{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,1]],"date-time":"2026-05-01T20:51:32Z","timestamp":1777668692106,"version":"3.51.4"},"reference-count":41,"publisher":"SAGE Publications","issue":"7-8","license":[{"start":{"date-parts":[[2025,4,1]],"date-time":"2025-04-01T00:00:00Z","timestamp":1743465600000},"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":[[2025,4]]},"abstract":"<jats:p>\n                    Mucopolysaccharidosis type II (MPS II) is an X-linked lysosomal storage disorder caused by pathogenic variants in the\n                    <jats:italic toggle=\"yes\">IDS<\/jats:italic>\n                    gene encoding iduronate-2-sulfatase (IDS), which hydrolyzes sulfate groups in dermatan sulfate and heparan sulfate. The current treatment for MPS II includes enzyme replacement therapy and hematopoietic stem cell transplantation (HSCT). Both therapies have shown limited penetration through the blood-brain barrier. Anecdotal cases have been reported with the HSCT benefit to treat neurological problems in MPS II. Herein, we generated an MPS II mouse model using CRISPR\/Cas9 to examine the effectiveness of CNS-directed, adeno-associated virus (AAV)2\/9-mediated human IDS gene transfer in expressing sustained IDS and improving behavior performance in this model. The intracerebroventricular administration of AAV2\/9-hIDS showed higher IDS activity in the central nervous system and better auditory function compared with those by intravenous administration. The results provide a strong proof of concept for the clinical translation of our approach to treating patients with MPS II and cognitive impairment.\n                  <\/jats:p>","DOI":"10.1089\/hum.2024.229","type":"journal-article","created":{"date-parts":[[2025,2,27]],"date-time":"2025-02-27T11:39:51Z","timestamp":1740656391000},"page":"738-749","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":0,"title":["Central Nervous System-Targeted Gene Therapy for the Treatment of Neurocognitive Deficits in Mucopolysaccharidosis Type II Mice"],"prefix":"10.1177","volume":"36","author":[{"ORCID":"https:\/\/orcid.org\/0009-0003-5130-4004","authenticated-orcid":false,"given":"Guoqing","family":"Chen","sequence":"first","affiliation":[{"name":"Xinhua Hospital Affiliated with Shanghai Jiao Tong University School of Medicine, Shanghai, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xia","family":"Zhan","sequence":"additional","affiliation":[{"name":"Xinhua Hospital Affiliated with Shanghai Jiao Tong University School of Medicine, Shanghai, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaolan","family":"Gao","sequence":"additional","affiliation":[{"name":"Xinhua Hospital Affiliated with Shanghai Jiao Tong University School of Medicine, Shanghai, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mengni","family":"Yi","sequence":"additional","affiliation":[{"name":"Xinhua Hospital Affiliated with Shanghai Jiao Tong University School of Medicine, Shanghai, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Huan","family":"Liang","sequence":"additional","affiliation":[{"name":"Xinhua Hospital Affiliated with Shanghai Jiao Tong University School of Medicine, Shanghai, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yixiong","family":"Chen","sequence":"additional","affiliation":[{"name":"Lingyi Biotech Co., Ltd., Shanghai, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qing","family":"Lin","sequence":"additional","affiliation":[{"name":"Lingyi Biotech Co., Ltd., Shanghai, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jun","family":"Yang","sequence":"additional","affiliation":[{"name":"Xinhua Hospital Affiliated with Shanghai Jiao Tong University School of Medicine, Shanghai, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shule","family":"Hou","sequence":"additional","affiliation":[{"name":"Xinhua Hospital Affiliated with Shanghai Jiao Tong University School of Medicine, Shanghai, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gustavo","family":"Maegawa","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Vagelos College of Physician &amp; Surgeons, Columbia University Irving Medical Center, New York, New York, USA."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Huiwen","family":"Zhang","sequence":"additional","affiliation":[{"name":"Xinhua Hospital Affiliated with Shanghai Jiao Tong University School of Medicine, Shanghai, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"179","published-online":{"date-parts":[[2025,4,16]]},"reference":[{"key":"e_1_3_6_2_2","first-page":"104","article-title":"A Rare Disease in Two Brothers","volume":"10","author":"Hunter C","year":"1917","unstructured":"Hunter C. 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