POLYREACTIVE ANTI-DNA MONOCLONAL-ANTIBODIES AND A DERIVED PEPTIDE AS VECTORS FOR THE INTRACYTOPLASMIC AND INTRANUCLEAR TRANSLOCATION OF MACROMOLECULES

Naturally occurring polyreactive anti-DNA mAbs derived from a nonimmun ized (NZB x NZW) F-1 mouse with spontaneous lupus erythematosus penetr ated and accumulated in the nuclei of a variety of cultured cells. The se mAbs and their F(ab')2 and Fab' fragments, covalently coupled to fl uorescein, peroxidase, or a 15-mer polynucleotide, also translocated t o the cell nuclei, A 30-amino acid peptide corresponding to the combin ed sequences of the complementary-determining regions 2 and 3 of the h eavy chain variable region of one mAb was able to penetrate into the c ytoplasm and nucleus of cells of several lines. This peptide recognize d DNA and was strongly polyreactive, Streptavidin-peroxidase conjugate s complexed with the N-biotinylated peptide were rapidly translocated into cells. Similarly, peroxidase or anti-peroxidase polyclonal antibo dies covalently coupled to the N-cysteinylated peptide through an hete robifunctional maleimide cross-linker were also rapidly internalized a nd frequently accumulated in nuclei, The peptide carrying 19 lysine re sidues at its N-terminal was highly effective in transfecting 3T3 cell s with a plasmid containing the luciferase gene. Thus, penetrating mAb s and derived peptides are versatile vectors for the intracellular del ivery of proteins and genes.