(62a) NSEF Forum Plenary: Mechanisms, Design and Fabrication of Non-Viral Gene Delivery Systems | AIChE

(62a) NSEF Forum Plenary: Mechanisms, Design and Fabrication of Non-Viral Gene Delivery Systems

Authors 

Pack, D. W. - Presenter, University of Kentucky
Human gene therapy holds the potential to revolutionize treatment of diseases ranging from cystic fibrosis to cardiovascular disease to cancer. The success of the technology awaits development of safe and efficient methods for gene delivery, however. Efficient gene delivery demands a material that is capable of escorting genes through the body to the desired tissue or cell type, as well as directing genes through an intracellular obstacle course and into the nucleus. Viruses are obviously very efficient vectors, but have critical disadvantages including potential pathogenicity and immunogenicity. Synthetic vectors, including liposomes and cationic polymers, are generally much safer but are orders of magnitude less efficient. We seek to design polymers for gene delivery by first building fundamental understanding of the pathways through which current vectors are transported in target cells. Thus, we quantify intracellular trafficking of polymer-DNA complexes (polyplexes) and synthesize new polymers designed to overcome the most important intracellular obstacles. In addition, we have designed a microfluidic device that provides reproducible fabrication of polyplexes with enhanced control of polyplex size and size distribution. Our results emphasize that fundamental and quantitative understanding of gene delivery mechanisms is critical to design of the next-generation vectors needed to advance human gene therapy from the bench to the clinic.