RNA Interference (RNAi)

Discovery of a natural post-transcriptional gene-silencing mechanism in which double-stranded RNA triggers sequence-specific degradation of matching messenger RNA. Fire, Xu, Montgomery, Kostas, Driver & Mello, "Potent and specific genetic interference by double-stranded RNA in Caenorhabditis elegans" (Nature 391, 806-811, 1998-02-01, OpenAlex W1647075334, 15,432 citations) showed dsRNA silences gene expression far more effectively than single-stranded antisense RNA, resolving earlier unexplained "co-suppression" observations in petunias. Fire and Mello shared the 2006 Nobel Prize in Physiology or Medicine. Directly translated into RNAi therapeutics -- Alnylam's patisiran (Onpattro), the first FDA-approved RNAi drug, 2018 -- and RNAi-based agricultural biopesticides.