关键词: 基因编辑, 碱基编辑, 先导编辑, RNA编辑, 遗传性视网膜病

Abstract: Gene editing refers to the process of modifying specific targets in an organism’s genome using gene-editing technologies, with the third-generation editing tools represented by clustered regularly interspaced short palindromic repeats/CRISPR-associated protein 9 (CRISPR/Cas9) currently being the primary approach. In Leber congenital amaurosis type 10, EDIT-101 yielded anatomical and functional improvements in a subset of patients. For autosomal dominant retinitis pigmentosa (RP), therapeutic strategies have evolved toward more precise prime editing; similarly, X-linked RP has shown favorable outcomes in murine models, alongside the establishment of optimized dog animal models. In Stargardt disease, efficient editing of photoreceptors and retinal pigment epithelial cells has been achieved in non-human primates. Regarding age-related macular degeneration (AMD), the HG202 therapy for neovascular AMD has entered clinical trials, with early data indicating favorable therapeutic efficacy; meanwhile, dry AMD studies have successfully targeted complement factor genes in cellular models. In glaucoma, editing genes associated with aqueous humor production effectively lowered intraocular pressure in mouse models and conferred protection to retinal ganglion cells. Furthermore, clinical investigations into herpes simplex keratitis and transforming growth factor beta induced corneal dystrophy have confirmed the safety profile and robust antiviral effects of gene editing interventions. Nevertheless, significant challenges remain, including limitations in delivery system efficiency and capacity, precision and off-target risks, and unknown long-term side effects.

Key words: Gene editing, Base editing, Prime editing, RNA base editing, Inherited retinal diseases