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The race is on to develop innovative tests that rapidly and accurately detect SARs-CoV-2. The launch of the National Institutes of Health’s (NIH) Rapid Acceleration of Diagnostic Technologies (RADx Tech) program in late April and other recent initiatives underscores this activity. Manufacturers have sprung into action to produce accessible and easy-to-use testing platforms for use in the lab and at home.
At the heart of NIH’s $500 million RADx Tech initiative is a solicitation to find at least five promising technologies for SARS-CoV-2, the novel coronavirus that causes COVID-19. Inventors and researchers alike will compete for a share of a $500 million fund to develop a test that achieves high sensitivity and specificity and would be easy to use, adopt, and scale up commercially. The winners would join forces with manufacturers to mass-produce the tests, with a tentative goal to deploy millions of tests per week by summer or fall. “Such widespread testing, which will facilitate the speedy identification and quarantine of infected individuals and their contacts, will likely be a critical component of making it possible for Americans to get safely back into public spaces, including returning to work and school,” wrote NIH Director Francis Collins, MD, PhD. Collins and Bruce Tromberg, PhD, director of the National Institute of Biomedical Imaging and Bioengineering, who also serves on the RADx Executive Committee, recently discussed RADx and SARS-CoV-2 diagnostic innovations and challenges.
At a Senate hearing in May on Capitol Hill, Collins said he expected that some of these technologies might involve CRISPR, a gene editing tool that precisely edits DNA.
The CRISPR method, which has shown promise as a point-of-care diagnostic, has already made inroads in the COVID-19 testing space. In May, the U.S. Food and Drug Administration granted the first emergency use authorization for a CRISPR-based COVID test. Sherlock Biosciences, Inc.’s CRISPR SARS-CoV-2 Kit programs a CRISPR nuclease to identify the genetic signature for SARS-CoV-2 in a nasal swab, nasopharyngeal swab, oropharyngeal swab, or bronchoalveolar lavage specimen. Discovery of the signature activates the CRISPR enzyme, which cuts both the target viral RNA and the reporter RNAs in the kit, which are used during the detection reaction. “This releases a detectable signal, yielding results in about an hour,” according to a statement from the company. Sherlock Biosciences recently partnered with Integrated DNA Technologies to enable large-scale manufacturing of the test.
“The test can detect 1.35 copies of the nucleocapsid target per microliter viral transport medium (VTM) and 6.75 copies of the ORF1ab target per microliter VTM, for a confirmed limit of detection of 6.75 copies per microliter VTM,” Will Blake, PhD, chief technology officer of Sherlock Biosciences, told CLN Stat. The test also showed 100% agreement with contrived clinical positive and negative nasopharyngeal specimens.
Sherlock Biosciences’ test does not require a dedicated instrument platform, Blake said: “Amplification can be performed using a heat block, and CRISPR complex activation and reporter cleavage can be run in a standard microplate reader capable of fluorescence detection.”
The science is based on the SHERLOCK method, which stands for Specific High-sensitivity Enzymatic Reporter unLOCKing. SHERLOCK uses a CRISPR-associated protein known as Cas13 that binds to nucleic acid material to find specific targets such as a virus or tumor DNA. The method has been used previously to target dengue and Zika virus and cancer mutations in cell-free DNA from saliva samples.
Sherlock Biosciences and binx health announced on July 1 that they are partnering to develop the first point-of-care SARS-CoV-2 diagnostic that utilizes CRISPR technology.
A pioneering developer of CRISPR technology now is engineering a method similar to a pregnancy test. Feng Zhang, PhD, a researcher at the Broad Institute in Cambridge, Massachusetts, is working with colleagues at MIT and the McGovern Institute on point-of-care and at-home tests, both highly sought after, as people seek simpler, more convenient SARS-CoV-2 testing options.
In addition, the British government announced on June 22 a trial in Hampshire, England, of a no-swab saliva test using reverse transcription-loop-mediated isothermal amplification technology developed by OptiGene.
Clinical Laboratory News summed up the latest efforts by LabCorp, Scanwell Health, and telemedicine startups to produce and distribute at-home kits for SARS-CoV-2 testing. Methods include nasal swabs, saliva, and urine testing. Other companies have developed blood tests for antibody testing. Neoteryx’s Mitra device, which collects 20 µL of blood from a finger prick, is slated for an NIH-sponsored nationwide COVID-19 antibody survey to determine how many adults without a confirmed virus history have antibodies.
Experts anticipate that labs will face hurdles in processing and interpreting these tests. Self-collection error by consumers could affect accuracy of results.
Challenges aside, the world continues to search for COVID-19 testing innovations. NIH has since branched out with three other programs:
- RADx Radical, which will support nontraditional platforms such as CRISPR, breath and community wastewater analysis to identify the virus, and noninvasive biosensors to detect metabolites.
- RADx Underserved Populations, an initiative to target and reduce COVID-19-related race disparities.
- RADx Advanced Technology Platforms, a program that seeks to scale up testing through existing or late-stage COVID-19 testing platforms.
In other technology developments:
- Researchers in New Zealand and Australia are using genome sequencing to track SARS-CoV-2 transmission and control outbreaks.
- Several companies are leveraging CRISPR and dry proteins to produce biosensor technology that rapidly detects SARS-CoV-2 viral RNA, antibodies, and antigens.
- A simple assay uses plasmonic gold nanoparticles to visually identify the virus in 10 minutes.
- Michigan State University scientists have proposed a point-of-care diagnostic platform that uses nanoparticles or magnetic levitation to diagnose SARS-CoV-2 infection and assess future risk.
- A large-scale, highly sensitive COVID-19 diagnostic platform uses an RNA extraction method that detects asymptomatic cases at more than 95% sensitivity.
- Danish robotics engineers have developed a no-contact method of sample collection: an automated robot that gently takes a throat swab, deposits the sample into a jar, and screws it shut.
- Researchers at Ohio State University have developed a breathalyzer test that identifies COVID-19 metabolites in 15 seconds. If successful, the device could be deployed at high-risk transmission venues such as mass gatherings and airports.