Gene Transfer Using Protamine Derivatives

摘要

Gene transfer represents an important advance in the treatment of both genetic and acquired diseases. Protamine as an efficient membrane translocating peptide has been widely employed for in vitro and in vivo delivery of various therapeutic genes. By far, there has been no attempt to determine the relatively efficacy, toxicity, and uptake mechanism of individual protamine derivative, the most effective form of protamine gene delivery systems therefore remains unknown. In the present study, we developed various protamine derivatives including low molecular weight protaminie (LMWP), PEG-modified protamine (PEGP), and disulfide linked dimerized protamine (DLDP) for gene delivery. These derivatives were complexing with pEGFP-C_2 and pCMVLuc reporter genes to study transfection efficacies and were incubated with HEK293 and U2OS cells to investigate cellular toxicity. Compared with protamine, these derivatives might be more suitable for gene transfer application due to the higher transfection efficacies and lower cellular toxicities.