Abstract
A novel gene transfer system was developed by using liposomes modified with cetylated polyethylenimine (PEI, MW 600). This polycation liposome, PCL, showed remarkable transfection efficiency as monitored by the expression of the GFP reporter gene. Most conventional cationic liposomes require phosphatidylethanolamine or cholesterol as a component, although PCLs did not. Egg yolk phosphatidylcholine- and dipalmitoylphosphatidylcholine-based PCL were as effective as dioleoylphosphatidylethanolamine-based PCLs for gene transfer. Concerning the cytotoxicity against COS-1 cells and hemolytic activity, the PCL was superior to conventional cationic liposome preparations. Furthermore, the transfection efficacy of PCLs was enhanced, instead of being diminished, in the presence of serum. Effective gene transfer was observed in all eight malignant and two normal cells line tested, as well as in COS-1 cells. We also examined the effect of the molecular weight of PEI on PCL-mediated gene transfer, and observed that PEI with a MW of 1800 Da was as effective as that with one of 600, but that PEI of 25 000 was far less effective. Finally, an in vivo study was done in which GFP was effectively expressed in mouse liver after injection of PCL via the portal vein. Thus, PCL represents a new system useful for transfection and gene therapy.
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Acknowledgements
We thank Drs K Takeda and H Miyazaki and Mr Y Suzuki at DNAVEC Research, for their helpful discussions; Mr T Iwasaki and Mr H Ori for technical assistance, and Dr Y Sadzuka of the University of Shizuoka for measurement of ζ-potentials. We also thank Dr Y Namba at Nippon Fine Chemical for the supply of phospholipids.
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Yamazaki, Y., Nango, M., Matsuura, M. et al. Polycation liposomes, a novel nonviral gene transfer system, constructed from cetylated polyethylenimine. Gene Ther 7, 1148–1155 (2000). https://doi.org/10.1038/sj.gt.3301217
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DOI: https://doi.org/10.1038/sj.gt.3301217
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