{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,8]],"date-time":"2026-03-08T14:45:45Z","timestamp":1772981145549,"version":"3.50.1"},"reference-count":31,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2025,4,17]],"date-time":"2025-04-17T00:00:00Z","timestamp":1744848000000},"content-version":"vor","delay-in-days":106,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,1,1]],"date-time":"2025-01-01T00:00:00Z","timestamp":1735689600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100006510","name":"Duke University","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100006510","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000069","name":"National Institute of Arthritis and Musculoskeletal and Skin Diseases","doi-asserted-by":"publisher","award":["AR079572"],"award-info":[{"award-number":["AR079572"]}],"id":[{"id":"10.13039\/100000069","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Advances in Cell and Gene Therapy"],"published-print":{"date-parts":[[2025,1]]},"abstract":"<jats:p>\n                    <jats:bold>Background:<\/jats:bold>\n                    We recently reported an innovative gene therapy approach for GSD III using a recombinant adeno\u2010associated virus serotype 9 vector (AAV9\u2010Dual\u2010Pull) expressing a bacterial debranching enzyme (pullulanase) driven by a tandem dual promoter that consists of an immunotolerizing liver\u2010specific promoter (LSP) and the ubiquitous CMV enhance\/chicken\n                    <jats:italic>\u03b2<\/jats:italic>\n                    \u2010actin (CB) promoter. In this follow\u2010up study, we evaluated the long\u2010term efficacy of this gene therapy in GSD IIIa mice.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>Methods:<\/jats:bold>\n                    Three\u2010month\u2010old GSD IIIa mice were intravenously injected with AAV9\u2010LSP\u2010Pull or AAV9\u2010Dual\u2010Pull at the same dose (2.5 \u00d7 10\n                    <jats:sup>13<\/jats:sup>\n                    \u2009vg\/kg). Tissues were collected after 9 months for AAV genome quantification, pullulanase expression determination, and glycogen content measurement. Liver and muscle enzymes in plasma and disease biomarker in urine were analyzed at multiple time points to examine the correction of liver and muscle damage. Behavioral tests were performed during the course of AAV treatment to evaluate the improvement of muscle function.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>Results:<\/jats:bold>\n                    The AAV\u2010Dual\u2010Pull treatment led to persistent pullulanase expression and effective glycogen reduction in the liver, heart, and skeletal muscle, accompanied by the reversal of liver fibrosis, decrease of plasma enzyme activities, and long\u2010term improvement of muscle function. The AAV\u2010LSP\u2010Pull treatment showed a better therapeutic efficacy in the liver but had no effect on the cardiac and skeletal muscles.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>Conclusion:<\/jats:bold>\n                    Our results demonstrated the long\u2010term efficacy and safety of systemic AAV9\u2010Dual\u2010Pull delivery in GSD IIIa mice. Future studies will test this gene therapy approach in GSD IIIa dogs prior to the clinical translation to GSD III patients.\n                  <\/jats:p>","DOI":"10.1155\/acg2\/4639392","type":"journal-article","created":{"date-parts":[[2025,4,17]],"date-time":"2025-04-17T03:07:46Z","timestamp":1744859266000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Long\u2010Term Correction of Murine Glycogen Storage Disease Type III by AAV\u2010Mediated Gene Therapy Using an Immunotolerizing Dual Promoter to Express Bacterial Pullulanase"],"prefix":"10.1155","volume":"2025","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4708-7479","authenticated-orcid":false,"given":"Kuo-An","family":"Liao","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4373-4800","authenticated-orcid":false,"given":"Jeong-A","family":"Lim","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7681-6493","authenticated-orcid":false,"given":"Su Jin","family":"Choi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2254-6226","authenticated-orcid":false,"given":"Haiqing","family":"Yi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2191-0025","authenticated-orcid":false,"given":"Baodong","family":"Sun","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2025,4,17]]},"reference":[{"key":"e_1_2_11_1_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-3476(05)81652-X"},{"key":"e_1_2_11_2_2","article-title":"Glycogen Storage Disease Type III","author":"Schreuder A. 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