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In vivo genome editing with a small Cas9 orthologue derived from Campylobacter jejuni

Author

Listed:
  • Eunji Kim

    (Center for Genome Engineering, Institute for Basic Science (IBS)
    ToolGen, Byucksan Digital Valley 6-cha)

  • Taeyoung Koo

    (Center for Genome Engineering, Institute for Basic Science (IBS)
    University of Science and Technology)

  • Sung Wook Park

    (Seoul National University College of Medicine
    FARB Laboratory, Biomedical Research Institute, Seoul National University Hospital)

  • Daesik Kim

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

  • Kyoungmi Kim

    (Center for Genome Engineering, Institute for Basic Science (IBS))

  • Hee-Yeon Cho

    (Center for Genome Engineering, Institute for Basic Science (IBS))

  • Dong Woo Song

    (ToolGen, Byucksan Digital Valley 6-cha)

  • Kyu Jun Lee

    (ToolGen, Byucksan Digital Valley 6-cha)

  • Min Hee Jung

    (ToolGen, Byucksan Digital Valley 6-cha)

  • Seokjoong Kim

    (ToolGen, Byucksan Digital Valley 6-cha)

  • Jin Hyoung Kim

    (Seoul National University College of Medicine
    FARB Laboratory, Biomedical Research Institute, Seoul National University Hospital)

  • Jeong Hun Kim

    (Seoul National University College of Medicine
    FARB Laboratory, Biomedical Research Institute, Seoul National University Hospital
    Seoul National University College of Medicine)

  • Jin-Soo Kim

    (Center for Genome Engineering, Institute for Basic Science (IBS)
    University of Science and Technology
    Seoul National University)

Abstract

Several CRISPR-Cas9 orthologues have been used for genome editing. Here, we present the smallest Cas9 orthologue characterized to date, derived from Campylobacter jejuni (CjCas9), for efficient genome editing in vivo. After determining protospacer-adjacent motif (PAM) sequences and optimizing single-guide RNA (sgRNA) length, we package the CjCas9 gene, its sgRNA sequence, and a marker gene in an all-in-one adeno-associated virus (AAV) vector and produce the resulting virus at a high titer. CjCas9 is highly specific, cleaving only a limited number of sites in the human or mouse genome. CjCas9, delivered via AAV, induces targeted mutations at high frequencies in mouse muscle cells or retinal pigment epithelium (RPE) cells. Furthermore, CjCas9 targeted to the Vegfa or Hif1a gene in RPE cells reduces the size of laser-induced choroidal neovascularization, suggesting that in vivo genome editing with CjCas9 is a new option for the treatment of age-related macular degeneration.

Suggested Citation

  • Eunji Kim & Taeyoung Koo & Sung Wook Park & Daesik Kim & Kyoungmi Kim & Hee-Yeon Cho & Dong Woo Song & Kyu Jun Lee & Min Hee Jung & Seokjoong Kim & Jin Hyoung Kim & Jeong Hun Kim & Jin-Soo Kim, 2017. "In vivo genome editing with a small Cas9 orthologue derived from Campylobacter jejuni," Nature Communications, Nature, vol. 8(1), pages 1-12, April.
    • Handle: RePEc:nat:natcom:v:8:y:2017:i:1:d:10.1038_ncomms14500
    DOI: 10.1038/ncomms14500
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    Cited by:

