Genome editing is a cutting-edge technology that generates DNA double strand breaks at the specific genomic DNA sequence through nuclease recognition and cleavage, and then achieves insertion, replacement, or deletion of the target gene via endogenous DNA repair mechanisms, such as non-homologous end joining, homology directed repair, and homologous recombination. So far, more than 600 human hereditary eye diseases and systemic hereditary diseases with ocular phenotypes have been found. However, most of these diseases are of incompletely elucidated pathogenesis and without effective therapies. Genome editing technology can precisely target and alter the genomes of animals, establish animal models of the hereditary diseases, and elucidate the relationship between the target gene and the disease phenotype, thereby providing a powerful approach to studying the pathogenic mechanisms underlying the hereditary eye diseases. In addition, correction of gene mutations by the genome editing brings a new hope to gene therapy for the hereditary eye diseases. This review introduces the molecular characteristics of 4 major enzymes used in the genome editing, including homing endonucleases, zinc finger nucleases, transcription activator-like effector nucleases, and clustered regularly interspaced short palindromic repeats (CRISPR)/ CRISPR-associated protein 9 (Cas9), and summarizes the current applications of this technology in investigating the pathogenic mechanisms underlying the hereditary eye diseases.%基因编辑是一项应用核酸酶识别并剪切特异性基因组DNA序列,导致DNA双链断裂后利用细胞内的DNA修复途径,如非同源末端连接、同源定向修复等,插入、替换或删除靶基因的技术.人类遗传性眼病和有眼部表现的全身遗传性疾病有600余种,其中大部分病因尚未完全阐明且无有效治疗方法.应用基因编辑技术,靶向改变动物基因组,建立眼部遗传性疾病的动物模型,可以明确目标基因与疾病表型之间的关系,为研究遗传性眼病的发病机制提供了有效的方法.此外,通过基因编辑改变致病基因也为遗传性眼病的基因治疗带来了希望.本文对归巢核酸内切酶、锌指核酸酶、转录激活因子样效应物核酸酶、成簇规律间隔短回文重复序列(CRISPR)/CRISPR相关蛋白9共4种基因编辑工具酶的分子特点进行综述,并总结现阶段基因编辑在遗传性眼病发病机制研究中的应用.
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