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Spatially resolved in vivo imaging of inflammation-associated mRNA via enzymatic fluorescence amplification in a molecular beacon
Nature Biomedical Engineering ( IF 26.8 ) Pub Date : 2022-09-01 , DOI: 10.1038/s41551-022-00932-z
Chuangui Sheng 1, 2 , Jian Zhao 1, 2 , Zhenghan Di 1, 2 , Yuanyu Huang 3 , Yuliang Zhao 1, 2, 4 , Lele Li 1, 2, 4
Affiliation  

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.



中文翻译:

通过分子信标中的酶促荧光放大对炎症相关 mRNA 进行空间分辨的体内成像

由于健康组织中的非特异性信号放大,炎症的 RNA 生物标志物的体内光学成像受到低信噪比的阻碍。在这里,我们报告了带有脱嘌呤/脱嘧啶位点的分子信标的设计和体内适用性,用于炎症相关信使 RNA (mRNA) 的成像,其荧光放大是由人类脱嘌呤/脱嘧啶核酸内切酶 1 在易位时触发的。细胞核进入细胞质,特别是在炎症细胞中。我们评估了靶向白细胞介素 6 ( IL-6 ) 的工程分子信标的敏感性和组织特异性。) mRNA,通过检测它们爪子中的急性炎症和它们肝脏中的药物引起的炎症。这种酶促扩增策略可以在体内对其他与疾病相关的 RNA 进行特异性和灵敏的成像。

更新日期:2022-09-02
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