Methods of preventing the transmission of a mitochondrial disease, disorder, or condition using mitochondria-targeted enzymes or mRNA encoding mitochondria-targeted enzymes. The methods as described herein can specifically eliminate mitochondrial DNA (mtDNA) mutations in the germline.
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1. A method of treating a mitochondrial-associated disease, disorder, or condition comprising introducing a composition, which has a mitochondria-targeted nuclease or a nucleic acid construct encoding the mitochondria-targeted nuclease, into a female gametocyte. 2. The method of claim 1, further com
1. A method of treating a mitochondrial-associated disease, disorder, or condition comprising introducing a composition, which has a mitochondria-targeted nuclease or a nucleic acid construct encoding the mitochondria-targeted nuclease, into a female gametocyte. 2. The method of claim 1, further comprising: introducing a composition that has the nucleic acid construct encoding the mitochondria-targeted nuclease into the female gametocyte such that the mitochondria-targeted nuclease is expressed in the female gametocyte. 3. The method of claim 1, wherein the mitochondria targeted nuclease targets a mutation in mtDNA associated with the mitochondrial-associated disease, disorder, or condition, the mitochondria-targeted nuclease being present in an amount sufficient to reduce or eliminate mutant mitochondrial DNA (mtDNA) in the female gametocyte. 4. The method of claim 1, wherein the mitochondria targeted nuclease is introduced in an amount sufficient to prevent the transgenerational transmission of mutant mtDNA associated with the mitochondrial-associated disease, disorder, or condition. 5. The method of claim 1, further comprising: fertilizing the female gametocyte after the introducing of the mitochondria targeted nuclease that eliminated the mitochondrial-associated disease, disorder, or condition. 6. The method of claim 1, wherein the mitochondria targeted nuclease comprises a restriction enzyme selected from the group consisting of mito-ApaLI, Xmal, mito-TALEN, ZFN, HindIII, BcII, and BsrI. 7. The method of claim 1, wherein the mitochondria targeted nuclease comprises a mitochondria-targeted transcription activator-like effector nuclease (TALEN). 8. The method of claim 1, wherein the mitochondrial associated disease disorder, or condition is selected from the group consisting of: Neuropathy ataxia retinitis pigmentosa (NARP) syndrome; mitochondrial encephalo-myopathy with lactic acidosis and stroke like episodes (MELAS); maternally inherited Leigh's syndrome (MILS) syndrome; NARP-MILS syndrome; hemolytic anemia; a neurodegenerative disease; diabetes; mitochondrial dysfunction-associated aging; gastro-intestinal disorders; cardiac disease; liver disease; diabetes; respiratory disease; seizures; visual/hearing loss; lactic acidosis; developmental delays; mitochondrial myopathy; diabetes mellitus; diabetes mellitus and deafness (DAD); Leber's hereditary optic neuropathy (LHON); Leber's hereditary optic neuropathy and dystonia (LHOND); Wolff-Parkinson-White syndrome; multiple sclerosis-type disease; Leigh syndrome; subacute sclerosing encephalopathy; seizures; altered states of consciousness; dementia; ventilatory failure; neuropathy, ataxia, retinitis pigmentosa, and ptosis (NARP); myoneurogenic gastrointestinal encephalopathy (MNGIE); gastrointestinal pseudo-obstruction; neuropathy; Myoclonic Epilepsy with Ragged Red Fibers (MERRF); progressive myoclonic epilepsy; hearing loss; Mitochondrial myopathy; encephalomyopathy; lactic acidosis; mtDNA depletion; mitochondrial neurogastrointestinal encephalomyopathy (MNGIE); and Friedreich's ataxia 9. The method of claim 1, further comprising: performing pre-implantation genetic diagnosis (PGD) on the female gametocyte or an embryo formed from the female gametocyte; and selecting a female gametocyte or an embryo with a sufficient mitochondrial DNA load based on the results of PGD, wherein the sufficient mitochondrial DNA load is an amount sufficient for an embryo to successfully implant into a uterus. 10. The method of claim 1, further comprising: implanting the female gametocyte after introduction of the mitochondria targeted nuclease into a female uterus; or implanting a fertilized female gametocyte after introduction of the mitochondria-targeted nuclease into a female uterus. 