Non-Viral Gene Therapy

This chapter is meant to serve as an introduction to non-viral gene transfer by highlighting therapeutic applications that have transitioned from preclinical research into the clinic. Non-viral gene therapy is the administration of plasmid DNA encoding a transgene gene locally or systemically yielding expression of a therapeutic protein, thereby correcting a disease state. Local administration of plasmid DNA results in gene transfer to cells at the site of injection. Gene transfer efficiency can be increased by applying electric current (electroporation) or sound waves (sonoporation). Alternatively, the plasmid DNA can be formulated with cationic lipids or polymers to increase gene transfer. All of these methods result in increased uptake by cells and therefore in increased gene expression. Clinical applications of this technology include: treatment of peripheral vascular disease following local administration at the sites of muscle ischemia; development of genetic vaccines resulting in immune activation against the specific expressed antigen; development of therapeutic cancer vaccines that induce surveillance and killing of tumor cells by the immune system; correction of genetic disease by expressing a functional wild type protein in cells that lack a functional protein.