Transluminal Gene Transfer into Brain Capillary Endothelial Cells In Vivo with HVJ-liposomes.

Bioactive proteins or peptides cannot be effectively delivered into brain capillary endothelial cells (BCECs) or brain parenchyma. In this study, we selectively transferred Escherichia coli β-galactosidase gene (β-gal) as a model gene into BCECs by using the hemagglutination virus of Japan (HVJ)-liposomes. HVJ-liposomes encapsulating a β-gal plasmid were used to transfect MBEC4 cells in vitro , and were administrated via the internal carotid artery to rat in vivo . Success of the procedure was confirmed by the detection of 116 kDa β-gal protein in transfected MBEC4 cells and in brain capillaries isolated from transfected rats, by Western blot analysis and histological staining. The enzymatic activities of β-galactosidase were 5- to 10-fold and 20-fold higher than when β-gal-containing liposomes without fusogenic activity (uncoated liposomes) or plasmid alone were employed in vitro and in vivo , respectively. Thus, HVJ-liposomes were demonstrated to be a useful vector to transfer a foreign gene into the brain capillary endothelium in vivo via the transluminal route. [ABSTRACT FROM AUTHOR]