Human genome-edited hematopoietic stem cells phenotypically correct Mucopolysaccharidosis type I

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dc.citation.articleNumber4045en_US
dc.citation.journalTitleNature Communicationsen_US
dc.citation.volumeNumber10en_US
dc.contributor.authorGomez-Ospina, Nataliaen_US
dc.contributor.authorScharenberg, Samantha G.en_US
dc.contributor.authorMostrel, Nathalieen_US
dc.contributor.authorBak, Rasmus O.en_US
dc.contributor.authorMantri, Sruthien_US
dc.contributor.authorQuadros, Rolen M.en_US
dc.contributor.authorGurumurthy, Channabasavaiah B.en_US
dc.contributor.authorLee, Ciaranen_US
dc.contributor.authorBao, Gangen_US
dc.contributor.authorSuarez, Carlos J.en_US
dc.contributor.authorKhan, Shaukaten_US
dc.contributor.authorSawamoto, Kazukien_US
dc.contributor.authorTomatsu, Shunjien_US
dc.contributor.authorRaj, Nitinen_US
dc.contributor.authorAttardi, Laura D.en_US
dc.contributor.authorAurelian, Laureen_US
dc.contributor.authorPorteus, Matthew H.en_US
dc.contributor.orgBioengineeringen_US
dc.date.accessioned2019-11-14T17:52:28Zen_US
dc.date.available2019-11-14T17:52:28Zen_US
dc.date.issued2019en_US
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.en_US
dc.identifier.citationGomez-Ospina, Natalia, Scharenberg, Samantha G., Mostrel, Nathalie, et al.. "Human genome-edited hematopoietic stem cells phenotypically correct Mucopolysaccharidosis type I." <i>Nature Communications,</i> 10, (2019) Springer Nature: https://doi.org/10.1038/s41467-019-11962-8.en_US
dc.identifier.digitals41467-019-11962-8en_US
dc.identifier.doihttps://doi.org/10.1038/s41467-019-11962-8en_US
dc.identifier.urihttps://hdl.handle.net/1911/107690en_US
dc.language.isoengen_US
dc.publisherSpringer Natureen_US
dc.rightsThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder.en_US
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/en_US
dc.titleHuman genome-edited hematopoietic stem cells phenotypically correct Mucopolysaccharidosis type Ien_US
dc.typeJournal articleen_US
dc.type.dcmiTexten_US
dc.type.publicationpublisher versionen_US
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