RNA interference (RNAi) was discovered by Andrew Fire and Craig Mello in 1998, earning them the 2006 Nobel Prize in Physiology or Medicine. The mechanism involves small double-stranded RNA molecules (siRNAs or miRNAs) that guide the RISC complex to complementary messenger RNA transcripts, triggering their degradation and thereby silencing the corresponding gene. RNAi has become an indispensable research tool for studying gene function and has been developed as both a therapeutic and agricultural technology.
In agriculture, RNAi is being applied as a novel crop protection strategy. RNAi-based biopesticides work by delivering double-stranded RNA molecules that target essential genes in pest insects or pathogens, silencing those genes and killing or disabling the pest. GreenLight Biosciences (now part of ADNOC's agriculture portfolio) developed cell-free manufacturing systems for producing dsRNA at agricultural scale. Bayer's SmartStax PRO corn, approved in 2022, incorporates plant-expressed RNAi targeting the western corn rootworm alongside traditional Bt proteins, representing the first commercial crop combining these two modes of action.
The therapeutic application of RNAi reached a milestone with Alnylam Pharmaceuticals' approval of Onpattro (patisiran) in 2018, the first RNAi therapeutic to receive FDA approval, treating hereditary transthyretin-mediated amyloidosis. Alnylam has since expanded its portfolio with additional approved products including Givlaari and Leqvio. The key enabling technology for therapeutic RNAi has been the development of delivery systems, particularly GalNAc conjugates that efficiently deliver siRNAs to hepatocytes. The convergence of RNAi with synthetic biology includes the design of synthetic regulatory RNA circuits in engineered organisms and the application of RNAi principles to microbiome engineering, where gene silencing in pathogenic or commensal organisms can modulate microbial community function.