Mammoth Biosciences Inc., of South San Francisco, and London-based Glaxosmithkline plc (GSK) have joined forces to develop a point-of-care test to detect active COVID-19 infections using Mammoth’s CRISPR-based DETECTR platform. The two companies hope to submit an application to the U.S. FDA for emergency use of the test before the end of the year.

The easy-to-use, disposable, hand-held, point-of-care, molecular nuclear acid test will identify the presence of viral RNA strands of SARS-CoV-2, the virus that causes COVID-19, from a nasal swab, providing results potentially as soon as 20 minutes.

DETECTR (DNA endonuclease-targeted CRISPR trans reporter) relies on Cas12, a protein specifically programmed to target SARS-CoV-2. “Similar to a search engine, DETECTR is programmed with a guide RNA to search and find the exact strand of RNA present in SARS-CoV-2,” Trevor Martin, CEO and co-founder of Mammoth Biosciences, told BioWorld. “If and only if the viral strand is present, the guide RNA will attach to the strand and begin cleaving the strand and other molecules around it at orders of magnitude larger to create an amplifying signal that the virus is present.”

He added that the companies will be working on mechanisms to ensure that a person who tests positive for COVID-19 is connected with a health care provider.

Ultimate goal is at-home test

The CRISPR-based test can be used with off-the-shelf reagents and lateral flow strips and won’t require laboratory equipment and multistep processes. Mammoth and GSK plan to offer it first to health care facilities eligible to use COVID-19 tests with emergency use authorization (EUA) and eventually as an over-the-counter test that consumers can take at home. While declining to speculate on how soon the new device could be available, Martin said the aim is “to ramp up manufacturing as quickly as possible” once the device is approved.

“Our mission at Mammoth has always been to redefine the relationship that consumers have with their health, and through our collaboration with GSK Consumer Healthcare, we’ll be able to do just that,” Martin said. “COVID-19 is, of course, a key focus right now, but as a society what we need is a foundational shift in diagnostics – a scalable means to widely address disease detection. With a CRIPSR-based diagnostic, we can achieve a rapid and true point-of-need test without compromising the accuracy of molecular testing for all types of infectious diseases.”

Work on the test has already begun.

Mammoth’s DETECTR chemistry is currently under EUA review for laboratory use. The device being developed with GSK will comprise a different format for at-home use, necessitating a separate EUA.

Peer-reviewed validation

A recent peer-reviewed study in Nature Biotechnology demonstrated the potential of DETECTR to detect SARS-CoV-2 from respiratory RNA samples in less than 45 minutes, showing results on a lateral flow strip similar to a home pregnancy test. The research team validated the method using contrived reference samples and critical samples from 78 U.S. patients, 38 with SARS-CoV-2 infection and 42 with other viral respiratory infections. The assay’s sensitivity and specificity were similar to EUA-approved quantitative real-time polymerase chain reaction (qRT-PCR) tests, with positive and negative predictive agreement for SARS-CoV-2 of 95% and 100%, respectively.

“We are excited to be working with Mammoth Biosciences and contributing our consumer insights and commercial expertise to develop a disposable rapid test that consumers can use to detect active COVID-19,” said Brian McNamara, CEO of GSK Consumer Healthcare. “We look forward to bringing the power of testing out of the lab and into people’s homes.”

Founded in 2017, Mammoth raised $45 million earlier this year in an oversubscribed series B round led by Decheng Capital. The proceeds were earmarked to advance new CRIPSR diagnostics, as well as applications in gene editing and therapeutics. Total venture funding to date is about $68 million.

Mammoth and GSK are looking to extend their collaboration beyond COVID-19 to explore other uses for DETECTR in consumer diagnostics.

“While tackling a diagnostic test for SARS-CoV-2 is the immediate priority, we see a bigger need to completely reimagine consumer diagnostics,” Martin said. “Using a CRISPR-based platform, we’re able to test any disease with DNA or RNA, from strep and flu and coronavirus to hepatitis, STDs and many more.”

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