Engineered Probiotics for Urinary Cancer Diagnosis

Technology

This technology uses a non-pathogenic microorganism that has been genetically engineered to encode three key components: an enzyme that processes a substrate into a detectable product, a polarization protein for genetic stability and plasmid inheritance, and a toxin/antidote combination for biocontainment and safety. For tumor diagnosis, the microorganism is administered to a subject and allowed time to colonize any tumor cells or tumor tissues present. Next, a substrate for the enzyme is administered. When the enzyme encounters the substrate in the bloodstream, it catalyzes the excitation of a portion of the substrate, producing a chromogenic or luminescent product. This product is absorbed and excreted in the subject's urine, where it can be detected visually or with simple reagent-based assays. This approach can also be used to quantify the number of cancer cells in a cell sample by contacting the sample with the microorganism and substrate, then measuring the amount of the excited portion of the substrate in the mixture. Proof of concept has been shown using E. coli Nissle 1917 (EcN) and other strains.

Problem Addressed

Current cancer diagnostics typically require advanced medical instruments, costly laboratory technology, and long periods of time to produce results. Existing synthetic biology-based approaches have been limited for clinical applications by safety concerns and difficulties achieving reliable performance in vivo. Previous bacterial imaging strategies (such as luminescence, PET, and MRI) require invasive delivery and expensive equipment, limiting their practical application. This technology addresses these limitations by enabling rapid, non-invasive, and equipment-free cancer detection and diagnosis.

Advantages

• Enables rapid, field-ready diagnostics by producing a visible color or luminescence
• Provides results through a simple urine test, eliminating the need for specialized equipment
• Well established safety due to the use of a probiotic which naturally colonizes human gut flora
• Strong signal amplification is enabled using bacteria and ability of enzymes to cleave multiple substrates
• Unique potential for integration with the substantial existing medical infrastructure for urinalysis
• Ultra-low production cost combined with increased diagnostic flexibility, including capability for simultaneous imaging across modalities