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INRA
24, chemin de Borde Rouge –Auzeville – CS52627
31326 Castanet Tolosan CEDEX - France

Dernière mise à jour : Mai 2018

Menu Logo Principal AgroParisTech Université Paris-Saclay

INRA GABI Unit

GABI : Génétique Animale et Biologie IntégrativeUnité Mixte de Recherche INRA - AgroParisTech

Can RNA therapy help get rid of SARS-CoV-2 during respiratory infection?

GABI-VIM parntership for antiviral SARS-CoV-2 RNA antisense therapy
Two INRAE teams (Jouy-en-Josas) and a laboratory in Santiago, Chili, are sharing their expertise in RNA virology and molecular biology to conceive via bioinformatics a series of antisense oligonucleotides that by linking specifically to key regions of the SARS-CoV-2 viral genome, allow their destruction and therefore block viral multiplication.

The COVID-19 pandemia has caused an important sanitary and economic crisis throughout the world, and for the moment there is no specific treatment. Future vaccines will be the right solution to fight the virus on the world population level but at the individual level, the virus which is well adapted to man, will continue to circulate among the population and it will continue making people sick that we must treat with efficient and more specific treatments.

The SARS-CoV-2 coronavirus possesses an RNA genome, which is both its strength and weakness. It is possible to specifically cut the genome using molecular tools called antisense oligonucleotides, which are chemically modified. With these molecular tools, key regions that allow the viral genome to replicate and transcribe viral genes into proteins will be targeted. 

By using RNA therapy techniques currently being developed clinically for many diseases like cancers, certain myopathies or degenerative diseases of the nervous system (such as for Huntington disease) but also against viruses, we have conceived a series of antisense oligonucleotides using bioinformatics tools. These oligonucleotides are chemically modified in order to remain stable over time, so that they will fix onto their targets, by irreversible complimentary hybridation, located in vital regions of the viral genome. Once collected, these antisense oligonucleotides  form a double strand viral DNA-RNA that will be systematically cleaved by two natural enzymes (RNAse H1) of the infected cells. These irreversible cleavages of the viral genome and/or their transcripts will block the virus' replication and as a consequence its multiplication. Our bioinformatics study therefore showed that RNA therapy using two different techniques would be theoretically usable to decrease viral infection of the cells infected by SARS-CoV-2. A previous experimental study by a similar method on SARS-CoV showed that this type of treatment is doable, which is encouraging for the rest of the project.

What are the perspectives after these preliminary results obtained through bioinformatics calculations? Now, we must demonstrate experimentally in a virology laboratory the efficiency of these treatments using antisense oligonucleotides on of SARS-CoV-2 infected cell models. If some of our candidates are shown to be efficient alone or combined, significantly decreasing viral multiplication, a preclinical assay on an in vivo model will be necessary before a real clinical trial in man may begin. Considering previous clinical trials of RNA assays of those currently underway, the great advantage of antisense oligonucleotides is their high specificity, good tolerance, low toxicity and reasonable production costs of these molecules. Finally, for COVID-19 which mainly affects the lungs, the administration by inhalation of an aqueous solution containing the antisense oligonucleotides will allow to reach directly the virus located in the respiratory tract at an early stage of the disease. In addition, these small antisense oligonucleotides are naturally absorbed by the cells and do not require a vector nor special solvent to reach their therapeutic targets.

There is still a long way to go but it is feasible with collaborative work. This is the reason why this paper is available on line before revision and publication in an international scientific journal, in order to share the results of these predictions with the scientific community and to stimulate partnerships and laboratory tests wherever this is feasible while respecting high standards of security and efficiency. At INRAE Jouy-en-Josas, the Molecular Virology and Immunology unit (UMR VIM) and Animal Genetics and Integrative Biology Unit (UMR GABI) are preparing their teams to this experimental approach.

Contacts:

  • Eric Barrey (RNA therapy): eric.barrey@inrae.fr
  • Bernard Delmas (SARS-CoV-2 Coronavirus ): bernard.delmas@inrae.fr

See also

Reference:    
Think Different with RNA Therapy: Can Antisense Oligonucleotides Be Used to Inhibit Replication and Transcription of SARS-Cov-2?
https://www.preprints.org/manuscript/202004.0412/v1

Eric Barrey 1 , Veronica Burzio 2, Sophie Dhorne-Pollet 1,   Jean-François Eléouët 3, Bernard Delmas 3  

Affiliations:

  1. Université Paris-Saclay, INRAE,  AgroParisTech,  GABI, 78350 Jouy-en-Josas, France.
  2. Department of Biological Sciences, Faculty of Life Sciences, Universidad Andrés Bello - Fundación Ciencia & Vida, Andes Biotechnologies SpA, Santiago, Chile
  3. Université Paris-Saclay, INRAE,  AgroParisTech,  UMR VIM, Virologie et Immunologie Moléculaire, 78350 Jouy-en-Josas, France.