Selective inhibition of hepatitis B virus replication by RNA interference.
Small interfering RNA (siRNA) is a powerful tool to silence gene expression in mammalian cells including genes of viral origin. To evaluate the therapeutic efficacy of siRNA against the hepatitis B virus (HBV), we studied the effect of transfection of the HBV-inducible cell lines HepAD38 and HepAD79 with siRNA specific for the core gene of the HBV genome. HepAD38 cells produce wild-type HBV, whereas HepAD79 cells produce the lamivudine resistant YMDD variant. Transfection of HepAD38 cells with either 1.6 or 4 microg/ml siRNA resulted in a profound inhibition (72% and 98%, respectively) of viral replication (as assessed by real-time quantitative PCR). The inhibitory effect was corroborated by a marked reduction of HBV core protein synthesis in induced HepAD38 cells. In HepAD79 cells, transfected with 1.6 or 4 microg/ml HBV-specific siRNA, virus production was reduced by 75% and 89%, respectively.
Ying
Chunxiao
C
Rega Institute for Medical Research, Faculty of Medicine, Katholieke Universiteit Leuven, B-3000 Louvain, Belgium.
De Clercq
Erik
E
Neyts
Johan
J
D000818:Animals; D002460:Cell Line; D004305:Dose-Response Relationship, Drug; D015967:Gene Expression Regulation, Viral / Q000187:drug effects / Q000235:genetics*; D020868:Gene Silencing / Q000187:drug effects; D006515:Hepatitis B virus / Q000187:drug effects* / Q000235:genetics* / Q000254:growth & development; D006801:Humans; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000235:genetics* / Q000494:pharmacology*; D012367:RNA, Viral / Q000187:drug effects / Q000235:genetics; D014162:Transfection; D014779:Virus Replication / Q000187:drug effects / Q000235:genetics*
D034741:RNA, Small Interfering; D012367:RNA, Viral