{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,18]],"date-time":"2026-05-18T12:09:50Z","timestamp":1779106190257,"version":"3.51.4"},"reference-count":0,"publisher":"SAGE Publications","issue":"11","license":[{"start":{"date-parts":[[2007,11,1]],"date-time":"2007-11-01T00:00:00Z","timestamp":1193875200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Human Gene Therapy"],"published-print":{"date-parts":[[2007,11]]},"abstract":"<jats:p>\n                    Salivary glands (SGs) have proven useful targets for clinical applications of gene therapeutics. In this toxicology and biodistribution study, which conforms to U.S. Food and Drug Administration Good Laboratory Practice regulations, four doses (10\n                    <jats:sup>7<\/jats:sup>\n                    \u201310\n                    <jats:sup>10<\/jats:sup>\n                    particles) of a serotype 2 adeno-associated viral (AAV2) vector encoding human erythropoietin were directly administered to the right submandibular gland of male and female BALB\/c mice (\n                    <jats:italic toggle=\"yes\">n<\/jats:italic>\n                    = 21 per gender dose group). Control-treated (saline administered;\n                    <jats:italic toggle=\"yes\">n<\/jats:italic>\n                    = 66) and vector-treated (\n                    <jats:italic toggle=\"yes\">n<\/jats:italic>\n                    = 168) animals did not differ in clinical appearance, morbidity and mortality rates, food and water consumption, weight gain ratios, and final weight. Clinical hematology values also were unaffected by AAV2 administration except for parameters influenced by the expression of the recombinant protein (e.g., hematocrit). Mice were killed on days 3, 30, 55, and 92. No major vector-related toxicity was uncovered after complete pathology and histopathology review. However, a significant gender-related difference in vector biodistribution was revealed by quantitative polymerase chain reaction. In male mice vector (group receiving 10\n                    <jats:sup>10<\/jats:sup>\n                    particles\/animal) effectively transduced, and was primarily confined within, the SGs (i.e., \u223c800 times more copies in SGs than in liver; day 3) and long lived. In contrast, in female mice, SG transduction was less efficient (260-fold less than in males; day 3) and short lived, and vector was disseminated widely via both the bloodstream (SG:liver copy ratio, \u223c1) and saliva (30-fold greater than in males). The observed vector biodistribution is likely due to differences in AAV2 receptor targets and structural differences affecting SG integrity. Sexual dimorphism is a factor of major significance that could potentially affect gene therapy clinical applications in SGs.\n                  <\/jats:p>","DOI":"10.1089\/hum.2007.072","type":"journal-article","created":{"date-parts":[[2007,10,16]],"date-time":"2007-10-16T09:28:20Z","timestamp":1192526900000},"page":"1109-1118","source":"Crossref","is-referenced-by-count":16,"title":["Gender Differences in Serotype 2 Adeno-Associated Virus Biodistribution After Administration to Rodent Salivary Glands"],"prefix":"10.1177","volume":"18","author":[{"given":"A.","family":"Voutetakis","sequence":"first","affiliation":[{"name":"Gene Therapy and Therapeutics Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD 20892."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"C.","family":"Zheng","sequence":"additional","affiliation":[{"name":"Gene Therapy and Therapeutics Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD 20892."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"J.","family":"Wang","sequence":"additional","affiliation":[{"name":"Gene Therapy and Therapeutics Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD 20892."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"C.M.","family":"Goldsmith","sequence":"additional","affiliation":[{"name":"Gene Therapy and Therapeutics Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD 20892."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"S.","family":"Afione","sequence":"additional","affiliation":[{"name":"Gene Therapy and Therapeutics Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD 20892."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"J.A.","family":"Chiorini","sequence":"additional","affiliation":[{"name":"Gene Therapy and Therapeutics Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD 20892."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M.L.","family":"Wenk","sequence":"additional","affiliation":[{"name":"Toxicology Division, BioReliance Invitrogen Bioservices, Rockville, MD 20850."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M.","family":"Vallant","sequence":"additional","affiliation":[{"name":"National Toxicology Program, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC 27709."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"R.D.","family":"Irwin","sequence":"additional","affiliation":[{"name":"National Toxicology Program, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC 27709."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"B.J.","family":"Baum","sequence":"additional","affiliation":[{"name":"Gene Therapy and Therapeutics Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD 20892."}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"179","published-online":{"date-parts":[[2007,11,1]]},"container-title":["Human Gene Therapy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1089\/hum.2007.072","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1089\/hum.2007.072","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,18]],"date-time":"2026-05-18T11:15:21Z","timestamp":1779102921000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.sagepub.com\/doi\/10.1089\/hum.2007.072"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2007,11]]},"references-count":0,"journal-issue":{"issue":"11","published-print":{"date-parts":[[2007,11]]}},"alternative-id":["10.1089\/hum.2007.072"],"URL":"https:\/\/doi.org\/10.1089\/hum.2007.072","relation":{},"ISSN":["1043-0342","1557-7422"],"issn-type":[{"value":"1043-0342","type":"print"},{"value":"1557-7422","type":"electronic"}],"subject":[],"published":{"date-parts":[[2007,11]]}}}