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

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

A promising therapeutic strategy for COVID-19: antisense oligonucleotide technology.

The current COVID-19 pandemic continues to require new and effective therapeutic strategies. We explored antisense therapy using oligonucleotides targeting the genome of the severe acute respiratory syndrome coronavirus (SARS-CoV-2). We are pleased to announce the publication of this GABI-VIM-Univ Andres Bello (Santiago, Chile) collaborative work on the experimental demonstration of the activity of Antisense Oligonucleotides to inhibit in vitro the replication of SARS-CoV-2 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 the viral regions ORF1a, ORF1b, N, and the 5′UTR of the SARS-CoV-2 genome. The efficacy of the ASOs was tested by transfection onto human CEA2-expressing HEK-293T cells and monkey VeroE6/TMPRSS2 cells infected with SARS-CoV-2.

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

These results demonstrate that anti-ORF1b ASO can specifically reduce SARS-CoV-2 genome replication in vitro in two different cell infection models. The present study presents a 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 : 02 November 2023 | Publication date : 28 October 2022 | Redactor : GABI - Edition P. Huan