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"
Altmetric Score
MSK Authors
  1. Lorenz Studer
    156 Studer
  2. Agnes Viale
    205 Viale
  3. Michel W J Sadelain
    462 Sadelain
  4. Isabelle C Riviere
    168 Riviere
  5. Gabsang Lee
    21 Lee
  6. Kyuichi Kadota
    82 Kadota
  7. Christina Leslie
    111 Leslie
  8. Manu Setty
    22 Setty