Inhibition of hepatitis B virus replication by stably expressed shRNA

被引:63
作者
Chen, Y
Du, D
Wu, J
Chan, CP
Tan, YQ
Kung, HF
He, ML [1 ]
机构
[1] Univ Hong Kong, Inst Mol Biol, Hong Kong, Hong Kong, Peoples R China
[2] Univ Hong Kong, Inst Mol Technol Drug Discovery & Synth, Open Lab, Hong Kong, Hong Kong, Peoples R China
关键词
shRNA; hepatitis B virus; U6; promoter; anti-HBV; RNA interference;
D O I
10.1016/j.bbrc.2003.10.009
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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. (C) 2003 Elsevier Inc. All rights reserved.
引用
收藏
页码:398 / 404
页数:7
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