Researchers led by Ludwig MIT’s Sangeeta Bhatia and alumnus Liangliang Hao devised and preclinically validated a multiplexed nanotech diagnostic that can not only detect malignant tumors but also discriminate between tumor types and states of disease progression through a simple urine test and could be dispensed at the point of care. The portable diagnostic employs synthetic biomarkers—DNA barcodes—each linked to distinct peptides known to be targets of specific proteases, which are themselves attached to nanoparticles (or nanobodies). When the peptides are cleaved by specific proteases in tumors, the DNA barcodes—chemically stabilized by phosphorothioate modifications, which are also used in RNA vaccines—are secreted into urine. Once secreted, they can then be run through a test in which they’re recognized by a programmable CRISPR-Cas nuclease, Cas12a, and read out as distinct fluorescent signals or as lines on a strip of paper. The particles can carry several barcodes capable of detecting multiple distinct proteases, dramatically boosting the sensitivity and information provided by the test. Reporting their work in a Nature Nanotechnology paper in April, Sangeeta, Liangliang and their colleagues showed that five DNA barcodes could distinguish primary from metastatic tumors in the lungs of mice and described a system for detecting up to 46 unique signals for highly sensitive, multiplexed cancer diagnostics.
CRISPR-Cas-amplified urinary biomarkers for multiplexed and portable cancer diagnostics
Nature Nanotechnology, 2023 April 24