CRISPR 碱基编辑和 prime 编辑可纠正的 CRB1 致病性变异分析。
Analysis of CRB1 Pathogenic Variants Correctable with CRISPR Base and Prime Editing.
机构信息
Department of Biomedical Engineering, Columbia University, New York, NY, USA.
Edward S. Harkness Eye Institute, Department of Ophthalmology, Columbia University Irving Medical Center/New York-Presbyterian Hospital, New York, NY, USA.
出版信息
Adv Exp Med Biol. 2023;1415:103-107. doi: 10.1007/978-3-031-27681-1_16.
The mouse and human retina contain three major Crumbs homologue-1 (CRB1) isoforms. CRB1-A and CRB1-B have cell-type-specific expression patterns making the choice of gene augmentation strategy unclear. Gene editing may be a viable alternative for the amelioration of CRB1-associated retinal degenerations. To assess the prevalence and spectrum of CRB1-associated pathogenic variants amenable to base and prime editing, we carried out an analysis of the Leiden Open Variation Database. Editable variants accounted for 54.5% for base editing and 99.8% for prime editing of all CRB1 pathogenic variants in the Leiden Open Variation Database. The 10 most common editable pathogenic variants for CRB1 accounted for 34.95% of all pathogenic variants, with the c.2843G>A, p.(Cys948Tyr) being the most common editable CRB1 variant. These findings outline the next step toward developing base and prime editing therapeutics as an alternative to gene augmentation for the amelioration of CRB1-associated retinal degenerations.
小鼠和人视网膜中含有三种主要的 Crumbs 同源物-1（CRB1）同种型。CRB1-A 和 CRB1-B 具有细胞类型特异性表达模式，使得基因增强策略的选择不明确。基因编辑可能是改善 CRB1 相关视网膜变性的可行替代方法。为了评估可进行碱基编辑和先导编辑的 CRB1 相关致病性变异的流行率和谱，我们对莱顿开放变异数据库进行了分析。对于莱顿开放变异数据库中的所有 CRB1 致病性变异，可编辑变异分别占碱基编辑的 54.5%和先导编辑的 99.8%。对于 CRB1 而言，10 个最常见的可编辑致病性变异占所有致病性变异的 34.95%，其中 c.2843G>A，p.（Cys948Tyr）是最常见的可编辑 CRB1 变异。这些发现概述了朝着开发碱基编辑和先导编辑治疗方法的下一步发展，作为改善 CRB1 相关视网膜变性的基因增强替代方法。
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