{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T05:28:45Z","timestamp":1780464525963,"version":"3.54.1"},"reference-count":36,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2021,3,1]],"date-time":"2021-03-01T00:00:00Z","timestamp":1614556800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2021,3,1]],"date-time":"2021-03-01T00:00:00Z","timestamp":1614556800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2020,10,20]],"date-time":"2020-10-20T00:00:00Z","timestamp":1603152000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100007449","name":"Takeda Science Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100007449","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100007877","name":"Fujita Health University","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100007877","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["cell.com","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Molecular Therapy - Methods &amp; Clinical Development"],"published-print":{"date-parts":[[2021,3]]},"DOI":"10.1016\/j.omtm.2020.10.017","type":"journal-article","created":{"date-parts":[[2020,10,23]],"date-time":"2020-10-23T10:25:57Z","timestamp":1603448757000},"page":"54-68","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":13,"special_numbering":"C","title":["Elimination of Mutant mtDNA by an Optimized mpTALEN Restores Differentiation Capacities of Heteroplasmic MELAS-iPSCs"],"prefix":"10.1016","volume":"20","author":[{"given":"Naoki","family":"Yahata","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroko","family":"Boda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ryuji","family":"Hata","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.omtm.2020.10.017_bib1","doi-asserted-by":"crossref","first-page":"530","DOI":"10.1038\/nrg3966","article-title":"The dynamics of mitochondrial DNA heteroplasmy: implications for human health and disease","volume":"16","author":"Stewart","year":"2015","journal-title":"Nat. Rev. Genet."},{"key":"10.1016\/j.omtm.2020.10.017_bib2","doi-asserted-by":"crossref","first-page":"458","DOI":"10.1002\/emmm.201303672","article-title":"Mitochondrially targeted ZFNs for selective degradation of pathogenic mitochondrial genomes bearing large-scale deletions or point mutations","volume":"6","author":"Gammage","year":"2014","journal-title":"EMBO Mol. Med."},{"key":"10.1016\/j.omtm.2020.10.017_bib3","doi-asserted-by":"crossref","first-page":"1111","DOI":"10.1038\/nm.3261","article-title":"Specific elimination of mutant mitochondrial genomes in patient-derived cells by mitoTALENs","volume":"19","author":"Bacman","year":"2013","journal-title":"Nat. Med."},{"key":"10.1016\/j.omtm.2020.10.017_bib4","doi-asserted-by":"crossref","first-page":"459","DOI":"10.1016\/j.cell.2015.03.051","article-title":"Selective elimination of mitochondrial mutations in the germline by genome editing","volume":"161","author":"Reddy","year":"2015","journal-title":"Cell"},{"key":"10.1016\/j.omtm.2020.10.017_bib5","doi-asserted-by":"crossref","first-page":"1592","DOI":"10.1038\/mt.2015.126","article-title":"MitoTALEN: a general approach to reduce mutant mtDNA loads and restore oxidative phosphorylation function in mitochondrial diseases","volume":"23","author":"Hashimoto","year":"2015","journal-title":"Mol. Ther."},{"key":"10.1016\/j.omtm.2020.10.017_bib6","doi-asserted-by":"crossref","first-page":"283","DOI":"10.1007\/s13238-017-0499-y","article-title":"Targeted elimination of mutant mitochondrial DNA in MELAS-iPSCs by mitoTALENs","volume":"9","author":"Yang","year":"2018","journal-title":"Protein Cell"},{"key":"10.1016\/j.omtm.2020.10.017_bib7","doi-asserted-by":"crossref","first-page":"e8084","DOI":"10.15252\/emmm.201708084","article-title":"mitoTev-TALE: a monomeric DNA editing enzyme to reduce mutant mitochondrial DNA levels","volume":"10","author":"Pereira","year":"2018","journal-title":"EMBO Mol. Med."