Qing Fa Guo, Ting Ting Liu, Xi Yan, Xiu Hong Wang, Shuai Shi, Feng Luo, Zhi Yong QianState Key Laboratory of Biotherapy and Cancer Center, West China Hospital, West China Medical School, Sichuan University, Chengdu, People's Republic of ChinaBackground: Gene therapy is a promising approach to the treatment of a wide range of diseases. The development of efficient and adequate gene delivery systems could be one of the most important factors. Polyethyleneimine, a cationic polymer, is one of the most successful and widely used vectors for nonviral transfection in vitro and in vivo.Methods: A novel biodegradable poly(ester amine) copolymer (PEA) was successfully prepared from low molecular weight polyethylenimine (PEI, 2000 Da) and poly(L-lactide) copolymers.Results: According to the results of agarose gel electrophoresis, particle size and zeta potential measurement, and transfection efficiency, the PEA copolymers showed a good ability to condense plasmid DNA effectively into nanocomplexes with a small particle size (≤150 nm) and moderate zeta potential (≥10 mV) at an appropriate polymeric carrier/DNA weight ratio. Compared with high molecular weight PEI (25kDa), the PEA obtained showed relatively high gene transfection efficiency as well as low cytotoxicity in vitro.Conclusion: These results indicate that such PEA might have potential application as a gene delivery system.Keywords: polyethylenimine, poly(L-lactide), gene delivery, cytotoxicity, transfection efficiency