The in vivo optical imaging of RNA biomarkers of inflammation is hindered by low signal-to-background ratios, owing to non-specific signal amplification in healthy tissues. Here we report the design and in vivo applicability, for the imaging of inflammation-associated messenger RNAs (mRNAs), of a molecular beacon bearing apurinic/apyrimidinic sites, whose amplification of fluorescence is triggered by human apurinic/apyrimidinic endonuclease 1 on translocation from the nucleus into the cytoplasm specifically in inflammatory cells. We assessed the sensitivity and tissue specificity of an engineered molecular beacon targeting interleukin-6 (IL-6) mRNA in live mice, by detecting acute inflammation in their paws and drug-induced inflammation in their livers. This enzymatic-amplification strategy may enable the specific and sensitive imaging of other disease-relevant RNAs in vivo.
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The main data supporting the results in this study are available within the paper and its Supplementary Information. The raw and analysed datasets generated during the study are too large to be publicly shared, yet they are available for research purposes from the corresponding authors on reasonable request. Source data are provided with this paper.
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This work was supported financially by the National Natural Science Foundation of China (22125402 (to L.L.) and 22004023 (to J.Z.)), the Youth Innovation Promotion Association CAS (to J.Z.), the National Key R&D Program of China (2021YFA1200104, to L.L.) and the Strategic Priority Research Program of Chinese Academy of Sciences (XDB36000000, to L.L. and Y.Z.).
The authors declare no competing interests.
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Sheng, C., Zhao, J., Di, Z. et al. Spatially resolved in vivo imaging of inflammation-associated mRNA via enzymatic fluorescence amplification in a molecular beacon. Nat. Biomed. Eng 6, 1074–1084 (2022). https://doi.org/10.1038/s41551-022-00932-z
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