Researchers at Peking University have developed a new platform leveraging programmable pseudouridine modifications to expand the genetic code without disrupting natural stop codon functions. By converting specific mRNA codons into pseudouridine-based “ΨCodons,” this technology allows orthogonal incorporation of noncanonical amino acids into proteins with high precision inside living mammalian cells. The method overcomes traditional challenges of stop codon reassignment and has broad implications for synthetic biology and therapeutic protein design.