SPINK5-transduced autologous epidermal sheets

SPINK5-transduced autologous epidermal sheets is an experimental ex vivo gene therapy designed to treat Netherton syndrome, a rare and severe autosomal recessive skin disorder caused by mutations in the SPINK5 gene. The therapy involves harvesting a patient's own keratinocytes and genetically modifying them using a lentiviral or retroviral vector to express a functional copy of the SPINK5 gene, which encodes the Lympho-epithelial Kazal-type-related inhibitor (LEKTI). These modified cells are then expanded and grown into cohesive epidermal sheets in a laboratory setting. Once prepared, the sheets are surgically grafted onto the patient's skin. The primary mechanism of action is the restoration of LEKTI protein production, which inhibits overactive serine proteases—specifically kallikrein-related peptidases such as KLK5 and KLK7. This inhibition prevents the premature breakdown of corneodesmosomes, thereby restoring the skin's barrier function and reducing the chronic inflammation and desquamation characteristic of the disease.

Other names

Autologous LEKTI-expressing epidermal sheetsSPINK5 gene-modified autologous keratinocytesSPINK-5 gene-modified autologous keratinocytesSPINK 5 gene-modified autologous keratinocytes