Use of RNA interference libraries to investigate oncogenic signalling in mammalian cells

Over the past decade, 'RNA interference' has emerged as a natural mechanism of silencing of gene expression. This ancient cellular antiviral response can be manipulated to provide an effective research tool to knock down the level of expression of selected target genes, providing a very powerful new method for the analysis of cell signalling pathways. Systematic silencing of genes on a genome-wide scale using large rationally designed libraries targeting many thousands of genes provides a novel functional genomics approach to the investigation of many aspects of mammalian cell behaviour, including oncogenic transformation. Here, the different approaches taken to use RNA interference libraries to study the cancer phenotype will be considered, including both selective and high throughput screens and the use of both vector-based and synthetic oligonucleotide-based methods for inducing RNA interference. The advantages and drawbacks of the competing methodologies will be discussed. RNA interference library technology holds great promise for enabling somatic cell genetics in tissue culture systems. Whether it can provide significant new insights into cancer will be its greatest challenge.