Ten Bio was a proud sponsor of the 2025 PC Project Patient Support Meeting held prior to the SID in San Diego last week. PC Project is a charity dedicated to supporting patients with pachyonychia congenita (PC) and driving research towards a treatment. The Ten Bio founding team has been involved in PC research since PC Project’s inception over 20 years ago. Specifically, Robyn Hickerson was the lead scientist at TransDerm advancing two therapeutic research programs into the clinic. However, delivery issues halted advancement of both. Research continues to move towards treatments for PC, including small molecule and RNAi therapies, and although none have been approved to date, recent advancements in gene-based therapies make this an exciting time to assess the current state of the field.
Gene therapies continue to stand at the forefront of modern medicine, offering the potential to correct genetic defects at their source or modify specific gene expression. As of 2025, the field has witnessed significant milestones, including the approval of CRISPR-based therapies for conditions like sickle cell disease and beta-thalassemia. Recent publication of sight-saving gene “transplants” will further spur investment and scientific advance. Just last month, the FDA approved gene therapy skin grafts developed at Stanford to treat a skin fragility disorder known as recessive dystrophic epidermolysis bullosa.
With over 1,100 active clinical trials, projections indicate that the flow of new agents into the market is soon to increase. However, a major challenge persists in the successful development and commercialisation of these new therapeutic assets. Activities in identifying, isolating, producing, and delivering each new therapeutic to its target site are key areas of focus. Although successes are being reported in the assays designed and deployed to show the gene-modulating effect of the active pharmaceutical ingredient, when evaluating clinical performance of the proposed therapies, the tone changes. Often, results do not match the expectations that were based on the data gathered from the preclinical phase. Why not?
The problem stems from numerous factors, not least the complexity of the science and protein translation or lack thereof. Targeted delivery and specificity remain hot topics for the industry. The launch of the Nucleic Acid Therapeutic Accelerator (NATA) & LifeArc funded consortium TransNAT is evidence of the emphasis on solving those problems. More fundamentally, the response of human patients to the introduction of gene-based therapies is highly unpredictable.
With over 1,100 active clinical trials, projections indicate that the flow of new agents into the market is soon to increase. However, a major challenge persists in the successful development and commercialisation of these new therapeutic assets. Activities in identifying, isolating, producing, and delivering each new therapeutic to its target site are key areas of focus. Although successes are being reported in the assays designed and deployed to show the gene-modulating effect of the active pharmaceutical ingredient, when evaluating clinical performance of the proposed therapies, the tone changes. Often, results do not match the expectations that were based on the data gathered from the preclinical phase. Why not?
The problem stems from numerous factors, not least the complexity of the science and protein translation or lack thereof. Targeted delivery and specificity remain hot topics for the industry. The launch of the Nucleic Acid Therapeutic Accelerator (NATA) & LifeArc funded consortium TransNAT is evidence of the emphasis on solving those problems. More fundamentally, the response of human patients to the introduction of gene-based therapies is highly unpredictable.
One of the most persistent limitations in preclinical gene therapy research is the reliance on animal models. While rodent and non-human primate models have historically contributed substantially to foundational knowledge, their predictive value for human outcomes—especially in skin-targeted or immune-mediated responses—is limited.
To overcome these limitations, small animal models—particularly mice—have been engineered to express humanized genes or carry human cells or tissues, enabling in vivo studies of disease mechanisms and therapeutic responses. As a result, a wide range of humanized mouse models have been developed and validated and are now widely used in preclinical research.
However, creating a relevant human genotype in animal models often requires complex genetic manipulation over several generations, involving significant time, cost, and animal use. Even with successful engraftment, major limitations remain. Dosing accuracy is difficult to achieve when therapeutics interact with non-human biological structures. Differences in skin structure, immune function, and gene expression profiles often result in translational gaps, where promising therapies ultimately fail in human trials despite encouraging animal data. Moreover, the routes of administration commonly used in animal studies—such as direct intradermal injection, high-pressure gene delivery, or intravenous dosing—often do not accurately reflect the intended method of delivery in human patients.
