Expression profiling reveals off-target gene regulation by RNAi Nature Biotechnology
June 2003 Volume 21 Number 6 pp 635 - 637
 

Aimee L Jackson^{1, 2}, Steven R Bartz^{1, 2}, Janell Schelter¹, Sumire V Kobayashi¹, Julja Burchard¹, Mao Mao1, Bin Li¹, Guy Cavet1 & Peter S Linsley¹

RNA interference is thought to require near-identity between the small interfering RNA (siRNA) and its cognate mRNA. Here, we used gene expression profiling to characterize the specificity of gene silencing by siRNAs in cultured human cells. Transcript profiles revealed siRNA-specific rather than target-specific signatures, including direct silencing of nontargeted genes containing as few as eleven contiguous nucleotides of identity to the siRNA. These results demonstrate that siRNAs may cross-react with targets of limited sequence similarity.

¹ Rosetta Inpharmatics LLC, 12040 115th Avenue NE, Kirkland, Washington 98034, USA.
²These authors contributed equally to this work.
Correspondence should be addressed to A L Jackson. e-mail: aimee_jackson@merck.com and S R Bartz. e-mail: steven_bartz@merck.com

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