Several peptide nucleic acid based artificial nucleases (PNAzymes) are designed to create a bulge in the target RNA, which is a short model of the leukemia related bcr/abl mRNA. The target RNA is cleaved by the PNAzymes with a half-life of down to 11 h (using a 1 : 1 ratio of PNA-conjugate to target) and only upon base-pairing with the substrate. The PNA based systems are also shown to act in a catalytic fashion with turnover of substrate and are thus the first reported peptide nucleic acid based artificial RNA-cleaving enzymes.