Last year, Stanford University Assistant Professor Stanley Qi began working on a technique called PAC-MAN - or Prophylactic Antiviral CRISPR in human cells - that uses the gene editing tool CRISPR to fight influenza. When news of COVID-19 pandemic emerged, Qi and his team thought to try PAC-MAN technology to fight the disease.
PAC-MAN is composed of an enzyme - in this case, the virus-killing enzyme Cas13 - and a strand of guide RNA, which commands Cas13 to destroy specific nucleotide sequences in the coronavirus's genome. By scrambling the virus's genetic code, PAC-MAN could neutralize the coronavirus and stop it from replicating inside cells. However, Qi said that the key challenge to translating PAC-MAN from a molecular tool into an anti-COVID-19 therapy is finding an effective way to deliver it into lung cells.
Researchers at the Molecular Foundry led by Michael Connolly are working on synthetic molecules called lipitoids, a synthetic peptide mimic known as peptoid that are effective in the delivery of DNA and RNA to a wide variety of cell lines. Lipitoids are non-toxic to the body and can deliver nucleotides by encapsulating them in tiny nanoparticles the size of a virus. The Lipitoid 1 tested by the Stanford team in late April 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 next plans to test the system against a live SARS-CoV-2 virus.
For more details, read the article in Berkeley Lab News Center.