Laboratory of Cell and Gene Therapy, Centre for Basic Research, Biomedical Research Foundation of the Academy of Athens (BRFAA), 115 27 Athens, Greece.
Stem Cells Int. 2011;2011:987980. doi: 10.4061/2011/987980. Epub 2011 Nov 13.
β-thalassemia is characterized by reduced or absence of β-globin production, resulting in anemia. Current therapies include blood transfusion combined with iron chelation. BM transplantation, although curative, is restricted by the matched donor limitation. Gene therapy, on the other hand, is promising, and its success lies primarily on designing efficient globin vectors that can effectively and stably transduce HSCs. The major breakthrough in β-thalassemia gene therapy occurred a decade ago with the development of globin LVs. Since then, researchers focused on designing efficient and safe vectors, which can successfully deliver the therapeutic transgene, demonstrating no insertional mutagenesis. Furthermore, as human HSCs have intrinsic barriers to HIV-1 infection, attention is drawn towards their ex vivo manipulation, aiming to achieve higher yield of genetically modified HSCs. This paper presents the current status of gene therapy for β-thalassemia, its success and limitations, and the novel promising strategies available involving the therapeutic role of HSCs.
β-地中海贫血的特征是β-球蛋白的产生减少或缺失，导致贫血。目前的治疗方法包括输血联合铁螯合。骨髓移植虽然是一种有效的治疗方法，但受到匹配供体的限制。基因治疗则很有前途，其成功主要取决于设计能够有效和稳定地转导造血干细胞的高效球蛋白载体。β-地中海贫血基因治疗的重大突破发生在十年前，随着球蛋白 LV 的发展。从那时起，研究人员专注于设计高效和安全的载体，能够成功地传递治疗性转基因，没有插入突变。此外，由于人类造血干细胞对 HIV-1 感染有内在的屏障，人们关注其体外操作，旨在获得更高产量的基因修饰造血干细胞。本文介绍了β-地中海贫血基因治疗的现状、成功和局限性，以及涉及造血干细胞治疗作用的新的有前途的策略。
