Topical CRISPR gene therapy corrects inherited skin disease in human skin

Researchers have reported that a topical gene therapy which can correct disease-causing mutations directly in human skin, raising the prospect of durable treatments for rare genetic skin disorders

Researchers have reported a significant step forward in the application of gene editing to dermatological disease, with the development of a topical gene therapy that can correct faulty genes directly in human skin. The work, led by scientists at the University of British Columbia, Vancouver, Canada, in collaboration with colleagues at the Berlin Institute of Health at Charité, Germany, has demonstrated that disease-causing mutations can be corrected when a gene-editing treatment is applied locally to the surface of skin.

The findings have indicated that this approach could support the development of treatments for a wide range of inherited skin conditions, including rare and life-threatening disorders as well as more prevalent inflammatory diseases.

“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, associate professor at the University of British Columbia School of Biomedical Engineering and senior author of the study.

“Importantly, the approach corrects the root cause of disease and our data suggests that a one-time treatment might even be enough to provide a lasting and durable cure,” she said.

The study has focused initially on autosomal recessive congenital ichthyosis (ARCI), a rare inherited disorder that typically presents at birth and affects around one in 100,000 people. The condition leads to severely dry and scaly skin, chronic inflammation and a high risk of infection, with patients currently required to manage symptoms throughout life due to the absence of curative treatments.

“For many patients, this condition is not only physically painful but also deeply stigmatising and isolating,” said Hedtrich.

Using laboratory models generated from living human skin, the researchers showed that the topical gene therapy restored up to 30 per cent of normal skin function. Previous clinical research has suggested that this level of functional recovery could prove sufficient to return skin physiology close to normal, with meaningful benefits for patients.

Although ARCI affects a relatively small population, the researchers reported that the underlying treatment strategy has broader relevance. The same platform could, in principle, be adapted to treat other inherited skin diseases such as epidermolysis bullosa – a severe blistering disorder known as ‘butterfly skin’ – and potentially more common inflammatory conditions including eczema or psoriasis.

“The approach we developed is a platform technology. It can be readily adapted to treat almost any skin disease,” Hedtrich said.

Despite major advances in gene editing over the past decade, application of these technologies to the skin has remained challenging. The skin’s biological role as a protective barrier makes it difficult for large biological molecules, including gene-editing tools, to penetrate to the relevant stem cell populations beneath the surface.

To address this barrier, the team developed a delivery strategy based on lipid nanoparticle technology. Lipid nanoparticles are microscopic fat-based carriers that can transport genetic material into cells and have gained prominence through their use in messenger RNA vaccines. The particles used in this study carried components of CRISPR – clustered regularly interspaced short palindromic repeats – a gene-editing system that can correct specific DNA mutations.

The researchers used a clinically approved laser to create microscopic and pain-free openings in the outer layers of the skin. These openings allowed the lipid nanoparticles to pass through the barrier and reach skin stem cells. Once inside the cells, the CRISPR gene editor corrected the underlying DNA mutation enabling the skin to begin to function more normally.

“This is a highly targeted, localised approach. The treatment stays in the skin and we saw no evidence of off-target effects which is a critical safety milestone,” Hedtrich said.

The research was conducted in close collaboration with NanoVation Therapeutics, a Vancouver-based biotechnology company and University of British Columbia spin-off that focuses on lipid nanoparticle-based genetic medicines. The team has reported that it has already begun discussions with regulatory authorities to define the safety and efficacy studies required to support clinical development.

“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,” Hedtrich concluded.

For further reading please visit: 10.1016/j.stem.2026.01.001