{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,1]],"date-time":"2026-05-01T21:19:18Z","timestamp":1777670358661,"version":"3.51.4"},"reference-count":30,"publisher":"SAGE Publications","issue":"9-10","license":[{"start":{"date-parts":[[2022,5,1]],"date-time":"2022-05-01T00:00:00Z","timestamp":1651363200000},"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":[[2022,5]]},"abstract":"<jats:p>\n                    Pompe disease is an autosomal recessive lysosomal storage disorder caused by deficiency of acid \u03b1-glucosidase (GAA), resulting in skeletal muscle weakness and cardiomyopathy. Muscle weakness progresses despite currently available therapy, which has prompted the development of gene therapy with adeno-associated virus (AAV) type 2 vectors cross-packaged as AAV8 (2\/8). Preclinical studies of gene therapy demonstrated that the minimum effective dose (MED) for biochemical correction with AAV2\/8-LSPhGAA was \u223c2\u2009\u00d7\u200910\n                    <jats:sup>11<\/jats:sup>\n                    vector genomes (vg)\/kg body weight. The current study examined the transduction of AAV2\/8-LSPeGFP vector in adult GAA-KO mice with Pompe disease, and correlated that degree of transduction with the biochemical correction achieved by the same dose of AAV2\/8-LSPhGAA. The MED was found to be \u223c2\u2009\u00d7\u200910\n                    <jats:sup>11<\/jats:sup>\n                    vg\/kg, with all hepatocytes variably transducing at this dose. At this dose, liver GAA significantly increased, while liver glycogen significantly decreased. The 2\u2009\u00d7\u200910\n                    <jats:sup>11<\/jats:sup>\n                    vg\/kg dose was sufficient to significantly decrease diaphragm glycogen.\n                  <\/jats:p>\n                  <jats:p>\n                    However, the heart, diaphragm, and quadriceps all required a fourfold higher dose to achieve correction of GAA deficiency in association with significant clearance of stored glycogen, which correlated with increased serum GAA activity. These data indicate that AAV2\/8-LSPeGFP transduced all hepatocytes when the 2\u2009\u00d7\u200910\n                    <jats:sup>11<\/jats:sup>\n                    vg\/kg dose was administered, which correlated with partial biochemical correction from the equivalent dose of AAV2\/8-LSPhGAA. Altogether, these data support the conclusion that substantial transduction of the liver is required to achieve biochemical correction from AAV2\/8-LSPhGAA.\n                  <\/jats:p>","DOI":"10.1089\/hum.2021.252","type":"journal-article","created":{"date-parts":[[2022,2,1]],"date-time":"2022-02-01T05:40:03Z","timestamp":1643694003000},"page":"492-498","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":11,"title":["Minimum Effective Dose to Achieve Biochemical Correction with Adeno-Associated Virus Vector-Mediated Gene Therapy in Mice with Pompe Disease"],"prefix":"10.1177","volume":"33","author":[{"given":"Sang-Oh","family":"Han","sequence":"first","affiliation":[{"name":"Department of Pediatrics, Duke University School of Medicine, Durham, North Carolina, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9636-1235","authenticated-orcid":false,"given":"Dorothy","family":"Gheorghiu","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Duke University School of Medicine, Durham, North Carolina, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Songtao","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Duke University School of Medicine, Durham, North Carolina, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hye Ri","family":"Kang","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Duke University School of Medicine, Durham, North Carolina, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dwight","family":"Koeberl","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Duke University School of Medicine, Durham, North Carolina, USA"},{"name":"Department of Molecular Genetics and Microbiology, Duke University, Durham, North Carolina, USA."}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"179","published-online":{"date-parts":[[2022,5,16]]},"reference":[{"key":"e_1_3_5_2_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00415-016-8219-8"},{"key":"e_1_3_5_3_2","doi-asserted-by":"publisher","DOI":"10.1097\/GIM.0b013e3182174703"},{"key":"e_1_3_5_4_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0067052"},{"key":"e_1_3_5_5_2","doi-asserted-by":"publisher","DOI":"10.1038\/gim.2011.4"},{"key":"e_1_3_5_6_2","doi-asserted-by":"publisher","DOI":"10.1097\/GIM.0b013e31819d0996"},{"key":"e_1_3_5_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymgme.2012.04.027"},{"key":"e_1_3_5_8_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa0909859"},{"key":"e_1_3_5_9_2","first-page":"47","article-title":"Clinical and histologic ocular findings in pompe disease","author":"Yanovitch TL","year":"2010","unstructured":"Yanovitch TL, , Banugaria SG, , Proia AD, et al. Clinical and histologic ocular findings in pompe disease. J Ped Ophthalm Strabis, 2010; 47.","journal-title":"J Ped Ophthalm Strabis"},{"key":"e_1_3_5_10_2","doi-asserted-by":"publisher","DOI":"10.1089\/hum.2008.010"},{"key":"e_1_3_5_11_2","doi-asserted-by":"publisher","DOI":"10.1086\/522236"},{"key":"e_1_3_5_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymthe.2003.11.015"},{"key":"e_1_3_5_13_2","first-page":"2686","article-title":"Immune response hinders therapy for lysosomal storage diseases","volume":"118","author":"Ponder KP","year":"2008","unstructured":"Ponder KP. Immune response hinders therapy for lysosomal storage diseases. 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