Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA 91125, USA; Howard Hughes Medical Institute, California Institute of Technology, Pasadena, CA 91125, USA.
Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA 91125, USA.
Cell. 2023 Aug 17;186(17):3642-3658.e32. doi: 10.1016/j.cell.2023.06.013. Epub 2023 Jul 11.
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.
一种可编程的从活细胞中输出 RNA 分子的系统将能够实现对细胞动力学的非破坏性监测，以及对能够向其他细胞输送可执行 RNA 程序的细胞进行工程改造。我们受病毒启发，开发了基因编码的细胞 RNA 外排器，该外排器能够在保护性纳米颗粒内有效地包装和分泌细胞内的货物 RNA 分子。通过对 RNA 条形码进行导出和测序，实现了对细胞群体动力学的非破坏性监测，达到了克隆分辨率。此外，通过将融合蛋白整合到纳米颗粒中，我们在受体细胞中证明了导出的 mRNA 的传递、表达和功能活性。我们将这些系统称为 COURIER（用于检测、表达和调控的 RNA 可控输出和摄取）。COURIER 能够测量细胞动力学，并为基于细胞间 RNA 传递的混合细胞和基因治疗奠定了基础。
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