ArticleAdvanced science (Weinheim, Baden-Wurttemberg, Germany)2024
Enhanced C-To-T and A-To-G Base Editing in Mitochondrial DNA with Engineered DdCBE and TALED.
Article in Advanced science (Weinheim, Baden-Wurttemberg, Germany), 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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16 citing papers in PubMed, 15 citations in OpenAlex.
- Programmable aging function-related mitochondrial DNA 5-methylcytosine (m5C) modification with a TALE-directed methyltransferase.Cell communication and signaling : CCS · 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
- Targeting Mitochondria in Aging-Related Diseases: Therapeutic Potential and Obstacles.MedComm · 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
- The Role of Mitochondrial Genome Stability and Metabolic Plasticity in Thyroid Cancer.Biomedicines · 2025Review
- Alterations in mitochondrial base editors enhance targeted editing efficiency for mouse model generation.Molecular therapy. Nucleic acids · 2025Article
- Mitochondrial DNA editing: Key to the treatment of neurodegenerative diseases.Genes & diseases · 2025Review
- Mitochondrial base editing: from principle, optimization to application.Cell & bioscience · 2025Review
- Mitochondrial diseases: from molecular mechanisms to therapeutic advances.Signal transduction and targeted therapy · 2025Review
- Unraveling the roles and mechanisms of mitochondrial translation in normal and malignant hematopoiesis.Journal of hematology & oncology · 2024Review
- Unconstrained Precision Mitochondrial Genome Editing with αDdCBEs.Human gene therapy · 2024Article
- Harnessing accurate mitochondrial DNA base editing mediated by DdCBEs in a predictable manner.Frontiers in bioengineering and biotechnology · 2024Article
- Enhanced C-To-T and A-To-G Base Editing in Mitochondrial DNA with Engineered DdCBE and TALED.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
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Authors and funding
15 authors at 6 institutions in 3 countries.
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Abstract
Mitochondrial base editing with DddA-derived cytosine base editor (DdCBE) is limited in the accessible target sequences and modest activity. Here, the optimized DdCBE tools is presented with improved editing activity and expanded C-to-T targeting scope by fusing DddA11 variant with different cytosine deaminases with single-strand DNA activity. Compared to previous DdCBE based on DddA11 variant alone, fusion of the activation-induced cytidine deaminase (AID) from Xenopus laevis not only permits cytosine editing of 5'-GC-3' sequence, but also elevates editing efficiency at 5'-TC-3', 5'-CC-3', and 5'-GC-3' targets by up to 25-, 10-, and 6-fold, respectively. Furthermore, the A-to-G editing efficiency is significantly improved by fusing the evolved DddA6 variant with TALE-linked deoxyadenosine deaminase (TALED). Notably, the authors introduce the reported high-fidelity mutations in DddA and add nuclear export signal (NES) sequences in DdCBE and TALED to reduce off-target editing in the nuclear and mitochondrial genome while improving on-target editing efficiency in mitochondrial DNA (mtDNA). Finally, these engineered mitochondrial base editors are shown to be efficient in installing mtDNA mutations in human cells or mouse embryos for disease modeling. Collectively, the study shows broad implications for the basic study and therapeutic applications of optimized DdCBE and TALED.
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