环状 RNA 降低免疫原性，并能延长体内翻译时间。
RNA Circularization Diminishes Immunogenicity and Can Extend Translation Duration In Vivo.
机构信息
David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02142, USA; Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02142, USA.
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.
出版信息
Mol Cell. 2019 May 2;74(3):508-520.e4. doi: 10.1016/j.molcel.2019.02.015. Epub 2019 Mar 19.
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.
环状 RNA（circRNA）是一类具有连续结构的单链 RNA，具有增强的稳定性和缺乏与各种细胞蛋白相互作用所需的末端基序。在这里，我们表明未经修饰的外源性 circRNA 能够绕过细胞 RNA 传感器，从而避免在 RIG-I 和 Toll 样受体 (TLR) 功能齐全的细胞和小鼠中引发免疫反应。circRNA 制剂的免疫原性和蛋白表达稳定性取决于纯度，少量污染的线性 RNA 会导致强烈的细胞免疫反应。未经修饰的 circRNA 在体外比未经修饰的线性 mRNA 的免疫原性低，部分原因是逃避了 TLR 的感应。最后，我们首次提供了外源性 circRNA 在体内递呈和翻译的证据，并且我们表明与未经修饰和尿嘧啶修饰的线性 mRNA 相比，circRNA 翻译在脂肪组织中得到了延长。
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