¹Laboratory of Systems Biology, Van Andel Research Institute, Grand Rapids, MI, USA

Correspondence: Dr JP MacKeigan, Laboratory of Systems Biology Van Andel Research Institute 333 Bostwick Ave., N.E. Grand Rapids, MI 49503, USA. Tel: 616 234 5682; Fax: 616 234 5733; E-mail: jeff.mackeigan@vai.org

Received 25 October 2007; Revised 13 December 2007; Accepted 13 December 2007; Published online 18 January 2008.

Abstract

RNA interference (RNAi) has emerged as one of the most powerful tools for functionally characterizing large sets of genomic data. Capabilities of RNAi place it at the forefront of high-throughput screens, which are able to span the human genome in search of novel targets. Although RNAi screens have been used to elucidate pathway components and discover potential drug targets in lower organisms, including Caenorhabditis elegans and Drosophila, only recently has the technology been advanced to a state in which large-scale screens can be performed in mammalian cells. In this review, we will evaluate the major advancements in the field of mammalian RNAi, specifically in terms of high-throughput assays. Crucial points of experimental design will be highlighted, as well as suggestions as to how to interpret and follow-up on potential cell death targets. Finally, we assess the prospective applications of high-throughput screens, the data they are capable of generating, and the potential for this technique to further our understanding of human disease.