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Yet a challenge is the susceptibility of SAM to degradation and the need for SAM to reach the cytosol fully intact to enable self\u2010amplification. Lipid nanoparticles are successfully deployed at incredible speed for mRNA vaccination, but aspects such as cold storage, manufacturing, efficiency of delivery, and the therapeutic window can benefit from further improvement. To investigate alternatives to lipid nanoparticles, a class of &gt;200 biodegradable end\u2010capped lipophilic poly(beta\u2010amino ester)s (PBAEs) that enable efficient delivery of SAM in vitro and in vivo as assessed by measuring expression of SAM encoding reporter proteins is developed. The ability of these polymers to deliver SAM intramuscularly in mice is evaluated, and a polymer\u2010based formulation that yields up to 37\u2010fold higher intramuscular (IM) expression of SAM compared to injected naked SAM is identified. Using the same nanoparticle formulation to deliver a SAM encoding rabies virus glycoprotein, the vaccine elicits superior immunogenicity compared to naked SAM delivery, leading to seroconversion in mice at low RNA injection doses. These biodegradable nanomaterials may be useful in the development of next\u2010generation RNA vaccines for infectious diseases.<\/jats:p>","DOI":"10.1002\/adtp.202200219","type":"journal-article","created":{"date-parts":[[2023,2,17]],"date-time":"2023-02-17T02:54:03Z","timestamp":1676602443000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Biodegradable Polyester Nanoparticle Vaccines Deliver Self\u2010Amplifying mRNA in Mice at Low Doses"],"prefix":"10.1002","volume":"6","author":[{"given":"David R.","family":"Wilson","sequence":"first","affiliation":[{"name":"Department of Biomedical Engineering, Institute for NanoBioTechnology, and the Translational Tissue Engineering Center Johns Hopkins University School of Medicine  Baltimore MD 21231 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephany Y.","family":"Tzeng","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering, Institute for NanoBioTechnology, and the Translational Tissue Engineering Center Johns Hopkins University School of Medicine  Baltimore MD 21231 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuan","family":"Rui","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering, Institute for NanoBioTechnology, and the Translational Tissue Engineering Center Johns Hopkins University School of Medicine  Baltimore MD 21231 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah Y.","family":"Neshat","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering, Institute for NanoBioTechnology, and the Translational Tissue Engineering Center Johns Hopkins University School of Medicine  Baltimore MD 21231 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marranne J.","family":"Conge","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering, Institute for NanoBioTechnology, and the Translational Tissue Engineering Center Johns Hopkins University School of Medicine  Baltimore MD 21231 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kathryn M.","family":"Luly","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering, Institute for NanoBioTechnology, and the Translational Tissue Engineering Center Johns Hopkins University School of Medicine  Baltimore MD 21231 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ellen","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering, Institute for NanoBioTechnology, and the Translational Tissue Engineering Center Johns Hopkins University School of Medicine  Baltimore MD 21231 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jessica L.","family":"Firestone","sequence":"additional","affiliation":[{"name":"GSK Vaccines  Rockville MD 20850 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Josie","family":"McAuliffe","sequence":"additional","affiliation":[{"name":"GSK Vaccines  Rockville MD 20850 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giulietta","family":"Maruggi","sequence":"additional","affiliation":[{"name":"GSK Vaccines  Rockville MD 20850 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rashmi","family":"Jalah","sequence":"additional","affiliation":[{"name":"GSK Vaccines  Rockville MD 20850 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Russell","family":"Johnson","sequence":"additional","affiliation":[{"name":"GSK Vaccines  Rockville MD 20850 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joshua C.","family":"Doloff","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering, Institute for NanoBioTechnology, and the Translational Tissue Engineering Center Johns Hopkins University School of Medicine  Baltimore MD 21231 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4176-3808","authenticated-orcid":false,"given":"Jordan J.","family":"Green","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering, Institute for NanoBioTechnology, and the Translational Tissue Engineering Center Johns Hopkins University School of Medicine  Baltimore MD 21231 USA"},{"name":"Departments of Chemical &amp; Biomolecular Engineering, Materials Science &amp; Engineering, Neurosurgery, Oncology, and Ophthalmology, Sidney Kimmel Comprehensive Cancer Center and Bloomberg\u223cKimmel Institute for Cancer Immunotherapy Johns Hopkins University  Baltimore MD 21231 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2023,3,9]]},"reference":[{"key":"e_1_2_9_1_1","volume":"27","author":"Parums D. 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