},{"key":"10.1016\/j.omtm.2020.10.017_bib8","doi-asserted-by":"crossref","first-page":"15557","DOI":"10.1038\/s41598-017-15871-y","article-title":"TALEN-mediated shift of mitochondrial DNA heteroplasmy in MELAS-iPSCs with m.13513G>A mutation","volume":"7","author":"Yahata","year":"2017","journal-title":"Sci. Rep."},{"key":"10.1016\/j.omtm.2020.10.017_bib9","doi-asserted-by":"crossref","first-page":"368","DOI":"10.1001\/archneurol.2007.67","article-title":"The G13513A mutation in the ND5 gene of mitochondrial DNA as a common cause of MELAS or Leigh syndrome: evidence from 12 cases","volume":"65","author":"Shanske","year":"2008","journal-title":"Arch. Neurol."},{"key":"10.1016\/j.omtm.2020.10.017_bib10","doi-asserted-by":"crossref","first-page":"7804","DOI":"10.1093\/nar\/gkw676","article-title":"Near-complete elimination of mutant mtDNA by iterative or dynamic dose-controlled treatment with mtZFNs","volume":"44","author":"Gammage","year":"2016","journal-title":"Nucleic Acids Res."},{"key":"10.1016\/j.omtm.2020.10.017_bib11","doi-asserted-by":"crossref","first-page":"234","DOI":"10.1038\/nature14546","article-title":"Metabolic rescue in pluripotent cells from patients with mtDNA disease","volume":"524","author":"Ma","year":"2015","journal-title":"Nature"},{"key":"10.1016\/j.omtm.2020.10.017_bib12","doi-asserted-by":"crossref","first-page":"1298","DOI":"10.1002\/stem.1389","article-title":"Disease-causing mitochondrial heteroplasmy segregated within induced pluripotent stem cell clones derived from a patient with MELAS","volume":"31","author":"Folmes","year":"2013","journal-title":"Stem Cells"},{"key":"10.1016\/j.omtm.2020.10.017_bib13","doi-asserted-by":"crossref","first-page":"19511","DOI":"10.1002\/jcp.28549","article-title":"The mutation m.13513G>A impairs cardiac function, favoring a neuroectoderm commitment, in a mutant-load dependent way","volume":"234","author":"Galera-Monge","year":"2019","journal-title":"J.\u00a0Cell. Physiol."},{"key":"10.1016\/j.omtm.2020.10.017_bib14","doi-asserted-by":"crossref","first-page":"e2551","DOI":"10.1038\/cddis.2016.484","article-title":"Mitochondrial respiratory dysfunction disturbs neuronal and cardiac lineage commitment of human iPSCs","volume":"8","author":"Yokota","year":"2017","journal-title":"Cell Death Dis."},{"key":"10.1016\/j.omtm.2020.10.017_bib15","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1186\/s40478-015-0227-x","article-title":"Molecular pathomechanisms and cell-type-specific disease phenotypes of MELAS caused by mutant mitochondrial tRNA(Trp)","volume":"3","author":"Hatakeyama","year":"2015","journal-title":"Acta Neuropathol. Commun."},{"key":"10.1016\/j.omtm.2020.10.017_bib16","doi-asserted-by":"crossref","first-page":"188","DOI":"10.1136\/jmg.40.3.188","article-title":"The mitochondrial DNA G13513A MELAS mutation in the NADH dehydrogenase 5 gene is a frequent cause of Leigh-like syndrome with isolated complex I deficiency","volume":"40","author":"Chol","year":"2003","journal-title":"J.\u00a0Med. Genet."