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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Main Authors: Jinling Tang, Kunzhao Du
Format: Article
Language:English
Published: BMC 2025-01-01
Series:Cell & Bioscience
Subjects:
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.
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institution Kabale University
issn 2045-3701
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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