{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,1]],"date-time":"2026-05-01T21:23:03Z","timestamp":1777670583785,"version":"3.51.4"},"reference-count":13,"publisher":"SAGE Publications","issue":"7-8","license":[{"start":{"date-parts":[[2024,4,1]],"date-time":"2024-04-01T00:00:00Z","timestamp":1711929600000},"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":[[2024,4]]},"abstract":"\n Mucopolysaccharidosis type II (MPS II) is a lysosomal storage disease caused by a mutation in the\n IDS<\/jats:italic>\n gene, resulting in deficiency of the enzyme iduronate-2-sulfatase (IDS) causing heparan sulfate (HS) and dermatan sulfate (DS) accumulation in all cells. This leads to skeletal and cardiorespiratory disease with severe neurodegeneration in two thirds of sufferers. Enzyme replacement therapy is ineffective at treating neurological disease, as intravenously delivered IDS is unable to cross the blood\u2013brain barrier (BBB). Hematopoietic stem cell transplant is also unsuccessful, presumably due to insufficient IDS enzyme production from transplanted cells engrafting in the brain. We used two different peptide sequences (rabies virus glycoprotein [RVG] and gh625), both previously published as BBB-crossing peptides, fused to IDS and delivered via hematopoietic stem cell gene therapy (HSCGT). HSCGT with\n LV.IDS<\/jats:uri>\n .RVG and\n LV.IDS<\/jats:uri>\n .gh625 was compared with\n LV.IDS<\/jats:uri>\n .ApoEII and\n LV.IDS<\/jats:uri>\n in MPS II mice at 6 months post-transplant. Levels of IDS enzyme activity in the brain and peripheral tissues were lower in\n LV.IDS<\/jats:uri>\n .RVG- and\n LV.IDS<\/jats:uri>\n .gh625-treated mice than in\n LV.IDS<\/jats:uri>\n .ApoEII- and\n LV.IDS-treated<\/jats:uri>\n mice, despite comparable vector copy numbers. Microgliosis, astrocytosis, and lysosomal swelling were partially normalized in MPS II mice treated with\n LV.IDS<\/jats:uri>\n .RVG and\n LV.IDS<\/jats:uri>\n .gh625. Skeletal thickening was normalized by both treatments to wild-type levels. Although reductions in skeletal abnormalities and neuropathology are encouraging, given the low levels of enzyme activity compared with control tissue from\n LV.IDS-<\/jats:uri>\n and\n LV.IDS<\/jats:uri>\n .ApoEII-transplanted mice, the RVG and gh625 peptides are unlikely to be ideal candidates for HSCGT in MPS II and are inferior to the ApoEII peptide that we have previously demonstrated to be more effective at correcting MPS II disease than IDS alone.\n <\/jats:p>","DOI":"10.1089\/hum.2023.025","type":"journal-article","created":{"date-parts":[[2023,5,22]],"date-time":"2023-05-22T05:53:32Z","timestamp":1684734812000},"page":"232-242","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":1,"title":["Fusion of Rabies Virus Glycoprotein or gh625 to Iduronate-2-Sulfatase for the Treatment of Mucopolysaccharidosis Type II"],"prefix":"10.1177","volume":"35","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6285-9919","authenticated-orcid":false,"given":"Shaun R.","family":"Wood","sequence":"first","affiliation":[{"name":"Division of Cell Matrix Biology and Regenerative Medicine, University of Manchester, Manchester, United Kingdom"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ahsan","family":"Chaudrhy","sequence":"additional","affiliation":[{"name":"Division of Cell Matrix Biology and Regenerative Medicine, University of Manchester, Manchester, United Kingdom"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stuart","family":"Ellison","sequence":"additional","affiliation":[{"name":"Division of Cell Matrix Biology and Regenerative Medicine, University of Manchester, Manchester, United Kingdom"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rachel","family":"Searle","sequence":"additional","affiliation":[{"name":"Division of Cell Matrix Biology and Regenerative Medicine, University of Manchester, Manchester, United Kingdom"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Constance","family":"Burgod","sequence":"additional","affiliation":[{"name":"Division of Cell Matrix Biology and Regenerative Medicine, University of Manchester, Manchester, United Kingdom"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ghazala","family":"Tehseen","sequence":"additional","affiliation":[{"name":"Division of Cell Matrix Biology and Regenerative Medicine, University of Manchester, Manchester, United