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

AIM: To assess the antiviral effects of hepatitis B virus (HBV) S gene-specific anti-gene locked nucleic acid (LNA) in transgenic mice. METHODS: Thirty HBV transgenic mice were acclimatized to laboratory conditions and positive for serum HBV surface antigen (HBsAg) and HBV DNA, were randomly divided into 5 groups (n = 7), including negative control (blank control, unrelated sequence control), positive control (lamivudine, anti-sense-LNA), and anti-gene-LNA experimental group. LNA was injected into transgenic mice by tail vein while lamivudine was administered by gavage. Serum HBV DNA and HBsAg levels were determined by fluorescence-based PCR and enzyme-linked immune sorbent assay, respectively. HBV S gene expression amounts were assessed by reverse transcription polymerase chain reaction. Positive rates of HBsAg in liver cells were evaluated immunohistochemistry. RESULTS: Average rate reductions of HBsAg after treatment on the 3(rd), 5(th), and 7(th) days were 32.34%, 45.96%, and 59.15%, respectively. The inhibitory effect of anti-gene-LNA on serum HBsAg peaked on day 7, with statistically significant differences compared with pre-treatment (0.96 ± 0.18 vs 2.35 ± 0.33, P < 0.05) and control values (P < 0.05 for all). Average reduction rates of HBV DNA on the 3(rd), 5(th), and 7(th) days were 38.55%, 50.95%, and 62.26%, respectively. This inhibitory effect peaked on the 7(th) day after treatment with anti-gene-LNA, with statistically significant differences compared with pre-treatment (4.17 ± 1.29 vs 11.05 ± 1.25, P < 0.05) and control values (P < 0.05 for all). The mRNA levels of the HBV S gene (P < 0.05 for all) and rates of HBsAg positive liver cells (P < 0.05 for all) were significantly reduced compared with the control groups. Liver and kidney function, and histology showed no abnormalities. CONCLUSION: Anti-gene-LNA targeting the S gene of HBV displays strong inhibitory effects on HBV in transgenic mice, providing theoretical and experimental bases for gene therapy in HBV.