RNA Interference (RNAi)

RNA Interference (RNAi) is a natural gene silencing mechanism where small RNA molecules suppress specific gene expression by targeting complementary mRNA sequences for degradation or translational inhibition. This powerful regulatory pathway, discovered in 1998 and recognised with the 2006 Nobel Prize in Physiology or Medicine, has evolved into both a research tool and a therapeutic platform enabling targeted modulation of previously undruggable targets.

The RNAi pathway begins when double-stranded RNA molecules are processed by the enzyme Dicer into small interfering RNAs (siRNAs) approximately 21-23 nucleotides long. These siRNAs are loaded into the RNA-induced silencing complex (RISC), where one strand guides the complex to mRNA molecules with complementary sequences. RISC either cleaves the message triggering its degradation, or blocks ribosome access preventing translation. The biopharmaceutical industry has successfully translated RNAi biology into approved therapeutics including patisiran for hereditary transthyretin amyloidosis and givosiran for acute hepatic porphyria, employing lipid nanoparticles or conjugated delivery systems that protect siRNAs from degradation. Development challenges including off-target effects, immune stimulation, and delivery to extrahepatic tissues have been largely overcome through chemical modifications and delivery innovations. Companies continue expanding RNAi applications into oncology, infectious diseases, and cardiovascular conditions, with the technology's ability to silence any gene substantially expanding the therapeutic landscape.