Gene therapy for skin diseases: A field still finding its footing

Gene therapy has been a very prolific technology across multiple indications, but what about skin diseases? Some conditions, like psoriasis, affect millions worldwide and can lead to chronic discomfort and social stigma. Others, such as epidermolysis bullosa, are rare but devastating, causing extreme skin fragility and constant blistering from the slightest touch. 

Treatments have long relied on topical creams, systemic drugs, or surgical removal. In many cases, these approaches aim to manage symptoms rather than address the root cause. For inherited or chronic skin conditions, options are particularly limited, often involving lifelong care with no curative potential.

This is where gene therapy offers a different proposition. Thanks to the skin’s accessibility, regenerative potential, and the ability to monitor changes directly, it has emerged as an especially promising organ for gene-based interventions. In contrast to systemic diseases where delivery remains a major challenge, the skin allows for localized application, whether through grafts of corrected cells, viral vectors, or even topical gene-based formulations.

Traditional treatments for skin conditions and their limitations

For most skin conditions, conventional treatments fall into three categories: topical creams, systemic drugs, and surgical interventions. These have formed the backbone of dermatological care for decades, effective to a point, but rarely curative.

Take inflammatory diseases like psoriasis. Mild cases are often managed with topical corticosteroids or vitamin D analogs, which help reduce inflammation and slow the overproduction of skin cells. When symptoms become more severe, patients may move to systemic drugs like methotrexate or cyclosporine, which suppress immune activity more broadly. But these medications require close monitoring due to risks such as liver damage, kidney toxicity, and increased vulnerability to infection. Even when effective, the benefit is often temporary as symptoms return if treatment is paused, and side effects may accumulate over time.

Phototherapy, using controlled exposure to ultraviolet light, can also help reduce inflammation and scaling in diseases like psoriasis or vitiligo. But access remains limited, and the long-term risks, including premature skin aging and higher cancer risk, make it unsuitable for sustained use in some patients.

For skin cancers, especially basal and squamous cell carcinomas, surgery remains the gold standard. Procedures like Mohs micrographic surgery can remove lesions with high precision. Yet surgery isn’t always an option — patients with large or recurring tumors, or those with cancer in cosmetically sensitive areas like the face, aren’t suited for repeated interventions.

In genetic disorders such as epidermolysis bullosa, where the skin lacks the structural proteins it needs to withstand mechanical stress, the situation is even more complex. Until quite recently, there were no approved treatments that addressed the root cause. Care focused on wound management, infection control, and pain relief without a curative path forward.

Across the board, these therapies share common drawbacks. They often aim to suppress symptoms rather than correct underlying dysfunctions. They can carry significant side effects or toxicities. And most importantly, they rarely offer lasting resolution.

It’s within these therapeutic gaps that gene therapy is beginning to gain traction.

Gene therapy: A new frontier in dermatology

What sets gene therapy apart from traditional dermatological treatments is its ambition to do more than manage surface-level symptoms. In diseases caused by clear genetic mutations, such as epidermolysis bullosa, the idea of correcting the underlying defect is now feasible.

One of the clearest examples of this shift came in April 2025, when the U.S. Food and Drug Administration (FDA) approved pz-cel (Zevaskyn), a skin graft therapy made from a patient’s own genetically corrected keratinocytes. These cells are modified ex vivo to restore a functional version of the COL7A1 gene, which encodes type VII collagen, a protein essential for skin integrity. Once grafted back, the corrected cells produce the missing collagen locally, improving wound closure and reducing pain over time.

Topical gene therapy is also gaining traction. Vyjuvek, approved in 2023, takes a different approach by delivering COL7A1 using a herpes simplex virus type 1 (HSV-1) vector, applied directly to open wounds as a gel. In clinical trials, over 80% of treated wounds achieved at least 50% closure after six months.

