体外研究
Incorporation of N1-methyl-pseudouridine into mRNA modifies mRNAs produced higher amounts of luc than the standard Luc mRNA in HEK293T cells. Incorporation of N1-methyl-pseudouridine nucleoside modification in both Luc and GFP mRNA enhances the initiation step of translation, in part by suppressing eIF2α phosphorylation. In addition, polysome formation and growth on the NN1-methyl-pseudouridine-containing Luc mRNA is enhanced due to the reduction of elongation rate. In all the in vitro translation systems, incorporation of N1-methyl-pseudouridine in Luc and GFP mRNAs dramatically enhanced translation. The N1-methyl-pseudouridine-Luc mRNA is associated with heavier polysomes than Luc mRNA.
体内研究
N1-methylpseudouridine-incorporated mRNA outperforms pseudouridine-incorporated mRNA by providing enhanced protein expression and reduced immunogenicity in mammalian cell lines and mice.
N1-methyl-pseudouridine (1-Methylpseudouridine) (20 μg; I.m. or i.d. routes for 21 days) and m5C/ N1-methyl-pseudouridine-modified mRNA respectively have a higher translational capacity than Ψ and m5C/Ψ-modified mRNA in vivo.
Animal Model:
7-week-old Balb/c mice
Dosage:
20 μg
Administration:
I.m. or i.d. routes for 21 days
Result:
had a higher translational capacity.
