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Targeted Delivery of DNA to the Mitochondrial Compartment via Import Sequence-Conjugated Peptide Nucleic Acid

A. Flierl,1,* C. Jackson,2 B. Cottrell,1,* D. Murdock,1,† P. Seibel,3 and D.C. Wallace1,‡
MOLECULAR THERAPY Vol. 7, No. 4, April 2003

We report that oligonucleotides can be introduced into the mitochondria of living mammalian cells by annealing them to peptide nucleic acids coupled to mitochondrial targeting peptides. These complexes are imported into the mitochondrial matrix through the outer and inner membrane import channels of isolated mitochondria. They are also imported into the mitochondria of cultured cells, provided that the cytosolic uptake of the complexes is facilitated by using synthetic polycations or membrane permeabilizing toxins. Our method now promises to provide a viable strategy for the genetic modification of the mitochondria in cultured cells, animals and patients.