Article

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

Department of Medicine, Hematology, Department of Cell Biology, Albert Einstein College of Medicine, Bronx, NY, United States.
Blood (Impact Factor: 9.78). 09/2012; DOI: 10.1182/blood-2012-03-420703

ABSTRACT Induced pluripotent stem 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 four constructs tested led to complete correction of globin chain imbalance in erythroid cells differentiated from the corrected iPS cells.

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