ENGINEERING BETTER BIOTHERAPEUTICS
Biotherapeutic drugs have revolutionized the treatment of many diseases, leading to dramatically improved health outcomes for countless people (and pets). Historically, progress in this area has centered on protein-based drugs, most notably therapeutic monoclonal antibodies and their derivatives. In recent years, the scope of biotherapeutic development has broadened from protein-based engineering to engineering the cells themselves to serve as living therapeutics.
Our research aims to capitalize and expand on the progress and promise across the spectrum of biotherapeutic advances to address unmet needs in human health, animal health, and the environment.
Engineering living therapeutics: The human body is a complex ecosystem supporting symbiotic relationships with thousands of microbial species. By some estimates, human commensal microbial cells outnumber human cells by a factor of ten. Such symbiotic microorganisms are integral to the health and metabolism of not only humans, but also animals, insects, and plants. Commensal microbes are already perfectly suited for safe and effective colonization of various physiological niches; what remains is to engineer them to function as robust biochemical factories capable of on-site, on-demand production and delivery of therapeutic cargo. Our efforts in this area focus on genomic and metabolic engineering to direct and optimize expression and secretion of therapeutic payloads from key human commensal species in the gut and respiratory tract.
Engineering biotherapeutic cargo: In addition to engineering the microbial chassis, we also engineer the therapeutic cargo being delivered. To accommodate efficient bacterial expression, we use small antibody fragments. Compared to full-length antibodies from which they are derived, antibody fragments are much smaller, less complex, and easier for bacteria to produce and secrete. However, small fragments lack some of the functions inherent in full-length antibodies, including long serum half-life. Our efforts in this area focus on protein engineering approaches to enhance serum half-life and optimize bacterial secretion of our therapeutic payloads.