Enhancement of liposome mediated gene transfer by adding cholesterol and cholesterol modulating drugs.
Cholesterol is an important cell membrane component and has been used as co-lipid for cationic liposome to enhance gene delivery. However, the role of cholesterol in transfection efficiency has not been fully understood. In this study, transfection efficiency of liposome was measured after cholesterol was added to the cell culture medium. As a result, addition of cholesterol increased transfection efficiency of several liposomes consisting of different lipid components in various cells (AGS, CHO, COS7 and, MCF7). Furthermore, treatment of cells with cholesterol modulating drugs, imipramine and U18666A, also increased transfection efficiency of liposomes. To elucidate the role of added cholesterol in gene transfer, endocytotic mechanism was studied and also revealed that adding cholesterol in culture media induced participation of caveolae-mediated endocytosis and micropinocytosis in CHO cell. Therefore, the results of this work suggest that modulation of intracellular cholesterol can be an important method to enhance gene delivery.
Department of Physiology, College of Medicine, Yeungnam University, Daegu 42415, Republic of Korea.
Yun-Ui
YU
Bae
Department of Biochemistry and Molecular Biology, University of Ulsan College of Medicine, Seoul 05505, Republic of Korea.
Jae-Wan
JW
Huh
School of Life Sciences and Biotechnology, Kyungpook National University, Daegu 41566, Republic of Korea.
Bieong-Kil
BK
Kim
Department of Physiology, College of Medicine, Yeungnam University, Daegu 42415, Republic of Korea.
Hyeon Young
HY
Park
School of Life Sciences and Biotechnology, Kyungpook National University, Daegu 41566, Republic of Korea.
Young-Bae
YB
Seu
Department of Physiology, College of Medicine, Yeungnam University, Daegu 42415, Republic of Korea. Electronic address: kodoh@ynu.ac.kr.
Kyung-Oh
KO
Doh
D000736:Androstenes / Q000494:pharmacology; D000818:Animals; D016466:CHO Cells; D019556:COS Cells; D002784:Cholesterol / Q000378:metabolism / Q000494:pharmacology*; D003412:Cricetulus; D004705:Endocytosis; D018014:Gene Transfer Techniques; D006801:Humans; D007099:Imipramine / Q000494:pharmacology; D008081:Liposomes / Q000378:metabolism*
D000736:Androstenes; D008081:Liposomes; C006261:3-beta-(2-(diethylamino)ethoxy)androst-5-en-17-one; D002784:Cholesterol; D007099:Imipramine
Cholesterol; Gene therapy; Liposomes; Transfection