Mammoth's COVID-19 CRISPR-based Assay Validates Company's Technology Approach

Approval process

As numerous clinical diagnostic companies roll out tests for SARS-CoV-2, the novel coronavirus that causes COVID-19, they all tend to use similar methods—a variation on antibodies that detect viral antigens or PCR-based tests that detect viral DNA or RNA. San Francisco-based Mammoth Biosciences just published the first peer-reviewed study validating its CRISPR-based diagnostic method for COVID-19. It appeared in the journal Nature Biotechnology.

CRISPR is a form of gene editing. The company’s DETECTR platform may have some advantages over traditional diagnostic methodology. In particular, the company notes that the system is easily reconfigurable for new viruses.

The Mammoth DETECTR assay was validated in less than two weeks and can deliver results in less than 45 minutes. The delivery of data is delivered in what the company dubs a “lateral flow strip,” which is similar to what is seen with at-home pregnancy tests. It also doesn’t necessarily require a laboratory, but can be operated with portable heat blocks and standard laboratory reagents.

The authors wrote, “We validated our method using contrived reference samples and clinical samples from patients in the United States, including 36 patients with COVID-19 infection and 42 patients with other viral respiratory infections. Our CRISPR-based DETECTR assay provides a visual and faster alternative to the U.S. Centers for Disease Control and Prevention SARS-CoV-2 real-time RT-PCR assay, with 95% positive predictive agreement and 100% negative predictive agreement.”

This does not mean DETECTR is ready for deployment. It will require larger-scale trials to support this early data, as well as any kind of commercial scale-up or manufacturing that might be required. More, this is a validation of the company’s test design and technology model.

On January 30, 2020, the company announced an oversubscribed Series B round of $45 million. The investment round was led by Decheng Capital with participation from Mayfield, NFX, Verily (a Google/Alphabet company), Brook Byers, Plum Alley, Pacific 8, aMoon, and others. The funds were used to continue developing the company’s CRISPR diagnostics and next-generation CRISPR products.

Most coverage of CRISPR is of its potential use for treating disease. And, of course, it became even more widely controversial when He Jiankui, a researcher in Shenzhen, China, used CRISPR gene editing to alter the DNA of embryos for seven couples, with a set of twins being born. This was met with widespread condemnation and a global moratorium on germ-line gene editing.

But Mammoth’s approach is to not only improve on various CRISPR gene editing technologies, but to develop clinical diagnostics using CRISPR. Also, the most common enzyme used in CRISPR gene editing is Cas9, but Mammoth’s focus is more on other enzymes, especially Cas14, which, the company said, “opens up new possibilities due to its extremely small size, diverse targeting ability and high-fidelity” In the case of the DETECTR system, it leverages another enzyme, Cas12.

The study’s authors wrote, “Assays using quantitative RT-PCR (qRT-PCR) approaches for detection of the virus in 4-6 hours have been developed by several laboratories, including an emergency use authorization (EUA)-approved assay developed by the U.S. Centers for Disease Control and Prevention (CDC). However, the typical turnaround time for screening and diagnosing patients with suspected SARS-CoV-2 has been >24 hours, given the need to ship samples overnight to reference laboratories.”

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