
GCCGCAGA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG ACAUCCAG
10251





438
AUCUUCUU G UUGGUUCU
1590
AGAACCAA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AAGAAGAU
10252





465
CAAGGUAU G UUGCCCGU
1591
ACGGGCAA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AUACCUUG
10253





476
GCCCGUUU G UCCUCUAA
1592
UUAGAGGA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AAACGGGC
10254





555
ACCUCUAU G UUUCCCUC
1593
GAGGGAAA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AUAGAGGU
10255





566
UCCCUCAU G UUGCUGUA
1594
UACAGCAA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AUGAGGGA
10256





572
AUGUUGCU G UACAAAAC
1595
GUUUUGUA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AGCAACAU
10257





602
CUGCACCU G UAUUCCCA
1596
UGGGAAUA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AGGUGCAG
10258





694
UGCCAUUU G UUCAGUGG
1597
CCACUGAA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AAAUGGCA
10259





724
CCCCCACU G UCUGGCUU
1598
AAGCCAGA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AGUGGGGG
10260





750
UGGAUGAU G UGGUUUUG
1599
CAAAACCA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AUCAUCCA
10261





771
CCAAGUCU G UACAACAU
1600
AUGUUGUA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AGACUUGG
10262





801
AUGCCGCU G UUACCAAU
1601
AUUGGUAA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AGCGGCAU
10263





818
UUUCUUUU G UCUUUGGG
1602
CCCAAAGA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AAAAGAAA
10264





888
UGGGAUAU G UAAUUGGG
1603
CCCAAUUA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AUAUCCCA
10265





927
AACAUAUU G UACAAAAA
1604
UUUUUGUA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AAUAUGUU
10266





944
AUCAAAAU G UGUUUUAG
1605
CUAAAACA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AUUUUGAU
10267





946
CAAAAUGU G UUUUAGGA
1606
UCCUAAAA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG ACAUUUUG
10268





963
AACUUCCU G UAAACAGG
1607
CCUGUUUA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AGGAAGUU
10269





991
GAAAGUAU G UCAACGAA
1608
UUCGUUGA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AUACUUUC
10270





1002
AACGAAUU G UGGGUCUU
1609
AAGACCCA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AAUUCGUU
10271





1039
CACGCAAU G UGGAUAUU
1610
AAUAUCCA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AUUGCGUG
10272





1137
AACAGUAU G UGAACCUU
1611
AAGGUUCA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AUACUGUU
10273





1184
UGCCAAGU G UUUGCUGA
1612
UCAGCAAA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG ACUUGGCA
10274





1251
GAACCUUU G UGUCUCCU
1613
AGGAGACA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AAAGGUUC
10275





1253
ACCUUUGU G UCUCCUCU
1614
AGAGGAGA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG ACAAAGGU
10276





1294
AGCCGCUU G UUUUGCUC
1615
GAGCAAAA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AAGCGGCU
10277





1344
ACAAUUCU G UCGUGCUC
1616
GAGCACGA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AGAAUUGU
10278





1390
GCUAGGCU G UGCUGCCA
1617
UGGCAGCA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AGCCUAGC
10279





1425
CGUCCUUU G UUUACGUC
1618
GACGUAAA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AAAGGACG
10280





1508
CGCCUAUU G UACCGACC
1619
GGUCGGUA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AAUAGGCG
10281





1557
CCCCGUCU G UGCCUUCU
1620
AGAAGGCA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AGACGGGG
10282





1581
CGGACCGU G UGCACUUC
1621
GAAGUGCA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG ACGGUCCG
10283





1684
UCAGCAAU G UCAACGAC
1622
GUCGUUGA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AUUGCUGA
10284





1719
CAAAGACU G UGUGUUUA
1623
UAAACACA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AGUCUUUG
10285





1721
AAGACUGU G UGUUUAAU
1624
AUUAAACA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG ACAGUCUU
10286





1723
GACUGUGU G UUUAAUGA
1625
UCAUUAAA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG ACACAGUC
10287





1772
AGGUCUUU G UACUAGGA
1626
UCCUAGUA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AAAGACCU
10288





1785
AGGAGGCU G UAGGCAUA
1627
UAUGCCUA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AGCCUCCU
10289





1801
AAAUUGGU G UGUUCACC
1628
GGUGAACA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG ACCAAUUU
10290





1803
AUUGGUGU G UUCACCAG
1629
CUGGUGAA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG ACACCAAU
10291





1850
CAUCUCAU G UUCAUGUC
1630
GACAUGAA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AUGAGAUG
10292





1856
AUGUUCAU G UCCUACUG
1631
CAGUAGGA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AUGAACAU
10293





1864
GUCCUACU G UUCAAGCC
1632
GGCUUGAA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AGUAGGAC
10294





1881
UCCAAGCU G UGCCUUGG
1633
CCAAGGCA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AGCUUGGA
10295





1939
GAGCUUCU G UGGAGUUA
1634
UAACUCCA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AGAAGCUC
10296





2013
UCUGCUCU G UAUCGGGG
1635
CCCCGAUA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AGAGCAGA
10297





2045
GGAACAUU G UUCACCUC
1636
GAGGUGAA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AAUGUUCC
10298





2082
GCUAUUCU G UGUUGGGG
1637
CCCCAACA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AGAAUAGC
10299





2084
UAUUCUGU G UUGGGGUG
1638
CACCCCAA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG ACAGAAUA
10300





2167
UCAGCUAU G UCAACGUU
1639
AACGUUGA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AUAGCUGA
10301





2205
CAACUAUU G UGGUUUCA
1640
UGAAACCA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AAUAGUUG
10302





2222
CAUUUCCU G UCUUACUU
1641
AAGUAAGA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AGGAAAUG
10303





2245
GAGAAACU G UUCUUGAA
1642
UUCAAGAA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AGUUUCUC
10304





2262
UAUUUGGU G UCUUUUGG
1643
CCAAAAGA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG ACCAAAUA
10305





2274
UUUGGAGU G UGGAUUCG
1644
CGAAUCCA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG ACUCCAAA
10306





2344
AAACUACU G UUGUUAGA
1645
UCUAACAA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AGUAGUUU
10307





2347
CUACUGUU G UUAGACGA
1646
UCGUCUAA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AACAGUAG
10308





2450
AUCUCAAU G UUAGUAUU
1647
AAUACUAA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AUUGAGAU
10309





2573
AGGACAUU G UUGAUAGA
1648
UCUAUCAA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AAUGUCCU
10310





2583
UGAUAGAU G UAAGCAAU
1649
AUUGCUUA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AUCUAUCA
10311





2594
AGCAAUUU G UGGGGCCC
1650
GGGCCCCA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AAAUUGCU
10312





2663
AUCCCAAU G UUACUAAA
1651
UUUAGUAA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AUUGGGAU
10313





2717
CAGAGUAU G UAGUUAAU
1652
AUUAACUA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AUACUCUG
10314





2901
AUCUUUCU G UCCCCAAU
1653
AUUGGGGA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AGAAAGAU
10315





3071
GGGGGACU G UUGGGGUG
1654
CACCCCAA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AGUCCCCC
10316





3111
UCACAACU G UGCCAGCA
1655
UGCUGGCA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AGUUGUGA
10317





40
AUCCCAGA G UCAGGGCC
1656
GGCCCUGA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UCUGGGAU
10318





46
GAGUCAGG G CCCUGUAC
1657
GUACAGGG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CCUGACUC
10319





65
UCCUGCUG G UGGCUCCA
1658
UGGAGCCA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CAGCAGGA
10320





68
UGCUGGUG G CUCCAGUU
1659
AACUGGAG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CACCAGCA
10321





74
UGGCUCCA G UUCAGGAA
1660
UUCCUGAA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UGGAGCCA
10322





85
CAGGAACA G UGAGCCCU
1661
AGGGCUCA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UGUUCCUG
10323





89
AACAGUGA G CCCUGCUC
1662
GAGCAGGG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UCACUGUU
10324





120
GCCAUAUC G UCAAUCUU
1663
AAGAUUGA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG GAUAUGGC
10325





196
CCCUGCUC G UGUUACAG
1664
CUGUAACA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG GAGCAGGG
10326





205
UGUUACAG G CGGGGUUU
1665
AAACCCCG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CUGUAACA
10327





210
CAGGCGGG G UUUUUCUU
1666
AAGAAAAA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CCCGCCUG
10328





248
ACCACAGA G UCUAGACU
1667
AGUCUAGA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UCUGUGGU
10329





258
CUAGACUC G UGGUGGAC
1668
GUCCACCA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG GAGUCUAG
10330





261
GACUCGUG G UGGACUUC
1669
GAAGUCCA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CACGAGUC
10331





295
GAACACCC G UGUGUCUU
1670
AAGACACA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG GGGUGUUC
10332





305
GUGUCUUG G CCAAAAUU
1671
AAUUUUGG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CAAGACAC
10333





318
AAUUCGCA G UCCCAAAU
1672
AUUUGGGA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UGCGAAUU
10334





332
AAUCUCCA G UCACUCAC
1673
GUGAGUGA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UGGAGAUU
10335





368
UUGUCCUG G UUAUCGCU
1674
AGCGAUAA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CAGGACAA
10336





390
UGUCUGCG G CGUUUUAU
1675
AUAAAACG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CGCAGACA
10337





392
UCUGCGGC G UUUUAUCA
1676
UGAUAAAA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG GCCGCAGA
10338





442
UCUUGUUG G UUCUUCUG
1677
CAGAAGAA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CAACAAGA
10339





461
CUAUCAAG G UAUGUUGC
1678
GCAACAUA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CUUGAUAG
10340





472
UGUUGCCC G UUUGUCCU
1679
AGGACAAA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG GGGCAACA
10341





506
AACAACCA G CACCGGAC
1680
GUCCGGUG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UGGUUGUU
10342





625
CAUCUUGG G CUUUCGCA
1681
UGCGAAAG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CCAAGAUG
10343





648
CUAUGGGA G UGGGCCUC
1682
GAGGCCCA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UCCCAUAG
10344





652
GGGAGUGG G CCUCAGUC
1683
GACUGAGG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CCACUCCC
10345





658
GGGCCUCA G UCCGUUUC
1684
GAAACGGA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UGAGGCCC
10346





662
CUCAGUCC G UUUCUCUU
1685
AAGAGAAA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG GGACUGAG
10347





672
UUCUCUUG G CUCAGUUU
1686
AAACUGAG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CAAGAGAA
10348





677
UUGGCUCA G UUUACUAG
1687
CUAGUAAA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UGAGCCAA
10349





685
GUUUACUA G UGCCAUUU
1688
AAAUGGCA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UAGUAAAC
10350





699
UUUGUUCA G UGGUUCGU
1689
ACGAACCA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UGAACAAA
10351





702
GUUCAGUG G UUCGUAGG
1690
CCUACGAA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CACUGAAC
10352





706
AGUGGUUC G UAGGGCUU
1691
AAGCCCUA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG GAACCACU
10353





711
UUCGUAGG G CUUUCCCC
1692
GGGGAAAG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CCUACGAA
10354





729
ACUGUCUG G CUUUCAGU
1693
ACUGAAAG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CAGACAGU
10355





736
GGCUUUCA G UUAUAUGG
1694
CCAUAUAA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UGAAAGCC
10356





753
AUGAUGUG G UUUUGGGG
1695
CCCCAAAA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CACAUCAU
10357





762
UUUUGGGG G CCAAGUCU
1696
AGACUUGG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CCCCAAAA
10358





767
GGGGCCAA G UGUGUACA
1697
UGUACAGA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UUGGCCCC
10359





785
CAUCUUGA G UCCCUUUA
1698
UAAAGGGA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UCAAGAUG
10360





826
GUCUUUGG G UAUACAUU
1699
AAUGUAUA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CCAAAGAC
10361





898
AAUUGGGA G UUGGGGCA
1700
UGCCCCAA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UCCCAAUU
10362





904
GAGUUGGG G CACAUUGC
1701
GCAAUGUG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CCCAACUC
10363





971
GUAAACAG G CCUAUUGA
1702
UCAAUAGG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CUGUUUAC
10364





987
AUUGGAAA G UAUGUCAA
1703
UUGACAUA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UUUCCAAU
10365





1006
AAUUGUGG G UCUUUUGG
1704
CCAAAAGA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CCACAAUU
10366





1016
CUUUUGGG G UUUGCCGC
1705
GCGGCAAA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CCCAAAAG
10367





1080
GCAUACAA G CAAAACAG
1706
CUGUUUUG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UUGUAUGC
10368





1089
CAAAACAG G CUUUUACU
1707
AGUAAAAG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CUGUUUUG
10369





1116
CUUACAAG G CCUUUCUA
1708
UAGAAAGG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CUUGUAAG
10370





1126
CUUUCUAA G UAAACAGU
1709
ACUGUUUA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UUAGAAAG
10371





1133
AGUAAACA G UAUGUGAA
1710
UUCACAUA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UGUUUACU
10372





1152
UUUACCCC G UUGCUCGG
1711
CCGAGCAA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG GGGGUAAA
10373





1160
GUUGCUCG G CAACGGCC
1712
GGCCGUUG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CGAGCAAC
10374





1166
CGGCAACG G CCUGGUCU
1713
AGACCAGG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CGUUGCCG
10375





1171
ACGGCCUG G UCUAUGCC
1714
GGCAUAGA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CAGGCCGU
10376





1182
UAUGCCAA G UGUUUGCU
1715
AGCAAACA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UUGGCAUA
10377





1207
CCCCACUG G UUGGGGCU
1716
AGCCCCAA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CAGUGGGG
10378





1213
UGGUUGGG G CUUGGCCA
1717
UGGCCAAG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CCCAACCA
10379





1218
GGGGCUUG G CCAUAGGC
1718
GCCUAUGG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CAAGCCCC
10380





1225
GGCCAUAG G CCAUCAGC
1719
GCUGAUGG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CUAUGGCC
10381





1232
GGCCAUCA G CGCAUGCG
1720
CGCAUGCG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UGAUGGCC
10382





1240
GCGCAUGC G UGGAACCU
1721
AGGUUCCA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG GCAUGCGC
10383





1287
AACUCCUA G CCGCUUGU
1722
ACAAGCGG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UAGGAGUU
10384





1306
UGCUCGCA G CAGGUCUG
1723
CAGACCUG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UGCGAGCA
10385





1310
CGCAGCAG G UCUGGGGC
1724
GCCCCAGA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CUGCUGCG
10386





1317
GGUCUGGG G CAAAACUC
1725
GAGUUUUG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CCCAGACC
10387





1347
AUUCUGUC G UGCUCUCC
1726
GGAGAGCA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG GACAGAAU
10388





1379
UUUCCAUG G CUGCUAGG
1727
CCUAGCAG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CAUGGAAA
10389





1387
GCUGCUAG G CUGUGCUG
1728
CAGCACAG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CUAGCAGC
10390





1418
CGCGGGAC G UCCUUUGU
1729
ACAAAGGA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG GUCCCGCG
10391





1431
UUGUUUAC G UCCCGUCG
1730
CGACGGGA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG GUAAACAA
10392





1436
UACGUCCC G UCGGCGCU
1731
AGCGCCGA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG GGGACGUA
10393





1440
UCCCGUCG G CGCUGAAU
1732
AUUCAGCG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CGACGGGA
10394





1471
CUCCCGGG G CCGCUUGG
1733
CCAAGCGG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CCCGGGAG
10395





1481
CGCUUGGG G CUCUACCG
1734
CGGUAGAG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CCCAAGCG
10396





1517
UACCGACC G UCCACGGG
1735
CCCGUGGA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG GGUCGGUA
10397





1526
UCCACGGG G CGCACCUC
1736
GAGGUGCG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CCCGUGGA
10398





1553
GACUCCCC G UCUGUGCC
1737
GGCACAGA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG GGGGAGUC
10399





1579
GCCGGACC G UGUGCACU
1738
AGUGCACA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG GGUCCGGC
10400





1605
CUCUGCAC G UCGCAUGG
1739
CCAUGCGA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG GUGCAGAG
10401





1622
AGACCACC G UGAACGCC
1740
GGCGUUCA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG GGUGGUCU
10402





1649
UGCCCAAG G UCUUGCAU
1741
AUGCAAGA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CUUGGGCA
10403





1679
GACUUUCA G CAAUGUCA
1742
UGACAUUG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UGAAAGUC
10404





1703
ACCUUGAG G CAUACUUC
1743
GAAGUAUG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CUCAAGGU
10405





1732
UUUAAUGA G UGGGAGGA
1744
UCCUCCCA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UCAUUAAA
10406





1741
UGGGAGGA G UUGGGGGA
1745
UCCCCCAA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UCCUCCCA
10407





1754
GGGAGGAG G UUAGGUUA
1746
UAACCUAA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CUCCUCCC
10408





1759
GAGGUUAG G UUAAAGGU
1747
ACCUUUAA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CUAACCUC
10409





1766
GGUUAAAG G UCUUUGUA
1748
UACAAAGA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CUUUAACC
10410





1782
ACUAGGAG G CUGUAGGC
1749
GCCUACAG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CUCCUAGU
10411





1789
GGCUGUAG G CAUAAAUU
1750
AAUUUAUG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CUACAGCC
10412





1799
AUAAAUUG G UGUGUUCA
1751
UGAACACA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CAAUUUAU
10413





1811
GUUCACCA G CACCAUGC
1752
GCAUGGUG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UGGUGAAC
10414





1870
CUGUUCAA G CCUCCAAG
1753
CUUGGAGG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UUGAACAG
10415





1878
GCCUCCAA G CUGUGCCU
1754
AGGCACAG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UUGGAGGC
10416





1890
UGCCUUGG G UGGCUUUG
1755
CAAAGCCA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CCAAGGCA
10417





1893
CUUGGGUG G CUUUGGGG
1756
CCCCAAAG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CACCCAAG
10418





1901
GCUUUGGG G CAUGGACA
1757
UGUCCAUG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CCCAAAGC
10419





1917
AUUGACCC G UAUAAAGA
1758
UCUUUAUA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG GGGUCAAU
10420





1933
AAUUUGGA G CUUCUGUG
1759
CACAGAAG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UCCAAAUU
10421





1944
UCUGUGGA G UUACUCUC
1760
GAGAGUAA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UCCACAGA
10422





2023
AUCGGGGG G CCUUAGAG
1761
CUCUAAGG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CCCCCGAU
10423





2031
GCCUUAGA G UCUCCGGA
1762
UCCGGAGA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UCUAAGGC
10424





2062
ACCAUACG G CACUCAGG
1763
CCUGAGUG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CGUAUGGU
10425





2070
GCACUCAG G CAAGCUAU
1764
AUAGCUUG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CUGAGUGC
10426





2074
UCAGGCAA G CUAUUCUG
1765
CAGAAUAG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UUGCCUGA
10427





2090
GUGUUGGG G UGAGUUGA
1766
UCAACUCA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CCCAACAC
10428





2094
UGGGGUGA G UUGAUGAA
1767
UUCAUCAA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UCACCCCA
10429





2107
UGAAUCUA G CCACCUGG
1768
CCAGGUGG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UAGAUUCA
10430





2116
CCACCUGG G UGGGAAGU
1769
ACUUCCCA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CCAGGUGG
10431





2123
GGUGGGAA G UAAUUUGG
1770
CCAAAUUA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UUCCCACC
10432





2140
AAGAUCCA G CAUCCAGG
1771
CCUGGAUG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UGGAUCUU
10433





2155
GGGAAUUA G UAGUCAGC
1772
GCUGACUA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UAAUUCCC
10434





2158
AAUUAGUA G UCAGCUAU
1773
AUAGCUGA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UACUAAUU
10435





2162
AGUAGUCA G CUAUGUCA
1774
UGACAUAG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UGACUACU
10436





2173
AUGUCAAC G UUAAUAUG
1775
CAUAUUAA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG GUUGACAU
10437





2183
UAAUAUGG G CCUAAAAA
1776
UUUUUAGG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CCAUAUUA
10438





2208
CUAUUGUG G UUUCACAU
1777
AUGUGAAA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CACAAUAG
10439





2235
ACUUUUGG G CGAGAAAC
1778
GUUUCUCG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CCAAAAGU
10440





2260
AAUAUUUG G UGUCUUUU
1779
AAAAGACA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CAAAUAUU
10441





2272
CUUUUGGA G UGUGGAUU
1780
AAUCCACA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UCCAAAAG
10442





2360
ACGAAGAG G CAGGUCCC
1781
GGGACCUG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CUCUUCGU
10443





2364
AGAGGCAG G UCCCCUAG
1782
CUAGGGGA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CUGCCUCU
10444





2403
AGACGAAG G UCUCAAUC
1783
GAUUGAGA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CUUCGUCU
10445





2417
AUCGCCGC G UCGCAGAA
1784
UUCUGCGA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG GCGGCGAU
10446





2454
CAAUGUUA G UAUUCCUU
1785
AAGGAAUA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UAACAUUG
10447





2474
CACAUAAG G UGGGAAAC
1786
GUUUCCCA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CUUAUGUG
10448





2491
UUUACGGG G CUUUAUUC
1787
GAAUAAAG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CCCGUAAA
10449





2507
CUUCUACG G UACCUUGC
1788
GCAAGGUA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CGUAGAAG
10450





2530
CCUAAAUG G CAAACUCC
1789
GGAGUUUG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CAUUUAGG
10451





2587
AGAUGUAA G CAAUUUGU
1790
ACAAAUUG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UUACAUCU
10452





2599
UUUGUGGG G CCCCUUAC
1791
GUAAGGGG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CCCACAAA
10453





2609
CCCUUACA G UAAAUGAA
1792
UUCAUUUA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UGUAAGGG
10454





2650
CCUGCUAG G UUUUAUCC
1793
GGAUAAAA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CUAGCAGG
10455





2701
AUCAAACC G UAUUAUCC
1794
GGAUAAUA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG GGUUUGAU
10456





2713
UAUCCAGA G UAUGUAGU
1795
ACUACAUA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UCUGGAUA
10457





2720
AGUAUGUA G UUAAUCAU
1796
AUGAUUAA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UACAUACU
10458





2768
UUUGGAAG G CGGGGAUC
1797
GAUCCCCG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CUUCCAAA
10459





2791
AAAAGAGA G UCCACACG
1798
CGUGUGGA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UCUCUUUU
10460





2799
GUCCACAC G UAGCGCCU
1799
AGGCGCUA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG GUGUGGAC
10461





2802
CACACGUA G CGCCUCAU
1800
AUGAGGCG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UACGUGUG
10462





2818
UUUUGCGG G UCACCAUA
1801
UAUGGUGA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CCGCAAAA
10463





2848
GAUCUACA G CAUGGGAG
1802
CUCCCAUG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UGUAGAUC
10464





2857
CAUGGGAG G UUGGUCUU
1803
AAGACCAA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CUCCCAUG
10465





2861
GGAGGUUG G UCUUCCAA
1804
UUGGAAGA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CAACCUCC
10466





2881
UCGAAAAG G CAUGGGGA
1805
UCCCCAUG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CUUUUCGA
10467





2936
GAUCAUCA G UUGGACCC
1806
GGGUCCAA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UGAUGAUC
10468





2955
CAUUCAAA G CCAACUCA
1807
UGAGUUGG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UUUGAAUG
10469





2964
CCAACUCA G UAAAUCCA
1808
UGGAUUUA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UGAGUUGG
10470





3005
GACAACUG G CCGGACGC
1809
GCGUCCGG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CAGUUGUC
10471





3021
CCAACAAG G UGGGAGUG
1810
CACUCCCA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CUUGUUGG
10472





3027
AGGUGGGA G UGGGAGCA
1811
UGCUCCCA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UCCCACCU
10473





3033
GAGUGGGA G CAUUCGGG
1812
CCCGAAUG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UCCCACUC
10474





3041
GCAUUCGG G CCAGGGUU
1813
AACCCUGG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CCGAAUGC
10475





3047
GGGCCAGG G UUCACCCC
1814
GGGGUGAA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CCUGGCCC
10476





3077
CUGUUGGG G UGGAGCCC
1815
GGGCUCCA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CCCAACAG
10477





3082
GGGGUGGA G CCCUCACG
1816
CGUGAGGG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UCCACCCC
10478





3097
CGCUCAGG G CCUACUCA
1817
UGAGUAGG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CCUGAGCG
10479





3117
CUGUGCCA G CAGCUCCU
1818
AGGAGCUG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UGGCACAG
10480





3120
UGCCAGCA G CUCCUCCU
1819
AGGAGGAG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UGCUGGCA
10481





3146
ACCAAUCG G CAGUCAGG
1820
CCUGACUG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CGAUUGGU
10482





3149
AAUCGGCA G UCAGGAAG
1821
CUUCCUGA GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UGCCGAUU
10483





3158
UCAGGAAG G CAGCCUAC
1822
GUAGGCUG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CUUCCUGA
10484





3161
GGAAGGCA G CCUACUCC
1823
GGAGUAGG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UGCCUUCC
10485





3204
AUCCUCAG G CCAUGCAG
1824
CUGCAUGG GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CUGAGGAU
10486





31
CUCUUCAA G AUCCCAGA
1999
UCUGGGAU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UUGAAGAG
10487





38
AGAUCCCA G AGUCAGGG
2000
CCCUGACU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UGGGAUCU
10488





44
CAGAGUCA G GGCCCUGU
2001
ACAGGGCC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UGACUCUG
10489





45
AGAGUCAG G GCCCUGUA
2002
UACAGGGC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CUGACUCU
10490





64
UUCCUGCU G GUGGCUCC
2003
GGAGCCAC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AGCAGGAA
10491





67
CUGCUGGU G GCUCCAGU
2004
ACUGGAGC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG ACCAGCAG
10492





79
CCAGUUCA G GAACAGUG
2005
CACUGUUC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UGAACUGG
10493





80
CAGUUCAG G AACAGUGA
2006
UCACUGUU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CUGAACUG
10494





99
CCUGCUCA G AAUACUGU
2007
ACAGUAUU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UGAGCAGG
10495





135
UUAUCGAA G ACUGGGGA
2008
UCCCCAGU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UUCGAUAA
10496





139
CGAAGACU G GGGACCCU
2009
AGGGUCCC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AGUCUUCG
10497





140
GAAGACUG G GGACCCUG
2010
CAGGGUCC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CAGUCUUC
10498





141
AAGACUGG G GACCCUGU
2011
ACAGGGUC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CCAGUCUU
10499





142
AGACUGGG G ACCCUGUA
2012
UACAGGGU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CCCAGUCU
10500





159
CCGAACAU G GAGAACAU
2013
AUGUUCUC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AUGUUCGG
10501





160
CGAACAUG G AGAACAUC
2014
GAUGUUCU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CAUGUUCG
10502





162
AACAUGGA G AACAUCGC
2015
GCGAUGUU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UCCAUGUU
10503





175
UCGCAUCA G GACUCCUA
2016
UAGGAGUC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UGAUGCGA
10504





176
CGCAUCAG G ACUCCUAG
2017
CUAGGAGU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CUGAUGCG
10505





184
GACUCCUA G GACCCCUG
2018
CAGGGGUC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UAGGAGUC
10506





185
ACUCCUAG G ACCCCUGC
2019
GCAGGGGU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CUAGGAGU
10507





204
GUGUUACA G GCGGGGUU
2020
AACCCCGC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UGUAACAC
10508





207
UUACAGGC G GGGUUUUU
2021
AAAAACCC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG GCCUGUAA
10509





208
UACAGGCG G GGUUUUUC
2022
GAAAAACC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CGCCUGUA
10510





209
ACAGGCGG G GUUUUUCU
2023
AGAAAAAC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CCGCCUGU
10511





246
AUACCACA G AGUCUAGA
2024
UCUAGACU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UGUGGUAU
10512





253
AGAGUCUA G ACUCGUGG
2025
CCACGAGU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UAGACUCU
10513





260
AGACUCGU G GUGGACUU
2026
AAGUCCAC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG ACGAGUCU
10514





263
CUCGUGGU G GACUUCUC
2027
GAGAAGUC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG ACCACGAG
10515





264
UCGUGGUG G ACUUCUCU
2028
AGAGAAGU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CACCACGA
10516





283
AUUUUCUA G GGGGAACA
2029
UGUUCCCC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UAGAAAAU
10517





284
UUUUCUAG G GGGAACAC
2030
GUGUUCCC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CUAGAAAA
10518





285
UUUCUAGG G GGAACACC
2031
GGUCUUCC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CCUAGAAA
10519





286
UUCUAGGG G GAACACCC
2032
GGGUGUUC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CCCUAGAA
10520





287
UCUAGGGG G AACACCCG
2033
CGGGUGUU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CCCCUAGA
10521





304
UGUGUCUU G GCCAAAAU
2034
AUUUUGGC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AAGACACA
10522





367
UUUGUCCU G GUUAUCGC
2035
GCGAUAAC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AGGACAAA
10523





377
UUAUCGCU G GAUGUGUC
2036
GACACAUC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AGCGAUAA
10524





378
UAUCGCUG G AUGUGUCU
2037
AGACACAU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CAGCGAUA
10525





389
CUGUCUGC G GCGUUUUA
2038
UAAAACGC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG GCAGACAC
10526





441
UUCUUGUU G GUUCUUCU
2039
AGAAGAAC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AACAAGAA
10527





450
GUUCUUCU G GACUAUCA
2040
UGAUAGUC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AGAAGAAC
10528





451
UUCUUCUG G ACUAUCAA
2041
UUGAUAGU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CAGAAGAA
10529





460
ACUAUCAA G GUAUGUUG
2042
CAACAUAC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UUGAUAGU
10530





490
UAAUUCCA G GAUCAUCA
2043
UGAUGAUC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UGGAAUUA
10531





491
AAUUCCAG G AUCAUCAA
2044
UUGAUGAU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CUGGAAUU
10532





511
CCAGCACC G GACCAUGC
2045
GGAUGGUC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG GGUGCUGG
10533





512
CAGCACCG G ACCAUGCA
2046
UGCAUGGU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CGGUGCUG
10534





544
CUGCUCAA G GAACCUCU
2047
AGAGGUUC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UUGAGCAG
10535





545
UGCUCAAG G AACCUCUA
2048
UAGAGGUU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CUUGAGCA
10536





585
AAACCUAC G GACGGAAA
2049
UUUCCGUC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG GUAGGUUU
10537





586
AACCUACG G ACGGAAAC
2050
GUUUCCGU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CGUAGGUU
10538





589
CUACGGAC G GAAACUGC
2051
GCAGUUUC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG GUCCGUAG
10539





590
UACGGACG G AAACUGCA
2052
UGCAGUUU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CGUCCGUA
10540





623
AUCAUCUU G GGCUUUCG
2053
CGAAAGCC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AAGAUGAU
10541





624
UCAUCUUG G GCUUUCGC
2054
GCGAAAGC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CAAGAUGA
10542





644
AUACCUAU G GGAGUGGG
2055
CCCACUCC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AUAGGUAU
10543





645
UACCUAUG G GAGUGGGC
2056
GCCCACUC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CAUAGGUA
10544





646
ACCUAUGG G AGUGGGCC
2057
GGCCCACU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CCAUAGGU
10545





650
AUGGGAGU G GGCCUCAG
2058
CUGAGGCC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG ACUCCCAU
10546





651
UGGGAGUG G GCCUCAGU
2059
ACUGAGGC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CACUCCCA
10547





671
UUUCUCUU G GCUCAGUU
2060
AACUGAGC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AAGAGAAA
10548





701
UGUUCAGU G GUUCGUAG
2061
CUACGAAC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG ACUGAACA
10549





709
GGUUCGUA G GGCUUUCC
2062
GGAAAGCC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UACGAACC
10550





710
GUUCGUAG G GCUUUCCC
2063
GGGAAAGC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CUACGAAC
10551





728
CACUGUCU G GCUUUCAG
2064
CUGAAAGC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AGACAGUG
10552





743
AGUUAUAU G GAUGAUGU
2065
ACAUCAUC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AUAUAACU
10553





744
GUUAUAUG G AUGAUGUG
2066
CACAUCAU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CAUAUAAC
10554





752
GAUGAUGU G GUUUUGGG
2067
CCCAAAAC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG ACAUCAUC
10555





758
GUGGUUUU G GGGGCCAA
2068
UUGGCCCC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AAAACCAC
10556





759
UGGUUUUG G GGGCCAAG
2069
CUUGGCCC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CAAAACCA
10557





760
GUUUUUGG G GGCCAAGU
2070
ACUUGGCC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CCAAAACC
10558





761
GUUUUGGG G GCCAAGUC
2071
GACUUGGC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CCCAAAAC
10559





824
UUGUCUUU G GGUAUACA
2072
UGUAUACC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AAAGACAA
10560





825
UGUCUUUG G GUAUACAU
2073
AUGUAUAC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CAAAGACA
10561





856
AACAAAAA G AUGGGGAU
2074
AUCCCCAU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UUUUUGUU
10562





859
AAAAAGAU G GGGAUAUU
2075
AAUAUCCC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AUCUUUUU
10563





860
AAAAGAUG G GGAUAUUC
2076
GAAUAUCC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CAUCUUUU
10564





861
AAAGAUGG G GAUAUUCC
2077
GGAAUAUC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CCAUCUUU
10565





862
AAGAUGGG G AUAUUCCC
2078
GGGAAUAU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CCCAUCUU
10566





881
AACUUCAU G GGAUAUGU
2079
ACAUAUCC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AUGAAGUU
10567





882
ACUUCAUG G GAUAUGUA
2080
UACAUAUC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CAUGAAGU
10568





883
CUUCAUGG G AUAUGUAA
2081
UUACAUAU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CCAUGAAG
10569





894
AUGUAAUU G GGAGUUGG
2082
CCAACUCC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AAUUACAU
10570





895
UGUAAUUG G GAGUUGGG
2083
CCCAACUC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CAAUUACA
10571





896
GUAAUUGG G AGUUGGGG
2084
CCCCAACU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CCAAUUAC
10572





901
UGGGAGUU G GGGCACAU
2085
AUGUGCCC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AACUCCCA
10573





902
GGGAGUUG G GGCACAUU
2086
AAUGUGCC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CAACUCCC
10574





903
GGAGUUGG G GCACAUUG
2087
CAAUGUGC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CCAACUCC
10575





917
UUGCCACA G GAACAUAU
2088
AUAUGUUC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UGUGGCAA
10576





918
UGCCACAG G AACAUAUU
2089
AAUAUGUU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CUGUGGCA
10577





952
GUGUUUUA G GAAACUUC
2090
GAAGUUUC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UAAAACAC
10578





953
UGUUUUAG G AAACUUCC
2091
GGAAGUUU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CUAAAACA
10579





970
UGUAAACA G GCCUAUUG
2092
CAAUAGGC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UGUUUACA
10580





982
UAUUGAUU G GAAAGUAU
2093
AUACUUUC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AAUCAAUA
10581





983
AUUGAUUG G AAAGUAUG
2094
CAUACUUU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CAAUCAAU
10582





1004
CGAAUUGU G GGUCUUUU
2095
AAAAGACC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG ACAAUUCG
10583





1005
GAAUUGUG G GUCUUUUG
2096
CAAAAGAC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CACAAUUC
10584





1013
GGUCUUUU G GGGUUUGC
2097
GCAAACCC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AAAAGACC
10585





1014
GUCUUUUG G GGUUUGCC
2098
GGCAAACC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CAAAAGAC
10586





1015
UCUUUUGG G GUUUGCCG
2099
CGGCAAAC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CCAAAAGA
10587





1041
CGCAAUGU G GAUAUUCU
2100
AGAAUAUC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG ACAUUGCG
10588





1042
GCAAUGUG G AUAUUCUG
2101
CAGAAUAU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CACAUUGC
10589





1088
GCAAAACA G GCUUUUAC
2102
GUAAAAGC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UGUUUUGC
10590





1115
ACUUACAA G GCCUUUCU
2103
AGAAAGGC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UUGUAAGU
10591





1159
CGUUGCUC G GCAACGGC
2104
GCCGUUGC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG GAGCAACG
10592





1165
UCGGCAAC G GCCUGGUC
2105
GACCAGGC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG GUUGCCGA
10593





1170
AACGGCCU G GUCUAUGC
2106
GCAUAGAC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AGGCCGUU
10594





1206
CCCCCACU G GUUGGGGC
2107
GCCCCAAC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AGUGGGGG
10595





1210
CACUGGUU G GGGCUUGG
2108
CCAAGCCC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AACCAGUG
10596





1211
ACUGGUUG G GGCUUGGC
2109
GCCAAGCC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CAACCAGU
10597





1212
CUGGUUGG G GCUUGGCC
2110
GGCCAAGC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CCAACCAG
10598





1217
UGGGGCUU G GCCAUAGG
2111
CCUAUGGC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AAGCCCCA
10599





1224
UGGCCAUA G GCCAUCAG
2112
CUGAUGGC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UAUGGCCA
10600





1242
GCAUGCGU G GAACCUUU
2113
AAAGGUUC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG ACGCAUGC
10601





1243
CAUGCGUG G AACCUUUG
2114
CAAAGGUU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CACGCAUG
10602





1277
CAUACCGC G GAACUCCU
2115
AGGAGUUC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG GCGGUAUG
10603





1278
AUACCGCG G AACUCCUA
2116
UAGGAGUU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CGCGGUAU
10604





1309
UCGCAGCA G GUCUGGGG
2117
CCCCAGAC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UGCUGCGA
10605





1314
GCAGGUCU G GGGCAAAA
2118
UUUUGCCC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AGACCUGC
10606





1315
CAGGUCUG G GGCAAAAC
2119
GUUUUGCC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CAGACCUG
10607





1316
AGGUCUGG G GCAAAACU
2120
AGUUUUGC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CCAGACCU
10608





1329
AACUCAUC G GGACUGAC
2121
GUCAGUCC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG GAUGAGUU
10609





1330
ACUCAUCG G GACUGACA
2122
UGUCAGUC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CGAUGAGU
10610





1331
CUCAUCGG G ACUGACAA
2123
UUGUCAGU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CCGAUGAG
10611





1378
AUUUCCAU G GCUGCUAG
2124
CUAGCAGC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AUGGAAAU
10612





1386
GGCUGCUA G GCUGUGCU
2125
AGCACAGC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UAGCAGCC
10613





1402
UGCCAACU G GAUCCUAC
2126
GUAGGAUC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AGUUGGCA
10614





1403
GCCAACUG G AUCCUACG
2127
CGUAGGAU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CAGUUGGC
10615





1413
UCCUACGC G GGACGUCC
2128
GGACGUCC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG GCGUAGGA
10616





1414
CCUACGCG G GACGUCCU
2129
AGGACGUC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CGCGUAGG
10617





1415
CUACGCGG G ACGUCCUU
2130
AAGGACGU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CCGCGUAG
10618





1439
GUCCCGUC G GCGCUGAA
2131
UUCAGCGC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG GACGGGAC
10619





1454
AAUCCCGC G GACGACCC
2132
GGGUCGUC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG GCGGGAUU
10620





1455
AUCCCGCG G ACGACCCC
2133
GGGGUCGU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CGCGGGAU
10621





1468
CCCCUCCC G GGGCCGCU
2134
AGCGGCCC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG GGGAGGGG
10622





1469
CCCUCCCG G GGCCGCUU
2135
AAGCGGCC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CGGGAGGG
10623





1470
CCUCCCGG G GCCGCUUG
2136
CAAGCGGC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CCGGGAGG
10624





1478
GGCCGCUU G GGGCUCUA
2137
UAGAGCCC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AAGCGGCC
10625





1479
GCCGCUUG G GGCUCUAC
2138
GUAGAGCC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CAAGCGGC
10626





1480
CCGCUUGG G GCUCUACC
2139
GGUAGAGC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CCAAGCGG
10627





1523
CCGUCCAC G GGGCGCAC
2140
GUGCGCCC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG GUGGACGG
10628





1524
CGUCCACG G GGCGCACC
2141
GGUGCGCC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CGUGGACG
10629





1525
GUCCACGG G GCGCACCU
2142
AGGUGCGC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CCGUGGAC
10630





1544
CUUUACGC G GACUCCCC
2143
GGGGAGUC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG GCGUAAAG
10631





1545
UUUACGCG G ACUCCCCG
2144
CGGGGAGU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CGCGUAAA
10632





1574
CAUCUGCC G GACCGUGU
2145
ACACGGUC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG GGCAGAUG
10633





1575
AUCUGCCG G ACCGUGUG
2146
CACACGGU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CGGCAGAU
10634





1612
CGUCGCAU G GAGACCAC
2147
GUGGUCUC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AUGCGACG
10635





1613
GUCGCAUG G AGACCACC
2148
GGUGGUCU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CAUGCGAC
10636





1615
CGCAUGGA G ACCACCGU
2149
ACGGUGGU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UCCAUGCG
10637





1635
CGCCCACA G GAACCUGC
2150
GCAGGUUC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UGUGGGCG
10638





1636
GCCCACAG G AACCUGCC
2151
GGCAGGUU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CUGUGGGC
10639





1648
CUGCCCAA G GUCUUGCA
2152
UGCAAGAC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UUGGGCAG
10640





1660
UUGCAUAA G AGGACUCU
2153
AGAGUCCU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UUAUGCAA
10641





1662
GCAUAAGA G GACUCUUG
2154
CAAGAGUC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UCUUAUGC
10642





1663
CAUAAGAG G ACUCUUGG
2155
CCAAGAGU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CUCUUAUG
10643





1670
GGACUCUU G GACUUUCA
2156
UGAAAGUC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AAGAGUCC
10644





1671
GACUCUUG G ACUUUCAG
2157
CUGAAAGU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CAAGAGUC
10645





1702
GACCUUGA G GCAUACUU
2158
AAGUAUGC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UCAAGGUC
10646





1715
ACUUCAAA G ACUGUGUG
2159
CACACAGU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UUUGAAGU
10647





1734
UAAUGAGU G GGAGGAGU
2160
ACUCCUCC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG ACUCAUUA
10648





1735
AAUGAGUG G GAGGAGUU
2161
AACUCCUC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CACUCAUU
10649





1736
AUGAGUGG G AGGAGUUG
2162
CAACUCCU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CCACUCAU
10650





1738
GAGUGGGA G GAGUUGGG
2163
CCCAACUC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UCCCACUC
10651





1739
AGUGGGAG G AGUUGGGG
2164
CCCCAACU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CUCCCACU
10652





1744
GAGGAGUU G GGGGAGGA
2165
UCCUCCCC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AACUCCUC
10653





1745
AGGAGUUG G GGGAGGAG
2166
CUCCUCCC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CAACUCCU
10654





1746
GGAGUUGG G GGAGGAGG
2167
CCUCCUCC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CCAACUCC
10655





1747
GAGUUGGG G GAGGAGGU
2168
ACCUCCUC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CCCAACUC
10656





1748
AGUUGGGG G AGGAGGUU
2169
AACCUCCU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CCCCAACU
10657





1750
UUGGGGGA G GAGGUUAG
2170
CUAACCUC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UCCCCCAA
10658





1751
UGGGGGAG G AGGUUAGG
2171
CCUAACCU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CUCCCCCA
10659





1753
GGGGAGGA G GUUAGGUU
2172
AACCUAAC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UCCUCCCC
10660





1758
GGAGGUUA G GUUAAAGG
2173
CCUUUAAC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UAACCUCC
10661





1765
AGGUUAAA G GUCUUUGU
2174
ACAAAGAC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UUUAACCU
10662





1778
UUGUACUA G GAGGCUGU
2175
ACAGCCUC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UAGUACAA
10663





1779
UGUACUAG G AGGCUGUA
2176
UACAGCCU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CUAGUACA
10664





1781
UACUAGGA G GCUGUAGG
2177
CCUACAGC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UCCUAGUA
10665





1788
AGGCUGUA G GCAUAAAU
2178
AUUUAUGC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UACAGCCU
10666





1798
CAUAAAUU G GUGUGUUC
2179
GAACACAC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AAUUUAUG
10667





1888
UGUGCCUU G GGUGGCUU
2180
AAGCCACC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AAGGCACA
10668





1889
GUGCCUUG G GUGGCUUU
2181
AAAGCCAC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CAAGGCAC
10669





1892
CCUUGGGU G GCUUUGGG
2182
CCCAAAGC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG ACCCAAGG
10670





1898
GUGGCUUU G GGGCAUGG
2183
CCAUGCCC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AAAGCCAC
10671





1899
UGGCUUUG G GGCAUGGA
2184
UCCAUGCC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CAAAGCCA
10672





1900
GGCUUUGG G GCAUGGAC
2185
GUCCAUGC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CCAAAGCC
10673





1905
UGGGGCAU G GACAUUGA
2186
UCAAUGUC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AUGCCCCA
10674





1906
GGGGCAUG G ACAUUGAC
2187
GUCAAUGU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CAUGCCCC
10675





1924
CGUAUAAA G AAUUUGGA
2188
UCCAAAUU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UUUAUACG
10676





1930
AAGAAUUU G GAGCUUCU
2189
AGAAGCUC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AAAUUCUU
10677





1931
AGAAUUUG G AGCUUCUG
2190
CAGAAGCU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CAAAUUCU
10678





1941
GCUUCUGU G GAGUUACU
2191
AGUAACUC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG ACAGAAGC
10679





1942
CUUCUGUG G AGUUACUC
2192
GAGUAACU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CACAGAAG
10680





1987
CUAUUCGA G AUCUCCUC
2193
GAGGAGAU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UCGAAUAG
10681





2018
UCUGUAUC G GGGGGCCU
2194
AGGCCCCC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG GAUACAGA
10682





2019
CUGUAUCG G GGGCCCUU
2195
AAGGCCCC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CGAUACAG
10683





2020
UGUAUCGG G GGGCCUUA
2196
UAAGGCCC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CCGAUACA
10684





2021
GUAUCGGG G GGCCUUAG
2197
CUAAGGCC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CCCGAUAC
10685





2022
UAUCGGGG G GCCUUAGA
2198
UCUAAGGC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CCCCGAUA
10686





2029
GGGCCUUA G AGUCUCCC
2199
CGGAGACU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UAAGGCCC
10687





2037
GAGUCUCC G GAACAUUG
2200
CAAUGUUC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG GGAGACUC
10688





2038
AGUCUCCG G AACAUUGU
2201
ACAAUGUU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CGGAGACU
10689





2061
CACCAUAC G GCACUCAG
2202
CUGAGUGC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG GUAUGGUG
10690





2069
GGCACUCA G GCAAGCUA
2203
UAGCUUGC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UGAGUGCC
10691





2087
UCUGUGUU G GGGUGAGU
2204
ACUCACCC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AACACAGA
10692





2088
CUGUGUUG G GGUGAGUU
2205
AACUCACC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CAACACAG
10693





2089
UGUGUUGG G GUGAGUUG
2206
CAACUCAC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CCAACACA
10694





2114
AGCCACCU G GGUGGGAA
2207
UUCCCACC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AGGUGGCU
10695





2115
GCCACCUG G GUGGGAAG
2208
CUUCCCAC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CAGGUGGC
10696





2118
ACCUGGGU G GGAAGUAA
2209
UUACUUCC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG ACCCAGGU
10697





2119
CCUGGGUG G GAAGUAAU
2210
AUUACUUC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CACCCAGG
10698





2120
CUGGGUGG G AAGUAAUU
2211
AAUUACUU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CCACCCAG
10699





2130
AGUAAUUU G GAAGAUCC
2212
GGAUCUUC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AAAUUACU
10700





2131
GUAAUUUG G AAGAUCCA
2213
UGGAUCUU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CAAAUUAC
10701





2134
AUUUGGAA G AUCCAGCA
2214
UGCUGGAU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UUCCAAAU
10702





2147
AGCAUCCA G GGAAUUAG
2215
CUAAUUCC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UGGAUGCU
10703





2148
GCAUCCAG G GAAUUAGU
2216
ACUAAUUC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CUGGAUGC
10704





2149
CAUCCAGG G AAUUAGUA
2217
UACUAAUU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CCUGGAUG
10705





2181
GUUAAUAU G GGCCUAAA
2218
UUUAGGCC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AUAUUAAC
10706





2182
UUAAUAUG G GCCUAAAA
2219
UUUUAGGC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CAUAUUAA
10707





2195
AAAAAUCA G ACAACUAU
2220
AUAGUUGU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UGAUUUUU
10708





2207
ACUAUUGU G GUUUCACA
2221
UGUGAAAC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG ACAAUAGU
10709





2233
UUACUUUU G GGCGAGAA
2222
UUCUCGCC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AAAAGUAA
10710





2234
UACUUUUG G GCGAGAAA
2223
UUUCUCGC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CAAAAGUA
10711





2239
UUGGGCGA G AAACUGUU
2224
AACAGUUU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UCGCCCAA
10712





2259
GAAUAUUU G GUGUCUUU
2225
AAAGACAC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AAAUAUUC
10713





2269
UGUCUUUU G GAGUGUGG
2226
CCACACUC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AAAAGACA
10714





2270
GUCUUUUG G AGUGUGGA
2227
UCCACACU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CAAAAGAC
10715





2276
UGGAGUGU G GAUUCGCA
2228
UGCGAAUC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG ACACUCCA
10716





2277
GGAGUGUG G AUUCGCAC
2229
GUGCGAAU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CACACUCC
10717





2300
UGCAUAUA G ACCACCAA
2230
UUGGUGGU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UAUAUGCA
10718





2334
ACACUUCC G GAAACUAC
2231
GUAGUUUC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG GGAAGUGU
10719





2335
CACUUCCG G AAACUACU
2232
AGUAGUUU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CGGAAGUG
10720





2351
UGUUGUUA G ACGAAGAG
2233
CUCUUCGU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UAACAACA
10721





2357
UAGACGAA G AGGCAGGU
2234
ACCUGCCU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UUCGUCUA
10722





2359
GACGAAGA G GCAGGUCC
2235
GGACCUGC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UCUUCGUC
10723





2363
AAGAGGCA G GUCCCCUA
2236
UAGGGGAC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UGCCUCUU
10724





2372
GUCCCCUA G AAGAAGAA
2237
UUCUUCUU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UAGGGGAC
10725





2375
CCCUAGAA G AAGAACUC
2238
GAGUUCUU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UUCUAGGG
10726





2378
UAGAAGAA G AACUCCCU
2239
AGGGAGUU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UUCUUCUA
10727





2396
GCCUCGCA G ACGAAGGU
2240
ACCUUCGU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UGCGAGGC
10728





2402
CAGACGAA G GUCUCAAU
2241
AUUGAGAC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UUCGUCUG
10729





2423
GCGUCGCA G AAGAUCUC
2242
GAGAUCUU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UGCGACGC
10730





2426
UCGCAGAA G AUCUCAAU
2243
AUUGAGAU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UUCUGCGA
10731





2438
UCAAUCUC G GGAAUCUC
2244
GAGAUUCC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG GAGAUUGA
10732





2439
CAAUCUCG G GAAUCUCA
2245
UGAGAUUC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CGAGAUUG
10733





2440
AAUCUCGG G AAUCUCAA
2246
UUGAGAUU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CCGAGAUU
10734





2463
UAUUCCUU G GACACAUA
2247
UAUGUGUC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AAGGAAUA
10735





2464
AUUCCUUG G ACACAUAA
2248
UUAUGUGU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CAAGGAAU
10736





2473
ACACAUAA G GUGGGAAA
2249
UUUCCCAC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UUAUGUGU
10737





2476
CAUAAGGU G GGAAACUU
2250
AAGUUUCC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG ACCUUAUG
10738





2477
AUAAGGUG G GAAACUUU
2251
AAAGUUUC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CACCUUAU
10739





2478
UAAGGUGG G AAACUUUA
2252
UAAAGUUU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CCACCUUA
10740





2488
AACUUUAC G GGGCUUUA
2253
UAAAGCCC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG GUAAAGUU
10741





2489
ACUUUACG G GGCUUUAU
2254
AUAAAGCC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CGUAAAGU
10742





2490
CUUUACGG G GCUUUAUU
2255
AAUAAAGC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CCGUAAAG
10743





2506
UCUUCUAC G GUACCUUG
2256
CAAGGUAC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG GUAGAAGA
10744





2529
UCCUAAAU G GCAAACUC
2257
GAGUUUGC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AUUUAGGA
10745





2563
CAUUUGCA G GAGGACAU
2258
AUGUCCUC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UGCAAAUG
10746





2564
AUUUGCAG G AGGACAUU
2259
AAUGUCCU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CUGCAAAU
10747





2566
UUGCAGGA G GACAUUGU
2260
ACAAUGUC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UCCUGCAA
10748





2567
UGCAGGAG G ACAUUGUU
2261
AACAAUGU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CUCCUGCA
10749





2580
UGUUGAUA G AUGUAAGC
2262
GCUUACAU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UAUCAACA
10750





2596
CAAUUUGU G GGGCCCCU
2263
AGGGGCCC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG ACAAAUUG
10751





2597
AAUUUGUG G GGCCCCUU
2264
AAGGGGCC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CACAAAUU
10752





2598
AUUUGUGG G GCCCCUUA
2265
UAAGGGGC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CCACAAAU
10753





2622
UGAAAACA G GAGACUUA
2266
UAAGUCUC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UGUUUUCA
10754





2623
GAAAACAG G AGACUUAA
2267
UUAAGUCU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CUGUUUUC
10755





2625
AAACAGGA G ACUUAAAU
2268
AUUUAAGU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UCCUGUUU
10756





2649
GCCUGCUA G GUUUUAUC
2269
GAUAAAAC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UAGCAGGC
10757





2684
UGCCCUUA G AUAAAGGG
2270
CCCUUUAU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UAAGGGCA
10758





2690
UAGAUAAA G GGAUCAAA
2271
UUUGAUCC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UUUAUCUA
10759





2691
AGAUAAAG G GAUCAAAC
2272
GUUUGAUC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CUUUAUCU
10760





2692
GAUAAAGG G AUCAAACC
2273
GGUUUGAU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CCUUUAUC
10761





2711
AUUAUCCA G AGUAUGUA
2274
UACAUACU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UGGAUAAU
10762





2737
UACUUCCA G ACGCGACA
2275
UGUCGCGU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UGGAAGUA
10763





2763
CACUCUUU G GAAGGCGG
2276
CCGCCUUC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AAAGAGUG
10764





2764
ACUCUUUG G AAGGCGGG
2277
CCCGCCUU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CAAAGAGU
10765





2767
CUUUGGAA G GCGGGGAU
2278
AUCCCCGC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UUCCAAAG
10766





2770
UGGAAGGC G GGGAUCUU
2279
AAGAUCCC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG GCCUUCCA
10767





2771
GGAAGGCG G GGAUCUUA
2280
UAAGAUCC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CGCCUUCC
10768





2772
GAAGGCGG G GAUCUUAU
2281
AUAAGAUC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CCGCCUUC
10769





2773
AAGGCGGG G AUCUUAUA
2282
UAUAAGAU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CCCGCCUU
10770





2787
AUAUAAAA G AGAGUCCA
2283
UGGACUCU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UUUUAUAU
10771





2789
AUAAAAGA G AGUCCACA
2284
UGUGGACU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UCUUUUAU
10772





2816
CAUUUUGC G GGUCACCA
2285
UGGUGACC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG GCAAAAUG
10773





2817
AUUUUGCG G GUCACCAU
2286
AUGGUGAC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CGCAAAAU
10774





2832
AUAUUCUU G GGAACAAG
2287
CUUGUUCC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AAGAAUAU
10775





2833
UAUUCUUG G GAACAAGA
2288
UCUUGUUC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CAAGAAUA
10776





2834
AUUCUUGG G AACAAGAU
2289
AUCUUGUU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CCAAGAAU
10777





2840
GGGAACAA G AUCUACAG
2290
CUGUAGAU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UUGUUCCC
10778





2852
UACAGCAU G GGAGGUUG
2291
CAACCUCC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AUGCUGUA
10779





2853
ACAGCAUG G GAGGUUGG
2292
CCAACCUC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CAUGCUGU
10780





2854
CAGCAUGG G AGGUUGGU
2293
ACCAACCU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CCAUGCUG
10781





2856
GCAUGGGA G GUUGGUCU
2294
AGACCAAC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UCCCAUGC
10782





2860
GGGAGGUU G GUCUUCCA
2295
UGGAAGAC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AACCUCCC
10783





2880
CUCGAAAA G GCAUGGGG
2296
CCCCAUGC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UUUUCGAG
10784





2885
AAAGGCAU G GGGACAAA
2297
UUUGUCCC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AUGCCUUU
10785





2886
AAGGCAUG G GGACAAAU
2298
AUUUGUCC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CAUGCCUU
10786





2887
AGGCAUGG G GACAAAUC
2299
GAUUUGUC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CCAUGCCU
10787





2888
GGCAUGGG G ACAAAUCU
2300
AGAUUUGU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CCCAUGCC
10788





2915
AAUCCCCU G GGAUUCUU
2301
AAGAAUCC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AGGGGAUU
10789





2916
AUCCCCUG G GAUUCUUC
2302
GAAGAAUC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CAGGGGAU
10790





2917
UCCCCUGG G AUUCUUCC
2303
GGAAGAAU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CCAGGGGA
10791





2939
CAUCAGUU G GACCCUGC
2304
GCAGGGUC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AACUGAUG
10792





2940
AUCAGUUG G ACCCUGCA
2305
UGCAGGGU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CAACUGAU
10793





2973
UAAAUCCA G AUUGGGAC
2306
GUCCCAAU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UGGAUUUA
10794





2977
UCCAGAUU G GGACCUCA
2307
UGAGGUCC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AAUCUGGA
10795





2978
CCAGAUUG G GACCUCAA
2308
UUGAGGUC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CAAUCUGG
10796





2979
CAGAUUGG G ACCUCAAC
2309
GUUGAGGU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CCAAUCUG
10797





2996
CCGCACAA G GACAACUG
2310
CAGUUGUC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UUGUGCGG
10798





2997
CGCACAAG G ACAACUGG
2311
CCAGUUGU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CUUGUGCG
10799





3004
GGACAACU G GCCGGACG
2312
CGUCCGGC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AGUUGUCC
10800





3008
AACUGGCC G GACGCCAA
2313
UUGGCGUC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG GGCCAGUU
10801





3009
ACUGGCCG G ACGCCAAC
2314
GUUGGCGU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CGGCCAGU
10802





3020
GCCAACAA G GUGGGAGU
2315
ACUCCCAC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UUGUUGGC
10803





3023
AACAAGGU G GGAGUGGG
2316
CCCACUCC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG ACCUUGUU
10804





3024
ACAAGGUG G GAGUGGGA
2317
UCCCACUC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CACCUUGU
10805





3025
CAAGGUGG G AGUGGGAG
2318
CUCCCACU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CCACCUUG
10806





3029
GUGGGAGU G GGAGCAUU
2319
AAUGCUCC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG ACUCCCAC
10807





3030
UGGGAGUG G GAGCAUUC
2320
GAAUGCUC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CACUCCCA
10808





3031
GGGAGUGG G AGCAUUCG
2321
CGAAUGCU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CCACUCCC
10809





3039
GAGCAUUC G GGCCAGGG
2322
CCCUGGCC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG GAAUGCUC
10810





3040
AGCAUUCG G GCCAGGGU
2323
ACCCUGGC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CGAAUGCU
10811





3045
UCGGGCCA G GGUUCACC
2324
GGUGAACC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UGGCCCGA
10812





3046
CGGGCCAG G GUUCACCC
2325
GGGUGAAC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CUGGCCCG
10813





3063
CUCCCCAU G GGGGACUG
2326
CAGUCCCC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AUGGGGAG
10814





3064
UCCCCAUG G GGGACUGU
2327
ACAGUCCC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CAUGGGGA
10815





3065
CCCCAUGG G GGACUGUU
2328
AACAGUCC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CCAUGGGG
10816





3066
CCCAUGGG G GACUGUUG
2329
CAACAGUC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CCCAUGGG
10817





3067
CCAUGGGG G ACUGUUGG
2330
CCAACAGU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CCCCAUGG
10818





3074
GGACUGUU G GGGUGGAG
2331
CUCCACCC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG AACAGUCC
10819





3075
GACUGUUG G GGUGGAGC
2332
GCUCCACC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CAACAGUC
10820





3076
ACUGUUGG G GUGGAGCC
2333
GGCUCCAC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CCAACAGU
10821





3079
GUUGGGGU G GAGCCCUC
2334
GAGGGCUC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG ACCCCAAC
10822





3080
UUGGGGUG G AGCCCUCA
2335
UGAGGGCU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CACCCCAA
10823





3095
CACGCUCA G GGCCUACU
2336
AGUAGGCC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UGAGCGUG
10824





3096
ACGCUCAG G GCCUACUC
2337
GAGUAGGC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CUGAGCGU
10825





3145
CACCAAUC G GCAGUCAG
2338
CUGACUGC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG GAUUGGUG
10826





3153
GGCAGUCA G GAAGGCAG
2339
CUGCCUUC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UGACUGCC
10827





3154
GCAGUCAG G AAGGCAGC
2340
GCUGCCUU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CUGACUGC
10828





3157
GUCAGGAA G GCAGCCUA
2341
UAGGCUGC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UUCCUGAC
10829





3187
ACCUCUAA G GGACACUC
2342
GAGUGUCC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UUAGAGGU
10830





3188
CCUCUAAG G GACACUCA
2343
UGAGUGUC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CUUAGAGG
10831





3189
CUCUAAGG G ACACUCAU
2344
AUGAGUGU GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG CCUUAGAG
10832





3203
CAUCCUCA G GCCAUGCA
2345
UGCAUGGC GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG UGAGGAUG
10833






Input Sequence = AF100308.




Cut Site = YG/M or UG/U.




Stem Length = 8.




Core Sequence = GGAGGAAACUCC CU UCAAGGACAUCGUCCGGG




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








[0559]

