Scientists and researchers around the world are working round the clock to fight the COVID-19 pandemic. Gene editing using CRISPR is one such recent study.

In 2019, Assistant Professor Stanley Qi and his team in the departments of bioengineering and chemical and systems biology at Stanford University began working on a technique called PAC-MAN to fight influenza. PAC-MAN stands for Prophylactic Antiviral CRISPR in human cells and uses the gene-editing tool called Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) technology.

The research team didnt know then that their technique could be used in fighting the global pandemic like COVID-19. When the pandemic emerged in Jan, the team decided to use their PAC-MAN technology to fight it. In collaboration with a group led by Michael Connolly, a principal scientific engineering associate in the Biological Nanostructures Facility at Berkeley Labs Molecular Foundry, the researchers have been developing a system to deliver PAC-MAN into the cells of a patient since March. Their preprint paper was recently peer-reviewed and published in the journalCell.

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Like all CRISPR systems, PAC-MAN comprises of the virus-killing enzyme Cas13 and a strand of guide RNA. The guide RNA commands Cas13 to destroy specific nucleotide sequences in the coronaviruss genome, effectively neutralizing it and stopping its replication.

Every gene-editing tool needs an efficient delivery system to deliver them to the molecular or cellular level. According to Qi, their lab doesnt work on cellular delivery methods, and Connollys work on synthetic molecules called lipitoids at the Molecular Foundry came to their rescue. Lipitoids were first discovered 20 years ago by Connollys mentor Ron Zuckermann is a type of synthetic peptide mimic known as a peptoid. In the decades since the discovery, Connolly and Zuckermann have developed peptoid delivery molecules such as lipitoids.

Qi hopes to add his CRISPR-based COVID-19 therapy to the Molecular Foundrys growing body of lipitoid delivery systems. Their late April tests performed well. When packaged with coronavirus-targeting PAC-MAN, the system reduced the amount of synthetic SARS-CoV-2 in solution by more than 90%. The team is planning to conduct further tests in an animal model against live SARS Coronavirus-2.

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If the tests prove successful, the team hopes to continue working with Connolly and his team to develop PAC-MAN/lipitoid therapies for SARS-CoV-2 and other coronaviruses. And also, explore options to scale up for a clinical trial.

The research is highly significant. It would be a powerful strategy to fight not just coronaviruses but possibly against new viral strains that can become a pandemic.

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Source: Phys.org, Berkeley Lab

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