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RNAi Timeline

Timeline Who What Organism Reference
1995 Guo S, and Kemphues KJ. First noticed that sense RNA was as effective as antisense RNA for suppressing gene expression in worm 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 Fire A, et al. First described RNAi phenomenon in C. elegans by injecting dsRNA into C. elegans which led to an efficient sequence-specific silencing and coined the term "RNA Interference". C. elegans Fire A. et al. Potent and specific genetic interference by double-stranded RNA in Caenorhabditis elegans.
Nature. 1998 Feb 19;391(6669):806-11.
1999 Hamilton AJ and Baulcombe DC. Reported posttranscriptional gene silencing (PTGS) in plants Plants Hamilton AJ and Baulcombe DC. A species of small antisense RNA in posttranscriptional gene silencing in plants. Science 1999; 286, 950952.
2000 Zamore PD, et al. Reported processing of long dsRNA by Rnase III (Dicer) into shorter fragments of 21-23-nt intervals in Drosophila extracts Drosophila Zamore PD, 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.


Bernstein E, et al. Cloned Dicer, the RNase III enzyme that is evolutionarily conserved and contains helicase and PAZ domains, as well as two dsRNA-binding domains. C. elegans  Bernstein E, et al. Role for a bidentate ribonuclease in the initiation step of RNA interference. Nature. 2001 Jan 18;409(6818):363-6.
2001 Tuschl T and colleagues  First described RNAi in mammalian cells Mammals Elbashir SM et al.  Duplexes of 21-nucleotide RNAs mediate RNA interference in cultured mammalian cells. Nature. 2001 May 24;411(6836):494-8.
2003 Paddison PJ, et al.
Sui G, et al.
Paul CP, et al.
Short hairpin RNAs (shRNAs) induce sequence-specific silencing in mammalian cells. Mammals Paddison PJ, et al. Genes Dev. 2002 Apr 15;16(8):948-58
Sui G, et al Proc Natl Acad Sci U S A. 2002 Apr 16;99(8):5515-20
Paul CP, et al. Nat Biotechnol. 2002 May;20(5):505-8
2003 Song  E, et al. First reported that siRNAs can be used therapeutically in whole animals. Mammals Song E, et al. RNA interference targeting Fas protects mice from fulminant hepatitis. Nat Med. 2003 Mar;9(3):347-51. 
2004 Kawasaki H and Taira K
Morris KV et al.
First observed that siRNA silences gene at transcriptional level possibly through directing de novo DNA methylation. Human Kawasaki H and Taira K Induction of DNA methylation and gene silencing by short interfering RNAs in human cells. [paper retracted from Nature]
Nature. 2004 Aug 15
Morris KV et al. Small Interfering RNA-Induced Transcriptional Gene Silencing in Human Cells.
Science. 2004 Aug 5
2004 Acuity Pharmaceuticals First phase I clinical trial of siRNA drug for age-related macular degeneration (AMD) Human Acuity news release
2006 Andrew Fire and Craig Mello Won Noble Prize in Physiology or Medicine for discovering RNAi mechanism.
2006 Li LC, et al First reported that small dsRNA induces transcriptional gene activation and coined the term "RNA activation" (RNAa). Human Li et al. Small dsRNAs induce transcriptional activation in human cells.
Proc Natl Acad Sci U S A. 2006 Nov 14;103(46):17337-42. Epub 2006 Nov 3.
2010 Davis ME et al. First demonstrated that siRNA administered systemically to humans can produce a specific gene inhibition (reduction in mRNA and protein) by an RNAi mechanism of action. Human Davis ME, et al.  Evidence of RNAi in humans from systemically administered siRNA via targeted nanoparticles. Nature. 2010 Apr 15;464(7291):1067-70. Epub 2010 Mar 21.

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