Interfering with disease: opportunities and roadblocks to harnessing RNA interference

被引:90
作者
Lieberman, J [1 ]
Song, E
Lee, SK
Shankar, P
机构
[1] Harvard Univ, Sch Med, Ctr Blood Res, Boston, MA 02115 USA
[2] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA
关键词
DOUBLE-STRANDED-RNA; HEPATITIS-B-VIRUS; SHORT HAIRPIN RNAS; MAMMALIAN-CELLS; GENE-EXPRESSION; HIV-1; INFECTION; MESSENGER-RNA; DIRECTED INHIBITION; FUNCTIONAL-ANATOMY; SYNTHETIC SIRNAS;
D O I
10.1016/S1471-4914(03)00143-6
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 (RNAi) is an evolutionarily conserved mechanism for silencing gene expression by targeted degradation of mRNA. Short double-stranded RNAs, known as small interfering RNAs (siRNA), are incorporated into an RNA-induced silencing complex that directs degradation of RNA containing a homologous sequence. RNAi has been shown to work in mammalian cells, and can inhibit viral infection and control tumor cell growth in vitro. Recently, it has been shown that intravenous injection of siRNA or of plasmids expressing sequences processed to siRNA can protect mice from autoimmune and viral hepatitis. RNAi could provide an exciting new therapeutic modality for treating infection, cancer, neurodegenerative disease and other illnesses.
引用
收藏
页码:397 / 403
页数:7
相关论文
共 94 条
[1]   Tolerance for mutations and chemical modifications in a siRNA [J].
Amarzguioui, M ;
Holen, T ;
Babaie, E ;
Prydz, H .
NUCLEIC ACIDS RESEARCH, 2003, 31 (02) :589-595
[2]   Control of developmental timing by small temporal RNAs: a paradigm for RNA-mediated regulation of gene expression [J].
Banerjee, D ;
Slack, F .
BIOESSAYS, 2002, 24 (02) :119-129
[3]   Role for a bidentate ribonuclease in the initiation step of RNA interference [J].
Bernstein, E ;
Caudy, AA ;
Hammond, SM ;
Hannon, GJ .
NATURE, 2001, 409 (6818) :363-366
[4]   Comparison of antisense oligonucleotides and siRNAs in cell culture and in vivo [J].
Bertrand, JR ;
Pottier, M ;
Vekris, A ;
Opolon, P ;
Maksimenko, A ;
Malvy, C .
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 2002, 296 (04) :1000-1004
[5]   An ATF2-derived peptide sensitizes melanomas to apoptosis and inhibits their growth and metastasis [J].
Bhoumik, A ;
Huang, TG ;
Ivanov, V ;
Gangi, L ;
Qiao, RF ;
Woo, SLC ;
Chen, SH ;
Ronai, Z .
JOURNAL OF CLINICAL INVESTIGATION, 2002, 110 (05) :643-650
[6]   Phenotypic silencing of cytoplasmic genes using sequence-specific double-stranded short interfering RNA and its application in the reverse genetics of wild type negative-strand RNA viruses [J].
Bitko V. ;
Barik S. .
BMC Microbiology, 1 (1) :1-11
[7]   Stable suppression of tumorigenicity by virus-mediated RNA interference [J].
Brummelkamp, TR ;
Bernards, R ;
Agami, R .
CANCER CELL, 2002, 2 (03) :243-247
[8]   Specific inhibition of gene expression by small double-stranded RNAs in invertebrate and vertebrate systems [J].
Caplen, NJ ;
Parrish, S ;
Imani, F ;
Fire, A ;
Morgan, RA .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2001, 98 (17) :9742-9747
[9]   Inhibition of HIV-1 infection by small interfering RNA-mediated RNA interference [J].
Capodici, J ;
Karikó, K ;
Weissman, D .
JOURNAL OF IMMUNOLOGY, 2002, 169 (09) :5196-5201
[10]   RNA interference is a functional pathway with therapeutic potential in human myeloid leukemia cell lines [J].
Cioca, DP ;
Aoki, Y ;
Kiyosawa, K .
CANCER GENE THERAPY, 2003, 10 (02) :125-133