A promising therapeutic strategy for COVID—19 : technology of antisens oligonucleotides

Publication Front. Microbiol, Dhorne-Pollet S. & al.

A promising therapeutic strategy for COVID—19 : technology of antisens oligonucleotides

The ongoing COVID-19 pandemic continues to pose a need for new and efficient therapeutic strategies. We explored antisense therapy using oligonucleotides targeting the severe acute responiratory syndrome (SARS-CoV-2). We are pleased to annouce the publication of this collaborative study involving GABI, the VIM Unit and The University Andres Bello (Santiago, Chili) on the experimental demonstration of active Antisens Oligonucleotide activity on the in vitro inhibition of SARS-CoV-2 virus replication, the virus responsible for COVID-19.

We predicted in silico four antisense oligonucleotides (ASO gapmers with 100% PTO linkages and LNA modifications at their 5′ and 3′ends) targeting viral regions ORF1a, ORF1b, N and the 5′UTR of the SARS-CoV-2 genome. Efficiency of ASOs was tested by transfection in human ACE2-expressing HEK-293T cells and monkey VeroE6/TMPRSS2 cells infected with SARS-CoV-2.

The ORF1b-targeting ASO was the most efficient, with a 71% reduction in the number of viral genome copies. N- and 5′UTR-targeting ASOs also significantly reduced viral replication by 55 and 63%, respectively, compared to non-related control ASO (ASO-C). Viral titration revealed a significant decrease in SARS-CoV-2 multiplication both in culture media and in cells.

These results show that anti-ORF1b ASO can specifically reduce SARS-CoV-2 genome replication in vitro in two different cell infection models. The present study presents proof-of concept of antisense oligonucleotide technology as a promising therapeutic strategy for COVID-19.

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Dhorne-Pollet S, Fitzpatrick C, Da Costa B, Bourgon C, Eléouët J-F, Meunier N, Burzio VA, Delmas B and Barrey E (2022) Antisense oligonucleotides targeting ORF1b block replication of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Front. Microbiol. 13:915202. doi: 10.3389/fmicb.2022.915202.

Modification date : 05 October 2023 | Publication date : 28 October 2022 | Redactor : GABI - Edition P. Huan - Translation W. Brand-Williams