《生命科学》 2022, 34(10): 1250-1263

CRISPR/Cas基因编辑技术治疗人类遗传性疾病的临床研究进展

胡思慧^1,2 , 刘倩宜^1,2 , 谢冬纯^1,2 , 黄军就^1,2,*

¹中山大学生命科学学院，基因功能与调控教育部重点实验室，广州 510275 ²中山大学生命科学学院和附属第一医院，广东省生殖医学重点实验室，广州 510275

摘　要：

随着人类基因组计划完成，人类遗传信息的解码推动着疾病诊疗迈入基因组学时代。许多医学领域中的“罕见病”和“不治之症”也被逐渐揭开了神秘的面纱，越来越多的疾病被确证为遗传性疾病。2012 年，CRISPR/Cas (clustered regularly interspaced short palindromic repeats/CRISPR-associated enzyme) 基因编辑技术的发现和应用，是近十年生物医学领域最具革命性的突破之一。该技术具有简便、高效、适用性广泛等特点，不但被广泛应用于基因功能研究，而且也在遗传病的基因治疗临床试验上取得重要进展。针对遗传背景明确的单基因遗传病，CRISPR/Cas 可通过对目的DNA 序列进行精准靶向编辑，实现对内源基因序列的改变或者基因功能的重新调控，为治愈部分重大遗传性疾病提供了新的工具和治疗策略。目前，多个基于CRISPR/Cas 技术研发的基因药物已经进入临床试验，并取得了令人鼓舞的阶段性成果。本文就目前已公布临床试验的基因编辑药物研究进展进行回顾与展望。

通讯作者：黄军就 , Email:hjunjiu@mail.sysu.edu.cn

Clinical research progress of CRISPR/Cas genome editing in the treatment of human genetic disorders

HU Si-Hui^1,2 , LIU Qian-Yi^1,2 , XIE Dong-Chun^1,2 , HUANG Jun-Jiu^1,2,*

¹MOE Key Laboratory of Gene Function and Regulation, School of Life Sciences, Sun Yat-sen University, Guangzhou 510275, China ²Key Laboratory of Reproductive Medicine of Guangdong Province, School of Life Sciences and the First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510275, China

Abstract:

With the completion of the Human Genome Project, the decoding of human genetic information promotes the diagnosis and treatment of diseases into the era of genomics. Many "rare diseases" and "incurable diseases" have also been gradually unveiled, and more and more diseases have been confirmed as genetic disorders. Clustered regularly interspaced short palindromic repeats/CRISPR-associated enzyme (CRISPR/Cas) gene editing technology which was discovered and applied in 2012 has been proved to be one of the most  breakthroughs in the biomedical field in the past decade. With the characteristics of simplicity, high efficiency and a wide range of applicability, this technique has not only been widely used in the study of gene function, but also made important progress in clinical trials of gene therapies for genetic disorders. For monogenic disorders with clear genetic background, CRISPR/Cas can change the endogenous gene sequence or re-regulate the gene function through editing the target DNA sequence precisely to cure this kind of genetic disorders. Up to now, several drugs based on CRISPR/Cas technology have been studied in clinical trials, and achieved encouraging results. In this paper, we review and prospect the research progress of gene editing drugs in clinical trials.

Communication Author：HUANG Jun-Jiu , Email:hjunjiu@mail.sysu.edu.cn