Journal
ADVANCED MATERIALS
Volume 32, Issue 40, Pages -Publisher
WILEY-V C H VERLAG GMBH
DOI: 10.1002/adma.202004452
Keywords
lipid-derived nanoparticles; mRNA engineering; mRNA vaccines; SARS-CoV-2; untranslated regions
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Funding
- National Institutes of Health (NIH) through the Maximizing Investigators' Research Award of the National Institute of General Medical Sciences [R35GM119679]
- College of Pharmacy at Ohio State University
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SARS-CoV-2 has become a pandemic worldwide; therefore, an effective vaccine is urgently needed. 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 ' and 3 ' UTR are identified and termed NASAR, which are 5- to 10-fold more efficient than the tested endogenous UTRs. More importantly, NASAR mRNAs delivered by lipid-derived TT3 nanoparticles trigger a dramatic expression of potential SARS-CoV-2 antigens. The antigen-specific antibodies induced by TT3-nanoparticles and NASAR mRNAs are over two orders of magnitude more than that induced by the FDA-approved lipid nanoparticle material MC3 in vaccinated mice. These NASAR mRNAs merit further development as alternative SARS-CoV-2 vaccines.
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