{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,20]],"date-time":"2026-09-20T00:52:12Z","timestamp":1789865532330,"version":"4.0.1"},"reference-count":37,"publisher":"Springer Science and Business Media LLC","issue":"9","license":[{"start":{"date-parts":[[2015,4,14]],"date-time":"2015-04-14T00:00:00Z","timestamp":1428969600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.springer.com\/tdm"},{"start":{"date-parts":[[2015,4,14]],"date-time":"2015-04-14T00:00:00Z","timestamp":1428969600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.springer.com\/tdm"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Gene Ther"],"published-print":{"date-parts":[[2015,9]]},"DOI":"10.1038\/gt.2015.36","type":"journal-article","created":{"date-parts":[[2015,4,14]],"date-time":"2015-04-14T14:42:44Z","timestamp":1429022564000},"page":"739-749","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":47,"title":["Ultrasound-assisted nonviral gene transfer of AQP1 to the irradiated minipig parotid gland restores fluid secretion"],"prefix":"10.1038","volume":"22","author":[{"given":"Z","family":"Wang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"L","family":"Zourelias","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"P C","family":"Edwards","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M","family":"Trombetta","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M J","family":"Passineau","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2015,4,14]]},"reference":[{"key":"BFgt201536_CR1","doi-asserted-by":"publisher","first-page":"277","DOI":"10.3322\/caac.20073","volume":"60","author":"A Jemal","year":"2010","unstructured":"Jemal A, Siegel R, Xu J, Ward E . Cancer statistics, 2010. CA Cancer J Clin 2010; 60: 277\u2013300.","journal-title":"CA Cancer J Clin"},{"key":"BFgt201536_CR2","unstructured":"NCI Statistics. Available at http:\/\/www.cancer.gov\/statistics."},{"key":"BFgt201536_CR3","doi-asserted-by":"publisher","first-page":"127","DOI":"10.1093\/jnci\/dju127","volume":"106","author":"BS Chera","year":"2014","unstructured":"Chera BS, Eisbruch A, Murphy BA, Ridge JA, Gavin P, Reeve BB et al. Recommended patient-reported core set of symptoms to measure in head and neck cancer treatment trials. J Natl Cancer Inst 2014; 106: 127.","journal-title":"J Natl Cancer Inst"},{"key":"BFgt201536_CR4","doi-asserted-by":"publisher","first-page":"19403","DOI":"10.1073\/pnas.1210662109","volume":"109","author":"BJ Baum","year":"2012","unstructured":"Baum BJ, Alevizos I, Zheng C, Cotrim AP, Liu S, McCullagh L et al. Early responses to adenoviral-mediated transfer of the aquaporin-1 cDNA for radiation-induced salivary hypofunction. Proc Natl Acad Sci USA 2012; 109: 19403\u201319407.","journal-title":"Proc Natl Acad Sci USA"},{"key":"BFgt201536_CR5","doi-asserted-by":"publisher","first-page":"1071","DOI":"10.1016\/j.bbamem.2005.11.006","volume":"1758","author":"BJ Baum","year":"2006","unstructured":"Baum BJ, Zheng C, Cotrim AP, Goldsmith CM, Atkinson JC, Brahim JS et al. Transfer of the AQP1 cDNA for the correction of radiation-induced salivary hypofunction. Biochim Biophys Acta 2006; 1758: 1071\u20131077.","journal-title":"Biochim Biophys Acta"},{"key":"BFgt201536_CR6","doi-asserted-by":"publisher","first-page":"12816","DOI":"10.1073\/pnas.96.22.12816","volume":"96","author":"N Morral","year":"1999","unstructured":"Morral N, O'Neal W, Rice K, Leland M, Kaplan J, Piedra PA et al. Administration