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
来源：
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS | 2003年 / 311卷 / 02期
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
相关论文
共 29 条
[11]   Modulation of HIV-1 replication by RNA interference [J].
Jacque, JM ;
Triques, K ;
Stevenson, M .
NATURE, 2002, 418 (6896) :435-438
[12]   Interference of hepatitis C virus RNA replication by short interfering RNAs [J].
Kapadia, SB ;
Brideau-Andersen, A ;
Chisari, FV .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2003, 100 (04) :2014-2018
[13]   A revised secondary structure model for the 3'-end of hepatitis B virus pregenomic RNA [J].
Kidd, AH ;
KiddLjunggren, K .
NUCLEIC ACIDS RESEARCH, 1996, 24 (17) :3295-3301
[14]   The hepatitis B virus pregenome: Prediction of RNA structure and implications for the emergence of deletions [J].
Kidd-Ljunggren, K ;
Zuker, M ;
Hofacker, IL ;
Kidd, AH .
INTERVIROLOGY, 2000, 43 (03) :154-164
[15]  
Lau G K, 2001, Clin Liver Dis, V5, P361, DOI 10.1016/S1089-3261(05)70170-7
[16]   Expression of small interfering RNAs targeted against HIV-1 rev transcripts in human cells [J].
Lee, NS ;
Dohjima, T ;
Bauer, G ;
Li, HT ;
Li, MJ ;
Ehsani, A ;
Salvaterra, P ;
Rossi, J .
NATURE BIOTECHNOLOGY, 2002, 20 (05) :500-505
[17]   Inhibition of hepatitis B virus in mice by RNA interference [J].
McCaffrey, AP ;
Nakai, H ;
Pandey, K ;
Huang, Z ;
Salazar, FH ;
Xu, H ;
Wieland, SF ;
Marion, PL ;
Kay, MA .
NATURE BIOTECHNOLOGY, 2003, 21 (06) :639-644
[18]  
MCCAFFREY AP, 2002, J IMMUNOL, V169, P5754
[19]   Gene silencing in mammals by small interfering RNAs [J].
McManus, MT ;
Sharp, PA .
NATURE REVIEWS GENETICS, 2002, 3 (10) :737-747
[20]   U6 promoter-driven siRNAs with four uridine 3′ overhangs efficiently suppress targeted gene expression in mammalian cells [J].
Miyagishi, M ;
Taira, K .
NATURE BIOTECHNOLOGY, 2002, 20 (05) :497-500
123