Pharmaceutical non-viral formulations for gene vaccines

Ever since the ground-breaking findings that immune responses can be provoked by biolistic application of pDNA and subsequent protein expression, no effort has been spared in order to make genetic vaccination feasible. Unfortunately, most approaches failed to convert the promising results from rodents to larger animals and human beings. To make such systems available for a global community, simple, safe and highly effective delivery systems are highly on demand. Since physical methods like the gene gun are neither cost-effective nor applicable in an everyday use and viral systems are still subject to heavy safety concerns, chemo-pharmaceutical approaches have become a major area of interest within the field of genetic vaccination. This chapter will shine a light on the barriers that need to be overcome by genetic vaccination systems and on the major approaches to achieve this aim. In particular, approaches based on (cationic) polymers, cationic lipids, combinations of these two major strategies and their in vivo performance will be discussed in detail. Besides, immunostimulatory agents and targeting ligands will be discussed as options to improve the in vivo efficiency of a genetic vaccination system. Finally, alternative routes to intradermal and intramuscular injections will be highlighted as part of future developments in this field.