Oh My Gut (Therapeutics)
Abstract
Chronic Kidney Disease (CKD) is a type of kidney disease where the kidney gradually loses its function over time. The kidney's function is to filter out metabolic wastes and help discard them out of the body. However, when the kidney begins to lose its function, the ability to filter out metabolic wastes, especially uremic toxins also begin to decrease. These metabolic wastes, especially p-Cresol that is considered toxic to humans, begin to accumulate inside the body. p-Cresol accumulation in body is associated with cardiovascular disease in hemodialysis patients and also induces the deterioration of CKD.
We plan to engineer two types of E. coli Nissle, the first one to produce bacteriocin to kill one of the major p-Cresol producers inside the gut, a bacteria called Clostridium difficile and the other to introduce an alternative pathway for tyrosine by adding Tyrosine Ammonia Lyase so that instead of being metabolized into p-Cresol, tyrosine is metabolized into p-Coumaric Acid, which is not dangerous for humans. We also wanted to ensure that the E. coli will not produce tryptophanase to turn tryptophan into indole (which will be metabolized into indoxyl sulfate, another uremic toxin that is dangerous for humans), so we have decided to knock out the tnaA gene, which encodes for tryptophanase.
With Oh My Gut, we will be able to slow down accumulation of the toxic p-Cresol inside the body. Thus allowing patients suffering from CKD to be able to live a more comfortable lifestyle, to live however they want without having to worry much about their health.
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