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CRISPR-based diagnostic test capable of identifying heart attacks and certain cancer types

A research group has developed a new diagnostic test that improves on current CRISPR-based testing methods and is capable of identifying various diseases. (Credit: Dean Calma, Flickr)

Innovation in diagnostic testing is important for combating disease around the world. Accurate diagnostic testing allows for healthcare providers to create effective treatment plans as efficiently as possible. Rapid improvements in this technology have occurred in the last few years due to the large research efforts dedicated to improving COVID-19 testing.

According to a newly published study, researchers from Imperial College London (ICL) have developed a CRISPR-based diagnostic test capable of identifying acute myocardial infarction (heart attacks) and differentiating between certain cancer types.

The diagnostic test, called CrisprZyme, works by combining the properties of a Cas-based reaction with a nanozyme-linked immunosorbent assay (NLISA). The test produces a color change that can be identified by the naked eye, allowing for a simple qualitative analysis. A more specific quantitative measure can also be identified using a spectrometer.

CrisprZyme improves on current CRISPR-based diagnostic testing methods by substituting colorimetric analysis for the typical amplification procedure, which determines the quantity of a biomarker present without amplification. This does away with the requirement for temperature control and extra procedures, and it can also effectively quantify the amount of a biomarker in a sample. 

Dr. Molly Stevens, Professor of Bioengineering at ICL, explained the newly developed test to Imperial Today by stating, “Our test, like others, indicates when a biomarker is present, but CrisprZyme is a simpler diagnostic than those currently available. What also sets it apart is that it can tell us just how much biomarker is present, which can help us not just with diagnosing a disease, but with monitoring its progress over time and in response to treatment.”

The test is able to quantify biomarkers such as lnc-LIPCAR, a long non-coding RNA chain that is upregulated in patients suffering from heart failure, to identify patients with severe myocardial infarction. The test was also shown to be capable of differentiating between two types of prostate cancer— prostate adenocarcinoma (ACA) and neuroendocrine prostate carcinoma (NEPC)— by quantifying the expression of certain circular RNA, which are known to vary depending on disease type.

The authors described CrisprZyme’s functionality in a clinical setting by stating, “we also challenged CrisprZyme with the analysis of lnc-LIPCAR in blood from patients presenting with chest pain at hospital emergency rooms and circ-AURKA in tumour biopsies from patients with prostate cancer. Our results showed a significant difference between the patient cohorts and a clear performance capability for non-communicable diseases, indicating the diagnostic potential of CrisprZyme in complex clinical specimens.”

The authors indicated that they plan to continue to improve the CrisprZyme diagnostic test, adding that they hope to reduce the assay time and have faster extraction of RNA from clinical samples.

The study was published in Nature Nanotechnology on August 4th, 2022.

Abstract. CRISPR-based diagnostics enable specific sensing of DNA and RNA biomarkers associated with human diseases. This is achieved through the binding of guide RNAs to a complementary sequence that activates Cas enzymes to cleave reporter molecules. Currently, most CRISPR-based diagnostics rely on target preamplification to reach sufficient sensitivity for clinical applications. This limits quantification capability and adds complexity to the reaction chemistry. Here we show the combination of a CRISPR–Cas-based reaction with a nanozyme-linked immunosorbent assay, which allows for the quantitative and colorimetric readout of Cas13-mediated RNA detection through catalytic metallic nanoparticles at room temperature (CrisprZyme). We demonstrate that CrisprZyme is easily adaptable to a lateral-flow-based readout and different Cas enzymes and enables the sensing of non-coding RNAs including microRNAs, long non-coding RNAs and circular RNAs. We utilize this platform to identify patients with acute myocardial infarction and to monitor cellular differentiation in vitro and in tissue biopsies from prostate cancer patients. We anticipate that CrisprZyme will serve as a universally applicable signal catalyst for CRISPR-based diagnostics, which will expand the spectrum of targets for preamplification-free, quantitative detection.

Broto, M., Kaminski, M.M., Adrianus, C. et al. Nanozyme-catalysed CRISPR assay for preamplification-free detection of non-coding RNAs. Nat. Nanotechnol. (2022).

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