[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.
Yao
Z Q
ZQ
Department of Infectious Disease, Tangdu Hospital Fourth Military Medical University, Xi'an.
Zhou
Y X
YX
Wang
A L
AL
D001483:Base Sequence; D002478:Cells, Cultured; D004279:DNA, Viral / Q000235:genetics; D015870:Gene Expression / Q000187:drug effects; D006514:Hepatitis B Surface Antigens / Q000096:biosynthesis / Q000235:genetics; D006513:Hepatitis B e Antigens / Q000096:biosynthesis / Q000235:genetics; D006515:Hepatitis B virus / Q000235:genetics*; D006801:Humans; D008969:Molecular Sequence Data; D016376:Oligonucleotides, Antisense / Q000494:pharmacology*; D014162:Transfection
D004279:DNA, Viral; D006514:Hepatitis B Surface Antigens; D006513:Hepatitis B e Antigens; D016376:Oligonucleotides, Antisense