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Cas9-derived peptides presented by MHC Class II that elicit proliferation of CD4+ T-cells

Author

Listed:
  • Vijaya L. Simhadri

    (Center for Biologics Evaluation and Research, Food and Drug Administration)

  • Louis Hopkins

    (Center for Biologics Evaluation and Research, Food and Drug Administration)

  • Joseph R. McGill

    (Center for Biologics Evaluation and Research, Food and Drug Administration)

  • Brian R. Duke

    (Editas Medicine)

  • Swati Mukherjee

    (Editas Medicine)

  • Kate Zhang

    (Editas Medicine)

  • Zuben E. Sauna

    (Center for Biologics Evaluation and Research, Food and Drug Administration)

Abstract

CRISPR–Cas9 mediated genome editing offers unprecedented opportunities for treating human diseases. There are several reports that demonstrate pre-existing immune responses to Cas9 which may have implications for clinical development of CRISPR-Cas9 mediated gene therapy. Here we use 209 overlapping peptides that span the entire sequence of Staphylococcus aureus Cas9 (SaCas9) and human peripheral blood mononuclear cells (PBMCs) from a cohort of donors with a distribution of Major Histocompatibility Complex (MHC) alleles comparable to that in the North American (NA) population to identify the immunodominant regions of the SaCas9 protein. We also use an MHC Associated Peptide Proteomics (MAPPs) assay to identify SaCas9 peptides presented by MHC Class II (MHC-II) proteins on dendritic cells. Using these two data sets we identify 22 SaCas9 peptides that are both presented by MHC-II proteins and stimulate CD4+ T-cells.

Suggested Citation

  • Vijaya L. Simhadri & Louis Hopkins & Joseph R. McGill & Brian R. Duke & Swati Mukherjee & Kate Zhang & Zuben E. Sauna, 2021. "Cas9-derived peptides presented by MHC Class II that elicit proliferation of CD4+ T-cells," Nature Communications, Nature, vol. 12(1), pages 1-7, December.
    • Handle: RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-25414-9
    DOI: 10.1038/s41467-021-25414-9
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    Cited by:

    1. Rumya Raghavan & Mirco J. Friedrich & Indigo King & Samuel Chau-Duy-Tam Vo & Daniel Strebinger & Blake Lash & Michael Kilian & Michael Platten & Rhiannon K. Macrae & Yifan Song & Lucas Nivon & Feng Zh, 2025. "Rational engineering of minimally immunogenic nucleases for gene therapy," Nature Communications, Nature, vol. 16(1), pages 1-13, December.

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