ENGINEERING PROBIOTIC YEAST DRUG DELIVERY SYSTEMS

Our understandings of the human microbiome have emerged novel mechanistic insights into how this community of bacteria, fungi, viruses, etc. that live within us, determine our mental state, responses to certain medications, and the progression of many disease pathologies. With the increased awareness of how the microbiomes of the gut, skin, vagina, nasal cavity, and lungs play critical roles in disease initiation and progression, a new therapeutic modality has emerged wherein live microbes interact with the human host in a specific and therapeutic manner. This new modality is termed live biotherapeutic products or ‘LBPs’. These living medicines can be designed as a consortium of many different microbial strains or may be a single microbial strain genetically engineered to perform specific functions within its target microbiome. With the emergence of this new modality in therapeutic intervention, there comes a myriad of challenges in optimizing design and delivery of these microbes to achieve efficacy. For applications in the gut microbiome, LBPs must pass through and survive the harsh environments of the stomach and the early gastrointestinal tract, which is designed to break materials down. Thereafter, LBPs must reach their target site to perform its therapeutic action. In this work, I explore ways in which microbes can be used to deliver protein therapeutics directly into the gastrointestinal lumen; ways to target these microbes to specific sites of inflammation within the gastrointestinal tract; and potential applications of engineered probiotic yeast in treatment of inflammatory bowel diseases.