Design of imidazole-containing endosomolytic biopolymers for gene delivery

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.