Liu Jia-Wei, Hong Tao, Qin Xin, Liang Ying-Min, Zhang Ping
Department of Medical Genetics and Developmental Biology, Fourth Military Medical University, Xi'an 710032, China.
Medical College, Hubei University of Arts and Science, Xiangyang 441053, China.
Yi Chuan. 2018 Feb 20;40(2):95-103. doi: 10.16288/j.yczz.17-215.
β-hemoglobinopathies are one of six groups of common illnesses affecting human health. Although the genetic mechanisms have been elucidated for several decades, curable treatment options, other than allogeneic bone marrow transplantation, are still lacking. In recent years, rapid development in genome editing technologies and their clinical applications have opened up new directions for treatment of β-hemoglobinopathies. Genome editing technologies, as applied in autologous CD34 hematopoietic stem and progenitor cells, represents a promising remedial means for the β-globin disorders. Hemoglobin gene mutations could be corrected with homologous recombination-mediated DNA repair pathway to repair the genetic defects, while the nonhomologous end-joining pathway may be used to silence the key repressor of fetal globin expression and reactivate fetal hemoglobin expression, thereby alleviating the clinical symptoms of β-hemoglobinopathies in patients. This review summarizes the recent advances on genome editing of β-hemoglobinopathies from the bench design to the establishment of clinical translational platforms, thereby providing critical insights and references on the application of genome editing technologies for the development of therapeutic strategies for β-hemoglobinopathies.
β-珠蛋白生成障碍性贫血是影响人类健康的六类常见疾病之一。尽管其遗传机制已被阐明数十年，但除了异基因骨髓移植外，仍缺乏可治愈的治疗方案。近年来，基因组编辑技术及其临床应用的快速发展为β-珠蛋白生成障碍性贫血的治疗开辟了新方向。应用于自体CD34造血干细胞和祖细胞的基因组编辑技术，是β-珠蛋白生成障碍性贫血一种有前景的治疗手段。血红蛋白基因突变可通过同源重组介导的DNA修复途径进行校正，以修复遗传缺陷，而非同源末端连接途径可用于沉默胎儿珠蛋白表达的关键抑制因子并重新激活胎儿血红蛋白表达，从而缓解β-珠蛋白生成障碍性贫血患者的临床症状。本文综述了从实验台设计到临床转化平台建立的β-珠蛋白生成障碍性贫血基因组编辑的最新进展，从而为基因组编辑技术在β-珠蛋白生成障碍性贫血治疗策略开发中的应用提供关键见解和参考。
