3′ UTR seed matches, but not overall identity, are associated with RNAi off-targets

被引：639

作者：

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

机构：

[1] Dharmaco Res, Lafayette, CO 80026 USA

[2] Agilent Technol, Palo Alto, CA 94034 USA

来源：

NATURE METHODS | 2006年 / 3卷 / 03期

关键词：

D O I：

10.1038/NMETH854

中图分类号：

Q5 [生物化学];

学科分类号：

071010 ; 081704 ;

摘要：

Off-target gene silencing can present a notable challenge in the interpretation of data from large-scale RNA interference (RNAi) screens. We performed a detailed analysis of off-targeted genes identified by expression profiling of human cells transfected with small interfering RNA (siRNA). Contrary to common assumption, analysis of the subsequent off-target gene database showed that overall identity makes little or no contribution to determining whether the expression of a particular gene will be affected by a given siRNA, except for near-perfect matches. Instead, off-targeting is associated with the presence of one or more perfect 3' untranslated region (UTR) matches with the hexamer or heptamer seed region (positions 2-7 or 2-8) of the antisense strand of the siRNA. These findings have strong implications for future siRNA design and the application of RNAi in high-throughput screening and therapeutic development.

引用

收藏

页码：199 / 204

页数：6

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