Antisense oligonucleotides targeting ORF1b block replication of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)

Vista sencilla de ítem
dc.contributor.authorDhorne-Pollet, Sophie
dc.contributor.authorFitzpatrick, Christopher
dc.contributor.authorDa Costa, Bruno
dc.contributor.authorBourgon, Clara
dc.contributor.authorEléouët, Jean-François
dc.contributor.authorMeunier, Nicolas
dc.contributor.authorBurzio, Verónica A.
dc.contributor.authorDelmas, Bernard
dc.contributor.authorBarrey, Eric
dc.date.accessioned2023-04-17T23:04:49Z
dc.date.available2023-04-17T23:04:49Z
dc.date.issued2022-10
dc.descriptionIndexación: Scopuses
dc.description.abstractThe 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 respiratory syndrome coronavirus (SARS-CoV-2) genome. 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. Copyright © 2022 Dhorne-Pollet, Fitzpatrick, Da Costa, Bourgon, Eléouët, Meunier, Burzio, Delmas and Barrey.es
dc.description.urihttps://www.frontiersin.org/articles/10.3389/fmicb.2022.915202/full
dc.identifier.citationFrontiers in Microbiology Volume 1326 October 2022 Article number 915202es
dc.identifier.doi10.3389/fmicb.2022.915202
dc.identifier.issn1664-302X
dc.identifier.urihttps://repositorio.unab.cl/xmlui/handle/ria/48639
dc.language.isoenes
dc.publisherFrontiers Media S.A.es
dc.rights.licenseAtribución 4.0 Internacional (CC BY 4.0)
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/deed.es
dc.subjectASOes
dc.subjectCoronavirus; oligonucleotide antisense therapyes
dc.subjectRNA therapyes
dc.subjectRNA viruses
dc.subjectSARS-CoV-2es
dc.subjectSARS-CoV-2es
dc.subjectAntisense therapy RNA viruses
dc.titleAntisense oligonucleotides targeting ORF1b block replication of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)es
dc.typeArtículoes
Archivos
Bloque original
Mostrando 1 - 1 de 1
Miniatura
Nombre:
Dhorne_S_Antisense_oligonucleotides_targeting_ORF1b_block_2022_Article.pdf
Tamaño:
1.95 MB
Formato:
Adobe Portable Document Format
Descripción:
TEXTO COMPLETO EN INGLES
Descargar
Bloque de licencias
Mostrando 1 - 1 de 1
No hay miniatura disponible
Nombre:
license.txt
Tamaño:
1.71 KB
Formato:
Item-specific license agreed upon to submission
Descripción:
Descargar
Colecciones
Fac.CV - Artículos de Revista