Kingdom"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gabriella","family":"Forte","sequence":"additional","affiliation":[{"name":"Division of Cell Matrix Biology and Regenerative Medicine, University of Manchester, Manchester, United Kingdom"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Claire","family":"O'Leary","sequence":"additional","affiliation":[{"name":"Division of Cell Matrix Biology and Regenerative Medicine, University of Manchester, Manchester, United Kingdom"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"H\u00e9l\u00e8ne","family":"Gleitz","sequence":"additional","affiliation":[{"name":"Division of Cell Matrix Biology and Regenerative Medicine, University of Manchester, Manchester, United Kingdom"},{"name":"Department of Developmental Biology, Erasmus University, Rotterdam, the Netherlands."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Aiyin","family":"Liao","sequence":"additional","affiliation":[{"name":"Division of Cell Matrix Biology and Regenerative Medicine, University of Manchester, Manchester, United Kingdom"},{"name":"Department of Infection, Immunity and Inflammation,University College London, London, United Kingdom."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"James","family":"Cook","sequence":"additional","affiliation":[{"name":"Division of Cell Matrix Biology and Regenerative Medicine, University of Manchester, Manchester, United Kingdom"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rebecca","family":"Holley","sequence":"additional","affiliation":[{"name":"Division of Cell Matrix Biology and Regenerative Medicine, University of Manchester, Manchester, United Kingdom"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9708-1112","authenticated-orcid":false,"given":"Brian W.","family":"Bigger","sequence":"additional","affiliation":[{"name":"Division of Cell Matrix Biology and Regenerative Medicine, University of Manchester, Manchester, United Kingdom"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"179","published-online":{"date-parts":[[2024,4,16]]},"reference":[{"key":"e_1_3_5_2_2","doi-asserted-by":"publisher","DOI":"10.1053\/siny.2001.0088"},{"key":"e_1_3_5_3_2","doi-asserted-by":"publisher","DOI":"10.3389\/fmolb.2022.965089"},{"key":"e_1_3_5_4_2","doi-asserted-by":"publisher","DOI":"10.15252\/emmm.201708730"},{"key":"e_1_3_5_5_2","doi-asserted-by":"publisher","DOI":"10.1038\/mt.2013.29"},{"key":"e_1_3_5_6_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature05901"},{"key":"e_1_3_5_7_2","doi-asserted-by":"publisher","DOI":"10.1007\/s12017-012-8196-8"},{"key":"e_1_3_5_8_2","first-page":"1885","article-title":"Peptide gH625 enters into neuron and astrocyte cell lines and crosses the blood-brain barrier in rats","volume":"10","author":"Valiante S","year":"2015","unstructured":"Valiante S, , Falanga A, , Cigliano L, et al. Peptide gH625 enters into neuron and astrocyte cell lines and crosses the blood-brain barrier in rats. Int J Nanomedicine, 2015; 10:1885\u20131898.","journal-title":"Int J Nanomedicine"},{"key":"e_1_3_5_9_2","doi-asserted-by":"publisher","DOI":"10.1038\/mt.2013.141"},{"key":"e_1_3_5_10_2","doi-asserted-by":"publisher","DOI":"10.1038\/mt.2012.82"},{"key":"e_1_3_5_11_2","doi-asserted-by":"publisher","DOI":"10.1023\/A:1012763026526"},{"key":"e_1_3_5_12_2","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awx311"},{"key":"e_1_3_5_13_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2010-04-278234"},{"key":"e_1_3_5_14_2","doi-asserted-by":"publisher","DOI":"10.1089\/hum.2014.158"}],"container-title":["Human Gene Therapy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.sagepub.com\/doi\/full-xml\/10.1089\/hum.2023.025","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1089\/hum.2023.025","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1089\/hum.2023.025","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T07:57:15Z","timestamp":1777449435000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.sagepub.com\/doi\/10.1089\/hum.2023.025"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,4]]},"references-count":13,"journal-issue":{"issue":"7-8","published-print":{"date-parts":[[2024,4]]}},"alternative-id":["10.1089\/hum.2023.025"],"URL":"https:\/\/doi.org\/10.1089\/hum.2023.025","relation":{},"ISSN":["1043-0342","1557-7422"],"issn-type":[{"value":"1043-0342","type":"print"},{"value":"1557-7422","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,4]]}}}