Synthetic biology has been used by Cambridge scientists to create artificial enzymes that can be programmed to destroy aviruses, an approach that could be used to develop a new generation of drugs.
The chemical transformations required for our bodies to function are enabled by the naturally occurring biological catalysts that are in the genes. ribozymes are catalyzed byRNA, a chemical cousin of DNA, which can fold into them. Some classes of ribozyme are able to cut a specific sequence from another molecule.
Artificial genetic material known as XNA could be used to create the world's first fully-artificial enzymes, which was named XNAzymes.
XNAzymes were not efficient at the beginning. A new generation of XNAzymes was reported by his lab earlier this year. If the target sequence is different than a single nucleotide, they will not cut it, but they will know. They can be programmed to attack the genes that cause cancer or other diseases.
In research published today in Nature Communications, Taylor and his team at the Cambridge Institute of Therapeutic Immunology & Infectious Disease (CITIID), University of Cambridge, show how they have used this technology to successfully kill the live SARS-coV-2 virus.
Taylor is a Sir Henry Dale Fellow and a researcher at St John's College. We began looking for the XNAzymes to attack after the scientists published theRNA sequence.
The XNAzyme, the machinery that operates the'scissors', doesn't change even though these artificial enzymes can be programmed. It is possible to create new XNAzymes in less time than it would take to make a antiviral drug.
It's similar to having a pair of scissors where the overall design remains the same, but you can change the blades or handles depending on the material you want to cut. In a matter of days, I was able to generate and screen a few of these XNAzymes, thanks to this approach.
The state-of-the-art Containment Level 3 Laboratory is the largest academic facility for studying high-risk biological agents.
"For the first time, we have them working inside cells and preventing the replication of live virus, which is a big goal of the field," said Dr. Pehuén.
It's still early days, but what we've shown is proof of principle, and it's worth remembering that the amazingly successful Pfizer and Moderna COVID-19 vaccines are themselves based on syntheticRNA molecules.
Taylor looked at the targets against the databases of humanRNAs to make sure they weren't in our own. Because the XNAzymes are highly specific, this should prevent some of the 'off-target' side-effects that may be caused by less accurate drugs.
The ability of the vaccine to evolve and change its genetic code leads to new versions that are less effective. Taylor designed three of the XNAzymes to self- assemble into a structure that cuts different parts of the virus genome, in order to get around this problem.
He said that for the virus to evade the therapy it would have to evolve at a number of sites at once. You could combine a lot of these XNAzymes into a cocktail. Even if a new variant is able to get around this, we can quickly make new enzymes to keep up with it.
XNAzymes can be used to protect people from exposure to COVID-19, to prevent the virus from taking hold, or to help rid the body of the virus. A weakened immune system may make it difficult for patients to clear the virus alone.
The next step for Taylor and his team is to make XNAzymes that are even more specific and robust, allowing them to remain in the body for longer.
There are XNAzymes that target the SARS-CoV-2 genome.
Journal information: Nature Communications
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