N2 modified dinucleotide cap analogs as a potent tool for mRNA engineering

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.

Automated summary

mRNA-based vaccines have gained significant attention in recent years as a new technology in the field of research and pharmaceutical development. They offer advantages over DNA-based vaccines by providing a risk-free material for use. By modifying mRNA, such as increasing translational efficiency or stability, it can be easily tailored for different applications. This study demonstrates the use of N2 modified dinucleotide cap analogs in mRNA transcripts, showing promising biological properties and efficient translation.