Multiple-Target Anti-miRNA Antisense Oligonucleotides Technology

Abstract

The multiple-target AMO technology or MT-AMO technology is an innovative strategy that confers a single AMO fragment the capability of targeting multiple miRNAs. These modified AMOs are single-stranded 2′-O-methyl-modified oligoribonucleotides carrying multiple AMO units that are engineered into a single unit and are able to simultaneously silence multiple target miRNAs or multiple miRNA seed families. Studies suggest the MT-AMO is an improved approach for miRNA target finding and miRNA function validation; it not only enhances the effectiveness of targeting miRNAs but also confers diversity of actions. It has been successfully used to identify target genes and cellular function of several oncogenic miRNAs and of the muscle-specific miRNAs [Lu Y, Xiao J, Lin H, Bai Y, Luo X, Wang Z, Yang B, Nucleic Acid Res. 2009]. This novel strategy may find its broad application as a useful tool in miRNA research for exploring biological processes involving multiple miRNAs and multiple genes and potential as a miRNA therapy for human disease such as cancer and cardiac disorders. This technology was developed by my research laboratory in collaboration with Yang's group (Lu Y, Xiao J, Lin H, Bai Y, Luo X, Wang Z, Yang B 2009). The MT-AMO technology belongs to the “targeting-miRNA” and “miRNA-loss-of-function” strategy. The MT-AMO technology is based on the ‘One-Drug, Multiple-Target’ concept (see Sect. 2.1.3 for detail).