Author(s) :

Nikita Mirghasemi, Nicole C. Guilz.

Volume/Issue :

Abstract :

Epidermolysis Bullosa (EB) is a genetic skin condition characterized by extensive skin fragility with blistering and open sores following mild mechanical stress or injury. Among several subtypes, Epidermolysis Bullosa Simplex (EBS) is the most common type, usually occurring through mutations in the KRT5, KRT14, and PLEC genes that weaken the integrity of keratinocytes in the basal epidermis. Current treatments are mainly supportive care and focus on making the symptoms more manageable through bandaging wounds, nutritional intervention, and surgical treatment. However, advances with gene-editing tools like CRISPR-Cas9 offer revolutionary opportunities for therapeutic strategies seeking a curative advantage. In this paper, we review the genetic basis of EBS, the molecular consequences of profound mutations, and the utility of CRISPR-based methods to correct these with high fidelity through homology-directed repair (HDR), base editing, and prime editing. Both in vitro and in vivo methods used to transplant gene-engineered keratinocytes and the emerging role played by in vivo delivery systems in targeting epidermal tissue by CRISPR are discussed. While current issues on delivery efficiency remain to be conquered, cell specificity and the long-term preservation of the edited phenotype are still matters to be addressed. However, CRISPR-based approaches offer a promising direction to correct EBS at the molecular level and offer hope for long-term therapeutic success..