The inventors have examined the means for providing more efficacious gene expression blocking compounds. The inventors have discovered new structural features that surprisingly improve the efficacy of gene expression 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 technologies.
