title: Zinc-finger nuclease-mediated correction of α-thalassemia in iPS cells.
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.
authors.affiliation: Department of Medicine, Division of Hematology, and Department of Cell Biology, Albert Einstein College of Medicine, Bronx, NY 10461, USA.
authors.forename: Chan-Jung
authors.initials: CJ
authors.lastname: Chang
authors.forename: Eric E
authors.initials: EE
authors.lastname: Bouhassira
mesh_terms: D002454:Cell Differentiation; D002460:Cell Line; D004720:Endonucleases / Q000378:metabolism*; D004900:Erythroblasts / Q000166:cytology / Q000378:metabolism; D004909:Erythrocyte Indices; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism; D005786:Gene Expression Regulation; D023061:Gene Order; D006720:Homozygote; D006801:Humans; D057026:Induced Pluripotent Stem Cells / Q000166:cytology / Q000378:metabolism*; D011995:Recombination, Genetic; D019076:Transgenes; D016335:Zinc Fingers; D055542:alpha-Globins / Q000235:genetics / Q000378:metabolism; D017085:alpha-Thalassemia / Q000235:genetics / Q000378:metabolism* / Q000628:therapy
chemical_list: D055542:alpha-Globins; D004720:Endonucleases