DRUG DETOXIFYING BACTERIA
OUR PRODUCT
Uridine glucuronyl transferase 1A1 (UGT1A1) is considered the most important enzyme responsible for the detoxification (glucuronidation) of SN-38 to SN-38 glucuronides. Several genetic polymorphisms in human UGT1A1, especially in the variant allele UGT1A1*28, are linked to increased irinotecan toxicity in the gut. In addition, many gut diseases and disorders have been related to imbalance in the homeostasis of several endogenous substrates (e.g., sex hormones, neurotransmitters, etc.) are closely regulated by the glucuronidation process.
Collaborative research from laboratories of Dr. Xiaoqiang Wang (University of North Texas) and Dr. Ming Hu (University of Houston) has shown that the plant (Medicago truncatula) UGT (pU71G1) could efficiently metabolize SN-38 to inactive SN-38 glucose in in vitro enzymatic assay.
The “drug-detoxifying bacteria” or “DDB” was then developed by overexpressing pU71G1 in E. coli. with glycosylation activity for successful detoxification of gut toxic molecules, such as SN-38. DDB will be equipped with genetic biocontainment technology developed in collaboration with Dr. Clement Chan at the University of North Texas.
Why plant UGT?
•Mammalian UGTs expressed in E.coli were functionally inactive in our research.
•Homeostasis of endogenous substrates may get imbalanced by the modulation of mammalian UGTs availability in the gut.
​
Why commensal bacteria?
•UGT enzyme does not work outside a cell as pure enzyme, so it needs a carrier and host.
•Commensal bacteria allows for better colonization and engrafting without disturbing the gut microbiome.
•Genetic biocontainment feature allows for protection against unwanted bacterial growth in the gut & environment, alleviating major safety concerns of the regulatory agencies.
Key Differentiator From Competitors
-
Platform technology that can be genetically manipulated for increase in specificity to different toxic substrates or metabolic functions in the gut environment.
-
Plant enzyme that makes glucose, so no interference with endogenous substrates homeostasis mediated wtih mammalian UGTs.
-
Use of Commensal bacteria so better engraftment in gut environment.
-
No long-term harmful effects to healthy gut microiiomer homeostasis due to genetic biocontainment feautre
-
No dependency or drug abuse
​
​
History of DDB Development
