Key result
Cas9 protein can be modified through targeted mutation to eliminate immunodominant epitopes, evading pre-existing human CD8+ T cell immunity while preserving its function and specificity.
Engineered Cas9 can evade pre-existing human CD8+ T cell immunity by eliminating immunodominant epitopes without losing function or specificity, potentially improving the safety of CRISPR/Cas9 therapies.
May necessitate Cas9 immunity screening or modification in CRISPR trials; leaves open human translation from animal data.
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 et al. (2018) studied Healthy individuals. Modified Cas9 protein with eliminated immunodominant epitopes vs. Wild-type Streptococcus pyogenes Cas9 was evaluated on Immunogenicity and preservation of function and specificity. Cas9 protein can be modified through targeted mutation to eliminate immunodominant epitopes, evading pre-existing human CD8+ T cell immunity while preserving its function and specificity.
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