THE REDUCTION OF THE POSITIVE CHARGES OF POLYLYSINE BY PARTIAL GLUCONOYLATION INCREASES THE TRANSFECTION EFFICIENCY OF POLYLYSINE DNA COMPLEXES/

A polylysine partially substituted with polyhydroxyalkanoyl residues a nd specially with gluconoyl residues was developed in order to increas e the transfection efficiency by decreasing the strength of the electr ostatic interactions between the DNA and the cationic polymer. Partial ly gluconoylated polylysine/DNA complexes were more easily dissociated in solution and their transfection efficiency in the presence of chlo roquine, evaluated with HepG2 cells, a human hepatocarcinoma line, was higher when 43 +/- 4% of the epsilon-amino groups of polylysine were blocked with gluconoyl residues. Partially gluconoylated polylysine/pl asmid complexes were efficient in transfecting different adherent as w ell as non-adherent eel lines. Partially gluconoylated polylysine form ed highly soluble (above 100 mu g/ml in DNA) complexes with DNA plasmi ds. In addition, partially gluconoylated polylysine bearing few lactos yl residues increased the transfection efficiency of HepG2 cells which express a galactose-specific membrane lectin.