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Leveraging mRNA Sequences and Nanoparticles to Deliver SARS‐CoV‐2 Antigens In Vivo
Author(s) -
Zeng Chunxi,
Hou Xucheng,
Yan Jingyue,
Zhang Chengxiang,
Li Wenqing,
Zhao Weiyu,
Du Shi,
Dong Yizhou
Publication year - 2020
Publication title -
advanced materials
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 10.707
H-Index - 527
eISSN - 1521-4095
pISSN - 0935-9648
DOI - 10.1002/adma.202004452
Subject(s) - materials science , in vivo , nanoparticle , nanotechnology , messenger rna , covid-19 , antigen , virology , biology , immunology , genetics , medicine , gene , infectious disease (medical specialty) , disease , pathology
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.