Engineering RNA export for measurement and manipulation of living cells

Cell. 2023 Aug 17;186(17):3642-3658.e32. doi: 10.1016/j.cell.2023.06.013. Epub 2023 Jul 11.

Abstract

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.

Keywords: RNA; delivery; export; extracellular vesicles; monitoring; non-destructive; reporter; virus-like particles.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Biological Transport
  • Cytological Techniques*
  • Genetic Techniques*
  • Mammals / metabolism
  • Molecular Typing
  • RNA* / genetics
  • RNA* / metabolism
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Sequence Analysis, RNA
  • Viruses / genetics

Substances

  • RNA
  • RNA, Messenger