of helper-dependent adenoviral vectors and sequential delivery of different vector serotype for long-term liver-directed gene transfer in baboons. Proc Natl Acad Sci USA 1999; 96: 12816\u201312821.","journal-title":"Proc Natl Acad Sci USA"},{"key":"BFgt201536_CR7","doi-asserted-by":"publisher","first-page":"754","DOI":"10.1038\/mt.2009.312","volume":"18","author":"A Fontanellas","year":"2010","unstructured":"Fontanellas A, Hervas-Stubbs S, Mauleon I, Dubrot J, Mancheno U, Collantes M et al. Intensive pharmacological immunosuppression allows for repetitive liver gene transfer with recombinant adenovirus in nonhuman primates. Mol Ther 2010; 18: 754\u2013765.","journal-title":"Mol Ther"},{"key":"BFgt201536_CR8","doi-asserted-by":"publisher","first-page":"1318","DOI":"10.1038\/gt.2010.86","volume":"17","author":"MJ Passineau","year":"2010","unstructured":"Passineau MJ, Zourelias L, Machen L, Edwards PC, Benza RL . Ultrasound-assisted non-viral gene transfer to the salivary glands. Gene Therapy 2010; 17: 1318\u20131324.","journal-title":"Gene Therapy"},{"key":"BFgt201536_CR9","doi-asserted-by":"publisher","first-page":"14007","DOI":"10.1038\/mtm.2014.7","volume":"1","author":"R Geguchadze","year":"2014","unstructured":"Geguchadze R, Wang Z, Zourelias L, Perez-Riveros P, Edwards P, Machen L et al. Proteomic profiling of salivary gland after nonviral gene transfer mediated by conventional plasmids and minicircles. Mol Ther Methods Clin Dev 2014; 1: 14007.","journal-title":"Mol Ther Methods Clin Dev"},{"key":"BFgt201536_CR10","unstructured":"Definity Package Insert. Available atm http:\/\/www.definityimaging.com\/pdf\/DEFINITY Prescribing information 515987-0413.pdf."},{"key":"BFgt201536_CR11","doi-asserted-by":"publisher","first-page":"4","DOI":"10.1016\/j.oraloncology.2009.09.004","volume":"46","author":"BJ Baum","year":"2010","unstructured":"Baum BJ, Zheng C, Alevizos I, Cotrim AP, Liu S, McCullagh L et al. Development of a gene transfer-based treatment for radiation-induced salivary hypofunction. Oral Oncol 2010; 46: 4\u20138.","journal-title":"Oral Oncol"},{"key":"BFgt201536_CR12","doi-asserted-by":"publisher","first-page":"3212","DOI":"10.1074\/jbc.M309639200","volume":"279","author":"SV Markova","year":"2004","unstructured":"Markova SV, Golz S, Frank LA, Kalthof B, Vysotski ES . Cloning and expression of cDNA for a luciferase from the marine copepod Metridia longa. A novel secreted bioluminescent reporter enzyme. J Biol Chem 2004; 279: 3212\u20133217.","journal-title":"J Biol Chem"},{"key":"BFgt201536_CR13","doi-asserted-by":"publisher","first-page":"3268","DOI":"10.1073\/pnas.94.7.3268","volume":"94","author":"C Delporte","year":"1997","unstructured":"Delporte C, O'Connell BC, He X, Lancaster HE, O'Connell AC, Agre P et al. Increased fluid secretion after adenoviral-mediated transfer of the aquaporin-1 cDNA to irradiated rat salivary glands. Proc Natl Acad Sci USA 1997; 94: 3268\u20133273.","journal-title":"Proc Natl Acad Sci USA"},{"key":"BFgt201536_CR14","doi-asserted-by":"publisher","first-page":"444","DOI":"10.1016\/j.ymthe.2004.11.007","volume":"11","author":"Z Shan","year":"2005","unstructured":"Shan Z, Li J, Zheng C, Liu X, Fan Z, Zhang C et al. Increased fluid secretion after adenoviral-mediated transfer of the human aquaporin-1 cDNA to irradiated miniature pig parotid glands. Mol Ther 2005; 11: 444\u2013451.","journal-title":"Mol