{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T02:09:50Z","timestamp":1790388590706,"version":"4.1.0"},"reference-count":63,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2023,5,24]],"date-time":"2023-05-24T00:00:00Z","timestamp":1684886400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Kazan Federal University","award":["FZSM-2023-0011"],"award-info":[{"award-number":["FZSM-2023-0011"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Metachromatic leukodystrophy (MLD) is a hereditary neurodegenerative disease characterized by demyelination and motor and cognitive impairments due to deficiencies of the lysosomal enzyme arylsulfatase A (ARSA) or the saposin B activator protein (SapB). Current treatments are limited; however, gene therapy using adeno-associated virus (AAV) vectors for ARSA delivery has shown promising results. The main challenges for MLD gene therapy include optimizing the AAV dosage, selecting the most effective serotype, and determining the best route of administration for ARSA delivery into the central nervous system. This study aims to evaluate the safety and efficacy of AAV serotype 9 encoding ARSA (AAV9-ARSA) gene therapy when administered intravenously or intrathecally in minipigs, a large animal model with anatomical and physiological similarities to humans. By comparing these two administration methods, this study contributes to the understanding of how to improve the effectiveness of MLD gene therapy and offers valuable insights for future clinical applications.<\/jats:p>","DOI":"10.3390\/ijms24119204","type":"journal-article","created":{"date-parts":[[2023,5,25]],"date-time":"2023-05-25T02:58:48Z","timestamp":1684983528000},"page":"9204","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["Safety and Efficacy of Intravenous and Intrathecal Delivery of AAV9-Mediated ARSA in Minipigs"],"prefix":"10.3390","volume":"24","author":[{"given":"Aysilu","family":"Mullagulova","sequence":"first","affiliation":[{"name":"Institute for Fundamental Medicine and Biology, Kazan Federal University, 420008 Kazan, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alisa","family":"Shaimardanova","sequence":"additional","affiliation":[{"name":"Institute for Fundamental Medicine and Biology, Kazan Federal University, 420008 Kazan, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8776-3662","authenticated-orcid":false,"given":"Valeriya","family":"Solovyeva","sequence":"additional","affiliation":[{"name":"Institute for Fundamental Medicine and Biology, Kazan Federal University, 420008 Kazan, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yana","family":"Mukhamedshina","sequence":"additional","affiliation":[{"name":"Institute for Fundamental Medicine and Biology, Kazan Federal University, 420008 Kazan, Russia"},{"name":"Department of Histology, Cytology, and Embryology, Kazan State Medical University, 420012 Kazan, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5546-840X","authenticated-orcid":false,"given":"Daria","family":"Chulpanova","sequence":"additional","affiliation":[{"name":"Institute for Fundamental Medicine and Biology, Kazan Federal University, 420008 Kazan, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander","family":"Kostennikov","sequence":"additional","affiliation":[{"name":"Institute for Fundamental Medicine and Biology, Kazan Federal University, 420008 Kazan, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1690-0199","authenticated-orcid":false,"given":"Shaza","family":"Issa","sequence":"additional","affiliation":[{"name":"Institute for Fundamental Medicine and Biology, Kazan Federal University, 420008 Kazan, Russia"},{"name":"Department of Genetics and Biotechnology, St. Petersburg State University, 199034 St. Petersburg, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9427-5739","authenticated-orcid":false,"given":"Albert","family":"Rizvanov","sequence":"additional","affiliation":[{"name":"Institute for Fundamental Medicine and Biology, Kazan Federal University, 420008 Kazan, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,5,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"576221","DOI":"10.3389\/fmed.2020.576221","article-title":"Metachromatic leukodystrophy: Diagnosis, modeling, and treatment approaches","volume":"7","author":"Shaimardanova","year":"2020","journal-title":"Front. 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