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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...
Autores principales: | , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2023
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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. |
format | Online Article Text |
id | pubmed-9897518 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
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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