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Leveraging mRNA Sequences and Nanoparticles to Deliver SARS-CoV-2 Antigens In Vivo #MMPMID32875709
Zeng C; Hou X; Yan J; Zhang C; Li W; Zhao W; Du S; Dong Y
Adv Mater 2020[Oct]; 32 (40): e2004452 PMID32875709show ga
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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Adv+Mater 2020 ; 32 (40): e2004452
