Viral vector-mediated RNA interference.

RNA interference (RNAi) is a powerful gene silencing mechanism that if properly harnessed has the potential to revolutionize medical interventions. Delivery of inhibitory RNAs to target tissues needs to be safe, efficient, and for many diseases, long-lasting, in order to exploit this endogenous mechanism for therapeutic purposes. Viral vector systems, based on adeno-associated viruses and lentiviruses, are ideally suited to mediate RNAi because they can safely transduce a wide range of tissues and provide sustained levels of gene expression. There are now many examples of the use of viral vector-mediated RNAi to inhibit gene expression in animal models of disease, and in many cases proof-of-principle has been demonstrated. The efficient delivery of RNAi has also uncovered a number of concerns that raise questions regarding the clinical application of this technology, including off-target effects, innate immune responses, and alterations in the endogenous microRNA (miRNA) pathway. However, over the past several years, work has been done to address these problems and a number of solutions are now being implemented to mitigate these potential risks. With a deeper understanding of RNAi and continued progress in designing RNAi effectors, viral vector-mediated RNAi has the potential to change the way many diseases are treated.