{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T15:36:59Z","timestamp":1790177819015,"version":"4.1.0"},"reference-count":33,"publisher":"SAGE Publications","issue":"2","license":[{"start":{"date-parts":[[2012,11,29]],"date-time":"2012-11-29T00:00:00Z","timestamp":1354147200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2012,11,29]],"date-time":"2012-11-29T00:00:00Z","timestamp":1354147200000},"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":[[2013,2]]},"abstract":"<jats:p>Liver gene transfer with adeno-associated viral (AAV) 2\/8 vectors is being considered for therapy of systemic diseases like mucopolysaccharidosis type VI (MPS VI), a lysosomal storage disease due to deficiency of arylsulfatase B (ARSB). We have previously reported that liver gene transfer with AAV2\/8 results in sustained yet variable expression of ARSB. We hypothesized that the variability we observed could be due to pre-existing immunity to wild-type AAV8. To test this, we compared the levels of AAV2\/8-mediated transduction in MPS VI cats with and without pre-existing immunity to AAV8. In addition, since levels of lysosomal enzymes as low as 5% of normal are expected to be therapeutic, we evaluated the impact of pre-existing immunity on MPS VI phenotypic rescue. AAV2\/8 administration to MPS VI cats without pre-existing neutralizing antibodies to AAV8 resulted in consistent and dose-dependent expression of ARSB, urinary glycosaminoglycan (GAG) reduction, and femur length amelioration. Conversely, animals with pre-existing immunity to AAV8 showed low levels of ARSB expression and limited phenotypic improvement. Our data support the use of AAV2\/8-mediated gene transfer for MPS VI and other systemic diseases, and highlight that pre-existing immunity to AAV8 should be considered in determining subject eligibility for therapy.<\/jats:p>","DOI":"10.1089\/hum.2012.179","type":"journal-article","created":{"date-parts":[[2012,11,29]],"date-time":"2012-11-29T15:22:46Z","timestamp":1354202566000},"page":"163-169","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":42,"title":["Gene Therapy for Mucopolysaccharidosis Type VI Is Effective in Cats Without Pre-Existing Immunity to AAV8"],"prefix":"10.1177","volume":"24","author":[{"given":"Rita","family":"Ferla","sequence":"first","affiliation":[{"name":"Telethon Institute of Genetics and Medicine (TIGEM)","place":["Italy"]},{"name":"\u201cFederico II\u201d University","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"O'Malley","sequence":"additional","affiliation":[{"name":"University of Pennsylvania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roberto","family":"Calcedo","sequence":"additional","affiliation":[{"name":"University of Pennsylvania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patricia","family":"O'Donnell","sequence":"additional","affiliation":[{"name":"University of Pennsylvania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ping","family":"Wang","sequence":"additional","affiliation":[{"name":"University of Pennsylvania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gabriella","family":"Cotugno","sequence":"additional","affiliation":[{"name":"Telethon Institute of Genetics and Medicine (TIGEM)","place":["Italy"]},{"name":"\u201cFederico II\u201d University","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pamela","family":"Claudiani","sequence":"additional","affiliation":[{"name":"Telethon Institute of Genetics and Medicine (TIGEM)","place":["Italy"]},{"name":"\u201cFederico II\u201d University","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James M.","family":"Wilson","sequence":"additional","affiliation":[{"name":"University of Pennsylvania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark","family":"Haskins","sequence":"additional","affiliation":[{"name":"University of Pennsylvania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alberto","family":"Auricchio","sequence":"additional","affiliation":[{"name":"Telethon Institute of Genetics and Medicine (TIGEM)","place":["Italy"]},{"name":"\u201cFederico II\u201d University","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2012,11,29]]},"reference":[{"key":"e_1_3_3_2_1","doi-asserted-by":"publisher","DOI":"10.1089\/hum.2009.182"},{"key":"e_1_3_3_3_1","volume-title":"The Online Metabolic and Molecular Bases of Inherited Diseases","author":"Brunetti-Pierri N.","year":"2010","unstructured":"Brunetti-Pierri N., , Auricchio A. 2010. 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