Figure 4. Mechanisms of Cas9 immunity seen in experimental studies.

Innate immunity is mediated by pattern recognition receptors present on the cell surface (shown in blue), in the endocytic vesicles (shown in green) and cytoplasm (shown in red) of phagocytic cells. Humoral immunity is mediated by antibodies which can neutralize Cas9 protein or delivery vehicles. Both IgG and IgM antibodies have been seen to Cas9 exposure. Cellular immunity is mediated by display of peptides from intracellular proteins on cell surface receptors that can be recognized by cytotoxic T cells mediating killing of Cas9 expressing cells.