SBIR Phase II: Bacteriophage-Based Microbial Gene Therapy Platform for In Situ Engineering of Microbiomes

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The broader impact of this Small Business Innovation Research (SBIR) Phase II project is to improve the health and quality of life for the 15-30 million Americans suffering from celiac disease (CD) and other gluten-related disorders, especially those with poor management of symptoms. Gluten-related disorders have a combined global prevalence of 5–10% and have been increasing over the past decade. Currently, the only effective treatment for these patients is adherence to a strict gluten-free diet, which fails to relieve symptoms in all patients and cannot prevent the severe gastrointestinal distress that follows accidental exposure. This project will advance a therapeutic solution to prevent persistent symptoms related to low-level or accidental gluten exposure. This will provide protection for people with CD and non-celiac gluten sensitivity when traveling, new patients adapting to a gluten-free diet, and individuals whose symptoms are poorly controlled despite adherence to a gluten-free diet. The proposed project will leverage a novel bacteriophage-based microbiome engineering platform to advance the development of a product to provide protection from gastrointestinal distress stemming from gluten exposure. To develop this therapeutic phage product, phages capable of infecting common gut bacteria like E. coli will be identified and engineered for efficient lysogenization. The phage or phage cocktail will be further engineered to express therapeutic modalities/proteins and tested in both human organoids derived from patients with CD and mouse models to demonstrate efficacy. The proposed work will provide a foundation for future extension of the platform to a wide range of microbiome-based applications.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.