ArticleEMBO molecular medicine2018
mitoTev-TALE: a monomeric DNA editing enzyme to reduce mutant mitochondrial DNA levels.
Article in EMBO molecular medicine, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
48 citing papers in PubMed, 80 citations in OpenAlex.
- Emerging therapeutic strategies for mitochondrial DNA-related diseases.Cell reports. Medicine · 2026Review
- Recent Advancements for Enhanced Biocatalyst and Biotransformation.Molecular biotechnology · 2026Review
- Mitochondrial DNA mutations and intercellular mitochondrial transfer in cancer: mechanisms, biological effects, and clinical potential.Biomarker research · 2026Review
- Advances in gene therapy for mitochondrial genetic disorders: current status and clinical implementation challenges.Journal of translational medicine · 2025Review
- Therapies for Mitochondrial Disease: Past, Present, and Future.Journal of inherited metabolic disease · 2025Review
- Mitochondrial diseases: from molecular mechanisms to therapeutic advances.Signal transduction and targeted therapy · 2025Review
- 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
- Tools for editing the mammalian mitochondrial genome.Human molecular genetics · 2024Review
- mitoTALEN reduces the mutant mtDNA load in neurons.Molecular therapy. Nucleic acids · 2024Article
- Potential Applications of Mitochondrial Therapy with a Focus on Parkinson's Disease and Mitochondrial Transplantation.Advanced pharmaceutical bulletin · 2024Review
- A Photoresponsive Homing Endonuclease for Programmed DNA Cleavage.ACS synthetic biology · 2024Article
- Harnessing accurate mitochondrial DNA base editing mediated by DdCBEs in a predictable manner.Frontiers in bioengineering and biotechnology · 2024Article
- Mitochondrial genome editing: strategies, challenges, and applications.BMB reports · 2024Review
- Efficient elimination of MELAS-associated m.3243G mutant mitochondrial DNA by an engineered mitoARCUS nuclease.Nature metabolism · 2023Article
- Trends and prospects in mitochondrial genome editing.Experimental & molecular medicine · 2023Review
- A conditional knockout rat resource of mitochondrial protein-coding genes via a DdCBE-induced premature stop codon.Science advances · 2023Article
- mtDNA Maintenance and Alterations in the Pathogenesis of Neurodegenerative Diseases.Current neuropharmacology · 2023Review
- Mitochondrial Dysfunction and Therapeutic Perspectives in Cardiovascular Diseases.International journal of molecular sciences · 2022Review
- Current advances in gene therapy of mitochondrial diseases.Journal of translational medicine · 2022Review
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 2 countries.
Funding
Abstract
Pathogenic mitochondrial DNA (mtDNA) mutations often co-exist with wild-type molecules (mtDNA heteroplasmy). Phenotypes manifest when the percentage of mutant mtDNA is high (70-90%). Previously, our laboratory showed that mitochondria-targeted transcription activator-like 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-YIG homing nuclease from T4 phage (I-TevI) provides a potential alternative. We tested whether molecular hybrids (mitoTev-TALEs) could specifically bind and cleave mtDNA of patient-derived cybrids harboring different levels of the m.8344A>G mtDNA point mutation, associated with myoclonic epilepsy with ragged-red fibers (MERRF). We tested two mitoTev-TALE designs, one of which robustly shifted the mtDNA ratio toward the wild type. When this mitoTev-TALE 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-TALE provides an effective architecture for mtDNA editing that could facilitate therapeutic delivery of mtDNA editing enzymes to affected tissues.
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What OpenQuestion holds
Registered trials
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.