Wednesday, August 12, 2020

CRISPR gene-editing can be used to fight the COVID-19 pandemic, Stanford researchers find

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 didn’t know then that their PAC-MAN technique could be used in fighting a global pandemic like COVID-19. When the pandemic emerged in January, the team decided to try and 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 Lab’s 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 peer-reviewed and published in the journal Cell in June.

Read Also: Gene-edited embryos experiment with CRISPR ends disastrously

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 coronavirus’s 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 doesn’t work on cellular delivery methods, and Connolly’s work on synthetic molecules called lipitoids at the Molecular Foundry came to their rescue. Lipitoids were first discovered 20 years ago by Connolly’s 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 (PAC-MAN) to the Molecular Foundry’s 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 a SARS-CoV-2 virus.

Read Also: It will cost $260 billion to help prevent a new pandemic, scientists say

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. CRISPR gene-editing technology has a lot of merits, even treating the first sick cell patient.

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Source: Phys.org, Berkeley Lab

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