β-血红蛋白病(β-hemoglobinopathies)是严重危害人类健康的6种常见疾病之一,尽管其遗传分子机制已被阐释清楚,但目前除异基因骨髓移植外尚还缺乏根治性的治疗策略。近年来,基因组编辑技术的迅速发展及其在人造血干祖细胞中的应用为β-血红蛋白病的治疗开辟了新的方向。针对血红蛋白的基因突变,可利用同源重组介导的细胞内源性DNA损伤修复途径直接修复遗传缺陷,也可以利用非同源末端连接机制沉默抑制胎儿血红蛋白表达的分子,重新激活胎儿血红蛋白的表达以缓解β-血红蛋白病人的临床症状。本文从β-血红蛋白病的基因组编辑策略及尝试、临床转化平台的要素分析等方面对该病的基因组编辑治疗的研究进展展开综述,以期为β-血红蛋白病新型治愈方案的研究以及基因组编辑技术的临床转化提供参考。

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.