The Combination of CRISPR/Cas9 and iPSC Technologies in the Gene Therapy of Human β-thalassemia in Mice

Zhanhui Ou, Xiaohua Niu, Wenyin He, Yuchang Chen, Bing Song, Yexing Xian, Di Fan, Daolin Tang, Xiaofang Sun

Research output: Contribution to journalArticle

32 Citations (Scopus)

Abstract

β-thalassemia results from point mutations or small deletions in the β-globin (HBB) gene that ultimately cause anemia. The generation of induced pluripotent stem cells (iPSCs) from the somatic cells of patients in combination with subsequent homologous recombination-based gene correction provides new approaches to cure this disease. CRISPR/Cas9 is a genome editing tool that is creating a buzz in the scientific community for treating human diseases, especially genetic disorders. Here, we reported that correction of β-thalassemia mutations in patient-specific iPSCs using the CRISPR/Cas9 tool promotes hematopoietic differentiation in vivo. CRISPR/Cas9-corrected iPSC-derived hematopoietic stem cells (HSCs) were injected into sublethally-irradiated NOD-scid-IL2Rg-/- (NSI) mice. HBB expression was observed in these HSCs after hematopoietic differentiation in the NSI mice. Importantly, no tumor was found in the livers, lungs, kidneys, or bone marrow at 10 weeks in the NSI mice after implantation with these HSCs. Collectively, our findings demonstrated that CRISPR/Cas9 successfully corrects β-thalassemia mutations in patient-specific iPSCs. These CRISPR/Cas9-corrected iPSC-derived HSCs express normal HBB in mice without tumorigenic potential, suggesting a safe strategy for personalized treatment of β-thalassemia.

Original languageEnglish (US)
Article number32463
JournalScientific reports
Volume6
DOIs
StatePublished - Sep 1 2016
Externally publishedYes

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Clustered Regularly Interspaced Short Palindromic Repeats
Induced Pluripotent Stem Cells
Thalassemia
Genetic Therapy
Hematopoietic Stem Cells
Technology
Mutation
Inborn Genetic Diseases
Globins
Homologous Recombination
Point Mutation
Genes
Anemia
Bone Marrow
Kidney
Lung
Liver
Neoplasms

ASJC Scopus subject areas

  • General

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The Combination of CRISPR/Cas9 and iPSC Technologies in the Gene Therapy of Human β-thalassemia in Mice. / Ou, Zhanhui; Niu, Xiaohua; He, Wenyin; Chen, Yuchang; Song, Bing; Xian, Yexing; Fan, Di; Tang, Daolin; Sun, Xiaofang.

In: Scientific reports, Vol. 6, 32463, 01.09.2016.

Research output: Contribution to journalArticle

Ou, Zhanhui ; Niu, Xiaohua ; He, Wenyin ; Chen, Yuchang ; Song, Bing ; Xian, Yexing ; Fan, Di ; Tang, Daolin ; Sun, Xiaofang. / The Combination of CRISPR/Cas9 and iPSC Technologies in the Gene Therapy of Human β-thalassemia in Mice. In: Scientific reports. 2016 ; Vol. 6.
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