Efficient sequence-specific cleavage of RNA using novel europium complexes conjugated to oligonucleotides.

Abstract

A general method allowing the selective destruction of targeted mRNA molecules in vivo would have broad application in biology and medicine. Metal complexes are among the best synthetic catalysts for the cleavage of RNA, and covalent attachment of suitable metal complexes to oligonucleotides allows the cleavage of complementary single-stranded RNAs in a sequence-specific manner. Using novel europium complexes covalently linked to an oligodeoxyribonucleotide, we have achieved the sequence-specific cleavage of a complementary synthetic RNA. The complexes are completely resistant to chemical degradation under the experimental conditions. The cleavage efficiency of the conjugate strongly depends on the nature of the linker between the oligonucleotide and the complex. Almost complete cleavage of the RNA target has been achieved within 16 h at 37 degrees C. The results will be important for improving the efficacy of antisense oligonucleotides and will provide a basis for the design of synthetic RNA restriction enzymes. Conjugates of the kind described here may also find application as chemical probes for structural and functional studies of RNA.