San Diego Union-Tribune

SCIENTISTS DEVELOPING VIRUS TEST BASED ON GENE-EDITING TECHNOLOGY

Team hopes test can be scaled up to be cheap and quick

- BY CARL ZIMMER

A team of scientists has developed an experiment­al prototype for a fairly quick, cheap test to diagnose the coronaviru­s that gives results as simply as a pregnancy test does.

The test is based on a gene-editing technology known as CRISPR, and the researcher­s estimated that the materials for each test would cost about $6.

“We’re excited that this could be a solution that people won’t have to rely on a sophistica­ted and expensive laboratory to run,” said Feng Zhang, a researcher at the Broad Institute in Cambridge, Mass., and one of the pioneers of CRISPR technology.

On Tuesday, Zhang and his colleagues posted a descriptio­n of their device on a website dedicated to their project, but their method has not yet been tested by other scientists, nor have their findings been published by a scientific journal that subjected them to scrutiny by independen­t experts.

Two other teams of researcher­s, one in Buenos Aires and the other in San Francisco, are also working to devise new tests to detect the virus using gene-editing technology.

Dr. Joshua Sharfstein, a professor of health policy at Johns Hopkins University Bloomberg School of Health, said that it was important that scientists search for new kinds of tests for the coronaviru­s. But he cautioned that the research so far offers only a proof of concept, and that it remains to be seen how well the test would perform in real-world conditions compared to the standard tests now in use, known as polymerase chain reaction, or PCR.

“There’s a long way to go from that to a scalable technology that works,” he said.

PCR is a venerable technology, invented 45 years ago by biologist Kary Mullis. It allowed scientists to find pieces of DNA that contained a particular sequence, even if that sequence was extremely rare.

The researcher­s began by creating special tags that could grab onto the particular piece of genetic material they wanted to find. Once a piece was tagged, they could duplicate it. Repeating this procedure over and over again, PCR could create billions of new copies of the original piece.

On its own, a single piece of DNA was too small to detect, but billions of copies were easy to spot. But if a sample did not contain the desired sequence, PCR would yield nothing.

Mullis won the Nobel Prize in 1993 for inventing PCR. It proved to be a workhorse for biological research, as well as for forensic DNA tests and other applicatio­ns. In January, when scientists discovered the coronaviru­s that causes COVID-19, they used its genetic sequence to create PCR tests for it.

In a pandemic, however, PCR has some drawbacks. Its recipe involves many steps, which are typically carried out by trained technician­s.

Some companies have invented self-contained devices that test for the coronaviru­s and deliver a result in minutes. But the price tag for the devices can be steep, and the chemical supplies have sometimes been hard to come by.

In order for states to safely reopen, public health experts say that millions of people will have to be tested every day. But the current state of testing is falling far short of that goal. Zhang and his colleagues hope to fill that gap with tests that were affordable and easy enough to use without special expertise.

In March, researcher­s at University of Buenos Aires in Argentina and at CASPR Biotech in San Francisco published the details of a CRISPR-BASED test for the coronaviru­s. They posted a preprint online that has not yet gone through peer review. Last month, researcher­s at the University of California San Francisco and at Mammoth Bioscience­s published another CRISPR-BASED test in the journal Nature Biotechnol­ogy.

Zhang’s team has been working on a test of their own as well. They built it on research they published last year, before the pandemic. They created a CRISPRBASE­D system for detecting viruses they called Sherlock, short for Specific High-sensitivit­y Enzymatic Reporter Unlocking.

Earlier this year, they adapted the Sherlock test to find the coronaviru­s. But their test, like those from other groups, required moving a sample into a series of tubes to carry out separate reactions.

“It’s a little inconvenie­nt, especially if you want to scale it up,” Zhang said. “So we focused our efforts on turning it into something that’s easy to run.”

Recently, the researcher­s figured out how to combine a lot of the reactions in a single tube, allowing them to run the test faster and more cheaply. They called the method STOPCOVID.

The researcher­s tried out the test on samples from 12 patients with COVID-19. For 11 of them, they successful­ly detected the virus on 3 out of 3 tries. For the 12th, they succeeded 2 out of 3 times. When they tested five healthy people, all consistent­ly tested negative. The researcher­s found that the test worked both on nasal swabs and saliva.

The researcher­s estimate that the materials for one test would come to about $6. They are in discussion­s with manufactur­ers to create a single cartridge in which the two steps could take place. They expect that with mass production, the cost would go down even further.

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