In a recent paper published in Cell, researchers from the California Institute of Technology discuss an engineered RNA output system called COURIER (Controlled Output and Uptake of RNA for Interrogation, Expression, and Regulation) as a new tool for cell biology and medical research.
Lead author of the study: Dr. Felix Horns
RNA is a crucial carrier of cellular life activity information, and through RNA sequencing, the functional state of cells can be analyzed. However, RNA molecules are typically confined within cells, limiting their application in analyzing cell states and intercellular communication.
To solve this problem, Caltech researchers highlight the potential of engineered RNA output systems to enhance the ability of cells to release RNA molecules, enabling sensitive and non-destructive monitoring of live cells. Their approach involves using RNA virus particles as efficient RNA output vehicles. By engineering these virus particles, researchers achieved a high output of target RNA molecules in cell culture. Moreover, they introduced a modular protein-based RNA output system using protein nanocages (EPN) that demonstrated excellent compatibility with different cell types.
Biomarker Discovery: The engineered RNA output system presents an exciting opportunity to uncover biomarkers to shed light on health and disease. RNA molecules released from extracellular vesicles or dying cells can serve as valuable indicators of cellular health.
Precision Medicine: With the ability to deliver RNA molecules to specific cell populations, COURIER holds promise for precision medicine and cell-based therapies. It could be used to reprogram cell fate, selectively eliminate disease-state cells, and regulate cellular behavior, opening new avenues for targeted treatments.
Cell Biology: The research demonstrates that the COURIER system is highly compatible with various cell types and mammalian species. This adaptability paves the way for broader applications in cell biology and medical research.
One significant advantage of the COURIER system is its potential to non-destructively monitor the dynamic behavior of cell populations in response to drugs or other treatments. By using RNA barcodes, researchers could track the response of cell populations to drug treatment with high resolution, sensitivity, and reproducibility. This ability opens new possibilities for understanding immune responses, viral pathogenesis, tumor growth, and other biological processes. Another remarkable feature of the system is its capacity for intercellular communication, enabling functional mRNA delivery between cells, and offering new opportunities for genetic and cell therapies.
In conclusion, the engineered RNA output system COURIER represents a groundbreaking development in the field of cell biology and medicine. Its ability to efficiently package and secrete target RNA molecules from mammalian cells, coupled with the quantification framework for RNA output efficiency and specificity, makes it an ideal platform for creating multifunctional RNA reporters and delivery systems. The COURIER system will significantly contribute to our understanding of cellular behavior and gene regulation mechanisms, furthering research in cell biology and supporting the development of more precise therapeutic approaches.
 Horns et al., Engineering RNA export for measurement and manipulation of living cells, Cell (2023), https://doi.org/10.1016/j.cell.2023.06.013