Extracellular vesicles (EVs) are fundamental for intercellular communication and influence nearly every process in cell physiology. However, because of their intricate molecular complexity, quantitative knowledge on their signaling mechanisms is missing, particularly impeding their therapeutic application. We used a complementary and quantitative engineering approach based on sequential synthetic bottom-up assembly of fully functional EVs with precisely controlled lipid, protein, and RNA composition. We show that the functionalities of synthetic EVs are analogous to natural EVs and demonstrate their programmable therapeutic administration for wound healing and neovascularization therapy. We apply transcriptome profiling to systematically decode synergistic effects between individual EV constituents, enabling analytical dissection and a fundamental understanding of EV signaling.

中文翻译：

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生物医学相关全合成细胞外囊泡的自下而上组装

细胞外囊泡 (EV) 是细胞间通讯的基础，几乎影响细胞生理学的每个过程。然而，由于它们错综复杂的分子复杂性，缺乏关于它们信号机制的定量知识，特别是阻碍了它们的治疗应用。我们使用了一种互补和定量工程方法，该方法基于具有精确控制的脂质、蛋白质和 RNA 成分的全功能 EV 的顺序合成自下而上组装。我们展示了合成 EV 的功能类似于天然 EV，并展示了它们用于伤口愈合和新血管形成治疗的可编程治疗管理。我们应用转录组分析系统地解码单个 EV 成分之间的协同效应，