Genomic safe harbors permit high β-globin transgene expression in thalassemia induced pluripotent stem cells View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2011-01

AUTHORS

Eirini 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

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. More... »

PAGES

73

Journal

TITLE

Nature Biotechnology

ISSUE

1

VOLUME

29

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/nbt.1717

DOI

http://dx.doi.org/10.1038/nbt.1717

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1007507053

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/21151124


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