人诱导多潜能干细胞与CRISPR/Cas9基因编辑技术在眼遗传病的应用研究进展

Current researches and prospects of human induced pluripotent stem cells and gene editing technology of CRISPR/Cas9 in inherited ocular diseases

人诱导多潜能干细胞(hiPSC)可定向分化为眼特定细胞组织,在视网膜细胞移植、角膜移植、晶状体再生等领域有应用前景;成簇规律间隔短回文重复序列/相关蛋白核酸酶(CRISPR/Cas9)基因编辑技术可以高效向hiPSC引入眼遗传病特异突变,将携带眼遗传病基因的hiPSC分化为特定的细胞类型,在体外建立眼遗传病模型或建立体外筛选平台寻找治疗性药物,还可纠正基因组中的遗传突变用于细胞治疗。两者的结合正在为眼再生医学及眼遗传病的基因治疗带来革命性的突破。本文对hiPSC的应用及其与基因编辑技术结合在眼相关遗传病的研究展开综述。(中华眼科杂志,2021,57:712-716)

Human induced pluripotent stem cells have the ability to differentiate into specific cell types or tissues of the eye in humans and have application prospects in retinal cell transplantation,corneal transplantation,and lens regeneration.Gene editing technology of clustered regularly interspaced short palindromic repeats/crispr-associated protein-9 nuclease(CRISPR/Cas9)can introduce causative mutations of inherited ocular diseases into human induced pluripotent stem cells effectively.Then they can be further differentiated into specific somatic cells maintaining a genetic disease background,which can mimic the occurrence of inherited ocular diseases in vitro.The cell model may help scientists study the mechanism of human disease development,establish an in vitro screening platform to find therapeutic drugs,and correct genetic mutations in the human genome for cell therapy.The combination of stem cells and gene editing technology is revolutionizing the regenerative medicine in ophthalmology and gene therapy of inherited ocular diseases.This review summarizes the current application of human induced pluripotent stem cells and its combination with gene editing technology in the study of inherited ocular diseases.(Chin J Ophthalmol,2021,57:712-716)