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DNA-encoded synthetic urine biomarkers are comprised of a nanocarrier (synthetic or biological) functionalized with protease-activated short peptides barcoded with oligonucleotides (1). After in vivo administration, activation of DNA-encoded sensors by disease-specific protease activity triggers release of synthetic DNA barcodes (2) that are size-specifically concentrated in the urine for disease monitoring (3). DNA barcodes in the urine activate programmable CRISPR-Cas nucleases to release the multiplexed reporter signals that are fluorescent, or detected on paper (4), enabling in situ disease classification at the PoC via the patterns of local proteolytic activities in the disease microenvironment (5).

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