11






TABLE XI










Human HBV Enzymatic Nucleic Acid and Target Sequence

















Seq



Seq



Pos
SUBSTRATE
ID
RPI#
Ribozyme Alias
ENZYMATIC NUCLEIC ACID
ID

















313
CCAAAAU U CGCAGUC
2346
18157
HBV-313 Rz-7 RNA
GACUGCG CUGAUGAGGCCGUUAGGCCGAA AUUUUGG B
10834






327
CCCAAAU C UCCAGUC
2347
18158
HBV-327 Rz-7 RNA
GACUGGA CUGAUGAGGCCGUUAGGCCGAA AUUUGGG B
10835





334
CUCCAGU C ACUCACC
2348
18159
HBV-334 Rz-7 RNA
GGUGAGU CUGAUGAGGCCGUUAGGCCGAA ACUGGAG B
10836





408
UCUUCCU C UGCAUCC
2349
18160
HBV-408 Rz-7 RNA
GGAUGCA CUGAUGAGGCCGUUAGGCCGAA AGGAAGA B
10837





557
UCUAUGU U UCCCUCA
2350
18161
HBV-557 Rz-7 RNA
UGAGGGA CUGAUGAGGCCGUUAGGCCGAA ACAUAGA B
10838





1255
UUUGUGU C UCCUCUG
2351
18162
HBV-1255 Rz-7 RNA
CAGAGGA CUGAUGAGGCCGUUAGGCCGAA ACACAAA B
10839





1538
CCUCUCU U UACGCGG
2352
18163
HBV-1538 Rz-7 RNA
CCGCGUA CUGAUGAGGCCGUUAGGCCGAA AGAGAGG B
10840





1756
AGGAGGU U AGGUUAA
2353
18164
HBV-1756 Rz-7 RNA
UUAACCU CUGAUGAGGCCGUUAGGCCGAA ACCUCCU B
10841





1861
AUGUCCU A CUGUUCA
2354
18165
HBV-1861 Rz-7 RNA
UGAACAG CUGAUGAGGCCGUUAGGCCGAA AGGACAU B
10842





2504
UUCUUCU A CGGUACC
2355
18166
HBV-2504 Rz-7 RNA
GGUACCG CUGAUGAGGCCGUUAGGCCGAA AGAAGAA B
10843





10
CUCCACC A CUUUCCA
2356
18197
HBV-10 CHz-7 RNA
UGGAAAG CUGAUGAGGCCGUUAGGCCGAA GGUGGAG B
10844





335
UCCAGUC A CUCACCA
2357
18198
HBV-335 CHz-7 RNA
UGGUGAG CUGAUGAGGCCGUUAGGCCGAA GACUGGA B
10845





1258
GUGUCUC C UCUGCCG
2358
18199
HBV-1258 CHz-7 RNA
CGGCAGA CUGAUGAGGCCGUUAGGCCGAA GAGACAC B
10846





2307
GACCACC A AAUGCCC
2359
18200
HBV-2307 CHz-7 RNA
GGGCAUU CUGAUGAGGCCGUUAGGCCGAA GGUGGUC B
10847





347
UCACCAACCU G UUGUC
2360
18216
HBV-347 GCl.Rz-5/10 RNA
GACAA UGAUGGCAUGCACUAUGCGCG AGGUUGGUGA B
10848





350
CCAACCUGUU G UCCUC
2361
18217
HBV-350 GCl.Rz-5/10 RNA
GAGGA UGAUGGCAUGCACUAUGCGCG AACAGGUUGG B
10849





1508
UCCGCCUAUU G UACCG
2362
18218
HBV-1508 GCl.Rz-5/10 RNA
CGGUA UGAUGGCAUGCACUAUGCGCG AAUAGGCGGA B
10850





234
AAUCCU C ACAAUA
2363
18334
HBV-234 Rz-6 allyl stab1
usasususgu cUGAuGaggccguuaggccGaa Aggauu B
10851





252
GAGUCU A GACUCG
2364
18335
HBV-252 Rz-6 allyl stab1
csgsasgsuc cUGAuGaggccguuaggccGaa Agacuc B
10852





268
UGGACU U CUCUCA
2365
18337
HBV-268 Rz-6 allyl stab1
usgsasgsag cUGAuGaggccguuaggccGaa Agucca B
10853





280
AAUUUU C UAGGGG
2366
18345
HBV-280 Rz-6 allyl stab1
cscscscsua cUGAuGaggccguuaggccGaa Aaaauu B
10854





313
CAAAAU U CGCAGU
2367
18346
HBV-313 Rz-6 allyl stab1
ascsusgscg cUGAuGaggccguuaggccGaa Auuuug B
10855





395
GGCGUU U UAUCAU
2368
18350
HBV-395 Rz-6 allyl stab1
asusgsasua cUGAuGaggccguuaggccGaa Aacgcc B
10856





402
UAUCAU C UUCCUC
2369
18351
HBV-402 Rz-6 allyl stab1
gsasgsgsaa cUGAuGaggccguuaggccGaa Augaua B
10857





607
UGUAUU C CCAUCC
2370
18355
HBV-607 Rz-6 allyl stab1
gsgsasusgg cUGAuGaggccguuaggccGaa Aauaca B
10858





697
UUUGUU C AGUGGU
2371
18362
HBV-697 Rz-6 allyl stab1
ascscsascu cUGAuGaggccguuaggccGaa Aacaaa B
10859





1539
UCUCUU U ACGCGG
2372
18366
HBV-1539 Rz-6 allyl stab1
cscsgscsgu cUGAuGaggccguuaggccGaa Aagaga B
10860





1599
UCACCU C UGCACG
2373
18367
HBV-1599 Rz-6 allyl stab1
csgsusgsca cUGAuGaggccguuaggccGaa Agguga B
10861





1607
GCACGU C GCAUGG
2374
18368
HBV-1607 Rz-6 allyl stab1
cscsasusgc cUGAuGaggccguuaggccGaa Acgugc B
10862





1833
UCACCU C UGCCUA
2375
18371
HBV-1833 Rz-6 allyl stab1
usasgsgsca cUGAuGaggccguuaggccGaa Agguga B
10863





2383
AGAACU C CCUCGC
2376
18374
HBV-2383 Rz-6 allyl stab1
gscsgsasgg cUGAuGaggccguuaggccGaa Aguucu B
10864





2429
GAAGAU C UCAAUC
2377
18376
HBV-2429 Rz-6 allyl stab1
gsasususga cUGAuGaggccguuaggccGaa Aucuuc B
10865





2831
UAUUCU U GGGAAC
2378
18379
HBV-2831 Rz-6 allyl stab1
gsususcscc cUGAuGaggccguuaggccGaa Agaaua B
10866





430
UGCCUC A UCUUCU
2379
18391
HBV-430 CHz-6 allyl stab1
asgsasasga cUGAuGaggccguuaggccGaa Iaggca B
10867





676
UGGCUC A GUUUAC
2380
18396
HBV-676 CHz-6 allyl stab1
gsusasasac cUGAuGaggccguuaggccGaa Iagcca B
10868





683
GUUUAC U AGUGCC
2381
18397
HBV-683 CHz-6 allyl stab1
gsgscsascu cUGAuGaggccguuaggccGaa Iuaaac B
10869





1150
UUUACC C CGUUGC
2382
18402
HBV-1150 CHz-6 allyl stab1
gscsasascg cUGAuGaggccguuaggccGaa Iguaaa B
10870





1200
GCAACC C CCACUG
2383
18403
HBV-1200 CHz-6 allyl stab1
csasgsusgg cUGAuGaggccguuaggccGaa Iguugc B
10871





1201
CAACCC C CACUGG
2384
18404
HBV-1201 CHz-6 allyl stab1
cscsasgsug cUGAuGaggccguuaggccGaa Igguug B
10872





1444
CGGCGC U GAAUCC
2385
18405
HBV-1444 CHz-6 allyl stab1
gsgsasusuc cUGAuGaggccguuaggccGaa Icgccg B
10873





1451
GAAUCC C GCGGAC
2386
18406
HBV-1451 CHz-6 allyl stab1
gsuscscsgc cUGAuGaggccguuaggccGaa Igauuc B
10874





1533
CGCACC U CUCUUU
2387
18407
HBV-1533 CHz-6 allyl stab1
asasasgsag cUGAuGaggccguuaggccGaa Igugcg B
10875





1600
CACCUC U GCACGU
2388
18410
HBV-1600 CHz-6 allyl stab1
ascsgsusgc cUGAuGaggccguuaggccGaa Iaggug B
10876





1698
CCGACC U UGAGGC
2389
18411
HBV-1698 CHz-6 allyl stab1
gscscsusca cUGAuGaggccguuaggccGaa Igucgg B
10877





1784
GGAGGC U GUAGGC
2390
18412
HBV-1784 CHz-6 allyl stab1
gscscsusac cUGAuGaggccguuaggccGaa Iccucc B
10878





1829
UUUUUC A CCUCUG
2391
18414
HBV-1829 CHz-6 allyl stab1
csasgsasgg cUGAuGaggccguuaggccGaa Iaaaaa B
10879





1876
GCCUCC A AGCUGU
2392
18420
HBV-1876 CHz-6 allyl stab1
ascsasgscu cUGAuGaggccguuaggccGaa Igaggc B
10880





1880
CCAAGC U GUGCCU
2393
18422
HBV-1880 CHz-6 allyl stab1
asgsgscsac cUGAuGaggccguuaggccGaa Icuugg B
10881





218
UUUUUCU U GUUGACA
2394
18333
HBV-218 Rz-7 allyl stab1
usgsuscsaac cUGAuGaggccguuaggccGaa Agaaaaa B
10882





257
CUAGACU C GUGGUGG
2395
18336
HBV-257 Rz-7 allyl stab1
cscsascscac cUGAuGaggccguuaggccGaa Agucuag B
10883





268
GUGGACU U CUCUCAA
2396
18338
HBV-268 Rz-7 allyl stab1
ususgsasgag cUGAuGaggccguuaggccGaa Aguccac B
10884





269
UGGACUU C UCUCAAU
2397
18339
HBV-269 Rz-7 allyl stab1
asususgsaga cUGAuGaggccguuaggccGaa Aagucca B
10885





271
GACUUCU C UCAAUUU
2398
18340
HBV-271 Rz-7 allyl stab1
asasasusuga cUGAuGaggccguuaggccGaa Agaaguc B
10886





273
CUUCUCU C AAUUUUC
2399
18341
HBV-273 Rz-7 allyl stab1
gsasasasauu cUGAuGaggccguuaggccGaa Agagaag B
10887





277
UCUCAAU U UUCUAGG
2400
18342
HBV-277 Rz-7 allyl stab1
cscsusasgaa cUGAuGaggccguuaggccGaa Auugaga B
10888





278
CUCAAUU U UCUAGGG
2401
18343
HBV-278 Rz-7 allyl stab1
cscscsusaga cUGAuGaggccguuaggccGaa Aauugag B
10889





279
UCAAUUU U CUAGGGG
2402
18344
HBV-279 Rz-7 allyl stab1
cscscscsuag cUGAuGaggccguuaggccGaa Aaauuga B
10890





314
CAAAAUU C GCAGUCC
2403
18347
HBV-314 Rz-7 allyl stab1
gsgsascsugc cUGAuGaggccguuaggccGaa Aauuuug B
10891





385
GAUGUGU C UGCGGCG
2404
18348
HBV-385 Rz-7 allyl stab1
csgscscsgca cUGAuGaggccguuaggccGaa Acacauc B
10892





394
GCGGCGU U UUAUCAU
2405
18349
HBV-394 Rz-7 allyl stab1
asusgsasuaa cUGAuGaggccguuaggccGaa Acgccgc B
10893





402
UUAUCAU C UUCCUCU
2406
18352
HBV-402 Rz-7 allyl stab1
asgsasgsgaa cUGAuGaggccguuaggccGaa Augauaa B
10894





423
UGCUGCU A UGCCUCA
2407
18353
HBV-423 Rz-7 allyl stab1
usgsasgsgca cUGAuGaggccguuaggccGaa Agcagca B
10895





429
UAUGCCU C AUCUUCU
2408
18354
HBV-429 Rz-7 allyl stab1
asgsasasgau cUGAuGaggccguuaggccGaa Aggcaua B
10896





679
GCUCAGU U UACUAGU
2409
18356
HBV-679 Rz-7 allyl stab1
ascsusasgua cUGAuGaggccguuaggccGaa Acugagc B
10897





680
CUCAGUU U ACUAGUG
2410
18357
HBV-680 Rz-7 allyl stab1
csascsusagu cUGAuGaggccguuaggccGaa Aacugag B
10898





681
UCAGUUU A CUAGUGC
2411
18358
HBV-681 Rz-7 allyl stab1
gscsascsuag cUGAuGaggccguuaggccGaa Aaacuga B
10899





684
GUUUACU A GUGCCAU
2412
18359
HBV-684 Rz-7 allyl stab1
asusgsgscac cUGAuGaggccguuaggccGaa Aguaaac B
10900





692
GUGCCAU U UGUUCAG
2413
18360
HBV-692 Rz-7 allyl stab1
csusgsasaca cUGAuGaggccguuaggccGaa Auggcac B
10901





693
UGCCAUU U GUUCAGU
2414
18361
HBV-693 Rz-7 allyl stab1
ascsusgsaac cUGAuGaggccguuaggccGaa Aauggca B
10902





1534
CGCACCU C UCUUUAC
2415
18363
HBV-1534 Rz-7 allyl stab1
gsusasasaga cUGAuGaggccguuaggccGaa Aggugcg B
10903





1536
CACCUCU C UUUACGC
2416
18364
HBV-1536 Rz-7 allyl stab1
gscsgsusaaa cUGAuGaggccguuaggccGaa Agaggug B
10904





1538
CCUCUCU U UACGCGG
2352
18365
HBV-1538 Rz-7 allyl stab1
cscsgscsgua cUGAuGaggccguuaggccGaa Agagagg B
10905





1787
AGGCUGU A GGCAUAA
2417
18369
HBV-1787 Rz-7 allyl stab1
ususasusgcc cUGAuGaggccguuaggccGaa Acagccu B
10906





1793
UAGGCAU A AAUUGGU
2418
18370
HBV-1793 Rz-7 allyl stab1
ascscsasauu cUGAuGaggccguuaggccGaa Augccua B
10907





1874
CAAGCCU C CAAGCUG
2419
18372
HBV-1874 Rz-7 allyl stab1
csasgscsuug cUGAuGaggccguuaggccGaa Aggcuug B
10908





1887
UGUGCCU U GGGUGGC
2420
18373
HBV-1887 Rz-7 allyl stab1
gscscsasccc cUGAuGaggccguuaggccGaa Aggcaca B
10909





2383
AAGAACU C CCUCGCC
2421
18375
HBV-2383 Rz-7 allyl stab1
gsgscsgsagg cUGAuGaggccguuaggccGaa Aguucuu B
10910





2828
ACCAUAU U CUUGGGA
2422
18377
HBV-2828 Rz-7 allyl stab1
uscscscsaag cUGAuGaggccguuaggccGaa Auauggu B
10911





2829
CCAUAUU C UUGGGAA
2423
18378
HBV-2829 Rz-7 allyl stab1
ususcscscaa cUGAuGaggccguuaggccGaa Aauaugg B
10912





2831
AUAUUCU U GGGAACA
2424
18380
HBV-2831 Rz-7 allyl stab1
usgsususccc cUGAuGaggccguuaggccGaa Agaauau B
10913





256
UCUAGAC U CGUGGUG
2425
18381
HBV-256 CHz-7 allyl stab1
csascscsacg cUGAuGaggccguuaggccGaa Iucuaga B
10914





267
GGUGGAC U UCUCUCA
2426
18382
HBV-267 CHz-7 allyl stab1
usgsasgsaga cUGAuGaggccguuaggccGaa Iuccacc B
10915





270
GGACUUC U CUCAAUU
2427
18383
HBV-270 CHz-7 allyl stab1
asasususgag cUGAuGaggccguuaggccGaa Iaagucc B
10916





272
ACUUCUC U CAAUUUU
2428
18384
HBV-272 CHz-7 allyl stab1
asasasasuug cUGAuGaggccguuaggccGaa Iagaagu B
10917





274
UUCUCUC A AUUUUCU
2429
18385
HBV-274 CHz-7 allyl stab1
asgsasasaau cUGAuGaggccguuaggccGaa Iagagaa B
10918





386
AUGUGUC U GCGGCGU
2430
18386
HBV-386 CHz-7 allyl stab1
ascsgscscgc cUGAuGaggccguuaggccGaa Iacacau B
10919





419
AUCCUGC U GCUAUGC
2431
18387
HBV-419 CHz-7 allyl stab1
gscsasusagc cUGAuGaggccguuaggccGaa Icaggau B
10920





422
CUGCUGC U AUGCCUC
2432
18388
HBV-422 CHz-7 allyl stab1
gsasgsgscau cUGAuGaggccguuaggccGaa Icagcag B
10921





427
GCUAUGC C UCAUCUU
2433
18389
HBV-427 CHz-7 allyl stab1
asasgsasuga cUGAuGaggccguuaggccGaa Icauagc B
10922





428
CUAUGCC U CAUCUUC
2434
18390
HBV-428 CHz-7 allyl stab1
gsasasgsaug cUGAuGaggccguuaggccGaa Igcauag B
10923





430
AUGCCUC A UCUUCUU
2435
18392
HBV-430 CHz-7 allyl stab1
asasgsasaga cUGAuGaggccguuaggccGaa Iaggcau B
10924





608
UGUAUUC C CAUCCCA
2436
18393
HBV-608 CHz-7 allyl stab1
usgsgsgsaug cUGAuGaggccguuaggccGaa Iaauaca B
10925





609
GUAUUCC C AUCCCAU
2437
18394
HBV-609 CHz-7 allyl stab1
asusgsgsgau cUGAuGaggccguuaggccGaa Igaauac B
10926





669
GUUUCUC U UGGCUCA
2438
18395
HBV-669 CHz-7 allyl stab1
usgsasgscca cUGAuGaggccguuaggccGaa Iagaaac B
10927





689
CUAGUGC C AUUUGUU
2439
18398
HBV-689 CHz-7 allyl stab1
asascsasaau cUGAuGaggccguuaggccGaa Icacuag B
10928





690
UAGUGCC A UUUGUUC
2440
18399
HBV-690 CHz-7 allyl stab1
gsasascsaaa cUGAuGaggccguuaggccGaa Igcacua B
10929





718
GCUUUCC C CCACUGU
2441
18400
HBV-718 CHz-7 allyl stab1
ascsasgsugg cUGAuGaggccguuaggccGaa Igaaagc B
10930





1149
CCUUUAC C CCGUUGC
2442
18401
HBV-1149 CHz-7 allyl stab1
gscsasascgg cUGAuGaggccguuaggccGaa Iuaaagg B
10931





1535
GCACCUC U CUUUACG
2443
18408
HBV-1535 CHz-7 allyl stab1
csgsusasaag cUGAuGaggccguuaggccGaa Iaggugc B
10932





1537
ACCUCUC U UUACGCG
2444
18409
HBV-1537 CHz-7 allyl stab1
csgscsgsuaa cUGAuGaggccguuaggccGaa Iagaggu B
10933





1791
UGUAGGC A UAAAUUG
2445
18413
HBV-1791 CHz-7 allyl stab1
csasasusuua cUGAuGaggccguuaggccGaa Iccuaca B
10934





1831
UUUUCAC C UCUGCCU
2446
18415
HBV-1831 CHz-7 allyl stab1
asgsgscsaga cUGAuGaggccguuaggccGaa Iugaaaa B
10935





1832
UUUCACC U CUGCCUA
2447
18416
HBV-1832 CHz-7 allyl stab1
usasgsgscag cUGAuGaggccguuaggccGaa Igugaaa B
10936





1872
UUCAAGC C UCCAAGC
2448
18417
HBV-1872 CHz-7 allyl stab1
gscsususgga cUGAuGaggccguuaggccGaa Icuugaa B
10937





1873
UCAAGCC U CCAAGCU
2449
18418
HBV-1873 CHz-7 allyl stab1
asgscsusugg cUGAuGaggccguuaggccGaa Igcuuga B
10938





1875
AAGCCUC C AAGCUGU
2450
18419
HBV-1875 CHz-7 allyl stab1
ascsasgscuu cUGAuGaggccguuaggccGaa Iaggcuu B
10939





1876
AGCCUCC A AGCUGUG
2451
18421
HBV-1876 CHz-7 allyl stab1
csascsasgcu cUGAuGaggccguuaggccGaa Igaggcu B
10940





1880
UCCAAGC U GUGCCUU
2452
18423
HBV-1880 CHz-7 allyl stab1
asasgsgscac cUGAuGaggccguuaggccGaa Icuugga B
10941





2382
GAAGAAC U CCCUCGC
2453
18424
HBV-2382 CHz-7 allyl stab1
gscsgsasggg cUGAuGaggccguuaggccGaa Iuucuuc B
10942





2384
AGAACUC C CUCGCCU
2454
18425
HBV-2384 CHz-7 allyl stab1
asgsgscsgag cUGAuGaggccguuaggccGaa Iaguucu B
10943





2385
GAACUCC C UCGCCUC
2455
18426
HBV-2385 CHz-7 allyl stab1
gsasgsgscga cUGAuGaggccguuaggccGaa Igaguuc B
10944





2422
GCGUCGC A GAAGAUC
2456
18427
HBV-2422 CHz-7 allyl stab1
gsasuscsuuc cUGAuGaggccguuaggccGaa Icgacgc B
10945





2830
CAUAUUC U UGGGAAC
2457
18428
HBV-2830 CHz-7 allyl stab1
gsususcscca cUGAuGaggccguuaggccGaa Iaauaug B
10946





234
AAUCCU C ACAAUA
2363
19179
HBV-234 Rz-6 amino stab1
usasususgu cUGAUGaggccguuaggccGaa Aggauu B
10947





252
GAGUCU A GACUCG
2364
19180
HBV-252 Rz-6 amino stab1
csgsasgsuc cUGAUGaggccguuaggccGaa Agacuc B
10948





268
UGGACU U CUCUCA
2365
19182
HBV-268 Rz-6 amino stab1
usgsasgsag cUGAUGaggccguuaggccGaa Agucca B
10949





280
AAUUUU C UAGGGG
2366
19190
HBV-280 Rz-6 amino stab1
cscscscsua cUGAUGaggccguuaggccGaa Aaaauu B
10950





313
CAAAAU U CGCAGU
2367
19191
HBV-313 Rz-6 amino stab1
ascsusgscg cUGAUGaggccguuaggccGaa Auuuug B
10951





395
GGCGUU U UAUCAU
2368
19195
HBV-395 Rz-6 amino stab1
asusgsasua cUGAUGaggccguuaggccGaa Aacgcc B
10952





402
UAUCAU C UUCCUC
2369
19196
HBV-402 Rz-6 amino stab1
gsasgsgsaa cUGAUGaggccguuaggccGaa Augaua B
10953





607
UGUAUU C CCAUCC
2370
19200
HBV-607 Rz-6 amino stab1
gsgsasusgg cUGAUGaggccguuaggccGaa Aauaca B
10954





697
UUUGUU C AGUGGU
2371
19207
HBV-697 Rz-6 amino stab1
ascscsascu cUGAUGaggccguuaggccGaa Aacaaa B
10955





1539
UCUCUU U ACGCGG
2372
19211
HBV-1539 Rz-6 amino stab1
cscsgscsgu cUGAUGaggccguuaggccGaa Aagaga B
10956





1599
UCACCU C UGCACG
2373
19212
HBV-1599 Rz-6 amino stab1
csgsusgsca cUGAUGaggccguuaggccGaa Agguga B
10957





1607
GCACGU C GCAUGG
2374
19213
HBV-1607 Rz-6 amino stab1
cscsasusgc cUGAUGaggccguuaggccGaa Acgugc B
10958





1833
UCACCU C UGCCUA
2375
19216
HBV-1833 Rz-6 amino stab1
usasgsgsca cUGAUGaggccguuaggccGaa Agguga B
10959





2383
AGAACU C CCUCGC
2376
19219
HBV-2383 Rz-6 amino stab1
gscsgsasgg cUGAUGaggccguuaggccGaa Aguucu B
10960





2429
GAAGAU C UCAAUC
2377
19221
HBV-2429 Rz-6 amino stab1
gsasususga cUGAUGaggccguuaggccGaa Aucuuc B
10961





2831
UAUUCU U GGGAAC
2378
19224
HBV-2831 Rz-6 amino stab1
gsususcscc cUGAUGaggccguuaggccGaa Agaaua B
10962





430
UGCCUC A UCUUCU
2379
19236
HBV-430 CHz-6 amino stab1
asgsasasga cUGAUGaggccguuaggccGaa Iaggca B
10963





676
UGGCUC A GUUUAC
2380
19241
HBV-676 CHz-6 amino stab1
gsusasasac cUGAUGaggccguuaggccGaa Iagcca B
10964





683
GUUUAC U AGUGCC
2381
19242
HBV-683 CHz-6 amino stab1
gsgscsascu cUGAUGaggccguuaggccGaa Iuaaac B
10965





1150
UUUACC C CGUUGC
2382
19247
HBV-1150 CHz-6 amino stab1
gscsasascg cUGAUGaggccguuaggccGaa Iguaaa B
10966





1200
GCAACC C CCACUG
2383
19248
HBV-1200 CHz-6 amino stab1
csasgsusgg cUGAUGaggccguuaggccGaa Iguugc B
10967





1201
CAACCC C CACUGG
2384
19249
HBV-1201 CHz-6 amino stab1
cscsasgsug cUGAUGaggccguuaggccGaa Igguug B
10968





1444
CGGCGC U GAAUCC
2385
19250
HBV-1444 CHz-6 amino stab1
gsgsasusuc cUGAUGaggccguuaggccGaa Icgccg B
10969





1451
GAAUCC C GCGGAC
2386
19251
HBV-1451 CHz-6 amino stab1
gsuscscsgc cUGAUGaggccguuaggccGaa Igauuc B
10970





1533
CGCACC U CUCUUU
2387
19252
HBV-1533 CHz-6 amino stab1
asasasgsag cUGAUGaggccguuaggccGaa Igugcg B
10971





1600
CACCUC U GCACGU
2388
19255
HBV-1600 CHz-6 amino stab1
ascsgsusgc cUGAUGaggccguuaggccGaa Iaggug B
10972





1698
CCGACC U UGAGGC
2389
19256
HBV-1698 CHz-6 amino stab1
gscscsusca cUGAUGaggccguuaggccGaa Igucgg B
10973





1784
GGAGGC U GUAGGC
2390
19257
HBV-1784 CHz-6 amino stab1
gscscsusac cUGAUGaggccguuaggccGaa Iccucc B
10974





1829
UUUUUC A CCUCUG
2391
19259
HBV-1829 CHz-6 amino stab1
csasgsasgg cUGAUGaggccguuaggccGaa Iaaaaa B
10975





1876
GCCUCC A AGCUGU
2392
19265
HBV-1876 CHz-6 amino stab1
ascsasgscu cUGAUGaggccguuaggccGaa Igaggc B
10976





1880
CCAAGC U GUGCCU
2393
19267
HBV-1880 CHz-6 amino stab1
asgsgscsac cUGAUGaggccguuaggccGaa Icuugg B
10977





218
UUUUCU U GUUGACA
2394
19178
HBV-218 Rz-7 amino stab1
usgsuscsaac cUGAUGaggccguuaggccGaa Agaaaaa B
10978





257
CUAGACU C GUGGUGG
2395
19181
HBV-257 Rz-7 amino stab1
cscsascscac cUGAUGaggccguuaggccGaa Agucuag B
10979





268
GUGGACU U CUCUCAA
2396
19183
HBV-268 Rz-7 amino stab1
ususgsasgag cUGAUGaggccguuaggccGaa Aguccac B
10980





269
UGGACUU C UCUCAAU
2397
19184
HBV-269 Rz-7 amino stab1
asususgsaga cUGAUGaggccguuaggccGaa Aagucca B
10981





271
GACUUCU C UCAAUUU
2398
19185
HBV-271 Rz-7 amino stab1
asasasusuga cUGAUGaggccguuaggccGaa Agaaguc B
10982





273
CUUCUCU C AAUUUUC
2399
19186
HBV-273 Rz-7 amino stab1
gsasasasauu cUGAUGaggccguuaggccGaa Agagaag B
10983





277
UCUCAAU U UUCUAGG
2400
19187
HBV-277 Rz-7 amino stab1
cscsusasgaa cUGAUGaggccguuaggccGaa Auugaga B
10984





278
CUCAAUU U UCUAGGG
2401
19188
HBV-278 Rz-7 amino stab1
cscscsusaga cUGAUGaggccguuaggccGaa Aauugag B
10985





279
UCAAUUU U CUAGGGG
2402
19189
HBV-279 Rz-7 amino stab1
cscscscsuag cUGAUGaggccguuaggccGaa Aaauuga B
10986





314
CAAAAUU C GCAGUCC
2403
19192
HBV-314 Rz-7 amino stab1
gsgsascsugc cUGAUGaggccguuaggccGaa Aauuuug B
10987





385
GAUGUGU C UGCGGCG
2404
19193
HBV-385 Rz-7 amino stab1
csgscscsgca cUGAUGaggccguuaggccGaa Acacauc B
10988





394
GCGGCGU U UUAUCAU
2405
19194
HBV-394 Rz-7 amino stab1
asusgsasuaa cUGAUGaggccguuaggccGaa Acgccgc B
10989





402
UUAUCAU C UUCCUCU
2406
19197
HBV-402 Rz-7 amino stab1
asgsasgsgaa cUGAUGaggccguuaggccGaa Augauaa B
10990





423
UGCUGCU A UGCCUCA
2407
19198
HBV-423 Rz-7 amino stab1
usgsasgsgca cUGAUGaggccguuaggccGaa Agcagca B
10991





429
UAUGCCU C AUCUUCU
2408
19199
HBV-429 Rz-7 amino stab1
asgsasasgau cUGAUGaggccguuaggccGaa Aggcaua B
10992





679
GCUCAGU U UACUAGU
2409
19201
HBV-679 Rz-7 amino stab1
ascsusasgua cUGAUGaggccguuaggccGaa Acugagc B
10993





680
CUCAGUU U ACUAGUG
2410
19202
HBV-680 Rz-7 amino stab1
csascsusagu cUGAUGaggccguuaggccGaa Aacugag B
10994





681
UCAGUUU A CUAGUGC
2411
19203
HBV-681 Rz-7 amino stab1
gscsascsuag cUGAUGaggccguuaggccGaa Aaacuga B
10995





684
GUUUACU A GUGCCAU
2412
19204
HBV-684 Rz-7 amino stab1
asusgsgscac cUGAUGaggccguuaggccGaa Aguaaac B
10996





692
GUGCCAU U UGUUCAG
2413
19205
HBV-692 Rz-7 amino stab1
csusgsasaca cUGAUGaggccguuaggccGaa Auggcac B
10997





693
UGCCAUU U GUUCAGU
2414
19206
HBV-693 Rz-7 amino stab1
ascsusgsaac cUGAUGaggccguuaggccGaa Aauggca B
10998





1534
CGCACCU C UCUUUAC
2415
19208
HBV-1534 Rz-7 amino stab1
gsusasasaga cUGAUGaggccguuaggccGaa Aggugcg B
10999





1536
CACCUCU C UUUACGC
2416
19209
HBV-1536 Rz-7 amino stab1
gscsgsusaaa cUGAUGaggccguuaggccGaa Agaggug B
11000





1538
CCUCUCU U UACGCGG
2352
19210
HBV-1538 Rz-7 amino stab1
cscsgscsgua cUGAUGaggccguuaggccGaa Agagagg B
11001





1787
AGGCUGU A GGCAUAA
2417
19214
HBV-1787 Rz-7 amino stab1
ususasusgcc cUGAUGaggccguuaggccGaa Acagccu B
11002





1793
UAGGCAU A AAUUGGU
2418
19215
HBV-1793 Rz-7 amino stab1
ascscsasauu cUGAUGaggccguuaggccGaa Augccua B
11003





1874
CAAGCCU C CAAGCUG
2419
19217
HBV-1874 Rz-7 amino stab1
csasgscsuug cUGAUGaggccguuaggccGaa Aggcuug B
11004





1887
UGUGCCU U GGGUGGC
2420
19218
HBV-1887 Rz-7 amino stab1
gscscsasccc cUGAUGaggccguuaggccGaa Aggcaca B
11005





2383
AAGAACU C CCUCGCC
2421
19220
HBV-2383 Rz-7 amino stab1
gsgscsgsagg cUGAUGaggccguuaggccGaa Aguucuu B
11006





2828
ACCAUAU U CUUGGGA
2422
19222
HBV-2828 Rz-7 amino stab1
uscscscsaag cUGAUGaggccguuaggccGaa Auauggu B
11007





2829
CCAUAUU C UUGGGAA
2423
19223
HBV-2829 Rz-7 amino stab1
ususcscscaa cUGAUGaggccguuaggccGaa Aauaugg B
11008





2831
AUAUUCU U GGGAACA
2424
19225
HBV-2831 Rz-7 amino stab1
usgsususccc cUGAUGaggccguuaggccGaa Agaauau B
11009





256
UCUAGAC U CGUGGUG
2425
19226
HBV-256 CHz-7 amino stab1
csascscsacg cUGAUGaggccguuaggccGaa Iucuaga B
11010





267
GGUGGAC U UCUCUCA
2426
19227
HBV-267 CHz-7 amino stab1
usgsasgsaga cUGAUGaggccguuaggccGaa Iuccacc B
11011





270
GGACUUC U CUCAAUU
2427
19228
HBV-270 CHz-7 amino stab1
asasususgag cUGAUGaggccguuaggccGaa Iaagucc B
11012





272
ACUUCUC U CAAUUUU
2428
19229
HBV-272 CHz-7 amino stab1
asasasasuug cUGAUGaggccguuaggccGaa Iagaagu B
11013





274
UUCUCUC A AUUUUCU
2429
19230
HBV-274 CHz-7 amino stab1
asgsasasaau cUGAUGaggccguuaggccGaa Iagagaa B
11014





386
AUGUGUC U GCGGCGU
2430
19231
HBV-386 CHz-7 amino stab1
ascsgscscgc cUGAUGaggccguuaggccGaa Iacacau B
11015





419
AUCCUGC U GCUAUGC
2431
19232
HBV-419 CHz-7 amino stab1
gscsasusagc cUGAUGaggccguuaggccGaa Icaggau B
11016





422
CUGCUGC U AUGCCUC
2432
19233
HBV-422 CHz-7 amino stab1
gsasgsgscau cUGAUGaggccguuaggccGaa Icagcag B
11017





427
GCUAUGC C UCAUCUU
2433
19234
HBV-427 CHz-7 amino stab1
asasgsasuga cUGAUGaggccguuaggccGaa Icauagc B
11018





428
CUAUGCC U CAUCUUC
2434
19235
HBV-428 CHz-7 amino stab1
gsasasgsaug cUGAUGaggccguuaggccGaa Igcauag B
11019





430
AUGCCUC A UCUUCUU
2435
19237
HBV-430 CHz-7 amino stab1
asasgsasaga cUGAUGaggccguuaggccGaa Iaggcau B
11020





608
UGUAUUC C CAUCCCA
2436
19238
HBV-608 CHz-7 amino stab1
usgsgsgsaug cUGAUGaggccguuaggccGaa Iaauaca B
11021





609
GUAUUCC C AUCCCAU
2437
19239
HBV-609 CHz-7 amino stab1
asusgsgsgau cUGAUGaggccguuaggccGaa Igaauac B
11022





669
GUUUCUC U UGGCUCA
2438
19240
HBV-669 CHz-7 amino stab1
usgsasgscca cUGAUGaggccguuaggccGaa Iagaaac B
11023





689
CUAGUGC C AUUUGUU
2439
19243
HBV-689 CHz-7 amino stab1
asascsasaau cUGAUGaggccguuaggccGaa Icacuag B
11024





690
UAGUGCC A UUUGUUC
2440
19244
HBV-690 CHz-7 amino stab1
gsasascsaaa cUGAUGaggccguuaggccGaa Igcacua B
11025





718
GCUUUCC C CCACUGU
2441
19245
HBV-718 CHz-7 amino stab1
ascsasgsugg cUGAUGaggccguuaggccGaa Igaaagc B
11026





1149
CCUUUAC C CCGUUGC
2442
19246
HBV-1149 CHz-7 amino stab1
gscsasascgg cUGAUGaggccguuaggccGaa Iuaaagg B
11027





1535
GCACCUC U CUUUACG
2443
19253
HBV-1535 CHz-7 amino stab1
csgsusasaag cUGAUGaggccguuaggccGaa Iaggugc B
11028





1537
ACCUCUC U UUACGCG
2444
19254
HBV-1537 CHz-7 amino stab1
csgscsgsuaa cUGAUGaggccguuaggccGaa Iagaggu B
11029





1791
UGUAGGC A UAAAUUG
2445
19258
HBV-1791 CHz-7 amino stab1
csasasusuua cUGAUGaggccguuaggccGaa Iccuaca B
11030





1831
UUUUCAC C UCUGCCU
2446
19260
HBV-1831 CHz-7 amino stab1
asgsgscsaga cUGAUGaggccguuaggccGaa Iugaaaa B
11031





1832
UUUCACC U CUGCCUA
2447
19261
HBV-1832 CHz-7 amino stab1
usasgsgscag cUGAUGaggccguuaggccGaa Igugaaa B
11032





1872
UUCAAGC C UCCAAGC
2448
19262
HBV-1872 CHz-7 amino stab1
gscsususgga cUGAUGaggccguuaggccGaa Icuugaa B
11033





1873
UCAAGCC U CCAAGCU
2449
19263
HBV-1873 CHz-7 amino stab1
asgscsusugg cUGAUGaggccguuaggccGaa Igcuuga B
11034





1875
AAGCCUC C AAGCUGU
2450
19264
HBV-1875 CHz-7 amino stab1
ascsasgscuu cUGAUGaggccguuaggccGaa Iaggcuu B
11035





1876
AGCCUCC A AGCUGUG
2451
19266
HBV-1876 CHz-7 amino stab1
csascsasgcu cUGAUGaggccguuaggccGaa Igaggcu B
11036





1880
UCCAAGC U GUGCCUU
2452
19268
HBV-1880 CHz-7 amino stab1
asasgsgscac cUGAUGaggccguuaggccGaa Icuugga B
11037





2382
GAAGAAC U CCCUCGC
2453
19269
HBV-2382 CHz-7 amino stab1
gscsgsasggg cUGAUGaggccguuaggccGaa Iuucuuc B
11038





2384
AGAACUC C CUCGCCU
2454
19270
HBV-2384 CHz-7 amino stab1
asgsgscsgag cUGAUGaggccguuaggccGaa Iaguucu B
11039





2385
GAACUCC C UCGCCUC
2455
19271
HBV-2385 CHz-7 amino stab1
gsasgsgscga cUGAUGaggccguuaggccGaa Igaguuc B
11040





2422
GCGUCGC A GAAGAUC
2456
19272
HBV-2422 CHz-7 amino stab1
gsasuscsuuc cUGAUGaggccguuaggccGaa Icgacgc B
11041





2830
CAUAUUC U UGGGAAC
2457
19273
HBV-2830 CHz-7 amino stab1
gsususcscca cUGAUGaggccguuaggccGaa Iaauaug B
11042





315
GCCAAAAUUC G CAGUC
2458
20079
HBV-315 GCl.Rz-5/10 stab2
gsascsg uGAUsg gcauGcacuaugc gcg gaauuuuggc B
11043





381
AUCGCUGGAU G UGUCU
2459
20080
HBV-381 GCl.Rz-5/10 stab2
asgsasa uGAUsg gcauGcacuaugc gcg auccagcgau B
11044





476
UUGCCCGUUU G UCCUC
2460
20081
HBV-476 GCl.Rz-5/10 stab2
gsasgsa uGAUsg gcauGcacuaugc gcg aaacgggcaa B
11045





694
AGUGCCAUUU G UUCAG
2461
20082
HBV-694 GCl.Rz-5/10 stab2
csusgsa uGAUsg gcauGcacuaugc gcg aaauggcacu B
11046





1265
CUCCUCUGCC G AUCCA
2462
20083
HBV-1265 GCl.Rz-5/10 stab2
usgsgsu uGAUsg gcauGcacuaugc gcg ggcagaggag B
11047





1601
CUUCACCUCU G CACGU
2463
20084
HBV-1601 GCl.Rz-5/10 stab2
ascsgsg uGAUsg gcauGcacuaugc gcg agaggugaag B
11048





1881
CCUCCAAGCU G UGCCU
2464
20085
HBV-1881 GCl.Rz-5/10 stab2
asgsgsa uGAUsg gcauGcacuaugc gcg agcuuggagg B
11049





1883
UCCAAGCUGU G CCUUG
2465
20086
HBV-1883 GCl.Rz-5/10 stab2
csasasg uGAUsg gcauGcacuaugc gcg acagcuugga B
11050





2388
GAACUCCCUC G CCUCG
2466
20087
HBV-2388 GCl.Rz-5/10 stab2
csgsasg uGAUsg gcauGcacuaugc gcg gagggaguuc B
11051





381
GCUGGAU G UGUCUGC
2467
20091
HBV-381 Zin.Rz-7 amino stab2
gscsasgsaca GccgaaagGCGaGugaGGuCu auccagc B





392
CUGCGGC G UUUUAUC
2468
20092
HBV-392 Zin.Rz-7 amino stab2
gsasusasaaa GccgaaagGCGaGugaGGuCu gccgcag B





420
UCCUGCU G CUAUGCC
2469
20093
HBV-420 Zin.Rz-7 amino stab2
gsgscsasuag GccgaaagGCGaGugaGGuCu agcagga B





648
UAUGGGA G UGGGCCU
2470
20094
HBV-648 Zin.Rz-7 amino stab2
asgsgscscca GccgaaagGCGaGugaGGuCu ucccaua B





711
UCGUAGG G CUUUCCC
2471
20095
HBV-711 Zin.Rz-7 amino stab2
gsgsgsasaag GccgaaagGCGaGugaGGuCu ccuacga B





1262
CUCCUCU G CCGAUCC
2472
20096
HBV-1262 Zin.Rz-7 amino stab2
gsgsasuscgg GccgaaagGCGaGugaGGuCu agaggag B





1835
CACCUCU G CCUAAUC
2473
20097
HBV-1835 Zin.Rz-7 amino stab2
gsasususagg GccgaaagGCGaGugaGGuCu agaggug B





2388
CUCCCUC G CCUCGCA
2474
20098
HBV-2388 Zin.Rz-7 amino stab2
usgscsgsagg GccgaaagGCGaGugaGGuCu gagggag B





192
GACCCCU G CUCGUGU
2475
20099
HBV-192 Zin.Rz-7 amino stab2
ascsascsgag GccgaaagGCGaGugaGGuCu agggguc B





198
UGCUCGU C UUACAGG
2476
20100
HBV-198 Zin.Rz-7 amino stab2
cscsusgsuaa GccgaaagGCGaGugaGGuCu acgagca B





315
AAAAUUC G CAGUCCC
2477
20101
HBV-315 Zin.Rz-7 amino stab2
gsgsgsascug GccgaaagGCGaGugaGGuCu gaauuuu B





383
GGAUGU G UCUGCG
2478
20102
HBV-383 Zin.Rz-6 amino stab2
csgscsasga GccgaaagGCGaGugaGGuCu acaucc B





383
UGGAUGU G UCUGCGG
2479
20103
HBV-383 Zin.Rz-7 amino stab2
cscsgscsaga GccgaaagGCGaGugaGGuCu acaucca B





387
GUGUCU G CGGCGU
2480
20104
HBV-387 Zin.Rz-6 amino stab2
ascsgscscg GccgaaagGCGaGugaGGuCu agacac B





390
GUCUGCG G CGUUUUA
2481
20105
HBV-390 Zin.Rz-7 amino stab2
usasasasacg GccgaaagGCGaGugaGGuCu cgcagac B





392
UGCGGC G UUUUAU
2482
20106
HBV-392 Zin.Rz-6 amino stab2
asusasasaa GccgaaagGCGaGugaGGuCu gccgca B





425
UGCUAU G CCUCAU
2483
20107
HBV-425 Zin.Rz-6 amino stab2
asusgsasgg GccgaaagGCGaGugaGGuCu auagca B





425
CUGCUAU G CCUCAUC
2484
20108
HBV-425 Zin.Rz-7 amino stab2
gsasusgsagg GccgaaagGCGaGugaGGuCu auagcag B





468
GUAUGUU G CCCGUUU
2485
20109
HBV-468 Zin.Rz-7 amino stab2
asasascsggg GccgaaagGCGaGugaGGuCu aacauac B





476
CCCGUUU G UCCUCUA
2486
20110
HBV-476 Zin.Rz-7 amino stab2
usasgsasgga GccgaaagGCGaGugaGGuCu aaacggg B





648
AUGGGA G UGGGCC
2487
20111
HBV-648 Zin.Rz-6 amino stab2
gsgscscsca GccgaaagGCGaGugaGGuCu ucccau B





694
GCCAUUU G UUCAGUG
2488
20112
HBV-694 Zin.Rz-7 amino stab2
csascsusgaa GccgaaagGCGaGugaGGuCu aaauggc B





699
UUGUUCA G UGGUUCG
2489
20113
HBV-699 Zin.Rz-7 amino stab2
csgsasascca GccgaaagGCGaGugaGGuCu ugaacaa B





1262
UCCUCU G CCGAUC
2490
20114
HBV-1262 Zin.Rz-6 amino stab2
gsasuscsgg GccgaaagGCGaGugaGGuCu agagga B





1440
CCCGUCG G CGCUGAA
2491
20115
HBV-1440 Zin.Rz-7 amino stab2
ususcsasgcg GccgaaagGCGaGugaGGuCu cgacggg B





1526
CACGGG G CGCACC
2492
20116
HBV-1526 Zin.Rz-6 amino stab2
gsgsusgscg GccgaaagGCGaGugaGGuCu cccgug B





1526
CCACGGG G CGCACCU
2493
20117
HBV-1526 Zin.Rz-7 amino stab2
asgsgsusgcg GccgaaagGCGaGugaGGuCu cccgugg B





1557
CCCGUCU G UGCCUUC
2494
20118
HBV-1557 Zin.Rz-7 amino stab2
gsasasgsgca GccgaaagGCGaGugaGGuCu agacggg B





1559
CGUCUGU G CCUUCUC
2495
20119
HBV-1559 Zin.Rz-7 amino stab2
gsasgsasagg GccgaaagGCGaGugaGGuCu acagacg B





1590
GCACUUC G CUUCACC
2496
20120
HBV-1590 Zin.Rz-7 amino stab2
gsgsusgsaag GccgaaagGCGaGugaGGuCu gaagugc B





1835
ACCUCU G CCUAAU
2497
20121
HBV-1835 Zin.Rz-6 amino stab2
asususasgg GccgaaagGCGaGugaGGuCu agaggu B





2311
ACCAAAU G CCCCUAU
2498
20122
HBV-2311 Zin.Rz-7 amino stab2
asusasgsggg GccgaaagGCGaGugaGGuCu auuuggu B





2420
CCGCGUC G CAGAAGA
2499
20123
HBV-2420 Zin.Rz-7 amino stab2
uscsususcug GccgaaagGCGaGugaGGuCu gacgcgg B





65
CCUGCUG G UGGCUCC
2500
20124
HBV-65 Zin.Rz-7 amino stab2
gsgsasgscca GccgaaagGCGaGugaGGuCu cagcagg B





192
ACCCCU G CUCGUG
2501
20125
HBV-192 Zin.Rz-6 amino stab2
csascsgsag GccgaaagGCGaGugaGGuCu aggggu B





198
GCUCGU G UUACAG
2502
20126
HBV-198 Zin.Rz-6 amino stab2
csusgsusaa GccgaaagGCGaGugaGGuCu acgagc B





258
UAGACUC G UGGUGGA
2503
20127
HBV-258 Zin.Rz-7 amino stab2
uscscsascca GccgaaagGCGaGugaGGuCu gagucua B





261
ACUCGUG G UGGACUU
2504
20128
HBV-261 Zin.Rz-7 amino stab2
asasgsuscca GccgaaagGCGaGugaGGuCu cacgagu B





315
AAAUUC G CAGUCC
2505
20129
HBV-315 Zin.Rz-6 amino stab2
gsgsascsug GccgaaagGCGaGugaGGuCu gaauuu B





381
CUGGAU G UGUCUG
2506
20130
HBV-381 Zin.Rz-6 amino stab2
csasgsasca GccgaaagGCGaGugaGGuCu auccag B





387
UGUGUCU G CGGCGUU
2507
20131
HBV-387 Zin.Rz-7 amino stab2
asascsgsccg GccgaaagGCGaGugaGGuCu agacaca B





390
UCUGCG G CGUUUU
2508
20132
HBV-390 Zin.Rz-6 amino stab2
asasasascg GccgaaagGCGaGugaGGuCu cgcaga B





417
CAUCCU G CUGCUA
2509
20133
HBV-417 Zin.Rz-6 amino stab2
usasgscsag GccgaaagGCGaGugaGGuCu aggaug B





420
CCUGCU G CUAUGC
2510
20134
HBV-420 Zin.Rz-6 amino stab2
gscsasusag GccgaaagGCGaGugaGGuCu agcagg B





468
UAUGUU G CCCGUU
2511
20135
HBV-468 Zin.Rz-6 amino stab2
asascsgsgg GccgaaagGCGaGugaGGuCu aacaua B





476
CCGUUU G UCCUCU
2512
20136
HBV-476 Zin.Rz-6 amino stab2
asgsasgsga GccgaaagGCGaGugaGGuCu aaacgg B





677
GGCUCA G UUUACU
2513
20137
HBV-677 Zin.Rz-6 amino stab2
asgsusasaa GccgaaagGCGaGugaGGuCu ugagcc B





677
UGGCUCA G UUUACUA
2514
20138
HBV-677 Zin.Rz-7 amino stab2
usasgsusaaa GccgaaagGCGaGugaGGuCu ugagcca B





685
UUACUA G UGCCAU
2515
20139
HBV-685 Zin.Rz-6 amino stab2
asusgsgsca GccgaaagGCGaGugaGGuCu uaguaa B





685
UUUACUA G UGCCAUU
2516
20140
HBV-685 Zin.Rz-7 amino stab2
asasusgsgca GccgaaagGCGaGugaGGuCu uaguaaa B





687
UACUAGU G CCAUUUG
2517
20141
HBV-687 Zin.Rz-7 amino stab2
csasasasugg GccgaaagGCGaGugaGGuCu acuagua B





699
UGUUCA G UGGUUC
2518
20142
HBV-699 Zin.Rz-6 amino stab2
gsasascsca GccgaaagGCGaGugaGGuCu ugaaca B





702
UCAGUG G UUCGUA
2519
20143
HBV-702 Zin.Rz-6 amino stab2
usascsgsaa GccgaaagGCGaGugaGGuCu cacuga B





702
UUCAGUG G UUCGUAG
2520
20144
HBV-702 Zin.Rz-7 amino stab2
csusascsgaa GccgaaagGCGaGugaGGuCu cacugaa B





711
CGUAGG G CUUUCC
2521
20145
HBV-711 Zin.Rz-6 amino stab2
gsgsasasag GccgaaagGCGaGugaGGuCu ccuacg B





1006
UUGUGG G UCUUUU
2522
20146
HBV-1006 Zin.Rz-6 amino stab2
asasasasga GccgaaagGCGaGugaGGuCu ccacaa B





1103
UUUCUC G CCAACU
2523
20147
HBV-1103 Zin.Rz-6 amino stab2
asgsususgg GccgaaagGCGaGugaGGuCu gagaaa B





1103
CUUUCUC G CCAACUU
2524
20148
HBV-1103 Zin.Rz-7 amino stab2
asasgsusugg GccgaaagGCGaGugaGGuCu gagaaag B





1184
GCCAAGU G UUUGCUG
2525
20149
HBV-1184 Zin.Rz-7 amino stab2
csasgscsaaa GccgaaagGCGaGugaGGuCu acuuggc B





1440
CCGUCG G CGCUGA
2526
20150
HBV-1440 Zin.Rz-6 amino stab2
uscsasgscg GccgaaagGCGaGugaGGuCu cgacgg B





1442
GUCGGC G CUGAAU
2527
20151
HBV-1442 Zin.Rz-6 amino stab2
asususcsag GccgaaagGCGaGugaGGuCu gccgac B





1442
CGUCGGC G CUGAAUC
2528
20152
HBV-1442 Zin.Rz-7 amino stab2
gsasususcag GccgaaagGCGaGugaGGuCu gccgacg B





1553
CUCCCC G UCUGUG
2529
20153
HBV-1553 Zin.Rz-6 amino stab2
csascsasga GccgaaagGCGaGugaGGuCu ggggag B





1557
CCGUCU G UGCCUU
2530
20154
HBV-1557 Zin.Rz-6 amino stab2
asasgsgsca GccgaaagGCGaGugaGGuCu agacgg B





1559
GUCUGU G CCUUCU
2531
20155
HBV-1559 Zin.Rz-6 amino stab2
asgsasasgg GccgaaagGCGaGugaGGuCu acagac B





1583
CCGUGU G CACUUC
2532
20156
HBV-1583 Zin.Rz-6 amino stab2
gsasasgsug GccgaaagGCGaGugaGGuCu acacgg B





1590
CACUUC G CUUCAC
2533
20157
HBV-1590 Zin.Rz-6 amino stab2
gsusgsasag GccgaaagGCGaGugaGGuCu gaagug B





1622
ACCACC G UGAACG
2534
20158
HBV-1622 Zin.Rz-6 amino stab2
csgsususca GccgaaagGCGaGugaGGuCu gguggu B





1870
UGUUCAA G CCUCCAA
2535
20159
HBV-1870 Zin.Rz-7 amino stab2
ususgsgsagg GccgaaagGCGaGugaGGuCu uugaaca B





1881
CCAAGCU G UGCCUUG
2536
20160
HBV-1881 Zin.Rz-7 amino stab2
csasasgsgca GccgaaagGCGaGugaGGuCu agcuugg B





1883
AGCUGU G CCUUGG
2537
20161
HBV-1883 Zin.Rz-6 amino stab2
cscsasasgg GccgaaagGCGaGugaGGuCu acagcu B





1883
AAGCUGU G CCUUGGG
2538
20162
HBV-1883 Zin.Rz-7 amino stab2
cscscsasagg GccgaaagGCGaGugaGGuCu acagcuu B





2311
CCAAAU G CCCCUA
2539
20163
HBV-2311 Zin.Rz-6 amino stab2
usasgsgsgg GccgaaagGCGaGugaGGuCu auuugg B





2347
ACUGUU G UUAGAC
2540
20164
HBV-2347 Zin.Rz-6 amino stab2
gsuscsusaa GccgaaagGCGaGugaGGuCu aacagu B





2364
AGGCAG G UCCCCU
2541
20165
HBV-2364 Zin.Rz-6 amino stab2
asgsgsgsga GccgaaagGCGaGugaGGuCu cugccu B





2364
GAGGCAG G UCCCCUA
2542
20166
HBV-2364 Zin.Rz-7 amino stab2
usasgsgsgga GccgaaagGCGaGugaGGuCu cugccuc B





2388
UCCCUC G CCUCGC
2543
20167
HBV-2388 Zin.Rz-6 amino stab2
gscsgsasgg GccgaaagGCGaGugaGGuCu gaggga B





2393
CGCCUC G CAGACG
2544
20168
HBV-2393 Zin.Rz-6 amino stab2
csgsuscsug GccgaaagGCGaGugaGGuCu gaggcg B





2417
CGCCGC G UCGCAG
2545
20169
HBV-2417 Zin.Rz-6 amino stab2
csusgscsga GccgaaagGCGaGugaGGuCu gcggcg B





2420
CGCGUC G CAGAAG
2546
20170
HBV-2420 Zin.Rz-6 amino stab2
csususcsug GccgaaagGCGaGugaGGuCu gacgcg B





2474
CAUAAG G UGGGAA
2547
20171
HBV-2474 Zin.Rz-6 amino stab2
ususcscsca GccgaaagGCGaGugaGGuCu cuuaug B





381
GCUGGAU G UGUCUGC
2467
20172
HBV-381 Amb.Rz-7 stab2
gscsasgsaca gga L ucCCUUCaagga L ucCGGG auccagc B
11133





648
UAUGGGA G UGGGCCU
2470
20173
HBV-648 Amb.Rz-7 stab2
asgsgscscca gga L ucCCUUCaagga L ucCGGG ucccaua B
11134





198
UGCUCGU G UUACAGG
2476
20174
HBV-198 Amb.Rz-7 stab2
cscsusgsuaa gga L ucCCUUCaagga L ucCGGG acgagca B
11135





377
UAUCGCU G GAUGUGU
2548
20175
HBV-377 Amb.Rz-7 stab2
ascsascsauc gga L ucCCUUCaagga L ucCGGG agcgaua B
11136





378
AUCGCUG G AUGUGUC
2549
20176
HBV-378 Amb.Rz-7 stab2
gsascsascau gga L ucCCUUCaagga L ucCGGG cagcgau B
11137





383
UGGAUGU G UCUGCGG
2479
20177
HBV-383 Amb.Rz-7 stab2
cscsgscsaga gga L ucCCUUCaagga L ucCGGG acaucca B
11138





383
GGAUGU G UCUGCG
2478
20178
HBV-383 Amb.Rz-6 stab2
csgscsasga gga L ucCCUUCaagga L ucCGGG acaucc B
11139





648
AUGGGA G UGGGCC
2487
20179
HBV-648 Amb.Rz-6 stab2
gsgscscsca gga L ucCCUUCaagga L ucCGGG ucccau B
11140





650
UGGGAGU G GGCCUCA
2550
20180
HBV-650 Amb.Rz-7 stab2
usgsasgsgcc gga L ucCCUUCaagga L ucCGGG acuccca B
11141





650
GGGAGU G GGCCUC
2551
20181
HBV-650 Amb.Rz-6 stab2
gsasgsgscc gga L ucCCUUCaagga L ucCGGG acuccc B
11142





694
GCCAUUU G UUCAGUG
2488
20182
HBV-694 Amb.Rz-7 stab2
csascsusgaa gga L ucCCUUCaagga L ucCGGG aaauggc B
11143





699
UUGUUCA G UGGUUCG
2489
20183
HBV-699 Amb.Rz-7 stab2
csgsasascca gga L ucCCUUCaagga L ucCGGG ugaacaa B
11144





701
GUUCAGU G GUUCGUA
2552
20184
HBV-701 Amb.Rz-7 stab2
usascsgsaac gga L ucCCUUCaagga L ucCGGG acugaac B
11145





710
UUCGUAG G GCUUUCC
2553
20185
HBV-710 Amb.Rz-7 stab2
gsgsasasagc gga L ucCCUUCaagga L ucCGGG cuacgaa B
11146





1525
CCACGG G GCGCAC
2554
20186
HBV-1525 Amb.Rz-6 stab2
gsusgscsgc gga L ucCCUUCaagga L ucCGGG ccgugg B
11147





1624
CACCGU G AACGCC
2555
20187
HBV-1624 Amb.Rz-6 stab2
gsgscsgsuu gga L ucCCUUCaagga L ucCGGG acggug B
11148





2069
CACUCA G GCAAGC
2556
20188
HBV-2069 Amb.Rz-6 stab2
gscsususgc gga L ucCCUUCaagga L ucCGGG ugagug B
11149





2375
CCUAGAA G AAGAACU
2557
20189
HBV-2375 Amb.Rz-7 stab2
asgsususcuu gga L ucCCUUCaagga L ucCGGG uucuagg B
11150





2476
AUAAGGU G GGAAACU
2558
20190
HBV-2476 Amb.Rz-7 stab2
asgsususucc gga L ucCCUUCaagga L ucCGGG accuuau B
11151





65
CCUGCUG G UGGCUCC
2500
20191
HBV-65 Amb.Rz-7 stab2
gsgsasgscca gga L ucCCUUCaagga L ucCGGG cagcagg B
11152





67
GCUGGU G GCUCCA
2559
20192
HBV-67 Amb.Rz-6 stab2
usgsgsasgc gga L ucCCUUCaagga L ucCGGG accagc B 11153





198
GCUCGU G UUACAG
2502
20193
HBV-198 Amb.Rz-6 stab2
csusgsusaa gga L ucCCUUCaagga L ucCGGG acgagc B
11154





260
GACUCGU G GUGGACU
2560
20194
HBV-260 Amb.Rz-7 stab2
asgsuscscac gga L ucCCUUCaagga L ucCGGG acgaguc B
11155





263
UCGUGGU G GACUUCU
2561
20195
HBV-263 Amb.Rz-7 stab2
asgsasasguc gga L ucCCUUCaagga L ucCGGG accacga B
11156





377
AUCGCU G GAUGUG
2562
20196
HBV-377 Amb.Rz-6 stab2
csascsasuc gga L ucCCUUCaagga L ucCGGG agcgau B
11157





378
UCGCUG G AUGUGU
2563
20197
HBV-378 Amb.Rz-6 stab2
ascsascsau gga L ucCCUUCaagga L ucCGGG cagcga B
11158





476
CCGUUU G UCCUCU
2512
20198
HBV-476 Amb.Rz-6 stab2
asgsasgsga gga L ucCCUUCaagga L ucCGGG aaacgg B
11159





651
GGGAGUG G GCCUCAG
2564
20199
HBV-651 Amb.Rz-7 stab2
csusgsasggc gga L ucCCUUCaagga L ucCGGG cacuccc B
11160





677
UGGCUCA G UUUACUA
2514
20200
HBV-677 Amb.Rz-7 stab2
usasgsusaaa gga L ucCCUUCaagga L ucCGGG ugagcca B
11161





685
UUUACUA G UGCCAUU
2516
20201
HBV-685 Amb.Rz-7 stab2
asasusgsgca gga L ucCCUUCaagga L ucCGGG uaguaaa B
11162





702
UUCAGUG G UUCGUAG
2520
20202
HBV-702 Amb.Rz-7 stab2
csusascsgaa gga L ucCCUUCaagga L ucCGGG cacugaa B
11163





709
GUUCGUA G GGCUUUC
2565
20203
HBV-709 Amb.Rz-7 stab2
gsasasasgcc gga L ucCCUUCaagga L ucCGGG uacgaac B
11164





710
UCGUAG G GCUUUC
2566
20204
HBV-710 Amb.Rz-6 stab2
gsasasasgc gga L ucCCUUCaagga L ucCGGG cuacga B
11165





747
UAUGGAU G AUGUGGU
2567
20205
HBV-747 Amb.Rz-7 stab2
ascscsascau gga L ucCCUUCaagga L ucCGGG auccaua B
11166





1557
CCGUCU G UGCCUU
2530
20206
HBV-1557 Amb.Rz-6 stab2
asasgsgsca gga L ucCCUUCaagga L ucCGGG agacgg B
11167





1881
CCAAGCU G UGCCUUG
2536
20207
HBV-1881 Amb.Rz-7 stab2
csasasgsgca gga L ucCCUUCaagga L ucCGGG agcuugg B
11168





2347
ACUGUU G UUAGAC
2540
20208
HBV-2347 Amb.Rz-6 stab2
gsuscsusaa gga L ucCCUUCaagga L ucCGGG aacagu B
11169





2375
CUAGAA G AAGAAC
2568
20209
HBV-2375 Amb.Rz-6 stab2
gsususcsuu gga L ucCCUUCaagga L ucCGGG uucuag B
11170





2378
GAAGAA G AACUCC
2569
20210
HBV-2378 Amb.Rz-6 stab2
gsgsasgsuu gga L ucCCUUCaagga L ucCGGG uucuuc B
11171





2423
CGUCGCA G AAGAUCU
2570
20211
HBV-2423 Amb.Rz-7 stab2
asgsasuscuu gga L ucCCUUCaagga L ucCGGG ugcgacg B
11172





2426
GCAGAA G AUCUCA
2571
20212
HBV-2426 Amb.Rz-6 stab2
usgsasgsau gga L ucCCUUCaagga L ucCGGG uucugc B
11173





2426
CGCAGAA G AUCUCAA
2572
20213
HBV-2426 Amb.Rz-7 stab2
ususgsasgau gga L ucCCUUCaagga L ucCGGG uucugcg B
11174





2476
UAAGGU G GGAAAC
2573
20214
HBV-2476 Amb.Rz-6 stab2
gsusususcc gga L ucCCUUCaagga L ucCGGG accuua B
11175





2477
UAAGGUG G GAAACUU
2574
20215
HBV-2477 Amb.Rz-7 stab2
asasgsusuuc gga L ucCCUUCaagga L ucCGGG caccuua B
11176





2477
AAGGUG G GAAACU
2575
20216
HBV-2477 Amb.Rz-6 stab2
asgsususuc gga L ucCCUUCaagga L ucCGGG caccuu B
11177





1607
UGCACGU C GCAUGGA
2576
20697
HBV-1607 Rz-7 allyl stab1 (7/4)
uscscsasugc cUGAuGaggccguuaggccGaa Acgugca B





1887
GUGCCU U GGGUGG
2577
20698
HBV-1887 Rz-6 allyl stab1 (6/4)
cscsascscc cUGAuGaggccguuaggccGaa Aggcac B





1607
GCACGU C GCAUGG
2374
20699
HBV-1607 Rz-6 allyl stab1 (6/3)
cscsasusgc cUGAuGaggcguuagccGaa Acgugc B





1607
UGCACGU C GCAUGGA
2576
20700
HBV-1607 Rz-7 allyl stab1 (7/3)
uscscsasugc cUGAuGaggcguuagccGaa Acgugca B





1887
GUGCCU U GGGUGG
2577
20701
HBV-1887 Rz-6 allyl stab1 (6/3)
cscsascscc cUGAuGaggcguuagccGaa Aggcac B





1887
UGUGCCU U GGGUGGC
2420
20702
HBV-1887 Rz-7 allyl stab1 (7/3)
gscscsasccc cUGAuGaggcguuagccGaa Aggcaca B





313
CCAAAAU U CGCAGUC
2346
22798
HBV-313 Rz-7 Ome stab1
gacugcg CUGAUGAggccguuaggccGAA Auuuugg B
11184





408
UCUUCCU C UGCAUCC
2349
22799
HBV-408 Rz-7 Ome stab1
ggaugca CUGAUGAggccguuaggccGAA Aggaaga B
11185





1756
AGGAGGU U AGGUUAA
2353
22800
HBV-1756 Rz-7 Ome stab1
uuaaccu CUGAUGAggccguuaggccGAA Accuccu B
11186





10
CUCCACC A CUUUCCA
2356
22770
HBV-10 CHz-7 Ome stab1
uggaaag CUGAUGAggccguuaggccGAA Iguggag B
11187





335
UCCAGUC A CUCACCA
2357
22771
HBV-335 CHz-7 Ome stab1
uggugag CUGAUGAggccguuaggccGAA Iacugga B
11188





273
CUUCUCU C AAUUUUC
2399

22645
HBV-273 Rz-7 allyl stab1 (7/3-GUUA)
gsasasasauu cUGAuGagccguuaggcGaa Agagaag B
11189





273
CUUCUCU C AAUUUUC
2399
22646
HBV-273 Rz-7 allyl stab1 (7/4-GUUA)
gsasasasauu cUGAuGaggccguuaggccGaa Agagaag B
11190





273
CUUCUCU C AAUUUUC
2399
22648
HBV-273 Rz-7 allyl stab1 (7/3-GAAA)
gsasasasauu cUGAuGagccgaaaggcGaa Agagaag B
11191





273
CUUCUCU C AAUUUUC
2578
22650
HBV-273 Rz-7 allyl stab1 (7/4-GAAA)
gsasasasauu cUGAuGaggccgaaaggccGaa Agagaag B
11192





273
UUCUCU C AAUUUU

22644
HBV-273 Rz-6 allyl stab1 (6/3-GUUA)
asasasasuu cUGAuGagccguuaggcGaa Agagaa B
11193





273
UUCUCU C AAUUUU

22647
HBV-273 Rz-6 allyl stab1 (6/3-GAAA)
asasasasuu cUGAuGagccgaaaggcGaa Agagaa B
11194





273
UUCUCU C AAUUUU
2579
22649
HBV-273 Rz-6 allyl stab1 (6/4-GAAA)
asasasasuu cUGAuGaggccgaaaggccGaa Agagaa B
11195





350
ACCUGUU G UCCUCCA
2580
22714
HBV-350 GCl.Rz-7 5ribo stab3
uggagga uGAUg gcauGcacuaugc gCg aacaggu B
11196





1253
CCUUUGU G UCUCCUC
2581
22715
HBV-1253 GCl.Rz-7 5ribo stab3
gaggaga uGAUg gcauGcacuaugc gCg acaaagg B
11197





1856
UGUUCAU G UCCUACU
2582
22716
HBV-1856 GCl.Rz-7 5ribo stab3
aguagga uGAUg gcauGcacuaugc gCg augaaca B
11198





1966
GCCUUCU G ACUUCUU
2583
22717
HBV-1966 GCl.Rz-7 5ribo stab3
aagaagu uGAUg gcauGcacuaugc gCg agaaggc B
11199





3132
UCCUCCU G CCUCCAC
2584
22718
HBV-3132 GCl.Rz-7 5ribo stab3
guggagg uGAUg gcauGcacuaugc gCg aggagga B
11200





332
AUCUCCA G UCACUCA
2579
22742
HBV-332 Zin.Rz-7 amino stab4
ugaguga gccgaaaggCgagugaGGuCu uggagau B
11201





350
ACCUGUU G UCCUCCA
2585
22743
HBV-350 Zin.Rz-7 amino stab4
uggagga gccgaaaggCgagugaGGuCu aacaggu B
11202





410
UUCCUCU G CAUCCUG
2580
22744
HBV-410 Zin.Rz-7 amino stab4
caggaug gccgaaaggCgagugaGGuCu agaggaa B
11203





1253
CCUUUGU G UCUCCUC
2586
22745
HBV-1253 Zin.Rz-7 amino stab4
gaggaga gccgaaaggCgagugaGGuCu acaaagg B
11204





1754
GGAGGAG G UUAGGUU
2587
22746
HBV-1754 Zin.Rz-7 amino stab4
aaccuaa gccgaaaggCgagugaGGuCu cuccucc B
11205





407
AUCUUCC U CUGCAUC
2588
22772
HBV-407 CHz-7 Ome stab1
gaugcag CUGAUGAggccguuaggccGAA Igaagau B
11206





1848
UCAUCUC A UGUUCAU
2589
22773
HBV-1848 CHz-7 Ome stab1
augaaca CUGAUGAggccguuaggccGAA Iagauga B
11207





3124
GCAGCUC C UCCUCCU
2590
22774
HBV-3124 CHz-7 Ome stab1
aggagga CUGAUGAggccguuaggccGAA Iagcugc B
11208





2165
GUCAGCU A UGUCAAC
2591
22801
HBV-2165 Rz-7 Ome stab1
guugaca CUGAUGAggccguuaggccGAA Agcugac B
11209





2706
CCGUAUU A UCCAGAG
2579
22802
HBV-2706 Rz-7 Ome stab1
cucugga CUGAUGAggccguuaggccGAA Aauacgg B
11210





350
ACCUGUU G UCCUCCA
2584
22966
HBV-350 Dz-7 stab3
uggagga GGCTAGCTACAACGA aacaggu B
11211





332
AUCUCCA G UCACUCA
2592
22967
HBV-332 Dz-7 stab3
ugaguga GGCTAGCTACAACGA uggagau B
11212





1840
CUGCCUA A UCAUCUC
2593
22968
HBV-1840 Dz-7 stab3
gagauga GGCTAGCTACAACGA uaggcag B
11213





358
UCCUCCA A UUUGUCC
2580
22969
HBV-358 Dz-7 stab3
ggacaaa GGCTAGCTACAACGA uggagga B
11214





1253
CCUUUGU G UCUCCUC
2346
22970
HBV-1253 Dz-7 stab3
gaggaga GGCTAGCTACAACGA acaaagg B
11215








20599
SAC
csgsasusgu cUAGuGacccgaaagggGaa AagaggB
10834






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








[0560]

12





TABLE XII










Group Designation and Dosage levels


for HBV transgenic mouse study














Number
Duration of


Group
Compound
Dose
of 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








[0561]

13





TABLE XIII










GROUP DESIGNATION AND DOSAGE LEVELS FOR HBV


TRANSGENIC MOUSE STUDY















Duration





Number
of


Group
Compound
Dose
of Mice
Treatment














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 (RPI.20599)
100 mg/kg/day*
15 (M or F)
14 days


8
SAC (RPI.20599)
 30 mg/kg/day*
15 (M or F)
14 days


9
SAC (RPI.20599)
 10 mg/kg/day*
15 (M or F)
14 days


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


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




PO






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








[0562]

14





TABLE XIV










HBV RT primer Decoy sequences












Seq ID



Length
Decoy Sequence
No.













4
AUUC
11216






4
CAUU
11217





4
UCAU
11218





4
UUCA
11219





5
AUUCA
11220





5
CAUUC
11221





5
UCAUU
11222





5
UUCAU
11223





6
AUUCAU
11224





6
CAUUCA
11225





6
UCAUUC
11226





6
UUCAUU
11227





7
AUUCAUU
11228





7
CAUUCAU
11229





7
UCAUUCA
11230





7
UUCAUUC
11231





8
AUUCAUUC
11232





8
CAUUCAUU
11233





8
UCAUUCAU
11234





8
UUCAUUCA
11235





9
AUUCAUUCA
11236





9
CAUUCAUUC
11237





9
UCAUUCAUU
11238





9
UUCAUUCAU
11239





10
AUUCAUUCAU
11240





10
CAUUCAUUCA
11241





10
UCAUUCAUUC
11242





10
UUCAUUCAUU
11243





11
AUUCAUUCAUU
11244





11
CAUUCAUUCAU
11245





11
UCAUUCAUUCA
11246





11
UUCAUUCAUUC
11247





12
AUUCAUUCAUUC
11248





12
CAUUCAUUCAUU
11249





12
UCAUUCAUUCAU
11250





12
UUCAUUCAUUCA
11251





13
AUUCAUUCAUUCA
11252





13
CAUUCAUUCAUUC
11253





13
UCAUUCAUUCAUU
11254





13
UUCAUUCAUUCAU
11255





14
AUUCAUUCAUUCAU
11256





14
CAUUCAUUCAUUCA
11257





14
UCAUUCAUUCAUUC
11258





14
UUCAUUCAUUCAUU
11259





15
AUUCAUUCAUUCAUU
11260





15
CAUUCAUUCAUUCAU
11261





15
UCAUUCAUUCAUUCA
11262





15
UUCAUUCAUUCAUUC
11263





16
AUUCAUUCAUUCAUUC
11264





16
CAUUCAUUCAUUCAUU
11265





16
UCAUUCAUUCAUUCAU
11266





16
UUCAUUCAUUCAUUCA
11267





17
AUUCAUUCAUUCAUUCA
11268





17
CAUUCAUUCAUUCAUUC
11269





17
UCAUUCAUUCAUUCAUU
11270





17
UUCAUUCAUUCAUUCAU
11271





18
AUUCAUUCAUUCAUUCAU
11272





18
CAUUCAUUCAUUCAUUCA
11273





18
UCAUUCAUUCAUUCAUUC
11274





18
UUCAUUCAUUCAUUCAUU
11275





19
AUUCAUUCAUUCAUUCAUU
11276





19
CAUUCAUUCAUUCAUUCAU
11277





19
UCAUUCAUUCAUUCAUUCA
11278





19
UUCAUUCAUUCAUUCAUUC
11279





20
AUUCAUUCAUUCAUUCAUUC
11280





20
CAUUCAUUCAUUCAUUCAUU
11281





20
UCAUUCAUUCAUUCAUUCAU
11282





20
UUCAUUCAUUCAUUCAUUCA
11283





21
AUUCAUUCAUUCAUUCAUUCA
11284





21
CAUUCAUUCAUUCAUUCAUUC
11285





21
UCAUUCAUUCAUUCAUUCAUU
11286





21
UUCAUUCAUUCAUUCAUUCAU
11287





22
CAUUCAUUCAUUCAUUCAUUCA
11288





22
UCAUUCAUUCAUUCAUUCAUUC
11289





22
UUCAUUCAUUCAUUCAUUCAUU
11290





23
UCAUUCAUUCAUUCAUUCAUUCA
11291





23
UUCAUUCAUUCAUUCAUUCAUUC
11292





24
UUCAUUCAUUCAUUCAUUCAUUCA
11293










[0563]

15






TABLE XV










Synthetic Nucleic acid molecules











RPI#
Alias
Sequence
SeqID














24961
HBV DR1 2′Oallyl P═S


g


s


c


s


a


s


g


s


a


s


g


s


g


s


u


s


g


s


a


s


a


s


B


11294






24997
HBV DR1 2′Oallyl P═S control


a


s


a


s


g


s


u


s


g


s


g


s


a


s


g


s


a


s


c


s


g


s


B


11295






HBV 1866-1869 1 × 2′Oallyl




24956
P═S


u


s


u


s


c


s


a


s


B


11296






HBV 1866-1869 1 × 2′Oallyl




24992
P═S control


a


s


c


s


u


s


u


s


B


11297






HBV 1866-1869 2 × 2′Oallyl




24941
P═S


u


s


u


s


c


s


a


s


u


s


u


s


c


s


a


s


B


11298






HBV 1866-1869 2 × 2′Oallyl




24959
P═S control


a


s


c


s


u


s


u


s


a


s


c


s


u


s


u


s


B


11299






HBV 1866-1869 3 × 2′Oallyl




24944
P═S


u


s


u


s


c


s


a


s


u


s


u


s


c


s


a


s


u


s


u


s


c


s


a


s


B


11300






HBV 1866-1869 3 × 2′Oallyl




24962
P═S control


a


s


c


s


u


s


u


s


a


s


c


s


u


s


u


s


a


s


c


s


u


s


u


s


B


11301






HBV 1866-1869 4 × 2′Oallyl




24945
P═S


u


s


u


s


c


s


a


s


u


s


u


s


c


s


a


s


u


s


u


s


c


s


a


s


u


s


u


s


c


s


a


s


B


11302






HBV 1866-1869 4 × 2′Oallyl




24963
P═S control


a


s


c


s


u


s


u


s


a


s


c


s


u


s


u


s


a


s


c


s


u


s


u


s


a


s


c


s


u


s


u


s


B


11303





24938
HBV 1866-1869 2′Oallyl P═S


u


s


g


s


a


s


a


s


B


11304






HBV 1866-1869 2′Oallyl P═S




24974
control


a


s


a


s


g


s


u


s


B


11305





24940
HBV 1866-1872 2′Oallyl P═S


g


s


c


s


u


s


u


s


g


s


a


s


a


s


B


11306






HBV 1866-1872 2′Oallyl P═S




24958
control


a


s


a


s


g


s


u


s


u


s


c


s


g


s


B


11307





24943
HBV 1866-1876 2′Oallyl P═S


g


s


g


s


a


s


g


s


g


s


c


s


u


s


u


s


g


s


a


s


aB


11308






HBV 1866-1876 2′Oallyl P═S




24979
control


a


s


a


s


g


s


u


s


u


s


c


s


g


s


g


s


a


s


g


s


g


s


B


11309







gsasasauu cUGAuGaggccguuaggccGaa



18341
HBV-273 UH.Rz-7 allyl stab1
Agagaag B
10887






HBV-273 UH.Rz-7 allyl stab1
asasusgsagg cUAGuGacgccguuaggcgGaa



24588
inact3 scram1 (GUUA SAC)
Aaaugaa B
11310





24929
HBV 1866-1969 2′Omethyl
ugaaB
11311






HBV 1866-1969 2′Omethyl




24965
control
aaguB
11312





24934
HBV 1866-1876 2′Omethyl
ggaggcuugaaB
11313






HBV 1866-1876 2′Omethyl




24970
control
aaguucggaggB
11314





24976
HBV 1866-1872 2′Omethyl
gcuugaaB
11315






HBV 1866-1872 2′Omethyl




24949
control
aaguucgB
11316





24952
HBV DR1 2′Omethyl
gcagaggugaaB
11317





24988
HBV DR1 2′Omethyl control
aaguggagacgB
11318





24947
HBV 1866-1869 1 × 2′Omethyl
uucaB
11319






HBV 1866-1869 1 × 2′Omethyl




24983
control
acuuB
11320





24986
HBV 1866-1869 2 × 2′Omethyl
uucauucaB
11321






HBV 1866-1869 2 × 2′Omethyl




24950
control
acuuacuuB
11322





24989
HBV 1866-1869 3 × 2′Omethyl
uucauucauucaB
11323






HBV 1866-1869 3 × 2′Omethyl




24953
control
acuuacuuacuuB
11324





24936
HBV 1866-1869 4 × 2′Omethyl
uucauucauucauucaB
11325






HBV 1866-1869 4 × 2′Omethyl




24954
control
acuuacuuacuuacuuB
11326





25639
HBV 5′ EnI pos OMe P═S
B usususcsusasasgsusasasascsasgsu B
11327





25640
HBV 5′ EnI neg OMe P═S
B ascsusgsusususascsususasgsasasa B
11328





25641
HBV 5′ EnI sc OMe P═S
B asasgsusasascsuscsusasusgsususa B
11329







B





usascsasusgsasascscsusususascscscsc



25642
HBV 3′ EnI pos OMe P═S
B
11330







B gsgsgsusasasasgsgsususcsasusgsusa



25643
HBV 3′ EnI neg OMe P═S
B
11331







B





ascscsusasuscsgscscsusascsuscsusasa



25644
HBV 3′ EnI pos sc OMe P═S
B
11332







B usgsasusasgscsgsgsasusgsasgsasusu



25645
HBV 5′ EnI neg sc OMe P═S
B
11333





25646
HBV DR1 pos OMe P═s
B ususcsascscsuscsusgsc B
11334





25651
HBV 5′ EnI pos Oallyl P═S


B u


s


u


s


u


s


c


s


u


s


a


s


a


s


g


s


u


s


a


s


a


s


a


s


c


s


a


s


g


s


u B


11335





25652
HBV 5′ EnI neg Oallyl P═S


B a


s


c


s


u


s


g


s


u


s


u


s


u


s


a


s


c


s


u


s


u


s


a


s


g


s


a


s


a


s


a B


11336





25653
HBV 5′ EnI sc Oallyl P═S


B a


s


a


s


g


s


u


s


a


s


a


s


c


s


u


s


c


s


u


s


a


s


u


s


g


s


u


s


u


s


a B


11337









B









u


s


a


s


c


s


a


s


u


s


g


s


a


s


a


s


c


s


c


s


u


s


u


s


u


s


a


s


c


s


c


s


c


s


c





25654
HBV 3′ EnI pos Oallyl P═S


B


11338









B g


s


g


s


g


s


u


s


a


s


a


s


a


s


g


s


g


s


u


s


u


s


c


s


a


s


u


s


g


s


u


s


a





25655
HBV 3′ EnI neg Oallyl P═S


B


11339









B









a


s


c


s


c


s


u


s


a


s


u


s


c


s


g


s


c


s


c


s


u


s


a


s


c


s


u


s


c


s


u


s


a


s


a





25656
HBV 3′ EnI pos sc Oallyl P═S


B


11340









B u


s


g


s


a


s


u


s


a


s


g


s


c


s


g


s


g


s


a


s


u


s


g


s


a


s


g


s


a


s


u


s


u





25657
HBV 5′ EnI neg sc Oallyl P═S


B


11341





25658
HBV DR1 pos Oallyl P═S


B u


s


u


s


c


s


a


s


c


s


c


s


u


s


c


s


u


s


g


s


c B


11342








a, g, c, u
= all 2′-O-allyl





a, g, c, u = 2′-O-methyl








U


 = 2′-C-allyl Uridine





S = phosphorothioate




B = inverted deoxyabasic








[0564]

16





TABLE XVI










Comparison of Tumor Weight to HBV


DNA concentration in mice


inoculated with HepG2.2.15 cells









Time point
HBV DNA
Tumor weight


(days)
copies/mL serum
(milligrams)












1
Below detection
No tumor


1
Below detection
No tumor


1
Below detection
No tumor


1
Below detection
No tumor


7
Below detection
No tumor


7
Below detection
No tumor


7
Below detection
No tumor


7
Below detection
No tumor


14
Below detection
No tumor


14
Below detection
No tumor


14
Below detection
No tumor


14
Below detection
No tumor


35
  356
 33


35
125083
 167


35
  578
No tumor


35
  386
 56


42
  493
No tumor


42
114431
 790


42
 94025
 359


42
111882
 647


49
189885
 816


49
Below detection
No tumor


49
  293
 90


49
 41477
2521










[0565]

17





TABLE XVII










Comparison of Tumor Weight to


HBV DNA concentration in mice


inoculated with G418 resistant HepG2.2.15 cells









Time point
HBV DNA copies/mL
Tumor weight


(days)
serum
(milligrams)












37
7000
1120.0


37
no sample
no sample


37
400000
1962.3


37
26000
558.5


37
380000
2286.0


37
100
317.2


37
52000
1429.0


37
100
427.4


37
26000
813.2


37
1400
631.6


37
186000
1101.5


37
134000
1573.0


37
17800
1040.0


37
16600
1327.2


37
8200
275.7


37
68000
632.8


37
24000
1090.0


37
58000
1082.7


37
12400
1116.3


37
100
763.3










[0566]

