ArticleNature metabolism2023
Efficient elimination of MELAS-associated m.3243G mutant mitochondrial DNA by an engineered mitoARCUS nuclease.
Article in Nature metabolism, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed.
- Advanced gene editing technologies for oncology mechanisms, applications, and clinical implementation.Cancer gene therapy · 2026Review
- Adeno-Associated virus-based approaches for mitochondrial diseases: advances and challenges.Molecular psychiatry · 2026Review
- Mitochondrial DNA A3243G variant-associated MELAS: Recent advances in clinical trials, therapeutic interventions, and disease-modifying strategies.Intractable & rare diseases research · 2026Review
- Mitochondrial DNA heteroplasmy drives cortical neuronal disturbances in human organoids harbouring the common m.3243A>G mutation.Nature communications · 2026Article
- 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
- 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
- Mesenchymal Stromal Cells and Extracellular Vesicles: A Novel Therapeutic Paradigm for Mitochondrial Dysfunctions.International journal of molecular sciences · 2026Review
- Targeting mitochondria for the treatment of neurodegenerative diseases.Frontiers in neuroscience · 2026Review
- Advances in gene therapy for mitochondrial genetic disorders: current status and clinical implementation challenges.Journal of translational medicine · 2025Review
- The Role of Mitochondrial Genome Stability and Metabolic Plasticity in Thyroid Cancer.Biomedicines · 2025Review
- Genomic medicine in hepatology: mechanisms and liver treatment strategies.Molecular medicine (Cambridge, Mass.) · 2025Review
- High-efficiency homology-directed insertion into the genome using the engineered homing endonuclease ARCUS.Nucleic acids research · 2025Article
- Rewriting nuclear epigenetic scripts in mitochondrial diseases as a strategy for heteroplasmy control.EMBO molecular medicine · 2025Article
- Integrative Approaches to Myopathies and Muscular Dystrophies: Molecular Mechanisms, Diagnostics, and Future Therapies.International journal of molecular sciences · 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
- An alternative model for maternal mtDNA inheritance.Nature genetics · 2025Article
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Abstract
Nuclease-mediated editing of heteroplasmic mitochondrial DNA (mtDNA) seeks to preferentially cleave and eliminate mutant mtDNA, leaving wild-type genomes to repopulate the cell and shift mtDNA heteroplasmy. Various technologies are available, but many suffer from limitations based on size and/or specificity. The use of ARCUS nucleases, derived from naturally occurring I-CreI, avoids these pitfalls due to their small size, single-component protein structure and high specificity resulting from a robust protein-engineering process. Here we describe the development of a mitochondrial-targeted ARCUS (mitoARCUS) nuclease designed to target one of the most common pathogenic mtDNA mutations, m.3243A>G. mitoARCUS robustly eliminated mutant mtDNA without cutting wild-type mtDNA, allowing for shifts in heteroplasmy and concomitant improvements in mitochondrial protein steady-state levels and respiration. In vivo efficacy was demonstrated using a m.3243A>G xenograft mouse model with mitoARCUS delivered systemically by adeno-associated virus. Together, these data support the development of mitoARCUS as an in vivo gene-editing therapeutic for m.3243A>G-associated diseases.
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