The development of safe and effective gene delivery,agents poses a great ch
allenge in the quest to make human gene therapy a reality. Cationic polymer
s represent,one important class of materials for gene delivery but to date
they have shown only moderate efficiency. Improving the efficiency will req
uire the design of new polymers incorporating optimized gene delivery prope
rties. For example, inefficient release of the DNA/polymer, complex from en
docytic vesicles into the cytoplasm is one of the primary causes of poor ge
ne delivery. Here we report the synthesis of a biocompatible, imidazole-con
taining polymer designed to overcome this obstacle. DNA/polymer polyplexes
incorporating this polymer were Shown to have desirable physico-chemical pr
operties for gene delivery and are essentially nontoxic. Using this system,
mammalian cells in vitro were transfected in the absence of any exogenous
endosomolytic agent such as chloroquine. (C) 2000 John Wiley & Sons, Inc.