RNA interference is a natural mechanism for living cells to control whether specific genes are being used. Crowned with the 2006 Nobel Prize in Physiology or Medicine, the discovery of RNA interference has since been harnessed by scientists to create a powerful and growing class of drugs capable of suppressing disease-related genes. Seven such drugs have already received Food and Drug Administration (FDA) approval, including inclisiran, which can replace daily cholesterol-lowering pills with twice-yearly injections. Despite these clinical successes, the molecular details of how the system executes its cuts remained poorly understood.