The success of these therapies isn’t just about the corrected genes themselves, it’s also about how they’re delivered. HSV-1 vectors have proven particularly useful in skin applications because they can carry relatively large genetic payloads and target skin cells efficiently. Lentiviruses, commonly used in ex vivo therapies like pz-cel, allow for stable, long-term gene expression by integrating into the genome of non-dividing skin cells.

Adeno-associated viruses (AAVs), while widely used in other gene therapy applications, have seen more limited use in skin disease so far. Their relatively small carrying capacity makes them less suited for conditions requiring the delivery of large or complex genes. Additionally, recent industry trends point to a broader pullback in AAV-based programs due to manufacturing and scalability challenges, a shift that may influence how future dermatological applications evolve.

At the same time, researchers are exploring how to go beyond viral approaches. Lipid nanoparticles (LNPs), made famous by mRNA vaccines, are under investigation for delivering RNA or even DNA to skin cells. These systems are seen as safer and more scalable, but still face challenges in efficiency, especially in penetrating the skin barrier. Other non-viral options, like polymer nanoparticles or microneedle patches, are also in development and may hold potential for localized, repeatable delivery in chronic conditions such as psoriasis or atopic dermatitis.

Not all gene therapies aim to replace or edit defective genes. In inflammatory skin diseases like atopic dermatitis or psoriasis, which are driven not by inherited mutations but by chronic immune dysregulation, the therapeutic goal often shifts toward gene silencing. In these cases, the problem isn’t the absence of a functional protein, but rather the excessive or misdirected expression of pro-inflammatory mediators such as IL-4, IL-13, IL-17, or transcription factors like NF-κB.

This is where RNA interference (RNAi) and antisense oligonucleotide (ASO) technologies come into play. By selectively targeting messenger RNA (mRNA) transcripts before they’re translated into proteins, these approaches allow researchers to dial down specific pathways implicated in inflammation.

Gene therapy in skin diseases: Two approvals in, but few in the pipeline

Gene therapy has achieved notable milestones in dermatology, particularly with the FDA approvals of Vyjuvek by Krystal Biotech and Zevaskyn by Abeona Therapeutics for treating dystrophic epidermolysis bullosa. 

Despite these successes, the broader landscape of gene therapy in dermatology remains relatively nascent. The pipeline is limited, with few programs advancing beyond early-stage development. Challenges such as efficient gene delivery to skin cells, potential immunogenicity, and the complex nature of skin diseases contribute to the cautious pace of progress.

While gene therapy has made significant inroads in fields like oncology, ophthalmology, and neurology, its footprint in dermatology remains comparatively small. Most gene therapy pipelines today concentrate on areas such as hemophilia, spinal muscular atrophy, and various forms of cancer — conditions with either large therapeutic markets or well-characterized single-gene targets that lend themselves to intervention. In contrast, relatively few programs are directed toward skin diseases.

Only a handful of companies, including Krystal Biotech, Castle Creek Biosciences, and Abeona Therapeutics, are actively pursuing gene therapy candidates in the dermatological space. Even among these, the programs are mostly focused on rare monogenic disorders such as epidermolysis bullosa, with limited activity beyond that scope. The number of clinical-stage dermatology-focused gene therapies remains modest, suggesting that despite some high-profile successes, the field has not yet attracted widespread industry prioritization.

However, the field holds promise, and the fact that it hasn’t been an industry focus until today doesn’t mean it won’t be in the years to come. Indeed, a report by MarketAndResearch.com said, “the global dermatology treatment and care market is experiencing a period of unprecedented technological innovation, with advancements permeating every segment.” The report indicated that improvements are being made from biologics and gene therapy in skin disease treatment to nanotechnology and artificial intelligence (AI) in topical applications. 

But while this is encouraging and promising for the future, indicating a potential increased interest, it is still a bit early to identify the gene therapy programs that will become the new standard of care in skin diseases. And since the field isn’t receiving as much attention as more characterized disease areas, it might take more time to see a second wave of programs reach the market.