Could a new bioluminescent imaging technology transform how RNA dynamics are visualized in living systems? In Nature Communications, researchers detail the development of "RNA lanterns" – a genetically encoded platform that tracks RNA transcripts in real-time and without invasive procedures or tissue autofluorescence.
Specifically, the system relies on split luciferase fragments (NanoBiT) attached to bacteriophage coat proteins that bind RNA aptamers engineered into target transcripts. Upon binding, the luciferase fragments reassemble and emit light when exposed to luciferin, enabling precise RNA visualization with high sensitivity and minimal background interference. Unlike traditional fluorescence-based methods, the new approach does not require external light excitation, avoiding issues such as phototoxicity and shallow imaging depth.
The team demonstrated that a single RNA bait sequence was sufficient for detecting transcripts in various biological contexts – from cellular models to live animal tissues. The RNA lanterns were also shown to work across multiple RNA targets and split reporter systems, including color-shifted variants for deeper tissue imaging. Imaging RNA transcripts associated with stress responses and cellular structures revealed dynamic localization patterns, showcasing the system’s potential in studying complex biological processes.
In live animal models, the researchers achieved subcutaneous RNA imaging, where luminescence correlated with RNA expression levels, setting the stage for real-time monitoring of gene expression in vivo and opening doors to applications in disease modeling and therapeutic development.
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