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Furthermore, patients typically prefer orally administered drugs to those that are given parenterally. We therefore investigated whether GI LNP administration to buccal, gastric, small intestinal, colonic, and rectal submucosal tissues could simultaneously circumvent parenteral administration while enhancing LNP delivery to previously inaccessible locations. We found that, in addition to local targeting, gastric LNP administration achieved an order of magnitude greater pancreas delivery in rodents than intravenous administration. Gastric dosing of glucagon-like peptide-1 mRNA also improved blood glucose regulation in mice compared with phosphate-buffered saline controls. Additionally, we found that buccal LNP administration targeted local and lymphatic tissues. Furthermore, dosing mice with ovalbumin mRNA resulted in equivalent immunoglobulin G blood titers to those of intramuscular delivery. These results suggest that GI administration can reprogram LNP biodistribution, expanding therapeutic opportunities for both local and systemic nucleic acid delivery.<\/jats:p>","DOI":"10.1021\/acsnano.5c18549","type":"journal-article","created":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T13:02:14Z","timestamp":1790600534000},"page":"26992-27001","source":"Crossref","is-referenced-by-count":0,"title":["Targeted Gastrointestinal\nDelivery of mRNA Lipid Nanoparticles\nEnables Systemic Vaccination and Glucagon-like Peptide-1 Metabolic\nTherapy"],"prefix":"10.1021","volume":"20","author":[{"given":"Abdulraouf M.","family":"Abbas","sequence":"first","affiliation":[{"name":"Emory University School of Medicine and Georgia Institute of Technology , , , ,","place":["Atlanta, Georgia, United States, 30332"]},{"name":"Emory Global Diabetes Research Center of the Woodruff Health Sciences Center and Emory University , , ,","place":["Atlanta, Georgia, United States, 30322"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ramy","family":"Ghanim","sequence":"additional","affiliation":[{"name":"Georgia Institute of Technology , , , ,","place":["Atlanta, Georgia, United States, 30332"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sebastian","family":"Rudden","sequence":"additional","affiliation":[{"name":"Emory University School of Medicine and Georgia Institute of Technology , , , ,","place":["Atlanta, Georgia, United States, 30332"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Schultz","sequence":"additional","affiliation":[{"name":"Georgia Institute of Technology , , , ,","place":["Atlanta, Georgia, United States, 30332"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9698-3934","authenticated-orcid":true,"given":"Bora","family":"Jang","sequence":"additional","affiliation":[{"name":"Emory University School of Medicine and Georgia Institute of Technology , , , ,","place":["Atlanta, Georgia, United States, 30332"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Avraham","family":"Shakked","sequence":"additional","affiliation":[{"name":"Emory University School of Medicine and Georgia Institute of Technology , , , ,","place":["Atlanta, Georgia, United States, 30332"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7937-2733","authenticated-orcid":true,"given":"Hyejin","family":"Kim","sequence":"additional","affiliation":[{"name":"Emory University School of Medicine and Georgia Institute of Technology , , , ,","place":["Atlanta, Georgia, United States, 30332"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James E.","family":"Dahlman","sequence":"additional","affiliation":[{"name":"Emory University School of Medicine and Georgia Institute of Technology , , , ,","place":["Atlanta, Georgia, United States, 30332"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4876-9751","authenticated-orcid":true,"given":"Alex","family":"Abramson","sequence":"additional","affiliation":[{"name":"Emory University School of Medicine and Georgia Institute of Technology , , , ,","place":["Atlanta, Georgia, United States, 30332"]},{"name":"Georgia Institute of Technology , , , ,","place":["Atlanta, Georgia, United States, 30332"]},{"name":"Institute for Matters and Systems, Georgia Institute of Technology , , , ,","place":["Atlanta, Georgia, United States, 30332"]},{"name":"Emory University School of Medicine , , , ,","place":["Atlanta, Georgia, United States, 30332"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2026,9,28]]},"reference":[{"issue":"9","key":"2026101310082530600_cit1","doi-asserted-by":"publisher","DOI":"10.1038\/s41392-024-02035-4","article-title":"Nucleic acid\ndrugs: recent progress and future perspectives","volume":"9","author":"Sun","year":"2024","journal-title":"Signal Transduction Targeted Ther."