Lena Peter, Berlin Institute of Health Center for Regenerative Therapies, Berlin, Germany, provides an overview of strategies to overcome immunogenic barriers in vivo CRISPR-Cas9-based treatments face. As humans have existing immunity to Cas9 of various bacterial strains, safety and efficacy may be affected when they are treated with gene therapies using modified Cas9 proteins. She also highlights the suppressive nature of Cas9-specific regulatory T cells (Tregs), which can inhibit production of effector T cells targeting Cas 9. However, the ratio of effector T cells and Tregs should be monitored in patients to assess safety. This interview took place at the International Conference on Lymphocyte Engineering (ICLE) 2022.