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

Dauksaite, V.; Tas, A.; Wachowius, F.; Spruit, A.; van Hemert, M.; Snijder, E.; van der Veer, E. P.; van Zonneveld, A. J.

2022-11-28 molecular biology
10.1101/2022.11.28.518195 bioRxiv
Show 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 summaryASOs (LNA gapmers) targeting the SARS-CoV-2 RNA genome have been effective in viral RNA (load) reduction in vitro.

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