N2 modified dinucleotide cap analogs as a potent tool for mRNA engineering
- Renata Grzela1,
- Karolina Piecyk2,
- Anna Stankiewicz-Drogon1,
- Paulina Pietrow2,
- Maciej Lukaszewicz1,
- Karol Kurpiejewski2,
- Edward Darzynkiewicz1,3 and
- Marzena Jankowska-Anyszka2
- 1Division of Biophysics, Institute of Experimental Physics, University of Warsaw, 02-093 Warsaw, Poland
- 2Faculty of Chemistry, University of Warsaw, 02-093 Warsaw, Poland
- 3Center of New Technologies, University of Warsaw, 02-097 Warsaw, Poland
- Corresponding author: marzena{at}chem.uw.edu.pl
Abstract
mRNA-based vaccines are relatively new technologies that have been in the field of interest of research centers and pharmaceutical companies in recent 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, for example, to increase translational efficiency or stability, which is not available for DNA vectors. Here, we describe the use of N2 modified dinucleotide cap analogs as components of mRNA transcripts. The compounds obtained showed very promising biological properties while incorporated into mRNA. The presented N2-guanine modifications within the cap structure ensure proper attachment of the dinucleotide to the transcripts in the IVT reaction, guarantees their incorporation only in the correct orientation, and enables highly efficient translation of mRNA both in the in vitro translation system and in human HEK293 cells.
Keywords
- Received September 22, 2022.
- Accepted November 3, 2022.
This article, published in RNA, is available undera Creative Commons License (Attribution-NonCommercial 4.0 International), as described at http://creativecommons.org/licenses/by-nc/4.0/.
