tetano
Editor, Senior Moderator
Nucleic Acids Res
. 2021 Nov 24;gkab1096.
doi: 10.1093/nar/gkab1096. Online ahead of print.
Inhibition of SARS-CoV-2 coronavirus proliferation by designer antisense-circRNAs
Christina Pfafenrot[SUP] 1 [/SUP], Tim Schneider[SUP] 1 [/SUP], Christin Müller[SUP] 2 [/SUP], Lee-Hsueh Hung[SUP] 1 [/SUP], Silke Schreiner[SUP] 1 [/SUP], John Ziebuhr[SUP] 2 [/SUP], Albrecht Bindereif[SUP] 1 [/SUP]
Affiliations
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.
. 2021 Nov 24;gkab1096.
doi: 10.1093/nar/gkab1096. Online ahead of print.
Inhibition of SARS-CoV-2 coronavirus proliferation by designer antisense-circRNAs
Christina Pfafenrot[SUP] 1 [/SUP], Tim Schneider[SUP] 1 [/SUP], Christin Müller[SUP] 2 [/SUP], Lee-Hsueh Hung[SUP] 1 [/SUP], Silke Schreiner[SUP] 1 [/SUP], John Ziebuhr[SUP] 2 [/SUP], Albrecht Bindereif[SUP] 1 [/SUP]
Affiliations
- PMID: 34850109
- DOI: 10.1093/nar/gkab1096
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.