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Multifunctional CRISPR/Cas9 with engineered immunosilenced human T cell epitopes

Shayesteh R. Ferdosi, Radwa Ewaisha, Farzaneh Moghadam, Sri Krishna, Jin G. Park, Mo R. Ebrahimkhani, Samira Kiani, Karen S. Anderson
doi: https://doi.org/10.1101/360198
Shayesteh R. Ferdosi
Biodesign Institute - Arizona State University;
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Radwa Ewaisha
Arizona State University;
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Farzaneh Moghadam
School of Biological and Health Systems Engineering - Arizona State University
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Sri Krishna
Biodesign Institute - Arizona State University;
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Jin G. Park
Biodesign Institute - Arizona State University;
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Mo R. Ebrahimkhani
School of Biological and Health Systems Engineering - Arizona State University
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Samira Kiani
School of Biological and Health Systems Engineering - Arizona State University
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Karen S. Anderson
Biodesign Institute - Arizona State University;
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  • For correspondence: karen.anderson.1@asu.edu
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Abstract

The application of Cas9 for genetic and epigenetic therapies in humans raises concerns over immunogenicity of this foreign protein. We report pre-existing human CD8+ T cell immunity to Streptococcus pyogenes Cas9 in the majority of healthy individuals screened. In a proof-of-principle study, we demonstrate that Cas9 protein can be modified to eliminate immunodominant epitopes through targeted mutation while preserving its function and specificity.

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The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
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Posted July 02, 2018.
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Multifunctional CRISPR/Cas9 with engineered immunosilenced human T cell epitopes
Shayesteh R. Ferdosi, Radwa Ewaisha, Farzaneh Moghadam, Sri Krishna, Jin G. Park, Mo R. Ebrahimkhani, Samira Kiani, Karen S. Anderson
bioRxiv 360198; doi: https://doi.org/10.1101/360198
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Multifunctional CRISPR/Cas9 with engineered immunosilenced human T cell epitopes
Shayesteh R. Ferdosi, Radwa Ewaisha, Farzaneh Moghadam, Sri Krishna, Jin G. Park, Mo R. Ebrahimkhani, Samira Kiani, Karen S. Anderson
bioRxiv 360198; doi: https://doi.org/10.1101/360198

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