Artificial Ribonucleases as Antisense Compounds

Antisense oligonucleotides can be used to inhibit gene expression. It is generally accepted that most of the antisense oligonucleotides developed so far act by an RNase H-mediated mechanism, and thereby cleavage of specific mRNAs occurs. Recently, chemical agents that cleave RNA site-specifically, without enzymatic assistance, have been developed. Such artificial chemical nucleases, which are conjugates of an antisense oligonucleotide and an RNA-cleaving catalyst(s), are potentially important in antisense chemotherapy and would also be useful for molecular biology, including RNA engineering. Metal complexes, oligoamines and imidazoles have been used as RNA cleavage catalysts. This review highlights the recent developments in the field of artificial RNases, with metal complexes cleaving RNA via the transesterification and/or hydrolysis of the target phosphodiester linkage.