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An experimental model of Netherton syndrome created using skin of healthy patients modified with CRISPR/Cas9

Manos y brazo
Tuesday, July 21, 2020

A team coordinated by researchers Fernando Lacher and Marta Carretero (U714 CIBERER) has generated a model of Netherton syndrome in genetically modified skin cells from healthy donors. The gene responsible for Netherton syndrome, SPINK5, has been removed with CRISPR/ Cas9. This syndrome is a skin disorder characterized by congenital ichthyosiform erythroderma, a specific capillary abnormality and atopic manifestations. The incidence is estimated at 1 in 200,000 births. Patients usually present generalized erythroderma since birth, skin desquamation and delayed development. Frequent complications include diarrhea and intestinal malabsorption, dehydration and recurrent infections.

The development of a skin model for this type of disease is essential to analyze experimental treatments before proceeding to conduct clinical trials. To date, no models in which the SPINK5 gene is inactivated had been achieved in primary human keratinocytes — predominant cells of the epidermis — to study this type of skin pathology.

On this occasion, the researchers have used a methodology that had been previously used to correct recessive dystrophic epidermolysis bullosa — a subtype of butterfly skin disease — by which a sequence of the SPINK5 gene is removed. This mutation led to an absence of the expression of the protein encoded by this gene, the LEKTI protein, and thus skin cells with the disease phenotype could be generated.

This finding will possibly lead in the near future to the generation of other models of similar skin diseases that have not yet been studied experimentally.

Access to the original article: Efficient CRISPR-Cas9-mediated gene ablation in human keratinocytes to recapitulate genodermatoses: modeling of Netherton syndrome. Molecular Therapy Methods and Clinical Development.

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