A novel nonviral gene delivery system for treating Leber's congenital amaurosis

摘要

Leber's congenital amaurosis & gene therapy: Leber's congenital amaurosis (LCA) is a congenital retinal dystrophy that involves a series of autosomal recessive genetic mutations and results in severe vision loss and retinal degeneration at an early age. In North America, it has a prevalence of 1/81,000 which is also the most prevalent genetic cause of visual defects in children and infants. One subtype of LCA is the LCA2 form caused by mutations in the RPE65 gene, which encodes the retinal pigment epithelium-specific protein 65-kDa (RPE65) that is predominantly expressed in the retinal pigmented epithelium (RPE). As a key enzyme in retinoid metabolism, RPE65 is accountable for the hydrolysis and isomerization of all-trans-retinyl esters to 11-cis-retinal, whose deficiency results in the accumulation of all-trans-retinyl esters and further induces rod and cone photoreceptor dysfunction.