期刊
NATURE BIOTECHNOLOGY
卷 29, 期 1, 页码 73-+出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/nbt.1717
关键词
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资金
- Starr Foundation (Tri-Institutional Stem Cell Initiative) [Tri-SCI-018]
- New York State Stem Cell Science, NYSTEM [N08T-060]
- National Heart, Blood, and Lung Institute [HL053750]
- National Institutes of Health [AI052845, AI082020]
- New York Stem Cell Foundation
- NATIONAL HEART, LUNG, AND BLOOD INSTITUTE [P01HL053750] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES [R01AI082020, R01AI052845] Funding Source: NIH RePORTER
Realizing the therapeutic potential of human induced pluripotent stem (iPS) cells will require robust, precise and safe strategies for genetic modification, as cell therapies that rely on randomly integrated transgenes pose oncogenic risks. Here we describe a strategy to genetically modify human iPS cells at 'safe harbor' sites in the genome, which fulfill five criteria based on their position relative to contiguous coding genes, microRNAs and ultraconserved regions. We demonstrate that similar to 10% of integrations of a lentivirally encoded beta-globin transgene in beta-thalassemia-patient iPS cell clones meet our safe harbor criteria and permit high-level beta-globin expression upon erythroid differentiation without perturbation of neighboring gene expression. This approach, combining bioinformatics and functional analyses, should be broadly applicable to introducing therapeutic or suicide genes into patient-specific iPS cells for use in cell therapy.
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