Diagnostics
crRNA (annotated Guide RNA here) locates the target DNA sequence, allowing the Cas9 enzyme to selectively cleave a section and prevent the host cell from replicating viral DNA.
clouded CRISPR in the past 5-6 years have focused on “germline applications” – gene editing practices that apply to reproductive cells, where any
modifications would be passed on to offspring. “They do not apply to developing lab or home- based diagnostic tests,” he says. What is a relevant challenge for those developing CRISPR-based
diagnostics, is making a product hospitals want
choosing the perfect tool from a toolbox – each has its own unique abilities. Even with a molecular GPS there’s a certain degree of amplification required to maximise the accuracy of a diagnostic test. The choice of amplification technology in a CRISPR-based diagnostic assay depends on various factors, including the specific target, the intended application, and the desired level of sensitivity and specificity. “It can be hard to select an appropriate amplification technology, pair it with a CRISPR Cas enzyme that works in real- time at the given amplification temperature, and design both amplification primers and a CRISPR guide to detect the desired DNA and RNA target with the highest sensitivity and specificity,” notes Dechario. “But, AI algorithms can accomplish all these tasks swiftly and efficiently, in silico, typically within hours.” Legacy diagnostics have historically been unable to meet the demand for decentralised testing due to a trio of historical barriers: cost, convenience, and test performance. “Traditional diagnostic approaches require leaving work and home to visit a physician and wait for results, but with CRISPR, that can be done in a matter of minutes at home,” Dechario explains. “For events that require urgent public health interventions in low-resource settings — such as a field response to an emerging disease — current diagnostics can be too expensive and slow to process enough tests to control an outbreak, for example. Now, advances in CRISPR diagnostic technology can make rapid tests for a range of infectious diseases available to low and middle- income countries.”
An exciting future? Like any other emerging technology, the CRISPR-Cas system has challenges. One significant drawback is its tendency for off-target effects – non-specific binding on the organism’s genome. To mitigate this, specialised bioinformatic tools can enhance precise guide RNA design selection. According to Davies though, these safety and ethical questions that have
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to use. “These systems show great promise for the future but must prove that they outstrip existing diagnostic procedures to become mainstream tools in the diagnostic industry,” Davies adds. For Dechario, gaining this acceptance among clinicians is the major challenge to overcome if patients are to benefit from CRISPR-based diagnostics. “In clinical settings, the challenge is the clinical community embracing the change in patient flow,” he says. “Rather than a patient coming in looking for a diagnosis, with CRISPR decentralised diagnostics – patients will more frequently arrive with a diagnosis for reflex testing and treatment,” says Dechario. “Upon regulatory clearance, it will be critical for the medical community to accept these diagnostic results as equivalent to what they would have traditionally been ordered from central labs after a patient visit.” Regarding the future of diagnostics, Dechario sees the decentralising of tests, driven by new products leveraging CRISPR, as being key to improving global health and eliminating healthcare inequities. “This month, we announced funding from the Bill & Melinda Gates Foundation to advance rapid, instrument-free molecular diagnostics for Human Papillomavirus (HPV),” he says. “Of individuals with this condition, 81% live in low and middle-income countries and lack access to essential diagnostics — as such — there is a global opportunity to bring decentralised testing to these patient populations by engineering diagnostics through synthetic biology so we can bridge the gap in delivering life-saving medicines.” Davies is likewise excited for the future of medical science as it pertains to the use of CRISPR as a diagnostic tool – especially if it means we’re better prepared for another virus like SARS-CoV-2. “With two biotech companies, Sherlock and Mammoth, leading the way in driving the development of CRISPR diagnostics, I expect to see more exciting advances in the future – hopefully in time for the next pandemic.”
Practical Patient Care /
www.practical-patient-care.com
Soleil Nordic/
Shutterstock.com
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