Near-infrared fluorogenic RNA for in vivo imaging and sensing

Zhenyin Chen, Wei Chen, Cun Xu, Haozhi Song, Xin Ji, Haodong Jiang, Hongtao Duan, Zehao Li, Wankai Gao, Tuoxin Yao, Zhongxuan Zhang, Liuqin He, Yulong Yin, Nanyang Yang, Wenjing Tian, Jiahui Wu and Xing Li ()
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Zhenyin Chen: Chinese Academy of Sciences
Wei Chen: Central South University
Cun Xu: Chinese Academy of Sciences
Haozhi Song: Chinese Academy of Sciences
Xin Ji: Chinese Academy of Sciences
Haodong Jiang: Chinese Academy of Sciences
Hongtao Duan: Hebei University
Zehao Li: Hebei University
Wankai Gao: Chinese Academy of Sciences
Tuoxin Yao: Hunan Normal University
Zhongxuan Zhang: Chinese Academy of Sciences
Liuqin He: Hunan Normal University
Yulong Yin: Yuelushan Laboratory
Nanyang Yang: Central South University
Wenjing Tian: Jilin University
Jiahui Wu: University of Massachusetts
Xing Li: Chinese Academy of Sciences

Nature Communications, 2025, vol. 16, issue 1, 1-15

Abstract: Abstract Fluorogenic RNA aptamers have various applications, including use as fluorescent tags for imaging RNA trafficking and as indicators of RNA-based sensors that exhibit fluorescence upon binding small-molecule fluorophores in living cells. Current fluorogenic RNA:fluorophore complexes typically emit visible fluorescence. However, it is challenging to develop fluorogenic RNA with near-infrared (NIR) fluorescence for in vivo imaging and sensing studies. To address this issue, we identify and modulate red fluorescent protein-like fluorophores to bind Squash, a highly folded fluorogenic RNA. One of these fluorophores, DFQL-1T, exhibits photostable NIR fluorescence when bound to Squash, enabling RNA visualization in living mammalian cells and mice. With Squash:DFQL-1T complexes, we generate RNA-based sensors for detecting non-coding RNAs and small molecule targets in living mammalian cells and in mice. These studies reveal a fluorogenic RNA:fluorophore complex that can be readily developed into NIR fluorescent RNA tags for in vivo imaging and sensing.

Date: 2025
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DOI: 10.1038/s41467-024-55093-1

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