抄録
Asialofetuin-labeled liposomes (AF-liposomes) have been developed as an advantageous vector for asialoglycoprotein receptor (AgpR)-mediated gene transfer to hepatic cells. Plasmid pSV2CAT DNA which encodes bacterial chloraniphenicol acetyltransferase (CAT) was almost completely associated to AF-liposomes (AF-liposome-pSV2CAT) containing N-(α-trimethylammonio-acetyl)-didodecyl-D-glutamate chloride (TMAG), and approximately two-thirds of the associated DNA was encapsulated in the internal phase. AF-liposome-pSV2CAT was efficiently incorporated into the cultured human hepatoblastoma cell line, HepG2, by the RMF and significantly high CAT activity was expressed in the cells. The cat activity in A431 and Swiss/3T3 cells transfected with AF-liposome-pSV2CAT was low and almost the same as those transfected by pSV2CAT associated with non-labeled control liposomes. After injection of AF-liposome-pSV2CAT into a portal or femoral vein of BALB/c mice, CAT activity was expressed specifically in the liver. Immunohistochemical staining revealed that the CAT was developed in a large number of parenchymal cells localizing in the periportal area. Pretreatment of the cells or animals with EDTA-encapsulated AF-liposomes increased the gene expression efficiency of AF-liposome-pSV2CAT in vitro and in vivo. AF-liposomes are capable of protecting the encapsulated plasmid DNAs from environmental degradation in circulating blood and targeting them into hepatocytes by way of AgpR.