This mismatch can distort pharmacokinetics, biodistribution, and immune response assessments, leading to misleading conclusions about efficacy and safety, compromising the predictive value of such models, particularly for gene therapies. These limitations underscore the urgent need for more physiologically relevant, human-based models to evaluate gene therapy strategies under conditions that closely mimic clinical application.
Ten Bio’s business focus is on dermatology research, including gene therapies that hold significant promise for the treatment of dermatological conditions particularly those rooted in genetic mutations. Indeed, Ten Bio’s core TenSkin™ technology was born from the business’s founding team’s need for more human-relevant models while working towards developing oligonucleotide-based therapeutics for rare genetic skin disorders such as epidermolysis bullosa and pachyonychia congenita. The development of these therapies is inherently iterative and complex, often involving costly delays and setbacks. These challenges highlight the urgent need for preclinical models that more closely replicate human biology and treatment conditions. To accelerate progress and improve translational success, it is essential to adopt models that more accurately predict human responses to investigational agents.
Ten Bio’s TenSkin™ is a unique, physiologically relevant explant platform which provides more predictive data on human responses to novel therapeutics. Unlike traditional animal models, which often fail to replicate the complexities of human skin biology, ex vivo human skin maintains native architecture, cell-cell interactions, and key biochemical pathways that influence drug absorption, metabolism, and immune response. The TenSkin™ brand also provides an optimal surface on which to test and evaluate new methods of introducing a new agent. Traditional subcutaneous and intradermal injection along with advanced microneedle delivery methods are all readily accommodated for evaluation by TenSkin™. Ten Bio is excited to be currently working with leading academic and industry groups to support development of delivery technologies.
We highlight here a list of the advantages offered by Ten Bio to research and new product development against genetic skin diseases:
Closing the gap between preclinical and clinical outcomes
While rodent and even humanized mouse models offer valuable insights, they often lack the ability to faithfully replicate human skin responses. Human skin explants allow researchers to assess direct patient-like responses to gene-based interventions, study immune and inflammatory reactions in a native human tissue environment, and analyze prolonged effects over extended timeframes, ensuring therapeutic durability. By maintaining skin at physiological tension, TenSkin™ retains native mechanical and biochemical properties, ensuring that gene therapies are tested under realistic conditions that deliver predictive results before progressing to human trials.
Ethical and regulatory compliance
The 3Rs principles (Replacement, Reduction, Refinement) pose another challenge for evaluating gene therapies. Regulatory bodies, including the FDA and EMA, are actively encouraging the adoption of non-animal testing models wherever possible. Ex vivo human skin models align with the 3Rs principles by replacing or reducing the reliance on animal testing, refining experimental designs to obtain human-relevant data earlier in drug development, and enhancing regulatory acceptance, as agencies increasingly support human-based preclinical models for safety and efficacy evaluation. This not only supports compliance but also improves public perception and acceptance of gene-based therapies.
Optimizing the development program
Developing a new therapy is time-consuming and expensive, particularly when unexpected failures occur in late-stage clinical trials. Ex vivo skin models reduce costly late-stage failures by identifying efficacy and toxicity concerns earlier, enable rapid iteration and optimization of gene therapies in a human-relevant setting, and minimize the number of animal studies required, reducing regulatory burdens and addressing ethical concerns. By using explant models, companies can streamline their development process, increase the success rate of gene therapies, and accelerate time to market.
Beyond skin diseases
Although ex vivo skin models are primarily used for dermatological diseases, their applications extend beyond skin-only conditions. Many systemic therapies, including gene-based treatments for metabolic disorders, autoimmune conditions, and cancer, interact with skin as a primary exposure site. Thus, understanding skin reactions can serve as an important proxy for broader systemic effects.
TenSkin™ offers an unparalleled combination of human relevance, ethical compliance, cost efficiency, and regulatory alignment. Its ability to bridge the translational gap between preclinical and clinical research is an essential tool for accelerating the development of gene-based therapies.
The Ten Bio team is committed to working with researchers, industry partners, and regulatory agencies to advance the adoption of ex vivo models, ensuring the success of next-generation therapeutics. We welcome inquiries and collaborations to explore how these innovative models can support your research objectives.
Ten Bio team – May 2025
Supporting references
High, K.A. Turning genes into medicines—what have we learned from gene therapy drug development in the past decade?. Nat Commun 11, 5821 (2020).