18






TABLE XVIII










HCV DNAzyme and Substrate Sequence














SEQ

SEQ



Pos
Substrate
ID
DNAZYME
ID















10
UGGGGGCG A CACUCCAC
2594
GTGGAGTG GGCTAGCTACAACGA CGCCCCCA
11343






12
GGGGCGAC A CUCCACCA
2595
TGGTGGAG GCCTAGCTACAACGA GTCGCCCC
11344





17
GACACUCC A CCAUAGAU
2596
ATCTATGG GGCTAGCTACAACGA CGAGTGTC
11345





20
ACUCCACC A UAGAUCAC
2597
GTGATCTA GGCTAGCTACAACGA GGTGGAGT
11346





24
CACCAUAG A UCACUCCC
2598
GGGAGTGA GGCTAGCTACAACGA CTATGGTG
11347





27
CAUAGAUC A CUCCCCUG
2599
CAGGGGAG GGCTAGCTACAACGA GATCTATG
11348





35
ACUCCCCU G UGAGGAAC
2600
GTTCCTCA GGCTAGCTACAACGA AGGGGAGT
11349





42
UGUGAGGA A CUACUGUC
2601
GACAGTAG GGCTAGCTACAACGA TCCTCACA
11350





45
GAGGAACU A CUGUCUUC
2602
GAAGACAG GGCTAGCTACAACGA AGTTCCTC
11351





48
GAACUACU G UCUUCACG
2603
CGTGAAGA GGCTAGCTACAACGA AGTAGTTC
11352





54
CUGUCUUC A CGCAGAAA
2604
TTTCTGCG GGCTAGCTACAACGA GAAGACAG
11353





56
GUCUUCAC G CAGAAAGC
2605
GCTTTCTG GGCTAGCTACAACGA GTGAAGAC
11354





63
CGCAGAAA G CGUCUAGC
2606
GCTAGACG GGCTAGCTACAACGA TTTCTGCG
11355





65
CAGAAAGC G UCUAGCCA
2607
TGGCTAGA GGCTAGCTACAACGA GCTTTCTG
11356





70
AGCGUCUA G CCAUGGCG
2608
CGCCATGG GGCTAGCTACAACGA TAGACGCT
11357





73
GUCUAGCC A UGGCGUUA
2609
TAACGCCA GGCTAGCTACAACGA GGCTAGAC
11358





76
UAGCCAUG G CGUUAGUA
2610
TACTAACG GGCTAGCTACAACGA CATGGCTA
11359





78
GCCAUGGC G UUAGUAUG
2611
CATACTAA GGCTAGCTACAACGA GCCATGGC
11360





82
UGGCGUUA G UAUGAGUG
2612
CACTCATA GGCTAGCTACAACGA TAACGCCA
11361





84
GCGUUAGU A UGAGUGUC
2613
GACACTCA GGCTAGCTACAACGA ACTAACGC
11362





88
UAGUAUGA G UGUCGUGC
2614
GCACGACA GGCTAGCTACAACGA TCATACTA
11363





90
GUAUGAGU G UCGUGCAG
2615
CTGCACGA GGCTAGCTACAACGA ACTCATAC
11364





93
UGAGUGUC G UGCAGCCU
2616
AGGCTGCA GGCTAGCTACAACGA GACACTCA
11365





95
AGUGUCGU G CAGCCUCC
2617
GGAGGCTG GGCTAGCTACAACGA ACGACACT
11366





98
GUCGUGCA G CCUCCAGG
2618
CCTGGAGG GGCTAGCTACAACGA TGCACGAC
11367





107
CCUCCAGG A CCCCCCCU
2619
AGGGGGGG GGCTAGCTACAACGA CCTGGAGG
11368





125
CCGGGAGA G CCAUAGUG
2620
CACTATGG GGCTAGCTACAACGA TCTCCCGG
11369





128
GGAGAGCC A UAGUGGUC
2621
GACCACTA GGCTAGCTACAACGA GGCTCTCC
11370





131
GAGCCAUA G UGGUCUGC
2622
GCAGACCA GGCTAGCTACAACGA TATGGCTC
11371





134
CCAUAGUG G UCUGCGGA
2623
TCCGCAGA GGCTAGCTACAACGA CACTATGG
11372





138
AGUGGUCU G CGGAACCG
2624
CGGTTCCG GGCTAGCTACAACGA AGACCACT
11373





143
UCUGCGGA A CCGGUGAG
2625
CTCACCGG GGCTAGCTACAACGA TCCGCAGA
11374





147
CGGAACCG G UGAGUACA
2626
TGTACTCA GGCTAGCTACAACGA CGGTTCCG
11375





151
ACCGGUGA G UACACCGG
2627
CCGGTGTA GGCTAGCTACAACGA TCACCGGT
11376





153
CGGUGAGU A CACCGGAA
2628
TTCCGGTG GGCTAGCTACAACGA ACTCACCG
11377





155
GUGAGUAC A CCGGAAUU
2629
AATTCCGG GGCTAGCTACAACGA GTACTCAC
11378





161
ACACCGGA A UUGCCAGG
2630
CCTGGCAA GGCTAGCTACAACGA TCCGGTGT
11379





164
CCGGAAUU G CCAGGACG
2631
CGTCCTGG GGCTAGCTACAACGA AATTCCGG
11380





170
UUGCCAGG A CGACCGGG
2632
CCCGGTCG GGCTAGCTACAACGA CCTGGCAA
11381





173
CCAGGACG A CCGGGUCC
2633
GGACCCGG GGCTAGCTACAACGA CGTCCTGG
11382





178
ACGACCGG G UCCUUUCU
2634
AGAAAGGA GGCTAGCTACAACGA CCGGTCGT
11383





190
UUUCUUGG A UCAACCCG
2635
CGGGTTGA GGCTAGCTACAACGA CCAAGAAA
11384





194
UUGGAUCA A CCCGCUCA
2636
TGAGCGGG GGCTAGCTACAACGA TGATCCAA
11385





198
AUCAACCC G CUCAAUGC
2637
GCATTGAG GGCTAGCTACAACGA GGGTTGAT
11386





203
CCCGCUCA A UGCCUGGA
2638
TCCAGGCA GGCTAGCTACAACGA TGAGCGGG
11387





205
CGCUCAAU G CCUGGAGA
2639
TCTCCAGG GGCTAGCTACAACGA ATTGAGCG
11388





213
GCCUGGAG A UUUGGGCG
2640
CGCCCAAA GGCTAGCTACAACGA CTCCAGGC
11389





219
AGAUUUGG G CGUGCCCC
2641
GGGGCACG GGCTAGCTACAACGA CCAAATCT
11390





221
AUUUGGGC G UGCCCCCG
2642
CGGGGGCA GGCTAGCTACAACGA GCCCAAAT
11391





223
UUGGGCGU G CCCCCGCG
2643
CGCGGGGG GGCTAGCTACAACGA ACGCCCAA
11392





229
GUGCCCCC G CGAGACUG
2644
CAGTCTCG GGCTAGCTACAACGA GGGGGCAC
11393





234
CCCGCGAG A CUGCUAGC
2645
GCTAGCAG GGCTAGCTACAACGA CTCGCGGG
11394





237
GCGAGACU G CUAGCCGA
2646
TCGGCTAG GGCTAGCTACAACGA AGTCTCGC
11395





241
GACUGCUA G CCGAGUAG
2647
CTACTCGG GGCTAGCTACAACGA TAGCAGTC
11396





246
CUAGCCGA G UAGUGUUG
2648
CAACACTA GGCTAGCTACAACGA TCGGCTAG
11397





249
GCCGAGUA G UGUUGGGU
2649
ACCCAACA GGCTAGCTACAACGA TACTCGGC
11398





251
CGAGUAGU G UUGGGUCG
2650
CGACCCAA GGCTAGCTACAACGA ACTACTCG
11399





256
AGUGUUGG G UCGCGAAA
2651
TTTCGCGA GGCTAGCTACAACGA CCAACACT
11400





259
GUUGGGUC G CGAAAGGC
2652
GCCTTTCG GGCTAGCTACAACGA GACCCAAC
11401





266
CGCGAAAG G CCUUGUGG
2653
CCACAAGG GGCTAGCTACAACGA CTTTCGCG
11402





271
AAGGCCUU G UGGUACUG
2654
CAGTACCA GGCTAGCTACAACGA AAGGCCTT
11403





274
GCCUUGUG G UACUGCCU
2655
AGGCAGTA GGCTAGCTACAACGA CACAAGGC
11404





276
CUUGUGGU A CUGCCUGA
2656
TCAGGCAG GGCTAGCTACAACGA ACCACAAG
11405





279
GUGGUACU G CCUGAUAG
2657
CTATCAGG GGCTAGCTACAACGA AGTACCAC
11406





284
ACUGCCUG A UAGGGUGC
2658
GCACCCTA GGCTAGCTACAACGA CAGGCAGT
11407





289
CUGAUAGG G UGCUUGCG
2659
CGCAAGCA GGCTAGCTACAACGA CCTATCAG
11408





291
GAUAGGGU G CUUGCGAG
2660
CTCGCAAG GGCTAGCTACAACGA ACCCTATC
11409





295
GGGUGCUU G CGAGUGCC
2661
GGCACTCG GGCTAGCTACAACGA AAGCACCC
11410





299
GCUUGCGA G UGCCCCGG
2662
CCGGGGCA GGCTAGCTACAACGA TCGCAAGC
11411





301
UUGCGAGU G CCCCGGGA
2663
TCCCGGGG GGCTAGCTACAACGA ACTCGCAA
11412





311
CCCGGGAG G UCUCGUAG
2664
CTACGAGA GGCTAGCTACAACGA CTCCCGGG
11413





316
GAGGUCUC G UAGACCGU
2665
ACGGTCTA GGCTAGCTACAACGA GAGACCTC
11414





320
UCUCGUAG A CCGUGCAC
2666
GTGCACGG GGCTAGCTACAACGA CTACGAGA
11415





323
CGUAGACC G UGCACCAU
2667
ATGGTGCA GGCTAGCTACAACGA GGTCTACG
11416





325
UAGACCGU G CACCAUGA
2668
TCATGGTG GGCTAGCTACAACGA ACGGTCTA
11417





327
GACCGUGC A CCAUGAGC
2669
GCTCATGG GGCTAGCTACAACGA GCACGGTC
11418





330
CGUGCACC A UGAGCACG
2670
CGTGCTCA GGCTAGCTACAACGA GGTGCACG
11419





334
CACCAUGA G CACGAAUC
2671
GATTCGTG GGCTAGCTACAACGA TCATGGTG
11420





336
CCAUGAGC A CGAAUCCU
2672
AGGATTCG GGCTAGCTACAACGA GCTCATGG
11421





340
GAGCACGA A UCCUAAAC
2673
GTTTAGGA GGCTAGCTACAACGA TCGTGCTC
11422





347
AAUCCUAA A CCUCAAAG
2674
CTTTGAGG GGCTAGCTACAACGA TTAGGATT
11423





360
AAAGAAAA A CCAAACGU
2675
ACGTTTGG GGCTAGCTACAACGA TTTTCTTT
11424





365
AAAACCAA A CGUAACAC
2676
GTGTTACG GGCTAGCTACAACGA TTGGTTTT
11425





367
AACCAAAC G UAACACCA
2677
TGGTGTTA GGCTAGCTACAACGA GTTTGGTT
11426





370
CAAACGUA A CACCAACC
2678
GGTTGGTG GGCTAGCTACAACGA TACGTTTG
11427





372
AACGUAAC A CCAACCGC
2679
GCGGTTGG GGCTAGCTACAACGA GTTACGTT
11428





376
UAACACCA A CCGCCGCC
2680
GGCGGCGG GGCTAGCTACAACGA TGGTGTTA
11429





379
CACCAACC G CCGCCCAC
2681
GTGGGCGG GGCTAGCTACAACGA GGTTGGTG
11430





382
CAACCGCC G CCCACAGG
2682
CCTGTGGG GGCTAGCTACAACGA GGCGGTTG
11431





386
CGCCGCCC A CAGGACGU
2683
ACGTCCTG GGCTAGCTACAACGA GGGCGGCG
11432





391
CCCACAGG A CGUCAAGU
2684
ACTTGACG GGCTAGCTACAACGA CCTGTGGG
11433





393
CACAGGAC G UCAAGUUC
2685
GAACTTGA GGCTAGCTACAACGA GTCCTGTG
11434





398
GACGUCAA G UUCCCGGG
2686
CCCGGGAA GGCTAGCTACAACGA TTGACGTC
11435





406
GUUCCCGG G CGGUGGUC
2687
GACCACCG GGCTAGCTACAACGA CCGGGAAC
11436





409
CCCGGGCG G UGGUCAGA
2688
TCTGACCA GGCTAGCTACAACGA CGCCCGGG
11437





412
GGGCGGUG G UCAGAUCG
2689
CGATCTGA GGCTAGCTACAACGA CACCGCCC
11438





417
GUGGUCAG A UCGUUGGU
2690
ACCAACGA GGCTAGCTACAACGA CTGACCAC
11439





420
GUCAGAUC G UUGGUGGA
2691
TCCACCAA GGCTAGCTACAACGA GATCTGAC
11440





424
GAUCGUUG G UGGAGUUU
2692
AAACTCCA GGCTAGCTACAACGA CAACGATC
11441





429
UUGGUGGA G UUUACCUG
2693
CAGGTAAA GGCTAGCTACAACGA TCCACCAA
11442





433
UGGAGUUU A CCUGUUGC
2694
GCAACAGG GGCTAGCTACAACGA AAACTCCA
11443





437
GUUUACCU G UUGCCGCG
2695
CGCGGCAA GGCTAGCTACAACGA AGGTAAAC
11444





440
UACCUGUU G CCGCGCAG
2696
CTGCGCGG GGCTAGCTACAACGA AACAGGTA
11445





443
CUGUUGCC G CGCAGGGG
2697
CCCCTGCG GGCTAGCTACAACGA GGCAACAG
11446





445
GUUGCCGC G CAGGGGCC
2698
GGCCCCTG GGCTAGCTACAACGA GCGGCAAC
11447





451
GCGCAGGG G CCCCAGGU
2699
ACCTGGGG GGCTAGCTACAACGA CCCTGCGC
11448





458
GGCCCCAG G UUGGGUGU
2700
ACACCCAA GGCTAGCTACAACGA CTGGGGCC
11449





463
CAGGUUGG G UGUGCGCG
2701
CGCGCACA GGCTAGCTACAACGA CCAACCTG
11450





465
GGUUGGGU G UGCGCGCG
2702
CGCGCGCA GGCTAGCTACAACGA ACCCAACC
11451





467
UUGGGUGU G CGCGCGAC
2703
GTCGCGCG GGCTAGCTACAACGA ACACCCAA
11452





469
GGGUGUGC G CGCGACUA
2704
TAGTCGCG GGCTAGCTACAACGA GCACACCC
11453





471
GUGUGCGC G CGACUAGG
2705
CCTAGTCG GGCTAGCTACAACGA GCGCACAC
11454





474
UGCGCGCG A CUAGGAAG
2706
CTTCCTAG GGCTAGCTACAACGA CGCGCGCA
11455





483
CUAGGAAG A CUUCCGAG
2707
CTCGGAAG GGCTAGCTACAACGA CTTCCTAG
11456





491
ACUUCCGA G CGGUCGCA
2708
TGCGACCG GGCTAGCTACAACGA TCGGAAGT
11457





494
UCCGAGCG G UCGCAACC
2709
GGTTGCGA GGCTAGCTACAACGA CGCTCGGA
11458





497
GAGCGGUC G CAACCUCG
2710
CGAGGTTG GGCTAGCTACAACGA GACCGCTC
11459





500
CGGUCGCA A CCUCGUGG
2711
CCACGAGG GGCTAGCTACAACGA TGCGACCG
11460





505
GCAACCUC G UGGAAGGC
2712
GCCTTCCA GGCTAGCTACAACGA GAGGTTGC
11461





512
CGUGGAAG G CGACAACC
2713
GGTTGTCG GGCTAGCTACAACGA CTTCCACG
11462





515
GGAAGGCG A CAACCUAU
2714
ATAGGTTG GGCTAGCTACAACGA CGCCTTCC
11463





518
AGGCGACA A CCUAUCCC
2715
GGGATAGG GGCTAGCTACAACGA TGTCGCCT
11464





522
GACAACCU A UCCCCAAG
2716
CTTGGGGA GGCTAGCTACAACGA AGGTTGTC
11465





531
UCCCCAAG G CUCGCCGG
2717
CCGGCGAG GGCTAGCTACAACGA CTTGGGGA
11466





535
CAAGGCUC G CCGGCCCG
2718
CGGGCCGG GGCTAGCTACAACGA GAGCCTTG
11467





539
GCUCGCCG G CCCGAGGG
2719
CCCTCGGG GGCTAGCTACAACGA CGGCGAGC
11468





547
GCCCGAGG G CAGGGCCU
2720
AGGCCCTG GGCTAGCTACAACGA CCTCGGGC
11469





552
AGGGCAGG G CCUGGGCU
2721
AGCCCAGG GGCTAGCTACAACGA CCTGCCCT
11470





558
GGGCCUGG G CUCAGCCC
2722
GGGCTGAG GGCTAGCTACAACGA CCAGGCCC
11471





563
UGGGCUCA G CCCGGGUA
2723
TACCCGGG GGCTAGCTACAACGA TGAGCCCA
11472





569
CAGCCCGG G UACCCUUG
2724
CAAGGGTA GGCTAGCTACAACGA CCGGGCTG
11473





571
GCCCGGGU A CCCUUGGC
2725
GCCAAGGG GGCTAGCTACAACGA ACCCGGGC
11474





578
UACCCUUG G CCCCUCUA
2726
TAGAGGGG GGCTAGCTACAACGA CAAGGGTA
11475





586
GCCCCUCU A UGGCAAUG
2727
CATTGCCA GGCTAGCTACAACGA AGAGGGGC
11476





589
CCUCUAUG G CAAUGAGG
2728
CCTCATTG GGCTAGCTACAACGA CATAGAGG
11477





592
CUAUGGCA A UGAGGGCU
2729
AGCCCTCA GGCTAGCTACAACGA TGCCATAG
11478





598
CAAUGAGG G CUUAGGGU
2730
ACCCTAAG GGCTAGCTACAACGA CCTCATTG
11479





605
GGCUUAGG G UGGGCAGG
2731
CCTGCCCA GGCTAGCTACAACGA CCTAAGCC
11480





609
UAGGGUGG G CAGGAUGG
2732
CCATCCTG GGCTAGCTACAACGA CCACCCTA
11481





614
UGGGCAGG A UGGCUCCU
2733
AGGAGCCA GGCTAGCTACAACGA CCTGCCCA
11482





617
GCAGGAUG G CUCCUGUC
2734
GACAGGAG GGCTAGCTACAACGA CATCCTGC
11483





623
UGGCUCCU G UCACCCCG
2735
CGGGGTGA GGCTAGCTACAACGA AGGAGCCA
11484





626
CUCCUGUC A CCCCGCGG
2736
CCGCGGGG GGCTAGCTACAACGA GACAGGAG
11485





631
GUCACCCC G CGGCUCCC
2737
GGGAGCCG GGCTAGCTACAACGA GGGGTGAC
11486





634
ACCCCGCG G CUCCCGGC
2738
GCCGGGAG GGCTAGCTACAACGA CGCGGGGT
11487





641
GGCUCCCG G CCUAGUUG
2739
CAACTAGG GGCTAGCTACAACGA CGGGAGCC
11488





646
CCGGCCUA G UUGGGGCC
2740
GGCCCCAA GGCTAGCTACAACGA TAGGCCGG
11489





652
UAGUUGGG G CCCCACGG
2741
CCGTGGGG GGCTAGCTACAACGA CCCAACTA
11490





657
GGGGCCCC A CGGACCCC
2742
GGGGTCCG GGCTAGCTACAACGA GGGGCCCC
11491





661
CCCCACGG A CCCCCGGC
2743
GCCGGGGG GGCTAGCTACAACGA CCGTGGGG
11492





668
GACCCCCG G CGUAGGUC
2744
GACCTACG GGCTAGCTACAACGA CGGGGGTC
11493





670
CCCCCGGC G UAGGUCGC
2745
GCGACCTA GGCTAGCTACAACGA GCCGGGGG
11494





674
CGGCGUAG G UCGCGUAA
2746
TTACGCGA GGCTAGCTACAACGA CTACGCCG
11495





677
CGUAGGUC G CGUAACUU
2747
AAGTTACG GGCTAGCTACAACGA GACCTACG
11496





679
UAGGUCGC G UAACUUGG
2748
CCAAGTTA GGCTAGCTACAACGA GCGACCTA
11497





682
GUCGCGUA A CUUGGGUA
2749
TACCCAAG GGCTAGCTACAACGA TACGCGAC
11498





688
UAACUUGG G UAAGGUCA
2750
TGACCTTA GGCTAGCTACAACGA CCAAGTTA
11499





693
UGGGUAAG G UCAUCGAU
2751
ATCGATGA GGCTAGCTACAACGA CTTACCCA
11500





696
GUAAGGUC A UCGAUACC
2752
GGTATCGA GGCTAGCTACAACGA GACCTTAC
11501





700
GGUCAUCG A UACCCUCA
2753
TGAGGGTA GGCTAGCTACAACGA CGATGACC
11502





702
UCAUCGAU A CCCUCACA
2754
TGTGAGGG GGCTAGCTACAACGA ATCGATGA
11503





708
AUACCCUC A CAUGCGGC
2755
GCCGCATG GGCTAGCTACAACGA GAGGGTAT
11504





710
ACCCUCAC A UGCGGCUU
2756
AAGCCGCA GGCTAGCTACAACGA GTGAGGGT
11505





712
CCUCACAU G CGGCUUCG
2757
CGAAGCCG GGCTAGCTACAACGA ATGTGAGG
11506





715
CACAUGCG G CUUCGCCG
2758
CGGCGAAG GGCTAGCTACAACGA CGCATGTG
11507





720
GCGGCUUC G CCGACCUC
2759
GAGGTCGG GGCTAGCTACAACGA GAAGCCGC
11508





724
CUUCGCCG A CCUCAUGG
2760
CCATGAGG GGCTAGCTACAACGA CGGCGAAG
11509





729
CCGACCUC A UGGGGUAC
2761
GTACCCCA GGCTAGCTACAACGA GAGGTCGG
11510





734
CUCAUGGG G UACAUUCC
2762
GGAATGTA GGCTAGCTACAACGA CCCATGAG
11511





736
CAUGGGGU A CAUUCCGC
2763
GCGGAATG GGCTAGCTACAACGA ACCCCATG
11512





738
UGGGGUAC A UUCCGCUC
2764
GAGCGGAA GGCTAGCTACAACGA GTACCCCA
11513





743
UACAUUCC G CUCGUCGG
2765
CCGACGAG GGCTAGCTACAACGA GGAATGTA
11514





747
UUCCGCUC G UCGGCGCC
2766
GGCGCCGA GGCTAGCTACAACGA GAGCGGAA
11515





751
GCUCGUCG G CGCCCCCU
2767
AGGGGGCG GGCTAGCTACAACGA CGACGAGC
11516





753
UCGUCGGC G CCCCCUUG
2768
CAAGGGGG GGCTAGCTACAACGA GCCGACGA
11517





766
CUUGGGAG G CACUGCCA
2769
TGGCAGTG GGCTAGCTACAACGA CTCCCAAG
11518





768
UGGGAGGC A CUGCCAGG
2770
CCTGGCAG GGCTAGCTACAACGA GCCTCCCA
11519





771
GAGGCACU G CCAGGGCC
2771
GGCCCTGG GGCTAGCTACAACGA AGTGCCTC
11520





777
CUGCCAGG G CCCUGGCG
2772
CGCCAGGG GGCTAGCTACAACGA CCTGGCAG
11521





783
GGGCCCUG G CGCAUGGC
2773
GCCATGCG GGCTAGCTACAACGA CAGGGCCC
11522





785
GCCCUGGC G CAUGGCGU
2774
ACGCCATG GGCTAGCTACAACGA GCCAGGGC
11523





787
CCUGGCGC A UGGCGUCC
2775
GGACGCCA GGCTAGCTACAACGA GCGCCAGG
11524





790
GGCGCAUG G CGUCCGGG
2776
CCCGGACG GGCTAGCTACAACGA CATGCGCC
11525





792
CGCAUGGC G UCCGGGUU
2777
AACCCGGA GGCTAGCTACAACGA GCCATGCG
11526





798
GCGUCCGG G UUCUGGAA
2778
TTCCAGAA GGCTAGCTACAACGA CCGGACGC
11527





808
UCUGGAAG A CGGCGUGA
2779
TCACGCCG GGCTAGCTACAACGA CTTCCAGA
11528





811
GGAAGACG G CGUGAACU
2780
AGTTCACG GGCTAGCTACAACGA CGTCTTCC
11529





813
AAGACGGC G UGAACUAU
2781
ATAGTTCA GGCTAGCTACAACGA GCCGTCTT
11530





817
CGGCGUGA A CUAUGCAA
2782
TTGCATAG GGCTAGCTACAACGA TCACGCCG
11531





820
CGUGAACU A UGCAACAG
2783
CTGTTGCA GGCTAGCTACAACGA AGTTCACG
11532





822
UGAACUAU G CAACAGGG
2784
CCCTGTTG GGCTAGCTACAACGA ATAGTTCA
11533





825
ACUAUGCA A CAGGGAAU
2785
ATTCCCTG GGCTAGCTACAACGA TGCATAGT
11534





832
AACAGGGA A UCUGCCCG
2786
CGGGCAGA GGCTAGCTACAACGA TCCCTGTT
11535





836
GGGAAUCU G CCCGGUUG
2787
CAACCGGG GGCTAGCTACAACGA AGATTCCC
11536





841
UCUGCCCG G UUGCUCUU
2788
AAGAGCAA GGCTAGCTACAACGA CGGGCAGA
11537





844
GCCCGGUU G CUCUUUCU
2789
AGAAAGAG GGCTAGCTACAACGA AACCGGGC
11538





855
CUUUCUCU A UCUUCCUC
2790
GAGGAAGA GGCTAGCTACAACGA AGAGAAAG
11539





867
UCCUCUUG G CUCUGCUG
2791
CAGCAGAG GGCTAGCTACAACGA CAAGAGGA
11540





872
UUGGCUCU G CUGCCCUG
2792
CAGGGCAG GGCTAGCTACAACGA AGAGCCAA
11541





875
GCUCUGCU G CCCUGUCU
2793
AGACAGGG GGCTAGCTACAACGA AGCAGAGC
11542





880
GCUGCCCU G UCUGACCA
2794
TGGTCAGA GGCTAGCTACAACGA AGGGCAGC
11543





885
CCUGUCUG A CCAUCCCA
2795
TGGGATGG GGCTAGCTACAACGA CAGACAGG
11544





888
GUCUGACC A UCCCAGCC
2796
GGCTGGGA GGCTAGCTACAACGA GGTCAGAC
11545





894
CCAUCCCA G CCUCCGCU
2797
AGCGGAGG GGCTAGCTACAACGA TGGGATGG
11546





900
CAGCCUCC G CUUAUGAG
2798
CTCATAAG GGCTAGCTACAACGA GGAGGCTG
11547





904
CUCCGCUU A UGAGGUGU
2799
ACACCTCA GGCTAGCTACAACGA AAGCGGAG
11548





909
CUUAUGAG G UGUGCAAC
2800
GTTGCACA GGCTAGCTACAACGA CTCATAAG
11549





911
UAUGAGGU G UGCAACGC
2801
GCGTTGCA GGCTAGCTACAACGA ACCTCATA
11550





913
UGAGGUGU G CAACGCGU
2802
ACGCGTTG GGCTAGCTACAACGA ACACCTCA
11551





916
GGUGUGCA A CGCGUCCG
2803
CGGACGCG GGCTAGCTACAACGA TGCACACC
11552





918
UGUGCAAC G CGUCCGGG
2804
CCCGGACG GGCTAGCTACAACGA GTTGCACA
11553





920
UGCAACGC G UCCGGGCU
2805
AGCCCGGA GGCTAGCTACAACGA GCGTTGCA
11554





926
GCGUCCGG G CUGUACCA
2806
TGGTACAG GGCTAGCTACAACGA CCGGACGC
11555





929
UCCGGGCU G UACCAUGU
2807
ACATGGTA GGCTAGCTACAACGA AGCCCGGA
11556





931
CGGGCUGU A CCAUGUCA
2808
TGACATGG GGCTAGCTACAACGA ACAGCCCG
11557





934
GCUGUACC A UGUCACGA
2809
TCGTGACA GGCTAGCTACAACGA GGTACAGC
11558





936
UGUACCAU G UCACGAAC
2810
GTTCGTGA GGCTAGCTACAACGA ATGGTACA
11559





939
ACCAUGUC A CGAACGAU
2811
ATCGTTCG GGCTAGCTACAACGA GACATGGT
11560





943
UGUCACGA A CGAUUGCU
2812
AGCAATCG GGCTAGCTACAACGA TCGTGACA
11561





946
CACGAACG A UUGCUCCA
2813
TGGAGCAA GGCTAGCTACAACGA CGTTCGTG
11562





949
GAACGAUU G CUCCAACU
2814
AGTTGGAG GGCTAGCTACAACGA AATCGTTC
11563





955
UUGCUCCA A CUCAAGCA
2815
TGCTTGAG GGCTAGCTACAACGA TGGAGCAA
11564





961
CAACUCAA G CAUUGUGU
2816
ACACAATG GGCTAGCTACAACCA TTGAGTTG
11565





963
ACUCAAGC A UUGUGUAU
2817
ATACACAA GGCTAGCTACAACGA GCTTGAGT
11566





966
CAAGCAUU G UGUAUGAG
2818
CTCATACA GGCTAGCTACAACGA AATGCTTG
11567





968
AGCAUUGU G UAUGAGGC
2819
GCCTCATA GGCTAGCTACAACGA ACAATGCT
11568





970
CAUUGUGU A UGAGGCAG
2820
CTGCCTCA GGCTAGCTACAACGA ACACAATG
11569





975
UGUAUGAG G CAGAGGAC
2821
GTCCTCTG GGCTAGCTACAACGA CTCATACA
11570





982
GGCAGAGG A CAUGAUCA
2822
TGATCATG GGCTAGCTACAACGA CCTCTGCC
11571





984
CAGAGGAC A UGAUCAUG
2823
CATGATCA GGCTAGCTACAACGA GTCCTCTG
11572





987
AGGACAUG A UCAUGCAC
2824
GTGCATGA GGCTAGCTACAACGA CATGTCCT
11573





990
ACAUGAUC A UGCACACC
2825
GGTGTGCA GGCTAGCTACAACGA GATCATGT
11574





992
AUGAUCAU G CACACCCC
2826
GGGGTGTG GGCTAGCTACAACGA ATGATCAT
11575





994
GAUCAUGC A CACCCCGG
2827
CCGGGGTG GGCTAGCTACAACGA GCATGATC
11576





996
UCAUGCAC A CCCCGGGG
2828
CCCCGGGG GGCTAGCTACAACGA GTGCATGA
11577





1004
ACCCCGGG G UGCGUGCC
2829
GGCACGCA GGCTAGCTACAACGA CCCGGGGT
11578





1006
CCCGGGGU G CGUGCCCU
2830
AGGGCACG GGCTAGCTACAACGA ACCCCGGG
11579





1008
CGGGGUGC G UGCCCUGC
2831
GCAGGGCA GGCTAGCTACAACGA GCACCCCG
11580





1010
GGGUGCGU G CCCUGCGU
2832
ACGCAGGG GGCTAGCTACAACGA ACGCACCC
11581





1015
CGUGCCCU G CGUUCGGG
2833
CCCGAACG GGCTAGCTACAACGA AGGGCACG
11582





1017
UGCCCUGC G UUCGGGAG
2834
CTCCCGAA GGCTAGCTACAACGA GCAGGGCA
11583





1027
UCGGGAGA A CAACUCCU
2835
AGGAGTTG GGCTAGCTACAACGA TCTCCCGA
11584





1030
GGAGAACA A CUCCUCCC
2836
GGGAGGAG GGCTAGCTACAACGA TGTTCTCC
11585





1039
CUCCUCCC G CUGCUGGG
2837
CCCAGCAG GGCTAGCTACAACGA GGGAGGAG
11586





1042
CUCCCGCU G CUGGGUAG
2838
CTACCCAG GGCTAGCTACAACGA AGCGGGAG
11587





1047
GCUGCUGG G UAGCGCUC
2839
GAGCGCTA GGCTAGCTACAACGA CCAGCAGC
11588





1050
GCUGGGUA G CGCUCACU
2840
AGTGAGCG GGCTAGCTACAACGA TACCCAGC
11589





1052
UGGGUAGC G CUCACUCC
2841
GGAGTGAG GGCTAGCTACAACGA GCTACCCA
11590





1056
UAGCGCUC A CUCCCACG
2842
CGTGGGAG GGCTAGCTACAACGA GAGCGCTA
11591





1062
UCACUCCC A CGCUCGCG
2843
CGCGAGCG GGCTAGCTACAACGA GGGAGTGA
11592





1064
ACUCCCAC G CUCGCGGC
2844
GCCGCGAG GGCTAGCTACAACGA GTGGGAGT
11593





1068
CCACGCUC G CGGCCAGG
2845
CCTGGCCG GGCTAGCTACAACGA GAGCGTGG
11594





1071
CGCUCGCG G CCAGGAAU
2846
ATTCCTGG GGCTAGCTACAACGA CGCGAGCG
11595





1078
GGCCAGGA A UGCCAGCA
2847
TGCTGGCA GGCTAGCTACAACGA TCCTGGCC
11596





1080
CCAGGAAU G CCAGCAUC
2848
GATGCTGG GGCTAGCTACAACGA ATTCCTGG
11597





1084
GAAUGCCA G CAUCCCCA
2849
TGGGGATG GGCTAGCTACAACGA TGGCATTC
11598





1086
AUGCCAGC A UCCCCACU
2850
AGTGGGGA GGCTAGCTACAACGA GCTGGCAT
11599





1092
GCAUCCCC A CUACGACG
2851
CGTCGTAG GGCTAGCTACAACGA GGGGATGC
11600





1095
UCCCCACU A CGACGAUA
2852
TATCGTCG GGCTAGCTACAACGA AGTGGGGA
11601





1098
CCACUACG A CGAUACGG
2853
CCGTATCG GGCTAGCTACAACGA CGTAGTGG
11602





1101
CUACGACG A UACGGCGU
2854
ACGCCGTA GGCTAGCTACAACGA CGTCGTAG
11603





1103
ACGACGAU A CGGCGUCA
2855
TGACGCCG GGCTAGCTACAACGA ATCGTCGT
11604





1106
ACGAUACG G CGUCACGU
2856
ACGTGACG GGCTAGCTACAACGA CGTATCGT
11605





1108
GAUACGGC G UCACGUCG
2857
CGACGTGA GGCTAGCTACAACGA GCCGTATC
11606





1111
ACGGCGUC A CGUCGAUU
2858
AATCGACG GGCTAGCTACAACGA GACGCCGT
11607





1113
GGCGUCAC G UCGAUUUG
2859
CAAATCGA GGCTAGCTACAACGA GTGACGCC
11608





1117
UCACGUCG A UUUGCUCG
2860
CGAGCAAA GGCTAGCTACAACGA CGACGTGA
11609





1121
GUCGAUUU G CUCGUUGG
2861
CCAACGAG GGCTAGCTACAACGA AAATCGAC
11610





1125
AUUUGCUC G UUGGGGCG
2862
CGCCCCAA GGCTAGCTACAACGA GAGCAAAT
11611





1131
UCGUUGGG G CGGCUGCU
2863
AGCAGCCG GGCTAGCTACAACGA CCCAACGA
11612





1134
UUGGGGCG G CUGCUUUC
2864
GAAAGCAG GGCTAGCTACAACGA CGCCCCAA
11613





1137
GGGCGGCU G CUUUCUGC
2865
GCAGAAAG GGCTAGCTACAACGA AGCCGCCC
11614





1144
UGCUUUCU G CUCUGCUA
2866
TAGCAGAG GGCTAGCTACAACGA AGAAAGCA
11615





1149
UCUGCUCU G CUAUGUAC
2867
GTACATAG GGCTAGCTACAACGA AGAGCAGA
11616





1152
GCUCUGCU A UGUACGUG
2868
CACGTACA GGCTAGCTACAACGA AGCAGAGC
11617





1154
UCUGCUAU G UACGUGGG
2869
CCCACGTA GGCTAGCTACAACGA ATAGCAGA
11618





1156
UGCUAUGU A CGUGGGGG
2870
CCCCCACG GGCTAGCTACAACGA ACATAGCA
11619





1158
CUAUGUAC G UGGGGGAU
2871
ATCCCCCA GGCTAGCTACAACGA GTACATAG
11620





1165
CGUGGGGG A UCUCUGCG
2872
CGCAGAGA GGCTAGCTACAACGA CCCCCACG
11621





1171
GGAUCUCU G CGGAUCUG
2873
CAGATCCG GGCTAGCTACAACGA AGAGATCC
11622





1175
CUCUGCGG A UCUGUCUU
2874
AAGACAGA GGCTAGCTACAACGA CCGCAGAG
11623





1179
GCGGAUCU G UCUUCCUC
2875
GAGGAAGA GGCTAGCTACAACGA AGATCCGC
11624





1188
UCUUCCUC G UCUCUCAG
2876
CTGAGAGA GGCTAGCTACAACGA GAGGAAGA
11625





1196
GUCUCUCA G CUGUUCAC
2877
GTGAACAG GGCTAGCTACAACGA TGAGAGAC
11626





1199
UCUCAGCU G UUCACCUU
2878
AAGGTGAA GGCTAGCTACAACGA AGCTGAGA
11627





1203
AGCUGUUC A CCUUCUCG
2879
CGAGAAGG GGCTAGCTACAACGA GAACAGCT
11628





1211
ACCUUCUC G CCUCGCCG
2880
CGGCGAGG GGCTAGCTACAACGA GAGAAGGT
11629





1216
CUCGCCUC G CCGGUAUG
2881
CATACCGG GGCTAGCTACAACGA GAGGCGAG
11630





1220
CCUCGCCG G UAUGAGAC
2882
GTCTCATA GGCTAGCTACAACGA CGGCGAGG
11631





1222
UCGCCGGU A UGAGACAG
2883
CTGTCTCA GGCTAGCTACAACGA ACCGGCGA
11632





1227
GGUAUGAG A CAGUACAG
2884
CTGTACTG GGCTAGCTACAACGA CTCATACC
11633





1230
AUGAGACA G UACAGGAC
2885
GTCCTGTA GGCTAGCTACAACGA TGTCTCAT
11634





1232
GAGACAGU A CAGGACUG
2886
CAGTCCTG GGCTAGCTACAACGA ACTGTCTC
11635





1237
AGUACAGG A CUGUAAUU
2887
AATTACAG GGCTAGCTACAACGA CCTGTACT
11636





1240
ACAGGACU G UAAUUGCU
2888
AGCAATTA GGCTAGCTACAACGA AGTCCTGT
11637





1243
GGACUGUA A UUGCUCGA
2889
TCGAGCAA GGCTAGCTACAACGA TACAGTCC
11638





1246
CUGUAAUU G CUCGAUCU
2890
AGATCGAG GGCTAGCTACAACGA AATTACAG
11639





1251
AUUGCUCG A UCUAUCCC
2891
GGGATAGA GGCTAGCTACAACGA CGAGCAAT
11640





1255
CUCGAUCU A UCCCGGCC
2892
GGCCGGGA GGCTAGCTACAACGA AGATCGAG
11641





1261
CUAUCCCG G CCACGUAU
2893
ATACGTGG GGCTAGCTACAACGA CGGGATAG
11642





1264
UCCCGGCC A CGUAUCAG
2894
CTGATACG GGCTAGCTACAACGA GGCCGGGA
11643





1266
CCGGCCAC G UAUCAGGC
2895
GCCTGATA GGCTAGCTACAACGA GTGGCCGG
11644





1268
GGCCACGU A UCAGGCCA
2896
TGGCCTGA GGCTAGCTACAACGA ACGTGGCC
11645





1273
CGUAUCAG G CCAUCGCA
2897
TGCGATGG GGCTAGCTACAACGA CTGATACG
11646





1276
AUCAGGCC A UCGCAUGG
2898
CCATGCGA GGCTAGCTACAACGA GGCCTGAT
11647





1279
AGGCCAUC G CAUGGCUU
2899
AAGCCATG GGCTAGCTACAACGA GATGGCCT
11648





1281
GCCAUCGC A UGGCUUGG
2900
CCAAGCCA GGCTAGCTACAACGA GCGATGGC
11649





1284
AUCGCAUG G CUUGGGAU
2901
ATCCCAAG GGCTAGCTACAACGA CATGCGAT
11650





1291
GGCUUGGG A UAUGAUGA
2902
TCATCATA GGCTAGCTACAACGA CCCAAGCC
11651





1293
CUUGGGAU A UGAUGAUG
2903
CATCATCA GGCTAGCTACAACGA ATCCCAAG
11652





1296
GGGAUAUG A UGAUGAAU
2904
ATTCATCA GGCTAGCTACAACGA CATATCCC
11653





1299
AUAUGAUG A UGAAUUGG
2905
CCAATTCA GGCTAGCTACAACGA CATCATAT
11654





1303
GAUGAUGA A UUGGUCAC
2906
GTGACCAA GGCTAGCTACAACGA TCATCATC
11655





1307
AUGAAUUG G UCACCUAC
2907
GTAGGTGA GGCTAGCTACAACGA CAATTCAT
11656





1310
AAUUGGUC A CCUACAAC
2908
GTTGTAGG GGCTAGCTACAACGA GACCAATT
11657





1314
GGUCACCU A CAACAGCC
2909
GGCTGTTG GGCTAGCTACAACGA AGGTGACC
11658





1317
CACCUACA A CAGCCCUA
2910
TAGGGCTG GGCTAGCTACAACGA TGTAGGTG
11659





1320
CUACAACA G CCCUAGUG
2911
CACTAGGG GGCTAGCTACAACGA TGTTGTAG
11660





1326
CAGCCCUA G UGGUAUCG
2912
CGATACCA GGCTAGCTACAACGA TAGGGCTG
11661





1329
CCCUAGUG G UAUCGCAG
2913
CTGCGATA GGCTAGCTACAACGA CACTAGGG
11662





1331
CUAGUGGU A UCGCAGUU
2914
AACTGCGA GGCTAGCTACAACGA ACCACTAG
11663





1334
GUGGUAUC G CAGUUGCU
2915
AGCAACTG GGCTAGCTACAACGA GATACCAC
11664





1337
GUAUCGCA G UUGCUCCG
2916
CGGAGCAA GGCTAGCTACAACGA TGCGATAC
11665





1340
UCGCAGUU G CUCCGGAU
2917
ATCCGGAG GGCTAGCTACAACGA AACTGCGA
11666





1347
UGCUCCGG A UCCCACAA
2918
TTGTGGGA GGCTAGCTACAACGA CCGGAGCA
11667





1352
CGGAUCCC A CAAGCCGU
2919
ACGGCTTG GGCTAGCTACAACGA GGGATCCG
11668





1356
UCCCACAA G CCGUCGUG
2920
CACGACGG GGCTAGCTACAACGA TTGTGGGA
11669





1359
CACAAGCC G UCGUGGAC
2921
GTCCACGA GGCTAGCTACAACGA GGCTTGTG
11670





1362
AAGCCGUC G UGGACAUG
2922
CATGTCCA GGCTAGCTACAACGA GACGGCTT
11671





1366
CGUCGUGG A CAUGGUGG
2923
CCACCATG GGCTAGCTACAACGA CCACGACG
11672





1368
UCGUGGAC A UGGUGGCG
2924
CGCCACCA GGCTAGCTACAACGA GTCCACGA
11673





1371
UGGACAUG G UGGCGGGG
2925
CCCCGCCA GGCTAGCTACAACGA CATGTCCA
11674





1374
ACAUGGUG G CGGGGGCC
2926
GGCCCCCG GGCTAGCTACAACGA CACCATGT
11675





1380
UGGCGGGG G CCCACUGG
2927
CCAGTGGG GGCTAGCTACAACGA CCCCGCCA
11676





1384
GGGGGCCC A CUGGGGAG
2928
CTCCCCAG GGCTAGCTACAACGA GGGCCCCC
11677





1392
ACUGGGGA G UCCUGGCG
2929
CGCCAGGA GGCTAGCTACAACGA TCCCCAGT
11678





1398
GAGUCCUG G CGGGCCUU
2930
AAGGCCCG GGCTAGCTACAACGA CAGGACTC
11679





1402
CCUGGCGG G CCUUGCCU
2931
AGGCAAGG GGCTAGCTACAACGA CCGCCAGG
11680





1407
CGGGCCUU G CCUAUUAU
2932
ATAATAGG GGCTAGCTACAACGA AAGGCCCG
11681





1411
CCUUGCCU A UUAUUCCA
2933
TGGAATAA GGCTAGCTACAACGA AGGCAAGG
11682





1414
UGCCUAUU A UUCCAUGG
2934
CCATGGAA GGCTAGCTACAACGA AATAGGCA
11683





1419
AUUAUUCC A UGGUGGGG
2935
CCCCACCA GGCTAGCTACAACGA GGAATAAT
11684





1422
AUUCCAUG G UGGGGAAC
2936
GTTCCCCA GGCTAGCTACAACGA CATGGAAT
11685





1429
GGUGGGGA A CUGGGCUA
2937
TAGCCCAG GGCTAGCTACAACGA TCCCCACC
11686





1434
GGAACUGG G CUAAGGUG
2938
CACCTTAG GGCTAGCTACAACGA CCAGTTCC
11687





1440
GGGCUAAG G UGUUGAUU
2939
AATCAACA GGCTAGCTACAACGA CTTAGCCC
11688





1442
GCUAAGGU G UUGAUUGU
2940
ACAATCAA GGCTAGCTACAACGA ACCTTAGC
11689





1446
AGGUGUUG A UUGUGAUG
2941
CATCACAA GGCTAGCTACAACGA CAACACCT
11690





1449
UGUUGAUU G UGAUGCUA
2942
TAGCATCA GGCTAGCTACAACGA AATCAACA
11691





1452
UGAUUGUG A UGCUACUC
2943
GAGTAGCA GGCTAGCTACAACGA CACAATCA
11692





1454
AUUGUGAU G CUACUCUU
2944
AAGAGTAG GGCTAGCTACAACGA ATCACAAT
11693





1457
GUGAUGCU A CUCUUUGC
2945
GCAAAGAG GGCTAGCTACAACGA AGCATCAC
11694





1464
UACUCUUU G CCGGCGUU
2946
AACGCCGG GGCTAGCTACAACGA AAAGAGTA
11695





1468
CUUUGCCG G CGUUGACG
2947
CGTCAACG GGCTAGCTACAACGA CGGCAAAG
11696





1470
UUGCCGGC G UUGACGGG
2948
CCCGTCAA GGCTAGCTACAACGA GCCGGCAA
11697





1474
CGGCGUUG A CGGGGACA
2949
TGTCCCCG GGCTAGCTACAACGA CAACGCCG
11698





1480
UGACGGGG A CACCUACA
2950
TGTAGGTG GGCTAGCTACAACGA CCCCGTCA
11699





1482
ACGGGGAC A CCUACACG
2951
CGTGTAGG GGCTAGCTACAACGA GTCCCCGT
11700





1486
GGACACCU A CACGACAG
2952
CTGTCGTG GGCTAGCTACAACGA AGGTGTCC
11701





1488
ACACCUAC A CGACAGGG
2953
CCCTGTCG GGCTAGCTACAACGA GTAGGTGT
11702





1491
CCUACACG A CAGGGGGG
2954
CCCCCCTG GGCTAGCTACAACGA CGTGTAGG
11703





1500
CAGGGGGG G CGCAGGGC
2955
GCCCTGCG GGCTAGCTACAACGA CCCCCCTG
11704





1502
GGGGGGGC G CAGGGCCA
2956
TGGCCCTG GGCTAGCTACAACGA GCCCCCCC
11705





1507
GGCGCAGG G CCACACCA
2957
TGGTGTGG GGCTAGCTACAACGA CCTGCGCC
11706





1510
GCAGGGCC A CACCACUA
2958
TAGTGGTG GGCTAGCTACAACGA GGCCCTGC
11707





1512
AGGGCCAC A CCACUAGU
2959
ACTAGTGG GGCTAGCTACAACGA GTGGCCCT
11708





1515
GCCACACC A CUAGUAGG
2960
CCTACTAG GGCTAGCTACAACGA GGTGTGGC
11709





1519
CACCACUA G UAGGGUGG
2961
CCACCCTA GGCTAGCTACAACGA TAGTGGTG
11710





1524
CUAGUAGG G UGGCAUCC
2962
GGATGCCA GGCTAGCTACAACGA CCTACTAG
11711





1527
GUAGGGUG G CAUCCCUC
2963
GAGGGATG GGCTAGCTACAACGA CACCCTAC
11712





1529
AGGGUGGC A UCCCUCUU
2964
AAGAGGGA GGCTAGCTACAACGA GCCACCCT
11713





1539
CCCUCUUU A CAUCUGGA
2965
TCCAGATG GGCTAGCTACAACGA AAAGAGGG
11714





1541
CUCUUUAC A UCUGGAGC
2966
GCTCCAGA GGCTAGCTACAACGA GTAAAGAG
11715





1548
CAUCUGGA G CAUCUCAG
2967
CTGAGATG GGCTAGCTACAACGA TCCAGATG
11716





1550
UCUGGAGC A UCUCAGAA
2968
TTCTGAGA GGCTAGCTACAACGA GCTCCAGA
11717





1558
AUCUCAGA A UAUCCAGC
2969
GCTGGATA GGCTAGCTACAACGA TCTGAGAT
11718





1560
CUCAGAAU A UCCAGCUU
2970
AAGCTGGA GGCTAGCTACAACGA ATTCTGAG
11719





1565
AAUAUCCA G CUUAUUAA
2971
TTAATAAG GGCTAGCTACAACGA TGGATATT
11720





1569
UCCAGCUU A UUAACACC
2972
GGTGTTAA GGCTAGCTACAACGA AAGCTGGA
11721





1573
GCUUAUUA A CACCAACG
2973
CGTTGGTG GGCTACCTACAACGA TAATAAGC
11722





1575
UUAUUAAC A CCAACGGC
2974
GCCGTTGG GGCTAGCTACAACGA GTTAATAA
11723





1579
UAACACCA A CGGCAGCU
2975
AGCTGCCG GGCTAGCTACAACGA TGGTGTTA
11724





1582
CACCAACG G CAGCUGGC
2976
GCCAGCTG GGCTAGCTACAACGA CGTTGGTG
11725





1585
CAACGGCA G CUGGCACA
2977
TGTGCCAG GGCTAGCTACAACGA TGCCGTTG
11726





1589
GGCAGCUG G CACAUUAA
2978
TTAATGTG GGCTAGCTACAACGA CAGCTGCC
11727





1591
CAGCUGGC A CAUUAACA
2979
TGTTAATG GGCTAGCTACAACGA GCCAGCTG
11728





1593
GCUGGCAC A UUAACAGG
2980
CCTGTTAA GGCTAGCTACAACGA GTGCCAGC
11729





1597
GCACAUUA A CAGGACUG
2981
CAGTCCTG GGCTAGCTACAACGA TAATGTGC
11730





1602
UUAACAGG A CUGCCCUG
2982
CAGGGCAG GGCTAGCTACAACGA CCTGTTAA
11731





1605
ACAGGACU G CCCUGAAC
2983
GTTCAGGG GGCTAGCTACAACGA AGTCCTGT
11732





1612
UGCCCUGA A CUGCAAUG
2984
CATTGCAG GGCTAGCTACAACGA TCAGGGCA
11733





1615
CCUGAACU G CAAUGACU
2985
AGTCATTG GGCTAGCTACAACGA AGTTCAGG
11734





1618
GAACUGCA A UGACUCCC
2986
GGGAGTCA GGCTAGCTACAACGA TGCAGTTC
11735





1621
CUGCAAUG A CUCCCUCC
2987
GGAGGGAG GGCTAGCTACAACGA CATTGCAG
11736





1632
CCCUCCAA A CCGGGUUC
2988
GAACCCGG GGCTAGCTACAACGA TTGGAGGG
11737





1637
CAAACCGG G UUCAUUGC
2989
GCAATGAA GGCTAGCTACAACGA CCGGTTTG
11738





1641
CCGGGUUC A UUGCUGCA
2990
TGCAGCAA GGCTAGCTACAACGA GAACCCGG
11739





1644
GGUUCAUU G CUGCACUG
2991
CAGTGCAG GGCTAGCTACAACGA AATGAACC
11740





1647
UCAUUGCU G CACUGUUC
2992
GAACAGTG GGCTAGCTACAACGA AGCAATGA
11741





1649
AUUGCUGC A CUGUUCUA
2993
TAGAACAG GGCTAGCTACAACGA GCAGCAAT
11742





1652
GCUGCACU G UUCUAUGC
2994
GCATAGAA GGCTAGCTACAACGA AGTGCAGC
11743





1657
ACUGUUCU A UGCACACA
2995
TGTGTGCA GGCTAGCTACAACGA AGAACAGT
11744





1659
UGUUCUAU G CACACAGG
2996
CCTGTGTG GGCTAGCTACAACGA ATAGAACA
11745





1661
UUCUAUGC A CACAGGUU
2997
AACCTGTG GGCTAGCTACAACGA GCATAGAA
11746





1663
CUAUGCAC A CAGGUUCA
2998
TGAACCTG GGCTAGCTACAACGA GTGCATAG
11747





1667
GCACACAG G UUCAACUC
2999
GAGTTGAA GGCTAGCTACAACGA CTGTGTGC
11748





1672
CAGGUUCA A CUCGUCCG
3000
CGGACGAG GGCTAGCTACAACGA TGAACCTG
11749





1676
UUCAACUC G UCCGGAUG
3001
CATCCGGA GGCTAGCTACAACGA GAGTTGAA
11750





1682
UCGUCCGG A UGCCCACA
3002
TGTGGGCA GGCTAGCTACAACGA CCGGACGA
11751





1684
GUCCGGAU G CCCACAGC
3003
GCTGTGGG GGCTAGCTACAACGA ATCCGGAC
11752





1688
GGAUGCCC A CAGCGCUU
3004
AAGCGCTG GGCTAGCTACAACGA GGGCATCC
11753





1691
UGCCCACA G CGCUUGGC
3005
GCCAAGCG GGCTAGCTACAACGA TGTGGGCA
11754





1693
CCCACAGC G CUUGGCCA
3006
TGGCCAAG GGCTAGCTACAACGA GCTGTGGG
11755





1698
AGCGCUUG G CCAGCUGC
3007
GCAGCTGG GGCTAGCTACAACGA CAAGCGCT
11756





1702
CUUGGCCA G CUGCCGCU
3008
AGCGGCAG GGCTAGCTACAACGA TGGCCAAG
11757





1705
GGCCAGCU G CCGCUCCA
3009
TGGAGCGG GGCTAGCTACAACGA AGCTGGCC
11758





1708
CAGCUGCC G CUCCAUUG
3010
CAATGGAG GGCTAGCTACAACGA GGCAGCTG
11759





1713
GCCGCUCC A UUGACAAG
3011
CTTGTCAA GGCTAGCTACAACGA GGAGCGGC
11760





1717
CUCCAUUG A CAAGUUCG
3012
CGAACTTG GGCTAGCTACAACGA CAATGGAG
11761





1721
AUUGACAA G UUCGCUCA
3013
TGAGCGAA GGCTAGCTACAACGA TTGTCAAT
11762





1725
ACAAGUUC G CUCAGGGG
3014
CCCCTGAG GGCTAGCTACAACGA GAACTTGT
11763





1733
GCUCAGGG G UGGGGUCC
3015
GGACCCCA GGCTAGCTACAACGA CCCTGAGC
11764





1738
GGGGUGGG G UCCUAUCA
3016
TGATAGGA GGCTAGCTACAACGA CCCACCCC
11765





1743
GGGGUCCU A UCACCUAC
3017
GTAGGTGA GGCTAGCTACAACGA AGGACCCC
11766





1746
GUCCUAUC A CCUACACC
3018
GGTGTAGG GGCTAGCTACAACGA GATAGGAC
11767





1750
UAUCACCU A CACCGAGG
3019
CCTCGGTG GGCTAGCTACAACGA AGGTGATA
11768





1752
UCACCUAC A CCGAGGGC
3020
GCCCTCGG GGCTAGCTACAACGA GTAGGTGA
11769





1759
CACCGAGG G CCACAACU
3021
AGTTGTGG GGCTAGCTACAACGA CCTCGGTG
11770





1762
CGAGGGCC A CAACUCGG
3022
CCGAGTTG GGCTAGCTACAACGA GGCCCTCG
11771





1765
GGGCCACA A CUCGGACC
3023
GGTCCGAG GGCTAGCTACAACGA TGTGGCCC
11772





1771
CAACUCGG A CCAGAGGC
3024
GCCTCTGG GGCTAGCTACAACGA CCGAGTTG
11773





1778
GACCAGAG G CCCUAUUG
3025
CAATAGGG GGCTAGCTACAACGA CTCTGGTC
11774





1783
GAGGCCCU A UUGCUGGC
3026
GCCAGCAA GGCTAGCTACAACGA AGGGCCTC
11775





1786
GCCCUAUU G CUGGCACU
3027
AGTGCCAG GGCTAGCTACAACGA AATAGGGC
11776





1790
UAUUGCUG G CACUACGC
3028
GCGTAGTG GGCTAGCTACAACGA CAGCAATA
11777





1792
UUGCUGGC A CUACGCAC
3029
GTGCGTAG GGCTAGCTACAACGA GCCAGCAA
11778





1795
CUGGCACU A CGCACCGC
3030
GCGGTGCG GGCTAGCTACAACGA AGTGCCAG
11779





1797
GGCACUAC G CACCGCGG
3031
CCGCGGTG GGCTAGCTACAACGA GTAGTGCC
11780





1799
CACUACGC A CCGCGGCC
3032
GGCCGCGG GGCTAGCTACAACGA GCGTAGTG
11781





1802
UACGCACC G CGGCCGUG
3033
CACGGCCG GGCTAGCTACAACGA GGTGCGTA
11782





1805
GCACCGCG G CCGUGUGG
3034
CCACACGG GGCTAGCTACAACGA CGCGGTGC
11783





1808
CCGCGGCC G UGUGGUAU
3035
ATACCACA GGCTAGCTACAACGA GGCCGCGG
11784





1810
GCGGCCGU G UGGUAUCG
3036
CGATACCA GGCTAGCTACAACGA ACGGCCGC
11785





1813
GCCGUGUG G UAUCGUAC
3037
GTACGATA GGCTAGCTACAACGA CACACGGC
11786





1815
CGUGUGGU A UCGUACCC
3038
GGGTACGA GGCTAGCTACAACGA ACCACACG
11787





1818
GUGGUAUC G UACCCGCA
3039
TGCGGGTA GGCTAGCTACAACGA GATACCAC
11788





1820
GGUAUCGU A CCCGCAUC
3040
GATGCGGG GGCTAGCTACAACGA ACGATACC
11789





1824
UCGUACCC G CAUCGCAG
3041
CTGCGATG GGCTAGCTACAACGA GGGTACGA
11790





1826
GUACCCGC A UCGCAGGU
3042
ACCTGCGA GGCTAGCTACAACGA GCGGGTAC
11791





1829
CCCGCAUC G CAGGUAUG
3043
CATACCTG GGCTAGCTACAACGA GATGCGGG
11792





1833
CAUCGCAG G UAUGUGGU
3044
ACCACATA GGCTAGCTACAACGA CTGCGATG
11793





1835
UCGCAGGU A UGUGGUCC
3045
GGACCACA GGCTAGCTACAACGA ACCTGCGA
11794





1837
GCAGGUAU G UGGUCCAG
3046
CTGGACCA GGCTAGCTACAACGA ATACCTGC
11795





1840
GGUAUGUG G UCCAGUGU
3047
ACACTGGA GGCTAGCTACAACGA CACATACC
11796





1845
GUGGUCCA G UGUAUUGC
3048
GCAATACA GGCTAGCTACAACGA TGGACCAC
11797





1847
GGUCCAGU G UAUUGCUU
3049
AAGCAATA GGCTAGCTACAACGA ACTGGACC
11798





1849
UCCAGUGU A UUGCUUCA
3050
TGAAGCAA GGCTAGCTACAACGA ACACTGGA
11799





1852
AGUGUAUU G CUUCACCC
3051
GGGTGAAG GGCTAGCTACAACGA AATACACT
11800





1857
AUUGCUUC A CCCCAAGC
3052
GCTTGGGG GGCTAGCTACAACGA GAAGCAAT
11801





1864
CACCCCAA G CCCUGUUG
3053
CAACAGGG GGCTAGCTACAACGA TTGGGGTG
11802





1869
CAAGCCCU G UUGUGGUG
3054
CACCACAA GGCTAGCTACAACGA AGGGCTTG
11803





1872
GCCCUGUU G UGGUGGGG
3055
CCCCACCA GGCTAGCTACAACGA AACAGGGC
11804





1875
CUGUUGUG G UGGGGACG
3056
CGTCCCCA GGCTAGCTACAACGA CACAACAG
11805





1881
UGGUGGGG A CGACCGAC
3057
GTCGGTCG GGCTAGCTACAACGA CCCCACCA
11806





1884
UGGGGACG A CCGACCGU
3058
ACGGTCGG GGCTAGCTACAACGA CGTCCCCA
11807





1888
GACGACCG A CCGUUUCG
3059
CGAAACGG GGCTAGCTACAACGA CGGTCGTC
11808





1891
GACCGACC G UUUCGGCG
3060
CGCCGAAA GGCTAGCTACAACGA GGTCGGTC
11809





1897
CCGUUUCG G CGCCCCCA
3061
TGGGGGCG GGCTAGCTACAACGA CGAAACGG
11810





1899
GUUUCGGC G CCCCCACG
3062
CGTGGGGG GGCTAGCTACAACGA GCCGAAAC
11811





1905
GCGCCCCC A CGUAUAAC
3063
GTTATACG GGCTAGCTACAACGA GGGGGCGC
11812





1907
GCCCCCAC G UAUAACUG
3064
CAGTTATA GGCTAGCTACAACGA GTGGGGGC
11813





1909
CCCCACGU A UAACUGGG
3065
CCCAGTTA GGCTAGCTACAACGA ACGTGGGG
11814





1912
CACGUAUA A CUGGGGGG
3066
CCCCCCAG GGCTAGCTACAACGA TATACGTG
11815





1920
ACUGGGGG G CGAACGAG
3067
CTCGTTCG GGCTAGCTACAACGA CCCCCAGT
11816





1924
GGGGGCGA A CGAGACGG
3068
CCGTCTCG GGCTAGCTACAACGA TCGCCCCC
11817





1929
CGAACGAG A CGGACGUG
3069
CACGTCCG GGCTAGCTACAACGA CTCGTTCG
11818





1933
CGAGACGG A CGUGCUGC
3070
GCAGCACG GGCTAGCTACAACGA CCGTCTCG
11819





1935
AGACGGAC G UGCUGCUC
3071
GAGCAGCA GGCTAGCTACAACGA GTCCGTCT
11820





1937
ACGGACGU G CUGCUCCU
3072
AGGAGCAG GGCTAGCTACAACGA ACGTCCGT
11821





1940
GACGUGCU G CUCCUCAA
3073
TTGAGGAG GGCTAGCTACAACGA AGCACGTC
11822





1948
GCUCCUCA A CAACACGC
3074
GCGTGTTG GGCTAGCTACAACGA TGAGGAGC
11823





1951
CCUCAACA A CACGCGGC
3075
GCCGCGTG GGCTAGCTACAACGA TGTTGAGG
11824





1953
UCAACAAC A CGCGGCCG
3076
CGGCCGCG GGCTAGCTACAACGA GTTGTTGA
11825





1955
AACAACAC G CGGCCGCC
3077
GGCGGCCG GGCTAGCTACAACGA GTGTTGTT
11826





1958
AACACGCG G CCGCCGCA
3078
TGCGGCGG GGCTAGCTACAACGA CGCGTGTT
11827





1961
ACGCGGCC G CCGCAAGG
3079
CCTTGCGG GGCTAGCTACAACGA GGCCGCGT
11828





1964
CGGCCGCC G CAAGGCAA
3080
TTGCCTTG GGCTAGCTACAACGA GGCGGCCG
11829





1969
GCCGCAAG G CAACUGGU
3081
ACCAGTTG GGCTAGCTACAACGA CTTGCGGC
11830





1972
GCAAGGCA A CUGGUUCG
3082
CGAACCAG GGCTAGCTACAACGA TGCCTTGC
11831





1976
GGCAACUG G UUCGGCUG
3083
CAGCCGAA GGCTAGCTACAACGA CAGTTGCC
11832





1981
CUGGUUCG G CUGCACAU
3084
ATGTGCAG GGCTAGCTACAACGA CGAACCAG
11833





1984
GUUCGGCU G CACAUGGA
3085
TCCATGTG GGCTAGCTACAACGA AGCCGAAC
11834





1986
UCGGCUGC A CAUGGAUG
3086
CATCCATG GGCTAGCTACAACGA GCAGCCGA
11835





1988
GGCUGCAC A UGGAUGAA
3087
TTCATCCA GGCTAGCTACAACGA GTGCAGCC
11836





1992
GCACAUGG A UGAAUGGC
3088
GCCATTCA GGCTAGCTACAACGA CCATGTGC
11837





1996
AUGGAUGA A UGGCACUG
3089
CAGTGCCA GGCTAGCTACAACGA TCATCCAT
11838





1999
GAUGAAUG G CACUGGGU
3090
ACCCAGTG GGCTAGCTACAACGA CATTCATC
11839





2001
UGAAUGGC A CUGGGUUC
3091
GAACCCAG GGCTAGCTACAACGA GCCATTCA
11840





2006
GGCACUGG G UUCACCAA
3092
TTGGTGAA GGCTAGCTACAACGA CCAGTGCC
11841





2010
CUGGGUUC A CCAAGACG
3093
CGTCTTGG GGCTAGCTACAACGA GAACCCAG
11842





2016
UCACCAAG A CGUGCGGG
3094
CCCGCACG GGCTAGCTACAACGA CTTGGTGA
11843





2018
ACCAAGAC G UGCGGGGG
3095
CCCCCGCA GGCTAGCTACAACGA GTCTTGGT
11844





2020
CAAGACGU G CGGGGGCC
3096
GGCCCCCG GGCTAGCTACAACGA ACGTCTTG
11845





2026
GUGCGGGG G CCCCCCGU
3097
ACGGGGGG GGCTAGCTACAACGA CCCCGCAC
11846





2033
GGCCCCCC G UGCAACAU
3098
ATGTTGCA GGCTAGCTACAACGA GGGGGGCC
11847





2035
CCCCCCGU G CAACAUCG
3099
CGATGTTG GGCTAGCTACAACGA ACGGGGGG
11848





2038
CCCGUGCA A CAUCGGGG
3100
CCCCGATG GGCTAGCTACAACGA TGCACGGG
11849





2040
CGUGCAAC A UCGGGGGG
3101
CCCCCCGA GGCTAGCTACAACGA GTTGCACG
11850





2049
UCGGGGGG G CCGGUAAC
3102
GTTACCGG GGCTAGCTACAACGA CCCCCCGA
11851





2053
GGGGGCCG G UAACGACA
3103
TGTCGTTA GGCTAGCTACAACGA CGGCCCCC
11852





2056
GGCCGGUA A CGACACCU
3104
AGGTGTCG GGCTAGCTACAACGA TACCGGCC
11853





2059
CGGUAACG A CACCUUAA
3105
TTAAGGTG GGCTAGCTACAACGA CGTTACCG
11854





2061
GUAACGAC A CCUUAACC
3106
GGTTAAGG GGCTAGCTACAACGA GTCGTTAC
11855





2067
ACACCUUA A CCUGCCCC
3107
GGGGCAGG GGCTAGCTACAACGA TAAGGTGT
11856





2071
CUUAACCU G CCCCACGG
3108
CCGTGGGG GGCTAGCTACAACGA AGGTTAAG
11857





2076
CCUGCCCC A CGGACUGC
3109
GCAGTCCG GGCTAGCTACAACGA GGGGCAGG
11858





2080
CCCCACGG A CUGCUUCC
3110
GGAAGCAG GGCTAGCTACAACGA CCGTGGGG
11859





2083
CACGGACU G CUUCCGGA
3111
TCCGGAAG GGCTAGCTACAACGA AGTCCGTG
11860





2093
UUCCGGAA G CACCCCGA
3112
TCGGGGTG GGCTAGCTACAACGA TTCCGGAA
11861





2095
CCGGAAGC A CCCCGAGG
3113
CCTCGGGG GGCTAGCTACAACGA GCTTCCGG
11862





2103
ACCCCGAG G CCACUUAC
3114
GTAAGTGG GGCTAGCTACAACGA CTCGGGGT
11863





2106
CCGAGGCC A CUUACGCA
3115
TGCGTAAG GGCTAGCTACAACGA GGCCTCGG
11864





2110
GGCCACUU A CGCAAAGU
3116
ACTTTGCG GGCTAGCTACAACGA AAGTGGCC
11865





2112
CCACUUAC G CAAAGUGC
3117
GCACTTTG GGCTAGCTACAACGA GTAAGTGG
11866





2117
UACGCAAA G UGCGGUUC
3118
GAACCGCA GGCTAGCTACAACGA TTTGCGTA
11867





2119
CGCAAAGU G CGGUUCGG
3119
CCGAACCG GGCTAGCTACAACGA ACTTTGCG
11868





2122
AAAGUGCG G UUCGGCGC
3120
GCCCCGAA GGCTAGCTACAACGA CGCACTTT
11869





2129
GGUUCGGC G CCUUGGUU
3121
AACCAAGG GGCTAGCTACAACGA CCCGAACC
11870





2135
GGGCCUUG G UUAACACC
3122
GGTGTTAA GGCTAGCTACAACGA CAAGGCCC
11871





2139
CUUGGUUA A CACCUAGA
3123
TCTAGGTG GGCTAGCTACAACGA TAACCAAG
11872





2141
UGGUUAAC A CCUAGAUG
3124
CATCTAGG GGCTAGCTACAACGA GTTAACCA
11873





2147
ACACCUAG A UGCAUAGU
3125
ACTATGCA GGCTAGCTACAACGA CTAGGTGT
11874





2149
ACCUAGAU G CAUAGUUG
3126
CAACTATG GGCTAGCTACAACGA ATCTAGGT
11875





2151
CUAGAUGC A UAGUUGAC
3127
GTCAACTA GGCTAGCTACAACGA GCATCTAG
11876





2154
GAUGCAUA G UUGACUAC
3128
GTAGTCAA GGCTAGCTACAACGA TATGCATC
11877





2158
CAUAGUUG A CUACCCAU
3129
ATGGGTAG GGCTAGCTACAACGA CAACTATG
11878





2161
AGUUGACU A CCCAUACA
3130
TGTATGGG GGCTAGCTACAACGA AGTCAACT
11879





2165
GACUACCC A UACAGGCU
3131
AGCCTGTA GGCTAGCTACAACGA GGGTAGTC
11880





2167
CUACCCAU A CAGGCUUU
3132
AAAGCCTG GGCTAGCTACAACGA ATGGGTAG
11881





2171
CCAUACAG G CUUUGGCA
3133
TGCCAAAG GGCTAGCTACAACGA CTGTATGG
11882





2177
AGGCUUUG G CACUACCC
3134
GGGTAGTG GGCTAGCTACAACGA CAAAGCCT
11883





2179
GCUUUGGC A CUACCCCU
3135
AGGGGTAG GGCTAGCTACAACGA GCCAAAGC
11884





2182
UUGGCACU A CCCCUGCA
3136
TGCAGGGG GGCTAGCTACAACGA AGTGCCAA
11885





2188
CUACCCCU G CACUGUCA
3137
TGACAGTG GGCTAGCTACAACGA AGGGGTAG
11886





2190
ACCCCUGC A CUGUCAAU
3138
ATTGACAG GGCTAGCTACAACGA GCAGGGGT
11887





2193
CCUGCACU G UCAAUUUU
3139
AAAATTGA GGCTAGCTACAACGA AGTGCAGG
11888





2197
CACUGUCA A UUUUUCCA
3140
TGGAAAAA GGCTAGCTACAACGA TGACAGTG
11889





2205
AUUUUUCC A UCUUUAAG
3141
CTTAAAGA GGCTAGCTACAACGA GGAAAAAT
11890





2214
UCUUUAAG G UUAGGAUG
3142
CATCCTAA GGCTAGCTACAACGA CTTAAAGA
11891





2220
AGGUUAGG A UGUAUGUG
3143
CACATACA GGCTAGCTACAACGA CCTAACCT
11892





2222
GUUAGGAU G UAUGUGGG
3144
CCCACATA GGCTAGCTACAACGA ATCCTAAC
11893





2224
UAGGAUGU A UGUGGGGG
3145
CCCCCACA GGCTAGCTACAACGA ACATCCTA
11894





2226
GGAUGUAU G UGGGGGGC
3146
GCCCCCCA GGCTAGCTACAACGA ATACATCC
11895





2233
UGUGGGGG G CGUGGAGC
3147
GCTCCACG GGCTAGCTACAACGA CCCCCACA
11896





2235
UGGGGGGC G UGGAGCAC
3148
GTGCTCCA GGCTAGCTACAACGA GCCCCCCA
11897





2240
GGCGUGGA G CACAGGCU
3149
AGCCTGTG GGCTAGCTACAACGA TCCACGCC
11898





2242
CGUGGAGC A CAGGCUCA
3150
TGAGCCTG GGCTAGCTACAACGA GCTCCACG
11899





2246
GAGCACAG G CUCACCGC
3151
GCGGTGAG GGCTAGCTACAACGA CTGTGCTC
11900





2250
ACAGGCUC A CCGCCGCA
3152
TGCGGCGG GGCTAGCTACAACGA GAGCCTGT
11901





2253
GGCUCACC G CCGCAUGC
3153
GCATGCGG GGCTAGCTACAACGA GGTGAGCC
11902





2256
UCACCGCC G CAUGCAAU
3154
ATTGCATG GGCTAGCTACAACGA GGCGGTGA
11903





2258
ACCGCCGC A UGCAAUUG
3155
CAATTGCA GGCTAGCTACAACGA GCGGCGGT
11904





2260
CGCCGCAU G CAAUUGGA
3156
TCCAATTG GGCTAGCTACAACGA ATGCGGCG
11905





2263
CGCAUGCA A UUGGACUC
3157
GAGTCCAA GGCTAGCTACAACGA TGCATGCG
11906





2268
GCAAUUGG A CUCGAGGA
3158
TCCTCGAG GGCTAGCTACAACGA CCAATTGC
11907





2279
CGAGGAGA G CGUUGUGA
3159
TCACAACG GGCTAGCTACAACGA TCTCCTCG
11908





2281
AGGAGAGC G UUGUGAUU
3160
AATCACAA GGCTAGCTACAACGA GCTCTCCT
11909





2284
AGAGCGUU G UGAUUUGG
3161
CCAAATCA GGCTAGCTACAACGA AACGCTCT
11910





2287
GCGUUGUG A UUUGGAGG
3162
CCTCCAAA GGCTAGCTACAACGA CACAACGC
11911





2296
UUUGGAGG A CAGGGACA
3163
TGTCCCTG GGCTAGCTACAACGA CCTCCAAA
11912





2302
GGACAGGG A CAGAUCAG
3164
CTGATCTG GGCTAGCTACAACGA CCCTGTCC
11913





2306
AGGGACAG A UCAGAGCU
3165
AGCTCTGA GGCTAGCTACAACGA CTGTCCCT
11914





2312
AGAUCAGA G CUCAGCCC
3166
GGGCTGAG GGCTAGCTACAACGA TCTGATCT
11915





2317
AGAGCUCA G CCCGCUGC
3167
GCAGCGGG GGCTAGCTACAACGA TGAGCTCT
11916





2321
CUCAGCCC G CUGCUGUU
3168
AACAGCAG GGCTAGCTACAACGA GGGCTGAG
11917





2324
AGCCCGCU G CUGUUGUC
3169
GACAACAG GGCTAGCTACAACGA AGCGGGCT
11918





2327
CCGCUGCU G UUGUCCAC
3170
GTGGACAA GGCTAGCTACAACGA AGCAGCGG
11919





2330
CUGCUGUU G UCCACUAC
3171
GTAGTGGA GGCTAGCTACAACGA AACAGCAG
11920





2334
UGUUGUCC A CUACAGAG
3172
CTCTGTAG GGCTAGCTACAACGA GGACAACA
11921





2337
UGUCCACU A CAGAGUGG
3173
CCACTCTG GGCTAGCTACAACGA AGTGGACA
11922





2342
ACUACAGA G UGGCAAAU
3174
ATTTGCCA GGCTAGCTACAACGA TCTGTAGT
11923





2345
ACAGAGUG G CAAAUACU
3175
AGTATTTG GGCTAGCTACAACGA CACTCTGT
11924





2349
AGUGGCAA A UACUGCCC
3176
GGGCAGTA GGCTAGCTACAACGA TTGCCACT
11925





2351
UGGCAAAU A CUGCCCUG
3177
CAGGGCAG GGCTAGCTACAACGA ATTTGCCA
11926





2354
CAAAUACU G CCCUGCUC
3178
GAGCAGGG GGCTAGCTACAACGA AGTATTTG
11927





2359
ACUGCCCU G CUCCUUCA
3179
TGAAGGAG GGCTAGCTACAACGA AGGGCAGT
11928





2367
GCUCCUUC A CCACCCUA
3180
TAGGGTGG GGCTAGCTACAACGA GAAGGAGC
11929





2370
CCUUCACC A CCCUACCG
3181
CGGTAGGG GGCTAGCTACAACGA GGTGAAGG
11930





2375
ACCACCCU A CCGGCUCU
3182
AGAGCCGG GGCTAGCTACAACGA AGGGTGGT
11931





2379
CCCUACCG G CUCUGUCC
3183
GGACAGAG GGCTAGCTACAACGA CGGTAGGG
11932





2384
CCGGCUCU G UCCACUGG
3184
CCAGTGGA GGCTAGCTACAACGA AGAGCCGG
11933





2388
CUCUGUCC A CUGGUUUG
3185
CAAACCAG GGCTAGCTACAACGA GGACAGAG
11934





2392
GUCCACUG G UUUGAUCC
3186
GGATCAAA GGCTAGCTACAACGA CAGTGGAC
11935





2397
CUGGUUUG A UCCAUCUC
3187
GAGATGGA GGCTAGCTACAACGA CAAACCAG
11936





2401
UUUGAUCC A UCUCCACC
3188
GGTGGAGA GGCTAGCTACAACGA GGATCAAA
11937





2407
CCAUCUCC A CCAGAACA
3189
TGTTCTGG GGCTAGCTACAACGA GGAGATGG
11938





2413
CCACCAGA A CAUCGUGG
3190
CCACGATG GGCTAGCTACAACGA TCTGGTGG
11939





2415
ACCAGAAC A UCGUGGAC
3191
GTCCACGA GGCTAGCTACAACGA GTTCTGGT
11940





2418
AGAACAUC G UGGACGUG
3192
CACGTCCA GGCTAGCTACAACGA GATGTTCT
11941





2422
CAUCGUGG A CGUGCAAU
3193
ATTGCACG GGCTAGCTACAACGA CCACGATG
11942





2424
UCGUGGAC G UGCAAUAC
3194
GTATTGCA GGCTAGCTACAACGA GTCCACGA
11943





2426
GUGGACGU G CAAUACCU
3195
AGGTATTG GGCTAGCTACAACGA ACGTCCAC
11944





2429
GACGUGCA A UACCUGUA
3196
TACAGGTA GGCTAGCTACAACGA TGCACGTC
11945





2431
CGUGCAAU A CCUGUACG
3197
CGTACAGG GGCTAGCTACAACGA ATTGCACG
11946





2435
CAAUACCU G UACGGUGU
3198
ACACCGTA GGCTAGCTACAACGA AGGTATTG
11947





2437
AUACCUGU A CGGUGUAG
3199
CTACACCG GGCTAGCTACAACGA ACAGGTAT
11948





2440
CCUGUACG G UGUAGGGU
3200
ACCCTACA GGCTAGCTACAACGA CGTACAGG
11949





2442
UGUACGGU G UAGGGUCA
3201
TGACCCTA GGCTAGCTACAACGA ACCGTACA
11950





2447
GGUGUAGG G UCAGCGGU
3202
ACCGCTGA GGCTAGCTACAACGA CCTACACC
11951





2451
UAGGGUCA G CGGUUGUC
3203
GACAACCG GGCTAGCTACAACGA TGACCCTA
11952





2454
GGUCAGCG G UUGUCUCC
3204
GGAGACAA GGCTAGCTACAACGA CGCTGACC
11953





2457
CAGCGGUU G UCUCCUUC
3205
GAAGGAGA GGCTAGCTACAACGA AACCGCTG
11954





2466
UCUCCUUC G CAAUCAAA
3206
TTTGATTG GGCTAGCTACAACGA GAAGGAGA
11955





2469
CCUUCGCA A UCAAAUGG
3207
CCATTTGA GGCTAGCTACAACGA TGCGAAGG
11956





2474
GCAAUCAA A UGGGAGUA
3208
TACTCCCA GGCTAGCTACAACGA TTGATTGC
11957





2480
AAAUGGGA G UAUGUCCU
3209
AGGACATA GGCTAGCTACAACGA TCCCATTT
11958





2482
AUGGGAGU A UGUCCUGU
3210
ACAGGACA GGCTAGCTACAACGA ACTCCCAT
11959





2484
GGGAGUAU G UCCUGUUG
3211
CAACAGGA GGCTAGCTACAACGA ATACTCCC
11960





2489
UAUGUCCU G UUGCUUUU
3212
AAAAGCAA GGCTAGCTACAACGA AGGACATA
11961





2492
GUCCUGUU G CUUUUCCU
3213
AGGAAAAG GGCTAGCTACAACGA AACAGGAC
11962





2508
UUCUCCUG G CAGACGCG
3214
CGCGTCTG GGCTAGCTACAACGA CAGGAGAA
11963





2512
CCUGGCAG A CGCGCGCG
3215
CGCGCGCG GGCTAGCTACAACGA CTGCCAGG
11964





2514
UGGCAGAC G CGCGCGUC
3216
GACGCGCG GGCTAGCTACAACGA GTCTGCCA
11965





2516
GCAGACGC G CGCGUCUG
3217
CAGACGCG GGCTAGCTACAACGA GCGTCTGC
11966





2518
AGACGCGC G CGUCUGUG
3218
CACAGACG GGCTAGCTACAACGA GCGCGTCT
11967





2520
ACGCGCGC G UCUGUGCC
3219
GGCACAGA GGCTAGCTACAACGA GCGCGCGT
11968





2524
GCGCGUCU G UGCCUGUU
3220
AACAGGCA GGCTAGCTACAACGA AGACGCGC
11969





2526
GCGUCUGU G CCUGUUUG
3221
CAAACAGG GGCTAGCTACAACGA ACAGACGC
11970





2530
CUGUGCCU G UUUGUGGA
3222
TCCACAAA GGCTAGCTACAACGA AGGCACAG
11971





2534
GCCUGUUU G UGGAUGAU
3223
ATCATCCA GGCTAGCTACAACGA AAACAGGC
11972





2538
GUUUGUGG A UGAUGCUG
3224
CAGCATCA GGCTAGCTACAACGA CCACAAAC
11973





2541
UGUGGAUG A UGCUGUUG
3225
CAACAGCA GGCTAGCTACAACGA CATCCACA
11974





2543
UGGAUGAU G CUGUUGGU
3226
ACCAACAG GGCTAGCTACAACGA ATCATCCA
11975





2546
AUGAUGCU G UUGGUAGC
3227
GCTACCAA GGCTAGCTACAACGA AGCATCAT
11976





2550
UGCUGUUG G UAGCCCAG
3228
CTGGGCTA GGCTAGCTACAACGA CAACAGCA
11977





2553
UGUUGGUA G CCCAGGCC
3229
GGCCTGGG GGCTAGCTACAACGA TACCAACA
11978





2559
UAGCCCAG G CCGAGGCU
3230
ACCCTCGG GGCTAGCTACAACGA CTGGGCTA
11979





2565
AGGCCGAG G CUGCCCUA
3231
TAGGGCAG GGCTAGCTACAACGA CTCGGCCT
11980





2568
CCGAGGCU G CCCUAGAG
3232
CTCTAGGG GCCTAGCTACAACGA AGCCTCGG
11981





2578
CCUAGAGA A CCUGGUGG
3233
CCACCAGG GGCTAGCTACAACGA TCTCTAGG
11982





2583
AGAACCUG G UGGUCCUC
3234
GAGGACCA GGCTAGCTACAACGA CAGGTTCT
11983





2586
ACCUGGUG G UCCUCAAU
3235
ATTGAGGA GGCTAGCTACAACGA CACCAGGT
11984





2593
GGUCCUCA A UGCAGCAU
3236
ATGCTGCA GGCTAGCTACAACGA TGAGGACC
11985





2595
UCCUCAAU G CAGCAUCC
3237
GGATGCTG GGCTAGCTACAACGA ATTGAGGA
11986





2598
UCAAUGCA G CAUCCUUG
3238
CAAGGATG GGCTAGCTACAACGA TGCATTGA
11987





2600
AAUGCAGC A UCCUUGGC
3239
GCCAAGGA GGCTAGCTACAACGA GCTGCATT
11988





2607
CAUCCUUG G CCGGAGUG
3240
CACTCCGG GGCTAGCTACAACGA CAAGGATG
11989





2613
UGGCCGGA G UGCAUGGC
3241
GCCATGCA GGCTAGCTACAACGA TCCGGCCA
11990





2615
GCCGGAGU G CAUGGCAU
3242
ATGCCATG GGCTAGCTACAACGA ACTCCGGC
11991





2617
CGGAGUGC A UGGCAUCC
3243
GGATGCCA GGCTAGCTACAACGA GCACTCCG
11992





2620
AGUGCAUG G CAUCCUCU
3244
AGAGGATG GGCTAGCTACAACGA CATGCACT
11993





2622
UGCAUGGC A UCCUCUCC
3245
GGAGAGGA GGCTAGCTACAACGA GCCATGCA
11994





2637
CCUUCCUC G UGUUCUUC
3246
GAAGAACA GGCTAGCTACAACGA GAGGAAGG
11995





2639
UUCCUCGU G UUCUUCUG
3247
CAGAAGAA GGCTAGCTACAACGA ACGAGGAA
11996





2647
GUUCUUCU G UGCUGCCU
3248
AGGCAGCA GGCTAGCTACAACCA AGAAGAAC
11997





2649
UCUUCUGU G CUGCCUGG
3249
CCAGGCAG GGCTAGCTACAACGA ACAGAAGA
11998





2652
UCUGUGCU G CCUGGUAC
3250
GTACCAGG GGCTAGCTACAACGA AGCACAGA
11999





2657
GCUGCCUG G UACAUCAA
3251
TTGATGTA GGCTAGCTACAACGA CAGGCAGC
12000





2659
UGCCUGGU A CAUCAAAG
3252
CTTTGATG GGCTAGCTACAACGA ACCAGGCA
12001





2661
CCUGGUAC A UCAAAGGC
3253
GCCTTTGA GGCTAGCTACAACGA GTACCAGG
12002





2668
CAUCAAAG G CAAGCUGG
3254
CCAGCTTG GGCTAGCTACAACGA CTTTGATG
12003





2672
AAAGGCAA G CUGGUCCC
3255
GGGACCAG GGCTAGCTACAACGA TTGCCTTT
12004





2676
GCAAGCUG G UCCCUGGG
3256
CCCAGGGA GGCTAGCTACAACGA CAGCTTGC
12005





2685
UCCCUGGG G CGGCAUAU
3257
ATATGCCG GGCTAGCTACAACGA CCCAGGGA
12006





2688
CUGGGGCG G CAUAUGCU
3258
AGCATATG GGCTAGCTACAACGA CGCCCCAG
12007





2690
GGGGCGGC A UAUGCUCU
3259
AGAGCATA GGCTAGCTACAACGA GCCGCCCC
12008





2692
GGCGGCAU A UGCUCUCU
3260
AGAGAGCA GGCTAGCTACAACGA ATGCCGCC
12009





2694
CGGCAUAU G CUCUCUAC
3261
GTAGAGAG GGCTAGCTACAACGA ATATGCCG
12010





2701
UGCUCUCU A CGGCGUAU
3262
ATACGCCG GGCTAGCTACAACGA AGAGAGCA
12011





2704
UCUCUACG G CGUAUGGC
3263
GCCATACG GGCTAGCTACAACGA CGTAGAGA
12012





2706
UCUACGGC G UAUGGCCG
3264
CGGCCATA GGCTAGCTACAACGA GCCGTAGA
12013





2708
UACGGCGU A UGGCCGCU
3265
AGCGGCCA GGCTAGCTACAACGA ACGCCGTA
12014





2711
GGCGUAUG G CCGCUACU
3266
AGTAGCGG GGCTAGCTACAACGA CATACGCC
12015





2714
GUAUGGCC G CUACUCCU
3267
AGGAGTAG GGCTAGCTACAACGA GGCCATAC
12016





2717
UGGCCGCU A CUCCUGCU
3268
AGCAGGAG GGCTAGCTACAACGA AGCGGCCA
12017





2723
CUACUCCU G CUCCUGCU
3269
AGCAGGAG GGCTAGCTACAACGA AGGAGTAG
12018





2729
CUGCUCCU G CUGGCGUU
3270
AACGCCAG GGCTAGCTACAACGA AGGAGCAG
12019





2733
UCCUGCUG G CGUUACCA
3271
TGGTAACG GGCTAGCTACAACGA CAGCAGGA
12020





2735
CUGCUGGC G UUACCACC
3272
GGTGGTAA GGCTAGCTACAACGA GCCAGCAG
12021





2738
CUGGCGUU A CCACCACG
3273
CGTGGTGG GGCTAGCTACAACGA AACGCCAG
12022





2741
GCGUUACC A CCACGGGC
3274
GCCCGTGG GGCTAGCTACAACGA GGTAACGC
12023





2744
UUACCACC A CGGGCGUA
3275
TACGCCCG GGCTAGCTACAACGA GGTGGTAA
12024





2748
CACCACGG G CGUACGCC
3276
GGCGTACG GGCTAGCTACAACGA CCGTGGTG
12025





2750
CCACGGGC G UACGCCAU
3277
ATGGCGTA GGCTAGCTACAACGA GCCCGTGG
12026





2752
ACGGGCGU A CGCCAUGG
3278
CCATGGCG GGCTAGCTACAACGA ACGCCCGT
12027





2754
GGGCGUAC G CCAUGGAC
3279
GTCCATGG GGCTAGCTACAACGA GTACGCCC
12028





2757
CGUACGCC A UGGACCGG
3280
CCGGTCCA GGCTAGCTACAACGA GGCGTACG
12029





2761
CGCCAUGG A CCGGGAGA
3281
TCTCCCGG GGCTAGCTACAACGA CCATGGCG
12030





2769
ACCGGGAG A UGGCCGCA
3282
TGCGGCCA GGCTAGCTACAACGA CTCCCGGT
12031





2772
GGGAGAUG G CCGCAUCG
3283
CGATGCGG GGCTAGCTACAACGA CATCTCCC
12032





2775
AGAUGGCC G CAUCGUGC
3284
GCACGATG GGCTAGCTACAACGA GGCCATCT
12033





2777
AUGGCCGC A UCGUGCGG
3285
CCGCACGA GGCTAGCTACAACGA GCGGCCAT
12034





2780
GCCGCAUC G UGCGGAGG
3286
CCTCCGCA GGCTAGCTACAACGA GATGCGGC
12035





2782
CGCAUCGU G CGGAGGCG
3287
CGCCTCCG GGCTAGCTACAACGA ACGATGCG
12036





2788
GUGCGGAG G CGUGGUUU
3288
AAACCACG GGCTAGCTACAACGA CTCCGCAC
12037





2790
GCGGAGGC G UGGUUUUU
3289
AAAAACCA GGCTAGCTACAACGA GCCTCCGC
12038





2793
GAGGCGUG G UUUUUGUA
3290
TACAAAAA GGCTAGCTACAACGA CACGCCTC
12039





2799
UGGUUUUU G UAGGUCUA
3291
TAGACCTA GGCTAGCTACAACGA AAAAACCA
12040





2803
UUUUGUAG G UCUAGCAC
3292
GTGCTAGA GGCTAGCTACAACGA CTACAAAA
12041





2808
UAGGUCUA G CACUCUUG
3293
CAAGAGTG GGCTAGCTACAACGA TAGACCTA
12042





2810
GGUCUAGC A CUCUUGAC
3294
GTCAAGAG GGCTAGCTACAACGA GCTAGACC
12043





2817
CACUCUUG A CCUUGUCA
3295
TGACAAGG GGCTAGCTACAACGA CAAGAGTG
12044





2822
UUGACCUU G UCACCAUA
3296
TATGGTGA GGCTAGCTACAACGA AAGGTCAA
12045





2825
ACCUUGUC A CCAUACUA
3297
TAGTATGG GGCTAGCTACAACGA GACAAGGT
12046





2828
UUGUCACC A UACUACAA
3298
TTGTAGTA GGCTAGCTACAACGA GGTGACAA
12047





2830
GUCACCAU A CUACAAAG
3299
CTTTGTAG GGCTAGCTACAACGA ATGGTGAC
12048





2833
ACCAUACU A CAAAGUGU
3300
ACACTTTG GGCTAGCTACAACGA AGTATGGT
12049





2838
ACUACAAA G UGUUCCUC
3301
GAGGAACA GGCTAGCTACAACGA TTTGTAGT
12050





2840
UACAAAGU G UUCCUCGC
3302
GCGAGGAA GGCTAGCTACAACGA ACTTTGTA
12051





2847
UGUUCCUC G CUAGGCUC
3303
GAGCCTAG GGCTAGCTACAACGA GAGGAACA
12052





2852
CUCGCUAG G CUCAUAUG
3304
CATATGAG GGCTAGCTACAACGA CTAGCGAG
12053





2856
CUAGGCUC A UAUGGUGG
3305
CCACCATA GGCTAGCTACAACGA GAGCCTAG
12054





2858
AGGCUCAU A UGGUGGUU
3306
AACCACCA GGCTAGCTACAACGA ATGAGCCT
12055





2861
CUCAUAUG G UGGUUGCA
3307
TGCAACCA GGCTAGCTACAACGA CATATGAG
12056





2864
AUAUGGUG G UUGCAAUA
3308
TATTGCAA GGCTAGCTACAACGA CACCATAT
12057





2867
UGGUGGUU G CAAUACCU
3309
AGGTATTG GGCTAGCTACAACGA AACCACCA
12058





2870
UGGUUGCA A UACCUUAU
3310
ATAAGGTA GGCTAGCTACAACGA TGCAACCA
12059





2872
GUUGCAAU A CCUUAUCA
3311
TGATAAGG GGCTAGCTACAACGA ATTGCAAC
12060





2877
AAUACCUU A UCACCAGA
3312
TCTGGTGA GGCTAGCTACAACGA AAGGTATT
12061





2880
ACCUUAUC A CCAGAGCC
3313
GGCTCTGG GGCTAGCTACAACGA GATAAGGT
12062





2886
UCACCAGA G CCGAGGCG
3314
CGCCTCGG GGCTAGCTACAACGA TCTGGTGA
12063





2892
GAGCCGAG G CGCAGUUG
3315
CAACTGCG GGCTAGCTACAACGA CTCGGCTC
12064





2894
GCCGAGGC G CAGUUGCA
3316
TGCAACTG GGCTAGCTACAACGA GCCTCGGC
12065





2897
GAGGCGCA G UUGCAAGU
3317
ACTTGCAA GGCTAGCTACAACGA TGCGCCTC
12066





2900
GCGCAGUU G CAAGUGUG
3318
CACACTTG GGCTAGCTACAACGA AACTGCGC
12067





2904
AGUUGCAA G UGUGGAUC
3319
GATCCACA GGCTAGCTACAACGA TTGCAACT
12068





2906
UUGCAAGU G UGGAUCCC
3320
GGGATCCA GGCTAGCTACAACGA ACTTGCAA
12069





2910
AAGUGUGG A UCCCCCCC
3321
GGGGGGGA GGCTAGCTACAACGA CCACACTT
12070





2923
CCCCCUCA A CGUUCGGG
3322
CCCGAACG GGCTAGCTACAACGA TGAGGGGG
12071





2925
CCCUCAAC G UUCGGGGG
3323
CCCCCGAA GGCTAGCTACAACGA GTTGAGGG
12072





2936
CGGGGGGG G CGCGGUGC
3324
GCACCGCG GGCTAGCTACAACGA CCCCCCCG
12073





2938
GGGGGGGC G CGGUGCCA
3325
TGGCACCG GGCTAGCTACAACGA GCCCCCCC
12074





2941
GGGGCGCG G UGCCAUCA
3326
TGATGGCA GGCTAGCTACAACGA CGCGCCCC
12075





2943
GGCGCGGU G CCAUCAUU
3327
AATGATGG GGCTAGCTACAACGA ACCGCGCC
12076





2946
GCGGUGCC A UCAUUCUC
3328
GAGAATGA GGCTAGCTACAACGA GGCACCGC
12077





2949
GUGCCAUC A UUCUCCUC
3329
GAGCAGAA GGCTAGCTACAACGA GATGGCAC
12078





2958
UUCUCCUC A CGUGUGUG
3330
CACACACG GGCTAGCTACAACGA GAGGAGAA
12079





2960
CUCCUCAC G UGUGUGGU
3331
ACCACACA GGCTAGCTACAACGA GTGAGGAG
12080





2962
CCUCACGU G UGUGGUCC
3332
GGACCACA GGCTAGCTACAACGA ACGTGAGG
12081





2964
UCACGUGU G UGGUCCAC
3333
GTGGACCA GGCTAGCTACAACGA ACACGTGA
12082





2967
CGUGUGUG G UCCACCCA
3334
TGGGTGGA GGCTAGCTACAACGA CACACACG
12083





2971
UGUGGUCC A CCCAGAGC
3335
GCTCTGGG GGCTAGCTACAACGA GGACCACA
12084





2978
CACCCAGA G CUAAUCUU
3336
AAGATTAG GGCTAGCTACAACGA TCTGGGTG
12085





2982
CAGAGCUA A UCUUUGAC
3337
GTCAAAGA GGCTAGCTACAACGA TAGCTCTG
12086





2989
AAUCUUUG A CAUCACCA
3338
TGGTGATG GGCTAGCTACAACGA CAAAGATT
12087





2991
UCUUUGAC A UCACCAAA
3339
TTTGGTGA GGCTAGCTACAACGA GTCAAAGA
12088





2994
UUGACAUC A CCAAAAUU
3340
AATTTTGG GGCTAGCTACAACGA GATGTCAA
12089





3000
UCACCAAA A UUAUGCUC
3341
GAGCATAA GGCTAGCTACAACGA TTTGGTGA
12090





3003
CCAAAAUU A UGCUCGCC
3342
GGCGAGCA GGCTAGCTACAACGA AATTTTGG
12091





3005
AAAAUUAU G CUCGCCAU
3343
ATGGCGAG GGCTAGCTACAACGA ATAATTTT
12092





3009
UUAUGCUC G CCAUACUC
3344
GAGTATGG GGCTAGCTACAACGA GAGCATAA
12093





3012
UGCUCGCC A UACUCGGC
3345
GCCGAGTA GGCTAGCTACAACGA GGCGAGCA
12094





3014
CUCGCCAU A CUCGGCCC
3346
GGGCCGAG GGCTAGCTACAACGA ATGGCGAG
12095





3019
CAUACUCG G CCCGCUCA
3347
TGAGCGGG GGCTAGCTACAACGA CGAGTATG
12096





3023
CUCGGCCC G CUCAUGGU
3348
ACCATGAG GGCTAGCTACAACGA GGGCCGAG
12097





3027
GCCCGCUC A UGGUGCUC
3349
GAGCACCA GGCTAGCTACAACGA GAGCGGGC
12098





3030
CGCUCAUG G UGCUCCAG
3350
CTGGAGCA GGCTAGCTACAACGA CATGAGCG
12099





3032
CUCAUGGU G CUCCAGGC
3351
GCCTGGAG GGCTAGCTACAACGA ACCATGAG
12100





3039
UGCUCCAG G CUGGUAUA
3352
TATACCAG GGCTAGCTACAACGA CTGGAGCA
12101





3043
CCAGGCUG G UAUAGCAA
3353
TTGCTATA GGCTAGCTACAACGA CAGCCTGG
12102





3045
AGGCUGGU A UAGCAAAA
3354
TTTTGCTA GGCTAGCTACAACGA ACCAGCCT
12103





3048
