PMID- 14592428 OWN - NLM STAT- MEDLINE DCOM- 20040210 LR - 20190612 IS - 0006-291X (Print) IS - 0006-291X (Linking) VI - 311 IP - 2 DP - 2003 Nov 14 TI - Inhibition of hepatitis B virus replication by stably expressed shRNA. PG - 398-404 AB - The major challenges for anti-hepatitis B Virus (HBV) therapy are the low efficacy of current drugs and the occurrence of drug resistant HBV mutations. A drug with new target sites or independent metabolic pathways may overcome these shortcomings. Small interfering RNA (siRNA) offers the possibility of developing a new anti-HBV therapy. Here we describe the almost complete inhibition of HBV replication by stably expressed 21-mer short hairpin RNAs (shRNA). Besides the conventional targets on HBV reverse-transcriptase, we also systemically targeted other sites of pregenomic RNA, including direct repeat (DR) elements, S, core, and X gene. Our results indicated that shRNAs can serve as efficient alternative anti-HBV agents. They can also be used in combination with chemotherapy, because they showed better effects on the inhibition of HBV replication due to different mechanisms of drug actions. FAU - Chen, Ying AU - Chen Y AD - The Institute of Molecular Biology and Open Laboratory of the Institute of Molecular Technology for Drug Discovery and Synthesis, The University of Hong Kong, Hong Kong, China. FAU - Du, Dan AU - Du D FAU - Wu, Jun AU - Wu J FAU - Chan, Chun-Pong AU - Chan CP FAU - Tan, Yuequi AU - Tan Y FAU - Kung, Hsiang-fu AU - Kung HF FAU - He, Ming-Liang AU - He ML LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - Biochem Biophys Res Commun JT - Biochemical and biophysical research communications JID - 0372516 RN - 0 (RNA, Small Interfering) RN - 2T8Q726O95 (Lamivudine) SB - IM MH - Carcinoma, Hepatocellular/*genetics/*virology MH - Cell Line, Tumor MH - Gene Expression Regulation, Viral/drug effects/*genetics MH - Genetic Therapy/methods MH - Hepatitis B virus/drug effects/*genetics/*growth & development MH - Humans MH - Lamivudine/pharmacology MH - RNA, Small Interfering/*genetics MH - *Virus Replication EDAT- 2003/11/01 05:00 MHDA- 2004/02/11 05:00 CRDT- 2003/11/01 05:00 PHST- 2003/11/01 05:00 [pubmed] PHST- 2004/02/11 05:00 [medline] PHST- 2003/11/01 05:00 [entrez] AID - S0006291X03020643 [pii] AID - 10.1016/j.bbrc.2003.10.009 [doi] PST - ppublish SO - Biochem Biophys Res Commun. 2003 Nov 14;311(2):398-404. doi: 10.1016/j.bbrc.2003.10.009.