Artificial Enzymes Programmed To Fight COVID-19 Virus Formed by Scientists Using Synthetic Biology

Cambridge biologists utilized synthetic biology to produce artificial enzymes designed to target the SARS-CoV-2 genetic code and kill the virus, a strategy that might be exploited to create an entirely new era of antiviral medications.

Enzymes occur naturally in biological catalysts that allow our bodies to operate by facilitating chemical changes ranging from translating genetic information into proteins to digesting food. Since most enzymes contain proteins, RNA, a chemical relative of DNA, may wrap into enzymes known as ribozymes and catalyze some of these critical activities. Some ribozyme types can accurately target and cut particular sections in other RNA molecules.

Dr. Alex Taylor and colleagues revealed in 2014 that synthetic genetic material known as XNA-synthetic chemical alternatives to DNA and RNA not present in nature-could be utilized to build the first artificially created enzymes, dubbed XNAzymes by Taylor.

XNAzymes Promising Capabilities

XNAzymes were initially inefficient, needing excessive laboratory conditions to work. Later this year, nevertheless, his group published a new class of XNAzymes that have been built to be far more efficient and stable inside cells. These synthetic enzymes are capable of cutting large, complicated RNA molecules and they are so accurate that when the target sequence varies by just a nucleotide sequence (the significant structural component of RNA), they will identify it and refuse to cut it. It thus implies that they can be taught to target mutant RNAs implicated in cancer or even other disorders while keeping normal RNA molecules alone.

Taylor and his colleagues at the Cambridge Institute of Therapeutic Immunology & Infectious Disease (CITIID), the University of Cambridge, reveal how they utilized this technique to successfully 'kill' live SARS-CoV-2 virus in a study published today in Nature Communications.

Taylor, a Sir Henry Dale Fellow as well as an Affiliated Researcher at St John's College, Cambridge, explained that XNAzymes are molecular scissors that detect a certain sequence in the RNA and then slice it up. They began screening potential patterns for the XNAzymes to assault as soon as scientists disclosed the RNA structure of SARS-CoV-2.

While these synthetic enzymes may be designed to detect certain RNA sequences, the XNAzyme's catalytic core-the machinery that controls the 'scissors'-remains unchanged. This means that developing new XNAzymes will take significantly less time than developing antiviral medicines.

'Programmable Molecular Scissor'

As Taylor put it, it's like possessing a set of scissors with the same overall design but different edges or grips based on the substance you want to cut. The strength of this method is that, despite working alone in the lab during the beginning of the outbreak, he was able to create and screen a small number of such XNAzymes in a couple of days, as described in a My Science report.

Taylor next collaborated with Dr. Nicholas Matheson to demonstrate that his XNAzymes are active against live SARS-CoV-2 virus, utilizing CITIID's state-of-the-art Containment Level 3 Research lab country's biggest academic facility for investigating high-risk biological agents like SARS-CoV-2.

It's incredibly exciting because for the first time - and this has been a key aim of the research - they have them acting as enzymes within cells, blocking reproduction of viral vector, commented Dr. Pehuén Pereyra Gerber, who completed the SARS-CoV-2 tests in Matheson's group.

Everything they've demonstrated is proof of concept, and it's still early stages, added Matheson. It's worth noting, however, that the incredibly successful Pfizer as well as Moderna COVID-19 vaccines also are predicated on artificial RNA molecules-so it's extremely innovative and rapidly continuing to develop the field with enormous potential.

Taylor compared the target virus sequences to human RNA databases to confirm they weren't present in our RNA. Since the XNAzymes are very specific, they should be able to avoid a number of the 'off-target' adverse effects that other, less precise molecular therapies may produce, such as liver damage.

Cocktail of XNAzymes

In a Phys report, SARS-CoV-2 has the potential to adapt and modify its genetic coding, resulting in new versions that are less effective against vaccinations. Taylor not only selected viral RNA sections that change less often, but he also engineered three of XNAzymes to self-assemble to form a 'nanostructure' that cuts distinct areas of the virus genome.

Taylor also explained that they're targeting many genomes, so the virus would have to evolve at numerous locations at the same time to avoid the therapy. In theory, one could make a cocktail out of many of such XNAzymes. Even if a new variety appears that is capable of circumventing this, given that the researchers already have had the catalytic core, they can swiftly create new enzymes to keep up.

XNAzymes might be used as medications to protect persons who have been subjected to COVID-19, to avoid the virus from gaining traction, or to receive treatment who have been infected and to rid the system of the virus. This method may be especially useful for people who are unable to clear the infection on their own due to a weaker immune system.

Taylor and his team's next goal is to create XNAzymes that are further selective and robust-"bulletproof," he asserts them to stay in the body for longer and function as even more potent catalysts in lower dosages.

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