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• W2023456870 abstract "Abstract 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 gp91phox 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 gp91phox therapeutic minigene into one allele of the “safe harbor” AAVS1 locus in X-CGD iPSCs without off-target inserts resulted in sustained expression of gp91phox 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." @default.
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• W2023456870 date "2011-05-26" @default.
• W2023456870 modified "2023-10-02" @default.
• W2023456870 title "Oxidase-deficient neutrophils from X-linked chronic granulomatous disease iPS cells: functional correction by zinc finger nuclease–mediated safe harbor targeting" @default.
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• W2023456870 doi "https://doi.org/10.1182/blood-2010-12-328161" @default.
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