CATIONIC LIPIDS DELAY THE TRANSFER OF PLASMID DNA TO LYSOSOMES

Plasmid S-35 DNA, naked or associated with different cationic lipid pr eparations was injected to rats. Subcellular distribution of radioacti vity in the liver one hour after injection, was established by centrif ugation methods. Results show that at that time, S-35 DNA has reached lysosomes. On the contrary, when S-35 DNA was complexed with lipids, r adioactivity remains located in organelles whose distribution after di fferential and isopycnic centrifugation, is clearly distinct from that of arylsulfatase, a lysosome marker enzyme. Injection of Triton WR 13 39, a specific density perturbant of lysosomes, four days before S-35 DNA injection causes a density decrease of radioactivity bearing struc tures, apparent one hour after naked S-35 DNA injection but visible on ly after more than five hours, when S-35 DNA associated with a cationi c lipid is injected. These observations show that cationic lipids dela y the transfer to lysosomes, of plasmid DNA taken up by the liver. (C) 1996 Academic Press, Inc.