Zhou Weilin, Yang Jinrong, Zhang Yalan, Hu Xiaoyi, Wang Wei
Department of Biotherapyy State Key Laboratory of Biotherapy and Cancer Center West China Hospital Sichuan University Chengdu People's Republic of China.
Department of Hematology Hematology Research Laboratory State Key Laboratory of Biotherapy and Cancer Center West China Hospital Sichuan University Chengdu Sichuan P. R. China.
MedComm (2020). 2022 Jul 14;3(3):e155. doi: 10.1002/mco2.155. eCollection 2022 Sep.
The expanding genome editing toolbox has revolutionized life science research ranging from the bench to the bedside. These "molecular scissors" have offered us unprecedented abilities to manipulate nucleic acid sequences precisely in living cells from diverse species. Continued advances in genome editing exponentially broaden our knowledge of human genetics, epigenetics, molecular biology, and pathology. Currently, gene editing-mediated therapies have led to impressive responses in patients with hematological diseases, including sickle cell disease and thalassemia. With the discovery of more efficient, precise and sophisticated gene-editing tools, more therapeutic gene-editing approaches will enter the clinic to treat various diseases, such as acquired immunodeficiency sydrome (AIDS), hematologic malignancies, and even severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. These initial successes have spurred the further innovation and development of gene-editing technology. In this review, we will introduce the architecture and mechanism of the current gene-editing tools, including clustered regularly interspaced short palindromic repeats (CRISPR) and CRISPR-associated nuclease-based tools and other protein-based DNA targeting systems, and we summarize the meaningful applications of diverse technologies in preclinical studies, focusing on the establishment of disease models and diagnostic techniques. Finally, we provide a comprehensive overview of clinical information using gene-editing therapeutics for treating various human diseases and emphasize the opportunities and challenges.
不断扩展的基因组编辑工具箱彻底改变了从实验室到临床的生命科学研究。这些“分子剪刀”为我们提供了前所未有的能力，能够在来自不同物种的活细胞中精确操纵核酸序列。基因组编辑技术的持续进步极大地拓宽了我们对人类遗传学、表观遗传学、分子生物学和病理学的认识。目前，基因编辑介导的疗法已在患有血液系统疾病（包括镰状细胞病和地中海贫血）的患者中取得了令人瞩目的疗效。随着更高效、精确和先进的基因编辑工具的发现，更多治疗性基因编辑方法将进入临床，用于治疗各种疾病，如获得性免疫缺陷综合征（艾滋病）、血液系统恶性肿瘤，甚至严重急性呼吸综合征冠状病毒2（SARS-CoV-2）感染。这些初步成功推动了基因编辑技术的进一步创新和发展。在这篇综述中，我们将介绍当前基因编辑工具的结构和作用机制，包括成簇规律间隔短回文重复序列（CRISPR）及基于CRISPR相关核酸酶的工具和其他基于蛋白质的DNA靶向系统，并总结各种技术在临床前研究中的有意义应用，重点是疾病模型的建立和诊断技术。最后，我们全面概述了使用基因编辑疗法治疗各种人类疾病的临床信息，并强调了机遇和挑战。
