Table I.
Genetic approaches tested in mouse models of mitochondrial diseases.
| Therapeutic approach | Mouse model | Effects of the therapeutic intervention | References | ||
|---|---|---|---|---|---|
| mtDNA heteroplasmic shift | Gene therapy | Local injection of Ad5- and AAV1,2-mito-ApaLI restriction endonuclease | NZB/BALB adult mice | mtDNA shift towards NZB haplotype in skeletal muscle | (Bayona-Bafaluy, 2005) |
| Systemic injection of AAV6 and Ad5-mito-ApaLI restriction endonuclease to heart and liver | NZB/BALB adult mice | mtDNA shift towards NZB haplotype in heart and liver | (Bacman, 2010) | ||
| Systemic injection of AVV9-mito-ApaLI restriction endonuclease to striated muscle | NZB/BALB newborn mice | mtDNA shift towards the NZB haplotype in all striated muscles | (Bacman, 2012) | ||
| Gene Replacement Replacement of the defective gene |
Nuclear gene expression | Local injection of AAV2-Ant1construct in skeletal muscle | Ant1−/− mice | Increased export of ATP and restored the morphology of the affected muscles | (Flierl, 2005) |
| Intravitreal injection of AVV2-Aif1 construct | Harlequin-CI deficient mice | Protection of retinal ganglion cells and optic nerve integrity, preservation of CI function in optic nerves, as well as the prevention of glial response | (Bouaita, 2012) | ||
| Local injection of AAV1-Ndufs4 construct to the vestibular nucleus | Vestibular nucleus specific Ndufs4 KO mice | Delay of disease onset, increased lifespan and improved breathing response | (Quintana, 2012) | ||
| Intravenous injection of AVV2/8-human TYMP | Tymp−/− Upp1−/− | Reduced accumulation of dThd and dUrd in serum, liver, muscle and brain but not small intestine | (Torres-Torronteras, 2014) | ||
| AVV2/8-Mpv17 | Mpv17 −/− | Prevented liver failure induced by the ketogenic diet and restored liver mtDNA copy number and OXPHOS ability | (Bottani, 2014) | ||
| Intravenous injection of AAVrh10-human Fxn construct | Heart-skeletal muscle specific Fxn KO | Prevented the onset of cardiac failure and reversed the cardiac contractile dysfunction | (Perdomini, 2014) | ||
| Allotopic expression | AAV2-mediated delivery of human ND4 to inner retinal neurons | Mice injected with the human mutated form of ND4 (G11778A) | Suppression of the visual loss and optic atrophy induced by the mutant ND4 homolog | (Yu, 2012) | |
| Modulation of gene expression | Histone deacetylase inhibitors (pimelic o aminoben zamides) | Friedreich’s ataxia | Increased Frataxin protein levels and improvement in the phenotype. | (Sandi, 2011) | |