CRISPR And Spit Might Be Keys To Faster, Cheaper, Easier Tests For The Coronavirus

Apr 17, 2020
Originally published on April 20, 2020 8:13 am

Being able to test for coronavirus infections is a critical component to reopening society — even a little bit — after the initial wave of COVID-19. So there is an urgent need for faster, cheaper tests than the ones available at present.

One approach to the next generation of tests is being developed by the University of California, San Francisco Medical School and Mammoth Biosciences. In a paper released Thursday in the journal Nature Biotechnology, researchers describe a test based on a new technology known as CRISPR.

CRISPR systems have been widely used by researchers to modify the genetic material in living cells. In this case, a system known as CRISPR-Cas12 is used to recognize genetic signatures of the coronavirus that causes COVID-19 and then make cuts in it to release a fluorescent molecule that will show whether the virus is present.

Like the test developed by the Centers for Disease Control and Prevention, this CRISPR-based test can run multiple samples at once. And while the CDC version delivers answers in hours, the test from UCSF and Mammoth Biosciences is faster — providing results in 30-45 minutes.

The test is self-contained, so it doesn't require sophisticated, expensive equipment that is used in other tests for the virus.

"I can run it now myself at home," explains Dr. Charles Chiu, professor of laboratory medicine at UCSF and co-lead developer of the new test — although he notes it does require some expertise to conduct it. He says he and his colleagues hope to submit the current version of their test next week for FDA approval. But it probably won't be the final iteration.

"What we really want to develop is something like a handheld, pocket-sized device using disposable cartridges," says Chiu — something that could even be used by nonexperts as a home-based test. Chiu is confident such tests could be manufactured at a scale that would be widely available.

Other labs, including two at the Broad Institute in Cambridge, Mass., are also working on CRISPR-based diagnostic tests.

Sara Sawyer, a virologist at the University of Colorado, is trying to go one step further in the testing world. She's trying to develop a low-cost test people could use at home that would reveal whether they are infected — days before they show any symptoms.

"For two years, we've been working on trying to develop a diagnostic that can pick up on the earliest stages of common respiratory diseases," Sawyer says. Her test doesn't look for the virus itself. Instead, it looks for a response to the virus by the cells of a person who is infected.

The idea is that once cells in the nose and throat are infected, certain genes are switched on that aren't normally switched on. Sawyer says it's possible to detect those "up-regulated" genes in saliva — instead of the nasal swab other coronavirus tests rely on. The question is, can she distinguish the new coronavirus from other viruses. She thinks she can.

But do others agree?

"The answer is maybe," says Benjamin tenOever, a virologist at the Icahn School of Medicine at Mount Sinai in New York City. He says yes, infection by the virus that causes COVID-19 results in different genes being up-regulated, compared with flu or other viruses. He's just skeptical the technology exists to be able to detect those differences.

"I'd say theoretically it is possible," tenOever says. "She's a very smart scientist. And so if she says she can do it, I would give her the benefit of the doubt."

Sawyer has formed a company to build her test kit. If society is to reopen, she says, there will have to be easy ways for people to check their infection status. She's in the process of designing and raising money for a study to validate her test's accuracy.

"We think saliva is the key to moving these tests out of the doctor's office," Sawyer says, because all people would have to do to collect a sample is spit in a cup. No blood draws, no nasal swabs. Easy.

If it works.

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SCOTT SIMON, HOST:

There's several different kinds of tests available to detect the virus that causes COVID-19. Researchers are working on more. They want to make them cheaper and easier to use. NPR's Joe Palca joins us now.

Joe, thanks for being with us.

JOE PALCA, BYLINE: Oh, you're very welcome.

SIMON: And what are scientists doing?

PALCA: Well, there are several teams of scientists who are talking about using a tool called CRISPR. You might remember CRISPR. It sort of took the biological world by storm. It's a technique for altering genetic material in living cells, but it can also be used to identify genetic material in viruses. And that's what they're talking about using it here.

SIMON: And what are the advantages of a CRISPR-based system?

PALCA: Well, the advantages are that you can do it fast, and you can do it cheap. And right now, the gold standard test for detecting the virus is something called PCR, polymerase chain reaction. And that requires a rather large machine. And even the smaller machines that are made by some of the diagnostic companies still require special equipment that can be expensive. And the other thing about the CRISPR test is it doesn't use some of the chemicals that have been reported to be in short supply. Apparently, the ones for CRISPR are a lot more plentiful.

SIMON: What else is in the testing pipeline?

PALCA: Well, interestingly enough, the tests that have - are being done now for viral infection look for the virus itself, which is - make sense. But I talked to a virologist named Sara Sawyer from the University of Colorado. And she has a very different approach. She says, think about the five days or so between the time you actually get infected to the time you start experiencing symptoms.

SARA SAWYER: The virus is beginning to establish a factory where it can produce many more copies of itself. And so while that's happening, cells are responding.

PALCA: And she says, essentially, those cells respond. And they kind of give off signal that says, hey, I've been infected by a virus. This isn't good. And they start putting out these protein factors. And those cells are at the back of the throat and in the nose. And so Sawyer thinks that the chemical signals from those cells wind up in your saliva. And she thinks she can make a test that will measure these signals.

SAWYER: We think saliva is kind of the key to moving these tests out of the doctor's office because we're not going to draw our on blood every morning. But we can spit in a cup.

SIMON: That would be a lot easier. How far along is she in developing this test?

PALCA: Well, she was working on a different approach somewhat. She had gotten a grant to - a contract from the Department of Defense to look for any kind of viral infection. And, of course, when COVID-19 came along, she tweaked the program to look specifically for the indication of COVID-19 infection. So she's about to start, or she wants to start a clinical trial that will test a lot of people and see who goes on to develop symptoms and whether or not she can predict that's the case or not.

SIMON: And the CRISPR test that began by mentioning, do we know when they'll be available?

PALCA: Well, the one that was developed at the University of California, San Francisco is built, and it's supposedly going for FDA approval next week or at least emergency use authorization. And then the company says they'll start using it for testing in California and try and get it out to other labs as soon as they can.

SIMON: NPR's Joe Palca, thanks so much.

PALCA: You're welcome. Transcript provided by NPR, Copyright NPR.