Cell-specific delivery of genes with glycosylated carriers.
Cationic liposomes and polymers have been accepted as effective non-viral vectors for gene delivery with low immunogenicity unlike viral vectors. However, the lack of organ or cell specificity sometimes hampers their application and the development of a cell-specific targeting technology for them attracts great interest in gene therapy. In this review, the potential of cell-specific delivery of genes with glycosylated liposomes or polymers is discussed. Galactosylated liposomes and poly(amino acids) are selectively taken up by the asialoglycoprotein receptor-positive liver parenchymal cells in vitro and in vivo after intravenous injection. DNA-galactosylated cationic liposome complexes show higher DNA uptake and gene expression in the liver parenchymal cells in vitro than DNA complexes with bare cationic liposomes. In the in vitro gene transfer experiment, galactosylated liposome complexes are more efficient than DNA-galactosylated poly(amino acids) complexes but they have some difficulties in their biodistribution control. On the other hand, introduction of mannose residues to carriers resulted in specific delivery of genes to non-parenchymal liver cells. These results suggest advantages of these glycosylated carriers in cell-specific targeted delivery of genes.
Hashida
M
M
Department of Drug Delivery Research, Graduate School of Pharmaceutical Sciences, Kyoto University, Sakyo-ku, Kyoto 606-8501, Japan. hashidam@pharm.kyoto-u.ac.jp
Nishikawa
M
M
Yamashita
F
F
Takakura
Y
Y
D000595:Amino Acid Sequence; D000818:Animals; D002477:Cells / Q000378:metabolism; D004337:Drug Carriers / Q000493:pharmacokinetics*; D016503:Drug Delivery Systems / Q000379:methods*; D015316:Genetic Therapy / Q000379:methods*; D006031:Glycosylation; D006801:Humans; D008969:Molecular Sequence Data; D009928:Organ Specificity / Q000235:genetics*; D014162:Transfection / Q000379:methods*
D004337:Drug Carriers