CRISPR was first mentioned in a European medical journal in 1993, and the technique has been built upon by researchers across the globe ever since. Now, the gene-editing tool with the unusual name is being used in the fight against the novel coronavirus, not only to diagnose COVID-19 but also to inhibit it.
CRISPR stands for Clustered Regularly Interspaced Short Palindromic Repeats. In an educational video, the Mayo Clinic explains the basics of how it works. “CRISPR consists of two components. The Cas9 protein, that can cut DNA, and a guide RNA that can recognize the sequence of DNA to be edited.”
Charles Chiu, a UCSF professor of laboratory medicine as well as an MD, published a paper in the journal Nature in April 2020 that is expanding the way CRISPR can be used. The paper details a new test that he developed that uses CRISPR to diagnose COVID-19 called DETECTR. The advantage of this assay over other diagnostic tools is that it provides expedited results, and does not require hospitals to invest in special equipment. DETECTR is going through clinical trials now and has not been granted widespread authority to be used by the FDA yet. It is an exciting development in CRISPR science nonetheless. “The introduction and availability of CRISPR technology will accelerate deployment of the next generation of tests to diagnose COVID-19 infection,” Chiu said.
Sherlock Biosciences also has a COVID-19 diagnostic test that has received emergency use authorization by the FDA. The SHERLOCK COVID-19 detection protocol uses CRISPR technology and has a quick turnaround time for results. It was developed by Dr. Feng Zhang, a Chinese-born scientist at the Broad Institute of MIT and Harvard, who is also a co-founder of Sherlock Biosciences. Dr. Zhang has been called the most transformational biologist of our era for his work on CRISPR systems. Gene therapy is not without its criticisms, however.
In an interview with Medscape, Dr. Zhang acknowledged that there are important ethical questions that need to be considered when manipulating genes. “There are a lot of ethical concerns about where to draw the line,” Dr. Zhang told Medscape Editor-in-Chief Eric Topol. “You can start with very grievous diseases, but what do you define as disease? The line can get quite blurry. The good thing is that there are a lot of very smart people—experts in ethics and science—all coming together to think about these issues.”
Researchers at Stanford are also using CRISPR to develop a tool that can assist in the pandemic, and expand the utility of the technique beyond diagnosis. The Stanford research is undertaken with the Department of Energy’s Lawrence Berkeley National Lab and began as a way to fight the flu by scrambling the genetic code of the virus. When the pandemic hit in January, researchers pivoted toward finding solutions for the novel coronavirus. PAC-MAN stands for prophylactic antiviral CRISPR in human cells, and preliminary results show that it can inhibit 90% of coronaviruses, including COVID-19. This is an important advancement because unlike previous CRISPR assays, PAC-MAN seeks to fight the virus rather than diagnose it.
A paper published in the Cell journal, states that PAC-MAN strategy can be used for “viral inhibition that can effectively degrade RNA from SARS-CoV-2 sequences and live influenza A virus (IAV) in human lung epithelial cells.” In other words, PAC-MAN can inhibit both COVID-19 and flu sequences in the lungs. The ‘Development of CRISPR as an Antiviral Strategy to Combat SARS-CoV-2 and Influenza‘ paper concludes that with the “development of a safe and effective system for respiratory tract delivery, PAC-MAN has the potential to become an important pan-coronavirus inhibition strategy.