Citation: Yue Jin, Kun Dai, Lu Song, Xiaolei Zuo, Guangbao Yao, Min Li. Valence-programmed RNA origami for potent innate immune activation[J]. Chinese Chemical Letters, ;2025, 36(10): 110744. doi: 10.1016/j.cclet.2024.110744 shu

Valence-programmed RNA origami for potent innate immune activation

Yue Jin ^{a, c} ,
Kun Dai ^b ,
Lu Song ^a ,
Xiaolei Zuo ^a ,
Guangbao Yao ^{b, *,} ,
Min Li ^{a, *,}

a.
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
b.
School of Chemistry and Chemical Engineering, Frontiers Science Center for Transformative Molecules, Zhangjiang Institute for Advanced Study and National Center for Translational Medicine, Shanghai Jiao Tong University, Shanghai 200240, China
c.
Department of Obstetrics and Gynecology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200127, China

yaoguangbao@sjtu.edu.cn

limin2021@sjtu.edu.cn

Received Date: 16 August 2024
Revised Date: 15 October 2024
Accepted Date: 9 December 2024
Available Online: 10 December 2024

Figures(4)

RNA offers distinct advantages for molecular self-assembly as a unique and programmable biomaterial. Recently, single-stranded RNA (ssRNA) origamis, capable of self-folding into defined nanostructures within a single-stranded RNA molecule, are considered a promising platform for immune recognition and therapy. Here, we utilize single-stranded rod RNA origami (Rod RNA-OG) as functional nucleic acid to synthesize valence-programmed RNA structures in a one-pot manner. We discover that the polyvalent RNA origamis are resistant to RNase degradation and can be efficiently internalized by macrophages for subsequent innate immune activation, even in the absence of any external protective agents such as lipids or polymers. The valence-programmed RNA origamis thus hold great promise as novel agonists for immunotherapy.
- RNA nanotechnology,
- ssRNA origamis,
- Valence-engineering,
- Innate immunity
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