Ther"},{"key":"BFgt201536_CR15","doi-asserted-by":"publisher","first-page":"385","DOI":"10.1080\/01926230600815189","volume":"34","author":"S Elmore","year":"2006","unstructured":"Elmore S, Lanning L, Allison N, Vallant M, Nyska A . The transduction of rat submandibular glands by an adenoviral vector carrying the human growth hormone gene is associated with limited and reversible changes at the infusion site. Toxicol Pathol 2006; 34: 385\u2013392.","journal-title":"Toxicol Pathol"},{"key":"BFgt201536_CR16","doi-asserted-by":"publisher","first-page":"137","DOI":"10.1111\/j.1601-0825.2005.01170.x","volume":"12","author":"C Zheng","year":"2006","unstructured":"Zheng C, Voutetakis A, Kok MR, Goldsmith CM, Smith GB, Elmore S et al. Toxicity and biodistribution of a first-generation recombinant adenoviral vector, in the presence of hydroxychloroquine, following retroductal delivery to a single rat submandibular gland. Oral Dis 2006; 12: 137\u2013144.","journal-title":"Oral Dis"},{"key":"BFgt201536_CR17","doi-asserted-by":"publisher","first-page":"34","DOI":"10.1111\/j.1600-0714.1998.tb02088.x","volume":"27","author":"C Delporte","year":"1998","unstructured":"Delporte C, Miller G, Kagami H, Lillibridge CD, O'Connell BC, Atkinson JC et al. Safety of salivary gland-administered replication-deficient recombinant adenovirus in rats. J Oral Pathol Med 1998; 27: 34\u201338.","journal-title":"J Oral Pathol Med"},{"key":"BFgt201536_CR18","doi-asserted-by":"publisher","first-page":"1085","DOI":"10.1089\/hum.1996.7.9-1085","volume":"7","author":"MR Adesanya","year":"1996","unstructured":"Adesanya MR, Redman RS, Baum BJ, O'Connell BC . Immediate inflammatory responses to adenovirus-mediated gene transfer in rat salivary glands. Hum Gene Ther 1996; 7: 1085\u20131093.","journal-title":"Hum Gene Ther"},{"key":"BFgt201536_CR19","doi-asserted-by":"publisher","first-page":"1122","DOI":"10.1089\/hum.2006.17.1122","volume":"17","author":"C Zheng","year":"2006","unstructured":"Zheng C, Goldsmith CM, Mineshiba F, Chiorini JA, Kerr A, Wenk ML et al. Toxicity and biodistribution of a first-generation recombinant adenoviral vector, encoding aquaporin-1, after retroductal delivery to a single rat submandibular gland. Hum Gene Ther 2006; 17: 1122\u20131133.","journal-title":"Hum Gene Ther"},{"key":"BFgt201536_CR20","first-page":"1524","volume":"1840","author":"C Delporte","year":"2013","unstructured":"Delporte C . Role of aquaporins in saliva secretion. OA Biochem 2013; 1840: 1524\u20131532.","journal-title":"OA Biochem"},{"key":"BFgt201536_CR21","doi-asserted-by":"crossref","unstructured":"Wong DT, Salivaomics J . Am Dent Assoc 2012; 143: 19S\u201324S.","DOI":"10.14219\/jada.archive.2012.0339"},{"key":"BFgt201536_CR22","first-page":"G1146","volume":"266","author":"A Mastrangeli","year":"1994","unstructured":"Mastrangeli A, O'Connell B, Aladib W, Fox PC, Baum BJ . Crystal RG. Direct in vivo adenovirus-mediated gene transfer to salivary glands. Am J Physiol 1994; 266: G1146\u2013G1155.","journal-title":"Am J Physiol"},{"key":"BFgt201536_CR23","doi-asserted-by":"publisher","first-page":"983","DOI":"10.1016\/j.ijrobp.2010.06.052","volume":"78","author":"A Vissink","year":"2010","unstructured":"Vissink A, Mitchell JB, Baum BJ, Limesand KH, Jensen SB, Fox PC et al. Clinical management of salivary gland hypofunction and xerostomia in head-and-neck cancer patients: successes and barriers. Int J Radiat Oncol Biol Phys 2010; 78: 983\u2013991.","journal-title":"Int J Radiat Oncol