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

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Data availability

HTS data were deposited to the National Center for Biotechnology Information Sequence Read Archive database under accession code PRJNA1252023. There are no restrictions on data availability. Source data are provided with this paper.

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Acknowledgements

We thank Y. Zhang from the Flow Cytometry Core Facility of School of Life Sciences at ECNU and support from the ECNU Public Platform for innovation (011). We thank L. Ji (HAVAS) for designing schematic diagrams. This work was partially supported by grants from the National Key R&D Program of China (2023YFC3403400 and 2023YFE0209200 to D.L.; 2024YFC3407900 to L.C.), National Natural Science Foundation of China (32025023, 32230064 and 32311530111 to D.L.; 31930016 to W.W.; 82230002 to M.L.), Innovation Program of Shanghai Municipal Education Commission (2019-01-07-00-05-E00054 to D.L.), Shanghai Municipal Commission for Science and Technology (24J22800400 to D.L.), Young Elite Scientist Sponsorship Program by China Association for Science and Technology (2023QNRC001 to L.C.), Shanghai Oriental Talent Plan (QNZH2024131 to L.C.), Fellowship of China Postdoctoral Science Foundation (8206400139 to Z.Y.) and Lingang Laboratory. D.L. is a Shanghai Academy of Natural Sciences Exploration Scholar.

Author information

Author notes

  1. These authors contributed equally: Liang Chen, Changming Luan, Mengjia Hong.

Authors and Affiliations

  1. Lingang Laboratory, Shanghai, China

    Liang Chen & Zhengxin Chen

  2. School of Pharmacy, East China Normal University, Shanghai, China

    Liang Chen & Dali Li

  3. Shanghai Frontiers Science Center of Genome Editing and Cell Therapy, Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai, China

    Changming Luan, Mengjia Hong, Meng Yuan, Hao Huang, Xinyuan Guo, Yongmei Li, Lei Yang, Liangcai Gao, Honghui Han & Dali Li

  4. School of Pharmacy, East China University of Science and Technology, Shanghai, China

    Debo Gao

  5. Biomedical 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

    Zongyi Yi & Wensheng Wei

  6. Changping Laboratory, Beijing, China

    Wensheng Wei

  7. BRL Medicine, Inc., Shanghai, China

    Mingyao Liu

  8. Shanghai Academy of Natural Sciences (SANS), Shanghai, China

    Dali Li

Contributions

L.C. and D.L. designed the experiments. L.C., C.L., M.H., M.Y., H. Huang, D.G., X.G., Y.L., L.Y., L.G. and H. Han performed the experiments. L.C., C.L., M.H., M.Y., H. Huang, D.G., X.G., Z.C., Z.Y., W.W., M.L. and D.L. analyzed the data. L.C. and D.L. wrote the paper with input from all authors. L.C. and D.L. supervised the research.

Corresponding authors

Correspondence to
Liang Chen or Dali Li.

Ethics declarations

Competing interests

The authors have submitted patent applications based on the results reported in this study (L.C., D.L., M.H. and C.L.). The other authors declare no competing interests.

Peer review

Peer review information

Nature Biotechnology thanks the anonymous reviewers for their contribution to the peer review of this work.

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Supplementary information

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Cite this article

Chen, L., Luan, C., Hong, M. et al. A mitochondrial disease model is generated and corrected using engineered base editors in rat zygotes.
Nat Biotechnol (2025). https://doi.org/10.1038/s41587-025-02684-y

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  • DOI: https://doi.org/10.1038/s41587-025-02684-y

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