Nature BE: Li Lele's team achieved real-time dynamic imaging and early diagnosis of inflammation-related mRNA in vivo

Inflammation is considered a key factor

Routine diagnostic methods include blood biomarker testing, tissue biopsy, and urinalysis, but these are usually single-point tests and cannot be used for real-time, dynamic monitoring

Some recent studies have shown that RNA can regulate the occurrence, development, and regression of inflammation by changing expression and localization, and is a key regulator of the inflammatory process, so RNA may serve as a biomarker for inflammation diagnosis, but in vivo optical imaging using RNA as a biomarker for inflammation has not been demonstrated

On September 1, 2022, the Li Lele Research Group of the National Center for Nanoscience published a paper in the journal Nature Biomedical Engineering titled Spatially resolved in vivo imaging of inflammation-associated mRNA via enzymatic fluorescence amplification in a Molecular Beacon's research paper

The study designed and constructed an inflammatory cell-specific signal amplification method based on enzyme-triggered molecular beacons, which achieved real-time dynamic imaging and early diagnosis of inflammation by spatially selectively amplifying inflammation-related RNA imaging signals

Over the past two decades, scientists have developed a range of techniques that can sensitively detect RNA, including fluorescence in situ hybridization (FISH), in situ sequencing, and other methods that can provide RNA detection

However, amplification of RNA signals is required when performing RNA imaging, but these methods often require early fixation and permeation of cells

Molecular Beacon (MB) provides a straightforward and widely applicable tool for RNA analysis, and MB-assisted signal amplification can improve RNA detection sensitivity, but it is only suitable for detection in test tubes and has not yet been applied to RNA imaging

In March 2019, Li Lele's research group published a paper in JACS, which realized spatiotemporal controllable live-cell RNA imaging by constructing photosensitive molecular beacons and combining with conversion luminescence

However, in this method, a molecular beacon can only recognize one target RNA, so the signal output is insufficient and the detection sensitivity is not high

In this latest study, Li Lele's team designed and developed a molecular beacon (MB) probe triggered by human deminine/despyrimidine endonuclease 1 (APE1) - E-MBP, based on previous research, for specifically magnifying RNA in vivo, so that inflammation can be directly assessed

APE1 is a versatile enzyme that repairs DNA damage by removing the depurine/depyrimidine site, and the signal amplification mechanism of this method is the selective cleavage of APE1 target RNA-dependent inflammatory cells to molecular beacons, which can specifically multiply the response signal within inflammatory cells, enabling high-letter-back ratio imaging

Enzymatic signal amplification enables instem-resolved imaging of inflammation-related mRNAs

Next, the team selected the mRNA of the important inflammatory biomarker IL-6 as a target to verify the sensitivity and tissue specificity of E-MBP in living animals, delivering E-MBP into cells through polymer nanocarriers

Overall, this study provides a new approach to highly sensitive imaging of inflammation-related RNA that is expected to be applied to the early diagnosis and real-time evaluation of the treatment process of inflammation-related diseases

Sheng Chuangui and Associate Researcher Zhao Jian of the National Nanoscience Center are the co-first authors of the article, Li Lele, a researcher at the National Nanoscience Center, is the corresponding author, and Professor Huang Yuanyu of Beijing Institute of Technology and Academician Zhao Yuliang of the National Center for Nanoscience provide strong support

Original source:

Sheng， C.