{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,1,15]],"date-time":"2026-01-15T20:49:34Z","timestamp":1768510174186,"version":"3.49.0"},"posted":{"date-parts":[[2024,1,23]]},"group-title":"Molecular Biology","reference-count":41,"publisher":"openRxiv","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2024,1,23]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                <jats:p>\n                  A fundamental challenge for cystic fibrosis (CF) gene therapy is ensuring sufficient ransduction of airway epithelia to achieve therapeutic correction. Hypertonic saline (HTS) is frequently administered to people with CF to enhance mucus clearance. HTS transiently disrupts epithelial cell tight unctions, but its ability to improve gene transfer has not been investigated. Here we asked if increasing the concentration of NaCl enhances the transduction efficiency of three gene therapy vectors: adenovirus, AAV, and lentiviral vectors. Vectors formulated with 3-7% NaCl exhibited markedly increased transduction for all hree platforms, leading to anion channel correction in primary cultures of human CF epithelial cells and enhanced gene transfer in mouse and pig airways\n                  <jats:italic>in vivo<\/jats:italic>\n                  . The mechanism of transduction enhancement nvolved tonicity but not osmolarity or pH. Formulating vectors with a high ionic strength solution is a simple strategy to greatly enhance efficacy and immediately improve preclinical or clinical applications.\n                <\/jats:p>\n                <jats:sec>\n                  <jats:title>One Sentence Summary<\/jats:title>\n                  <jats:p>Formulating adenoviral, AAV, and lentiviral vectors with hypertonic saline remarkably enhances lung gene transfer. (114 characters, including spaces)<\/jats:p>\n                <\/jats:sec>","DOI":"10.1101\/2024.01.22.576687","type":"posted-content","created":{"date-parts":[[2024,1,23]],"date-time":"2024-01-23T08:15:12Z","timestamp":1705997712000},"source":"Crossref","is-referenced-by-count":0,"title":["High ionic strength vector formulations enhance gene transfer to airway epithelia"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2717-9138","authenticated-orcid":false,"given":"Ashley L.","family":"Cooney","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0149-2727","authenticated-orcid":false,"given":"Laura Marquez","family":"Loza","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kenan","family":"Najdawi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christian M.","family":"Brommel","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4067-577X","authenticated-orcid":false,"suffix":"Jr.","given":"Paul B.","family":"McCray","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9746-966X","authenticated-orcid":false,"given":"Patrick L.","family":"Sinn","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"54368","reference":[{"key":"2024012620301027000_2024.01.22.576687v1.1","doi-asserted-by":"crossref","unstructured":"Cooney, A.L. , et al. 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