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Nucleic Acid Ther . Highly Potent Antisense Oligonucleotides Locked Nucleic Acid Gapmers Targeting the SARS-CoV-2 RNA Genome

tetano

Editor, Senior Moderator
Nucleic Acid Ther


. 2023 Sep 29.
doi: 10.1089/nat.2023.0012. Online ahead of print. Highly Potent Antisense Oligonucleotides Locked Nucleic Acid Gapmers Targeting the SARS-CoV-2 RNA Genome

Vita Dauksaite[SUP] 1 [/SUP], Ali Tas[SUP] 2 [/SUP], Falk Wachowius[SUP] 3 [/SUP], Anouk Spruit[SUP] 1 [/SUP], Martijn J van Hemert[SUP] 2 [/SUP], Eric J Snijder[SUP] 2 [/SUP], Eric P van der Veer[SUP] 3 [/SUP], Anton Jan van Zonneveld[SUP] 1 [/SUP]



Affiliations
Abstract

The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has caused the current worldwide pandemic and the associated coronavirus disease 2019 with potentially lethal outcome. Although effective vaccines strongly contributed to reduce disease severity, establishing a toolbox to control current and newly emerging coronaviruses of epidemic concern requires the development of novel therapeutic compounds, to treat severely infected individuals and to prevent virus transmission. Here we present a therapeutic strategy targeting the SARS-CoV-2 RNA genome using antisense oligonucleotides (ASOs). We demonstrate that selected locked nucleic acid gapmers have the potency to reduce the in vitro intracellular viral load by up to 96%. Our promising results strongly support the case for further development of our preselected ASOs as therapeutic or prophylactic antiviral agents.

Keywords: LNA gapmers; SARS-CoV-2; antisense oligonucleotides; coronavirus; positive-sense RNA virus; therapeutic oligonucleotides.

 
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