Bouchard Camille, Rousseau Joël, Lamothe Gabriel, Dubost Marie, Bastrenta Laura, Ramezani Sina, Tremblay Jacques P
Département de Médecine Moléculaire, Université Laval, Québec, QC G1V 0A6, Canada.
Centre de Recherche du Centre Hospitalier Universitaire de Québec, Québec, QC G1E 6W2, Canada.
Int J Mol Sci. 2025 Jun 12;26(12):5647. doi: 10.3390/ijms26125647.
Dysferlinopathy is caused by over 500 mutations in the gene encoding dysferlin, including close to 300 point mutations. One option to cure the disease is to use a gene therapy to correct these mutations at the root. Prime editing is a technique which can replace the mutated nucleotide with the wild-type nucleotide. In this article, prime editing is used to correct several point mutations in the DYSF gene responsible for dysferlinopathy. In vitro editing of HEK293T cells reaches up to 31%. Notably, editing was more efficient in myoblasts than in patient-derived fibroblasts. The prime editing technique was also used to create a new myoblast clone containing a patient mutation from a healthy myoblast cell line.
肌膜蛋白病由编码肌膜蛋白的基因中的500多个突变引起，其中包括近300个点突变。治愈该疾病的一种选择是使用基因疗法从根本上纠正这些突变。碱基编辑是一种可以用野生型核苷酸替换突变核苷酸的技术。在本文中，碱基编辑被用于纠正导致肌膜蛋白病的DYSF基因中的几个点突变。对HEK293T细胞的体外编辑效率高达31%。值得注意的是，在成肌细胞中的编辑比在患者来源的成纤维细胞中更有效。碱基编辑技术还被用于从健康的成肌细胞系中创建一个含有患者突变的新成肌细胞克隆。
