ArticleNature biotechnology2026
Leveraging base excision repair for efficient adenine base editing of mitochondrial DNA.
Article in Nature biotechnology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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The trial behind it
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Who cites it
12 citing papers in PubMed.
- Harnessing mitochondrial genome editing for crop improvement: principles and applications.aBIOTECH · 2026Review
- Adeno-Associated virus-based approaches for mitochondrial diseases: advances and challenges.Molecular psychiatry · 2026Review
- Emerging therapeutic strategies for mitochondrial DNA-related diseases.Cell reports. Medicine · 2026Review
- Targeting Mitochondria in Aging-Related Diseases: Therapeutic Potential and Obstacles.MedComm · 2026Review
- Mitochondria in T‑cell tumor immunity and tumor therapies targeting mitochondria (Review).Oncology reports · 2026Review
- Glutamine metabolism and its roles in tumor radiotherapy by regulating DNA damage repair.Frontiers in cell and developmental biology · 2026Review
- Advances in gene therapy for mitochondrial genetic disorders: current status and clinical implementation challenges.Journal of translational medicine · 2025Review
- Double-stranded DNA deaminase DddAGenome biology · 2025Article
- Alterations in mitochondrial base editors enhance targeted editing efficiency for mouse model generation.Molecular therapy. Nucleic acids · 2025Article
- Advances in the regulation of macrophage polarization by the tumor microenvironment.Discover oncology · 2025Review
- Mitochondrial DNA damage in HIV infection: a mechanistic driver of immunometabolic dysfunction and chronic inflammation.Frontiers in immunology · 2025Review
- Effect of mitochondrial dysfunction on scar formation after spinal cord injury.Frontiers in neurologyReview
Corrections and comments
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Authors and funding
13 authors.
Funding
Abstract
Transcription activator-like effector-linked deaminases (TALEDs) use their single-stranded DNA (ssDNA)-specific adenosine deaminase TadA8e to mediate A-to-G editing in mitochondrial DNA (mtDNA). The working mechanism of this process is unknown, hindering the development of more effective TALEDs. Here we reveal that TALED-mediated A-to-G editing relies on the formation of an ssDNA region through base excision repair (BER), which is triggered by double-stranded DNA-specific cytidine deaminase (DddA)-induced C-to-U deamination. We develop a series of enhanced TALEDs (eTALED6s) with increased editing efficiency by replacing DddA with the high-activity variant DddA6 and fusing human uracil DNA glycosylase to TadA8e. By further engineering TadA8e, the resulting eTALED6Rs induces efficient on-target editing with reduced bystander editing and off-target editing at the DNA and RNA levels. Lastly, we use eTALED6 and eTALED6R to install a pathogenic mutation in mtDNA. Revealing the mechanism of TALED-mediated A-to-G editing demonstrates that enhancing BER increases editing efficiency.
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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.