An intranasal ASO therapeutic targeting SARS-CoV-2
In: Nature Communications, Jg. 13 (2022), Heft 1
Online
academicJournal
- 4503
The COVID-19 pandemic is exacting an increasing toll worldwide, with new SARS-CoV-2 variants emerging that exhibit higher infectivity rates and that may partially evade vaccine and antibody immunity. Rapid deployment of non-invasive therapeutic avenues capable of preventing infection by all SARS-CoV-2 variants could complement current vaccination efforts and help turn the tide on the COVID-19 pandemic. Here, we describe a novel therapeutic strategy targeting the SARS-CoV-2 RNA using locked nucleic acid antisense oligonucleotides (LNA ASOs). We identify an LNA ASO binding to the 5' leader sequence of SARS-CoV-2 that disrupts a highly conserved stem-loop structure with nanomolar efficacy in preventing viral replication in human cells. Daily intranasal administration of this LNA ASO in the COVID-19 mouse model potently suppresses viral replication (>80-fold) in the lungs of infected mice. We find that the LNA ASO is efficacious in countering all SARS-CoV-2 "variants of concern" tested both in vitro and in vivo. Hence, inhaled LNA ASOs targeting SARS-CoV-2 represents a promising therapeutic approach to reduce or prevent transmission and decrease severity of COVID-19 in infected individuals. LNA ASOs are chemically stable and can be flexibly modified to target different viral RNA sequences and could be stockpiled for future coronavirus pandemics.
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An intranasal ASO therapeutic targeting SARS-CoV-2
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Autor/in / Beteiligte Person: | Zhu, Chi ; Lee, Justin Y ; Woo, Jia Z ; Xu, Lei ; Nguyenla, Xammy ; Yamashiro, Livia H ; Ji, Fei ; Biering, Scott B ; Van Dis, Erik ; Gonzalez, Federico ; Fox, Douglas ; Wehri, Eddie ; Rustagi, Arjun ; Pinsky, Benjamin A ; Schaletzky, Julia ; Blish, Catherine A ; Chiu, Charles ; Harris, Eva ; Sadreyev, Ruslan I ; Stanley, Sarah ; Kauppinen, Sakari ; Rouskin, Silvi ; Näär, Anders M |
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Zeitschrift: | Nature Communications, Jg. 13 (2022), Heft 1 |
Veröffentlichung: | eScholarship, University of California, 2022 |
Medientyp: | academicJournal |
Umfang: | 4503 |
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