Journal article

Publication year: 2021

Pages: 12502-12516

Journal: Nucleic Acids Research

Volume number: 49

Issue number: 21

ISSN: 0305-1048

Open access status: Gold

DOI Link: https://doi.org/10.1093/nar/gkab1096

Publisher: Oxford University Press

Abstract: 
Circular RNAs (circRNAs) are noncoding RNAs that exist in all eukaryotes investigated and are derived from back-splicing of certain pre-mRNA exons. Here, we report the application of artificial circRNAs designed to act as antisense-RNAs. We systematically tested a series of antisense-circRNAs targeted to the SARS-CoV-2 genome RNA, in particular its structurally conserved 5'-untranslated region. Functional assays with both reporter transfections as well as with SARS-CoV-2 infections revealed that specific segments of the SARS-CoV-2 5'-untranslated region can be efficiently accessed by specific antisense-circRNAs, resulting in up to 90% reduction of virus proliferation in cell culture, and with a durability of at least 48 h. Presenting the antisense sequence within a circRNA clearly proved more efficient than in the corresponding linear configuration and is superior to modified antisense oligonucleotides. The activity of the antisense-circRNA is surprisingly robust towards point mutations in the target sequence. This strategy opens up novel applications for designer circRNAs and promising therapeutic strategies in molecular medicine.

Harvard Citation style: Pfafenrot, C., Schneider, T., Müller, C., Hung, L., Schreiner, S., Ziebuhr, J., et al. (2021) Inhibition of SARS-CoV-2 coronavirus proliferation by designer antisense-circRNAs, Nucleic Acids Research, 49(21), pp. 12502-12516. https://doi.org/10.1093/nar/gkab1096

APA Citation style: Pfafenrot, C., Schneider, T., Müller, C., Hung, L., Schreiner, S., Ziebuhr, J., & Bindereif, A. (2021). Inhibition of SARS-CoV-2 coronavirus proliferation by designer antisense-circRNAs. Nucleic Acids Research. 49(21), 12502-12516. https://doi.org/10.1093/nar/gkab1096