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Building on the experience of <jats:italic>ex vivo<\/jats:italic> gene therapy for severe combined immunodeficiencies, it is likely that genome editing of haematopoietic stem\/progenitor cells (HSPC) for correction of inherited blood diseases will be an early clinical application. We show molecular evidence of gene correction in a mouse model of primary immunodeficiency. <jats:italic>In vitro<\/jats:italic> experiments in DNA-dependent protein kinase catalytic subunit severe combined immunodeficiency (<jats:italic>Prkdc scid)<\/jats:italic> fibroblasts using designed zinc finger nucleases (ZFN) and a repair template demonstrated molecular and functional correction of the defect. Following transplantation of <jats:italic>ex vivo<\/jats:italic> gene-edited <jats:italic>Prkdc scid<\/jats:italic> HSPC, some of the recipient animals carried the expected genomic signature of ZFN-driven gene correction. In some primary and secondary transplant recipients we detected double-positive CD4\/CD8 T-cells in thymus and single-positive T-cells in blood, but no other evidence of immune reconstitution. However, the leakiness of this model is a confounding factor for the interpretation of the possible T-cell reconstitution. Our results provide support for the feasibility of rescuing inherited blood disease by <jats:italic>ex vivo<\/jats:italic> genome editing followed by transplantation, and highlight some of the challenges.<\/jats:p>","DOI":"10.1038\/s41598-018-26439-9","type":"journal-article","created":{"date-parts":[[2018,5,22]],"date-time":"2018-05-22T11:57:38Z","timestamp":1526990258000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Molecular Evidence of Genome Editing in a Mouse Model of Immunodeficiency"],"prefix":"10.1038","volume":"8","author":[{"given":"H. 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