The “genetic scissors” technique will help in the fight against COVID-19?

“Genetic Scissors”, a method developed by Nobel laureates in chemistry, could be effective in reducing the coronavirus pandemic. – This technique, called CRISPR-Cas9, used to manipulate genes enables precise modification of the genome of cells – writes Prof. Józef Dulak. According to the biologist, this method may degrade the SARS-CoV-2 virus, thus preventing the multiplication and infection of subsequent cells.

1. The several-month-long coronavirus pandemic has already resulted in the death of over 4,2 million people worldwide. Almost 200 million fell ill
2. Vaccines are still the only effective method of preventing the spread of SARS-CoV-2 virus
3. Scientists, however, are constantly looking for other methods of counteracting infections
4. The breakthrough may be brought by the “genetic scissors” technique, for which two scientists won the Nobel Prize last year
5. You can find more such stories on the TvoiLokony home page

“Genetic scissors” – what is it?

In October 2020, the 2020 Nobel Prize in Chemistry was awarded to the founders of “Gene Scissors”, Emmanuelle Charpentier and Jennifer A. Doudna. A French microbiologist and an American biochemist discovered this method in 2012.

With the “genetic scissors” CRISPR / Cas9 developed by Charpentier and Doudn, scientists can make very specific modifications to certain DNA sequences and alter the DNA of animals, plants and microorganisms with extreme precision. Their method not only revolutionized life sciences, but also allowed for the development of new anti-cancer therapies, and possibly also the treatment of genetically determined diseases.

Now it turns out that it can be helpful in the fight against the SARS-CoV-2 virus.

“Genetic scissors” versus the coronavirus?

– This technique of “genetic scissors”, called CRISPR-Cas9, used to manipulate genes enables precise modification of the genome of cells – writes Prof. dr hab. Józef Dulak, head of the Department of Medical Biotechnology at the Faculty of Biochemistry, Biophysics and Biotechnology of the Jagiellonian University

– Gene editing is already being tested in the treatment of, for example, blood diseases such as b-thalassemia and sickle cell anemia. However, CRISPR-Cas9 only allows the manipulation of DNA, as the Cas9 nuclease can only cut through this double-stranded nucleic acid. Meanwhile, as we know, SARS-CoV-2, like most known human viruses (e.g. influenza or HIV), are viruses whose genetic material is RNA.

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Other types of Cas enzymes come in handy here, in particular, the bacterium Leptotrichia buccalis Cas13a nuclease. This enzyme as well as its other variants show specificity for single-stranded RNA, not DNA. Thus, directing Cas13 to the appropriate sequences in the RNA, e.g. SARS-Cov-2 virus, may cause its degradation, and thus prevent the multiplication and infection of subsequent cells, and consequently the development of COVID-19 – informs prof. Dulak on the website of the Jagiellonian University

“Genetic scissors” limit the reproduction of SARS-CoV-2

– In recently published experiments in Nature Communications, the team of Mohamed Fareh and colleagues led by Joseph Trapani from the University of Melbourne in Australia showed the possibility of digesting SARS-Cov-2 virus RNA using appropriately designed crRNA sequences. Importantly, researchers also designed crRNAs so that they could recognize a specific part of the viral RNA even when there were some nucleotide changes in it – a process that is typical of the emergence of new variants. This creates an opportunity to develop appropriate cocktails of crRNA molecules, targeting not only the spike protein, but also other SARS-CoV-2 RNA sequences. The methods of introducing crRNA and Cas13 nuclease used by these researchers made it possible to effectively limit the proliferation of SARS-CoV-2 in human cells grown in the laboratory, including respiratory epithelial cells. – writes professor Dulak.

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The biology expert points out that in vitro research is the starting point for now. Animal studies are needed to develop safe and effective ways of administering such drugs to patients.

– The conducted research shows that this strategy can be further tested and developed in terms of its application in humans. In the case of the SARS-CoV-2 virus, it will probably be necessary to research on appropriately selected animal models, e.g. transgenic mice expressing the human form of the ACE2 receptor, through which SARS-CoV-2 enters our cells (mice are normally insensitive to infection with this virus) . The combination of different crRNAs to target Cas13 to different SARS-Cov-2 genes will need to be tested, including whether the engineered crRNAs are able to recognize new virus variants. The research from the first publication discussed here gives hope that it is possible – emphasizes prof. Dulak.

Molecular biology in the fight against viruses

– The possibility of obtaining another, specific group of drugs not only against SARS-Cov-2 infections but also against other viruses is extremely important. According to the authors of the work in Nature Biotechnology, there are currently 219 viruses known to infect humans, of which 214 are viruses whose genetic material is RNA. Viral disease accounts for about 6,6% of deaths worldwide, and we only have about 90 drugs registered against viruses, and these only work against nine types of viruses. There are only vaccines available against 15 species of viruses, the professor writes.

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– The use of modern methods of molecular biology and the development of effective vaccines and other drugs, which also enable their rapid modification in the event of the emergence of new variants of viruses that mutate frequently, such as the influenza virus or SARS-CoV-2. As indicated by other research and bioinformatics analyzes, several appropriately selected crRNAs will be able to be used for over 90 percent. known coronaviruses. Of course, it is necessary to test not only the effectiveness of the method, but also the safety of the bacterial Cas13 protein in humans. It can, as a protein foreign to the body, trigger an immune response, he sums up.

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