全球首个用于输血依赖的β⁃地中海贫血的基因疗法Zynteglo

Zynteglo,the world's first gene therapy for transfusion⁃dependent β⁃thalassemia

Zynteglo(betibeglogene autotemcel)是2022年8月17日被美国FDA批准的全球首个用于需要定期输血的成人和儿童β⁃地中海贫血患者的基因疗法。Zynteglo是一种一次性的基因治疗产品,以单剂量给药。Zynteglo每个剂量都是使用患者自身来源的CD_(34)^(+)骨髓造血干细胞创建的定制治疗,这些造血干细胞经过体外的基因改造后进行自体移植,在体内分化成能够产生功能性血红蛋白的红细胞,从而达到治疗β⁃地中海贫血的目的。本文从该疗法的慢病毒载体和作用机制、非临床研究、临床有效性研究、临床安全性研究、适用人群和使用方法以及注意事项6个方面对该基因疗法进行全面介绍。

Zynteglo(betibeglogene autotemcel)is the world's first gene therapy approved by the U.S.Food and Drug Administration on August 17,2022 for adults and children withβ⁃thalassemia who require regular blood transfusions.Zynteglo is a one⁃time gene therapy product administered as a single dose.Each dose of Zynteglo is a customized treatment created using the patient's own CD_(34)^(+) bone marrow hematopoietic stem cells which are genetically modified in vitro and then autologously transplanted.The modified stem cells will differentiate into red blood cells which are capable of producing functional hemoglobin,therefore achieving the purpose ofβ⁃thalassemia treatment.This paper provides a comprehensive introduction to the gene therapy from six aspects:lentiviral vector and mechanism of action,non⁃clinical research,clinical efficacy research,clinical safety research,indications and methods of use,and precautions.