ArticleGene therapy2010
Organ-specific shifts in mtDNA heteroplasmy following systemic delivery of a mitochondria-targeted restriction endonuclease.
Article in Gene therapy, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 55 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
55 citing papers in PubMed, 103 citations in OpenAlex.
- Shifting the Balance: Mitochondrial Heteroplasmy as a Driver of Cardiac Disease.Circulation research · 2026Review
- Transient muscle expression of mitoARCUS in mice leads to sustained reductions in pathogenic mtDNA and reduces fatigability.Molecular therapy : the journal of the American Society of Gene Therapy · 2026Article
- Advances in gene therapy for mitochondrial genetic disorders: current status and clinical implementation challenges.Journal of translational medicine · 2025Review
- Mitochondrial diseases: from molecular mechanisms to therapeutic advances.Signal transduction and targeted therapy · 2025Review
- Modulating Mitochondrial DNA Heteroplasmy with Mitochondrially Targeted Endonucleases.Annals of biomedical engineering · 2024Review
- High fat diet ameliorates mitochondrial cardiomyopathy in CHCHD10 mutant mice.EMBO molecular medicine · 2024Article
- Tools for editing the mammalian mitochondrial genome.Human molecular genetics · 2024Review
- Molecular and cellular consequences of mitochondrial DNA double-stranded breaks.Human molecular genetics · 2024Review
- Emerging technology has a brilliant future: the CRISPR-Cas system for senescence, inflammation, and cartilage repair in osteoarthritis.Cellular & molecular biology letters · 2024Review
- Linear DNA-driven recombination in mammalian mitochondria.Nucleic acids research · 2024Article
- mitoTALEN reduces the mutant mtDNA load in neurons.Molecular therapy. Nucleic acids · 2024Article
- Efficient elimination of MELAS-associated m.3243G mutant mitochondrial DNA by an engineered mitoARCUS nuclease.Nature metabolism · 2023Article
- Nanoparticle-Based Artificial Mitochondrial DNA Transcription Regulator:Nano letters · 2023Article
- Mitochondrial Dysfunction and Therapeutic Perspectives in Cardiovascular Diseases.International journal of molecular sciences · 2022Review
- Mitochondrial genome engineering coming-of-age.Trends in genetics : TIG · 2022Review
- Gene Therapy for Mitochondrial Diseases: Current Status and Future Perspective.Pharmaceutics · 2022Review
- The Mitochondrial Genome in Aging and Disease and the Future of Mitochondrial Therapeutics.Biomedicines · 2022Review
- Mitochondrial Genome Editing to Treat Human Osteoarthritis-A Narrative Review.International journal of molecular sciences · 2022Review
- Mitochondrial noncoding RNAs: new wine in an old bottle.RNA biology · 2021Review
- Mitochondrial targeted meganuclease as a platform to eliminate mutant mtDNA in vivo.Nature communications · 2021Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Most pathogenic mtDNA mutations are heteroplasmic and there is a clear correlation between high levels of mutated mtDNA in a tissue and pathology. We have found that in vivo double-strand breaks (DSBs) in mtDNA lead to digestion of cleaved mtDNA and replication of residual mtDNA. Therefore, if DSB could be targeted to mutations in mtDNA, mutant genomes could be eliminated and the wild-type mtDNA would repopulate the cells. This can be achieved by using mitochondria-targeted restriction endonucleases as a means to degrade specific mtDNA haplotypes in heteroplasmic cells or tissues. In this work, we investigated the potential of systemic delivery of mitochondria-targeted restriction endonucleases to reduce the proportion of mutant mtDNA in specific tissues. Using the asymptomatic NZB/BALB mtDNA heteroplasmic mouse as a model, we found that a mitochondria-targeted ApaLI (that cleaves BALB mtDNA at a single site and does not cleave NZB mtDNA) increased the proportion of NZB mtDNA in target tissues. This was observed in heart, using a cardiotropic adeno-associated virus type-6 (AAV6) and in liver, using the hepatotropic adenovirus type-5 (Ad5). No mtDNA depletion or loss of cytochrome c oxidase activity was observed in any of these tissues. These results show the potential of systemic delivery of viral vectors to specific organs for the therapeutic application of mitochondria-targeted restriction enzymes in mtDNA disorders.
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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.