美国加州理工学院Michael B. Elowitz和Felix Horns共同合作，近期取得重要工作进展。他们研究开发出了用于活细胞测量和操作的工程RNA输出系统。相关研究成果2023年7月11日在线发表于《细胞》杂志上。

据介绍，从活细胞中可编程输出RNA分子的系统将能够对细胞动力学进行无损监测，并能够对可以向其它细胞递送可执行RNA程序的细胞进行工程改造。

受病毒的启发，研究人员开发了基因编码的细胞RNA输出器，可以有效地将哺乳动物细胞中的货物RNA分子包装并分泌到保护性纳米颗粒中。RNA条形码的导出和测序能够以克隆分辨率对细胞群体动态进行无损监测。

此外，通过将融合蛋白掺入纳米颗粒中，研究人员证明了受体细胞中输出mRNA的递送、表达和功能活性。研究人员将这些系统称为COURIER（用于询问、表达和调节的RNA的控制输出和摄取）。

总之， COURIER能够测量细胞动力学，并为基于细胞间RNA递送的混合细胞和基因疗法奠定基础。

附：英文原文

Title: Engineering RNA export for measurement and manipulation of living cells

Author: Felix Horns, Joe A. Martinez, Chengcheng Fan, Mehernaz Haque, James M. Linton, Victoria Tobin, Leah Santat, Ailiena O. Maggiolo, Pamela J. Bjorkman, Carlos Lois, Michael B. Elowitz

Issue&Volume: 2023-07-11

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.

DOI: 10.1016/j.cell.2023.06.013

Source: https://www.cell.com/cell/fulltext/S0092-8674(23)00689-X