siRNA-directed inhibition of HIV-1 infection

被引:627
作者
Novina, CD [1 ]
Murray, MF
Dykxhoorn, DM
Beresford, PJ
Riess, J
Lee, SK
Collman, RG
Lieberman, J
Shankar, P
Sharp, PA
机构
[1] Harvard Univ, Sch Med, Ctr Blood Res, Boston, MA 02115 USA
[2] MIT, Ctr Canc Res, Cambridge, MA 02139 USA
[3] MIT, Dept Biol, Cambridge, MA USA
[4] MIT, McGovern Inst Brain Res, Cambridge, MA 02139 USA
[5] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA
[6] Univ Penn, Sch Med, Philadelphia, PA 19104 USA
关键词
D O I
10.1038/nm725
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
RNA interference silences gene expression through short interfering 21-23-mer double-strand RNA segments that guide mRNA degradation in a sequence-specific fashion. Here we report that siRNAs inhibit virus production by targeting the mRNAs for either the HIV-1 cellular receptor CD4, the viral structural Gag protein or green fluorescence protein substituted for the Nef regulatory protein. siRNAs effectively inhibit pre- and/or post-integration infection events in the HIV-1 life cycle. Thus, siRNAs may have potential for therapeutic intervention in HIV-1 and other viral infections.
引用
收藏
页码:681 / 686
页数:6
相关论文
共 45 条
[21]   Antisense RNA: Function and fate of duplex RNA in cells of higher eukaryotes [J].
Kumar, M ;
Carmichael, GG .
MICROBIOLOGY AND MOLECULAR BIOLOGY REVIEWS, 1998, 62 (04) :1415-+
[22]   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
[23]   Frequency of CCR5 genotypes in HIV-infected patients in Roraima, Brazil [J].
Guerra Corado, Andre de Lima ;
Villarouco da Silva, George Allan ;
Carvalho Leao, Renato Augusto ;
Granja, Fabiana ;
Naveca, Felipe Gomes .
BRAZILIAN JOURNAL OF INFECTIOUS DISEASES, 2016, 20 (03) :314-315
[24]   THE T4 GENE ENCODES THE AIDS VIRUS RECEPTOR AND IS EXPRESSED IN THE IMMUNE-SYSTEM AND THE BRAIN [J].
MADDON, PJ ;
DALGLEISH, AG ;
MCDOUGAL, JS ;
CLAPHAM, PR ;
WEISS, RA ;
AXEL, R .
CELL, 1986, 47 (03) :333-348
[25]   HIV-1 STRUCTURAL GENE-EXPRESSION REQUIRES BINDING OF THE REV TRANS-ACTIVATOR TO ITS RNA TARGET SEQUENCE [J].
MALIM, MH ;
TILEY, LS ;
MCCARN, DF ;
RUSCHE, JR ;
HAUBER, J ;
CULLEN, BR .
CELL, 1990, 60 (04) :675-683
[26]   Gene silencing using micro-RNA designed hairpins [J].
McManus, MT ;
Petersen, CP ;
Haines, BB ;
Chen, JZ ;
Sharp, PA .
RNA, 2002, 8 (06) :842-850
[27]   Short hairpin RNAs (shRNAs) induce sequence-specific silencing in mammalian cells [J].
Paddison, PJ ;
Caudy, AA ;
Bernstein, E ;
Hannon, GJ ;
Conklin, DS .
GENES & DEVELOPMENT, 2002, 16 (08) :948-958
[28]   Use of a green fluorescent protein as a marker for human immunodeficiency virus type 1 infection [J].
Page, KA ;
Liegler, T ;
Feinberg, MB .
AIDS RESEARCH AND HUMAN RETROVIRUSES, 1997, 13 (13) :1077-1081
[29]   Cosuppression of nonhomologous transgenes in Drosophila involves mutually related endogenous sequences [J].
Pal-Bhadra, M ;
Bhadra, U ;
Birchler, JA .
CELL, 1999, 99 (01) :35-46
[30]   Effective expression of small interfering RNA in human cells [J].
Paul, CP ;
Good, PD ;
Winer, I ;
Engelke, DR .
NATURE BIOTECHNOLOGY, 2002, 20 (05) :505-508