N1-Methylpseudo-UTP

N1-methylpseudo-UTP is a nucleobase-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 the current state-of-the-art 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 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. Thus, N1-methylpseudo-UTP might serve as a useful ingredient for synthesizing drugable mRNAs with better performance.

Reference:

1. Andries O, Mc Cafferty S, De Smedt SC, et al. N1-methylpseudouridine-incorporated mRNA outperforms pseudouridine-incorporated mRNA by providing enhanced protein expression and reduced immunogenicity in mammalian cell lines and mice. Journal of Controlled Release, 2015, 217: 337-344.