1 Institute for Transfusion Medicine and Gene Therapy, Medical Center - University of Freiburg , Germany .
2 Center for Chronic Immunodeficiency, Medical Center - University of Freiburg , Germany .
Hum Gene Ther. 2017 Nov;28(11):1105-1115. doi: 10.1089/hum.2017.149. Epub 2017 Aug 14.
The possibility of editing complex genomes in a targeted fashion has revolutionized basic research as well as biomedical and biotechnological applications in the last 5 years. The targeted introduction of genetic changes has allowed researchers to create smart model systems for basic research, bio-engineers to modify crops and farm animals, and translational scientists to develop novel treatment approaches for inherited and acquired disorders for which curative treatment options are not yet available. With the rapid development of genome editing tools, in particular zinc-finger nucleases (ZFNs), transcription activator-like effector nucleases (TALENs), and the CRISPR-Cas system, a wide range of therapeutic options have been-and will be-developed at an unprecedented speed, which will change the clinical routine of various disciplines in a revolutionary way. This review summarizes the fundamentals of genome editing and the current state of research. It particularly focuses on the advances made in employing engineered nucleases in hematopoietic stem cells for the treatment of primary immunodeficiencies and hemoglobinopathies, provides a perspective of combining gene editing with the chimeric antigen receptor T cell technology, and concludes by presenting targeted epigenome editing as a novel potential treatment option.
在过去的 5 年中，靶向编辑复杂基因组的可能性彻底改变了基础研究以及生物医学和生物技术的应用。通过靶向引入遗传变化，研究人员得以创建用于基础研究的智能模型系统，生物工程师得以修饰农作物和农场动物，转化科学家得以开发针对尚无治愈方法的遗传性和获得性疾病的新型治疗方法。随着基因组编辑工具的快速发展，特别是锌指核酸酶（ZFNs）、转录激活因子样效应核酸酶（TALENs）和 CRISPR-Cas 系统的发展，各种治疗方法以前所未有的速度得到了开发，并且将从根本上改变各个学科的临床常规。这篇综述总结了基因组编辑的基本原理和研究现状。它特别侧重于在造血干细胞中利用工程化核酸酶治疗原发性免疫缺陷和血红蛋白病方面的进展，提出了将基因编辑与嵌合抗原受体 T 细胞技术相结合的观点，并通过靶向表观基因组编辑作为一种新的潜在治疗方法进行了总结。
