Cellular RNA folds into complex helical structures that are attractive targets for controlling biological activity and treating diseases using RNA-binding ligands. Peptide nucleic acid (PNA) is a neutral DNA analog uniquely suited for triple-helical recognition of RNA. However, the applications of triplex-forming PNAs have been limited by sequence restrictions, as stable base triples are formed only with purines. Hoogsteen recognition of pyrimidines has been a long-standing challenge. The presen