{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,29]],"date-time":"2026-10-29T02:41:35Z","timestamp":1793241695879,"version":"4.5.0"},"reference-count":71,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2025,12,14]],"date-time":"2025-12-14T00:00:00Z","timestamp":1765670400000},"content-version":"vor","delay-in-days":13,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,12,1]],"date-time":"2025-12-01T00:00:00Z","timestamp":1764547200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J of Extracellular Vesicle"],"published-print":{"date-parts":[[2025,12]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Extracellular vesicles (EVs) are an attractive delivery vehicle with biological activity, intrinsic homing, low immunogenicity, and engineerability; however, challenges remain regarding loading and functional delivery of mRNA. Here, we developed a novel approach to load mRNA through low pH\u2010induced fusion of EVs with lipid nanoparticles (LNPs) to generate hybrid EVs (HEVs). Conventional characterization showed that HEVs preserved classical features of EVs. Single particle analysis revealed successful loading of mRNA and incorporation of LNP components into HEVs. The combined properties from EV and LNP contributed to the excellent cell tolerability of HEV, overcoming dose\u2010limit toxicity, and functional delivery of mRNA by HEV. We further elucidated the mechanism of HEV\u2010mediated intracellular delivery of mRNA. Our results showed that in contrast to source EVs, HEVs were capable of inducing endosomal escape, facilitating intracellular delivery of mRNA. Furthermore, HEVs functionally delivered mRNA\n                    <jats:italic>in<\/jats:italic>\n                    <jats:italic>vivo<\/jats:italic>\n                    and displayed extrahepatic delivery capacity with predominant functional distribution in spleen. Our results suggest HEVs as a promising EV\u2010based delivery platform for mRNA delivery.\n                  <\/jats:p>","DOI":"10.1002\/jev2.70201","type":"journal-article","created":{"date-parts":[[2025,12,15]],"date-time":"2025-12-15T07:27:24Z","timestamp":1765783644000},"source":"Crossref","is-referenced-by-count":22,"title":["Hybrid Extracellular Vesicles for Efficient Loading and Functional Delivery of mRNA"],"prefix":"10.1002","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9779-5089","authenticated-orcid":false,"given":"Xiaoqin","family":"Wang","sequence":"first","affiliation":[{"name":"Discovery Biology, Discovery Sciences BioPharmaceuticals R&amp;D, AstraZeneca  Gothenburg Sweden"},{"name":"Advanced Drug Delivery, Pharmaceutical Sciences BioPharmaceuticals R&amp;D, AstraZeneca  Gothenburg Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael J.","family":"Munson","sequence":"additional","affiliation":[{"name":"Advanced Drug Delivery, Pharmaceutical Sciences BioPharmaceuticals R&amp;D, AstraZeneca  Gothenburg Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kristina","family":"Friis","sequence":"additional","affiliation":[{"name":"Advanced Drug Delivery, Pharmaceutical Sciences BioPharmaceuticals R&amp;D, AstraZeneca  Gothenburg Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Marzeda","sequence":"additional","affiliation":[{"name":"Discovery Bioanalysis, Clinical Pharmacology and Safety Sciences BioPharmaceuticals R&amp;D, AstraZeneca  Gothenburg Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andreia M.","family":"Silva","sequence":"additional","affiliation":[{"name":"Discovery Biology, Discovery Sciences BioPharmaceuticals R&amp;D, AstraZeneca  Gothenburg Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Franziska","family":"Kohl","sequence":"additional","affiliation":[{"name":"Genomic Research, Discovery Sciences BioPharmaceuticals R&amp;D, AstraZeneca  Gothenburg Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leif","family":"Hultin","sequence":"additional","affiliation":[{"name":"Imaging Sciences, Clinical Pharmacology and Safety Sciences BioPharmaceuticals R&amp;D, AstraZeneca  Gothenburg Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raymond M.","family":"Schiffelers","sequence":"additional","affiliation":[{"name":"CDL Research University Medical Center Utrecht  Utrecht the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Niek","family":"Dekker","sequence":"additional","affiliation":[{"name":"Discovery Biology, Discovery Sciences BioPharmaceuticals R&amp;D, AstraZeneca  Gothenburg Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,12,14]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/anie.202310395"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/jev2.12130"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/jev2.12079"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/advs.202404860"},{"key":"e_1_2_9_6_1","unstructured":"Beer J. D.2016.Hybridosomes Compositions Comprising the Same Processes for Their Production and Uses Thereof. 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