nonspecific cellular responses - vector system vs synthetic siRNA - (Oct/18/2005 )
When you use a vector system for RNAi, it result in induction of genes related to nonspecific responses, such as the interferon and stress response pathways. Induction of these pathways results in growth inhibition and cytotoxicity.
When you use synthetic siRNA less than 30 bp long it does not activate nonspecific cellular responses.
Why did the nonspecific cellular responses become activated with the use of the vector system en not with the synthetic siRNA?
If you use vector system, the vector will express a short RNA which forms a hairpin structure by internal base pairing. According to this paper, why vector system induces interferon response is because shRNAs compete for processing to siRNA, and the accumulation of unprocessed or aberrantly processed Pol III transcripts triggers interferon expression.