RNA interference (RNAi) is a powerful approach for reducing expression of endogenously expressed proteins for biological applications, or targeting the expression of pathological proteins for therapy.
Several delivery methods are available to achieve RNAi in ex vivo and in vivo settings for therapeutic results.
The development of RNAi-based therapeutics has advanced sufficiently to allow human clinical trials to begin.
Here we outline the broad range of cell-, tissue- and disease-specific approaches under investigation for RNAi therapeutics.
The barriers posed by certain cells and tissues are described, as are issues with off-target silencing.
RNA interference can elicit specific gene silencing and so holds great potential for treating infectious or genetic diseases. Several small-RNA-based therapies have now reached clinical trials, but further work is still needed to improve delivery and efficacy.
RNA interference (RNAi) is a powerful approach for reducing expression of endogenously expressed proteins. It is widely used for biological applications and is being harnessed to silence mRNAs encoding pathogenic proteins for therapy. Various methods — including delivering RNA oligonucleotides and expressing RNAi triggers from viral vectors — have been developed for successful RNAi in cell culture and in vivo. Recently, RNAi-based gene silencing approaches have been demonstrated in humans, and ongoing clinical trials hold promise for treating fatal disorders or providing alternatives to traditional small molecule therapies. Here we describe the broad range of approaches to achieve targeted gene silencing for therapy, discuss important considerations when developing RNAi triggers for use in humans, and review the current status of clinical trials.