ABSTRACT
Advances in molecular diagnostics have enabled identification of the mutations responsible for many genodermatoses, paving the way for gene editing therapies to permanently reverse them and cure the disease. Gene editing for genodermatoses can be compared to gene-addition therapy, which instead introduces an exogenous copy of a gene to recapitulate protein expression. Clustered regularly interspaced short palindromic repeat (CRISPR) sequences combined with a CRISPR-associated nuclease protein enables targeting and manipulation of the genome with a high degree of specificity. In vivo systems, in which direct genome editing occurs in situ on a patient, could allow the targeting of multiple tissues simultaneously and is therefore clinically relevant in genodermatoses that have systemic manifestation or a large region to treat. The continuous advances of base editing into a safer and more effective tool bode well for its future therapeutic use in genodermatoses. Prime editing pioneers a double-strand break-free strategy of introducing targeted insertions, deletions, and all base substitutions.
