| 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, 950–952. |
| 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. |
| 2001 | 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. | |
http://nobelprize.org/nobel_prizes/medicine/laureates/2006/press.html |
| 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. |
