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임종은,Irina Krier,임정묵,심수진,한동근,Jeffrey A. Hubbell 한국고분자학회 2015 Macromolecular Research Vol.23 No.4
Polyethylenimine (PEI) is a promising gene carrier among polymeric vectors because of its high transfectionefficiency, buffering capacity, which is responsible for its escape from endosomes, facility of modification,reasonable price and wide range of molecular weight. However, toxicity of PEI is an important obstacle to overcomefor using it as a gene carrier in gene therapy protocols. In our study, PEI (10 kDa) was modified with urocanic acid,which has an imidazole ring (PEIU). This modification of PEI played an important role by improving transfectionefficiency and reducing toxicity. The PEIU was condensed with DNA in different nitrogen of polycation/phosphateof DNA (N/P) ratios starting from 1.25. The PEIU/DNA complexes formed smaller (60-80 versus 100-400 nm) andless dispersible particles than PEI/DNA complexes. Cell viability test showed that in all the transfection experimentsPEIU was always found less toxic than the PEI on three different cell-lines, Cos-7, HeLa, and 293T. The PEIUdemonstrated improved biocompatibility as compared to the PEI. The in vitro transfection experiments showed thatthe PEIU displayed similar or lower transfection efficiencies than the PEI in the absence of serum. In medium complementedwith serum, the PEIU had higher transfection efficiencies than the PEI. In vivo transfection experimentswere carried out with intravenous and subcutaneous injections into mice. Five different organs were taken and lysedfor quantification of expressed GFP. The quantification of the fluorescence of these organs exhibited that the PEIUhas better transfection efficiency in in vivo experiments compared to the PEI. This study generated a strong evidenceindicating that PEIU can be considered as a promising versatile gene carrier because of its biocompatibility and goodtransfection efficiency.