CUGGUAUA G CAAAAGUG
3355
CACTTTTG GGCTAGCTACAACGA TATACCAG
12104





3054
UAGCAAAA G UGCCGGAC
3356
GTCCGGCA GGCTAGCTACAACGA TTTTGCTA
12105





3056
GCAAAAGU G CCGGACUU
3357
AAGTCCGG GGCTAGCTACAACGA ACTTTTGC
12106





3061
AGUGCCGG A CUUUGUGC
3358
GCACAAAG GGCTAGCTACAACGA CCGGCACT
12107





3066
CGGACUUU G UGCGGGCU
3359
AGCCCGCA GGCTAGCTACAACGA AAAGTCCG
12108





3068
GACUUUGU G CGGGCUCA
3360
TGAGCCCG GGCTAGCTACAACGA ACAAAGTC
12109





3072
UUGUGCGG G CUCAAGGG
3361
CCCTTGAG GGCTAGCTACAACGA CCGCACAA
12110





3081
CUCAAGGG G UCAUCCGU
3362
ACGGATGA GGCTAGCTACAACGA CCCTTGAG
12111





3084
AAGGGGUC A UCCGUGAA
3363
TTCACGGA GGCTAGCTACAACGA GACCCCTT
12112





3088
GGUCAUCC G UGAAUGCA
3364
TGCATTCA GGCTAGCTACAACGA GGATGACC
12113





3092
AUCCGUGA A UGCAUUUU
3365
AAAATGCA GGCTAGCTACAACGA TCACGGAT
12114





3094
CCGUGAAU G CAUUUUGG
3366
CCAAAATG GGCTAGCTACAACGA ATTCACGG
12115





3096
GUGAAUGC A UUUUGGUG
3367
CACCAAAA GGCTAGCTACAACGA GCATTCAC
12116





3102
GCAUUUUG G UGCGGAAA
3368
TTTCCGCA GGCTAGCTACAACGA CAAAATGC
12117





3104
AUUUUGGU G CGGAAAGU
3369
ACTTTCCG GGCTAGCTACAACGA ACCAAAAT
12118





3111
UGCGGAAA G UCGGUGGG
3370
CCCACCGA GGCTAGCTACAACGA TTTCCGCA
12119





3115
GAAAGUCG G UGGGGGGC
3371
GCCCCCCA GGCTAGCTACAACGA CGACTTTC
12120





3122
GGUGGGGG G CAAUAUGU
3372
ACATATTG GGCTAGCTACAACGA CCCCCACC
12121





3125
GGGGGGCA A UAUGUCCA
3373
TGGACATA GGCTAGCTACAACGA TGCCCCCC
12122





3127
GGGGCAAU A UGUCCAAA
3374
TTTGGACA GGCTAGCTACAACGA ATTGCCCC
12123





3129
GGCAAUAU G UCCAAAUG
3375
CATTTGGA GGCTAGCTACAACGA ATATTGCC
12124





3135
AUGUCCAA A UGGCCUUC
3376
GAAGGCCA GGCTAGCTACAACGA TTGGACAT
12125





3138
UCCAAAUG G CCUUCAUG
3377
CATGAAGG GGCTAGCTACAACGA CATTTGGA
12126





3144
UGGCCUUC A UGAAGUUG
3378
CAACTTCA GGCTAGCTACAACGA GAAGGCCA
12127





3149
UUCAUGAA G UUGGCCCA
3379
TCGGCCAA GGCTAGCTACAACGA TTCATGAA
12128





3153
UGAAGUUG G CCGAAUUG
3380
CAATTCGG GGCTAGCTACAACGA CAACTTCA
12129





3158
UUGGCCGA A UUGAAAGG
3381
CCTTTCAA GGCTAGCTACAACGA TCGGCCAA
12130





3166
AUUGAAAG G UACGUCCG
3382
CGGACGTA GGCTAGCTACAACGA CTTTCAAT
12131





3168
UGAAAGGU A CGUCCGUC
3383
GACGGACG GGCTAGCTACAACGA ACCTTTCA
12132





3170
AAAGGUAC G UCCGUCUA
3384
TAGACGGA GGCTAGCTACAACGA GTACCTTT
12133





3174
GUACGUCC G UCUAUGAC
3385
GTCATAGA GGCTAGCTACAACGA GGACGTAC
12134





3178
GUCCGUCU A UGACCACC
3386
GGTGGTCA GGCTAGCTACAACGA AGACGGAC
12135





3181
CGUCUAUG A CCACCUCA
3387
TGAGGTGG GGCTAGCTACAACGA CATAGACG
12136





3184
CUAUGACC A CCUCACUC
3388
GAGTGAGG GGCTAGCTACAACGA GGTCATAG
12137





3189
ACCACCUC A CUCCACUG
3389
CAGTGGAG GGCTAGCTACAACGA GAGGTGGT
12138





3194
CUCACUCC A CUGCAGGA
3390
TCCTGCAG GGCTAGCTACAACGA GGAGTGAG
12139





3197
ACUCCACU G CAGGACUG
3391
CAGTCCTG GGCTAGCTACAACGA AGTGGAGT
12140





3202
ACUGCAGG A CUGGGCCC
3392
GGGCCCAG GGCTAGCTACAACGA CCTGCAGT
12141





3207
AGGACUGG G CCCACACA
3393
TGTGTGGG GGCTAGCTACAACGA CCAGTCCT
12142





3211
CUGGGCCC A CACAGGUC
3394
GACCTGTG GGCTAGCTACAACGA GGGCCCAG
12143





3213
GGGCCCAC A CAGGUCUA
3395
TAGACCTG GGCTAGCTACAACGA GTGGGCCC
12144





3217
CCACACAG G UCUACGAG
3396
CTCGTAGA GGCTAGCTACAACGA CTGTGTGG
12145





3221
ACAGGUCU A CGAGACCU
3397
AGGTCTCG GGCTAGCTACAACGA AGACCTGT
12146





3226
UCUACGAG A CCUGGCGG
3398
CCGCCAGG GGCTAGCTACAACGA CTCGTAGA
12147





3231
GAGACCUG G CGGUAGCG
3399
CGCTACCG GGCTAGCTACAACGA CAGGTCTC
12148





3234
ACCUGGCG G UAGCGGUC
3400
GACCGCTA GGCTAGCTACAACGA CGCCAGGT
12149





3237
UGGCGGUA G CGGUCGAG
3401
CTCGACCG GGCTAGCTACAACGA TACCGCCA
12150





3240
CGGUAGCG G UCGAGCCC
3402
GGGCTCGA GGCTAGCTACAACGA CGCTACCG
12151





3245
GCGGUCGA G CCCGUCGU
3403
ACGACGGG GGCTAGCTACAACGA TCGACCGC
12152





3249
UCGAGCCC G UCGUCUUC
3404
GAAGACGA GGCTAGCTACAACGA GGGCTCGA
12153





3252
AGCCCGUC G UCUUCUCC
3405
GGAGAAGA GGCTAGCTACAACGA GACGGGCT
12154





3262
CUUCUCCG A CAUGGAAA
3406
TTTCCATG GGCTAGCTACAACGA CGGAGAAG
12155





3264
UCUCCGAC A UGGAAAUC
3407
GATTTCCA GGCTAGCTACAACGA GTCGGAGA
12156





3270
ACAUGGAA A UCAAGAUC
3408
GATCTTGA GGCTAGCTACAACGA TTCCATGT
12157





3276
AAAUCAAG A UCAUCACC
3409
GGTGATGA GGCTAGCTACAACGA CTTGATTT
12158





3279
UCAAGAUC A UCACCUGG
3410
CCAGGTGA GGCTAGCTACAACGA GATCTTGA
12159





3282
AGAUCAUC A CCUGGGGG
3411
CCCCCAGG GGCTAGCTACAACGA GATGATCT
12160





3295
GGGGGGAG A CACCGCGG
3412
CCGCGGTG GGCTAGCTACAACGA CTCCCCCC
12161





3297
GGGGAGAC A CCGCGGCG
3413
CGCCGCGG GGCTAGCTACAACGA GTCTCCCC
12162





3300
GAGACACC G CGGCGUGU
3414
ACACGCCG GGCTAGCTACAACGA GGTGTCTC
12163





3303
ACACCGCG G CGUGUGGG
3415
CCCACACG GGCTAGCTACAACGA CGCGGTGT
12164





3305
ACCGCGGC G UGUGGGGA
3416
TCCCCACA GGCTAGCTACAACGA GCCGCGGT
12165





3307
CGCGGCGU G UGGGGACA
3417
TGTCCCCA GGCTAGCTACAACGA ACGCCGCG
12166





3313
GUGUGGGG A CAUCAUUA
3418
TAATGATG GGCTAGCTACAACGA CCCCACAC
12167





3315
GUGGGGAC A UCAUUAUG
3419
CATAATGA GGCTAGCTACAACGA GTCCCCAC
12168





3318
GGGACAUC A UUAUGGGU
3420
ACCCATAA GGCTAGCTACAACGA GATGTCCC
12169





3321
ACAUCAUU A UGGGUCUA
3421
TAGACCCA GGCTAGCTACAACGA AATGATGT
12170





3325
CAUUAUGG G UCUACCUG
3422
CAGGTAGA GGCTAGCTACAACGA CCATAATG
12171





3329
AUGGGUCU A CCUGUCUC
3423
GAGACAGG GGCTAGCTACAACGA AGACCCAT
12172





3333
GUCUACCU G UCUCCGCC
3424
GGCGGAGA GGCTAGCTACAACGA AGGTAGAC
12173





3339
CUGUCUCC G CCCGAAGG
3425
CCTTCGGG GGCTAGCTACAACGA GGAGACAG
12174





3357
GGAGGGAG A UACUCCUA
3426
TAGGAGTA GGCTAGCTACAACGA CTCCCTCC
12175





3359
AGGGAGAU A CUCCUAGG
3427
CCTAGGAG GGCTAGCTACAACGA ATCTCCCT
12176





3368
CUCCUAGG A CCAGCCGA
3428
TCGGCTGG GGCTAGCTACAACGA CCTAGGAG
12177





3372
UAGGACCA G CCGACAGU
3429
ACTGTCGG GGCTAGCTACAACGA TGGTCCTA
12178





3376
ACCAGCCG A CAGUCUUG
3430
CAAGACTG GGCTAGCTACAACGA CGGCTGGT
12179





3379
AGCCGACA G UCUUGAGG
3431
CCTCAAGA GGCTAGCTACAACGA TGTCGGCT
12180





3389
CUUGAGGG G CAGGGGUG
3432
CACCCCTG GGCTAGCTACAACGA CCCTCAAG
12181





3395
GGGCAGGG G UGGCGACU
3433
AGTCGCCA GGCTAGCTACAACGA CCCTGCCC
12182





3398
CAGGGGUG G CGACUCCU
3434
AGGAGTCG GGCTAGCTACAACGA CACCCCTG
12183





3401
GGGUGGCG A CUCCUCGC
3435
GCGAGGAG GGCTAGCTACAACGA CGCCACCC
12184





3408
GACUCCUC G CGCCCAUU
3436
AATGGGCG GGCTAGCTACAACGA GAGGAGTC
12185





3410
CUCCUCGC G CCCAUUAC
3437
GTAATGGG GGCTAGCTACAACGA GCGAGGAG
12186





3414
UCGCGCCC A UUACGGCC
3438
GGCCGTAA GGCTAGCTACAACGA GGGCGCGA
12187





3417
CGCCCAUU A CGGCCUAC
3439
GTAGGCCG GGCTAGCTACAACGA AATGGGCG
12188





3420
CCAUUACG G CCUACUCC
3440
GGAGTAGG GGCTAGCTACAACGA CGTAATGG
12189





3424
UACGGCCU A CUCCCAAC
3441
GTTGGGAG GGCTAGCTACAACGA AGGCCGTA
12190





3431
UACUCCCA A CAGACGCG
3442
CGCGTCTG GGCTAGCTACAACGA TGGGAGTA
12191





3435
CCCAACAG A CGCGGGGC
3443
GCCCCGCG GGCTAGCTACAACGA CTGTTGGG
12192





3437
CAACAGAC G CGGGGCCU
3444
AGGCCCCG GGCTAGCTACAACGA GTCTGTTG
12193





3442
GACGCGGG G CCUGUUUG
3445
CAAACAGG GGCTAGCTACAACGA CCCGCGTC
12194





3446
CGGGGCCU G UUUGGCUG
3446
CAGCCAAA GGCTAGCTACAACGA AGGCCCCG
12195





3451
CCUGUUUG G CUGCAUUA
3447
TAATGCAG GGCTAGCTACAACGA CAAACAGG
12196





3454
GUUUGGCU G CAUUAUCA
3448
TGATAATG GGCTAGCTACAACGA AGCCAAAC
12197





3456
UUGGCUGC A UUAUCACC
3449
GGTGATAA GGCTAGCTACAACGA GCAGCCAA
12198





3459
GCUGCAUU A UCACCAGC
3450
GCTGGTGA GGCTAGCTACAACGA AATGCAGC
12199





3462
GCAUUAUC A CCAGCCUC
3451
GAGGCTGG GGCTAGCTACAACGA GATAATGC
12200





3466
UAUCACCA G CCUCACGG
3452
CCGTGAGG GGCTAGCTACAACGA TGGTGATA
12201





3471
CCAGCCUC A CGGGCCGG
3453
CCGGCCCG GGCTAGCTACAACGA GAGGCTGG
12202





3475
CCUCACGG G CCGGGACA
3454
TGTCCCGG GGCTAGCTACAACGA CCGTGAGG
12203





3481
GGGCCGGG A CAAGAACC
3455
GGTTCTTG GGCTAGCTACAACGA CCCGGCCC
12204





3487
GGACAAGA A CCAAGUCG
3456
CGACTTGG GGCTAGCTACAACGA TCTTGTCC
12205





3492
AGAACCAA G UCGAGGGG
3457
CCCCTCGA GGCTAGCTACAACGA TTGGTTCT
12206





3504
AGGGGGAA G UUCAAGUG
3458
CACTTGAA GGCTAGCTACAACGA TTCCCCCT
12207





3510
AAGUUCAA G UGGUUUCC
3459
GGAAACCA GGCTAGCTACAACGA TTGAACTT
12208





3513
UUCAAGUG G UUUCCACC
3460
GGTGGAAA GGCTAGCTACAACGA CACTTGAA
12209





3519
UGGUUUCC A CCGCGACG
3461
CGTCGCGG GGCTAGCTACAACGA GGAAACCA
12210





3522
UUUCCACC G CGACGCAG
3462
CTGCGTCG GGCTAGCTACAACGA GGTGGAAA
12211





3525
CCACCGCG A CGCAGUCU
3463
AGACTGCG GGCTAGCTACAACGA CGCGGTGG
12212





3527
ACCGCGAC G CAGUCUUU
3464
AAAGACTG GGCTAGCTACAACGA GTCGCGGT
12213





3530
GCGACGCA G UCUUUCCU
3465
AGGAAAGA GGCTAGCTACAACGA TGCGTCGC
12214





3540
CUUUCCUA G CGACCUGC
3466
GCAGGTCC GGCTAGCTACAACGA TAGGAAAG
12215





3543
UCCUAGCG A CCUGCGUC
3467
GACGCAGG GGCTAGCTACAACGA CGCTAGGA
12216





3547
AGCGACCU G CGUCAACG
3468
CGTTGACG GGCTAGCTACAACGA AGGTCGCT
12217





3549
CGACCUGC G UCAACGGC
3469
GCCGTTGA GGCTAGCTACAACGA GCAGGTCG
12218





3553
CUGCGUCA A CGGCGUGU
3470
ACACGCCG GGCTAGCTACAACGA TGACGCAG
12219





3556
CGUCAACG G CGUGUGCU
3471
AGCACACG GGCTAGCTACAACGA CGTTGACG
12220





3558
UCAACGGC G UGUGCUGG
3472
CCAGCACA GGCTAGCTACAACGA GCCGTTGA
12221





3560
AACGGCGU G UGCUGGAC
3473
GTCCAGCA GGCTAGCTACAACGA ACGCCGTT
12222





3562
CGGCGUGU G CUGGACUG
3474
CAGTCCAG GGCTAGCTACAACGA ACACGCCG
12223





3567
UGUGCUGG A CUGUCUAC
3475
GTAGACAG GGCTAGCTACAACGA CCAGCACA
12224





3570
GCUGGACU G UCUACCAC
3476
GTGGTAGA GGCTAGCTACAACGA AGTCCAGC
12225





3574
GACUGUCU A CCACGGCG
3477
CGCCGTGG GGCTAGCTACAACGA AGACAGTC
12226





3577
UGUCUACC A CGGCGCCG
3478
CGGCGCCG GGCTAGCTACAACGA GGTAGACA
12227





3580
CUACCACG G CGCCGGCU
3479
AGCCGGCG GGCTAGCTACAACGA CGTGGTAG
12228





3582
ACCACGGC G CCGGCUCA
3480
TGAGCCGG GGCTAGCTACAACGA GCCGTGGT
12229





3586
CGGCGCCG G CUCAAAGA
3481
TCTTTGAG GGCTAGCTACAACGA CGGCGCCG
12230





3594
GCUCAAAG A CCCUAGCC
3482
GGCTAGGG GGCTAGCTACAACGA CTTTGAGC
12231





3600
AGACCCUA G CCGGCCCA
3483
TGGGCCGG GGCTAGCTACAACGA TAGGGTCT
12232





3604
CCUAGCCG G CCCAAAGG
3484
CCTTTGGG GGCTAGCTACAACGA CGGCTAGG
12233





3613
CCCAAAGG G UCCAAUCA
3485
TGATTGGA GGCTAGCTACAACGA CCTTTGGG
12234





3618
AGGGUCCA A UCACCCAA
3486
TTGGGTGA GGCTAGCTACAACGA TGGACCCT
12235





3621
GUCCAAUC A CCCAAAUG
3487
CATTTGGG GGCTAGCTACAACGA GATTGGAC
12236





3627
UCACCCAA A UGUACACC
3488
GGTGTACA GGCTAGCTACAACGA TTGGGTGA
12237





3629
ACCCAAAU G UACACCAA
3489
TTGGTGTA GGCTAGCTACAACGA ATTTGGGT
12238





3631
CCAAAUGU A CACCAAUG
3490
CATTGGTG GGCTAGCTACAACGA ACATTTGG
12239





3633
AAAUGUAC A CCAAUGUA
3491
TACATTGG GGCTAGCTACAACGA GTACATTT
12240





3637
GUACACCA A UGUAGACC
3492
GGTCTACA GGCTAGCTACAACGA TGGTGTAC
12241





3639
ACACCAAU G UAGACCAG
3493
CTGGTCTA GGCTAGCTACAACGA ATTGGTGT
12242





3643
CAAUGUAG A CCAGGACC
3494
GGTCCTGG GGCTAGCTACAACGA CTACATTG
12243





3649
AGACCAGG A CCUCGUCG
3495
CGACGAGG GGCTAGCTACAACGA CCTGGTCT
12244





3654
AGGACCUC G UCGGAUGG
3496
CCATCCGA GGCTAGCTACAACGA GAGGTCCT
12245





3659
CUCGUCGG A UGGCCGGC
3497
GCCGGCCA GGCTAGCTACAACGA CCGACGAG
12246





3662
GUCGGAUG G CCGGCGCC
3498
GGCGCCGG GGCTAGCTACAACGA CATCCGAC
12247





3666
GAUGGCCG G CGCCCCCC
3499
GGGGGGCG GGCTAGCTACAACGA CGGCCATC
12248





3668
UGGCCGGC G CCCCCCGG
3500
CCGGGGGG GGCTAGCTACAACGA GCCGGCCA
12249





3678
CCCCCGGA G CGCGGUCC
3501
GGACCGCG GGCTAGCTACAACGA TCCGGGGG
12250





3680
CCCGGAGC G CGGUCCUU
3502
AAGGACCG GGCTAGCTACAACGA GCTCCGGG
12251





3683
GGAGCGCG G UCCUUGAC
3503
GTCAAGGA GGCTAGCTACAACGA CGCGCTCC
12252





3690
GGUCCUUG A CACCAUGC
3504
GCATGGTG GGCTAGCTACAACGA CAAGGACC
12253





3692
UCCUUGAC A CCAUGCAC
3505
GTGCATGG GGCTAGCTACAACGA GTCAAGGA
12254





3695
UUGACACC A UGCACCUG
3506
CAGGTGCA GGCTAGCTACAACGA GGTGTCAA
12255





3697
GACACCAU G CACCUGCG
3507
CGCAGGTG GGCTAGCTACAACGA ATGGTGTC
12256





3699
CACCAUGC A CCUGCGGC
3508
GCCGCAGG GGCTAGCTACAACGA GCATGGTG
12257





3703
AUGCACCU G CGGCGGCU
3509
AGCCGCCG GGCTAGCTACAACGA AGGTGCAT
12258





3706
CACCUGCG G CGGCUCGG
3510
CCGAGCCG GGCTAGCTACAACGA CGCAGGTG
12259





3709
CUGCGGCG G CUCGGACC
3511
GGTCCGAG GGCTAGCTACAACGA CGCCGCAG
12260





3715
CGGCUCGG A CCUUUACU
3512
AGTAAAGG GGCTAGCTACAACGA CCGAGCCG
12261





3721
GGACCUUU A CUUGGUCA
3513
TGACCAAG GGCTAGCTACAACGA AAAGGTCC
12262





3726
UUUACUUG G UCACGAGA
3514
TCTCGTGA GGCTAGCTACAACGA CAAGTAAA
12263





3729
ACUUGGUC A CGAGACAC
3515
GTGTCTCG GGCTAGCTACAACGA GACCAAGT
12264





3734
GUCACGAG A CACGCUGA
3516
TCAGCGTG GGCTAGCTACAACGA CTCGTGAC
12265





3736
CACGAGAC A CGCUGAUG
3517
CATCAGCG GGCTAGCTACAACGA GTCTCGTG
12266





3738
CGAGACAC G CUGAUGUC
3518
GACATCAG GGCTAGCTACAACGA GTGTCTCG
12267





3742
ACACGCUG A UGUCAUUC
3519
GAATGACA GGCTAGCTACAACGA CAGCGTGT
12268





3744
ACGCUGAU G UCAUUCCG
3520
CGGAATGA GGCTAGCTACAACGA ATCAGCGT
12269





3747
CUGAUGUC A UUCCGGUG
3521
CACCGGAA GGCTAGCTACAACGA GACATCAG
12270





3753
UCAUUCCG G UGCGCCGG
3522
CCGGCGCA GGCTAGCTACAACGA CGGAATGA
12271





3755
AUUCCGGU G CGCCGGCG
3523
CGCCGGCG GGCTAGCTACAACGA ACCGGAAT
12272





3757
UCCGGUGC G CCGGCGGG
3524
CCCGCCGG GGCTAGCTACAACGA GCACCGGA
12273





3761
GUGCGCCG G CGGGGUGA
3525
TCACCCCG GGCTAGCTACAACGA CGGCGCAC
12274





3766
CCGGCGGG G UGACAGCA
3526
TGCTGTCA GGCTAGCTACAACGA CCCGCCGG
12275





3769
GCGGGGUG A CAGCAGGG
3527
CCCTGCTG GGCTAGCTACAACGA CACCCCGC
12276





3772
GGGUGACA G CAGGGGGA
3528
TCCCCCTG GGCTAGCTACAACGA TGTCACCC
12277





3781
CAGGGGGA G CUUACUAU
3529
ATAGTAAG GGCTAGCTACAACGA TCCCCCTG
12278





3785
GGGAGCUU A CUAUCCCC
3530
GGGGATAG GGCTAGCTACAACGA AAGCTCCC
12279





3788
AGCUUACU A UCCCCCAG
3531
CTGGGGGA GGCTAGCTACAACGA AGTAAGCT
12280





3797
UCCCCCAG G CCCAUCUC
3532
GAGATGGG GGCTAGCTACAACGA CTGGGGGA
12281





3801
CCAGGCCC A UCUCCUAC
3533
GTAGGAGA GGCTAGCTACAACGA GGGCCTGG
12282





3808
CAUCUCCU A CUUGAAGG
3534
CCTTCAAG GGCTAGCTACAACGA AGGAGATG
12283





3817
CUUGAAGG G CUCCUCGG
3535
CCGAGGAG GGCTAGCTACAACGA CCTTCAAG
12284





3826
CUCCUCGG G CGGUCCAC
3536
GTGGACCG GGCTAGCTACAACGA CCGAGGAG
12285





3829
CUCGGGCG G UCCACUGC
3537
GCAGTGGA GGCTAGCTACAACGA CGCCCGAG
12286





3833
GGCGGUCC A CUGCUCUG
3538
CAGAGCAG GGCTAGCTACAACGA GGACCGCC
12287





3836
GGUCCACU G CUCUGCCC
3539
GGGCAGAG GGCTAGCTACAACGA AGTGGACC
12288





3841
ACUGCUCU G CCCUUCGG
3540
CCGAAGGG GGCTAGCTACAACGA AGAGCAGT
12289





3851
CCUUCGGG G CACGUUGU
3541
ACAACGTG GGCTAGCTACAACGA CCCGAAGG
12290





3853
UUCGGGGC A CGUUGUGG
3542
CCACAACG GGCTAGCTACAACGA GCCCCGAA
12291





3855
CGGGGCAC G UUGUGGGC
3543
GCCCACAA GGCTAGCTACAACGA GTGCCCCG
12292





3858
GGCACGUU G UGGGCAUC
3544
GATGCCCA GGCTAGCTACAACGA AACGTGCC
12293





3862
CGUUGUGG G CAUCUUCC
3545
GGAAGATG GGCTAGCTACAACGA CCACAACG
12294





3864
UUGUGGGC A UCUUCCGG
3546
CCGGAAGA GGCTAGCTACAACGA GCCCACAA
12295





3873
UCUUCCGG G CUGCUGUG
3547
CACAGCAG GGCTAGCTACAACGA CCGGAAGA
12296





3876
UCCGGGCU G CUGUGUGC
3548
GCACACAG GGCTAGCTACAACGA AGCCCGGA
12297





3879
GGGCUGCU G UGUGCACC
3549
GGTGCACA GGCTAGCTACAACGA AGCAGCCC
12298





3881
GCUGCUGU G UGCACCCG
3550
CGGGTGCA GGCTAGCTACAACGA ACAGCAGC
12299





3883
UGCUGUGU G CACCCGGG
3551
CCCGGGTG GGCTAGCTACAACGA ACACAGCA
12300





3885
CUGUGUGC A CCCGGGGG
3552
CCCCCGGG GGCTAGCTACAACGA GCACACAG
12301





3894
CCCGGGGG G UUGCGAAG
3553
CTTCGCAA GGCTAGCTACAACGA CCCCCGGG
12302





3897
GGGGGGUU G CGAAGGCG
3554
CGCCTTCG GGCTAGCTACAACGA AACCCCCC
12303





3903
UUGCGAAG G CGGUGGAC
3555
GTCCACCG GGCTAGCTACAACGA CTTCGCAA
12304





3906
CGAAGGCG G UGGACUUU
3556
AAAGTCCA GGCTAGCTACAACGA CGCCTTCG
12305





3910
GGCGGUGG A CUUUGUAC
3557
GTACAAAG GGCTAGCTACAACGA CCACCGCC
12306





3915
UGGACUUU G UACCCGUU
3558
AACGGGTA GGCTAGCTACAACGA AAAGTCCA
12307





3917
GACUUUGU A CCCGUUGA
3559
TCAACGGG GGCTAGCTACAACGA ACAAAGTC
12308





3921
UUGUACCC G UUCAGUCU
3560
AGACTCAA GGCTAGCTACAACGA GGGTACAA
12309





3926
CCCGUUGA G UCUAUGGA
3561
TCCATAGA GGCTAGCTACAACGA TCAACGGG
12310





3930
UUGAGUCU A UGGAAACU
3562
AGTTTCCA GGCTAGCTACAACGA AGACTCAA
12311





3936
CUAUGGAA A CUACCAUG
3563
CATGGTAG GGCTAGCTACAACGA TTCCATAG
12312





3939
UGGAAACU A CCAUGCGG
3564
CCGCATGG GGCTAGCTACAACGA AGTTTCCA
12313





3942
AAACUACC A UGCCGUCC
3565
GGACCGCA GGCTAGCTACAACGA GGTAGTTT
12314





3944
ACUACCAU G CGGUCCCC
3566
GGGGACCG GGCTAGCTACAACGA ATGGTAGT
12315





3947
ACCAUGCG G UCCCCGGU
3567
ACCGGGGA GGCTAGCTACAACGA CGCATGGT
12316





3954
GGUCCCCG G UCUUCACG
3568
CGTGAAGA GGCTAGCTACAACGA CGGGGACC
12317





3960
CGGUCUUC A CGGACAAC
3569
GTTGTCCG GGCTAGCTACAACGA GAAGACCG
12318





3964
CUUCACGG A CAACUCGU
3570
ACGAGTTG GGCTAGCTACAACGA CCGTGAAG
12319





3967
CACGGACA A CUCGUCCC
3571
GGGACGAG GGCTAGCTACAACGA TGTCCGTG
12320





3971
GACAACUC G UCCCCCCC
3572
GGGGGGGA GGCTAGCTACAACGA GAGTTGTC
12321





3981
CCCCCCCA G CCGUACCG
3573
CGGTACGG GGCTAGCTACAACGA TGGGGGGG
12322





3984
CCCCAGCC G UACCGCAG
3574
CTGCGGTA GGCTAGCTACAACGA GGCTGGGG
12323





3986
CCAGCCGU A CCGCAGAC
3575
GTCTGCGG GGCTAGCTACAACGA ACGGCTGG
12324





3989
GCCGUACC G CAGACAUU
3576
AATGTCTG GGCTAGCTACAACGA GGTACGGC
12325





3993
UACCGCAG A CAUUCCAA
3577
TTGGAATG GGCTAGCTACAACGA CTGCGGTA
12326





3995
CCGCAGAC A UUCCAAGU
3578
ACTTGGAA GGCTAGCTACAACGA GTCTGCGG
12327





4002
CAUUCCAA G UGGCCCAC
3579
GTGGGCCA GGCTAGCTACAACGA TTGGAATG
12328





4005
UCCAAGUG G CCCACCUA
3580
TAGGTGGG GGCTAGCTACAACGA CACTTGGA
12329





4009
AGUGGCCC A CCUACACG
3581
CGTGTAGG GGCTAGCTACAACGA GGGCCACT
12330





4013
GCCCACCU A CACGCUCC
3582
GGAGCGTG GGCTAGCTACAACGA AGGTGGGC
12331





4015
CCACCUAC A CGCUCCCA
3583
TGGGAGCG GGCTAGCTACAACGA GTAGGTGG
12332





4017
ACCUACAC G CUCCCACU
3584
AGTGGGAG GGCTAGCTACAACGA GTGTAGGT
12333





4023
ACGCUCCC A CUGGCAGC
3585
GCTGCCAG GGCTAGCTACAACGA GGGAGCGT
12334





4027
UCCCACUG G CAGCGGCA
3586
TGCCGCTG GGCTAGCTACAACGA CAGTGGGA
12335





4030
CACUGGCA G CGGCAAGA
3587
TCTTGCCG GGCTAGCTACAACGA TGCCAGTG
12336





4033
UGGCAGCG G CAAGAGCA
3588
TGCTCTTG GGCTAGCTACAACGA CGCTGCCA
12337





4039
CGGCAAGA G CACUAAGG
3589
CCTTAGTG GGCTAGCTACAACGA TCTTGCCG
12338





4041
GCAAGAGC A CUAAGGUA
3590
TACCTTAG GGCTAGCTACAACGA GCTCTTGC
12339





4047
GCACUAAG G UACCGGCU
3591
AGCCGGTA GGCTAGCTACAACGA CTTAGTGC
12340





4049
ACUAAGGU A CCGGCUGC
3592
GCAGCCGG GGCTAGCTACAACGA ACCTTAGT
12341





4053
AGGUACCG G CUGCAUAU
3593
ATATGCAG GGCTAGCTACAACGA CGGTACCT
12342





4056
UACCGGCU G CAUAUGCA
3594
TGCATATG GGCTAGCTACAACGA AGCCGGTA
12343





4058
CCGGCUGC A UAUGCAGC
3595
GCTGCATA GGCTAGCTACAACGA GCAGCCGG
12344





4060
GGCUGCAU A UGCAGCCC
3596
GGGCTGCA GGCTAGCTACAACGA ATGCAGCC
12345





4062
CUGCAUAU G CAGCCCAA
3597
TTGGGCTG GGCTAGCTACAACGA ATATGCAG
12346





4065
CAUAUGCA G CCCAAGGG
3598
CCCTTGGG GGCTAGCTACAACGA TGCATATG
12347





4073
GCCCAAGG G UACAAAGU
3599
ACTTTGTA GGCTAGCTACAACGA CCTTGGGC
12348





4075
CCAAGGGU A CAAAGUGC
3600
GCACTTTG GGCTAGCTACAACGA ACCCTTGG
12349





4080
GGUACAAA G UGCUCGUC
3601
GACGAGCA GGCTAGCTACAACGA TTTGTACC
12350





4082
UACAAAGU G CUCGUCCU
3602
AGGACGAG GGCTAGCTACAACGA ACTTTGTA
12351





4086
AAGUGCUC G UCCUAAAU
3603
ATTTAGGA GGCTAGCTACAACGA GAGCACTT
12352





4093
CGUCCUAA A UCCGUCCG
3604
CGGACGGA GGCTAGCTACAACGA TTAGGACG
12353





4097
CUAAAUCC G UCCGUUAC
3605
GTAACGGA GGCTAGCTACAACGA GGATTTAG
12354





4101
AUCCGUCC G UUACCGCC
3606
GGCGGTAA GGCTAGCTACAACGA GGACGGAT
12355





4104
CGUCCGUU A CCGCCACC
3607
GGTGGCGG GGCTAGCTACAACGA AACGGACG
12356





4107
CCGUUACC G CCACCUUA
3608
TAAGGTGG GGCTAGCTACAACGA GGTAACGG
12357





4110
UUACCGCC A CCUUAGGG
3609
CCCTAAGG GGCTAGCTACAACGA GGCGGTAA
12358





4118
ACCUUAGG G UUUGGGGC
3610
GCCCCAAA GGCTAGCTACAACGA CCTAAGGT
12359





4125
GGUUUGGG G CGUAUAUG
3611
CATATACG GGCTAGCTACAACGA CCCAAACC
12360





4127
UUUGGGGC G UAUAUGUC
3612
GACATATA GGCTAGCTACAACGA GCCCCAAA
12361





4129
UGGGGCGU A UAUGUCUA
3613
TAGACATA GGCTAGCTACAACGA ACGCCCCA
12362





4131
GGGCGUAU A UGUCUAAG
3614
CTTAGACA GGCTAGCTACAACGA ATACGCCC
12363





4133
GCGUAUAU G UCUAAGGC
3615
GCCTTAGA GGCTAGCTACAACGA ATATACGC
12364





4140
UGUCUAAG G CACACGGU
3616
ACCGTGTG GGCTAGCTACAACGA CTTAGACA
12365





4142
UCUAAGGC A CACGGUGU
3617
ACACCGTG GGCTAGCTACAACGA GCCTTAGA
12366





4144
UAAGGCAC A CGGUGUCG
3618
CGACACCG GGCTAGCTACAACGA GTGCCTTA
12367





4147
GGCACACG G UGUCGAUC
3619
GATCGACA GGCTAGCTACAACGA CGTGTGCC
12368





4149
CACACGGU G UCGAUCCU
3620
AGGATCGA GGCTAGCTACAACGA ACCGTGTG
12369





4153
CGGUGUCG A UCCUAACA
3621
TGTTAGGA GGCTAGCTACAACGA CGACACCG
12370





4159
CGAUCCUA A CAUCAGAA
3622
TTCTGATG GGCTAGCTACAACGA TAGGATCG
12371





4161
AUCCUAAC A UCAGAACU
3623
AGTTCTGA GGCTAGCTACAACGA GTTAGGAT
12372





4167
ACAUCAGA A CUGGGGUA
3624
TACCCCAG GGCTAGCTACAACGA TCTGATGT
12373





4173
GAACUGGG G UAAGGACC
3625
GGTCCTTA GGCTAGCTACAACGA CCCAGTTC
12374





4179
GGGUAAGG A CCAUCACC
3626
GGTGATGG GGCTAGCTACAACGA CCTTACCC
12375





4182
UAAGGACC A UCACCACG
3627
CGTGGTGA GGCTAGCTACAACGA GGTCCTTA
12376





4185
GGACCAUC A CCACGGGC
3628
GCCCGTGG GGCTAGCTACAACGA GATGGTCC
12377





4188
CCAUCACC A CGGGCGCC
3629
GGCGCCCG GGCTAGCTACAACGA GGTGATGG
12378





4192
CACCACGG G CGCCCCCA
3630
TGGGGGCG GGCTAGCTACAACGA CCGTGGTG
12379





4194
CCACGGGC G CCCCCAUC
3631
GATGGGGG GGCTAGCTACAACGA GCCCGTGG
12380





4200
GCGCCCCC A UCACGUAC
3632
GTACGTGA GGCTAGCTACAACGA GGGGGCGC
12381





4203
CCCCCAUC A CGUACUCC
3633
GGAGTACG GGCTAGCTACAACGA GATGGGGG
12382





4205
CCCAUCAC G UACUCCAC
3634
GTGGAGTA GGCTAGCTACAACGA GTGATGGG
12383





4207
CAUCACGU A CUCCACCU
3635
AGGTGGAG GGCTAGCTACAACGA ACGTGATG
12384





4212
CGUACUCC A CCUAUGGC
3636
GCCATAGG GGCTAGCTACAACGA GGAGTACG
12385





4216
CUCCACCU A UGGCAAGU
3637
ACTTGCCA GGCTAGCTACAACGA AGGTGGAG
12386





4219
CACCUAUG G CAAGUUCC
3638
GGAACTTG GGCTAGCTACAACGA CATAGGTG
12387





4223
UAUGGCAA G UUCCUUGC
3639
GCAAGGAA GGCTAGCTACAACGA TTGCCATA
12388





4230
AGUUCCUU G CCGACGGU
3640
ACCGTCGG GGCTAGCTACAACGA AAGGAACT
12389





4234
CCUUGCCG A CGGUGGUU
3641
AACCACCG GGCTAGCTACAACGA CGGCAAGG
12390





4237
UGCCGACG G UGGUUGCU
3642
AGCAACCA GGCTAGCTACAACGA CGTCGGCA
12391





4240
CGACGGUG G UUGCUCUG
3643
CAGAGCAA GGCTAGCTACAACGA CACCGTCG
12392





4243
CGGUGGUU G CUCUGGGG
3644
CCCCAGAG GGCTAGCTACAACGA AACCACCG
12393





4252
CUCUGGGG G CCCCUAUG
3645
CATAGCCG GGCTAGCTACAACGA CCCCAGAG
12394





4254
CUGGGGGC G CCUAUGAC
3646
GTCATAGG GGCTAGCTACAACGA GCCCCCAG
12395





4258
GGGCGCCU A UGACAUCA
3647
TGATGTCA GGCTAGCTACAACGA AGGCGCCC
12396





4261
CGCCUAUG A CAUCAUAA
3648
TTATGATG GGCTAGCTACAACGA CATAGGCG
12397





4263
CCUAUGAC A UCAUAAUG
3649
CATTATGA GGCTAGCTACAACGA GTCATAGG
12398





4266
AUGACAUC A UAAUGUGU
3650
ACACATTA GGCTAGCTACAACGA GATGTCAT
12399





4269
ACAUCAUA A UGUGUGAU
3651
ATCACACA GGCTAGCTACAACGA TATGATGT
12400





4271
AUCAUAAU G UGUGAUGA
3652
TCATCACA GGCTAGCTACAACGA ATTATGAT
12401





4273
CAUAAUGU G UGAUGAGU
3653
ACTCATCA GGCTAGCTACAACGA ACATTATG
12402





4276
AAUGUGUG A UGAGUGCC
3654
GGCACTCA GGCTAGCTACAACGA CACACATT
12403





4280
UGUGAUGA G UGCCACUC
3655
GAGTGGCA GGCTAGCTACAACGA TCATCACA
12404





4282
UGAUGAGU G CCACUCAA
3656
TTGAGTGG GGCTAGCTACAACGA ACTCATCA
12405





4285
UGAGUGCC A CUCAAUUG
3657
CAATTGAG GGCTAGCTACAACGA GGCACTCA
12406





4290
GCCACUCA A UUGACUCG
3658
CGAGTCAA GGCTAGCTACAACGA TGAGTGGC
12407





4294
CUCAAUUG A CUCGACUU
3659
AAGTCGAG GGCTAGCTACAACGA CAATTGAG
12408





4299
UUGACUCG A CUUCCAUU
3660
AATGGAAG GGCTAGCTACAACGA CGAGTCAA
12409





4305
CGACUUCC A UUUUGGGC
3661
GCCCAAAA GGCTAGCTACAACGA GGAAGTCG
12410





4312
CAUUUUGG G CAUCGGCA
3662
TGCCGATG GGCTAGCTACAACGA CCAAAATG
12411





4314
UUUUGGGC A UCGGCACA
3663
TGTGCCGA GGCTAGCTACAACGA GCCCAAAA
12412





4318
GGGCAUCG G CACAGUCC
3664
GGACTGTG GGCTAGCTACAACGA CGATGCCC
12413





4320
GCAUCGGC A CAGUCCUG
3665
CAGGACTG GGCTAGCTACAACGA GCCGATGC
12414





4323
UCGGCACA G UCCUGGAC
3666
GTCCAGGA GGCTAGCTACAACGA TGTGCCGA
12415





4330
AGUCCUGG A CCAAGCGG
3667
CCGCTTGG GGCTAGCTACAACGA CCAGGACT
12416





4335
UGGACCAA G CGGAGACG
3668
CGTCTCCG GGCTAGCTACAACGA TTGGTCCA
12417





4341
AAGCGGAG A CGGCUGGA
3669
TCCAGCCG GGCTAGCTACAACGA CTCCGCTT
12418





4344
CGGAGACG G CUGGAGCG
3670
CGCTCCAG GGCTAGCTACAACGA CGTCTCCG
12419





4350
CGGCUGGA G CGCGGCUC
3671
GAGCCGCG GGCTAGCTACAACGA TCCAGCCG
12420





4352
GCUGGAGC G CGGCUCGU
3672
ACGAGCCG GGCTAGCTACAACGA GCTCCAGC
12421





4355
GGAGCGCG G CUCGUCGU
3673
ACGACGAG GGCTAGCTACAACGA CGCGCTCC
12422





4359
CGCGGCUC G UCGUGCUC
3674
GAGCACGA GGCTAGCTACAACGA GAGCCGCG
12423





4362
GGCUCGUC G UGCUCGCC
3675
GGCGAGCA GGCTAGCTACAACGA GACGAGCC
12424





4364
CUCGUCGU G CUCGCCAC
3676
GTGGCGAG GGCTAGCTACAACGA ACGACGAG
12425





4368
UCGUGCUC G CCACCGCU
3677
AGCGGTGG GGCTAGCTACAACGA GAGCACGA
12426





4371
UGCUCGCC A CCGCUACG
3678
CGTAGCGG GGCTAGCTACAACGA GGCGAGCA
12427





4374
UCGCCACC G CUACGCCU
3679
AGGCGTAG GGCTAGCTACAACGA GGTGGCGA
12428





4377
CCACCGCU A CGCCUCCG
3680
CGGAGGCG GGCTAGCTACAACGA AGCGGTGG
12429





4379
ACCGCUAC G CCUCCGGG
3681
CCCGGAGG GGCTAGCTACAACGA GTAGCGGT
12430





4388
CCUCCGGG A UCGGUCAC
3682
GTGACCGA GGCTAGCTACAACGA CCCGGAGG
12431





4392
CGGGAUCG G UCACCGUG
3683
CACGGTGA GGCTAGCTACAACGA CGATCCCG
12432





4395
GAUCGGUC A CCGUGCCA
3684
TGGCACGG GGCTAGCTACAACGA GACCGATC
12433





4398
CGGUCACC G UGCCACAU
3685
ATGTGGCA GGCTAGCTACAACGA GGTGACCG
12434





4400
GUCACCGU G CCACAUCC
3686
GGATGTGG GGCTAGCTACAACGA ACGGTGAC
12435





4403
ACCGUGCC A CAUCCCAA
3687
TTGGGATG GGCTAGCTACAACGA GGCACGGT
12436





4405
CGUGCCAC A UCCCAACA
3688
TGTTGGGA GGCTAGCTACAACGA GTGGCACG
12437





4411
ACAUCCCA A CAUCGAGG
3689
CCTCGATG GGCTAGCTACAACGA TGGGATGT
12438





4413
AUCCCAAC A UCGAGGAG
3690
CTCCTCGA GGCTAGCTACAACGA GTTGGGAT
12439





4422
UCGAGGAG A UAGCCUUG
3691
CAAGGCTA GGCTAGCTACAACGA CTCCTCGA
12440





4425
AGGAGAUA G CCUUGUCC
3692
GGACAAGG GGCTAGCTACAACGA TATCTCCT
12441





4430
AUAGCCUU G UCCAACAC
3693
GTGTTGGA GGCTAGCTACAACGA AAGGCTAT
12442





4435
CUUGUCCA A CACCGGAG
3694
CTCCGGTG GGCTAGCTACAACGA TGGACAAG
12443





4437
UGUCCAAC A CCGGAGAG
3695
CTCTCCGG GGCTAGCTACAACGA GTTGGACA
12444





4446
CCGGAGAG A UCCCCUUC
3696
GAAGGGGA GGCTAGCTACAACGA CTCTCCGG
12445





4456
CCCCUUCU A UGGCAAAG
3697
CTTTGCCA GGCTAGCTACAACGA AGAAGGGG
12446





4459
CUUCUAUG G CAAAGCCA
3698
TGGCTTTG GGCTAGCTACAACGA CATAGAAG
12447





4464
AUGGCAAA G CCAUCCCC
3699
GGGGATGG GGCTAGCTACAACGA TTTGCCAT
12448





4467
GCAAAGCC A UCCCCAUC
3700
GATGGGGA GGCTAGCTACAACGA GGCTTTGC
12449





4473
CCAUCCCC A UCGAGACC
3701
GGTCTCGA GGCTAGCTACAACGA GGGGATGG
12450





4479
CCAUCGAG A CCAUCAAA
3702
TTTGATGG GGCTAGCTACAACGA CTCGATGG
12451





4482
UCGAGACC A UCAAAGGG
3703
CCCTTTGA GGCTAGCTACAACGA GGTCTCGA
12452





4496
GGGGGGAG G CAUCUCAU
3704
ATGAGATG GGCTAGCTACAACGA CTCCCCCC
12453





4498
GGGGAGGC A UCUCAUCU
3705
AGATGAGA GGCTAGCTACAACGA GCCTCCCC
12454





4503
GGCAUCUC A UCUUCUGC
3706
GCAGAAGA GGCTAGCTACAACGA GAGATGCC
12455





4510
CAUCUUCU G CCAUUCCA
3707
TGGAATGG GGCTAGCTACAACGA AGAAGATG
12456





4513
CUUCUGCC A UUCCAAGA
3708
TCTTGGAA GGCTAGCTACAACGA GGCAGAAG
12457





4526
AAGAAGAA A UGUGACGA
3709
TCGTCACA GGCTAGCTACAACGA TTCTTCTT
12458





4528
GAAGAAAU G UGACGAGC
3710
GCTCGTCA GGCTAGCTACAACGA ATTTCTTC
12459





4531
GAAAUGUG A CGAGCUCG
3711
CGAGCTCG GGCTAGCTACAACGA CACATTTC
12460





4535
UGUGACGA G CUCGCUGC
3712
GCAGCGAG GGCTAGCTACAACGA TCGTCACA
12461





4539
ACGAGCUC G CUGCAAAG
3713
CTTTGCAG GGCTAGCTACAACGA GAGCTCGT
12462





4542
AGCUCGCU G CAAAGCUG
3714
CAGCTTTG GGCTAGCTACAACGA AGCGAGCT
12463





4547
GCUGCAAA G CUGUCGGG
3715
CCCGACAG GGCTAGCTACAACGA TTTGCAGC
12464





4550
GCAAAGCU G UCGGGCCU
3716
AGGCCCGA GGCTAGCTACAACGA AGCTTTGC
12465





4555
GCUGUCGG G CCUCGGAC
3717
GTCCGAGG GGCTAGCTACAACGA CCGACAGC
12466





4562
GGCCUCGG A CUUAACGC
3718
GCGTTAAG GGCTAGCTACAACGA CCGAGGCC
12467





4567
CGGACUUA A CGCUGUAG
3719
CTACAGCG GGCTAGCTACAACGA TAAGTCCG
12468





4569
GACUUAAC G CUGUAGCG
3720
CGCTACAG GGCTAGCTACAACGA GTTAAGTC
12469





4572
UUAACGCU G UAGCGUAU
3721
ATACGCTA GGCTAGCTACAACGA AGCGTTAA
12470





4575
ACGCUGUA G CGUAUUAC
3722
GTAATACG GGCTAGCTACAACGA TACAGCGT
12471





4577
GCUGUAGC G UAUUACCG
3723
CGGTAATA GGCTAGCTACAACGA GCTACAGC
12472





4579
UGUAGCGU A UUACCGGG
3724
CCCGGTAA GGCTAGCTACAACGA ACGCTACA
12473





4582
AGCGUAUU A CCGGGGUC
3725
GACCCCGG GGCTAGCTACAACGA AATACGCT
12474





4588
UUACCGGG G UCUCGACG
3726
CGTCGAGA GGCTAGCTACAACGA CCCGGTAA
12475





4594
GGGUCUCG A CGUGUCCG
3727
CGGACACG GGCTAGCTACAACGA CGAGACCC
12476





4596
GUCUCGAC G UGUCCGUC
3728
GACGGACA GGCTAGCTACAACGA GTCGAGAC
12477





4598
CUCGACGU G UCCGUCAU
3729
ATGACGGA GGCTAGCTACAACGA ACGTCGAG
12478





4602
ACGUGUCC G UCAUACCG
3730
CGGTATGA GGCTAGCTACAACGA GGACACGT
12479





4605
UGUCCGUC A UACCGGCC
3731
GGCCGGTA GGCTAGCTACAACGA GACGGACA
12480





4607
UCCGUCAU A CCGGCCAG
3732
CTGGCCGG GGCTAGCTACAACGA ATGACGGA
12481





4611
UCAUACCG G CCAGCGGG
3733
CCCGCTGG GGCTAGCTACAACGA CGGTATGA
12482





4615
ACCGGCCA G CGGGGACG
3734
CGTCCCCG GGCTAGCTACAACGA TGGCCGGT
12483





4621
CAGCGGGG A CGUCGUUG
3735
CAACGACG GGCTAGCTACAACGA CCCCGCTG
12484





4623
GCGGGGAC G UCGUUGUC
3736
GACAACGA GGCTAGCTACAACGA GTCCCCGC
12485





4626
GGGACGUC G UUGUCGUG
3737
CACGACAA GGCTAGCTACAACGA GACGTCCC
12486





4629
ACGUCGUU G UCGUGGCA
3738
TGCCACGA GGCTAGCTACAACGA AACGACGT
12487





4632
UCGUUGUC G UGGCAACA
3739
TGTTGCCA GGCTAGCTACAACGA GACAACGA
12488





4635
UUGUCGUG G CAACAGAC
3740
GTCTGTTG GGCTAGCTACAACGA CACGACAA
12489





4638
UCGUGGCA A CAGACGCU
3741
AGCGTCTG GGCTAGCTACAACGA TGCCACGA
12490





4642
GGCAACAG A CGCUCUAA
3742
TTAGAGCG GGCTAGCTACAACGA CTGTTGCC
12491





4644
CAACAGAC G CUCUAAUG
3743
CATTAGAG GGCTAGCTACAACGA GTCTGTTG
12492





4650
ACGCUCUA A UGACGGGC
3744
GCCCGTCA GGCTAGCTACAACGA TAGAGCGT
12493





4653
CUCUAAUG A CGGGCUAU
3745
ATAGCCCG GGCTAGCTACAACGA CATTAGAG
12494





4657
AAUGACGG G CUAUACCG
3746
CGGTATAG GGCTAGCTACAACGA CCGTCATT
12495





4660
GACGGGCU A UACCGGCG
3747
CGCCGGTA GGCTAGCTACAACGA AGCCCGTC
12496





4662
CGGGCUAU A CCGGCGAU
3748
ATCGCCGG GGCTAGCTACAACGA ATAGCCCG
12497





4666
CUAUACCG G CGAUUUUG
3749
CAAAATCG GGCTAGCTACAACGA CGGTATAG
12498





4669
UACCGGCG A UUUUGACU
3750
AGTCAAAA GGCTAGCTACAACGA CGCCGGTA
12499





4675
CGAUUUUG A CUCGGUGA
3751
TCACCGAG GGCTAGCTACAACGA CAAAATCG
12500





4680
UUGACUCG G UGAUCGAC
3752
GTCGATCA GGCTAGCTACAACGA CGAGTCAA
12501





4683
ACUCGGUG A UCGACUGU
3753
ACAGTCGA GGCTAGCTACAACGA CACCGAGT
12502





4687
GGUGAUCG A CUGUAAUA
3754
TATTACAG GGCTAGCTACAACGA CGATCACC
12503





4690
GAUCGACU G UAAUACAU
3755
ATGTATTA GGCTAGCTACAACGA AGTCGATC
12504





4693
CGACUGUA A UACAUGUG
3756
CACATGTA GGCTAGCTACAACGA TACAGTCG
12505





4695
ACUGUAAU A CAUGUGUC
3757
GACACATG GGCTAGCTACAACGA ATTACAGT
12506





4697
UGUAAUAC A UGUGUCAC
3758
GTGACACA GGCTAGCTACAACGA GTATTACA
12507





4699
UAAUACAU G UGUCACCC
3759
GGGTGACA GGCTAGCTACAACGA ATGTATTA
12508





4701
AUACAUGU G UCACCCAA
3760
TTGGGTGA GGCTAGCTACAACGA ACATGTAT
12509





4704
CAUGUGUC A CCCAAACA
3761
TGTTTCGG GCCTAGCTACAACGA GACACATG
12510





4710
UCACCCAA A CAGUCGAC
3762
GTCGACTG GGCTAGCTACAACGA TTGGGTGA
12511





4713
CCCAAACA G UCGACUUC
3763
GAAGTCGA GGCTAGCTACAACGA TGTTTGCG
12512





4717
AACAGUCG A CUUCAGCU
3764
AGCTGAAG GGCTAGCTACAACGA CGACTGTT
12513





4723
CGACUUCA G CUUGGACC
3765
GGTCCAAG GGCTAGCTACAACGA TGAAGTCG
12514





4729
CAGCUUGG A CCCUACCU
3766
AGGTAGGG GGCTAGCTACAACGA CCAAGCTG
12515





4734
UGGACCCU A CCUUCACC
3767
GGTGAAGG GGCTAGCTACAACGA AGGGTCCA
12516





4740
CUACCUUC A CCAUUGAG
3768
CTCAATGG GGCTAGCTACAACGA GAAGGTAG
12517





4743
CCUUCACC A UUGAGACG
3769
CGTCTCAA GGCTAGCTACAACGA GGTGAAGG
12518





4749
CCAUUGAG A CGACGACC
3770
GGTCGTCG GGCTAGCTACAACGA CTCAATGG
12519





4752
UUGAGACG A CGACCGUG
3771
CACGGTCG GGCTAGCTACAACGA CGTCTCAA
12520





4755
AGACGACG A CCGUGCCC
3772
GGGCACGG GGCTAGCTACAACGA CGTCGTCT
12521





4758
CGACGACC G UGCCCCAA
3773
TTGGGGCA GGCTAGCTACAACGA GGTCGTCG
12522





4760
ACGACCGU G CCCCAAGA
3774
TCTTGGGG GGCTAGCTACAACGA ACGGTCGT
12523





4768
GCCCCAAG A CGCAGUGU
3775
ACACTGCG GGCTAGCTACAACGA CTTGGGGC
12524





4770
CCCAAGAC G CAGUGUCC
3776
GGACACTG GGCTAGCTACAACGA GTCTTGGG
12525





4773
AAGACGCA G UGUCCCGC
3777
GCGGGACA GGCTAGCTACAACGA TGCGTCTT
12526





4775
GACGCAGU G UCCCGCUC
3778
GAGCGGGA GGCTAGCTACAACGA ACTGCGTC
12527





4780
AGUGUCCC G CUCGCAGA
3779
TCTGCGAG GGCTAGCTACAACGA GGGACACT
12528





4784
UCCCGCUC G CAGAGGCG
3780
CGCCTCTG GGCTAGCTACAACGA GAGCGGGA
12529





4790
UCGCAGAG G CGAGGUAG
3781
CTACCTCG GGCTAGCTACAACGA CTCTGCGA
12530





4795
GAGGCGAG G UAGGACCG
3782
CGGTCCTA GGCTAGCTACAACGA CTCGCCTC
12531





4800
GAGGUAGG A CCGGUAGG
3783
CCTACCGG GGCTAGCTACAACGA CCTACCTC
12532





4804
UAGGACCG G UAGGGGCA
3784
TGCCCCTA GGCTAGCTACAACGA CGGTCCTA
12533





4810
CGGUAGGG G CAGGAGAG
3785
CTCTCCTG GGCTAGCTACAACGA CCCTACCG
12534





4819
CAGGAGAG G CAUAUACA
3786
TGTATATG GGCTAGCTACAACGA CTCTCCTG
12535





4821
GGAGAGGC A UAUACAGG
3787
CCTGTATA GGCTAGCTACAACGA GCCTCTCC
12536





4823
AGAGGCAU A UACAGGUU
3788
AACCTGTA GGCTAGCTACAACGA ATGCCTCT
12537





4825
AGGCAUAU A CAGGUUUG
3789
CAAACCTG GGCTAGCTACAACGA ATATGCCT
12538





4829
AUAUACAG G UUUGUGAC
3790
GTCACAAA GGCTAGCTACAACGA CTGTATAT
12539





4833
ACAGGUUU G UGACUCCA
3791
TGGAGTCA GGCTAGCTACAACGA AAACCTGT
12540





4836
GGUUUGUG A CUCCAGGA
3792
TCCTGGAG GGCTAGCTACAACGA CACAAACC
12541





4847
CCAGGAGA G CGGCCUUC
3793
GAAGGCCG GGCTAGCTACAACGA TCTCCTGG
12542





4850
GGAGAGCG G CCUUCGGG
3794
CCCGAAGG GGCTAGCTACAACGA CGCTCTCC
12543





4858
GCCUUCGG G CAUGUUCG
3795
CGAACATG GGCTAGCTACAACGA CCGAAGGC
12544





4860
CUUCGGGC A UGUUCGAC
3796
GTCGAACA GGCTAGCTACAACGA GCCCGAAG
12545





4862
UCGGGCAU G UUCGACUC
3797
GAGTCGAA GGCTAGCTACAACGA ATGCCCGA
12546





4867
CAUGUUCG A CUCCUCGG
3798
CCGAGGAG GGCTAGCTACAACGA CGAACATG
12547





4875
ACUCCUCG G UCCUGUGU
3799
ACACAGGA GGCTAGCTACAACGA CGAGGAGT
12548





4880
UCGGUCCU G UGUGAGUG
3800
CACTCACA GGCTAGCTACAACGA AGGACCGA
12549





4882
GGUCCUGU G UGAGUGCU
3801
AGCACTCA GGCTAGCTACAACGA ACAGGACC
12550





4886
CUGUGUGA G UGCUAUGA
3802
TCATAGCA GGCTAGCTACAACGA TCACACAG
12551





4888
GUGUGAGU G CUAUGACG
3803
CGTCATAG GGCTAGCTACAACGA ACTCACAC
12552





4891
UGAGUGCU A UGACGCGG
3804
CCGCGTCA GGCTAGCTACAACGA AGCACTCA
12553





4894
GUGCUAUG A CGCGGGAU
3805
ATCCCGCG GGCTAGCTACAACGA CATAGCAC
12554





4896
GCUAUGAC G CGGGAUGU
3806
ACATCCCG GGCTAGCTACAACGA GTCATAGC
12555





4901
GACGCGGG A UGUGCUUG
3807
CAAGCACA GGCTAGCTACAACGA CCCGCGTC
12556





4903
CGCGGGAU G UGCUUGGU
3808
ACCAAGCA GGCTAGCTACAACGA ATCCCGCG
12557





4905
CGGGAUGU G CUUGGUAC
3809
GTACCAAG GGCTAGCTACAACGA ACATCCCG
12558





4910
UGUGCUUG G UACGAGCU
3810
AGCTCGTA GGCTAGCTACAACGA CAAGCACA
12559





4912
UGCUUGGU A CGAGCUCA
3811
TGAGCTCG GGCTAGCTACAACGA ACCAAGCA
12560





4916
UGGUACGA G CUCACGCC
3812
GGCGTGAG GGCTAGCTACAACGA TCGTACCA
12561





4920
ACGAGCUC A CGCCCGCC
3813
GGCGGGCG GGCTAGCTACAACGA GAGCTCGT
12562





4922
GAGCUCAC G CCCGCCGA
3814
TCGGCGGG GGCTAGCTACAACGA GTGAGCTC
12563





4926
UCACGCCC G CCGAGACC
3815
GGTCTCGG GGCTAGCTACAACGA GGGCGTGA
12564





4932
CCGCCGAG A CCUCCGUU
3816
AACGGAGG GGCTAGCTACAACGA CTCGGCGG
12565





4938
AGACCUCC G UUAGGUUG
3817
CAACCTAA GGCTAGCTACAACGA GGAGGTCT
12566





4943
UCCGUUAG G UUGCGGGC
3818
GCCCGCAA GGCTAGCTACAACGA CTAACGGA
12567





4946
GUUAGGUU G CGGGCUUA
3819
TAAGCCCG GGCTAGCTACAACGA AACCTAAC
12568





4950
GGUUGCGG G CUUACCUA
3820
TAGGTAAG GGCTAGCTACAACGA CCGCAACC
12569





4954
GCGGGCUU A CCUAAAUA
3821
TATTTAGG GGCTAGCTACAACGA AAGCCCGC
12570





4960
UUACCUAA A UACACCAG
3822
CTGGTGTA GGCTAGCTACAACGA TTAGGTAA
12571





4962
ACCUAAAU A CACCAGGG
3823
CCCTGGTG GGCTAGCTACAACGA ATTTAGGT
12572





4964
CUAAAUAC A CCAGGGUU
3824
AACCCTGG GGCTAGCTACAACGA GTATTTAG
12573





4970
ACACCAGG G UUGCCCUU
3825
AAGGGCAA GGCTAGCTACAACGA CCTGGTGT
12574





4973
CCAGGGUU G CCCUUCUG
3826
CAGAAGGG GGCTAGCTACAACGA AACCCTGG
12575





4981
GCCCUUCU G CCAGGACC
3827
GGTCCTGG GGCTAGCTACAACGA AGAAGGGC
12576





4987
CUGCCAGG A CCAUCUGG
3828
CCAGATGG GGCTAGCTACAACGA CCTGGCAG
12577





4990
CCAGGACC A UCUGGAGU
3829
ACTCCAGA GGCTAGCTACAACGA GGTCCTGG
12578





4997
CAUCUGGA G UUCUGGGA
3830
TCCCAGAA GGCTAGCTACAACGA TCCAGATG
12579





5008
CUGGGAGG G UGUCUUCA
3831
TGAAGACA GGCTAGCTACAACGA CCTCCCAG
12580





5010
GGGAGGGU G UCUUCACA
3832
TGTGAAGA GGCTAGCTACAACGA ACCCTCCC
12581





5016
GUGUCUUC A CAGGCCUC
3833
GAGGCCTG GGCTAGCTACAACGA GAAGACAC
12582





5020
CUUCACAG G CCUCACCC
3834
GGGTGAGG GGCTAGCTACAACGA CTGTGAAG
12583





5025
CAGGCCUC A CCCACAUA
3835
TATGTGGG GGCTAGCTACAACGA GAGGCCTG
12584





5029
CCUCACCC A CAUAGAUG
3836
CATCTATG GGCTAGCTACAACGA GGGTGAGG
12585





5031
UCACCCAC A UAGAUGCC
3837
GGCATCTA GGCTAGCTACAACGA GTGGGTGA
12586





5035
CCACAUAG A UGCCCACU
3838
AGTGGGCA GGCTAGCTACAACGA CTATGTGG
12587





5037
ACAUAGAU G CCCACUUC
3839
GAAGTGGG GGCTAGCTACAACGA ATCTATGT
12588





5041
AGAUGCCC A CUUCUUGU
3840
ACAAGAAG GGCTAGCTACAACGA GGGCATCT
12589





5048
CACUUCUU G UCCCAGAC
3841
GTCTGGGA GGCTAGCTACAACGA AAGAAGTG
12590





5055
UGUCCCAG A CCAAGCAG
3842
CTGCTTGG GGCTAGCTACAACGA CTGGGACA
12591





5060
CAGACCAA G CAGGCAGG
3843
CCTGCCTG GGCTAGCTACAACGA TTGGTCTG
12592





5064
CCAAGCAG G CAGGAGAA
3844
TTCTCCTG GGCTAGCTACAACGA CTGCTTGG
12593





5074
AGGAGAAA A CCUCCCCU
3845
AGGGGAGG GGCTAGCTACAACGA TTTCTCCT
12594





5083
CCUCCCCU A CCUGGUAG
3846
CTACCAGG GGCTAGCTACAACGA AGGGGAGG
12595





5088
CCUACCUG G UAGCAUAC
3847
GTATGCTA GGCTAGCTACAACGA CAGGTAGG
12596





5091
ACCUGGUA G CAUACCAA
3848
TTGGTATG GGCTAGCTACAACGA TACCAGGT
12597





5093
CUGGUAGC A UACCAAGC
3849
GCTTGGTA GGCTAGCTACAACGA GCTACCAG
12598





5095
GGUAGCAU A CCAAGCCA
3850
TGGCTTGG GGCTAGCTACAACGA ATGCTACC
12599





5100
CAUACCAA G CCACAGUG
3851
CACTGTGG GGCTAGCTACAACGA TTGGTATG
12600





5103
ACCAAGCC A CAGUGUGC
3852
GCACACTG GGCTAGCTACAACGA GGCTTGGT
12601





5106
AAGCCACA G UGUGCGCC
3853
GGCGCACA GGCTAGCTACAACGA TGTGGCTT
12602





5108
GCCACAGU G UGCGCCAG
3854
CTGGCGCA GGCTAGCTACAACGA ACTGTGGC
12603





5110
CACAGUGU G CGCCAGGG
3855
CCCTGGCG GGCTAGCTACAACGA ACACTGTG
12604





5112
CAGUGUGC G CCAGGGCU
3856
AGCCCTGG GGCTAGCTACAACGA GCACACTG
12605





5118
GCGCCAGG G CUCAGGCU
3857
AGCCTGAG GGCTAGCTACAACGA CCTGGCGC
12606





5124
GGGCUCAG G CUCCACCC
3858
GGGTGGAG GGCTAGCTACAACGA CTGAGCCC
12607





5129
CAGGCUCC A CCCCCAUC
3859
GATGGGGG GGCTAGCTACAACGA GGAGCCTG
12608





5135
CCACCCCC A UCGUGGGA
3860
TCCCACGA GGCTAGCTACAACGA GGGGGTGG
12609





5138
CCCCCAUC G UGGGAUCA
3861
TGATCCCA GGCTAGCTACAACGA GATGGGGG
12610





5143
AUCGUGGG A UCAAAUGU
3862
ACATTTGA GGCTAGCTACAACGA CCCACGAT
12611





5148
GGGAUCAA A UGUGGAAG
3863
CTTCCACA GGCTAGCTACAACGA TTGATCCC
12612





5150
GAUCAAAU G UGGAAGUG
3864
CACTTCCA GGCTAGCTACAACGA ATTTGATC
12613





5156
AUGUGGAA G UGUCUCAC
3865
GTGAGACA GGCTAGCTACAACGA TTCCACAT
12614





5158
GUGGAAGU G UCUCACAC
3866
GTGTGAGA GGCTAGCTACAACGA ACTTCCAC
12615





5163
AGUGUCUC A CACGGCUA
3867
TAGCCGTG GGCTAGCTACAACGA GAGACACT
12616





5165
UGUCUCAC A CGGCUAAA
3868
TTTAGCCG GGCTAGCTACAACGA GTGAGACA
12617





5168
CUCACACG G CUAAAGCC
3869
GGCTTTAG GGCTAGCTACAACGA CGTGTGAG
12618





5174
CGGCUAAA G CCUACGCU
3870
AGCGTAGG GGCTAGCTACAACGA TTTAGCCG
12619





5178
UAAAGCCU A CGCUACAC
3871
GTGTAGCG GGCTAGCTACAACGA AGGCTTTA
12620





5180
AAGCCUAC G CUACACGG
3872
CCGTGTAG GGCTAGCTACAACGA GTAGGCTT
12621





5183
CCUACGCU A CACGGGCC
3873
GGCCCGTG GGCTAGCTACAACGA AGCGTAGG
12622





5185
UACGCUAC A CGGGCCAA
3874
TTGGCCCG GGCTAGCTACAACGA GTAGCGTA
12623





5189
CUACACGG G CCAACACC
3875
GGTGTTGG GGCTAGCTACAACGA CCGTGTAG
12624





5193
ACGGGCCA A CACCCCUG
3876
CAGGGGTG GGCTAGCTACAACGA TGGCCCGT
12625





5195
GGGCCAAC A CCCCUGCU
3877
AGCAGGGG GGCTAGCTACAACGA GTTGGCCC
12626





5201
ACACCCCU G CUGUAUAG
3878
CTATACAC GGCTACCTACAACGA AGGGGTGT
12627





5204
CCCCUGCU G UAUAGGCU
3879
AGCCTATA GGCTAGCTACAACGA AGCAGGGG
12628





5206
CCUGCUGU A UAGGCUAG
3880
CTAGCCTA GGCTAGCTACAACCA ACAGCAGG
12629





5210
CUGUAUAG G CUAGGAGC
3881
GCTCCTAG GGCTAGCTACAACGA CTATACAG
12630





5217
GGCUAGGA G CCGUCCAA
3882
TTGGACGG GGCTAGCTACAACGA TCCTAGCC
12631





5220
UAGGAGCC G UCCAAAAU
3883
ATTTTGGA GGCTAGCTACAACGA GGCTCCTA
12632





5227
CGUCCAAA A UGAUGUCA
3884
TGACATCA GGCTAGCTACAACGA TTTGGACG
12633





5230
CCAAAAUG A UGUCACCC
3885
GGGTGACA GGCTAGCTACAACGA CATTTTGG
12634





5232
AAAAUGAU G UCACCCUC
3886
GAGGGTGA GGCTAGCTACAACGA ATCATTTT
12635





5235
AUGAUGUC A CCCUCACA
3887
TGTGAGGG GGCTAGCTACAACGA GACATCAT
12636





5241
UCACCCUC A CACACCCC
3888
GGGGTGTG GGCTAGCTACAACGA GAGGGTGA
12637





5243
ACCCUCAC A CACCCCAU
3889
ATGGGGTG GGCTAGCTACAACGA GTGAGGGT
12638





5245
CCUCACAC A CCCCAUAA
3890
TTATGGGG GGCTAGCTACAACGA GTGTGAGG
12639





5250
CACACCCC A UAACCAAA
3891
TTTGGTTA GGCTAGCTACAACGA GGGGTGTG
12640





5253
ACCCCAUA A CCAAAUAC
3892
GTATTTGG GGCTAGCTACAACGA TATGGGGT
12641





5258
AUAACCAA A UACAUCAU
3893
ATGATGTA GGCTAGCTACAACGA TTGGTTAT
12642





5260
AACCAAAU A CAUCAUCA
3894
TCATGATG GGCTAGCTACAACGA ATTTGGTT
12643





5262
CCAAAUAC A UCAUGACA
3895
TGTCATGA GGCTAGCTACAACGA GTATTTGG
12644





5265
AAUACAUC A UGACAUGC
3896
GCATGTCA GGCTAGCTACAACGA GATGTATT
12645





5268
ACAUCAUG A CAUGCAUG
3897
CATGCATG GGCTAGCTACAACGA CATGATGT
12646





5270
AUCAUGAC A UGCAUGUC
3898
GACATGCA GGCTAGCTACAACGA GTCATGAT
12647





5272
CAUGACAU G CAUGUCGG
3899
CCGACATG GGCTAGCTACAACGA ATGTCATG
12648





5274
UGACAUGC A UGUCGGCU
3900
AGCCGACA GGCTAGCTACAACGA GCATGTCA
12649





5276
ACAUGCAU G UCGGCUGA
3901
TCAGCCGA GGCTAGCTACAACGA ATGCATGT
12650





5280
GCAUGUCG G CUGACCUG
3902
CAGGTCAG GGCTAGCTACAACGA CGACATGC
12651





5284
GUCGGCUG A CCUGGAGG
3903
CCTCCAGG GGCTAGCTACAACGA CAGCCGAC
12652





5292
ACCUGGAG G UCGUCACC
3904
GGTGACGA GGCTAGCTACAACGA CTCCAGGT
12653





5295
UGGAGGUC G UCACCAGC
3905
GCTGGTGA GGCTAGCTACAACGA GACCTCCA
12654





5298
AGGUCGUC A CCAGCACC
3906
GGTGCTGG GGCTAGCTACAACGA GACGACCT
12655





5302
CGUCACCA G CACCUGGG
3907
CCCAGGTG GGCTAGCTACAACGA TGGTGACG
12656





5304
UCACCAGC A CCUGGGUG
3908
CACCCAGG GGCTAGCTACAACGA GCTGGTGA
12657





5310
GCACCUGG G UGCUAGUA
3909
TACTAGCA GGCTAGCTACAACGA CCAGGTGC
12658





5312
ACCUGGGU G CUAGUAGG
3910
CCTACTAG GGCTAGCTACAACGA ACCCAGGT
12659





5316
GGGUGCUA G UAGGUGGC
3911
GCCACCTA GGCTAGCTACAACGA TAGCACCC
12660





5320
GCUAGUAG G UGGCGUCC
3912
GGACGCCA GGCTAGCTACAACGA CTACTAGC
12661





5323
AGUAGGUG G CGUCCUGG
3913
CCAGGACG GGCTAGCTACAACGA CACCTACT
12662





5325
UAGGUGGC G UCCUGGCA
3914
TGCCAGGA GGCTAGCTACAACGA GCCACCTA
12663





5331
GCGUCCUG G CAGCUCUG
3915
CAGAGCTG GGCTAGCTACAACGA CAGGACGC
12664





5334
UCCUGGCA G CUCUGACC
3916
GGTCAGAG GGCTAGCTACAACGA TGCCAGGA
12665





5340
CAGCUCUG A CCGCGUAU
3917
ATACGCGG GGCTAGCTACAACGA CAGAGCTG
12666





5343
CUCUGACC G CGUAUUGC
3918
GCAATACG GGCTAGCTACAACGA GGTCAGAG
12667





5345
CUGACCGC G UAUUGCCU
3919
AGGCAATA GGCTAGCTACAACGA GCGGTCAG
12668





5347
GACCGCGU A UUGCCUGA
3920
TCAGGCAA GGCTAGCTACAACGA ACGCGGTC
12669





5350
CGCGUAUU G CCUGACGA
3921
TCGTCAGG GGCTAGCTACAACGA AATACGCG
12670





5355
AUUGCCUG A CGACAGGC
3922
GCCTGTCG GGCTAGCTACAACGA CAGGCAAT
12671





5358
GCCUGACG A CAGGCAGC
3923
GCTGCCTG GGCTAGCTACAACGA CGTCAGGC
12672





5362
GACGACAG G CAGCGUGG
3924
CCACGCTG GGCTAGCTACAACGA CTGTCGTC
12673





5365
GACAGGCA G CGUGGUCA
3925
TGACCACG GGCTAGCTACAACGA TGCCTGTC
12674





5367
CAGGCAGC G UGGUCAUU
3926
AATGACCA GGCTAGCTACAACGA GCTGCCTG
12675





5370
GCAGCGUG G UCAUUGUG
3927
CACAATGA GGCTAGCTACAACGA CACGCTGC
12676





5373
GCGUGGUC A UUGUGGGC
3928
GCCCACAA GGCTAGCTACAACGA GACCACGC
12677





5376
UGGUCAUU G UGGGCAGA
3929
TCTGCCCA GGCTAGCTACAACGA AATGACCA
12678





5380
CAUUGUGG G CAGAAUCA
3930
TGATTCTG GGCTAGCTACAACGA CCACAATG
12679





5385
UGGGCAGA A UCAUCUUG
3931
CAAGATGA GGCTAGCTACAACGA TCTGCCCA
12680





5388
GCAGAAUC A UCUUGUCC
3932
GGACAAGA GGCTAGCTACAACGA GATTCTGC
12681





5393
AUCAUCUU G UCCGGGAA
3933
TTCCCGGA GGCTAGCTACAACGA AAGATGAT
12682





5402
UCCGGGAA G CCGGCUGU
3934
ACAGCCGG GGCTAGCTACAACGA TTCCCGGA
12683





5406
GGAAGCCG G CUGUUAUC
3935
GATAACAG GGCTAGCTACAACGA CGGCTTCC
12684





5409
AGCCGGCU G UUAUCCCC
3936
GGGGATAA GGCTAGCTACAACGA AGCCGGCT
12685





5412
CGGCUGUU A UCCCCGAC
3937
GTCGGGGA GGCTAGCTACAACGA AACAGCCG
12686





5419
UAUCCCCG A CAGGGAGG
3938
CCTCCCTG GGCTAGCTACAACGA CGGGGATA
12687





5427
ACAGGGAG G CUCUCUAC
3939
GTAGAGAG GGCTAGCTACAACGA CTCCCTGT
12688





5434
GGCUCUCU A CCAGGAGU
3940
ACTCCTGG GGCTAGCTACAACGA AGAGAGCC
12689





5441
UACCAGGA G UUCGAUGA
3941
TCATCGAA GGCTAGCTACAACGA TCCTGGTA
12690





5446
GGAGUUCG A UGAGAUGG
3942
CCATCTCA GGCTAGCTACAACGA CGAACTCC
12691





5451
UCGAUGAG A UGGAGGAG
3943
CTCCTCCA GGCTAGCTACAACGA CTCATCGA
12692





5459
AUGGAGGA G UGUGCCUC
3944
GAGGCACA GGCTAGCTACAACGA TCCTCCAT
12693





5461
GGAGGAGU G UGCCUCAC
3945
GTGAGGCA GGCTAGCTACAACGA ACTCCTCC
12694





5463
AGGAGUGU G CCUCACAC
3946
GTGTGAGG GGCTAGCTACAACGA ACACTCCT
12695





5468
UGUGCCUC A CACCUCCC
3947
GGGAGGTG GGCTAGCTACAACGA GAGGCACA
12696





5470
UGCCUCAC A CCUCCCUU
3948
AAGGGAGG GGCTAGCTACAACGA GTGAGGCA
12697





5479
CCUCCCUU A CAUCGAAC
3949
GTTCGATG GGCTAGCTACAACGA AAGGGAGG
12698





5481
UCCCUUAC A UCGAACAG
3950
CTGTTCGA GGCTAGCTACAACGA GTAAGGGA
12699





5486
UACAUCGA A CAGGGGAU
3951
ATCCCCTG GGCTAGCTACAACGA TCGATGTA
12700





5493
AACAGGGG A UGCAGCUC
3952
GAGCTGCA GGCTAGCTACAACGA CCCCTGTT
12701





5495
CAGGGGAU G CAGCUCGC
3953
GCGAGCTG GGCTAGCTACAACGA ATCCCCTG
12702





5498
GGGAUGCA G CUCGCCGA
3954
TCGGCGAG GGCTAGCTACAACGA TGCATCCC
12703





5502
UGCAGCUC G CCGAGCAG
3955
CTGCTCGG GGCTAGCTACAACGA GAGCTGCA
12704





5507
CUCGCCGA G CAGUUCAA
3956
TTGAACTG GGCTAGCTACAACGA TCGGCGAG
12705





5510
GCCGAGCA G UUCAAGCA
3957
TGCTTGAA GGCTAGCTACAACGA TGCTCGGC
12706





5516
CAGUUCAA G CAGAAGGC
3958
GCCTTCTG GGCTAGCTACAACGA TTGAACTG
12707





5523
AGCAGAAG G CGCUCGGA
3959
TCCGAGCG GGCTAGCTACAACGA CTTCTGCT
12708





5525
CAGAAGGC G CUCGGAUU
3960
AATCCGAG GGCTAGCTACAACGA GCCTTCTG
12709





5531
GCGCUCGG A UUGCUGCA
3961
TGCAGCAA GGCTAGCTACAACGA CCGAGCGC
12710





5534
CUCGGAUU G CUGCAAAC
3962
GTTTGCAG GGCTAGCTACAACGA AATCCGAG
12711





5537
GGAUUGCU G CAAACAGC
3963
GCTGTTTG GGCTAGCTACAACGA AGCAATCC
12712





5541
UGCUGCAA A CAGCCACC
3964
GGTGGCTG GGCTAGCTACAACGA TTGCAGCA
12713





5544
UGCAAACA G CCACCAAC
3965
GTTGGTGG GGCTAGCTACAACGA TGTTTGCA
12714





5547
AAACAGCC A CCAACCAA
3966
TTGGTTGG GGCTAGCTACAACGA GGCTGTTT
12715





5551
AGCCACCA A CCAAGCGG
3967
CCGCTTGG GGCTAGCTACAACGA TGGTGGCT
12716





5556
CCAACCAA G CGGAGGCU
3968
AGCCTCCG GGCTAGCTACAACGA TTGGTTGG
12717





5562
AAGCGGAG G CUGCUGCU
3969
AGCAGCAG GGCTAGCTACAACGA CTCCGCTT
12718





5565
CGGAGGCU G CUGCUCCC
3970
GGGAGCAG GGCTAGCTACAACGA AGCCTCCG
12719





5568
AGGCUGCU G CUCCCGUG
3971
CACGGGAG GGCTAGCTACAACGA AGCAGCCT
12720





5574
CUGCUCCC G UGGUGGAA
3972
TTCCACCA GGCTAGCTACAACGA GGGAGCAG
12721





5577
CUCCCGUG G UGGAAUCC
3973
GGATTCCA GGCTAGCTACAACGA CACGGGAG
12722





5582
GUGGUGGA A UCCAAGUG
3974
CACTTGGA GGCTAGCTACAACGA TCCACCAC
12723





5588
GAAUCCAA G UGGCGAGC
3975
GCTCGCCA GGCTAGCTACAACGA TTGGATTC
12724





5591
UCCAAGUG G CGAGCCCU
3976
AGGGCTCG GGCTAGCTACAACGA CACTTGGA
12725





5595
AGUGGCGA G CCCUUGAG
3977
CTCAAGGG GGCTAGCTACAACGA TCGCCACT
12726





5604
CCCUUGAG G CUUUCUGG
3978
CCAGAAAG GGCTAGCTACAACGA CTCAAGGG
12727





5613
CUUUCUGG G CGAAGCAC
3979
GTGCTTCG GGCTAGCTACAACGA CCAGAAAG
12728





5618
UGGGCGAA G CACAUGUG
3980
CACATGTG GGCTAGCTACAACGA TTCGCCCA
12729





5620
GGCGAAGC A CAUGUGGA
3981
TCCACATG GGCTAGCTACAACGA GCTTCGCC
12730





5622
CGAAGCAC A UGUGGAAU
3982
ATTCCACA GGCTAGCTACAACGA GTGCTTCG
12731





5624
AAGCACAU G UGGAAUUU
3983
AAATTCCA GGCTAGCTACAACGA ATGTGCTT
12732





5629
CAUGUGGA A UUUCAUCA
3984
TGATGAAA GGCTAGCTACAACGA TCCACATG
12733





5634
GGAAUUUC A UCAGCGGG
3985
CCCGCTGA GGCTAGCTACAACGA GAAATTCC
12734





5638
UUUCAUCA G CGGGAUAC
3986
GTATCCCG GGCTAGCTACAACGA TGATGAAA
12735





5643
UCAGCGGG A UACAGUAC
3987
GTACTGTA GGCTAGCTACAACGA CCCGCTGA
12736





5645
AGCGGGAU A CAGUACCU
3988
AGGTACTG GGCTAGCTACAACGA ATCCCGCT
12737





5648
GGGAUACA G UACCUAGC
3989
GCTAGGTA GGCTAGCTACAACGA TGTATCCC
12738





5650
GAUACAGU A CCUAGCAG
3990
CTGCTAGG GGCTAGCTACAACGA ACTGTATC
12739





5655
AGUACCUA G CAGGCUUG
3991
CAAGCCTG GGCTAGCTACAACGA TAGGTACT
12740





5659
CCUAGCAG G CUUGUCCA
3992
TGGACAAG GGCTAGCTACAACGA CTGCTAGG
12741





5663
GCAGGCUU G UCCACUCU
3993
AGAGTGGA GGCTAGCTACAACGA AAGCCTGC
12742





5667
GCUUGUCC A CUCUGCCU
3994
AGGCAGAG GGCTAGCTACAACGA GGACAAGC
12743





5672
UCCACUCU G CCUGGGAA
3995
TTCCCAGG GGCTAGCTACAACGA AGAGTGGA
12744





5680
GCCUGGGA A CCCCGCGA
3996
TCGCGGGG GGCTAGCTACAACGA TCCCAGOC
12745





5685
GGAACCCC G CGAUAGCA
3997
TGCTATCG GGCTAGCTACAACGA GGGGTTCC
12746





5688
ACCCCGCG A UAGCAUCA
3998
TGATGCTA GGCTAGCTACAACGA CGCGGGGT
12747





5691
CCGCGAUA G CAUCAUUG
3999
CAATGATG GGCTAGCTACAACGA TATCGCGG
12748





5693
GCGAUAGC A UCAUUGAU
4000
ATCAATGA GGCTAGCTACAACGA GCTATCGC
12749





5696
AUAGCAUC A UUGAUGGC
4001
GCCATCAA GGCTAGCTACAACGA GATGCTAT
12750





5700
CAUCAUUG A UGGCAUUC
4002
GAATGCCA GGCTAGCTACAACGA CAATGATG
12751





5703
CAUUGAUG G CAUUCACA
4003
TGTGAATG GGCTAGCTACAACGA CATCAATG
12752





5705
UUGAUGGC A UUCACAGC
4004
GCTGTGAA GGCTAGCTACAACGA GCCATCAA
12753





5709
UGGCAUUC A CAGCCUCC
4005
GGAGGCTG GGCTAGCTACAACGA GAATGCCA
12754





5712
CAUUCACA G CCUCCAUC
4006
GATGGAGG GGCTAGCTACAACGA TGTGAATG
12755





5718
CAGCCUCC A UCACCAGC
4007
GCTGGTGA GGCTAGCTACAACGA GGAGGCTG
12756





5721
CCUCCAUC A CCAGCCCG
4008
CGGGCTGG GGCTAGCTACAACGA GATGGAGG
12757





5725
CAUCACCA G CCCGCUCA
4009
TGAGCGGG GGCTAGCTACAACGA TGGTGATG
12758





5729
ACCAGCCC G CUCACCAC
4010
GTGGTGAG GGCTAGCTACAACGA GGGCTGGT
12759





5733
GCCCGCUC A CCACCCAA
4011
TTGGGTGG GGCTAGCTACAACGA GAGCGGGC
12760





5736
CGCUCACC A CCCAAAGC
4012
GCTTTGGG GGCTAGCTACAACGA GGTGAGCG
12761





5743
CACCCAAA G CACCCUCC
4013
GGAGGGTG GGCTAGCTACAACGA TTTGGGTG
12762





5745
CCCAAAGC A CCCUCCUG
4014
CAGGAGGG GGCTAGCTACAACGA GCTTTGGG
12763





5753
ACCCUCCU G UUCAACAU
4015
ATGTTGAA GGCTAGCTACAACGA AGGAGGGT
12764





5758
CCUGUUCA A CAUCUUGG
4016
CCAAGATG GGCTAGCTACAACGA TGAACAGG
12765





5760
UGUUCAAC A UCUUGGGA
4017
TCCCAAGA GGCTAGCTACAACGA GTTGAACA
12766





5771
UUGGGAGG G UGGGUGGC
4018
GCCACCCA GGCTAGCTACAACGA CCTCCCAA
12767





5775
GAGGGUGG G UGGCCGCC
4019
GGCGGCCA GGCTAGCTACAACGA CCACCCTC
12768





5778
GGUGGGUG G CCGCCCAA
4020
TTGGGCGG GGCTAGCTACAACGA CACCCACC
12769





5781
GGGUGGCC G CCCAACUC
4021
GAGTTGGG GGCTAGCTACAACGA GGCCACCC
12770





5786
GCCGCCCA A CUCGCUCC
4022
GGAGCGAG GGCTAGCTACAACGA TGGGCGGC
12771





5790
CCCAACUC G CUCCCCCC
4023
GGGGGGAG GGCTAGCTACAACGA GAGTTGGG
12772





5802
CCCCCAGA G CCGUUUCG
4024
CGAAACGG GGCTAGCTACAACGA TCTGGGGG
12773





5805
CCAGAGCC G UUUCGGCC
4025
GGCCGAAA GGCTAGCTACAACGA GGCTCTGG
12774





5811
CCGUUUCG G CCUUCGUG
4026
CACGAAGG GGCTAGCTACAACGA CGAAACGG
12775





5817
CGGCCUUC G UGGGCGCC
4027
GGCGCCCA GGCTAGCTACAACGA GAAGGCCG
12776





5821
CUUCGUGG G CGCCGGCA
4028
TGCCGGCG GGCTAGCTACAACGA CCACGAAG
12777





5823
UCGUGGGC G CCGGCAUC
4029
GATGCCGG GGCTAGCTACAACGA GCCCACGA
12778





5827
GGGCGCCG G CAUCGCUG
4030
CAGCGATG GGCTAGCTACAACGA CGGCGCCC
12779





5829
GCGCCGGC A UCGCUGGC
4031
GCCAGCGA GGCTAGCTACAACGA GCCGGCGC
12780





5832
CCGGCAUC G CUGGCGCG
4032
CGCGCCAG GGCTAGCTACAACGA GATGCCGG
12781





5836
CAUCGCUG G CGCGGCUG
4033
CAGCCGCG GGCTAGCTACAACGA CAGCGATG
12782





5838
UCGCUGGC G CGGCUGUU
4034
AACAGCCG GGCTAGCTACAACGA GCCAGCGA
12783





5841
CUGGCGCG G CUGUUGGC
4035
GCCAACAG GGCTAGCTACAACGA CGCGCCAG
12784





5844
GCGCGGCU G UUGGCAGC
4036
GCTGCCAA GGCTAGCTACAACGA AGCCGCGC
12785





5848
GGCUGUUG G CAGCAUAG
4037
CTATGCTG GGCTAGCTACAACGA CAACAGCC
12786





5851
UGUUGGCA G CAUAGGCC
4038
GGCCTATG GGCTAGCTACAACGA TGCCAACA
12787





5853
UUGGCAGC A UAGGCCUU
4039
AAGGCCTA GGCTAGCTACAACGA GCTGCCAA
12788





5857
CAGCAUAG G CCUUGGGA
4040
TCCCAAGG GGCTAGCTACAACGA CTATGCTG
12789





5868
UUGGGAAG G UGCUUGUA
4041
TACAAGCA GGCTAGCTACAACGA CTTCCCAA
12790





5870
GGGAAGGU G CUUGUAGA
4042
TCTACAAG GGCTAGCTACAACGA ACCTTCCC
12791





5874
AGGUGCUU G UAGACAUU
4043
AATGTCTA GGCTAGCTACAACGA AAGCACCT
12792





5878
GCUUGUAG A CAUUCUGG
4044
CCAGAATG GGCTAGCTACAACGA CTACAAGC
12793





5880
UUGUAGAC A UUCUGGCG
4045
CGCCAGAA GGCTAGCTACAACGA GTCTACAA
12794





5886
ACAUUCUG G CGGGCUAU
4046
ATAGCCCG GGCTAGCTACAACCA CAGAATGT
12795





5890
UCUGGCGC G CUAUGGAG
4047
CTCCATAG GGCTAGCTACAACGA CCGCCAGA
12796





5893
GGCGGGCU A UGGAGCAG
4048
CTGCTCCA GGCTAGCTACAACGA AGCCCGCC
12797





5898
GCUAUGCA G CAGGAGUG
4049
CACTCCTG GGCTAGCTACAACGA TCCATAGC
12798





5904
GAGCAGGA G UGGCGGGU
4050
ACCCGCCA GGCTAGCTACAACGA TCCTGCTC
12799





5907
CAGGAGUG G CGGGUGCU
4051
AGCACCCG GGCTAGCTACAACGA CACTCCTG
12800





5911
AGUGGCGG G UGCUCUCG
4052
CGAGAGCA GGCTAGCTACAACGA CCGCCACT
12801





5913
UGGCGGGU G CUCUCGUG
4053
CACGAGAG GGCTAGCTACAACGA ACCCGCCA
12802





5919
GUGCUCUC G UGGCCUUC
4054
GAAGGCCA GGCTAGCTACAACGA GAGAGCAC
12803





5922
CUCUCCUG G CCUUCAAG
4055
CTTGAAGG GGCTAGCTACAACGA CACGAGAG
12804





5931
CCUUCAAG G UCAUGAGC
4056
GCTCATGA GGCTAGCTACAACGA CTTGAAGG
12805





5934
UCAAGGUC A UGAGCGGG
4057
CCCGCTCA GGCTAGCTACAACGA GACCTTGA
12806





5938
GGUCAUGA G CGGGGAGA
4058
TCTCCCCG GGCTAGCTACAACGA TCATGACC
12807





5946
GCGGGGAG A UGCCUUCU
4059
AGAAGGCA GGCTAGCTACAACGA CTCCCCGC
12808





5948
GGGGAGAU G CCUUCUAC
4060
GTAGAAGG GGCTAGCTACAACGA ATCTCCCC
12809





5955
UGCCUUCU A CCGAGGAC
4061
GTCCTCGG GGCTAGCTACAACGA AGAAGGCA
12810





5962
UACCGAGG A CCUGGUCA
4062
TGACCAGG GGCTAGCTACAACGA CCTCGGTA
12811





5967
AGGACCUG G UCAACUUA
4063
TAAGTTGA GGCTAGCTACAACGA CAGGTCCT
12812





5971
CCUGGUCA A CUUACUCC
4064
GGAGTAAG GGCTAGCTACAACGA TGACCAGG
12813





5975
GUCAACUU A CUCCCUGC
4065
GCAGGGAG GGCTAGCTACAACGA AAGTTGAC
12814





5982
UACUCCCU G CCAUCCUC
4066
GAGGATGG GGCTAGCTACAACGA AGGGAGTA
12815





5985
UCCCUGCC A UCCUCUCU
4067
AGAGAGGA GGCTAGCTACAACGA GGCAGGGA
12816





5998
CUCUCCUG G CGCCCUGG
4068
CCAGGGCG GGCTAGCTACAACGA CAGGAGAG
12817





6000
CUCCUGGC G CCCUGGUC
4069
GACCAGGG GGCTAGCTACAACGA GCCAGGAG
12818





6006
GCGCCCUG G UCGUCGGG
4070
CCCGACGA GGCTAGCTACAACGA CAGGGCGC
12819





6009
CCCUGGUC G UCGGGGUG
4071
CACCCCGA GGCTAGCTACAACGA GACCAGGG
12820





6015
UCGUCGGG G UGGUGUGC
4072
GCACACCA GGCTAGCTACAACGA CCCGACGA
12821





6018
UCGGGGUG G UGUGCGCA
4073
TGCGCACA GGCTAGCTACAACGA CACCCCGA
12822





6020
GGGGUGGU G UGCGCAGC
4074
GCTGCGCA GGCTAGCTACAACGA ACCACCCC
12823





6022
GGUGGUGU G CGCAGCGA
4075
TCGCTGCG GGCTAGCTACAACGA ACACCACC
12824





6024
UGGUGUGC G CAGCGAUA
4076
TATCGCTG GGCTAGCTACAACGA GCACACCA
12825





6027
UGUGCGCA G CGAUACUG
4077
CAGTATCG GGCTAGCTACAACGA TGCGCACA
12826





6030
GCGCAGCG A UACUGCGU
4078
ACGCAGTA GGCTAGCTACAACGA CGCTGCGC
12827





6032
GCAGCGAU A CUGCGUCG
4079
CGACGCAG GGCTAGCTACAACGA ATCGCTGC
12828





6035
GCGAUACU G CGUCGGCA
4080
TGCCGACG GGCTAGCTACAACGA AGTATCGC
12829





6037
GAUACUGC G UCGGCAUG
4081
CATGCCGA GGCTAGCTACAACGA GCAGTATC
12830





6041
CUGCGUCG G CAUGUGGG
4082
CCCACATG GGCTAGCTACAACGA CGACGCAG
12831





6043
GCGUCGGC A UGUGGGCC
4083
GGCCCACA GGCTAGCTACAACGA GCCGACGC
12832





6045
GUCGGCAU G UGGGCCCA
4084
TGGGCCCA GGCTAGCTACAACGA ATGCCGAC
12833





6049
GCAUGUGG G CCCAGGAG
4085
CTCCTGGG GGCTAGCTACAACGA CCACATGC
12834





6061
AGGAGAGG G CGCUGUGC
4086
GCACAGCG GGCTAGCTACAACGA CCTCTCCT
12835





6063
GAGAGGGC G CUGUGCAG
4087
CTGCACAG GGCTAGCTACAACGA GCCCTCTC
12836





6066
AGGGCGCU G UGCAGUGG
4088
CCACTGCA GGCTAGCTACAACGA AGCGCCCT
12837





6068
GGCGCUGU G CAGUGGAU
4089
ATCCACTG GGCTAGCTACAACGA ACAGCGCC
12838





6071
GCUGUGCA G UGGAUGAA
4090
TTCATCCA GGCTAGCTACAACGA TGCACAGC
12839





6075
UGCAGUGG A UGAAUCGG
4091
CCGATTCA GGCTAGCTACAACGA CCACTGCA
12840





6079
GUGGAUGA A UCGGCUGA
4092
TCAGCCGA GGCTAGCTACAACGA TCATCCAC
12841





6083
AUGAAUCG G CUGAUAGC
4093
GCTATCAG GGCTAGCTACAACGA CGATTCAT
12842





6087
AUCGGCUG A UAGCGUUC
4094
GAACGCTA GGCTAGCTACAACGA CAGCCGAT
12843





6090
GGCUGAUA G CGUUCGCU
4095
AGCGAACG GGCTAGCTACAACGA TATCAGCC
12844





6092
CUGAUAGC G UUCGCUUC
4096
GAAGCGAA GGCTAGCTACAACGA GCTATCAG
12845





6096
UAGCGUUC G CUUCGCGG
4097
CCGCGAAG GGCTAGCTACAACGA GAACGCTA
12846





6101
UUCGCUUC G CGGGGCAA
4098
TTGCCCCG GGCTAGCTACAACGA GAAGCGAA
12847





6106
UUCGCGGG G CAACCAUG
4099
CATGGTTG GGCTAGCTACAACGA CCCGCGAA
12848





6109
GCGGGGCA A CCAUGUCU
4100
AGACATGG GGCTAGCTACAACGA TGCCCCGC
12849





6112
GGGCAACC A UGUCUCCC
4101
GGGAGACA GGCTAGCTACAACGA GGTTGCCC
12850





6114
GCAACCAU G UCUCCCCC
4102
GGGGGAGA GGCTAGCTACAACGA ATGGTTGC
12851





6123
UCUCCCCC A CGCACUAU
4103
ATAGTGCG GGCTAGCTACAACGA GGGGGAGA
12852





6125
UCCCCCAC G CACUAUGU
4104
ACATAGTG GGCTAGCTACAACGA GTGGGGGA
12853





6127
CCCCACGC A CUAUGUGC
4105
GCACATAG GGCTAGCTACAACGA GCGTGGGG
12854





6130
CACGCACU A UGUGCCUG
4106
CAGGCACA GGCTAGCTACAACGA AGTGCGTG
12855





6132
CGCACUAU G UGCCUGAG
4107
CTCAGGCA GGCTAGCTACAACGA ATAGTGCG
12856





6134
CACUAUGU G CCUGAGAG
4108
CTCTCAGG GGCTAGCTACAACGA ACATAGTG
12857





6142
GCCUGAGA G CGACGCAG
4109
CTGCGTCG GGCTAGCTACAACGA TCTCAGGC
12858





6145
UGAGAGCG A CGCAGCGG
4110
CCGCTGCG GGCTAGCTACAACGA CGCTCTCA
12859





6147
AGAGCGAC G CAGCGGCG
4111
CGCCGCTG GGCTAGCTACAACGA GTCGCTCT
12860





6150
GCGACGCA G CGGCGCGC
4112
GCGCGCCG GGCTAGCTACAACGA TGCGTCGC
12861





6153
ACGCAGCG G CGCGCGUC
4113
GACGCGCG GGCTAGCTACAACGA CGCTGCGT
12862





6155
GCAGCGGC G CGCGUCAC
4114
GTGACGCG GGCTAGCTACAACGA GCCGCTGC
