Enhancing mRNA stability and translational potential through tailored modifications at the 3′ end

-consistently performed best, increasing the cumulative GLuc production up to 163% in HEK293 and up to 79% in A549. These results establish dinucleotide ligation as a minimal and modular 3'-end engineering approach that enhances resistance to deadenylation and can improve the translational performance of therapeutic mRNA candidates.