What goes around comes around: Artificial circular RNAs bypass cellular antiviral responses.
Mol Ther Nucleic Acids
; 28: 623-635, 2022 Jun 14.
Article
in En
| MEDLINE
| ID: mdl-35497503
ABSTRACT
Natural circular RNAs have been found to sequester microRNAs and suppress their function. We have used this principle as a molecular tool and produced artificial circular RNA sponges in a cell-free system by in vitro transcription and ligation. Formerly, we were able to inhibit hepatitis C virus propagation by applying a circular RNA decoy strategy against microRNA-122, which is essential for the viral life cycle. In another proof-of-principle study, we used circular RNAs to sequester microRNA-21, an oncogenic and pro-proliferative microRNA. This strategy slowed tumor growth in a 3D cell culture model system, as well as in xenograft mice upon systemic delivery. In the wake of the global use of an in vitro transcribed RNA in coronavirus disease 2019 (COVID-19) vaccines, the question arose whether therapeutic circular RNAs trigger cellular antiviral defense mechanisms when delivered systemically. In this study, we present data on the cellular innate immune response as a consequence of liposome-based transfection of the circular RNA sponges we previously used to inhibit microRNA function. We find that circular RNAs produced by the presented methodology do not trigger the antiviral response and do not activate innate immune-signaling pathways.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Language:
En
Journal:
Mol Ther Nucleic Acids
Year:
2022
Type:
Article
Affiliation country:
Germany