12863





6157
AGCGGCGC G CGUCACAC
4115
GTGTGACG GGCTAGCTACAACGA GCGCCGCT
12864





6159
CGGCGCGC G UCACACAA
4116
TTGTGTGA GGCTAGCTACAACGA GCGCGCCG
12865





6162
CGCGCGUC A CACAAAUC
4117
GATTTGTG GGCTAGCTACAACGA GACGCGCG
12866





6164
CGCGUCAC A CAAAUCCU
4118
AGGATTTG GGCTAGCTACAACGA GTGACGCG
12867





6168
UCACACAA A UCCUCUCC
4119
GGAGAGGA GGCTAGCTACAACGA TTGTGTGA
12868





6178
CCUCUCCA G CCUCACCA
4120
TGGTGAGG GGCTAGCTACAACGA TGGAGAGG
12869





6183
CCAGCCUC A CCAUCACU
4121
AGTGATGG GGCTAGCTACAACGA GAGGCTGG
12870





6186
GCCUCACC A UCACUCAG
4122
CTGAGTGA GGCTAGCTACAACGA GGTGAGGC
12871





6189
UCACCAUC A CUCAGCUG
4123
CAGCTGAG GGCTAGCTACAACGA GATGGTGA
12872





6194
AUCACUCA G CUGCUGAG
4124
CTCAGCAG GGCTAGCTACAACGA TGAGTGAT
12873





6197
ACUCAGCU G CUGAGGAG
4125
CTCCTCAG GGCTAGCTACAACGA AGCTGAGT
12874





6206
CUGAGGAG G CUCCAUCA
4126
TGATGGAG GGCTAGCTACAACGA CTCCTCAG
12875





6211
GAGGCUCC A UCAGUGGA
4127
TCCACTGA GGCTAGCTACAACGA GGAGCCTC
12876





6215
CUCCAUCA G UGGAUCAA
4128
TTGATCCA GGCTAGCTACAACGA TGATGGAG
12877





6219
AUCAGUGG A UCAAUGAG
4129
CTCATTGA GGCTAGCTACAACGA CCACTGAT
12878





6223
GUGGAUCA A UGAGGACU
4130
AGTCCTCA GGCTAGCTACAACGA TGATCCAC
12879





6229
CAAUGAGG A CUGCUCCA
4131
TGGAGCAG GGCTAGCTACAACGA CCTCATTG
12880





6232
UGAGGACU G CUCCACGC
4132
GCGTGGAG GGCTAGCTACAACGA AGTCCTCA
12881





6237
ACUGCUCC A CGCCAUGU
4133
ACATGGCG GGCTAGCTACAACGA GGAGCAGT
12882





6239
UGCUCCAC G CCAUGUUC
4134
GAACATGG GGCTAGCTACAACGA GTGGAGCA
12883





6242
UCCACGCC A UGUUCCGG
4135
CCGGAACA GGCTAGCTACAACGA GGCGTGGA
12884





6244
CACGCCAU G UUCCGGCU
4136
AGCCGGAA GGCTAGCTACAACGA ATGGCGTG
12885





6250
AUGUUCCG G CUCGUGGC
4137
GCCACGAG GGCTAGCTACAACGA CGGAACAT
12886





6254
UCCGGCUC G UGGCUAAG
4138
CTTAGCCA GGCTAGCTACAACGA GAGCCGGA
12887





6257
GGCUCGUG G CUAAGGGA
4139
TCCCTTAG GGCTAGCTACAACGA CACGAGCC
12888





6265
GCUAAGGG A UGUUUGGG
4140
CCCAAACA GGCTAGCTACAACGA CCCTTAGC
12889





6267
UAAGGGAU G UUUGGGAC
4141
GTCCCAAA GGCTAGCTACAACGA ATCCCTTA
12890





6274
UGUUUGGG A CUGGAUAU
4142
ATATCCAG GGCTAGCTACAACGA CCCAAACA
12891





6279
GGGACUGG A UAUGCACG
4143
CGTGCATA GGCTAGCTACAACGA CCAGTCCC
12892





6281
GACUGGAU A UGCACGGU
4144
ACCOTGCA GGCTAGCTACAACGA ATCCAGTC
12893





6283
CUGGAUAU G CACGGUGU
4145
ACACCGTG GGCTAGCTACAACGA ATATCCAG
12894





6285
GGAUAUGC A CGGUGUUG
4146
CAACACCG GGCTAGCTACAACGA GCATATCC
12895





6288
UAUGCACG G UGUUGACU
4147
AGTCAACA GGCTAGCTACAACGA CGTGCATA
12896





6290
UGCACGGU G UUGACUGA
4148
TCAGTCAA GGCTAGCTACAACGA ACCGTGCA
12897





6294
CGGUGUUG A CUGACUUC
4149
GAAGTCAG GGCTAGCTACAACGA CAACACCG
12898





6298
GUUGACUG A CUUCAAGA
4150
TCTTGAAG GGCTAGCTACAACGA CAGTCAAC
12899





6306
ACUUCAAG A CCUGGCUU
4151
AAGCCAGG GGCTAGCTACAACGA CTTGAAGT
12900





6311
AAGACCUG G CUUCAGUC
4152
GACTGAAG GGCTAGCTACAACGA CAGGTCTT
12901





6317
UGGCUUCA G UCCAAGCU
4153
AGCTTGGA GGCTAGCTACAACGA TGAAGCCA
12902





6323
CAGUCCAA G CUCCUGCC
4154
GGCAGGAG GGCTAGCTACAACGA TTGGACTG
12903





6329
AAGCUCCU G CCGCGGUU
4155
AACCGCGG GGCTAGCTACAACGA AGGAGCTT
12904





6332
CUCCUGCC G CGGUUGCC
4156
GGCAACCG GGCTAGCTACAACGA GGCAGGAG
12905





6335
CUGCCGCG G UUGCCGGG
4157
CCCGGCAA GGCTAGCTACAACGA CGCGGCAG
12906





6338
CCGCGGUU G CCGGGAGU
4158
ACTCCCGG GGCTAGCTACAACGA AACCGCGG
12907





6345
UGCCCGGA G UCCCUUUC
4159
GAAAGGGA GGCTAGCTACAACGA TCCCGGCA
12908





6359
UUCUUCUC A UGCCAACG
4160
CGTTGGCA GGCTAGCTACAACGA GAGAAGAA
12909





6361
CUUCUCAU G CCAACGUG
4161
CACGTTGG GGCTAGCTACAACGA ATGAGAAG
12910





6365
UCAUGCCA A CGUGGGUA
4162
TACCCACG GGCTAGCTACAACGA TGGCATGA
12911





6367
AUGCCAAC G UGGGUACA
4163
TGTACCCA GGCTAGCTACAACGA GTTGGCAT
12912





6371
CAACGUGG G UACAGGGG
4164
CCCCTGTA GGCTAGCTACAACGA CCACGTTG
12913





6373
ACGUGGGU A CAGGGGGG
4165
CCCCCCTG GGCTAGCTACAACGA ACCCACGT
12914





6381
ACAGGGGG G UCUGGCGG
4166
CCGCCAGA GGCTAGCTACAACGA CCCCCTGT
12915





6386
GGGGUCUG G CGGGGAGA
4167
TCTCCCCG GGCTAGCTACAACGA CAGACCCC
12916





6394
GCGGGGAG A CGGUAUCA
4168
TGATACCG GGCTAGCTACAACGA CTCCCCGC
12917





6397
GGGAGACG G UAUCAUGC
4169
GCATGATA GGCTAGCTACAACGA CGTCTCCC
12918





6399
GAGACGGU A UCAUGCAA
4170
TTGCATGA GGCTAGCTACAACGA ACCGTCTC
12919





6402
ACGGUAUC A UGCAAACC
4171
GGTTTGCA GGCTAGCTACAACGA GATACCGT
12920





6404
GGUAUCAU G CAAACCAC
4172
GTGGTTTG GGCTAGCTACAACGA ATGATACC
12921





6408
UCAUGCAA A CCACCUGC
4173
GCAGGTGG GGCTAGCTACAACGA TTGCATGA
12922





6411
UGCAAACC A CCUGCCCA
4174
TGGGCAGG GGCTAGCTACAACGA GGTTTGCA
12923





6415
AACCACCU G CCCAUGCG
4175
CGCATGGG GGCTAGCTACAACGA AGGTGGTT
12924





6419
ACCUGCCC A UGCGGAGC
4176
GCTCCGCA GGCTAGCTACAACGA GGGCAGGT
12925





6421
CUGCCCAU G CGGAGCGC
4177
GCGCTCCG GGCTAGCTACAACGA ATGGGCAG
12926





6426
CAUGCGGA G CGCAGAUC
4178
GATCTGCG GGCTAGCTACAACGA TCCGCATG
12927





6428
UGCGGAGC G CAGAUCAC
4179
GTGATCTG GGCTAGCTACAACGA GCTCCGCA
12928





6432
GAGCGCAG A UCACUGGA
4180
TCCAGTGA GGCTAGCTACAACGA CTGCGCTC
12929





6435
CGCAGAUC A CUGGACAU
4181
ATGTCCAG GGCTAGCTACAACGA GATCTGCG
12930





6440
AUCACUGG A CAUGUCAA
4182
TTGACATG GGCTAGCTACAACGA CCAGTGAT
12931





6442
CACUGGAC A UGUCAAGA
4183
TCTTGACA GGCTAGCTACAACGA GTCCAGTG
12932





6444
CUGGACAU G UCAAGAAC
4184
GTTCTTGA GGCTAGCTACAACGA ATGTCCAG
12933





6451
UGUCAAGA A CGGUUCCA
4185
TGGAACCG GGCTAGCTACAACGA TCTTGACA
12934





6454
CAAGAACG G UUCCAUGA
4186
TCATGGAA GGCTAGCTACAACGA CGTTCTTG
12935





6459
ACGGUUCC A UGAGGAUC
4187
GATCCTCA GGCTAGCTACAACGA GGAACCGT
12936





6465
CCAUGAGG A UCGUCGGG
4188
CCCGACGA GGCTAGCTACAACGA CCTCATGG
12937





6468
UGAGGAUC G UCGGGCCU
4189
AGGCCCGA GGCTAGCTACAACGA GATCCTCA
12938





6473
AUCGUCGG G CCUAAGAC
4190
GTCTTAGG GGCTAGCTACAACGA CCGACGAT
12939





6480
GGCCUAAG A CCUGUAGC
4191
GCTACAGG GGCTAGCTACAACGA CTTAGGCC
12940





6484
UAAGACCU G UAGCAACA
4192
TGTTGCTA GGCTAGCTACAACGA AGGTCTTA
12941





6487
GACCUGUA G CAACACGU
4193
ACGTGTTG GGCTAGCTACAACGA TACAGGTC
12942





6490
CUGUAGCA A CACGUGGC
4194
GCCACGTG GGCTAGCTACAACGA TGCTACAG
12943





6492
GUAGCAAC A CGUGGCAU
4195
ATGCCACG GGCTAGCTACAACGA GTTGCTAC
12944





6494
AGCAACAC G UGGCAUGG
4196
CCATGCCA GGCTAGCTACAACGA GTGTTGCT
12945





6497
AACACGUG G CAUGGAAC
4197
GTTCCATG GGCTAGCTACAACGA CACGTGTT
12946





6499
CACGUGGC A UGGAACAU
4198
ATGTTCCA GGCTAGCTACAACGA GCCACGTG
12947





6504
GGCAUGGA A CAUUCCCC
4199
GGGGAATG GGCTAGCTACAACGA TCCATGCC
12948





6506
CAUGGAAC A UUCCCCAU
4200
ATGGGGAA GGCTAGCTACAACGA GTTCCATG
12949





6513
CAUUCCCC A UCAACGCA
4201
TGCGTTGA GGCTAGCTACAACGA GGGGAATG
12950





6517
CCCCAUCA A CGCAUACA
4202
TGTATGCG GGCTAGCTACAACGA TGATGGGG
12951





6519
CCAUCAAC G CAUACACC
4203
GGTGTATG GGCTAGCTACAACGA GTTGATGG
12952





6521
AUCAACGC A UACACCAC
4204
GTGGTGTA GGCTAGCTACAACGA GCGTTGAT
12953





6523
CAACGCAU A CACCACGG
4205
CCGTGGTG GGCTAGCTACAACGA ATGCGTTG
12954





6525
ACGCAUAC A CCACGGGC
4206
GCCCGTGG GGCTAGCTACAACGA GTATGCGT
12955





6528
CAUACACC A CGGGCCCC
4207
GGGGCCCG GGCTAGCTACAACGA GGTGTATG
12956





6532
CACCACGG G CCCCUGCA
4208
TGCAGGGG GGCTAGCTACAACGA CCGTGGTG
12957





6538
GGCCCCCU G CACACCCU
4209
AGGGTGTG GGCTAGCTACAACGA AGGGGCCC
12958





6540
GCCCCUGC A CACCCUCC
4210
GGAGGGTG GGCTAGCTACAACGA GCAGGGGC
12959





6542
CCCUGCAC A CCCUCCCC
4211
GGGGAGGG GGCTAGCTACAACGA GTGCAGGG
12960





6552
CCUCCCCG G CGCCAAAC
4212
GTTTGGCG GGCTAGCTACAACGA CGGGGAGG
12961





6554
UCCCCGGC G CCAAACUA
4213
TAGTTTGG GGCTAGCTACAACGA GCCGGGGA
12962





6559
GGCGCCAA A CUAUUCUA
4214
TAGAATAG GGCTAGCTACAACGA TTGGCGCC
12963





6562
GCCAAACU A UUCUAGGG
4215
CCCTAGAA GGCTAGCTACAACGA AGTTTGGC
12964





6570
AUUCUAGG G CGCUAUGG
4216
CCATAGCG GGCTAGCTACAACGA CCTAGAAT
12965





6572
UCUAGGGC G CUAUGGCG
4217
CGCCATAG GGCTAGCTACAACGA GCCCTAGA
12966





6575
AGGGCGCU A UGGCGGGU
4218
ACCCGCCA GGCTAGCTACAACGA AGCGCCCT
12967





6578
GCGCUAUG G CGGGUGGC
4219
GCCACCCG GGCTAGCTACAACGA CATAGCGC
12968





6582
UAUGGCGG G UGGCCGCU
4220
AGCGGCCA GGCTAGCTACAACGA CCGCCATA
12969





6585
GGCGGGUG G CCGCUGAG
4221
CTCAGCGG GGCTAGCTACAACGA CACCCGCC
12970





6588
GGGUGGCC G CUGAGGAG
4222
CTCCTCAG GGCTAGCTACAACGA GGCCACCC
12971





6596
GCUGAGGA G UACGUGGA
4223
TCCACGTA GGCTAGCTACAACGA TCCTCAGC
12972





6598
UGAGGAGU A CGUGGAGG
4224
CCTCCACG GGCTAGCTACAACGA ACTCCTCA
12973





6600
AGGAGUAC G UGGAGGUU
4225
AACCTCCA GGCTAGCTACAACGA GTACTCCT
12974





6606
ACGUGGAG G UUACGCGG
4226
CCGCGTAA GGCTAGCTACAACGA CTCCACGT
12975





6609
UGGAGGUU A CGCGGGUG
4227
CACCCGCG GGCTAGCTACAACGA AACCTCCA
12976





6611
GAGGUUAC G CGGGUGGG
4228
CCCACCCG GGCTAGCTACAACGA GTAACCTC
12977





6615
UUACGCGG G UGGGGGAU
4229
ATCCCCCA GGCTAGCTACAACGA CCGCGTAA
12978





6622
GGUGGGGG A UUUCCACU
4230
AGTGGAAA GGCTAGCTACAACGA CCCCCACC
12979





6628
GGAUUUCC A CUACGUGA
4231
TCACGTAG GGCTAGCTACAACGA GGAAATCC
12980





6631
UUUCCACU A CGUGACGG
4232
CCGTCACG GGCTAGCTACAACGA AGTGGAAA
12981





6633
UCCACUAC G UGACGGGC
4233
GCCCGTCA GGCTAGCTACAACGA GTAGTGGA
12982





6636
ACUACGUG A CGGGCAUG
4234
CATGCCCG GGCTAGCTACAACGA CACGTAGT
12983





6640
CGUGACGG G CAUGACCA
4235
TGGTCATG GGCTAGCTACAACGA CCGTCACG
12984





6642
UGACGGGC A UGACCACU
4236
AGTGGTCA GGCTAGCTACAACGA GCCCGTCA
12985





6645
CGGGCAUG A CCACUGAC
4237
GTCAGTGG GGCTAGCTACAACGA CATGCCCG
12986





6648
GCAUGACC A CUGACAAC
4238
GTTGTCAG GGCTAGCTACAACGA GGTCATGC
12987





6652
GACCACUG A CAACGUAA
4239
TTACGTTG GGCTAGCTACAACGA CAGTGGTC
12988





6655
CACUGACA A CGUAAAAU
4240
ATTTTACG GGCTAGCTACAACGA TGTCAGTG
12989





6657
CUGACAAC G UAAAAUGC
4241
GCATTTTA GGCTAGCTACAACGA GTTGTCAG
12990





6662
AACGUAAA A UGCCCGUG
4242
CACGGGCA GGCTAGCTACAACGA TTTACGTT
12991





6664
CGUAAAAU G CCCGUGCC
4243
GGCACGGG GGCTAGCTACAACGA ATTTTACG
12992





6668
AAAUGCCC G UGCCAGGU
4244
ACCTGGCA GGCTAGCTACAACGA GGGCATTT
12993





6670
AUGCCCGU G CCAGGUUC
4245
GAACCTGG GGCTAGCTACAACGA ACGGGCAT
12994





6675
CGUGCCAG G UUCCGCCC
4246
GGGCGGAA GGCTAGCTACAACGA CTGGCACG
12995





6680
CAGGUUCC G CCCCCCGA
4247
TCGGGGGG GGCTAGCTACAACGA GGAACCTG
12996





6689
CCCCCCGA A UUCUUCAC
4248
GTGAAGAA GGCTAGCTACAACGA TCGGGGGG
12997





6696
AAUUCUUC A CGGAAGUG
4249
CACTTCCG GGCTAGCTACAACGA GAAGAATT
12998





6702
UCACGGAA G UGGAUGGG
4250
CCCATCCA GGCTAGCTACAACGA TTCCGTGA
12999





6706
GGAAGUGG A UGGGGUAC
4251
GTACCCCA GGCTAGCTACAACGA CCACTTCC
13000





6711
UGGAUGGG G UACGCCUG
4252
CAGGCGTA GGCTAGCTACAACGA CCCATCCA
13001





6713
GAUGGGGU A CGCCUGCA
4253
TGCAGGCG GGCTAGCTACAACGA ACCCCATC
13002





6715
UGGGGUAC G CCUGCACA
4254
TGTGCAGG GGCTAGCTACAACGA GTACCCCA
13003





6719
GUACGCCU G CACAGAAA
4255
TTTCTGTG GGCTAGCTACAACGA AGGCGTAC
13004





6721
ACGCCUGC A CAGAAACG
4256
CGTTTCTG GGCTAGCTACAACGA GCAGGCGT
13005





6727
GCACAGAA A CGCUCCGG
4257
CCGGAGCG GGCTAGCTACAACGA TTCTGTGC
13006





6729
ACAGAAAC G CUCCGGCG
4258
CGCCGGAG GGCTAGCTACAACGA GTTTCTGT
13007





6735
ACGCUCCG G CGUGUGGA
4259
TCCACACG GGCTAGCTACAACGA CGGAGCGT
13008





6737
GCUCCGGC G UGUGGACC
4260
GGTCCACA GGCTAGCTACAACGA GCCGGAGC
13009





6739
UCCGGCGU G UGGACCUC
4261
GAGGTCCA GGCTAGCTACAACGA ACGCCGGA
13010





6743
GCGUGUGG A CCUCUCCU
4262
AGGAGAGG GGCTAGCTACAACGA CCACACGC
13011





6752
CCUCUCCU A CGGGAGGA
4263
TCCTCCCG GGCTAGCTACAACGA AGGAGAGG
13012





6762
GGGAGGAG G UCACAUUC
4264
GAATGTGA GGCTAGCTACAACGA CTCCTCCC
13013





6765
AGGAGGUC A CAUUCCAG
4265
CTGGAATG GGCTAGCTACAACGA GACCTCCT
13014





6767
GAGGUCAC A UUCCAGGU
4266
ACCTGGAA GGCTAGCTACAACGA GTGACCTC
13015





6774
CAUUCCAG G UCGGGCUC
4267
GAGCCCGA GGCTAGCTACAACGA CTGGAATG
13016





6779
CAGGUCGG G CUCAACCA
4268
TGGTTGAG GGCTAGCTACAACGA CCGACCTG
13017





6784
CGGGCUCA A CCAAUACC
4269
GGTATTGG GGCTAGCTACAACGA TGAGCCCG
13018





6788
CUCAACCA A UACCUGGU
4270
ACCAGGTA GGCTAGCTACAACGA TGGTTGAG
13019





6790
CAACCAAU A CCUGGUUG
4271
CAACCAGG GGCTAGCTACAACGA ATTGGTTG
13020





6795
AAUACCUG G UUGGGUCA
4272
TGACCCAA GGCTAGCTACAACGA CAGGTATT
13021





6800
CUGGUUGG G UCACAGCU
4273
AGCTGTGA GGCTAGCTACAACGA CCAACCAG
13022





6803
GUUGGGUC A CAGCUCCC
4274
GGGAGCTG GGCTAGCTACAACGA GACCCAAC
13023





6806
GGGUCACA G CUCCCAUG
4275
CATGGGAG GGCTAGCTACAACGA TGTGACCC
13024





6812
CAGCUCCC A UGCGAGCC
4276
GGCTCGCA GGCTAGCTACAACGA GGGAGCTG
13025





6814
GCUCCCAU G CGAGCCCG
4277
CGGGCTCG GGCTAGCTACAACGA ATGGGAGC
13026





6818
CCAUGCGA G CCCGAACC
4278
GGTTCGGG GGCTAGCTACAACGA TCGCATGG
13027





6824
GAGCCCGA A CCGGAUGU
4279
ACATCCGG GGCTAGCTACAACGA TCGGGCTC
13028





6829
CGAACCGG A UGUACCAG
4280
CTGCTACA GGCTAGCTACAACGA CCGGTTCG
13029





6831
AACCGGAU G UAGCAGUG
4281
CACTGCTA GGCTAGCTACAACGA ATCCGGTT
13030





6834
CGGAUGUA G CAGUGCUC
4282
GAGCACTC GGCTAGCTACAACGA TACATCCG
13031





6837
AUGUAGCA G UGCUCACG
4283
CGTGAGCA GGCTAGCTACAACGA TGCTACAT
13032





6839
GUAGCAGU G CUCACGUC
4284
GACGTGAG GGCTAGCTACAACGA ACTGCTAC
13033





6843
CAGUCCUC A CGUCCAUG
4285
CATGGACG GGCTAGCTACAACGA GAGCACTG
13034





6845
GUGCUCAC G UCCAUGCU
4286
AGCATGGA GGCTAGCTACAACGA GTGAGCAC
13035





6849
UCACGUCC A UGCUCACC
4287
GGTGAGCA GGCTAGCTACAACGA GGACGTGA
13036





6851
ACGUCCAU G CUCACCGA
4288
TCGGTGAG GGCTAGCTACAACGA ATGGACGT
13037





6855
CCAUGCUC A CCGACCCC
4289
GGGGTCGG GGCTAGCTACAACGA GAGCATGG
13038





6859
GCUCACCG A CCCCUCCC
4290
GGGAGGGG GGCTAGCTACAACGA CGGTGAGC
13039





6868
CCCCUCCC A CAUUACAG
4291
CTGTAATG GGCTAGCTACAACGA GGGAGGGG
13040





6870
CCUCCCAC A UUACAGGA
4292
TCCTGTAA GGCTAGCTACAACGA GTGGGAGG
13041





6873
CCCACAUU A CAGGAGAG
4293
CTCTCCTG GGCTAGCTACAACGA AATGTGGG
13042





6882
CAGGAGAG A CGGCUAAG
4294
CTTAGCCG GGCTAGCTACAACGA CTCTCCTG
13043





6885
GAGAGACG G CUAAGCGU
4295
ACGCTTAG GGCTAGCTACAACGA CGTCTCTC
13044





6890
ACGGCUAA G CGUAGGCU
4296
AGCCTACG GGCTAGCTACAACGA TTAGCCGT
13045





6892
GGCUAAGC G UAGGCUGG
4297
CCAGCCTA GGCTAGCTACAACGA GCTTAGCC
13046





6896
AAGCGUAG G CUGGCCAG
4298
CTGGCCAG GGCTAGCTACAACGA CTACGCTT
13047





6900
GUAGGCUG G CCAGGGGG
4299
CCCCCTGG GGCTAGCTACAACGA CAGCCTAC
13048





6908
GCCAGGGG G UCUCCCCC
4300
GGGGGAGA GGCTAGCTACAACGA CCCCTGGC
13049





6924
CCUCCUUG G CCAGCUCC
4301
GGAGCTGG GGCTAGCTACAACGA CAAGGAGG
13050





6928
CUUGGCCA G CUCCUCAG
4302
CTGAGGAG GGCTAGCTACAACGA TGGCCAAG
13051





6936
GCUCCUCA G CUAGCCAG
4303
CTGGCTAG GGCTAGCTACAACGA TGAGGAGC
13052





6940
CUCAGCUA G CCAGCUGU
4304
ACAGCTGG GGCTAGCTACAACGA TAGCTGAG
13053





6944
GCUAGCCA G CUGUCUGC
4305
GCAGACAG GGCTAGCTACAACGA TGGCTAGC
13054





6947
AGCCAGCU G UCUGCGCC
4306
GGCGCAGA GGCTAGCTACAACGA AGCTGGCT
13055





6951
AGCUGUCU G CGCCUUCU
4307
AGAAGGCG GGCTAGCTACAACGA AGACAGCT
13056





6953
CUGUCUGC G CCUUCUUC
4308
GAAGAAGG GGCTAGCTACAACGA GCAGACAG
13057





6966
CUUCGAAG G CGACAUAC
4309
GTATGTCG GGCTAGCTACAACGA CTTCGAAG
13058





6969
CGAAGGCG A CAUACAUU
4310
AATGTATG GGCTAGCTACAACGA CGCCTTCG
13059





6971
AAGGCGAC A UACAUUAC
4311
GTAATGTA GGCTAGCTACAACGA GTCGCCTT
13060





6973
GGCGACAU A CAUUACCC
4312
GGGTAATG GGCTAGCTACAACGA ATGTCGCC
13061





6975
CGACAUAC A UUACCCAA
4313
TTGGGTAA GGCTAGCTACAACGA GTATGTCG
13062





6978
CAUACAUU A CCCAAUAU
4314
ATATTGGG GGCTAGCTACAACGA AATGTATG
13063





6983
AUUACCCA A UAUGACUC
4315
GAGTCATA GGCTAGCTACAACGA TGGGTAAT
13064





6985
UACCCAAU A UGACUCCC
4316
GGGAGTCA GGCTAGCTACAACGA ATTGGGTA
13065





6988
CCAAUAUG A CUCCCCAG
4317
CTGGGGAG GGCTAGCTACAACGA CATATTGG
13066





6997
CUCCCCAG A CUUUGACC
4318
GGTCAAAG GGCTAGCTACAACGA CTGGGGAG
13067





7003
AGACUUUG A CCUCAUCG
4319
CGATGAGG GGCTAGCTACAACGA CAAAGTCT
13068





7008
UUGACCUC A UCGAGGCC
4320
GGCCTCGA GGCTAGCTACAACGA GAGGTCAA
13069





7014
UCAUCGAG G CCAACCUC
4321
GAGGTTGG GGCTAGCTACAACGA CTCGATGA
13070





7018
CGAGGCCA A CCUCCUGU
4322
ACAGGAGG GGCTAGCTACAACGA TGGCCTCG
13071





7025
AACCUCCU G UGGCGGCA
4323
TGCCGCCA GGCTAGCTACAACGA AGGAGGTT
13072





7028
CUCCUGUG G CGGCAGGA
4324
TCCTGCCG GGCTAGCTACAACGA CACAGGAG
13073





7031
CUGUGGCG G CAGGAGAU
4325
ATCTCCTG GGCTAGCTACAACGA CGCCACAG
13074





7038
GGCAGGAG A UGGGCGGU
4326
ACCGCCCA GGCTAGCTACAACGA CTCCTGCC
13075





7042
GGAGAUGG G CGGUAACA
4327
TGTTACCG GGCTAGCTACAACGA CCATCTCC
13076





7045
GAUGGGCG G UAACAUCA
4328
TGATGTTA GGCTAGCTACAACGA CGCCCATC
13077





7048
GGGCGCUA A CAUCACUC
4329
GAGTCATG GGCTAGCTACAACGA TACCGCCC
13078





7050
GCCGUAAC A UCACUCGC
4330
GCGAGTGA GGCTAGCTACAACGA GTTACCGC
13079





7053
GUAACAUC A CUCGCGUG
4331
CACGCGAG GGCTAGCTACAACGA GATGTTAC
13080





7057
CAUCACUC G CCUGGAGU
4332
ACTCCACG GGCTAGCTACAACGA GAGTGATG
13081





7059
UCACUCGC G UCCAGUCA
4333
TGACTCCA GGCTAGCTACAACGA GCGAGTGA
13082





7064
CGCGUGGA G UCAGAGAA
4334
TTCTCTGA GGCTAGCTACAACGA TCCACGCG
13083





7072
GUCAGAGA A UAAGGUAG
4335
CTACCTTA GGCTAGCTACAACGA TCTCTGAC
13084





7077
AGAAUAAG G UAGUUACC
4336
GGTAACTA GGCTAGCTACAACGA CTTATTCT
13085





7080
AUAAGGUA G UUACCCUG
4337
CAGGGTAA GGCTAGCTACAACGA TACCTTAT
13086





7083
AGGUAGUU A CCCUGGAC
4338
GTCCAGGG GGCTAGCTACAACGA AACTACCT
13087





7090
UACCCUGG A CUCUUUUG
4339
CAAAAGAG GGCTAGCTACAACGA CCAGGGTA
13088





7099
CUCUUUUG A CCCGCUUC
4340
GAAGCGGG GGCTAGCTACAACGA CAAAAGAG
13089





7103
UUUGACCC G CUUCGAGC
4341
GCTCGAAG GGCTAGCTACAACGA GGGTCAAA
13090





7110
CGCUUCGA G CGGAGGAG
4342
CTCCTCCG GGCTAGCTACAACGA TCGAAGCG
13091





7120
GGAGGAGG A UGAGAGAG
4343
CTCTCTCA GGCTAGCTACAACGA CCTCCTCC
13092





7131
AGAGAGAG G UGUCCAUU
4344
AATGGACA GGCTAGCTACAACGA CTCTCTCT
13093





7133
AGAGAGGU G UCCAUUCC
4345
GGAATGGA GGCTAGCTACAACGA ACCTCTCT
13094





7137
AGGUGUCC A UUCCGGCG
4346
CGCCGGAA GGCTAGCTACAACGA GGACACCT
13095





7143
CCAUUCCG G CGGAGAUC
4347
GATCTCCG GGCTAGCTACAACGA CGGAATGG
13096





7149
CGGCGGAG A UCCUGCGG
4348
CCGCAGGA GGCTAGCTACAACGA CTCCGCCG
13097





7154
GAGAUCCU G CGGAAAUC
4349
GATTTCCG GGCTAGCTACAACGA AGGATCTC
13098





7160
CUGCGGAA A UCCAAGAA
4350
TTCTTGGA GGCTAGCTACAACGA TTCCGCAG
13099





7169
UCCAAGAA G UUUCCUUC
4351
GAAGGAAA GGCTAGCTACAACGA TTCTTGGA
13100





7179
UUCCUUCA G CGUUACCC
4352
GGGTAACG GGCTAGCTACAACGA TGAAGGAA
13101





7181
CCUUCAGC G UUACCCAU
4353
ATGGGTAA GGCTAGCTACAACGA GCTGAAGG
13102





7184
UCAGCGUU A CCCAUAUG
4354
CATATGGG GGCTAGCTACAACGA AACGCTGA
13103





7188
CGUUACCC A UAUGGGCA
4355
TGCCCATA GGCTAGCTACAACGA GGGTAACG
13104





7190
UUACCCAU A UGGGCACG
4356
CGTGCCCA GGCTAGCTACAACGA ATGGGTAA
13105





7194
CCAUAUGG G CACGCCCG
4357
CGGGCGTG GGCTAGCTACAACGA CCATATGG
13106





7196
AUAUGGGC A CGCCCGGA
4358
TCCGGGCG GGCTAGCTACAACGA GCCCATAT
13107





7198
AUGGGCAC G CCCGGAUU
4359
AATCCGGG GGCTAGCTACAACGA GTGCCCAT
13108





7204
ACGCCCGG A UUACAACC
4360
GGTTGTAA GGCTAGCTACAACGA CCGGGCGT
13109





7207
CCCGGAUU A CAACCCUC
4361
GAGGGTTG GGCTAGCTACAACGA AATCCGGG
13110





7210
GGAUUACA A CCCUCCAC
4362
GTGGAGGG GGCTAGCTACAACGA TGTAATCC
13111





7217
AACCCUCC A CUACUAGA
4363
TCTAGTAG GGCTAGCTACAACGA GGAGGGTT
13112





7220
CCUCCACU A CUAGAGCC
4364
GGCTCTAG GGCTAGCTACAACGA AGTGGAGG
13113





7226
CUACUAGA G CCCUGGAA
4365
TTCCAGGG GGCTAGCTACAACGA TCTAGTAG
13114





7237
CUGGAAAG A CCCAGACU
4366
AGTCTGGG GGCTAGCTACAACGA CTTTCCAG
13115





7243
AGACCCAG A CUACGUCC
4367
GGACGTAG GGCTAGCTACAACGA CTGGGTCT
13116





7246
CCCAGACU A CGUCCCUC
4368
GAGGGACG GGCTAGCTACAACGA AGTCTGGG
13117





7248
CAGACUAC G UCCCUCCG
4369
CGGAGGGA GGCTAGCTACAACGA GTAGTCTG
13118





7257
UCCCUCCG G UGGUACAC
4370
GTGTACCA GGCTAGCTACAACGA CGGAGGGA
13119





7260
CUCCGGUG G UACACGGG
4371
CCCGTGTA GGCTAGCTACAACGA CACCGGAG
13120





7262
CCGGUGGU A CACGGGUG
4372
CACCCGTG GGCTAGCTACAACGA ACCACCGG
13121





7264
GGUGGUAC A CGGGUGCC
4373
GGCACCCG GGCTAGCTACAACGA GTACCACC
13122





7268
GUACACGG G UGCCCAUU
4374
AATGGGCA GGCTAGCTACAACGA CCGTGTAC
13123





7270
ACACGGGU G CCCAUUGC
4375
GCAATGGG GGCTAGCTACAACGA ACCCGTGT
13124





7274
GGGUGCCC A UUGCCACC
4376
GGTGGCAA GGCTAGCTACAACGA GGGCACCC
13125





7277
UGCCCAUU G CCACCUGC
4377
GCAGGTGG GGCTAGCTACAACGA AATGGGCA
13126





7280
CCAUUGCC A CCUGCCAA
4378
TTGGCAGG GGCTAGCTACAACGA GGCAATGG
13127





7284
UGCCACCU G CCAAGGCC
4379
GGCCTTGG GGCTAGCTACAACGA AGGTGGCA
13128





7290
CUGCCAAG G CCCCUCCA
4380
TGGAGGGG GGCTAGCTACAACGA CTTGGCAG
13129





7299
CCCCUCCA A UACCACCU
4381
AGGTGGTA GGCTAGCTACAACGA TGGAGGGG
13130





7301
CCUCCAAU A CCACCUCC
4382
GGAGGTGG GGCTAGCTACAACGA ATTGGAGG
13131





7304
CCAAUACC A CCUCCACG
4383
CGTGGAGG GGCTAGCTACAACGA GGTATTGG
13132





7310
CCACCUCC A CGGAGGAA
4384
TTCCTCCG GGCTAGCTACAACGA GGAGGTGG
13133





7323
GGAAGAGG A CGGUUGUU
4385
AACAACCG GGCTAGCTACAACGA CCTCTTCC
13134





7326
AGAGGACG G UUGUUCUG
4386
CAGAACAA GGCTAGCTACAACGA CGTCCTCT
13135





7329
GGACGGUU G UUCUGACA
4387
TGTCAGAA GGCTAGCTACAACGA AACCGTCC
13136





7335
UUGUUCUG A CAGAGUCC
4388
GGACTCTG GGCTAGCTACAACGA CAGAACAA
13137





7340
CUGACAGA G UCCACCGU
4389
ACGGTGGA GGCTAGCTACAACGA TCTGTCAG
13138





7344
CAGAGUCC A CCGUGUCU
4390
AGACACGG GGCTAGCTACAACGA GGACTCTG
13139





7347
AGUCCACC G UGUCUUCU
4391
AGAAGACA GGCTAGCTACAACGA GGTGGACT
13140





7349
UCCACCGU G UCUUCUGC
4392
GCAGAAGA GGCTAGCTACAACGA ACGGTGGA
13141





7356
UGUCUUCU G CCUUGGCG
4393
CGCCAAGG GGCTAGCTACAACGA AGAAGACA
13142





7362
CUGCCUUG G CGGAGCUC
4394
GAGCTCCG GGCTAGCTACAACGA CAAGGCAG
13143





7367
UUGGCGGA G CUCGCCAC
4395
GTGGCGAG GGCTAGCTACAACGA TCCGCCAA
13144





7371
CGGAGCUC G CCACAAAG
4396
CTTTGTGG GGCTAGCTACAACGA GAGCTCCG
13145





7374
AGCUCGCC A CAAAGACC
4397
GGTCTTTG GGCTAGCTACAACGA GGCGAGCT
13146





7380
CCACAAAG A CCUUCGGC
4398
GCCGAAGG GGCTAGCTACAACGA CTTTGTGG
13147





7387
GACCUUCG G CAGCUCUG
4399
CAGAGCTG GGCTAGCTACAACGA CGAAGGTC
13148





7390
CUUCGGCA G CUCUGAAU
4400
ATTCAGAG GGCTAGCTACAACGA TGCCGAAG
13149





7397
AGCUCUGA A UCAUCGGC
4401
GCCGATGA GGCTAGCTACAACGA TCAGAGCT
13150





7400
UCUGAAUC A UCGGCCGC
4402
GCGGCCGA GGCTAGCTACAACGA GATTCAGA
13151





7404
AAUCAUCG G CCGCUGAU
4403
ATCAGCGG GGCTAGCTACAACGA CGATGATT
13152





7407
CAUCGGCC G CUGAUAGA
4404
TCTATCAG GGCTAGCTACAACGA GGCCGATG
13153





7411
GGCCGCUG A UAGAGGUA
4405
TACCTCTA GGCTAGCTACAACGA CAGCGGCC
13154





7417
UGAUAGAG G UACGGCAA
4406
TTGCCGTA GGCTAGCTACAACGA CTCTATCA
13155





7419
AUAGAGGU A CGGCAACC
4407
GGTTGCCG GGCTAGCTACAACGA ACCTCTAT
13156





7422
GAGGUACG G CAACCGCC
4408
GGCGGTTG GGCTAGCTACAACGA CGTACCTC
13157





7425
GUACGGCA A CCGCCCCC
4409
GGGGGCGG GGCTAGCTACAACGA TGCCGTAC
13158





7428
CGGCAACC G CCCCCCCC
4410
GGGGGGGG GGCTAGCTACAACGA GGTTGCCG
13159





7438
CCCCCCCG A CCAGACCU
4411
AGGTCTGG GGCTAGCTACAACGA CGGGGGGG
13160





7443
CCGACCAG A CCUCCAAU
4412
ATTGGAGG GGCTAGCTACAACGA CTGGTCGG
13161





7450
GACCUCCA A UGACGGUG
4413
CACCGTCA GGCTAGCTACAACGA TGGAGGTC
13162





7453
CUCCAAUG A CGGUGACG
4414
CGTCACCG GGCTAGCTACAACGA CATTGGAG
13163





7456
CAAUGACG G UGACGCAG
4415
CTGCGTCA GGCTAGCTACAACGA CGTCATTG
13164





7459
UGACGGUG A CGCAGGAU
4416
ATCCTGCG GGCTAGCTACAACGA CACCGTCA
13165





7461
ACGGUGAC G CAGGAUCC
4417
GGATCCTG GGCTAGCTACAACGA GTCACCGT
13166





7466
GACGCAGG A UCCGACGU
4418
ACGTCGGA GGCTAGCTACAACGA CCTGCGTC
13167





7471
AGGAUCCG A CGUUGAGU
4419
ACTCAACG GGCTAGCTACAACGA CGGATCCT
13168





7473
GAUCCGAC G UUGAGUCG
4420
CGACTCAA GGCTAGCTACAACGA GTCGGATC
13169





7478
GACGUUGA G UCGUACUC
4421
GAGTACGA GGCTAGCTACAACGA TCAACGTC
13170





7481
GUUGAGUC G UACUCCUC
4422
GAGGAGTA GGCTAGCTACAACGA GACTCAAC
13171





7483
UGAGUCGU A CUCCUCUA
4423
TAGAGGAG GGCTAGCTACAACGA ACGACTCA
13172





7491
ACUCCUCU A UGCCCCCC
4424
GGGGGGCA GGCTAGCTACAACGA AGAGGAGT
13173





7493
UCCUCUAU G CCCCCCCU
4425
AGGGGGGG GGCTAGCTACAACGA ATAGAGGA
13174





7511
GAGGGGGA G CCGGGGGA
4426
TCCCCCGG GGCTAGCTACAACGA TCCCCCTC
13175





7519
GCCGGGGG A UCCCGAUC
4427
GATCGGGA GGCTAGCTACAACGA CCCCCGGC
13176





7525
GGAUCCCG A UCUCAGCG
4428
CGCTGAGA GGCTAGCTACAACGA CGGGATCC
13177





7531
CGAUCUCA G CGACGGGU
4429
ACCCGTCG GGCTAGCTACAACGA TGAGATCG
13178





7534
UCUCAGCG A CGGGUCUU
4430
AAGACCCG GGCTAGCTACAACGA CGCTGAGA
13179





7538
AGCGACGG G UCUUGGUC
4431
GACCAAGA GGCTAGCTACAACGA CCGTCGCT
13180





7544
GGGUCUUG G UCUACCGU
4432
ACGGTAGA GGCTAGCTACAACGA CAAGACCC
13181





7548
CUUGGUCU A CCGUGAGC
4433
GCTCACGG GGCTAGCTACAACGA AGACCAAG
13182





7551
GGUCUACC G UGAGCGAA
4434
TTCGCTCA GGCTAGCTACAACGA GGTAGACC
13183





7555
UACCGUGA G CGAAGAGG
4435
CCTCTTCG GGCTAGCTACAACGA TCACGGTA
13184





7563
GCGAAGAG G CUGGCGAG
4436
CTCGCCAG GGCTAGCTACAACGA CTCTTCGC
13185





7567
AGAGGCUG G CGAGGAUG
4437
CATCCTCG GGCTAGCTACAACGA CAGCCTCT
13186





7573
UGGCGAGG A UGUCGUCU
4438
AGACGACA GGCTAGCTACAACGA CCTCGCCA
13187





7575
GCGAGGAU G UCGUCUGC
4439
GCAGACGA GGCTAGCTACAACGA ATCCTCGC
13188





7578
AGGAUGUC G UCUGCUGC
4440
GCAGCAGA GGCTAGCTACAACGA GACATCCT
13189





7582
UGUCGUCU G CUGCUCGA
4441
TCGAGCAG GGCTAGCTACAACGA ACACGACA
13190





7585
CGUCUGCU G CUCGAUGU
4442
ACATCGAG GGCTAGCTACAACGA AGCAGACG
13191





7590
GCUGCUCG A UGUCCUAC
4443
GTAGGACA GGCTAGCTACAACGA CGAGCAGC
13192





7592
UGCUCGAU G UCCUACAC
4444
GTGTAGGA GGCTAGCTACAACGA ATCGAGCA
13193





7597
GAUGUCCU A CACAUGGA
4445
TCCATGTG GGCTAGCTACAACGA AGGACATC
13194





7599
UGUCCUAC A CAUGGACG
4446
CGTCCATG GGCTAGCTACAACGA GTAGGACA
13195





7601
UCCUACAC A UGGACGGG
4447
CCCGTCCA GGCTAGCTACAACGA GTGTAGGA
13196





7605
ACACAUGG A CGGGCGCC
4448
GGCGCCCG GGCTAGCTACAACGA CCATGTGT
13197





7609
AUGGACGG G CGCCCUGA
4449
TCAGGGCG GGCTAGCTACAACGA CCGTCCAT
13198





7611
GGACGGGC G CCCUGAUC
4450
GATCAGGG GGCTAGCTACAACGA GCCCGTCC
13199





7617
GCGCCCUG A UCACGCCA
4451
TGGCGTGA GGCTAGCTACAACGA CAGGGCGC
13200





7620
CCCUGAUC A CGCCAUGC
4452
GCATGGCG GGCTAGCTACAACGA GATCAGGG
13201





7622
CUGAUCAC G CCAUGCGC
4453
GCGCATGG GGCTAGCTACAACGA GTGATCAG
13202





7625
AUCACGCC A UGCGCUGC
4454
GCAGCGCA GGCTAGCTACAACGA GGCGTGAT
13203





7627
CACGCCAU G CGCUGCGG
4455
CCGCAGCG GGCTAGCTACAACGA ATGGCGTG
13204





7629
CGCCAUGC G CUGCGGAG
4456
CTCCGCAG GGCTAGCTACAACGA GCATGGCG
13205





7632
CAUGCGCU G CGGAGGAA
4457
TTCCTCCG GGCTAGCTACAACGA AGCGCATG
13206





7642
GGAGGAAA G CAAGUUGC
4458
GCAACTTG GGCTAGCTACAACGA TTTCCTCC
13207





7646
GAAAGCAA G UUGCCCAU
4459
ATGGGCAA GGCTAGCTACAACGA TTGCTTTC
13208





7649
AGCAAGUU G CCCAUCAA
4460
TTGATGGG GGCTAGCTACAACGA AACTTGCT
13209





7653
ACUUGCCC A UCAACGCG
4461
CGCGTTGA GGCTAGCTACAACGA GGGCAACT
13210





7657
GCCCAUCA A CGCGUUGA
4462
TCAACGCG GGCTAGCTACAACCA TGATGCGC
13211





7659
CCAUCAAC G CGUUGAGC
4463
GCTCAACG GGCTAGCTACAACGA GTTGATGG
13212





7661
AUCAACGC G UUGAGCAA
4464
TTGCTCAA GGCTAGCTACAACGA GCGTTGAT
13213





7666
CGCGUUGA G CAACUCUU
4465
AAGAGTTG GGCTAGCTACAACGA TCAACGCG
13214





7669
GUUGAGCA A CUCUUUGC
4466
GCAAAGAG GGCTAGCTACAACGA TGCTCAAC
13215





7676
AACUCUUU G CUGCGUCA
4467
TGACGCAG GGCTAGCTACAACGA AAAGAGTT
13216





7679
UCUUUGCU G CGUCACCA
4468
TGGTGACG GGCTAGCTACAACGA AGCAAAGA
13217





7681
UUUGCUGC G UCACCACA
4469
TGTGGTGA GGCTAGCTACAACGA GCAGCAAA
13218





7684
GCUGCGUC A CCACAACA
4470
TGTTGTGG GGCTAGCTACAACGA GACGCAGC
13219





7687
GCGUCACC A CAACAUGG
4471
CCATGTTG GGCTAGCTACAACGA GGTGACGC
13220





7690
UCACCACA A CAUGGUCU
4472
AGACCATG GGCTAGCTACAACGA TGTGGTGA
13221





7692
ACCACAAC A UGGUCUAC
4473
GTAGACCA GGCTAGCTACAACGA GTTGTGGT
13222





7695
ACAACAUG G UCUACGCU
4474
AGCGTAGA GGCTAGCTACAACGA CATGTTGT
13223





7699
CAUGGUCU A CGCUACAA
4475
TTGTAGCG GGCTAGCTACAACGA AGACCATG
13224





7701
UGGUCUAC G CUACAACA
4476
TGTTGTAG GGCTAGCTACAACGA GTAGACCA
13225





7704
UCUACGCU A CAACAUCU
4477
AGATGTTG GGCTAGCTACAACGA AGCGTAGA
13226





7707
ACGCUACA A CAUCUCGC
4478
GCGAGATG GGCTAGCTACAACGA TGTAGCGT
13227





7709
GCUACAAC A UCUCGCAG
4479
CTGCGAGA GGCTAGCTACAACGA GTTGTAGC
13228





7714
AACAUCUC G CAGCGCAA
4480
TTGCGCTG GGCTAGCTACAACGA GAGATGTT
13229





7717
AUCUCGCA G CGCAAGCC
4481
GGCTTGCG GGCTAGCTACAACGA TGCGAGAT
13230





7719
CUCGCAGC G CAAGCCAG
4482
CTGGCTTG GGCTAGCTACAACGA GCTGCGAG
13231





7723
CAGCGCAA G CCAGCGGC
4483
GCCGCTGG GGCTAGCTACAACGA TTGCGCTG
13232





7727
GCAAGCCA G CGGCAGAA
4484
TTCTGCCG GGCTAGCTACAACGA TGGCTTGC
13233





7730
AGCCAGCG G CAGAAGAA
4485
TTCTTCTG GGCTAGCTACAACGA CGCTGGCT
13234





7740
AGAAGAAG G UCACCUUU
4486
AAAGGTGA GGCTAGCTACAACGA CTTCTTCT
13235





7743
AGAAGGUC A CCUUUGAC
4487
GTCAAAGG GGCTAGCTACAACGA GACCTTCT
13236





7750
CACCUUUG A CAGACUGC
4488
GCAGTCTG GGCTAGCTACAACGA CAAAGGTG
13237





7754
UUUGACAG A CUGCAAGU
4489
ACTTGCAG GGCTAGCTACAACGA CTGTCAAA
13238





7757
GACAGACU G CAAGUCCU
4490
AGGACTTG GGCTAGCTACAACGA AGTCTGTC
13239





7761
GACUGCAA G UCCUGGAC
4491
GTCCAGGA GGCTAGCTACAACGA TTGCAGTC
13240





7768
AGUCCUGG A CGACCACU
4492
AGTGGTCG GGCTAGCTACAACGA CCAGGACT
13241





7771
CCUGGACG A CCACUACC
4493
GGTAGTGG GGCTAGCTACAACGA CGTCCAGG
13242





7774
GGACGACC A CUACCGGG
4494
CCCGGTAG GGCTAGCTACAACGA GGTCGTCC
13243





7777
CGACCACU A CCGGGACG
4495
CGTCCCGG GGCTAGCTACAACGA AGTGGTCG
13244





7783
CUACCGGG A CGUGCUCA
4496
TGAGCACG GGCTAGCTACAACGA CCCGGTAG
13245





7785
ACCGGGAC G UGCUCAAG
4497
CTTGAGCA GGCTAGCTACAACGA GTCCCGGT
13246





7787
CGGGACGU G CUCAAGGA
4498
TCCTTGAG GGCTAGCTACAACGA ACGTCCCG
13247





7797
UCAAGGAG A UGAAGGCG
4499
CGCCTTCA GGCTAGCTACAACGA CTCCTTGA
13248





7803
AGAUGAAG G CGAAGGCG
4500
CGCCTTCG GGCTAGCTACAACGA CTTCATCT
13249





7809
AGGCGAAG G CGUCCACA
4501
TGTGGACG GGCTAGCTACAACGA CTTCGCCT
13250





7811
GCGAAGGC G UCCACAGU
4502
ACTGTGGA GGCTAGCTACAACGA GCCTTCGC
13251





7815
AGGCGUCC A CACUUAAG
4503
CTTAACTG GGCTAGCTACAACGA GGACGCCT
13252





7818
CGUCCACA G UUAAGGCU
4504
AGCCTTAA GGCTAGCTACAACGA TGTGGACG
13253





7824
CACUUAAG G CUAAACUU
4505
AAGTTTAG GGCTAGCTACAACGA CTTAACTG
13254





7829
AAGGCUAA A CUUCUAUC
4506
GATAGAAG GGCTAGCTACAACGA TTAGCCTT
13255





7835
AAACUUCU A UCCGUAGA
4507
TCTACGGA GGCTAGCTACAACGA AGAAGTTT
13256





7839
UUCUAUCC G UAGAGGAA
4508
TTCCTCTA GGCTAGCTACAACGA GGATAGAA
13257





7848
UAGAGGAA G CCUGCAGA
4509
TCTGCAGG GGCTAGCTACAACGA TTCCTCTA
13258





7852
GGAAGCCU G CAGACUGA
4510
TCAGTCTG GGCTAGCTACAACGA AGGCTTCC
13259





7856
GCCUCCAG A CUGACGCC
4511
GGCGTCAG GGCTAGCTACAACGA CTGCAGGC
13260





7860
GCAGACUG A CGCCCCCA
4512
TGGGGGCG GGCTAGCTACAACGA CAGTCTGC
13261





7862
AGACUGAC G CCCCCACA
4513
TGTGGGGG GGCTAGCTACAACGA GTCAGTCT
13262





7868
ACGCCCCC A CAUUCGGC
4514
GCCGAATG GGCTAGCTACAACGA CGGGGCGT
13263





7870
GCCCCCAC A UUCGGCCA
4515
TGGCCGAA GGCTAGCTACAACGA GTGGGGGC
13264





7875
CACAUUCG G CCAGGUCC
4516
GGACCTGG GGCTAGCTACAACGA CGAATGTG
13265





7880
UCGGCCAG G UCCAAAUU
4517
AATTTGGA GGCTAGCTACAACGA CTGGCCGA
13266





7886
AGGUCCAA A UUUGGUUA
4518
TAACCAAA GGCTAGCTACAACGA TTGGACCT
13267





7891
CAAAUUUG G UUAUGGGG
4519
CCCCATAA GGCTAGCTACAACGA CAAATTTG
13268





7894
AUUUGGUU A UGGGGCAA
4520
TTGCCCCA GGCTAGCTACAACGA AACCAAAT
13269





7899
GUUAUGGG G CAAAGGAC
4521
GTCCTTTG GGCTAGCTACAACGA CCCATAAC
13270





7906
GGCAAAGG A CGUCCGGA
4522
TCCGGACG GGCTAGCTACAACGA CCTTTGCC
13271





7908
CAAAGGAC G UCCGGAAC
4523
GTTCCGGA GGCTAGCTACAACGA GTCCTTTG
13272





7915
CGUCCGGA A CCUAUCCA
4524
TGGATAGG GGCTAGCTACAACGA TCCGGACG
13273





7919
CGGAACCU A UCCAGCGG
4525
CCGCTGGA GGCTAGCTACAACGA AGGTTCCG
13274





7924
CCUAUCCA G CGGGGCCG
4526
CGGCCCCG GGCTAGCTACAACGA TGGATAGG
13275





7929
CCAGCGGG G CCGUCAAC
4527
GTTGACGG GGCTAGCTACAACGA CCCGCTGG
13276





7932
GCGGGGCC G UCAACCAC
4528
GTGGTTGA GGCTAGCTACAACGA GGCCCCGC
13277





7936
GGCCGUCA A CCACAUCC
4529
GGATGTGG GGCTAGCTACAACGA TGACGGCC
13278





7939
CGUCAACC A CAUCCGCU
4530
AGCGGATG GGCTAGCTACAACGA GGTTGACG
13279





7941
UCAACCAC A UCCGCUCC
4531
GGAGCGGA GGCTAGCTACAACGA GTGGTTGA
13280





7945
CCACAUCC G CUCCGUGU
4532
ACACGGAG GGCTAGCTACAACGA GGATGTGG
13281





7950
UCCGCUCC G UGUGGAAG
4533
CTTCCACA GGCTAGCTACAACGA GGAGCGGA
13282





7952
CGCUCCGU G UGGAAGGA
4534
TCCTTCCA GGCTAGCTACAACGA ACGGAGCG
13283





7960
GUGGAAGG A CUUGCUGG
4535
CCAGCAAG GGCTAGCTACAACGA CCTTCCAC
13284





7964
AAGGACUU G CUGGAAGA
4536
TCTTCCAG GGCTAGCTACAACGA AAGTCCTT
13285





7972
GCUGGAAG A CACUGAGA
4537
TCTCAGTG GGCTAGCTACAACGA CTTCCAGC
13286





7974
UGGAAGAC A CUGAGACA
4538
TGTCTCAG GGCTAGCTACAACGA GTCTTCCA
13287





7980
ACACUGAG A CACCAAUU
4539
AATTGGTG GGCTAGCTACAACGA CTCAGTGT
13288





7982
ACUGAGAC A CCAAUUGA
4540
TCAATTGG GGCTAGCTACAACGA GTCTCAGT
13289





7986
AGACACCA A UUGAUACC
4541
GGTATCAA GGCTAGCTACAACGA TGGTGTCT
13290





7990
ACCAAUUG A UACCACCA
4542
TGGTGGTA GGCTAGCTACAACGA CAATTGGT
13291





7992
CAAUUGAU A CCACCAUC
4543
GATGGTGG GGCTAGCTACAACGA ATCAATTG
13292





7995
UUGAUACC A CCAUCAUG
4544
CATGATGG GGCTAGCTACAACGA GGTATCAA
13293





7998
AUACCACC A UCAUGGCA
4545
TGCCATGA GGCTAGCTACAACGA GGTGGTAT
13294





8001
CCACCAUC A UGGCAAAA
4546
TTTTGCCA GGCTAGCTACAACGA GATGGTGG
13295





8004
CCAUCAUG G CAAAAAAU
4547
ATTTTTTG GGCTAGCTACAACGA CATGATGG
13296





8011
GGCAAAAA A UGAGGUUU
4548
AAACCTCA GGCTAGCTACAACGA TTTTTGCC
13297





8016
AAAAUGAG G UUUUCUGC
4549
GCAGAAAA GGCTAGCTACAACGA CTCATTTT
13298





8023
GGUUUUCU G CGUCCAAC
4550
GTTGGACG GGCTAGCTACAACGA AGAAAACC
13299





8025
UUUUCUGC G UCCAACCA
4551
TGGTTGGA GGCTAGCTACAACGA GCAGAAAA
13300





8030
UGCGUCCA A CCAGAGAA
4552
TTCTCTGG GGCTAGCTACAACGA TGGACGCA
13301





8044
GAAAGGAG G CCGCAAGC
4553
GCTTGCGG GGCTAGCTACAACGA CTCCTTTC
13302





8047
AGGAGGCC G CAAGCCAG
4554
CTGGCTTG GGCTAGCTACAACGA GGCCTCCT
13303





8051
GGCCGCAA G CCAGCUCG
4555
CGAGCTGG GGCTAGCTACAACGA TTGCGGCC
13304





8055
GCAAGCCA G CUCGCCUU
4556
AAGGCGAG GGCTAGCTACAACGA TGGCTTGC
13305





8059
GCCAGCUC G CCUUAUCG
4557
CGATAAGG GGCTAGCTACAACGA GAGCTGGC
13306





8064
CUCGCCUU A UCGUGUUC
4558
GAACACGA GGCTAGCTACAACGA AAGGCGAG
13307





8067
GCCUUAUC G UGUUCCCA
4559
TGGGAACA GGCTAGCTACAACGA GATAAGGC
13308





8069
CUUAUCGU G UUCCCAGA
4560
TCTGCGAA GGCTAGCTACAACGA ACGATAAG
13309





8077
GUUCCCAG A CUUGGGGG
4561
CCCCCAAG GGCTAGCTACAACGA CTGGGAAC
13310





8085
ACUUGGGG G UUCGUGUG
4562
CACACGAA GGCTAGCTACAACGA CCCCAAGT
13311





8089
GGGGGUUC G UGUGUGCG
4563
CGCACACA GGCTAGCTACAACGA GAACCCCC
13312





8091
GGGUUCGU G UGUGCGAG
4564
CTCGCACA GGCTAGCTACAACGA ACGAACCC
13313





8093
GUUCGUGU G UGCGAGAA
4565
TTCTCGCA GGCTAGCTACAACGA ACACGAAC
13314





8095
UCGUGUGU G CGAGAAAA
4566
TTTTCTCG GGCTAGCTACAACGA ACACACGA
13315





8103
GCGAGAAA A UGGCCCUU
4567
AAGGGCCA GGCTAGCTACAACGA TTTCTCGC
13316





8106
AGAAAAUG G CCCUUUAC
4568
GTAAAGGG GGCTAGCTACAACGA CATTTTCT
13317





8113
GGCCCUUU A CGACGUGG
4569
CCACGTCG GGCTAGCTACAACGA AAAGGGCC
13318





8116
CCUUUACG A CGUGGUCU
4570
AGACCACG GGCTAGCTACAACGA CGTAAAGG
13319





8118
UUUACGAC G UGGUCUCC
4571
GGAGACCA GGCTAGCTACAACGA GTCGTAAA
13320





8121
ACGACGUG G UCUCCACC
4572
GGTGGAGA GGCTAGCTACAACGA CACGTCGT
13321





8127
UGGUCUCC A CCCUUCCU
4573
AGGAAGGG GGCTAGCTACAACGA GGAGACCA
13322





8139
UUCCUCAG G CCGUGAUG
4574
CATCACGG GGCTAGCTACAACGA CTGAGGAA
13323





8142
CUCAGGCC G UGAUGGGC
4575
GCCCATCA GGCTAGCTACAACGA GGCCTGAG
13324





8145
AGGCCGUG A UGGGCUCU
4576
AGAGCCCA GGCTAGCTACAACGA CACGGCCT
13325





8149
CGUGAUGG G CUCUUCAU
4577
ATGAAGAG GGCTAGCTACAACGA CCATCACG
13326





8156
GGCUCUUC A UACCGAUU
4578
AATCCGTA GGCTAGCTACAACGA GAAGAGCC
13327





8158
CUCUUCAU A CGGAUUCC
4579
GGAATCCG GGCTAGCTACAACGA ATGAAGAG
13328





8162
UCAUACGG A UUCCAGUA
4580
TACTGGAA GGCTAGCTACAACGA CCGTATGA
13329





8168
GGAUUCCA G UACUCUCC
4581
GGAGAGTA GGCTAGCTACAACGA TGGAATCC
13330





8170
AUUCCAGU A CUCUCCUG
4582
CAGGAGAG GGCTAGCTACAACGA ACTGGAAT
13331





8180
UCUCCUGG G CAGCGGGU
4583
ACCCGCTG GGCTAGCTACAACGA CCAGGAGA
13332





8183
CCUGGGCA G CGGGUUGA
4584
TCAACCCG GGCTAGCTACAACGA TGCCCAGG
13333





8187
GGCAGCGG G UUGAGUUC
4585
GAACTCAA GGCTAGCTACAACGA CCGCTGCC
13334





8192
CGGGUUGA G UUCCUGGU
4586
ACCAGGAA GGCTAGCTACAACGA TCAACCCG
13335





8199
AGUUCCUG G UGAAUGCC
4587
GGCATTCA GGCTAGCTACAACGA CAGGAACT
13336





8203
CCUGGUGA A UGCCUGGA
4588
TCCAGGCA GGCTAGCTACAACGA TCACCAGG
13337





8205
UGGUGAAU G CCUGGAAA
4589
TTTCCAGG GGCTAGCTACAACGA ATTCACCA
13338





8213
GCCUGGAA A UCAAAGAA
4590
TTCTTTGA GGCTAGCTACAACGA TTCCAGGC
13339





8222
UCAAAGAA A UGCCCUAU
4591
ATAGGGCA GGCTAGCTACAACGA TTCTTTGA
13340





8224
AAAGAAAU G CCCUAUGG
4592
CCATAGGG GGCTAGCTACAACGA ATTTCTTT
13341





8229
AAUGCCCU A UGGGCUUU
4593
AAAGCCCA GGCTAGCTACAACGA AGGGCATT
13342





8233
CCCUAUGG G CUUUGCAU
4594
ATGCAAAG GGCTAGCTACAACGA CCATAGGG
13343





8238
UGGGCUUU G CAUAUGAC
4595
GTCATATG GGCTAGCTACAACGA AAAGCCCA
13344





8240
GGCUUUGC A UAUGACAC
4596
GTGTCATA GGCTAGCTACAACGA GCAAAGCC
13345





8242
CUUUGCAU A UGACACCC
4597
GGGTGTCA GGCTAGCTACAACGA ATGCAAAG
13346





8245
UGCAUAUG A CACCCGCU
4598
AGCGGGTG GGCTAGCTACAACGA CATATGCA
13347





8247
CAUAUGAC A CCCGCUGU
4599
ACAGCGGG GGCTAGCTACAACGA GTCATATG
13348





8251
UGACACCC G CUGUUUCG
4600
CGAAACAG GGCTAGCTACAACGA GGGTGTCA
13349





8254
CACCCGCU G UUUCGACU
4601
AGTCGAAA GGCTAGCTACAACGA AGCGGGTG
13350





8260
CUGUUUCG A CUCAACAG
4602
CTGTTGAG GGCTAGCTACAACGA CGAAACAG
13351





8265
UCGACUCA A CAGUCACC
4603
GGTGACTG GGCTAGCTACAACGA TGAGTCGA
13352





8268
ACUCAACA G UCACCGAG
4604
CTCGGTGA GGCTAGCTACAACGA TGTTGAGT
13353





8271
CAACAGUC A CCGAGAGU
4605
ACTCTCGG GGCTAGCTACAACGA GACTGTTG
13354





8278
CACCGAGA G UGACAUCC
4606
GGATGTCA GGCTAGCTACAACGA TCTCGGTG
13355





8281
CGAGAGUG A CAUCCGUG
4607
CACGGATG GGCTAGCTACAACGA CACTCTCG
13356





8283
AGAGUGAC A UCCGUGUC
4608
GACACGGA GGCTAGCTACAACGA GTCACTCT
13357





8287
UGACAUCC G UGUCGAGG
4609
CCTCGACA GGCTAGCTACAACGA GGATGTCA
13358





8289
ACAUCCGU G UCCAGGAG
4610
CTCCTCGA GGCTAGCTACAACGA ACGGATGT
13359





8297
GUCGAGGA G UCAAUUUA
4611
TAAATTGA GGCTAGCTACAACGA TCCTCGAC
13360





8301
AGGAGUCA A UUUACCAA
4612
TTGGTAAA GGCTAGCTACAACGA TGACTCCT
13361





8305
GUCAAUUU A CCAAUGUU
4613
AACATTGG GGCTAGCTACAACGA AAATTGAC
13362





8309
AUUUACCA A UGUUGUGA
4614
TCACAACA GGCTAGCTACAACGA TGGTAAAT
13363





8311
UUACCAAU G UUGUGACU
4615
AGTCACAA GGCTAGCTACAACGA ATTGGTAA
13364





8314
CCAAUGUU G UGACUUGG
4616
CCAAGTCA GGCTAGCTACAACGA AACATTGG
13365





8317
AUGUUGUG A CUUGGCCC
4617
GGGCCAAG GGCTAGCTACAACGA CACAACAT
13366





8322
GUGACUUG G CCCCCGAA
4618
TTCGGGGG GGCTAGCTACAACGA CAAGTCAC
13367





8331
CCCCCGAA G CCAGACAG
4619
CTGTCTGG GGCTAGCTACAACGA TTCGGGGG
13368





8336
GAAGCCAG A CAGGCCAU
4620
ATGGCCTG GGCTAGCTACAACGA CTGGCTTC
13369





8340
CCAGACAG G CCAUAAGG
4621
CCTTATGG GGCTAGCTACAACGA CTGTCTGG
13370





8343
GACAGGCC A UAAGGUCG
4622
CGACCTTA GGCTAGCTACAACGA GGCCTGTC
13371





8348
GCCAUAAG G UCGCUCAC
4623
GTGAGCGA GGCTAGCTACAACGA CTTATGGC
13372





8351
AUAAGGUC G CUCACAGA
4624
TCTGTGAG GGCTAGCTACAACGA GACCTTAT
13373





8355
GGUCGCUC A CAGAGCGG
4625
CCGCTCTG GGCTAGCTACAACGA GAGCGACC
13374





8360
CUCACAGA G CGGCUUUA
4626
TAAAGCCG GGCTAGCTACAACGA TCTGTGAG
13375





8363
ACAGAGCG G CUUUAUAU
4627
ATATAAAG GGCTAGCTACAACGA CGCTCTGT
13376





8368
GCGGCUUU A UAUCGGGG
4628
CCCCGATA GGCTAGCTACAACGA AAAGCCGC
13377





8370
GGCUUUAU A UCGGGGGU
4629
ACCCCCGA GGCTAGCTACAACGA ATAAAGCC
13378





8377
UAUCGGGG G UCCUCUGA
4630
TCAGAGGA GGCTAGCTACAACGA CCCCGATA
13379





8385
GUCCUCUG A CUAAUUCA
4631
TGAATTAG GGCTAGCTACAACGA CAGAGGAC
13380





8389
UCUGACUA A UUCAAAAG
4632
CTTTTGAA GGCTAGCTACAACGA TAGTCAGA
13381





8399
UCAAAAGG G CAGAACUG
4633
CAGTTCTG GGCTAGCTACAACGA CCTTTTGA
13382





8404
AGGGCAGA A CUGCGGUU
4634
AACCGCAG GGCTAGCTACAACGA TCTGCCCT
13383





8407
GCAGAACU G CGGUUAUC
4635
GATAACCG GGCTAGCTACAACGA AGTTCTGC
13384





8410
GAACUGCG G UUAUCGCC
4636
GGCGATAA GGCTAGCTACAACGA CGCAGTTC
13385





8413
CUGCGGUU A UCGCCGGU
4637
ACCGGCGA GGCTAGCTACAACGA AACCGCAG
13386





8416
CGGUUAUC G CCGGUGCC
4638
GGCACCGG GGCTAGCTACAACGA GATAACCG
13387





8420
UAUCGCCG G UGCCGCGC
4639
GCGCGGCA GGCTAGCTACAACGA CGGCGATA
13388





8422
UCGCCGGU G CCGCGCGA
4640
TCGCGCGG GGCTAGCTACAACGA ACCGGCGA
13389





8425
CCGGUGCC G CGCGAGCG
4641
CGCTCGCG GGCTAGCTACAACGA GGCACCGG
13390





8427
GGUGCCGC G CGAGCGGC
4642
GCCGCTCG GGCTAGCTACAACGA GCGGCACC
13391





8431
CCGCGCGA G CGGCGUGC
4643
GCACGCCG GGCTAGCTACAACGA TCGCGCGG
13392





8434
CGCGAGCG G CGUGCUGA
4644
TCAGCACG GGCTAGCTACAACGA CGCTCGCG
13393





8436
CGAGCGGC G UGCUGACG
4645
CGTCAGCA GGCTAGCTACAACGA GCCGCTCG
13394





8438
AGCGGCGU G CUGACGAC
4646
GTCGTCAG GGCTAGCTACAACGA ACGCCGCT
13395





8442
GCGUGCUG A CGACCAGC
4647
GCTGGTCG GGCTAGCTACAACGA CAGCACGC
13396





8445
UGCUGACG A CCAGCUGU
4648
ACAGCTGG GGCTAGCTACAACGA CGTCAGCA
13397





8449
GACGACCA G CUGUGGUA
4649
TACCACAG GGCTAGCTACAACGA TGGTCGTC
13398





8452
GACCAGCU G UGGUAAUA
4650
TATTACCA GGCTAGCTACAACGA AGCTGGTC
13399





8455
CAGCUGUG G UAAUACCC
4651
GGGTATTA GGCTAGCTACAACGA CACAGCTG
13400





8458
CUGUGGUA A UACCCUCA
4652
TGAGGGTA GGCTAGCTACAACGA TACCACAG
13401





8460
GUGGUAAU A CCCUCACA
4653
TGTGAGGG GGCTAGCTACAACGA ATTACCAC
13402





8466
AUACCCUC A CAUGUUAC
4654
GTAACATG GGCTAGCTACAACGA GAGGGTAT
13403





8468
ACCCUCAC A UGUUACUU
4655
AAGTAACA GGCTAGCTACAACGA GTGAGGGT
13404





8470
CCUCACAU G UUACUUGA
4656
TCAAGTAA GGCTAGCTACAACGA ATGTGAGG
13405





8473
CACAUGUU A CUUGAAAG
4657
CTTTCAAG GGCTAGCTACAACGA AACATGTG
13406





8481
ACUUGAAA G CCUCUGCG
4658
CGCAGAGG GGCTAGCTACAACGA TTTCAAGT
13407





8487
AAGCCUCU G CGGCCUGU
4659
ACAGGCCG GGCTAGCTACAACGA AGAGGCTT
13408





8490
CCUCUGCG G CCUGUCGA
4660
TCGACAGG GGCTAGCTACAACGA CGCAGAGG
13409





8494
UGCGGCCU G UCGAGCUG
4661
CAGCTCGA GGCTAGCTACAACGA AGGCCGCA
13410





8499
CCUGUCGA G CUGCGAAG
4662
CTTCGCAG GGCTAGCTACAACGA TCGACAGG
13411





8502
GUCGAGCU G CGAAGCUC
4663
GAGCTTCG GGCTAGCTACAACGA AGCTCGAC
13412





8507
GCUGCGAA G CUCCAGGA
4664
TCCTGGAG GGCTAGCTACAACGA TTCGCAGC
13413





8515
GCUCCAGG A CUGCACGA
4665
TCGTGCAG GGCTAGCTACAACGA CCTGGAGC
13414





8518
CCAGGACU G CACGAUGC
4666
GCATCGTG GGCTAGCTACAACGA AGTCCTGG
13415





8520
AGGACUGC A CGAUGCUC
4667
GAGCATCG GGCTAGCTACAACGA GCAGTCCT
13416





8523
ACUGCACG A UGCUCGUG
4668
CACGAGCA GGCTAGCTACAACGA CGTGCAGT
13417





8525
UGCACGAU G CUCCUGUG
4669
CACACGAG GGCTAGCTACAACGA ATCGTGCA
13418





8529
CGAUGCUC G UGUGUGGA
4670
TCCACACA GGCTAGCTACAACGA GAGCATCG
13419





8531
AUGCUCGU G UGUGGAGA
4671
TCTCCACA GGCTAGCTACAACGA ACGAGCAT
13420





8533
GCUCGUGU G UGGAGACG
4672
CGTCTCCA GGCTAGCTACAACGA ACACGAGC
13421





8539
GUGUGGAG A CGACCUGG
4673
CCAGGTCG GGCTAGCTACAACGA CTCCACAC
13422





8542
UGGAGACG A CCUGGUCG
4674
CGACCAGG GGCTAGCTACAACGA CGTCTCCA
13423





8547
ACGACCUG G UCGUUAUC
4675
GATAACGA GGCTAGCTACAACGA CAGGTCGT
13424





8550
ACCUGGUC G UUAUCUGU
4676
ACAGATAA GGCTAGCTACAACGA GACCAGGT
13425





8553
UGGUCGUU A UCUGUGAA
4677
TTCACAGA GGCTAGCTACAACGA AACGACCA
13426





8557
CGUUAUCU G UGAAAGUG
4678
CACTTTCA GGCTAGCTACAACGA AGATAACG
13427





8563
CUGUGAAA G UGCGGGGA
4679
TCCCCGCA GGCTAGCTACAACGA TTTCACAG
13428





8565
GUGAAAGU G CGGGGACC
4680
GGTCCCCG GGCTAGCTACAACGA ACTTTCAC
13429





8571
GUGCGGGG A CCCAAGAG
4681
CTCTTGGG GGCTAGCTACAACGA CCCCGCAC
13430





8581
CCAAGAGG A CGCGGCGA
4682
TCGCCGCG GGCTAGCTACAACGA CCTCTTGG
13431





8583
AAGAGGAC G CGGCGAGC
4683
GCTCGCCG GGCTAGCTACAACGA GTCCTCTT
13432





8586
AGGACGCG G CGAGCCUA
4684
TAGGCTCG GGCTAGCTACAACGA CGCGTCCT
13433





8590
CGCGGCGA G CCUACGAG
4685
CTCGTAGG GGCTAGCTACAACGA TCGCCGCG
13434





8594
GCGAGCCU A CGAGUCUU
4686
AAGACTCG GGCTAGCTACAACGA AGGCTCGC
13435





8598
GCCUACGA G UCUUCACG
4687
CGTGAAGA GGCTAGCTACAACGA TCGTAGGC
13436





8604
GAGUCUUC A CGGAGGCU
4688
AGCCTCCG GGCTAGCTACAACGA GAAGACTC
13437





8610
UCACGGAG G CUAUGACU
4689
AGTCATAG GGCTAGCTACAACGA CTCCGTGA
13438





8613
CGGAGGCU A UGACUAGG
4690
CCTAGTCA GGCTAGCTACAACGA AGCCTCCG
13439





8616
AGGCUAUG A CUAGGUAC
4691
GTACCTAG GGCTAGCTACAACGA CATAGCCT
13440





8621
AUGACUAG G UACUCUGC
4692
GCAGAGTA GGCTAGCTACAACGA CTAGTCAT
13441





8623
GACUAGGU A CUCUGCCC
4693
GGGCAGAG GGCTAGCTACAACGA ACCTAGTC
13442





8628
GGUACUCU G CCCCCCCC
4694
GGGGGGGG GGCTAGCTACAACGA AGAGTACC
13443





8641
CCCCGGGG A CCCGCCCC
4695
GGGGCGGG GGCTAGCTACAACGA CCCCGGGG
13444





8645
GGGGACCC G CCCCAACC
4696
GGTTGGGG GGCTAGCTACAACGA GGGTCCCC
13445





8651
CCGCCCCA A CCGGAAUA
4697
TATTCCGG GGCTAGCTACAACGA TGGGGCGG
13446





8657
CAACCGGA A UACGACUU
4698
AAGTCGTA GGCTAGCTACAACGA TCCGGTTG
13447





8659
ACCGGAAU A CGACUUGG
4699
CCAAGTCG GGCTAGCTACAACGA ATTCCGGT
13448





8662
GGAAUACG A CUUGGAGU
4700
ACTCCAAG GGCTAGCTACAACGA CGTATTCC
13449





8669
GACUUGGA G UUGAUAAC
4701
GTTATCAA GGCTAGCTACAACGA TCCAAGTC
13450





8673
UGGAGUUG A UAACAUCA
4702
TGATGTTA GGCTAGCTACAACGA CAACTCCA
13451





8676
AGUUGAUA A CAUCAUGC
4703
GCATGATG GGCTAGCTACAACGA TATCAACT
13452





8678
UUGAUAAC A UCAUGCUC
4704
GAGCATGA GGCTAGCTACAACGA GTTATCAA
13453





8681
AUAACAUC A UGCUCCUC
4705
GAGGAGCA GGCTAGCTACAACGA GATGTTAT
13454





8683
AACAUCAU G CUCCUCCA
4706
TGGAGGAG GGCTAGCTACAACGA ATGATGTT
13455





8692
CUCCUCCA A CGUAUCAG
4707
CTGATACG GGCTAGCTACAACGA TGGAGGAG
13456





8694
CCUCCAAC G UAUCAGUU
4708
AACTGATA GGCTAGCTACAACGA GTTGGAGG
13457





8696
UCCAACGU A UCAGUUGC
4709
GCAACTGA GGCTAGCTACAACGA ACGTTGGA
13458





8700
ACGUAUCA G UUGCACAC
4710
GTGTGCAA GGCTAGCTACAACGA TGATACGT
13459





8703
UAUCAGUU G CACACGAU
4711
ATCGTGTG GGCTAGCTACAACGA AACTGATA
13460





8705
UCAGUUGC A CACGAUGC
4712
GCATCGTG GGCTAGCTACAACGA GCAACTGA
13461





8707
AGUUGCAC A CGAUGCAU
4713
ATGCATCG GGCTAGCTACAACGA GTGCAACT
13462





8710
UGCACACG A UGCAUCUG
4714
CAGATGCA GGCTAGCTACAACGA CGTGTGCA
13463





8712
CACACGAU G CAUCUGGC
4715
GCCAGATG GGCTAGCTACAACGA ATCGTGTG
13464





8714
CACGAUGC A UCUGGCAA
4716
TTGCCAGA GGCTAGCTACAACGA GCATCGTG
13465





8719
UGCAUCUG G CAAAAGGG
4717
CCCTTTTG GGCTAGCTACAACGA CAGATGCA
13466





8727
GCAAAAGG G UGUACUAC
4718
GTAGTACA GGCTAGCTACAACGA CCTTTTGC
13467





8729
AAAAGGGU G UACUACCU
4719
AGGTAGTA GGCTAGCTACAACGA ACCCTTTT
13468





8731
AAGGGUGU A CUACCUCA
4720
TGAGGTAG GGCTAGCTACAACGA ACACCCTT
13469





8734
GGUGUACU A CCUCACCC
4721
GGGTGAGG GGCTAGCTACAACGA AGTACACC
13470





8739
ACUACCUC A CCCGUGAC
4722
GTCACGGG GGCTAGCTACAACGA GAGGTAGT
13471





8743
CCUCACCC G UGACCCCA
4723
TGGGGTCA GGCTAGCTACAACGA GGGTGAGG
13472





8746
CACCCGUG A CCCCACCA
4724
TGGTGGGG GGCTAGCTACAACGA CACGGGTG
13473





8751
GUGACCCC A CCACCCCC
4725
GGGGGTGG GGCTAGCTACAACGA GGGGTCAC
13474





8754
ACCCCACC A CCCCCCUU
4726
AAGGGGGG GGCTAGCTACAACGA GGTGGGGT
13475





8763
CCCCCCUU G CGCGGGCU
4727
AGCCCGCG GGCTAGCTACAACGA AAGGGGGG
13476





8765
CCCCUUGC G CGGGCUGC
4728
GCAGCCCG GGCTAGCTACAACGA GCAAGGGG
13477





8769
UUGCGCGG G CUGCGUGG
4729
CCACGCAG GGCTAGCTACAACGA CCGCGCAA
13478





8772
CGCGGGCU G CGUGGGAG
4730
CTCCCACG GGCTAGCTACAACGA AGCCCGCG
13479





8774
CGGGCUGC G UGGUAGAC
4731
GTCTCCCA GGCTAGCTACAACGA GCAGCCCG
13480





8781
CGUGGGAG A CAGCUAGA
4732
TCTAGCTG GGCTAGCTACAACGA CTCCCACG
13481





8784
GGGAGACA G CUAGAAGC
4733
GCTTCTAG GGCTAGCTACAACGA TGTCTCCC
13482





8791
AGCUAGAA G CACUCCAG
4734
CTGGAGTG GGCTAGCTACAACGA TTCTAGCT
13483





8793
CUAGAAGC A CUCCAGUC
4735
GACTGGAG GGCTAGCTACAACGA GCTTCTAG
13484





8799
GCACUCCA G UCAACUCC
4736
GGAGTTGA GGCTAGCTACAACGA TGGAGTGC
13485





8803
UCCAGUCA A CUCCUGGC
4737
GCCAGGAG GGCTAGCTACAACGA TGACTGGA
13486





8810
AACUCCUG G CUAGGCAA
4738
TTGCCTAG GGCTAGCTACAACGA CAGGAGTT
13487





8815
CUGGCUAG G CAACAUCA
4739
TGATGTTG GGCTAGCTACAACGA CTAGCCAG
13488





8818
GCUAGGCA A CAUCAUCA
4740
TGATGATG GGCTAGCTACAACGA TGCCTAGC
13489





8820
UAGGCAAC A UCAUCAUG
4741
CATGATGA GGCTAGCTACAACGA GTTGCCTA
13490





8823
GCAACAUC A UCAUGUUU
4742
AAACATGA GGCTAGCTACAACGA GATGTTGC
13491





8826
ACAUCAUC A UGUUUGCA
4743
TGCAAACA GGCTAGCTACAACGA GATGATGT
13492





8828
AUCAUCAU G UUUGCACC
4744
GGTGCAAA GGCTAGCTACAACGA ATGATGAT
13493





8832
UCAUGUUU G CACCCACU
4745
AGTGGGTG GGCTAGCTACAACGA AAACATGA
13494





8834
AUGUUUGC A CCCACUCU
4746
AGAGTGGG GGCTAGCTACAACGA GCAAACAT
13495





8838
UUGCACCC A CUCUAUGG
4747
CCATAGAG GGCTAGCTACAACGA GGGTGCAA
13496





8843
CCCACUCU A UGGGUAAG
4748
CTTACCCA GGCTAGCTACAACGA AGAGTGGG
13497





8847
CUCUAUGG G UAAGGAUG
4749
CATCCTTA GGCTAGCTACAACGA CCATAGAG
13498





8853
GGGUAAGG A UGAUUCUG
4750
CAGAATCA GGCTAGCTACAACGA CCTTACCC
13499





8856
UAAGGAUG A UUCUGAUG
4751
CATCAGAA GGCTAGCTACAACGA CATCCTTA
13500





8862
UGAUUCUG A UGACUCAC
4752
GTGAGTCA GGCTAGCTACAACGA CAGAATCA
13501





8865
UUCUGAUG A CUCACUUC
4753
GAAGTGAG GGCTAGCTACAACGA CATCAGAA
13502





8869
GAUGACUC A CUUCUUCU
4754
AGAAGAAG GGCTAGCTACAACGA GAGTCATC
13503





8880
UCUUCUCC A UCCUUCUA
4755
TAGAAGGA GGCTAGCTACAACGA GGAGAAGA
13504





8889
UCCUUCUA G CCCAGGAG
4756
CTCCTGGG GGCTAGCTACAACGA TAGAAGGA
13505





8897
GCCCAGGA G CAACUUGA
4757
TCAAGTTG GGCTAGCTACAACGA TCCTGGGC
13506





8900
CAGGAGCA A CUUGAGAA
4758
TTCTCAAG GGCTAGCTACAACGA TGCTCCTG
13507





8910
UUGAGAAA G CCCUAGAC
4759
GTCTAGGG GGCTAGCTACAACGA TTTCTCAA
13508





8917
AGCCCUAG A CUGCCAGA
4760
TCTGGCAG GGCTAGCTACAACGA CTAGGGCT
13509





8920
CCUAGACU G CCAGAUCU
4761
AGATCTGG GGCTAGCTACAACGA AGTCTAGG
13510





8925
ACUGCCAG A UCUACGGG
4762
CCCGTAGA GGCTAGCTACAACGA CTGGCAGT
13511





8929
CCAGAUCU A CGGGGCUU
4763
AAGCCCCG GGCTAGCTACAACGA AGATCTGG
13512





8934
UCUACGGG G CUUGUUAC
4764
GTAACAAG GGCTAGCTACAACGA CCCGTAGA
13513





8938
CGGGGCUU G UUACUCCA
4765
TGGAGTAA GGCTAGCTACAACGA AAGCCCCG
13514





8941
GGCUUGUU A CUCCAUUG
4766
CAATGCAG GGCTAGCTACAACGA AACAAGCC
13515





8946
GUUACUCC A UUGAGCCA
4767
TGGCTCAA GGCTAGCTACAACGA GGAGTAAC
13516





8951
UCCAUUGA G CCACUUGA
4768
TCAAGTGG GGCTAGCTACAACGA TCAATGGA
13517





8954
AUUGAGCC A CUUGACCU
4769
AGGTCAAG GGCTAGCTACAACGA GGCTCAAT
13518





8959
GCCACUUG A CCUACCUC
4770
GAGGTAGG GGCTAGCTACAACGA CAAGTGGC
13519





8963
CUUGACCU A CCUCAGAU
4771
ATCTGAGG GGCTAGCTACAACGA AGGTCAAG
13520





8970
UACCUCAG A UCAUUCAG
4772
CTGAATGA GGCTAGCTACAACGA CTGAGGTA
13521





8973
CUCAGAUC A UUCAGCGA
4773
TCGCTGAA GGCTAGCTACAACGA GATCTGAG
13522





8978
AUCAUUCA G CGACUCCA
4774
TGGAGTCG GGCTAGCTACAACGA TGAATGAT
13523





8981
AUUCAGCG A CUCCAUGG
4775
CCATGGAG GGCTAGCTACAACGA CGCTGAAT
13524





8986
GCGACUCC A UGGUCUUA
4776
TAAGACCA GGCTAGCTACAACGA GGAGTCGC
13525





8989
ACUCCAUG G UCUUAGCG
4777
CGCTAAGA GGCTAGCTACAACGA CATGGAGT
13526





8995
UGGUCUUA G CGCAUUUU
4778
AAAATGCG GGCTAGCTACAACGA TAAGACCA
13527





8997
GUCUUAGC G CAUUUUCA
4779
TGAAAATG GGCTAGCTACAACGA GCTAAGAC
13528





8999
CUUAGCGC A UUUUCACU
4780
AGTGAAAA GGCTAGCTACAACGA GCGCTAAG
13529





9005
GCAUUUUC A CUCCAUAG
4781
CTATGGAG GGCTAGCTACAACGA GAAAATGC
13530





9010
UUCACUCC A UAGUUACU
4782
AGTAACTA GGCTAGCTACAACGA GGAGTGAA
13531





9013
ACUCCAUA G UUACUCCC
4783
GGGAGTAA GGCTAGCTACAACGA TATGGAGT
13532





9016
CCAUAGUU A CUCCCCAG
4784
CTGGGGAG GGCTAGCTACAACGA AACTATGG
13533





9025
CUCCCCAG G UGAAAUCA
4785
TGATTTCA GGCTAGCTACAACGA CTGGGGAG
13534





9030
CAGGUGAA A UCAAUAGG
4786
CCTATTGA GGCTAGCTACAACGA TTCACCTG
13535





9034
UGAAAUCA A UAGGGUGG
4787
CCACCCTA GGCTAGCTACAACGA TGATTTCA
13536





9039
UCAAUAGG G UGGCAUCA
4788
TGATGCCA GGCTAGCTACAACGA CCTATTGA
13537





9042
AUAGGGUG G CAUCAUGC
4789
GCATGATG GGCTAGCTACAACGA CACCCTAT
13538





9044
AGGGUGGC A UCAUGCCU
4790
AGGCATGA GGCTAGCTACAACGA GCCACCCT
13539





9047
GUGGCAUC A UGCCUCAG
4791
CTGAGGCA GGCTAGCTACAACGA GATGCCAC
13540





9049
GGCAUCAU G CCUCAGGA
4792
TCCTGAGG GGCTAGCTACAACGA ATGATGCC
13541





9059
CUCAGGAA A CUUGGGGU
4793
ACCCCAAG GGCTAGCTACAACGA TTCCTGAG
13542





9066
AACUUGGG G UACCACCC
4794
GGGTGGTA GGCTAGCTACAACGA CCCAAGTT
13543





9068
CUUGGGGU A CCACCCUU
4795
AAGGGTGG GGCTAGCTACAACGA ACCCCAAG
13544





9071
GGGGUACC A CCCUUGCG
4796
CGCAAGGG GGCTAGCTACAACGA GGTACCCC
13545





9077
CCACCCUU G CGAACCUG
4797
CAGGTTCG GGCTAGCTACAACGA AAGGGTGG
13546





9081
CCUUGCGA A CCUGGAGA
4798
TCTCCAGG GGCTAGCTACAACGA TCGCAAGG
13547





9089
ACCUGGAG A CAUCGGGC
4799
GCCCGATG GGCTAGCTACAACGA CTCCAGGT
13548





9091
CUGGAGAC A UCGGGCCA
4800
TGGCCCGA GGCTAGCTACAACGA GTCTCCAG
13549





9096
GACAUCGG G CCAGAAGU
4801
ACTTCTGG GGCTAGCTACAACGA CCGATGTC
13550





9103
GGCCAGAA G UGUUCGCG
4802
CGCGAACA GGCTAGCTACAACGA TTCTGGCC
13551





9105
CCAGAAGU G UUCGCGCU
4803
AGCGCGAA GGCTAGCTACAACGA ACTTCTGG
13552





9109
AAGUGUUC G CGCUAAGC
4804
GCTTAGCG GGCTAGCTACAACGA GAACACTT
13553





9111
GUGUUCGC G CUAAGCUA
4805
TAGCTTAG GGCTAGCTACAACGA GCGAACAC
13554





9116
CGCGCUAA G CUACUGUC
4806
GACAGTAG GGCTAGCTACAACGA TTAGCGCG
13555





9119
GCUAAGCU A CUGUCCCA
4807
TGGGACAG GGCTAGCTACAACGA AGCTTAGC
13556





9122
AAGCUACU G UCCCAGGG
4808
CCCTGGGA GGCTAGCTACAACGA AGTAGCTT
13557





9138
GGGGGAGG G CCGCCACC
4809
GGTGGCGG GGCTAGCTACAACGA CCTCCCCC
13558





9141
GGAGGGCC G CCACCUGU
4810
ACAGGTGG GGCTAGCTACAACGA GGCCCTCC
13559





9144
GGGCCGCC A CCUGUGGC
4811
GCCACAGG GGCTAGCTACAACGA GGCGGCCC
13560





9148
CGCCACCU G UGGCAGGU
4812
ACCTGCCA GGCTAGCTACAACGA AGGTGGCG
13561





9151
CACCUGUG G CAGGUACC
4813
GGTACCTG GGCTAGCTACAACGA CACAGGTG
13562





9155
UGUGGCAG G UACCUCUU
4814
AAGAGGTA GGCTAGCTACAACGA CTGCCACA
13563





9157
UGGCAGGU A CCUCUUCA
4815
TGAAGAGG GGCTAGCTACAACGA ACCTGCCA
13564





9166
CCUCUUCA A CUGGGCAG
4816
CTGCCCAG GGCTAGCTACAACGA TGAAGAGG
13565





9171
UCAACUGG G CAGUAAAG
4817
CTTTACTG GGCTAGCTACAACGA CCAGTTGA
13566





9174
ACUGGGCA G UAAAGACC
4818
GGTCTTTA GGCTAGCTACAACGA TGCCCAGT
13567





9180
CAGUAAAG A CCAAACUC
4819
GAGTTTGG GGCTAGCTACAACGA CTTTACTG
13568





9185
AAGACCAA A CUCAAACU
4820
AGTTTGAG GGCTAGCTACAACGA TTGGTCTT
13569





9191
AAACUCAA A CUCACUCC
4821
GGAGTGAG GGCTAGCTACAACGA TTGAGTTT
13570





9195
UCAAACUC A CUCCAAUC
4822
GATTGGAG GGCTAGCTACAACGA GAGTTTGA
13571





9201
UCACUCCA A UCCCAGCU
4823
AGCTGGGA GGCTAGCTACAACGA TGGAGTGA
13572





9207
CAAUCCCA G CUGCGUCU
4824
AGACGCAG GGCTAGCTACAACGA TGGGATTG
13573





9210
UCCCAGCU G CGUCUCAG
4825
CTGAGACG GGCTAGCTACAACGA AGCTGGGA
13574





9212
CCAGCUGC G UCUCAGUU
4826
AACTGAGA GGCTAGCTACAACGA GCAGCTGG
13575





9218
GCGUCUCA G UUGGACUU
4827
AAGTCCAA GGCTAGCTACAACGA TGAGACGC
13576





9223
UCAGUUGG A CUUGUCCA
4828
TGGACAAG GGCTAGCTACAACGA CCAACTGA
13577





9227
UUGGACUU G UCCAACUG
4829
CAGTTGGA GGCTAGCTACAACGA AAGTCCAA
13578





9232
CUUGUCCA A CUGGUUCG
4830
CGAACCAG GGCTAGCTACAACGA TGGACAAG
13579





9236
UCCAACUG G UUCGUUGC
4831
GCAACGAA GGCTAGCTACAACGA CAGTTGGA
13580





9240
ACUGGUUC G UUGCUGGC
4832
GCCAGCAA GGCTACCTACAACGA GAACCAGT
13581





9243
GGUUCGUU G CUGGCUAC
4833
GTACCCAG GGCTAGCTACAACGA AACGAACC
13582





9247
CGUUGCUG G CUACAGCG
4834
CGCTGTAG GGCTAGCTACAACGA CAGCAACG
13583





9250
UGCUGGCU A CAGCGGGG
4835
CCCCGCTG GGCTAGCTACAACGA AGCCAGCA
13584





9253
UGGCUACA G CGGGGGAG
4836
CTCCCCCG GGCTAGCTACAACGA TGTAGCCA
13585





9262
CGGGGGAG A CGUGUAUC
4837
GATACACG GGCTAGCTACAACGA CTCCCCCG
13586





9264
GGGGAGAC G UGUAUCAC
4838
GTGATACA GGCTAGCTACAACGA GTCTCCCC
13587





9266
GGAGACGU G UAUCACAG
4839
CTGTGATA GGCTAGCTACAACGA ACGTCTCC
13588





9268
AGACGUGU A UCACAGCC
4840
GGCTGTGA GGCTAGCTACAACGA ACACGTCT
13589





9271
CGUGUAUC A CAGCCUGU
4841
ACAGGCTG GGCTAGCTACAACGA GATACACG
13590





9274
GUAUCACA G CCUGUCUC
4842
GAGACAGG GGCTAGCTACAACGA TGTGATAC
13591





9278
CACAGCCU G UCUCGUGC
4843
GCACGAGA GGCTAGCTACAACGA AGGCTGTG
13592





9283
CCUGUCUC G UGCCCGAC
4844
GTCGGGCA GGCTAGCTACAACGA GAGACAGG
13593





9285
UGUCUCGU G CCCGACCC
4845
GGGTCGGG GGCTAGCTACAACGA ACGAGACA
13594





9290
CGUGCCCG A CCCCGCUG
4846
CAGCGGGG GGCTAGCTACAACGA CGGGCACG
13595





9295
CCGACCCC G CUGGUUCA
4847
TGAACCAG GGCTAGCTACAACGA GGGGTCGG
13596





9299
CCCCGCUG G UUCAUGCU
4848
AGCATGAA GGCTAGCTACAACGA CAGCGGGG
13597





9303
GCUGGUUC A UGCUUUGC
4849
GCAAAGCA GGCTAGCTACAACGA GAACCAGC
13598





9305
UGGUUCAU G CUUUGCCU
4850
AGGCAAAG GGCTAGCTACAACGA ATGAACCA
13599





9310
CAUGCUUU G CCUACUCC
4851
GGAGTAGG GGCTAGCTACAACGA AAAGCATG
13600





9314
CUUUGCCU A CUCCUACU
4852
AGTAGGAG GGCTAGCTACAACGA AGGCAAAG
13601





9320
CUACUCCU A CUCUCCGU
4853
ACGGAGAG GGCTAGCTACAACGA AGGAGTAG
13602





9327
UACUCUCC G UAGGGGUA
4854
TACCCCTA GGCTAGCTACAACGA GGAGAGTA
13603





9333
CCGUAGGG G UAGGCAUC
4855
GATGCCTA GGCTAGCTACAACGA CCCTACGG
13604





9337
AGGGGUAG G CAUCUACC
4856
GGTAGATG GGCTAGCTACAACGA CTACCCCT
13605





9339
GGGUAGGC A UCUACCUG
4857
CAGGTAGA GGCTAGCTACAACGA GCCTACCC
13606





9343
AGGCAUCU A CCUGCUCC
4858
GGAGCAGG GGCTAGCTACAACGA AGATGCCT
13607





9347
AUCUACCU G CUCCCCAA
4859
TTGGGGAG GGCTAGCTACAACGA AGGTAGAT
13608





9355
GCUCCCCA A CCGAUGAA
4860
TTCATCGG GGCTAGCTACAACGA TGGGGAGC
13609





9359
CCCAACCG A UGAACAGG
4861
CCTGTTCA GGCTAGCTACAACGA CGGTTGGG
13610





9363
ACCGAUGA A CAGGGAGC
4862
GCTCCCTG GGCTAGCTACAACGA TCATCGGT
13611





9370
AACAGGGA G CUAAACAC
4863
GTGTTTAG GGCTAGCTACAACGA TCCCTGTT
13612





9375
GGAGCUAA A CACUCCAG
4864
CTGGAGTG GGCTAGCTACAACGA TTAGCTCC
13613





9377
AGCUAAAC A CUCCAGGC
4865
GCCTGGAG GGCTAGCTACAACGA GTTTAGCT
13614





9384
CACUCCAG G CCAAUAGG
4866
CCTATTGG GGCTAGCTACAACGA CTGGAGTG
13615





9388
CCACGCCA A UAGGCCAU
4867
ATGGCCTA GGCTAGCTACAACGA TGGCCTGG
13616





9392
GCCAAUAG G CCAUCCCG
4868
CGGGATGG GGCTAGCTACAACGA CTATTGGC
13617





9395
AAUAGGCC A UCCCGUUU
4869
AAACGGGA GGCTAGCTACAACGA GGCCTATT
13618





9400
GCCAUCCC G UUUUUUUU
4870
AAAAAAAA GGCTAGCTACAACGA GGGATGGC
13619






Input Sequence = HPCK1S1.




Cut Site = R/Y




Arm Length = 8.




Core Sequence = GGCTAGCTACAACGA




HPCK1S1 Hepatitis C virus (strain HCV-1b, clone HCV-K1-S1), complete genome; acc# gi|1030702|dbj|D50483.1; 9410 nt








[0567]

