Gene Editing for CEP290 -Associated Retinal Degeneration

作者：Eric A. Pierce, Tomás S. Alemán, Kanishka T. Jayasundera, Bright S. Ashimatey, Keunpyo Kim, Alia Rashid, Michael C. Jaskolka, R Myers, Byron L Lam, Steven T. Bailey, Jason Comander, Andreas Katsuya Lauer, Albert M. Maguire, Mark Edward Pennesi · 发表于：New England Journal of Medicine · 年份：2024 · DOI：10.1056/nejmoa2309915 · 被引用次数：226 · 研究领域：Retinal Development and Disorders、Ophthalmology and Visual Impairment Studies、Retinal Diseases and Treatments

Background CEP290 -associated inherited retinal degeneration causes severe early-onset vision loss due to pathogenic variants in CEP290 . EDIT-101 is a clustered regularly interspaced short palindromic repeats (CRISPR)–CRISPR-associated protein 9 (Cas9) gene-editing complex designed to treat inherited retinal degeneration caused by a specific damaging variant in intron 26 of CEP290 (IVS26 variant). Methods We performed a phase 1–2, open-label, single-ascending-dose study in which persons 3 years of age or older with CEP290 -associated inherited retinal degeneration caused by a homozygous or compound heterozygous IVS26 variant received a subretinal injection of EDIT-101 in the worse (study) eye. The primary outcome was safety, which included adverse events and dose-limiting toxic effects. Key secondary efficacy outcomes were the change from baseline in the best corrected visual acuity, the retinal sensitivity detected with the use of full-field stimulus testing (FST), the score on the Ora–Visual Navigation Challenge mobility test, and the vision-related quality-of-life score on the National Eye Institute Visual Function Questionnaire–25 (in adults) or the Children’s Visual Function Questionnaire (in children). Results EDIT-101 was injected in 12 adults 17 to 63 years of age (median, 37 years) at a low dose (in 2 participants), an intermediate dose (in 5), or a high dose (in 5) and in 2 children 9 and 14 years of age at the intermediate dose. At baseline, the median best correc...