Bioengineers at Stanford University were working on a system to fight the flu with the gene-editing technology CRISPR when the COVID-19 pandemic emerged in January. So they quickly pivoted to address the new disease—and now they’re reporting they’ve developed a way to inhibit 90% of coronaviruses, including SARS-CoV-2, the cause of COVID-19.
The Stanford team worked with researchers at the Department of Energy's Lawrence Berkeley National Laboratory to develop a technique called prophylactic antiviral CRISPR in human cells, or PAC-MAN. The technology disables viruses by scrambling their genetic code. The researchers developed a new way to deliver the technology into lung cells, they reported in the journal Cell.
PAC-MAN combines a guide RNA with the virus-killing enzyme Cas13. The RNA directs Cas13 to destroy certain nucleotide sequences in the SARS-CoV-2 genome, effectively neutralizing it.
But the Stanford team that developed PAC-MAN needed an effective way to deliver it to the lung, where COVID-19 often does the most damage. So they turned to the Berkeley Lab's Molecular Foundry, which has been working on lipitoids, synthetic peptides that can deliver DNA and RNA into cells.
When the researchers packaged their COVID-targeting PAC-MAN with the lipitoids they were able to reduce the amount of SARS-CoV-2 virus in solution by more than 90%. They are now planning animal trials with collaborators at New York University and Karolinska Institute in Sweden.
"An effective lipitoid delivery, coupled with CRISPR targeting, could enable a very powerful strategy for fighting viral disease not only against COVID-19 but possibly against newly viral strains with pandemic potential," said Michael Connolly, a principal scientific engineering associate at Berkeley Lab, in a statement.
CRISPR is already being used in the fight against COVID-19—but for diagnosing the disease. In May, the FDA gave an emergency authorization for a CRISPR-based test from Sherlock Biosciences that can diagnose COVID-19 in about an hour. The test uses the enzyme Cas13a to identify an RNA sequence that’s unique to SARS-CoV-2.
The potential for using CRISPR to eliminate viruses has already generated some enthusiasm in the research community. Last year, for example, Excision BioTherapeutics licensed a technology from Temple University that uses CRISPR, combined with antiretroviral therapy, to eliminate HIV, the virus that causes AIDS.
The Stanford researchers working on COVID-19 are confident their PAC-MAN system will also prove useful for fighting influenza. In the Cell article, they reported that their CRISPR-Cas13 technology was not only effective against SARS-CoV-2, it also lowered the viral load in human lung epithelial cells infected with the H1N1 strain of the flu.