关键词: 反义锁核酸, 乙型肝炎病毒, 转基因小鼠, 半乳糖配体

Abstract: Objective To investigate the inhibitory effects on hepatitis B virus(HBV) replication of antisense locked nucleic acid (LNA) targeting to C gene in transgenic mice. Methods Antisense LNA were injected into transgenic mice via the tail vein. Serum HBV DNA was tested by real-time PCR. Serum HBeAg was tested by time-resolved fluorescence immune assay.The expression of HBcAg in the liver was detected by immuneohistochemistry. Results Five days after LNA injection,serum HBV DNA levels in the AS-LNA group were reduced by 44.47%,and serum HBeAg levels were decreased by 63.46%.These values were significantly higher than those in the control groups(all P<0.05). The expression levels of HBcAg in the liver were significantly lower than those in the control groups. Conclusion The present study proves that antisense LNA targeting to C gene has strong inhibition effect on HBV replication and expression in transgenic mice, and suggests that C gene being the effected site for gene therapy.

Key words: locked nucleic acid, Hepatitis B virus, transgenic mice, galactose ligand