RNA interference: Natural, experimental, and clinical roles in cancer biology

Abstract

The old idea of using antisense RNA to block messenger RNA has recently led to powerful new techniques for knocking down expression of individual protein-coding genes. The simplicity and general applicability of these new methods for RNA interference (RNAi) have turned them into fundamental tools in molecular and cellular biology, with more than 5000 publications using them during the few years since they were developed. These experimental methods are now known to exploit fundamental cellular processes that regulate differentiation via genomically encoded RNAi sequences known as microRNAs (miRNAs); changes in endogenous microRNA regulation have now been implicated in oncogenesis. Clinical trials based on local delivery of interfering RNA have already begun. More general methods for safe and effective delivery of interfering RNA to intact organisms are being developed, which could open the way to widespread clinical applications. Because RNAi can provide selective knockdown of almost any protein, it may soon provide an approach to individualized cancer therapy.