RNA Interference: A New Targeted Tumour Therapy?

RNA interference (RNAi) is a mechanism in which double-stranded (ds) RNA acts as a guide to sequence-specifically suppress gene expression. To achieve targeted 'knock-downs' of gene function in mammalian cells, in vitro synthesised small interfering RNAs (siRNAs) can be introduced transiently into cells or, for more stable suppression by RNAi, various vector strategies can be employed to achieve prolonged in vivo synthesis of targeting RNA sequences. RNAi, beyond being a powerful experimental tool, has been widely promoted as a future gene-targeted therapeutic strategy of exquisite specificity. In the context of cancer, in which mutation, over-expression and de-novo acquisition of tumour-promoting genes are of central importance to the pathology, multiple molecular targets have been proposed for RNAi-based therapies. In this review, we will summarise what is known about the biology of RNAi in mammalian cells, outline the various expression and delivery strategies that have been developed, and discuss the features of possible therapeutic gene targets. We will also highlight the present technical limitations of RNAi that will need to be addressed if it is to be developed therapeutically, including the important issues of effective delivery and the potential for development of tumour resistance.