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Altering the balance between healthy and mutated mitochondrial DNA
Author(s) -
Smith Paul M.,
Lightowlers Robert N.
Publication year - 2011
Publication title -
journal of inherited metabolic disease
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.462
H-Index - 102
eISSN - 1573-2665
pISSN - 0141-8955
DOI - 10.1007/s10545-010-9122-6
Subject(s) - heteroplasmy , mitochondrial dna , genetics , biology , human mitochondrial genetics , gene , genome , mutation , zinc finger nuclease , phenotype , mitochondrial disease , human genetics , dna , mitochondrion , genome editing
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.