    1. Eleonora Pedrazzoli & Michele Demozzi & Elisabetta Visentin & Matteo Ciciani & Ilaria Bonuzzi & Laura Pezzè & Lorenzo Lucchetta & Giulia Maule & Simone Amistadi & Federica Esposito & Mariangela Lupo &, 2024. "CoCas9 is a compact nuclease from the human microbiome for efficient and precise genome editing," Nature Communications, Nature, vol. 15(1), pages 1-12, December.
    2. Daniela S. Aliaga Goltsman & Lisa M. Alexander & Jyun-Liang Lin & Rodrigo Fregoso Ocampo & Benjamin Freeman & Rebecca C. Lamothe & Andres Perez Rivas & Morayma M. Temoche-Diaz & Shailaja Chadha & Nata, 2022. "Compact Cas9d and HEARO enzymes for genome editing discovered from uncultivated microbes," Nature Communications, Nature, vol. 13(1), pages 1-11, December.
    3. Jianhang Yin & Kailun Fang & Yanxia Gao & Liqiong Ou & Shaopeng Yuan & Changchang Xin & Weiwei Wu & Wei-wei Wu & Jiaxu Hong & Hui Yang & Jiazhi Hu, 2022. "Safeguarding genome integrity during gene-editing therapy in a mouse model of age-related macular degeneration," Nature Communications, Nature, vol. 13(1), pages 1-8, December.
    4. Jian Wang & Yuxi Teng & Ruihua Zhang & Yifei Wu & Lei Lou & Yusong Zou & Michelle Li & Zhong-Ru Xie & Yajun Yan, 2021. "Engineering a PAM-flexible SpdCas9 variant as a universal gene repressor," Nature Communications, Nature, vol. 12(1), pages 1-10, December.
    5. Burcu Bestas & Sandra Wimberger & Dmitrii Degtev & Alexandra Madsen & Antje K. Rottner & Fredrik Karlsson & Sergey Naumenko & Megan Callahan & Julia Liz Touza & Margherita Francescatto & Carl Ivar Möl, 2023. "A Type II-B Cas9 nuclease with minimized off-targets and reduced chromosomal translocations in vivo," Nature Communications, Nature, vol. 14(1), pages 1-15, December.
    6. Raed Ibraheim & Phillip W. L. Tai & Aamir Mir & Nida Javeed & Jiaming Wang & Tomás C. Rodríguez & Suk Namkung & Samantha Nelson & Eraj Shafiq Khokhar & Esther Mintzer & Stacy Maitland & Zexiang Chen &, 2021. "Self-inactivating, all-in-one AAV vectors for precision Cas9 genome editing via homology-directed repair in vivo," Nature Communications, Nature, vol. 12(1), pages 1-17, December.
    7. Dmitrii Degtev & Jack Bravo & Aikaterini Emmanouilidi & Aleksandar Zdravković & Oi Kuan Choong & Julia Liz Touza & Niklas Selfjord & Isabel Weisheit & Margherita Francescatto & Pinar Akcakaya & Michel, 2024. "Engineered PsCas9 enables therapeutic genome editing in mouse liver with lipid nanoparticles," Nature Communications, Nature, vol. 15(1), pages 1-15, December.
    8. Boris Kantor & Bernadette O’Donovan & Joseph Rittiner & Dellila Hodgson & Nicholas Lindner & Sophia Guerrero & Wendy Dong & Austin Zhang & Ornit Chiba-Falek, 2024. "The therapeutic implications of all-in-one AAV-delivered epigenome-editing platform in neurodegenerative disorders," Nature Communications, Nature, vol. 15(1), pages 1-15, December.
    9. Zhaohui Zhong & Guanqing Liu & Zhongjie Tang & Shuyue Xiang & Liang Yang & Lan Huang & Yao He & Tingting Fan & Shishi Liu & Xuelian Zheng & Tao Zhang & Yiping Qi & Jian Huang & Yong Zhang, 2023. "Efficient plant genome engineering using a probiotic sourced CRISPR-Cas9 system," Nature Communications, Nature, vol. 14(1), pages 1-16, December.
    10. Eman A. Ageely & Ramadevi Chilamkurthy & Sunit Jana & Leonora Abdullahu & Daniel O’Reilly & Philip J. Jensik & Masad J. Damha & Keith T. Gagnon, 2021. "Gene editing with CRISPR-Cas12a guides possessing ribose-modified pseudoknot handles," Nature Communications, Nature, vol. 12(1), pages 1-15, December.

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