RNAi applications in target validation.
The emergence of systems biology is certain to transform the identification and validation of therapeutic targets in modern drug discovery. A relatively recent systems biology approach is functional genomics, which identifies the molecular mechanisms responsible for a specific phenotype by interrogating the activity of all of an organism's genes. Initially undertaken in model organisms such as Caenorhabditis elegans, Saccharomyces cerevisiae, and Drosophila melanogaster, functional genomics has now moved into the realm of mammalian cells both in vitro and in vivo due to the development of RNA interference. RNA interference is a conserved biological process that has evolved to specifically and efficiently silence genes. Genome-wide screens using RNA interference have proven powerful in elucidating components of functionally related pathways and have therefore become integral for the development of new and improved therapeutic targets. This article provides an overview of many of the systems biology approaches taken, using RNA interference, in order to demonstrate how it may be used today for drug discovery and tomorrow as a targeted therapy.
Kourtidis
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Department of Biomedical Sciences, Gen"NY"Sis Center for Excellence Cancer Genomics, University at Albany, Rensselaer, NY 12144, USA.
Eifert
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Conklin
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D001943:Breast Neoplasms / Q000175:diagnosis* / Q000235:genetics*; D005821:Genetic Techniques; D023281:Genomics / Q000379:methods*; D006801:Humans; D008954:Models, Biological; D009369:Neoplasms / Q000628:therapy; D034622:RNA Interference