Induction of an interferon response by RNAi vectors in mammalian cells

By A. Bridge, S. Pebernard, A. Ducraux, Anne-Laure Nicoulaz, R. Iggo. Nature Genetics, 2003

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siRNAs: applications in functional genomics and potential as therapeutics (2004, background): “Three recent reports, however, have demonstrated that the application of RNAi in mammalian cells can affect gene expression nonspecifically, depending on siRNA concentration, cell type, delivery reagent and mode of siRNA expressio”
Exportin-5 mediates the nuclear export of pre-microRNAs and short hairpin RNAs. (2003, background): “Given recent data suggesting that RNA interference can sometimes exert a nonspecific inhibitory effect (Bridge et al. 2003), we wished to confirm that the inhibition in miRNA or shRNA function shown in Figure 2 was specific.”
Large-scale production of dsRNA and siRNA pools for RNA interference utilizing bacteriophage ϕ6 RNA-dependent RNA polymerase (2007, background): “However, dsRNA and siRNAs have been shown to elicit various undesired cellular responses, including the activation of interferon-mediated pathways and offtargeting (Bridge et al. 2003; Jackson et al. 2003; Sledz and Williams 2004).”
Sequence-dependent stimulation of the mammalian innate immune response by synthetic siRNA (2005, background): “, and in vitro evidence suggests that siRNA can also activate this pathway under certain condition”