期刊
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
卷 60, 期 24, 页码 13280-13286出版社
WILEY-V C H VERLAG GMBH
DOI: 10.1002/anie.202100352
关键词
non-natural modifications; RNA modification; RNA vaccine; translation
资金
- European Research Council (ERC) under the European Union's Horizon 2020 research and innovation programme [772280]
- DFG [RE 2796/6-1]
- Projekt DEAL
Eukaryotic mRNAs can be modified with site-specific chemo-enzymatic methods to enhance immune response, offering a potential strategy for future therapeutic applications.
Eukaryotic mRNAs are emerging modalities for protein replacement therapy and vaccination. Their 5 ' cap is important for mRNA translation and immune response and can be naturally methylated at different positions by S-adenosyl-l-methionine (AdoMet)-dependent methyltransferases (MTases). We report on the cosubstrate scope of the MTase CAPAM responsible for methylation at the N-6-position of adenosine start nucleotides using synthetic AdoMet analogs. The chemo-enzymatic propargylation enabled production of site-specifically modified reporter-mRNAs. These cap-propargylated mRNAs were efficiently translated and showed approximate to 3-fold increased immune response in human cells. The same effects were observed when the receptor binding domain (RBD) of SARS-CoV-2-a currently tested epitope for mRNA vaccination-was used. Site-specific chemo-enzymatic modification of eukaryotic mRNA may thus be a suitable strategy to modulate translation and immune response of mRNAs for future therapeutic applications.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据