RE: RNAi
> Better understanding of mechanisms that lead to toxicity and biosafety issues are essential before RNAi can become a practical therapeutic. Important aspects related to toxicity that need consideration include immune activation and off-target effects.
> Both siRNA and shRNA can induce off-target effects by fortuitous base pairing with unintended mRNAs resulting in suppression of important cellular components
> Because miRNAs are essential for the regulation of cell growth, differentiation and apoptosis, if the machinery for miRNA biogenesis is diverted to handle exogenous siRNA or shRNA, then a dearth of miRNAs can potentially manifest as toxicity
Expert Opinion on Biological Therapy: RNA interference-based therapeutics
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