The Cutting Room Floor

Since the start of the COVID-19 pandemic, our understanding of RNA viruses – possibly the most important group involved in zoonotic disease transmission (1) – has heightened significantly. Their biological diversity and adaptive capabilities pose considerable challenges for researchers, often pushing the limits of modern medical technology.

Enter, researchers from A*STAR’s Genome Institute of Singapore (GIS) and the Yong Loo Lin School of Medicine, who have – contrary to traditional therapeutic modalities – used a CRISPR-Cas13 editor to eliminate the EV-A71 RNA virus, a causative agent responsible for hand, foot, and mouth disease (2). The adeno-associated virus (AAV)-delivered CRISPR-Cas13 can be programmed by guide RNAs that cleave conserved viral sequences across the virus phylogeny, targeting specific RNA sequences. Once bound to these RNA sequences, the CRISPR-Cas13 cuts the target into pieces, immobilizing the RNA.

Results suggest their approach can effectively block viral replication and substantially reduce viral load. In fact, they found that less than 0.1 percent of the viruses remained in previously infected mouse tissues. The research findings also show that the AAV-CRISPR-Cas13 therapy cleared the EV-A71 infection, while preventing organ damage and death in a lethally challenged mouse model.

“The CRISPR technology allows the rewriting of the genetic code in almost any organism,” said Liu Jian Jun, Acting Executive Director of A*STAR’s GIS. “This joint research with [the National University of Singapore] is an extremely important development which can potentially treat many diseases caused by RNA viruses, and open many avenues for further therapeutic solutions.”

Chew Wei Leong, Associate Director and Principal Scientist at A*STAR’s GIS, suggests the team is now taking the research one step further (3). He said, “This is a stunning demonstration that one dose of CRISPR-Cas13 can mean a difference between life and death. We are building on this research to develop further life-changing nucleic acid therapeutics.”