Abstract: Objective To investigate the inhibitory effects of hepatitis B virus(HBV) S gene-specific anti-gene locked nucleic acid(LNA) on HBV replication and expression in hepG2.2.15 cells. Methods The anti-gene LNA which were complementary to the purine rich region of the HBV S gene were designed,synthesized,and transfected by cationic liposomes into HepG2 2.2.15 cells. The HBsAg, HBeAg and HBV DNA of supernatants was tested by time-resolved fluorescence immune Assay(TRFIA) and real-time fluorescent quantitative polymerase chain reaction(FQ-PCR) at 2, 4, 6, 8 and 10 d after treatment. LNA’s cyto-toxicity on cell was evaluated by methyl thiazolyl tetrazolium(MTT) method. Results The anti-gene LNA that targeting on the purine rich region of HBV S gene showed strong inhibitory effects on replication of HBV DNA and the expression of HBsAg and HBeAg with the inhibition rates of 52.14%, 57.48% and 29.63% respectively after 6 days.There’s no obvious toxicity on cell. Conclusions Anti-gene locked nucleic acid that targeting on the purine rich region of HBV S gene has show strong inhibition on HBV in vitro.It has a therapeutic potential in the treatment of patients infected with HBV.

Key words: Cationic liposomes, Hepatitis B virus, Locked nucleic acid, anti-gene therapy