Gene-transferring efficiencies of novel diamino cationic lipids with varied hydrocarbon chains.
Utilizing three biocompatible components, a series of novel cationic lipids has been chemically synthesized and tested for their gene-transferring capabilities in 293 transformed kidney cells and B16BL6 mouse melanoma cells. The synthesized cationic lipids consisting of a core of lysine and aspartic acid with hydrocarbon chains of varied length were assigned the acronyms DLKD (O,O'-dilauryl N-lysylaspartate), DMKD (O,O'-dimyristyl N-lysylaspartate), DPKD (O,O'-dipalmityl N-lysylaspartate), and DSKD (O,O'-distearyl N-lysylaspartate). The gene-transferring capabilities of these cationic lipids were found to be dependent on the hydrocarbon chain length. Under similar experimental conditions, the order of gene transfection efficiency was DMKD > DLKD > DPKD > DSKD. Addition of cholesterol or dioleoyl phosphatidylethanolamine (DOPE) as a colipid did not change this order. Colipid addition affected the transfection efficiency positively or negatively depending on the length of the cationic lipid acyl chain. On the whole, the length of the hydrophobic carbon chain was a major factor governing the gene-transferring capabilities of this series of cationic lipids. The observed differences in transfection efficiency may be due to differing binding affinities to DNA molecules as well as differences in the surface charge potential of the liposome-DNA complexes (lipoplexes) in the aqueous environment.
Kim
Hong Sung
HS
Department of Biomedical Laboratory Science, Yonsei University, Wonju 220-710, Korea.
Moon
Jaeho
J
Kim
Keun Sik
KS
Choi
Myung Min
MM
Lee
Ji Eun
JE
Heo
Yeon
Y
Cho
Dae Hyan
DH
Jang
Doo Ok
DO
Park
Yong Serk
YS
D000818:Animals; D002461:Cell Line, Transformed; D045744:Cell Line, Tumor; D004305:Dose-Response Relationship, Drug; D018014:Gene Transfer Techniques; D006801:Humans; D006838:Hydrocarbons / Q000008:administration & dosage*; D008081:Liposomes / Q000008:administration & dosage*; D051379:Mice; D014162:Transfection
D006838:Hydrocarbons; D008081:Liposomes