Nonenzymatically modified mRNA for regulating translation and apoptosis by modulating Cancer epigenetics.

In this study, we employed imidazole-activated natural or modified guanosine derivatives to extend the 3' ends of mRNA using a nonenzymatic method beyond 30 poly-A tails. We evaluated their impact on the translation activity in cell studies using three genes: GFP, Luciferase, and Apoptin. The assessments were conducted through cell imaging, fluorescence, luminescence, western blot analysis, and RT-qPCR to evaluate varying apoptosis-mediated EZH2 expression in cancer epigenetics, among the compounds tested GMP-2-amino-IM, 2'O-Me-2-amino-IM, and N7-(2-MePy)-GMP-IM.

mRNA incorporation of C(5)-halogenated pyrimidine ribonucleotides and induced high expression of corresponding protein for the development of mRNA vaccine.

In this report, we present our studies on mRNA, which was modified by introducing various halogen substituents at the C(5) position of the pyrimidine base. Specifically, we synthesized C(5)-halogenated (F, Cl, Br, I) pyrimidine ribonucleoside triphosphates and incorporated them into mRNA during in-vitro transcription. The efficiency of the in-vitro transcription reaction of halogenated pyrimidine was observed to decrease as the size of the halogen substituent increased and the electronegativity thereof decreased (F > Cl > Br) except for iodine.