Targeting of synthetically glycosylated human placental glucocerebrosidase

Abstract

Human placental β-glucocerebrosidase modified by covalent attachment of N²-{N²,N⁶-bis[3-(α-d-mannopyranosylthio)propionyl]-l-lysyl}-N⁶-[3-(α-d-mannopyr-anosylthio) propionyl]-l-lysine was administered to rats by intravenous injection. Comparison of enzyme distribution in isolated liver cell populations indicates an increase in enzyme-specific activity of 18-fold in nonparenchymal cells and only 1.5-fold to hepatocytes compared to uninjected control animals. This macrophage-specific delivery of an active lysosomal enzyme has potential for application in enzyme replacement trials.