Compositions for Inhibiting Gene Expression and Uses Thereof

摘要

The inventors have examined the means for providing more efficacious miRNA blocking compounds. The inventors have discovered new structural features that surprisingly improve the efficacy of miRNA blocking molecules. These features include the presence of multiple 3′ ends and a linker at the 5′ ends. Surprisingly, these features improve the efficacy of the gene expression blocking compounds in a manner that decreases the compound's biologic instability. Even more surprisingly, this effect has been found to be applicable to both DNA and RNA oligonucleotide-based compounds and to have application in traditional antisense and RNAi technology.

主权项

1. A method for therapeutically treating a mammal having a disease or disorder mediated by a miRNA, the method comprising administering to the mammal a synthetic oligonucleotide-based compound comprising two single stranded oligonucleotides that are complementary to a miRNA sequence, wherein the oligonucleotides are linked at their 5′-ends such that the oligonucleotide-based compound has two accessible 3′-ends, and the oligonucleotides specifically hybridize to and inhibit the activity of the miRNA sequence.