Bioengineered microbes are a promising strategy to develop live biotherapeutic products that canintroduce novel metabolic activities into the gut microbiome and digestive system for theprevention and treatment of several gut-related diseases/disorders. Sanarentero is developingnovel drug detoxifying bacteria (DDB), which is a bioengineered live biotherapeutic product thatcan detoxify gut-toxic drugs causing chemotherapy-induced diarrhea in cancer patients.Successfully addressing a major biosafety concern (i.e., the transmission of genetically modifiedmicrobes into humans and environments) will make our product much more competitive since itwill improve clinical adaptability and aid the regulatory approval of our product. Towards improvingthe safety profile of DDB, we are introducing a genetic biocontainment switch in our product thatcan be triggered to contain the engineered metabolic function as and when needed. Our uniquegenetic biocontainment switch (GBS) not only is designed to prevent the engineered metabolicpathway genes to escape from a designated environment but also performs its function withoutkilling the microbes to minimize the cellular burden and genetic instability. The overall goal of theproject is to establish the activity and safety of drug detoxifying bacteria equipped with theproposed genetic biocontainment switch (DDB_GBS) in an animal model. To achieve this goal,the three specific aims of this phase 1 STTR proposal are 1) to bioengineer geneticbiocontainment switch into DDB; 2) to develop a delayed-release formulation of DDB_GBSfor improved intestinal engraftment; and 3) to evaluate the safety, glycosylation function, andbiocontainment efficiency of DDB_GBS. The success of this project is the proof-of-concept evidence of our approach for developing novel drug detoxifying bacteria with a safetyfeature that can detoxify cancer chemotherapeutic drugs in the gut environmenttowards preventing chemotherapeutic-induced diarrhea in cancer patients. Once thebiocontainment efficiency of DDB_GBS is established, we will work on establishing thepreclinical efficacy and manufacturing scale-up in the GMP facility for a phase II SBIR proposal.
Public Health Relevance Statement: PROJECT NARRATIVE
This project develops a novel Genetic Biocontainment Switch for improving the safety profile of
our drug detoxifying bacteria, currently under development for preventing chemotherapy-induced
diarrhea in cancer patients. Our innovative biocontainment switch is designed to remove the
engineered metabolic function without killing the bacteria, such that the commensal bacteria is
returned to its native state in the gut microbial environment once the treatment is over. The project
will develop proof-of-concept preclinical evidence of the delivery of engineered bacteria to the
lower intestine, engraftment of bacteria, and efficiency of the genetic biocontainment switch.
Project Terms: | 