840. Novel Receptor-Mediated Gene Transfection Systems Comprising Plasmid / Polycation / RGD-PEG-COOH Ternary Complexes

Abstract

In the non-viral gene delivery systems using cationic polymers, DNA / polycation complexes are usually positively charged, and their adsorption to the extracellular matrix and the coaggulation by the serum proteins have been the problems. We have reported1 that coating of the DNA complex by the PEG derivative having propionic acid side chains (PEG-C) could recharge it to negative, and effectively suppress these interactions. It also improved the transgene expression efficiency probably due to the proton sponge effect of the carboxyl groups. However, the ternary polyion complex of DNA / polycation / PEG-C was not always stable against the high concentration of albumin as in the serum. In order to obtain a more stable ternary complex, a PEG derivative with succinic acid side chains, PEG-Suc, was synthesized, which would have two-fold more carboxyl side chains than PEG-C.