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SHERLOCK-based one-step test provides rapid and sensitive Covid-19 detection

New CRISPR-based research tool delivers results in an hour; researchers share protocol and kits to advance research and move toward clinical validation.
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Results of the STOPCovid test appear as a single or double line on a paper strip akin to a pregnancy test. In this photo, test strips showing a single line (left panel) indicate no infection. Test strips revealing double lines (right panel) indicate the presence of the virus.
Results of the STOPCovid test appear as a single or double line on a paper strip akin to a pregnancy test. In this photo, test strips showing a single line (left panel) indicate no infection. Test strips revealing double lines (right panel) indicate the presence of the virus.
Credit: Abudayyeh-Gootenberg lab, McGovern Institute for Brain Research at MIT and Zhang lab, McGovern Institute/Broad Institute
McGovern Institute Fellows Jonathan Gootenberg (far left) and Omar Abudayyeh and have developed a CRISPR research tool to detect Covid-19 with McGovern Investigator Feng Zhang (far right).
McGovern Institute Fellows Jonathan Gootenberg (far left) and Omar Abudayyeh and have developed a CRISPR research tool to detect Covid-19 with McGovern Investigator Feng Zhang (far right).
Credit: Justin Knight

A team of researchers at the McGovern Institute for Brain Research at MIT, the Broad Institute of MIT and Harvard, the Ragon Institute, and the Howard Hughes Medical Institute (HHMI) has developed a new diagnostics platform called STOP (SHERLOCK Testing in One Pot). The test can be run in an hour as a single-step reaction with minimal handling, advancing the CRISPR-based SHERLOCK diagnostic technology closer to a point-of-care or at-home testing tool. The test has not been reviewed or approved by the FDA and is currently for research purposes only.

The team began developing tests for COVID-19 in January after learning about the emergence of a new virus which has challenged the health care system in China. The first version of the team’s SHERLOCK-based Covid-19 diagnostics system is already being used in hospitals in Thailand to help screen patients for Covid-19 infection. 

The new test is named “STOPCovid” and is based on the STOP platform. In research, it has been shown to enable rapid, accurate, and highly sensitive detection of the Covid-19 virus SARS-CoV-2, with a simple protocol that requires minimal training and uses simple, readily available equipment, such as test tubes and water baths. STOPCovid has been validated in research settings using nasopharyngeal swabs from patients diagnosed with Covid-19. It has also been tested successfully in saliva samples to which SARS-CoV-2 RNA has been added as a proof of principle. 

The team is posting the open protocol today on a new website called It is being made openly available in line with the COVID-19 Technology Access Framework organized by Harvard University, MIT, and Stanford University. The framework sets a model by which critically important technologies that may help prevent, diagnose, or treat Covid-19 infections may be deployed for the greatest public benefit without delay.

There is an urgent need for widespread, accurate COVID-19 testing to rapidly detect new cases, ideally without the need for specialized lab equipment. Such testing would enable early detection of new infections and drive effective “test-trace-isolate” measures to quickly contain new outbreaks. However, current testing capacity is limited by a combination of requirements for complex procedures and laboratory instrumentation, and dependence on limited supplies. STOPCovid can be performed without RNA extraction, and while all patient tests have been performed with samples from nasopharyngeal swabs, preliminary experiments suggest that eventually swabs may not be necessary. Removing these barriers could help enable broad distribution.

“The ability to test for Covid-19 at home, or even in pharmacies or places of employment, could be a game-changer for getting people safely back to work and into their communities,” says Feng Zhang, a co-inventor of the CRISPR genome editing technology, an investigator at the McGovern Institute and HHMI, and a core member at the Broad Institute. “Creating a point-of-care tool is a critically important goal to allow timely decisions for protecting patients and those around them.”

To meet this need, Zhang, McGovern Fellows Omar Abudayyeh and Jonathan Gootenberg, and their colleagues initiated a push to develop STOPCovid. They are sharing their findings and packaging reagents so other research teams can rapidly follow up with additional testing or development. The group is also sharing data on the website and via a submitted preprint. The website is also a hub where the public can find the latest information on the team’s developments. 

How it works

The STOPCovid test combines CRISPR enzymes, programmed to recognize signatures of the SARS-CoV-2 virus, with complementary amplification reagents. This combination allows detection of as few as 100 copies of SARS-CoV-2 virus in a sample. As a result, the STOPCovid test allows for rapid, accurate, and highly sensitive detection of Covid-19 that can be conducted outside clinical laboratory settings. 

STOPCovid has been tested on patient nasopharyngeal swab in parallel with clinically validated tests. In these head-to-head comparisons, STOPCovid detected infection with 97 percent sensitivity and 100 percent specificity. Results appear on an easy-to-read strip that is akin to a pregnancy test, in the absence of any expensive or specialized lab equipment. Moreover, the researchers spiked mock SARS-CoV-2 genomes into healthy saliva samples and showed that STOPCovid is capable of sensitive detection from saliva, which would obviate the need for swabs in short supply and potentially make sampling much easier.

