Artero Castro Ana, Long Kathleen, Bassett Andrew, Machuca Candela, León Marian, Ávila-Fernandez Almudena, Cortón Marta, Vidal-Puig Toni, Ayuso Carmen, Lukovic Dunja, Erceg Slaven
Stem Cells Therapies in Neurodegenerative Diseases Lab, Centro de Investigacion Principe Felipe (CIPF), Valencia, Spain.
Wellcome Sanger Institute, Wellcome Genome Campus, Hinxton, Cambridge CB10 1SA, UK.
Stem Cell Res. 2019 Jan;34:101341. doi: 10.1016/j.scr.2018.11.003. Epub 2018 Nov 16.
The human induced pluripotent stem cell (hiPSC) line RP1-FiPS4F1 generated from the patient with autosomal recessive retinitis pigmentosa (arRP) caused by homozygous Ser331Cysfs*5 mutation in Mer tyrosine kinase receptor (MERTK) was genetically corrected using CRISPR/Cas9 system. Two isogenic hiPSCs lines, with heterozygous and homozygous correction of c.992_993delCA mutation in the MERTK gene were generated. These cell lines demonstrate normal karyotype, maintain a pluripotent state, and can differentiate toward three germ layers in vitro. These genetically corrected hiPSCs represent accurate controls to study the contribution of the specific genetic change to the disease, and potentially therapeutic material for cell-replacement therapy.
通过CRISPR/Cas9系统对由Mer酪氨酸激酶受体（MERTK）纯合Ser331Cysfs*5突变导致常染色体隐性视网膜色素变性（arRP）的患者所产生的人诱导多能干细胞（hiPSC）系RP1-FiPS4F1进行了基因校正。生成了两个MERTK基因c.992_993delCA突变杂合和纯合校正的同基因hiPSC系。这些细胞系显示出正常的核型，维持多能状态，并能在体外分化为三个胚层。这些基因校正的hiPSC代表了研究特定基因变化对疾病的作用的精确对照，以及细胞替代疗法潜在的治疗材料。
