Zinc-finger nuclease-mediated correction of α-thalassemia in iPS cells

Chan Jung Chang, Eric E. Bouhassira

Research output: Contribution to journalArticle

69 Scopus citations

Abstract

Induced pluripotent stem (iPS) cell technology holds vast promises for a cure to the hemoglobinopathies. Constructs and methods to safely insert therapeutic genes to correct the genetic defect need to be developed. Site-specific insertion is a very attractive method for gene therapy because the risks of insertional mutagenesis are eliminated provided that a "safe harbor" is identified, and because a single set of validated constructs can be used to correct a large variety of mutations simplifying eventual clinical use. We report here the correction of α-thalassemia major hydrops fetalis in transgene-free iPS cells using zinc finger-mediated insertion of a globin transgene in the AAVS1 site on human chromosome 19. Homozygous insertion of the best of the 4 constructs tested led to complete correction of globin chain imbalance in erythroid cells differentiated from the corrected iPS cells.

Original languageEnglish (US)
Pages (from-to)3906-3914
Number of pages9
JournalBlood
Volume120
Issue number19
DOIs
StatePublished - Nov 8 2012

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

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