Specific elimination of mutant mitochondrial genomes in patient-derived cells by mitoTALENs

Nat Med. 2013 Sep;19(9):1111-3. doi: 10.1038/nm.3261. Epub 2013 Aug 4.


Mitochondrial diseases are commonly caused by mutated mitochondrial DNA (mtDNA), which in most cases coexists with wild-type mtDNA, resulting in mtDNA heteroplasmy. We have engineered transcription activator-like effector nucleases (TALENs) to localize to mitochondria and cleave different classes of pathogenic mtDNA mutations. Mitochondria-targeted TALEN (mitoTALEN) expression led to permanent reductions in deletion or point-mutant mtDNA in patient-derived cells, raising the possibility that these mitochondrial nucleases can be therapeutic for some mitochondrial diseases.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Cell Line, Tumor
  • DNA, Mitochondrial / genetics*
  • Deoxyribonucleases, Type II Site-Specific / metabolism*
  • Deoxyribonucleases, Type II Site-Specific / pharmacology
  • Genome, Mitochondrial
  • Humans
  • Mitochondria / genetics
  • Mitochondrial Diseases / drug therapy
  • Mitochondrial Diseases / genetics*
  • Molecular Sequence Data
  • Mutation
  • Osteosarcoma / drug therapy
  • Osteosarcoma / genetics*


  • DNA, Mitochondrial
  • Deoxyribonucleases, Type II Site-Specific