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

Abstract

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.

• Authors: Sandra R Bacman, Siôn L Williams, Milena Pinto, Susana Peralta, Carlos T Moraes
• Journal: Nature medicine (Nat Med) Vol. 19 Issue 9 Pg. 1111-3 (Sep 2013) ISSN: 1546-170X [Electronic] United States
• PMID: 23913125 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

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

Topics

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