Ontology type: schema:ScholarlyArticle Open Access: True
2011-01
AUTHORSEirini P Papapetrou, Gabsang Lee, Nirav Malani, Manu Setty, Isabelle Riviere, Laxmi M S Tirunagari, Kyuichi Kadota, Shoshannah L Roth, Patricia Giardina, Agnes Viale, Christina Leslie, Frederic D Bushman, Lorenz Studer, Michel Sadelain
ABSTRACTRealizing 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. More... »
PAGES73
http://scigraph.springernature.com/pub.10.1038/nbt.1717
DOIhttp://dx.doi.org/10.1038/nbt.1717
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PUBMEDhttps://www.ncbi.nlm.nih.gov/pubmed/21151124
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"description": "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 \u223c10% of integrations of a lentivirally encoded \u03b2-globin transgene in \u03b2-thalassemia-patient iPS cell clones meet our safe harbor criteria and permit high-level \u03b2-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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384 TRIPLES
21 PREDICATES
88 URIs
39 LITERALS
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