Efficient delivery of plasmid DNA using cholesterol-based cationic lipids containing polyamines and ether linkages.
Cationic liposomes are broadly used as non-viral vectors to deliver genetic materials that can be used to treat various diseases including cancer. To circumvent problems associated with cationic liposome-mediated delivery systems such as low transfection efficiency and serum-induced inhibition, cholesterol-based cationic lipids have been synthesized that resist the effects of serum. The introduction of an ether-type linkage and extension of the aminopropyl head group on the cholesterol backbone increased the transfection efficiency and DNA binding affinity compared to a carbamoyl-type linkage and a mono aminopropyl head group, respectively. Under optimal conditions, each liposome formulation showed higher transfection efficiency in AGS and Huh-7 cells than commercially available cationic liposomes, particularly in the presence of serum. The following molecular structures were found to have a positive effect on transfection properties: (i) extended aminopropyl head groups for a strong binding affinity to plasmid DNA; (ii) an ether linkage that favors electrostatic binding to plasmid DNA; and (iii) a cholesterol backbone for serum resistance.
School of Life Sciences & Biotechnology, Kyungpook National University, 1370 Sangyeokdong, Bookgu, Daegu 702-701, Korea. kbk8516@hanmail.net.
Bieong-Kil
BK
Kim
School of Life Sciences & Biotechnology, Kyungpook National University, 1370 Sangyeokdong, Bookgu, Daegu 702-701, Korea. ybseu@knu.ac.kr.
Young-Bae
YB
Seu
Department of Physiology, Yeungnam University College of Medicine, 317-1 Daemyungdong, Daegu 705-717, Korea. neerg@hanmail.net.
Yun-Ui
YU
Bae
School of Life Sciences & Biotechnology, Kyungpook National University, 1370 Sangyeokdong, Bookgu, Daegu 702-701, Korea. micro00tw@nate.com.
Tae-Won
TW
Kwak
School of Life Sciences & Biotechnology, Kyungpook National University, 1370 Sangyeokdong, Bookgu, Daegu 702-701, Korea. hymnhim1@gmail.com.
Hyungu
H
Kang
WelGENE Inc., 71B-4L, Hightech Sector 2, Sungseo Industrial Park 3, Dalseogu, Daegu 704-230, Korea. moonikjae@clearlab.com.sg.
Ik-Jae
IJ
Moon
School of Life Sciences & Biotechnology, Kyungpook National University, 1370 Sangyeokdong, Bookgu, Daegu 702-701, Korea. daekom@hanmail.net.
Guen-Bae
GB
Hwang
Department of Physiology, Yeungnam University College of Medicine, 317-1 Daemyungdong, Daegu 705-717, Korea. sypark@med.yu.ac.kr.
So-Young
SY
Park
Department of Physiology, Yeungnam University College of Medicine, 317-1 Daemyungdong, Daegu 705-717, Korea. kodoh@ynu.ac.kr.
Kyung-Oh
KO
Doh
D000818:Animals; D019556:COS Cells; D002412:Cations / Q000737:chemistry; D002460:Cell Line; D002522:Chlorocebus aethiops; D002784:Cholesterol / Q000031:analogs & derivatives*; D004247:DNA / Q000008:administration & dosage* / Q000235:genetics; D006801:Humans; D008081:Liposomes / Q000737:chemistry; D010957:Plasmids / Q000008:administration & dosage* / Q000235:genetics; D014162:Transfection
D002412:Cations; D008081:Liposomes; D004247:DNA; D002784:Cholesterol