FIGURE 2.

Assessment, mitigation, and monitoring of immune responses to CRISPR therapeutics. Strategies for mitigation of immune responses can be personalized to each patient’s needs, history, immune status, and treatment plan. Pre-treatment assessment protocols can include screening for immune responses to different CRISPR effector proteins, HLA typing, and other tests that are relevant to the treatment approach such as pre-existing immune responses to the viral vector if one is used for delivery. According to the assessment results, appropriate mitigation strategies can then be implemented. These can include selection of a CRISPR effector ortholog which the patient has no pre-existing immunity against and engineering the selected protein to silence the immunodominant epitope(s) based on the individual’s MHC haplotype. Following administration of the CRISPR therapeutic, the patient should be monitored for the development of innate or adaptive immune responses and appropriate intervention strategies can be implemented accordingly. The assessment process can be repeated for each subsequent dose or for future administration of a different CRISPR therapeutic.