Raja J V, Rachchh M A, Gokani R H
Department of Pharmacology, S. J. Thakkar Pharmacy College, Rajkot, Gujarat, India.
J Pharm Bioallied Sci. 2012 Jul;4(3):194-201. doi: 10.4103/0975-7406.99020.
Thalassemias are genetically transmitted disorders. Depending upon whether the genetic defects or deletion lies in transmission of α or β globin chain gene, thalassemias are classified into α and β-thalassemias. Thus, thalassemias could be cured by introducing or correcting a gene into the hematopoietic compartment or a single stem cell. Initial attempts at gene transfer have proved unsuccessful due to limitations of available gene transfer vectors. The present review described the newer approaches to overcome these limitations, includes the introduction of lentiviral vectors. New approaches have also focused on targeting the specific mutation in the globin genes, correcting the DNA sequence or manipulating the development in DNA translocation and splicing to restore globin chain synthesis. This review mainly discusses the gene therapy strategies for the thalassemias, including the use of lentiviral vectors, generation of induced pluripotent stem (iPS) cells, gene targeting, splice-switching and stop codon readthrough.
地中海贫血是遗传性疾病。根据遗传缺陷或缺失是位于α或β珠蛋白链基因的传递中，地中海贫血可分为α地中海贫血和β地中海贫血。因此，通过将基因导入造血区室或单个干细胞或纠正基因，可治愈地中海贫血。由于现有基因转移载体的局限性，最初的基因转移尝试已证明是不成功的。本综述描述了克服这些局限性的新方法，包括慢病毒载体的引入。新方法还专注于靶向珠蛋白基因中的特定突变、纠正DNA序列或操纵DNA易位和剪接中的发育以恢复珠蛋白链合成。本综述主要讨论地中海贫血的基因治疗策略，包括慢病毒载体的使用、诱导多能干细胞（iPS）的生成、基因靶向、剪接转换和终止密码子通读。
