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<i>N</i><sup>4</sup>-Acetylcytidine enhances synthetic mRNA translation yield and fidelity

nature.com·Jul 1, 2026

The study reveals that N4-acetylcytidine (ac4C) serves as a superior alternative to the industry-standard N1-methylpseudouridine (m1Ψ) for enhancing synthetic mRNA translation, yielding higher protein production while effectively suppressing inflammatory responses. This research highlights the importance of selecting appropriate ribonucleotide modifications to optimize the efficacy and safety of mRNA therapeutics.

The study highlights _N_ 4-acetylcytidine (ac4C) as a promising alternative to the current industry standard _N_ 1-methylpseudouridine (m1Ψ) for synthetic mRNA modifications, particularly in therapeutic applications. ac4C not only enhances protein yield and translational efficiency but also maintains translational fidelity, reducing issues like premature termination and ribosomal frameshifting associated with m1Ψ. This insight suggests ac4C could improve the safety and efficacy of mRNA therapeutics, making it a significant area for further research and application in developing mRNA-based treatments.

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