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A research team at MHH wants to use the CRISPR-Cas13 system to cut up viral RNA and thus stop the pathogens from multiplying. The Volkswagen Foundation is funding the project with one million euros over two years.
Every year, more than 17 billion people worldwide fall ill with respiratory diseases caused by viruses. Around 2.4 million of those infected die. Because viruses mutate rapidly and are no longer recognisable by the immune system in their altered form, it is difficult to control or even prevent the transmission of pathogens. In addition, newly emerging viruses pose an enormous challenge to the immune system. Treatment options are limited, and even drugs already approved for use against other viruses often have little effect. A research team led by Dr Dr Simon Krooss, physician and scientist at the Department of Gastroenterology, Hepatology, Infectiology and Endocrinology at Hanover Medical School (MHH), is pursuing a completely different approach. The researchers want to not only stop the viruses in the body, but destroy them completely. This is done with the help of CRISPR-Cas13 technology. The special gene scissors are designed to cut only the viral RNA genetic information. The human mRNA, which translates the information in our genes into instructions for building various proteins, remains intact. The research project is being carried out in cooperation with the Fraunhofer Institute for Toxicology and Experimental Medicine ITEM and is being funded by the Volkswagen Foundation with around one million euros over two years.
RNA gene scissors successfully tested on coronavirus
The research team has already demonstrated the promise of this approach in cell culture in connection with the SARS-CoV-2 coronavirus as part of the project ‘Innovative approaches to the development of antiviral drugs’. ‘The gene scissors work very well and were able to cut up to 90 percent of the viral genetic material in our studies,’ says Dr Dr Krooss. In the follow-up project, the researchers are now focusing on human parainfluenza virus 3 (HPIV3). This virus causes flu-like symptoms and can lead to severe lung damage in infants and immunocompromised individuals. To date, there is no treatment or vaccine available. The aim is to administer the gene scissors directly into the respiratory tract via inhalation to stop the virus from spreading.
Biological navigation system guides Cas13
‘We are using the CRISPR-Cas13 system to target regions of viral RNA that are conserved across different virus variants, meaning they do not change or change only slightly and therefore cannot trick the immune system,’ explains the scientist. At the heart of the whole process is Cas13, a protein normally used by bacteria to defend themselves against attacks from certain viruses. Here, the enzyme is now to be used against HPIV3. To ensure that Cas13 cuts at the desired location, the researchers first search for suitable CRISPR guide RNAs (crRNAs) against HPIV3. These guide the enzyme like a biological navigation system to the location where it is to destroy the viral RNA strand.
Lipid vesicles as a new means of transport
In order to get the gene scissors into the infected cells in the first place, viral vectors, also known as gene ferries or gene taxis, were initially used. However, researchers are now focusing on a different type of packaging: lipid nanoparticles. These are tiny, round fat vesicles that are used as a means of transport for a range of medical applications, such as therapeutic vaccines. With support from industry, researchers are looking for mixtures that can withstand nebulisation and the associated shear forces in order to deliver the blueprint for the gene scissors deep into the affected areas of the lungs. The researchers want to test the antiviral activity and safety of the lipid nanoparticle system in cell culture and animal models in order to develop a usable drug for clinical implementation. They also need to investigate how long the gene scissors survive in the airways and how long they can curb virus replication.
The end goal is to develop a drug that can be quickly and precisely delivered to the affected airways via a spray or inhaler, where it stops the viral infection. Because the system works like a construction kit and the crRNA can be adapted and exchanged as needed, the gene scissors can also be used against other viral pathogens. ‘In our experiments, the replication of other highly dangerous viruses, including the Nipah virus and the measles virus, was also very well contained,’ reports the doctor and scientist. ‘CRISPR-Cas13 is an excellent tool for inhibiting the replication of various RNA viruses that cause severe infections in humans.’
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For further information, please contact Dr Dr Simon Krooss, krooss.simon@mh-hannover.de.
Using gene scissors to cut up viral genetic material and thus stop the spread of pathogens: Dr Dr Si ...
Quelle: Copyright: Karin Kaiser/MHH
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Using gene scissors to cut up viral genetic material and thus stop the spread of pathogens: Dr Dr Si ...
Quelle: Copyright: Karin Kaiser/MHH
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