I-Corps: Translation potential of probiotic bacterial extracellular vesicle technology for inflammatory bowel disease

The broader impact of this I-Corps project is the development of a new class of therapeutics based on bacterial extracellular vesicles for treatment of numerous diseases. Bacterial extracellular vesicles can potentially be produced at low cost and have numerous biotechnological applications including vaccines, therapeutics for inflammatory diseases, and drug delivery vehicles. In particular, most inflammatory diseases lack desirable treatments or cures, with an unmet need existing between first line therapies and more aggressive antibody-based therapies that require costly and laborious administration via intravenous infusions. This unmet need is particularly noteworthy for inflammatory gastrointestinal diseases (e.g., inflammatory bowel disease) and inflammatory skin conditions (e.g., dermatitis). Bacterial extracellular vesicles offer the safety and convenience of first line therapies, which are typically oral small molecule drugs with favorable safety profiles, and with the potential for improved efficacy like later line therapies. Clinical translation of bacterial extracellular vesicles has been hindered by low production rates from cells and lack of tools to further improve efficacy. These challenges present untenable manufacturing costs and biologic risk when translating results from mice to humans. This I-Corps project utilizes experiential learning coupled with a first-hand investigation of the industry ecosystem to assess the translation potential of the technology. This solution is based on the development of vectors for oral delivery of immunotherapies for treatment of gastrointestinal diseases. Most therapeutics for inflammatory bowel diseases lack desirable delivery. Drugs unstable in the gastrointestinal tract require injection, and drugs with poor biodistribution and pharmacokinetics have limited efficacy and potential for systemic toxicity. The technology addresses these limitations in gastrointestinal disease treatment by leveraging bacterial extracellular vesicles - cell-secreted biologic nanoparticles naturally used by the healthy gut microbiome to communicate with human cells. The technology exploits this phenomenon by solving the most immediate bottlenecks facing bacterial extracellular vesicles therapeutics: potency and scalable biomanufacturing. The technology enables mass production of probiotic bacterial extracellular vesicles with high potency. Preclinical data in small animal models has demonstrated the technology function. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.