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RNA Circularization Diminishes Immunogenicity and Can Extend Translation Duration In Vivo. | LitMetric

RNA Circularization Diminishes Immunogenicity and Can Extend Translation Duration In Vivo.

Mol Cell

David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02142, USA; Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, MA 02142, USA; Institute for Medical Engineering and Science, Massachusetts Institute of Technology, Cambridge, MA 02142, USA; Harvard and MIT Division of Health Science and Technology, Massachusetts Institute of Technology, Cambridge, MA 02142, USA. Electronic address:

Published: May 2019

AI Article Synopsis

Article Abstract

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.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6724735PMC
http://dx.doi.org/10.1016/j.molcel.2019.02.015DOI Listing

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