CRISPR: a genetic surgical strike against COVID-19
CRISPR technology, a gene editing tool that has been heralded as a revolutionary discovery of the decade, is now being explored as an alternative therapeutic strategy against the novel coronavirus, SARS-CoV-2.
The novelty of CRISPR lies in its ability to precisely locate, delete and repair mutations in genomes, making it a copy editor like no other. From identifying and editing genes that make tumor cells chemotherapy-resistant, to repairing genetic mutations that cause sickle-cell anemia, CRISPR is well poised for diverse applications in clinical settings.
In a new study, a research group from Stanford University proposes that a CRISPR-based strategy called PAC-MAN (Prophylactic Antiviral CRISPR in huMAN cells) could potentially inhibit the activity of SARS-CoV-2 inside epithelial cells that line the surface of the human lung.
By using PAC-MAN to degrade the RNA ‒ the virus’s genetic material, which it injects into a patient’s cells ‒ the researchers were able to limit the replication of the virus in human lung cells cultured in the lab. True to its video game-inspired moniker, PAC-MAN was found to not only reduce the concentration of the viral genome, but also block the gene-mediated expression and production of certain viral proteins. These proteins catalyse the replication of the virus and protect it while it replicates.
The study, published in the journal Cell, makes a case for the edge that such an approach can give over the traditional route of therapeutics and vaccines.
Vaccines, including the relatively new types based on DNA and RNA, prime our immune system by exposing it to surface proteins of the virus called spike proteins. However, the genes encoding these spike proteins are prone to mutation, and the virus can evolve to evade the host’s immune response over time.
The CRISPR-based strategy outlined in the new study, on the other hand, targets regions of the SARS-CoV-2 genome that are highly conserved across the family of coronaviruses, and hence resistant to mutations. This makes the strategy potentially effective against threats from other coronaviruses as well.
One major caveat of the study, however, is that the researchers did not test PAC-MAN on live SARS-CoV-2 strains, but on lab-made fragments of the virus as well as on live influenza virus strains. At best a proof-of-concept at the moment, the researchers are seeking approval for the use of live SARS-CoV-2 virus strains as an immediate next step to this study.
So far, only a few CRISPR-based strategies have passed FDA approvals to reach human clinical trials. Deploying PAC-MAN to fight the current pandemic appears promising, but can be a long haul.