Bifunctional compounds for targeted hepatic gene delivery.
A series of bifunctional compounds with galactosyl residues as targeting ligand for asialoglycoprotein receptors on hepatocytes and various dendrimers as the DNA-binding domain was synthesized. When mixed with plasmid DNA, these compounds self assembled into particles that exhibited high transfection activity both in vitro and in vivo. Optimal activity in liver cells was observed with compounds containing three galactosyl residues and 16 dendrimer arms. These results suggest that domain-based design is an effective strategy for development of a new generation of synthetic gene carriers.
Kim
K S
KS
Department of Pharmaceutical Sciences, School of Pharmacy, University of Pittsburgh, Pittsburgh, PA 15261, USA.
Lei
Y
Y
Stolz
D B
DB
Liu
D
D
D001212:Asialoglycoproteins / Q000235:genetics; D004247:DNA / Q000008:administration & dosage* / Q000235:genetics / Q000378:metabolism; D004337:Drug Carriers; D005696:Galactosidases / Q000235:genetics; D015870:Gene Expression; D018390:Gene Targeting / Q000379:methods*; D015316:Genetic Therapy / Q000379:methods*; D006801:Humans; D008099:Liver / Q000378:metabolism* / Q000648:ultrastructure; D008854:Microscopy, Electron; D013194:Staining and Labeling; D013329:Structure-Activity Relationship; D014162:Transfection / Q000379:methods*
D001212:Asialoglycoproteins; D004337:Drug Carriers; D004247:DNA; D005696:Galactosidases