title: Anticancer drug development incorporating high-content screening and RNAi: synergistic approaches to improve target identification and validation.
abstract: RNA interference (RNAi) and high-content screening (HCS) are powerful technologies that have converged on the early drug discovery process within the last year. RNAi emerged from basic science, where it has become a standard and accepted method for examining gene function. RNAi has achieved this level of recognition because it is a robust technology; however, it is not simple to use, and care needs to be taken to manage the sources of artifacts that can occur when using RNAi. HCS was developed for advanced drug development studies, particularly for toxicology. Recently developed HCS systems are tailored to target validation and high-throughput screening applications. These newer platforms are both faster, and capable of studying many more cellular events than previously possible. It follows that combining RNAi, particularly the screening of RNAi libraries, with HCS would be an obvious step. However, obvious is not synonymous with simple, and combining the technologies requires an understanding of strengths and challenges to each. This review describes RNAi and HCS technologies as they apply to drug target validation, and discusses efforts to integrate them. Particular focus is applied to aspects of HCS that mitigate some of the challenges inherent to RNAi.
authors.affiliation: Wyeth Research, Department of Biological Technologies, 87 Cambridge Park Drive, Cambridge, MA 02140, USA. shaney@wyeth.com.
authors.forename: Steven A
authors.initials: SA
authors.lastname: Haney