{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T02:11:19Z","timestamp":1790820679504,"version":"4.1.0"},"reference-count":43,"publisher":"SAGE Publications","issue":"23-24","license":[{"start":{"date-parts":[[2022,12,1]],"date-time":"2022-12-01T00:00:00Z","timestamp":1669852800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2022,12,1]],"date-time":"2022-12-01T00:00:00Z","timestamp":1669852800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Human Gene Therapy"],"published-print":{"date-parts":[[2022,12]]},"abstract":"<jats:p>\n                    Mucopolysaccharidosis type II (MPS II, Hunter syndrome) is an X-linked recessive lysosomal disease caused by deficiency of iduronate-2-sulfatase (IDS). The absence of IDS results in the accumulation of the glycosaminoglycans (GAGs) heparan sulfate and dermatan sulfate. Currently, the only approved treatment option for MPS II is enzyme replacement therapy (ERT), Elaprase. However, ERT is demanding for the patient and does not ameliorate neurological manifestations of the disease. Using an IDS-deficient mouse model that phenocopies the human disease, we evaluated hematopoietic stem and progenitor cells (HSPCs) transduced with a lentiviral vector (LVV) carrying a codon-optimized human IDS coding sequence regulated by a ubiquitous MNDU3 promoter (MNDU3-IDS). Mice treated with MNDU3-IDS LVV-transduced cells showed supraphysiological levels of IDS enzyme activity in plasma, peripheral blood mononuclear cells, and in most analyzed tissues. These enzyme levels were sufficient to normalize GAG storage in analyzed tissues. Importantly, IDS levels in the brains of MNDU3-IDS-engrafted animals were restored to 10\u201320% than that of wild-type mice, sufficient to normalize GAG content and prevent emergence of cognitive deficit as evaluated by neurobehavioral testing. These results demonstrate the potential effectiveness of\n                    <jats:italic toggle=\"yes\">ex vivo<\/jats:italic>\n                    MNDU3-IDS LVV-transduced HSPCs for treatment of MPS II.\n                  <\/jats:p>","DOI":"10.1089\/hum.2022.141","type":"journal-article","created":{"date-parts":[[2022,10,13]],"date-time":"2022-10-13T03:31:48Z","timestamp":1665631908000},"page":"1279-1292","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":14,"title":["Phenotypic Correction of Murine Mucopolysaccharidosis Type II by Engraftment of\n                    <i>Ex Vivo<\/i>\n                    Lentiviral Vector-Transduced Hematopoietic Stem and Progenitor Cells"],"prefix":"10.1177","volume":"33","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9152-8681","authenticated-orcid":false,"given":"Miles C.","family":"Smith","sequence":"first","affiliation":[{"name":"Center for Genome Engineering, Department of Genetics, Cell Biology and Development, University of Minnesota, Minneapolis, Minnesota, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2188-299X","authenticated-orcid":false,"given":"Lalitha R.","family":"Belur","sequence":"additional","affiliation":[{"name":"Center for Genome Engineering, Department of Genetics, Cell Biology and Development, University of Minnesota, Minneapolis, Minnesota, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea D.","family":"Karlen","sequence":"additional","affiliation":[{"name":"Center for Genome Engineering, Department of Genetics, Cell Biology and Development, University of Minnesota, Minneapolis, Minnesota, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olivia","family":"Erlanson","sequence":"additional","affiliation":[{"name":"Center for Genome Engineering, Department of Genetics, Cell Biology and Development, University of Minnesota, Minneapolis, Minnesota, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kelly M.","family":"Podetz-Pedersen","sequence":"additional","affiliation":[{"name":"Center for Genome Engineering, Department of Genetics, Cell Biology and Development, University of Minnesota, Minneapolis, Minnesota, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jessica","family":"McKenzie","sequence":"additional","affiliation":[{"name":"bluebird bio, Inc., Cambridge, Massachusetts, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jenn","family":"Detellis","sequence":"additional","affiliation":[{"name":"bluebird bio, Inc., Cambridge, Massachusetts, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Khatuna","family":"Gagnidze","sequence":"additional","affiliation":[{"name":"bluebird bio, Inc., Cambridge, Massachusetts, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Geoffrey","family":"Parsons","sequence":"additional","affiliation":[{"name":"bluebird bio, Inc., Cambridge, Massachusetts, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicholas","family":"Robinson","sequence":"additional","affiliation":[{"name":"bluebird bio, Inc., Cambridge, Massachusetts, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shelby","family":"Labarre","sequence":"additional","affiliation":[{"name":"bluebird bio, Inc., Cambridge, Massachusetts, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saumil","family":"Shah","sequence":"additional","affiliation":[{"name":"bluebird bio, Inc., Cambridge, Massachusetts, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Justin","family":"Furcich","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University of Minnesota, Minneapolis, Minnesota, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Troy C.","family":"Lund","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University of Minnesota, Minneapolis, Minnesota, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hsing-Chen","family":"Tsai","sequence":"additional","affiliation":[{"name":"bluebird bio, Inc., Cambridge, Massachusetts, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R. Scott","family":"McIvor","sequence":"additional","affiliation":[{"name":"Center for Genome Engineering, Department of Genetics, Cell Biology and Development, University of Minnesota, Minneapolis, Minnesota, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melissa","family":"Bonner","sequence":"additional","affiliation":[{"name":"bluebird bio, Inc., Cambridge, Massachusetts, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2022,12,14]]},"reference":[{"key":"e_1_3_6_2_2","doi-asserted-by":"publisher","DOI":"10.3390\/ijms22157888"},{"key":"e_1_3_6_3_2","doi-asserted-by":"publisher","DOI":"10.3390\/ijms22115490"},{"key":"e_1_3_6_4_2","first-page":"3421","volume-title":"The Mucopolysaccharidoses","author":"Neufeld EF","year":"2019","unstructured":"Neufeld EF, , Muenzer J. The Mucopolysaccharidoses. In: The Online Metabolic and Molecular Bases of Inherited Disease. 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