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1990 Over-expressing transgenes leads to "co-suppression" in plants Napoli C, Lemieux C, Jorgensen R. Introduction of a chimeric chalcone synthase gene into petunia results in reversible co-suppression of homologous gene in trans. Plant Cell 1990;2:279-89 1995 Noted sense RNA was as effective as antisense RNA for suppressing gene expression in C. elegans Guo S, and Kemphues KJ. par-1, a gene required for establishing polarity in C. elegans embryos, encodes a putative Ser/Thr kinase that is asymmetrically distributed. Cell 1995 May 19;81(4):611-20.1998 1998 dsRNA leads to silencing in C. elegans Fire et al. Potent and specific genetic interference by double-stranded RNA in Caenorhabditis elegans. Nature 1998 Feb 19;391(6669):806-11 2000 dsRNA processed to siRNAs in RNAi pathway Zamore et al. RNAi: double-stranded RNA directs the ATP-dependent cleavage of mRNA at 21 to 23 nucleotide intervals. Cell 2000 Mar 31;101(1):25-33 2001 Cloned Dicer Bernstein et al. Role for a bidentate ribonuclease in the initiation step of RNA interference. Nature 2001 Jan 18;409(6818):363-6 siRNAs trigger RNAi in mammalian cells Elbashir et al. Duplexes of 21-nucleotide RNAs mediate RNA interference in cultured mammalian cells. Nature 2001;411:494-8 2002 Science names RNAi "Technology of the Year" siRNA shown to inhibit viral infections in human cells Jiang M, Milner J. Selective silencing of viral gene expression in HPV-positive human cervical carcinoma cells treated with siRNA, a primer of RNA interference. Oncogene 2002;21:6041-8 siRNA shown to function in mice and rats McCaffrey et al. RNA interference in adult mice. Nature 2002;418 (6893): 38-9 2003 siRNAs can be used thrapeutically in animals Song et al. RNA interference targeting Fas protects mice from fulminant hepatitis. Nat Med. 2003 Mar;9(3):347-51 2004 siRNA silences genes at transcriptional level Morris et al. Small Interfering RNA-Induced Transcriptional Gene Silencing in Human Cells. Science 2004 Aug 27;305(5688):1289-92 Acuity Pharmaceutical is the first to enter Phase I clinical trial with an siRNA drug for age-related macular degeneration (AMD) 2006 Noble Prize in Physiology or Medicine for discovering RNAi mechanism awarded to Andrew Fire and Craig Mello Printer Friendly Page