[Inhibition of hepatitis B viral gene expression by antisense phosphrothioate oligonucleotides]

Hep G2 cells transfected with HBV genomes were used to study the inhibitory effect of antisense phosphrothiate oligodeoxynucleotides on HBsAg and HBeAg production. The synthetic antisense 15-s-oligomers against the cap site of mRNA transcribed from the SPII promoter and regions of the translational initiation site of the S gene showed a dose-dependent and sequence-specific inhibitory effect on HBV gene expression between concentrations of 1.0-5.0 mumol/L. But the oligomers directed on the middle site of the S gene exerted little effect on HBsAg and HBeAg expression as well as the non-complementary random sequence control. The cells remained viable throughout the experiments and no morphological abnormalities and cytotoxicity were observed with antisense S-oligomers at concentrations below 20.0 mumol/L. These results suggest a therapeutic potential for antisense oligonucleotides in the treatment of patients who are chronically infected with HBV.