CycleHCR: A New Imaging Technique Revolutionizes RNA and Protein Visualization in Thick Biological Samples

Researchers at the Howard Hughes Medical Institute's Janelia Research Campus have developed cycleHCR, a novel imaging technique that significantly improves the visualization of RNA and protein molecules within thick biological samples. This method addresses limitations of traditional techniques, which struggled to image numerous molecules in thick tissues. CycleHCR uses a DNA barcode system to tag and track hundreds of RNA and protein molecules in individual cells, providing a comprehensive view of their organization within tissues. The technique employs hybridization chain reaction (HCR) with multiple fluorophores to enhance visibility. Unlike previous methods limited by the number of available fluorescent colors, cycleHCR's DNA barcodes enable the tagging of each specific molecule, allowing for multiple rounds of imaging on the same sample. This allows the detection of hundreds or thousands of RNAs in a single sample. The technique also extends to protein detection, offering a comprehensive toolkit for analyzing both RNA and protein distributions. Automated measurement processes have increased throughput, enabling the detection of up to a dozen molecular species in a single day. Researchers are exploring cycleHCR's potential for clinical use in diagnostic imaging, particularly for diseases where gene expression patterns are informative. The Liu Lab provides open access to barcode sequences to facilitate wider adoption of cycleHCR.