A CRISPR-p53 interactome with potential implications for clinical CRISPR/Cas9 use.

CRISPR/Cas9-based tools are anticipated to transform the gene therapy field by facilitating the correction of disease-causing mutations. However, CRISPR/Cas9 generates DNA damage, which triggers a DNA damage response centered around the tumor-suppressor p53. In this research perspective, we discuss implications of this and describe a CRISPR-p53 interactome with cancer-related genes that, if mutated, can give cells a selective advantage following exposure to CRISPR/Cas9. We propose that the genes in the CRISPR-p53 interactome should be monitored in the clinical setting and describe that transient p53 inhibition could be used to limit the enrichment of cells with such mutations.