Mitochondrial base editing: from principle, optimization to application
Abstract In recent years, mitochondrial DNA (mtDNA) base editing systems have emerged as bioengineering tools. DddA-derived cytosine base editors (DdCBEs) have been developed to specifically induce C-to-T conversion in mtDNA by the fusion of sequence-programmable transcription activator-like effecto...
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BMC
2025-01-01
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Online Access: | https://doi.org/10.1186/s13578-025-01351-8 |
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author | Jinling Tang Kunzhao Du |
author_facet | Jinling Tang Kunzhao Du |
author_sort | Jinling Tang |
collection | DOAJ |
description | Abstract In recent years, mitochondrial DNA (mtDNA) base editing systems have emerged as bioengineering tools. DddA-derived cytosine base editors (DdCBEs) have been developed to specifically induce C-to-T conversion in mtDNA by the fusion of sequence-programmable transcription activator-like effector nucleases (TALENs) or zinc-finger nucleases (ZFNs), and split deaminase derived from interbacterial toxins. Similar to DdCBEs, mtDNA adenine base editors have been developed with the ability to introduce targeted A-to-G conversions into human mtDNA. In this review, we summarize the principles of mtDNA base-editing systems and elaborate on the evolution of different platforms of mtDNA base editors, including their deaminase replacement, engineering of DddAtox variants, structure optimization and editing outcomes. Finally, we highlight their applications in animal models and human embroys and discuss the future developmental direction and challenges of mtDNA base editors. |
format | Article |
id | doaj-art-20833752aa644d87bf5d6e5f83b69d7f |
institution | Kabale University |
issn | 2045-3701 |
language | English |
publishDate | 2025-01-01 |
publisher | BMC |
record_format | Article |
series | Cell & Bioscience |
spelling | doaj-art-20833752aa644d87bf5d6e5f83b69d7f2025-01-26T12:54:21ZengBMCCell & Bioscience2045-37012025-01-0115111710.1186/s13578-025-01351-8Mitochondrial base editing: from principle, optimization to applicationJinling Tang0Kunzhao Du1Clinical Laboratory Center, The First Affiliated Hospital of Guangxi Medical UniversityJinshan Hospital Center for Neurosurgery, Jinshan Hospital, Institute for Translational Brain Research, State Key Laboratory of Medical Neurobiology, MOE Frontiers Center for Brain Science, Fudan UniversityAbstract In recent years, mitochondrial DNA (mtDNA) base editing systems have emerged as bioengineering tools. DddA-derived cytosine base editors (DdCBEs) have been developed to specifically induce C-to-T conversion in mtDNA by the fusion of sequence-programmable transcription activator-like effector nucleases (TALENs) or zinc-finger nucleases (ZFNs), and split deaminase derived from interbacterial toxins. Similar to DdCBEs, mtDNA adenine base editors have been developed with the ability to introduce targeted A-to-G conversions into human mtDNA. In this review, we summarize the principles of mtDNA base-editing systems and elaborate on the evolution of different platforms of mtDNA base editors, including their deaminase replacement, engineering of DddAtox variants, structure optimization and editing outcomes. Finally, we highlight their applications in animal models and human embroys and discuss the future developmental direction and challenges of mtDNA base editors.https://doi.org/10.1186/s13578-025-01351-8Mitochondrial DNAmtDNA base editingDdCBEsTALENsGenetic engineering |
spellingShingle | Jinling Tang Kunzhao Du Mitochondrial base editing: from principle, optimization to application Cell & Bioscience Mitochondrial DNA mtDNA base editing DdCBEs TALENs Genetic engineering |
title | Mitochondrial base editing: from principle, optimization to application |
title_full | Mitochondrial base editing: from principle, optimization to application |
title_fullStr | Mitochondrial base editing: from principle, optimization to application |
title_full_unstemmed | Mitochondrial base editing: from principle, optimization to application |
title_short | Mitochondrial base editing: from principle, optimization to application |
title_sort | mitochondrial base editing from principle optimization to application |
topic | Mitochondrial DNA mtDNA base editing DdCBEs TALENs Genetic engineering |
url | https://doi.org/10.1186/s13578-025-01351-8 |
work_keys_str_mv | AT jinlingtang mitochondrialbaseeditingfromprincipleoptimizationtoapplication AT kunzhaodu mitochondrialbaseeditingfromprincipleoptimizationtoapplication |