Structure, dispersion stability and dynamics of DNA and poly cation complexes
INTRODUCTION Polycation-based non-viral gene delivery systems have recently attracted significant attention. Polyplexes form spontaneously as a result of cooperative electrostatic interactions between phosphate groups of the DNA and oppositely charged groups of the polycation. A number of review manuscripts and book issues have appeared recently that discuss physicochemical, biochemical and therapeutic aspects of these systems (Felgner et al., 1996; Kabanov et al., 1998a; Rolland, 1999; Garnett, 1999; Chesnoy and Huang, 1999). However, the field of non-viral gene therapy is developing extremely fast and requires continuous appraisal. This chapter focuses on the biophysical and polymer aspects of the polyplexes. The biochemical and therapeutic aspects are considered in detail in other chapters of this book. Furthermore, several works are available that discuss the relationship of the physicochemical properties of the polyplexes and their biological performance in vitro and in vivo (Kabanov and Kabanov, 1995; Kabanov et al., 1998b; Kabanov, 1999). The most important physicochemical properties considered here include: (i) the reactions of polyplex formation; (ii) the colloidal properties and stability of polyplex dispersions; (iii) the effects of the polycation on the structure and properties of the DNA in the complexes, and; (iv) the processes underlying the DNA release from the polyplexes.