Prospects for gene therapy of inherited retinal disease

Gene-based therapies offer the means to address gene defects responsible for inherited retinal disorders. A number of studies in experimental and preclinical models have demonstrated proof-of-principle that gene replacement therapy can mediate significant quantifiable improvements in ocular morphology and visual function. The first results of clinical trials of gene therapy for early-onset severe retinal dystrophy caused by defects in RPE65 show proof-of-concept for efficacy and short-term safety in humans. The challenges for gene therapy of conditions caused by gain-of-abnormal function are being addressed by strategies to knock down expression of the disease allele. Vector-mediated expression of neuroprotective proteins may offer a generic approach for preserving vision in single-gene and multi-gene retinal degenerations. Gene therapy is likely to be most successful where stable expression of the therapeutic transgene can be achieved at an appropriate level in diseases in which retinal development is unaffected and a significant number of target cells survive at the point of intervention.