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Leveraging mRNAs sequences to express SARS-CoV-2 antigens in vivo

Zeng, C.; Hou, X.; Yan, J.; Zhang, C.; Li, W.; Zhao, W.; Du, S.; Dong, Y.

2020-04-05 bioengineering
10.1101/2020.04.01.019877 bioRxiv
Show abstract

SARS-CoV-2 has rapidly become a pandemic worldwide; therefore, an effective vaccine is urgently needed. Recently, messenger RNAs (mRNAs) have emerged as a promising platform for vaccination. Here, we systematically investigated the untranslated regions (UTRs) of mRNAs in order to enhance protein production. Through a comprehensive analysis of endogenous gene expression and de novo design of UTRs, we identified the optimal combination of 5 and 3 UTR, termed as NASAR, which was five to ten-fold more efficient than the tested endogenous UTRs. More importantly, NASAR mRNAs delivered by lipid-derived nanoparticles showed dramatic expression of potential SARS-CoV-2 antigens both in vitro and in vivo. These NASAR mRNAs merit further development as alternative SARS-CoV-2 vaccines.

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