Nature Biotechnology
21, 635 - 637 (2003)
Published online: 18 May 2003; Corrected online: 30 May 2003 | doi:10.1038/nbt831
Expression profiling reveals off-target gene regulation by RNAiAimee L Jackson1, 2, Steven R Bartz1, 2, Janell Schelter1, Sumire V Kobayashi1, Julja Burchard1, Mao Mao1, Bin Li1, Guy Cavet1
& Peter S Linsley11
Rosetta Inpharmatics LLC, 12040
115th Avenue NE, Kirkland,
Washington 98034, USA. 2
These authors contributed equally to this work.
Correspondence should be addressed to Aimee L Jackson aimee_jackson@merck.com or Steven R Bartz steven_bartz@merck.comRNA 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.
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