Gene Therapy Approaches to Hemoglobinopathies
Gene Therapy Approaches to Hemoglobinopathies
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DOI：
10.1016/j.hoc.2017.06.010
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发表时间：
2017-10-01
影响因子：
2.4
通讯作者：
Mavilio, Fulvio
中科院分区：
文献类型：
--
作者：
Ferrari, Giuliana;Cavazzana, Marina;Mavilio, Fulvio
目前对血红蛋白疾病的基因治疗是基于移植基因修饰的自体造血干细胞，慢病毒载体在珠蛋白转录调控元件的控制下表达珠蛋白基因。临床前和早期临床研究表明，这种治疗方法的安全性和潜在有效性，以及仍然限制其普遍应用的障碍。此外，对于β-地中海贫血和镰状细胞疾病，骨髓微环境的改变降低了干细胞采集和植入的效率。这些障碍需要解决，以使血红蛋白疾病的基因治疗成为临床现实。
Gene therapy for hemoglobinopathies is currently based on transplantation of autologous hematopoietic stem cells genetically modified with a lentiviral vector expressing a globin gene under the control of globin transcriptional regulatory elements. Preclinical and early clinical studies showed the safety and potential efficacy of this therapeutic approach, as well as the hurdles still limiting its general application. In addition, for both beta-thalassemia and sickle cell disease, an altered bone marrow microenvironment reduces the efficiency of stem cell harvesting and engraftment. These hurdles need to be addressed for gene therapy for hemoglobinopathies to become a clinical reality.