N2 modified dinucleotide cap analogues as a potent tool for mRNA engineering
- Renata Grzela1,
- Karolina Piecyk2,
- Anna Stankiewicz-Drogon3,
- Paulina Pietrow2,
- Maciej Lukaszewicz4,
- Karol Kurpiejewski2,
- Edward Darzynkiewicz1 and
- Marzena Jankowska-Anyszka2,5
- 1 Centre of New Technologies, University of Warsaw, Warsaw, Poland; Division of Biophysics, Institute of Experimental Physics, University of Warsaw, Poland;
- 2 Faculty of Chemistry, University of Warsaw, Warsaw, Poland;
- 3 Centre of New Technologies, University of Warsaw, Warsaw, Poland;
- 4 Division of Biophysics, Institute of Experimental Physics, University of Warsaw, Poland
- ↵* Corresponding author; email: marzena{at}chem.uw.edu.pl
Abstract
mRNA-based vaccines are relative new technologies that have been in the field of interest of research centers and pharmaceutical companies for last years. Such therapeutics are an attractive alternative for DNA-based vaccines since they provide material that can be used with no risk of genomic integration. Additionally, mRNA can be quite easily engineered to introduce modifications for different applications or to modulate its properties, e.g. to increase translational efficiency or stability, which is not available for DNA vectors. Here, we describe the use of N2 modified dinucleotide cap analogues as a components of mRNA transcripts. Obtained compounds showed very promising biological properties whilst incorporated into mRNA. Presented N2-guanine modification within the cap structure ensure proper attachment of the dinucleotide to the transcripts in IVT reaction, guaranteed their incorporation only in the correct orientation and enabled highly efficient translation of mRNA both in the in vitro translation system and in the human HEK293 cells.
Keywords
- Received September 22, 2022.
- Accepted November 3, 2022.
- Published by Cold Spring Harbor Laboratory Press for the RNA Society
This article, published in RNA, is available under a Creative Commons License (Attribution-NonCommercial 4.0 International), as described at http://creativecommons.org/licenses/by-nc/4.0/.
