How will RNAi facilitate drug development?
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.
Bartz
Steven
S
Rosetta Inpharmatics, LLC., a wholly owned subsidiary of Merck & Co., Inc., 401 Terry Avenue North, Seattle, WA 98109, USA. steven_bartz@merck.com
Jackson
Aimee L
AL
D000818:Animals; D017209:Apoptosis / Q000235:genetics; D002455:Cell Division / Q000235:genetics; D002460:Cell Line; D004353:Drug Evaluation, Preclinical / Q000379:methods*; D005188:False Negative Reactions; D015723:Gene Library; D018390:Gene Targeting; D006801:Humans; D046912:Multiprotein Complexes; D010749:Phosphoprotein Phosphatases / Q000502:physiology; D011494:Protein Kinases / Q000502:physiology; D034622:RNA Interference; D012333:RNA, Messenger / Q000037:antagonists & inhibitors; D034741:RNA, Small Interfering / Q000494:pharmacology / Q000627:therapeutic use*
D046912:Multiprotein Complexes; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D011494:Protein Kinases; D010749:Phosphoprotein Phosphatases