Uncovering Immunogenic Peptides of Clinical Significance in CRISPR/Cas9

The risk of adverse immune responses following exposure to foreign-bacterial proteins is a potential hurdle to the successful broad implementation of CRISPR/Cas9 based gene and cell therapies. Anti-Cas9 adaptive responses, such as those mediated by neutralizing antibodies or cytotoxic T cell responses, can also impact the efficacy of CRISPR/Cas9 based therapies and potentially negate its benefits to some patients.

These risks have been highlighted by studies analyzing in vitro B and T cell responses against Cas9 in human samples. For example, work in the Porteus lab confirmed that, as expected, previous encounters with common pathogens such as Staphylococcus aureus and Staphylococcus pyogenes trigger anti-Cas9 adaptive immune responses against SaCas9 and SpCas9, respectively. In fact, the Porteus team found a high prevalence of antibody and T cell-mediated responses in serum and peripheral blood mononuclear cell (PBMC) samples from donors following in vitro testing (Charlesworth et al. 2019). These findings agree with previous work, which similarly supported the high prevalence of CD4+ and CD8+ T cell responses against SpCas9 amongst adult donors' samples (Wagner et al. 2018). 

T cell activation assays

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