Clinical OMICS

JUL-AUG 2019

Healthcare magazine for research scientists, labs, pathologists, hospitals, cancer centers, physicians and biopharma companies providing news articles, expert interviews and videos about molecular diagnostics in precision medicine

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12 Clinical OMICs July/August 2019 Martin says Mammoth plans to pair its diagnostic system, dubbed DNA Endonuclease Targeted CRISPR Trans Reporter, or DETECTR, with a smart phone application. He said a patient would be able to take a test at home, upload a picture of the testing strip once it changes color, and receive a result from the app within 30 minutes. Ideally, the app would also be able to link a person to telemedicine services to schedule an appointment with a doctor or get a prescription once the app renders a result. "One of the first promises of CRISPR diagnostics is allowing you to have a test that has molecular-style results in a rapid-style format," he said. Martin sees opportunity for CRIS- PR-based tests to improve accessibility to diagnostics and drive down testing costs by eliminating the need for cen- tralized labs. In the U.S., that means patients could get tested at their local pharmacies for things like flu or strep throat or even test themselves at home without going into a doctor 's office. CRISPR diagnostics could also be programmed to detect pathogens like Ebola, Zika, or Escherichia coli in the field, or as a point-of-care diagnostic. Using these simple tests, scientists could monitor viral and bacterial dis- ease outbreaks, as well as antibiotic resistance, in resource-poor areas. The quick turnaround time for results would be especially useful in an emer- gency during a disease outbreak when patients need to start receiving treat- ment immediately. Current molecular diagnostics and culture methods take hours or days to return results. "The technology really is a plat- form. The exciting part for us is the broad applicability," said Rahul Dhanda, co-founder, president, and CEO of Sherlock Biosciences, which (continued from previous page) The CRISPR-Chip NanoSens Innovations, based in San Di- ego, is another startup getting in the CRISPR diagnostics game. Co-founded by Kiana Aran, Ph.D., of the Keck Grad- uate Institute, the company has built a slightly more high-tech testing tool called CRISPR-Chip. The hand-held device com- bines thousands of Cas9 molecules with electronic transistors made of graphene manufactured by Cardea Bio, also head- quartered in San Diego. The Cas9 proteins are deactivated so that they can bind to certain DNA se- quences but not cut them. The binding creates an electrical charge on the surface of the graphene, which can be picked up by a digital biosensor in the CRISPR-Chip. The tool allows for detection of a specif- ic genetic mutation from a patient's DNA sample, without the need for amplifica- tion or sequencing, in about 15 minutes. In a recent paper in Nature Biomedical Engineering, Aran and her team tested the sensitivity of their CRISPR-Chip by using it to detect two common genetic mutations in blood samples from Duchenne muscu- lar dystrophy (DMD) patients. The team is also testing it for sickle cell disease, which is more difficult to detect, and hopes to increase the sensitivity so it can be used to identify infectious diseases as well. Rapid genetic testing could allow doctors to start patients on treatment sooner than they can currently. It could also quickly identify genetic variations that make some people unresponsive to certain drugs—like the blood thinner Plavix—to help doctors personalize treat- ment plans. A nurse or physician can take a blood sample and process it with the CRISPR-Chip without the need for special- ly trained lab technicians. Aran said the CRISPR-Chip can also be programmed to look for a healthy gene or region of a gene. If the CRISPR-Chip doesn't find its target, that would indi- cate a negative result, or a mutation in the gene. In an interview, Aran said the CRIS- PR-Chip is "very close to a commercial system" but still needs to go through rigorous testing before it can be used as a health diagnostic. In the meantime, she thinks the tool will be useful for bio- tech and pharma companies pursuing CRISPR-based therapeutics. She said the CRISPR-Chip can be used to test and monitor gene editing efficiency and help speed CRISPR therapies to the clinic. "We're trying to make a quality control tool to help companies design better CRISPR complexes and make sure they actually do what they're supposed to do," Aran said. n

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