Gene transfer to humans requires carriers for the plasmid DNA which can eff
iciently and safely carry the gene into the nucleus of the desired cells. A
series of chemically different cationic polymers are currently being inves
tigated for these purposes. Although many cationic polymers indeed condense
DNA spontaneously, which is a requirement for gene transfer in most types
of cells, the physicochemical and biopharmaceutical behavior of the current
generation of polyplexes severely limits an efficient gene transfer in vit
ro and especially in vivo. This paper summarizes recent physicochemical and
biological information on polyplexes and aims to provide new insights with
respect to this type of gene delivery system. Firstly, the chemical struct
ure of frequently studied cationic polymers is represented. Secondly, the p
arameters influencing condensation of DNA by cationic polymers are describe
d. Thirdly, the surface properties, solubility, aggregration behavior, degr
adation and dissociation of polyplexes are considered. The review ends by d
escribing the in vitro and in vivo gene transfection behavior of polyplexes
.