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RESEARCH PRODUCT

Asialofetuin Liposomes for Receptor-Mediated Gene Transfer into Hepatic Cells

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description

Publisher Summary The liver is an excellent organ for gene transfer in treating a wide variety of diseases that affect liver function. It is an ideal organ for a high amount of expression of therapeutic genes and efficient systemic distribution of the resulting therapeutic proteins secreted into the bloodstream. For strategies of liver-destined gene therapy, the liver sinusoid endothelium contains pores with a mean diameter of 100 nm, which allow small vectors to leave the blood circulation and reach the hepatocytes. The preparation of asialofetuin–liposomes targeted to hepatocytes can be made by covalent coupling of asialofetuin glycoprotein (ASF) onto the liposome surface, by the use of heterobifunctional reagent N-succinimidyl 3-(2-pyridyldithio) propionate (SPDP). Changes in liposome charge can be made by inclusion on the liposome backbone of anionic or cationic lipids, cationic lipopeptides, and cationic polymers. Because the nuclear localization signal (NLS) is also a cationic polypeptide, it can interact directly with DNA by electrostatic interaction, increasing the nuclear availability of delivered DNA and thereby contributing to increase the efficacy or gene transfer.