Testa Ugo, Leone Giuseppe, Cappellini Maria Domenica
Istituto Superiore Sanità, Roma, Italy.
Department of Radiological and Hematological Sciences, Catholic University, Rome, Italy.
Mediterr J Hematol Infect Dis. 2024 Sep 1;16(1):e2024068. doi: 10.4084/MJHID.2024.068. eCollection 2024.
In the last ten years, a consistent number of clinical studies have evaluated different gene approaches for the treatment of patients with sickle cell disease (SCD) and transfusion-dependent β-thalassemia (TDT). Initial studies of gene therapy for hemoglobinopathies involved the use of lentiviral vectors to add functional copies of the gene encoding β-globin in defective CD34 cells; more recently, gene editing techniques have been used involving either CRISPR-Cas9, transcription activation-like effector protein nuclease, zinc finger nuclease, and base editing to either induce fetal hemoglobin production at therapeutic levels or to genetically repair the underlying molecular defect causing the disease. Here, we review recent gene editing studies that have started the development of a new era in the treatment of hemoglobinopathies and, in general, monoallelic hereditary diseases.
在过去十年中，有一定数量的临床研究评估了用于治疗镰状细胞病（SCD）和输血依赖型β地中海贫血（TDT）患者的不同基因方法。血红蛋白病基因治疗的初步研究涉及使用慢病毒载体在有缺陷的CD34细胞中添加编码β珠蛋白的基因的功能拷贝；最近，已使用基因编辑技术，包括CRISPR-Cas9、转录激活样效应蛋白核酸酶、锌指核酸酶和碱基编辑，以诱导治疗水平的胎儿血红蛋白产生或从基因上修复导致该疾病的潜在分子缺陷。在此，我们回顾了最近的基因编辑研究，这些研究开启了血红蛋白病以及一般单等位基因遗传性疾病治疗新时代的发展。