11. The method of claim 1, wherein the introducing includes implementing a transfection process that targets a mutated mitochondrial genome by: transfecting a single cell having mutated mitochondrial deoxyribonucleic acid (mtDNA) with the mitochondria-targeted nuclease or the nucleic acid construct encoding the mitochondria-targeted nuclease of the composition to effect induction of mtDNA heteroplasmy shift to destroy a sufficient quantity of mutated mtDNA so as to lessen a percentage of mutated mtDNA in the single cell with respect to total mtDNA so as to yield a percentage of mutated mDNA remaining that is below a threshold of 60 to 90 percent so that the single cell does not exhibit a diseased state from the mutated mtDNA, the single cell being selected from the group consisting of an oocyte and a zygote; wherein the transfecting is effected with the mitochondria targeted nuclease or the nucleic acid construct encoding the mitochondria-targeted nuclease of the composition in a sufficiently purified form that targets just the mutated mtDNA for destruction without impairing funcundity of the single cell after subsequent mitosis of the single cell. 12. The transfection process of claim 11, wherein the mitochondria targeted nuclease or the nucleic acid construct encoding the mitochondria-targeted nuclease of the composition is selected from the group consisting of a restriction endonuclease and a transcription activator-like effector nuclease (TALENs). 13. The transfection process of claim 11, wherein the transfecting is carried out by transfecting the single cell with a messenger ribonucleic acid (mRNA) having the mitochondria targeted nuclease. 14. The transfection process of claim 11, further comprising the step of: synthesizing the mitochondria targeted nuclease or the nucleic acid construct encoding the mitochondria-targeted nuclease of the composition in a sufficient quantity and purity to destroy a sufficient amount of the mtDNA to lower the percentage of the mutated mtDNA remaining to below the threshold. 15. The transfection process of claim 11, wherein the synthesizing includes performing in vitro transcription of messenger ribonucleic acid (mRNA) with a linearized and gel purified (Qiagen) plasmid template and then purifying and quantifying the mRNA, the transfecting being carried out by transfecting the single cell with the mRNA, which has the mitochondria targeted nuclease or the nucleic acid construct encoding the mitochondria-targeted nuclease of the composition. 16. An apparatus for administering treatment for a mitochondrial-associated disease, disorder, or condition comprising: means for introducing a composition, which has a mitochondria-targeted nuclease or a nucleic acid construct encoding the mitochondria-targeted nuclease, into a female gametocyte. 17. The apparatus of claim 16, wherein said means for introducing includes means for effecting a transfection process that targets a mutated mitochondrial genome by transfecting a single cell having mutated mitochondrial deoxyribonucleic acid (mtDNA) with mitochondria targeted nuclease or the nucleic acid construct encoding the mitochondria-targeted nuclease of the composition to effect the induction of the mtDNA heteroplasmy shift to destroy a sufficient quantity of the mutated mtDNA so as to lessen a percentage of mutated mtDNA in the single cell with respect to total mtDNA so as to yield a percentage of mutated mDNA remaining that is below a threshold of 60 to 90 percent so that the single cell does not exhibit a diseased state from the mutated mtDNA, the single cell being selected from the group consisting of an oocyte and a zygote, wherein the transfecting is effected with the mitochondria targeted nuclease or the nucleic acid construct encoding the mitochondria-targeted nuclease of the composition in a sufficiently purified form that targets just the mutated mtDNA for destruction without impairing funcundity of the single cell after subsequent mitosis of the single cell. 18. The apparatus of claim 16, wherein the mitochondria targeted nuclease is selected from the group consisting of restriction endonuclease and transcription activator-like effector nuclease (TALEN). 19. The apparatus of claim 17, wherein the means for effecting the transfection process is configured to transfect the single cell with a messenger ribonucleic acid (mRNA) having the synthesized mitochondria targeted nuclease or the nucleic acid construct encoding the mitochondria-targeted nuclease of the composition that is encoding mitochondria targeted ApaLI restriction enzyme. 20. The apparatus of claim 17, wherein the means for effecting the transfection process synthesizes the mitochondria targeted nuclease or the nucleic acid construct encoding the mitochondria-targeted nuclease of the composition in a sufficient quantity and purity to destroy a sufficient amount of the mtDNA to lower the percentage of the mutated mtDNA remaining to below the threshold.
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