Toward development of a non-viral gene therapeutic

Abstract

Gene therapy is an emerging field that has reached the early clinical stages of development for some disease states. However, the demonstration of safety in animals and the introduction of gene-based formulations in humans hides the fact that numerous developmental and basic research questions remain. This article highlights progress and emerging issues in the area of liposome-based non-viral gene delivery. The colloidal nature of these formulations render them complicated at the physico-chemical and biological levels. Instrumentation and methodologies need to be developed to better understand the subtleties of plasmid DNA, complexing agents, delivery mode and the route of entry into the cell and the nucleus. Major hurdles to entry include membrane binding, endosomal release, nuclear uptake and decomplexation. Each 'stage' is poorly understood but numerous approaches are being directed to increase cellular delivery. These research efforts, coupled with sensible formulation research and a multi-disciplinary, long-term effort, are necessary for success.