CRISPR-Based Gene Therapy for Inherited Retinal Diseases

A research team at Johns Hopkins University has successfully developed a CRISPR-Cas9 gene therapy that reverses blindness in mice with inherited retinal diseases. The therapy targets mutations in the RPE65 gene, which cause Leber congenital amaurosis (LCA), a severe form of inherited retinal dystrophy that affects about 1 in 40,000 newborns. Unlike previous gene therapies that add a functional copy of the gene, this approach directly corrects the mutation in existing cells. This breakthrough was achieved by packaging the CRISPR-Cas9 system into a modified adeno-associated virus (AAV) that can efficiently deliver the components to retinal cells. When injected into the subretinal space, the therapy successfully edited the target mutation in over 60% of retinal pigment epithelium cells. The treated mice showed significant improvements in retinal function, with electroretinogram responses reaching nearly normal levels eight weeks after treatment. Even more promising, the therapy was effective in adult mice with established disease, suggesting that the approach could help patients who have already experienced vision loss. The researchers are now preparing for human clinical trials, which they hope to begin within two years. If successful, the approach could be adapted to target dozens of other genetic mutations responsible for inherited retinal diseases, potentially offering treatment options for forms of blindness currently considered untreatable.