Friday, November 25, 2022

Researchers created artificial enzymes programmed to target the genetic code of SARS-CoV-2 or cancer and destroy the virus or cancer

Amazing stuff! Sounds very promising!

"... 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, ... 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 ... named XNAzymes.
At the beginning, XNAzymes were inefficient, requiring unrealistic laboratory conditions to function. Earlier this year, however, ... 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 ... report how they have used this technology to successfully ‘kill’ live SARS-CoV-2 virus. ... 
“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. ...
“It’s worth remembering, however, that the amazingly successful Pfizer and Moderna COVID-19 vaccines are themselves based on synthetic RNA molecules – so it’s a really exciting and rapidly developing field, with enormous potential.” ..."

From the abstract:
"The unprecedented emergence and spread of SARS-CoV-2, the coronavirus responsible for the COVID-19 pandemic, underscores the need for diagnostic and therapeutic technologies that can be rapidly tailored to novel threats. Here, we show that site-specific RNA endonuclease XNAzymes – artificial catalysts composed of single-stranded synthetic xeno-nucleic acid oligonucleotides (in this case 2’-deoxy-2’-fluoro-β-D-arabino nucleic acid) – may be designed, synthesised and screened within days, enabling the discovery of a range of enzymes targeting SARS-CoV-2 ORF1ab, ORF7b, spike- and nucleocapsid-encoding RNA. Three of these are further engineered to self-assemble into a catalytic nanostructure with enhanced biostability. This XNA nanostructure is capable of cleaving genomic SARS-CoV-2 RNA under physiological conditions, and when transfected into cells inhibits infection with authentic SARS-CoV-2 virus by RNA knockdown. These results demonstrate the potential of XNAzymes to provide a platform for the rapid generation of antiviral reagents."

‘Programmable molecular scissors’ could help fight COVID-19 infection | University of Cambridge 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.


Fig. 1: RNA endonuclease XNAzymes retargeted to the SARS-CoV-2 genome.


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