Traditional treatments for skin diseases have primarily relied on topical creams, systemic medications, or surgical removal, generally focusing on managing symptoms rather than curing underlying causes. This approach is especially limiting for inherited or chronic skin conditions, which often require lifelong management without curative options.
Gene therapy presents a novel approach in dermatology by targeting the root genetic causes of certain skin disorders. The skin’s accessibility, its capacity for regeneration, and the ability to observe changes directly make it an attractive candidate for gene-based interventions. Unlike systemic diseases where delivery of therapy is complex, the skin allows localized application through corrected cell grafts, viral vectors, or topical gene therapies.
Limitations of Conventional Skin Treatments
Conventional treatments for skin diseases fall into three main categories: topical creams, systemic drugs, and surgery. While these have long been standard care, they often provide only temporary relief and are rarely curative.
For example, inflammatory diseases such as psoriasis are typically treated with topical corticosteroids or vitamin D analogs in mild cases to reduce inflammation and slow excessive skin cell production. More severe cases require systemic immunosuppressants like methotrexate or cyclosporine, which carry risks of liver and kidney toxicity and increased infection susceptibility. Even then, symptoms often return once treatment stops, and long-term use can cause significant side effects.
Phototherapy, involving ultraviolet light exposure, also helps reduce inflammation and scaling in conditions like psoriasis or vitiligo. However, its limited availability and long-term risks such as premature aging and increased cancer risk restrict its sustained use.
Surgical methods remain the gold standard for treating many skin cancers, especially basal and squamous cell carcinomas. Procedures like Mohs surgery offer precise lesion removal but may be unsuitable for large or recurrent tumors or those located in cosmetically sensitive areas.
In rare genetic disorders such as epidermolysis bullosa—where skin lacks key structural proteins—treatment options have been particularly scarce. Until recently, care was limited to wound management, infection prevention, and pain relief, with no therapies addressing the root genetic defects.
Across these treatments, a common limitation is symptom management without resolving underlying dysfunction, often accompanied by side effects and lack of lasting cures. It is in these therapeutic gaps that gene therapy is beginning to gain attention.
Gene Therapy: A New Era in Dermatology
Gene therapy distinguishes itself by aiming to correct the genetic causes of skin diseases rather than merely alleviating symptoms. For conditions caused by specific gene mutations, such as epidermolysis bullosa, gene therapy now offers feasible solutions.
A landmark moment occurred in April 2025 when the U.S. Food and Drug Administration approved pz-cel (Zevaskyn), a skin graft therapy using a patient’s genetically corrected keratinocytes. These cells are modified outside the body to restore the COL7A1 gene, which produces type VII collagen essential for skin integrity. After grafting, the corrected cells generate the missing collagen locally, promoting wound healing and pain reduction.
Topical gene therapy also shows progress. Vyjuvek, approved in 2023, employs a herpes simplex virus type 1 (HSV-1) vector to deliver the COL7A1 gene directly to wounds as a gel. Clinical trials demonstrated that over 80% of treated wounds achieved at least 50% closure within six months.
The success of these therapies depends not only on gene correction but also on delivery methods. HSV-1 vectors efficiently target skin cells and carry relatively large genetic payloads. Lentiviral vectors, used in therapies like pz-cel, enable stable, long-term gene expression by integrating into skin cell genomes.
Adeno-associated viruses (AAVs), widely used in other gene therapies, have seen limited application in dermatology due to their smaller carrying capacity and challenges with manufacturing and scalability. This has influenced the direction of future skin disease gene therapy development.
Researchers are also exploring non-viral delivery methods. Lipid nanoparticles (LNPs), known from mRNA vaccines, are under investigation to deliver RNA or DNA to skin cells, offering potentially safer and more scalable options, though challenges remain in penetrating the skin barrier. Other approaches such as polymer nanoparticles and microneedle patches are in early development for repeated, localized delivery in chronic conditions like psoriasis and atopic dermatitis.
Gene therapy applications extend beyond gene replacement. In inflammatory skin diseases driven by immune dysregulation—such as atopic dermatitis and psoriasis—gene silencing techniques aim to reduce expression of inflammatory mediators like IL-4, IL-13, IL-17, and NF-κB. RNA interference (RNAi) and antisense oligonucleotides (ASOs) can selectively target messenger RNA to diminish these pro-inflammatory signals.
Current Status and Future Outlook
Gene therapy in dermatology has achieved notable milestones with FDA approvals of Vyjuvek and Zevaskyn for dystrophic epidermolysis bullosa. However, the broader gene therapy pipeline for skin diseases remains limited, with few programs advancing beyond early development. Challenges related to efficient gene delivery, immune responses, and the complex nature of skin conditions contribute to a cautious progression.
While gene therapy has made significant strides in oncology, ophthalmology, and neurology, dermatology remains a comparatively small area of focus. Most gene therapy development currently targets diseases with large markets or well-defined single-gene causes, such as hemophilia and spinal muscular atrophy. Only a few companies—including Krystal Biotech, Castle Creek Biosciences, and Abeona Therapeutics—are developing dermatology-specific gene therapies, primarily for rare monogenic disorders.
Despite the modest pipeline, the dermatology treatment market is undergoing unprecedented innovation. Advances in biologics, gene therapy, nanotechnology, and artificial intelligence are creating new opportunities for skin disease management.
While the gene therapy field for skin diseases is still in its early stages, its growing promise signals that future years may bring expanded focus and new treatments. For now, gene therapy in dermatology remains a developing frontier, gradually finding its footing among more established therapeutic areas.
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