POLYETHYLENIMINE BUT NOT CATIONIC LIPIDS PROMOTES TRANSGENE DELIVERY TO THE NUCLEUS IN MAMMALIAN-CELLS

The beta-galactosidase reporter gene, either free or complexed with va rious cationic vectors, was microinjected into mammalian cells. Cation ic lipids but not polyethylenimine or polylysine prevent transgene exp ression when complexes are injected in the nucleus. Polyethylenimine a nd to a lesser extent polylysine, but not cationic lipids, enhance tra nsgene expression when complexes are injected into the cytoplasm, This latter effect was independent of the polymer vector/cDNA ionic charge ratio, suggesting that nucleic acid compaction rather than surface ch arge was critical for efficient nuclear trafficking. Cell division was not required for nuclear entry. Finally, comparative transfection and microinjection experiments with various cell lines confirm that barri ers to gene transfer vary with cell type. We conclude that polymers bu t not cationic lipids promote gene delivery from the cytoplasm to the nucleus and that transgene expression in the nucleus is prevented by c omplexation with cationic lipids but not with cationic polymers.