Applications of RNA interference: current state and prospects for siRNA-based strategies in vivo

被引:99
作者
Aigner, Achim [1 ]
机构
[1] Univ Marburg, Sch Med, Dept Pharmacol & Toxicol, D-35033 Marburg, Germany
关键词
RNA interference; RNAi; siRNA; gene-targeting; gene knockdown; nonviral siRNA delivery; nanoplexes;
D O I
10.1007/s00253-007-0984-y
中图分类号
Q81 [生物工程学(生物技术)]; Q93 [微生物学];
学科分类号
071005 ; 0836 ; 090102 ; 100705 ;
摘要
Within the recent years, RNA interference (RNIAi) has become an almost-standard method for in vitro knockdown of any target gene of interest. Now, one major focus is to further explore its potential in vivo, including the development of novel therapeutic strategies. From the mechanism, it becomes clear that small interfering RNAs (siRNAs) play a pivotal role in triggering RNAi. Thus, the efficient delivery of target gene-specific siRNAs is one major challenge in the establishment of therapeutic RNAi. Numerous studies, based on different modes of administration and various siRNA formulations and/or modifications, have already accumulated promising results. This applies to various animal models covering viral infections, cancer and multiple other diseases. Continuing efforts will lead to the development of efficient and "double-specific" drugs, comprising of siRNAs with high target gene specificity and of nanoparticles enhancing siRNA delivery and target organ specificity.
引用
收藏
页码:9 / 21
页数:13
相关论文
共 133 条
[21]   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
[22]   Reconstituted influenza virus envelopes as an efficient carrier system for cellular delivery of small-interfering RNAs [J].
de Jonge, J ;
Holtrop, M ;
Wilschut, J ;
Huckriede, A .
GENE THERAPY, 2006, 13 (05) :400-411
[23]   Transcriptional and phenotypic comparisons of Ppara knockout and siRNA knockdown mice [J].
De Souza, Angus T. ;
Dai, Xudong ;
Spencer, Andrew G. ;
Reppen, Tom ;
Menzie, Ann ;
Roesch, Paula L. ;
He, Yudong ;
Caguyong, Michelle J. ;
Bloomer, Sherri ;
Herweijer, Hans ;
Wolff, Jon A. ;
Hagstrom, James E. ;
Lewis, David L. ;
Linsley, Peter S. ;
Ulrich, Roger G. .
NUCLEIC ACIDS RESEARCH, 2006, 34 (16) :4486-4494
[24]   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
[25]   Systemic siRNA-mediated gene silencing - A new approach to targeted therapy of cancer [J].
Duxbury, MS ;
Matros, E ;
Ito, H ;
Zinner, MJ ;
Ashley, SW ;
Whang, EE .
ANNALS OF SURGERY, 2004, 240 (04) :667-674
[26]   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
[27]   RNA interference is mediated by 21-and 22-nucleotide RNAs [J].
Elbashir, SM ;
Lendeckel, W ;
Tuschl, T .
GENES & DEVELOPMENT, 2001, 15 (02) :188-200
[28]   Duplexes of 21-nucleotide RNAs mediate RNA interference in cultured mammalian cells [J].
Elbashir, SM ;
Harborth, J ;
Lendeckel, W ;
Yalcin, A ;
Weber, K ;
Tuschl, T .
NATURE, 2001, 411 (6836) :494-498
[29]   Locked nucleic acid (LNA) mediated improvements in siRNA stability and functionality [J].
Elmén, J ;
Thonberg, H ;
Ljungberg, K ;
Frieden, M ;
Westergaard, M ;
Xu, YH ;
Wahren, B ;
Liang, ZC ;
Urum, H ;
Koch, T ;
Wahlestedt, C .
NUCLEIC ACIDS RESEARCH, 2005, 33 (01) :439-447
[30]  
Filleur S, 2003, CANCER RES, V63, P3919