Award type：Award from international society, conference, symposium, etc. 

Award type：Award from international society, conference, symposium, etc. 

Award type：Award from publisher, newspaper, foundation, etc. 

Language：Japanese   Publisher：THE JAPAN SOCIETY OF DRUG DELIVERY SYSTEM  

Recently messenger RNA （mRNA） therapeutics is received much attention as one of the vaccination therapies to compete against the coronavirus disease 2019 （COVID-19） pandemic. mRNA therapeutics are generally produced by <i>in vitro</i> transcription utilizing RNA polymerase mediated elongation. However, its purity, stability, and protein synthesis ability, are difficult to be precisely controlled, which is pointed out as drawbacks that must be overcome. To overcome these issues, the introduction of chemically modified nucleic acids is focusing attention. However, it is difficult to flexible molecular design due to the requirement of RNA polymerase recognition ability of chemically modified nucleic acids under <i>in vitro</i> transcription reaction. In the future, the development of a new mRNA design concept based on a flexible molecular design by the progress of chemically modified mRNA therapeutics synthesis method. Under the situation, the authors are focusing on the translation mechanism of mRNA and proposing a new mRNA molecular design to accelerate the translation reaction cycle. In this paper, we introduce an update on therapeutic mRNA design.

DOI： 10.2745/dds.37.196

Scopus

CiNii Research

Language：Japanese   Publisher：ACS Chemical Biology  

Site-specific chemical modification of mRNA can improve its translational efficiency and stability. For this purpose, it is desirable to develop a complete chemical synthesis method for chemically modified mRNA. The key is a chemical reaction that introduces a cap structure into the chemically synthesized RNA. In this study, we developed a fast and quantitative chemical capping reaction between 5′-phosphorylated RNA and N7-methylated GDP imidazolide in the presence of 1-methylimidazole in the organic solvent dimethyl sulfoxide. It enabled quantitative preparation of capping RNA within 3 h. We prepared chemically modified 107-nucleotide mRNAs, including N6-methyladenosine, insertion of non-nucleotide linkers, and 2′-O-methylated nucleotides at the 5′ end and evaluated their effects on translational activity in cultured HeLa cells. The results showed that mRNAs with non-nucleotide linkers in the untranslated regions were sufficiently tolerant to translation and that mRNAs with the Cap_2 structure had higher translational activity than those with the Cap_0 structure.

DOI： 10.1021/acschembio.1c00996

Web of Science

Scopus

PubMed

Authorship：Lead author   Language：English  

DOI： 10.1246/cl.181048