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

Jason Moffat; Jan H. Reiling; David M. Sabatini

doi:10.1016/j.tips.2007.02.009

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

Jason Moffat, Jan H. Reiling, David M. Sabatini

Research output: Contribution to journal › Short survey › peer-review

43 Scopus citations

Abstract

Evidence of off-target effects (OTEs) associated with small interfering (si)RNAs (19-29 bp) 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.

Original language	English (US)
Pages (from-to)	149-151
Number of pages	3
Journal	Trends in Pharmacological Sciences
Volume	28
Issue number	4
DOIs	https://doi.org/10.1016/j.tips.2007.02.009
State	Published - Apr 2007
Externally published	Yes

ASJC Scopus subject areas

Toxicology
Pharmacology

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10.1016/j.tips.2007.02.009

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title = "Off-target effects associated with long dsRNAs in Drosophila RNAi screens",

abstract = "Evidence of off-target effects (OTEs) associated with small interfering (si)RNAs (19-29 bp) 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.",

author = "Jason Moffat and Reiling, {Jan H.} and Sabatini, {David M.}",

note = "Funding Information: We acknowledge Tom DiCesare for assistance with the figure. Our work is supported by a Human Frontiers Longterm Fellowship (to J.H.R.), a Natural Sciences and Engineering Research Council of Canada postdoctoral fellowship (to J.M.) and grants from the National Institutes of Health and the Keck Foundation (to D.M.S.). We apologize to those authors whose primary works have not been cited owing to space constraints.",

year = "2007",

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doi = "10.1016/j.tips.2007.02.009",

language = "English (US)",

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journal = "Trends in Pharmacological Sciences",

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T1 - Off-target effects associated with long dsRNAs in Drosophila RNAi screens

AU - Moffat, Jason

AU - Reiling, Jan H.

AU - Sabatini, David M.

N1 - Funding Information: We acknowledge Tom DiCesare for assistance with the figure. Our work is supported by a Human Frontiers Longterm Fellowship (to J.H.R.), a Natural Sciences and Engineering Research Council of Canada postdoctoral fellowship (to J.M.) and grants from the National Institutes of Health and the Keck Foundation (to D.M.S.). We apologize to those authors whose primary works have not been cited owing to space constraints.

PY - 2007/4

Y1 - 2007/4

N2 - Evidence of off-target effects (OTEs) associated with small interfering (si)RNAs (19-29 bp) 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.

AB - Evidence of off-target effects (OTEs) associated with small interfering (si)RNAs (19-29 bp) 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.

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DO - 10.1016/j.tips.2007.02.009

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EP - 151

JO - Trends in Pharmacological Sciences

JF - Trends in Pharmacological Sciences

IS - 4

ER -

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

Abstract

ASJC Scopus subject areas

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