What goes around comes around: Artificial circular RNAs bypass cellular antiviral responses

被引：17

作者：

Breuer, Janina ^{[1
]}

Barth, Patrick ^{[2
]}

Noe, Yannic ^{[1
]}

Shalamova, Lyudmila ^{[3
]}

Goesmann, Alexander ^{[2
]}

Weber, Friedemann ^{[3
]}

Rossbach, Oliver ^{[1
]}

机构：

[1] Justus Liebig Univ Giessen, Inst Biochem, Fac Biol & Chem FB08, Heinrich Buff Ring 17, D-35392 Giessen, Germany

[2] Univ Giessen, Bioinformat & Syst Biol, Heinrich Buff Ring 58, D-35392 Giessen, Germany

[3] Univ Giessen, Inst Virol, Fac Vet Med, Schubertstr 81, D-35392 Giessen, Germany

来源：

MOLECULAR THERAPY NUCLEIC ACIDS | 2022年 / 28卷

关键词：

NON-SELF; INTRON; DISCRIMINATION; TRANSLATION; BIOGENESIS; ACTIVATION; SUPPRESS; CIRCLES; BINDING; SPLICE;

D O I：

10.1016/j.omtn.2022.04.017

中图分类号：

R-3 [医学研究方法]; R3 [基础医学];

学科分类号：

1001 ;

摘要：

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 tic 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 We find that circular RNAs produced by the presented methodology do not trigger the antiviral response and do not activate innate immune-signaling pathways.

引用

页码：623 / 635

页数：13