19






TABLE XIX










HCV minus strand DNAzyme and Substrate Sequence












Pos
Substrate
Seq ID
DNAzyme
Seq ID















9413
AAAAAAAA A CGGGAUGG
4871
CCATCCCG GGCTAGCTACAACGA TTTTTTTT
13620



9408
AAAACGGG A UGGCCUAU
4872
ATAGGCCA GGCTAGCTACAACGA CCCGTTTT
13621


9405
ACGGGAUG G CCUAUUGG
4873
CCAATAGG GGCTAGCTACAACGA CATCCCGT
13622


9401
GAUGGCCU A UUGGCCUG
4874
CAGGCCAA GGCTAGCTACAACGA AGGCCATC
13623


9397
GCCUAUUG G CCUGGAGU
4875
ACTCCAGG GGCTAGCTACAACGA CAATAGGC
13624


9390
GGCCUGGA G UGUUUAGC
4876
GCTAAACA GGCTAGCTACAACGA TCCAGGCC
13625


9388
CCUGGAGU G UUUAGCUC
4877
GAGCTAAA GGCTAGCTACAACGA ACTCCAGG
13626


9383
AGUGUUUA G CUCCCUGU
4878
ACAGGGAG GGCTAGCTACAACGA TAAACACT
13627


9376
AGCUCCCU G UUCAUCGG
4879
CCGATGAA GGCTAGCTACAACGA AGGGAGCT
13628


9372
CCCUGUUC A UCGGUUGG
4880
CCAACCGA GGCTAGCTACAACGA GAACAGGG
13629


9368
GUUCAUCG G UUGGGGAG
4881
CTCCCCAA GGCTAGCTACAACGA CGATGAAC
13630


9360
GUUGGGGA G CAGGUAGA
4882
TCTACCTG GGCTAGCTACAACGA TCCCCAAC
13631


9356
GGGAGCAG G UAGAUGCC
4883
GGCATCTA GGCTAGCTACAACGA CTGCTCCC
13632


9352
GCAGGUAG A UGCCUACC
4884
GGTAGGCA GGCTAGCTACAACGA CTACCTGC
13633


9350
AGGUAGAU G CCUACCCC
4885
GGGGTAGG GGCTAGCTACAACGA ATCTACCT
13634


9346
AGAUGCCU A CCCCUACG
4886
CGTAGGGG GGCTAGCTACAACGA AGGCATCT
13635


9340
CUACCCCU A CGGAGAGU
4887
ACTCTCCG GGCTAGCTACAACGA AGGGGTAG
13636


9333
UACGGAGA G UAGGAGUA
4888
TACTCCTA GGCTAGCTACAACGA TCTCCGTA
13637


9327
GAGUAGGA G UAGGCAAA
4889
TTTGCCTA GGCTAGCTACAACGA TCCTACTC
13638


9323
AGGAGUAG G CAAAGCAU
4890
ATGCTTTG GGCTAGCTACAACGA CTACTCCT
13639


9318
UAGGCAAA G CAUGAACC
4891
GGTTCATG GGCTAGCTACAACGA TTTGCCTA
13640


9316
GGCAAAGC A UGAACCAG
4892
CTGGTTCA GGCTAGCTACAACGA GCTTTGCC
13641


9312
AAGCAUGA A CCAGCGGG
4893
CCCGCTGG GGCTAGCTACAACGA TCATGCTT
13642


9308
AUGAACCA G CGGGGUCG
4894
CGACCCCG GGCTAGCTACAACGA TGGTTCAT
13643


9303
CCAGCGGG G UCGGGCAC
4895
GTGCCCGA GGCTAGCTACAACGA CCCGCTGG
13644


9298
GGGGUCGG G CACGAGAC
4896
GTCTCGTG GGCTAGCTACAACGA CCGACCCC
13645


9296
GGUCGGGC A CGAGACAG
4897
CTGTCTCG GGCTAGCTACAACGA GCCCGACC
13646


9291
GGCACGAG A CAGGCUGU
4898
ACAGCCTG GGCTAGCTACAACGA CTCGTGCC
13647


9287
CGAGACAG G CUGUGAUA
4899
TATCACAG GGCTAGCTACAACGA CTGTCTCG
13648


9284
GACAGGCU G UGAUACAC
4900
GTGTATCA GGCTAGCTACAACGA AGCCTGTC
13649


9281
AGGCUGUG A UACACGUC
4901
GACGTGTA GGCTAGCTACAACGA CACAGCCT
13650


9279
GCUGUGAU A CACGUCUC
4902
GAGACGTG GGCTAGCTACAACGA ATCACAGC
13651


9277
UGUGAUAC A CGUCUCCC
4903
GGGAGACG GGCTAGCTACAACGA GTATCACA
13652


9275
UGAUACAC G UCUCCCCC
4904
GGGGGAGA GGCTAGCTACAACGA GTGTATCA
13653


9266
UCUCCCCC G CUGUAGCC
4905
GGCTACAG GGCTAGCTACAACGA GGGGGAGA
13654


9263
CCCCCGCU G UAGCCAGC
4906
GCTGGCTA GGCTAGCTACAACGA AGCGGGGG
13655


9260
CCGCUGUA G CCAGCAAC
4907
GTTGCTGG GGCTAGCTACAACGA TACAGCGG
13656


9256
UGUAGCCA G CAACGAAC
4908
GTTCGTTG GGCTAGCTACAACGA TGGCTACA
13657


9253
AGCCAGCA A CGAACCAG
4909
CTGGTTCG GGCTAGCTACAACGA TGCTGGCT
13658


9249
AGCAACGA A CCAGUUGG
4910
CCAACTGG GGCTAGCTACAACGA TCGTTGCT
13659


9245
ACGAACCA G UUGGACAA
4911
TTGTCCAA GGCTAGCTACAACGA TGGTTCGT
13660


9240
CCAGUUGG A CAAGUCCA
4912
TGGACTTG GGCTAGCTACAACGA CCAACTGG
13661


9236
UUGGACAU G UCCAACUG
4913
CAGTTGGA GGCTAGCTACAACGA TTGTCCAA
13662


9231
CAAGUCCA A CUGAGACG
4914
CGTCTCAG GGCTAGCTACAACGA TGGACTTG
13663


9225
CAACUGAG A CGCAGCUG
4915
CAGCTGCG GGCTAGCTACAACGA CTCAGTTG
13664


9223
ACUGAGAC G CAGCUGGG
4916
CCCAGCTG GGCTAGCTACAACGA GTCTCAGT
13665


9220
GAGACGCA G CUGGGAUU
4917
AATCCCAG GGCTAGCTACAACGA TGCGTCTC
13666


9214
CAGCUGGG A UUGGAGUG
4918
CACTCCAA GGCTAGCTACAACGA CCCAGCTG
13667


9208
GGAUUGGA G UGAGUUUG
4919
CAAACTCA GGCTAGCTACAACGA TCCAATCC
13668


9204
UGGAGUGA G UUUGAGUU
4920
AACTCAAA GGCTAGCTACAACGA TCACTCCA
13669


9198
GAGUUUGA G UUUGGUCU
4921
AGACCAAA GGCTAGCTACAACGA TCAAACTC
13670


9193
UGAGUUUG G UCUUUACU
4922
AGTAAAGA GGCTAGCTACAACGA CAAACTCA
13671


9187
UGGUCUUU A CUGCCCAG
4923
CTGGGCAG GGCTAGCTACAACGA AAAGACCA
13672


9184
UCUUUACU G CCCAGUUG
4924
CAACTGGG GGCTAGCTACAACGA AGTAAAGA
13673


9179
ACUGCCCA G UUGAAGAG
4925
CTCTTCAA GGCTAGCTACAACGA TGGGCAGT
13674


9170
UUGAAGAG G UACCUGCC
4926
GGCAGGTA GGCTAGCTACAACGA CTCTTCAA
13675


9168
GAAGAGGU A CCUGCCAC
4927
GTGGCAGG GGCTAGCTACAACGA ACCTCTTC
13676


9164
AGGUACCU G CCACAGGU
4928
ACCTGTGG GGCTAGCTACAACGA AGGTACCT
13677


9161
UACCUGCC A CAGGUGGC
4929
GCCACCTG GGCTAGCTACAACGA GGCAGGTA
13678


9157
UGCCACAG G UGGCGGCC
4930
GGCCGCCA GGCTAGCTACAACGA CTGTGGCA
13679


9154
CACAGGUG G CGGCCCUC
4931
GAGGGCCG GGCTAGCTACAACGA CACCTGTG
13680


9151
AGGUGGCG G CCCUCCCC
4932
GGGGAGGG GGCTAGCTACAACGA CGCCACCT
13681


9135
CCCCUGGG A CAGUAGCU
4933
AGCTACTG GGCTAGCTACAACGA CCCAGGGG
13682


9132
CUGGGACA G UAGCUUAG
4934
CTAAGCTA GGCTAGCTACAACGA TGTCCCAG
13683


9129
GGACAGUA G CUUAGCGC
4935
GCGCTAAG GGCTAGCTACAACGA TACTGTCC
13684


9124
GUAGCUUA G CGCGAACA
4936
TGTTCGCG GGCTAGCTACAACGA TAAGCTAC
13685


9122
AGCUUAGC G CGAACACU
4937
AGTGTTCG GGCTAGCTACAACGA GCTAAGCT
13686


9118
UAGCGCGA A CACUUCUG
4938
CAGAAGTG GGCTAGCTACAACGA TCGCGCTA
13687


9116
GCGCGAAC A CUUCUGGC
4939
GCCAGAAG GGCTAGCTACAACGA GTTCGCGC
13688


9109
CACUUCUG G CCCGAUGU
4940
ACATCGGG GGCTAGCTACAACGA CAGAAGTG
13689


9104
CUGGCCCG A UGUCUCCA
4941
TGGAGACA GGCTAGCTACAACGA CGGGCCAG
13690


9102
GGCCCGAU G UCUCCAGG
4942
CCTGGAGA GGCTAGCTACAACGA ATCGGGCC
13691


9094
GUCUCCAG G UUCGCAAG
4943
CTTGCGAA GGCTAGCTACAACGA CTGGAGAC
13692


9090
CCAGGUUC G CAAGGGUG
4944
CACCCTTG GGCTAGCTACAACGA GAACCTGG
13693


9084
UCGCAAGG G UGGUACCC
4945
GGGTACCA GGCTAGCTACAACGA CCTTGCGA
13694


9081
CAAGGGUG G UACCCCAA
4946
TTGGGGTA GGCTAGCTACAACGA CACCCTTG
13695


9079
AGGGUGGU A CCCCAAGU
4947
ACTTGGGG GGCTAGCTACAACGA ACCACCCT
13696


9072
UACCCCAA G UUUCCUGA
4948
TCAGGAAA GGCTAGCTACAACGA TTGGGGTA
13697


9062
UUCCUGAG G CAUGAUGC
4949
GCATCATG GGCTAGCTACAACGA CTCAGGAA
13698


9060
CCUGAGGC A UGAUGCCA
4950
TGGCATCA GGCTAGCTACAACGA GCCTCAGG
13699


9057
GAGGCAUG A UGCCACCC
4951
GGGTGGCA GGCTAGCTACAACGA CATGCCTC
13700


9055
GGCAUGAU G CCACCCUA
4952
TAGGGTGG GGCTAGCTACAACGA ATCATGCC
13701


9052
AUGAUGCC A CCCUAUUG
4953
CAATAGGG GGCTAGCTACAACGA GGCATCAT
13702


9047
GCCACCCU A UUGAUUUC
4954
GAAATCAA GGCTAGCTACAACGA AGGGTGGC
13703


9043
CCCUAUUG A UUUCACCU
4955
AGGTGAAA GGCTAGCTACAACGA CAATAGGG
13704


9038
UUGAUUUC A CCUGGGGA
4956
TCCCCAGG GGCTAGCTACAACGA GAAATCAA
13705


9029
CCUGGGGA G UAACUAUG
4957
CATAGTTA GGCTAGCTACAACGA TCCCCAGG
13706


9026
GGGGAGUA A CUAUGGAG
4958
CTCCATAG GGCTAGCTACAACGA TACTCCCC
13707


9023
GAGUAACU A UGGAGUGA
4959
TCACTCCA GGCTAGCTACAACGA AGTTACTC
13708


9018
ACUAUGGA G UGAAAAUG
4960
CATTTTCA GGCTAGCTACAACGA TCCATAGT
13709


9012
GAGUGAAA A UGCGCUAA
4961
TTAGCGCA GGCTAGCTACAACGA TTTCACTC
13710


9010
GUGAAAAU G CGCUAAGA
4962
TCTTAGCG GGCTAGCTACAACGA ATTTTCAC
13711


9008
GAAAAUGC G CUAAGACC
4963
GGTCTTAG GGCTAGCTACAACGA GCATTTTC
13712


9002
GCGCUAAG A CCAUGGAG
4964
CTCCATGG GGCTAGCTACAACGA CTTAGCGC
13713


8999
CUAAGACC A UGGAGUCG
4965
CGACTCCA GGCTAGCTACAACGA GGTCTTAG
13714


8994
ACCAUGGA G UCGCUGAA
4966
TTCAGCGA GGCTAGCTACAACGA TCCATGGT
13715


8991
AUGGAGUC G CUGAAUGA
4967
TCATTCAG GGCTAGCTACAACGA GACTCCAT
13716


8986
GUCGCUGA A UGAUCUGA
4968
TCAGATCA GGCTAGCTACAACGA TCAGCGAC
13717


8983
GCUGAAUG A UCUGAGGU
4969
ACCTCAGA GGCTAGCTACAACGA CATTCAGC
13718


8976
GAUCUGAG G UAGGUCAA
4970
TTGACCTA GGCTAGCTACAACGA CTCAGATC
13719


8972
UGAGGUAG G UCAAGUGG
4971
CCACTTGA GGCTAGCTACAACGA CTACCTCA
13720


8967
UAGGUCAA G UGGCUCAA
4972
TTGAGCCA GGCTAGCTACAACGA TTGACCTA
13721


8964
GUCAAGUG G CUCAAUGG
4973
CCATTGAG GGCTAGCTACAACGA CACTTGAC
13722


8959
GUGGCUCA A UGGAGUAA
4974
TTACTCCA GGCTAGCTACAACGA TGAGCCAC
13723


8954
UCAAUGGA G UAACAAGC
4975
GCTTGTTA GGCTAGCTACAACGA TCCATTGA
13724


8951
AUGGAGUA A CAAGCCCC
4976
GGGGCTTG GGCTAGCTACAACGA TACTCCAT
13725


8947
AGUAACAA G CCCCGUAG
4977
CTACGGGG GGCTAGCTACAACGA TTGTTACT
13726


8942
CAAGCCCC G UAGAUCUG
4978
CAGATCTA GGCTAGCTACAACGA GGGGCTTG
13727


8938
CCCCGUAG A UCUGGCAG
4979
CTGCCAGA GGCTAGCTACAACGA CTACGGGG
13728


8933
UAGAUCUG G CAGUCUAG
4980
CTAGACTG GGCTAGCTACAACGA CAGATCTA
13729


8930
AUCUGGCA G UCUAGGGC
4981
GCCCTAGA GGCTAGCTACAACGA TGCCAGAT
13730


8923
AGUCUAGG G CUUUCUCA
4982
TGAGAAAG GGCTAGCTACAACGA CCTAGACT
13731


8913
UUUCUCAA G UUGCUCCU
4983
AGGAGCAA GGCTAGCTACAACGA TTGAGAAA
13732


8910
CUCAAGUU G CUCCUGGG
4984
CCCAGGAG GGCTAGCTACAACGA AACTTGAG
13733


8902
GCUCCUGG G CUAGAAGG
4985
CCTTCTAG GGCTAGCTACAACGA CCAGGAGC
13734


8893
CUAGAAGG A UGGAGAAG
4986
CTTCTCCA GGCTAGCTACAACGA CCTTCTAG
13735


8882
GAGAAGAA G UGAGUCAU
4987
ATGACTCA GGCTAGCTACAACGA TTCTTCTC
13736


8878
AGAAGUGA G UCAUCAGA
4988
TCTGATGA GGCTAGCTACAACGA TCACTTCT
13737


8875
AGUGAGUC A UCAGAAUC
4989
GATTCTGA GGCTAGCTACAACGA GACTCACT
13738


8869
UCAUCAGA A UCAUCCUU
4990
AAGGATGA GGCTAGCTACAACGA TCTGATGA
13739


8866
UCAGAAUC A UCCUUACC
4991
GGTAAGGA GGCTAGCTACAACGA GATTCTGA
13740


8860
UCAUCCUU A CCCAUAGA
4992
TCTATGGG GGCTAGCTACAACGA AAGGATGA
13741


8856
CCUUACCC A UAGAGUGG
4993
CCACTCTA GGCTAGCTACAACGA GGGTAAGG
13742


8851
CCCAUAGA G UGGGUGCA
4994
TGCACCCA GGCTAGCTACAACGA TCTATGGG
13743


8847
UAGAGUGG G UGCAAACA
4995
TGTTTGCA GGCTAGCTACAACGA CCACTCTA
13744


8845
GAGUGGGU G CAAACAUG
4996
CATGTTTG GGCTAGCTACAACGA ACCCACTC
13745


8841
GGGUGCAA A CAUGAUGA
4997
TCATCATG GGCTAGCTACAACGA TTGCACCC
13746


8839
GUGCAAAC A UGAUGAUG
4998
CATCATCA GGCTAGCTACAACGA GTTTGCAC
13747


8836
CAAACAUG A UGAUGUUG
4999
CAACATCA GGCTAGCTACAACGA CATGTTTG
13748


8833
ACAUGAUG A UGUUGCCU
5000
AGGCAACA GGCTAGCTACAACGA CATCATGT
13749


8831
AUGAUGAU G UUGCCUAG
5001
CTAGGCAA GGCTAGCTACAACGA ATCATCAT
13750


8828
AUGAUGUU G CCUAGCCA
5002
TGGCTAGG GGCTAGCTACAACGA AACATCAT
13751


8823
GUUGCCUA G CCAGGAGU
5003
ACTCCTGG GGCTAGCTACAACGA TAGGCAAC
13752


8816
AGCCAGGA G UUGACUGG
5004
CCAGTCAA GGCTAGCTACAACGA TCCTGGCT
13753


8812
AGGAGUUG A CUGGAGUG
5005
CACTCCAG GGCTAGCTACAACGA CAACTCCT
13754


8806
UGACUGGA G UGCUUCUA
5006
TAGAAGCA GGCTAGCTACAACGA TCCAGTCA
13755


8804
ACUGGAGU G CUUCUAGC
5007
GCTAGAAG GGCTAGCTACAACGA ACTCCAGT
13756


8797
UGCUUCUA G CUGUCUCC
5008
GGAGACAG GGCTAGCTACAACGA TAGAAGCA
13757


8794
UUCUAGCU G UCUCCCAC
5009
GTGGGAGA GGCTAGCTACAACGA AGCTAGAA
13758


8787
UGUCUCCC A CGCAGCCC
5010
GGGCTGCG GGCTAGCTACAACGA GGGAGACA
13759


8785
UCUCCCAC G CAGCCCGC
5011
GCGGGCTG GGCTAGCTACAACGA GTGGGAGA
13760


8782
CCCACGCA G CCCGCGCA
5012
TGCGCGGG GGCTAGCTACAACGA TGCGTGGG
13761


8778
CGCAGCCC G CGCAAGGG
5013
CCCTTGCG GGCTAGCTACAACGA GGGCTGCG
13762


8776
CAGCCCGC G CAAGGGGG
5014
CCCCCTTG GGCTAGCTACAACGA GCGGGCTG
13763


8767
CAAGGGGG G UGGUGGGG
5015
CCCCACCA GGCTAGCTACAACGA CCCCCTTG
13764


8764
GGGGGGUG G UGGGGUCA
5016
TGACCCCA GGCTAGCTACAACGA CACCCCCC
13765


8759
GUGGUGGG G UCACGGGU
5017
ACCCGTGA GGCTAGCTACAACGA CCCACCAC
13766


8756
GUGGGGUC A CGGGUGAG
5018
CTCACCCG GGCTAGCTACAACGA GACCCCAC
13767


8752
GGUCACGG G UGAGGUAG
5019
CTACCTCA GGCTAGCTACAACGA CCGTGACC
13768


8747
CGGGUGAG G UAGUACAC
5020
GTGTACTA GGCTAGCTACAACGA CTCACCCG
13769


8744
GUGAGGUA G UACACCCU
5021
AGGGTGTA GGCTAGCTACAACGA TACCTCAC
13770


8742
GAGGUAGU A CACCCUUU
5022
AAAGGGTG GGCTAGCTACAACGA ACTACCTC
13771


8740
GGUAGUAC A CCCUUUUG
5023
CAAAAGGG GGCTAGCTACAACGA GTACTACC
13772


8732
ACCCUUUU G CCAGAUGC
5024
GCATCTGG GGCTAGCTACAACGA AAAAGGGT
13773


8727
UUUGCCAG A UGCAUCGU
5025
ACGATGCA GGCTAGCTACAACGA CTGGCAAA
13774


8725
UGCCAGAU G CAUCGUGU
5026
ACACGATG GGCTAGCTACAACGA ATCTGGCA
13775


8723
CCAGAUGC A UCGUGUGC
5027
GCACACGA GGCTAGCTACAACGA GCATCTGG
13776


8720
GAUGCAUC G UGUGCAAC
5028
GTTGCACA GGCTAGCTACAACGA GATGCATC
13777


8718
UGCAUCGU G UGCAACUG
5029
CAGTTGCA GGCTAGCTACAACGA ACGATGCA
13778


8716
CAUCGUGU G CAACUGAU
5030
ATCAGTTG GGCTAGCTACAACGA ACACGATG
13779


8713
CGUGUGCA A CUGAUACG
5031
CGTATCAG GGCTAGCTACAACGA TGCACACG
13780


8709
UGCAACUG A UACGUUGG
5032
CCAACGTA GGCTAGCTACAACGA CAGTTGCA
13781


8707
CAACUGAU A CGUUGGAG
5033
CTCCAACG GGCTAGCTACAACGA ATCAGTTG
13782


8705
ACUCAUAC G UUGGAGGA
5034
TCCTCCAA GGCTAGCTACAACGA GTATCAGT
13783


8696
UUGCAGGA G CAUGAUGU
5035
ACATCATG GGCTAGCTACAACGA TCCTCCAA
13784


8694
GGAGGAGC A UGAUGUUA
5036
TAACATCA GGCTAGCTACAACGA GCTCCTCC
13785


8691
GGAGCAUG A UGUUAUCA
5037
TGATAACA GGCTAGCTACAACGA CATGCTCC
13786


8689
AGCAUGAU G UUAUCAAC
5038
GTTGATAA GGCTAGCTACAACGA ATCATGCT
13787


8686
AUGAUGUU A UCAACUCC
5039
GGAGTTGA GGCTAGCTACAACGA AACATCAT
13788


8682
UGUUAUCA A CUCCAAGU
5040
ACTTGGAG GGCTAGCTACAACGA TGATAACA
13789


8675
AACUCCAA G UCGUAUUC
5041
GAATACGA GGCTAGCTACAACGA TTGGAGTT
13790


8672
UCCAAGUC G UAUUCCGG
5042
CCGGAATA GGCTAGCTACAACGA CACTTGGA
13791


8670
CAAGUCGU A UUCCGGUU
5043
AACCGGAA GGCTAGCTACAACGA ACGACTTG
13792


8664
GUAUUCCG G UUGGGGCG
5044
CGCCCCAA GGCTAGCTACAACGA CGGAATAC
13793


8658
CGGUUGGG G CGGGUCCC
5045
GGGACCCG GGCTAGCTACAACGA CCCAACCG
13794


8654
UGGGGCGG G UCCCCGGG
5046
CCCGGGGA GGCTAGCTACAACGA CCGCCCCA
13795


8641
CGGGGGGG G CAGAGUAC
5047
GTACTCTG GGCTAGCTACAACGA CCCCCCCG
13796


8636
GGGGCAGA G UACCUAGU
5048
ACTAGGTA GGCTAGCTACAACGA TCTGCCCC
13797


8634
GGCAGAGU A CCUAGUCA
5049
TGACTAGG GGCTAGCTACAACGA ACTCTGCC
13798


8629
AGUACCUA G UCAUAGCC
5050
GGCTATGA GGCTAGCTACAACGA TAGGTACT
13799


8626
ACCUAGUC A UAGCCUCC
5051
GGAGGCTA GGCTAGCTACAACGA GACTAGGT
13800


8623
UAGUCAUA G CCUCCGUG
5052
CACGGAGG GGCTAGCTACAACGA TATGACTA
13801


8617
UAGCCUCC G UGAAGACU
5053
AGTCTTCA GGCTAGCTACAACGA GGAGGCTA
13802


8611
CCGUGAAG A CUCGUAGG
5054
CCTACGAG GGCTAGCTACAACGA CTTCACGG
13803


8607
GAAGACUC G UAGGCUCG
5055
CGAGCCTA GGCTAGCTACAACGA GAGTCTTC
13804


8603
ACUCGUAG G CUCGCCGC
5056
GCGGCGAG GGCTAGCTACAACGA CTACGAGT
13805


8599
GUAGGCUC G CCGCGUCC
5057
GGACGCGG GGCTAGCTACAACGA GAGCCTAC
13806


8596
GGCUCGCC G CGUCCUCU
5058
AGAGGACG GGCTAGCTACAACGA GGCGAGCC
13807


8594
CUCGCCGC G UCCUCUUG
5059
CAAGAGGA GGCTAGCTACAACGA GCGGCGAG
13808


8584
CCUCUUGG G UCCCCGCA
5060
TGCGGGGA GGCTAGCTACAACGA CCAAGAGG
13809


8578
GGGUCCCC G CACUUUCA
5061
TGAAAGTG GGCTAGCTACAACGA GGGGACCC
13810


8576
GUCCCCGC A CUUUCACA
5062
TGTGAAAG GGCTAGCTACAACGA GCGGGGAC
13811


8570
GCACUUUC A CAGAUAAC
5063
GTTATCTG GGCTAGCTACAACGA GAAAGTGC
13812


8566
UUUCACAG A UAACGACC
5064
GGTCGTTA GGCTAGCTACAACGA CTGTGAAA
13813


8563
CACAGAUA A CGACCAGG
5065
CCTGGTCG GGCTAGCTACAACGA TATCTGTG
13814


8560
AGAUAACG A CCAGGUCG
5066
CGACCTGG GGCTAGCTACAACGA CGTTATCT
13815


8555
ACGACCAG G UCGUCUCC
5067
GGAGACGA GGCTAGCTACAACGA CTGGTCGT
13816


8552
ACCAGGUC G UCUCCACA
5068
TGTGGAGA GGCTAGCTACAACGA GACCTGGT
13817


8546
UCGUCUCC A CACACGAG
5069
CTCGTGTG GGCTAGCTACAACGA GGAGACGA
13818


8544
GUCUCCAC A CACGAGCA
5070
TGCTCGTG GGCTAGCTACAACGA GTGGAGAC
13819


8542
CUCCACAC A CGAGCAUC
5071
GATGCTCG GGCTAGCTACAACGA GTGTGGAG
13820


8538
ACACACGA G CAUCGUGC
5072
GCACGATG GGCTAGCTACAACGA TCGTGTGT
13821


8536
ACACGAGC A UCGUGCAG
5073
CTGCACGA GGCTAGCTACAACGA GCTCGTGT
13822


8533
CGAGCAUC G UGCAGUCC
5074
GGACTGCA GGCTAGCTACAACGA GATGCTCG
13823


8531
AGCAUCGU G CAGUCCUG
5075
CAGGACTG GGCTAGCTACAACGA ACGATGCT
13824


8528
AUCGUGCA G UCCUGGAG
5076
CTCCAGGA GGCTAGCTACAACGA TGCACGAT
13825


8520
GUCCUGGA G CUUCGCAG
5077
CTGCGAAG GGCTAGCTACAACGA TCCAGGAC
13826


8515
GGAGCUUC G CAGCUCGA
5078
TCGAGCTG GGCTAGCTACAACGA GAAGCTCC
13827


8512
GCUUCGCA G CUCGACAG
5079
CTGTCGAG GGCTAGCTACAACGA TGCGAAGC
13828


8507
GCAGCUCG A CAGGCCGC
5080
GCGGCCTG GGCTAGCTACAACGA CGAGCTGC
13829


8503
CUCGACAG G CCGCAGAG
5081
CTCTGCGG GGCTAGCTACAACGA CTGTCGAG
13830


8500
GACAGGCC G CAGAGGCU
5082
AGCCTCTG GGCTAGCTACAACGA GGCCTGTC
13831


8494
CCGCAGAG G CUUUCAAG
5083
CTTGAAAG GGCTAGCTACAACGA CTCTGCGG
13832


8486
GCUUUCAA G UAACAUGU
5084
ACATGTTA GGCTAGCTACAACGA TTGAAAGC
13833


8483
UUCAAGUA A CAUGUGAG
5085
CTCACATG GGCTAGCTACAACGA TACTTGAA
13834


8481
CAAGUAAC A UGUGAGGG
5086
CCCTCACA GGCTAGCTACAACGA GTTACTTG
13835


8479
AGUAACAU G UGAGGGUA
5087
TACCCTCA GGCTAGCTACAACGA ATGTTACT
13836


8473
AUGUGAGG G UAUUACCA
5088
TGGTAATA GGCTAGCTACAACGA CCTCACAT
13837


8471
GUGAGGGU A UUACCACA
5089
TGTGGTAA GGCTAGCTACAACGA ACCCTCAC
13838


8468
AGGGUAUU A CCACAGCU
5090
AGCTGTGG GGCTAGCTACAACGA AATACCCT
13839


8465
GUAUUACC A CAGCUGGU
5091
ACCAGCTG GGCTAGCTACAACGA GGTAATAC
13840


8462
UUACCACA G CUGGUCGU
5092
ACGACCAG GGCTAGCTACAACGA TGTGGTAA
13841


8458
CACAGCUG G UCGUCAGC
5093
GCTGACGA GGCTAGCTACAACGA CAGCTGTG
13842


8455
AGCUGGUC G UCAGCACG
5094
CGTGCTGA GGCTAGCTACAACGA GACCAGCT
13843


8451
GGUCGUCA G CACGCCGC
5095
GCGGCGTG GGCTAGCTACAACGA TGACGACC
13844


8449
UCGUCAGC A CGCCGCUC
5096
GAGCGGCG GGCTAGCTACAACGA GCTGACGA
13845


8447
GUCAGCAC G CCGCUCGC
5097
GCGAGCCG GGCTAGCTACAACGA GTGCTGAC
13846


8444
AGCACGCC G CUCGCGCG
5098
CGCGCGAG GGCTAGCTACAACGA GGCGTGCT
13847


8440
CGCCGCUC G CGCGGCAC
5099
GTCCCGCG GGCTAGCTACAACGA GAGCGGCG
13848


8438
CCGCUCGC G CGGCACCG
5100
CGGTGCCG GGCTAGCTACAACGA GCGAGCGG
13849


8435
CUCGCCCG G CACCCCCG
5101
CGCCGCTG GGCTAGCTACAACGA CGCGCCAG
13850


8433
CGCGCGGC A CCGGCGAU
5102
ATCGCCGG GGCTAGCTACAACGA GCCGCGCG
13851


8429
CGGCACCG G CGAUAACC
5103
GCTTATCG GGCTAGCTACAACGA CGGTGCCG
13852


8426
CACCGGCG A UAACCGCA
5104
TGCGGTTA GGCTAGCTACAACGA CGCCCCTG
13853


8423
CGGCGAUA A CCGCACUU
5105
AACTGCCC GGCTAGCTACAACGA TATCGCCG
13854


8420
CGAUAACC G CAGUUCUG
5106
CAGAACTG GGCTAGCTACAACGA GGTTATCG
13855


8417
UAACCGCA G UUCUGCCC
5107
GGGCACAA GGCTAGCTACAACGA TGCGGTTA
13856


8412
GCACUUCU G CCCUUUUG
5108
CAAAACCG GGCTAGCTACAACGA ACAACTGC
13857


8402
CCUUUUGA A UUAGUCAG
5109
CTGACTAA GGCTAGCTACAACGA TCAAAAGG
13858


8398
UUGAAUUA G UCAGAGGA
5110
TCCTCTGA GGCTAGCTACAACGA TAATTCAA
13859


8390
GUCAGAGG A CCCCCGAU
5111
ATCGGGGG GGCTAGCTACAACGA CCTCTGAC
13860


8383
GACCCCCG A UAUAAAGC
5112
GCTTTATA GGCTAGCTACAACGA CGGGGGTC
13861


8381
CCCCCGAU A UAAAGCCG
5113
CGGCTTTA GGCTAGCTACAACGA ATCGGGGG
13862


8376
GAUAUAAA G CCGCUCUG
5114
CAGAGCGG GGCTAGCTACAACGA TTTATATC
13863


8373
AUAAAGCC G CUCUGUGA
5115
TCACAGAG GGCTAGCTACAACGA GGCTTTAT
13864


8368
GCCGCUCU G UGAGCGAC
5116
GTCGCTCA GGCTAGCTACAACGA AGAGCGGC
13865


8364
CUCUGUGA G CGACCUUA
5117
TAAGGTCG GGCTAGCTACAACGA TCACAGAG
13866


8361
UGUGAGCG A CCUUAUGG
5118
CCATAAGG GGCTAGCTACAACGA CGCTCACA
13867


8356
GCGACCUU A UGGCCUGU
5119
ACAGGCCA GGCTAGCTACAACGA AAGGTCGC
13868


8353
ACCUUAUG G CCUGUCUG
5120
CAGACAGG GGCTAGCTACAACGA CATAAGGT
13869


8349
UAUGGCCU G UCUGGCUU
5121
AAGCCAGA GGCTAGCTACAACGA AGGCCATA
13870


8344
CCUGUCUG G CUUCGGGG
5122
CCCCGAAG GGCTAGCTACAACGA CAGACAGG
13871


8335
CUUCGGGG G CCAAGUCA
5123
TGACTTGG GGCTAGCTACAACGA CCCCGAAG
13872


8330
GGGGCCAA G UCACAACA
5124
TGTTGTGA GGCTAGCTACAACGA TTGGCCCC
13873


8327
GCCAAGUC A CAACAUUG
5125
CAATGTTG GGCTAGCTACAACGA GACTTGGC
13874


8324
AAGUCACA A CAUUGGUA
5126
TACCAATG GGCTAGCTACAACGA TGTGACTT
13875


8322
GUCACAAC A UUGGUAAA
5127
TTTACCAA GGCTAGCTACAACGA GTTGTGAC
13876


8318
CAACAUUG G UAAAUUGA
5128
TCAATTTA GGCTAGCTACAACGA CAATGTTG
13877


8314
AUUGGUAA A UUGACUCC
5129
GGAGTCAA GGCTAGCTACAACGA TTACCAAT
13878


8310
GUAAAUUG A CUCCUCGA
5130
TCGAGGAG GGCTAGCTACAACGA CAATTTAC
13879


8302
ACUCCUCG A CACGGAUG
5131
CATCCGTG GGCTAGCTACAACGA CGAGGAGT
13880


8300
UCCUCGAC A CGGAUGUC
5132
GACATCCG GGCTAGCTACAACGA GTCGAGGA
13881


8296
CGACACGG A UGUCACUC
5133
GAGTGACA GGCTAGCTACAACGA CCGTGTCG
13882


8294
ACACGGAU G UCACUCUC
5134
GAGAGTGA GGCTAGCTACAACGA ATCCGTGT
13883


8291
CGGAUGUC A CUCUCGGU
5135
ACCGAGAG GGCTAGCTACAACGA GACATCCG
13884


8284
CACUCUCG G UGACUGUU
5136
AACAGTCA GGCTAGCTACAACGA CGAGAGTG
13885


8281
UCUCGGUG A CUGUUGAG
5137
CTCAACAG GGCTAGCTACAACGA CACCGAGA
13886


8278
CGGUGACU G UUGAGUCG
5138
CGACTCAA GGCTAGCTACAACGA AGTCACCG
13887


8273
ACUGUUGA G UCGAAACA
5139
TGTTTCGA GGCTAGCTACAACGA TCAACAGT
13888


8267
GAGUCGAA A CAGCGGGU
5140
ACCCGCTG GGCTAGCTACAACGA TTCGACTC
13889


8264
UCGAAACA G CGGGUGUC
5141
GACACCCG GGCTAGCTACAACGA TGTTTCGA
13890


8260
AACAGCGG G UGUCAUAU
5142
ATATGACA GGCTAGCTACAACGA CCGCTGTT
13891


8258
CAGCGGGU G UCAUAUGC
5143
GCATATGA GGCTAGCTACAACGA ACCCGCTG
13892


8255
CGGGUGUC A UAUGCAAA
5144
TTTGCATA GGCTAGCTACAACGA GACACCCG
13893


8253
GGUGUCAU A UGCAAAGC
5145
GCTTTGCA GGCTAGCTACAACGA ATGACACC
13894


8251
UGUCAUAU G CAAAGCCC
5146
GGGCTTTG GGCTAGCTACAACGA ATATGACA
13895


8246
UAUGCAAA G CCCAUAGG
5147
CCTATGGG GGCTAGCTACAACGA TTTGCATA
13896


8242
CAAAGCCC A UAGGGCAU
5148
ATGCCCTA GGCTAGCTACAACGA GGGCTTTG
13897


8237
CCCAUAGG G CAUUUCUU
5149
AAGAAATG GGCTAGCTACAACGA CCTATGGG
13898


8235
CAUAGGGC A UUUCUUUG
5150
CAAAGAAA GGCTAGCTACAACGA GCCCTATG
13899


8226
UUUCUUUG A UUUCCAGG
5151
CCTGGAAA GGCTAGCTACAACGA CAAAGAAA
13900


8218
AUUUCCAG G CAUUCACC
5152
GGTGAATG GGCTAGCTACAACGA CTGGAAAT
13901


8216
UUCCAGGC A UUCACCAG
5153
CTGGTGAA GGCTAGCTACAACGA GCCTGGAA
13902


8212
AGGCAUUC A CCAGGAAC
5154
GTTCCTGG GGCTAGCTACAACGA GAATGCCT
13903


8205
CACCAGGA A CUCAACCC
5155
GGGTTGAG GGCTAGCTACAACGA TCCTGGTG
13904


8200
GGAACUCA A CCCGCUGC
5156
GCAGCGGG GGCTAGCTACAACGA TGAGTTCC
13905


8196
CUCAACCC G CUGCCCAG
5157
CTGGGCAG GGCTAGCTACAACGA GGGTTGAG
13906


8193
AACCCGCU G CCCAGGAG
5158
CTCCTGGG GGCTAGCTACAACGA AGCGGGTT
13907


8183
CCAGGAGA G UACUGGAA
5159
TTCCAGTA GGCTAGCTACAACGA TCTCCTGG
13908


8181
AGGAGAGU A CUGGAAUC
5160
GATTCCAG GGCTAGCTACAACGA ACTCTCCT
13909


8175
GUACUGGA A UCCGUAUG
5161
CATACGGA GGCTAGCTACAACGA TCCAGTAC
13910


8171
UGGAAUCC G UAUGAAGA
5162
TCTTCATA GGCTAGCTACAACGA GGATTCCA
13911


8169
GAAUCCGU A UGAAGAGC
5163
GCTCTTCA GGCTAGCTACAACGA ACGGATTC
13912


8162
UAUGAAGA G CCCAUCAC
5164
GTGATGGG GGCTAGCTACAACGA TCTTCATA
13913


8158
AAGAGCCC A UCACGGCC
5165
GGCCGTGA GGCTAGCTACAACGA GGGCTCTT
13914


8155
AGCCCAUC A CGGCCUGA
5166
TCAGGCCG GGCTAGCTACAACGA GATGGGCT
13915


8152
CCAUCACG G CCUGAGGA
5167
TCCTCAGG GGCTAGCTACAACGA CGTGATGG
13916


8140
GAGGAAGG G UGGAGACC
5168
GGTCTCCA GGCTAGCTACAACGA CCTTCCTC
13917


8134
GGGUGGAG A CCACGUCG
5169
CGACGTGG GGCTAGCTACAACGA CTCCACCC
13918


8131
UGGAGACC A CGUCGUAA
5170
TTACGACG GGCTAGCTACAACGA GGTCTCCA
13919


8129
GAGACCAC G UCGUAAAG
5171
CTTTACGA GGCTAGCTACAACGA GTGGTCTC
13920


8126
ACCACGUC G UAAAGGGC
5172
GCCCTTTA GGCTAGCTACAACGA GACGTGGT
13921


8119
CGUAAAGG G CCAUUUUC
5173
GAAAATGG GGCTAGCTACAACGA CCTTTACG
13922


8116
AAAGGGCC A UUUUCUCG
5174
CGAGAAAA GGCTAGCTACAACGA GGCCCTTT
13923


8108
AUUVUCUC G CACACACG
5175
CGTGTGTG GGCTAGCTACAACGA GAGAAAAT
13924


8106
UUUCUCGC A CACACGAA
5176
TTCGTGTG GGCTAGCTACAACGA GCGAGAAA
13925


8104
UCUCGCAC A CACGAACC
5177
GGTTCGTG GGCTAGCTACAACGA GTGCGAGA
13926


8102
UCGCACAC A CGAACCCC
5178
GGGGTTCG GGCTAGCTACAACGA GTGTGCGA
13927


8098
ACACACGA A CCCCCAAG
5179
CTTGGGGG GGCTAGCTACAACGA TCGTGTGT
13928


8090
ACCCCCAA G UCUGGGAA
5180
TTCCCAGA GGCTAGCTACAACGA TTGGGGGT
13929


8082
GUCUGGGA A CACGAUAA
5181
TTATCGTG GGCTAGCTACAACGA TCCCAGAC
13930


8080
CUGGGAAC A CGAUAAGG
5182
CCTTATCG GGCTAGCTACAACGA GTTCCCAG
13931


8077
GGAACACG A UAAGGCGA
5183
TCGCCTTA GGCTAGCTACAACGA CGTGTTCC
13932


8072
ACGAUAAG G CGAGCUGG
5184
CCAGCTCG GGCTAGCTACAACGA CTTATCGT
13933


8068
UAAGGCGA G CUGGCUUG
5185
CAAGCCAG GGCTAGCTACAACGA TCGCCTTA
13934


8064
GCGAGCUG G CUUGCGGC
5186
GCCGCAAG GGCTAGCTACAACGA CAGCTCGC
13935


8060
GCUGGCUU G CGGCCUCC
5187
GGAGGCCG GGCTAGCTACAACGA AAGCCAGC
13936


8057
GGCUUGCG G CCUCCUUU
5188
AAAGGAGG GGCTAGCTACAACGA CGCAAGCC
13937


8043
UUUCUCUG G UUGGACGC
5189
GCGTCCAA GGCTAGCTACAACGA CAGAGAAA
13938


8038
CUGGUUGG A CGCAGAAA
5190
TTTCTGCG GGCTAGCTACAACGA CCAACCAG
13939


8036
GGUUGGAC G CAGAAAAC
5191
GTTTTCTG GGCTAGCTACAACGA GTCCAACC
13940


8029
CGCAGAAA A CCUCAUUU
5192
AAATGAGG GGCTAGCTACAACGA TTTCTGCG
13941


8024
AAAACCUC A UUUUUUGC
5193
GCAAAAAA GGCTAGCTACAACGA GAGGTTTT
13942


8017
CAUUUUUU G CCAUGAUG
5194
CATCATGG GGCTAGCTACAACGA AAAAAATG
13943


8014
UUUUUGCC A UGAUGGUG
5195
CACCATCA GGCTAGCTACAACGA GGCAAAAA
13944


8011
UUGCCAUG A UGGUGGUA
5196
TACCACCA GGCTAGCTACAACGA CATGGCAA
13945


8008
CCAUGAUG G UGGUAUCA
5197
TGATACCA GGCTAGCTACAACGA CATCATGG
13946


8005
UGAUGGUG G UAUCAAUU
5198
AATTGATA GGCTAGCTACAACGA CACCATCA
13947


8003
AUGGUGGU A UCAAUUGG
5199
CCAATTGA GGCTAGCTACAACGA ACCACCAT
13948


7999
UGGUAUCA A UUGGUGUC
5200
GACACCAA GGCTAGCTACAACGA TGATACCA
13949


7995
AUCAAUUG G UGUCUCAG
5201
CTGAGACA GGCTAGCTACAACGA CAATTGAT
13950


7993
CAAUUGGU G UCUCAGUG
5202
CACTGAGA GGCTAGCTACAACGA ACCAATTG
13951


7987
GUGUCUCA G UGUCUUCC
5203
GGAAGACA GGCTAGCTACAACGA TGAGACAC
13952


7985
GUCUCAGU G UCUUCCAG
5204
CTGGAAGA GGCTAGCTACAACGA ACTGAGAC
13953


7977
GUCUUCCA G CAAGUCCU
5205
AGGACTTG GGCTAGCTACAACGA TGGAAGAC
13954


7973
UCCAGCAA G UCCUUCCA
5206
TGGAAGGA GGCTAGCTACAACGA TTGCTGGA
13955


7965
GUCCUUCC A CACGGAGC
5207
GCTCCGTG GGCTAGCTACAACGA GGAAGGAC
13956


7963
CCUUCCAC A CGGAGCGG
5208
CCGCTCCG GGCTAGCTACAACGA GTGGAAGG
13957


7958
CACACGGA G CGGAUGUG
5209
CACATCCG GGCTAGCTACAACGA TCCGTGTG
13958


7954
CGGAGCGG A UGUGGUUG
5210
CAACCACA GGCTAGCTACAACGA CCGCTCCG
13959


7952
GAGCGGAU G UGGUUGAC
5211
GTCAACCA GGCTAGCTACAACGA ATCCGCTC
13960


7949
CGGAUGUG G UUGACGGC
5212
GCCGTCAA GGCTAGCTACAACGA CACATCCG
13961


7945
UGUGGUUG A CGGCCCCG
5213
CGGGGCCG GGCTAGCTACAACGA CAACCACA
13962


7942
GGUUGACG G CCCCGCUG
5214
CAGCGGGG GGCTAGCTACAACGA CGTCAACC
13963


7937
ACGGCCCC G CUGGAUAG
5215
CTATCCAG GGCTAGCTACAACGA GGGGCCGT
13964


7932
CCCGCUGG A UAGGUUCC
5216
GGAACCTA GGCTAGCTACAACGA CCAGCGGG
13965


7928
CUGGAUAG G UUCCGGAC
5217
GTCCGGAA GGCTAGCTACAACGA CTATCCAG
13966


7921
GGUUCCGG A CGUCCUUU
5218
AAAGGACG GGCTAGCTACAACGA CCGGAACC
13967


7919
UUCCGGAC G UCCUUUGC
5219
GCAAAGGA GGCTAGCTACAACGA GTCCGGAA
13968


7912
CGUCCUUU G CCCCAUAA
5220
TTATGGGG GGCTAGCTACAACGA AAAGGACG
13969


7907
UUUGCCCC A UAACCAAA
5221
TTTGGTTA GGCTAGCTACAACGA GGGGCAAA
13970


7904
GCCCCAUA A CCAAAUUU
5222
AAATTTGG GGCTAGCTACAACGA TATGGGGC
13971


7899
AUAACCAA A UUUGGACC
5223
GGTCCAAA GGCTAGCTACAACGA TTGGTTAT
13972


7893
AAAUUUGG A CCUGGCCG
5224
CGGCCAGG GGCTAGCTACAACGA CCAAATTT
13973


7888
UGGACCUG G CCGAAUGU
5225
ACATTCGG GGCTAGCTACAACGA CAGGTCCA
13974


7883
CUGGCCGA A UGUGGGGG
5226
CCCCCACA GGCTAGCTACAACGA TCGGCCAG
13975


7881
GGCCGAAU G UGGGGGCG
5227
CGCCCCCA GGCTAGCTACAACGA ATTCGGCC
13976


7875
AUGUGGGG G CGUCAGUC
5228
GACTGACG GGCTAGCTACAACGA CCCCACAT
13977


7873
GUGGGGGC G UCAGUCUG
5229
CAGACTGA GGCTAGCTACAACGA GCCCCCAC
13978


7869
GGGCGUCA G UCUGCAGG
5230
CCTGCAGA GGCTAGCTACAACGA TGACGCCC
13979


7865
GUCAGUCU G CAGGCUUC
5231
GAAGCCTG GGCTAGCTACAACGA AGACTGAC
13980


7861
GUCUGCAG G CUUCCUCU
5232
AGAGGAAG GGCTAGCTACAACGA CTGCAGAC
13981


7852
CUUCCUCU A CGGAUAGA
5233
TCTATCCG GGCTAGCTACAACGA AGAGGAAG
13982


7848
CUCUACGG A UAGAAGUU
5234
AACTTCTA GGCTAGCTACAACGA CCGTAGAG
13983


7842
GGAUAGAA G UUUAGCCU
5235
AGGCTAAA GGCTAGCTACAACGA TTCTATCC
13984


7837
GAAGUUUA G CCUUAACU
5236
AGTTAAGG GGCTAGCTACAACGA TAAACTTC
13985


7831
UAGCCUUA A CUGUGGAC
5237
GTCCACAG GGCTAGCTACAACGA TAAGGCTA
13986


7828
CCUUAACU G UGGACGCC
5238
GGCGTCCA GGCTAGCTACAACGA AGTTAAGG
13987


7824
AACUGUGG A CGCCUUCG
5239
CGAAGGCG GGCTAGCTACAACGA CCACAGTT
13988


7822
CUGUGGAC G CCUUCGCC
5240
GGCGAAGG GGCTAGCTACAACGA GTCCACAG
13989


7816
ACGCCUUC G CCUUCAUC
5241
GATGAAGG GGCTAGCTACAACGA GAAGGCGT
13990


7810
UCGCCUUC A UCUCCUUG
5242
CAAGGAGA GGCTAGCTACAACGA GAAGGCGA
13991


7800
CUCCUUGA G CACGUCCC
5243
GGGACGTG GGCTAGCTACAACGA TCAAGGAG
13992


7798
CCUUGAGC A CGUCCCGG
5244
CCGGGACG GGCTAGCTACAACGA GCTCAAGG
13993


7796
UUGAGCAC G UCCCGGUA
5245
TACCGGGA GGCTAGCTACAACGA GTGCTCAA
13994


7790
ACGUCCCG G UAGUGGUC
5246
GACCACTA GGCTAGCTACAACGA CGGGACGT
13995


7787
UCCCGGUA G UGGUCGUC
5247
GACGACCA GGCTAGCTACAACGA TACCGGGA
13996


7784
CGGUAGUG G UCGUCCAG
5248
CTGGACGA GGCTAGCTACAACGA CACTACCG
13997


7781
UAGUGGUC G UCCAGGAC
5249
GTCCTGGA GGCTAGCTACAACGA GACCACTA
13998


7774
CGUCCAGG A CUUGCAGU
5250
ACTGCAAG GGCTAGCTACAACGA CCTGGACG
13999


7770
CAGGACUU G CAGUCUGU
5251
ACAGACTG GGCTAGCTACAACGA AAGTCCTG
14000


7767
GACUUGCA G UCUGUCAA
5252
TTGACAGA GGCTAGCTACAACGA TGCAAGTC
14001


7763
UGCAGUCU G UCAAAGGU
5253
ACCTTTGA GGCTAGCTACAACGA AGACTGCA
14002


7756
UGUCAAAG G UGACCUUC
5254
GAAGGTCA GGCTAGCTACAACGA CTTTGACA
14003


7753
CAAAGGUG A CCUUCUUC
5255
GAAGAAGG GGCTAGCTACAACGA CACCTTTG
14004


7743
CUUCUUCU G CCGCUGGC
5256
GCCAGCGG GGCTAGCTACAACGA AGAAGAAG
14005


7740
CUUCUGCC G CUGGCUUG
5257
CAAGCCAG GGCTAGCTACAACGA GGCAGAAG
14006


7736
UGCCGCUG G CUUGCGCU
5258
AGCGCAAG GGCTAGCTACAACGA CAGCGGCA
14007


7732
GCUGGCUU G CGCUGCGA
5259
TCGCAGCG GGCTAGCTACAACGA AAGCCAGC
14008


7730
UGGCUUGC G CUGCGAGA
5260
TCTCGCAG GGCTAGCTACAACGA GCAAGCCA
14009


7727
CUUGCGCU G CGAGAUGU
5261
ACATCTCG GGCTAGCTACAACGA AGCGCAAG
14010


7722
GCUGCGAG A UGUUGUAG
5262
CTACAACA GGCTAGCTACAACGA CTCGCAGC
14011


7720
UGCGAGAU G UUGUAGCG
5263
CGCTACAA GGCTAGCTACAACGA ATCTCGCA
14012


7717
GAGAUGUU G UAGCGUAG
5264
CTACGCTA GGCTAGCTACAACGA AACATCTC
14013


7714
AUGUUGUA G CGUAGACC
5265
GGTCTACG GGCTAGCTACAACGA TACAACAT
14014


7712
GUUGUAGC G UAGACCAU
5266
ATGGTCTA GGCTAGCTACAACGA GCTACAAC
14015


7708
UAGCGUAG A CCAUGUUG
5267
CAACATGG GGCTAGCTACAACGA CTACGCTA
14016


7705
CGUAGACC A UGUUGUGG
5268
CCACAACA GGCTAGCTACAACGA GGTCTACG
14017


7703
UAGACCAU G UUGUGGUG
5269
CACCACAA GGCTAGCTACAACGA ATGGTCTA
14018


7700
ACCAUGUU G UGGUGACG
5270
CGTCACCA GGCTAGCTACAACGA AACATGGT
14019


7697
AUGUUGUG G UGACGCAG
5271
CTGCGTCA GGCTAGCTACAACGA CACAACAT
14020


7694
UUGUGGUG A CGCAGCAA
5272
TTGCTGCG GGCTAGCTACAACGA CACCACAA
14021


7692
GUGGUGAC G CAGCAAAG
5273
CTTTGCTG GGCTAGCTACAACGA GTCACCAC
14022


7689
GUGACGCA G CAAAGAGU
5274
ACTCTTTG GGCTAGCTACAACGA TGCGTCAC
14023


7682
AGCAAAGA G UUGCUCAA
5275
TTGAGCAA GGCTAGCTACAACGA TCTTTGCT
14024


7679
AAAGAGUU G CUCAACGC
5276
GCGTTGAG GGCTAGCTACAACGA AACTCTTT
14025


7674
GUUGCUCA A CGCGUUGA
5277
TCAACGCG GGCTAGCTACAACGA TGAGCAAC
14026


7672
UGCUCAAC G CGUUGAUG
5278
CATCAACG GGCTAGCTACAACGA GTTGAGCA
14027


7670
CUCAACGC G UUGAUGGG
5279
CCCATCAA GGCTAGCTACAACGA GCGTTGAG
14028


7666
ACGCGUUG A UGGGCAAC
5280
GTTGCCCA GGCTAGCTACAACGA CAACGCGT
14029


7662
GUUGAUGG G CAACUUGC
5281
GCAAGTTG GGCTAGCTACAACGA CCATCAAC
14030


7659
GAUGGGCA A CUUGCUUU
5282
AAAGCAAG GGCTAGCTACAACGA TGCCCATC
14031


7655
GGCAACUU G CUUUCCUC
5283
GAGGAAAG GGCTAGCTACAACGA AAGTTGCC
14032


7645
UUUCCUCC G CAGCGCAU
5284
ATGCGCTG GGCTAGCTACAACGA GGAGGAAA
14033


7642
CCUCCGCA G CGCAUGGC
5285
GCCATGCG GGCTAGCTACAACGA TGCGGAGG
14034


7640
UCCGCAGC G CAUGGCGU
5286
ACGCCATG GGCTAGCTACAACGA GCTGCGGA
14035


7638
CGCAGCGC A UGGCGUGA
5287
TCACGCCA GGCTAGCTACAACGA GCGCTGCG
14036


7635
AGCGCAUG G CGUGAUCA
5288
TGATCACG GGCTAGCTACAACGA CATGCGCT
14037


7633
CGCAUGGC G UGAUCAGG
5289
CCTGATCA GGCTAGCTACAACGA GCCATGCG
14038


7630
AUGGCGUG A UCAGGGCG
5290
CGCCCTGA GGCTAGCTACAACGA CACGCCAT
14039


7624
UGAUCAGG G CGCCCGUC
5291
GACGGGCG GGCTAGCTACAACGA CCTGATCA
14040


7622
AUCAGGGC G CCCGUCCA
5292
TGGACGGG GGCTAGCTACAACGA GCCCTGAT
14041


7618
GGGCGCCC G UCCAUGUG
5293
CACATGGA GGCTAGCTACAACGA GGGCGCCC
14042


7614
GCCCGUCC A UGUGUAGG
5294
CCTACACA GGCTAGCTACAACGA GGACGGGC
14043


7612
CCGUCCAU G UGUAGGAC
5295
GTCCTACA GGCTAGCTACAACGA ATGGACGG
14044


7610
GUCCAUGU G UAGGACAU
5296
ATGTCCTA GGCTAGCTACAACGA ACATGGAC
14045


7605
UGUGUAGG A CAUCGAGC
5297
GCTCGATG GGCTAGCTACAACGA CCTACACA
14046


7603
UGUAGGAC A UCGAGCAG
5298
CTGCTCGA GGCTAGCTACAACGA GTCCTACA
14047


7598
GACAUCGA G CAGCAGAC
5299
GTCTGCTG GGCTAGCTACAACGA TCGATGTC
14048


7595
AUCGAGCA G CAGACGAC
5300
GTCGTCTG GGCTAGCTACAACGA TGCTCGAT
14049


7591
AGCAGCAG A CGACAUCC
5301
GGATGTCG GGCTAGCTACAACGA CTGCTGCT
14050


7588
AGCAGACG A CAUCCUCG
5302
CGAGGATG GGCTAGCTACAACGA CGTCTGCT
14051


7586
CAGACGAC A UCCUCGCC
5303
GGCGAGGA GGCTAGCTACAACGA GTCGTCTG
14052


7580
ACAUCCUC G CCAGCCUC
5304
GAGGCTGG GGCTAGCTACAACGA GAGGATGT
14053


7576
CCUCGCCA G CCUCUUCG
5305
CGAAGAGG GGCTAGCTACAACGA TGGCGAGG
14054


7568
GCCUCUUC G CUCACGGU
5306
ACCGTGAG GGCTAGCTACAACGA GAAGAGGC
14055


7564
CUUCGCUC A CGGUAGAC
5307
GTCTACCG GGCTAGCTACAACGA GAGCGAAG
14056


7561
CGCUCACG G UAGACCAA
5308
TTGGTCTA GGCTAGCTACAACGA CGTGAGCG
14057


7557
CACGGUAG A CCAAGACC
5309
GGTCTTGG GGCTAGCTACAACGA CTACCGTG
14058


7551
AGACCAAG A CCCGUCGC
5310
GCGACGGG GGCTAGCTACAACGA CTTGGTCT
14059


7547
CAAGACCC G UCGCUGAG
5311
CTCAGCGA GGCTAGCTACAACGA GGGTCTTG
14060


7544
GACCCGUC G CUGAGAUC
5312
GATCTCAG GGCTAGCTACAACGA GACGGGTC
14061


7538
UCGCUGAG A UCGGGAUC
5313
GATCCCGA GGCTAGCTACAACGA CTCAGCGA
14062


7532
AGAUCGGG A UCCCCCGG
5314
CCGGGGGA GGCTAGCTACAACGA CCCGATCT
14063


7524
AUCCCCCG G CUCCCCCU
5315
AGGGGGAG GGCTAGCTACAACGA CGGGGGAT
14064


7506
AAGGGGGG G CAUAGAGG
5316
CCTCTATG GGCTAGCTACAACGA CCCCCCTT
14065


7504
GGGGGGGC A UAGAGGAG
5317
CTCCTCTA GGCTAGCTACAACGA GCCCCCCC
14066


7496
AUAGAGGA G UACGACUC
5318
GAGTCGTA GGCTAGCTACAACGA TCCTCTAT
14067


7494
AGAGGAGU A CGACUCAA
5319
TTGAGTCG GGCTAGCTACAACGA ACTCCTCT
14068


7491
GGAGUACG A CUCAACGU
5320
ACGTTGAG GGCTAGCTACAACGA CGTACTCC
14069


7486
ACGACUCA A CGUCGGAU
5321
ATCCGACG GGCTAGCTACAACGA TGAGTCGT
14070


7484
GACUCAAC G UCGGAUCC
5322
GGATCCGA GGCTAGCTACAACGA GTTGAGTC
14071


7479
AACGUCGG A UCCUGCGU
5323
ACGCAGGA GGCTAGCTACAACGA CCGACGTT
14072


7474
CGGAUCCU G CGUCACCG
5324
CGGTGACG GGCTAGCTACAACGA AGGATCCG
14073


7472
GAUCCUGC G UCACCGUC
5325
GACGGTGA GGCTAGCTACAACGA GCAGGATC
14074


7469
CCUGCGUC A CCGUCAUU
5326
AATGACGG GGCTAGCTACAACGA GACGCAGG
14075


7466
GCGUCACC G UCAUUGGA
5327
TCCAATGA GGCTAGCTACAACGA GGTGACGC
14076


7463
UCACCGUC A UUGGAGGU
5328
ACCTCCAA GGCTAGCTACAACGA GACGGTGA
14077


7456
CAUUGGAG G UCUGGUCG
5329
CGACCAGA GGCTAGCTACAACGA CTCCAATG
14078


7451
GAGGUCUG G UCGGGGGG
5330
CCCCCCGA GGCTAGCTACAACGA CAGACCTC
14079


7441
CGGGGGGG G CGGUUGCC
5331
GGCAACCG GGCTAGCTACAACGA CCCCCCCG
14080


7438
GGGGGGCG G UUGCCGUA
5332
TACGGCAA GGCTAGCTACAACGA CGCCCCCC
14081


7435
GGGCGGUU G CCGUACCU
5333
AGGTACGG GGCTAGCTACAACGA AACCGCCC
14082


7432
CGGUUGCC G UACCUCUA
5334
TAGAGGTA GGCTAGCTACAACGA GGCAACCG
14083


7430
GUUGCCGU A CCUCUAUC
5335
GATAGAGG GGCTAGCTACAACGA ACGGCAAC
14084


7424
GUACCUCU A UCAGCGGC
5336
GCCGCTGA GGCTAGCTACAACGA AGAGGTAC
14085


7420
CUCUAUCA G CGGCCGAU
5337
ATCGGCCG GGCTAGCTACAACGA TGATAGAG
14086


7417
UAUCAGCG G CCGAUGAU
5338
ATCATCGG GGCTAGCTACAACGA CGCTGATA
14087


7413
AGCGGCCG A UGAUUCAG
5339
CTGAATCA GGCTAGCTACAACGA CGGCCGCT
14088


7410
GGCCGAUG A UUCAGAGC
5340
GCTCTGAA GGCTAGCTACAACGA CATCGGCC
14089


7403
GAUUCAGA G CUGCCGAA
5341
TTCGGCAG GGCTAGCTACAACGA TCTGAATC
14090


7400
UCAGAGCU G CCGAAGGU
5342
ACCTTCGG GGCTAGCTACAACGA AGCTCTGA
14091


7393
UGCCGAAG G UCUUUGUG
5343
CACAAAGA GGCTAGCTACAACGA CTTCGGCA
14092


7387
AGGUCUUU G UGGCGAGC
5344
GCTCGCCA GGCTAGCTACAACGA AAAGACCT
14093


7384
UCUUUGUG G CGAGCUCC
5345
GGAGCTCG GGCTAGCTACAACGA CACAAAGA
14094


7380
UGUGGCGA G CUCCGCCA
5346
TGGCGGAG GGCTAGCTACAACGA TCGCCACA
14095


7375
CGAGCUCC G CCAAGGCA
5347
TGCCTTGG GGCTAGCTACAACGA GGAGCTCG
14096


7369
CCGCCAAG G CAGAAGAC
5348
GTCTTCTG GGCTAGCTACAACGA CTTGGCGG
14097


7362
GGCAGAAG A CACGGUGG
5349
CCACCGTG GGCTAGCTACAACGA CTTCTGCC
14098


7360
CAGAAGAC A CGGUGGAC
5350
GTCCACCG GGCTAGCTACAACGA GTCTTCTG
14099


7357
AAGACACG G UGGACUCU
5351
AGAGTCCA GGCTAGCTACAACGA CGTGTCTT
14100


7353
CACGGUGG A CUCUGUCA
5352
TGACAGAG GGCTAGCTACAACGA CCACCGTG
14101


7348
UGGACUCU G UCAGAACA
5353
TGTTCTGA GGCTAGCTACAACGA AGAGTCCA
14102


7342
CUGUCAGA A CAACCGUC
5354
GACGGTTG GGCTAGCTACAACGA TCTGACAG
14103


7339
UCAGAACA A CCGUCCUC
5355
GAGGACGG GGCTAGCTACAACGA TGTTCTGA
14104


7336
GAACAACC G UCCUCUUC
5356
GAAGAGGA GGCTAGCTACAACGA GGTTGTTC
14105


7323
CUUCCUCC G UGGAGGUG
5357
CACCTCCA GGCTAGCTACAACGA GGAGGAAG
14106


7317
CCGUGGAG G UGGUAUUG
5358
CAATACCA GGCTAGCTACAACGA CTCCACGG
14107


7314
UGGAGGUG G UAUUGGAG
5359
CTCCAATA GGCTAGCTACAACGA CACCTCCA
14108


7312
GAGGUGGU A UUGGAGGG
5360
CCCTCCAA GGCTAGCTACAACGA ACCACCTC
14109


7303
UUGGAGGG G CCUUGGCA
5361
TGCCAAGG GGCTAGCTACAACGA CCCTCCAA
14110


7297
GGGCCUUG G CAGGUGGC
5362
GCCACCTG GGCTAGCTACAACGA CAAGGCCC
14111


7293
CUUGGCAG G UGGCAAUG
5363
CATTGCCA GGCTAGCTACAACGA CTGCCAAG
14112


7290
GGCAGGUG G CAAUGGGC
5364
GCCCATTG GGCTAGCTACAACGA CACCTGCC
14113


7287
AGGUGGCA A UGGGCACC
5365
GGTGCCCA GGCTAGCTACAACGA TGCCACCT
14114


7283
GGCAAUGG G CACCCGUG
5366
CACGGGTG GGCTAGCTACAACGA CCATTGCC
14115


7281
CAAUGGGC A CCCGUGUA
5367
TACACGGG GGCTAGCTACAACGA GCCCATTG
14116


7277
GGGCACCC G UGUACCAC
5368
GTGGTACA GGCTAGCTACAACGA GGGTGCCC
14117


7275
GCACCCGU G UACCACCG
5369
CGGTGGTA GGCTAGCTACAACGA ACGGGTGC
14118


7273
ACCCGUGU A CCACCGGA
5370
TCCGGTGG GGCTAGCTACAACGA ACACGGGT
14119


7270
CGUGUACC A CCGGAGGG
5371
CCCTCCGG GGCTAGCTACAACGA GGTACACG
14120


7261
CCGGAGGG A CGUAGUCU
5372
AGACTACG GGCTAGCTACAACGA CCCTCCGG
14121


7259
GGAGGGAC G UAGUCUGG
5373
CCAGACTA GGCTAGCTACAACGA GTCCCTCC
14122


7256
GGGACGUA G UCUGGGUC
5374
GACCCAGA GGCTAGCTACAACGA TACGTCCC
14123


7250
UAGUCUGG G UCUUUCCA
5375
TGGAAAGA GGCTAGCTACAACGA CCAGACTA
14124


7239
UUUCCAGG G CUCUAGUA
5376
TACTAGAG GGCTAGCTACAACGA CCTGGAAA
14125


7233
GGGCUCUA G UAGUGGAG
5377
CTCCACTA GGCTAGCTACAACGA TAGAGCCC
14126


7230
CUCUAGUA G UGGAGGGU
5378
ACCCTCCA GGCTAGCTACAACGA TACTAGAG
14127


7223
AGUGGAGG G UUGUAAUC
5379
GATTACAA GGCTAGCTACAACGA CCTCCACT
14128


7220
GGAGGGUU G UAAUCCGG
5380
CCGGATTA GGCTAGCTACAACGA AACCCTCC
14129


7217
GGGUUGUA A UCCGGGCG
5381
CGCCCGGA GGCTAGCTACAACGA TACAACCC
14130


7211
UAAUCCGG G CGUGCCCA
5382
TGGGCACG GGCTAGCTACAACGA CCGGATTA
14131


7209
AUCCGGGC G UGCCCAUA
5383
TATGGGCA GGCTAGCTACAACGA GCCCGGAT
14132


7207
CCGGGCGU G CCCAUAUG
5384
CATATGGG GGCTAGCTACAACGA ACGCCCGG
14133


7203
GCGUGCCC A UAUGGGUA
5385
TACCCATA GGCTAGCTACAACGA GGGCACGC
14134


7201
GUGCCCAU A UGGGUAAC
5386
GTTACCCA GGCTAGCTACAACGA ATGGGCAC
14135


7197
CCAUAUGG G UAACGCUG
5387
CAGCGTTA GGCTAGCTACAACGA CCATATGG
14136


7194
UAUGGGUA A CGCUGAAG
5388
CTTCAGCG GGCTAGCTACAACGA TACCCATA
14137


7192
UGGGUAAC G CUGAAGGA
5389
TCCTTCAG GGCTAGCTACAACGA GTTACCCA
14138


7182
UGAAGGAA A CUUCUUGG
5390
CCAAGAAG GGCTAGCTACAACGA TTCCTTCA
14139


7173
CUUCUUGG A UUUCCGCA
5391
TGCGGAAA GGCTAGCTACAACGA CCAAGAAG
14140


7167
GGAUUUCC G CAGGAUCU
5392
AGATCCTG GGCTAGCTACAACGA GGAAATCC
14141


7162
UCCGCAGG A UCUCCGCC
5393
GGCGGAGA GGCTAGCTACAACGA CCTGCGGA
14142


7156
GGAUCUCC G CCGGAAUG
5394
CATTCCGG GGCTAGCTACAACGA GGAGATCC
14143


7150
CCGCCGGA A UGGACACC
5395
GGTGTCCA GGCTAGCTACAACGA TCCGGCGG
14144


7146
CGGAAUGG A CACCUCUC
5396
GAGAGGTG GGCTAGCTACAACGA CCATTCCG
14145


7144
GAAUGGAC A CCUCUCUC
5397
GAGAGAGG GGCTAGCTACAACGA GTCCATTC
14146


7133
UCUCUCUC A UCCUCCUC
5398
GAGGAGGA GGCTAGCTACAACGA GAGAGAGA
14147


7123
CCUCCUCC G CUCGAAGC
5399
GCTTCGAG GGCTAGCTACAACGA GGAGGAGG
14148


7116
CGCUCGAA G CGGGUCAA
5400
TTGACCCG GGCTAGCTACAACGA TTCGAGCG
14149


7112
CGAAGCGG G UCAAAAGA
5401
TCTTTTGA GGCTAGCTACAACGA CCGCTTCG
14150


7103
UCAAAAGA G UCCAGGGU
5402
ACCCTGGA GGCTAGCTACAACGA TCTTTTGA
14151


7096
AGUCCAGG G UAACUACC
5403
GGTAGTTA GGCTAGCTACAACGA CCTGGACT
14152


7093
CCAGGGUA A CUACCUUA
5404
TAAGGTAG GGCTAGCTACAACGA TACCCTGG
14153


7090
GGGUAACU A CCUUAUUC
5405
GAATAAGG GGCTAGCTACAACGA AGTTACCC
14154


7085
ACUACCUU A UUCUCUGA
5406
TCAGAGAA GGCTAGCTACAACGA AAGGTAGT
14155


7077
AUUCUCUG A CUCCACGC
5407
GCGTGGAG GGCTAGCTACAACGA CAGAGAAT
14156


7072
CUGACUCC A CGCGAGUG
5408
CACTCGCG GGCTAGCTACAACGA GGAGTCAG
14157


7070
GACUCCAC G CGAGUGAU
5409
ATCACTCG GGCTAGCTACAACGA GTGGAGTC
14158


7066
CCACGCGA G UGAUGUUA
5410
TAACATCA GGCTAGCTACAACGA TCGCGTGG
14159


7063
CGCGAGUG A UGUUACCG
5411
CGGTAACA GGCTAGCTACAACGA CACTCGCG
14160


7061
CGAGUGAU G UUACCGCC
5412
GGCGGTAA GGCTAGCTACAACGA ATCACTCG
14161


7058
GUGAUGUU A CCGCCCAU
5413
ATGGGCGG GGCTAGCTACAACGA AACATCAC
14162


7055
AUGUUACC G CCCAUCUC
5414
GAGATGGG GGCTAGCTACAACGA GGTAACAT
14163


7051
UACCGCCC A UCUCCUGC
5415
GCAGGAGA GGCTAGCTACAACGA GGGCGGTA
14164


7044
CAUCUCCU G CCGCCACA
5416
TGTGGCGG GGCTAGCTACAACGA AGGAGATG
14165


7041
CUCCUGCC G CCACAGGA
5417
TCCTGTGG GGCTAGCTACAACGA GGCAGGAG
14166


7038
CUGCCGCC A CAGGAGGU
5418
ACCTCCTG GGCTAGCTACAACGA GGCGGCAG
14167


7031
CACAGGAG G UUGGCCUC
5419
GAGGCCAA GGCTAGCTACAACGA CTCCTGTG
14168


7027
GGAGGUUG G CCUCGAUG
5420
CATCGAGG GGCTAGCTACAACGA CAACCTCC
14169


7021
UGGCCUCG A UGAGGUCA
5421
TGACCTCA GGCTAGCTACAACGA CGAGGCCA
14170


7016
UCGAUGAG G UCAAAGUC
5422
GACTTTGA GGCTAGCTACAACGA CTCATCGA
14171


7010
AGGUCAAA G UCUGGGGA
5423
TCCCCAGA GGCTAGCTACAACGA TTTGACCT
14172


7001
UCUGGGGA G UCAUAUUG
5424
CAATATGA GGCTAGCTACAACGA TCCCCAGA
14173


6998
GGGGAGUC A UAUUGGGU
5425
ACCCAATA GGCTAGCTACAACGA GACTCCCC
14174


6996
GGAGUCAU A UUGGGUAA
5426
TTACCCAA GGCTAGCTACAACGA ATGACTCC
14175


6991
CAUAUUGG G UAAUGUAU
5427
ATACATTA GGCTAGCTACAACGA CCAATATG
14176


6988
AUUGGGUA A UGUAUGUC
5428
GACATACA GGCTAGCTACAACGA TACCCAAT
14177


6986
UGGGUAAU G UAUGUCGC
5429
GCGACATA GGCTAGCTACAACGA ATTACCCA
14178


6984
GGUAAUGU A UGUCGCCU
5430
AGGCGACA GGCTAGCTACAACGA ACATTACC
14179


6982
UAAUGUAU G UCGCCUUC
5431
GAAGGCGA GGCTAGCTACAACGA ATACATTA
14180


6979
UGUAUGUC G CCUUCGAA
5432
TTCGAAGG GGCTAGCTACAACGA GACATACA
14181


6966
CGAAGAAG G CGCAGACA
5433
TGTCTGCG GGCTAGCTACAACGA CTTCTTCG
14182


6964
AAGAAGGC G CAGACAGC
5434
GCTGTCTG GGCTAGCTACAACGA GCCTTCTT
14183


6960
AGGCGCAG A CAGCUGGC
5435
GCCAGCTG GGCTAGCTACAACGA CTGCGCCT
14184


6957
CGCAGACA G CUGGCUAG
5436
CTAGCCAG GGCTAGCTACAACGA TGTCTGCG
14185


6953
GACAGCUG G CUAGCUGA
5437
TCAGCTAG GGCTAGCTACAACGA CAGCTGTC
14186


6949
GCUGGCUA G CUGAGGAG
5438
CTCCTCAG GGCTAGCTACAACGA TAGCCAGC
14187


6941
GCUGAGGA G CUGGCCAA
5439
TTGGCCAG GGCTAGCTACAACGA TCCTCAGC
14188


6937
AGGAGCUG G CCAAGGAG
5440
CTCCTTGG GGCTAGCTACAACGA CAGCTCCT
14189


6921
GGGGGGAG A CCCCCUGG
5441
CCAGGGGG GGCTAGCTACAACGA CTCCCCCC
14190


6913
ACCCCCUG G CCAGCCUA
5442
TAGGCTGG GGCTAGCTACAACGA CAGGGGGT
14191


6909
CCUGGCCA G CCUACGCU
5443
AGCGTAGG GGCTAGCTACAACGA TGGCCAGG
14192


6905
GCCAGCCU A CGCUUAGC
5444
GCTAAGCG GGCTAGCTACAACGA AGGCTGGC
14193


6903
CAGCCUAC G CUUAGCCG
5445
CGGCTAAG GGCTAGCTACAACGA GTAGGCTG
14194


6898
UACGCUUA G CCGUCUCU
5446
AGAGACGG GGCTAGCTACAACGA TAAGCGTA
14195


6895
GCUUAGCC G UCUCUCCU
5447
AGGAGAGA GGCTAGCTACAACGA GGCTAAGC
14196


6886
UCUCUCCU G UAAUGUGG
5448
CCACATTA GGCTAGCTACAACGA AGGAGAGA
14197


6883
CUCCUGUA A UGUGGGAG
5449
CTCCCACA GGCTAGCTACAACGA TACAGGAG
14198


6881
CCUGUAAU G UGGGAGGG
5450
CCCTCCCA GGCTAGCTACAACGA ATTACAGG
14199


6872
UGGGAGGG G UCGGUGAG
5451
CTCACCGA GGCTAGCTACAACGA CCCTCCCA
14200


6868
AGGGGUCG G UGAGCAUG
5452
CATGCTCA GGCTAGCTACAACGA CGACCCCT
14201


6864
GUCGGUGA G CAUGGACG
5453
CGTCCATG GGCTAGCTACAACGA TCACCGAC
14202


6862
CGGUGAGC A UGGACGUG
5454
CACGTCCA GGCTAGCTACAACGA GCTCACCG
14203


6858
GAGCAUGG A CGUGAGCA
5455
TGCTCACG GGCTAGCTACAACGA CCATGCTC
14204


6856
GCAUGGAC G UGAGCACU
5456
AGTGCTCA GGCTAGCTACAACGA GTCCATGC
14205


6852
GGACGUGA G CACUGCUA
5457
TAGCAGTG GGCTAGCTACAACGA TCACGTCC
14206


6850
ACGUGAGC A CUGCUACA
5458
TGTAGCAG GGCTAGCTACAACGA GCTCACGT
14207


6847
UGAGCACU G CUACAUCC
5459
GGATGTAG GGCTAGCTACAACGA AGTGCTCA
14208


6844
GCACUGCU A CAUCCGGU
5460
ACCGGATG GGCTAGCTACAACGA AGCAGTGC
14209


6842
ACUGCUAC A UCCGGUUC
5461
GAACCGGA GGCTAGCTACAACGA GTAGCAGT
14210


6837
UACAUCCG G UUCGGGCU
5462
AGCCCGAA GGCTAGCTACAACGA CGGATGTA
14211


6831
CGGUUCGG G CUCGCAUG
5463
CATGCGAG GGCTAGCTACAACGA CCGAACCG
14212


6827
UCGGGCUC G CAUGGGAG
5464
CTCCCATG GGCTAGCTACAACGA GAGCCCGA
14213


6825
GGGCUCGC A UGGGAGCU
5465
AGCTCCCA GGCTAGCTACAACGA GCGAGCCC
14214


6819
GCAUGGGA G CUGUGACC
5466
GGTCACAG GGCTAGCTACAACGA TCCCATGC
14215


6816
UGGGAGCU G UGACCCAA
5467
TTGGGTCA GGCTAGCTACAACGA AGCTCCCA
14216


6813
GAGCUGUG A CCCAACCA
5468
TGGTTGGG GGCTAGCTACAACGA CACAGCTC
14217


6808
GUGACCCA A CCAGGUAU
5469
ATACCTGG GGCTAGCTACAACGA TGGGTCAC
14218


6803
CCAACCAG G UAUUGGUU
5470
AACCAATA GGCTAGCTACAACGA CTGGTTGG
14219


6801
AACCAGGU A UUGGUUGA
5471
TCAACCAA GGCTAGCTACAACGA ACCTGGTT
14220


6797
AGGUAUUG G UUGAGCCC
5472
GGGCTCAA GGCTAGCTACAACGA CAATACCT
14221


6792
UUGGUUGA G CCCGACCU
5473
AGGTCGGG GGCTAGCTACAACGA TCAACCAA
14222


6787
UGAGCCCG A CCUGGAAU
5474
ATTCCAGG GGCTAGCTACAACGA CGGGCTCA
14223


6780
GACCUGGA A UGUGACCU
5475
AGGTCACA GGCTAGCTACAACGA TCCAGGTC
14224


6778
CCUGGAAU G UGACCUCC
5476
GGAGGTCA GGCTAGCTACAACGA ATTCCAGG
14225


6775
GGAAUGUG A CCUCCUCC
5477
GGAGGAGG GGCTAGCTACAACGA CACATTCC
14226


6765
CUCCUCCC G UAGGAGAG
5478
CTCTCCTA GGCTAGCTACAACGA GGGAGGAG
14227


6756
UAGGAGAG G UCCACACG
5479
CGTGTGGA GGCTAGCTACAACGA CTCTCCTA
14228


6752
AGAGGUCC A CACGCCGG
5480
CCGGCGTG GGCTAGCTACAACGA GGACCTCT
14229


6750
AGGUCCAC A CGCCGGAG
5481
CTCCGGCG GGCTAGCTACAACGA GTGGACCT
14230


6748
GUCCACAC G CCGGAGCG
5482
CGCTCCGG GGCTAGCTACAACGA GTGTGGAC
14231


6742
ACGCCGGA G CGUUUCUG
5483
CAGAAACG GGCTAGCTACAACGA TCCGGCGT
14232


6740
GCCGGAGC G UUUCUGUG
5484
CACAGAAA GGCTAGCTACAACGA GCTCCGGC
14233


6734
GCGUUUCU G UGCAGGCG
5485
CGCCTGCA GGCTAGCTACAACGA AGAAACGC
14234


6732
GUUUCUGU G CAGGCGUA
5486
TACGCCTG GGCTAGCTACAACGA ACAGAAAC
14235


6728
CUGUGCAG G CGUACCCC
5487
GGGGTACG GGCTAGCTACAACGA CTGCACAG
14236


6726
GUGCAGGC G UACCCCAU
5488
ATGGGGTA GGCTAGCTACAACGA GCCTGCAC
14237


6724
GCAGGCGU A CCCCAUCC
5489
GGATGGGG GGCTAGCTACAACGA ACGCCTGC
14238


6719
CGUACCCC A UCCACUUC
5490
GAAGTGGA GGCTAGCTACAACGA GGGGTACG
14239


6715
CCCCAUCC A CUUCCGUG
5491
CACGGAAG GGCTAGCTACAACGA GGATGGGG
14240


6709
CCACUUCC G UGAAGAAU
5492
ATTCTTCA GGCTAGCTACAACGA GGAAGTGG
14241


6702
CGUGAAGA A UUCGGGGG
5493
CCCCCGAA GGCTAGCTACAACGA TCTTCACG
14242


6693
UUCGGGGG G CGGAACCU
5494
AGGTTCCG GGCTAGCTACAACGA CCCCCGAA
14243


6688
GGGGCGGA A CCUGGCAC
5495
GTGCCAGG GGCTAGCTACAACGA TCCGCCCC
14244


6683
GGAACCUG G CACGGGCA
5496
TGCCCGTG GGCTAGCTACAACGA CAGGTTCC
14245


6681
AACCUGGC A CGGGCAUU
5497
AATGCCCG GGCTAGCTACAACGA GCCAGGTT
14246


6677
UGGCACGG G CAUUUUAC
5498
GTAAAATG GGCTAGCTACAACGA CCGTGCCA
14247


6675
GCACGGGC A UUUUACGU
5499
ACGTAAAA GGCTAGCTACAACGA GCCCGTGC
14248


6670
GGCAUUUU A CGUUGUCA
5500
TGACAACG GGCTAGCTACAACGA AAAATGCC
14249


6668
CAUUUUAC G UUGUCAGU
5501
ACTGACAA GGCTAGCTACAACGA GTAAAATG
14250


6665
UUUACGUU G UCAGUGGU
5502
ACCACTGA GGCTAGCTACAACGA AACGTAAA
14251


6661
CGUUGUCA G UGGUCAUG
5503
CATGACCA GGCTAGCTACAACGA TGACAACG
14252


6658
UGUCAGUG G UCAUGCCC
5504
GGGCATGA GGCTAGCTACAACGA CACTGACA
14253


6655
CAGUGGUC A UGCCCGUC
5505
GACGGGCA GGCTAGCTACAACGA GACCACTG
14254


6653
GUGGUCAU G CCCGUCAC
5506
GTGACGGG GGCTAGCTACAACGA ATGACCAC
14255


6649
UCAUGCCC G UCACGUAG
5507
CTACGTGA GGCTAGCTACAACGA GGGCATGA
14256


6646
UGCCCGUC A CGUAGUGG
5508
CCACTACG GGCTAGCTACAACGA GACGGGCA
14257


6644
CCCGUCAC G UAGUGGAA
5509
TTCCACTA GGCTAGCTACAACGA GTGACGGG
14258


6641
GUCACGUA G UGGAAAUC
5510
GATTTCCA GGCTAGCTACAACGA TACGTGAC
14259


6635
UAGUGGAA A UCCCCCAC
5511
GTGGGGGA GGCTAGCTACAACGA TTCCACTA
14260


6628
AAUCCCCC A CCCGCGUA
5512
TACGCGGG GGCTAGCTACAACGA GGGGGATT
14261


6624
CCCCACCC G CGUAACCU
5513
AGGTTACG GGCTAGCTACAACGA GGGTGGGG
14262


6622
CCACCCGC G UAACCUCC
5514
GGAGGTTA GGCTAGCTACAACGA GCGGGTGG
14263


6619
CCCGCGUA A CCUCCACG
5515
CGTGGAGG GGCTAGCTACAACGA TACGCGGG
14264


6613
UAACCUCC A CGUACUCC
5516
GGAGTACG GGCTAGCTACAACGA GGAGGTTA
14265


6611
ACCUCCAC G UACUCCUC
5517
GAGGAGTA GGCTAGCTACAACGA GTGGAGGT
14266


6609
CUCCACGU A CUCCUCAG
5518
CTGAGGAG GGCTAGCTACAACGA ACGTGGAG
14267


6601
ACUCCUCA G CGGCCACC
5519
GGTGGCCG GGCTAGCTACAACGA TGAGGAGT
14268


6598
CCUCAGCG G CCACCCGC
5520
GCGGGTGG GGCTAGCTACAACGA CGCTGAGG
14269


6595
CAGCGGCC A CCCGCCAU
5521
ATGGCGGG GGCTAGCTACAACGA GGCCGCTG
14270


6591
GGCCACCC G CCAUAGCG
5522
CGCTATGG GGCTAGCTACAACGA GGGTGGCC
14271


6588
CACCCGCC A UAGCGCCC
5523
GGGCGCTA GGCTAGCTACAACGA GGCGGGTG
14272


6585
CCGCCAUA G CGCCCUAG
5524
CTAGGGCG GGCTAGCTACAACGA TATGGCGG
14273


6583
GCCAUAGC G CCCUAGAA
5525
TTCTAGGG GGCTAGCTACAACGA GCTATGGC
14274


6575
GCCCUAGA A UAGUUUGG
5526
CCAAACTA GGCTAGCTACAACGA TCTAGGGC
14275


6572
CUAGAAUA G UUUGGCGC
5527
GCGCCAAA GGCTAGCTACAACGA TATTCTAG
14276


6567
AUAGUUUG G CGCCGGGG
5528
CCCCGGCC GGCTAGCTACAACGA CAAACTAT
14277


6565
AGUUUGGC G CCGGGGAG
5529
CTCCCCGG GGCTAGCTACAACGA GCCAAACT
14278


6555
CGGGGAGG G UGUGCAGG
5530
CCTGCACA GGCTAGCTACAACGA CCTCCCCG
14279


6553
GGGAGGGU G UGCAGGGG
5531
CCCCTGCA GGCTAGCTACAACGA ACCCTCCC
14280


6551
GAGGGUGU G CAGGGGCC
5532
GGCCCCTG GGCTAGCTACAACGA ACACCCTC
14281


6545
GUGCAGGG G CCCGUGGU
5533
ACCACGGG GGCTAGCTACAACGA CCCTGCAC
14282


6541
AGGGGCCC G UGGUGUAU
5534
ATACACCA GGCTAGCTACAACGA GGGCCCCT
14283


6538
GGCCCGUG G UGUAUGCG
5535
CGCATACA GGCTAGCTACAACGA CACGGGCC
14284


6536
CCCGUGGU G UAUGCGUU
5536
AACGCATA GGCTAGCTACAACGA ACCACGGG
14285


6534
CGUGGUGU A UGCGUUGA
5537
TCAACGCA GGCTAGCTACAACGA ACACCACG
14286


6532
UGGUGUAU G CGUUGAUG
5538
CATCAACG GGCTAGCTACAACGA ATACACCA
14287


6530
GUGUAUGC G UUGAUGGG
5539
CCCATCAA GGCTAGCTACAACGA GCATACAC
14288


6526
AUGCGUUG A UGGGGAAU
5540
ATTCCCCA GGCTAGCTACAACGA CAACGCAT
14289


6519
GAUGGGGA A UGUUCCAU
5541
ATGGAACA GGCTAGCTACAACGA TCCCCATC
14290


6517
UGGGGAAU G UUCCAUGC
5542
GCATGGAA GGCTAGCTACAACGA ATTCCCCA
14291


6512
AAUGUUCC A UGCCACGU
5543
ACGTGGCA GGCTAGCTACAACGA GGAACATT
14292


6510
UGUUCCAU G CCACGUGU
5544
ACACGTGG GGCTAGCTACAACGA ATGGAACA
14293


6507
UCCAUGCC A CGUGUUGC
5545
GCAACACG GGCTAGCTACAACGA GGCATGGA
14294


6505
CAUGCCAC G UGUUGCUA
5546
TAGCAACA GGCTAGCTACAACGA GTGGCATG
14295


6503
UGCCACGU G UUGCUACA
5547
TGTAGCAA GGCTAGCTACAACGA ACGTGGCA
14296


6500
CACGUGUU G CUACAGGU
5548
ACCTGTAG GGCTAGCTACAACGA AACACGTG
14297


6497
GUGUUGCU A CAGGUCUU
5549
AAGACCTG GGCTAGCTACAACGA AGCAACAC
14298


6493
UGCUACAG G UCUUAGGC
5550
GCCTAAGA GGCTAGCTACAACGA CTGTAGCA
14299


6486
GGUCUUAG G CCCGACGA
5551
TCGTCGGG GGCTAGCTACAACGA CTAAGACC
14300


6481
UAGGCCCG A CGAUCCUC
5552
GAGGATCG GGCTAGCTACAACGA CGGGCCTA
14301


6478
GCCCGACG A UCCUCAUG
5553
CATGAGGA GGCTAGCTACAACGA CGTCGGGC
14302


6472
CGAUCCUC A UGGAACCG
5554
CGGTTCCA GGCTAGCTACAACGA GAGGATCG
14303


6467
CUCAUGGA A CCGUUCUU
5555
AAGAACGG GGCTAGCTACAACGA TCCATGAG
14304


6464
AUGGAACC G UUCUUGAC
5556
GTCAAGAA GGCTAGCTACAACGA GGTTCCAT
14305


6457
CGUUCUUG A CAUGUCCA
5557
TGGACATG GGCTAGCTACAACGA CAAGAACG
14306


6455
UUCUUGAC A UGUCCAGU
5558
ACTGGACA GGCTAGCTACAACGA GTCAAGAA
14307


6453
CUUGACAU G UCCAGUGA
5559
TCACTGGA GGCTAGCTACAACGA ATGTCAAG
14308


6448
CAUGUCCA G UGAUCUGC
5560
GCAGATCA GGCTAGCTACAACGA TGGACATG
14309


6445
GUCCAGUG A UCUGCGCU
5561
AGCGCAGA GGCTAGCTACAACGA CACTGGAC
14310


6441
AGUGAUCU G CGCUCCGC
5562
GCGGAGCG GGCTAGCTACAACGA AGATCACT
14311


6439
UGAUCUGC G CUCCGCAU
5563
ATGCGGAG GGCTAGCTACAACGA GCAGATCA
14312


6434
UGCGCUCC G CAUGGGCA
5564
TGCCCATG GGCTAGCTACAACGA GGAGCGCA
14313


6432
CGCUCCGC A UGGGCAGG
5565
CCTGCCCA GGCTAGCTACAACGA GCGGAGCG
14314


6428
CCGCAUGG G CAGGUGGU
5566
ACCACCTG GGCTAGCTACAACGA CCATGCGG
14315


6424
AUGGGCAG G UGGUUUGC
5567
GCAAACCA GGCTAGCTACAACGA CTGCCCAT
14316


6421
GGCAGGUG G UUUGCAUG
5568
CATGCAAA GGCTAGCTACAACGA CACCTGCC
14317


6417
GGUGGUUU G CAUGAUAC
5569
GTATCATG GGCTAGCTACAACGA AAACCACC
14318


6415
UGGUUUGC A UGAUACCG
5570
CGGTATCA GGCTAGCTACAACGA GCAAACCA
14319


6412
UUUGCAUG A UACCGUCU
5571
AGACGGTA GGCTAGCTACAACGA CATGCAAA
14320


6410
UGCAUGAU A CCGUCUCC
5572
GGAGACGG GGCTAGCTACAACGA ATCATGCA
14321


6407
AUGAUACC G UCUCCCCG
5573
CGGGGAGA GGCTAGCTACAACGA GGTATCAT
14322


6399
GUCUCCCC G CCAGACCC
5574
GGGTCTGG GGCTAGCTACAACGA GGGGAGAC
14323


6394
CCCGCCAG A CCCCCCUG
5575
CAGGGGGG GGCTAGCTACAACGA CTGGCGGG
14324


6386
ACCCCCCU G UACCCACG
5576
CGTGGGTA GGCTAGCTACAACGA AGGGGGGT
14325


6384
CCCCCUGU A CCCACGUU
5577
AACGTGGG GGCTAGCTACAACGA ACAGGGGG
14326


6380
CUGUACCC A CGUUGGCA
5578
TGCCAACG GGCTAGCTACAACGA GGGTACAG
14327


6378
GUACCCAC G UUGGCAUG
5579
CATGCCAA GGCTAGCTACAACGA GTGGGTAC
14328


6374
CCACGUUG G CAUGAGAA
5580
TTCTCATG GGCTAGCTACAACGA CAACGTGG
14329


6372
ACGUUGGC A UGAGAAGA
5581
TCTTCTCA GGCTAGCTACAACGA GCCAACGT
14330


6358
AGAAAGGG A CUCCCGGC
5582
GCCGGGAG GGCTAGCTACAACGA CCCTTTCT
14331


6351
GACUCCCG G CAACCGCG
5583
CGCGGTTG GGCTAGCTACAACGA CGGGAGTC
14332


6348
UCCCGGCA A CCGCGGCA
5584
TGCCGCGG GGCTAGCTACAACGA TGCCGGGA
14333


6345
CGGCAACC G CGGCAGGA
5585
TCCTGCCG GGCTAGCTACAACGA GGTTGCCG
14334


6342
CAACCGCG G CAGGAGCU
5586
AGCTCCTG GGCTAGCTACAACGA CGCGGTTG
14335


6336
CGGCAGGA G CUUGGACU
5587
AGTCCAAG GGCTAGCTACAACGA TCCTGCCG
14336


6330
GAGCUUGG A CUGAAGCC
5588
GGCTTCAG GGCTAGCTACAACGA CCAAGCTC
14337


6324
GGACUGAA G CCAGGUCU
5589
AGACCTGG GGCTAGCTACAACGA TTCAGTCC
14338


6319
GAAGCCAG G UCUUGAAG
5590
CTTCAAGA GGCTAGCTACAACGA CTGGCTTC
14339


6311
GUCUUGAA G UCAGUCAA
5591
TTGACTGA GGCTAGCTACAACGA TTCAAGAC
14340


6307
UGAAGUCA G UCAACACC
5592
GGTGTTGA GGCTAGCTACAACGA TGACTTCA
14341


6303
GUCAGUCA A CACCGUGC
5593
GCACGGTG GGCTAGCTACAACGA TGACTGAC
14342


6301
CAGUCAAC A CCGUGCAU
5594
ATGCACGG GGCTAGCTACAACGA GTTGACTG
14343


6298
UCAACACC G UGCAUAUC
5595
GATATGCA GGCTAGCTACAACGA GGTGTTGA
14344


6296
AACACCGU G CAUAUCCA
5596
TGGATATG GGCTAGCTACAACGA ACGGTGTT
14345


6294
CACCGUGC A UAUCCAGU
5597
ACTGGATA GGCTAGCTACAACGA GCACGGTG
14346


6292
CCGUGCAU A UCCAGUCC
5598
GGACTGGA GGCTAGCTACAACGA ATGCACGG
14347


6287
CAUAUCCA G UCCCAAAC
5599
GTTTGGGA GGCTAGCTACAACGA TGGATATG
14348


6280
AGUCCCAA A CAUCCCUU
5600
AAGGGATG GGCTAGCTACAACGA TTGGGACT
14349


6278
UCCCAAAC A UCCCUUAG
5601
CTAAGGGA GGCTAGCTACAACGA GTTTGGGA
14350


6270
AUCCCUUA G CCACGAGC
5602
GCTCGTGG GGCTAGCTACAACGA TAAGGGAT
14351


6267
CCUUAGCC A CGAGCCGG
5603
CCGGCTCG GGCTAGCTACAACGA GGCTAAGG
14352


6263
AGCCACGA G CCGGAACA
5604
TGTTCCGG GGCTAGCTACAACGA TCGTGGCT
14353


6257
GAGCCGGA A CAUGGCGU
5605
ACGCCATG GGCTAGCTACAACGA TCCGGCTC
14354


6255
GCCGGAAC A UGGCGUGG
5606
CCACGCCA GGCTAGCTACAACGA GTTCCGGC
14355


6252
GGAACAUG G CGUGGAGC
5607
GCTCCACG GGCTAGCTACAACGA CATGTTCC
14356


6250
AACAUGGC G UGGAGCAG
5608
CTGCTCCA GGCTAGCTACAACGA GCCATGTT
14357


6245
GGCGUGGA G CAGUCCUC
5609
GAGGACTG GGCTAGCTACAACGA TCCACGCC
14358


6242
GUGGAGCA G UCCUCAUU
5610
AATGAGGA GGCTAGCTACAACGA TGCTCCAC
14359


6236
CAGUCCUC A UUGAUCCA
5611
TGGATCAA GGCTAGCTACAACGA GAGGACTG
14360


6232
CCUCAUUG A UCCACUGA
5612
TCAGTGGA GGCTAGCTACAACGA CAATGAGG
14361


6228
AUUGAUCC A CUGAUGGA
5613
TCCATCAG GGCTAGCTACAACGA GGATCAAT
14362


6224
AUCCACUG A UGGAGCCU
5614
AGGCTCCA GGCTAGCTACAACGA CAGTGGAT
14363


6219
CUGAUGGA G CCUCCUCA
5615
TGAGGAGG GGCTAGCTACAACGA TCCATCAG
14364


6210
CCUCCUCA G CAGCUGAG
5616
CTCAGCTG GGCTAGCTACAACGA TGAGGAGG
14365


6207
CCUCAGCA G CUGAGUGA
5617
TCACTCAG GGCTAGCTACAACGA TGCTGAGG
14366


6202
GCAGCUGA G UGAUGGUG
5618
CACCATCA GGCTAGCTACAACGA TCAGCTGC
14367


6199
GCUGAGUG A UGGUGAGG
5619
CCTCACCA GGCTAGCTACAACGA CACTCAGC
14368


6196
GAGUGAUG G UGAGGCUG
5620
CAGCCTCA GGCTAGCTACAACGA CATCACTC
14369


6191
AUGGUGAG G CUGGAGAG
5621
CTCTCCAG GGCTAGCTACAACGA CTCACCAT
14370


6181
UGGAGAGG A UUUGUGUG
5622
CACACAAA GGCTAGCTACAACGA CCTCTCCA
14371


6177
GAGGAUUU G UGUGACGC
5623
GCGTCACA GGCTAGCTACAACGA AAATCCTC
14372


6175
GGAUUUGU G UGACGCGC
5624
GCGCGTCA GGCTAGCTACAACGA ACAAATCC
14373


6172
UUUGUGUG A CGCGCGCC
5625
GGCGCGCG GGCTAGCTACAACGA CACACAAA
14374


6170
UGUGUGAC G CGCGCCGC
5626
GCGGCGCG GGCTAGCTACAACGA GTCACACA
14375


6168
UGUGACGC G CGCCGCUG
5627
CAGCGGCG GGCTAGCTACAACGA GCGTCACA
14376


6166
UGACGCGC G CCGCUGCG
5628
CGCAGCGG GGCTAGCTACAACGA GCGCGTCA
14377


6163
CGCGCGCC G CUGCGUCG
5629
CGACGCAG GGCTAGCTACAACGA GGCGCGCG
14378


6160
GCGCCGCU G CGUCGCUC
5630
GAGCGACG GGCTAGCTACAACGA AGCGGCGC
14379


6158
GCCGCUGC G UCGCUCUC
5631
GAGAGCGA GGCTAGCTACAACGA GCAGCGGC
14380


6155
GCUGCGUC G CUCUCAGG
5632
CCTGAGAG GGCTAGCTACAACGA GACGCAGC
14381


6147
GCUCUCAG G CACAUAGU
5633
ACTATGTG GGCTAGCTACAACGA CTGAGAGC
14382


6145
UCUCAGGC A CAUAGUGC
5634
GCACTATG GGCTAGCTACAACGA GCCTGAGA
14383


6143
UCAGGCAC A UAGUGCGU
5635
ACGCACTA GGCTAGCTACAACGA GTGCCTGA
14384


6140
GGCACAUA G UGCGUGGG
5636
CCCACGCA GGCTAGCTACAACGA TATGTGCC
14385


6138
CACAUAGU G CGUGGGGG
5637
CCCCCACG GGCTAGCTACAACGA ACTATGTG
14386


6136
CAUAGUGC G UGGGGGAG
5638
CTCCCCCA GGCTAGCTACAACGA GCACTATG
14387


6127
UGGGGGAG A CAUGGUUG
5639
CAACCATG GGCTAGCTACAACGA CTCCCCCA
14388


6125
GGGGAGAC A UGGUUGCC
5640
GGCAACCA GGCTAGCTACAACGA GTCTCCCC
14389


6122
GAGACAUG G UUGCCCCG
5641
CGGGGCAA GGCTAGCTACAACGA CATGTCTC
14390


6119
ACAUGGUU G CCCCGCGA
5642
TCGCGGGG GGCTAGCTACAACGA AACCATGT
14391


6114
GUUGCCCC G CGAAGCGA
5643
TCGCTTCG GGCTAGCTACAACGA GGGGCAAC
14392


6109
CCCGCGAA G CGAACGCU
5644
AGCGTTCG GGCTAGCTACAACGA TTCGCGGG
14393


6105
CGAAGCGA A CGCUAUCA
5645
TGATAGCG GGCTAGCTACAACGA TCGCTTCG
14394


6103
AAGCGAAC G CUAUCAGC
5646
GCTGATAG GGCTAGCTACAACGA GTTCGCTT
14395


6100
CGAACGCU A UCAGCCGA
5647
TCGGCTGA GGCTAGCTACAACGA AGCGTTCG
14396


6096
CGCUAUCA G CCGAUUCA
5648
TGAATCGG GGCTAGCTACAACGA TGATAGCG
14397


6092
AUCAGCCG A UUCAUCCA
5649
TGGATGAA GGCTAGCTACAACGA CGGCTGAT
14398


6088
GCCGAUUC A UCCACUGC
5650
GCAGTGGA GGCTAGCTACAACGA GAATCGGC
14399


6084
AUUCAUCC A CUGCACAG
5651
CTGTGCAG GGCTAGCTACAACGA GGATGAAT
14400


6081
CAUCCACU G CACAGCGC
5652
GCGCTGTG GGCTAGCTACAACGA AGTGGATG
14401


6079
UCCACUGC A CAGCGCCC
5653
GGGCGCTG GGCTAGCTACAACGA GCAGTGGA
14402


6076
ACUGCACA G CGCCCUCU
5654
AGAGGGCG GGCTAGCTACAACGA TGTGCAGT
14403


6074
UGCACAGC G CCCUCUCC
5655
GGAGAGGG GGCTAGCTACAACGA GCTGTGCA
14404


6062
UCUCCUGG G CCCACAUG
5656
CATGTGGG GGCTAGCTACAACGA CCAGGAGA
14405


6058
CUGGGCCC A CAUGCCGA
5657
TCGGCATG GGCTAGCTACAACGA GGGCCCAG
14406


6056
GGGCCCAC A UGCCGACG
5658
CGTCGGCA GGCTAGCTACAACGA GTGGGCCC
14407


6054
GCCCACAU G CCGACGCA
5659
TGCGTCGG GGCTAGCTACAACGA ATGTGGGC
14408


6050
ACAUGCCG A CGCAGUAU
5660
ATACTGCG GGCTAGCTACAACGA CGGCATGT
14409


6048
AUGCCGAC G CAGUAUCG
5661
CGATACTG GGCTAGCTACAACGA GTCGGCAT
14410


6045
CCGACGCA G UAUCGCUG
5662
CAGCGATA GGCTAGCTACAACGA TGCGTCGG
14411


6043
GACGCAGU A UCGCUGCG
5663
CGCAGCGA GGCTAGCTACAACGA ACTGCGTC
14412


6040
GCAGUAUC G CUGCGCAC
5664
GTGCGCAG GGCTAGCTACAACGA GATACTGC
14413


6037
GUAUCGCU G CGCACACC
5665
GGTGTGCG GGCTAGCTACAACGA AGCGATAC
14414


6035
AUCGCUGC G CACACCAC
5666
GTGGTGTG GGCTAGCTACAACGA GCAGCGAT
14415


6033
CGCUGCGC A CACCACCC
5667
GGGTGGTG GGCTAGCTACAACGA GCGCAGCG
14416


6031
CUGCGCAC A CCACCCCG
5668
CGGGGTGG GGCTAGCTACAACGA GTGCGCAG
14417


6028
CGCACACC A CCCCGACG
5669
CGTCGGGG GGCTAGCTACAACGA GGTGTGCG
14418


6022
CCACCCCG A CGACCAGG
5670
CCTGGTCG GGCTAGCTACAACGA CGGGGTGG
14419


6019
CCCCGACG A CCAGGGCG
5671
CGCCCTGG GGCTAGCTACAACGA CGTCGGGG
14420


6013
CGACCAGG G CGCCAGGA
5672
TCCTGGCG GGCTAGCTACAACGA CCTGGTCG
14421


6011
ACCAGGGC G CCAGGAGA
5673
TCTCCTGG GGCTAGCTACAACGA GCCCTGGT
14422


5998
GAGAGAGG A UGGCAGGG
5674
CCCTGCCA GGCTAGCTACAACGA CCTCTCTC
14423


5995
AGAGGAUG G CAGGGAGU
5675
ACTCCCTG GGCTAGCTACAACGA CATCCTCT
14424


5988
GGCAGGGA G UAAGUUGA
5676
TCAACTTA GGCTAGCTACAACGA TCCCTGCC
14425


5984
GGGAGUAA G UUGACCAG
5677
CTGGTCAA GGCTAGCTACAACGA TTACTCCC
14426


5980
GUAAGUUG A CCAGGUCC
5678
GGACCTGG GGCTAGCTACAACGA CAACTTAC
14427


5975
UUGACCAG G UCCUCGGU
5679
ACCGAGGA GGCTAGCTACAACGA CTGGTCAA
14428


5968
GGUCCUCG G UAGAAGGC
5680
GCCTTCTA GGCTAGCTACAACGA CGAGGACC
14429


5961
GGUAGAAG G CAUCUCCC
5681
GGGAGATG GGCTAGCTACAACGA CTTCTACC
14430


5959
UAGAAGGC A UCUCCCCG
5682
CGGGGAGA GGCTAGCTACAACGA GCCTTCTA
14431


5951
AUCUCCCC G CUCAUGAC
5683
GTCATGAG GGCTAGCTACAACGA GGGGAGAT
14432


5947
CCCCGCUC A UGACCUUG
5684
CAAGGTCA GGCTAGCTACAACGA GAGCGGGG
14433


5944
CGCUCAUG A CCUUGAAG
5685
CTTCAAGG GGCTAGCTACAACGA CATGAGCG
14434


5935
CCUUGAAG G CCACGAGA
5686
TCTCGTGG GGCTAGCTACAACGA CTTCAAGG
14435


5932
UGAAGGCC A CGAGAGCA
5687
TGCTCTCG GGCTAGCTACAACGA GGCCTTCA
14436


5926
CCACGAGA G CACCCGCC
5688
GGCGGGTG GGCTAGCTACAACGA TCTCGTGG
14437


5924
ACGAGAGC A CCCGCCAC
5689
GTGGCGGG GGCTAGCTACAACGA GCTCTCGT
14438


5920
GAGCACCC G CCACUCCU
5690
AGGAGTGG GGCTAGCTACAACGA GGGTGCTC
14439


5917
CACCCGCC A CUCCUGCU
5691
AGCAGGAG GGCTAGCTACAACGA GGCGGGTG
14440


5911
CCACUCCU G CUCCAUAG
5692
CTATGGAG GGCTAGCTACAACGA AGGAGTGG
14441


5906
CCUGCUCC A UAGCCCGC
5693
GCGGGCTA GGCTAGCTACAACGA GGAGCAGG
14442


5903
GCUCCAUA G CCCGCCAG
5694
CTGGCGGG GGCTAGCTACAACGA TATGGAGC
14443


5899
CAUAGCCC G CCAGAAUG
5695
CATTCTGG GGCTAGCTACAACGA GGGCTATG
14444


5893
CCGCCAGA A UGUCUACA
5696
TGTAGACA GGCTAGCTACAACGA TCTGGCGG
14445


5891
GCCAGAAU G UCUACAAG
5697
CTTGTAGA GGCTAGCTACAACGA ATTCTGGC
14446


5887
GAAUGUCU A CAAGCACC
5698
GGTGCTTG GGCTAGCTACAACGA AGACATTC
14447


5883
GUCUACAA G CACCUUCC
5699
GGAAGGTG GGCTAGCTACAACGA TTGTAGAC
14448


5881
CUACAAGC A CCUUCCCA
5700
TGGGAAGG GGCTAGCTACAACGA GCTTGTAG
14449


5870
UUCCCAAG G CCUAUGCU
5701
AGCATAGG GGCTAGCTACAACGA CTTGGGAA
14450


5866
CAAGGCCU A UGCUGCCA
5702
TGGCAGCA GGCTAGCTACAACGA AGGCCTTG
14451


5864
AGGCCUAU G CUGCCAAC
5703
GTTGGCAG GGCTAGCTACAACGA ATAGGCCT
14452


5861
CCUAUGCU G CCAACAGC
5704
GCTGTTGG GGCTAGCTACAACGA AGCATAGG
14453


5857
UGCUGCCA A CAGCCGCG
5705
CGCGGCTG GGCTAGCTACAACGA TGGCAGCA
14454


5854
UGCCAACA G CCGCGCCA
5706
TGGCGCGG GGCTAGCTACAACGA TGTTGGCA
14455


5851
CAACAGCC G CGCCAGCG
5707
CGCTGGCG GGCTAGCTACAACGA GGCTGTTG
14456


5849
ACAGCCGC G CCAGCGAU
5708
ATCGCTGG GGCTAGCTACAACGA GCGGCTGT
14457


5845
CCGCGCCA G CGAUGCCG
5709
CGGCATCG GGCTAGCTACAACGA TGGCGCGG
14458


5842
CGCCAGCG A UGCCGGCG
5710
CGCCGGCA GGCTAGCTACAACGA CGCTGGCG
14459


5840
CCAGCGAU G CCGGCGCC
5711
GGCGCCGG GGCTAGCTACAACGA ATCGCTGG
14460


5836
CGAUGCCG G CGCCCACG
5712
CGTGGGCG GGCTAGCTACAACGA CGGCATCG
14461


5834
AUGCCGGC G CCCACGAA
5713
TTCGTGGG GGCTAGCTACAACGA GCCGGCAT
14462


5830
CGGCGCCC A CGAAGGCC
5714
GGCCTTCG GGCTAGCTACAACGA GGGCGCCG
14463


5824
CCACGAAG G CCGAAACG
5715
CGTTTCGG GGCTAGCTACAACGA CTTCGTGG
14464


5818
AGGCCGAA A CGGCUCUG
5716
CAGAGCCG GGCTAGCTACAACGA TTCGGCCT
14465


5815
CCGAAACG G CUCUGGGG
5717
CCCCAGAG GGCTAGCTACAACGA CGTTTCGG
14466


5803
UGGGGGGA G CGAGUUGG
5718
CCAACTCG GGCTAGCTACAACGA TCCCCCCA
14467


5799
GGGAGCGA G UUGGGCGG
5719
CCGCCCAA GGCTAGCTACAACGA TCGCTCCC
14468


5794
CGAGUUGG G CGGCCACC
5720
GGTGGCCG GGCTAGCTACAACGA CCAACTCG
14469


5791
GUUGGGCG G CCACCCAC
5721
GTGGGTGG GGCTAGCTACAACGA CGCCCAAC
14470


5788
GGGCGGCC A CCCACCCU
5722
AGGGTGGG GGCTAGCTACAACGA GGCCGCCC
14471


5784
GGCCACCC A CCCUCCCA
5723
TGGGAGGG GGCTAGCTACAACGA GGGTGGCC
14472


5773
CUCCCAAG A UGUUGAAC
5724
GTTCAACA GGCTAGCTACAACGA CTTGGGAG
14473


5771
CCCAAGAU G UUGAACAG
5725
CTGTTCAA GGCTAGCTACAACGA ATCTTGGG
14474


5766
GAUGUUGA A CAGGAGGG
5726
CCCTCCTG GGCTAGCTACAACGA TCAACATC
14475


5758
ACAGGAGG G UGCUUUGG
5727
CCAAAGCA GGCTAGCTACAACGA CCTCCTGT
14476


5756
AGGAGGGU G CUUUGGGU
5728
ACCCAAAG GGCTAGCTACAACGA ACCCTCCT
14477


5749
UGCUUUGG G UGGUGAGC
5729
GCTCACCA GGCTAGCTACAACGA CCAAAGCA
14478


5746
UUUGGGUG G UGAGCGGG
5730
CCCGCTCA GGCTAGCTACAACGA CACCCAAA
14479


5742
GGUGGUGA G CGGGCUGG
5731
CCAGCCCG GGCTAGCTACAACGA TCACCACC
14480


5738
GUGAGCGG G CUGGUGAU
5732
ATCACCAG GGCTAGCTACAACGA CCGCTCAC
14481


5734
GCGGGCUG G UGAUGGAG
5733
CTCCATCA GGCTAGCTACAACGA CAGCCCGC
14482


5731
GGCUGGUG A UGGAGGCU
5734
AGCCTCCA GGCTAGCTACAACGA CACCAGCC
14483


5725
UGAUGGAG G CUGUGAAU
5735
ATTCACAG GGCTAGCTACAACGA CTCCATCA
14484


5722
UGGAGGCU G UGAAUGCC
5736
GGCATTCA GGCTAGCTACAACGA AGCCTCCA
14485


5718
GGCUGUGA A UGCCAUCA
5737
TGATGGCA GGCTAGCTACAACGA TCACAGCC
14486


5716
CUGUGAAU G CCAUCAAU
5738
ATTGATGG GGCTAGCTACAACGA ATTCACAG
14487


5713
UGAAUGCC A UCAAUGAU
5739
ATCATTGA GGCTAGCTACAACGA GGCATTCA
14488


5709
UGCCAUCA A UGAUGCUA
5740
TAGCATCA GGCTAGCTACAACGA TGATGGCA
14489


5706
CAUCAAUG A UGCUAUCG
5741
CGATAGCA GGCTAGCTACAACGA CATTGATG
14490


5704
UCAAUGAU G CUAUCGCG
5742
CGCGATAG GGCTAGCTACAACGA ATCATTGA
14491


5701
AUGAUGCU A UCGCGGGG
5743
CCCCGCGA GGCTAGCTACAACGA AGCATCAT
14492


5698
AUGCUAUC G CGGGGUUC
5744
GAACCCCG GGCTAGCTACAACGA GATAGCAT
14493


5693
AUCGCGGG G UUCCCAGG
5745
CCTGGGAA GGCTAGCTACAACGA CCCGCGAT
14494


5685
GUUCCCAG G CAGAGUGG
5746
CCACTCTG GGCTAGCTACAACGA CTGGGAAC
14495


5680
CAGGCAGA G UGGACAAG
5747
CTTGTCCA GGCTAGCTACAACGA TCTGCCTG
14496


5676
CAGAGUGG A CAAGCCUG
5748
CAGGCTTG GGCTAGCTACAACGA CCACTCTG
14497


5672
GUGGACAA G CCUGCUAG
5749
CTAGCAGG GGCTAGCTACAACGA TTGTCCAC
14498


5668
ACAAGCCU G CUAGGUAC
5750
GTACCTAG GGCTAGCTACAACGA AGGCTTGT
14499


5663
CCUGCUAG G UACUGUAU
5751
ATACAGTA GGCTAGCTACAACGA CTAGCAGG
14500


5661
UGCUAGGU A CUGUAUCC
5752
GGATACAG GGCTAGCTACAACGA ACCTAGCA
14501


5658
UAGGUACU G UAUCCCGC
5753
GCGGGATA GGCTAGCTACAACGA AGTACCTA
14502


5656
GGUACUGU A UCCCGCUG
5754
CAGCGGGA GGCTAGCTACAACGA ACAGTACC
14503


5651
UGUAUCCC G CUGAUGAA
5755
TTCATCAG GGCTAGCTACAACGA GGGATACA
14504


5647
UCCCGCUG A UGAAAUUC
5756
GAATTTCA GGCTAGCTACAACGA CAGCGGGA
14505


5642
CUGAUGAA A UUCCACAU
5757
ATGTGGAA GGCTAGCTACAACGA TTCATCAG
14506


5637
GAAAUUCC A CAUGUGCU
5758
AGCACATG GGCTAGCTACAACGA GGAATTTC
14507


5635
AAUUCCAC A UGUGCUUC
5759
GAAGCACA GGCTAGCTACAACGA GTGGAATT
14508


5633
UUCCACAU G UGCUUCGC
5760
GCGAAGCA GGCTAGCTACAACGA ATGTGGAA
14509


5631
CCACAUGU G CUUCGCCC
5761
GGGCGAAG GGCTAGCTACAACGA ACATGTGG
14510


5626
UGUGCUUC G CCCAGAAA
5762
TTTCTGGG GGCTAGCTACAACGA GAAGCACA
14511


5617
CCCAGAAA G CCUCAAGG
5763
CCTTGAGG GGCTAGCTACAACGA TTTCTGGG
14512


5608
CCUCAAGG G CUCGCCAC
5764
GTGGCGAG GGCTAGCTACAACGA CCTTGAGG
14513


5604
AAGGGCUC G CCACUUGG
5765
CCAAGTGG GGCTAGCTACAACGA GAGCCCTT
14514


5601
GGCUCGCC A CUUGGAUU
5766
AATCCAAG GGCTAGCTACAACGA GGCGAGCC
14515


5595
CCACUUGG A UUCCACCA
5767
TGGTGGAA GGCTAGCTACAACGA CCAAGTGG
14516


5590
UGGAUUCC A CCACGGGA
5768
TCCCGTGG GGCTAGCTACAACGA GGAATCCA
14517


5587
AUUCCACC A CGGGAGCA
5769
TGCTCCCG GGCTAGCTACAACGA GGTGGAAT
14518


5581
CCACGGGA G CAGCAGCC
5770
GGCTGCTG GGCTAGCTACAACGA TCCCGTGG
14519


5578
CGGGAGCA G CAGCCUCC
5771
GGAGGCTG GGCTAGCTACAACGA TGCTCCCG
14520


5575
GAGCAGCA G CCUCCGCU
5772
AGCGGAGG GGCTAGCTACAACGA TGCTGCTC
14521


5569
CAGCCUCC G CUUGGUUG
5773
CAACCAAG GGCTAGCTACAACGA GGAGGCTG
14522


5564
UCCGCUUG G UUGGUGGC
5774
GCCACCAA GGCTAGCTACAACGA CAAGCGGA
14523


5560
CUUGGUUG G UGGCUGUU
5775
AACAGCCA GGCTAGCTACAACGA CAACCAAG
14524


5557
GGUUGGUG G CUGUUUGC
5776
GCAAACAG GGCTAGCTACAACGA CACCAACC
14525


5554
UGGUGGCU G UUUGCAGC
5777
GCTGCAAA GGCTAGCTACAACGA AGCCACCA
14526


5550
GGCUGUUU G CAGCAAUC
5778
GATTGCTG GGCTAGCTACAACGA AAACAGCC
14527


5547
UGUUUGCA G CAAUCCGA
5779
TCGGATTG GGCTAGCTACAACGA TGCAAACA
14528


5544
UUGCAGCA A UCCGAGCG
5780
CGCTCGGA GGCTAGCTACAACGA TGCTGCAA
14529


5538
CAAUCCGA G CGCCUUCU
5781
AGAAGGCG GGCTAGCTACAACGA TCGGATTG
14530


5536
AUCCGAGC G CCUUCUGC
5782
GCAGAAGG GGCTAGCTACAACGA GCTCGGAT
14531


5529
CGCCUUCU G CUUGAACU
5783
AGTTCAAG GGCTAGCTACAACGA AGAAGGCG
14532


5523
CUGCUUGA A CUGCUCGG
5784
CCGAGCAG GGCTAGCTACAACGA TCAAGCAG
14533


5520
CUUGAACU G CUCGGCGA
5785
TCGCCGAG GGCTAGCTACAACGA AGTTCAAG
14534


5515
ACUGCUCG G CGAGCUGC
5786
GCAGCTCG GGCTAGCTACAACGA CGAGCAGT
14535


5511
CUCGGCGA G CUGCAUCC
5787
GGATGCAG GGCTAGCTACAACGA TCGCCGAG
14536


5508
GGCGAGCU G CAUCCCCU
5788
AGGGGATG GGCTAGCTACAACGA AGCTCGCC
14537


5506
CGAGCUGC A UCCCCUGU
5789
ACAGGGGA GGCTAGCTACAACGA GCAGCTCG
14538


5499
CAUCCCCU G UUCGAUGU
5790
ACATCGAA GGCTAGCTACAACGA AGGGGATG
14539


5494
CCUGUUCG A UGUAAGGG
5791
CCCTTACA GGCTAGCTACAACGA CGAACAGG
14540


5492
UGUUCGAU G UAAGGGAG
5792
CTCCCTTA GGCTAGCTACAACGA ATCGAACA
14541


5483
UAAGGGAG G UGUGAGGC
5793
GCCTCACA GGCTAGCTACAACGA CTCCCTTA
14542


5481
AGGGAGGU G UGAGGCAC
5794
GTGCCTCA GGCTAGCTACAACGA ACCTCCCT
14543


5476
GGUGUGAG G CACACUCC
5795
GGAGTGTG GGCTAGCTACAACGA CTCACACC
14544


5474
UGUGAGGC A CACUCCUC
5796
GAGGAGTG GGCTAGCTACAACGA GCCTCACA
14545


5472
UGAGGCAC A CUCCUCCA
5797
TGGAGGAG GGCTAGCTACAACGA GTGCCTCA
14546


5464
ACUCCUCC A UCUCAUCG
5798
CGATGAGA GGCTAGCTACAACGA GGAGGAGT
14547


5459
UCCAUCUC A UCGAACUC
5799
GAGTTCGA GGCTAGCTACAACGA GAGATGGA
14548


5454
CUCAUCGA A CUCCUGGU
5800
ACCAGGAG GGCTAGCTACAACGA TCGATGAG
14549


5447
AACUCCUG G UAGAGAGC
5801
GCTCTCTA GGCTAGCTACAACGA CAGGAGTT
14550


5440
GGUAGAGA G CCUCCCUG
5802
CAGGGAGG GGCTAGCTACAACGA TCTCTACC
14551


5432
GCCUCCCU G UCGGGGAU
5803
ATCCCCGA GGCTAGCTACAACGA AGGGAGGC
14552


5425
UGUCGGGG A UAACAGCC
5804
GGCTGTTA GGCTAGCTACAACGA CCCCGACA
14553


5422
CGGGGAUA A CAGCCGGC
5805
GCCGGCTG GGCTAGCTACAACGA TATCCCCG
14554


5419
GGAUAACA G CCGGCUUC
5806
GAAGCCGG GGCTAGCTACAACGA TGTTATCC
14555


5415
AACAGCCG G CUUCCCGG
5807
CCGGGAAG GGCTAGCTACAACGA CGGCTGTT
14556


5406
CUUCCCGG A CAAGAUGA
5808
TCATCTTG GGCTAGCTACAACGA CCGGGAAG
14557


5401
CGGACAAG A UGAUUCUG
5809
CAGAATCA GGCTAGCTACAACGA CTTGTCCG
14558


5398
ACAAGAUG A UUCUGCCC
5810
GGGCAGAA GGCTAGCTACAACGA CATCTTGT
14559


5393
AUGAUUCU G CCCACAAU
5811
ATTGTGGG GGCTAGCTACAACGA AGAATCAT
14560


5389
UUCUGCCC A CAAUGACC
5812
GGTCATTG GGCTAGCTACAACGA GGGCAGAA
14561


5386
UGCCCACA A UGACCACG
5813
CGTGGTCA GGCTAGCTACAACGA TGTGGGCA
14562


5383
CCACAAUG A CCACGCUG
5814
CAGCGTGG GGCTAGCTACAACGA CATTGTGG
14563


5380
CAAUGACC A CGCUGCCU
5815
AGGCAGCG GGCTAGCTACAACGA GGTCATTG
14564


5378
AUGACCAC G CUGCCUGU
5816
ACAGGCAG GGCTAGCTACAACGA GTGGTCAT
14565


5375
ACCACGCU G CCUGUCGU
5817
ACGACAGG GGCTAGCTACAACGA AGCGTGGT
14566


5371
CGCUGCCU G UCGUCAGG
5818
CCTGACGA GGCTAGCTACAACGA AGGCAGCG
14567


5368
UGCCUGUC G UCAGGCAA
5819
TTGCCTGA GGCTAGCTACAACGA GACAGGCA
14568


5363
GUCGUCAG G CAAUACGC
5820
GCGTATTG GGCTAGCTACAACGA CTGACGAC
14569


5360
GUCAGGCA A UACGCGGU
5821
ACCGCGTA GGCTAGCTACAACGA TGCCTGAC
14570


5358
CAGGCAAU A CGCGGUCA
5822
TGACCGCG GGCTAGCTACAACGA ATTGCCTG
