N 1-Methylpseudouridine substitution enhances the performance of synthetic mRNA switches in cells.

ABSTRACT: Synthetic messenger RNA (mRNA) tools often use pseudouridine and 5-methyl cytidine as substitutions for uridine and cytidine to avoid the immune response and cytotoxicity induced by introducing mRNA into cells. However, the influence of base modifications on the functionality of the RNA tools is poorly understood. Here we show that synthetic mRNA switches containing N1-methylpseudouridine (m1Ψ) as a substitution of uridine substantially out-performed all other modified bases studied, exhibiting enhanced microRNA and protein sensitivity, better cell-type separation ability, and comparably low immune stimulation. We found that the observed phenomena stem from the high protein expression from m1Ψ containing mRNA and efficient translational repression in the presence of target microRNAs or pro

SUBMITTER: Parr CJC 

PROVIDER: S-EPMC7102939 | biostudies-literature | 2020 Apr

REPOSITORIES: biostudies-literature