PEPTIDE NUCLEIC ACID-OLIGOADENYLATE CHIMERIC MOLECULES

摘要

Covalent conjugation of a 5'-phosphorylated-2',5'-linked oligoadenylate (2-5A) moiety to an antisense peptide nucleic acid oligomer (PNA) provides a novel chimeric reagent which effects the selective and specific cleavage of a selected target RNA. The 2-5A-antisense PNA chimeras bind the target RNA with high specificity and affinity, and are stable to nucleases. The antisense portion of the chimera recruits a chosen RNA as substrate for cleavage, and the 2-5A portion of the chimera binds and activates RNase L, thus providing a new approach for the targeted ablation of a target mRNA and a reduction in expression of the protein which it specifies. The chimeric molecules are expected to have utility as research tools and as therapeutic agents.