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Compared with lipid nanoparticles (LNPs), native or surface-modified EVs may have favorable immunogenicity and biodistribution profiles. However, when administered intravenously (IV), EVs are rapidly cleared and accumulate mostly in the liver and spleen. With the goal of modifying EV biodistribution, we engineered EVs to display the human endogenous retrovirus (HERV) envelope glycoprotein Syncytin-1, an SLC1A5-binding fusogenic viral protein essential for syncytiotrophoblast formation in pregnancy. Here, we comprehensively characterize engineered Syncytin-1+ EVs, examine their interactions with cells\n                  <jats:italic>in vitro<\/jats:italic>\n                  , and assay biodistribution, immunogenicity, and pharmacokinetics\n                  <jats:italic>ex vivo<\/jats:italic>\n                  and\n                  <jats:italic>in vivo<\/jats:italic>\n                  in non-human primates. IV-administered Syncytin-1+ EVs are well tolerated, persist in the blood stream, and have altered organ biodistribution compared with unmodified EVs, suggesting therapeutic potential of Syncytin-1+ EVs at specific sites.\n                <\/jats:p>","DOI":"10.64898\/2026.04.30.722014","type":"posted-content","created":{"date-parts":[[2026,5,5]],"date-time":"2026-05-05T22:00:22Z","timestamp":1778018422000},"source":"Crossref","is-referenced-by-count":0,"title":["Human endogenous retrovirus envelope proteins alter extracellular vesicle cellular interactions and biodistribution"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1821-7334","authenticated-orcid":false,"given":"Zach","family":"Troyer","sequence":"first","affiliation":[{"name":"Department of Molecular and Comparative Pathobiology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, 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Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-7850-804X","authenticated-orcid":false,"given":"Taekyung","family":"Ryu","sequence":"additional","affiliation":[{"name":"Center for Proteomics Discovery, Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3622-2938","authenticated-orcid":false,"given":"Chan-Hyun","family":"Na","sequence":"additional","affiliation":[{"name":"Center for Proteomics Discovery, Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0517-6131","authenticated-orcid":false,"given":"Natalie","family":"Castell","sequence":"additional","affiliation":[{"name":"Department of Comparative Medicine, Division of Discovery Science, The University of Texas MD Anderson Cancer Center, Bastrop, Texas, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-0031-6898","authenticated-orcid":false,"given":"Isabella","family":"Baumann","sequence":"additional","affiliation":[{"name":"Department of Molecular and Comparative Pathobiology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-7220-5254","authenticated-orcid":false,"given":"Suzanne","family":"Queen","sequence":"additional","affiliation":[{"name":"Department of Molecular and Comparative Pathobiology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6283-4727","authenticated-orcid":false,"given":"Joseph L.","family":"Mankowski","sequence":"additional","affiliation":[{"name":"Department of 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Failure to detect functional transfer of active K-Ras protein from extracellular vesicles into recipient cells in culture. 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K. , Shen, T.-L. & Lim, S. K . Engineered EVs with pathogen proteins: promising vaccine alternatives to LNP-mRNA vaccines. 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Engineering of dendritic cell bispecific extracellular vesicles for tumor-targeting immunotherapy. Cell Reports 42, (2023).","DOI":"10.1016\/j.celrep.2023.113138"},{"key":"2026050710300743000_2026.04.30.722014v1.24","doi-asserted-by":"crossref","first-page":"2305891","DOI":"10.1002\/advs.202305891","article-title":"Truncated PD1 Engineered Gas-Producing Extracellular Vesicles for Ultrasound Imaging and Subsequent Degradation of PDL1 in Tumor Cells","volume":"11","year":"2024","journal-title":"Adv Sci (Weinh)"},{"key":"2026050710300743000_2026.04.30.722014v1.25","doi-asserted-by":"crossref","unstructured":"Edelmann, M. J. & Kima, P. E . Current understanding of extracellular vesicle homing\/tropism. 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