iGEM Unesp Brazil presents a new framework to engineer and test probiotics!
Designer probiotics have the power to revolutionize the way we diagnose, treat, cure and prevent diseases. Acting as a biofabric in the human's gut, genetically engineered probiotics targets and controls therapeutics delivery to treat disease, metabolic disorders and infections directly in the patient's microbiome. They provide a promising alternative for the production of pharmaceuticals, which eliminate the high-cost steps of downstream processes such as final product purification. Not to mention the major benefit to patients by offering a treatment that can be used via oral instead of intravenous administration, commonly used for biopharmaceuticals.
The lack of well-established platforms and protocols to engineer probiotics motivated our team to design a robust framework to enable the iGEM community to access the full potential of this novel approach. Going from design, fine-tuned expression, biocontainment to real-world application, our framework provides:
i) a standardized system designed to improve and facilitate secretion and uptake of the molecule of interest in the human gut;
ii) a fine-tuned regulatory circuit engineered to perform a robust output signal that computes gradually and dynamically a specific input, allowing it to be interchangeable and adapted to different signals;
iii) a biocontainment system responsive to light and based on the CRISPR/Cas machinery, providing it to be also programmed to target specific DNA sequences of the desired chassis;
iv) a DIY and open-source bioreactors system that simulates the human gut and microbiome to test and validate the functionality of genetically engineered probiotics.
As a proof of concept, we’ve focused on type 1 diabetes, one of the most common metabolic diseases, that remains uncured and the main therapy is invasive, based on insulin injections. Named "Insubiota", our proposal is to develop a designer probiotic to offer an alternative treatment for type 1 diabetes. We have designed our probiotic to act in response to a glucose signal through a modular, robust and orthogonal genetic circuit that activates the insulin production that will be secreted and absorbed by the patient.
Our framework aims to offer an easy, modular, robust and open-source solution to engineer probiotics and validate them, bringing the next generation of therapeutics one step closer.