Recent trends in the gene therapy of β-thalassemia.
Recent trends in the gene therapy of β-thalassemia.
复制标题
DOI：
10.2147/jbm.s46256
复制
发表时间：
2015
影响因子：
2
通讯作者：
Gambari R
中科院分区：
文献类型：
--
作者：
Finotti A;Breda L;Lederer CW;Bianchi N;Zuccato C;Kleanthous M;Rivella S;Gambari R
β-地中海贫血是一组由成人β-珠蛋白基因300多个突变引起的遗传性血液病。地中海贫血综合征与镰状细胞性贫血一起，是发展中国家最具影响力的疾病之一，在这些国家，缺乏遗传咨询和产前诊断导致这些遗传疾病在人口中的发病率非常高。β-地中海贫血的基因治疗最近稳步加速进展，并已达到其发展的十字路口。目前，来自过去和正在进行的临床试验的数据指导了基于基因增强的进一步临床和临床前研究的设计，而对珠蛋白转换和新技术发展的基本见解激发了对新型基因治疗方法的研究。此外，来自β-地中海贫血患者的人红细胞生成干细胞是迄今为止选择的细胞靶点，而未来的基因治疗研究可能会越来越多地利用诱导多能干细胞。在此，我们总结了过去十年中β-地中海贫血基因治疗的最重要进展，特别强调了最新的研究结果，包括β-地中海贫血模型系统; β-，γ-和抗镰状β-珠蛋白基因添加和组合方法，包括临床试验的最新结果;以及新方法，如转基因介导的γ-珠蛋白激活和使用设计核酸酶的基因组编辑。
The β-thalassemias are a group of hereditary hematological diseases caused by over 300 mutations of the adult β-globin gene. Together with sickle cell anemia, thalassemia syndromes are among the most impactful diseases in developing countries, in which the lack of genetic counseling and prenatal diagnosis have contributed to the maintenance of a very high frequency of these genetic diseases in the population. Gene therapy for β-thalassemia has recently seen steadily accelerating progress and has reached a crossroads in its development. Presently, data from past and ongoing clinical trials guide the design of further clinical and preclinical studies based on gene augmentation, while fundamental insights into globin switching and new technology developments have inspired the investigation of novel gene-therapy approaches. Moreover, human erythropoietic stem cells from β-thalassemia patients have been the cellular targets of choice to date whereas future gene-therapy studies might increasingly draw on induced pluripotent stem cells. Herein, we summarize the most significant developments in β-thalassemia gene therapy over the last decade, with a strong emphasis on the most recent findings, for β-thalassemia model systems; for β-, γ-, and anti-sickling β-globin gene addition and combinatorial approaches including the latest results of clinical trials; and for novel approaches, such as transgene-mediated activation of γ-globin and genome editing using designer nucleases.