Topical CRISPR‑based therapy shows promise for treating skin disorders

A topical CRISPR-based genome-editing therapy has been developed to address disease-causing mutations responsible for inherited human skin disorders.

Researchers in Canada used CRISPR base editing – enabling precise modification of single DNA letters without cutting both DNA strands – in a model made from human skin cells. They were able to restore up to 30 percent of normal skin function, a level considered clinically significant.

'With this work, we show that it is possible to correct disease-causing mutations in human skin using a topical treatment that is safe, scalable and easy to use,' said Dr Sarah Hedtrich from the University of British Columbia, Canada, and senior author of the study published in Cell Stem Cell.

The skin model used to develop the therapy was made from patient-derived keratinocytes, the primary cell type found in the outermost layer of human skin. The researchers showed that the therapy was able to correct a gene mutation that causes the most common form of autosomal recessive congenital ichthyosis (ARCI) in about 12 percent of cells.

ARCI is a group of rare and sometimes life-threatening skin disorders that causes severely dry and scaly skin across the body. Currently, these conditions have no cure, and treatment can require hours of daily bathing and moisturising, as well as systemic retinoids.

Applying technology to skin diseases has been a major challenge due to the skin's inherent role in protecting from the external environment. To overcome this, researchers encapsulated the genome-editing complex in lipid nanoparticles and used clinically approved lasers to create microscopic, minimally invasive openings in the outer layer of the skin. This allows the lipid-encapsulated therapy to penetrate to the skin stem cells beneath the surface and limit off-target effects.

This is the first CRISPR-based gene therapy delivered through the skin surface to correct mutations in situ. The researchers hope the design can be adapted to many other genetic skin disorders, including epidermolysis bullosa (previously the target of other types of gene therapy – see BioNews 1139), as well as more common conditions such as eczema and psoriasis.

'Our goal now is to take this from the laboratory into first-in-human clinical trials. We hope this work will ultimately lead to a safe and effective treatment that can transform the lives of patients who currently have no real therapeutic options,' concluded Dr Hedtrich.