A mitochondrial disease model is generated and corrected using engineered base editors in rat zygotes

Liang Chen; Changming Luan; Mengjia Hong; Meng Yuan; Hao Huang; Debo Gao; Xinyuan Guo; Zhengxin Chen; Yongmei Li; Lei Yang; Zongyi Yi; Wensheng Wei; Mingyao Liu; Liangcai Gao; Honghui Han; Dali Li

doi:10.1038/s41587-025-02684-y

A mitochondrial disease model is generated and corrected using engineered base editors in rat zygotes

Liang Chen^*
, Changming Luan
, Mengjia Hong
, Meng Yuan
, Hao Huang
, Debo Gao
, Xinyuan Guo
, Zhengxin Chen
, Yongmei Li
, Lei Yang
, Zongyi Yi
, Wensheng Wei
, Mingyao Liu
, Liangcai Gao
, Honghui Han
, Dali Li^*

^*Corresponding author for this work

School of Life Sciences

Research output: Contribution to journal › Article › peer-review

5 Scopus citations

Abstract

Efficient generation and correction of mutations in mitochondrial DNA (mtDNA) is challenging. Here, through embryonic injection of an mtDNA adenine base editor (eTd-mtABE), Leigh syndrome rat models were generated efficiently (up to 74%) in the F₀ generation, exhibiting severe defects. To correct this mutation, a precise mtDNA C-to-T base editor was engineered and injected into mutated embryos. It achieved restoration of wild-type alleles to an average of 53%, leading to amelioration of disease symptoms.

Original language	English
Journal	Nature Biotechnology
DOIs	https://doi.org/10.1038/s41587-025-02684-y
State	Accepted/In press - 2025

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title = "A mitochondrial disease model is generated and corrected using engineered base editors in rat zygotes",

abstract = "Efficient generation and correction of mutations in mitochondrial DNA (mtDNA) is challenging. Here, through embryonic injection of an mtDNA adenine base editor (eTd-mtABE), Leigh syndrome rat models were generated efficiently (up to 74\%) in the F0 generation, exhibiting severe defects. To correct this mutation, a precise mtDNA C-to-T base editor was engineered and injected into mutated embryos. It achieved restoration of wild-type alleles to an average of 53\%, leading to amelioration of disease symptoms.",

author = "Liang Chen and Changming Luan and Mengjia Hong and Meng Yuan and Hao Huang and Debo Gao and Xinyuan Guo and Zhengxin Chen and Yongmei Li and Lei Yang and Zongyi Yi and Wensheng Wei and Mingyao Liu and Liangcai Gao and Honghui Han and Dali Li",

note = "Publisher Copyright: {\textcopyright} The Author(s), under exclusive licence to Springer Nature America, Inc. 2025.",

year = "2025",

doi = "10.1038/s41587-025-02684-y",

language = "英语",

journal = "Nature Biotechnology",

issn = "1087-0156",

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TY - JOUR

T1 - A mitochondrial disease model is generated and corrected using engineered base editors in rat zygotes

AU - Chen, Liang

AU - Luan, Changming

AU - Hong, Mengjia

AU - Yuan, Meng

AU - Huang, Hao

AU - Gao, Debo

AU - Guo, Xinyuan

AU - Chen, Zhengxin

AU - Li, Yongmei

AU - Yang, Lei

AU - Yi, Zongyi

AU - Wei, Wensheng

AU - Liu, Mingyao

AU - Gao, Liangcai

AU - Han, Honghui

AU - Li, Dali

PY - 2025

Y1 - 2025

N2 - Efficient generation and correction of mutations in mitochondrial DNA (mtDNA) is challenging. Here, through embryonic injection of an mtDNA adenine base editor (eTd-mtABE), Leigh syndrome rat models were generated efficiently (up to 74%) in the F0 generation, exhibiting severe defects. To correct this mutation, a precise mtDNA C-to-T base editor was engineered and injected into mutated embryos. It achieved restoration of wild-type alleles to an average of 53%, leading to amelioration of disease symptoms.

AB - Efficient generation and correction of mutations in mitochondrial DNA (mtDNA) is challenging. Here, through embryonic injection of an mtDNA adenine base editor (eTd-mtABE), Leigh syndrome rat models were generated efficiently (up to 74%) in the F0 generation, exhibiting severe defects. To correct this mutation, a precise mtDNA C-to-T base editor was engineered and injected into mutated embryos. It achieved restoration of wild-type alleles to an average of 53%, leading to amelioration of disease symptoms.

UR - https://www.scopus.com/pages/publications/105007217160

U2 - 10.1038/s41587-025-02684-y

DO - 10.1038/s41587-025-02684-y

M3 - 文章

AN - SCOPUS:105007217160

SN - 1087-0156

JO - Nature Biotechnology

JF - Nature Biotechnology

ER -

A mitochondrial disease model is generated and corrected using engineered base editors in rat zygotes

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