Low Molecular Weight Protamine Peptides As Gene Delivery Carrier: a Novel Gene Delivery Agent

Non viral gene delivery systems such as cationic lipids, synthetic polymers and peptides demonstrate significant advantages over the viral delivery systems that are usually associated with immunological responses and safety risks. Protamine, is a cationic peptide, used as a gene delivery carrier and has been widely used for various therapeutic purposes including heparin neutralization and long-acting insulin formulation. Well-designed enzyme digestion method was used to obtain the minimal functional sequences of low molecular weight protamine (LMWPs). In vivo experiments exhibited that LMWPs maintained their heparin neutralization but have lesser toxicity compared to native protamine. LMWPs demonstrated DNA binding and condensation ability and could form nanoparticles with various DNA. In vitro gene transfection studies showed that LMWPs have the same or even strong gene transfection ability than that of lipofectamine, a commercially available gene transfection reagent. These results suggest that LMWP can be useful and safe gene carriers to replace protamine in gene delivery.