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Expression profiling reveals off-target gene regulation by RNAi

Nature Biotechnology volume 21, pages 635637 (2003) | Download Citation

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Abstract

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.

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Change history

  • 30 May 2003

    replaced PDF with correct version (print was correct), ammended PDF with errata, footnote in SGML at Figure 1 callouts and legend

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Acknowledgements

We thank G. Schimmack, S. Kim, M. Imakura and J. McLarnan for expert technical assistance, M. Biery for assistance with computer graphics and the Rosetta Gene Expression Laboratory for microarray work.

Author information

Author notes

    • Aimee L Jackson
    •  & Steven R Bartz

    These authors contributed equally to this work.

Affiliations

  1. Rosetta Inpharmatics LLC, 12040 115th Avenue NE, Kirkland, Washington 98034, USA.

    • Aimee L Jackson
    • , Steven R Bartz
    • , Janell Schelter
    • , Sumire V Kobayashi
    • , Julja Burchard
    • , Mao Mao
    • , Bin Li
    • , Guy Cavet
    •  & Peter S Linsley

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Competing interests

The authors declare no competing financial interests.

Corresponding authors

Correspondence to Aimee L Jackson or Steven R Bartz.

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DOI

https://doi.org/10.1038/nbt831

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