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Phenotypes manifest when the percentage of mutant mtDNA is high (70\u201390%). Previously, our laboratory showed that mitochondria\u2010targeted transcription activator\u2010like effector nucleases (mitoTALENs) can eliminate mutant mtDNA from heteroplasmic cells. However, mitoTALENs are dimeric and relatively large, making it difficult to package their coding genes into viral vectors, limiting their clinical application. The smaller monomeric GIY\u2010YIG homing nuclease from T4 phage (I\u2010TevI) provides a potential alternative. We tested whether molecular hybrids (mitoTev\u2010TALEs) could specifically bind and cleave mtDNA of patient\u2010derived cybrids harboring different levels of the m.8344A&gt;G mtDNA point mutation, associated with myoclonic epilepsy with ragged\u2010red fibers (MERRF). We tested two mitoTev\u2010TALE designs, one of which robustly shifted the mtDNA ratio toward the wild type. When this mitoTev\u2010TALE was tested in a clone with high levels of the MERRF mutation (91% mutant), the shift in heteroplasmy resulted in an improvement of oxidative phosphorylation function. mitoTev\u2010TALE provides an effective architecture for mtDNA editing that could facilitate therapeutic delivery of mtDNA editing enzymes to affected tissues.<\/jats:p>","DOI":"10.15252\/emmm.201708084","type":"journal-article","created":{"date-parts":[[2018,7,16]],"date-time":"2018-07-16T09:25:31Z","timestamp":1531733131000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":80,"title":["mitoTev\u2010TALE: a monomeric DNA editing enzyme to\u00a0reduce mutant mitochondrial DNA levels"],"prefix":"10.1038","volume":"10","author":[{"given":"Claudia V","family":"Pereira","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sandra R","family":"Bacman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tania","family":"Arguello","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ugne","family":"Zekonyte","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sion L","family":"Williams","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David R","family":"Edgell","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8077-7092","authenticated-orcid":false,"given":"Carlos T","family":"Moraes","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2018,7,16]]},"reference":[{"key":"BFEMMM201708084_CR1","doi-asserted-by":"crossref","first-page":"516","DOI":"10.1038\/gt.2008.11","volume":"15","author":"MF Alexeyev","year":"2008","unstructured":"Alexeyev MF, Venediktova N, Pastukh V, Shokolenko I, Bonilla G, Wilson GL (2008) Selective elimination of mutant mitochondrial genomes as therapeutic strategy for the treatment of NARP and MILS syndromes. 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