},{"key":"2026101310082530600_cit2","unstructured":"FDA.\n          .  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Biotechnol."},{"key":"2026101310082530600_cit23","doi-asserted-by":"publisher","first-page":"362","DOI":"10.1002\/jps.24182","article-title":"Microneedles for drug\ndelivery via the gastrointestinal tract","volume":"104","author":"Traverso","year":"2015","journal-title":"J.\nPharm. Sci."},{"key":"2026101310082530600_cit24","doi-asserted-by":"publisher","first-page":"481","DOI":"10.1038\/s41586-024-08202-5","article-title":"Cephalopod-inspired\njetting devices for gastrointestinal drug delivery","volume":"636","author":"Arrick","year":"2024","journal-title":"Nature"},{"key":"2026101310082530600_cit25","doi-asserted-by":"publisher","first-page":"219","DOI":"10.1007\/s10198-010-0224-8","article-title":"Utilities\nand disutilities\nfor attributes of injectable treatments for type 2 diabetes","volume":"12","author":"Boye","year":"2011","journal-title":"Eur. J. Health Econ."},{"key":"2026101310082530600_cit26","doi-asserted-by":"publisher","first-page":"1547","DOI":"10.2147\/PPA.S463354","article-title":"Preference\nfor a Novel Oral Alternative to Parenterally Administered Medications","volume":"18","author":"Myers","year":"2024","journal-title":"Patient Prefer. Adherence"},{"key":"2026101310082530600_cit27","doi-asserted-by":"publisher","first-page":"650","DOI":"10.1016\/j.jconrel.2024.01.008","article-title":"Electromechanical\nconvective drug delivery devices for overcoming diffusion barriers","volume":"366","author":"Park","year":"2024","journal-title":"J. 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Eng."},{"key":"2026101310082530600_cit31","doi-asserted-by":"publisher","DOI":"10.1002\/adma.202404830","article-title":"pH-Responsive \u03b2-Glucans-Complexed mRNA\nin LNPs as an Oral Vaccine for Enhancing Cancer Immunotherapy","volume":"36","author":"Luo","year":"2024","journal-title":"Adv. Mater."},{"key":"2026101310082530600_cit32","doi-asserted-by":"publisher","DOI":"10.1016\/j.biomaterials.2022.121707","article-title":"Oral delivery\nof IL-22 mRNA-loaded lipid nanoparticles targeting the injured intestinal\nmucosa: A novel therapeutic solution to treat ulcerative colitis","volume":"288","author":"Sung","year":"2022","journal-title":"Biomaterials"},{"key":"2026101310082530600_cit33","doi-asserted-by":"publisher","first-page":"P1","DOI":"10.1016\/j.omtn.2019.01.013","article-title":"Optimization of Lipid\nNanoparticles for Intramuscular Administration of mRNA Vaccines","volume":"15","author":"Hassett","year":"2019","journal-title":"Mol. 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Biol."},{"key":"2026101310082530600_cit42","doi-asserted-by":"publisher","first-page":"1331","DOI":"10.1080\/17435390.2022.2025467","article-title":"Nanoparticle-protein\ncorona complex: understanding multiple interactions between environmental\nfactors, corona formation, and biological activity","volume":"15","author":"Tomak","year":"2021","journal-title":"Nanotoxicology"}],"container-title":["ACS Nano"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pubs.acs.org\/doi\/pdf\/10.1021\/acsnano.5c18549","content-type":"application\/pdf","content-version":"vor","intended-application":"unspecified"},{"URL":"https:\/\/pubs.acs.org\/ancac3\/article-pdf\/20\/40\/26992\/68677529\/acsnano.5c18549.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/pubs.acs.org\/ancac3\/article-pdf\/20\/40\/26992\/68677529\/acsnano.5c18549.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T19:26:12Z","timestamp":1791919572000},"score":1,"resource":{"primary":{"URL":"https:\/\/pubs.acs.org\/ancac3\/article\/20\/40\/26992\/5440015\/Targeted-Gastrointestinal-Delivery-of-mRNA-Lipid"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,28]]},"references-count":38,"journal-issue":{"issue":"40","published-online":{"date-parts":[[2026,9,28]]},"published-print":{"date-parts":[[2026,10,13]]}},"URL":"https:\/\/doi.org\/10.1021\/acsnano.5c18549","relation":{},"ISSN":["1936-0851","1936-086X"],"issn-type":[{"value":"1936-0851","type":"print"},{"value":"1936-086X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,28]]}}}