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Antisense oligonucleotides to therapeutically target SARS-CoV-2 infection

Although the COVID-19 pandemic began over three years ago, the virus responsible for the disease, SARS-CoV-2, continues to infect people across the globe. As such, there remains a critical need for development of novel therapeutics against SARS-CoV-2. One technology that has remained relatively unex...

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Autores principales: Qiao, Yuanyuan, Wotring, Jesse W., Zhang, Charles J., Jiang, Xia, Xiao, Lanbo, Watt, Andy, Gattis, Danielle, Scandalis, Eli, Freier, Susan, Zheng, Yang, Pretto, Carla D., Ellison, Stephanie J., Swayze, Eric E., Guo, Shuling, Sexton, Jonathan Z., Chinnaiyan, Arul M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9897518/
https://www.ncbi.nlm.nih.gov/pubmed/36735698
http://dx.doi.org/10.1371/journal.pone.0281281
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author Qiao, Yuanyuan
Wotring, Jesse W.
Zhang, Charles J.
Jiang, Xia
Xiao, Lanbo
Watt, Andy
Gattis, Danielle
Scandalis, Eli
Freier, Susan
Zheng, Yang
Pretto, Carla D.
Ellison, Stephanie J.
Swayze, Eric E.
Guo, Shuling
Sexton, Jonathan Z.
Chinnaiyan, Arul M.
author_facet Qiao, Yuanyuan
Wotring, Jesse W.
Zhang, Charles J.
Jiang, Xia
Xiao, Lanbo
Watt, Andy
Gattis, Danielle
Scandalis, Eli
Freier, Susan
Zheng, Yang
Pretto, Carla D.
Ellison, Stephanie J.
Swayze, Eric E.
Guo, Shuling
Sexton, Jonathan Z.
Chinnaiyan, Arul M.
author_sort Qiao, Yuanyuan
collection PubMed
description Although the COVID-19 pandemic began over three years ago, the virus responsible for the disease, SARS-CoV-2, continues to infect people across the globe. As such, there remains a critical need for development of novel therapeutics against SARS-CoV-2. One technology that has remained relatively unexplored in COVID-19 is the use of antisense oligonucleotides (ASOs)—short single-stranded nucleic acids that bind to target RNA transcripts to modulate their expression. In this study, ASOs targeted against the SARS-CoV-2 genome and host entry factors, ACE2 and TMPRSS2, were designed and tested for their ability to inhibit cellular infection by SARS-CoV-2. Using our previously developed SARS-CoV-2 bioassay platform, we screened 180 total ASOs targeting various regions of the SARS-CoV-2 genome and validated several ASOs that potently blocked SARS-CoV-2 infection in vitro. Notably, select ASOs retained activity against both the WA1 and B.1.1.7 (commonly known as alpha) variants. Screening of ACE2 and TMPRSS2 ASOs showed that targeting of ACE2 also potently prevented infection by the WA1 and B.1.1.7 SARS-CoV-2 viruses in the tested cell lines. Combined with the demonstrated success of ASOs in other disease indications, these results support further research into the development of ASOs targeting SARS-CoV-2 and host entry factors as potential COVID-19 therapeutics.
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spelling pubmed-98975182023-02-04 Antisense oligonucleotides to therapeutically target SARS-CoV-2 infection Qiao, Yuanyuan Wotring, Jesse W. Zhang, Charles J. Jiang, Xia Xiao, Lanbo Watt, Andy Gattis, Danielle Scandalis, Eli Freier, Susan Zheng, Yang Pretto, Carla D. Ellison, Stephanie J. Swayze, Eric E. Guo, Shuling Sexton, Jonathan Z. Chinnaiyan, Arul M. PLoS One Research Article Although the COVID-19 pandemic began over three years ago, the virus responsible for the disease, SARS-CoV-2, continues to infect people across the globe. As such, there remains a critical need for development of novel therapeutics against SARS-CoV-2. One technology that has remained relatively unexplored in COVID-19 is the use of antisense oligonucleotides (ASOs)—short single-stranded nucleic acids that bind to target RNA transcripts to modulate their expression. In this study, ASOs targeted against the SARS-CoV-2 genome and host entry factors, ACE2 and TMPRSS2, were designed and tested for their ability to inhibit cellular infection by SARS-CoV-2. Using our previously developed SARS-CoV-2 bioassay platform, we screened 180 total ASOs targeting various regions of the SARS-CoV-2 genome and validated several ASOs that potently blocked SARS-CoV-2 infection in vitro. Notably, select ASOs retained activity against both the WA1 and B.1.1.7 (commonly known as alpha) variants. Screening of ACE2 and TMPRSS2 ASOs showed that targeting of ACE2 also potently prevented infection by the WA1 and B.1.1.7 SARS-CoV-2 viruses in the tested cell lines. Combined with the demonstrated success of ASOs in other disease indications, these results support further research into the development of ASOs targeting SARS-CoV-2 and host entry factors as potential COVID-19 therapeutics. Public Library of Science 2023-02-03 /pmc/articles/PMC9897518/ /pubmed/36735698 http://dx.doi.org/10.1371/journal.pone.0281281 Text en © 2023 Qiao et al https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Qiao, Yuanyuan
Wotring, Jesse W.
Zhang, Charles J.
Jiang, Xia
Xiao, Lanbo
Watt, Andy
Gattis, Danielle
Scandalis, Eli
Freier, Susan
Zheng, Yang
Pretto, Carla D.
Ellison, Stephanie J.
Swayze, Eric E.
Guo, Shuling
Sexton, Jonathan Z.
Chinnaiyan, Arul M.
Antisense oligonucleotides to therapeutically target SARS-CoV-2 infection
title Antisense oligonucleotides to therapeutically target SARS-CoV-2 infection
title_full Antisense oligonucleotides to therapeutically target SARS-CoV-2 infection
title_fullStr Antisense oligonucleotides to therapeutically target SARS-CoV-2 infection
title_full_unstemmed Antisense oligonucleotides to therapeutically target SARS-CoV-2 infection
title_short Antisense oligonucleotides to therapeutically target SARS-CoV-2 infection
title_sort antisense oligonucleotides to therapeutically target sars-cov-2 infection
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9897518/
https://www.ncbi.nlm.nih.gov/pubmed/36735698
http://dx.doi.org/10.1371/journal.pone.0281281
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