Gene-editing tools like CRISPR have revolutionized the treatment landscape for diseases once deemed incurable. Now, researchers at the University of British Columbia (UBC) are pushing these boundaries further by developing the first gene-editing therapy for human skin. This pioneering work, conducted in collaboration with the Berlin Institute of Health at Charité in Germany, was published today in the journal Cell Stem Cell.
The innovative therapy offers a potential lifeline for individuals suffering from a variety of genetic skin conditions, ranging from rare inherited disorders to more prevalent issues like eczema. Dr. Sarah Hedtrich, an associate professor at UBC’s School of Biomedical Engineering and the study’s senior author, emphasized the significance of this breakthrough. “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,” she stated. “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
The study highlights the therapy’s ability to correct the most common genetic mutation responsible for autosomal recessive congenital ichthyosis (ARCI), a severe and life-threatening skin disorder present from birth. Affecting approximately one in 100,000 people, ARCI leads to lifelong complications such as extremely dry and scaly skin, chronic inflammation, and a heightened risk of infections. Currently, there is no cure or effective treatment, leaving patients to manage symptoms throughout their lives.
“For many patients, this condition is not only physically painful but also deeply stigmatizing and isolating,” Dr. Hedtrich noted. The research demonstrated that the treatment could restore up to 30 percent of normal skin function in models made from living human skin—a level that previous studies suggest could be clinically significant in returning skin function to normal.
While ARCI is relatively rare, the researchers believe their strategy could be adapted to treat a wide array of genetic skin diseases, including epidermolysis bullosa, a severe blistering condition often referred to as ‘butterfly skin,’ and potentially more common conditions such as eczema or psoriasis. “The approach we developed is a platform technology,” Dr. Hedtrich explained. “It can be readily adapted to treat almost any skin disease.”
A New Way to Deliver CRISPR Gene Editing
Despite the significant progress in gene editing, applying this technology to skin diseases has posed a persistent challenge. The skin’s primary role as a protective barrier makes it difficult to deliver large biological therapies, such as gene editors, past its defenses. To address this, the research team developed a novel delivery method using lipid nanoparticle technology (LNPs). These microscopic “bubbles of fat,” pioneered by UBC professor Dr. Pieter Cullis and popularized through mRNA vaccines, are capable of transporting gene-editing technology into cells.
Utilizing a clinically approved laser, researchers create microscopic, pain-free openings in the skin’s outer layers. This allows the lipid nanoparticles to penetrate the skin barrier and reach 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,” Dr. Hedtrich remarked. “The treatment stays in the skin, and we saw no evidence of off-target effects, which is a critical safety milestone.”
Looking Forward: Clinical Trials and Future Implications
The study was conducted in close collaboration with NanoVation Therapeutics, a Vancouver-based biotech company and UBC spin-off focused on developing LNP-based genetic medicines. The researchers are now eager to transition from laboratory success to clinical testing. They have already engaged with regulatory authorities to outline the necessary safety and efficacy studies required for human trials.
“Our goal now is to take this from the lab into first-in-human clinical trials,” Dr. Hedtrich stated. “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.”
This development represents a significant milestone in the field of gene therapy, offering hope to those affected by genetic skin conditions. As the research progresses towards clinical trials, the potential for this treatment to revolutionize care for skin diseases remains a promising prospect.
