The broader impact/commercial potential of this Small Business Technology Transfer (STTR) Phase I project will be a new approach to treat gastrointestinal (GI) diseases, metabolic disorders, and autoimmune disorders, with an initial application of inflammatory bowel disease, which affects approximately 1.5 million people in the US. The proposed technology will address the microbial population in the gut, which significantly affects GI health. This technology uses advanced techniques of microbiology to develop a new set of therapeutics geared toward sustaining a healthy microbial population in the GI system.This Small Business Technology Transfer Phase I grant proposes to develop phage-resistant bacterial therapeutics to effectively alter the gut microbiome and treat disease. A key impediment to the use of live bacteria as therapeutics is their failure to reliably establish colonization in the gut. Although most focus to date has been on the bacterial components of the microbiome, bacteriophages, viruses which directly attack bacteria, make up at least half of the organisms in the human gut. Significantly, phages have been shown to influence the colonization dynamics of bacteria in every ecosystem studied thus far. Virulent populations of bacteriophages in the gut, which deplete commensal bacterial species, have been identified in patients with disease. Bacterial therapies with engineered immunity to gut phages will be developed to drive effective colonization in the gut. The endogenous immune system of bacteria, the CRISPR-Cas system, will be harnessed to engineer immune strains and develop targeted bacterial immunity against virulent phages. This work will enable development of a new class of bacterial therapeutics that overcome previous challenges and effectively colonize the gut. These therapies can be applied to treat the wide range of conditions associated with the microbiome.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.
