201. Selective Targeting of Nucleic Acid Nanoparticles to Hepatocytes In Vivo

A critical step for liver-directed gene therapy is the selective targeting of nucleic acids to hepatocytes. There are a variety of physical characteristics that affect a nucleic acid particle's hepatocyte-targeting ability: size, surface charge, particle stability, and targeting ligand. Using a variety of formulation methods we are able to control a particle's size, charge, and stability to maximize hepatocyte targeting. Size and stability are controlled using bifunctional crosslinking reagents to cage the nucleic acid inside a net composed of a condensing polycation. The surface charge may be reduced via acetylation, which converts cationic ammonium groups to nonbasic amide groups. Selective hepatocyte targeting is finally conferred by attachment of galactose groups, which are ligands for the asiologlycoprotein receptor.