Evidence map›Paper›PMID 40461783›Full record

ArticleNature biotechnology2026

Efficient mitochondrial A-to-G base editors for the generation of mitochondrial disease models.

Liang Chen, Mengjia Hong, Changming Luan, Meng Yuan, Yiming Wang, Xinyuan Guo, Yue Fang, Hao Huang, Xiaohua Dong, Hongyi Gao and 11 more

Abstract read
PubMed Publisher
In one paragraph

Article in Nature biotechnology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.

0numbers the graph read from it
0cells of the map it votes in
12citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

12 citing papers in PubMed.

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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

21 authors.

Liang Chen *Shanghai Frontiers Science Center of Genome Editing and Cell Therapy, Shanghai Key Laboratory of Regulatory Biology, School of Life Sciences, East China Normal University, Shanghai, China. chenliang@lglab.ac.cn.ORCID http://orcid.org/0000-0001-6206-1077
Mengjia Hong *Shanghai Frontiers Science Center of Genome Editing and Cell Therapy, Shanghai Key Laboratory of Regulatory Biology, School of Life Sciences, East China Normal University, Shanghai, China.
Changming Luan *Shanghai Frontiers Science Center of Genome Editing and Cell Therapy, Shanghai Key Laboratory of Regulatory Biology, School of Life Sciences, East China Normal University, Shanghai, China.
Meng YuanShanghai Frontiers Science Center of Genome Editing and Cell Therapy, Shanghai Key Laboratory of Regulatory Biology, School of Life Sciences, East China Normal University, Shanghai, China.
Yiming WangLingang Laboratory, Shanghai, China.
Xinyuan GuoShanghai Frontiers Science Center of Genome Editing and Cell Therapy, Shanghai Key Laboratory of Regulatory Biology, School of Life Sciences, East China Normal University, Shanghai, China.
Yue FangKey Laboratory of Brain Functional Genomics of Ministry of Education, Shanghai Key Laboratory of Brain Functional Genomics, School of Life Sciences, East China Normal University, Shanghai, China.
Hao HuangShanghai Frontiers Science Center of Genome Editing and Cell Therapy, Shanghai Key Laboratory of Regulatory Biology, School of Life Sciences, East China Normal University, Shanghai, China.
Xiaohua DongLingang Laboratory, Shanghai, China.
Hongyi GaoShanghai Frontiers Science Center of Genome Editing and Cell Therapy, Shanghai Key Laboratory of Regulatory Biology, School of Life Sciences, East China Normal University, Shanghai, China.
Dan ZhangShanghai Frontiers Science Center of Genome Editing and Cell Therapy, Shanghai Key Laboratory of Regulatory Biology, School of Life Sciences, East China Normal University, Shanghai, China.
Xi ChenBRL Medicine, Inc., Shanghai, China.
Dihao MengShanghai Frontiers Science Center of Genome Editing and Cell Therapy, Shanghai Key Laboratory of Regulatory Biology, School of Life Sciences, East China Normal University, Shanghai, China.
Molin HuangShanghai Frontiers Science Center of Genome Editing and Cell Therapy, Shanghai Key Laboratory of Regulatory Biology, School of Life Sciences, East China Normal University, Shanghai, China.
Zongyi YiBiomedical Pioneering Innovation Center, Peking-Tsinghua Center for Life Sciences, Peking University Genome Editing Research Center, State Key Laboratory of Protein and Plant Gene Research, School of Life Sciences, Peking University, Beijing, China.ORCID http://orcid.org/0000-0002-5654-4221
Mingyao LiuShanghai Frontiers Science Center of Genome Editing and Cell Therapy, Shanghai Key Laboratory of Regulatory Biology, School of Life Sciences, East China Normal University, Shanghai, China.ORCID http://orcid.org/0000-0001-7339-5048
Wensheng WeiBiomedical Pioneering Innovation Center, Peking-Tsinghua Center for Life Sciences, Peking University Genome Editing Research Center, State Key Laboratory of Protein and Plant Gene Research, School of Life Sciences, Peking University, Beijing, China.ORCID http://orcid.org/0000-0002-8053-2423
Liangcai GaoShanghai Frontiers Science Center of Genome Editing and Cell Therapy, Shanghai Key Laboratory of Regulatory Biology, School of Life Sciences, East China Normal University, Shanghai, China.
Gaojie SongShanghai Frontiers Science Center of Genome Editing and Cell Therapy, Shanghai Key Laboratory of Regulatory Biology, School of Life Sciences, East China Normal University, Shanghai, China.ORCID http://orcid.org/0000-0002-7787-6452
Xiaoming ZhouKey Laboratory of Brain Functional Genomics of Ministry of Education, Shanghai Key Laboratory of Brain Functional Genomics, School of Life Sciences, East China Normal University, Shanghai, China.
Dali LiShanghai Frontiers Science Center of Genome Editing and Cell Therapy, Shanghai Key Laboratory of Regulatory Biology, School of Life Sciences, East China Normal University, Shanghai, China. dlli@bio.ecnu.edu.cn.ORCID http://orcid.org/0000-0002-0046-8493

Funding

National Natural Science Foundation of China (National Science Foundation of China) No.32025023
6 · The paper itself

Abstract

Existing A-to-G base editors for mitochondrial DNA (mtDNA) are limited by low efficiency. We used directed evolution to discover variants of the TadA-8e base editors that have substantially increased activity and expanded targeting compatibility for both nuclear and mitochondrial adenine base editing, especially in previously unfavored sequence contexts. The engineered mtDNA editors (eTd-mtABEs) showed up to 87% editing efficiency in human cells, with greatly reduced DNA and RNA off-target effects. Strand-selective A-to-G editing was enhanced by an average of 3.2-fold with substitution of DddA to DNA nickases in eTd-mtABE backbones compared to mitochondrial ABEs. In rat cells, editing efficiencies of eTd-mtABEs were up to 145-fold higher compared to split DddA transcription activator-like effector-linked deaminase. We also generated rats with sensorineural hearing loss by installing targeted mutations with frequencies of up to 44% through embryonic injection. The developed eTd-mtABEs are efficient and precise mtDNA-engineering tools for basic research and translational studies.

Indexed as

DNA, MitochondrialGene EditingMitochondriaMitochondrial DiseasesAnimalsDisease Models, AnimalHumansRatsDNA, Mitochondrial

Identifiers

PMID40461783

What OpenQuestion holds

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Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.