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Mitochondrial DNA editing in mice with DddA-TALE fusion deaminases

Author

Listed:
  • Hyunji Lee

    (Center for Genome Engineering, Institute for Basic Science)

  • Seonghyun Lee

    (Center for Genome Engineering, Institute for Basic Science)

  • Gayoung Baek

    (Center for Genome Engineering, Institute for Basic Science)

  • Annie Kim

    (Center for Genome Engineering, Institute for Basic Science
    Seoul National University)

  • Beum-Chang Kang

    (Center for Genome Engineering, Institute for Basic Science)

  • Huiyun Seo

    (Center for Genome Engineering, Institute for Basic Science)

  • Jin-Soo Kim

    (Center for Genome Engineering, Institute for Basic Science
    Seoul National University)

Abstract

DddA-derived cytosine base editors (DdCBEs), composed of the split interbacterial toxin DddAtox, transcription activator-like effector (TALE), and uracil glycosylase inhibitor (UGI), enable targeted C-to-T base conversions in mitochondrial DNA (mtDNA). Here, we demonstrate highly efficient mtDNA editing in mouse embryos using custom-designed DdCBEs. We target the mitochondrial gene, MT-ND5 (ND5), which encodes a subunit of NADH dehydrogenase that catalyzes NADH dehydration and electron transfer to ubiquinone, to obtain several mtDNA mutations, including m.G12918A associated with human mitochondrial diseases and m.C12336T that incorporates a premature stop codon, creating mitochondrial disease models in mice and demonstrating a potential for the treatment of mitochondrial disorders.

Suggested Citation

  • Hyunji Lee & Seonghyun Lee & Gayoung Baek & Annie Kim & Beum-Chang Kang & Huiyun Seo & Jin-Soo Kim, 2021. "Mitochondrial DNA editing in mice with DddA-TALE fusion deaminases," Nature Communications, Nature, vol. 12(1), pages 1-6, December.
    • Handle: RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-21464-1
    DOI: 10.1038/s41467-021-21464-1
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    Cited by:

    1. Friedrich Fauser & Bhakti N. Kadam & Sebastian Arangundy-Franklin & Jessica E. Davis & Vishvesha Vaidya & Nicola J. Schmidt & Garrett Lew & Danny F. Xia & Rakshaa Mureli & Colman Ng & Yuanyue Zhou & N, 2024. "Compact zinc finger architecture utilizing toxin-derived cytidine deaminases for highly efficient base editing in human cells," Nature Communications, Nature, vol. 15(1), pages 1-11, December.
    2. Haifeng Sun & Zhaojun Wang & Limini Shen & Yeling Feng & Lu Han & Xuezhen Qian & Runde Meng & Kangming Ji & Dong Liang & Fei Zhou & Xin Lou & Jun Zhang & Bin Shen, 2023. "Developing mitochondrial base editors with diverse context compatibility and high fidelity via saturated spacer library," Nature Communications, Nature, vol. 14(1), pages 1-14, December.
    3. Pedro Silva-Pinheiro & Pavel A. Nash & Lindsey Van Haute & Christian D. Mutti & Keira Turner & Michal Minczuk, 2022. "In vivo mitochondrial base editing via adeno-associated viral delivery to mouse post-mitotic tissue," Nature Communications, Nature, vol. 13(1), pages 1-9, December.
    4. Young Geun Mok & Ji Min Lee & Eugene Chung & Jaesuk Lee & Kayeong Lim & Sung-Ik Cho & Jin-Soo Kim, 2022. "Base editing in human cells with monomeric DddA-TALE fusion deaminases," Nature Communications, Nature, vol. 13(1), pages 1-10, December.

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