Researchers studying RNA directly in cells have faced a trade-off: They could either view many genes with little detail or fewer genes in high detail. Yale scientists have now developed an approach that offers the best of both worlds, described in Cell (October 2025). The lab of Siyuan (Steven) Wang, PhD, associate professor of genetics and cell biology, developed a technique called Reverse-padlock Amplicon Encoding Fluorescence In Situ Hybridization (RAEFISH), which attaches special probes to RNA molecules inside cells. The probes then make copies of targeted RNAs, and fluorescent tags allow researchers to view the copies under a microscope. RAEFISH enables researchers to see which genes in a cell are active, the locations in a cell or tissue where the genes’ RNAs are working, and how cells interact with one another. “We could potentially discover new therapeutic biomarkers to treat diseases such as cancer where it’s critical to understand how cancer cells interact with other cells in the surrounding tissue microenvironment,” says Wang.
Related article: New Technique Offers Bigger and Better Window into RNA Activity in Complex Tissue (Yale News, October 2, 2025)