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

页码：398 / 404

页数：7

共 29 条

[1] The efficacy of small interfering RNAs targeted to the type 1 insulin-like growth factor receptor (IGF1R) is influenced by secondary structure in the IGF1R transcript
Bohula, EA
Salisbury, AJ
Sohail, M
Playford, MP
Riedemann, J
Southern, EM
Macaulay, VM
[J]. JOURNAL OF BIOLOGICAL CHEMISTRY, 2003, 278 (18) : 15991 - 15997
[2] RNAi in human cells: Basic structural and functional features of small interfering RNA
Chiu, YL
Rana, TM
[J]. MOLECULAR CELL, 2002, 10 (03) : 549 - 561
[3] Short-interfering-RNA-mediated gene silencing in mammalian cells requires dicer and eIF2C translation initiation factors
Doi, N
Zenno, S
Ueda, R
Ohki-Hamazaki, H
Ui-Tei, K
Saigo, K
[J]. CURRENT BIOLOGY, 2003, 13 (01) : 41 - 46
[4] Role of additional mutations outside the YMDD motif of hepatitis B virus polymerase in L(-)SddC (3TC) resistance
Fu, L
Cheng, YC
[J]. BIOCHEMICAL PHARMACOLOGY, 1998, 55 (10) : 1567 - 1572
[5] FU L, 1997, CHINESE J VIROL, V13, P215
[6] RNA interference of influenza virus production by directly targeting rnRNA for degradation and indirectly inhibiting all viral RNA transcription
Ge, Q
McManus, MT
Nguyen, T
Shen, CH
Sharp, PA
Eisen, HN
Chen, JZ
[J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2003, 100 (05) : 2718 - 2723
[7] Short interfering RNA-directed inhibition of hepatitis B virus replication
Hamasaki, K
Nakao, K
Matsumoto, K
Ichikawa, T
Ishikawa, H
Eguchi, K
[J]. FEBS LETTERS, 2003, 543 (1-3) : 51 - 54
[8] Two classes of short interfering RNA in RNA silencing
Hamilton, A
Voinnet, O
Chappell, L
Baulcombe, D
[J]. EMBO JOURNAL, 2002, 21 (17) : 4671 - 4679
[9] Transcription repression by Xenopus ET and its human ortholog TBX3, a gene involved in ulnar-mammary syndrome
He, ML
Wen, L
Campbell, CE
Wu, JY
Rao, Y
[J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1999, 96 (18) : 10212 - 10217
[10] A new and sensitive method for the quantification of HBV cccDNA by real-time PCR
He, ML
Wu, J
Chen, Y
Lin, MC
Lau, GKK
Kung, HF
[J]. BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 2002, 295 (05) : 1102 - 1107

← 1 2 3 →