Novel RNA-based Strategies for Therapeutic Gene Silencing

被引：99

作者：

Sibley, Christopher R. ^{[1
]}

Seow, Yiqi ^{[1
]}

Wood, Matthew J. A. ^{[1
]}

机构：

[1] Univ Oxford, Dept Physiol Anat & Genet, Oxford OX1 3QX, England

来源：

MOLECULAR THERAPY | 2010年 / 18卷 / 03期

基金：

英国生物技术与生命科学研究理事会; 英国惠康基金;

关键词：

SMALL INTERFERING RNAS; SHORT-HAIRPIN RNA; IMMUNODEFICIENCY-VIRUS TYPE-1; DOUBLE-STRANDED-RNA; IN-VIVO; NUCLEAR EXPORT; MICRORNA PRECURSORS; COMBINATORIAL RNAI; ENDOGENOUS SIRNAS; MULTIPLE SIRNAS;

D O I：

10.1038/mt.2009.306

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：

The past decade has seen intense scientific interest in non-coding RNAs. In particular, the discovery and subsequent exploitation of gene silencing via RNA interference (RNAi) has revolutionized the way in which gene expression is now studied and understood. It is now well established that post-transcriptional gene silencing (PTGS) by the microRNA (miRNA) and other RNAi-associated pathways represents an essential layer of complexity to gene regulation. Gene silencing using RNAi additionally demonstrates huge potential as a therapeutic strategy for eliminating pathogenic gene expression. Yet despite the early promise and excitement of gene-specific silencing, several critical hurdles remain to be overcome before widespread clinical adoption. These include off-target effects, toxicity due to saturation of the endogenous RNAi functions, limited duration of silencing, and effective targeted delivery. In recent years, a range of novel strategies for producing RNA-mediated silencing have been developed that can circumvent many of these hurdles, including small internally segmented interfering RNAs, tandem hairpin RNAs, and pri-miRNA cluster mimics. This review discusses RNA-mediated silencing in light of this recent research, and highlights the benefits and limitations conferred by these novel gene-silencing strategies.

引用

页码：466 / 476

页数：11

共 127 条

[1] Engineering and optimization of the miR-106b cluster for ectopic expression of multiplexed anti-HIV RNAs [J].

Aagaard L.A. ;

Zhang J. ;

von Eije K.J. ;

Li H. ;

Sætrom P. ;

Amarzguioui M. ;

Rossi J.J. .

Gene Therapy, 2008, 15 (23) :1536-1549

[2]

Abrams M.T., 2009, MOL THER

[3] Escape from the interferon response associated with RNA interference using vectors that encode long modified hairpin-RNA [J].

Akashi, H ;

Miyagishi, M ;

Yokota, T ;

Watanabe, T ;

Hino, T ;

Nishina, K ;

Kohara, M ;

Taira, K .

MOLECULAR BIOSYSTEMS, 2005, 1 (5-6) :382-390

[4] Orally delivered siRNA targeting macrophage Map4k4 suppresses systemic inflammation [J].

Aouadi, Myriam ;

Tesz, Gregory J. ;

Nicoloro, Sarah M. ;

Wang, Mengxi ;

Chouinard, My ;

Soto, Ernesto ;

Ostroff, Gary R. ;

Czech, Michael P. .

NATURE, 2009, 458 (7242) :1180-U116

[5] The role of exportin-t in selective nuclear export of mature tRNAs [J].

Arts, GJ ;

Kuersten, S ;

Romby, P ;

Ehresmann, B ;

Mattaj, IW .

EMBO JOURNAL, 1998, 17 (24) :7430-7441

[6] Mouse ES cells express endogenous shRNAs, siRNAs, and other Microprocessor-independent, Dicer-dependent small RNAs [J].

Babiarz, Joshua E. ;

Ruby, J. Graham ;

Wang, Yangming ;

Bartel, David P. ;

Blelloch, Robert .

GENES & DEVELOPMENT, 2008, 22 (20) :2773-2785

[7]

Barik Sailen, 2009, V487, P331, DOI 10.1007/978-1-60327-547-7_16

[8] Impact of tumor-specific targeting on the biodistribution and efficacy of siRNA nanoparticles measured by multimodality in vivo imaging [J].

Bartlett, Derek W. ;

Su, Helen ;

Hildebrandt, Isabel J. ;

Weber, Wolfgang A. ;

Davis, Mark E. .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2007, 104 (39) :15549-15554

[9] Chemical Modification of siRNAs for In Vivo Use [J].

Behlke, Mark A. .

OLIGONUCLEOTIDES, 2008, 18 (04) :305-319

[10] Mammalian mirtron genes [J].

Berezikov, Eugene ;

Chung, Wei-Jen ;

Willis, Jason ;

Cuppen, Edwin ;

Lai, Eric C. .

MOLECULAR CELL, 2007, 28 (02) :328-336

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