iGEM AQA_Unesp
INSUBIOTA
treating diabetes with genetically engineered probiotic
ABSTRACT
Our project was inspired on the alarming and increasing number of diabetic people, especially diabetes mellitus type 1 patients, who are insulin dependent. The lack of less invasive treatments has motivated us to develop a new treatment based on the probiotic bacteria Lactococcus lactis, that was engineered to produce a single-chain analog insulin in human diabetic’s microbiota. The bacteria will be able to produce the insulin associated with a secretion signal sequence and cell-penetrating peptides, to ensure its uptake. Moreover, the synthesis of the insulin will be controlled by the natural bacteria system of catabolite repression with regulation by a small RNA. At the presence of glucose, the insulin gene expression will be activated, and then, it will be ready to be secreted and absorbed, reaching the blood and performing its biological function. Also, in order to contain the release of our engineered probiotic to the environment, we built a kill switch based on light exposure that uses the CRISPR/Cas9 system to destroy essential genes for the bacterial survival. The final product could be a fermented milk or a lyophilized that could be easily ingested by patients.