Engineered probiotics for urinary detection of cancer metastases

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Tal Danino, Arthur Prindle, Gabe Kwong, Jeff Hasty, Sangeeta N. Bhatia

MIT, United States

Synthetic biology has progressed rapidly over the last decade and is now positioned to impact important problems in energy and health. Accelerating high impact medical applications will require utilizing methods that interface directly with medical infrastructure, genetic circuits that function outside of the controlled lab setting, and safe and clinically-accepted microbial hosts. The ability of certain bacteria to undergo tumor-specific exponential growth can be exploited to create sensitive and specific cancer detectors that overcome challenges of traditional cancer diagnostics. Previously, such bacteria have been genetically engineered to participate in luminescence-, PET-, and MRI-based imaging modalities for tumor detection. Although these diagnostics each have specific utility, they have required intravenous or intratumoral delivery and expensive equipment, limiting their application to select cases. Our cancer diagnostic platform utilizes oral delivery of the currently-prescribed probiotic E. coli Nissle 1917 (EcN) to detect cancer metastases within 24 hours, demonstrating tumor-specific colonization via translocation from the GI-tract for the first time by EcN. Once colonized, our platform uses tumor-specific exponential growth coupled with bacterially produced indicator substrates or enzymes to produce a sensitive and cost-effective system for detection of tumors. We envision this platform to ultimately function in at-home paper tests, field diagnostics, and integrated with existing medical infrastructure for urinalysis.