RELATIONSHIP BETWEEN PHYSICOCHEMICAL CHARACTERISITCS, DISTRIBUTION OF DNA-CATIONIC LIPOSOME COMPLEXES AND THEIR GENE EXPRESSION, AND APPLICATION TO GENE THERAPY

Abstract

Cationic liposome-mediated transfection is a useful method for in vitro and in vivo gene transfer. However, there is little information on the relationship between physicochemical and structural properties of DNA-cationic liposome complexes and their transfection efficiency. In this study, we have systemically studied the relationship between various properties of DNA-cationic liposome complexes and their transfection efficiency in vivo and in vitro. Our results demonstrated that for both in vitro and in vivo transfection, structural and physicochemical characteristics of the complexes were significantly related to their transfection efficiency. In in vitro transfection, the charge ratio between DNA and cationic liposome significantly affects the release of plasmid DNA complexed with the cationic liposomes from the complexes, which is an important determinant of the optimal charge ratio. For in vivo intravenous transfection, Chol-containing complexes with a higher transfection activity showed a stable lamellar structure and was more stable to the interaction with erythrocytes. DOPE-containing complexes, a less efficient vector, induced the fusion between erythrocytes due to its fusogenic property and lost their transfection activity. These results indicate that the interaction with erythrocytes is an important factor for intravenous gene delivery.