14571


5356
GGCAAUAC G CGGUCAGA
5823
TCTGACCG GGCTAGCTACAACGA GTATTGCC
14572


5353
AAUACGCG G UCAGAGCU
5824
AGCTCTGA GGCTAGCTACAACGA CGCGTATT
14573


5347
CGGUCAGA G CUGCCAGG
5825
CCTGGCAG GGCTAGCTACAACGA TCTGACCG
14574


5344
UCAGAGCU G CCAGGACG
5826
CGTCCTGG GGCTAGCTACAACGA AGCTCTGA
14575


5338
CUGCCAGG A CGCCACCU
5827
AGGTGGCG GGCTAGCTACAACGA CCTGGCAG
14576


5336
GCCAGGAC G CCACCUAC
5828
GTAGGTGG GGCTAGCTACAACGA GTCCTGGC
14577


5333
AGGACGCC A CCUACUAG
5829
CTAGTAGG GGCTAGCTACAACGA GGCGTCCT
14578


5329
CGCCACCU A CUAGCACC
5830
GGTGCTAG GGCTAGCTACAACGA AGGTGGCG
14579


5325
ACCUACUA G CACCCAGG
5831
CCTGGGTG GGCTAGCTACAACGA TAGTAGGT
14580


5323
CUACUAGC A CCCAGGUG
5832
CACCTGGG GGCTAGCTACAACGA GCTAGTAG
14581


5317
GCACCCAG G UGCUGGUG
5833
CACCAGCA GGCTAGCTACAACGA CTGGGTGC
14582


5315
ACCCAGGU G CUGGUGAC
5834
GTCACCAG GGCTAGCTACAACGA ACCTGGGT
14583


5311
AGGUGCUG G UGACGACC
5835
GGTCGTCA GGCTAGCTACAACGA CAGCACCT
14584


5308
UGCUGGUG A CGACCUCC
5836
GGAGGTCG GGCTAGCTACAACGA CACCAGCA
14585


5305
UGGUGACG A CCUCCAGG
5837
CCTGGAGG GGCTAGCTACAACGA CGTCACCA
14586


5297
ACCUCCAG G UCAGCCGA
5838
TCGGCTGA GGCTAGCTACAACGA CTGGAGGT
14587


5293
CCAGGUCA G CCGACAUG
5839
CATGTCGG GGCTAGCTACAACGA TGACCTGG
14588


5289
GUCAGCCG A CAUGCAUG
5840
CATGCATG GGCTAGCTACAACGA CGGCTGAC
14589


5287
CAGCCGAC A UGCAUGUC
5841
GACATGCA GGCTAGCTACAACGA GTCGGCTG
14590


5285
GCCGACAU G CAUGUCAU
5842
ATGACATG GGCTAGCTACAACGA ATGTCGGC
14591


5283
CGACAUGC A UGUCAUGA
5843
TCATGACA GGCTAGCTACAACGA GCATGTCG
14592


5281
ACAUGCAU G UCAUGAUG
5844
CATCATGA GGCTAGCTACAACGA ATGCATGT
14593


5278
UGCAUGUC A UGAUGUAU
5845
ATACATCA GGCTAGCTACAACGA GACATGCA
14594


5275
AUGUCAUG A UGUAUUUG
5846
CAAATACA GGCTAGCTACAACGA CATGACAT
14595


5273
GUCAUGAU G UAUUUGGU
5847
ACCAAATA GGCTAGCTACAACGA ATCATGAC
14596


5271
CAUGAUGU A UUUGGUUA
5848
TAACCAAA GGCTAGCTACAACGA ACATCATG
14597


5266
UGUAUUUG G UUAUGGGG
5849
CCCCATAA GGCTAGCTACAACGA CAAATACA
14598


5263
AUUUGGUU A UGGGGUGU
5850
ACACCCCA GGCTAGCTACAACGA AACCAAAT
14599


5258
GUUAUGGG G UGUGUGAG
5851
CTCACACA GGCTAGCTACAACGA CCCATAAC
14600


5256
UAUGGGGU G UGUGAGGG
5852
CCCTCACA GGCTAGCTACAACGA ACCCCATA
14601


5254
UGGGGUGU G UGAGGGUG
5853
CACCCTCA GGCTAGCTACAACGA ACACCCCA
14602


5248
GUGUGAGG G UGACAUCA
5854
TGATGTCA GGCTAGCTACAACGA CCTCACAC
14603


5245
UGAGGGUG A CAUCAUUU
5855
AAATGATG GGCTAGCTACAACGA CACCCTCA
14604


5243
AGGGUGAC A UCAUUUUG
5856
CAAAATGA GGCTAGCTACAACGA GTCACCCT
14605


5240
GUGACAUC A UUUUGGAC
5857
GTCCAAAA GGCTAGCTACAACGA GATGTCAC
14606


5233
CAUUUUGG A CGGCUCCU
5858
AGGAGCCG GGCTAGCTACAACGA CCAAAATG
14607


5230
UUUGGACG G CUCCUAGC
5859
GCTAGGAG GGCTAGCTACAACGA CGTCCAAA
14608


5223
GGCUCCUA G CCUAUACA
5860
TGTATAGG GGCTAGCTACAACGA TAGGAGCC
14609


5219
CCUAGCCU A UACAGCAG
5861
CTGCTGTA GGCTAGCTACAACGA AGGCTAGG
14610


5217
UAGCCUAU A CAGCAGGG
5862
CCCTGCTG GGCTAGCTACAACGA ATAGGCTA
14611


5214
CCUAUACA G CAGGGGUG
5863
CACCCCTG GGCTAGCTACAACGA TGTATAGG
14612


5208
CAGCAGGG G UGUUGGCC
5864
GGCCAACA GGCTAGCTACAACGA CCCTGCTG
14613


5206
GCAGGGGU G UUGGCCCG
5865
CGGGCCAA GGCTAGCTACAACGA ACCCCTGC
14614


5202
GGGUGUUG G CCCGUGUA
5866
TACACGGG GGCTAGCTACAACGA CAACACCC
14615


5198
GUUGGCCC G UGUAGCGU
5867
ACGCTACA GGCTAGCTACAACGA GGGCCAAC
14616


5196
UGGCCCGU G UAGCGUAG
5868
CTACGCTA GGCTAGCTACAACGA ACGGGCCA
14617


5193
CCCGUGUA G CGUAGGCU
5869
AGCCTACG GGCTAGCTACAACGA TACACGGG
14618


5191
CGUGUAGC G UAGGCUUU
5870
AAAGCCTA GGCTAGCTACAACGA GCTACACG
14619


5187
UAGCGUAG G CUUUAGCC
5871
GGCTAAAG GGCTAGCTACAACGA CTACGCTA
14620


5181
AGGCUUUA G CCGUGUGA
5872
TCACACGG GGCTAGCTACAACGA TAAAGCCT
14621


5178
CUUUAGCC G UGUGAGAC
5873
GTCTCACA GGCTAGCTACAACGA GGCTAAAG
14622


5176
UUAGCCGU G UGAGACAC
5874
GTGTCTCA GGCTAGCTACAACGA ACGGCTAA
14623


5171
CGUGUGAG A CACUUCCA
5875
TGGAAGTG GGCTAGCTACAACGA CTCACACG
14624


5169
UGUGAGAC A CUUCCACA
5876
TGTGGAAG GGCTAGCTACAACGA GTCTCACA
14625


5163
ACACUUCC A CAUUUGAU
5877
ATCAAATG GGCTAGCTACAACGA GGAAGTGT
14626


5161
ACUUCCAC A UUUGAUCC
5878
GGATCAAA GGCTAGCTACAACGA GTGGAAGT
14627


5156
CACAUUUG A UCCCACGA
5879
TCGTGGGA GGCTAGCTACAACGA CAAATGTG
14628


5151
UUGAUCCC A CGAUGGGG
5880
CCCCATCG GGCTAGCTACAACGA GGGATCAA
14629


5148
AUCCCACG A UGGGGGUG
5881
CACCCCCA GGCTAGCTACAACGA CGTGGGAT
14630


5142
CGAUGGGG G UGGAGCCU
5882
AGGCTCCA GGCTAGCTACAACGA CCCCATCG
14631


5137
GGGGUGGA G CCUGAGCC
5883
GGCTCAGG GGCTAGCTACAACGA TCCACCCC
14632


5131
GAGCCUGA G CCCUGGCG
5884
CGCCAGGG GGCTAGCTACAACGA TCAGGCTC
14633


5125
GAGCCCUG G CGCACACU
5885
AGTGTGCG GGCTAGCTACAACGA CAGGGCTC
14634


5123
GCCCUGGC G CACACUGU
5886
ACAGTGTG GGCTAGCTACAACGA GCCAGGGC
14635


5121
CCUGGCGC A CACUGUGG
5887
CCACAGTG GGCTAGCTACAACGA GCGCCAGG
14636


5119
UGGCGCAC A CUGUGGCU
5888
AGCCACAG GGCTAGCTACAACGA GTGCGCCA
14637


5116
CGCACACU G UGGCUUGG
5889
CCAAGCCA GGCTAGCTACAACGA AGTGTGCG
14638


5113
ACACUGUG G CUUGGUAU
5890
ATACCAAG GGCTAGCTACAACGA CACAGTGT
14639


5108
GUGGCUUG G UAUGCUAC
5891
GTAGCATA GGCTAGCTACAACGA CAAGCCAC
14640


5106
GGCUUGGU A UGCUACCA
5892
TGGTAGCA GGCTAGCTACAACGA ACCAAGCC
14641


5104
CUUGGUAU G CUACCAGG
5893
CCTGGTAG GGCTAGCTACAACGA ATACCAAG
14642


5101
GGUAUGCU A CCAGGUAG
5894
CTACCTGG GGCTAGCTACAACGA AGCATACC
14643


5096
GCUACCAG G UAGGGGAG
5895
CTCCCCTA GGCTAGCTACAACGA CTGGTAGC
14644


5087
UAGGGGAG G UUUUCUCC
5896
GGAGAAAA GGCTAGCTACAACGA CTCCCCTA
14645


5077
UUUCUCCU G CCUGCUUG
5897
CAAGCAGG GGCTAGCTACAACGA AGGAGAAA
14646


5073
UCCUGCCU G CUUGGUCU
5898
AGACCAAG GGCTAGCTACAACGA AGGCAGGA
14647


5068
CCUGCUUG G UCUGGGAC
5899
GTCCCAGA GGCTAGCTACAACGA CAAGCAGG
14648


5061
GGUCUGGG A CAAGAAGU
5900
ACTTCTTG GGCTAGCTACAACGA CCCAGACC
14649


5054
GACAAGAA G UGGGCAUC
5901
GATGCCCA GGCTAGCTACAACGA TTCTTGTC
14650


5050
AGAAGUGG G CAUCUAUG
5902
CATAGATG GGCTAGCTACAACGA CCACTTCT
14651


5048
AAGUGGGC A UCUAUGUG
5903
CACATAGA GGCTAGCTACAACGA GCCCACTT
14652


5044
GGGCAUCU A UGUGGGUG
5904
CACCCACA GGCTAGCTACAACGA AGATGCCC
14653


5042
GCAUCUAU G UGGGUGAG
5905
CTCACCCA GGCTAGCTACAACGA ATAGATGC
14654


5038
CUAUGUGG G UGAGGCCU
5906
AGGCCTCA GGCTAGCTACAACGA CCACATAG
14655


5033
UGGGUGAG G CCUGUGAA
5907
TTCACAGG GGCTAGCTACAACGA CTCACCCA
14656


5029
UGAGGCCU G UGAAGACA
5908
TGTCTTCA GGCTAGCTACAACGA AGGCCTCA
14657


5023
CUGUGAAG A CACCCUCC
5909
GGAGGGTG GGCTAGCTACAACGA CTTCACAG
14658


5021
GUGAAGAC A CCCUCCCA
5910
TGGGAGGG GGCTAGCTACAACGA GTCTTCAC
14659


5010
CUCCCAGA A CUCCAGAU
5911
ATCTGGAG GGCTAGCTACAACGA TCTGGGAG
14660


5003
AACUCCAG A UGGUCCUG
5912
CAGGACCA GGCTAGCTACAACGA CTGGAGTT
14661


5000
UCCAGAUG G UCCUGGCA
5913
TGCCAGGA GGCTAGCTACAACGA CATCTGGA
14662


4994
UGGUCCUG G CAGAAGGG
5914
CCCTTCTG GGCTAGCTACAACGA CAGGACCA
14663


4986
GCAGAAGG G CAACCCUG
5915
CAGGGTTG GGCTAGCTACAACGA CCTTCTGC
14664


4983
GAAGGGCA A CCCUGGUG
5916
CACCAGGG GGCTAGCTACAACGA TGCCCTTC
14665


4977
CAACCCUG G UGUAUUUA
5917
TAAATACA GGCTAGCTACAACGA CAGGGTTG
14666


4975
ACCCUGGU G UAUUUAGG
5918
CCTAAATA GGCTAGCTACAACGA ACCAGGGT
14667


4973
CCUGGUGU A UUUAGGUA
5919
TACCTAAA GGCTAGCTACAACGA ACACCAGG
14668


4967
GUAUUUAG G UAAGCCCG
5920
CGGGCTTA GGCTAGCTACAACGA CTAAATAC
14669


4963
UUAGGUAA G CCCGCAAC
5921
GTTGCGGG GGCTAGCTACAACGA TTACCTAA
14670


4959
GUAAGCCC G CAACCUAA
5922
TTAGGTTG GGCTAGCTACAACGA GGGCTTAC
14671


4956
AGCCCGCA A CCUAACGG
5923
CCGTTAGG GGCTAGCTACAACGA TGCGGGCT
14672


4951
GCAACCUA A CGGAGGUC
5924
GACCTCCG GGCTAGCTACAACGA TAGGTTGC
14673


4945
UAACGGAG G UCUCGGCG
5925
CGCCGAGA GGCTAGCTACAACGA CTCCGTTA
14674


4939
AGGUCUCG G CGGGCGUG
5926
CACGCCCG GGCTAGCTACAACGA CGAGACCT
14675


4935
CUCGGCGG G CGUGAGCU
5927
AGCTCACG GGCTAGCTACAACGA CCGCCGAG
14676


4933
CGGCGGGC G UGAGCUCG
5928
CGAGCTCA GGCTAGCTACAACGA GCCCGCCG
14677


4929
GGGCGUGA G CUCGUACC
5929
GGTACGAG GGCTAGCTACAACGA TCACGCCC
14678


4925
GUGAGCUC G UACCAAGC
5930
GCTTGGTA GGCTAGCTACAACGA GAGCTCAC
14679


4923
GAGCUCGU A CCAAGCAC
5931
GTGCTTGG GGCTAGCTACAACGA ACGAGCTC
14680


4918
CGUACCAA G CACAUCCC
5932
GGGATGTG GGCTAGCTACAACGA TTGGTACG
14681


4916
UACCAAGC A CAUCCCGC
5933
GCGGGATG GGCTAGCTACAACGA GCTTGGTA
14682


4914
CCAAGCAC A UCCCGCGU
5934
ACGCGGGA GGCTAGCTACAACGA GTGCTTGG
14683


4909
CACAUCCC G CGUCAUAG
5935
CTATGACG GGCTAGCTACAACGA GGGATGTG
14684


4907
CAUCCCGC G UCAUAGCA
5936
TGCTATGA GGCTAGCTACAACGA GCGGGATG
14685


4904
CCCGCGUC A UAGCACUC
5937
GAGTGCTA GGCTAGCTACAACGA GACGCGGG
14686


4901
GCGUCAUA G CACUCACA
5938
TGTGAGTG GGCTAGCTACAACGA TATGACGC
14687


4899
GUCAUAGC A CUCACACA
5939
TGTGTGAG GGCTAGCTACAACGA GCTATGAC
14688


4895
UAGCACUC A CACAGGAC
5940
GTCCTGTG GGCTAGCTACAACGA GAGTGCTA
14689


4893
GCACUCAC A CAGGACCG
5941
CGGTCCTG GGCTAGCTACAACGA GTGAGTGC
14690


4888
CACACAGG A CCGAGGAG
5942
CTCCTCGG GGCTAGCTACAACGA CCTGTGTG
14691


4880
ACCGAGGA G UCGAACAU
5943
ATGTTCGA GGCTAGCTACAACGA TCCTCGGT
14692


4875
GGAGUCGA A CAUGCCCG
5944
CGGGCATG GGCTAGCTACAACGA TCGACTCC
14693


4873
AGUCGAAC A UGCCCGAA
5945
TTCGGGCA GGCTAGCTACAACGA GTTCGACT
14694


4871
UCGAACAU G CCCGAAGG
5946
CCTTCGGG GGCTAGCTACAACGA ATGTTCGA
14695


4863
GCCCGAAG G CCGCUCUC
5947
GAGAGCGG GGCTAGCTACAACGA CTTCGGGC
14696


4860
CGAAGGCC G CUCUCCUG
5948
CAGGAGAG GGCTAGCTACAACGA GGCCTTCG
14697


4849
CUCCUGGA G UCACAAAC
5949
GTTTGTGA GGCTAGCTACAACGA TCCAGGAG
14698


4846
CUGGAGUC A CAAACCUG
5950
CAGGTTTG GGCTAGCTACAACGA GACTCCAG
14699


4842
AGUCACAA A CCUGUAUA
5951
TATACAGG GGCTAGCTACAACGA TTGTGACT
14700


4838
ACAAACCU G UAUAUGCC
5952
GGCATATA GGCTAGCTACAACGA AGGTTTGT
14701


4836
AAACCUGU A UAUGCCUC
5953
GAGGCATA GGCTAGCTACAACGA ACAGGTTT
14702


4834
ACCUGUAU A UGCCUCUC
5954
GAGAGGCA GGCTAGCTACAACGA ATACAGGT
14703


4832
CUGUAUAU G CCUCUCCU
5955
AGGAGAGG GGCTAGCTACAACGA ATATACAG
14704


4823
CCUCUCCU G CCCCUACC
5956
GGTAGGGG GGCTAGCTACAACGA AGGAGAGG
14705


4817
CUGCCCCU A CCGGUCCU
5957
AGGACCGG GGCTAGCTACAACGA AGGGGCAG
14706


4813
CCCUACCG G UCCUACCU
5958
AGGTAGGA GGCTAGCTACAACGA CGGTAGGG
14707


4808
CCGGUCCU A CCUCGCCU
5959
AGGCGAGG GGCTAGCTACAACGA AGGACCGG
14708


4803
CCUACCUC G CCUCUGCG
5960
CGCAGAGG GGCTAGCTACAACGA GAGGTAGG
14709


4797
UCGCCUCU G CGAGCGGG
5961
CCCGCTCG GGCTAGCTACAACGA AGAGGCGA
14710


4793
CUCUGCGA G CGGGACAC
5962
GTGTCCCG GGCTAGCTACAACGA TCGCAGAG
14711


4788
CGAGCGGG A CACUGCGU
5963
ACGCAGTG GGCTAGCTACAACGA CCCGCTCG
14712


4786
AGCGGGAC A CUGCGUCU
5964
AGACGCAG GGCTAGCTACAACGA GTCCCGCT
14713


4783
GGGACACU G CGUCUUGG
5965
CCAAGACG GGCTAGCTACAACGA AGTGTCCC
14714


4781
GACACUGC G UCUUGGGG
5966
CCCCAAGA GGCTAGCTACAACGA GCAGTGTC
14715


4773
GUCUUGGG G CACGGUCG
5967
CGACCGTG GGCTAGCTACAACGA CCCAAGAC
14716


4771
CUUGGGGC A CGGUCGUC
5968
GACGACCG GGCTAGCTACAACGA GCCCCAAG
14717


4768
GGGGCACG G UCGUCGUC
5969
GACGACGA GGCTAGCTACAACGA CGTGCCCC
14718


4765
GCACGGUC G UCGUCUCA
5970
TGAGACGA GGCTAGCTACAACGA GACCGTGC
14719


4762
CGGUCGUC G UCUCAAUG
5971
CATTGAGA GGCTAGCTACAACGA GACGACCG
14720


4756
UCGUCUCA A UGGUGAAG
5972
CTTCACCA GGCTAGCTACAACGA TGAGACGA
14721


4753
UCUCAAUG G UGAAGGUA
5973
TACCTTCA GGCTAGCTACAACGA CATTGAGA
14722


4747
UGGUGAAG G UAGGGUCC
5974
GGACCCTA GGCTAGCTACAACGA CTTCACCA
14723


4742
AAGGUAGG G UCCAAGCU
5975
AGCTTGGA GGCTAGCTACAACGA CCTACCTT
14724


4736
GGGUCCAA G CUGAAGUC
5976
GACTTCAG GGCTAGCTACAACGA TTGGACCC
14725


4730
AAGCUGAA G UCGACUGU
5977
ACAGTCGA GGCTAGCTACAACGA TTCAGCTT
14726


4726
UGAAGUCG A CUGUUUGG
5978
CCAAACAG GGCTAGCTACAACGA CGACTTCA
14727


4723
AGUCGACU G UUUGGGUG
5979
CACCCAAA GGCTAGCTACAACGA AGTCGACT
14728


4717
CUGUUUGG G UGACACAU
5980
ATGTGTCA GGCTAGCTACAACGA CCAAACAG
14729


4714
UUUGGGUG A CACAUGUA
5981
TACATGTG GGCTAGCTACAACGA CACCCAAA
14730


4712
UGGGUGAC A CAUGUAUU
5982
AATACATG GGCTAGCTACAACGA GTCACCCA
14731


4710
GGUGACAC A UGUAUUAC
5983
GTAATACA GGCTAGCTACAACGA GTGTCACC
14732


4708
UGACACAU G UAUUACAG
5984
CTGTAATA GGCTAGCTACAACGA ATGTGTCA
14733


4706
ACACAUGU A UUACAGUC
5985
GACTGTAA GGCTAGCTACAACGA ACATGTGT
14734


4703
CAUGUAUU A CAGUCGAU
5986
ATCGACTG GGCTAGCTACAACGA AATACATG
14735


4700
GUAUUACA G UCGAUCAC
5987
GTGATCGA GGCTAGCTACAACGA TGTAATAC
14736


4696
UACAGUCG A UCACCGAG
5988
CTCGGTGA GGCTAGCTACAACGA CGACTGTA
14737


4693
AGUCGAUC A CCGAGUCA
5989
TGACTCGG GGCTAGCTACAACGA GATCGACT
14738


4688
AUCACCGA G UCAAAAUC
5990
GATTTTGA GGCTAGCTACAACGA TCGGTGAT
14739


4682
GAGUCAAA A UCGCCGGU
5991
ACCGGCGA GGCTAGCTACAACGA TTTGACTC
14740


4679
UCAAAAUC G CCGGUAUA
5992
TATACCGG GGCTAGCTACAACGA GATTTTGA
14741


4675
AAUCGCCG G UAUAGCCC
5993
GGGCTATA GGCTAGCTACAACGA CGGCGATT
14742


4673
UCGCCGGU A UAGCCCGU
5994
ACGGGCTA GGCTAGCTACAACGA ACCGGCGA
14743


4670
CCGGUAUA G CCCGUCAU
5995
ATGACGGG GGCTAGCTACAACGA TATACCGG
14744


4666
UAUAGCCC G UCAUUAGA
5996
TCTAATGA GGCTAGCTACAACGA GGGCTATA
14745


4663
AGCCCGUC A UUAGAGCG
5997
CGCTCTAA GGCTAGCTACAACGA GACGGGCT
14746


4657
UCAUUAGA G CGUCUGUU
5998
AACAGACG GGCTAGCTACAACGA TCTAATGA
14747


4655
AUUAGAGC G UCUGUUGC
5999
GCAACAGA GGCTAGCTACAACGA GCTCTAAT
14748


4651
GAGCGUCU G UUGCCACG
6000
CGTGGCAA GGCTAGCTACAACGA AGACGCTC
14749


4648
CGUCUGUU G CCACGACA
6001
TGTCGTGG GGCTAGCTACAACGA AACAGACG
14750


4645
CUGUUGCC A CGACAACG
6002
CGTTGTCG GGCTAGCTACAACGA GGCAACAG
14751


4642
UUGCCACG A CAACGACG
6003
CGTCGTTG GGCTAGCTACAACGA CGTGGCAA
14752


4639
CCACGACA A CGACGUCC
6004
GGACGTCG GGCTAGCTACAACGA TGTCGTGG
14753


4636
CGACAACG A CGUCCCCG
6005
CGGGGACG GGCTAGCTACAACGA CGTTGTCG
14754


4634
ACAACGAC G UCCCCGCU
6006
AGCGGGGA GGCTAGCTACAACGA GTCGTTGT
14755


4628
ACGUCCCC G CUGGCCGG
6007
CCGGCCAG GGCTAGCTACAACGA GGGGACGT
14756


4624
CCCCGCUG G CCGGUAUG
6008
CATACCGG GGCTAGCTACAACGA CAGCGGGG
14757


4620
GCUGGCCG G UAUGACGG
6009
CCGTCATA GGCTAGCTACAACGA CGGCCAGC
14758


4618
UGGCCGGU A UGACGGAC
6010
GTCCGTCA GGCTAGCTACAACGA ACCGGCCA
14759


4615
CCGGUAUG A CGGACACG
6011
CGTGTCCG GGCTAGCTACAACGA CATACCGG
14760


4611
UAUGACGG A CACGUCGA
6012
TCGACGTG GGCTAGCTACAACGA CCGTCATA
14761


4609
UGACGGAC A CGUCGAGA
6013
TCTCGACG GGCTAGCTACAACGA GTCCGTCA
14762


4607
ACGGACAC G UCGAGACC
6014
GGTCTCGA GGCTAGCTACAACGA GTGTCCGT
14763


4601
ACGUCGAG A CCCCGGUA
6015
TACCGGGG GGCTAGCTACAACGA CTCGACGT
14764


4595
AGACCCCG G UAAUACGC
6016
GCGTATTA GGCTAGCTACAACGA CGGGGTCT
14765


4592
CCCCGGUA A UACGCUAC
6017
GTAGCGTA GGCTAGCTACAACGA TACCGGGG
14766


4590
CCGGUAAU A CGCUACAG
6018
CTGTAGCG GGCTAGCTACAACGA ATTACCGG
14767


4588
GGUAAUAC G CUACAGCG
6019
CGCTGTAG GGCTAGCTACAACGA GTATTACC
14768


4585
AAUACGCU A CAGCGUUA
6020
TAACGCTG GGCTAGCTACAACGA AGCGTATT
14769


4582
ACGCUACA G CGUUAAGU
6021
ACTTAACG GGCTAGCTACAACGA TGTAGCGT
14770


4580
GCUACAGC G UUAAGUCC
6022
GGACTTAA GGCTAGCTACAACGA GCTGTAGC
14771


4575
AGCGUUAA G UCCGAGGC
6023
GCCTCGGA GGCTAGCTACAACGA TTAACGCT
14772


4568
AGUCCGAG G CCCGACAG
6024
CTGTCGGG GGCTAGCTACAACGA CTCGGACT
14773


4563
GAGGCCCG A CAGCUUUG
6025
CAAAGCTG GGCTAGCTACAACGA CGGGCCTC
14774


4560
GCCCGACA G CUUUGCAG
6026
CTGCAAAG GGCTAGCTACAACGA TGTCGGGC
14775


4555
ACAGCUUU G CAGCGAGC
6027
GCTCGCTG GGCTAGCTACAACGA AAAGCTGT
14776


4552
GCUUUGCA G CGAGCUCG
6028
CGAGCTCG GGCTAGCTACAACGA TGCAAAGC
14777


4548
UGCAGCGA G CUCGUCAC
6029
GTGACGAG GGCTAGCTACAACGA TCGCTGCA
14778


4544
GCGAGCUC G UCACAUUU
6030
AAATGTGA GGCTAGCTACAACGA GAGCTCGC
14779


4541
AGCUCGUC A CAUUUCUU
6031
AAGAAATG GGCTAGCTACAACGA GACGAGCT
14780


4539
CUCGUCAC A UUUCUUCU
6032
AGAAGAAA GGCTAGCTACAACGA GTGACGAG
14781


4526
UUCUUGGA A UGGCAGAA
6033
TTCTGCCA GGCTAGCTACAACGA TCCAAGAA
14782


4523
UUGGAAUG G CAGAAGAU
6034
ATCTTCTG GGCTAGCTACAACGA CATTCCAA
14783


4516
GGCAGAAG A UGAGAUGC
6035
GCATCTCA GGCTAGCTACAACGA CTTCTGCC
14784


4511
AAGAUGAG A UGCCUCCC
6036
GGGAGGCA GGCTAGCTACAACGA CTCATCTT
14785


4509
GAUGAGAU G CCUCCCCC
6037
GGGGGAGG GGCTAGCTACAACGA ATCTCATC
14786


4495
CCCCUUUG A UGGUCUCG
6038
CGAGACCA GGCTAGCTACAACGA CAAAGGGG
14787


4492
CUUUGAUG G UCUCGAUG
6039
CATCGAGA GGCTAGCTACAACGA CATCAAAG
14788


4486
UGGUCUCG A UGGGGAUG
6040
CATCCCCA GGCTAGCTACAACGA CGAGACCA
14789


4480
CGAUGGGG A UGGCUUUG
6041
CAAAGCCA GGCTAGCTACAACGA CCCCATCG
14790


4477
UGGGGAUG G CUUUGCCA
6042
TGGCAAAG GGCTAGCTACAACGA CATCCCCA
14791


4472
AUGGCUUU G CCAUAGAA
6043
TTCTATGG GGCTAGCTACAACGA AAAGCCAT
14792


4469
GCUUUGCC A UAGAAGGG
6044
CCCTTCTA GGCTAGCTACAACGA GGCAAAGC
14793


4459
AGAAGGGG A UCUCUCCG
6045
CGGAGAGA GGCTAGCTACAACGA CCCCTTCT
14794


4450
UCUCUCCG G UGUUGGAC
6046
GTCCAACA GGCTAGCTACAACGA CGGAGAGA
14795


4448
UCUCCGGU G UUGGACAA
6047
TTGTCCAA GGCTAGCTACAACGA ACCGGAGA
14796


4443
GGUGUUGG A CAAGGCUA
6048
TAGCCTTG GGCTAGCTACAACGA CCAACACC
14797


4438
UGGACAAG G CUAUCUCC
6049
GGAGATAG GGCTAGCTACAACGA CTTGTCCA
14798


4435
ACAAGGCU A UCUCCUCG
6050
CGAGGAGA GGCTAGCTACAACGA AGCCTTGT
14799


4426
UCUCCUCG A UGUUGGGA
6051
TCCCAACA GGCTAGCTACAACGA CGAGGAGA
14800


4424
UCCUCGAU G UUGGGAUG
6052
CATCCCAA GGCTAGCTACAACGA ATCGAGGA
14801


4418
AUGUUGGG A UGUGGCAC
6053
GTGCCACA GGCTAGCTACAACGA CCCAACAT
14802


4416
GUUGGGAU G UGGCACGG
6054
CCGTGCCA GGCTAGCTACAACGA ATCCCAAC
14803


4413
GGGAUGUG G CACGGUGA
6055
TCACCGTG GGCTAGCTACAACGA CACATCCC
14804


4411
GAUGUGGC A CGGUGACC
6056
GGTCACCG GGCTAGCTACAACGA GCCACATC
14805


4408
GUGGCACG G UGACCGAU
6057
ATCGGTCA GGCTAGCTACAACGA CGTGCCAC
14806


4405
GCACGGUG A CCGAUCCC
6058
GGGATCGG GGCTAGCTACAACGA CACCGTGC
14807


4401
GGUGACCG A UCCCGGAG
6059
CTCCGGGA GGCTAGCTACAACGA CGGTCACC
14808


4392
UCCCGGAG G CGUAGCGG
6060
CCGCTACG GGCTAGCTACAACGA CTCCGGGA
14809


4390
CCGGAGGC G UAGCGGUG
6061
CACCGCTA GGCTAGCTACAACGA GCCTCCGG
14810


4387
GAGGCGUA G CGGUGGCG
6062
CGCCACCG GGCTAGCTACAACGA TACGCCTC
14811


4384
GCGUAGCG G UGGCGAGC
6063
GCTCGCCA GGCTAGCTACAACGA CGCTACGC
14812


4381
UAGCGGUG G CGAGCACG
6064
CGTGCTCG GGCTAGCTACAACGA CACCGCTA
14813


4377
GGUGGCGA G CACGACGA
6065
TCGTCGTG GGCTAGCTACAACGA TCGCCACC
14814


4375
UGGCGAGC A CGACGAGC
6066
GCTCGTCG GGCTAGCTACAACGA GCTCGCCA
14815


4372
CGAGCACG A CGAGCCGC
6067
GCGGCTCG GGCTAGCTACAACGA CGTGCTCG
14816


4368
CACGACGA G CCGCGCUC
6068
GAGCGCGG GGCTAGCTACAACGA TCGTCGTG
14817


4365
GACGAGCC G CGCUCCAG
6069
CTGGAGCG GGCTAGCTACAACGA GGCTCGTC
14818


4363
CGAGCCGC G CUCCAGCC
6070
GGCTGGAG GGCTAGCTACAACGA GCGGCTCG
14819


4357
GCGCUCCA G CCGUCUCC
6071
GGAGACGG GGCTAGCTACAACGA TGGAGCGC
14820


4354
CUCCAGCC G UCUCCGCU
6072
AGCGGAGA GGCTAGCTACAACGA GGCTGGAG
14821


4348
CCGUCUCC G CUUGGUCC
6073
GGACCAAG GGCTAGCTACAACGA GGAGACGG
14822


4343
UCCGCUUG G UCCAGGAC
6074
GTCCTGGA GGCTAGCTACAACGA CAAGCGGA
14823


4336
GGUCCAGG A CUGUGCCG
6075
CGGCACAG GGCTAGCTACAACGA CCTGGACC
14824


4333
CCAGGACU G UGCCGAUG
6076
CATCGGCA GGCTAGCTACAACGA AGTCCTGG
14825


4331
AGGACUGU G CCGAUGCC
6077
GGCATCGG GGCTAGCTACAACGA ACAGTCCT
14826


4327
CUGUGCCG A UGCCCAAA
6078
TTTGGGCA GGCTAGCTACAACGA CGGCACAG
14827


4325
GUGCCGAU G CCCAAAAU
6079
ATTTTGGG GGCTAGCTACAACGA ATCGGCAC
14828


4318
UGCCCAAA A UGGAAGUC
6080
GACTTCCA GGCTAGCTACAACGA TTTGGGCA
14829


4312
AAAUGGAA G UCGAGUCA
6081
TGACTCGA GGCTAGCTACAACGA TTCCATTT
14830


4307
GAAGUCGA G UCAAUUGA
6082
TCAATTGA GGCTAGCTACAACGA TCGACTTC
14831


4303
UCGAGUCA A UUGAGUGG
6083
CCACTCAA GGCTAGCTACAACGA TGACTCGA
14832


4298
UCAAUUGA G UGGCACUC
6084
GAGTGCCA GGCTAGCTACAACGA TCAATTGA
14833


4295
AUUGAGUG G CACUCAUC
6085
GATGAGTG GGCTAGCTACAACGA CACTCAAT
14834


4293
UGAGUGGC A CUCAUCAC
6086
GTGATGAG GGCTAGCTACAACGA GCCACTCA
14835


4289
UGGCACUC A UCACACAU
6087
ATGTGTGA GGCTAGCTACAACGA GAGTGCCA
14836


4286
CACUCAUC A CACAUUAU
6088
ATAATGTG GGCTAGCTACAACGA GATGAGTG
14837


4284
CUCAUCAC A CAUUAUGA
6089
TCATAATG GGCTAGCTACAACGA GTGATGAG
14838


4282
CAUCACAC A UUAUGAUG
6090
CATCATAA GGCTAGCTACAACGA GTGTGATG
14839


4279
CACACAUU A UGAUGUCA
6091
TGACATCA GGCTAGCTACAACGA AATGTGTG
14840


4276
ACAUUAUG A UGUCAUAG
6092
CTATGACA GGCTAGCTACAACGA CATAATGT
14841


4274
AUUAUGAU G UCAUAGGC
6093
GCCTATGA GGCTAGCTACAACGA ATCATAAT
14842


4271
AUGAUGUC A UAGGCGCC
6094
GGCGCCTA GGCTAGCTACAACGA GACATCAT
14843


4267
UGUCAUAG G CGCCCCCA
6095
TGGGGGCG GGCTAGCTACAACGA CTATGACA
14844


4265
UCAUAGGC G CCCCCAGA
6096
TCTGGGGG GGCTAGCTACAACGA GCCTATGA
14845


4256
CCCCCAGA G CAACCACC
6097
GGTGGTTG GGCTAGCTACAACGA TCTGGGGG
14846


4253
CCAGAGCA A CCACCGUC
6098
GACGGTGG GGCTAGCTACAACGA TGCTCTGG
14847


4250
GAGCAACC A CCGUCGGC
6099
GCCGACGG GGCTAGCTACAACGA GGTTGCTC
14848


4247
CAACCACC G UCGGCAAG
6100
CTTGCCGA GGCTAGCTACAACGA GGTGGTTG
14849


4243
CACCGUCG G CAAGGAAC
6101
GTTCCTTG GGCTAGCTACAACGA CGACGGTG
14850


4236
GGCAAGGA A CUUGCCAU
6102
ATGGCAAG GGCTAGCTACAACGA TCCTTGCC
14851


4232
AGGAACUU G CCAUAGGU
6103
ACCTATGG GGCTAGCTACAACGA AAGTTCCT
14852


4229
AACUUGCC A UAGGUGGA
6104
TCCACCTA GGCTAGCTACAACGA GGCAAGTT
14853


4225
UGCCAUAG G UGGAGUAC
6105
GTACTCCA GGCTAGCTACAACGA CTATGGCA
14854


4220
UAGGUGGA G UACGUGAU
6106
ATCACGTA GGCTAGCTACAACGA TCCACCTA
14855


4218
GGUGGAGU A CGUGAUGG
6107
CCATCACG GGCTAGCTACAACGA ACTCCACC
14856


4216
UGGAGUAC G UGAUGGGG
6108
CCCCATCA GGCTAGCTACAACGA GTACTCCA
14857


4213
AGUACGUG A UGGGGGCG
6109
CGCCCCCA GGCTAGCTACAACGA CACGTACT
14858


4207
UGAUGGGG G CGCCCGUG
6110
CACGGGCG GGCTAGCTACAACGA CCCCATCA
14859


4205
AUGGGGGC G CCCGUGGU
6111
ACCACGGG GGCTAGCTACAACGA GCCCCCAT
14860


4201
GGGCGCCC G UGGUGAUG
6112
CATCACCA GGCTAGCTACAACGA GGGCGCCC
14861


4198
CGCCCGUG G UGAUGGUC
6113
GACCATCA GGCTAGCTACAACGA CACGGGCG
14862


4195
CCGUGGUG A UGGUCCUU
6114
AAGGACCA GGCTAGCTACAACGA CACCACGG
14863


4192
UGGUGAUG G UCCUUACC
6115
GGTAAGGA GGCTAGCTACAACGA CATCACCA
14864


4186
UGGUCCUU A CCCCAGUU
6116
AACTGGGG GGCTAGCTACAACGA AAGGACCA
14865


4180
UUACCCCA G UUCUGAUG
6117
CATCAGAA GGCTAGCTACAACGA TGGGGTAA
14866


4174
CAGUUCUG A UGUUAGGA
6118
TCCTAACA GGCTAGCTACAACGA CAGAACTG
14867


4172
GUUCUGAU G UUAGGAUC
6119
GATCCTAA GGCTAGCTACAACGA ATCAGAAC
14868


4166
AUGUUAGG A UCGACACC
6120
GGTGTCGA GGCTAGCTACAACGA CCTAACAT
14869


4162
UAGGAUCG A CACCGUGU
6121
ACACGGTG GGCTAGCTACAACGA CGATCCTA
14870


4160
GGAUCGAC A CCGUGUGC
6122
GCACACGG GGCTAGCTACAACGA GTCGATCC
14871


4157
UCGACACC G UGUGCCUU
6123
AAGGCACA GGCTAGCTACAACGA GGTGTCGA
14872


4155
GACACCGU G UGCCUUAG
6124
CTAAGGCA GGCTAGCTACAACGA ACGGTGTC
14873


4153
CACCGUGU G CCUUAGAC
6125
GTCTAAGG GGCTAGCTACAACGA ACACGGTG
14874


4146
UGCCUUAG A CAUAUACG
6126
CGTATATG GGCTAGCTACAACGA CTAAGGCA
14875


4144
CCUUAGAC A UAUACGCC
6127
GGCGTATA GGCTAGCTACAACGA GTCTAAGG
14876


4142
UUAGACAU A UACGCCCC
6128
GGGGCGTA GGCTAGCTACAACGA ATGTCTAA
14877


4140
AGACAUAU A CGCCCCAA
6129
TTGGGGCG GGCTAGCTACAACGA ATATGTCT
14878


4138
ACAUAUAC G CCCCAAAC
6130
GTTTGGGG GGCTAGCTACAACGA GTATATGT
14879


4131
CGCCCCAA A CCCUAAGG
6131
CCTTAGGG GGCTAGCTACAACGA TTGGGGCG
14880


4123
ACCCUAAG G UGGCGGUA
6132
TACCGCCA GGCTAGCTACAACGA CTTAGGGT
14881


4120
CUAAGGUG G CGGUAACG
6133
CGTTACCG GGCTAGCTACAACGA CACCTTAG
14882


4117
AGGUGGCG G UAACGGAC
6134
GTCCGTTA GGCTAGCTACAACGA CGCCACCT
14883


4114
UGGCGGUA A CGGACGGA
6135
TCCGTCCG GGCTAGCTACAACGA TACCGCCA
14884


4110
GGUAACGG A CGGAUUUA
6136
TAAATCCG GGCTAGCTACAACGA CCGTTACC
14885


4106
ACGGACGG A UUUAGGAC
6137
GTCCTAAA GGCTAGCTACAACGA CCGTCCGT
14886


4099
GAUUUAGG A CGAGCACU
6138
AGTGCTCG GGCTAGCTACAACGA CCTAAATC
14887


4095
UAGGACGA G CACUUUGU
6139
ACAAAGTG GGCTAGCTACAACGA TCGTCCTA
14888


4093
GGACGAGC A CUUUGUAC
6140
GTACAAAG GGCTAGCTACAACGA GCTCGTCC
14889


4088
AGCACUUU G UACCCUUG
6141
CAAGGGTA GGCTAGCTACAACGA AAAGTGCT
14890


4086
CACUUUGU A CCCUUGGG
6142
CCCAAGGG GGCTAGCTACAACGA ACAAAGTG
14891


4078
ACCCUUGG G CUGCAUAU
6143
ATATGCAG GGCTAGCTACAACGA CCAAGGGT
14892


4075
CUUGGGCU G CAUAUGCA
6144
TGCATATG GGCTAGCTACAACGA AGCCCAAG
14893


4073
UGGGCUGC A UAUGCAGC
6145
GCTGCATA GGCTAGCTACAACGA GCAGCCCA
14894


4071
GGCUGCAU A UGCAGCCG
6146
CGGCTGCA GGCTAGCTACAACGA ATGCAGCC
14895


4069
CUGCAUAU G CAGCCGGU
6147
ACCGGCTG GGCTAGCTACAACGA ATATGCAG
14896


4066
CAUAUGCA G CCGGUACC
6148
GGTACCGG GGCTAGCTACAACGA TGCATATG
14897


4062
UGCAGCCG G UACCUUAG
6149
CTAAGGTA GGCTAGCTACAACGA CGGCTGCA
14898


4060
CAGCCGGU A CCUUAGUG
6150
CACTAAGG GGCTAGCTACAACGA ACCGGCTG
14899


4054
GUACCUUA G UGCUCUUG
6151
CAAGAGCA GGCTAGCTACAACGA TAAGGTAC
14900


4052
ACCUUAGU G CUCUUGCC
6152
GGCAAGAG GGCTAGCTACAACGA ACTAAGGT
14901


4046
GUGCUCUU G CCGCUGCC
6153
GGCAGCGG GGCTAGCTACAACGA AAGAGCAC
14902


4043
CUCUUGCC G CUGCCAGU
6154
ACTGGCAG GGCTAGCTACAACGA GGCAAGAG
14903


4040
UUGCCGCU G CCAGUGGG
6155
CCCACTGG GGCTAGCTACAACGA AGCGGCAA
14904


4036
CGCUGCCA G UGGGAGCG
6156
CGCTCCCA GGCTAGCTACAACGA TGGCAGCG
14905


4030
CAGUGGGA G CGUGUAGG
6157
CCTACACG GGCTAGCTACAACGA TCCCACTG
14906


4028
GUGGGAGC G UGUAGGUG
6158
CACCTACA GGCTAGCTACAACGA GCTCCCAC
14907


4026
GGGAGCGU G UAGGUGGG
6159
CCCACCTA GGCTAGCTACAACGA ACGCTCCC
14908


4022
GCGUGUAG G UGGGCCAC
6160
GTGGCCCA GGCTAGCTACAACGA CTACACGC
14909


4018
GUAGGUGG G CCACUUGG
6161
CCAAGTGG GGCTAGCTACAACGA CCACCTAC
14910


4015
GGUGGGCC A CUUGGAAU
6162
ATTCCAAG GGCTAGCTACAACGA GGCCCACC
14911


4008
CACUUGGA A UGUCUGCG
6163
CGCAGACA GGCTAGCTACAACGA TCCAAGTG
14912


4006
CUUGGAAU G UCUGCGGU
6164
ACCGCAGA GGCTAGCTACAACGA ATTCCAAG
14913


4002
GAAUGUCU G CGGUACGG
6165
CCGTACCG GGCTAGCTACAACGA AGACATTC
14914


3999
UGUCUGCG G UACGGCUG
6166
CAGCCGTA GGCTAGCTACAACGA CGCAGACA
14915


3997
UCUGCGGU A CGGCUGGG
6167
CCCAGCCG GGCTAGCTACAACGA ACCGCAGA
14916


3994
GCGGUACG G CUGGGGGG
6168
CCCCCCAG GGCTAGCTACAACGA CGTACCGC
14917


3984
UGGGGGGG A CGAGUUGU
6169
ACAACTCG GGCTAGCTACAACGA CCCCCCCA
14918


3980
GGGGACGA G UUGUCCGU
6170
ACGGACAA GGCTAGCTACAACGA TCGTCCCC
14919


3977
GACGAGUU G UCCGUGAA
6171
TTCACGGA GGCTAGCTACAACGA AACTCGTC
14920


3973
AGUUGUCC G UGAAGACC
6172
GGTCTTCA GGCTAGCTACAACGA GGACAACT
14921


3967
CCGUGAAG A CCGGGGAC
6173
GTCCCCGG GGCTAGCTACAACGA CTTCACGG
14922


3960
GACCGGGG A CCGCAUGG
6174
CCATGCGG GGCTAGCTACAACGA CCCCGGTC
14923


3957
CGGGGACC G CAUGGUAG
6175
CTACCATG GGCTAGCTACAACGA GGTCCCCG
14924


3955
GGGACCGC A UGGUAGUU
6176
AACTACCA GGCTAGCTACAACGA GCGGTCCC
14925


3952
ACCGCAUG G UAGUUUCC
6177
GGAAACTA GGCTAGCTACAACGA CATGCGGT
14926


3949
GCAUGGUA G UUUCCAUA
6178
TATGGAAA GGCTAGCTACAACGA TACCATGC
14927


3943
UAGUUUCC A UAGACUCA
6179
TGAGTCTA GGCTAGCTACAACGA GGAAACTA
14928


3939
UUCCAUAG A CUCAACGG
6180
CCGTTGAG GGCTAGCTACAACGA CTATGGAA
14929


3934
UAGACUCA A CGGGUACA
6181
TGTACCCG GGCTAGCTACAACGA TGAGTCTA
14930


3930
CUCAACGG G UACAAAGU
6182
ACTTTGTA GGCTAGCTACAACGA CCGTTGAG
14931


3928
CAACGGGU A CAAAGUCC
6183
GGACTTTG GGCTAGCTACAACGA ACCCGTTG
14932


3923
GGUACAAA G UCCACCGC
6184
GCGGTGGA GGCTAGCTACAACGA TTTGTACC
14933


3919
CAAAGUCC A CCGCCUUC
6185
GAAGGCGG GGCTAGCTACAACGA GGACTTTG
14934


3916
AGUCCACC G CCUUCGCA
6186
TGCGAAGG GGCTAGCTACAACGA GGTGGACT
14935


3910
CCGCCUUC G CAACCCCC
6187
GGGGGTTG GGCTAGCTACAACGA GAAGGCGG
14936


3907
CCUUCGCA A CCCCCCGG
6188
CCGGGGGG GGCTAGCTACAACGA TGCGAAGG
14937


3898
CCCCCCGG G UGCACACA
6189
TGTGTGCA GGCTAGCTACAACGA CCGGGGGG
14938


3896
CCCCGGGU G CACACAGC
6190
GCTGTGTG GGCTAGCTACAACGA ACCCGGGG
14939


3894
CCGGGUGC A CACAGCAG
6191
CTGCTGTG GGCTAGCTACAACGA GCACCCGG
14940


3892
GGGUGCAC A CAGCAGCC
6192
GGCTGCTG GGCTAGCTACAACGA GTGCACCC
14941


3889
UGCACACA G CAGCCCGG
6193
CCGGGCTG GGCTAGCTACAACGA TGTGTGCA
14942


3886
ACACAGCA G CCCGGAAG
6194
CTTCCGGG GGCTAGCTACAACGA TGCTGTGT
14943


3877
CCCGGAAG A UGCCCACA
6195
TGTGGGCA GGCTAGCTACAACGA CTTCCGGG
14944


3875
CGGAAGAU G CCCACAAC
6196
GTTGTGGG GGCTAGCTACAACGA ATCTTCCG
14945


3871
AGAUGCCC A CAACGUGC
6197
GCACGTTG GGCTAGCTACAACGA GGGCATCT
14946


3868
UGCCCACA A CGUGCCCC
6198
GGGGCACG GGCTAGCTACAACGA TGTGGGCA
14947


3866
CCCACAAC G UGCCCCGA
6199
TCGGGGCA GGCTAGCTACAACGA GTTGTGGG
14948


3864
CACAACGU G CCCCGAAG
6200
CTTCGGGG GGCTAGCTACAACGA ACGTTGTG
14949


3854
CCCGAAGG G CAGAGCAG
6201
CTGCTCTG GGCTAGCTACAACGA CCTTCGGG
14950


3849
AGGGCAGA G CAGUGGAC
6202
GTCCACTG GGCTAGCTACAACGA TCTGCCCT
14951


3846
GCAGAGCA G UGGACCGC
6203
GCGGTCCA GGCTAGCTACAACGA TGCTCTGC
14952


3842
AGCAGUGG A CCGCCCGA
6204
TCGGGCGG GGCTAGCTACAACGA CCACTGCT
14953


3839
AGUGGACC G CCCGAGGA
6205
TCCTCGGG GGCTAGCTACAACGA GGTCCACT
14954


3830
CCCGAGGA G CCCUUCAA
6206
TTGAAGGG GGCTAGCTACAACGA TCCTCGGG
14955


3821
CCCUUCAA G UAGGAGAU
6207
ATCTCCTA GGCTAGCTACAACGA TTGAAGGG
14956


3814
AGUAGGAG A UGGGCCUG
6208
CAGGCCCA GGCTAGCTACAACGA CTCCTACT
14957


3810
GGAGAUGG G CCUGGGGG
6209
CCCCCAGG GGCTAGCTACAACGA CCATCTCC
14958


3801
CCUGGGGG A UAGUAAGC
6210
GCTTACTA GGCTAGCTACAACGA CCCCCAGG
14959


3798
GGGGGAUA G UAAGCUCC
6211
GGAGCTTA GGCTAGCTACAACGA TATCCCCC
14960


3794
GAUAGUAA G CUCCCCCU
6212
AGGGGGAG GGCTAGCTACAACGA TTACTATC
14961


3785
CUCCCCCU G CUGUCACC
6213
GGTGACAG GGCTAGCTACAACGA AGGGGGAG
14962


3782
CCCCUGCU G UCACCCCG
6214
CGGGGTGA GGCTAGCTACAACGA AGCAGGGG
14963


3779
CUGCUGUC A CCCCGCCG
6215
CGGCGGGG GGCTAGCTACAACGA GACAGCAG
14964


3774
GUCACCCC G CCGGCGCA
6216
TGCGCCGG GGCTAGCTACAACGA GGGGTGAC
14965


3770
CCCCGCCG G CGCACCGG
6217
CCGGTGCG GGCTAGCTACAACGA CGGCGGGG
14966


3768
CCGCCGGC G CACCGGAA
6218
TTCCGGTG GGCTAGCTACAACGA GCCGGCGG
14967


3766
GCCGGCGC A CCGGAAUG
6219
CATTCCGG GGCTAGCTACAACGA GCGCCGGC
14968


3760
GCACCGGA A UGACAUCA
6220
TGATGTCA GGCTAGCTACAACGA TCCGGTGC
14969


3757
CCGGAAUG A CAUCAGCG
6221
CGCTGATG GGCTAGCTACAACGA CATTCCGG
14970


3755
GGAAUGAC A UCAGCGUG
6222
CACGCTGA GGCTAGCTACAACGA GTCATTCC
14971


3751
UGACAUCA G CGUGUCUC
6223
GAGACACG GGCTAGCTACAACGA TGATGTCA
14972


3749
ACAUCAGC G UGUCUCGU
6224
ACGAGACA GGCTAGCTACAACGA GCTGATGT
14973


3747
AUCAGCGU G UCUCGUGA
6225
TCACGAGA GGCTAGCTACAACGA ACGCTGAT
14974


3742
CGUGUCUC G UGACCAAG
6226
CTTGGTCA GGCTAGCTACAACGA GAGACACG
14975


3739
GUCUCGUG A CCAAGUAA
6227
TTACTTGG GGCTAGCTACAACGA CACGAGAC
14976


3734
GUGACCAA G UAAAGGUC
6228
GACCTTTA GGCTAGCTACAACGA TTGGTCAC
14977


3728
AAGUAAAG G UCCGAGCC
6229
GGCTCGGA GGCTAGCTACAACGA CTTTACTT
14978


3722
AGGUCCGA G CCGCCGCA
6230
TGCGGCGG GGCTAGCTACAACGA TCGGACCT
14979


3719
UCCGAGCC G CCGCAGGU
6231
ACCTGCGG GGCTAGCTACAACGA GGCTCGGA
14980


3716
GAGCCGCC G CAGGUGCA
6232
TGCACCTG GGCTAGCTACAACGA GGCGGCTC
14981


3712
CGCCGCAG G UGCAUGGU
6233
ACCATGCA GGCTAGCTACAACGA CTGCGGCG
14982


3710
CCGCAGGU G CAUGGUGU
6234
ACACCATG GGCTAGCTACAACGA ACCTGCGG
14983


3708
GCAGGUGC A UGGUGUCA
6235
TGACACCA GGCTAGCTACAACGA GCACCTGC
14984


3705
GGUGCAUG G UGUCAAGG
6236
CCTTGACA GGCTAGCTACAACGA CATGCACC
14985


3703
UGCAUGGU G UCAAGGAC
6237
GTCCTTGA GGCTAGCTACAACGA ACCATGCA
14986


3696
UGUCAAGG A CCGCGCUC
6238
GAGCGCGG GGCTAGCTACAACGA CCTTGACA
14987


3693
CAAGGACC G CGCUCCGG
6239
CCGGAGCG GGCTAGCTACAACGA GGTCCTTG
14988


3691
AGGACCGC G CUCCGGGG
6240
CCCCGGAG GGCTAGCTACAACGA GCGGTCCT
14989


3681
UCCGGGGG G CGCCGGCC
6241
GGCCGGCG GGCTAGCTACAACGA CCCCCGGA
14990


3679
CGGGGGGC G CCGGCCAU
6242
ATGGCCGG GGCTAGCTACAACGA GCCCCCCG
14991


3675
GGGCGCCG G CCAUCCGA
6243
TCGGATGG GGCTAGCTACAACGA CGGCGCCC
14992


3672
CGCCGGCC A UCCGACGA
6244
TCGTCGGA GGCTAGCTACAACGA GGCCGGCG
14993


3667
GCCAUCCG A CGAGGUCC
6245
GGACCTCG GGCTAGCTACAACGA CGGATGGC
14994


3662
CCGACGAG G UCCUGGUC
6246
GACCAGGA GGCTAGCTACAACGA CTCGTCGG
14995


3656
AGGUCCUG G UCUACAUU
6247
AATGTAGA GGCTAGCTACAACGA CAGGACCT
14996


3652
CCUGGUCU A CAUUGGUG
6248
CACCAATG GGCTAGCTACAACGA AGACCAGG
14997


3650
UGGUCUAC A UUGGUGUA
6249
TACACCAA GGCTAGCTACAACGA GTAGACCA
14998


3646
CUACAUUG G UGUACAUU
6250
AATGTACA GGCTAGCTACAACGA CAATGTAG
14999


3644
ACAUUGGU G UACAUUUG
6251
CAAATGTA GGCTAGCTACAACGA ACCAATGT
15000


3642
AUUGGUGU A CAUUUGGG
6252
CCCAAATG GGCTAGCTACAACGA ACACCAAT
15001


3640
UGGUGUAC A UUUGGGUG
6253
CACCCAAA GGCTAGCTACAACGA GTACACCA
15002


3634
ACAUUUGG G UGAUUGGA
6254
TCCAATCA GGCTAGCTACAACGA CCAAATGT
15003


3631
UUUGGGUG A UUGGACCC
6255
GGGTCCAA GGCTAGCTACAACGA CACCCAAA
15004


3626
GUGAUUGG A CCCUUUGG
6256
CCAAAGGG GGCTAGCTACAACGA CCAATCAC
15005


3617
CCCUUUGG G CCGGCUAG
6257
CTAGCCGG GGCTAGCTACAACGA CCAAAGGG
15006


3613
UUGGGCCG G CUAGGGUC
6258
GACCCTAG GGCTAGCTACAACGA CGGCCCAA
15007


3607
CGGCUAGG G UCUUUGAG
6259
CTCAAAGA GGCTAGCTACAACGA CCTAGCCG
15008


3599
GUCUUUGA G CCGGCGCC
6260
GGCGCCGG GGCTAGCTACAACGA TCAAAGAC
15009


3595
UUGAGCCG G CGCCGUGG
6261
CCACGGCG GGCTAGCTACAACGA CGGCTCAA
15010


3593
GAGCCGGC G CCGUGGUA
6262
TACCACGG GGCTAGCTACAACGA GCCGGCTC
15011


3590
CCGGCGCC G UGGUAGAC
6263
GTCTACCA GGCTAGCTACAACGA GGCGCCGG
15012


3587
GCGCCGUG G UAGACAGU
6264
ACTGTCTA GGCTAGCTACAACGA CACGGCGC
15013


3583
CGUGGUAG A CAGUCCAG
6265
CTGGACTG GGCTAGCTACAACGA CTACCACG
15014


3580
GGUAGACA G UCCAGCAC
6266
GTGCTGGA GGCTAGCTACAACGA TGTCTACC
15015


3575
ACAGUCCA G CACACGCC
6267
GGCGTGTG GGCTAGCTACAACGA TGGACTGT
15016


3573
AGUCCAGC A CACGCCGU
6268
ACGGCGTG GGCTAGCTACAACGA GCTGGACT
15017


3571
UCCAGCAC A CGCCGUUG
6269
CAACGGCG GGCTAGCTACAACGA GTGCTGGA
15018


3569
CAGCACAC G CCGUUGAC
6270
GTCAACGG GGCTAGCTACAACGA GTGTGCTG
15019


3566
CACACGCC G UUGACGCA
6271
TGCGTCAA GGCTAGCTACAACGA GGCGTGTG
15020


3562
CGCCGUUG A CGCAGGUC
6272
GACCTGCG GGCTAGCTACAACGA CAACGGCG
15021


3560
CCGUUGAC G CAGGUCGC
6273
GCGACCTG GGCTAGCTACAACGA GTCAACGG
15022


3556
UGACGCAG G UCGCUAGG
6274
CCTAGCGA GGCTAGCTACAACGA CTGCGTCA
15023


3553
CGCAGGUC G CUAGGAAA
6275
TTTCCTAG GGCTAGCTACAACGA GACCTGCG
15024


3543
UAGGAAAG A CUGCGUCG
6276
CGACGCAG GGCTAGCTACAACGA CTTTCCTA
15025


3540
GAAAGACU G CGUCGCGG
6277
CCGCGACG GGCTAGCTACAACGA AGTCTTTC
15026


3538
AAGACUGC G UCGCGGUG
6278
CACCGCGA GGCTAGCTACAACGA GCAGTCTT
15027


3535
ACUGCGUC G CGGUGGAA
6279
TTCCACCG GGCTAGCTACAACGA GACGCAGT
15028


3532
GCGUCGCG G UGGAAACC
6280
GGTTTCCA GGCTAGCTACAACGA CGCGACGC
15029


3526
CGGUGGAA A CCACUUGA
6281
TCAAGTGG GGCTAGCTACAACGA TTCCACCG
15030


3523
UGGAAACC A CUUGAACU
6282
AGTTCAAG GGCTAGCTACAACGA GGTTTCCA
15031


3517
CCACUUGA A CUUCCCCC
6283
GGGGGAAG GGCTAGCTACAACGA TCAAGTGG
15032


3505
CCCCCUCG A CUUGGUUC
6284
GAACCAAG GGCTAGCTACAACGA CGAGGGGG
15033


3500
UCGACUUG G UUCUUGUC
6285
GACAAGAA GGCTAGCTACAACGA CAAGTCGA
15034


3494
UGGUUCUU G UCCCGGCC
6286
GGCCGGGA GGCTAGCTACAACGA AAGAACCA
15035


3488
UUGUCCCG G CCCGUGAG
6287
CTCACGGG GGCTAGCTACAACGA CGGGACAA
15036


3484
CCCGGCCC G UGAGGCUG
6288
CAGCCTCA GGCTAGCTACAACGA GGGCCGGG
15037


3479
CCCGUGAG G CUGGUGAU
6289
ATCACCAG GGCTAGCTACAACGA CTCACGGG
15038


3475
UGAGGCUG G UGAUAAUG
6290
CATTATCA GGCTAGCTACAACGA CAGCCTCA
15039


3472
GGCUGGUG A UAAUGCAG
6291
CTGCATTA GGCTAGCTACAACGA CACCAGCC
15040


3469
UGGUGAUA A UGCAGCCA
6292
TGGCTGCA GGCTAGCTACAACGA TATCACCA
15041


3467
GUGAUAAU G CAGCCAAA
6293
TTTGGCTG GGCTAGCTACAACGA ATTATCAC
15042


3464
AUAAUGCA G CCAAACAG
6294
CTGTTTGG GGCTAGCTACAACGA TGCATTAT
15043


3459
GCAGCCAA A CAGGCCCC
6295
GGGGCCTG GGCTAGCTACAACGA TTGGCTGC
15044


3455
CCAAACAG G CCCCGCGU
6296
ACGCGGGG GGCTAGCTACAACGA CTGTTTGG
15045


3450
CAGGCCCC G CGUCUGUU
6297
AACAGACG GGCTAGCTACAACGA GGGGCCTG
15046


3448
GGCCCCGC G UCUGUUGG
6298
CCAACAGA GGCTAGCTACAACGA GCGGGGCC
15047


3444
CCGCGUCU G UUGGGAGU
6299
ACTCCCAA GGCTAGCTACAACGA AGACGCGG
15048


3437
UGUUGGGA G UAGGCCGU
6300
ACGGCCTA GGCTAGCTACAACGA TCCCAACA
15049


3433
GGGAGUAG G CCGUAAUG
6301
CATTACGG GGCTAGCTACAACGA CTACTCCC
15050


3430
AGUAGGCC G UAAUGGGC
6302
GCCCATTA GGCTAGCTACAACGA GGCCTACT
15051


3427
AGGCCGUA A UGGGCGCG
6303
CGCGCCCA GGCTAGCTACAACGA TACGGCCT
15052


3423
CGUAAUGG G CGCGAGGA
6304
TCCTCGCG GGCTAGCTACAACGA CCATTACG
15053


3421
UAAUGGGC G CGAGGAGU
6305
ACTCCTCG GGCTAGCTACAACGA GCCCATTA
15054


3414
CGCGAGGA G UCGCCACC
6306
GGTGGCGA GGCTAGCTACAACGA TCCTCGCG
15055


3411
GAGGAGUC G CCACCCCU
6307
AGGGGTGG GGCTAGCTACAACGA GACTCCTC
15056


3408
GAGUCGCC A CCCCUGCC
6308
GGCAGGGG GGCTAGCTACAACGA GGCGACTC
15057


3402
CCACCCCU G CCCCUCAA
6309
TTGAGGGG GGCTAGCTACAACGA AGGGGTGG
15058


3392
CCCUCAAG A CUGUCGGC
6310
GCCGACAG GGCTAGCTACAACGA CTTGAGGG
15059


3389
UCAAGACU G UCGGCUGG
6311
CCAGCCGA GGCTAGCTACAACGA AGTCTTGA
15060


3385
GACUGUCG G CUGGUCCU
6312
AGGACCAG GGCTAGCTACAACGA CGACAGTC
15061


3381
GUCGGCUG G UCCUAGGA
6313
TCCTAGGA GGCTAGCTACAACGA CAGCCGAC
15062


3372
UCCUAGGA G UAUCUCCC
6314
GGGAGATA GGCTAGCTACAACGA TCCTAGGA
15063


3370
CUAGGAGU A UCUCCCUC
6315
GAGGGAGA GGCTAGCTACAACGA ACTCCTAG
15064


3352
CCCUUCGG G CGGAGACA
6316
TGTCTCCG GGCTAGCTACAACGA CCGAAGGG
15065


3346
GGGCGGAG A CAGGUAGA
6317
TCTACCTG GGCTAGCTACAACGA CTCCGCCC
15066


3342
GGAGACAG G UAGACCCA
6318
TGGGTCTA GGCTAGCTACAACGA CTGTCTCC
15067


3338
ACAGGUAG A CCCAUAAU
6319
ATTATGGG GGCTAGCTACAACGA CTACCTGT
15068


3334
GUAGACCC A UAAUGAUG
6320
CATCATTA GGCTAGCTACAACGA GGGTCTAC
15069


3331
GACCCAUA A UGAUGUCC
6321
GGACATCA GGCTAGCTACAACGA TATGGGTC
15070


3328
CCAUAAUG A UGUCCCCA
6322
TGGGGACA GGCTAGCTACAACGA CATTATGG
15071


3326
AUAAUGAU G UCCCCACA
6323
TGTGGGGA GGCTAGCTACAACGA ATCATTAT
15072


3320
AUGUCCCC A CACGCCGC
6324
GCGGCGTG GGCTAGCTACAACGA GGGGACAT
15073


3318
GUCCCCAC A CGCCGCGG
6325
CCGCGGCG GGCTAGCTACAACGA GTGGGGAC
15074


3316
CCCCACAC G CCGCGGUG
6326
CACCGCGG GGCTAGCTACAACGA GTGTGGGG
15075


3313
CACACGCC G CGGUGUCU
6327
AGACACCG GGCTAGCTACAACGA GGCGTGTG
15076


3310
ACGCCGCG G UGUCUCCC
6328
GGGAGACA GGCTAGCTACAACGA CGCGGCGT
15077


3308
GCCGCGGU G UCUCCCCC
6329
GGGGGAGA GGCTAGCTACAACGA ACCGCGGC
15078


3295
CCCCCCAG G UGAUGAUC
6330
GATCATCA GGCTAGCTACAACGA CTGGGGGG
15079


3292
CCCAGGUG A UGAUCUUG
6331
CAAGATCA GGCTAGCTACAACGA CACCTGGG
15080


3289
AGGUGAUG A UCUUGAUU
6332
AATCAAGA GGCTAGCTACAACGA CATCACCT
15081


3283
UGAUCUUG A UUUCCAUG
6333
CATGGAAA GGCTAGCTACAACGA CAAGATCA
15082


3277
UGAUUUCC A UGUCGGAG
6334
CTCCGACA GGCTAGCTACAACGA GGAAATCA
15083


3275
AUUUCCAU G UCGGAGAA
6335
TTCTCCGA GGCTAGCTACAACGA ATGGAAAT
15084


3265
CGGAGAAG A CGACGGGC
6336
GCCCGTCG GGCTAGCTACAACGA CTTCTCCG
15085


3262
AGAAGACG A CGGGCUCG
6337
CGAGCCCG GGCTAGCTACAACGA CGTCTTCT
15086


3258
GACGACGG G CUCGACCG
6338
CGGTCGAG GGCTAGCTACAACGA CCGTCGTC
15087


3253
CGGGCUCG A CCGCUACC
6339
GGTAGCGG GGCTAGCTACAACGA CGAGCCCG
15088


3250
GCUCGACC G CUACCGCC
6340
GGCGGTAG GGCTAGCTACAACGA GGTCGAGC
15089


3247
CGACCGCU A CCGCCAGG
6341
CCTGGCGG GGCTAGCTACAACGA AGCGGTCG
15090


3244
CCGCUACC G CCAGGUCU
6342
AGACCTGG GGCTAGCTACAACGA GGTAGCGG
15091


3239
ACCGCCAG G UCUCGUAG
6343
CTACGAGA GGCTAGCTACAACGA CTGGCGGT
15092


3234
CAGGUCUC G UAGACCUG
6344
CAGGTCTA GGCTAGCTACAACGA GAGACCTG
15093


3230
UCUCGUAG A CCUGUGUG
6345
CACACAGG GGCTAGCTACAACGA CTACGAGA
15094


3226
GUAGACCU G UGUGGGCC
6346
GGCCCACA GGCTAGCTACAACGA AGGTCTAC
15095


3224
AGACCUGU G UGGGCCCA
6347
TGGGCCCA GGCTAGCTACAACGA ACAGGTCT
15096


3220
CUGUGUGG G CCCAGUCC
6348
GGACTGGG GGCTAGCTACAACGA CCACACAG
15097


3215
UGGGCCCA G UCCUGCAG
6349
CTGCAGGA GGCTAGCTACAACGA TGGGCCCA
15098


3210
CCAGUCCU G CAGUGGAG
6350
CTCCACTG GGCTAGCTACAACGA AGGACTGG
15099


3207
GUCCUGCA G UGGAGUGA
6351
TCACTCCA GGCTAGCTACAACGA TGCAGGAC
15100


3202
GCAGUGGA G UGAGGUGG
6352
CCACCTCA GGCTAGCTACAACGA TCCACTGC
15101


3197
GGAGUGAG G UGGUCAUA
6353
TATGACCA GGCTAGCTACAACGA CTCACTCC
15102


3194
GUGAGGUG G UCAUAGAC
6354
GTCTATGA GGCTAGCTACAACGA CACCTCAC
15103


3191
AGGUGGUC A UAGACGGA
6355
TCCGTCTA GGCTAGCTACAACGA GACCACCT
15104


3187
GGUCAUAG A CGGACGUA
6356
TACGTCCG GGCTAGCTACAACGA CTATGACC
15105


3183
AUAGACGG A CGUACCUU
6357
AAGGTACG GGCTAGCTACAACGA CCGTCTAT
15106


3181
AGACGGAC G UACCUUUC
6358
GAAAGGTA GGCTAGCTACAACGA GTCCGTCT
15107


3179
ACGGACGU A CCUUUCAA
6359
TTGAAAGG GGCTAGCTACAACGA ACGTCCGT
15108


3171
ACCUUUCA A UUCGGCCA
6360
TGGCCGAA GGCTAGCTACAACGA TGAAAGGT
15109


3166
UCAAUUCG G CCAACUUC
6361
GAAGTTGG GGCTAGCTACAACGA CGAATTGA
15110


3162
UUCGGCCA A CUUCAUGA
6362
TCATGAAG GGCTAGCTACAACGA TGGCCGAA
15111


3157
CCAACUUC A UGAAGGCC
6363
GGCCTTCA GGCTAGCTACAACGA GAAGTTGG
15112


3151
UCAUGAAG G CCAUUUGG
6364
CCAAATGG GGCTAGCTACAACGA CTTCATGA
15113


3148
UGAAGGCC A UUUGGACA
6365
TGTCCAAA GGCTAGCTACAACGA GGCCTTCA
15114


3142
CCAUUUGG A CAUAUUGC
6366
GCAATATG GGCTAGCTACAACGA CCAAATGG
15115


3140
AUUUGGAC A UAUUGCCC
6367
GGGCAATA GGCTAGCTACAACGA GTCCAAAT
15116


3138
UUGGACAU A UUGCCCCC
6368
GGGGGCAA GGCTAGCTACAACGA ATGTCCAA
15117


3135
GACAUAUU G CCCCCCAC
6369
GTGGGGGG GGCTAGCTACAACGA AATATGTC
15118


3128
UGCCCCCC A CCGACUUU
6370
AAAGTCGG GGCTAGCTACAACGA GGGGGGCA
15119


3124
CCCCACCG A CUUUCCGC
6371
GCGGAAAG GGCTAGCTACAACGA CGGTGGGG
15120


3117
GACUUUCC G CACCAAAA
6372
TTTTGGTG GGCTAGCTACAACGA GGAAAGTC
15121


3115
CUUUCCGC A CCAAAAUG
6373
CATTTTGG GGCTAGCTACAACGA GCGGAAAG
15122


3109
GCACCAAA A UGCAUUCA
6374
TGAATGCA GGCTAGCTACAACGA TTTGGTGC
15123


3107
ACCAAAAU G CAUUCACG
6375
CGTGAATG GGCTAGCTACAACGA ATTTTGGT
15124


3105
CAAAAUGC A UUCACGGA
6376
TCCGTGAA GGCTAGCTACAACGA GCATTTTG
15125


3101
AUGCAUUC A CGGAUGAC
6377
GTCATCCG GGCTAGCTACAACGA GAATGCAT
15126


3097
AUUCACGG A UGACCCCU
6378
AGGGGTCA GGCTAGCTACAACGA CCGTGAAT
15127


3094
CACGGAUG A CCCCUUGA
6379
TCAAGGGG GGCTAGCTACAACGA CATCCGTG
15128


3085
CCCCUUGA G CCCGCACA
6380
TGTGCGGG GGCTAGCTACAACGA TCAAGGGG
15129


3081
UUGAGCCC G CACAAAGU
6381
ACTTTGTG GGCTAGCTACAACGA GGGCTCAA
15130


3079
GAGCCCGC A CAAAGUCC
6382
GGACTTTG GGCTAGCTACAACGA GCGGGCTC
15131


3074
CGCACAAA G UCCGGCAC
6383
GTGCCGGA GGCTAGCTACAACGA TTTGTGCG
15132


3069
AAAGUCCG G CACUUUUG
6384
CAAAAGTG GGCTAGCTACAACGA CGGACTTT
15133


3067
AGUCCGGC A CUUUUGCU
6385
AGCAAAAG GGCTAGCTACAACGA GCCGGACT
15134


3061
GCACUUUU G CUAUACCA
6386
TGGTATAG GGCTAGCTACAACGA AAAAGTGC
15135


3058
CUUUUGCU A UACCAGCC
6387
GGCTGGTA GGCTAGCTACAACGA AGCAAAAG
15136


3056
UUUGCUAU A CCAGCCUG
6388
CAGGCTGG GGCTAGCTACAACGA ATAGCAAA
15137


3052
CUAUACCA G CCUGGAGC
6389
GCTCCAGG GGCTAGCTACAACGA TGGTATAG
15138


3045
AGCCUGGA G CACCAUGA
6390
TCATGGTG GGCTAGCTACAACGA TCCAGGCT
15139


3043
CCUGGAGC A CCAUGAGC
6391
GCTCATGG GGCTAGCTACAACGA GCTCCAGG
15140


3040
GGAGCACC A UGAGCGGG
6392
CCCGCTCA GGCTAGCTACAACGA GGTGCTCC
15141


3036
CACCAUGA G CGGGCCGA
6393
TCGGCCCG GGCTAGCTACAACGA TCATGGTG
15142


3032
AUGAGCGG G CCGAGUAU
6394
ATACTCGG GGCTAGCTACAACGA CCGCTCAT
15143


3027
CGGGCCGA G UAUGGCGA
6395
TCGCCATA GGCTAGCTACAACGA TCGGCCCG
15144


3025
GGCCGAGU A UGGCGAGC
6396
GCTCGCCA GGCTAGCTACAACGA ACTCGGCC
15145


3022
CGAGUAUG G CGAGCAUA
6397
TATGCTCG GGCTAGCTACAACGA CATACTCG
15146


3018
UAUGGCGA G CAUAAUUU
6398
AAATTATG GGCTAGCTACAACGA TCGCCATA
15147


3016
UGGCGAGC A UAAUUUUG
6399
CAAAATTA GGCTAGCTACAACGA GCTCGCCA
15148


3013
CGAGCAUA A UUUUGGUG
6400
CACCAAAA GGCTAGCTACAACGA TATGCTCG
15149


3007
UAAUUUUG G UGAUGUCA
6401
TGACATCA GGCTAGCTACAACGA CAAAATTA
15150


3004
UUUUGGUG A UGUCAAAG
6402
CTTTGACA GGCTAGCTACAACGA CACCAAAA
15151


3002
UUGGUGAU G UCAAAGAU
6403
ATCTTTGA GGCTAGCTACAACGA ATCACCAA
15152


2995
UGUCAAAG A UUAGCUCU
6404
AGAGCTAA GGCTAGCTACAACGA CTTTGACA
15153


2991
AAAGAUUA G CUCUGGGU
6405
ACCCAGAG GGCTAGCTACAACGA TAATCTTT
15154


2984
AGCUCUGG G UGGACCAC
6406
GTGGTCCA GGCTAGCTACAACGA CCAGAGCT
15155


2980
CUGGGUGG A CCACACAC
6407
GTGTGTGG GGCTAGCTACAACGA CCACCCAG
15156


2977
GGUGGACC A CACACGUG
6408
CACGTGTG GGCTAGCTACAACGA GGTCCACC
15157


2975
UGGACCAC A CACGUGAG
6409
CTCACGTG GGCTAGCTACAACGA GTGGTCCA
15158


2973
GACCACAC A CGUGAGGA
6410
TCCTCACG GGCTAGCTACAACGA GTGTGGTC
15159


2971
CCACACAC G UGAGGAGA
6411
TCTCCTCA GGCTAGCTACAACGA GTGTGTGG
15160


2962
UGAGGAGA A UGAUGGCA
6412
TGCCATCA GGCTAGCTACAACGA TCTCCTCA
15161


2959
GGAGAAUG A UGGCACCG
6413
CGGTGCCA GGCTAGCTACAACGA CATTCTCC
15162


2956
GAAUGAUG G CACCGCGC
6414
GCGCGGTG GGCTAGCTACAACGA CATCATTC
15163


2954
AUGAUGGC A CCGCGCCC
6415
GGGCGCGG GGCTAGCTACAACGA GCCATCAT
15164


2951
AUGGCACC G CGCCCCCC
6416
GGGGGGCG GGCTAGCTACAACGA GGTGCCAT
15165


2949
GGCACCGC G CCCCCCCC
6417
GGGGGGGG GGCTAGCTACAACGA GCGGTGCC
15166


2938
CCCCCCGA A CGUUGAGG
6418
CCTCAACG GGCTAGCTACAACGA TCGGGGGG
15167


2936
CCCCGAAC G UUGAGGGG
6419
CCCCTCAA GGCTAGCTACAACGA GTTCGGGG
15168


2923
GGGGGGGG A UCCACACU
6420
AGTGTGGA GGCTAGCTACAACGA CCCCCCCC
15169


2919
GGGGAUCC A CACUUGCA
6421
TGCAAGTG GGCTAGCTACAACGA GGATCCCC
15170


2917
GGAUCCAC A CUUGCAAC
6422
GTTGCAAG GGCTAGCTACAACGA GTGGATCC
15171


2913
CCACACUU G CAACUGCG
6423
CGCAGTTG GGCTAGCTACAACGA AAGTGTGG
15172


2910
CACUUGCA A CUGCGCCU
6424
AGGCGCAG GGCTAGCTACAACGA TGCAAGTG
15173


2907
UUGCAACU G CGCCUCGG
6425
CCGAGGCG GGCTAGCTACAACGA AGTTGCAA
15174


2905
GCAACUGC G CCUCGGCU
6426
AGCCGAGG GGCTAGCTACAACGA GCAGTTGC
15175


2899
GCGCCUCG G CUCUGGUG
6427
CACCAGAG GGCTAGCTACAACGA CGAGGCGC
15176


2893
CGGCUCUG G UGAUAAGG
6428
CCTTATCA GGCTAGCTACAACGA CAGAGCCG
15177


2890
CUCUGGUG A UAAGGUAU
6429
ATACCTTA GGCTAGCTACAACGA CACCAGAG
15178


2885
GUGAUAAG G UAUUGCAA
6430
TTGCAATA GGCTAGCTACAACGA CTTATCAC
15179


2883
GAUAAGGU A UUGCAACC
6431
GGTTGCAA GGCTAGCTACAACGA ACCTTATC
15180


2880
AAGGUAUU G CAACCACC
6432
GGTGGTTG GGCTAGCTACAACGA AATACCTT
15181


2877
GUAUUGCA A CCACCAUA
6433
TATGGTGG GGCTAGCTACAACGA TGCAATAC
15182


2874
UUGCAACC A CCAUAUGA
6434
TCATATGG GGCTAGCTACAACGA GGTTGCAA
15183


2871
CAACCACC A UAUGAGCC
6435
GGCTCATA GGCTAGCTACAACGA GGTGGTTG
15184


2869
ACCACCAU A UGAGCCUA
6436
TAGGCTCA GGCTAGCTACAACGA ATGGTGGT
15185


2865
CCAUAUGA G CCUAGCGA
6437
TCGCTAGG GGCTAGCTACAACGA TCATATGG
15186


2860
UGAGCCUA G CGAGGAAC
6438
GTTCCTCG GGCTAGCTACAACGA TAGGCTCA
15187


2853
AGCGAGGA A CACUUUGU
6439
ACAAAGTG GGCTAGCTACAACGA TCCTCGCT
15188


2851
CGAGGAAC A CUUUGUAG
6440
CTACAAAG GGCTAGCTACAACGA GTTCCTCG
15189


2846
AACACUUU G UAGUAUGG
6441
CCATACTA GGCTAGCTACAACGA AAAGTGTT
15190


2843
ACUUUGUA G UAUGGUGA
6442
TCACCATA GGCTAGCTACAACGA TACAAAGT
15191


2841
UUUGUAGU A UGGUGACA
6443
TGTCACCA GGCTAGCTACAACGA ACTACAAA
15192


2838
GUAGUAUG G UGACAAGG
6444
CCTTGTCA GGCTAGCTACAACGA CATACTAC
15193


2835
GUAUGGUG A CAAGGUCA
6445
TGACCTTG GGCTAGCTACAACGA CACCATAC
15194


2830
GUGACAAG G UCAAGAGU
6446
ACTCTTGA GGCTAGCTACAACGA CTTGTCAC
15195


2823
GGUCAAGA G UGCUAGAC
6447
GTCTAGCA GGCTAGCTACAACGA TCTTGACC
15196


2821
UCAAGAGU G CUAGACCU
6448
AGGTCTAG GGCTAGCTACAACGA ACTCTTGA
15197


2816
AGUGCUAG A CCUACAAA
6449
TTTGTAGG GGCTAGCTACAACGA CTAGCACT
15198


2812
CUAGACCU A CAAAAACC
6450
GGTTTTTG GGCTAGCTACAACGA AGGTCTAG
15199


2806
CUACAAAA A CCACGCCU
6451
AGGCGTGG GGCTAGCTACAACGA TTTTGTAG
15200


2803
CAAAAACC A CGCCUCCG
6452
CGGAGGCG GGCTAGCTACAACGA GGTTTTTG
15201


2801
AAAACCAC G CCUCCGCA
6453
TGCGGAGG GGCTAGCTACAACGA GTGGTTTT
15202


2795
ACGCCUCC G CACGAUGC
6454
GCATCGTG GGCTAGCTACAACGA GGAGGCGT
15203


2793
GCCUCCGC A CGAUGCGG
6455
CCGCATCG GGCTAGCTACAACGA GCGGAGGC
15204


2790
UCCGCACG A UGCGGCCA
6456
TGGCCGCA GGCTAGCTACAACGA CGTGCGGA
15205


2788
CGCACGAU G CGGCCAUC
6457
GATGGCCG GGCTAGCTACAACGA ATCGTGCG
15206


2785
ACGAUGCG G CCAUCUCC
6458
GGAGATGG GGCTAGCTACAACGA CGCATCGT
15207


2782
AUGCGGCC A UCUCCCGG
6459
CCGGGAGA GGCTAGCTACAACGA GGCCGCAT
15208


2774
AUCUCCCG G UCCAUGGC
6460
GCCATGGA GGCTAGCTACAACGA CGGGAGAT
15209


2770
CCCGGUCC A UGGCGUAC
6461
GTACGCCA GGCTAGCTACAACGA GGACCGGG
15210


2767
GGUCCAUG G CGUACGCC
6462
GGCGTACG GGCTAGCTACAACGA CATGGACC
15211


2765
UCCAUGGC G UACGCCCG
6463
CGGGCGTA GGCTAGCTACAACGA GCCATGGA
15212


2763
CAUGGCGU A CGCCCGUG
6464
CACGGGCG GGCTAGCTACAACGA ACGCCATG
15213


2761
UGGCGUAC G CCCGUGGU
6465
ACCACGGG GGCTAGCTACAACGA GTACGCCA
15214


2757
GUACGCCC G UGGUGGUA
6466
TACCACCA GGCTAGCTACAACGA GGGCGTAC
15215


2754
CGCCCGUG G UGGUAACG
6467
CGTTACCA GGCTAGCTACAACGA CACGGGCG
15216


2751
CCGUGGUG G UAACGCCA
6468
TGGCGTTA GGCTAGCTACAACGA CACCACGG
15217


2748
UGGUGGUA A CGCCAGCA
6469
TGCTGGCG GGCTAGCTACAACGA TACCACCA
15218


2746
GUGGUAAC G CCAGCAGG
6470
CCTGCTGG GGCTAGCTACAACGA GTTACCAC
15219


2742
UAACGCCA G CAGGAGCA
6471
TGCTCCTG GGCTAGCTACAACGA TGGCGTTA
15220


2736
CAGCAGGA G CAGGAGUA
6472
TACTCCTG GGCTAGCTACAACGA TCCTGCTG
15221


2730
GAGCAGGA G UAGCGGCC
6473
GGCCGCTA GGCTAGCTACAACGA TCCTGCTC
15222


2727
CAGGAGUA G CGGCCAUA
6474
TATGGCCG GGCTAGCTACAACGA TACTCCTG
15223


2724
GAGUAGCG G CCAUACGC
6475
GCGTATGG GGCTAGCTACAACGA CGCTACTC
15224


2721
UAGCGGCC A UACGCCGU
6476
ACGGCGTA GGCTAGCTACAACGA GGCCGCTA
15225


2719
GCGGCCAU A CGCCGUAG
6477
CTACGGCG GGCTAGCTACAACGA ATGGCCGC
15226


2717
GGCCAUAC G CCGUAGAG
6478
CTCTACGG GGCTAGCTACAACGA GTATGGCC
15227


2714
CAUACGCC G UAGAGAGC
6479
GCTCTCTA GGCTAGCTACAACGA GGCGTATG
15228


2707
CGUAGAGA G CAUAUGCC
6480
GGCATATG GGCTAGCTACAACGA TCTCTACG
15229


2705
UAGAGAGC A UAUGCCGC
6481
GCGGCATA GGCTAGCTACAACGA GCTCTCTA
15230


2703
GAGAGCAU A UGCCGCCC
6482
GGGCGGCA GGCTAGCTACAACGA ATGCTCTC
15231


2701
GAGCAUAU G CCGCCCCA
6483
TGGGGCGG GGCTAGCTACAACGA ATATGCTC
15232


2698
CAUAUGCC G CCCCAGGG
6484
CCCTGGGG GGCTAGCTACAACGA GGCATATG
15233


2689
CCCCAGGG A CCAGCUUG
6485
CAAGCTGG GGCTAGCTACAACGA CCCTGGGG
15234


2685
AGGGACCA G CUUGCCUU
6486
AAGGCAAG GGCTAGCTACAACGA TGGTCCCT
15235


2681
ACCAGCUU G CCUUUGAU
6487
ATCAAAGG GGCTAGCTACAACGA AAGCTGGT
15236


2674
UGCCUUUG A UGUACCAG
6488
CTGGTACA GGCTAGCTACAACGA CAAAGGCA
15237


2672
CCUUUGAU G UACCAGGC
6489
GCCTGGTA GGCTAGCTACAACGA ATCAAAGG
15238


2670
UUUGAUGU A CCAGGCAG
6490
CTGCCTGG GGCTAGCTACAACGA ACATCAAA
15239


2665
UGUACCAG G CAGCACAG
6491
CTGTGCTG GGCTAGCTACAACGA CTGGTACA
15240


2662
ACCAGGCA G CACAGAAG
6492
CTTCTGTG GGCTAGCTACAACGA TGCCTGGT
15241


2660
CAGGCAGC A CAGAAGAA
6493
TTCTTCTG GGCTAGCTACAACGA GCTGCCTG
15242


2652
ACAGAAGA A CACGAGGA
6494
TCCTCGTG GGCTAGCTACAACGA TCTTCTGT
15243


2650
AGAAGAAC A CGAGGAAG
6495
CTTCCTCG GGCTAGCTACAACGA GTTCTTCT
15244


2635
AGGAGAGG A UGCCAUGC
6496
GCATGGCA GGCTAGCTACAACGA CCTCTCCT
15245


2633
GAGAGGAU G CCAUGCAC
6497
GTGCATGG GGCTAGCTACAACGA ATCCTCTC
15246


2630
AGGAUGCC A UGCACUCC
6498
GGAGTGCA GGCTAGCTACAACGA GGCATCCT
15247


2628
GAUGCCAU G CACUCCGG
6499
CCGGAGTG GGCTAGCTACAACGA ATGGCATC
15248


2626
UGCCAUGC A CUCCGGCC
6500
GGCCGGAG GGCTAGCTACAACGA GCATGGCA
15249


2620
GCACUCCG G CCAAGGAU
6501
ATCCTTGG GGCTAGCTACAACGA CGGAGTGC
15250


2613
GGCCAAGG A UGCUGCAU
6502
ATGCAGCA GGCTAGCTACAACGA CCTTGGCC
15251


2611
CCAAGGAU G CUGCAUUG
6503
CAATGCAG GGCTAGCTACAACGA ATCCTTGG
15252


2608
AGGAUGCU G CAUUGAGG
6504
CCTCAATG GGCTAGCTACAACGA AGCATCCT
15253


2606
GAUGCUGC A UUGAGGAC
6505
GTCCTCAA GGCTAGCTACAACGA GCAGCATC
15254


2599
CAUUGAGG A CCACCAGG
6506
CCTGGTGG GGCTAGCTACAACGA CCTCAATG
15255


2596
UGAGGACC A CCAGGUUC
6507
GAACCTGG GGCTAGCTACAACGA GGTCCTCA
15256


2591
ACCACCAG G UUCUCUAG
6508
CTAGAGAA GGCTAGCTACAACGA CTGGTGGT
15257


2581
UCUCUAGG G CAGCCUCG
6509
CGAGGCTG GGCTAGCTACAACGA CCTAGAGA
15258


2578
CUAGGGCA G CCUCGGCC
6510
GGCCGAGG GGCTAGCTACAACGA TGCCCTAG
15259


2572
CAGCCUCG G CCUGGGCU
6511
AGCCCAGG GGCTAGCTACAACGA CGAGGCTG
15260


2566
CGGCCUGG G CUACCAAC
6512
GTTGGTAG GGCTAGCTACAACGA CCAGGCCG
15261


2563
CCUGGGCU A CCAACAGC
6513
GCTGTTGG GGCTAGCTACAACGA AGCCCAGG
15262


2559
GGCUACCA A CAGCAUCA
6514
TGATGCTG GGCTAGCTACAACGA TGGTAGCC
15263


2556
UACCAACA G CAUCAUCC
6515
GGATGATG GGCTAGCTACAACGA TGTTGGTA
15264


2554
CCAACAGC A UCAUCCAC
6516
GTGGATGA GGCTAGCTACAACGA GCTGTTGG
15265


2551
ACAGCAUC A UCCACAAA
6517
TTTGTGGA GGCTAGCTACAACGA GATGCTGT
15266


2547
CAUCAUCC A CAAACAGG
6518
CCTGTTTG GGCTAGCTACAACGA GGATGATG
15267


2543
AUCCACAA A CAGGCACA
6519
TGTGCCTG GGCTAGCTACAACGA TTGTGGAT
15268


2539
ACAAACAG G CACAGACG
6520
CGTCTGTG GGCTAGCTACAACGA CTGTTTGT
15269


2537
AAACAGGC A CAGACGCG
6521
CGCGTCTG GGCTAGCTACAACGA GCCTGTTT
15270


2533
AGGCACAG A CGCGCGCG
6522
CGCGCGCG GGCTAGCTACAACGA CTGTGCCT
15271


2531
GCACAGAC G CGCGCGUC
6523
GACGCGCG GGCTAGCTACAACGA GTCTGTGC
15272


2529
ACAGACGC G CGCGUCUG
6524
CAGACGCG GGCTAGCTACAACGA GCGTCTGT
15273


2527
AGACGCGC G CGUCUGCC
6525
GGCAGACG GGCTAGCTACAACGA GCGCGTCT
15274


2525
ACGCGCGC G UCUGCCAG
6526
CTGGCAGA GGCTAGCTACAACGA GCGCGCGT
15275


2521
GCGCGUCU G CCAGGAGA
6527
TCTCCTGG GGCTAGCTACAACGA AGACGCGC
15276


2505
AAGGAAAA G CAACAGGA
6528
TCCTGTTG GGCTAGCTACAACGA TTTTCCTT
15277


2502
GAAAAGCA A CAGGACAU
6529
ATGTCCTG GGCTAGCTACAACGA TGCTTTTC
15278


2497
GCAACAGG A CAUACUCC
6530
GGAGTATG GGCTAGCTACAACGA CCTGTTGC
15279


2495
AACAGGAC A UACUCCCA
6531
TGGGAGTA GGCTAGCTACAACGA GTCCTGTT
15280


2493
CAGGACAU A CUCCCAUU
6532
AATGGGAG GGCTAGCTACAACGA ATGTCCTG
15281


2487
AUACUCCC A UUUGAUUG
6533
CAATCAAA GGCTAGCTACAACGA GGGAGTAT
15282


2482
CCCAUUUG A UUGCGAAG
6534
CTTCGCAA GGCTAGCTACAACGA CAAATGGG
15283


2479
AUUUGAUU G CGAAGGAG
6535
CTCCTTCG GGCTAGCTACAACGA AATCAAAT
15284


2470
CGAAGGAG A CAACCGCU
6536
AGCGGTTG GGCTAGCTACAACGA CTCCTTCC
15285


2467
AGGAGACA A CCGCUGAC
6537
GTCAGCGG GGCTAGCTACAACGA TGTCTCCT
15286


2464
AGACAACC G CUGACCCU
6538
AGGGTCAG GGCTAGCTACAACGA GGTTGTCT
15287


2460
AACCGCUG A CCCUACAC
6539
GTGTAGGG GGCTAGCTACAACGA CAGCGGTT
15288


2455
CUGACCCU A CACCGUAC
6540
GTACGGTG GGCTAGCTACAACGA AGGGTCAG
15289


2453
GACCCUAC A CCGUACAG
6541
CTGTACGG GGCTAGCTACAACGA GTAGGGTC
15290


2450
CCUACACC G UACAGGUA
6542
TACCTGTA GGCTAGCTACAACGA GGTGTAGG
15291


2448
UACACCGU A CAGGUAUU
6543
AATACCTG GGCTAGCTACAACGA ACGGTGTA
15292


2444
CCGUACAG G UAUUGCAC
6544
GTGCAATA GGCTAGCTACAACGA CTGTACGG
15293


2442
GUACAGGU A UUGCACGU
6545
ACGTGCAA GGCTAGCTACAACGA ACCTGTAC
15294


2439
CAGGUAUU G CACGUCCA
6546
TGGACGTG GGCTAGCTACAACGA AATACCTG
15295


2437
GGUAUUGC A CGUCCACG
6547
CGTGGACG GGCTAGCTACAACGA GCAATACC
15296


2435
UAUUGCAC G UCCACGAU
6548
ATCGTGGA GGCTAGCTACAACGA GTGCAATA
15297


2431
GCACGUCC A CGAUGUUC
6549
GAACATCG GGCTAGCTACAACGA GGACGTGC
15298


2428
CGUCCACG A UGUUCUGG
6550
CCAGAACA GGCTAGCTACAACGA CGTGGACG
15299


2426
UCCACGAU G UUCUGGUG
6551
CACCAGAA GGCTAGCTACAACGA ATCGTGGA
15300


2420
AUGUUCUG G UGGAGAUG
6552
CATCTCCA GGCTAGCTACAACGA CAGAACAT
15301


2414
UGGUGGAG A UGGAUCAA
6553
TTGATCCA GGCTAGCTACAACGA CTCCACCA
15302


2410
GGAGAUGG A UCAAACCA
6554
TGGTTTGA GGCTAGCTACAACGA CCATCTCC
15303


2405
UGGAUCAA A CCAGUGGA
6555
TCCACTGG GGCTAGCTACAACGA TTGATCCA
15304


2401
UCAAACCA G UGGACAGA
6556
TCTGTCCA GGCTAGCTACAACGA TGGTTTGA
15305


2397
ACCAGUGG A CAGAGCCG
6557
CGGCTCTG GGCTAGCTACAACGA CCACTGGT
15306


2392
UGGACAGA G CCGGUAGG
6558
CCTACCGG GGCTAGCTACAACGA TCTGTCCA
15307


2388
CAGAGCCG G UAGGGUGG
6559
CCACCCTA GGCTAGCTACAACGA CGGCTCTG
15308


2383
CCGGUAGG G UGGUGAAG
6560
CTTCACCA GGCTAGCTACAACGA CCTACCGG
15309


2380
GUAGGGUG G UGAAGGAG
6561
CTCCTTCA GGCTAGCTACAACGA CACCCTAC
15310


2372
GUGAAGGA G CAGGGCAG
6562
CTGCCCTG GGCTAGCTACAACGA TCCTTCAC
15311


2367
GGAGCAGG G CAGUAUUU
6563
AAATACTG GGCTAGCTACAACGA CCTGCTCC
15312


2364
GCAGGGCA G UAUUUGCC
6564
GGCAAATA GGCTAGCTACAACGA TGCCCTGC
15313


2362
AGGGCAGU A UUUGCCAC
6565
GTGGCAAA GGCTAGCTACAACGA ACTGCCCT
15314


2358
CAGUAUUU G CCACUCUG
6566
CAGAGTGG GGCTAGCTACAACGA AAATACTG
15315


2355
UAUUUGCC A CUCUGUAG
6567
CTACAGAG GGCTAGCTACAACGA GGCAAATA
15316


2350
GCCACUCU G UAGUGGAC
6568
GTCCACTA GGCTAGCTACAACGA AGAGTGGC
15317


2347
ACUCUGUA G UGGACAAC
6569
GTTGTCCA GGCTAGCTACAACGA TACAGAGT
15318


2343
UGUAGUGG A CAACAGCA
6570
TGCTGTTG GGCTAGCTACAACGA CCACTACA
15319


2340
AGUGGACA A CAGCAGCG
6571
CGCTGCTG GGCTAGCTACAACGA TGTCCACT
15320


2337
GGACAACA G CAGCGGGC
6572
GCCCGCTG GGCTAGCTACAACGA TGTTGTCC
15321


2334
CAACAGCA G CGGGCUGA
6573
TCAGCCCG GGCTAGCTACAACGA TGCTGTTG
15322


2330
AGCAGCGG G CUGAGCUC
6574
GAGCTCAG GGCTAGCTACAACGA CCGCTGCT
15323


2325
CGGGCUGA G CUCUGAUC
6575
GATCAGAG GGCTAGCTACAACGA TCAGCCCG
15324


2319
GAGCUCUG A UCUGUCCC
6576
GGGACAGA GGCTAGCTACAACGA CAGAGCTC
15325


2315
UCUGAUCU G UCCCUGUC
6577
GACAGGGA GGCTAGCTACAACGA AGATCAGA
15326


2309
CUGUCCCU G UCCUCCAA
6578
TTGGAGGA GGCTAGCTACAACGA AGGGACAG
15327


2300
UCCUCCAA A UCACAACG
6579
CGTTGTGA GGCTAGCTACAACGA TTGGAGGA
15328


2297
UCCAAAUC A CAACGCUC
6580
GAGCGTTG GGCTAGCTACAACGA GATTTGGA
15329


2294
AAAUCACA A CGCUCUCC
6581
GGAGAGCG GGCTAGCTACAACGA TGTGATTT
15330


2292
AUCACAAC G CUCUCCUC
6582
GAGGAGAG GGCTAGCTACAACGA GTTGTGAT
15331


2281
CUCCUCGA G UCCAAUUG
6583
CAATTGGA GGCTAGCTACAACGA TCGAGGAG
15332


2276
CGAGUCCA A UUGCAUGC
6584
GCATGCAA GGCTAGCTACAACGA TGGACTCG
15333


2273
GUCCAAUU G CAUGCGGC
6585
GCCGCATG GGCTAGCTACAACGA AATTGGAC
15334


2271
CCAAUUGC A UGCGGCGG
6586
CCGCCGCA GGCTAGCTACAACGA GCAATTGG
15335


2269
AAUUGCAU G CGGCGGUG
6587
CACCGCCG GGCTAGCTACAACGA ATGCAATT
15336


2266
UGCAUGCG G CGGUGAGC
6588
GCTCACCG GGCTAGCTACAACGA CGCATGCA
15337


2263
AUGCGGCG G UGAGCCUG
6589
CAGGCTCA GGCTAGCTACAACGA CGCCGCAT
15338


2259
GGCGGUGA G CCUGUGCU
6590
AGCACAGG GGCTAGCTACAACGA TCACCGCC
15339


2255
GUGAGCCU G UGCUCCAC
6591
GTGGAGCA GGCTAGCTACAACGA AGGCTCAC
15340


2253
GAGCCUGU G CUCCACGC
6592
GCGTGGAG GGCTAGCTACAACGA ACAGGCTC
15341


2248
UGUGCUCC A CGCCCCCC
6593
GGGGGGCG GGCTAGCTACAACGA GGAGCACA
15342


2246
UGCUCCAC G CCCCCCAC
6594
GTGGGGGG GGCTAGCTACAACGA GTGGAGCA
15343


2239
CGCCCCCC A CAUACAUC
6595
GATGTATG GGCTAGCTACAACGA GGGGGGCG
15344


2237
CCCCCCAC A UACAUCCU
6596
AGGATGTA GGCTAGCTACAACGA GTGGGGGG
15345


2235
CCCCACAU A CAUCCUAA
6597
TTAGGATG GGCTAGCTACAACGA ATGTGGGG
15346


2233
CCACAUAC A UCCUAACC
6598
GGTTAGGA GGCTAGCTACAACGA GTATGTGG
15347


2227
ACAUCCUA A CCUUAAAG
6599
CTTTAAGG GGCTAGCTACAACGA TAGGATGT
15348


2218
CCUUAAAG A UGGAAAAA
6600
TTTTTCCA GGCTAGCTACAACGA CTTTAAGG
15349


2210
AUGGAAAA A UUGACAGU
6601
ACTGTCAA GGCTAGCTACAACGA TTTTCCAT
15350


2206
AAAAAUUG A CAGUGCAG
6602
CTGCACTG GGCTAGCTACAACGA CAATTTTT
15351


2203
AAUUGACA G UGCAGGGG
6603
CCCCTGCA GGCTAGCTACAACGA TGTCAATT
15352


2201
UUGACAGU G CAGGGGUA
6604
TACCCCTG GGCTAGCTACAACGA ACTGTCAA
15353


2195
GUGCAGGG G UAGUGCCA
6605
TGGCACTA GGCTAGCTACAACGA CCCTGCAC
15354


2192
CAGGGGUA G UGCCAAAG
6606
CTTTGGCA GGCTAGCTACAACGA TACCCCTG
15355


2190
GGGGUAGU G CCAAAGCC
6607
GGCTTTGG GGCTAGCTACAACGA ACTACCCC
15356


2184
GUGCCAAA G CCUGUAUG
6608
CATACAGG GGCTAGCTACAACGA TTTGGCAC
15357


2180
CAAAGCCU G UAUGGGUA
6609
TACCCATA GGCTAGCTACAACGA AGGCTTTG
15358


2178
AAGCCUGU A UGGGUAGU
6610
ACTACCCA GGCTAGCTACAACGA ACAGGCTT
15359


2174
CUGUAUGG G UAGUCAAC
6611
GTTGACTA GGCTAGCTACAACGA CCATACAG
15360


2171
UAUGGGUA G UCAACUAU
6612
ATAGTTGA GGCTAGCTACAACGA TACCCATA
15361


2167
GGUAGUCA A CUAUGCAU
6613
ATGCATAG GGCTAGCTACAACGA TGACTACC
15362


2164
AGUCAACU A UGCAUCUA
6614
TAGATGCA GGCTAGCTACAACGA AGTTGACT
15363


2162
UCAACUAU G CAUCUAGG
6615
CCTAGATG GGCTAGCTACAACGA ATAGTTGA
15364


2160
AACUAUGC A UCUAGGUG
6616
CACCTAGA GGCTAGCTACAACGA GCATAGTT
15365


2154
GCAUCUAG G UGUUAACC
6617
GGTTAACA GGCTAGCTACAACGA CTAGATGC
15366


2152
AUCUAGGU G UUAACCAA
6618
TTGGTTAA GGCTAGCTACAACGA ACCTAGAT
15367


2148
AGGUGUUA A CCAAGGCC
6619
GGCCTTGG GGCTAGCTACAACGA TAACACCT
15368


2142
UAACCAAG G CCCCGAAC
6620
GTTCGGGG GGCTAGCTACAACGA CTTGGTTA
15369


2135
GGCCCCGA A CCGCACUU
6621
AAGTGCGG GGCTAGCTACAACGA TCGGGGCC
15370


2132
CCCGAACC G CACUUUGC
6622
GCAAAGTG GGCTAGCTACAACGA GGTTCGGG
15371


2130
CGAACCGC A CUUUGCGU
6623
ACGCAAAG GGCTAGCTACAACGA GCGGTTCG
15372


2125
CGCACUUU G CGUAAGUG
6624
CACTTACG GGCTAGCTACAACGA AAAGTGCG
15373


2123
CACUUUGC G UAAGUGGC
6625
GCCACTTA GGCTAGCTACAACGA GCAAAGTG
15374


2119
UUGCGUAA G UGGCCUCG
6626
CGAGGCCA GGCTAGCTACAACGA TTACGCAA
15375


2116
CGUAAGUG G CCUCGGGG
6627
CCCCGAGG GGCTAGCTACAACGA CACTTACG
15376


2108
GCCUCGGG G UGCUUCCG
6628
CGGAAGCA GGCTAGCTACAACGA CCCGAGGC
15377


2106
CUCGGGGU G CUUCCGGA
6629
TCCGGAAG GGCTAGCTACAACGA ACCCCGAG
15378


2096
UUCCGGAA G CAGUCCGU
6630
ACGGACTG GGCTAGCTACAACGA TTCCGGAA
15379


2093
CGGAAGCA G UCCGUGGG
6631
CCCACGGA GGCTAGCTACAACGA TGCTTCCG
15380


2089
AGCAGUCC G UGGGGCAG
6632
CTGCCCCA GGCTAGCTACAACGA GGACTGCT
15381


2084
UCCGUGGG G CAGGUUAA
6633
TTAACCTG GGCTAGCTACAACGA CCCACGGA
15382


2080
UGGGGCAG G UUAAGGUG
6634
CACCTTAA GGCTAGCTACAACGA CTGCCCCA
15383


2074
AGGUUAAG G UGUCGUUA
6635
TAACGACA GGCTAGCTACAACGA CTTAACCT
15384


2072
GUUAAGGU G UCGUUACC
6636
GGTAACGA GGCTAGCTACAACGA ACCTTAAC
15385


2069
AAGGUGUC G UUACCGGC
6637
GCCGGTAA GGCTAGCTACAACGA GACACCTT
15386


2066
GUGUCGUU A CCGGCCCC
6638
GGGGCCGG GGCTAGCTACAACGA AACGACAC
15387


2062
CGUUACCG G CCCCCCCG
6639
CGGGGGGG GGCTAGCTACAACGA CGGTAACG
15388


2053
CCCCCCCG A UGUUGCAC
6640
GTGCAACA GGCTAGCTACAACGA CGGGGGGG
15389


2051
CCCCCGAU G UUGCACGG
6641
CCGTGCAA GGCTAGCTACAACGA ATCGGGGG
15390


2048
CCGAUGUU G CACGGGGG
6642
CCCCCGTG GGCTAGCTACAACGA AACATCGG
15391


2046
GAUGUUGC A CGGGGGGC
6643
GCCCCCCG GGCTAGCTACAACGA GCAACATC
15392


2039
CACGGGGG G CCCCCGCA
6644
TGCGGGGG GGCTAGCTACAACGA CCCCCGTG
15393


2033
GGGCCCCC G CACGUCUU
6645
AAGACGTG GGCTAGCTACAACGA GGGGGCCC
15394


2031
GCCCCCGC A CGUCUUGG
6646
CCAAGACG GGCTAGCTACAACGA GCGGGGGC
15395


2029
CCCCGCAC G UCUUGGUG
6647
CACCAAGA GGCTAGCTACAACGA GTGCGGGG
15396


2023
ACGUCUUG G UGAACCCA
6648
TGGGTTCA GGCTAGCTACAACGA CAAGACGT
15397


2019
CUUGGUGA A CCCAGUGC
6649
GCACTGGG GGCTAGCTACAACGA TCACCAAG
15398


2014
UGAACCCA G UGCCAUUC
6650
GAATGGCA GGCTAGCTACAACGA TGGGTTCA
15399


2012
AACCCAGU G CCAUUCAU
6651
ATGAATGG GGCTAGCTACAACGA ACTGGGTT
15400


2009
CCAGUGCC A UUCAUCCA
6652
TGGATGAA GGCTAGCTACAACGA GGCACTGG
15401


2005
UGCCAUUC A UCCAUGUG
6653
CACATGGA GGCTAGCTACAACGA GAATGGCA
15402


2001
AUUCAUCC A UGUGCAGC
6654
GCTGCACA GGCTAGCTACAACGA GGATGAAT
15403


1999
UCAUCCAU G UGCAGCCG
6655
CGGCTGCA GGCTAGCTACAACGA ATGGATGA
15404


1997
AUCCAUGU G CAGCCGAA
6656
TTCGGCTG GGCTAGCTACAACGA ACATGGAT
15405


1994
CAUGUGCA G CCGAACCA
6657
TGGTTCGG GGCTAGCTACAACGA TGCACATG
15406


1989
GCAGCCGA A CCAGUUGC
6658
GCAACTGG GGCTAGCTACAACGA TCGGCTGC
15407


1985
CCGAACCA G UUGCCUUG
6659
CAAGGCAA GGCTAGCTACAACGA TGGTTCGG
15408


1982
AACCAGUU G CCUUGCGG
6660
CCGCAAGG GGCTAGCTACAACGA AACTGGTT
15409


1977
GUUGCCUU G CGGCGGCC
6661
GGCCGCCG GGCTAGCTACAACGA AAGGCAAC
15410


1974
GCCUUGCG G CGGCCGCG
6662
CGCGGCCG GGCTAGCTACAACGA CGCAAGGC
15411


1971
UUGCGGCG G CCGCGUGU
6663
ACACGCGG GGCTAGCTACAACGA CGCCGCAA
15412


1968
CGGCGGCC G CGUGUUGU
6664
ACAACACG GGCTAGCTACAACGA GGCCGCCG
15413


1966
GCGGCCGC G UGUUGUUG
6665
CAACAACA GGCTAGCTACAACGA GCGGCCGC
15414


1964
GGCCGCGU G UUGUUGAG
6666
CTCAACAA GGCTAGCTACAACGA ACGCGGCC
15415


1961
CGCGUGUU G UUGAGGAG
6667
CTCCTCAA GGCTAGCTACAACGA AACACGCG
15416


1953
GUUGAGGA G CAGCACGU
6668
ACGTGCTG GGCTAGCTACAACGA TCCTCAAC
15417


1950
GAGGAGCA G CACGUCCG
6669
CGGACGTG GGCTAGCTACAACGA TGCTCCTC
15418


1948
GGAGCAGC A CGUCCGUC
6670
GACGGACG GGCTAGCTACAACGA GCTGCTCC
15419


1946
AGCAGCAC G UCCGUCUC
6671
GAGACGGA GGCTAGCTACAACGA GTGCTGCT
15420


1942
GCACGUCC G UCUCGUUC
6672
GAACGAGA GGCTAGCTACAACGA GGACGTGC
15421


1937
UCCGUCUC G UUCGCCCC
6673
GGGGCGAA GGCTAGCTACAACGA GAGACGGA
15422


1933
UCUCGUUC G CCCCCCAG
6674
CTGGGGGG GGCTAGCTACAACGA GAACGAGA
15423


1925
GCCCCCCA G UUAUACGU
6675
ACGTATAA GGCTAGCTACAACGA TGGGGGGC
15424


1922
CCCCAGUU A UACGUGGG
6676
CCCACGTA GGCTAGCTACAACGA AACTGGGG
15425


1920
CCAGUUAU A CGUGGGGG
6677
CCCCCACG GGCTAGCTACAACGA ATAACTGG
15426


1918
AGUUAUAC G UGGGGGCG
6678
CGCCCCCA GGCTAGCTACAACGA GTATAACT
15427


1912
ACGUGGGG G CGCCGAAA
6679
TTTCGGCG GGCTAGCTACAACGA CCCCACGT
15428


1910
GUGGGGGC G CCGAAACG
6680
CGTTTCGG GGCTAGCTACAACGA GCCCCCAC
15429


1904
GCGCCGAA A CGGUCGGU
6681
ACCGACCG GGCTAGCTACAACGA TTCGGCGC
15430


1901
CCGAAACG G UCGGUCGU
6682
ACGACCGA GGCTAGCTACAACGA CGTTTCGG
15431


1897
AACGGUCG G UCGUCCCC
6683
GGGGACGA GGCTAGCTACAACGA CGACCGTT
15432


1894
GGUCGGUC G UCCCCACC
6684
GGTGGGGA GGCTAGCTACAACGA GACCGACC
15433


1888
UCGUCCCC A CCACAACA
6685
TGTTGTGG GGCTAGCTACAACGA GGGGACGA
15434


1885
UCCCCACC A CAACAGGG
6686
CCCTGTTG GGCTAGCTACAACGA GGTGGGGA
15435


1882
CCACCACA A CAGGGCUU
6687
AAGCCCTG GGCTAGCTACAACGA TGTGGTGG
15436


1877
ACAACAGG G CUUGGGGU
6688
ACCCCAAG GGCTAGCTACAACGA CCTGTTGT
15437


1870
GGCUUGGG G UGAAGCAA
6689
TTGCTTCA GGCTAGCTACAACGA CCCAAGCC
15438


1865
GGGGUGAA G CAAUACAC
6690
GTGTATTG GGCTAGCTACAACGA TTCACCCC
15439


1862
GUGAAGCA A UACACUGG
6691
CCAGTGTA GGCTAGCTACAACGA TGCTTCAC
15440


1860
GAAGCAAU A CACUGGAC
6692
GTCCAGTG GGCTAGCTACAACGA ATTGCTTC
15441


1858
AGCAAUAC A CUGGACCA
6693
TGGTCCAG GGCTAGCTACAACGA GTATTGCT
15442


1853
UACACUGG A CCACAUAC
6694
GTATGTGG GGCTAGCTACAACGA CCAGTGTA
15443


1850
ACUGGACC A CAUACCUG
6695
CAGGTATG GGCTAGCTACAACGA GGTCCAGT
15444


1848
UGGACCAC A UACCUGCG
6696
CGCAGGTA GGCTAGCTACAACGA GTGGTCCA
15445


1846
GACCACAU A CCUGCGAU
6697
ATCGCAGG GGCTAGCTACAACGA ATGTGGTC
15446


1842
ACAUACCU G CGAUGCGG
6698
CCGCATCG GGCTAGCTACAACGA AGGTATGT
15447


1839
UACCUGCG A UGCGGGUA
6699
TACCCGCA GGCTAGCTACAACGA CGCAGGTA
15448


1837
CCUGCGAU G CGGGUACG
6700
CGTACCCG GGCTAGCTACAACGA ATCGCAGG
15449


1833
CGAUGCGG G UACGAUAC
6701
GTATCGTA GGCTAGCTACAACGA CCGCATCG
15450


1831
AUGCGGGU A CGAUACCA
6702
TGGTATCG GGCTAGCTACAACGA ACCCGCAT
15451


1828
CGGGUACG A UACCACAC
6703
GTGTGGTA GGCTAGCTACAACGA CGTACCCG
15452


1826
GGUACGAU A CCACACGG
6704
CCGTGTGG GGCTAGCTACAACGA ATCGTACC
15453


1823
ACGAUACC A CACGGCCG
6705
CGGCCGTG GGCTAGCTACAACGA GGTATCGT
15454


1821
GAUACCAC A CGGCCGCG
6706
CGCGGCCG GGCTAGCTACAACGA GTGGTATC
15455


1818
ACCACACG G CCGCGGUG
6707
CACCGCGG GGCTAGCTACAACGA CGTGTGGT
15456


1815
ACACGGCC G CGGUGCGU
6708
ACGCACCG GGCTAGCTACAACGA GGCCGTGT
15457


1812
CGGCCGCG G UGCGUAGU
6709
ACTACGCA GGCTAGCTACAACGA CGCGGCCG
15458


1810
GCCGCGGU G CGUAGUGC
6710
GCACTACG GGCTAGCTACAACGA ACCGCGGC
15459


1808
CGCGGUGC G UAGUGCCA
6711
TGGCACTA GGCTAGCTACAACGA GCACCGCG
15460


1805
GGUGCGUA G UGCCAGCA
6712
TGCTGGCA GGCTAGCTACAACGA TACGCACC
15461


1803
UGCGUAGU G CCAGCAAU
6713
ATTGCTGG GGCTAGCTACAACGA ACTACGCA
15462


1799
UAGUGCCA G CAAUAGGG
6714
CCCTATTG GGCTAGCTACAACGA TGGCACTA
15463


1796
UGCCAGCA A UAGGGCCU
6715
AGGCCCTA GGCTAGCTACAACGA TGCTGGCA
15464


1791
GCAAUAGG G CCUCUGGU
6716
ACCAGAGG GGCTAGCTACAACGA CCTATTGC
15465


1784
GGCCUCUG G UCCGAGUU
6717
AACTCGGA GGCTAGCTACAACGA CAGAGGCC
15466


1778
UGGUCCGA G UUGUGGCC
6718
GGCCACAA GGCTAGCTACAACGA TCGGACCA
15467


1775
UCCGAGUU G UGGCCCUC
6719
GAGGGCCA GGCTAGCTACAACGA AACTCGGA
15468


1772
GAGUUGUG G CCCUCGGU
6720
ACCGAGGG GGCTAGCTACAACGA CACAACTC
15469


1765
GGCCCUCG G UGUAGGUG
6721
CACCTACA GGCTAGCTACAACGA CGAGGGCC
15470


1763
CCCUCGGU G UAGGUGAU
6722
ATCACCTA GGCTAGCTACAACGA ACCGAGGG
15471


1759
CGGUGUAG G UGAUAGGA
6723
TCCTATCA GGCTAGCTACAACGA CTACACCG
15472


1756
UGUAGGUG A UAGGACCC
6724
GGGTCCTA GGCTAGCTACAACGA CACCTACA
15473


1751
GUGAUAGG A CCCCACCC
6725
GGGTGGGG GGCTAGCTACAACGA CCTATCAC
15474


1746
AGGACCCC A CCCCUGAG
6726
CTCAGGGG GGCTAGCTACAACGA GGGGTCCT
15475


1738
ACCCCUGA G CGAACUUG
6727
CAAGTTCG GGCTAGCTACAACGA TCAGGGGT
15476


1734
CUGAGCGA A CUUGUCAA
6728
TTGACAAG GGCTAGCTACAACGA TCGCTCAG
15477


1730
GCGAACUU G UCAAUGGA
6729
TCCATTGA GGCTAGCTACAACGA AAGTTCGC
15478


1726
ACUUGUCA A UGGAGCGG
6730
CCGCTCCA GGCTAGCTACAACGA TGACAAGT
15479


1721
UCAAUGGA G CGGCAGCU
6731
AGCTGCCG GGCTAGCTACAACGA TCCATTGA
15480


1718
AUGGAGCG G CAGCUGGC
6732
GCCAGCTG GGCTAGCTACAACGA CGCTCCAT
15481


1715
GAGCGGCA G CUGGCCAA
6733
TTGGCCAG GGCTAGCTACAACGA TGCCGCTC
15482


1711
GGCAGCUG G CCAAGCGC
6734
GCGCTTGG GGCTAGCTACAACGA CAGCTGCC
15483


1706
CUGGCCAA G CGCUGUGG
6735
CCACAGCG GGCTAGCTACAACGA TTGGCCAG
15484


1704
GGCCAAGC G CUGUGGGC
6736
GCCCACAG GGCTAGCTACAACGA GCTTGGCC
15485


1701
CAAGCGCU G UGGGCAUC
6737
GATGCCCA GGCTAGCTACAACGA AGCGCTTG
15486


1697
CGCUGUGG G CAUCCGGA
6738
TCCGGATG GGCTAGCTACAACGA CCACAGCG
15487


1695
CUGUGGGC A UCCGGACG
6739
CGTCCGGA GGCTAGCTACAACGA GCCCACAG
15488


1689
GCAUCCGG A CGAGUUGA
6740
TCAACTCG GGCTAGCTACAACGA CCGGATGC
15489


1685
CCGGACGA G UUGAACCU
6741
AGGTTCAA GGCTAGCTACAACGA TCGTCCGG
15490


1680
CGAGUUGA A CCUGUGUG
6742
CACACAGG GGCTAGCTACAACGA TCAACTCG
15491


1676
UUGAACCU G UGUGCAUA
6743
TATGCACA GGCTAGCTACAACGA AGGTTCAA
15492


1674
GAACCUGU G UGCAUAGA
6744
TCTATGCA GGCTAGCTACAACGA ACAGGTTC
15493


1672
ACCUGUGU G CAUAGAAC
6745
GTTCTATG GGCTAGCTACAACGA ACACAGGT
15494


1670
CUGUGUGC A UAGAACAG
6746
CTGTTCTA GGCTAGCTACAACGA GCACACAG
15495


1665
UGCAUAGA A CAGUGCAG
6747
CTGCACTG GGCTAGCTACAACGA TCTATGCA
15496


1662
AUAGAACA G UGCAGCAA
6748
TTGCTGCA GGCTAGCTACAACGA TGTTCTAT
15497


1660
AGAACAGU G CAGCAAUG
6749
CATTGCTG GGCTAGCTACAACGA ACTGTTCT
15498


1657
ACAGUGCA G CAAUGAAC
6750
GTTCATTG GGCTAGCTACAACGA TGCACTGT
15499


1654
GUGCAGCA A UGAACCCG
6751
CGGGTTCA GGCTAGCTACAACGA TGCTGCAC
15500


1650
AGCAAUGA A CCCGGUUU
6752
AAACCGGG GGCTAGCTACAACGA TCATTGCT
15501


1645
UGAACCCG G UUUGGAGG
6753
CCTCCAAA GGCTAGCTACAACGA CGGGTTCA
15502


1634
UGGAGGGA G UCAUUGCA
6754
TGCAATGA GGCTAGCTACAACGA TCCCTCCA
15503


1631
AGGGAGUC A UUGCAGUU
6755
AACTGCAA GGCTAGCTACAACGA GACTCCCT
15504


1628
GAGUCAUU G CAGUUCAG
6756
CTGAACTG GGCTAGCTACAACGA AATGACTC
15505


1625
UCAUUGCA G UUCAGGGC
6757
GCCCTGAA GGCTAGCTACAACGA TGCAATGA
15506


1618
AGUUCAGG G CAGUCCUG
6758
CAGGACTG GGCTAGCTACAACGA CCTGAACT
15507


1615
UCAGGGCA G UCCUGUUA
6759
TAACAGGA GGCTAGCTACAACGA TGCCCTGA
15508


1610
GCAGUCCU G UUAAUGUG
6760
CACATTAA GGCTAGCTACAACGA AGGACTGC
15509


1606
UCCUGUUA A UGUGCCAG
6761
CTGGCACA GGCTAGCTACAACGA TAACAGGA
15510


1604
CUGUUAAU G UGCCAGCU
6762
AGCTGGCA GGCTAGCTACAACGA ATTAACAG
15511


1602
GUUAAUGU G CCAGCUGC
6763
GCAGCTGG GGCTAGCTACAACGA ACATTAAC
15512


1598
AUGUGCCA G CUGCCGUU
6764
AACGGCAG GGCTAGCTACAACGA TGGCACAT
15513


1595
UGCCAGCU G CCGUUGGU
6765
ACCAACGG GGCTAGCTACAACGA AGCTGGCA
15514


1592
CAGCUGCC G UUGGUGUU
6766
AACACCAA GGCTAGCTACAACGA GGCAGCTG
15515


1588
UGCCGUUG G UGUUAAUA
6767
TATTAACA GGCTAGCTACAACGA CAACGGCA
15516


1586
CCGUUGGU G UUAAUAAG
6768
CTTATTAA GGCTAGCTACAACGA ACCAACGG
15517


1582
UGGUGUUA A UAAGCUGG
6769
CCAGCTTA GGCTAGCTACAACGA TAACACCA
15518


1578
GUUAAUAA G CUGGAUAU
6770
ATATCCAG GGCTAGCTACAACGA TTATTAAC
15519


1573
UAAGCUGG A UAUUCUGA
6771
TCAGAATA GGCTAGCTACAACGA CCAGCTTA
15520


1571
AGCUGGAU A UUCUGAGA
6772
TCTCAGAA GGCTAGCTACAACGA ATCCAGCT
15521


1563
AUUCUGAG A UGCUCCAG
6773
CTGGAGCA GGCTAGCTACAACGA CTCAGAAT
15522


1561
UCUGAGAU G CUCCAGAU
6774
ATCTGGAG GGCTAGCTACAACGA ATCTCAGA
15523


1554
UGCUCCAG A UGUAAAGA
6775
TCTTTACA GGCTAGCTACAACGA CTGGAGCA
15524


1552
CUCCAGAU G UAAAGAGG
