mRNA‐encoded fluorescent proteins enable superior organelle labeling for live cell imaging

Abstract Live cell labeling of various organelles is of great demand in the research field of cell biology. However, current approaches often lack an optimal balance between efficiency and versatility. We took advantage of chemical modified mRNA to express various organelle located fluorescent proteins. This approach facilitated highly efficient multi‐organelle labeling across diverse cell types, both in vitro and in vivo. The application of mRNA‐based organelle markers offers faster and more efficient transfection and expression compared to plasmids. When expressing fluorescent proteins in neuronal cells, it is faster and safer compared to viral vectors. Notably, this approach excels in rapidly labeling organelles, making it highly effective for dynamic live cell imaging applications. By leveraging this tool, we unveiled the unique behaviors of mitochondria and the endoplasmic reticulum during spike protein‐mediated cell fusion, a critical event in SARS‐CoV‐2 viral entry. Thus, our results demonstrate the potency of mRNA‐encoded fluorescent proteins as powerful tools for advancing biological research.