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Targeted Gene Transfer to Liver Using Protein-DNA Complexes

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The advantages of nonviral carriers are their ease of preparation and scaleup, capacity of DNA to be transferred, and safety in vivo. However, there also are disadvantages, including generally low efficiency and transience of transgene expression. To create more efficient systems, the use of approaches present in natural pathogens has been shown to be helpful. Based on an understanding of these natural components, ligand-polycation DNA delivery systems have been developed (1 3 ). In these systems, a DNA-binding polycation, such as polylysine (PL) was employed to compact plasmid DNA to a size that could be taken up by cells. To allow internalization by receptor-mediated endocytosis, cell binding ligands such as asialoglycoproteins for hepatocytes, antiCD3 and anti-CD5 antibodies for T-cells, transferrin for some cancer cells, and hyaluronic acid polymers for endothelial cells have been covalently attached to polylysine.
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