Abstract
Pathogenic mutations of the mitochondrial genome are frequently found to co-exist with wild-type mtDNA molecules, a state known as heteroplasmy. In most disease cases, the mutation is recessive with manifestation of a clinical phenotype occurring when the proportion of mutated mtDNA exceeds a high threshold. The concept of increasing the ratio of healthy to mutated mtDNA as a means to correcting the biochemical defect has received much attention. A number of strategies are highlighted in this article, including manipulation of the mitochondrial genome by antigenomic drugs or restriction endonucleases, zinc finger peptide-targeted nucleases and exercise-induced gene shifting. The feasibility of these approaches has been demonstrated in a number of models, however more work is necessary before use in human patients.
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Abbreviations
- ATP:
-
Adenosine 5′-triphosphate
- LHON:
-
Leber hereditary optic neuropathy
- MERRF:
-
Myoclonic epilepsy with ragged red fibres
- mtDNA:
-
Mitochondrial DNA
- NARP:
-
Neurogenic muscle weakness ataxia and retinitis
- OXPHOS:
-
Oxidative phosphorylation
- PNAs:
-
Peptide nucleic acids
- ZPFs:
-
Zinc finger peptides
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Communicated by: Jan Smeitink
Competing interests: None declared.
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Smith, P.M., Lightowlers, R.N. Altering the balance between healthy and mutated mitochondrial DNA. J Inherit Metab Dis 34, 309–313 (2011). https://doi.org/10.1007/s10545-010-9122-6
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DOI: https://doi.org/10.1007/s10545-010-9122-6