{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T15:30:30Z","timestamp":1790955030895,"version":"4.1.0"},"reference-count":44,"publisher":"SAGE Publications","issue":"2","license":[{"start":{"date-parts":[[2019,2,1]],"date-time":"2019-02-01T00:00:00Z","timestamp":1548979200000},"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":[[2019,2]]},"abstract":"<jats:p>\n                    Barth syndrome (BTHS) is a rare mitochondrial disease that affects heart and skeletal muscle and has no curative treatment. It is caused by recessive mutations in the X-linked gene\n                    <jats:italic toggle=\"yes\">TAZ<\/jats:italic>\n                    , which encodes tafazzin. To develop a clinically relevant gene therapy to restore tafazzin function and treat BTHS, three different adeno-associated virus serotype 9 vectors were tested and compared to identify the optimal promoter\u2014cytomegalovirus (CMV), desmin (Des), or a native tafazzin promoter (Taz)\u2014for\n                    <jats:italic toggle=\"yes\">TAZ<\/jats:italic>\n                    expression following intravenous administration of 1\u2009\u00d7\u200910\n                    <jats:sup>13<\/jats:sup>\n                    vector genomes\/kilogram to a mouse model of BTHS as either neonates (1\u20132 days of age) or adults (3 months of age). At 5 months of age, evaluations of biodistribution and\n                    <jats:italic toggle=\"yes\">TAZ<\/jats:italic>\n                    expression levels, mouse activity assessments, fatigue in response to exercise, muscle strength, cardiac function, mitochondrial structure, oxygen consumption, and electron transport chain complex activity assays were performed to measure the extent of improvement in treated mice. Each promoter was scored for significant improvement over untreated control mice and significant improvement compared with the other two promoters for every measurement and within each age of administration. All three of the promoters resulted in significant improvements in a majority of the assessments compared with untreated BTHS controls. When scored for overall effectiveness as a gene therapy, the Des promoter was found to provide improvement in the most assessments, followed by the CMV promoter, and finally Taz regardless of injection age. This study provides substantial support for translation of an adeno-associated virus serotype 9\u2013mediated\n                    <jats:italic toggle=\"yes\">TAZ<\/jats:italic>\n                    gene replacement strategy using a Des promoter for human BTHS patients in the clinic.\n                  <\/jats:p>","DOI":"10.1089\/hum.2018.020","type":"journal-article","created":{"date-parts":[[2018,8,2]],"date-time":"2018-08-02T06:56:14Z","timestamp":1533192974000},"page":"139-154","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":72,"title":["AAV-Mediated\n                    <i>TAZ<\/i>\n                    Gene Replacement Restores Mitochondrial and Cardioskeletal Function in Barth Syndrome"],"prefix":"10.1177","volume":"30","author":[{"given":"Silveli","family":"Suzuki-Hatano","sequence":"first","affiliation":[{"name":"Department of Pediatrics, University of Florida College of Medicine, Gainesville, Florida."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Madhurima","family":"Saha","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University of Florida College of Medicine, Gainesville, Florida."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Skylar A.","family":"Rizzo","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University of Florida College of Medicine, Gainesville, Florida."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rachael L.","family":"Witko","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University of Florida College of Medicine, Gainesville, Florida."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bennett J.","family":"Gosiker","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University of Florida College of Medicine, Gainesville, Florida."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manashwi","family":"Ramanathan","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University of Florida College of Medicine, Gainesville, Florida."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meghan S.","family":"Soustek","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University of Florida College of Medicine, Gainesville, Florida."},{"name":"Department of Molecular Genetics and Microbiology, University of Florida College of Medicine, Gainesville, Florida."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael D.","family":"Jones","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University of Florida College of Medicine, Gainesville, Florida."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter B.","family":"Kang","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University of Florida College of Medicine, Gainesville, Florida."},{"name":"Department of Molecular Genetics and Microbiology, University of Florida College of Medicine, Gainesville, Florida."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Barry J.","family":"Byrne","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University of Florida College of Medicine, Gainesville, Florida."},{"name":"Department of Molecular Genetics and Microbiology, University of Florida College of Medicine, Gainesville, Florida."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"W. Todd","family":"Cade","sequence":"additional","affiliation":[{"name":"Program in Physical Therapy, Washington University School of Medicine, St. Louis, Missouri."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christina A.","family":"Pacak","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University of Florida College of Medicine, Gainesville, Florida."},{"name":"Department of Molecular Genetics and Microbiology, University of Florida College of Medicine, Gainesville, Florida."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2019,2,8]]},"reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0960-9822(06)00237-5"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbamem.2009.07.009"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1194\/jlr.M800561-JLR200"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1194\/jlr.M500056-JLR200"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1038\/nm.3545"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1194\/jlr.R700018-JLR200"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M307382200"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.chemphyslip.2005.08.002"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2003.06.015"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1542\/peds.2005-2667"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.14814\/phy2.13130"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1007\/s10545-012-9486-x"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.00479.2010"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M305956200"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M109.016642"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.0000233378.95325.ce"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.77.6.3495-3504.2003"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymthe.2006.03.014"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.0000237661.18885.f6"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.1038\/mt.2008.76"},{"key":"e_1_3_3_22_2","doi-asserted-by":"publisher","DOI":"10.1089\/hum.2008.123"},{"key":"e_1_3_3_23_2","doi-asserted-by":"publisher","DOI":"10.1038\/gt.2016.20"},{"key":"e_1_3_3_24_2","doi-asserted-by":"publisher","DOI":"10.1186\/1479-0556-6-13"},{"key":"e_1_3_3_25_2","doi-asserted-by":"crossref","first-page":"776","DOI":"10.1111\/j.1610-0387.2010.07480.x","article-title":"Research in practice: More than skin deep\u2014aging of subcutaneous fat tissue","volume":"8","author":"Berneburg M","year":"2010","unstructured":"Berneburg M. 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