Researchers at MIT have developed a urine test that can distinguish between different types of cancer, and could even highlight if metastases are present. The test involves first administering nanoparticles to patients that can circulate around their blood before encountering a tumor. Enzymes that are overexpressed by the tumor can then cleave a linker on the particle surface, releasing a DNA barcode into the blood. These DNA strands are excreted in the urine, and if the patient places a urine sample on a paper strip designed by the researchers, the CRISPR/Cas system can amplify the signal to highlight its presence, which appears as a dark strip on the paper. If markers for metastases are included in the system, then it can also highlight these if present.
At present, researchers are getting better at finding markers that differentiate cancer from healthy tissue and also at developing diagnostic tests that can reveal the presence of these markers easily. It doesn’t come much easier than a urine test, albeit with a preceding injection of nanoparticles. This latest technology is also designed to assist those living in low-resource or remote areas where access to advanced diagnostic techniques and equipment is haphazard.
“We are trying to innovate in a context of making technology available to low- and middle-resource settings,” said Sangeeta Bhatia, one of the lead developers of the new testing tech. “Putting this diagnostic on paper is part of our goal of democratizing diagnostics and creating inexpensive technologies that can give you a fast answer at the point of care.”
Tumors often express enzymes that let them to fulfill certain functions. For example, tumors can express proteases that assist them in dissolving the extracellular matrix in their immediate vicinity, allowing them to more easily invade nearby tissues. These researchers have turned these enzymes into an Achilles heel, by placing them at the heart of their new diagnostic system.
“Our goal here is to build up disease signatures and to see whether we can use these barcoded panels not only read out a disease but also to classify a disease or distinguish different cancer types,” said Liangliang Hao, another researcher involved in the study.
The technology relies on administering nanoparticles to patients prior to the urine test. A chemical linker that can only be cut by a specific protease found on the target cancer joins a DNA fragment to the nanoparticle. If the nanoparticle encounters a tumor, and the associated protease, then the linker is cut and the DNA fragments are free to circulate in the blood before being excreted in the urine. A paper strip onto which the urine sample is placed amplifies this DNA signal through the magic of CRISPR/Cas, revealing its presence as a dark strip.
In tests in mice, the technology has worked quite well so far, even helping the researchers to distinguish between the presence of a tumor that originated in the lungs and one that originated elsewhere but which had metastasized to the lungs.
Study in journal Nature Communications: Enhancing CAR-T cell functionality in a patient-specific manner
Via: Wyss Institute