bioRxivImmunology
Multifunctional CRISPR/Cas9 with engineered immunosilenced human T cell epitopes
S. R. Ferdosi, R. Ewaisha, F. Moghadam, S. Krishna, J. G. Park, M. R. Ebrahimkhani, S. Kiani, K. S. Anderson
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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