How CRISPR might help diagnose and halt dangerous outbreaks faster

• The hope also is for CRISPR diagnostics to allow military personnel, clinical doctors or even people in their homes to be able to quickly and precisely narrow down the suspects for mysterious illnesses, says Jean-Paul Chretien, DIGET program manager at DARPA, which invests in breakthrough technologies for national security.

CRISPR diagnostics were on the cusp of a breakthrough before the COVID-19 pandemic started, says Amesh Adalja, senior scholar at Johns Hopkins Center for Health Security.

• PCR, which is considered the "golden standard" and antigen testing rose to prominence in this pandemic because they are "tried and tested," Adalja tells Axios.
• But, PCR tests require special lab equipment and can take days to alter an assay to match an evolving pathogen.
• CRISPR tests are "a promising technology and probably will be accelerated because of COVID and the need for better diagnostic tests that are much more widely distributed in the population," he adds. A CRISPR diagnostic test can be altered in hours to detect new variants or pathogens.

Multiple CRISPR tests are now under study for COVID-19, including ones using the Broad Institute's Sherlock system or Mammoth Bioscience's DETECTR system, which both received FDA emergency use authorizations in certain circumstances.

• DARPA was "excited" about a paper from Broad in early 2020 describing a CRISPR-based device called CARMEN, which could distinguish between 169 viruses, Chretien says.

"It really is a revolutionary new technology for infectious disease diagnostics that brings some key advantages over current methods," Chretien tells Axios.

• There's "proof of concept" that CRISPR tests are very sensitive, accurate and specific — similar to the "golden standard" PCR tests currently used for diagnostics, Chretien says.
• But there needs to be "substantial innovation" to get the technology where it needs to go, which is why DARPA has awarded several grants to companies, he adds.

DARPA's DIGET program has two tracks for developing devices to detect causes of sicknesses, with a focus on sepsis, respiratory, febrile, vector-borne and gastrointestinal illnesses.

1) Build a “massively multiplexed detection” device to screen for a thousand pathogens or strains. This will most likely be used in a central public health lab for biosurveillance, where it can run 100,000 specimens a day for a thousand targets at a time, taking us "way beyond where we are now," Chretien says.

2) Develop a mobile, point-of-need device that targets around 10 pathogens or strains that can be deployed more widely — for instance, with military forces or in doctor's offices.

The latest: DARPA awarded MRIGlobal a DIGET prime contract in mid-January to work on both projects, along with multiple partners, including Mammoth.

• Mammoth CEO Trevor Martin says he expects the team under MRIGlobal will succeed at tackling this "true grand challenge" to leverage CRISPR technology to "democratize access to molecular-type protections."
• Martin tells Axios it's "exciting" the technology has grown from an "amorphous concept of theory" to having a clear roadmap.
• "This is the exact type of technology we want to stockpile and have available so that we don't get to the state we are at today. So if there is any sort of emerging disease, we can have billions of these tests stockpiled and ready to be reprogrammed," Martin says.

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