Clinical trials and proof-of-concept pre-clinical work for different cancers has shown relatively positive outcomes and tumour killing when p53, a well-established tumour suppressor, levels and function is restored. Human papillomavirus (HPV) driven cancers encode the E6 oncoprotein that degrades p53 to allow HPV-driven carcinogenic process to proceed. Indeed, there have been several attempts in the past to revive p53 function in HPV driven cancers by pharmacological and genetic means to increase p53 bioavailability. Here, we employed a CRISPR activation (CRISPRa) approach to overcome HPV-mediated silencing of p53 by hyper expressing the p53 promoter. Hyperexpression of p53 led to HPV positive (+) cervical cancer cell killing and reduced cell proliferation. Increasing p53 bioavailability may have promising potential as a therapy for HPV driven cancers.

Clinical trials and proof-of-concept pre-clinical work for different cancers has shown relatively positive outcomes and tumour killing when p53, a well-established tumour suppressor, levels and function is restored. Human papillomavirus (HPV) driven cancers encode the E6 oncoprotein that degrades p53 to allow HPV-driven carcinogenic process to proceed. Indeed, there have been several attempts in the past to revive p53 function in HPV driven cancers by pharmacological and genetic means to increase p53 bioavailability. Here, we employed a CRISPR activation (CRISPRa) approach to overcome HPV-mediated silencing of p53 by hyper expressing the p53 promoter. Hyperexpression of p53 led to HPV positive (+) cervical cancer cell killing and reduced cell proliferation. Increasing p53 bioavailability may have promising potential as a therapy for HPV driven cancers.