Near-infrared fluorogenic RNA for in vivo imaging and sensing

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 typicall...

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Main Authors: 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, Xing Li
Format: Article
Language:English
Published: Nature Portfolio 2025-01-01
Series:Nature Communications
Online Access:https://doi.org/10.1038/s41467-024-55093-1
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Summary: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.
ISSN:2041-1723