Synthetic biology meets medicine: ‘Programmable molecular scissors’ could help fight COVID-19 infection

Cambridge scientists have used synthetic biology to create artificial enzymes programmed to target the genetic code of SARS-CoV-2 and destroy the virus, an approach that could be used to develop a new generation of antiviral drugs.

Enzymes are naturally occurring biological catalysts, which enable the chemical transformations required for our bodies to function — from translating the genetic code into proteins, right through to digesting food. Although most enzymes are proteins, some of these crucial reactions are catalysed by RNA, a chemical cousin of DNA, which can fold into enzymes known as ribozymes. Some classes of ribozyme are able to target specific sequences in other RNA molecules and cut them precisely.

In 2014, Dr Alex Taylor and colleagues discovered that artificial genetic material known as XNA — in other words, synthetic chemical alternatives to RNA and DNA not found in nature — could be used to create the world’s first fully-artificial enzymes, which Taylor named XNAzymes.

At the beginning, XNAzymes were inefficient, requiring unrealistic laboratory conditions to function. Earlier this year, however, his lab reported a new generation of XNAzymes, engineered to be much more stable and efficient under conditions inside cells. These artificial enzymes can cut long, complex RNA molecules and are so precise that if the target sequence differs by just a single nucleotide (the basic structural unit of RNA), they will recognise not to cut it. This means they can be programmed to attack mutated RNAs involved in cancer or other diseases, leaving normal RNA molecules well alone.

Now, in research published today in Nature Communications, Taylor and his team at the Cambridge Institute of Therapeutic Immunology & Infectious Disease (CITIID), University of Cambridge, report how they have used this technology to successfully ‘kill’ live SARS-CoV-2 virus.

Taylor, a Sir Henry Dale Fellow and Affiliated Researcher at St John’s College, Cambridge, said: “Put simply, XNAzymes are molecular scissors which recognise a particular sequence in the RNA, then chop it up. As soon as scientists published the RNA sequence of SARS-CoV-2, we started scanning through looking for sequences for our XNAzymes to attack.”

While these artificial enzymes can be programmed to recognise specific RNA sequences, the catalytic core of the XNAzyme — the machinery that operates the ‘scissors’ — does not change. This means that creating new XNAzymes can be done in far less time than it normally takes to develop antiviral drugs.

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