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As a novel solution to this issue, we employed SpyTag-SpyCatcher molecular glue technology to facilitate packaging of AAVs inside of recombinant protein vault nanoparticles. Vaults are endogenous particles produced by mammalian cells. We therefore hypothesized that they may shield packaged molecules from neutralizing antibodies. Vaults have previously been utilized to deliver drugs and proteins into cells, but our study represents the first time anyone has packaged an entire virus inside of a vault. We showed that our vaultAAV delivery vehicle transduces cells in the presence of anti-AAV neutralizing serum. VaultAAV is positioned as a new gene therapy delivery platform with potential to overcome the neutralizing antibody problem, expanding the scope of AAV treatments.<\/jats:p>","DOI":"10.1021\/acssynbio.6c00512","type":"journal-article","created":{"date-parts":[[2026,8,13]],"date-time":"2026-08-13T14:02:21Z","timestamp":1786629741000},"page":"3975-3982","source":"Crossref","is-referenced-by-count":0,"title":["Encapsulation of AAVs into Protein Vault Nanoparticles as a Novel Solution to Gene Therapy\u2019s Neutralizing Antibody Problem"],"prefix":"10.1021","volume":"15","author":[{"given":"Logan","family":"Thrasher Collins","sequence":"first","affiliation":[{"name":"Washington University in St. Louis , , 4950 Children\u2019s Pl , , ,","place":["St. Louis, Missouri, United States, 63110"]},{"name":"Washington University in St. Louis , , 4950 Children\u2019s Pl , , ,","place":["St. Louis, Missouri, United States, 63110"]},{"name":"Cathedral Therapeutics , 75 Kneeland Street , , ,","place":["Boston, Massachusetts, United States, 02111"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wandy","family":"Beatty","sequence":"additional","affiliation":[{"name":"Washington University in St. Louis , , 660 S. 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