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Editing of mouse and human immunoglobulin genes by CRISPR-Cas9 system

Author

Listed:
  • Taek-Chin Cheong

    (Children’s Hospital Boston and Harvard Medical School)

  • Mara Compagno

    (Children’s Hospital Boston and Harvard Medical School)

  • Roberto Chiarle

    (Children’s Hospital Boston and Harvard Medical School
    University of Torino)

Abstract

Applications of the CRISPR-Cas9 system to edit the genome have widely expanded to include DNA gene knock-out, deletions, chromosomal rearrangements, RNA editing and genome-wide screenings. Here we show the application of CRISPR-Cas9 technology to edit the mouse and human immunoglobulin (Ig) genes. By delivering Cas9 and guide-RNA (gRNA) with retro- or lenti-virus to IgM+ mouse B cells and hybridomas, we induce class-switch recombination (CSR) of the IgH chain to the desired subclass. Similarly, we induce CSR in all human B cell lines tested with high efficiency to targeted IgH subclass. Finally, we engineer mouse hybridomas to secrete Fab′ fragments instead of the whole Ig. Our results indicate that Ig genes in mouse and human cells can be edited to obtain any desired IgH switching helpful to study the biology of normal and lymphoma B cells. We also propose applications that could transform the technology of antibody production.

Suggested Citation

  • Taek-Chin Cheong & Mara Compagno & Roberto Chiarle, 2016. "Editing of mouse and human immunoglobulin genes by CRISPR-Cas9 system," Nature Communications, Nature, vol. 7(1), pages 1-10, April.
    • Handle: RePEc:nat:natcom:v:7:y:2016:i:1:d:10.1038_ncomms10934
    DOI: 10.1038/ncomms10934
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    Cited by:

    1. Taek-Chin Cheong & Ahram Jang & Qi Wang & Giulia C. Leonardi & Biagio Ricciuti & Joao V. Alessi & Alessandro Di Federico & Mark M. Awad & Maria K. Lehtinen & Marian H. Harris & Roberto Chiarle, 2024. "Mechanistic patterns and clinical implications of oncogenic tyrosine kinase fusions in human cancers," Nature Communications, Nature, vol. 15(1), pages 1-19, December.

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