单位：[1]School of Chemistry and Chemical Engineering, New Cornerstone Science Laboratory, Frontiers Science Center for Transformative Molecules, Zhangjiang Institute for Advanced Study and National Center for Translational Medicine, Shanghai Jiao Tong University, Shanghai 200240, China.[2]Department of Oncology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.肿瘤科华中科技大学同济医学院附属同济医院[3]School of Molecular Sciences and Biodesign Center for Molecular Design and Biomimetics, Biodesign Institute, Arizona State University, Tempe, Arizona 85287, United States.[4]Institute of Molecular Medicine, Shanghai Key Laboratory for Nucleic Acids Chemistry and Nanomedicine, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200127, China.[5]Institute of Materiobiology, Department of Chemistry, College of Science, Shanghai University, Shanghai 200444, China.
The integration of functional modules at the molecular level into RNA nanostructures holds great potential for expanding their applications. However, the quantitative integration of nucleoside analogue molecules into RNA nanostructures and their impact on the structure and function of RNA nanostructures remain largely unexplored. Here, we report a transcription-based approach to controllably integrate multiple nucleoside analogues into a 2000 nucleotide (nt) single-stranded RNA (ssRNA) origami nanostructure. The resulting integrated ssRNA origami preserves the morphology and biostability of the original ssRNA origami. Moreover, the integration of nucleoside analogues introduced new biomedical functions to ssRNA origamis, including innate immune recognition and regulation after the precise integration of epigenetic nucleoside analogues and synergistic effects on tumor cell killing after integration of therapeutic nucleoside analogues. This study provides a promising approach for the quantitative integration of functional nucleoside analogues into RNA nanostructures at the molecular level, thereby offering valuable insights for the development of multifunctional ssRNA origamis.
基金：
K.D., F.D., X.L., C.F., and G.Y. are grateful for financial
support from the National Key R&D Program of China
(2020YFA0908900), the National Natural Science Foundation
of China (22174093, 21834007, 21991134, 21934007, and
T2188102), the Fundamental Research Funds for the Central
Universities, and the New Cornerstone Science Foundation.
第一作者单位：[1]School of Chemistry and Chemical Engineering, New Cornerstone Science Laboratory, Frontiers Science Center for Transformative Molecules, Zhangjiang Institute for Advanced Study and National Center for Translational Medicine, Shanghai Jiao Tong University, Shanghai 200240, China.
通讯作者：
推荐引用方式(GB/T 7714)：
Dai Kun,Gong Chen,Xu Yang,et al.Single-Stranded RNA Origami-Based Epigenetic Immunomodulation[J].NANO LETTERS.2023,23(15):7188-7196.doi:10.1021/acs.nanolett.3c02185.
材料科学