Men Ke, Duan Xingmei, He Zhiyao, Yang Yang, Yao Shaohua, Wei Yuquan
State Key Laboratory of Biotherapy and Cancer Center/Collaborative Innovation Center for Biotherapy, West China Hospital, Sichuan University, Chengdu, 610041, China.
Individualized Medication Key Laboratory of Sichuan Province, Department of Pharmacy, Hospital of the University of Electronic Science and Technology of China and Sichuan Provincial People's Hospital, Sichuan Translational Medicine Hospital, Chengdu, 610072, China.
Sci China Life Sci. 2017 May;60(5):447-457. doi: 10.1007/s11427-017-9032-4. Epub 2017 May 3.
The clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated (Cas) protein 9 system (CRISPR/Cas9) provides a powerful tool for targeted genetic editing. Directed by programmable sequence-specific RNAs, this system introduces cleavage and double-stranded breaks at target sites precisely. Compared to previously developed targeted nucleases, the CRISPR/Cas9 system demonstrates several promising advantages, including simplicity, high specificity, and efficiency. Several broad genome-editing studies with the CRISPR/Cas9 system in different species in vivo and ex vivo have indicated its strong potential, raising hopes for therapeutic genome editing in clinical settings. Taking advantage of non-homologous end-joining (NHEJ) and homology directed repair (HDR)-mediated DNA repair, several studies have recently reported the use of CRISPR/Cas9 to successfully correct disease-causing alleles ranging from single base mutations to large insertions. In this review, we summarize and discuss recent preclinical studies involving the CRISPR/Cas9-mediated correction of human genetic diseases.
成簇规律间隔短回文重复序列（CRISPR）/CRISPR相关蛋白9系统（CRISPR/Cas9）为靶向基因编辑提供了一个强大的工具。在可编程的序列特异性RNA的引导下，该系统能在靶位点精确地引入切割和双链断裂。与先前开发的靶向核酸酶相比，CRISPR/Cas9系统具有几个有前景的优势，包括简单性、高特异性和高效性。在不同物种体内和体外进行的几项使用CRISPR/Cas9系统的广泛基因组编辑研究表明了其强大的潜力，为临床环境中的治疗性基因组编辑带来了希望。利用非同源末端连接（NHEJ）和同源定向修复（HDR）介导的DNA修复，最近有几项研究报道使用CRISPR/Cas9成功校正了从单碱基突变到大片段插入等各种致病等位基因。在这篇综述中，我们总结并讨论了最近涉及CRISPR/Cas9介导的人类遗传疾病校正的临床前研究。
