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Conventional drug delivery systems are plagued by problems such as non-specific targeting and low bioavailability. Bacterial-based drug delivery systems have gained much interest due to their ability to overcome the issue of non-specific delivery of drugs. This is achieved by engineering bacteria to sense and respond to specific stimuli present in the microenvironment of these pathogenic cells.

In this project, we propose the development of a dual-sensor bacteria which can only survive, and release therapeutics, within the targeted part of the human body (i.e., spatially specific). As our proof of concept, we will be engineering the Escherichia coli bacterium to target cancer tumors with high environmental lactate — see Warburg effect.

To ensure that the bacterium will only affect cancer cells, the bacterium is engineered to detect, and adhere to a cancer specific surface marker. Upon detection, a quorum sensing system and the production of invasin and listeriolysin O is triggered. The invasin and listeriolysin O then allows the bacteria to deliver its payload directly into the cytoplasm of the cancer cell. Since the production of invasin and listeriolysin O cannot occur in the absence of the said marker, this delivery system will only target cancer cells, concentrating drug payload at the intended site.

Our team has been working on cloning our desired biobrick parts and modelling our gene circuit. We hope to be able to characterise and optimise our parts, and demonstrate a functional spatially-specific drug delivery system, as well as complement our wet lab efforts with our model.