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Highly potent antisense oligonucleotides (ASOs) targeting the SARS-CoV-2 RNA genome

V. Dauksaite, A. Tas, F. Wachowius, A. Spruit, M.J. van Hemert, E.J. Snijder, E.P. van der Veer, View ORCID ProfileA.J. van Zonneveld
doi: https://doi.org/10.1101/2022.11.28.518195
V. Dauksaite
1Einthoven Laboratory of Vascular and Regenerative Medicine and the Department of Internal Medicine (Nephrology), Leiden University Medical Centre, Leiden, the Netherlands
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  • For correspondence: v.dauksaite@lumc.nl a.j.vanzonneveld@lumc.nl
A. Tas
2Department of Medical Microbiology, Leiden University Medical Centre, Leiden, the Netherlands
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F. Wachowius
4Hybridize Therapeutics BV, Leiden, the Netherlands
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A. Spruit
3Dutch Center for RNA Therapeutics, Leiden, the Netherlands
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M.J. van Hemert
2Department of Medical Microbiology, Leiden University Medical Centre, Leiden, the Netherlands
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E.J. Snijder
2Department of Medical Microbiology, Leiden University Medical Centre, Leiden, the Netherlands
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E.P. van der Veer
4Hybridize Therapeutics BV, Leiden, the Netherlands
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A.J. van Zonneveld
1Einthoven Laboratory of Vascular and Regenerative Medicine and the Department of Internal Medicine (Nephrology), Leiden University Medical Centre, Leiden, the Netherlands
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  • ORCID record for A.J. van Zonneveld
  • For correspondence: v.dauksaite@lumc.nl a.j.vanzonneveld@lumc.nl
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Abstract

Currently the world is dealing with the third outbreak of the human-infecting coronavirus with potential lethal outcome, cause by a member of the Nidovirus family, the SARS-CoV-2. The severe acute respiratory syndrome coronavirus (SARS-CoV-2) has caused the last worldwide pandemic. Successful development of vaccines highly contributed to reduce the severeness of the COVID-19 disease. To establish a control over the current and newly emerging coronaviruses of epidemic concern requires development of substances able to cure severely infected individuals and to prevent virus transmission. Here we present a therapeutic strategy targeting the SARS-CoV-2 RNA using antisense oligonucleotides (ASOs) and identify locked nucleic acid gapmers (LNA gapmers) potent to reduce by up to 96% the intracellular viral load in vitro. Our results strongly suggest promise of our preselected ASOs for further development as therapeutic or prophylactic anti-viral agents.

One sentence summary ASOs (LNA gapmers) targeting the SARS-CoV-2 RNA genome have been effective in viral RNA (load) reduction in vitro.

Competing Interest Statement

The authors have declared no competing interest.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission.
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Posted November 28, 2022.
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Highly potent antisense oligonucleotides (ASOs) targeting the SARS-CoV-2 RNA genome
V. Dauksaite, A. Tas, F. Wachowius, A. Spruit, M.J. van Hemert, E.J. Snijder, E.P. van der Veer, A.J. van Zonneveld
bioRxiv 2022.11.28.518195; doi: https://doi.org/10.1101/2022.11.28.518195
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Highly potent antisense oligonucleotides (ASOs) targeting the SARS-CoV-2 RNA genome
V. Dauksaite, A. Tas, F. Wachowius, A. Spruit, M.J. van Hemert, E.J. Snijder, E.P. van der Veer, A.J. van Zonneveld
bioRxiv 2022.11.28.518195; doi: https://doi.org/10.1101/2022.11.28.518195

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