Division of Pediatric Stem Cell Transplant and RM, Lucile Packard Children's Hospital, Stanford University, Palo Alto, California.
Am J Hematol. 2020 Sep;95(9):1099-1112. doi: 10.1002/ajh.25909.
Thalassemia is one of the most prevalent monogenic diseases usually caused by quantitative defects in the production of β-globin leading to severe anemia. Technological advances in genome sequencing, stem cell selection, viral vector development, transduction and gene editing strategies now allow for efficient exvivo genetic manipulation of human stem cells that can lead to production of hemoglobin, leading to a meaningful clinical benefit in thalassemia patients. In this review, the status of the gene-therapy approaches available for transfusion dependent thalassemia are discussed, along with the critical criteria that affect efficacy and lessons that have been learned from the early phase clinical trials. Salient steps necessary for the clinical development, manufacturing, and regulatory approvals of gene therapies for thalassemia are also highlighted, so that the potential of these therapies can be realized. It is highly anticipated that gene therapies will soon become a treatment option for patients lacking compatible donors for hematopoietic stem cell transplant and will offer an alternative for definitive treatment of β-thalassemia.
地中海贫血症是最常见的单基因疾病之一，通常由β-球蛋白产量的定量缺陷引起，导致严重贫血。基因组测序、干细胞选择、病毒载体开发、转导和基因编辑策略的技术进步，现在可以对人类干细胞进行高效的体外遗传操作，从而产生血红蛋白，为地中海贫血症患者带来有意义的临床益处。在这篇综述中，讨论了用于输血依赖型地中海贫血症的基因治疗方法的现状，以及影响疗效的关键标准和从早期临床试验中吸取的经验教训。还强调了地中海贫血症基因治疗的临床开发、制造和监管批准所需的显著步骤，以便能够实现这些疗法的潜力。人们高度期待基因疗法将很快成为造血干细胞移植缺乏相容供体的患者的治疗选择，并为β-地中海贫血症的根治治疗提供替代方案。
