Gene Therapy Protocols

M E T H O D S I N M O L E C U L A R M E D I C I N E TM Gene Therapy Protocols Second Edition Edited by Jeffrey R. Morgan Humana Press Poly-L-Lysine-Based Gene Delivery Systems 1 1 Poly-L-Lysine-Based Gene Delivery Systems Synthesis, Purification, and Application Charles P. Lollo, Mariusz G. Banaszczyk, Patricia M. Mullen, Christopher C. Coffin, Dongpei Wu, Alison T. Carlo, Donna L. Bassett, Erin K. Gouveia, and Dennis J. Carlo 1. Introduction Nonviral gene delivery has great potential for replacement of recombinant protein therapy. In many cases, gene therapies would be a considerable improvement over existing therapies because of putative advantages in dosing schedule, patient compliance, toxicity, immunogenicity, and cost. Development of a nonviral gene delivery vehicle capable of efficient, cell-specific delivery will be a valuable addition to the clinical armamentarium. The current situation has led to a focus on increasingly complex delivery systems as investigators try to achieve the delivery efficiency that viral systems already demonstrate. It will be very difficult to create a self-assembling gene delivery system that incorporates molecular mechanisms similar to those that allow viruses to trespass on vascular, cellular, and intracellular barriers and effectively deliver viral DNA to the nucleus of mammalian cells. However, much progress has been made with regard to production of uniform particles. Steric stabilization of materials in vascular compartments has been an area of intense investigation, and numerous strategies fo