Engineering RNA export for measurement and manipulation of living cells.

A system for programmable export of RNA molecules from living cells would enable both non-destructive monitoring of cell dynamics and engineering of cells capable of delivering executable RNA programs to other cells. We developed genetically encoded cellular RNA exporters, inspired by viruses, that efficiently package and secrete cargo RNA molecules from mammalian cells within protective nanoparticles. Exporting and sequencing RNA barcodes enabled non-destructive monitoring of cell population dynamics with clonal resolution. Further, by incorporating fusogens into the nanoparticles, we demonstrated the delivery, expression, and functional activity of exported mRNA in recipient cells. We term these systems COURIER (controlled output and uptake of RNA for interrogation, expression, and regulation). COURIER enables measurement of cell dynamics and establishes a foundation for hybrid cell and gene therapies based on cell-to-cell delivery of RNA. [Display omitted] • RNA exporters package and secrete RNA within protective nanoparticles • Engineered exporters achieve high specificity for cargo RNA • Sequencing exported RNA barcodes enables monitoring of cell population dynamics • Exporters enable cell-to-cell delivery and expression of mRNA cargo The development of RNA exporters, based on capsids and nanocages, for packaging and secretion of RNA, non-destructive monitoring of cells, and cell-to-cell delivery of mRNA. [ABSTRACT FROM AUTHOR]