Spatially resolved in vivo imaging of inflammation-associated mRNA via enzymatic fluorescence amplification in a molecular beacon

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. A molecular beacon engineered to be activated by the enzyme apurinic/apyrimidinic endonuclease 1 in inflammatory cells enables the specific and sensitive optical detection of inflammation in live mice.

Automated summary

The in vivo optical imaging of inflammation-associated messenger RNAs (mRNAs) is challenging due to the non-specific signal amplification in healthy tissues. In this study, researchers designed a molecular beacon with apurinic/apyrimidinic sites, which could be activated and amplified by human apurinic/apyrimidinic endonuclease 1 specifically in inflammatory cells translocating from the nucleus to the cytoplasm. The sensitivity and tissue specificity of this engineered molecular beacon targeting interleukin-6 (IL-6) mRNA were evaluated in live mice by detecting acute inflammation in paws and drug-induced inflammation in livers. This enzymatic-amplification strategy has the potential for specific and sensitive imaging of other disease-relevant RNAs in vivo.