Inhibition of hepatitis B viral gene expression by antisense phosphorothioate oligodeoxynucleotides.

The inhibitory effect of antisense phosphorothioate oligodeoxyribonucleotides (S-oligos) on the production of hepatitis B surface antigen (HBsAg) and hepatitis B e antigen (HBeAg) was studied using Hep G2 cells transfected with hepatitis B virus (HBV). Synthetic antisense oligos (15-mers) directed against the cap site of mRNA transcribed from the SP II promoter and regions of the translational initiation site of the S gene showed a sequence-specific, dose-dependent inhibitory effect on HBV gene expression between concentrations of 1.0 microM-5.0 microM. Oligos directed against the middle of the S gene had little effect on HBsAg and HBeAg expression, as did non-complementary random-sequence control. The cells remained viable throughout the experiments and no morphological abnormalities were observed with antisense S-oligos at concentrations below 20.0 microM. These results suggest a therapeutic potential for antisense oligonucleotides in the treatment of patients who are chronically infected with HBV.