Codon-dependent translation of N1-ethylpseudouridine-modified mRNA reduces innate immunity while preserving vaccine immunogenicity.

Codon-dependent translation of N1-ethylpseudouridine-modified mRNA reduces innate immunity while maintaining vaccine efficacy.

• Why it matters: Optimizing nucleoside modifications in mRNA vaccines is crucial to balance efficient protein production and minimized immune activation, which impacts vaccine safety and effectiveness.
• What they did: Researchers compared N1-ethylpseudouridine (Et1Ψ) to N1-methylpseudouridine (m1Ψ), using codon optimization to address translation sensitivity, and tested immune responses in vitro and in vivo across multiple vaccine antigens.
• The result: Codon optimization restored translation efficiency of Et1Ψ-modified mRNA and demonstrated that Et1Ψ reduces innate immune activation without compromising immunogenicity, supporting its use in safer, effective mRNA vaccines.