278 Gene therapy of an EPPK-causing K9 variant using a CRISPR/Cas9 nickase mediated approach in primary keratinocytes

Abstract

Epidermolytic palmoplantar keratoderma (EPPK) is a rare, autosomal dominantly inherited skin disorder. The disease is often caused by heterozygous point mutations in the keratin 9 gene coding for type I intermediate filament (IF) protein keratin 9 (K9). The integration of mutant K9 into the IF cytoskeleton has a dominant negative effect resulting in IF fragility and massive thickening of palmoplantar skin. The aim of this project was to correct the IF fragility in EPPK patient-derived primary keratinocyte (KC) cultures by gene editing.