{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,31]],"date-time":"2026-08-31T05:22:11Z","timestamp":1788153731333,"version":"build-2803163510"},"reference-count":42,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,8,30]],"date-time":"2026-08-30T00:00:00Z","timestamp":1788048000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,8,30]],"date-time":"2026-08-30T00:00:00Z","timestamp":1788048000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100000072","name":"National Institute of Dental and Craniofacial Research","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000072","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Oral Diseases"],"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Sj\u00f6gren's disease (SjD) is a systemic autoimmune disease characterized by dry mouth, dry eyes, and profound fatigue. Preclinical studies suggest that AQP1 gene expression in salivary glands corrects salivary hypofunction in preclinical and clinical studies of radiation\u2010induced xerostomia and improves salivary and lacrimal function in SjD mouse models.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Subjects and Methods<\/jats:title>\n                    <jats:p>To evaluate its therapeutic potential, we tested AQP1 gene therapy using labial salivary gland (LSG) biopsies from patients with SjD, non\u2010SjD, and healthy volunteer glands (HV).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Ex vivo cultures of LSG lobules were viable, responsive to stimulation, and transducible with an AAV2 vector encoding AQP1. AQP1 expression increased fluid secretion in most samples, with recovery reaching up to 80% of healthy volunteer levels. Baseline transcriptomic analysis identifies 94 genes that correlated with treatment response, with inflammatory and epithelial signature correlating with success and fibrotic signatures with non\u2010response. Histological evaluation confirmed greater fibrosis in non\u2010responding samples. Thus, treatment effects were functionally significant but transcriptionally minimal indicating targeted therapeutic action without altering homeostatic transcription.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>These findings demonstrate that AAV2\u2010AQP1 expression enhances fluid secretion in human LSGs and highlight fibrosis\u2010associated loss of glandular parenchyma as a major barrier to therapeutic efficacy.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/odi.70179","type":"journal-article","created":{"date-parts":[[2026,8,31]],"date-time":"2026-08-31T05:05:29Z","timestamp":1788152729000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["AQP1 Corrects Acinar Cells\u2019 Secretion Deficits in Sj\u00f6gren's Disease"],"prefix":"10.1111","author":[{"given":"Paola","family":"Perez","sequence":"first","affiliation":[{"name":"National Institute of Dental and Craniofacial Research, National Institutes of Health  Bethesda Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4961-018X","authenticated-orcid":false,"given":"Blake M.","family":"Warner","sequence":"additional","affiliation":[{"name":"National Institute of Dental and Craniofacial Research, National Institutes of Health  Bethesda Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Youngmi","family":"Ji","sequence":"additional","affiliation":[{"name":"National Institute of Dental and Craniofacial Research, National Institutes of Health  Bethesda Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sandra","family":"Afione","sequence":"additional","affiliation":[{"name":"National Institute of Dental and Craniofacial Research, National Institutes of Health  Bethesda Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas J. F.","family":"Pranzatelli","sequence":"additional","affiliation":[{"name":"National Institute of Dental and Craniofacial Research, National Institutes of Health  Bethesda Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Margaret E.","family":"Beach","sequence":"additional","affiliation":[{"name":"National Institute of Dental and Craniofacial Research, National Institutes of Health  Bethesda Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zohreh","family":"Khavandgar","sequence":"additional","affiliation":[{"name":"National Institute of Dental and Craniofacial Research, National Institutes of Health  Bethesda Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Margie","family":"Grisius","sequence":"additional","affiliation":[{"name":"National Institute of Dental and Craniofacial Research, National Institutes of Health  Bethesda Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eileen","family":"Pelayo","sequence":"additional","affiliation":[{"name":"National Institute of Dental and Craniofacial Research, National Institutes of Health  Bethesda Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Martin","sequence":"additional","affiliation":[{"name":"National Institute of Dental and Craniofacial Research, National Institutes of Health  Bethesda Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"NIDCD\/NIDCR Genomics and Computational Biology Core","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alan N.","family":"Baer","sequence":"additional","affiliation":[{"name":"National Institute of Dental and Craniofacial Research, National Institutes of Health  Bethesda Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John A.","family":"Chiorini","sequence":"additional","affiliation":[{"name":"National Institute of Dental and Craniofacial Research, National Institutes of Health  Bethesda Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,8,30]]},"reference":[{"issue":"7","key":"e_1_2_11_2_1","doi-asserted-by":"crossref","first-page":"1242","DOI":"10.1016\/j.ophtha.2010.12.016","article-title":"Treatment of Sjogren's Syndrome\u2010Associated Dry Eye an Evidence\u2010Based Review","volume":"118","author":"Akpek E. 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