Hopefully, CRISPR-based diagnostics will make an early debut amid COVID-19 outbreak. But what about a CRISPR prophylactic strategy to combat coronaviruses? The proof of concept is here, in bioRxiv, but it will be deployed in the next pandemic if we are lucky. It’s called PAC-MAN, like the videogame, stands for Prophylactic Antiviral CRISPR in huMAN cells, and comes from the Stanley Qi Lab.
This Cas13-based strategy for viral inhibition can effectively degrade Sars-CoV2 sequences and live influenza A virus genome in human epithelial cells. Bioinformatics analysis shows a set of only 6 guide RNAs can target all known human coronavirus with broad coverage against other animal coronaviruses.
Notably, the Sars-CoV2 gene targeted by the Stanford team is also the target of an antiviral drug developed to treat Ebola and already administered for Covid-19 through compassionate use requests (Remdesivir). Additional hints come from the paper on guide RNA design published in Nature Biotechnology by Neville Sanjana et. al.
If an effective in vivo delivery system is developed, according to Timothy Abbott et al., there are many potential benefits over traditional vaccines. “Traditional vaccines rely on priming the immune system through exposure to viral proteins or peptides often derived from surface proteins that exhibit a high rate of mutation, which increased the chances of viral evasion of the host immune response. In contrast, here we have demonstrated a genetic strategy that is able to target highly conserved regions, which would be expected to make it much more unlikely for the virus to escape inhibition through mutation”.
Also, multiple guide RNAs targeting different regions could be delivered simultaneously, further reducing the chances of viral escape. “As a further advantage, we demonstrate a potential pan-coronavirus strategy to target not only viruses that circulate in humans, but also those that currently are found in animal reservoirs that might transfer to humans to cause disease.” This could “greatly accelerate the development of countermeasures for future emergent threats.”
According to Fyodor Urnov, who was asked for a comment by Wired, there’s still a long horizon between preprint and clinical testing. “There is, frankly, zero chance that this approach can be tested in humans in the next four to six months,” says the genome-editing pioneer. “By analogy, if we were trying to go to the moon and come back safely, what this work shows is one can build a rocket that achieves escape velocity.”