Trends and prospects in mitochondrial genome editing

Abstract Mitochondria are of fundamental importance in programmed cell death, cellular metabolism, and intracellular calcium concentration modulation, and inheritable mitochondrial disorders via mitochondrial DNA (mtDNA) mutation cause several diseases in various organs and systems. Nevertheless, mt...

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Main Authors: Hong Thi Lam Phan, Hyunji Lee, Kyoungmi Kim
Format: Article
Language:English
Published: Nature Publishing Group 2023-05-01
Series:Experimental and Molecular Medicine
Online Access:https://doi.org/10.1038/s12276-023-00973-7
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author Hong Thi Lam Phan
Hyunji Lee
Kyoungmi Kim
author_facet Hong Thi Lam Phan
Hyunji Lee
Kyoungmi Kim
author_sort Hong Thi Lam Phan
collection DOAJ
description Abstract Mitochondria are of fundamental importance in programmed cell death, cellular metabolism, and intracellular calcium concentration modulation, and inheritable mitochondrial disorders via mitochondrial DNA (mtDNA) mutation cause several diseases in various organs and systems. Nevertheless, mtDNA editing, which plays an essential role in the treatment of mitochondrial disorders, still faces several challenges. Recently, programmable editing tools for mtDNA base editing, such as cytosine base editors derived from DddA (DdCBEs), transcription activator-like effector (TALE)-linked deaminase (TALED), and zinc finger deaminase (ZFD), have emerged with considerable potential for correcting pathogenic mtDNA variants. In this review, we depict recent advances in the field, including structural biology and repair mechanisms, and discuss the prospects of using base editing tools on mtDNA to broaden insight into their medical applicability for treating mitochondrial diseases.
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spelling doaj.art-e6c0f467abf1486782ae96b95a84ced02023-06-04T11:07:23ZengNature Publishing GroupExperimental and Molecular Medicine2092-64132023-05-0155587187810.1038/s12276-023-00973-7Trends and prospects in mitochondrial genome editingHong Thi Lam Phan0Hyunji Lee1Kyoungmi Kim2Department of Physiology, Korea University College of MedicineLaboratory Animal Resource and Research Center, Korea Research Institute of Bioscience and BiotechnologyDepartment of Physiology, Korea University College of MedicineAbstract Mitochondria are of fundamental importance in programmed cell death, cellular metabolism, and intracellular calcium concentration modulation, and inheritable mitochondrial disorders via mitochondrial DNA (mtDNA) mutation cause several diseases in various organs and systems. Nevertheless, mtDNA editing, which plays an essential role in the treatment of mitochondrial disorders, still faces several challenges. Recently, programmable editing tools for mtDNA base editing, such as cytosine base editors derived from DddA (DdCBEs), transcription activator-like effector (TALE)-linked deaminase (TALED), and zinc finger deaminase (ZFD), have emerged with considerable potential for correcting pathogenic mtDNA variants. In this review, we depict recent advances in the field, including structural biology and repair mechanisms, and discuss the prospects of using base editing tools on mtDNA to broaden insight into their medical applicability for treating mitochondrial diseases.https://doi.org/10.1038/s12276-023-00973-7
spellingShingle Hong Thi Lam Phan
Hyunji Lee
Kyoungmi Kim
Trends and prospects in mitochondrial genome editing
Experimental and Molecular Medicine
title Trends and prospects in mitochondrial genome editing
title_full Trends and prospects in mitochondrial genome editing
title_fullStr Trends and prospects in mitochondrial genome editing
title_full_unstemmed Trends and prospects in mitochondrial genome editing
title_short Trends and prospects in mitochondrial genome editing
title_sort trends and prospects in mitochondrial genome editing
url https://doi.org/10.1038/s12276-023-00973-7
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