Single-stranded microRNA mimics

被引：38

作者：

Chorn, Guillaume ^{[1
]}

Klein-McDowell, Molly ^{[1
]}

Zhao, Lihong ^{[1
]}

Saunders, Matthew A. ^{[1
]}

Flanagan, W. Michael ^{[1
]}

Willingham, Aarron T. ^{[1
]}

Lim, Lee P. ^{[1
]}

机构：

[1] Sirna Therapeut, San Francisco, CA 94158 USA

来源：

RNA | 2012年 / 18卷 / 10期

关键词：

miR-122; miR-124; microRNA; mimetic; MEDIATE RNA INTERFERENCE; CHEMICAL-MODIFICATION; MAMMALIAN-CELLS; TARGET; DUPLEXES;

D O I：

10.1261/rna.031278.111

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：

miRNAs are similar to 22-nt RNAs that bind to the Argonaute family of proteins and have important regulatory roles in plants and animals. Here, we show that miRNAs exhibit targeting activity in cells when delivered as single strands that are 5'-phosphorylated and that contain 2'-fluoro ribose modifications. Length preferences, chemical modification sensitivity, and genome-wide seed-based targeting all suggest that this activity is Ago-based. Activity could be enhanced by annealing of segmented passenger strands containing non-nucleic acid spacers. Furthermore, screening of randomly generated sequences identified pyrimidine rich 3' cassette sequences that increased single strand activity. These results provide an initial step in the development of single-stranded miRNA mimics for therapeutic use.

引用

收藏

页码：1796 / 1804

页数：9

相关论文

共 19 条

[1] MicroRNAs: Target Recognition and Regulatory Functions [J].

Bartel, David P. .

CELL, 2009, 136 (02) :215-233

[2] Improved silencing properties using small internally segmented interfering RNAs [J].

Bramsen, Jesper B. ;

Laursen, Maria B. ;

Damgaard, Christian K. ;

Lena, Suzy W. ;

Babu, B. Ravindra ;

Wengel, Jesper ;

Kjems, Jorgen .

NUCLEIC ACIDS RESEARCH, 2007, 35 (17) :5886-5897

[3]

Bramsen JB, 2011, METHODS MOL BIOL, V721, P77, DOI 10.1007/978-1-61779-037-9_5

[4] Persistence of seed-based activity following segmentation of a microRNA guide strand [J].

Chorn, Guillaume ;

Zhao, Lihong ;

Sachs, Alan B. ;

Flanagan, W. Michael ;

Lim, Lee P. .

RNA, 2010, 16 (12) :2336-2340

[5] Potent RNAi by short RNA triggers [J].

Chu, Chia-Ying ;

Rana, Tariq M. .

RNA, 2008, 14 (09) :1714-1719

[6] WebLogo: A sequence logo generator [J].

Crooks, GE ;

Hon, G ;

Chandonia, JM ;

Brenner, SE .

GENOME RESEARCH, 2004, 14 (06) :1188-1190

[7] 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

[8] mRNA knockdown by single strand RNA is improved by chemical modifications [J].

Haringsma, Henry J. ;

Li, Jenny J. ;

Soriano, Ferdie ;

Kenski, Denise M. ;

Flanagan, W. Michael ;

Willingham, Aarron T. .

NUCLEIC ACIDS RESEARCH, 2012, 40 (09) :4125-4136

[9] An HNF4α-miRNA Inflammatory Feedback Circuit Regulates Hepatocellular Oncogenesis [J].

Hatziapostolou, Maria ;

Polytarchou, Christos ;

Aggelidou, Eleni ;

Drakaki, Alexandra ;

Poultsides, George A. ;

Jaeger, Savina A. ;

Ogata, Hisanobu ;

Karin, Michael ;

Struhl, Kevin ;

Hadzopoulou-Cladaras, Margarita ;

Iliopoulos, Dimitrios .

CELL, 2011, 147 (06) :1233-1247

[10] microRNA Replacement Therapy for Cancer [J].

Henry, Jon C. ;

Azevedo-Pouly, Ana Clara P. ;

Schmittgen, Thomas D. .

PHARMACEUTICAL RESEARCH, 2011, 28 (12) :3030-3042