Inhibition of hepatitis B virus replication by stably expressed shRNA.
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.
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.
Ying
Y
Chen
Dan
D
Du
Jun
J
Wu
Chun-Pong
CP
Chan
Yuequi
Y
Tan
Hsiang-fu
HF
Kung
Ming-Liang
ML
He
D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000821:virology*; D045744:Cell Line, Tumor; D015967:Gene Expression Regulation, Viral / Q000187:drug effects / Q000235:genetics*; D015316:Genetic Therapy / Q000379:methods; D006515:Hepatitis B virus / Q000187:drug effects / Q000235:genetics* / Q000254:growth & development*; D006801:Humans; D019259:Lamivudine / Q000494:pharmacology; D034741:RNA, Small Interfering / Q000235:genetics*; D014779:Virus Replication
D034741:RNA, Small Interfering; D019259:Lamivudine