ArticleNucleic acids research2016
Near-complete elimination of mutant mtDNA by iterative or dynamic dose-controlled treatment with mtZFNs.
Article in Nucleic acids research, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 81 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.
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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
81 citing papers in PubMed, 120 citations in OpenAlex.
- 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
- Mitochondrial genome microhomology-mediated editing by donor DNA delivery into mitochondria in human cells.Molecular therapy. Nucleic acids · 2026Article
- Emerging therapeutic strategies for mitochondrial DNA-related diseases.Cell reports. Medicine · 2026Review
- Specific elimination of m.8993T>G mitochondrial haplotype in NARP cybrid cells by CRISPR-Cas9 system.Scientific reports · 2026Article
- Review
- Advances in gene therapy for mitochondrial genetic disorders: current status and clinical implementation challenges.Journal of translational medicine · 2025Review
- Review
- The Role of Mitochondrial DNA in Modulating Chemoresistance in Esophageal Cancer: Mechanistic Insights and Therapeutic Potential.Biomolecules · 2025Review
- Therapies for Mitochondrial Disease: Past, Present, and Future.Journal of inherited metabolic disease · 2025Review
- Optimization of mtDNA-targeted platinum TALENs for bi-directionally modifying heteroplasmy levels in patient-derived m.3243A>G-iPSCs.Molecular therapy. Nucleic acids · 2025Article
- Clinically translatable mitochondrial gene therapy in muscle using tandem mtZFN architecture.EMBO molecular medicine · 2025Article
- Engineered mitochondria in diseases: mechanisms, strategies, and applications.Signal transduction and targeted therapy · 2025Review
- Mitochondrial diseases: from molecular mechanisms to therapeutic advances.Signal transduction and targeted therapy · 2025Review
- Mitochondrial DNA damage in HIV infection: a mechanistic driver of immunometabolic dysfunction and chronic inflammation.Frontiers in immunology · 2025Review
- Technological advances in the diagnosis and management of inherited optic neuropathies.Frontiers in neurology · 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
- Emerging technology has a brilliant future: the CRISPR-Cas system for senescence, inflammation, and cartilage repair in osteoarthritis.Cellular & molecular biology letters · 2024Review
21 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
12 authors at 5 institutions in 3 countries.
Funding
Abstract
Mitochondrial diseases are frequently associated with mutations in mitochondrial DNA (mtDNA). In most cases, mutant and wild-type mtDNAs coexist, resulting in heteroplasmy. The selective elimination of mutant mtDNA, and consequent enrichment of wild-type mtDNA, can rescue pathological phenotypes in heteroplasmic cells. Use of the mitochondrially targeted zinc finger-nuclease (mtZFN) results in degradation of mutant mtDNA through site-specific DNA cleavage. Here, we describe a substantial enhancement of our previous mtZFN-based approaches to targeting mtDNA, allowing near-complete directional shifts of mtDNA heteroplasmy, either by iterative treatment or through finely controlled expression of mtZFN, which limits off-target catalysis and undesired mtDNA copy number depletion. To demonstrate the utility of this improved approach, we generated an isogenic distribution of heteroplasmic cells with variable mtDNA mutant level from the same parental source without clonal selection. Analysis of these populations demonstrated an altered metabolic signature in cells harbouring decreased levels of mutant m.8993T>G mtDNA, associated with neuropathy, ataxia, and retinitis pigmentosa (NARP). We conclude that mtZFN-based approaches offer means for mtDNA heteroplasmy manipulation in basic research, and may provide a strategy for therapeutic intervention in selected mitochondrial diseases.
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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.