},{"key":"10.1016\/j.omtm.2020.10.017_bib17","doi-asserted-by":"crossref","first-page":"606","DOI":"10.1111\/j.1440-1789.2010.01115.x","article-title":"Phenotypic patterns of MELAS\/LS overlap syndrome associated with m.13513G>A mutation, and neuropathological findings in one autopsy case","volume":"30","author":"Wang","year":"2010","journal-title":"Neuropathology"},{"key":"10.1016\/j.omtm.2020.10.017_bib18","doi-asserted-by":"crossref","first-page":"315","DOI":"10.1111\/gtc.12037","article-title":"Efficient TALEN construction and evaluation methods for human cell and animal applications","volume":"18","author":"Sakuma","year":"2013","journal-title":"Genes Cells"},{"key":"10.1016\/j.omtm.2020.10.017_bib19","doi-asserted-by":"crossref","first-page":"5390","DOI":"10.1093\/nar\/gku155","article-title":"Comprehensive analysis of the specificity of transcription activator-like effector nucleases","volume":"42","author":"Juillerat","year":"2014","journal-title":"Nucleic Acids Res."},{"key":"10.1016\/j.omtm.2020.10.017_bib20","doi-asserted-by":"crossref","first-page":"1551","DOI":"10.1099\/0022-1317-72-7-1551","article-title":"Identification of an epitope on the P and V proteins of simian virus 5 that distinguishes between two isolates with different biological characteristics","volume":"72","author":"Southern","year":"1991","journal-title":"J.\u00a0Gen. Virol."},{"key":"10.1016\/j.omtm.2020.10.017_bib21","doi-asserted-by":"crossref","first-page":"292","DOI":"10.1093\/nar\/28.1.292","article-title":"Codon usage tabulated from international DNA sequence databases: status for the year 2000","volume":"28","author":"Nakamura","year":"2000","journal-title":"Nucleic Acids Res."},{"key":"10.1016\/j.omtm.2020.10.017_bib22","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1016\/j.bbrc.2014.02.099","article-title":"TALE nickase mediates high efficient targeted transgene integration at the human multi-copy ribosomal DNA locus","volume":"446","author":"Wu","year":"2014","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"10.1016\/j.omtm.2020.10.017_bib23","doi-asserted-by":"crossref","first-page":"987","DOI":"10.1016\/0092-8674(87)90585-X","article-title":"Expression of a single transfected cDNA converts fibroblasts to myoblasts","volume":"51","author":"Davis","year":"1987","journal-title":"Cell"},{"key":"10.1016\/j.omtm.2020.10.017_bib24","doi-asserted-by":"crossref","first-page":"313","DOI":"10.1038\/nbt1383","article-title":"Marked differences in differentiation propensity among human embryonic stem cell lines","volume":"26","author":"Osafune","year":"2008","journal-title":"Nat. Biotechnol."},{"key":"10.1016\/j.omtm.2020.10.017_bib25","doi-asserted-by":"crossref","first-page":"720","DOI":"10.1126\/science.1215670","article-title":"Structural basis for sequence-specific recognition of DNA by TAL effectors","volume":"335","author":"Deng","year":"2012","journal-title":"Science"},{"key":"10.1016\/j.omtm.2020.10.017_bib26","doi-asserted-by":"crossref","first-page":"1691","DOI":"10.1038\/s41591-018-0165-9","article-title":"Genome editing in mitochondria corrects a pathogenic mtDNA mutation in\u00a0vivo","volume":"24","author":"Gammage","year":"2018","journal-title":"Nat. Med."},{"key":"10.1016\/j.omtm.2020.10.017_bib27","doi-asserted-by":"crossref","first-page":"1696","DOI":"10.1038\/s41591-018-0166-8","article-title":"MitoTALEN reduces mutant mtDNA load and restores tRNAAla levels in a mouse model of heteroplasmic mtDNA mutation","volume":"24","author":"Bacman","year":"2018","journal-title":"Nat. Med."},{"key":"10.1016\/j.omtm.2020.10.017_bib28","doi-asserted-by":"crossref","first-page":"437","DOI":"10.1038\/s41419-018-0488-y","article-title":"ATOH1\/RFX1\/RFX3 transcription factors facilitate the differentiation and characterisation of inner ear hair cell-like cells from patient-specific induced pluripotent stem cells harbouring A8344G mutation of mitochondrial DNA","volume":"9","author":"Chen","year":"2018","journal-title":"Cell Death Dis."