Targeted delivery of DNA to the mitochondrial compartment via import sequence-conjugated peptide nucleic acid.
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.
Flierl
A
A
Center for Molecular and Mitochondrial Medicine and Genetics, University of California, Irvine, 2122 Natural Sciences I, Irvine, California 92697-3940, USA.
Jackson
C
C
Cottrell
B
B
Murdock
D
D
Seibel
P
P
Wallace
D C
DC
D000818:Animals; D001426:Bacterial Proteins; D001692:Biological Transport; D051379:Mice; D008856:Microscopy, Fluorescence; D008928:Mitochondria / Q000737:chemistry / Q000378:metabolism* / Q000648:ultrastructure; D032446:Myoblasts / Q000378:metabolism / Q000648:ultrastructure; D009838:Oligodeoxyribonucleotides / Q000737:chemistry / Q000378:metabolism*; D020135:Peptide Nucleic Acids / Q000737:chemistry / Q000378:metabolism*; D011094:Polyethyleneimine / Q000737:chemistry; D021382:Protein Sorting Signals; D013301:Streptolysins / Q000378:metabolism
D001426:Bacterial Proteins; D009838:Oligodeoxyribonucleotides; D020135:Peptide Nucleic Acids; D021382:Protein Sorting Signals; D013301:Streptolysins; C025964:streptolysin O; D011094:Polyethyleneimine