Targeted Gene Delivery with a Low Molecular Weight Glycopeptide Carrier

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Abstract
A low molecular weight glycopeptide carrier was prepared by coupling a tyrosinamide-triantennary oligosaccharide to dp19 poly-L-lysine resulting in a 1:1 conjugate. The glycopeptide carrier complexed with plasmid DNA as evidenced by displacement of intercalated dye, light scattering by condensed DNA, and immobility of complexed DNA upon agarose gel electrophoresis. DNA-carrier complexes were endocytosed into HepG2 cells via the asialoglycoprotein receptor due to recognition of terminal galactose residues on the oligosaccharide. The resulting luciferase reporter gene expression was dramatically influenced by the solubility of complexes, the extent of complexation, and the presence of the lysosomotropic agent chloroquine. The results suggest that low molecular weight glycopeptides may be suitable for further development as well-defined DNA carriers for receptor-mediated gene delivery in vivo.

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