},{"key":"10.1016\/j.omtm.2020.10.017_bib29","doi-asserted-by":"crossref","first-page":"4698","DOI":"10.1093\/hmg\/ddv201","article-title":"Mitochondrial respiratory dysfunction caused by a heteroplasmic mitochondrial DNA mutation blocks cellular reprogramming","volume":"24","author":"Yokota","year":"2015","journal-title":"Hum. Mol. Genet."},{"key":"10.1016\/j.omtm.2020.10.017_bib30","doi-asserted-by":"crossref","first-page":"227","DOI":"10.1016\/j.tcb.2018.11.004","article-title":"The Cellular Mitochondrial Genome Landscape in Disease","volume":"29","author":"Hahn","year":"2019","journal-title":"Trends Cell Biol."},{"key":"10.1016\/j.omtm.2020.10.017_bib31","doi-asserted-by":"crossref","first-page":"3379","DOI":"10.1038\/srep03379","article-title":"Repeating pattern of non-RVD variations in DNA-binding modules enhances TALEN activity","volume":"3","author":"Sakuma","year":"2013","journal-title":"Sci. Rep."},{"key":"10.1016\/j.omtm.2020.10.017_bib32","doi-asserted-by":"crossref","first-page":"3594","DOI":"10.1038\/srep03594","article-title":"A novel efficient feeder-free culture system for the derivation of human induced pluripotent stem cells","volume":"4","author":"Nakagawa","year":"2014","journal-title":"Sci. Rep."},{"key":"10.1016\/j.omtm.2020.10.017_bib33","doi-asserted-by":"crossref","first-page":"e25788","DOI":"10.1371\/journal.pone.0025788","article-title":"Anti-A\u03b2 drug screening platform using human iPS cell-derived neurons for the treatment of Alzheimer\u2019s disease","volume":"6","author":"Yahata","year":"2011","journal-title":"PLoS ONE"},{"key":"10.1016\/j.omtm.2020.10.017_bib34","doi-asserted-by":"crossref","first-page":"e61540","DOI":"10.1371\/journal.pone.0061540","article-title":"Efficient and reproducible myogenic differentiation from human iPS cells: prospects for modeling Miyoshi myopathy in\u00a0vitro","volume":"8","author":"Tanaka","year":"2013","journal-title":"PLoS ONE"},{"key":"10.1016\/j.omtm.2020.10.017_bib35","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1007\/978-1-4939-8651-4_11","article-title":"In\u00a0vitro evaluation of exon skipping in disease-specific iPSC-derived myocytes","volume":"1828","author":"Zhao","year":"2018","journal-title":"Methods Mol. Biol."},{"key":"10.1016\/j.omtm.2020.10.017_bib36","doi-asserted-by":"crossref","first-page":"313","DOI":"10.1007\/978-1-61779-504-6_21","article-title":"Quantification of mtDNA mutation heteroplasmy (ARMS qPCR)","volume":"837","author":"Venegas","year":"2012","journal-title":"Methods Mol. Biol."}],"container-title":["Molecular Therapy - Methods &amp; Clinical Development"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S2329050120302217?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S2329050120302217?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2025,11,6]],"date-time":"2025-11-06T09:23:50Z","timestamp":1762421030000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S2329050120302217"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,3]]},"references-count":36,"alternative-id":["S2329050120302217"],"URL":"https:\/\/doi.org\/10.1016\/j.omtm.2020.10.017","relation":{},"ISSN":["2329-0501"],"issn-type":[{"value":"2329-0501","type":"print"}],"subject":[],"published":{"date-parts":[[2021,3]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Elimination of Mutant mtDNA by an Optimized mpTALEN Restores Differentiation Capacities of Heteroplasmic MELAS-iPSCs","name":"articletitle","label":"Article Title"},{"value":"Molecular Therapy - Methods & Clinical Development","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.omtm.2020.10.017","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2020 The Authors.","name":"copyright","label":"Copyright"}]}}