Possible fly in the ointment:
>>Nat Biotechnol 2003 May 18; [epub ahead of print]
Expression profiling reveals off-target gene regulation by RNAi.
Jackson AL, Bartz SR, Schelter J, Kobayashi SV, Burchard J, Mao M, Li B, Cavet G, Linsley PS.
[1] Rosetta Inpharmatics LLC, 12040 115th Avenue NE, Kirkland, Washington 98034, USA. [2] These authors contributed equally to this work.
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.<<
I don't think this is the first time this concern has been raised, and it may have to do with technique. Nevertheless, it means designing the siRNA and choosing the right sequence to target is going to be a significant challenge. In therapeutic applications, it raises the specter of the kind of side effects that have plagued gene therapy.
Cheers, Tuck |
