Scientists at Peking University devised a novel RNA codon expansion platform that installs programmable pseudouridine modifications into mRNA codons to enable precise incorporation of noncanonical amino acids (ncAAs) in mammalian cells. This RNA-based approach circumvents limitations of conventional stop codon reassignment by creating bioorthogonal codons (ΨGA, ΨAA, ΨAG) distinct from the natural genetic code, reducing translation termination interference. The innovation enables expanded genetic code manipulation with high fidelity, advancing protein engineering capabilities beyond the standard 64 codons and promising significant impact in synthetic biology and therapeutic development.