“The test aims to ultimately be simple enough that anyone can operate it in low-resource settings, including in clinics, pharmacies, or workplaces, and it could potentially even be put into a turn-key format for use at home,” says Abudayyeh.

Gootenberg adds, “Since STOPCovid can work in less than an hour and does not require any specialized equipment, and if our preliminary results from testing synthetic virus in saliva bear out in patient samples, it could address the need for scalable testing to reopen our society.” 

Importantly, the full test — both the viral genome amplification and subsequent detection — can be completed in a single reaction, as outlined on the website, from swabs or saliva. To engineer this, the team tested a number of CRISPR enzymes to find one that works well at the same temperature needed by the enzymes that perform the amplification. Zhang, Abudayyeh, Gootenberg, and their teams, including graduate students Julia Joung and Alim Ladha, settled on a protein called AapCas12b, a CRISPR protein from the bacterium Alicyclobacillus acidophilus, responsible for the “off” taste associated with spoiled orange juice. With AapCas12b, the team was able to develop a test that can be performed at a constant temperature and does not require opening tubes midway through the process, a step that often leads to contamination and unreliable test results. 

Information sharing and next steps

The team has prepared reagents for 10,000 tests to share for free with scientists and clinical collaborators around the world who want to evaluate the STOPCovid test for potential diagnostic use, and they have set up a website to share the latest data and updates with the scientific and clinical community. Kits and reagents can also be requested via a form on the website. 

Patient samples were provided by Keith Jerome, Alex Greninger, Robert Bruneau, Mee-li W. Huang, Nam G. Kim, Xu Yu, Jonathan Li, and Bruce Walker. This work was supported by the Patrick J. McGovern Foundation and the McGovern Institute for Brain Research. F.Z is also supported by the NIH (1R01- MH110049 and 1DP1-HL141201 grants); Mathers Foundation; the Howard Hughes Medical Institute; Open Philanthropy Project; J. and P. Poitras; and R. Metcalfe.

Zhang, Abudayyeh, Gootenberg, Joung, and Ladha are inventors on patent applications related to this technology filed by the Broad Institute, with the specific aim of ensuring this technology can be made freely, widely, and rapidly available for research and deployment. Abudayyeh, Gootenberg, and Zhang are co-founders, scientific advisors, and hold equity interests in Sherlock Biosciences, Inc. Zhang is also a co-founder of Editas Medicine, Beam Therapeutics, Pairwise Plants, and Arbor Biotechnologies.

Press Mentions


WBUR’s Carey Goldberg explores how MIT researchers developed a new CRISPR-based research tool that can be used to detect Covid-19. "A lot of things that we try fail," says research scientist Jonathan Gootenberg. "And that’s OK. Because sometimes you find these things that are really, really awesome."

Boston Globe

Boston Globe reporter Jonathan Saltzman writes that a Covid-19 diagnostic test developed by MIT researchers has received FDA approval. Saltzman explains that the test works by “programming a molecule to detect the presence of a specific genetic signature ― in this case, the signature for the coronavirus. When the signature is found, an enzyme is activated and releases a detectable signal.”

The Washington Post

A CRISPR-based diagnostic tool for Covid-19 developed by researchers from MIT and other institutions has been granted emergency FDA approval, reports Joel Achenbach and Laurie McGinley for The Washington Post. “We think this has a lot of potential. The test doesn’t require any complicated or expensive equipment,” explains Prof. Feng Zhang.

New York Times

MIT researchers have developed a new Covid-19 diagnostic test using CRISPR that “gives results as simply as a pregnancy test does,” reports Carl Zimmer for The New York Times. “We’re excited that this could be a solution that people won’t have to rely on a sophisticated and expensive laboratory to run,” says Prof. Feng Zhang.

Boston 25 News

Boston 25 reporter Drew Karedes spotlights how MIT researchers developed a new test for identifying Covid-19 that could potentially be used at home. “One of our goals is to allow people to figure out if they have the virus in a safe environment, such as their own home,” explains Prof. Feng Zhang.


STAT reporter Sharon Begley writes that MIT researchers have used CRISPR to develop a rapid diagnostic for Covid-19. “It’s inexpensive, does not require a lab, and can return results within an hour using a paper strip, not unlike a pregnancy test,” explains Prof. Feng Zhang. “This helps address the urgent need for widespread, accurate, inexpensive, and accessible Covid-19 testing.”

National Public Radio (NPR)

A rapid new diagnostic test built by MIT researchers uses CRISPR to detect Covid-19, reports Joe Palca for NPR. Palca notes that the researchers hope the “simplicity of the test will make it easy to deploy. It also means there could even be a home version someday.”

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