ABSTRACT
The potential rewards for overcoming the biological barriers to gene delivery are not in doubt. At stake is a new quality of drug therapy based on selective, regulated expression of endogenous proteins, or exogenous vaccines, at the appropriate target site. Products of the first generation of non-viral gene therapy are in a preliminary phase of clinical evaluation, although most observers agree that these products do not lead to high enough levels of gene expression for widespread application. Consequently the mechanisms of action of non-viral gene delivery systems are the subject of intense investigation. In general the biological barriers which gene delivery systems will encounter can be readily identified. However there is often a lack of fundamental physiological information relating to the nature of each barrier, and how DNA delivery systems will interact with them. It is likely that more detailed knowledge of each barrier will be required to aid the design of future generations of advanced gene delivery systems. Against this background the aims of this chapter are to identify the key biological barriers, summarize our current knowledge of their impact on existing gene delivery systems, and discuss the research which will be required to facilitate progress in nonviral gene therapy.
