Genomic safe harbors permit high β-globin transgene expression in thalassemia induced pluripotent stem cells Journal Article
| Authors: | Papapetrou, E. P.; Lee, G.; Malani, N.; Setty, M.; Riviere, I.; Tirunagari, L. M. S.; Kadota, K.; Roth, S. L.; Giardina, P.; Viale, A.; Leslie, C.; Bushman, F. D.; Studer, L.; Sadelain, M. |
| Article Title: | Genomic safe harbors permit high β-globin transgene expression in thalassemia induced pluripotent stem cells |
| Abstract: | 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 ∼10% of integrations of a lentivirally encoded β-globin transgene in β-thalassemia-patient iPS cell clones meet our safe harbor criteria and permit high-level β-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. © 2011 Nature America, Inc. All rights reserved. |
| Keywords: | child; protein expression; school child; human cell; microrna; gene expression; hemoglobin; cell differentiation; dna modification; genetic engineering; human genome; gene therapy; lentivirus vector; beta thalassemia; erythroid cell; transgene; stem cells; cell therapy; pluripotent; pluripotent stem cell; cell clone; micrornas; bioinformatics; genetic code; clone cells; in-cell; therapeutic potentials; induced pluripotent stem cells; lentivirinae; beta globin; cell clones; coding genes; erythroid differentiation; genetic modifications; trans-genes; transgene expression; cell cloning; suicide gene |
| Journal Title: | Nature Biotechnology |
| Volume: | 29 |
| Issue: | 1 |
| ISSN: | 1087-0156 |
| Publisher: | Nature Publishing Group |
| Date Published: | 2011-01-01 |
| Start Page: | 73 |
| End Page: | 81 |
| Language: | English |
| DOI: | 10.1038/nbt.1717 |
| PROVIDER: | scopus |
| PUBMED: | 21151124 |
| PMCID: | PMC3356916 |
| DOI/URL: | |
| Notes: | --- - "Export Date: 4 March 2011" - "CODEN: NABIF" - "Source: Scopus" |
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