Multifunctional CRISPR/Cas9 with engineered immunosilenced human T cell epitopes

Ferdosi, S. R.; Ewaisha, R.; Moghadam, F.; Krishna, S.; Park, J. G.; Ebrahimkhani, M. R.; Kiani, S.; Anderson, K. S.

doi:10.1101/360198

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bioRxiv · 10.1101/360198

Multifunctional CRISPR/Cas9 with engineered immunosilenced human T cell epitopes

Ferdosi, S. R.·Ewaisha, R.·Moghadam, F.·Krishna, S.·Park, J. G.·Ebrahimkhani, M. R.·Kiani, S.·Anderson, K. S.

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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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Ferdosi, S. R., Ewaisha, R., Moghadam, F., Krishna, S., Park, J. G., Ebrahimkhani, M. R., Kiani, S., Anderson, K. S.. 2018-07-02. Multifunctional CRISPR/Cas9 with engineered immunosilenced human T cell epitopes. https://doi.org/10.1101/360198

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