Tuesday, October 15, 2019

Could CRISPR be Used as an Antiviral Drug?

Just last week, researchers published an article on the effectiveness of using a CRISPR Cas13 system to selectively target and cut viral ssRNA. This technique is possible because ssRNA genomes contain numerous unique recognition sites for the Cas13 enzyme that theoretically do not overlap with any (known) part of the human genome. The researchers tested the CRISPR system on three viruses: lymphocytic choriomeningitis virus (LCMV), influenza A virus (IAV) and vesicular stomatitis virus (VSV). First, they performed a screen of the viral genomes and confirmed highly conserved target sites for the Cas13. Next, they tested the enzyme’s antiviral activity in cell culture and it demonstrated remarkable ability to target and inhibit the viral genomes and reduce virus activity. Finally, they optimized the Cas13 detection capabilities, developing a platform (they call CARVER) to seek out and eliminate viral RNA. This research takes a novel approach to deal with the issues that arise from viruses that replicate within the cell, offering a new perspective on drug development and targeted therapies. The main weaknesses of the paper are that the authors did not yet test the system in vivo nor did they observe the cells and viruses over an extended period of time to see if the CRISPR-induced mutations remained. One of the remaining difficulties of a CRISPR-based drug approach is the challenge of delivering the technology into the infected cell. Researchers are still finding efficient ways to bring Cas13 - an RNA-seeking enzyme that was only recently discovered - into the affected cells. Nonetheless, the authors’ research is an exciting development in the world of viruses and our enduring battle against the microscopic parasites. 
~Avi Kaye

Article: Freije, C. et al. Programmable Inhibition and Detection of RNA Viruses Using Cas13. Molecular Cell, 2019; DOI: 10.1016/j.molcel.2019.09.013. https://www.sciencedirect.com/science/article/pii/S1097276519306987.

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