Chemo-Enzymatic Modification of the 5' Cap Maintains Translation and Increases Immunogenic Properties of mRNA.
Angew Chem Int Ed Engl
; 60(24): 13280-13286, 2021 06 07.
Article
in English
| MEDLINE | ID: covidwho-1384109
ABSTRACT
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 N6 -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 ≈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.
Keywords
Full text:
Available
Collection:
International databases
Database:
MEDLINE
Main subject:
RNA Caps
/
RNA, Messenger
Topics:
Vaccines
Limits:
Humans
Language:
English
Journal:
Angew Chem Int Ed Engl
Year:
2021
Document Type:
Article
Affiliation country:
ANIE.202100352
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