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Recently, messenger RNAs (mRNAs) have emerged as a promising platform for vaccination. In this work, the untranslated regions (UTRs) of mRNAs are systematically engineered in order to enhance protein production. Through a comprehensive analysis of endogenous gene expression and de novo design of UTRs, the optimal combination of 5\u2032 and 3\u2032 UTR are identified and termed NASAR, which are 5\u2010 to 10\u2010fold more efficient than the tested endogenous UTRs. More importantly, NASAR mRNAs delivered by lipid\u2010derived TT3 nanoparticles trigger a dramatic expression of potential SARS\u2010CoV\u20102 antigens. The antigen\u2010specific antibodies induced by TT3\u2010nanoparticles and NASAR mRNAs are over two orders of magnitude more than that induced by the FDA\u2010approved lipid nanoparticle material MC3 in vaccinated mice. These NASAR mRNAs merit further development as alternative SARS\u2010CoV\u20102 vaccines.<\/jats:p>","DOI":"10.1002\/adma.202004452","type":"journal-article","created":{"date-parts":[[2020,9,2]],"date-time":"2020-09-02T06:28:56Z","timestamp":1599028136000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":135,"title":["Leveraging mRNA Sequences and Nanoparticles to Deliver SARS\u2010CoV\u20102 Antigens In Vivo"],"prefix":"10.1002","volume":"32","author":[{"given":"Chunxi","family":"Zeng","sequence":"first","affiliation":[{"name":"Division of Pharmaceutics &amp; Pharmacology College of Pharmacy The Ohio State University  Columbus OH 43210 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xucheng","family":"Hou","sequence":"additional","affiliation":[{"name":"Division of Pharmaceutics &amp; Pharmacology College of Pharmacy The Ohio State University  Columbus OH 43210 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingyue","family":"Yan","sequence":"additional","affiliation":[{"name":"Division of Pharmaceutics &amp; Pharmacology College of Pharmacy The Ohio State University  Columbus OH 43210 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chengxiang","family":"Zhang","sequence":"additional","affiliation":[{"name":"Division of Pharmaceutics &amp; Pharmacology College of Pharmacy The Ohio State University  Columbus OH 43210 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenqing","family":"Li","sequence":"additional","affiliation":[{"name":"Division of Pharmaceutics &amp; Pharmacology College of Pharmacy The Ohio State University  Columbus OH 43210 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weiyu","family":"Zhao","sequence":"additional","affiliation":[{"name":"Division of Pharmaceutics &amp; Pharmacology College of Pharmacy The Ohio State University  Columbus OH 43210 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shi","family":"Du","sequence":"additional","affiliation":[{"name":"Division of Pharmaceutics &amp; Pharmacology College of Pharmacy The Ohio State University  Columbus OH 43210 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5786-0659","authenticated-orcid":false,"given":"Yizhou","family":"Dong","sequence":"additional","affiliation":[{"name":"Division of Pharmaceutics &amp; Pharmacology College of Pharmacy The Ohio State University  Columbus OH 43210 USA"},{"name":"Department of Biomedical Engineering Center for Clinical and Translational Science Comprehensive Cancer Center Dorothy M. 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