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Trends Pharmacol Sci. 2007 Apr;28(4):149-51. Epub 2007 Mar 9.

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

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


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.

[Indexed for MEDLINE]

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