{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,7]],"date-time":"2026-09-07T01:36:10Z","timestamp":1788744970665,"version":"build-2803163510"},"reference-count":51,"publisher":"SAGE Publications","issue":"2","license":[{"start":{"date-parts":[[2023,3,30]],"date-time":"2023-03-30T00:00:00Z","timestamp":1680134400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2023,3,30]],"date-time":"2023-03-30T00:00:00Z","timestamp":1680134400000},"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":["Nucleic Acid Therapeutics"],"published-print":{"date-parts":[[2023,4,1]]},"abstract":"<jats:p>\n                    Acute respiratory distress syndrome (ARDS), a rapid onset inflammatory lung disease with no effective specific therapy, typically has pathogenic etiology termed pneumonia. In previous studies nuclear factor-\u03baB (NF-\u03baB) inhibitor \u03b1 super-repressor (I\u03baB\u03b1-SR) and extracellular superoxide dismutase 3 (SOD3) reduced pneumonia severity when prophylactically delivered by viral vector. In this study, mRNA coding for green fluorescent protein, I\u03baB\u03b1-SR, or SOD3 was complexed with cationic lipid, passed through a vibrating mesh nebulizer, and delivered to cell culture or directly to rats undergoing\n                    <jats:italic toggle=\"yes\">Escherichia coli<\/jats:italic>\n                    pneumonia. Injury level was then assessed at 48\u2009h.\n                    <jats:italic toggle=\"yes\">In vitro<\/jats:italic>\n                    , expression was observed as early as 4\u2009h in lung epithelial cells. I\u03baB\u03b1-SR and wild-type I\u03baB\u03b1 mRNAs attenuated inflammatory markers, while SOD3 mRNA induced protective and antioxidant effects. In rat\n                    <jats:italic toggle=\"yes\">E. coli<\/jats:italic>\n                    pneumonia, I\u03baB\u03b1-SR mRNA reduced arterial carbon dioxide (pCO2) and reduced lung wet\/dry ratio. SOD3 mRNA improved static lung compliance and alveolar-arterial oxygen gradient (AaDO2) and decreased bronchoalveolar lavage (BAL) bacteria load. White cell infiltration and inflammatory cytokine concentrations in BAL and serum were reduced by both mRNA treatments compared to scrambled mRNA controls. These findings indicate nebulized mRNA therapeutics are a promising approach to ARDS therapy, with rapid expression of protein and observable amelioration of pneumonia symptoms.\n                  <\/jats:p>","DOI":"10.1089\/nat.2022.0049","type":"journal-article","created":{"date-parts":[[2023,2,22]],"date-time":"2023-02-22T10:01:12Z","timestamp":1677060072000},"page":"148-158","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":11,"title":["Aerosolized Pulmonary Delivery of mRNA Constructs Attenuates Severity of\n                    <i>Escherichia coli<\/i>\n                    Pneumonia in the Rat"],"prefix":"10.1177","volume":"33","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5474-5388","authenticated-orcid":false,"given":"Sean D.","family":"Mccarthy","sequence":"first","affiliation":[{"name":"C\u00daRAM and Regenerative Medicine Institute, University of Galway, Galway, Ireland."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher B.","family":"Rohde","sequence":"additional","affiliation":[{"name":"Factor Bioscience Ltd., Cambridge, Massachusetts, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matt","family":"Angel","sequence":"additional","affiliation":[{"name":"Factor Bioscience Ltd., Cambridge, Massachusetts, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claire H.","family":"Masterson","sequence":"additional","affiliation":[{"name":"C\u00daRAM and Regenerative Medicine Institute, University of Galway, Galway, Ireland."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3164-1607","authenticated-orcid":false,"given":"Ronan","family":"Macloughlin","sequence":"additional","affiliation":[{"name":"Aerogen Ltd., Galway, Ireland."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan","family":"Fandi\u00f1o","sequence":"additional","affiliation":[{"name":"C\u00daRAM and Regenerative Medicine Institute, University of Galway, Galway, Ireland."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"H\u00e9ctor E.","family":"Gonz\u00e1lez","sequence":"additional","affiliation":[{"name":"C\u00daRAM and Regenerative Medicine Institute, University of Galway, Galway, Ireland."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Declan","family":"Byrnes","sequence":"additional","affiliation":[{"name":"C\u00daRAM and Regenerative Medicine Institute, University of Galway, Galway, Ireland."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John G.","family":"Laffey","sequence":"additional","affiliation":[{"name":"C\u00daRAM and Regenerative Medicine Institute, University of Galway, Galway, Ireland."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"O'toole","sequence":"additional","affiliation":[{"name":"C\u00daRAM and Regenerative Medicine Institute, University of Galway, Galway, Ireland."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2023,3,30]]},"reference":[{"key":"e_1_3_4_2_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00134-020-06141-z"},{"key":"e_1_3_4_3_2","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2016.0291"},{"key":"e_1_3_4_4_2","first-page":"2526","article-title":"Acute respiratory distress syndrome: The Berlin Definition","volume":"307","author":"Ranieri VM","year":"2012","unstructured":"Ranieri VM, , Rubenfeld GD, , Thompson BT, , Ferguson ND, , Caldwell E, , Fan E, , Camporota L, and Slutsky AS. 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