siRNA for gene silencing: a route to drug target discovery

The identification of RNA interference in mammalian cells, mediated via both virally-derived short interference RNA (siRNA) and endogenously produced microRNA, has revolutionised our understanding of the translational control of gene expression. Indeed, since its initial discovery, siRNA has been rapidly deployed for the elucidation of gene function and the identification of potential drug targets, a process often known as target discovery. In this review, we briefly discuss the mechanism of RNA interference and then critically examine the use of siRNA in target discovery, with a particular emphasis upon issues such as efficacy, selectivity, delivery and application in high-throughput studies.