Several lines of research support the feasibility and broader impact of our technology across its three main applications. For ulcerative colitis (UC), engineered Lactococcus lactis secreting IL-10 has already demonstrated therapeutic benefit in mouse colitis models and even advanced to a phase I clinical trial, proving that oral probiotic-based cytokine delivery can be both safe and functional in humans. Similarly, L. lactis strains secreting anti-TNF nanobodies or scFvs have been shown to alleviate inflammation in murine colitis, providing a strong precedent for our anti-IL-23 strategy. Clinically, IL-23 is a validated therapeutic target, with monoclonal antibodies such as risankizumab recently approved for UC, underscoring the translational potential of targeting this pathway through a localized, probiotic-based system. Beyond UC, the modular nature of our platform allows for adaptation to other IL-23/Th17-driven diseases such as Crohn’s disease, psoriasis, and ankylosing spondylitis, where localized neutralization of inflammatory mediators could offer safer, more accessible alternatives to systemic biologics. Finally, our work contributes to the broader vision of developing a living probiotic drug-delivery platform: recent studies using engineered L. lactis and Saccharomyces boulardii to secrete therapeutic proteins highlight the promise of microbial chassis as oral, low-cost, and customizable “living factories.” These findings not only validate the concept but also suggest key design priorities — including secretion efficiency, colonization control, and biosafety modules — that guide our engineering choices and strengthen the potential of our system as a versatile synthetic biology framework for future therapeutic applications.
Several lines of research support the feasibility and broader impact of our technology across its three main applications. For ulcerative colitis (UC), engineered Lactococcus lactis secreting IL-10 has already demonstrated therapeutic benefit in mouse colitis models and even advanced to a phase I clinical trial, proving that oral probiotic-based cytokine delivery can be both safe and functional in humans (Steidler et al., 2000). Similarly, L. lactis strains secreting anti-TNF nanobodies or scFvs have been shown to alleviate inflammation in murine colitis, providing a strong precedent for our anti-IL-23 strategy. Clinically, IL-23 is a validated therapeutic target, with monoclonal antibodies such as risankizumab recently approved for UC, underscoring the translational potential of targeting this pathway through a localized, probiotic-based system (Feagan et al., 2022). Beyond UC, the modular nature of our platform allows for adaptation to other IL-23/Th17-driven diseases such as Crohn’s disease, psoriasis, and ankylosing spondylitis, where localized neutralization of inflammatory mediators could offer safer, more accessible alternatives to systemic biologics (Moschen et al., 2019). Finally, our work contributes to the broader vision of developing a living probiotic drug-delivery platform: recent studies using engineered L. lactis and Saccharomyces boulardii to secrete therapeutic proteins highlight the promise of microbial chassis as oral, low-cost, and customizable “living factories”. These findings not only validate the concept but also suggest key design priorities — including secretion efficiency, colonization control, and biosafety modules — that guide our engineering choices and strengthen the potential of our system as a versatile synthetic biology framework for future therapeutic applications.
Beyond ulcerative colitis, our probiotic-based delivery platform has strong potential to be extended to other chronic inflammatory and autoimmune diseases that are driven by the IL-23/Th17 axis. Elevated IL-23 signaling has been implicated in the pathogenesis of Crohn’s disease, psoriasis, and ankylosing spondylitis, all of which involve dysregulated Th17 responses and excessive production of proinflammatory cytokines (Moschen et al., 2019). Clinical studies have demonstrated that targeting IL-23 with monoclonal antibodies such as ustekinumab and risankizumab is effective in reducing disease activity in Crohn’s disease and psoriasis, establishing IL-23 as a validated therapeutic target beyond UC (Feagan et al., 2016). By engineering Lactobacillus to locally secrete an anti-IL-23 scFv in the gut, our approach offers a unique opportunity to provide non-invasive, cost-effective, and sustained therapy for these conditions, potentially reducing reliance on systemic biologics. Moreover, the modularity of our system allows for rapid adaptation to secrete alternative therapeutic proteins or antibody fragments, opening the door to treating a broader spectrum of IL-23/Th17-driven disorders with the same probiotic chassis.
Beyond its direct therapeutic potential, our work contributes to the establishment of a versatile and modular probiotic drug-delivery system. Traditional biologics face significant limitations, including high manufacturing costs, strict cold-chain storage requirements, and the need for invasive administration routes such as injections. By engineering safe microbial chassis like Lactococcus lactis or Saccharomyces boulardii to secrete therapeutic proteins in situ, it becomes possible to transform probiotics into “living factories” capable of producing biologics directly within the human gut. This platform approach offers unique flexibility: by swapping the genetic payload, the same engineered strain can be programmed to secrete antibody fragments, cytokines, antimicrobial peptides, or metabolic enzymes tailored to different diseases. Recent studies have highlighted the importance of modularity, showing that probiotic-based systems can be adapted to treat conditions ranging from intestinal inflammation to infections and metabolic disorders. In this sense, our project is not only a therapeutic solution for ulcerative colitis but also a step toward building a customizable synthetic biology framework for oral biologics. Such a platform could accelerate the development of next-generation “living medicines” that are affordable, scalable, and capable of addressing diverse unmet medical needs.
Our experimental approach directly supports and strengthens the potential applications of this technology. By engineering Lactobacillus to secrete an anti-IL-23 scFv and testing its expression, secretion efficiency, and neutralizing activity, we provide essential proof-of-concept data for using probiotics as living therapeutics in ulcerative colitis. These experiments demonstrate not only that therapeutic proteins can be functionally produced within the gut environment but also that targeted cytokine neutralization is feasible in a localized, non-invasive manner. At the same time, the modularity of our genetic constructs and secretion system allows us to adapt the platform to different targets, offering a foundation for extending the approach to other IL-23/Th17-driven diseases such as Crohn’s disease or psoriasis. Finally, our design-build-test-learn cycles and safety considerations—such as secretion signal optimization, potential anchoring strategies, and kill-switch modules—contribute to the broader development of a customizable probiotic delivery chassis. In this way, our experiments do not only validate a therapy for UC but also help establish the principles and technical tools needed for a scalable modular platform, paving the way toward next-generation living medicines.
Looking ahead, our project paves the way toward a new generation of living medicines that combine the safety of probiotics with the precision of biologics. In the near term, we aim to optimize secretion efficiency, validate neutralizing activity in preclinical models, and incorporate biosafety features such as kill-switches to ensure clinical feasibility. Beyond ulcerative colitis, our modular framework holds promise for rapidly adapting to other IL-23/Th17-driven diseases, offering a cost-effective and patient-friendly alternative to systemic biologics. In the long run, the establishment of a customizable probiotic delivery platform could transform the way we approach chronic diseases, enabling localized, sustainable, and personalized therapies that are accessible worldwide. By bridging synthetic biology, clinical medicine, and patient needs, we envision our technology contributing to a future where engineered probiotics serve as versatile therapeutic allies across multiple fields of healthcare.