RNA Circularization Diminishes Immunogenicity and Can Extend Translation Duration In Vivo
| Autor: | Frances C. Parker-Hale, Yuxuan Huang, R. Alexander Wesselhoeft, Daniel G. Anderson, Namita Bisaria, Piotr S. Kowalski |
|---|---|
| Rok vydání: | 2018 |
| Předmět: |
Biology
Article 03 medical and health sciences Mice 0302 clinical medicine Immune system Circular RNA Animals Gene Regulatory Networks RNA Messenger Receptor Molecular Biology Uridine 030304 developmental biology 0303 health sciences Messenger RNA Vaccines Synthetic RIG-I Immunogenicity Toll-Like Receptors RNA Translation (biology) Cell Biology RNA Circular Immunity Innate Cell biology MicroRNAs Gene Expression Regulation Protein Biosynthesis DEAD Box Protein 58 030217 neurology & neurosurgery |
| Zdroj: | Mol Cell PMC |
| ISSN: | 1097-4164 |
| Popis: | Circular RNAs (circRNAs) are a class of single-stranded RNAs with a contiguous structure that have enhanced stability and a lack of end motifs necessary for interaction with various cellular proteins. Here, we show that unmodified exogenous circRNA is able to bypass cellular RNA sensors and thereby avoid provoking an immune response in RIG-I and Toll-like receptor (TLR) competent cells and in mice. The immunogenicity and protein expression stability of circRNA preparations are found to be dependent on purity, with small amounts of contaminating linear RNA leading to robust cellular immune responses. Unmodified circRNA is less immunogenic than unmodified linear mRNA in vitro, in part due to the evasion of TLR sensing. Finally, we provide the first demonstration to our knowledge of exogenous circRNA delivery and translation in vivo, and we show that circRNA translation is extended in adipose tissue in comparison to unmodified and uridine-modified linear mRNAs. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|