Biol Phys"},{"key":"BFgt201536_CR24","doi-asserted-by":"publisher","first-page":"1510","DOI":"10.1016\/j.ijrobp.2005.04.029","volume":"62","author":"J Li","year":"2005","unstructured":"Li J, Shan Z, Ou G, Liu X, Zhang C, Baum BJ et al. Structural and functional characteristics of irradiation damage to parotid glands in the miniature pig. Int J Radiat Oncol Biol Phys 2005; 62: 1510\u20131516.","journal-title":"Int J Radiat Oncol Biol Phys"},{"key":"BFgt201536_CR25","doi-asserted-by":"publisher","first-page":"1267","DOI":"10.1152\/jn.01115.2007","volume":"99","author":"T Suwabe","year":"2008","unstructured":"Suwabe T, Fukami H, Bradley RM . Synaptic responses of neurons controlling the parotid and von Ebner salivary glands in rats to stimulation of the solitary nucleus and tract. J Neurophysiol 2008; 99: 1267\u20131273.","journal-title":"J Neurophysiol"},{"key":"BFgt201536_CR26","doi-asserted-by":"publisher","first-page":"155","DOI":"10.1016\/j.jns.2011.06.016","volume":"308","author":"EJ Kasarskis","year":"2011","unstructured":"Kasarskis EJ, Hodskins J St, Clair WH . Unilateral parotid electron beam radiotherapy as palliative treatment for sialorrhea in amyotrophic lateral sclerosis. J Neurol Sci 2011; 308: 155\u2013157.","journal-title":"J Neurol Sci"},{"key":"BFgt201536_CR27","doi-asserted-by":"publisher","first-page":"122","DOI":"10.1186\/1479-5876-10-122","volume":"10","author":"C Unzu","year":"2012","unstructured":"Unzu C, Hervas-Stubbs S, Sampedro A, Mauleon I, Mancheno U, Alfaro C et al. Transient and intensive pharmacological immunosuppression fails to improve AAV-based liver gene transfer in non-human primates. J Transl Med 2012; 10: 122.","journal-title":"J Transl Med"},{"key":"BFgt201536_CR28","doi-asserted-by":"publisher","first-page":"78","DOI":"10.1038\/gt.2011.64","volume":"19","author":"JH McIntosh","year":"2012","unstructured":"McIntosh JH, Cochrane M, Cobbold S, Waldmann H, Nathwani SA, Davidoff AM et al. Successful attenuation of humoral immunity to viral capsid and transgenic protein following AAV-mediated gene transfer with a non-depleting CD4 antibody and cyclosporine. Gene Therapy 2012; 19: 78\u201385.","journal-title":"Gene Therapy"},{"key":"BFgt201536_CR29","doi-asserted-by":"publisher","first-page":"361","DOI":"10.2174\/1566523054064986","volume":"5","author":"TR Flotte","year":"2005","unstructured":"Flotte TR . Recent developments in recombinant AAV-mediated gene therapy for lung diseases. Curr Gene Ther 2005; 5: 361\u2013366.","journal-title":"Curr Gene Ther"},{"key":"BFgt201536_CR30","doi-asserted-by":"publisher","first-page":"432","DOI":"10.1002\/jgm.678","volume":"7","author":"MR Kok","year":"2005","unstructured":"Kok MR, Voutetakis A, Yamano S, Wang J, Cotrim A, Katano H et al. Immune responses following salivary gland administration of recombinant adeno-associated virus serotype 2 vectors. J Gene Med 2005; 7: 432\u2013441.","journal-title":"J Gene Med"},{"key":"BFgt201536_CR31","doi-asserted-by":"publisher","first-page":"1016","DOI":"10.1177\/0022034510380414","volume":"89","author":"JA Loo","year":"2010","unstructured":"Loo JA, Yan W, Ramachandran P, Wong DT . Comparative human salivary and plasma proteomes. J Dent Res 2010; 89: 1016\u20131023.","journal-title":"J Dent Res"},{"key":"BFgt201536_CR32","doi-asserted-by":"publisher","first-page":"131","DOI":"10.1038\/mt.2012.244","volume":"21","author":"LE Gracey Maniar","year":"2013","unstructured":"Gracey Maniar