Evidence map›Paper›PMID 41249818›Full record

ArticleNature structural & molecular biology2025

Computational design of a high-precision mitochondrial DNA cytosine base editor.

Li Mi, Yu-Xuan Li, Xinchen Lv, Zi-Li Wan, Xu Liu, Kairan Zhang, Huican Li, Yue Yao, Leping Zhang, Zhe Xu and 5 more

Abstract read
PubMed Publisher
In one paragraph

Article in Nature structural & molecular biology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing 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

5 citing papers in PubMed.

  1. Review
  2. Review
  3. Article
  4. Review
  5. Expansion of artificial intelligence for genome editing.Nature structural & molecular biology · 2025
    Article
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

15 authors.

Li Mi *State Key Laboratory of Gene Expression, Research Center for Industries of the Future, School of Life Sciences, Westlake University, Hangzhou, China.ORCID http://orcid.org/0009-0001-9297-6742
Yu-Xuan Li *State Key Laboratory of Gene Function and Modulation Research, Institute of Molecular Medicine, College of Future Technology, Peking University, Beijing, China.ORCID http://orcid.org/0000-0002-8066-9569
Xinchen Lv *State Key Laboratory of Gene Expression, Research Center for Industries of the Future, School of Life Sciences, Westlake University, Hangzhou, China.ORCID http://orcid.org/0000-0001-5101-0004
Zi-Li WanState Key Laboratory of Gene Function and Modulation Research, Institute of Molecular Medicine, College of Future Technology, Peking University, Beijing, China.ORCID http://orcid.org/0009-0002-4131-6506
Xu LiuState Key Laboratory of Gene Expression, Research Center for Industries of the Future, School of Life Sciences, Westlake University, Hangzhou, China.
Kairan ZhangState Key Laboratory of Gene Expression, Research Center for Industries of the Future, School of Life Sciences, Westlake University, Hangzhou, China.
Huican LiState Key Laboratory of Gene Expression, Research Center for Industries of the Future, School of Life Sciences, Westlake University, Hangzhou, China.
Yue YaoState Key Laboratory of Gene Expression, Research Center for Industries of the Future, School of Life Sciences, Westlake University, Hangzhou, China.
Leping ZhangState Key Laboratory of Gene Expression, Research Center for Industries of the Future, School of Life Sciences, Westlake University, Hangzhou, China.
Zhe XuState Key Laboratory of Gene Expression, Research Center for Industries of the Future, School of Life Sciences, Westlake University, Hangzhou, China.
Xingyu ZhuangDepartment of Neurology, Shandong Key Laboratory of Mitochondrial Medicine and Rare Diseases, Research Institute of Neuromuscular and Neurodegenerative Diseases, Qilu Hospital of Shandong University, Jinan, China.
Kunqian JiDepartment of Neurology, Shandong Key Laboratory of Mitochondrial Medicine and Rare Diseases, Research Institute of Neuromuscular and Neurodegenerative Diseases, Qilu Hospital of Shandong University, Jinan, China.
Min JiangState Key Laboratory of Gene Expression, Research Center for Industries of the Future, School of Life Sciences, Westlake University, Hangzhou, China.ORCID http://orcid.org/0000-0002-7005-937X
Yangming WangState Key Laboratory of Gene Function and Modulation Research, Institute of Molecular Medicine, College of Future Technology, Peking University, Beijing, China. yangming.wang@pku.edu.cn.ORCID http://orcid.org/0000-0001-6974-6060
Peilong LuState Key Laboratory of Gene Expression, Research Center for Industries of the Future, School of Life Sciences, Westlake University, Hangzhou, China. lupeilong@westlake.edu.cn.ORCID http://orcid.org/0000-0001-5894-9268

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Bystander editing remains a major limitation of current base editors, hindering their precision and therapeutic potential. Here, we present a de novo protein design strategy that creates a structurally rigid interface between a DNA-binding TALE domain and a cytosine deaminase, forming a unified editing module termed TALE-oriented deaminase (TOD). Cryo-EM analysis of TOD-DNA complexes confirms that this precise spatial architecture tightly restricts the deaminase activity window, thereby minimizing unwanted deamination. To further enhance editing specificity, we develop a split version, termed DdCBE-TOD, which virtually eliminates off-target editing. As a proof of concept, we apply DdCBE-TOD to generate a mitochondrial disease mouse model and to correct a pathogenic mutation associated with MERRF syndrome in patient-derived cells, achieving single-nucleotide precision. This work introduces a generalizable and computationally guided approach for ultra-precise base editing, offering a promising platform for both mechanistic studies and therapeutic correction of single-nucleotide mutations.

Indexed as

CytosineDNA, MitochondrialGene EditingAnimalsCryoelectron MicroscopyDisease Models, AnimalHumansMiceMitochondrial DiseasesModels, MolecularMutationCytosineDNA, Mitochondrial

Identifiers

What Socratic holds

Textmetadata
Read underepoch 390

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 Socratic graph.