title: An approach to transgene expression in liver endothelial cells using a liposome-based gene vector coated with hyaluronic acid.
abstract: Dysfunctional sinusoidal liver endothelial cells (LECs) are associated with liver diseases, such as liver fibrosis, cirrhosis, and portal hypertension. Because of this, gene therapy targeted to LECs would be a useful and productive strategy for directly treating these diseases at the level of genes. Here, we report on the development of a transgene vector that specifically targets LECs. The vector is a liposome-based gene vector coated with hyaluronic acid (HA). HA is a natural ligand for LECs and confers desirable properties on particles, rendering them biodegradable, biocompatible, and nonimmunogenic. In this study, we constructed HA-modified carriers, and evaluated cellular uptake and transfection activity using cultured LECs from KSN nude mice (KSN-LECs). Cellular uptake analyses showed that KSN-LECs recognized the HA-modified carriers more effectively than skin endothelial cells. The transfection assay indicated that the efficient gene expression in KSN-LECs, using the HA-modified carriers, required an adequate lipid composition and a functional device to control intracellular trafficking. This finding contributes to our overall knowledge of transgene expression targeted to LECs.
authors.affiliation: Laboratory for Molecular Design of Pharmaceutics, Faculty of Pharmaceutical Sciences, Hokkaido University, Sapporo 060-0812, Japan.
authors.forename: Yuma
authors.initials: Y
authors.lastname: Yamada
authors.forename: Masahiro
authors.initials: M
authors.lastname: Hashida
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Hayashi
authors.forename: Mai
authors.initials: M
authors.lastname: Tabata
authors.forename: Mamoru
authors.initials: M
authors.lastname: Hyodo
authors.forename: Mst Naznin
authors.initials: MN
authors.lastname: Ara
authors.forename: Noritaka
authors.initials: N
authors.lastname: Ohga
authors.forename: Kyoko
authors.initials: K
authors.lastname: Hida
authors.forename: Hideyoshi
authors.initials: H
authors.lastname: Harashima
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D004247:DNA / Q000008:administration & dosage* / Q000235:genetics; D042783:Endothelial Cells / Q000378:metabolism*; D015870:Gene Expression; D005822:Genetic Vectors / Q000008:administration & dosage* / Q000235:genetics; D006820:Hyaluronic Acid / Q000737:chemistry / Q000378:metabolism*; D008081:Liposomes / Q000737:chemistry / Q000378:metabolism*; D008099:Liver / Q000166:cytology*; D051379:Mice; D008819:Mice, Nude; D014162:Transfection; D019076:Transgenes
chemical_list: D008081:Liposomes; D006820:Hyaluronic Acid; D004247:DNA
keywords: DNA delivery; hyaluronic acid; liposomes; liver endothelial cell; multifunctional envelope-type nano device; nanotechnology; non-viral gene vector; plasmid DNA; transfection; transgene expression