果蝇RNA干扰筛选中与长双链RNA相关的脱靶效应。

Off-target effects associated with long dsRNAs in Drosophila RNAi screens.

作者信息

Moffat Jason, Reiling Jan H, Sabatini David M

机构信息

Whitehead Institute, 9 Cambridge Center, Cambridge, MA 02142, USA.

出版信息

Trends Pharmacol Sci. 2007 Apr;28(4):149-51. doi: 10.1016/j.tips.2007.02.009. Epub 2007 Mar 9.

DOI:10.1016/j.tips.2007.02.009

PMID:17350110

Abstract

Evidence of off-target effects (OTEs) associated with small interfering (si)RNAs (19-29bp) in mammalian cells has existed for several years. Two recent articles demonstrate that short sequences within long double-stranded (ds)RNAs frequently cause undesirable OTEs in cultured Drosophila cells. These results reveal the potential for high false-positive rates in RNA interference (RNAi) screens using long dsRNAs and highlight the need for screening with multiple, non-overlapping long dsRNAs or siRNAs. Discovering multiple potent siRNAs with minimal off-target profiles for each target transcript will be invaluable for genome-based studies of gene function and for personalized RNAi therapeutics.

摘要

在哺乳动物细胞中，与小干扰（si）RNA（19 - 29个碱基对）相关的脱靶效应（OTE）证据已经存在数年。最近的两篇文章表明，长双链（ds）RNA中的短序列经常在培养的果蝇细胞中引起不良的脱靶效应。这些结果揭示了在使用长dsRNA的RNA干扰（RNAi）筛选中存在高假阳性率的可能性，并强调了使用多个非重叠长dsRNA或siRNA进行筛选的必要性。为每个靶转录本发现具有最小脱靶特征的多个有效siRNA，对于基于基因组的基因功能研究和个性化RNAi治疗将具有重要价值。