The potential for replacing a mutant gene in cells that are most severely affected and thereby causing a disease has long been desired. An alternative is inserting a normal copy of the defective gene in an organ that can produce the defective protein. After considerable research in animals, recent success in humans has shown promise in a few, serious genetic diseases. For example, an adeno-associated virus containing a normal copy of clotting factor IX was inserted into the liver of patients with hemophilia B and largely eliminated the need for intravenous infusions of the missing factor. In a different approach, a normal copy of a mutant gene that causes retinal dystrophy was injected into the retina of a patient resulting in restored vision. Numerous preclinical and clinical trials for other genetic disorders are underway.
et al. The next phase of human gene-therapy oversight. N Engl J Med. 2018;379:1393.
M. Closing in on treatment for hemophilia B. N Engl J Med 2017;377:2274.
et al. Efficacy and safety of voretigene neparvovec (AAV2-hRPE65v2) in patients with RPE65-mediated inherited retinal dystrophy: randomised, controlled, open-label, phase 3 trial. Lancet 2017;390:84.