It cuts genomes, edits DNA, and holds the potential to treat a vast range of diseases. Now, CRISPR is being put to a new test as a search-and-detect engine for Covid-19.
On Thursday, researchers at the University of California, San Francisco, and scientists at Mammoth Biosciences — whose advisory board includes CRISPR pioneer Jennifer Doudna — published research in Nature Biotechnology laying out a method for using CRISPR to quickly spot the coronavirus in samples from nose or throat swabs.
The test takes roughly 40 minutes, compared with four to six hours for traditional PCR-based Covid-19 tests, which are currently being used. But the test also appears it would produce false-negatives slightly more often than existing coronavirus tests, which are already raising eyebrows among clinicians who warn of people being wrongly told they tested negative when they have Covid-19.
“I think the technology has potential, and I’m in favor of it,” said Robert Garry, a professor of virology at Tulane University who was not involved in the research. But, he added,“I think they oversold it a bit” in regard to the test’s accuracy and convenience.
The researchers previously published a paper about the work on a preprint server and with a smaller pool of patients. The new study marks the tool’s entrance into the peer-reviewed literature as a coronavirus testing agent and represents the largest demonstration of its ability in real patient samples.
“What this moment has shown is the importance of a diagnostic like this,” said Trevor Martin, Mammoth’s co-founder and chief executive officer. “I think people are surprised that we don’t have the ability to do extremely specific, sensitive, rapid diagnostics in 2020.”
Like existing coronavirus tests being used by the Centers for Disease Control and Prevention and clinicians around the country, the new test requires that a provider swabs suspected coronavirus-positive patients deep in the back of their throat or nose.
Once the genetic material on the swabs is isolated and amplified in a test tube with a liquid solution, CRISPR gets to work. Using a protein called Cas-12, along with bits of viral genetic material designed to help guide it, CRISPR homes in on two coronavirus genes in the sample: what’s known as the coronavirus N gene, which the CDC’s tests detect, and the so-called E gene, which the World Health Organization’s tests are designed to spot.
“We picked both to develop a very robust test,” said Martin. “You could use one alone, but we’re really setting the bar high here.”
If and when it finds the genes, the tool starts cutting, prompting a reaction which changes color on the dipstick — somewhat akin to how a pregnancy test works. The process is faster and less resource-intensive than traditional PCR-based tests, which require sophisticated equipment and hours of labor.
Compared against the CDC’s existing PCR-based tests, the Mammoth-UCSF test was slightly less good at pinpointing true negative cases — a measure of a test known as its sensitivity. Because all Covid-19 tests are so new, hard-and-fast comparison figures don’t yet exist. But the CRISPR-based test requires higher concentrations of the virus to detect it than the CDC’s PCR-based test. That means the CRISPR test would be more likely to miss people with lower levels of the virus, including people at the beginning or end stages of infection.
One advantage of a CRISPR-based test over a traditional, PCR-based test is that it could potentially be run several times on the same sample, increasing the chance that a negative test truly means a patient does not have the virus.
“The problem now is we can barely run one test for every patient that needs it,” said Charles Chiu, associate director of the UCSF clinical microbiology laboratory and the scientist leading the study with Mammoth. “The advantage of this test is that it could be done rapidly, and even multiple times, if needed.”
Researchers at rival institution Sherlock Biosciences are also working on rapid, CRISPR-based coronavirus tests. At the end of February, Sherlock announced a partnership with Silicon Valley-based testing company Cepheid on a proof-of-concept test.
The researchers at UCSF and Mammoth are working at breakneck speed — not only to make it faster and more accurate, but also to get it approved by the federal regulators at the U.S. Food and Drug Administration.
“We literally went from nothing to an assay in three weeks,” said Chiu, who plans to submit the test for FDA approval next week.
“This is a state-of-the-art technology,” said Chiu, the UCSF researcher. “It’s going to undergo a lot of regulatory scrutiny because it’s going to be the first of its kind.”