Team:HKUST-Hong Kong/Prospect


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Team:HKUST-Hong Kong -


Through assembly of the target binding module, anti-tumor drug synthesis module and regulatory module, we would to introduce our genetically engineered Bacillus subtilis, B. hercules, as an anti-colon-tumor agent to provide direct tumoricidal effect during cancer therapy. It is applied as oral medicine which retains viability through digestive tract and executes anti-tumor activity when and only when it is binding to colon cancer cell.

Driven by pVeg constitutive promoter, RPMrel, the colon-tumor specific peptide will be displayed on the cell wall of B. hercules under the facilitation of LytC cell wall displaying system before it is orally intake. When B. Hercules is taken orally by patient, it is expected to reach colon after 8 hours without retaining or colonizing in gastrointestinal tract. However, once it reaches colon, it will be held up around colon tumor cells and colonize around them, waiting for signal to produce anti-tumor molecule, BMP2 to the local environment.
Since the expression of BMP2 is controlled by xylose inducible promoter and no xylose is present in colon, xylose is taken orally or injected from anus to induce the production of BMP2 when B. Hercules has successfully localized around colon tumor. The locally concentrated BMP2 is expected to suppress colon tumor grow and trigger the apoptosis of tumor while the low level BMP2 in colon introduces as little adverse effect as possible to normal colon tissues.
When BMP2 is intensively produced under the inducing from xylose, controlling by the same promoter, the expression of toxin ydcE will overwhelm the protection threshold from antitoxin ydcD. The overexpression of toxin with BMP2 production is to cause the suicide of B. hurcules and prevent any adverse effect from BMP overdose.