History / Timeline / Progress / Advancements / Milestones / Landmarks

1990: Injection of chalcone synthase mRNA in violet petunias turned them white instead of a deeper violet - Napoli, C., Lemieux, C. & Jorgensen, R. Introduction of a chimeric chalcone synthase gene into petunia results in reversible co-suppression of homologous genes in trans. Plant Cell. 2, 279–289 (1990).

1998: Discovery of RNAi mechanism in C. elegans - Fire, A. et al. Potent and specific genetic interference by double-stranded RNA in Caenorhabditis elegans. Nature 391, 806–811 (1998).

2001: First demonstration of RNAi in mammalian cells by exogenous siRNA - Elbashir, S. M. et al. Duplexes of 21-nucleotide RNAs mediate RNA interference in cultured mammalian cells. Nature 411, 494–498 (2001).

2002:Science magazine names RNAi the "Breakthrough of the Year", highlighting its potential to revolutionize biology and medicine. Major biotech companies focused on RNAi, such as Alnylam Pharmaceuticals and Sirna Therapeutics, are founded.

2004: First in vivo silencing of a gene after systemic administration of siRNAs - Soutschek, J. et al. Therapeutic silencing of an endogenous gene by systemic administration of modified siRNAs. Nature 432, 173–178 (2004).

2006: Nobel prize in Physiology or Medicine, 2006 - Fire, A. & Mello, C. C.

2006: First report of gene silencing usign LNPs - Zimmermann, T. S. et al. RNAi-mediated gene silencing in non-human primates. Nature 441, 111–114 (2006).

2014: First silencing of a liver gene with GalNAC conjugate - Nair, J. K. et al. Multivalent N-acetylgalactosamine-conjugated siRNA localizes in hepatocytes and elicits robust RNAi-mediated gene silencing. J. Am. Chem. Soc. 136, 16958–16961 (2014).

2016: Revusiran clinical trial stopped and development discontinued - Judge, D. P. et al. Phase 3 multicenter study of revusiran in patients with hereditary transthyretin-mediated (hATTR) amyloidosis with cardiomyopathy (ENDEAVOUR). Cardiovasc. Drugs Ther. 34, 357–370 (2020).

2018: Patisiran (LNP formulation) approved - Patisiran, an RNAi therapeutic, for hereditary transthyretin amyloidosis. N. Engl. J. Med. 379, 11–21 (2018).

2019: First GalNAc conjugate FDA-approved