Receptor-mediated transfer of pSV2CAT DNA to mouse liver cells using asialofetuin-labeled liposomes.
Asialofetuin-labeled liposomes (AF-liposomes) were developed as a nonviral vector having high transfection activity for receptor-mediated gene transfer to hepatocytes by systemic administration. Initially, the majority of pSV2CAT, a chloramphenicol acetyltransferase (CAT) gene expression plasmid, was associated with AF-liposomes (AF-liposome-pSV2CAT), and they were injected into the portal vein of an adult mouse. Significantly high CAT activity was observed in the liver. The CAT activity in the liver was further increased two-fold by using AF-liposomes completely encapsulating pSV2CAT. Nonlabeled control liposomes, on the other hand, showed lower CAT activity in the liver than in the spleen or lung. The level of CAT mRNA reflected the CAT activity obtained by each liposome preparation in each tissue. Immunohistochemical staining showed that CAT was produced in a large number of parenchymal cells localizing in the periportal area. The plasmid encapsulated in the internal aqueous layer of the liposomes was effectively protected from environmental degradation. Thus, by administration into the blood circulation, AF-liposomes would be successfully incorporated into hepatocytes through receptor-mediated endocytosis, and the encapsulated plasmid would be transferred to the intracellular pathway.
Hara
T
T
Department of Biopharmaceutics, Tokyo University of Pharmacy and Life Science, Japan.
Aramaki
Y
Y
Takada
S
S
Koike
K
K
Tsuchiya
S
S
D000818:Animals; D001212:Asialoglycoproteins; D001921:Brain / Q000378:metabolism; D015500:Chloramphenicol O-Acetyltransferase / Q000032:analysis / Q000096:biosynthesis*; D004337:Drug Carriers; D060748:Fetuins; D015870:Gene Expression; D007150:Immunohistochemistry; D007668:Kidney / Q000378:metabolism; D008081:Liposomes; D008099:Liver / Q000378:metabolism*; D051379:Mice; D009206:Myocardium / Q000378:metabolism; D009928:Organ Specificity; D010957:Plasmids / Q000008:administration & dosage*; D012333:RNA, Messenger / Q000032:analysis / Q000096:biosynthesis; D011994:Recombinant Proteins / Q000032:analysis / Q000096:biosynthesis*; D013154:Spleen / Q000378:metabolism; D014162:Transfection / Q000379:methods*; D000509:alpha-Fetoproteins
D001212:Asialoglycoproteins; D004337:Drug Carriers; D060748:Fetuins; D008081:Liposomes; D012333:RNA, Messenger; D011994:Recombinant Proteins; D000509:alpha-Fetoproteins; C017029:asialofetuin; D015500:Chloramphenicol O-Acetyltransferase