A peptide nucleic acid-nuclear localization signal fusion that mediates nuclear transport of DNA

We have combined a peptide nucleic acid (PNA) with the SV40 core nuclear lo calization signal (NLS), to create a bifunctional PNA-NLS peptide. The PNA- NLS peptide increased the nuclear uptake of oligonucleotides and enhanced t he transfection efficacy of plasmids. Gene expression from an enhanced gree n fluorescent protein plasmid and a lacZ plasmid was preserved when hybridi zed to PNA-NLS. In combination with the transfection agent polyethyleneimin e, we have improved both the nuclear translocation of fluorescence-marked o ligonucleotides, and the efficacy of plasmid transfection, up to eightfold. The technique obviates the use of cumbersome coupling procedures of the ve ctor due to DNA-PNA duplex formation or displacement of the antisense plasm id DNA strand by a PNA molecule.