Through assembly of the target binding module, anti-tumor drug synthesis module and regulatory module, we would like 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 an oral medicine which retains viability through gastrointestinal tract and executes anti-tumor activity when and only when it binds 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 taken. When B. Hercules is taken orally by the patient, it is expected to reach colon in 8 hours without retaining or colonizing in gastrointestinal tract. However, once it reaches colon, it will attach to colon tumor cells and colonize around them, waiting for signals to trigger the production and release of 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 growth and trigger the apoptosis of tumor while the low level BMP2 in non-tumor colon area introduces as little adverse effect as possible to normal colon tissues.
Driven by the same promoter that regulates BMP2, autotoxin-encoding gene ydcE is simutaneously expressed and will gradually overwhelm the protection machinery by antitoxin ydcD. The overexpression of the autotoxin with BMP2 production will eventually cause the apoptosis of B. hurcules and prevent any adverse effect from BMP overdose.