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 beta-galactosidase gene (beta-gal) as a model gene into BCECs by using the hemagglutination virus of Japan (HVJ)-liposomes. HVJ-liposomes encapsulating a beta-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 beta-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 beta-galactosidase were 5- to 10-fold and 20-fold higher than when beta-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.
Jiang
Chen
C
Graduate School of Pharmaceutical Sciences, Kyushu University, Fukuoka, Japan.
Matsuo
Hirotami
H
Koyabu
Noriko
N
Ohtani
Hisakazu
H
Fujimoto
Hidenori
H
Yonemitsu
Yoshikazu
Y
Kaneda
Yasufumi
Y
Narro
Mikihiko
M
Tsuruo
Takashi
T
Sawada
Yasufumi
Y
D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000201:enzymology; D002196:Capillaries / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology; D018014:Gene Transfer Techniques; D005822:Genetic Vectors / Q000008:administration & dosage; D008081:Liposomes / Q000008:administration & dosage*; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D014780:Viruses / Q000235:genetics; D001616:beta-Galactosidase / Q000235:genetics / Q000378:metabolism
D008081:Liposomes; D001616:beta-Galactosidase