Personalized preclinical gene editing protocols for the in vivo correction of pachyonychia congenita

It is possible to develop treatments for Pachyonychia Congenita based on gene editing techniques to reduce the pathological thickening of the plantar epidermis that causes pain and disability in these patients. These treatments could constitute a long-lasting curative therapy that could improve the patient’s quality of life. CRISPR-mediated gene editing will permit mutation-specific pathogenic allele inactivation in patient epidermis in vivo allowing for the disease phenotype to be mitigated by recovering the intermediate filament cytoskeleton in a fraction of keratinocytes. Our goal is to develop in vivo treatment protocols for therapeutic benefit in the pathology of plantar keratoderma, focusing on viral (third generation adenoviral) and non-viral (magnetofection for CRISPR RNPs for CRISPR-encoding mRNAs). We will investigate the long-term maintenance of gene-edited epidermal stem cells, potentially enabling lifelong mitigation of the pathology in PC patients.The comparison of the efficacy of viral and non-viral vectors to administer the CRISPR system in the skin in vivo, as well as the biosafety evaluation of these tools, will allow the design of preclinical protocols to advance towards the clinical use of gene-editing therapy with CRISPR in this pathology.

Personalized preclinical gene editing protocols for the in vivo correction of pachyonychia congenita Projects