Volume 22, No 4, Apr 2012
ISSN: 1001-0602
EISSN: 1748-7838 2018
impact factor 17.848*
(Clarivate Analytics, 2019)
Volume 22 Issue 4, April 2012: 637-648
ORIGINAL ARTICLES
Genetic correction of β-thalassemia patient-specific iPS cells and its use in improving hemoglobin production in irradiated SCID mice
Yixuan Wang1,*, Chen-Guang Zheng2,*, Yonghua Jiang1, Jiqin Zhang1, Jiayu Chen1, Chao Yao1, Qingguo Zhao1, Sheng Liu1, Ke Chen2, Juan Du2, Ze
1National Institute of Biological Sciences, Zhongguancun Life Science Park, #7 Science Park Road, Beijing 102206, China
2Guangxi Zhuang Autonomous Region Women and Children Care Hospital, Nanning, Guangxi 530003, China
3National Institute of Geriatrics, Beijing Hospital, Chinese Ministry of Health, Beijing 100730, China
Correspondence: Shaorong Gao, Ze Yang,(gaoshaorong@nibs.ac.cn; yangze016@yahoo.com.cn)
The generation of induced pluripotent stem cells (iPSCs) from differentiated somatic cells by over-expression of several transcription factors has the potential to cure many genetic and degenerative diseases currently recalcitrant to traditional clinical approaches. One such genetic disease is β-thalassemia major (Cooley's anemia). This disease is caused by either a point mutation or the deletion of several nucleotides in the β-globin gene, and it threatens the lives of millions of people in China. In the present study, we successfully generated iPSCs from fibroblasts collected from a 2-year-old patient who was diagnosed with a homozygous 41/42 deletion in his β-globin gene. More importantly, we successfully corrected this genetic mutation in the β-thalassemia iPSCs by homologous recombination. Furthermore, transplantation of the genetically corrected iPSCs-derived hematopoietic progenitors into sub-lethally irradiated immune deficient SCID mice showed improved hemoglobin production compared with the uncorrected iPSCs. Moreover, the generation of human β-globin could be detected in the mice transplanted with corrected iPSCs-derived hematopietic progenitors. Our study provides strong evidence that iPSCs generated from a patient with a genetic disease can be corrected by homologous recombination and that the corrected iPSCs have potential clinical uses.
Cell Research (2012) 22:637-648. doi:10.1038/cr.2012.23; published online 7 February 2012
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