Allele-specific CRISPR- engineered Cpf1 genome editing to treat ocular surface disorder in ectrodactyly–ectodermal dysplasia–clefting (EEC) syndrome

EEC syndrome is a rare multiple congenital anomaly disease characterized by the combination of ectrodactyly ("claw-like hand") and anomalies of the palate and other tissues of ectodermal origin (nervous tissue, stratified epithelia and annex such as hair, nails, etc.). The disease is dominantly inherited and, in most cases (over 90%), is due to mutations in the TP63 gene, which produces a protein (p63) essential for the development and maintenance of various epithelial tissues including the epidermis and the corneal surface. Indeed, most patients with EEC have corneal defects also linked to the progressive depletion of stem cells responsible for the constant regeneration of the ocular surface, which is essential to maintain the transparency of the cornea and the visual acuity. The project aims to study a new therapeutic approach to treat the progressive opacification of the cornea and the consequent loss of vision (which strongly affects the quality of life of these patients and represents their main unmet medical need) using an innovative genetic editing system capable of correcting the diseased gene and restoring correct operation of p63. The project benefits from the expertise developed by the research team in the field of both cell therapy for ocular surface reconstruction (which led to the development of Holoclar, the first advanced therapy approved in Europe) and gene therapy (applied as a life-saving therapy in disease of the so-called "Butterfly Children") that could accelerate the translation from bench to bedside.