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dc.contributor.authorGomez-Ospina, N.
dc.contributor.authorScharenberg, S.G.
dc.contributor.authorAurelian, L.
dc.date.accessioned2019-09-17T14:27:02Z
dc.date.available2019-09-17T14:27:02Z
dc.date.issued2019
dc.identifier.urihttps://www.scopus.com/inward/record.uri?eid=2-s2.0-85071896825&doi=10.1038%2fs41467-019-11962-8&partnerID=40&md5=cd1f9923ad62048338cc2dbfeeee8a84
dc.identifier.urihttp://hdl.handle.net/10713/10897
dc.description.abstractLysosomal enzyme deficiencies comprise a large group of genetic disorders that generally lack effective treatments. A potential treatment approach is to engineer the patient’s own hematopoietic system to express high levels of the deficient enzyme, thereby correcting the biochemical defect and halting disease progression. Here, we present an efficient ex vivo genome editing approach using CRISPR-Cas9 that targets the lysosomal enzyme iduronidase to the CCR5 safe harbor locus in human CD34+ hematopoietic stem and progenitor cells. The modified cells secrete supra-endogenous enzyme levels, maintain long-term repopulation and multi-lineage differentiation potential, and can improve biochemical and phenotypic abnormalities in an immunocompromised mouse model of Mucopolysaccharidosis type I. These studies provide support for the development of genome-edited CD34+ hematopoietic stem and progenitor cells as a potential treatment for Mucopolysaccharidosis type I. The safe harbor approach constitutes a flexible platform for the expression of lysosomal enzymes making it applicable to other lysosomal storage disorders. Copyright 2019, The Author(s).en_US
dc.description.sponsorshipThis work was supported by the Stanford's Child Health Research Institute (CHRI), the National Organization of Rare Disorders (NORD), the Thrasher Research Fund, the National Institute of Neurological Disorders and Stroke (NINDS, 1K08NS102398-01 to N.G-O), and in part by the Cancer Prevention and Research Institute of Texas (RR140081 and RR170721 to G.B.).en_US
dc.description.urihttps://doi.org/10.1038/s41467-019-11962-8en_US
dc.language.isoen-USen_US
dc.publisherNature Publishing Groupen_US
dc.relation.ispartofNature Communications
dc.subject.meshHematopoietic Stem Cellsen_US
dc.subject.meshMucopolysaccharidoses--therapyen_US
dc.titleHuman genome-edited hematopoietic stem cells phenotypically correct Mucopolysaccharidosis type Ien_US
dc.typeArticleen_US
dc.identifier.doi10.1038/s41467-019-11962-8
dc.identifier.pmid31492863


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