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MicroSCALE Screening Reveals Genetic Modifiers of Therapeutic Response in Melanoma

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Science Signaling  15 May 2012:
Vol. 5, Issue 224, pp. rs4
DOI: 10.1126/scisignal.2002612

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Scaling Up Drug Discovery with Functional Genomics

The ability to perform high-throughput gain- and loss-of-function screens with mammalian cells in culture is a potentially important tool for exploring both basic cellular biology and drug discovery. Wood et al. describe a method they call “MicroSCALE screening,” which overcomes several technical limitations and enables rapid, high-throughput screening of mammalian cells plated on patterned surfaces and infected with viral libraries to achieve overexpression of specific proteins or with RNA interference vectors to achieve protein knockdown. Their procedure overcomes issues related to cellular migration and lack of uniformity in cellular infection. In addition, the authors devised simple, inexpensive image-based screening methods that allow rapid data collection. With this MicroSCALE screening system, Wood et al. overexpressed a kinome library and identified proteins that influenced the sensitivity of melanoma cells to various clinically used antineoplastic agents. Thus, this method should advance drug discovery and enhance identification of effective combination therapies.

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