Pioneering Gene Therapy Corrects Faulty Genes Directly in Human Skin
Gene-editing tools, such as CRISPR, have enabled new treatments for previously incurable diseases. Researchers at the University of British Columbia (UBC), in collaboration with the Berlin Institute of Health at Charité in Germany, have now developed the first gene therapy capable of correcting faulty genes when applied directly to human skin.
This significant development, detailed in Cell Stem Cell, holds the potential to lead to new treatments for various genetic skin conditions. This includes rare inherited diseases and common disorders like eczema.
"The approach corrects the root cause of the disease and suggests a one-time treatment might provide a lasting cure." – Dr. Sarah Hedtrich, an associate professor at UBC's school of biomedical engineering and senior author.
Therapeutic Potential
The study successfully demonstrated the gene therapy's ability to correct the most common genetic mutation linked to autosomal recessive congenital ichthyosis (ARCI). ARCI is a rare, inherited skin disorder that affects approximately one in 100,000 people. It causes lifelong complications, including extremely dry, scaly skin, chronic inflammation, and a high risk of infections. Currently, there is no cure or effective treatment, requiring patients to manage symptoms for life.
Tests using models made from living human skin showed that the treatment can restore up to 30% of normal skin function. Previous research indicates that this level of restoration could be clinically significant for normalizing skin function. The researchers suggest this treatment strategy could be adapted for other genetic skin diseases, including epidermolysis bullosa, and potentially conditions such as eczema or psoriasis.
Gene Editing Delivery Mechanism
Applying gene editing technology to skin diseases has been challenging due to the skin's protective barrier. To address this, the team developed a novel delivery method utilizing lipid nanoparticle (LNP) technology. These microscopic "bubbles of fat" transport gene-editing technology directly into cells.
Clinically approved lasers are used to create microscopic openings in the skin's outer layers. This allows LNPs to pass through the barrier and reach skin stem cells beneath the surface. Once inside, the gene editor corrects the underlying DNA mutation, enabling more normal skin function. Dr. Hedtrich noted that this is a highly targeted, localized approach, with the treatment remaining in the skin and no evidence of off-target effects observed.
Future Outlook
The study was conducted in collaboration with NanoVation Therapeutics, a UBC spin-off company. The researchers plan to advance the treatment into clinical testing and have engaged with regulatory authorities to define the necessary safety and efficacy studies.