Despite the success of mRNA vaccines, improving the translational efficiency of mRNA therapeutics remains a critical challenge to their widespread clinical application. Here, the authors systematically evaluate chemical modifications to improve the translational activity and stability of uncapped mRNA and show that the 2´-F modification at the first nucleoside of the codon in the open reading frame significantly bolsters the stability of mRNA without compromising its translation.
- Hiroto Iwai
- Yasuaki Kimura
- Hiroshi Abe