Stanford Scientists Develop A New CRISPR Therapy To Fight COVID-19
Stanley Qi, an assistant professor in the departments of bioengineering and chemical and systems biology at Stanford University, developed a technique that uses a gene-editing tool to fight influenza, called PAC-MAN – or Prophylactic Antiviral CRISPR in human cells.
As the COVID-19 pandemic emerged in January, Qi and his team thought, why don’t they try using their PAC-MAN to fight the novel coronavirus.
To develop a system that delivers PAC-MAN into the cells of a patient, Qi and his team started working with a principal scientific engineering associate in the Biological Nanostructures Facility at Berkeley Lab’s Molecular Foundry since late March.
PAC-MAN is composed of an enzyme, like all CRISPR systems, but in this case, its a virus killing enzyme called Cas13. PAC-MAN also consists of a strand of guide RNA that stop coronavirus from replicating inside cells by commanding Cas13 to destroy specific nucleotide sequences of the coronavirus genome.
Finding an effective way to deliver the PAC-MAN into lung cells was the key challenge in translating it from a molecular tool into an anti-COVID-19 therapy. When a person is infected with COVID-19, his air sacs in the lungs get
inflamed and filled with fluid, hijacking a patient’s ability to breathe.Since Qi’s lab doesn’t work on delivery methods, they published a preprint of the paper about their CRISPR system to fight COVID-19 and also tweeted on March 14 to find a potential collaborator with expertise in cellular delivery techniques.
Eventually, they came to know about Connolly’s work on lipitoids, kind of synthetic molecules at the Molecular Foundry.
Connolly’s mentor Ron Zuckermann discovered lipitoids 20 years ago, as a type of synthetic peptide mimics called “peptoid.” Zuckermann and Connolly worked for decades to develop peptoid delivery molecules such as lipitoids. They collaborated with Molecular Foundry users and demonstrated the effectiveness of lipitoids in delivering RNA and DNA to a wide variety of cells.
These lipitoids are non-toxic to the body, and according to the researchers studying lipitoids, they can deliver nucleotides by encapsulating them in tiny nanoparticles of the size of a virus, just one billionth of a meter wide.
Qi is now hoping that he could use Molecular Foundry’s growing body of lipitoid delivery systems tp deliver his CRISPR-based COVID-19 therapy to lung cells.
The lipitoids performed very well, according to Qi. The amount of synthetic SARS-CoV-2 in solution was reduced by more than 90% when packaged with coronavirus-targeting PAC-MAN.
The researchers are planning to test the PAC-MAN/lipitoid system in animals against a live novel coronavirus. The researchers at Karolinska Institute in Stockholm, Sweden, and New York University will join the team.
If successful, together, they will develop the PAC-MAN/lipitoid therapies for COVID-19 and scale up their experiments for preclinical tests.
Connolly said this new CRISPR based system to fight COVID-19 could be a very powerful strategy for fighting COVID-19 and other emerging viral diseases.
The Defense Advanced Research Projects Agency supported the Stanford team’s work.
