CRISPR Technology in the Treatment of Leber Congenital Amaurosis (LCA)

Abstract

Leber congenital amaurosis (LCA) is a severe inherited retinal disease and one of the leading causes of childhood blindness. With the rise of gene therapy, CRISPR-Cas9 gene editing technology has brought new hope for the treatment of LCA. This article reviews the research progress of CRISPR in LCA treatment. This article focuses on key experiments in LCA treatment, particularly animal models and clinical studies targeting core pathogenic genes such as CEP290, RPE65, and GUCY2D. Among them, the EDIT-101 clinical trial targeting CEP290 mutations achieved the first-ever CRISPR gene editing in humans and preliminarily validated its safety and efficacy in selected patients, confirming the feasibility of the nonhomologous end joining (NHEJ) strategy in non-dividing retinal cells. Although animal studies have shown that CRISPR can effectively repair mutations and restore some visual function, it still faces many challenges, including the low efficiency of HDR strategies in non-dividing cells, the need to optimize vector delivery efficiency for clinical applications, and the commercialization challenges posed by rare diseases. This article aims to provide reference and insights for future research directions in the field of LCA treatment using CRISPR.