Scientists develop first gene-editing treatment for skin conditions

Gene-editing tools like CRISPR have unlocked new treatments for previously uncurable diseases. Now, researchers at the University of British Columbia are extending those possibilities to the skin for the first time.

The UBC team, together with researchers from the Berlin Institute of Health at Charité in Germany, has developed the first gene therapy capable of correcting faulty genes when applied directly to human skin. Outlined today in a paper published in Cell Stem Cell, the breakthrough could lead to new treatments for a wide range of genetic skin conditions, from rare inherited diseases to more common disorders like eczema.

“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, an associate professor at UBC’s 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.”

Broad therapeutic potential 

In the study, the researchers show the gene therapy can correct the most common genetic mutation behind autosomal recessive congenital ichthyosis (ARCI), a rare and life-threatening inherited skin disorder that appears at birth.

Affecting approximately one in 100,000 people, ARCI causes lifelong complications including extremely dry and scaly skin, chronic inflammation and a high risk of infections. There is currently no cure or effective treatment, and patients must manage their symptoms for life.

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

By testing the treatment in models made from living human skin, the team showed it can restore up to 30 per cent of normal skin function—a level that previous research suggests could be clinically meaningful for returning skin function to normal.

While ARCI affects relatively few people, the researchers say the treatment strategy could be adapted to many other genetic skin diseases, including epidermolysis bullosa—a severe skin blistering condition often called ‘butterfly skin’—and potentially more common conditions such as eczema or psoriasis.

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

A new way to deliver CRISPR gene editing 

Despite major advances in gene editing, applying the technology to skin diseases has remained a long-standing challenge. The skin’s primary role is to protect the body from the outside world, making it difficult to deliver large biological therapies, such as gene editors, past its protective barrier.

To overcome this, the team developed a novel delivery method that uses lipid nanoparticle technology, or LNPs. These microscopic “bubbles of fat,” pioneered by UBC professor Dr. Pieter Cullis and brought to global prominence through mRNA vaccines, are able to carry gene-editing technology into cells.

Using a clinically approved laser, the researchers first create microscopic, pain-free openings in the outer layers of the skin. This allows the lipid nanoparticles to pass through the skin barrier and reach skin stem cells beneath the surface. Once inside, the gene editor corrects the underlying DNA mutation, enabling the skin to begin functioning more normally.

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

The study was conducted in close collaboration with Vancouver-based biotech company NanoVation Therapeutics, a UBC spin-off focused on developing LNP-based genetic medicines. The researchers now hope to bring the treatment into clinical testing and have already been working with regulatory authorities to define the necessary safety and efficacy studies.

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

Interview language(s): English, German.