Validating rnai targets

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Researchers can now combine the two tools to screen potential targets systematically, exploiting the rich information set provided by HCS to make what may turn out to be better decisions about the molecules they will send to chemists.

This new wealth of information, however, creates information management challenges for both pharmaceutical researchers and instrument vendors.

Part 1 of a two-part series on assay development High-content screening can be combined with RNAi to screen potential targets, but the wealth of data provided creates information management challenges JR Minke The advent of genomics and transcriptional profiling makes it seem as if new drug targets are a dime a dozen.

Just plop the RNA contents of a cancer cell onto a chip and voilà—targets galore! "It's sort of a myth that there's a glut of targets," says Mark Cockett, Ph D, vice president of applied genomics at Bristol-Myers Squibb (BMS) Pharmaceutical Research Institute, Hopewell, N. "There's a glut of potential targets, but actually choosing which targets are the best ones in a cellular system or a model system is really the challenge." That, he says, is where high-content screening (HCS) has come into its own.

HCS Helps Validation The HTS group at Abbott complements its standard plate-based readers with the Discovery-1 HCS instrument from Molecular Devices Corp., Sunnyvale, Calif.

Researchers needed a faster way to validate the targets coming out of those experiments, and management wanted to begin implementing mammalian target screens."You now have targets that are highly validated before we begin looking for compounds.I think that ensures a higher success rate, although that has not yet been proven." Throughput is another advantage of HCS instrumentation."Initially, we had a variety of plate readers and confocal microscopy to validate targets one at a time, but it was rather laborious.The idea was to develop a uniform platform to handle multiple targets simultaneously.

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