Delivery of Antisense Morpholino Oligonucleotides

Antisense therapies hold tremendous promise for treating a wide variety of human diseases. These therapies are based on the selective inhibition of expression of specific messenger RNA or pre-messenger RNAs. Because they are highly specific, antisense agents could in theory have fewer side effects and display less toxicity than traditional drugs. In addition, because antisense agents exert their effects by binding to a complementary sequence in a target RNA molecule, designing antisense agents to specifically inhibit a particular RNA species is extremely straightforward. A major factor hindering the effective use of anfsense agents is the low efficiency at which these molecules are delivered to, and internalized by, cells in vivo. Recently, researchers at Mirus Corporation have developed a novel, non-viral particle technology that has been shown to be highly effective at delivering plasmid DNA to hepatocytes in vivo. A major goal of the research proposed in this Phase 1 study is to determine if this particle technology can be utilized to deliver a new, highly effective class of antisense agents, named morpholino oligonucleotides, to hepatocytes in vivo. In these studies, we will also develop an assay to assess the ability of antisense morpholino oligonucleotides to inhibit the expression of an endogenous gene in hepatocytes in vivo. PROPOSED COMMERCIAL APPLICATIONS: A roadblock in the development of antisense reagents for use in treating disease is the lack of efficient delivery methods. An efficient in vivo delivery system for antisense morpholino oligonucleotides would immediately be licensed for use by larger pharmaceutical and biotechnology companies.