Attenuated strains of the intracellular pathogen can deliver genetically encoded payloads inside tumor cells. preferentially accumulates and propagates inside immune-suppressed tumor microenvironments. To maximize the payload impact in tumors and minimize damage to healthy tissues, it is desirable to induce payload synthesis when bacteria are eliminated from the healthy tissues but are grown to high numbers intratumorally. Here, we have engineered a tightly controlled gene expression system for intracellular inducible with a cumin derivative, cumate. Upon cumate addition, expression of a reporter gene is increased in growing by 80-fold, and in intracellular in murine tumors by 10-fold. This study demonstrates the feasibility of activating gene expression in intracellular bacteria in live animals using an edible inducer. The system is expected to enhance the efficacy and safety of the attenuated strains as antitumor payload delivery bacterial drones.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC11160606 | PMC |
| http://dx.doi.org/10.1101/2024.05.28.596178 | DOI Listing |
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