We have developed induced pluripotent stem cells (iPSCs) from a patient with 
X-linked chronic granulomatous disease (X-CGD), a defect of neutrophil 
microbicidal reactive oxygen species (ROS) generation resulting from gp91(phox) 
deficiency. We demonstrated that mature neutrophils differentiated from X-CGD 
iPSCs lack ROS production, reproducing the pathognomonic CGD cellular phenotype. 
Targeted gene transfer into iPSCs, with subsequent selection and full 
characterization to ensure no off-target changes, holds promise for correction 
of monogenic diseases without the insertional mutagenesis caused by multisite 
integration of viral or plasmid vectors. Zinc finger nuclease-mediated gene 
targeting of a single-copy gp91(phox) therapeutic minigene into one allele of 
the "safe harbor" AAVS1 locus in X-CGD iPSCs without off-target inserts resulted 
in sustained expression of gp91(phox) and substantially restored neutrophil ROS 
production. Our findings demonstrate how precise gene targeting may be applied 
to correction of X-CGD using zinc finger nuclease and patient iPSCs.