Interaction between DNA-cationic liposome complexes and erythrocytes is animportant factor in systemic gene transfer via the intravenous route in mice: the role of the neutral helper lipid

Recent studies have indicated that there are many barriers to successful sy stemic gene delivery via cationic lipid vectors using the intravenous route . The purpose of this study was to investigate the effect of binding and in teraction between erythrocytes, a major constituent of blood cells, and the complexes, in relation to the role of the helper lipid, on the in vivo gen e delivery to the lung following intravenous injection. We used three types of cationic lipid vectors, DNA-DOTMA/Chol liposome complexes, DNA-DOTMA li posome complexes, and DNA-DOTMA/DOPE liposome complexes. Although the three types of vectors bind to murine blood cells in vivo and in vitro. DOTMA/Ch ol and DOTMA complexes with a higher in vivo transfection activity do not i nduce fusion between erythrocytes, whereas DOTMA/DOPE complexes, a less eff icient vector in vivo, induce fusion between the erythrocytes after a short incubation period. Pre-incubation of DOTMA/DOPE complexes with erythrocyte s significantly reduced the transfection efficiency while DOTMA/Chol- and D OTMA complexes were more resistant to such treatment. The differences in th e physicochemical and structural properties of these complexes could explai n the differences in interaction with erythrocytes and subsequent gene expr ession. Lipids in DOTMA/Chol and DOTMA complexes have a stable lamellar str ucture. However, lipids in DOTMA/DOPE complexes have a highly curved struct ure with high fluidity. These results indicate that the interaction with er ythrocytes depends on the properties of the cationic lipid vectors and this is an important factor for intravenous gene delivery using cationic lipid vectors.