Good news! Cancer is history (soon)! This might be a breakthrough for cheap at home diagnostics for everyone!
What the article does not really describe is how the nanoparticles are introduced into the body or did I miss it?
" ... engineers have designed a new nanoparticle sensor that could enable early diagnosis of cancer with a simple urine test. The sensors, which can detect many different cancerous proteins, could also be used to distinguish the type of a tumor or how it is responding to treatment.
The nanoparticles are designed so that when they encounter a tumor, they shed short sequences of DNA that are excreted in the urine. Analyzing these DNA “barcodes” can reveal distinguishing features of a particular patient’s tumor. The researchers designed their test so that it can be performed using a strip of paper, similar to an at-home Covid test ...
In tests in mice, the researchers showed that they could use the sensors to detect the activity of five different enzymes that are expressed in tumors. They also showed that their approach could be scaled up to distinguish at least 46 different DNA barcodes in a single sample, using a microfluidic device to analyze the samples. ...
For this approach to work, the researchers had to use a chemical modification called phosphorothioate to protect the circulating DNA reporter barcodes from being broken down in the blood. This modification has already been used to improve the stability of modern RNA vaccines, allowing them to survive longer in the body. ...
The particles can be designed to carry many different DNA barcodes, each of which detects a different type of protease activity, which allows for “multiplexed” sensing. Using a larger number of sensors provides a boost in both sensitivity and specificity, allowing the test to more easily distinguish between tumor types. ... In tests in mice, the researchers showed that a panel of five DNA barcodes could accurately distinguish tumors that first arose in the lungs from tumors formed by colorectal cancer cells that had metastasized to the lungs. ...
This kind of testing could be used not only for detecting cancer, but also for measuring how well a patient’s tumor responds to treatment and whether it has recurred after treatment. ..."
In tests in mice, the researchers showed that they could use the sensors to detect the activity of five different enzymes that are expressed in tumors. They also showed that their approach could be scaled up to distinguish at least 46 different DNA barcodes in a single sample, using a microfluidic device to analyze the samples. ...
For this approach to work, the researchers had to use a chemical modification called phosphorothioate to protect the circulating DNA reporter barcodes from being broken down in the blood. This modification has already been used to improve the stability of modern RNA vaccines, allowing them to survive longer in the body. ...
The particles can be designed to carry many different DNA barcodes, each of which detects a different type of protease activity, which allows for “multiplexed” sensing. Using a larger number of sensors provides a boost in both sensitivity and specificity, allowing the test to more easily distinguish between tumor types. ... In tests in mice, the researchers showed that a panel of five DNA barcodes could accurately distinguish tumors that first arose in the lungs from tumors formed by colorectal cancer cells that had metastasized to the lungs. ...
This kind of testing could be used not only for detecting cancer, but also for measuring how well a patient’s tumor responds to treatment and whether it has recurred after treatment. ..."
From the abstract:
"Synthetic biomarkers, bioengineered sensors that generate molecular reporters in diseased microenvironments, represent an emerging paradigm in precision diagnostics. Despite the utility of DNA barcodes as a multiplexing tool, their susceptibility to nucleases in vivo has limited their utility. Here we exploit chemically stabilized nucleic acids to multiplex synthetic biomarkers and produce diagnostic signals in biofluids that can be ‘read out’ via CRISPR nucleases. The strategy relies on microenvironmental endopeptidase to trigger the release of nucleic acid barcodes and polymerase-amplification-free, CRISPR-Cas-mediated barcode detection in unprocessed urine. Our data suggest that DNA-encoded nanosensors can non-invasively detect and differentiate disease states in transplanted and autochthonous murine cancer models. We also demonstrate that CRISPR-Cas amplification can be harnessed to convert the readout to a point-of-care paper diagnostic tool. Finally, we employ a microfluidic platform for densely multiplexed, CRISPR-mediated DNA barcode readout that can potentially evaluate complex human diseases rapidly and guide therapeutic decisions."
CRISPR-Cas-amplified urinary biomarkers for multiplexed and portable cancer diagnostics (open access)
A new nanoparticle sensor that can enable cancer diagnosis with a simple urine test. The nanoparticles (blue) carry DNA barcodes (zigzag lines) that can be cleaved by cancer-associated proteases in the body (pac-man shapes). Once cleaved, the DNA barcodes can be detected in a urine sample.
Fig. 1: Engineering DNA-encoded synthetic urine biomarkers with CRISPR-Cas-mediated disease detection.
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