N1-methylpseudo-UTP is a modified nucleotide, used for synthesizing mRNA with reduced immunogenicity and improved stability. It was reported that N1-methylpseudouridine (m1Ψ) modification alone or in combination with 5-methylcytidine (m5C) exhibited superiority over pseudouridine (Ψ) or m5C/Ψ-modified mRNA platform by providing up to ~ 44-fold (when comparing double modified mRNAs) and ~ 13-fold (when comparing single modified mRNAs) higher reporter gene expression in mammalian cells and mice, respectively. Moreover, compared with (m5C/)Ψ-modified mRNAs, (m5C/)m1Ψ-modified mRNAs showed reduced intracellular innate immunogenicity and resulted in improved cellular viability after in vitro transfection.^[1] Therefore, N1-methylpseudouridine Triphosphate can serve as a powerful ingredient for synthesizing new mRNA drugs with better performance.

LITERATURE

[1] N1-methylpseudouridine-incorporated mRNA outperforms pseudouridine-incorporated mRNA by providing enhanced protein expression and reduced immunogenicity in mammalian cell lines and mice, O. Andries et al., 2015, Journal of Controlled Release, Vol. 217, p. 337-344.

https://doi.org/10.1016/j.jconrel.2015.08.051

Multicomponent Lipid Nanoparticles for RNA Transfection, N. Gretskaya et al., 2023, Pharmaceutics, Vol. 15(4), 1289.

https://doi.org/10.3390/pharmaceutics15041289

CpG oligodeoxynucleotide developed to activate primate immune responses promotes antitumoral effects in combination with a neoantigen-based mRNA cancer vaccine, Q. Li et al., 2021, Drug Design, Development and Therapy, p. 3953-3963.

https://doi.org/10.2147/DDDT.S325790