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Antiviral effect of hepatitis B virus S gene-specific anti-gene locked nucleic acid in hepatitis B virus transgenic mice

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Journal Title:
World Chinese Journal of Digestology
Key Word:
乙型肝炎病毒;锁核酸;反基因治疗;乙型肝炎;Hepatitis B virus;Locked nucleic acid;Anti-gene therapy;Hepatitis B

Abstract´╝Ü AIM To investigate the antiviral effect of hepatitis B virus (HBV) S gene-specific anti-gene locked nucleic acid (LNA) in transgenic mice.METHODS Thirty HBV transgenic mice were randomly divided into 5 groups (n =6 each):blank control group,negative control group (unrelated sequence),lamivudine group,antisense-LNA treatment group,and anti-gene LNA treatment group.LNA was injected into transgenic mice via the tail vein,and lamivudine was given by gavage.Serum HBV DNA was tested by realtime PCR;serum hepatitis B surface antigen (HBsAg) was determined by ELISA;the mRNA level of HBV S gene was detected by RT-PCR;and the positive rate of HBsAg in liver cells was detected by immunohistochemistry.RESULTS On 3,5,and 7 d after anti-gene LNA treatment,HBV DNA was reduced by 37.18%,50.27%,and 61.46%,respectively,and HBsAg was reduced by 30.17%,44%,and 57.76%,respectively;there was a significant difference in HBV DNA and HBsAg compared with those before administration (P < 0.05) or compared with control groups (blank control,negative control,lamivudine,and antisense-LNA) (P < 0.05).The mRNA level of HBV S gene (0.33) and the HBsAg positive rate of liver cells (31%) were significantly reduced compared with control groups (P < 0.05).The function of liver and kidney tests and tissue HE staining showed no abnormal changes.CONCLUSION Anti-gene LNA targeting the S gene has a strong inhibitory effect on HBV replication and expression in HBV transgenic mice,and this provides experimental basis for gene therapy of HBV.

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