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Long-term expression with a cationic polymer derived from a natural polysaccharide: schizophyllan
Authors:Nagasaki Takeshi  Hojo Masaya  Uno Atsushi  Satoh Taku  Koumoto Kazuya  Mizu Masami  Sakurai Kazuo  Shinkai Seiji
Institution:Department of Applied & Bioapplied Chemistry, Graduate School of Engineering, Osaka City University, Sugimoto, Sumiyoshi, Osaka 558-8585, Japan. nagasaki@bioa.eng.osaka-cu.ac.jp
Abstract:Among the various synthetic gene carriers based on biomaterials, cationic polymers with polysaccharide backbones have long been studied as nonviral vectors due to their low immunogenicity and high water solubility. Schizophyllan, a beta-(1,3)-glucan, is one of the various polysaccharides that are clinically administered. Furthermore, its safety in the human body has already been confirmed. Various functional groups can be selectively introduced into the side chain, not into the main chain of schizophyllan. Therefore, we have synthesized various oligoamine conjugates from schizophyllan. It was confirmed that their in vitro transfection efficiencies are superior to that of polyethylenimine by adjusting the molecular weight and the degree of amination of cationic schizophyllan. While it was possible to reduce cytotoxicity by adjusting the amount of DNA complex per cell, as seen with poly-L-lysine, polyethylenimine, and chitosan, PEGylation was the most effective means of reducing toxicity. Furthermore, using cationic schizophyllan carriers, it was also possible to express a reporter protein for a long period of time due to a long residence time of plasmid DNA in cells.
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