Hardly a day goes by that we don't read an article or watch a television segment about the coronavirus pandemic that broaches the topic of COVID-19 testing. Do we have enough tests? Are we testing the right people? How should we prioritize testing? What kind of test should we conduct on certain individuals? When will other testing options be available?
It looks as if precision medicine is entering the fray, in the form of the genetic engineering technology CRISPR. The acronym is derived from a family of DNA sequences that are, as explained here, "copies of small pieces of viruses. Bacteria use them like collections of mug shots to identify bad viruses." COVID-19 certainly fits the description of a "bad virus," which is why CRISPR technology is getting attention in the midst of the pandemic.
The US Food and Drug Administration (FDA) recently issued an Emergency Use Authorization for the CRISPR SARS-CoV-2 Kit from Sherlock BioSciences. "This test is the first authorized use of CRISPR technology for an infectious disease test," the FDA noted in a press release. The diagnostic test "looks for the specific target RNA or DNA sequences of the SARS-CoV-2 virus in upper respiratory specimens, such as nasal swabs, and bronchoalveolar lavage specimens, such as from fluid in the lungs, from individuals suspected of COVID-19." Use is limited to labs certified by CLIA to perform high-complexity tests, the FDA added.
The test was developed on a platform named "Specific High-Sensitivity Enzymatic Reporter unLOCKing" or SHERLOCK. A description was published last year in Nature Protocols, where investigators provided "step-by-step instructions for setting up … assays with recombinase-mediated polymerase pre-amplification of DNA or RNA and subsequent Cas13- or Cas12-mediated detection via fluorescence and colorimetric readouts that provide results in less than 1 hour with a setup time of less than 15 minutes."
Feng Zhang, PhD (above), is credited with inventing CRISPR technology which now has been configured and is being tested for rapid detection of SARS-CoV-2. (Photo copyright: The McGovern Institute for Brain Research)
The hope is this test-which is based on an approach developed by Feng Zhang, PhD, a molecular biologist at the Broad Institute in Cambridge, MA-will "help to alleviate backlogs and increase testing," said Mitchell R. O'Connell, PhD, a biochemist at the University of Rochester in New York, in an article published in Nature. He was quick to add that the jury is still out on how well the test will perform in real-world settings. However, that is not stopping others from joining the fray:
- Zhang recently posted information about a device described by The New York Times as "an experimental prototype for a fairly quick, cheap test to diagnose the coronavirus that gives results as simply as a pregnancy test does." According to Zhang, "our test relies on a number of enzyme innovations to enable rapid detection in less than an hour without any complex instrumentation." Further descriptions appear in medRxiv, a preprint publication that includes information still awaiting peer review. The articles include "A 5-min RNA preparation method for COVID-19 detection with RT-qPCR" and "Point-of-care testing for COVID-19 using SHERLOCK diagnostics."
- Researchers in Buenos Aires and San Francisco posted proof-of-principle evaluation of a test of their own in bioRxiv (another preprint publication) entry titled, "An ultrasensitive, rapid, and portable coronavirus SARS-CoV-2 sequence detection method based on CRISPR-Cas12."
- Piyush K. Jain, PhD, Assistant Professor at the University of Florida Health Cancer Center, recently described his CRISPR-ENHANCE rapid test in an article he authored for The Conversation. Jain described his test in the same way Zhang's has been depicted-as an assay that "works like a pregnancy test." It "shows two purple colored lines if the sample is positive for the virus." He goes on to say he envisions "a test kit that would allow rapid detection of SARS-CoV-2 RNA in saliva within 45 to 60 minutes at home without needing any expensive equipment."
- Mammoth Biosciences and GSK Consumer Healthcare are teaming up to develop a COVID-19 test that utilizes Mammoth's CRISPR-based DETECTR platform, which, according to a news release, has been subjected to peer review. Mammoth says the test has the potential to deliver point-of-use results in less than 20 minutes outside of the lab setting.