title: Recombinant AAV2-mediated β-globin expression in human fetal hematopoietic cells from the aborted fetuses with β-thalassemia major.
abstract: Genetic correction of autologous hematopoietic stem cells has been proposed as an attractive treatment method for β-thalassemia. Our previous study has shown that recombinant adeno-associated virus 2 (rAAV2) efficiently transduces human fetal liver hematopoietic cells, and mediates the expression of the human β-globin gene in vivo. In this study, we investigated whether rAAV2 could also mediate the expression of normal β-globin gene in human hematopoietic cells from β-thalassemia patients. Human hematopoietic cells were isolated from aborted β-thalassemia major fetuses, transduced with rAAV2-β-globin, and then transplanted into nude mice. We found that rAAV2-β-globin transduced human fetal hematopoietic cells, as determined by allele-specific PCR analysis. Furthermore, β-globin transgene expression was detected in human hematopoietic cells up to 70 days post-transplantation in the recipient mice. High-pressure liquid chromatography analysis showed that human β-globin expression levels increased significantly compared with control, as indicated by a 1.2-2.8-fold increase in the ratio of β/α-globin chain. These novel data demonstrate that rAAV2 can transduce and mediate the normal β-globin gene expression in fetal hematopoietic cells from β-thalassemia patients. Our findings further support the potential use of rAAV-based gene therapy in the treatment of human β-thalassemia.
authors: Experimental Hematology Laboratory, Department of Physiology, Xiangya School of Medicine, Central South University, 110 Xiang-Ya Road, Changsha, 410078, Hunan, People's Republic of China.|Xiangya Biological Medicine Institute, Shenzhen, 518057, China.
authors: Jing
authors: J
authors: Tian
authors: Experimental Hematology Laboratory, Department of Physiology, Xiangya School of Medicine, Central South University, 110 Xiang-Ya Road, Changsha, 410078, Hunan, People's Republic of China.|Xiangya Biological Medicine Institute, Shenzhen, 518057, China.
authors: Feng
authors: F
authors: Wang
authors: Experimental Hematology Laboratory, Department of Physiology, Xiangya School of Medicine, Central South University, 110 Xiang-Ya Road, Changsha, 410078, Hunan, People's Republic of China.|Xiangya Biological Medicine Institute, Shenzhen, 518057, China.
authors: Jin-Feng
authors: JF
authors: Xue
authors: Experimental Hematology Laboratory, Department of Physiology, Xiangya School of Medicine, Central South University, 110 Xiang-Ya Road, Changsha, 410078, Hunan, People's Republic of China.|Xiangya Biological Medicine Institute, Shenzhen, 518057, China.
authors: Fei
authors: F
authors: Zhao
authors: Experimental Hematology Laboratory, Department of Physiology, Xiangya School of Medicine, Central South University, 110 Xiang-Ya Road, Changsha, 410078, Hunan, People's Republic of China.|Xiangya Biological Medicine Institute, Shenzhen, 518057, China.
authors: Liu-Jiang
authors: LJ
authors: Song
authors: Experimental Hematology Laboratory, Department of Physiology, Xiangya School of Medicine, Central South University, 110 Xiang-Ya Road, Changsha, 410078, Hunan, People's Republic of China. mqtan26@hotmail.com.|Xiangya Biological Medicine Institute, Shenzhen, 518057, China. mqtan26@hotmail.com.
authors: Meng-Qun
authors: MQ
authors: Tan
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