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

Area of Science:

• Biotechnology
• Genetics
• Cancer Research

Background:

• CRISPR/Cas9 gene editing holds promise for correcting disease-causing mutations.
• CRISPR/Cas9 induces DNA damage, activating the tumor suppressor p53 and its associated DNA damage response.
• The implications of this p53-centered response in the context of gene therapy are not fully understood.

Purpose of the Study:

• To discuss the implications of CRISPR/Cas9-induced DNA damage and the p53 response in gene therapy.
• To identify a CRISPR-p53 interactome comprising cancer-related genes.
• To propose strategies for monitoring and mitigating potential risks associated with CRISPR/Cas9 use in clinics.

Main Methods:

• Literature review and analysis of CRISPR/Cas9 mechanisms.
• Bioinformatic identification of a CRISPR-p53 interactome.
• Conceptualization of clinical monitoring and therapeutic intervention strategies.

Main Results:

• CRISPR/Cas9-induced DNA damage activates a p53-dependent response.
• A specific CRISPR-p53 interactome was identified, containing cancer-related genes.
• Mutations in these interactome genes can confer a selective advantage to cells post-CRISPR/Cas9 exposure.

Conclusions:

• The CRISPR-p53 interactome represents a potential risk in clinical gene therapy settings.
• Monitoring genes within this interactome is recommended for patients undergoing CRISPR/Cas9 treatment.
• Transient inhibition of p53 may reduce the enrichment of cells with advantageous mutations.