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.