RNAi therapeutics: a potential new class of pharmaceutical drugs

被引：880
作者：
Bumcrot, David [1 ]
Manoharan, Muthiah [1 ]
Koteliansky, Victor [1 ]
Sah, Dinah W. Y. [1 ]
机构：
[1] Alnylam Pharmaceut Inc, Cambridge, MA 02142 USA
来源：
NATURE CHEMICAL BIOLOGY | 2006年 / 2卷 / 12期
关键词：
D O I：
10.1038/nchembio839
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 rapid identification of highly specific and potent drug candidates continues to be a substantial challenge with traditional pharmaceutical approaches. Moreover, many targets have proven to be intractable to traditional small-molecule and protein approaches. Therapeutics based on RNA interference (RNAi) offer a powerful method for rapidly identifying specific and potent inhibitors of disease targets from all molecular classes. Numerous proof-of-concept studies in animal models of human disease demonstrate the broad potential application of RNAi therapeutics. The major challenge for successful drug development is identifying delivery strategies that can be translated to the clinic. With advances in this area and the commencement of multiple clinical trials with RNAi therapeutic candidates, a transformation in modern medicine may soon be realized.
引用
收藏
页码：711 / 719
页数：9
相关论文
共 82 条
[1]   Fully 2′-modified oligonucleotide duplexes with improved in vitro potency and stability compared to unmodified small interfering RNA [J].
Allerson, CR ;
Sioufi, N ;
Jarres, R ;
Prakash, TP ;
Naik, N ;
Berdeja, A ;
Wanders, L ;
Griffey, RH ;
Swayze, EE ;
Bhat, B .
JOURNAL OF MEDICINAL CHEMISTRY, 2005, 48 (04) :901-904
[2]   3′ UTR seed matches, but not overall identity, are associated with RNAi off-targets [J].
Birmingham, A ;
Anderson, EM ;
Reynolds, A ;
Ilsley-Tyree, D ;
Leake, D ;
Fedorov, Y ;
Baskerville, S ;
Maksimova, E ;
Robinson, K ;
Karpilow, J ;
Marshall, WS ;
Khvorova, A .
NATURE METHODS, 2006, 3 (03) :199-204
[3]   Inhibition of respiratory viruses by nasally administered siRNA [J].
Bitko, V ;
Musiyenko, A ;
Shulyayeva, O ;
Barik, S .
NATURE MEDICINE, 2005, 11 (01) :50-55
[4]   Mechanistic insights aid computational short interfering RNA design [J].
Boese, Q ;
Leake, D ;
Reynolds, A ;
Read, S ;
Scaringe, SA ;
Marshall, WS ;
Khvorova, A .
RNA INTERFERENCE, 2005, 392 :73-+
[5]   Characterization and modulation of immune stimulation by modified oligonucleotides [J].
Boggs, RT ;
McGraw, K ;
Condon, T ;
Flournoy, S ;
Villiet, P ;
Bennett, CF ;
Monia, BP .
ANTISENSE & NUCLEIC ACID DRUG DEVELOPMENT, 1997, 7 (05) :461-471
[6]   Adenovirus-mediated small-interference RNA for in vivo silencing of angiotensin AT1a receptors in mouse brain [J].
Chen, YF ;
Chen, H ;
Hoffmann, A ;
Cool, DR ;
Diz, DI ;
Chappell, MC ;
Chen, A ;
Morris, M .
HYPERTENSION, 2006, 47 (02) :230-237
[7]   Chemical modification of siRNAs to improve serum stability without loss of efficacy [J].
Choung, S ;
Kim, YJ ;
Kim, S ;
Park, HO ;
Choi, YC .
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 2006, 342 (03) :919-927
[8]   Improving RNA interference in mammalian cells by 4′-thio-modified small interfering RNA (siRNA):: Effect on siRNA activity and nuclease stability when used in combination with 2′-O-alkyl modifications [J].
Dande, P ;
Prakash, TP ;
Sioufi, N ;
Gaus, H ;
Jarres, R ;
Berdeja, A ;
Swayze, EE ;
Griffey, RH ;
Bhat, B .
JOURNAL OF MEDICINAL CHEMISTRY, 2006, 49 (05) :1624-1634
[9]   siRNA relieves chronic neuropathic pain [J].
Dorn, G ;
Patel, S ;
Wotherspoon, G ;
Hemmings-Mieszczak, M ;
Barclay, J ;
Natt, FJC ;
Martin, P ;
Bevan, S ;
Fox, A ;
Ganju, P ;
Wishart, W ;
Hall, J .
NUCLEIC ACIDS RESEARCH, 2004, 32 (05) :e49
[10]   Running interference: Prospects and obstacles to using small interfering RNAs as small molecule drugs [J].
Dykxhoorn, Derek M. ;
Lieberman, Judy .
ANNUAL REVIEW OF BIOMEDICAL ENGINEERING, 2006, 8 (377-402) :377-402
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