PURPOSE: The purpose of this study is to elucidate the in vivo gene transfer for galactosylated liposomes containing cholesten-5-yloxy-N-(4-((1-imino-2-beta-D-thiogalactosyle thyl)amino)butyl)formamide(Gal-C4-Chol) in relation to lipid composition and charge ratio. METHODS: Galactosylated cationic liposomes containing N-[1-(2,3-dioleyloxy)propyl]-n,n,n-trimethylammonium chloride(DOTMA), Gal-C4-Chol and cholesterol(Chol), and similar liposomes were prepared. Plasmid DNA complexed with a galactosylated liposome preparation was injected intraportally into mice. The mice were sacrificed after 6 hours. The tissues were subjected to luciferase assay. RESULTS: A markedly higher gene expression in the liver following injection of plasmid DNA that has been complexed with DOTMA/ Chol/Gal-C4-Chol(1:0.5:0.5) and DOTMA/Gal-C4-Chol(1:1) liposomes was observed. The effect was one order of magnitude higher than naked DNA and DOTMA/Chol(1:1) liposomes. Pre-exposing with galactosylated bovine serum albumin significantly reduced the hepatic gene expression. By comparison, the gene expression for galactosylated cationic liposomes containing 3beta[N-(N',N'-dimethylaminoethane)carbamoyl]cholesterol, Gal-C4-Chol and dioleoylphosphatidylethanolamine was 10 times lower. As far as the charge ratio of DOTMA/ Chol/Gal-CA-Chol(1:0.5:0.5) liposomes to plasmid DNA(1.6-7.0) was concerned, complexes with charge ratios of 2.3-3.1 produced maximal gene expression in the liver. Whereas, higher ratios resulted in enhanced expression in the lung. CONCLUSIONS: By optimizing lipid composition and charge ratio, galactosylated liposome/DNA complexes allow superior in vivo gene transfection in the liver via asialoglycoprotein receptor-mediated endocytosis.
PURPOSE: The purpose of this study is to elucidate the in vivo gene transfer for galactosylated liposomes containing cholesten-5-yloxy-N-(4-((1-imino-2-beta-D-thiogalactosyle thyl)amino)butyl)formamide(Gal-C4-Chol) in relation to lipid composition and charge ratio. METHODS: Galactosylated cationic liposomes containing N-[1-(2,3-dioleyloxy)propyl]-n,n,n-trimethylammonium chloride(DOTMA), Gal-C4-Chol and cholesterol(Chol), and similar liposomes were prepared. Plasmid DNA complexed with a galactosylated liposome preparation was injected intraportally into mice. The mice were sacrificed after 6 hours. The tissues were subjected to luciferase assay. RESULTS: A markedly higher gene expression in the liver following injection of plasmid DNA that has been complexed with DOTMA/ Chol/Gal-C4-Chol(1:0.5:0.5) and DOTMA/Gal-C4-Chol(1:1) liposomes was observed. The effect was one order of magnitude higher than naked DNA and DOTMA/Chol(1:1) liposomes. Pre-exposing with galactosylated bovine serum albumin significantly reduced the hepatic gene expression. By comparison, the gene expression for galactosylated cationic liposomes containing 3beta[N-(N',N'-dimethylaminoethane)carbamoyl]cholesterol, Gal-C4-Chol and dioleoylphosphatidylethanolamine was 10 times lower. As far as the charge ratio of DOTMA/ Chol/Gal-CA-Chol(1:0.5:0.5) liposomes to plasmid DNA(1.6-7.0) was concerned, complexes with charge ratios of 2.3-3.1 produced maximal gene expression in the liver. Whereas, higher ratios resulted in enhanced expression in the lung. CONCLUSIONS: By optimizing lipid composition and charge ratio, galactosylated liposome/DNA complexes allow superior in vivo gene transfection in the liver via asialoglycoprotein receptor-mediated endocytosis.
Authors: R I Mahato; K Anwer; F Tagliaferri; C Meaney; P Leonard; M S Wadhwa; M Logan; M French; A Rolland Journal: Hum Gene Ther Date: 1998-09-20 Impact factor: 5.695
Authors: Bo Yoon Choi; Jin Wook Chung; Jae Hyung Park; Keon Ha Kim; Young Il Kim; Young Hwan Koh; Jong Won Kwon; Kyoung Ho Lee; Hyuk Jae Choi; Tae Woo Kim; Young Jin Kim; Hesson Chung; Ik Chan Kwon; Seo Young Jeong Journal: Korean J Radiol Date: 2002 Jul-Sep Impact factor: 3.500