Bartz Steven, Jackson Aimee L
Rosetta Inpharmatics, LLC., a wholly owned subsidiary of Merck & Co., Inc., 401 Terry Avenue North, Seattle, WA 98109, USA.
Sci STKE. 2005 Aug 2;2005(295):pe39. doi: 10.1126/stke.2952005pe39.
Development of effective drugs for treatment of human disease relies on identification of therapeutic molecular targets. The identification of targets to treat human disease has previously relied on genetic screens in model organisms, and less robust or lower throughput approaches in mammalian systems. RNA interference (RNAi) makes possible, for the first time, the use of large-scale functional genomics approaches for target identification in human cells. This remarkable breakthrough has the potential to influence every facet of the drug discovery process, and is poised to revolutionize drug development. Reports of RNAi screens for the identification of novel genes implicated in apoptosis, cell division, and drug resistance support the enormous promise of this technology. Here, we discuss the potential impact of RNAi screens on target identification and validation and consider issues that warrant caution when interpreting RNAi screening results.
开发用于治疗人类疾病的有效药物依赖于治疗性分子靶点的识别。此前，治疗人类疾病靶点的识别依赖于模式生物中的遗传筛选，以及哺乳动物系统中可靠性较低或通量较低的方法。RNA干扰（RNAi）首次使大规模功能基因组学方法用于人类细胞中的靶点识别成为可能。这一重大突破有可能影响药物发现过程的方方面面，并有望彻底改变药物开发。有关用于识别与细胞凋亡、细胞分裂和耐药性相关新基因的RNAi筛选报告，支持了这项技术的巨大前景。在此，我们讨论RNAi筛选对靶点识别和验证的潜在影响，并考虑在解释RNAi筛选结果时需要谨慎对待的问题。
