Netherton syndrome (NS) is a serious inherited skin disorder caused by mutations 
in the gene SPINK5 (serine protease inhibitor Kazal type 5) which encodes for a 
serine protease inhibitor LEKTI (lymphoepithelial Kazal type-related inhibitor). 
Patients with NS have defective keratinization, hair shaft defects, recurrent 
infections, atopy and a predisposition to skin malignancies. Historically, one 
in ten infants has died before their first birthday. Currently there are no 
proven treatments to cure this condition. A SIN-lentiviral vector encoding the 
codon optimized SPINK5 gene under the control of a 572bp element derived from 
the human involucrin promoter (INVO) can confer compartment specific LEKTI 
expression in NS keratinocytes with restoration of normal skin architecture. 
Here we detail a study protocol for a phase I trial for feasibility and safety 
evaluations of autologous epidermal sheets generated from ex-vivo gene corrected 
keratinocyte stem cells, which will be grafted onto patients with mutation 
proven NS.