Engineered enzymes could fight the virus that causes COVID by selectively cleaving the RNA genome, new research suggests. Researchers say the technology could overcome a major problem with previous techniques and could help create rapid antiviral treatments when threats emerge.
When the COVID pandemic hit, Cambridge University chemical biologist Alexander Taylor scrambled to repurpose the gene-cutting technique he and his colleagues were developing. It’s a synthase called his XNAzyme (heterologous nucleic acid) formed from artificial RNA. Working single-handedly during lockdown, Taylor generated five of his XNAzymes in a matter of days, targeting sequences in the genome of SARS-CoV-2.
Enzymes are natural catalysts that facilitate chemical transformations. In this case, it is done by cleaving other molecules. However, previous DNA- and RNA-based enzymes struggled to cleave long and highly structured molecules such as viral genomes. Instead, it destroys targets by recruiting pre-existing enzymes within the cell. This is an imprecise process that leads to “off-target” cuts and increased side effects.
Taylor and his colleagues last year showed that XNAzymes can recognize and not cut sequences that differ by one “letter” in the genetic code. It also performs better than previous efforts because it forms tighter chemical bonds and maintains structure and function under the conditions unfolded by DNA and RNA enzymes, researchers say.
Common CRISPR gene-editing tools can also target RNA, but the human immune system may be less responsive to the bacterial enzymes used. XNAzymes do not occur naturally, making them less likely to trigger immune system attacks. Also, it doesn’t rely on bringing in extra components from within the cell. This may reduce side effects. “All current RNA therapeutics exploit cellular machinery,” says Roy van der Meel, a biomedical engineer at Eindhoven University of Technology in the Netherlands, who was not involved in the new research. not. “This is an independent scissor.”
In a new study published in Nature CommunicationsXNAzymes reduced SARS-CoV-2 viral replication in infected cells by up to 75%. “We’re pretty comparable to other approaches that were developed years ago,” Taylor says, but notes that no direct comparison has yet been made.
Scientists used XNAzymes to target three parts of the virus’ genome, making the mutations more difficult to fend off. This approach is readily adaptable to other viruses as the core system remains the same. Only the part that binds the target is reprogrammed. “XNAzymes have great potential for precision medicine,” said study co-author Maria Donde, also from the University of Cambridge. Previous work in this group suggests that XNAzymes may be effective against numerous diseases.
The researchers say they have not yet designed a method to introduce these XNAzymes into human cells, but van der Meel said methods used for other RNA therapeutics may work. I’m here. The team is currently working on the stability and accuracy of XNAzymes and testing additional target sequences.
