DNA VECTOR CHEMISTRY - THE COVALENT ATTACHMENT OF SIGNAL PEPTIDES TO PLASMID DNA

The nuclear entry of exogenous DNA in mammalian cells is critical for efficient gene transfer. A novel technique was developed for the coval ent attachment of cationic peptides to double-stranded DNA using a cyc lo-propapyrroloindole cross-linker. The attachment of the SV40 large T antigen nuclear localization signal peptide induced the nuclear accum ulation of the conjugated DNA in digitonin-permeabilized cells via the classical pathway for the nuclear transport of karyophilic proteins. Increased nuclear uptake of the modified DNA, however, did not occur a fter it was microinjected into the cytoplasm of cultured cells. This d emonstration that the covalent modification of DNA with a signal pepti de alters its behavior and interaction with other cellular factors por tends the potential of DNA vector chemistry to enhance the efficiency of cellular gene transfer.