Proof of Concept

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SilenshR was borne from an identified shortcoming in chemotherapy. Systemic administration of cytotoxic agents leads to death even in healthy cells causing diarrhea, vomiting, temporary sterility and hair loss1. Additionally, our SilenshR innovation works in tandem with radiotherapy, the efficacy of which is diminished when the solid tumor microenvironment becomes hypoxic. Diatomic oxygen assists in radiotherapy by forming free radicals that damage DNA, causing apoptosis within solid tumor cancers. In fact, cells that are anoxic at the time of irradiation are 3 times more resistant to the radiotherapy than cells under normoxic conditions2. However, when the cancer cells preferentially adopt an aerobic glycolysis metabolism over aerobic respiration, the intratumoral pH decreases along with the oxygen content of the cancer. This is one significant limitation of radiotherapy.

SilenshR is able to pick up the slack where radiotherapy is limited, as bacteria have been known to innately colonize and proliferate within the hypoxic and immune-privileged cores of tumors. Assuming SilenshR bacteria can grow within tumors, would this therapy be otherwise effective? Would the metabolic burden of shRNA production be too much for the bacteria, given the shRNA sequence is in a high-copy number pUC plasmid? Could the shRNA transcribed within the SilenshR vector quantifiably reduce gene expression in a host-mammalian cell? Will the quorum sensing invasiveness circuit reliably promote bacterial uptake by cancer cells?