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

Chan Jung Chang, Eric E. Bouhassira

Research output: Contribution to journalArticle

68 Citations (Scopus)

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

Fingerprint

Induced Pluripotent Stem Cells
Thalassemia
Zinc Fingers
Stem cells
Zinc
Globins
Transgenes
Hydrops Fetalis
Chromosomes, Human, Pair 19
Gene therapy
Hemoglobinopathies
Mutagenesis
Erythroid Cells
Insertional Mutagenesis
beta-Thalassemia
Human Chromosomes
Chromosomes
Ports and harbors
Genetic Therapy
Genes

ASJC Scopus subject areas

  • Hematology
  • Biochemistry
  • Cell Biology
  • Immunology

Cite this

Zinc-finger nuclease-mediated correction of α-thalassemia in iPS cells. / Chang, Chan Jung; Bouhassira, Eric E.

In: Blood, Vol. 120, No. 19, 08.11.2012, p. 3906-3914.

Research output: Contribution to journalArticle

Chang, Chan Jung ; Bouhassira, Eric E. / Zinc-finger nuclease-mediated correction of α-thalassemia in iPS cells. In: Blood. 2012 ; Vol. 120, No. 19. pp. 3906-3914.
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