ArticleProtein & cell2018
Targeted elimination of mutant mitochondrial DNA in MELAS-iPSCs by mitoTALENs.
Article in Protein & cell, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 75 papers.
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Who cites it
75 citing papers in PubMed, 130 citations in OpenAlex.
- Adeno-Associated virus-based approaches for mitochondrial diseases: advances and challenges.Molecular psychiatry · 2026Review
- Shifting the Balance: Mitochondrial Heteroplasmy as a Driver of Cardiac Disease.Circulation research · 2026Review
- Targeting mtDNA to Modulate Mitochondrial Dysfunction in Neurodegenerative Diseases.Molecular neurobiology · 2026Review
- Gene Therapy Tools for Diseases Caused by Mutations of the Mitochondrial Genome.International journal of molecular sciences · 2026Review
- Emerging therapeutic strategies for mitochondrial DNA-related diseases.Cell reports. Medicine · 2026Review
- Mitochondrial genome microhomology-mediated editing by donor DNA delivery into mitochondria in human cells.Molecular therapy. Nucleic acids · 2026Article
- Patient specific regulation of metabolism and cell death pathways in m.3243A>G mutated iPS-cells.Scientific reports · 2026Article
- Mitochondrial cardiovascular diseases: molecular mechanisms, multi-omics exploration and therapeutic strategies.Journal of advanced research · 2026Review
- Towards CRISPR-based editing of the mitochondrial genome in yeast.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Advances in gene therapy for mitochondrial genetic disorders: current status and clinical implementation challenges.Journal of translational medicine · 2025Review
- Mitochondrial Mutation Leads to Cardiomyocyte Hypertrophy by Disruption of Mitochondria-Associated ER Membrane.Cell proliferation · 2025Article
- Optimization of mtDNA-targeted platinum TALENs for bi-directionally modifying heteroplasmy levels in patient-derived m.3243A>G-iPSCs.Molecular therapy. Nucleic acids · 2025Article
- Mitochondrial tRNA modifications: functions, diseases caused by their loss, and treatment strategies.RNA (New York, N.Y.) · 2025Review
- Mitochondrial diseases: from molecular mechanisms to therapeutic advances.Signal transduction and targeted therapy · 2025Review
- Next-generation CRISPR technology for genome, epigenome and mitochondrial editing.Transgenic research · 2024Review
- Integrating Mitochondrial Biology into Innovative Cell Therapies for Neurodegenerative Diseases.Brain sciences · 2024Review
- Modulating Mitochondrial DNA Heteroplasmy with Mitochondrially Targeted Endonucleases.Annals of biomedical engineering · 2024Review
- Mitochondrial diseases and mtDNA editing.Genes & diseases · 2024Review
- Mitochondria: A Potential Rejuvenation Tool against Aging.Aging and disease · 2024Review
- TALE-based organellar genome editing and gene expression in plants.Plant cell reports · 2024Review
15 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
25 authors at 8 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Mitochondrial diseases are maternally inherited heterogeneous disorders that are primarily caused by mitochondrial DNA (mtDNA) mutations. Depending on the ratio of mutant to wild-type mtDNA, known as heteroplasmy, mitochondrial defects can result in a wide spectrum of clinical manifestations. Mitochondria-targeted endonucleases provide an alternative avenue for treating mitochondrial disorders via targeted destruction of the mutant mtDNA and induction of heteroplasmic shifting. Here, we generated mitochondrial disease patient-specific induced pluripotent stem cells (MiPSCs) that harbored a high proportion of m.3243A>G mtDNA mutations and caused mitochondrial encephalomyopathy and stroke-like episodes (MELAS). We engineered mitochondrial-targeted transcription activator-like effector nucleases (mitoTALENs) and successfully eliminated the m.3243A>G mutation in MiPSCs. Off-target mutagenesis was not detected in the targeted MiPSC clones. Utilizing a dual fluorescence iPSC reporter cell line expressing a 3243G mutant mtDNA sequence in the nuclear genome, mitoTALENs displayed a significantly limited ability to target the nuclear genome compared with nuclear-localized TALENs. Moreover, genetically rescued MiPSCs displayed normal mitochondrial respiration and energy production. Moreover, neuronal progenitor cells differentiated from the rescued MiPSCs also demonstrated normal metabolic profiles. Furthermore, we successfully achieved reduction in the human m.3243A>G mtDNA mutation in porcine oocytes via injection of mitoTALEN mRNA. Our study shows the great potential for using mitoTALENs for specific targeting of mutant mtDNA both in iPSCs and mammalian oocytes, which not only provides a new avenue for studying mitochondrial biology and disease but also suggests a potential therapeutic approach for the treatment of mitochondrial disease, as well as the prevention of germline transmission of mutant mtDNA.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.