6776
CCTCTTTA GGCTAGCTACAACGA ATCTGGAG
15525


1542
AAAGAGGG A UGCCACCC
6777
GGGTGGCA GGCTAGCTACAACGA CCCTCTTT
15526


1540
ACACCCAU G GGAGGGUA
6778
TAGGGTGG GGCTAGCTACAACGA ATCCCTCT
15527


1537
GGGAUGCC A CCCUACUA
6779
TAGTAGGG GGCTAGCTACAACGA GGCATCCC
15528


1532
GCCACCCU A CUAGUGGU
6780
ACCACTAG GGCTAGCTACAACGA AGGGTGGC
15529


1528
CCCUACUA G UGGUGUGG
6781
CCACACCA GGCTAGCTACAACGA TAGTAGGG
15530


1525
UACUAGUG G UGUGGCCC
6782
GGGCCACA GGCTAGCTACAACGA CACTAGTA
15531


1523
CUAGUGGU G UGGCCCUG
6783
CAGGGCCA GGCTAGCTACAACGA ACCACTAG
15532


1520
GUGGUGUG G CCCUGCGC
6784
GCGCAGGG GGCTAGCTACAACGA CACACCAC
15533


1515
GUGGCCCU G CGCCCCCC
6785
GGGGGGCG GGCTAGCTACAACGA AGGGCCAC
15534


1513
GGCCCUGC G CCCCCCCU
6786
AGGGGGGG GGCTAGCTACAACGA GCAGGGCC
15535


1504
CCCCCCCU G UCGUGUAG
6787
CTACACGA GGCTAGCTACAACGA AGGGGGGG
15536


1501
CCCCUGUC G UGUAGGUG
6788
CACCTACA GGCTAGCTACAACGA GACAGGGG
15537


1499
CCUGUCGU G UAGGUGUC
6789
GACACCTA GGCTAGCTACAACGA ACGACAGG
15538


1495
UCGUGUAG G UGUCCCCG
6790
CGGGGACA GGCTAGCTACAACGA CTACACGA
15539


1493
GUGUAGGU G UCCCCGUC
6791
GACGGGGA GGCTAGCTACAACGA ACCTACAC
15540


1487
GUGUCCCC G UCAACGCC
6792
GGCGTTGA GGCTAGCTACAACGA GGGGACAC
15541


1483
CCCCGUCA A CGCCGGCA
6793
TGCCGGCG GGCTAGCTACAACGA TGACGGGG
15542


1481
CCGUCAAC G CCGGCAAA
6794
TTTGCCGG GGCTAGCTACAACGA GTTGACGG
15543


1477
CAACGCCG G CAAAGAGU
6795
ACTCTTTG GGCTAGCTACAACGA CGGCGTTG
15544


1470
GGCAAAGA G UAGCAUCA
6796
TGATGCTA GGCTAGCTACAACGA TCTTTGCC
15545


1467
AAAGAGUA G CAUCACAA
6797
TTGTGATG GGCTAGCTACAACGA TACTCTTT
15546


1465
AGAGUAGC A UCACAAUG
6798
GATTGTGA GGCTAGCTACAACGA GCTACTCT
15547


1462
GUAGCAUC A CAAUCAAC
6799
GTTGATTG GGCTAGCTACAACGA GATGCTAC
15548


1459
GCAUCACA A UCAACACC
6800
GGTGTTGA GGCTAGCTACAACGA TGTGATGC
15549


1455
CACAAUCA A CACCUUAG
6801
CTAAGGTG GGCTAGCTACAACGA TGATTGTG
15550


1453
CAAUCAAC A CCUUAGCC
6802
GGCTAAGG GGCTAGCTACAACGA GTTGATTG
15551


1447
ACACCUUA G CCCAGUUC
6803
GAACTGGG GGCTAGCTACAACGA TAAGGTGT
15552


1442
UUAGCCCA G UUCCCCAC
6804
GTGGGGAA GGCTAGCTACAACGA TGGGCTAA
15553


1435
AGUUCCCC A CCAUGGAA
6805
TTCCATGG GGCTAGCTACAACGA GGGGAACT
15554


1432
UCCCCACC A UGGAAUAA
6806
TTATTCCA GGCTAGCTACAACGA GGTGGGGA
15555


1427
ACCAUGGA A UAAUAGGC
6807
GCCTATTA GGCTAGCTACAACGA TCCATGGT
15556


1424
AUGGAAUA A UAGGCAAG
6808
CTTGCCTA GGCTAGCTACAACGA TATTCCAT
15557


1420
AAUAAUAG G CAAGGCCC
6809
GGGCCTTG GGCTAGCTACAACGA CTATTATT
15558


1415
UAGGCAAG G CCCGCCAG
6810
CTGGCGGG GGCTAGCTACAACGA CTTGCCTA
15559


1411
CAAGGCCC G CCAGGACU
6811
AGTCCTGG GGCTAGCTACAACGA GGGCCTTG
15560


1405
CCGCCAGG A CUCCCCAG
6812
CTGGGGAG GGCTAGCTACAACGA CCTGGCGG
15561


1397
ACUCCCCA G UGGGCCCC
6813
GGGGCCCA GGCTAGCTACAACGA TGGGGAGT
15562


1393
CCCAGUGG G CCCCCGCC
6814
GGCGGGGG GGCTAGCTACAACGA CCACTGGG
15563


1387
GGGCCCCC G CCACCAUG
6815
CATGGTGG GGCTAGCTACAACGA GGGGGCCC
15564


1384
CCCCCGCC A CCAUGUCC
6816
GGACATGG GGCTAGCTACAACGA GGCGGGGG
15565


1381
CCGCCACC A UGUCCACG
6817
CGTGGACA GGCTAGCTACAACGA GGTGGCGG
15566


1379
GCCACCAU G UCCACGAC
6818
GTCGTGGA GGCTAGCTACAACGA ATGGTGGC
15567


1375
CCAUGUCC A CGACGGCU
6819
AGCCGTCG GGCTAGCTACAACGA GGACATGG
15568


1372
UGUCCACG A CGGCUUGU
6820
ACAAGCCG GGCTAGCTACAACGA CGTGGACA
15569


1369
CCACGACG G CUUGUGGG
6821
CCCACAAG GGCTAGCTACAACGA CGTCGTGG
15570


1365
GACGGCUU G UGGGAUCC
6822
GGATCCCA GGCTAGCTACAACGA AAGCCGTC
15571


1360
CUUGUGGG A UCCGGAGC
6823
GCTCCGGA GGCTAGCTACAACGA CCCACAAG
15572


1353
GAUCCGGA G CAACUGCG
6824
CGCAGTTG GGCTAGCTACAACGA TCCGGATC
15573


1350
CCGGAGCA A CUGCGAUA
6825
TATCGCAG GGCTAGCTACAACGA TGCTCCGG
15574


1347
GAGCAACU G CGAUACCA
6826
TGGTATCG GGCTAGCTACAACGA AGTTGCTC
15575


1344
CAACUGCG A UACCACUA
6827
TAGTGGTA GGCTAGCTACAACGA CGCAGTTG
15576


1342
ACUGCGAU A CCACUAGG
6828
CCTAGTGG GGCTAGCTACAACGA ATCGCAGT
15577


1339
GCGAUACC A CUAGGGCU
6829
AGCCCTAG GGCTAGCTACAACGA GGTATCGC
15578


1333
CCACUAGG G CUGUUGUA
6830
TACAACAG GGCTAGCTACAACGA CCTAGTGG
15579


1330
CUAGGGCU G UUGUAGGU
6831
ACCTACAA GGCTAGCTACAACGA AGCCCTAG
15580


1327
GGGCUGUU G UAGGUGAC
6832
GTCACCTA GGCTAGCTACAACGA AACAGCCC
15581


1323
UGUUGUAG G UGACCAAU
6833
ATTGGTCA GGCTAGCTACAACGA CTACAACA
15582


1320
UGUAGGUG A CCAAUUCA
6834
TCAATTGG GGCTAGCTACAACGA CACCTACA
15583


1316
GGUGACCA A UUCAUCAU
6835
ATGATGAA GGCTAGCTACAACGA TGGTCACC
15584


1312
ACCAAUUC A UCAUCAUA
6836
TATGATGA GGCTAGCTACAACGA GAATTGGT
15585


1309
AAUUCAUC A UCAUAUCC
6837
GGATATGA GGCTAGCTACAACGA GATGAATT
15586


1306
UCAUCAUC A UAUCCCAA
6838
TTGGGATA GGCTAGCTACAACGA GATGATGA
15587


1304
AUCAUCAU A UCCCAAGC
6839
GCTTGGGA GGCTAGCTACAACGA ATGATGAT
15588


1297
UAUCCCAA G CCAUGCGA
6840
TCGCATGG GGCTAGCTACAACGA TTGGGATA
15589


1294
CCCAAGCC A UGCGAUGG
6841
CCATCGCA GGCTAGCTACAACGA GGCTTGGG
15590


1292
CAAGCCAU G CGAUGGCC
6842
GGCCATCG GGCTAGCTACAACGA ATGGCTTG
15591


1289
GCCAUGCG A UGGCCUGA
6843
TCAGGCCA GGCTAGCTACAACGA CGCATGGC
15592


1286
AUGCGAUG G CCUGAUAC
6844
GTATCAGG GGCTAGCTACAACGA CATCGCAT
15593


1281
AUGGCCUG A UACGUGGC
6845
GCCACGTA GGCTAGCTACAACGA CAGGCCAT
15594


1279
GGCCUGAU A CGUGGCCG
6846
CGGCCACG GGCTAGCTACAACGA ATCAGGCC
15595


1277
CCUGAUAC G UGGCCGGG
6847
CCCGGCCA GGCTAGCTACAACGA GTATCAGG
15596


1274
GAUACGUG G CCGGGAUA
6848
TATCCCGG GGCTAGCTACAACGA CACGTATC
15597


1268
UGGCCGGG A UAGAUCGA
6849
TCGATCTA GGCTAGCTACAACGA CCCGGCCA
15598


1264
CGGGAUAG A UCGAGCAA
6850
TTGCTCGA GGCTAGCTACAACGA CTATCCCG
15599


1259
UAGAUCGA G CAAUUACA
6851
TGTAATTG GGCTAGCTACAACGA TCGATCTA
15600


1256
AUCGAGCA A UUACAGUC
6852
GACTGTAA GGCTAGCTACAACGA TGCTCGAT
15601


1253
GAGCAAUU A CAGUCCUG
6853
CAGGACTG GGCTAGCTACAACGA AATTGCTC
15602


1250
CAAUUACA G UCCUGUAC
6854
GTACAGGA GGCTAGCTACAACGA TGTAATTG
15603


1245
ACAGUCCU G UACUGUCU
6855
AGACAGTA GGCTAGCTACAACGA AGGACTGT
15604


1243
AGUCCUGU A CUGUCUCA
6856
TGAGACAG GGCTAGCTACAACGA ACAGGACT
15605


1240
CCUGUACU G UCUCAUAC
6857
GTATGAGA GGCTAGCTACAACGA AGTACAGG
15606


1235
ACUGUCUC A UACCGGCG
6858
CGCCGGTA GGCTAGCTACAACGA GAGACAGT
15607


1233
UGUCUCAU A CCGGCGAG
6859
CTCGCCGG GGCTAGCTACAACGA ATGAGACA
15608


1229
UCAUACCG G CGAGGCGA
6860
TCGCCTCG GGCTAGCTACAACGA CGGTATGA
15609


1224
CCGGCGAG G CGAGAAGG
6861
CCTTCTCG GGCTAGCTACAACGA CTCGCCGG
15610


1216
GCGAGAAG G UGAACAGC
6862
GCTGTTCA GGCTAGCTACAACGA CTTCTCGC
15611


1212
GAAGGUGA A CAGCUGAG
6863
CTCAGCTG GGCTAGCTACAACGA TCACCTTC
15612


1209
GGUGAACA G CUGAGAGA
6864
TCTCTCAG GGCTAGCTACAACGA TGTTCACC
15613


1201
GCUGAGAG A CGAGGAAG
6865
CTTCCTCG GGCTAGCTACAACGA CTCTCAGC
15614


1192
CGAGGAAG A CAGAUCCG
6866
CGGATCTG GGCTAGCTACAACGA CTTCCTCG
15615


1188
GAAGACAG A UCCGCAGA
6867
TCTGCGGA GGCTAGCTACAACGA CTGTCTTC
15616


1184
ACAGAUCC G CAGAGAUC
6868
GATCTCTG GGCTAGCTACAACGA GGATCTGT
15617


1178
CCGCAGAG A UCCCCCAC
6869
GTGGGGGA GGCTAGCTACAACGA CTCTGCGG
15618


1171
GAUCCCCC A CGUACAUA
6870
TATGTACC GGCTAGCTACAACGA GGGGGATC
15619


1169
UCCCCCAC G UACAUAGC
6871
GCTATGTA GGCTAGCTACAACGA GTGGGGGA
15620


1167
CCCCACGU A CAUAGCAG
6872
CTGCTATG GGCTAGCTACAACGA ACGTGGGG
15621


1165
CCACGUAC A UAGCAGAG
6873
CTCTGCTA GGCTAGCTACAACGA GTACGTGG
15622


1162
CGUACAUA G CAGAGCAG
6874
CTGCTCTG GGCTAGCTACAACGA TATGTACG
15623


1157
AUAGCAGA G CAGAAAGC
6875
GCTTTCTG GGCTAGCTACAACGA TCTGCTAT
15624


1150
AGCAGAAA G CAGCCGCC
6876
GGCGGCTG GGCTAGCTACAACGA TTTCTGCT
15625


1147
AGAAAGCA G CCGCCCCA
6877
TGGGGCGG GGCTAGCTACAACGA TGCTTTCT
15626


1144
AAGCAGCC G CCCCAACG
6878
CGTTGGGG GGCTAGCTACAACGA GGCTGCTT
15627


1138
CCGCCCCA A CGAGCAAA
6879
TTTGCTCG GGCTAGCTACAACGA TGGGGCGG
15628


1134
CCCAACGA G CAAAUCGA
6880
TCGATTTG GGCTAGCTACAACGA TCGTTGGG
15629


1130
ACGAGCAA A UCGACGUG
6881
CACGTCGA GGCTAGCTACAACGA TTGCTCGT
15630


1126
GCAAAUCG A CGUGACGC
6882
GCGTCACG GGCTAGCTACAACGA CGATTTGC
15631


1124
AAAUCGAC G UGACGCCG
6883
CGGCGTCA GGCTAGCTACAACGA GTCGATTT
15632


1121
UCGACGUG A CGCCGUAU
6884
ATACGGCG GGCTAGCTACAACGA CACGTCGA
15633


1119
GACGUGAC G CCGUAUCG
6885
CGATACGG GGCTAGCTACAACGA GTCACGTC
15634


1116
GUGACGCC G UAUCGUCG
6886
CGACGATA GGCTAGCTACAACGA GGCGTCAC
15635


1114
GACGCCGU A UCGUCGUA
6887
TACGACGA GGCTAGCTACAACGA ACGGCGTC
15636


1111
GCCGUAUC G UCGUAGUG
6888
CACTACGA GGCTAGCTACAACGA GATACGGC
15637


1108
GUAUCGUC G UAGUGGGG
6889
CCCCACTA GGCTAGCTACAACGA GACGATAC
15638


1105
UCGUCGUA G UGGGGAUG
6890
CATCCCCA GGCTAGCTACAACGA TACGACGA
15639


1099
UAGUGGGG A UGCUGGCA
6891
TGCCAGCA GGCTAGCTACAACGA CCCCACTA
15640


1097
GUGGGGAU G CUGGCAUU
6892
AATGCCAG GGCTAGCTACAACGA ATCCCCAC
15641


1093
GGAUGCUG G CAUUCCUG
6893
CAGGAATG GGCTAGCTACAACGA CAGCATCC
15642


1091
AUGCUGGC A UUCCUGGC
6894
GCCAGGAA GGCTAGCTACAACGA GCCAGCAT
15643


1084
CAUUCCUG G CCGCGAGC
6895
GCTCGCGG GGCTAGCTACAACGA CAGGAATG
15644


1081
UCCUGGCC G CGAGCGUG
6896
CACGCTCG GGCTAGCTACAACGA GGCCAGGA
15645


1077
GGCCGCGA G CGUGGGAG
6897
CTCCCACG GGCTAGCTACAACGA TCGCGGCC
15646


1075
CCGCGAGC G UGGGAGUG
6898
CACTCCCA GGCTAGCTACAACGA GCTCGCGG
15647


1069
GCGUGGGA G UGAGCGCU
6899
AGCGCTCA GGCTAGCTACAACGA TCCCACGC
15648


1065
GGGAGUGA G CGCUACCC
6900
GGGTAGCG GGCTAGCTACAACGA TCACTCCC
15649


1063
GAGUGAGC G CUACCCAG
6901
CTGGGTAG GGCTAGCTACAACGA GCTCACTC
15650


1060
UGAGCGCU A CCCAGCAG
6902
CTGCTGGG GGCTAGCTACAACGA AGCGCTCA
15651


1055
GCUACCCA G CAGCGGGA
6903
TCCCGCTG GGCTAGCTACAACGA TGGGTAGC
15652


1052
ACCCAGCA G CGGGAGGA
6904
TCCTCCCG GGCTAGCTACAACGA TGCTGGGT
15653


1043
CGGGAGGA G UUGUUCUC
6905
GAGAACAA GGCTAGCTACAACGA TCCTCCCG
15654


1040
GAGGAGUU G UUCUCCCG
6906
CGGGAGAA GGCTAGCTACAACGA AACTCCTC
15655


1030
UCUCCCGA A CGCAGGGC
6907
GCCCTGCG GGCTAGCTACAACGA TCGGGAGA
15656


1028
UCCCGAAC G CAGGGCAC
6908
GTGCCCTG GGCTAGCTACAACGA GTTCGGGA
15657


1023
AACGCAGG G CACGCACC
6909
GGTGCGTG GGCTAGCTACAACGA CCTGCGTT
15658


1021
CGCAGGGC A CGCACCCC
6910
GGGGTGCG GGCTAGCTACAACGA GCCCTGCG
15659


1019
CAGGGCAC G CACCCCGG
6911
CCGGGGTG GGCTAGCTACAACGA GTGCCCTG
15660


1017
GGGCACGC A CCCCGGGG
6912
CCCCGGGG GGCTAGCTACAACGA GCGTGCCC
15661


1009
ACCCCGGG G UGUGCAUG
6913
CATGCACA GGCTAGCTACAACGA CCCGGGGT
15662


1007
CCCGGGGU G UGCAUGAU
6914
ATCATGCA GGCTAGCTACAACGA ACCCCGGG
15663


1005
CGGGGUGU G CAUGAUCA
6915
TGATCATG GGCTAGCTACAACGA ACACCCCG
15664


1003
GGGUGUGC A UGAUCAUG
6916
CATGATCA GGCTAGCTACAACGA GCACACCC
15665


1000
UGUGCAUG A UCAUGUCC
6917
GGACATGA GGCTAGCTACAACGA CATGCACA
15666


997
GCAUGAUC A UGUCCUCU
6918
AGAGGACA GGCTAGCTACAACGA GATCATGC
15667


995
AUGAUCAU G UCCUCUGC
6919
GCAGAGGA GGCTAGCTACAACGA ATGATCAT
15668


988
UGUCCUCU G CCUCAUAC
6920
GTATGAGG GGCTAGCTACAACGA AGAGGACA
15669


983
UCUGCCUC A UACACAAU
6921
ATTGTGTA GGCTAGCTACAACGA GAGGCAGA
15670


981
UGCCUCAU A CACAAUGC
6922
GCATTGTG GGCTAGCTACAACGA ATGAGGCA
15671


979
CCUCAUAC A CAAUGCUU
6923
AAGCATTG GGCTAGCTACAACGA GTATGAGG
15672


976
CAUACACA A UGCUUGAG
6924
CTCAAGCA GGCTAGCTACAACGA TGTGTATG
15673


974
UACACAAU G CUUGAGUU
6925
AACTCAAG GGCTAGCTACAACGA ATTGTGTA
15674


968
AUGCUUGA G UUGGAGCA
6926
TGCTCCAA GGCTAGCTACAACGA TCAAGCAT
15675


962
GAGUUGGA G CAAUCGUU
6927
AACGATTG GGCTAGCTACAACGA TCCAACTC
15676


959
UUGGAGCA A UCGUUCGU
6928
ACGAACGA GGCTAGCTACAACGA TGCTCCAA
15677


956
GAGCAAUC G UUCGUGAC
6929
GTCACGAA GGCTAGCTACAACGA GATTGCTC
15678


952
AAUCGUUC G UGACAUGG
6930
CCATGTCA GGCTAGCTACAACGA GAACGATT
15679


949
CGUUCGUG A CAUGGUAC
6931
GTACCATG GGCTAGCTACAACGA CACGAACG
15680


947
UUCGUGAC A UGGUACAG
6932
CTGTACCA GGCTAGCTACAACGA GTCACGAA
15681


944
GUGACAUG G UACAGCCC
6933
GGGCTGTA GGCTAGCTACAACGA CATGTCAC
15682


942
GACAUGGU A CAGCCCGG
6934
CCGGGCTG GGCTAGCTACAACGA ACCATGTC
15683


939
AUGGUACA G CCCGGACG
6935
CGTCCGGG GGCTAGCTACAACGA TGTACCAT
15684


933
CAGCCCGG A CGCGUUGC
6936
GCAACGCG GGCTAGCTACAACGA CCGGGCTG
15685


931
GCCCGGAC G CGUUGCAC
6937
GTGCAACG GGCTAGCTACAACGA GTCCGGGC
15686


929
CCGGACGC G UUGCACAC
6938
GTGTGCAA GGCTAGCTACAACGA GCGTCCGG
15687


926
GACGCGUU G CACACCUC
6939
GAGGTGTG GGCTAGCTACAACGA AACGCGTC
15688


924
CGCGUUGC A CACCUCAU
6940
ATGAGGTG GGCTAGCTACAACGA GCAACGCG
15689


922
CGUUGCAC A CCUCAUAA
6941
TTATGAGG GGCTAGCTACAACGA GTGCAACG
15690


917
CACACCUC A UAAGCGGA
6942
TCCGCTTA GGCTAGCTACAACGA GAGGTGTG
15691


913
CCUCAUAA G CGGAGGCU
6943
AGCCTCCG GGCTAGCTACAACGA TTATGAGG
15692


907
AAGCGGAG G CUGGGAUG
6944
CATCCCAG GGCTAGCTACAACGA CTCCGCTT
15693


901
AGGCUGGG A UGGUCAGA
6945
TCTGACCA GGCTAGCTACAACGA CCCAGCCT
15694


898
CUGGGAUG G UCAGACAG
6946
CTGTCTGA GGCTAGCTACAACGA CATCCCAG
15695


893
AUGGUCAG A CAGGGCAG
6947
CTGCCCTG GGCTAGCTACAACGA CTGACCAT
15696


888
CAGACAGG G CAGCAGAG
6948
CTCTGCTG GGCTAGCTACAACGA CCTGTCTG
15697


885
ACAGGGCA G CAGAGCCA
6949
TGGCTCTG GGCTAGCTACAACGA TGCCCTGT
15698


880
GCAGCAGA G CCAAGAGG
6950
CCTCTTGG GGCTAGCTACAACGA TCTGCTGC
15699


868
AGAGGAAG A UAGAGAAA
6951
TTTCTCTA GGCTAGCTACAACGA CTTCCTCT
15700


857
GAGAAAGA G CAACCGGG
6952
CCCGGTTG GGCTAGCTACAACGA TCTTTCTC
15701


854
AAAGAGCA A CCGGGCAG
6953
CTGCCCGG GGCTAGCTACAACGA TGCTCTTT
15702


849
GCAACCGG G CAGAUUCC
6954
GGAATCTG GGCTAGCTACAACGA CCGGTTGC
15703


845
CCGGGCAG A UUCCCUGU
6955
ACAGGGAA GGCTAGCTACAACGA CTGCCCGG
15704


838
GAUUCCCU G UUGCAUAG
6956
CTATGCAA GGCTAGCTACAACGA AGGGAATC
15705


835
UCCCUGUU G CAUAGUUC
6957
GAACTATG GGCTAGCTACAACGA AACAGGGA
15706


833
CCUGUUGC A UAGUUCAC
6958
GTGAACTA GGCTAGCTACAACGA GCAACAGG
15707


830
GUUGCAUA G UUCACGCC
6959
GGCGTGAA GGCTAGCTACAACGA TATGCAAC
15708


826
CAUAGUUC A CGCCGUCU
6960
AGACGGCG GGCTAGCTACAACGA GAACTATG
15709


824
UAGUUCAC G CCGUCUUC
6961
GAAGACGG GGCTAGCTACAACGA GTGAACTA
15710


821
UUCACGCC G UCUUCCAG
6962
CTGGAAGA GGCTAGCTACAACGA GGCGTGAA
15711


811
CUUCCAGA A CCCGGACG
6963
CGTCCGGG GGCTAGCTACAACGA TCTGGAAG
15712


805
GAACCCGG A CGCCAUGC
6964
GCATGGCG GGCTAGCTACAACGA CCGGGTTC
15713


803
ACCCGGAC G CCAUGCGC
6965
GCGCATGG GGCTAGCTACAACGA GTCCGGGT
15714


800
CGGACGCC A UGCGCCAG
6966
CTGGCGCA GGCTAGCTACAACGA GGCGTCCG
15715


798
GACGCCAU G CGCCAGGG
6967
CCCTGGCG GGCTAGCTACAACGA ATGGCGTC
15716


796
CGCCAUGC G CCAGGGCC
6968
GGCCCTGG GGCTAGCTACAACGA GCATGGCG
15717


790
GCGCCAGG G CCCUGGCA
6969
TGCCAGGG GGCTAGCTACAACGA CCTGGCGC
15718


784
GGGCCCUG G CAGUGCCU
6970
AGGCACTG GGCTAGCTACAACGA CAGGGCCC
15719


781
CCCUGGCA G UGCCUCCC
6971
GGGAGGCA GGCTAGCTACAACGA TGCCAGGG
15720


779
CUGGCAGU G CCUCCCAA
6972
TTGGGAGG GGCTAGCTACAACGA ACTGCCAG
15721


766
CCAAGGGG G CGCCGACG
6973
CGTCGGCG GGCTAGCTACAACGA CCCCTTGG
15722


764
AAGGGGGC G CCGACGAG
6974
CTCGTCGG GGCTAGCTACAACGA GCCCCCTT
15723


760
GGGCGCCG A CGAGCGGA
6975
TCCGCTCG GGCTAGCTACAACGA CGGCGCCC
15724


756
GCCGACGA G CGGAAUGU
6976
ACATTCCG GGCTAGCTACAACGA TCGTCGGC
15725


751
CGAGCGGA A UGUACCCC
6977
GGGGTACA GGCTAGCTACAACGA TCCGCTCG
15726


749
AGCGGAAU G UACCCCAU
6978
ATGGGGTA GGCTAGCTACAACGA ATTCCGCT
15727


747
CGGAAUGU A CCCCAUGA
6979
TCATGGGG GGCTAGCTACAACGA ACATTCCG
15728


742
UGUACCCC A UGAGGUCG
6980
CGACCTCA GGCTAGCTACAACGA GGGGTACA
15729


737
CCCAUGAG G UCGGCGAA
6981
TTCGCCGA GGCTAGCTACAACGA CTCATGGG
15730


733
UGAGGUCG G CGAAGCCG
6982
CGGCTTCG GGCTAGCTACAACGA CGACCTCA
15731


728
UCGGCGAA G CCGCAUGU
6983
ACATGCGG GGCTAGCTACAACGA TTCGCCGA
15732


725
GCGAAGCC G CAUGUGAG
6984
CTCACATG GGCTAGCTACAACGA GGCTTCGC
15733


723
GAAGCCGC A UGUGAGGG
6985
CCCTCACA GGCTAGCTACAACGA GCGGCTTC
15734


721
AGCCGCAU G UGAGGGUA
6986
TACCCTCA GGCTAGCTACAACGA ATGCGGCT
15735


715
AUGUGAGG G UAUCGAUG
6987
CATCGATA GGCTAGCTACAACGA CCTCACAT
15736


713
GUGAGGGU A UCGAUGAC
6988
GTCATCGA GGCTAGCTACAACGA ACCCTCAC
15737


709
GGGUAUCG A UGACCUUA
6989
TAAGGTCA GGCTAGCTACAACGA CGATACCC
15738


706
UAUCGAUG A CCUUACCC
6990
GGGTAAGG GGCTAGCTACAACGA CATCGATA
15739


701
AUGACCUU A CCCAAGUU
6991
AACTTGGG GGCTAGCTACAACGA AAGGTCAT
15740


695
UUACCCAA G UUACGCGA
6992
TCGCGTAA GGCTAGCTACAACGA TTGGGTAA
15741


692
CCCAACUU A CGCGACCU
6993
AGGTCGCG GGCTAGCTACAACGA AACTTGGG
15742


690
GAACUUAG G CGACCUAC
6994
GTAGGTCG GGCTAGCTACAACGA GTAACTTG
15743


687
GUUACGCG A CCUACGCC
6995
GGCGTAGG GGCTAGCTACAACGA CGCGTAAC
15744


683
CGCGACCU A CGCCGGGG
6996
CCCCGGCG GGCTAGCTACAACGA AGGTCGCG
15745


681
CGACCUAC G CCGGGGGU
6997
ACCCCCGG GGCTAGCTACAACGA GTAGGTCG
15746


674
CGCCGGGG G UCCGUGGG
6998
CCCACGGA GGCTAGCTACAACGA CCCCGGCG
15747


670
GGGGGUCC G UGGGGCCC
6999
GGGCCCCA GGCTAGCTACAACGA GGACCCCC
15748


665
UCCGUGGG G CCCCAACU
7000
AGTTGGGG GGCTAGCTACAACGA CCCACGGA
15749


659
GGGCCCCA A CUAGGCCG
7001
CGGCCTAG GGCTAGCTACAACGA TGGGGCCC
15750


654
CCAACUAG G CCGGGAGC
7002
GCTCCCGG GGCTAGCTACAACGA CTAGTTGG
15751


647
GGCCGGGA G CCGCGGGG
7003
CCCCGCGG GGCTAGCTACAACGA TCCCGGCC
15752


644
CGGGAGCC G CGGGGUGA
7004
TCACCCCG GGCTAGCTACAACGA GGCTCCCG
15753


639
GCCGCGGG G UGACAGGA
7005
TCCTGTCA GGCTAGCTACAACGA CCCGCGGC
15754


636
GCGGGGUG A CAGGAGCC
7006
GGCTCCTG GGCTAGCTACAACGA CACCCCGC
15755


630
UGACAGGA G CCAUCCUG
7007
CAGGATGG GGCTAGCTACAACGA TCCTGTCA
15756


627
CAGGAGCC A UCCUGCCC
7008
GGGCAGGA GGCTAGCTACAACGA GGCTCCTG
15757


622
GCCAUCCU G CCCACCCU
7009
AGGGTGGG GGCTAGCTACAACGA AGGATGGC
15758


618
UCCUGCCC A CCCUAAGC
7010
GCTTAGGG GGCTAGCTACAACGA GGGCAGGA
15759


611
CACCCUAA G CCCUCAUU
7011
AATGAGGG GGCTAGCTACAACGA TTAGGGTG
15760


605
AAGCCCUC A UUGCCAUA
7012
TATGGCAA GGCTAGCTACAACGA GAGGGCTT
15761


602
CCCUCAUU G CCAUAGAG
7013
CTCTATGG GGCTAGCTACAACGA AATGAGGG
15762


599
UCAUUGCC A UAGAGGGG
7014
CCCCTCTA GGCTAGCTACAACGA GGCAATGA
15763


591
AUAGAGGG G CCAAGGGU
7015
ACCCTTGG GGCTAGCTACAACGA CCCTCTAT
15764


584
GGCCAAGG G UACCCGGG
7016
CCCGGGTA GGCTAGCTACAACGA CCTTGGCC
15765


582
CCAAGGGU A CCCGGGCU
7017
AGCCCGGG GGCTAGCTACAACGA ACCCTTGG
15766


576
GUACCCGG G CUGAGCCC
7018
GGGCTCAG GGCTAGCTACAACGA CCGGGTAC
15767


571
CGGGCUGA G CCCAGGCC
7019
GGCCTGGG GGCTAGCTACAACGA TCAGCCCG
15768


565
GAGCCCAG G CCCUGCCC
7020
GGGCAGGG GGCTAGCTACAACGA CTGGGCTC
15769


560
CAGGCCCU G CCCUCGGG
7021
CCCGAGGG GGCTAGCTACAACGA AGGGCCTG
15770


552
GCCCUCGG G CCGGCGAG
7022
CTCGCCGG GGCTAGCTACAACGA CCGAGGGC
15771


548
UCGGGCCG G CGAGCCUU
7023
AAGGCTCG GGCTAGCTACAACGA CGGCCCGA
15772


544
GCCGGCGA G CCUUGGGG
7024
CCCCAAGG GGCTAGCTACAACGA TCGCCGGC
15773


535
CCUUGGGG A UAGGUUGU
7025
ACAACCTA GGCTAGCTACAACGA CCCCAAGG
15774


531
GGGGAUAG G UUGUCGCC
7026
GGCGACAA GGCTAGCTACAACGA CTATCCCC
15775


528
GAUAGGUU G UCGCCUUC
7027
GAAGGCGA GGCTAGCTACAACGA AACCTATC
15776


525
AGGUUGUC G CCUUCCAC
7028
GTGGAAGG GGCTAGCTACAACGA GACAACCT
15777


518
CGCCUUCC A CGAGGUUG
7029
CAACCTCG GGCTAGCTACAACGA GGAAGGCG
15778


513
UCCACGAG G UUGCGACC
7030
GGTCGCAA GGCTAGCTACAACGA CTCGTGGA
15779


510
ACGAGGUU G CGACCGCU
7031
AGCGGTCG GGCTAGCTACAACGA AACCTCGT
15780


507
AGGUUGCG A CCGCUCGG
7032
CCGAGCGG GGCTAGCTACAACGA CGCAACCT
15781


504
UUGCGACC G CUCGGAAG
7033
CTTCCGAG GGCTAGCTACAACGA GGTCGCAA
15782


496
GCUCGGAA G UCUUCCUA
7034
TAGGAAGA GGCTAGCTACAACGA TTCCGAGC
15783


487
UCUUCCUA G UCGCGCGC
7035
GCGCGCGA GGCTAGCTACAACGA TAGGAAGA
15784


484
UCCUAGUC G CGCGCACA
7036
TGTGCGCG GGCTAGCTACAACGA GACTAGGA
15785


482
CUAGUCGC G CGCACACC
7037
GGTGTGCG GGCTAGCTACAACGA GCGACTAG
15786


480
AGUCGCGC G CACACCCA
7038
TGGGTGTG GGCTAGCTACAACGA GCGCGACT
15787


478
UCGCGCGC A CACCCAAC
7039
GTTGGGTG GGCTAGCTACAACGA GCGCGCGA
15788


476
GCGCGCAC A CCCAACCU
7040
AGGTTGGG GGCTAGCTACAACGA GTGCGCGC
15789


471
CACACCCA A CCUGGGGC
7041
GCCCCAGG GGCTAGCTACAACGA TGGGTGTG
15790


464
AACCUGGG G CCCCUGCG
7042
CGCAGGGG GGCTAGCTACAACGA CCCAGGTT
15791


458
GGGCCCCU G CGCGGCAA
7043
TTGCCGCG GGCTAGCTACAACGA AGGGGCCC
15792


456
GCCCCUGC G CGGCAACA
7044
TGTTGCCG GGCTAGCTACAACGA GCAGGGGC
15793


453
CCUGCGCG G CAACAGGU
7045
ACCTGTTG GGCTAGCTACAACGA CGCGCAGG
15794


450
GCGCGGCA A CAGGUAAA
7046
TTTACCTG GGCTAGCTACAACGA TGCCGCGC
15795


446
GGCAACAG G UAAACUCC
7047
GGAGTTTA GGCTAGCTACAACGA CTGTTGCC
15796


442
ACAGGUAA A CUCCACCA
7048
TGGTGGAG GGCTAGCTACAACGA TTACCTGT
15797


437
UAAACUCC A CCAACGAU
7049
ATCGTTGG GGCTAGCTACAACGA GGAGTTTA
15798


433
CUCCACCA A CGAUCUGA
7050
TCAGATCG GGCTAGCTACAACGA TGGTGGAG
15799


430
CACCAACG A UCUGACCA
7051
TGGTCAGA GGCTAGCTACAACGA CGTTGGTG
15800


425
ACGAUCUG A CCACCGCC
7052
GGCGGTGG GGCTAGCTACAACGA CAGATCGT
15801


422
AUCUGACC A CCGCCCGG
7053
CCGGGCGG GGCTAGCTACAACGA GGTCAGAT
15802


419
UGACCACC G CCCGGGAA
7054
TTCCCGGG GGCTAGCTACAACGA GGTGGTCA
15803


411
GCCCGGGA A CUUGACGU
7055
ACGTCAAG GGCTAGCTACAACGA TCCCGGGC
15804


406
GGAACUUG A CGUCCUGU
7056
ACAGGACG GGCTAGCTACAACGA CAAGTTCC
15805


404
AACUUGAC G UCCUGUGG
7057
CCACAGGA GGCTAGCTACAACGA GTCAAGTT
15806


399
GACGUCCU G UGGGCGGC
7058
GCCGCCCA GGCTAGCTACAACGA AGGACGTC
15807


395
UCCUGUGG G CGGCGGUU
7059
AACCGCCG GGCTAGCTACAACGA CCACAGGA
15808


392
UGUGGGCG G CGGUUGGU
7060
ACCAACCG GGCTAGCTACAACGA CGCCCACA
15809


389
GGGCGGCG G UUGGUGUU
7061
AACACCAA GGCTAGCTACAACGA CGCCGCCC
15810


385
GGCGGUUG G UGUUACGU
7062
ACGTAACA GGCTAGCTACAACGA CAACCGCC
15811


383
CGGUUGGU G UUACGUUU
7063
AAACGTAA GGCTAGCTACAACGA ACCAACCG
15812


380
UUGGUGUU A CGUUUGGU
7064
ACCAAACG GGCTAGCTACAACGA AACACCAA
15813


378
GGUGUUAC G UUUGGUUU
7065
AAACCAAA GGCTAGCTACAACGA GTAACACC
15814


373
UACGUUUG G UUUUUCUU
7066
AAGAAAAA GGCTAGCTACAACGA CAAACGTA
15815


360
UCUUUGAG G UUUAGGAU
7067
ATCCTAAA GGCTAGCTACAACGA CTCAAAGA
15816


353
GGUUUAGG A UUCGUGCU
7068
AGCACGAA GGCTAGCTACAACGA CCTAAACC
15817


349
UAGGAUUC G UGCUCAUG
7069
CATGAGCA GGCTAGCTACAACGA GAATCCTA
15818


347
GGAUUCGU G CUCAUGGU
7070
ACCATGAG GGCTAGCTACAACGA ACGAATCC
15819


343
UCGUGCUC A UGGUGCAC
7071
GTGCACCA GGCTAGCTACAACGA GAGCACGA
15820


340
UGCUCAUG G UGCACGGU
7072
ACCGTGCA GGCTAGCTACAACGA CATGAGCA
15821


338
CUCAUGGU G CACGGUCU
7073
AGACCGTG GGCTAGCTACAACGA ACCATGAG
15822


336
CAUGGUGC A CGGUCUAC
7074
GTAGACCG GGCTAGCTACAACGA GCACCATG
15823


333
GGUGCACG G UCUACGAG
7075
CTCGTAGA GGCTAGCTACAACGA CGTGCACC
15824


329
CACGGUCU A CGAGACCU
7076
AGGTCTCG GGCTAGCTACAACGA AGACCGTG
15825


324
UCUACGAG A CCUCCCGG
7077
CCGGGAGG GGCTAGCTACAACGA CTCGTAGA
15826


314
CUCCCGGG G CACUCGCA
7078
TGCGAGTG GGCTAGCTACAACGA CCCGGGAG
15827


312
CCCGGGGC A CUCGCAAG
7079
CTTGCGAG GGCTAGCTACAACGA GCCCCGGG
15828


308
GGGCACUC G CAAGCACC
7080
GGTGCTTG GGCTAGCTACAACGA GAGTGCCC
15829


304
ACUCGCAA G CACCCUAU
7081
ATAGGGTG GGCTAGCTACAACGA TTGCGAGT
15830


302
UCGCAAGC A CCCUAUCA
7082
TGATAGGG GGCTAGCTACAACGA GCTTGCGA
15831


297
AGCACCCU A UCAGGCAG
7083
CTGCCTGA GGCTAGCTACAACGA AGGGTGCT
15832


292
CCUAUCAG G CAGUACCA
7084
TGGTACTG GGCTAGCTACAACGA CTGATAGG
15833


289
AUCAGGCA G UACCACAA
7085
TTGTGGTA GGCTAGCTACAACGA TGCCTGAT
15834


287
CAGGCAGU A CCACAAGG
7086
CCTTGTGG GGCTAGCTACAACGA ACTGCCTG
15835


284
CGACUAGG A CAAGGCCU
7087
AGGCCTTG GGCTAGCTACAACGA GGTACTGC
15836


279
ACCACAAG G CCUUUCGC
7088
GCGAAAGG GGCTAGCTACAACGA CTTGTGGT
15837


272
GGCCUUUC G CGACCCAA
7089
TTGGGTCG GGCTAGCTACAACGA GAAAGGCC
15838


269
CUUUCGCG A CCCAACAC
7090
GTGTTGGG GGCTAGCTACAACGA CGCGAAAG
15839


264
GCGACCCA A CACUACUC
7091
GAGTAGTG GGCTAGCTACAACGA TGGGTCGC
15840


262
GACCCAAC A CUACUCGG
7092
CCGAGTAG GGCTAGCTACAACGA GTTGGGTC
15841


259
CCAACACU A CUCGGCUA
7093
TAGCCGAG GGCTAGCTACAACGA AGTGTTGG
15842


254
ACUACUCG G CUAGCAGU
7094
ACTGCTAG GGCTAGCTACAACGA CGAGTAGT
15843


250
CUCGGCUA G CAGUCUCG
7095
CGAGACTG GGCTAGCTACAACGA TAGCCGAG
15844


247
GGCUAGCA G UCUCGCGG
7096
CCGCGAGA GGCTAGCTACAACGA TGCTAGCC
15845


242
GCAGUCUC G CGGGGGCA
7097
TGCCCCCG GGCTAGCTACAACGA GAGACTGC
15846


236
UCGCGGGG G CACGCCCA
7098
TGGGCGTG GGCTAGCTACAACGA CCCCGCGA
15847


234
GCGGGGGC A CGCCCAAA
7099
TTTGGGCG GGCTAGCTACAACGA GCCCCCGC
15848


232
GGGGGCAC G CCCAAAUC
7100
GATTTGGG GGCTAGCTACAACGA GTGCCCCC
15849


226
ACGCCCAA A UCUCCAGG
7101
CCTGGAGA GGCTAGCTACAACGA TTGGGCGT
15850


218
AUCUCCAG G CAUUGAGC
7102
GCTCAATG GGCTAGCTACAACGA CTGGAGAT
15851


216
CUCCAGGC A UUGAGCGG
7103
CCGCTCAA GGCTAGCTACAACGA GCCTGGAG
15852


211
GGCAUUGA G CGGGUUGA
7104
TCAACCCG GGCTAGCTACAACGA TCAATGCC
15853


207
UUGAGCGG G UUGAUCCA
7105
TGGATCAA GGCTAGCTACAACGA CCGCTCAA
15854


203
GCGGGUUG A UCCAAGAA
7106
TTCTTGGA GGCTAGCTACAACGA CAACCCGC
15855


191
AAGAAAGG A CCCGGUCG
7107
CGACCGGG GGCTAGCTACAACGA CCTTTCTT
15856


186
AGGACCCG G UCGUCCUG
7108
CAGGACGA GGCTAGCTACAACGA CGGGTCCT
15857


183
ACCCGGUC G UCCUGGCA
7109
TGCCAGGA GGCTAGCTACAACGA GACCGGGT
15858


177
UCGUCCUG G CAAUUCCG
7110
CGGAATTG GGCTAGCTACAACGA CAGGACGA
15859


174
UCCUGGCA A UUCCGGUG
7111
CACCGGAA GGCTAGCTACAACGA TGCCAGGA
15860


168
CAAUUCCG G UGUACUCA
7112
TGAGTACA GGCTAGCTACAACGA CGGAATTG
15861


166
AUUCCGGU G UACUCACC
7113
GGTGAGTA GGCTAGCTACAACGA ACCGGAAT
15862


164
UCCGGUGU A CUCACCGG
7114
CCGGTGAG GGCTAGCTACAACGA ACACCGGA
15863


160
GUGUACUC A CCGGUUCC
7115
GGAACCGG GGCTAGCTACAACGA GAGTACAC
15864


156
ACUCACCG G UUCCGCAG
7116
CTGCGGAA GGCTAGCTACAACGA CGGTGAGT
15865


151
CCGGUUCC G CAGACCAC
7117
GTGGTCTG GGCTAGCTACAACGA GGAACCGG
15866


147
UUCCGCAG A CCACUAUG
7118
CATAGTGG GGCTAGCTACAACGA CTGCGGAA
15867


144
CGCAGACC A CUAUGGCU
7119
AGCCATAG GGCTAGCTACAACGA GGTCTGCG
15868


141
AGACCACU A UGGCUCUC
7120
GAGAGCCA GGCTAGCTACAACGA AGTGGTCT
15869


138
CCACUAUG G CUCUCCCG
7121
CGGGAGAG GGCTAGCTACAACGA CATAGTGG
15870


120
GAGGGGGG G UCCUGGAG
7122
CTCCAGGA GGCTAGCTACAACGA CCCCCCTC
15871


111
UCCUGGAG G CUGCACGA
7123
TCGTGCAG GGCTAGCTACAACGA CTCCAGGA
15872


108
UGGAGGCU G CACGACAC
7124
GTGTCGTG GGCTAGCTACAACGA AGCCTCCA
15873


106
GAGGCUGC A CGACACUC
7125
GAGTGTCG GGCTAGCTACAACGA GCAGCCTC
15874


103
GCUGCACG A CACUCAUA
7126
TATGAGTG GGCTAGCTACAACGA CGTGCAGC
15875


101
UGCACGAC A CUCAUACU
7127
AGTATGAG GGCTAGCTACAACGA GTCGTGCA
15876


97
CGACACUC A UACUAACG
7128
CGTTAGTA GGCTAGCTACAACGA GAGTGTCG
15877


95
ACACUCAU A CUAACGCC
7129
GGCGTTAG GGCTAGCTACAACGA ATGAGTGT
15878


91
UCAUACUA A CGCCAUGG
7130
CCATGGCG GGCTAGCTACAACGA TAGTATGA
15879


89
AUACUAAC G CCAUGGCU
7131
AGCCATGG GGCTAGCTACAACGA GTTAGTAT
15880


86
CUAACGCC A UGGCUAGA
7132
TCTAGCCA GGCTAGCTACAACGA GGCGTTAG
15881


83
ACGCCAUG G CUAGACGC
7133
GCGTCTAG GGCTAGCTACAACGA CATGGCGT
15882


78
AUGGCUAG A CGCUUUCU
7134
AGAAAGCG GGCTAGCTACAACGA CTAGCCAT
15883


76
GGCUAGAC G CUUUCUGC
7135
GCAGAAAG GGCTAGCTACAACGA GTCTAGCC
15884


69
CGCUUUCU G CGUGAAGA
7136
TCTTCACG GGCTAGCTACAACGA AGAAAGCG
15885


67
CUUUCUGC G UGAAGACA
7137
TGTCTTCA GGCTAGCTACAACGA GCAGAAAG
15886


61
GCGUGAAG A CAGUAGUU
7138
AACTACTG GGCTAGCTACAACGA CTTCACGC
15887


58
UGAAGACA G UAGUUCCU
7139
AGGAACTA GGCTAGCTACAACGA TGTCTTCA
15888


55
AGACAGUA G UUCCUCAC
7140
GTGAGGAA GGCTAGCTACAACGA TACTGTCT
15889


48
AGUUCCUC A CAGGGGAG
7141
CTCCCCTG GGCTAGCTACAACGA GAGGAACT
15890


40
ACAGGGGA G UGAUCUAU
7142
ATAGATCA GGCTAGCTACAACGA TCCCCTCT
15891


37
GGGGAGUG A UCUAUGGU
7143
ACCATAGA GGCTAGCTACAACGA CACTCCCC
15892


33
AGUGAUCU A UGGUGGAG
7144
CTCCACCA GGCTAGCTACAACGA AGATCACT
15893


30
GAUCUAUG G UGGAGUGU
7145
ACACTCCA GGCTAGCTACAACGA CATAGATC
15894


25
AUGGUGGA G UGUCGCCC
7146
GGGCGACA GGCTAGCTACAACGA TCCACCAT
15895


23
GGUGGAGU G UCGCCCCC
7147
GGGGGCGA GGCTAGCTACAACGA ACTCCACC
15896






Input Sequence = HPCK1S1.




Cut Site = R/Y




Arm Length = 8.




Core Sequence = GGCTAGCTACAACGA




HPCK1S1 Hepatitis G virus (strain HCV-1b, clone HCV-K1-S1), complete genome; acc# gi|1030702|dbj|D50483.1; 9410 nt








[0568]

20






TABLE XX










Synthetic anti-HCV nucleic acid molecule and Target Sequences















ref pos
Ref Seq
Target
Seq ID
RPI#
NUCLEIC ACID
Seq ID
Nucleic Acid Alias


















195
HCV+
GGGUCCU U UCUUGCA
7148
15364
cScSaSaSga cUGAuGaggcgaaagccGaa uuAggacc B
15897
Hammerhead






342
HCV+
AGACCGUGCAUCAUGAGCAC
7149
17501
GsTsGsCSTsCSASTsGsASTsGsCSASCSGsGsTsCST
15898
Antisense





195
HCV+
GGGUCCU U UCUUGGA
7148
17558
CSCSaSaSga cUGAuGaggcguuagccGaZ Aggacc B
15899
Hammerhead





195
HCV+
GGGUCCU U UCUUGGA
7148
17559
CScSaSaSga cUGAuGaggcguuagccGaa AggaZc B
15900
Hammerhead





195
HCV+
GGGUCCU U UCUUGGA
7148
17560
Z5CSaSaSga cUGAuGaggcguuagccGaa Aggace B
15901
Hammerhead





195
HCV+
GGGUCCU U UCUUGGA
7148
17561
Z CSaSaSga cUGAuGaggcguuagccCaa Aggacc B
15902
Hammerhead





195
HCV+
GGGUCCU U UCUUGGA
7148
18012
ccaaga cUGAuGaggcguuagccGaa Aggaca B
15903
Hammerhead





82
HCV+
GCGUCUA G CCAUGGC
7150
18744
gSCSCSaSugg GccgaaagGCGaGucaaGGuCu uagacgc B
15904
Zinzyme





100
HCV+
AGUAUGA G UGUCGUG
7151
18745
CSaSCSgSaca GccgaaagGCGaGucaaGGuCu ucauacu B
15905
Zinzyme





102
HCV+
UAUGAGU G UCGUGCA
7152
18746
uSgSCSaScga GccgaaagGCGaGucaaGGuCu acucaua B
15906
Zinzyme





105
HCV+
GAGUGUC G UGCAGCC
7153
18747
gSgSCSuSgca GccgaaagGCGaGucaaGGuCu gacacuc B
15907
Zinzyme





107
HCV+
GUGUCGU G CAGCCUC
7154
18748
gSaSg8gScug GccgaaagGCGaGucaaGGuCu acgacac B
15908
Zinzyme





146
HCV+
CAUAGUG G UCUGCGG
7155
18749
CSCSgSCSaga GccgaaagGCGaGucaaGGuCu cacuaug B
15909
Zinzyme





190
HCV+
CGACCGG G UCCUUUC
7156
18750
gSaSaSaSgga GccgaaagGCGaGucaaGGuCu ccggucg B
15910
Zinzyme





217
HCV+
GCUCAAU G CCUGGAG
7157
18751
CSuSCSCSagg GccgaaagGCGaGucaaGGuCu auugagc B
15911
Zinzyme





231
HCV+
GAUUUGG C CGUGCCC
7158
18752
gSgSgSCSacg GccgaaagGCCaGucaaGGuCu ccaaauc B
15912
Zinzyme





258
HCV+
UAGCCGA C UAGUGUU
7159
18753
asascsascua GccgaaagGCGaGucaaGGuCu ucggcua B
15913
Zinzyme





307
HCV+
GGUGCUU G CGAGUGC
7160
18754
gScSaSc9ucg GccgaaagGCGaGucaaGGuCu aagcacc B
15914
Zinzyme





77
HCV+
GAAAGC G UCUAGC
7161
18755
gSCSuSaSga GccgaaagGCGaGucaaGGuCu gcuuuc B
15915
Zinzyme





77
HCV+
AGAAAGC G UCUAGCC
7162
18756
gSgSCSuSaga GccgaaagGCGaGucaaGGuCu gcuuucu B
15916
Zinzyme





88
HCV+
AGCCAUG C CGUUAGU
7163
18757
aSCSu6aSacg GccgaaagGCGaGucaaGGuCu cauggcu B
15917
Zinzyme





94
HCV+
CGCGUUA C UAUGAGU
7164
18758
ascsuscsaua GccgaaagGCGaGucaaGGucu uaacgcc B
15918
Zinzyme





102
HCV+
AUGAGU G UCGUGC
7165
18759
gSCSaScSga CccgaaagGCGaCucaaGGuCu acucau B
15919
Zinzyme





105
HCV+
AGUGUC G UGCAGC
7166
18760
gScSuSgSca GccgaaagGCGaGucaaGGuCu gacacu B
15920
Zinzyme





110
HCV+
UCGUGCA C CCUCCAG
7167
18761
CSuSgSgSagg GccgaaagCCGaGucaaGGuCu ugcacga B
15921
Zinzyme





137
HCV+
GGGAGA G CCAUAG
7168
18762
CSuSaSuSgg GccgaaagGCGaGucaaGGuCu ucuccc B
15922
Zinzyme





137
HCV+
CGGGAGA G CCAUAGU
7169
18763
aSCSuSaSugg GccgaaagGCGaGucaaGGuCu ucucccg B
15923
Zinzyme





146
HCV+
AUAGUG G UCUGCG
7170
18764
CSgSCSaSga GccgaaagGCGaGucaaGGuCu cacuau B
15924
Zinzyme





150
HCV+
GUGGUCU G CGGAACC
7171
18765
gSgSuSuSccg GccgaaagGCGaGucaaGGuCu agaccac B
15925
Zinzyme





176
HCV+
CGGAAUU C CCAGGAC
7172
18766
gSuSCScSugg GccgaaagCCCaCucaaGGuCu aauuccg B
15926
Zinzyme





190
HCV+
GACCGG GUCCUUU
7173
18767
aSaSaSgSgaGccgaaagGCGaGucaaGGuCu ccgguc B
15927
Zinzyme





253
HSV+
CUGCUA G CCGAGU
7174
18768
aSCSugcSggGccgaaagGCGaGucaaGGuCu uagcag B
15928
Zinzyme





253
HCV+
ACUGCUA GCCGAGAA
7175
18769
uSaScSuScggGccgaaagGCGaGucaaGGuCu uagcagu B
15929
Zinzyme





258
HCV+
AGCCGA GUAGUGU
7176
18770
aSCSaScSuaGccgaaagGCGaGucaaGGuCu ucggcu B
15930
Zinzyme





263
HCV+
GAGUAGU GUUGGGUC
7177
18771
gSaScScScaaGccgaaagGcGaGucaaGGuCu acuacuc B
15931
Zinzyme





268
HCV+
UGUUGG GUCGCGA
7178
18772
uScSgScSgaGccgaaagGCGaGucaaGGuCu ccaaca B
15932
Zinzyme





268
HCV+
GUGUUGG GUCGCGAA
7179
18773
uSuScSgScgaGccgaaagGcGaGucaaGGuCu ccaacac B
15933
Zinzyme





271
HCV+
UUGGGUC GCGAAAGG
7180
18774
cScguSuSucgGccgaaagGCGaGucaaGGuCu gacccaa B
15934
Zinzyme





283
HCV+
AGGCCUU GUGGUACU
7181
18775
aSgSuSaSccaGccgaaagGCGaGucaaGGuCu aaggccu B
15935
Zinzyme





286
HCV+
CCUUGUG GUACUGCC
7182
18776
gSgScSaSguaGccgaaagGCGacucaaGGuCu cacaagg B
15936
Zinzyme





291
HCV+
UGGUACU GCCUGAUA
7183
18777
uSaSuSCSaggGccgaaagGCGaGucaaGGuCu aguacca B
15937
Zinzyme





301
HCV+
UGAUAGG GUGCUUGC
7184
18778
gSCSaSaSgcaGccgaaagGCGaGucaaGGuCu ccuauca B
15938
Zinzyme





303
HCV+
AUAGGGU GCUUGCGA
7185
18779
uScSgScSaagGccgaaagGCGaGucaaGGuCu acccuau B
15939
Zinzyme





60
HCV+
ACUACU GUCUUCA
7186
18780
uSgSaSaSgaGccgaaagGCGaGucaaGGuCu aguagu B
15940
Zinzyme





60
HCV+
AACUACU GUCUUCAC
7187
18781
gSuSgSaSagaGccgaaagGCGaGucaaGGuCu aguaguu B
15941
Zinzyme





68
HCV+
UCUUCAC GCAGAAAG
7188
18782
cSuSuSuScugGccgaaagGCGaGucaaGGuCu gugaaga B
15942
Zinzyme





75
HCV+
CAGAAA GCGUCUA
7189
18783
uSaSgSaScgGccgaaagGCGaGucaaGGuCu uuucug B
15943
Zinzyme





82
HCV+
CGUCUA GCCAUGG
7190
18784
cgCSaSuSggGccgaaagGCGaGucaaGGuCu uagacg B
15944
Zirizyme





88
HCV+
GCCAUG GCGUUAG
7191
18785
CSuSaSaScgGccgaaagGCGaGucaacGuCu cauggc B
15945
Zinzyme





90
HCV+
CAUGGC GUUAGUA
7192
18786
usascsusaaGccgaaagGCGaGucaaGGuCu gccaug B
15946
Zinzyme





90
HCV+
CCAUGGC GUUAGUAU
7193
18787
aSuSaScSuaaGccgaaagGCGaGucaaGGucu gccaugg B
15947
Zinzyme





100
HCV+
GUAUGA G UGUCGU
7194
18788
aScSgSaScaGccgaaagGCGaGucaaGGuCu ucauac B
15948
Zinzyme





107
HCV+
UGUCGU GCAGCCU
7195
18789
aSgSgSCSugGccgaaagGCGaGucaaGGuCu acgaca B
15949
Zinzyme





110
HCV+
CGUGCA GCCUCCA
7196
18790
uSgSgSaSggGccgaaagGCGaGucaaGGuCu ugcacg B
15950
Zinzyme





150
HCV+
UGGUCU GCGGAAC
7197
18791
gSuSuSCScgGccgaaagGCGaGucaaGGuCu agacca B
15951
Zinzyme





159
HCV+
GGAACCG GUGAGUAC
7198
18792
gSuSaScSucaGccgaaagGCGaGucaaGGuCu cgguucc B
15952
Zinzyme





176
HCV+
GGAAUU GCCAGGA
7199
18793
uScScSuSggGccgaaagGCGaGucaaGGuCu aauucc B
15953
Zinzyme





217
HCV+
CUCAAU GCCUGGA
7200
18794
uSCScSaSggGccgaaagGCGaGucaaGGuCu auugag B
15954
Zinzyme





231
HCV+
AUUUGG GCGUGCC
7201
18795
gSgScSaScgGccgaaagGCGaGucaaGGuCu ccaaau B
15955
Zinzyme





261
HCV+
CGAGUA GUGUUGG
7202
18796
cScSaSaScaGccgaaagGCGaGucaaGGuCu uacucg B
15956
Zinzyme





261
HCV+
CCGAGUA GUGUUGGG
7203
18797
CScSCSaSacaGccgaaagGCGaGucaaGGuCu uacucgg B
15957
Zinzyrne





263
HCV+
AGUAGU GUUGGGU
7204
18798
aScScScSaaGccgaaagGCGaGucaaGGuCu acuacu B
15958
Zinzyrne





271
HCV+
UGGGUC GCGAAAG
7205
18799
CSuSuSuScgGccgaaagGCGaGucaaGGuCu gaccca B
15959
Zinzyme





283
HCV+
GGCCUU GUGGUAC
7206
18800
gSuSaScScaGccgaaagGCGaGucaaGGuCu aaggcc B
15960
Zinzyme





291
HCV+
GGUACU GCCUGAU
7207
18801
aSuScSaSggGccgaaagGCGaGucaaGGuCu aguacc B
15961
Zinzyme





303
HCV+
UAGGGU G CUGCG
7208
18802
CSgScSaSagGccgaaagGCGaGucaaGGuCu acccua B
15962
Zinzyme





307
HCV+
GUGCUU G CGAGUG
7209
18803
cSaScSuScgGccgaaagGCGaGucaaGGuCu aagcac B
15963
Zinzyme





323
HCV+
CGGGAG G UCUCGU
7210
18804
aScSgSaSgaGccgaaagGCGaGucaaGGuCu cucccg B
15964
Zinzyme





323
HCV+
CCGGGAG G UCUCGUA
7211
18805
uSaScSgSagaGccgaaagGCGaGucaaGGuCu cucccgg B
15965
Zinzyme





75
HCV+
GCAGAAA G CGUCUAG
7212
18806
cSuSaSgSacgGccgaaagGCGaGucaaGGuCu uuucugc B
15966
Zinzyme





143
HCV+
GCCAUA G UGGUCU
7213
18807
aSgSaSCScaGccgaaagGCGaGucaaGGuCu uauggc B
15967
Zinzyme





278
HCV+
GCGAAAG G CCUUGUG
7214
18808
cSaScSaSaggCCC gaaagGCGaGucaaGGucu cuuucgc B
15968
Zinzyme





163
HCV+
CGGUGA G UACACC
7215
18809
gSgSuSgSuaCccgaaagGCGaGucaaGGuCu ucaccg B
15969
Zinzyme





68
HCV+
CUUCAC C CAGAAA
7216
18810
uSuSuScSugCccgaaagGCCaGucaaCGuCu gugaag B
15970
Zinzyme





94
HCV+
CCGUUA G UAUGAC
7217
18811
cSuSCSaSuaCccgaaagCCCaCucaaGCuCu uaacgc B
15971
Zinzyme





143
HCV+
ACCCAUA G UGCUCUC
7218
18812
cSaSgSaSccaGccgaaagGCGaCucaaCCuCu uauggcu B
15972
Zinzyme





159
HCV+
GAACCG G UGAGUA
7219
18813
uSaScSuScaCccgaaagGCCaCucaaGGuCu cgguuc B
15973
Zinzyme





163
HCV+
CCGGUCA G UACACCG
7220
18814
cSgSgSuSguaCccgaaagCCCaGucaaCGuCu ucaccgg B
15974
Zinzyme





249
HCV+
CACACU C CUACCC
7221
18815
gSgSCSuSagCCcgaaagGCGaGucaaGGucu agucuc B
15975
Zinzyme





249
HCV+
CCAGACU C CUAGCCG
7222
18816
cSgSgSCSuagGCCgaaagCCCaCUCaaGCUCU agucucg B
15976
Zinzyme





278
HCV+
CGAAAC C CCUUCU
7223
18817
aScSaSaSggCccgaaagCCGaGucaaGGuCu cuuucg B
15977
Zinzyme





286
HCV+
CUUCUC C UACUCC
7224
18818
gSCSaSgSuaCccgaaagCCGaCucaaGCuCu cacaag B
15978
Zinzyme





301
HCV+
CAUACC C UCCUUC
7225
18819
cSaSaSgScaCccgaaagCCCaCucaaCCuCu ccuauc B
15979
Zinzyme





328
HCV+
CCUCUC C UACACC
7226
18820
gSgSuSCSuaCccgaaagCCCaCucaaCCuCu gagacc B
15980
Zinzyme





328
HCV+
ACCUCUC C UACACCC
7227
18821
cSgSgSuScuaCccgaaagCCCaCucaaCCuCu gagaccu B
15981
Zinzyme





335
HCV+
UACACC C UCCACC
7228
18822
gSgSuSgScaCccgaaagCCCaCucaaCCuCu ggucua B
15982
Zinzyme





30
C
UAAACCU C AAACAAA
7229
19108
uSuSuScSuuucuCAuCaggccguuaggccCaa Agguuua B
15983
Hammerhead





48
C
CAAACCU A ACACCAA
7230
19109
uSuSgSgSugucT3CAuCaggccguuaggccCaa Acguuug B
15984
Hammerhead





60
C
CAACCCU C CCCCACA
7231
19110
uSgSuSgSggccUCAuCaggccguuaggccCaa Acgguug B
15985
Hammerhead





175
C
CACCCCU C ACAACCU
7232
19111
aSgSgSuSugucuCAuCaggccguuaggccCaa Accgcuc B
15986
Hammerhead





374
C
CUAACCU C AUCCAUA
7233
19112
uSaSuScSgaucUCAuCaggccguuaggccCaa Accuuac B
15987
Hammerhead





258
S27
UCCUCCCUCCAUCUUACCCCUAC
7234
22022
uSgSgSuSgSgScSuScScSaSuScSuSuSaSgScScScSuSaSg
15988
Antisense





259
S27
CCUCCCUCCAUCUUACCCCUACU
7235
22023
gSgSuSgSgSCSuSCSCSaSuScSuSuSaSgSCScScSuSaSgSu
15989
Antisense





260
S27
CUCCCUCCAUCUUACCCCUACUC
7236
22024
gSuSgSgSCSuScScSaSuScSuSuSaSgSCScSCSuSaSgSuSc
15990
Antisense





261
S27
UCCCUCCAUCUUACCCCUACUCA
7237
22025
uSgSgSCSuSCSCSaSuSCSuSuSaSgSCSCSCSuSaSgSuSCSa
15991
Antisense





262
S27
CCCUCCAUCUUACCCCUACUCAC
7238
22026
gSgSCSuSCSCSaSuSCSuSuSaSgSCSCSCSuSaSgSuSCSaSc
15992
Antisense





263
S27
CCUCCAUCUUACCCCUACUCACC
7239
22027
gSCSuSCSCSaSuSCSuSuSaSgSCSCSCSuSaSgSuSCSaScSg
15993
Antisense





264
S27
CUCCAUCUUACCCCUACUCACCC
7240
22028
CSuScScSaSuSCSuSuSaSgScSCSCSuSaSgSuSCSaSCSgSg
15994
Antisense





265
S27
UCCAUCUUACCCCUACUCACCCC
7241
22029
uSCSCSaSuSCSuSuSaSgSCSCSCSuSaSgSuSCSaSCSgSgSc
15995
Antisense





266
S27
CCAUCUUACCCCUACUCACCCCU
7242
22030
CSCSaSuSCSuSuSaSgSCSCScSuSaSgSuSCSaSCSgSgSCSu
15996
Antisense





267
S27
CAUCUUAGCCCUAGUCACGGCUA
7243
22031
cSaSuS08uSuSaSgSCSCSCSuSaSgSuSCSaSCSgSgSCSuSa
15997
Antisense





268
S27
AUCUUAGCCCUAGUCACCGCUAG
7244
22032
aSuSCSuSuSaSgS06CScSuSaSgSuScSaSCSgSgSCSuSaSg
15998
Antisense





269
S27
UCUUAGCCCUAGUCACGGCUAGC
7245
22033
uScSuSuSaSgSCScScSuSaSgSuSCSaScSgSgSCSuSaSgSc
15999
Antisense





270
S27
CUUAGCCCUAGUCACGGCUAGCU
7246
22034
CSuSuSaSgSCSCSCSuSaSgSuSCSaSCSgSgScSuSaSgSCSu
16000
Antisense





271
S27
UUAGCCCUAGUCACGGCUAGCUG
7247
22035
uSuSaSgSCSCSCSuSaSgSuSCSaSCSgSgSCSuSaSgSCSuSg
16001
Antisense





272
S27
UAGCCCUAGUCACGGCUAGCUGU
7248
22036
uSaSgSCSCSCSuSaSgSuSCSaSCSgSgSCSuSaSgSCSuSgSu
16002
Antisense





273
S27
AGCCCUAGUCACGGCUAGCUGUG
7249
22037
aSgSCSCSCSuSaSgSuSCSaSCSgSgSCSuSaSgSCSuSgSuSg
16003
Antisense





274
S27
GCCCUAGUCACGGCUAGCUGUGA
7250
22038
gSCSCSCSuSa 5gSuSCSaSCSgSgSCSuSaSgSCSuSgSuSgSa
16004
Antisense





275
S27
CCCUAGUCACGGCUAGCUGUGAA
7251
22039
CSCSCSuSaSgSuSCSaSCSgSgSCSuSaSgSCSuSgSuSgSaSa
16005
Antisense





276
S27
CCUAGUCACGGCUAGCUGUGAAA
7252
22040
CSCSuSaSgSuSC5aSCSgSgSC5uSaSgSC5uSgSuSgSaSaSa
16006
Antisense





277
S27
CUAGUCACGGCUAGCUGUGAAAG
7253
22041
CSuSaSgSuSCSaSCSgSgSC5uSaSgSCSuSgSuSgSaSaSaSg
16007
Antisense





278
S27
UAGUCACGGCUAGCUGUGAAAGG
7254
22042
uSaSgSuSCSaSCSgSgSCSuSaSgSCSuSgSuSgSaSaSaSgSg
16008
Antisense





279
S27
AGUCACGGCUAGCUGUGAAAGGU
7255
22043
aSgSuSCSaSCSgSgSC5uSaSgSCSuSgSuSgSaSaSaSgSgSu
16009
Antisense





280
S27
GUCACGGCUAGCUGUGAAAGGUC
7256
22044
gSuSCSaSCSgSgSCSuSaSgSCSuSgSuSgSaSaSaSgSgSuSc
16010
Antisense





281
S27
UCACGGCUAGCUGUGAAAGGUCC
7257
22045
uSCSaSCSgSgSCSuSaSgSCSuSgSuSgSaSaSaSgSgSuSCSc
16011
Antisense





282
S27
CACGGCUAGCUGUGAAAGGUCCG
7258
22046
CSaSCSgSgSCSuSaSgSCSuSgSuSgSaSaSaSgSgSuSCSCSg
16012
Antisense





283
S27
ACGGCUAGCUGUGAAAGGUCCGU
7259
22047
aSCSgSgSCSuSaSgSCSuSgSuSgSaSaSaSgSgSuSCSCSgSu
16013
Antisense





284
S27
CGGCUAGCUGUGAAAGGUCCGUG
7260
22048
CSgSgSCSuSaSgSC6uSgSuSgSaSaSaSgSgSuSCSCSgSuSg
16014
Antisense





285
S27
GGCUAGCUGUGAAAGGUCCGUGA
7261
22049
gSgSCSuSaSgSCSuSgSuSgSaSaSaSgSgSuSCSCSgSuSgSa
16015
Antisense





286
S27
GCUAGCUGUGAAAGGUCCGUGAG
7262
22050
gSCSuSaSgSCSuS95uSgSaSaSaSgSgSuSCSCSgSuSgSaSg
16016
Antisense





287
S27
CUAGCUGUGAAAGGUCCGUGAGC
7263
22051
CSuSaSgScSuSgSuSgSaSaSaSgSgSuSCSCSgSuSgSaSgSc
16017
Antisense





311
S27
GCAUGACUGCAGAGAGUGCUGAU
7264
22052
gSCSaSuSgSaSCSuSgSCSaSgSaSgSaSgSuSgSCSuSgSaSu
16018
Antisense





312
S27
CAUGACUGCAGAGAGUGCUGAUA
7265
22053
CSaSuSgSaSCSuSgS05aS95aSgSaSgSuSgS05uSgSaSuSa
16019
Antisense





313
S27
AUGACUGCAGAGAGUGCUGAUAC
7266
22054
aSuSgSaSCSuSgSCSaSgSaSgSaSgSuSgSCSuSgSaSuSaSc
16020
Antisense





314
S27
UGACUGCAGAGAGUGCUGAUACU
7267
22055
uSgSaSe5uSgSCSaSgSaSgSaSgSuSgSCSuSgSaSuSaSCSu
16021
Antisense





315
S27
GACUGCAGAGAGUGCUGAUACUG
7268
22056
gSaSCSuSgSCSaSgSaSgSaSgSuSgSCSuSgSaSuSaSCSuSg
16022
Antisense





316
S27
ACUGCAGAGAGUGCUGAUACUGG
7269
22057
aSCSuSgSCSaSgSaSgSaSgSuSgSCSuSgSaSuSaSCSuSgSg
16023
Antisense





317
S27
CUGCAGAGAGUGCUGAUACUGGC
7270
22058
CSuSgSCSaSgSaSgSaSgSuSgSCSuSgSaSuSaSCSuSgSgSc
16024
Antisense





318
S27
UGCAGAGAGUGCUGAUACUGGCC
7271
22059
uSgSCSaSgSaSgSaSgSuSgSCSuSgSaSuSaSCSuSgSgSCSc
16025
Antisense





319
S27
GCAGAGAGUGCUGAUACUGGCCU
727
222060
gSCSaSgSaSgSaSgSuSgSCSuSgSaSuSaSCSuSgSgSCSCSu
16026
Antisense





320
S27
CAGAGAGUGCUGAUACUGGCCUC
7273
22061
cSaSgSaSgSaSgSuSgSCSuSgSaSuSaSCSuSgSgSCSCSuSc
16027
Antisense





321
S27
AGAGAGUGCUGAUACUGGCCUCU
7274
22062
aSgSaSgSaS95uSgSCSuSgSaSuSaSCSuSgSgSCSCSuSCSu
16028
Antisense





322
S27
GAGAGUGCUGAUACUGGCCUCUC
7275
22063
gSaSgSaSgSuSgSCSuSgSaSuSaSCSuSgSgSCSCSuScSuSc
16029
Antisense





157
HCV+
CGGAACCGGUGAG
7276
22524
cSuSCSaScc cUGAuGaggccguuaggccGaa Iuuccg B
16030
Inozyme





167
HCV+
GAGUACACCGGAA
7277
22525
uSuSCSCSgg cuGAuGaggccguuaggccGaa luacuc B
16031
Inozyme





139
HCV+
GAGAGCCAUAGUG
7278
22526
cSaScSuSaucTGAuGaggccguuaggccGaa Icucuc B
16032
Inozyme





140
HCV+
AGAGCCAUAGUGG
7279
22527
cScSaScSuacuGAuGaggccguuaggccGaa Igcucu B
16033
Inozyme





281
HCV+
AAGGCCUUGUGGU
7280
22528
aScScSaScacUGAuGaggccguuaggccGaa Igccuu B
16034
Inozyme





130
HCV+
CCCUCCCGGGAGA
7281
22529
uScSuScScccUGAuGaggccguuaggccGaa Igaggg B
16035
Inozyme





280
HCV+
AAAGGCCUUGUGG
728
222530
cScSaScSaacuGAuGaggccguuaggccGaa Iccuuu B
16036
Inozyme





149
HCV+
GUGGUCUGCGGAA
7283
22531
uSuSCScSgccUGAuGaggccguuaggccGaa laccac B
16037
Inozyme





194
HCV+
GGGUCCUUUCUUG
7284
22532
cSaSaSgSaacUGAuGaggccguuaggccGaa Igaccc B
16038
Inozyme





255
HCV+
GCUAGCCGAGUAG
7285
22533
cSuSaScSuccUGAuGaggccguuaggccGaa Icuago B
16039
Inozyme





294
HCV+
ACUGCCUGAUAGG
7286
22534
cScSuSaSucctlGAuGaggccguuaggccGaa Igcagu B
16040
Inozyme





293
HCV+
UACUGCCUGAUAG
7287
22535
cSuSaSuScacuGAuGaggccguuaggccGaa Icagua B
16041
Inozyme





290
HCV+
UGGUACUGCCUGA
7288
22536
uScSaSgSgccUGAuGaggccguuaggccGaa luacca B
16042
Inozyme





169
HCV+
GUACACCGGAAUU
7289
22537
aSaSuSuScccUGAuGaggccguuaggccGaa luguac B
16043
Inozyme





293
HCV+
GUACUGCCUGAUAGG
7290
22544
cScSuSaSucacTlGAuGaggccguuaggccGaa Icaguac B
16044
Inozyme





294
HCV+
UACUGCCUCAUAGGG
7291
22545
cScScSuSauccUGAuGaggccguuaggccGaa Igcagua B
16045
Inozyme





281
HCV+
AAAGGCCUUGUGGUA
729
222546
uSaScScSacacUGAuGaggccguuaggccGaa Igccuuu B
16046
Inozyme





166
HCV+
UGAGUACACCGGA
7293
22549
uScScSgSgucUGAUGaggccguuaggccGaa Uacuca B
16047
Amberzyme





168
HCV+
AGUACACCGGAAU
7294
22550
aSuSuScScgcUGAUGaggccguuaggccGaa Uguacu B
16048
Amberzyme





141
HCV+
GAGCCAUAGUGGU
7295
22551
aScScSaScucUGAUGaggccguuaggccGaa Uggcuc B
16049
Amberzyme





156
HCV+
GCGGAACCGGUGA
7296
22552
uScSaSCScgcuGAUGaggccguuaggccGaa Uuccgc B
16050
Amberzyme





155
HCV+
UGCGGAACCGGUG
7297
22553
cSaSCScSggcUGAuGaggccguuaggccGaa Uccgca B
16051
Amberzyme





289
HCV+
GUGGUACUGCCUG
7298
22554
cSaSgSgScacUGAtlGaggccguuaggccGaa Uaccac B
16052
Arnberzyme





297
HCV+
GCCUGAUAGGGUG
7299
22555
cSaScScScucuGAUGaggccguuaggccGaa Ucaggc B
16053
Amberzyme





166
HCV+
GUGAGUACACCGGAA
7300
22556
uSuScSCSggucuGAuGaggccguuaggccGaa Uacucac B
16054
Amberzyme





141
HCV+
AGAGCCAUAGUGGUC
7301
22557
gSaSCScSacucUGAUGaggccguuaggccGaa Uggcucu B
16055
Amberzyine





156
HCV+
UGCGGAACCGGUGAG
730
222558
cSuScSaSccgcUGAUGaggccguuaggccGaa Uuccgca B
16056
Amberzyme





155
HCV+
CUGCGGAACCGGUGA
7303
22559
uScSaScScggcUGAUGaggccguuaggccGaa Uccgcag B
16057
Amberzyme





289
HCV+
UGUGGUACUGCCUGA
7304
22560
uScSaSgSgcacUGAUGaggccguuaggccGaa Uaccaca B
16058
Amberzyme





297
HCV+
UGCCUGAUAGGGUGC
7305
22561
gScSaScSccucUGAUGaggccguuaggccGaa Ucaggca B
16059
Amberzyme





168
HCV+
GAGUACACCGGAAUU
7306
22562
aSaguSuSccgcUGAuGaggccguuaggccGaa Uguacuc B
16060
Amberzyme





166
HCV−
UCCGGUGUACUCA
7307
22563
uSgSaSgSuagccgaaaggCgagugaGguCu accgga B
16061
Zinzyme





168
HCV−
ATCCGCUGUACU
7308
22564
aSgSuSaScagccgaaaggCgagugaGguCu cggaau B
16062
Zinzyme





138
HCV−
ACUAUGGCUCUCC
7309
22565
gSgSaSgSaggccgaaaggCgagugaGguCu cauagu B
16063
Zinzyme





156
HCV−
UCACCGGUUCCGC
7310
22566
gScSgSgSaagccgaaaggCgagugaGgucu cgguga B
16064
Zinzyme





236
HCV−
GCGGGGGCACGCC
7311
22567
gSgScSgSuggccgaaaggCgagugaGguCu ccccgc B
16065
Zinzyme





279
HCV−
CACAAGGCCUUUC
731
222568
gSaSaSaSgggccgaaaggCgagugaGguCu cuugug B
16066
Zinzyme





151
HCV−
GGUUCCGCAGACC
7313
22569
gSgSuScSuggccgaaaggCgagugaGguCu ggaacc B
16067
Zinzyme





292
HCV−
UAUCAGGCAGUAC
7314
22570
gSuSaScSuggccgaaaggCgagugaGguCu cugaua B
16068
Zinzyme





289
HCV−
CAGGCAGUACCAC
7315
22571
gSuSgSgSuagccgaaaggCgagugaGguCu ugccug B
16069
Zinzyme





166
HCV−
UUCCGGUGUACUCAC
7316
22572
gSuSgSaSguagccgaaaggCgagugaGguCu accggaa B
16070
Zinzyme





279
HCV−
CCACAAGGCCUUUCG
7317
22573
cSgSaSaSagggccgaaaggCgagugaGguCu cuugugg B
16071
Zinzyme





156
HCV−
CUCACCGGUUCCGCA
7318
22574
uSgScSgSgaagccgaaagSCgagugaGguCu cggugag B
16072
Zinzyme





138
HCV−
CACUAUGGCUCUCCC
7319
22575
gSgSgSaSgaggccgaaaggCgagugaGgucu cauagug B
16073
Zinzyme





151
HCV−
CGGUUCCGCAGACCA
7320
22576
uSgSgSuScuggccgaaaggCgagugaGguCu ggaaccg B
16074
Zinzyme





292
HCV−
CUAUCAGGCAGUACC
7321
22577
gSgSuSaScuggccgaaaggCgagugaGguCu cugauag B
16075
Zinzyme





289
HCV−
UCAGGCAGUACCACA
7322
22578
uSgSuSgSguagccgaaaggCgagugaGguCu ugccuga B
16076
Zinzyme





168
HCV−
AAUUCCGGUGUACUC
7323
22579
gSaSgSuSacagccgaaaggCgagugaGguCu cggaauu B
16077
Zinzyme





163
HCV−
GGUGUACUCACCG
7324
22580
CSgSgSuSgacuGAUGaggccguuaggccGaa Uacacc B
16078
Amberzyme





159
HCV−
UACUCACCGGUUC
7325
22581
gSaSaSCScgcuGAUGaggccguuaggccGaa Ugagua B
16079
Amberzyme





140
HCV−
CCACUAUGGCUCU
7326
22582
aSgSaSgScccuGAUGaggccguuaggccGaa Uagugg B
16080
Arnberzyme





281
HCV−
ACCACAAGGCCUU
7327
22583
aSaSgSgScccUGAUGaggccguuaggccGaa Uguggu B
16081
Amberzyme





233
HCV−
GGGGCACGCCCAA
7328
22584
uSuSgSgSgccuGAUGaggccguuaggccGaa Ugcccc B
16082
Amberzyrne





143
HCV−
AGACCACUAUGGC
7329
22585
gScScSaSuacuGAUGaggccguuaggccGaa Uggucu B
16083
Arnberzyrne





146
HCV−
CGCAGACCACUAU
7330
22586
aSuSaSgSugcUGAUGaggccguuaggccGaa Ucugcg B
16084
Amberzyme





195
HCV−
CCAAGAAAGGACC
7331
22587
gSgSuScScucUGAuGaggccguuaggccGaa Ucuugg B
16085
Amberzyme





194
HCV−
CAAGAAAGGACCC
733
222588
gSgSgSuScccUGAUGaggccguuaggccGaa Uucuug B
16086
Amberzyme





283
HCV−
GUACCACAAGGCC
7333
22589
gSgSCSCSuucUGAUGaggccguuaggccGaa Ugguac B
16087
Atnberzyme





286
HCV−
GCAGUACCACAAG
7334
22590
cguSuSggugcUGAuGaggccguuaggccGaa Uacugc B
16088
Amberzyme





296
HCV−
ACCCUAUCAGGCA
7335
22591
uSgScScSugcuCAuGaggccguuaggccGaa Uagggu B
16089
Amberzyme





190
HCV−
AAAGGACCCGGUC
7336
22592
gSaScScSggcUGAUGaggccguuaggccGaa Uccuuu B
16090
Amberzyme





163
HCV−
CGGUGUACUCACCGC
7337
22593
CScSgSgSugacUGAUCaggccguuaggccCaa Uacaccg B
16091
Amberzyme





140
HCV−
ACCACUAUGGCUCUC
7338
22594
gSaSgSaSgcccUGAUGaggccguuaggccGaa Uaguggu B
16092
Amberzyme





159
HCV−
GUACUCACCGGUUCC
7339
22595
gSgSaSaSccgcuGAUGaggccguuaggccGaa Ugaguac B
16093
Amberzyme





233
HCV−
GGGGGCACGCCCAAA
7340
22596
uSuSuSgSggccUGAUGaggccguuaggccGaa Ugccccc B
16094
Amberzyme





143
HCV−
CAGACCACUAUGCCU
7341
22597
aSgScScSauacUGAUcaggccguuaggccCaa Uggucug B
16095
Amberzyme





146
HCV−
CCGCAGACCACUAUG
734
222598
cSaSuSaSgugcUGAUGaggccguuaggccGaa Ucugcgg B
16096
Arnberzyme





195
HCV−
UCCAAGAAAGGACCC
7343
22599
gSgSgSuSccucuGAUGaggccguuaggccGaa Ucuugga B
16097
Amberzyme





283
HCV−
AGUACCACAAGGCCU
7344
22600
aSgSgSCScuucUGAUGaggccguuaggccGaa Ugguacu B
16098
Amberzyme





281
HCV−
UACCACAAGCCCUUU
7345
22601
aSaSaSgSgcccUGAUGaggccguuaggccGaa Uguggua B
16099
Arnberzyme





296
HCV−
CACCCUAUCAGGCAG
7346
22602
cSuSgScScugcUGAuGaggccguuaggccGaa Uagggug B
16100
Amberzyme





286
HCV−
GGCAGUACCACAAGG
7347
22603
cScSuSuSgugcUGAUGaggccguuaggccGaa Uacugcc B
16101
Amberzyme





7985
HCV−
UCUCAGU G UCUUCCA
7348
22719
uggaaga uGAUg gcauGcacuaugc gCg acugaga B
16102
G-cleaver





4832
HCV−
UGUAUAU G CCUCUCC
7349
22720
ggagagg uGAUg gcauGcacuaugc gCg auauaca B
16103
G-cleaver





4153
HCV−
ACCGUGU G CCUUAGA
7350
22721
ucuaagg uGAUg gcauGcacuaugc gCg acacggu B
16104
0-cleaver





3200
HCV−
GUGGAGU G AGGUGGU
7351
22722
accaccu uGAUg gcauGcacuaugc gCg acuccac B
16105
0-cleaver





1682
HCV−
ACGAGUU G AACCUGU
7352
22723
acagguu uGAUg gcauocacuaugc gCg aacucgu B
16106
0-cleaver





896
HCV+
CCUGUCU G ACCAUCC
7353
22724
ggauggu uGAUg gcauocacuaugc gCg agacagg B
16107
0-cleaver





2504
HCV+
UCCUGUU G CUUUUCC
7354
22725
ggaaaag UGAUg gcauGcacuaugc gCg aacagga B
16108
0-cleaver





2651
HCV+
UCCUCGU G UUCUUCU
7355
22726
agaagaa uGAUg gcauGcacuaugc gCg acgagga B
16109
0-cleaver





4094
HCV+
ACAAAGU G CUCGUCC
7356
22727
ggacgag uGAUg gcauGcacuaugc gCg acuuugu B
16110
G-cleaver





8970
HCV+
GCCACUU G ACCUACC
7357
22728
gguaggu uGAUg gcauGcacuaugc gCg aaguggc B
16111
0-cleaver





1200
HCV+
CUUCCUC G UCUCUCA
7358
22747
ugagaga gccgaaaggCgagugaGGuCu gaggaag B
16112
Zinzyme





1211
HCV+
CUCAOCU G UUCACCU
7359
22748
aggugaa gccgaaaggCgaguga0GuCu agcugag B
16113
Zinzyme





2504
HCV+
UCCUGUU G CUUUUCC
7354
22749
ggaaaag gccgaaaggCgagugaGGuCu aacagga B
16114
Zinzyme





2651
HCV+
UCCUCGU G UUCUUCU
7355
22750
agaagaa gccgaaaggCgagugaoGuCu acgagga B
16115
Zinzyme





8811
HCV+
CACUCCA G UCAACUC
7360
22751
gaguuga gccgaaaggCgagugaoouCu uggagug B
16116
Zinzyme





8594
HCV−
UCOCCGC G UCCUCUU
7361
22752
aagagga gccgaaaggCgagugaoouCu gcggcga B
16117
Zinzyme





7985
HCV−
UCUCAGU G UCUUCCA
7348
22753
uggaaga gccgaaaggCgagugaoouCu acugaga B
16118
Zinzyme





6611
HCV−
CCUCCAC G UACUCCU
7362
22754
aggagua gccgaaaggCgagugaGGuCu guggagg B
16119
Zinzyme





5633
HCV−
UCCACAU G UGCUUCG
7363
22755
cgaagca gccgaaaggCgagugaoouCu augugga B
16120
Zinzyme





821
HCV−
UCACGCC G UCUUCCA
7364
22756
uggaaga gccgaaaggCgagugagguCu ggcguga B
16121
Zinzyme





870
HCV+
CUCUAUC U UCCUCUU
7365
22775
aagagga CUgAUgAggccguuaggccgAA Iauagag B
16122
Inozyme





1210
HCV+
UCUCAGC U GUUCACC
7366
22776
ggugaac CUgAUgAggccguuaggccgAA Icugaga B
16123
Inozyme





2642
HCV+
UCCUCUC C UUCCUCG
7367
22777
cgaggaa CUgAUgAggccguuaggccgAA lagagga B
16124
Inozyme





5726
HCV+
UCACAGC C UCCAUCA
7368
22778
ugaugga CUgAUgAggccguuaggccgAA Icuguga B
16125
Inozyme





8142
HCV+
CUCCACC C UUCCUCA
7369
22779
ugaggaa CUgAUgAggccguuaggccgAA Iguggag B
16126
Inozyme





7990
HCV−
UGGUGUC U CAGUGUC
7370
22780
gacacug CUgAUgAggccguuaggccgAA lacacca B
16127
Inozyme





7813
HCV−
CUUCGCC U UCAUCUC
7371
22781
gagauga CUgAUgAggccguuaggccgAA Igcgaag B
16128
Inozyme





7137
HCV−
ACCUCUC U CUCAUCC
7372
22782
ggaugag CUgAUgAggccguuaggccgAA Iagaggu B
16129
Inozyme





6084
HCV−
UUCAUCC A CUOCACA
7373
22783
ugugcag CUgAUgAggccguuaggccgAA Igaugaa B
16130
Inozyme





2554
HCV−
CAACAGC A UCAUCCA
7374
22784
uggauga CUgAUgAggccguuaggccgAA Icuguug B
16131
Inozyme





1202
HCV+
UCCUCGU C UCUCAAC
7375
22943
gcugaga CUgAUgAggccguuaggccgAA Acgagga B
16132
Hammerhead





1607
HCV−
CGCACAU U AACAGGA
7376
22944
uccuguu CU0AUGAggccguuaggccgAA Augugcc B
16133
Hammerhead





2639
HCV+
CCAUCCU C UCCUUCC
7377
22945
ggaagga CUgAUgAggccguuaggccgAA Aggaugc B
16134
Hammerhead





6610
HCV+
GAGGAGU A COUGGAG
7378
22946
cuccacg CUgAUgAggccguuaggccgAA Acuccuc B
16135
Hammerhead





9014
HCV+
GCGCAUU U UCACUCC
7379
22947
ggaguga CUgAUgAggccguuaggccgAA Aaugcgc B
16136
Hammerhead





8605
HCV−
GACUCGU A GGCUCGC
7380
22948
gcgagcc CUGAUGAggccguuaggccgAA Acgaguc B
16137
Hammerhead





7983
HCV−
UCAGUGU C UUCCAGC
7381
22949
gcuggaa CUgAUgAggccguuaggccgAA Acacuga B
16138
Hammerhead





7136
HCV−
CCUCUCU C UCAUCCU
7382
22950
aggauga CUgAUgAggccguuaggccgAA Agagagg B
16139
Hammerhead





6609
HCV−
UCCACGU A CUCCUCA
7383
22951
ugaggag CUgAUgAggccguuaggccGAA Acgugga B
16140
Hammerhead





6292
HCV−
CGUGCAU A UCCAGUC
7384
22952
gacugga CUgAUgAggccguuaggccgAA Augcacg B
16141
Hammerhead





867
HCV+
UUUCUCU A UCUUCCU
7385
22971
aggaaga GGCTAGCTACAACGA agagaaa B
16142
DNAzyme





1200
HCV+
CUUCCUC G UCUCUCA
7358
22972
ugagaga GGCTAGCTACAACGA gaggaag B
16143
DNAzyme





1211
HCV+
CUCAOCU G UUCACCU
7359
22973
aggugaa GGCTAGCTACAACGA agcugag B
16144
DNAzyme





5730
HCV+
AGCCUCC A UCACCAG
7386
22974
cugguga GGCTAGCTACAACGA ggaggcu B
16145
DNAzyme





6533
HCV+
UCAACGC A UACACCA
7387
22975
uggugua GGCTAGCTACAACGA gcguuga B
16146
DNAzyme





8594
HCV−
UCGCCGC G UCCUCUU
7361
22976
aagagga GGCTAGCTACAACGA gcggcga B
16147
DNAzyme





7810
HCV−
CGCCUUC A UCUCCUU
7388
22977
aaggaga GGCTAGCTACAACGA gaaggcg B
16148
DNAzyme





7133
HCV−
CUCUCUC A UCCUCCU
7389
22978
aggagga GGCTAGCTACAACGA gagagag B
16149
DNAzyme





6611
HCV−
CCUCCAC G UACUCCU
736
222979
aggagua GGCTAGCTACAACGA guggagg B
16150
DNAzyme





2300
HCV−
CCUCCAA A UCACAAC
7390
22980
guuguga GGCTAGCTACAACGA uuggagg B
16151
DNAzyme





195
HCV+
GGGUCCU U UCUUGGA
7148
23072
cScSaSaSga cUGAuGaggcgWWagccGaa Aggacc B
16152
Hammerhead





195
HCV+
GGGUCCU U UCUUGGA
7148
23076
WWWWWcScSaSaSga cUGAuGaggcguuagccGaa Aggacc B
16153
Hammerhead





195
HCV+
GGGUCCU U UCUUGGA
7148
23077
WWWcScSaSaSga cUGAuGaggcgWWwagccGaa Aggacg B
16154
Hammerhead





195
HCV+
GGGUCCU U UCUUGGA
7148
23086
cScSaSaSga cuGAuGaggcgWWWagccGaa Aggacc B
16155
Hammerhead






lower caSe=2+-O-methyl




UPPER CASE=RIBO




B=inverted deoxy abasic




U=2′-deoxy-2′-aming Uridine




C=2′-deoxy-2′-aming Cytidine






U
=2′-deoxy-2′-aming Uridine





Z=BRdU (5-brgmg-2′-deoxy Uridine)




W=acyclic galactgse-amine linker






UNDERLINE
=deoxy nuclegtide









[0569]

21






TABLE XXI










ANTI HCV AMINO CONTAINING HAMMERHEAD RIBOZYME



AND CONTROL SEQUENCES















HCV 5′UTR


Rz Seq



pos
RPI#
Site

Core
ID



















Ribozyme Sequences (5′-3′)








62
12257
HCV-62
gScSgSugaa cUGAUGaggccguuaggccGaa AcaguagB
Active
15897





79
12258
HCV-79
aSuSgSgcua cUGAUGaggccguuaggccGaa AcgcuuuB
Active
15898





81
12249
HCV-81
cSCSaSuggc cUGAUGaggccguuaggccGaa AgacgcuB
Active
15899





104
12259
HCV-104
gScSuSgcac cUGAUGaggccguuaggccGaa AcacucaB
Active
15900





142
12250
HCV-142
aSgSaSccac cUGAUGaggccguuaggccGaa AuggcucB
Active
15901





148
12251
HCV-148
uSu9cScgca cUGAUGaggccguuaggccGaa AccacuaB
Active
15902





165
12260
HCV-165
uSCScSggug cUGAUGaggccguuaggccGaa AcucaccB
Active
15903





192
12261
HCV-192
aSaSgSaaag cUGAuGaggccguuaggccGaa AcccgguB
Active
15904





195
12252
HCV-195
uScScSaaga cUGAUGaggccguuaggccGaa AggacccB
Active
15905





196
12262
HCV-196
aSugCScaag cUGAUGaggccguuaggccGaa AaggaccB
Active
15906





270
12263
HCV-270
cSuSuSucgc cuGAUGaggccguuaggccGaa AcccaacB
Active
15907





282
12264
HCV-282
gSuSaSccac cUGAUGaggccguuaggccGaa AggccuuB
Active
15908





306
12265
HCV-306
cSaSCSucgc cUGAuGaggccguua9gccGaa AgcacccB
Active
15909





325
12253
HCV-325
uScSuSacga cUGAUGaggccguuaggccGaa AccucccB
Active
15910





330
12254
HCV-330
cSaScSgguc cUGAUGaggccguuaggccGaa AcgagacB
Active
15911








Control Sequences


79
13274
HCV-79AC2
cSuSuSaggu cUAGUGaggccguuaggccGau AguucucB
Attenuated
16171





81
13271
HCV-81AC
uScSuSgccg cuAGuGaggccguuaggccGau AgugaccB
Attenuated
16172





142
13270
HCV-142AC
aSaScSccug cUAGUGaggccguuaggccGau AgcucguB
Attenuated
16173





192
13272
HCV-192AC
aSgSuSagaa cUAGUGaggccguuaggccGau AgcugccB
Attenuated
16174





195
13269
HCV-195AC
gsaSuSucca cUAGUcaggccguuaggccGau AcgcgacS
Attenuated
16175





282
13273
HCV-282AC
gScScSauuc cUAGuGaggccguuaggccGau AucuggcB
Attenuated
16176





330
13268
14CV-330AC
cScSaSggcu cUAGUGaggccguuaggccGau AaugcgcB
Attenuated
16177





195
15291
HCV-195BAC3
uScScSaaga cUAGUGacgccguuaggcgGaa AggacccB
Attenuated
16178





195
15292
HCV-195SAC3
aSgSaScuac cUAGuGacgccguuaggcgGaa AcccgagS
Attenuated
16179





330
15294
HCV-330BAC
cSaSCSgguc cUAGt7GacgccguuaggcgGaa AcgagacB
Attenuated
16180





330
15295
HCV-330SAC
gScSuSccga cUAGUGacgccguuaggcgGaa AgacacgB
Attenuated
16181






UPPER CASE = RIBO;




lower case = 2′-O-methyl;




B = inverted deoxyabasic;




s = phosphorothioate linkage




U = 2′-deoxy-2′-amino uridine








[0570]

22






TABLE XXII










ANTI HCV SITE 330 ANTISENSE NUCLEIC ACID AND



SCRAMBLED CONTROL SEQUENCES











pos
RPI#
Alias

Seq ID #


















Antisense Nucleic Acid




330
17501
HCV.5-330
GsTsGsCSTsCSASTsGsASTsGsCSASCSGSGsTsCST
15898




antisense





330
17498
HCV.5-330
GSTSGSCSTSCSA6T8GSGSTSG5 CSASCSGSGSTSCST
16182




antisense








Control Sequence


330
17499
HCV.5-330
TSGSASTsCSASGSGSTSCSTSGSCSTSGSCSGSTSGsC
16183




scrambled





330
17502
HCV.5-330
TSGSASTSCSASGSGSTSCSTSGSCSTSGSCSASTSGSC
16184




Scrambled






UPPER CASE = Deoxy Nucleotide




s = phosphorothioate








[0571]

23






TABLE XXIII










IN VITRO CLEAVAGE DATA, ANTI-HCV ENZYMATIC NUCLEIC ACIDS






















% Substrate






Seq ID #
RPI#
Motif
Site (+/−)
Enzymatic Nucleic Acid Sequence
Cleaved in 3 hours
Substrate Sequence
Seq ID #
Substrate RPI#



















16132
22943
Hammerhead
1190 (+)
gcugaga CUGAUGAggccguuaggccGAA Acgagga B
89.67
UCCUCGU C UCUCAGC B
7391
22897






16133
22944
Hammerhead
1595 (+)
uccuguu CUGAUGAggccguuaggccGAA Augugcc B
90.33
GGCACAU U AACAGGA B
7392
22898





16134
22945
Hammerhead
2627 (+)
ggaagga CUGAUGAggccguuaggccGAA Aggaugc B
82.54
GCAUCCU C UCCUUCC B
7393
22899





16135
22946
Hammerhead
6598 (+)
cuccacg CUGAUGAggccguuaggccGAA Acuccuc B
78.06
GAGGAGU A CGUGGAG B
7394
22900





16136
22947
Hammerhead
9002 (+)
ggaguga CUGAUGAggccguuaggccGAA Aaugcgc B
81.88
GCGCAUU U UCACUCC B
7395
22901





16137
22948
Hammerhead
 818 (−)
gcgagcc CUGAUGAggccguuaggccGAA Acgaguc B
88.34
GACUCGU A GGCUCGC B
7396
22902





16138
22949
Hammerhead
1440 (−)
gcuggaa CUGAUGAggccguuaggccGAA Acacuga B
89.16
UCAGUGU C UUCCAGC B
7397
22903





16139
22950
Hammerhead
2287 (−)
aggauga CUGAUGAggccguuaggccGAA Agagagg B
83.43
CCUCUCU C UCAUCCU B
7398
22904





16140
22951
Hammerhead
2814 (−)
ugaggag CUGAUGAggccguuaggccGAA Acgugga B
83.25
UCCACGU A CUCCUCA B
7399
22905





16141
22952
Hammerhead
3131 (−)
gacugga CUGAUGAggccguuaggccGAA Augcacg B
86.96
CGUGCAU A UCCAGUC B
7400
22906





16142
22971
DNAzyme
 855 (+)
aggaaga GGCTAGCTACAACGA agagaaa B
92.11
UUUCUCU A UCUUCCU B
7401
22925





16143
22972
DNAzyme
1188 (+)
ugagaga GGCTAGCTACAACGA gaggaag B
86.38
CUUCCUC G UCUCUCA B
7402
22926





16144
22973
DNAzyme
1199 (+)
aggugaa GGCTAGCTACAACGA agcugag B
83.15
CUCAGCU G UUCACCU B
7403
22927





16145
22974
DNAzyme
5718 (+)
cugguga GGCTAGCTACAACGA ggaggcu B
57.82
AGCCUCC A UCACCAG B
7404
22928





16146
22975
DNAzyme
6521 (+)
uggugua GGCTAGCTACAACGA gcguuga B
75.77
UCAACGC A UACACCA B
7405
22929





16147
22976
DNAzyme
 829 (−)
aagagga GGCTAGCTACAACGA gcggcga B
66.06
UCGCCGC G UCCUCUU B
7406
22930





16148
22977
DNAzyme
1613 (−)
aaggaga GGCTAGCTACAACGA gaaggcg B
71.28
CGCCUUC A UCUCCUU B
7407
22931





16149
22978
DNAzyme
2290 (−)
aggagga GGCTAGCTACAACGA gagagag B
61.60
CUCUCUC A UCCUCCU B
7408
22932





16150
22979
DNAzyme
2812 (−)
aggagua GGCTAGCTACAACGA guggagg B
85.53
CCUCCAC G UACUCCU B
7409
22933





16151
22980
DNAzyme
7123 (−)
guuguga GGCTAGCTACAACGA uuggagg B
34.60
CCUCCAA A UCACAAC B
7410
22934





16102
22719
G-cleaver
1438 (+)
uggaaga uGAUg gcaugcacuaugcgCg acugaga B
69.88
UCUCAGU G UCUUCCA B
7411
22813





16103
22720
G-cleaver
4591 (+)
ggagagg uGAUg gcaugcacuaugcgCg auauaca B
77.74
UGUAUAU G CCUCUCC B
7412
22814





16104
22721
G-cleaver
5270 (+)
ucuaagg uGAUg gcaugcacuaugcgCg acacggu B
47.37
ACCGUGU G CCUUAGA B
7413
22815





16105
22722
G-cleaver
6223 (+)
accaccu uGAUg gcaugcacuaugcgCg acuccac B
75.84
GUGGAGU G AGGUGGU B
7414
22816





16106
22723
G-cleaver
7741 (+)
acagguu uGAUg gcaugcacuaugcgCg aacucgu B
61.58
ACGAGUU G AACCUGU B
7415
22817





16107
22724
G-cleaver
 884 (−)
ggauggu uGAUg gcaugcacuaugcgCg agacagg B
65.16
CCUGUCU G ACCAUCC B
7416
22818





16108
22725
G-cleaver
2492 (−)
ggaaaag uGAUg gcaugcacuaugcgCg aacagga B
94.66
UCCUGUU G CUUUUCC B
7417
22819





16109
22726
G-cleaver
2639 (−)
agaagaa uGAUg gcaugcacuaugcgCg acgagga B
82.14
UCCUCGU G UUCUUCU B
7418
22820





16110
22727
G-cleaver
4082 (−)
ggacgag uGAUg gcauGcacuaugcgCg acuuugu B
67.20
ACAAAGU G CUCGUCG B
7419
22821





16111
22728
G-cleaver
8958 (−)
gguaggu uGAUg gcauGcacuaugcgCg aaguggc B
81.06
GCCACUU G ACCUACC B
7420
22822





1611
222747
Zinzyme
1188 (+)
ugagaga gccgaaaggCgagugaGGuCu gaggaag B
66.11
CUUCCUC G UCUCUCA B
7402
22841





16113
22748
Zinzyme
1199 (+)
aggugaa gccgaaaggCgagugaGGuCu agcugag B
80.28
CUCAGCU G UUCACCU B
7403
22842





16114
22749
Zinzyme
2492 (+)
ggaaaag gccgaaaggCgagugaGGuCu aacagga B
90.80
UCCUGUU G CUUUUCC B
7417
22843





16115
22750
Zinzyme
2639 (+)
agaagaa gccgaaaggCgagugaGGuCu acgagga B
80.64
UCCUCGU G UUCUUCU B
7418
22844





16116
22751
Zinzyme
8799 (+)
gaguuga gccgaaaggCgagugagGuCu uggagug B
14.85
CACUCCA G UCAACUC B
7421
22845





16117
22752
Zinzyme
 829 (−)
aagagga gccgaaaggCgagugaGGuCu gcggcga B
27.83
UCGCCGC G UCCUCUU B
7406
22846





16118
22753
Zinzyme
1438 (−)
uggaaga gccgaaaggCgagugaGGuCu acugaga B
89.39
UCUCAGU G UCUUCCA B
7411
22847





16119
22754
Zinzyme
2812 (−)
aggagua gccgaaaggCgagugaGGuCu guggagg 8
50.40
CCUCCAC G UACUCCU B
7409
22848





16120
22755
Zinzyme
3790 (−)
cgaagca gccgaaaggCgagugaGGuCu augugga B
81.10
UCCACAU G UGCUUCG B
7422
22849





16121
22756
Zinzyme
8602 (−)
uggaaga gccgaaaggCgagugaGGuCu ggcguga B
73.47
UCACGCC G UCUUCCA B
7423
22850





16122
22775
Inozyme
 858 (+)
aagagga CUGAUGAggccguuaggccGAA Iauagag B
87.74
CUCUAUC U UCCUCUU B
7424
22869





16123
22776
Inozyme
1198 (+)
ggugaac CUGAUGAggccguuaggccGAA Icugaga B
84.55
UCUCAGC U GUUCACC B
7425
22870





16124
22777
Inozyme
2630 (+)
cgaggaa CUGAUGAggccguuaggccGAA lagagga B
90.12
UCCUCUC C UUCCUCG B
7426
22871





16125
22778
Inozyme
5714 (+)
ugaugga CUGAUGAggccguuaggccGAA Icuguga B
83.77
UCACAGG C UCCAUCA B
7427
22872





16126
22779
Inozyme
8130 (+)
ugaggaa CUGAUGAggccguuaggccGAA Iguggag B
82.22
CUCCACC C UUCCUCA B
7428
22873





16127
22780
Inozyme
1433 (−)
gacacug CUGAUGAggccguuaggccGAA lacacca B
87.33
UGGUGUC U CAGUGUC B
7429
22874





16128
22781
Inozyme
1610 (−)
gagauga CUGAUGAggccguuaggccGAA Igcgaag B
70.67
CUUCGCC U UCAUCUC B
7430
22875





16129
22782
Inozyme
2286 (−)
ggaugag CUGAUGAggccguuaggccGAA Iagaggu B
78.83
ACCUCUC U CUCAUCC B
7431
22876





16130
22783
Inozyme
3339 (−)
ugugcag CUGAUGAggccguuaggccGAA Igaugaa B
86.93
UUCAUCC A CUGCACA B
7432
22877





16131
22784
Inozyme
6869 (−)
uggauga CUGAUGAggccguuaggccGAA Icuguug B
90.41
CAACAGC A UCAUCCA B
7433
22878






In vitro cleavage in 50 mM Tris-Cl, pH 8.0, 40 mM Mg2+at 37°, using trace substrate, and enzymatic nucleic acid concentration of 500 nM or greater.




UPPER CASE = RIBO






UNDERLINED
 = DEOXY





lower case = 2′-O-methyl




B = inverted deoxyabasic




C = 2′-amino C




(+/−) = plus strand/minus strand of HCV genome








[0572]


Claims
  • 1. A short interfering RNA (siRNA) molecule that down-regulates expression of hepatitis B virus (HBV) RNA, wherein said siRNA comprises nucleotide sequence complementary to said HBV RNA or a portion thereof.
  • 2. The siNA molecule of claim 1, wherein said siRNA molecule is double stranded.
  • 3. The siRNA molecule of claim 2, wherein each strand of said siRNA comprises about 21 nucleotides.
  • 4. The siRNA molecule of claim 2, wherein each strand of said siRNA comprises a 3′-nucleotide overhang.
  • 5. The siRNA molecule of claim 4, wherein said 3′-nucleotide overhang comprises two nucleotides.
  • 6. The siRNA molecule of claim 1, wherein said siRNA molecule is single stranded.
  • 7. The siRNA molecule of claim 1, wherein said siRNA molecule comprises one or more chemically modified nucleotides.
  • 8. The siRNA molecule of claim 7, wherein said chemically modified nucleotide is a 2′-O-alkyl nucleotide.
  • 9. The siRNA molecule of claim 8, wherein said 2′-O-alkyl nucleotides is a 2′-O-methyl nucleotide.
  • 10. The siRNA molecule of claim 8, wherein said 2′-O-alkyl nucleotides is a 2′-O-allyl nucleotide.
  • 11. The siRNA molecule of claim 7, wherein said chemically modified nucleotide is a 2′-deoxy-2′-fluoro nucleotide.
  • 12. The siRNA molecule of claim 7, wherein said chemically modified nucleotide is a 2′-deoxy nucleotide.
  • 13. The siRNA molecule of claim 7, wherein said chemically modified nucleotide comprises one or more phosphorothioate internucleotide linkages.
  • 14. The siRNA molecule of claim 7, wherein said chemically modified nucleotide is a 2′-O-alkyl nucleotide, 2′-deoxy-2′-fluoro nucleotide, 2′-deoxy nucleotide, phosphorothioate containing nucleotide, or any combination thereof.
  • 15. The siRNA molecule of claim 7, wherein said siRNA comprises one or more 2′-O-alkyl and one or more 2′-deoxy-2′-fluoro nucleotides.
  • 16. The siRNA molecule of claim 7, wherein said siRNA comprises one or more 2′-deoxy and one or more 2′-deoxy-2′-fluoro nucleotides.
  • 17. The siRNA molecule of claim 1, wherein said siRNA comprises a terminal cap modification.
  • 18. The siRNA molecule of claim 17, wherein said terminal cap modification comprises an inverted abasic moiety.
  • 19. The siRNA molecule of claim 17, wherein said terminal cap modification is at the 3′-end of said siRNA.
  • 20. The siRNA molecule of claim 1, wherein said siRNA is conjugated to a biologically active molecule.
  • 21. The siRNA molecule of claim 20, wherein said siRNA molecule is conjugated to said biologically active molecule via a biodegradable linker.
  • 22. The siRNA molecule of claim 20, wherein said biologically active molecule comprises a vitamin.
  • 23. The siRNA molecule of claim 20, wherein said biologically active molecule comprises an antibody.
  • 24. The siRNA molecule of claim 20, wherein said biologically active molecule comprises a hormone.
Parent Case Info

[0001] This patent application is a continuation of International Application No. PCT/US02/09187, with international filing date of Mar. 26, 2002, published in English under PCT Article 21(2), which claims the benefit of Macejak et al., USSN (60/296,876), filed Jun. 8, 2001, Macejak et al., USSN (60/335,059), filed Oct. 24, 2001, Morrissey et al., USSN (60/337,055), filed Dec. 5, 2001, Beigelman et al., USSN (60/358,580), filed Feb. 20, 2002, Beigelman et al., USSN (60/363,124), filed Mar. 11, 2002, and which is a continuation-in-part of Blatt et al., USSN (Ser. No. 09/817,879), filed Mar. 26, 2001, which is a continuation-in-part of Blatt et al., USSN (Ser. No. 09/740,332), filed Dec. 18, 2000, which is a continuation-in-part of Blatt et al., USSN (Ser. No. 09/611,931), filed Jul. 7, 2000, which is a continuation-in-part of Blatt et al., USSN (Ser. No. 09/504,321), filed Feb. 15, 2000, which is a continuation-in-part of Blatt et al., USSN (Ser. No. 09/274,553), filed Mar. 23, 1999, which is a continuation-in-part of Blatt et al., USSN (Ser. No. 09/257,608), filed Feb. 24, 1999 (abandoned), which claims the benefit of Blatt et al., USSN (60/100,842), filed Sep. 18, 1998, and McSwiggen et al., USSN (60/083,217) filed Apr. 27, 1998. This patent application is also a continuation-in-part of Draper et al., USSN (Ser. No. 09/877,478) filed Jun. 8, 2001, which is a continuation-in-part of Draper et al., USSN (Ser. No. 09/696,347), filed Oct. 24, 2000, which is a continuation-in-part of Draper et al., USSN (Ser. No. 09/636,385), filed Aug. 9, 2000, which is a continuation-in-part of Draper et al., USSN (Ser. No. 09/531,025), filed Mar. 20, 2000, which is a continuation-in-part of Draper et al., USSN (Ser. No. 09/436,430), filed Nov. 8, 1999, which is a continuation of Draper et al., USSN (Ser. No. 08/193,627), filed Feb. 7, 1994, now U.S. Pat. No. 6,017,756, which is a continuation of Draper et al., USSN (Ser. No. 07/882,712), filed May 14, 1992, now abandoned. All of these listed applications are hereby incorporated by reference herein in their entireties, including the drawings.

Provisional Applications (7)
Number Date Country
60296876 Jun 2001 US
60335059 Oct 2001 US
60337055 Dec 2001 US
60358580 Feb 2002 US
60363124 Mar 2002 US
60100842 Sep 1998 US
60083217 Apr 1998 US
Continuations (3)
Number Date Country
Parent PCT/US02/09187 Mar 2002 US
Child 10669841 Sep 2003 US
Parent 08193627 Feb 1994 US
Child 09436430 Nov 1999 US
Parent 07882712 May 1992 US
Child 08193627 Feb 1994 US
Continuation in Parts (11)
Number Date Country
Parent 09817879 Mar 2001 US
Child 10669841 Sep 2003 US
Parent 09740332 Dec 2000 US
Child 09817879 Mar 2001 US
Parent 09611931 Jul 2000 US
Child 09740332 Dec 2000 US
Parent 09504231 Feb 2000 US
Child 09611931 Jul 2000 US
Parent 09274553 Mar 1999 US
Child 09504231 Feb 2000 US
Parent 09257608 Feb 1999 US
Child 09274553 Mar 1999 US
Parent 09877478 Jun 2001 US
Child 10669841 Sep 2003 US
Parent 09696347 Oct 2000 US
Child 09877478 Jun 2001 US
Parent 09636385 Aug 2000 US
Child 09696347 Oct 2000 US
Parent 09531025 Mar 2000 US
Child 09636385 Aug 2000 US
Parent 09436430 Nov 1999 US
Child 09531025 Mar 2000 US