Long-term expression with a cationic polymer derived from a natural polysaccharide: schizophyllan.
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.
Nagasaki
Takeshi
T
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
Hojo
Masaya
M
Uno
Atsushi
A
Satoh
Taku
T
Koumoto
Kazuya
K
Mizu
Masami
M
Sakurai
Kazuo
K
Shinkai
Seiji
S
D000818:Animals; D016466:CHO Cells; D019556:COS Cells; D002412:Cations; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D002522:Chlorocebus aethiops; D006224:Cricetinae; D005786:Gene Expression Regulation / Q000187:drug effects; D005822:Genetic Vectors; D006367:HeLa Cells; D006801:Humans; D011092:Polyethylene Glycols / Q000737:chemistry / Q000494:pharmacology; D011108:Polymers / Q000737:chemistry / Q000494:pharmacology*; D012566:Sizofiran / Q000737:chemistry / Q000494:pharmacology*; D013995:Time; D014162:Transfection / Q000379:methods
D002412:Cations; D011108:Polymers; D011092:Polyethylene Glycols; D012566:Sizofiran