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

Chunxi Zeng, Xucheng Hou, Jingyue Yan, Chengxiang Zhang, Wenqing Li, Weiyu Zhao, Shi Du, Yizhou Dong
doi: https://doi.org/10.1101/2020.04.01.019877
Chunxi Zeng
1Division of Pharmaceutics & Pharmacology, College of Pharmacy, The Ohio State University, Columbus, OH, USA
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Xucheng Hou
1Division of Pharmaceutics & Pharmacology, College of Pharmacy, The Ohio State University, Columbus, OH, USA
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Jingyue Yan
1Division of Pharmaceutics & Pharmacology, College of Pharmacy, The Ohio State University, Columbus, OH, USA
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Chengxiang Zhang
1Division of Pharmaceutics & Pharmacology, College of Pharmacy, The Ohio State University, Columbus, OH, USA
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Wenqing Li
1Division of Pharmaceutics & Pharmacology, College of Pharmacy, The Ohio State University, Columbus, OH, USA
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Weiyu Zhao
1Division of Pharmaceutics & Pharmacology, College of Pharmacy, The Ohio State University, Columbus, OH, USA
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Shi Du
1Division of Pharmaceutics & Pharmacology, College of Pharmacy, The Ohio State University, Columbus, OH, USA
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Yizhou Dong
1Division of Pharmaceutics & Pharmacology, College of Pharmacy, The Ohio State University, Columbus, OH, USA
2Department of Biomedical Engineering, Center for Clinical and Translational Science, Comprehensive Cancer Center, Dorothy M. Davis Heart & Lung Research Institute, Department of Radiation Oncology, The Ohio State University, Columbus, OH, USA
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  • For correspondence: dong.525@osu.edu
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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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Posted April 05, 2020.
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Leveraging mRNAs sequences to express SARS-CoV-2 antigens in vivo
Chunxi Zeng, Xucheng Hou, Jingyue Yan, Chengxiang Zhang, Wenqing Li, Weiyu Zhao, Shi Du, Yizhou Dong
bioRxiv 2020.04.01.019877; doi: https://doi.org/10.1101/2020.04.01.019877
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Leveraging mRNAs sequences to express SARS-CoV-2 antigens in vivo
Chunxi Zeng, Xucheng Hou, Jingyue Yan, Chengxiang Zhang, Wenqing Li, Weiyu Zhao, Shi Du, Yizhou Dong
bioRxiv 2020.04.01.019877; doi: https://doi.org/10.1101/2020.04.01.019877

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