LE, Maniar JM, Chen ZY, Lu J, Fire AZ, Kay MA . Minicircle DNA vectors achieve sustained expression reflected by active chromatin and transcriptional level. Mol Ther 2013; 21: 131\u2013138.","journal-title":"Mol Ther"},{"key":"BFgt201536_CR33","doi-asserted-by":"publisher","first-page":"954","DOI":"10.1038\/mt.2013.33","volume":"21","author":"J Lu","year":"2013","unstructured":"Lu J, Zhang F, Kay MA . A mini-intronic plasmid (MIP): a novel robust transgene expression vector in vivo and in vitro. Mol Ther 2013; 21: 954\u2013963.","journal-title":"Mol Ther"},{"key":"BFgt201536_CR34","doi-asserted-by":"publisher","first-page":"548","DOI":"10.1038\/sj.mt.6300399","volume":"16","author":"ZY Chen","year":"2008","unstructured":"Chen ZY, Riu E, He CY, Xu H, Kay MA . Silencing of episomal transgene expression in liver by plasmid bacterial backbone DNA is independent of CpG methylation. Mol Ther 2008; 16: 548\u2013556.","journal-title":"Mol Ther"},{"key":"BFgt201536_CR35","doi-asserted-by":"publisher","first-page":"6969","DOI":"10.1128\/JVI.75.15.6969-6976.2001","volume":"75","author":"H Nakai","year":"2001","unstructured":"Nakai H, Yant SR, Storm TA, Fuess S, Meuse L, Kay MA . Extrachromosomal recombinant adeno-associated virus vector genomes are primarily responsible for stable liver transduction in vivo. J Virol 2001; 75: 6969\u20136976.","journal-title":"J Virol"},{"key":"BFgt201536_CR36","doi-asserted-by":"publisher","first-page":"2111","DOI":"10.1038\/mt.2012.65","volume":"20","author":"J Lu","year":"2012","unstructured":"Lu J, Zhang F, Xu S, Fire AZ, Kay MA . The extragenic spacer length between the 5' and 3' ends of the transgene expression cassette affects transgene silencing from plasmid-based vectors. Mol Ther 2012; 20: 2111\u20132119.","journal-title":"Mol Ther"},{"key":"BFgt201536_CR37","doi-asserted-by":"publisher","first-page":"2262","DOI":"10.1074\/mcp.M110.000034","volume":"9","author":"C Wu","year":"2010","unstructured":"Wu C, Liu T, Chen W, Oka S, Fu C, Jain MR et al. Redox regulatory mechanism of transnitrosylation by thioredoxin. Mol Cell Proteomics 2010; 9: 2262\u20132275.","journal-title":"Mol Cell Proteomics"}],"container-title":["Gene Therapy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/gt201536.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/gt201536","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/gt201536.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,3,29]],"date-time":"2022-03-29T13:34:52Z","timestamp":1648560892000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/gt201536"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2015,4,14]]},"references-count":37,"journal-issue":{"issue":"9","published-print":{"date-parts":[[2015,9]]}},"alternative-id":["BFgt201536"],"URL":"https:\/\/doi.org\/10.1038\/gt.2015.36","relation":{},"ISSN":["0969-7128","1476-5462"],"issn-type":[{"value":"0969-7128","type":"print"},{"value":"1476-5462","type":"electronic"}],"subject":[],"published":{"date-parts":[[2015,4,14]]},"assertion":[{"value":"21 December 2014","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"17 March 2015","order":2,"name":"revised","label":"Revised","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"31 March 2015","order":3,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"14 April 2015","order":4,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no conflict of interest.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}]}}