Cationic lipids delay the transfer of plasmid DNA to lysosomes

Plasmid S-35 DNA, naked or associated with different cationic lipid preparations was injected to rats. Subcellular distribution of radioactivity in the liver one hour after injection, was established by centrifugation methods. Results show that at that time, S-35 DNA has reached lysosomes. On the contrary, when S-35 DNA was complexed with lipids, radioactivity remains located in organelles whose distribution after differential and isopycnic centrifugation, is clearly distinct from that of arylsulfatase, a lysosome marker enzyme. Injection of Triton WR 1339, a specific density perturbant of lysosomes, four days before S-35 DNA injection causes a density decrease of radioactivity bearing structures, apparent one hour after naked S-35 DNA injection but visible only after more than five hours, when S-35 DNA associated with a cationic lipid is injected. These observations show that cationic lipids delay the transfer to lysosomes, of plasmid DNA taken up by the liver. (C) 1996 Academic Press, Inc.