Expression profiling reveals off-target gene regulation by RNAi

Nat Biotechnol. 2003 Jun;21(6):635-7. doi: 10.1038/nbt831. Epub 2003 May 18.


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.

Publication types

  • Comparative Study

MeSH terms

  • Base Sequence
  • Conserved Sequence
  • Gene Expression Profiling / methods*
  • Gene Expression Regulation*
  • Gene Silencing
  • Gene Targeting / methods*
  • HeLa Cells
  • Humans
  • Molecular Sequence Data
  • RNA Interference*
  • RNA, Messenger
  • RNA, Small Interfering / genetics*
  • Transformation, Genetic


  • RNA, Messenger
  • RNA, Small Interfering