Cell publishes DARPA-funded study of CRISPR-based COVID-19 strategy

Research from Stanford University on using genome manipulation to inhibit the virus that causes COVID-19, previously available as a pre-print draft version that had not undergone peer review, was formally published on April 29 by the open-access journal Cell.

The study, which was funded by the Defense Advanced Research Projects Agency (DARPA), suggests that the Stanford approach "has the potential to become an important pan-coronavirus inhibition strategy," the authors wrote.

The strategy involves using clustered regularly interspaced short palindromic repeats (CRISPR) to impair the virus's ability to penetrate human cells. Its inventors have dubbed it "PAC-MAN" (Prophylactic Antiviral CRISPR in human cells), inspired by the way the CRISPR Cas-13d enzyme functions like a "power cookie" in the arcade-era video game, making the therapeutic attack much more powerful.

"I like video games," Stanley Qi, principal investigator and assistant professor of bioengineering and chemical and systems biology at Stanford, Qi told Wired magazine in March. "The Pac-Man tries to eat the cookies and it is chased by a ghost. But when it encounters a specific kind of cookie called the power cookie--in our case a CRISPR Cas13 design--suddenly it turns itself to be so powerful. It can start eating the ghosts and start cleaning up the whole battlefield."

Because active laboratory strains of SARS-CoV-2 were not available when the study was conducted, the researchers tested their approach using synthesized fragments of SARS-CoV-2, as well as with live H1N1 IAV. They demonstrated that the approach could cleave SARS-CoV-2 fragments and reduce the replication of influenza A virus in human lung epithelial cells, and identified a group of six crRNAs that can target 91% of sequenced coronaviruses, as well as a group of 22 crRNAs able to target all sequenced coronaviruses.

The published proof-of-concept study will need to be validated in animal models, using viruses capable of replicating, before it can be tested in humans. The team will also need to find a way to deliver the treatment to the right cells. Qi told Wired one reason for publishing a draft of the study prior to peer review was to solicit delivery-system suggestions from other scientists.

"This system could possibly buffer against viral evolution and escape, as well as enable rapid development and deployment against emerging viruses," the authors wrote. "When combined with an effective delivery platform, PAC-MAN is a promising strategy to combat not only coronaviruses including that causing COVID-19, but also a broad range of other genera of viruses."

Read the study: https://www.ncbi.nlm.nih.gov/pubmed/32353252

Read more in Wired magazine: https://www.wired.com/story/could-crispr-be-the-next-virus-killer/