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CoCas9 is a compact nuclease from the human microbiome for efficient and precise genome editing

Author

Listed:
  • Eleonora Pedrazzoli

    (University of Trento)

  • Michele Demozzi

    (University of Trento)

  • Elisabetta Visentin

    (University of Trento)

  • Matteo Ciciani

    (University of Trento)

  • Ilaria Bonuzzi

    (University of Trento)

  • Laura Pezzè

    (Alia Therapeutics)

  • Lorenzo Lucchetta

    (University of Trento)

  • Giulia Maule

    (University of Trento)

  • Simone Amistadi

    (University of Trento
    INSERM)

  • Federica Esposito

    (Telethon Institute of Genetics and Medicine (TIGEM))

  • Mariangela Lupo

    (Telethon Institute of Genetics and Medicine (TIGEM))

  • Annarita Miccio

    (INSERM)

  • Alberto Auricchio

    (Telethon Institute of Genetics and Medicine (TIGEM)
    University of Naples “Federico II”)

  • Antonio Casini

    (Alia Therapeutics)

  • Nicola Segata

    (University of Trento)

  • Anna Cereseto

    (University of Trento)

Abstract

The expansion of the CRISPR-Cas toolbox is highly needed to accelerate the development of therapies for genetic diseases. Here, through the interrogation of a massively expanded repository of metagenome-assembled genomes, mostly from human microbiomes, we uncover a large variety (n = 17,173) of type II CRISPR-Cas loci. Among these we identify CoCas9, a strongly active and high-fidelity nuclease with reduced molecular size (1004 amino acids) isolated from an uncultivated Collinsella species. CoCas9 is efficiently co-delivered with its sgRNA through adeno associated viral (AAV) vectors, obtaining efficient in vivo editing in the mouse retina. With this study we uncover a collection of previously uncharacterized Cas9 nucleases, including CoCas9, which enriches the genome editing toolbox.

Suggested Citation

  • 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.
    • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-47800-9
    DOI: 10.1038/s41467-024-47800-9
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