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.
D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D004305:Dose-Response Relationship, Drug; D015870:Gene Expression / Q000187:drug effects* / Q000235:genetics; D005814:Genes, Viral; D006515:Hepatitis B virus / Q000235:genetics*; D006801:Humans; D016376:Oligonucleotides, Antisense / Q000494:pharmacology*; D013873:Thionucleotides / Q000494:pharmacology*; D014162:Transfection
D016376:Oligonucleotides, Antisense; D013873:Thionucleotides