Identification and engineering of TCR epitopes in Cas9 protein helps reduce T cell response against CRISPR CRISPR is a bacterial-derived gene editing tools that can potentially cure various genetic disorders. CRISPR consist of a Cas9 protein that creates a nick in the specific site of double-stranded DNA that is recognized by guide RNA. During the double strand break repairs, the target site may be engineered to obtain the intended outcomes. The adeno-associated viral vectors are most commonly used for delivery of gene and long term expression of Cas9 proteins. These endogenously synthesized Cas9 proteins are processed and presented via MHC-I in the target cells. Any preexisting reactive T cells recognize to MHC- Cas9 peptide complex and elicit cell-mediated cytotoxicity. This may have a detrimental effect on the tissues that express Cas9 transgene. When T cell encounters the target cells, T cell receptor bind to the MHC class I presented with short antigenic peptides (8-10 amino a...