Staufer Oskar, Dietrich Franziska, Rimal Rahul, Schröter Martin, Fabritz Sebastian, Boehm Heike, Singh Smriti, Möller Martin, Platzman Ilia, Spatz Joachim Pius
Department for Cellular Biophysics, Max Planck Institute for Medical Research, Jahnstraße 29, 69120 Heidelberg, Germany.
Institute for Molecular Systems Engineering (IMSE), Heidelberg University, 69120 Heidelberg, Germany.
Sci Adv. 2021 Sep 3;7(36):eabg6666. doi: 10.1126/sciadv.abg6666.
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.
细胞外囊泡（EVs）是细胞间通讯的基础，几乎影响细胞生理学中的每个过程。然而，由于其复杂的分子复杂性，关于其信号传导机制的定量知识缺失，这尤其阻碍了它们的治疗应用。我们采用了一种互补的定量工程方法，该方法基于具有精确控制的脂质、蛋白质和RNA组成的全功能EVs的顺序合成自下而上组装。我们表明，合成EVs的功能类似于天然EVs，并证明了它们在伤口愈合和新血管形成治疗中的可编程治疗应用。我们应用转录组分析来系统地解码单个EV成分之间的协同效应，从而能够对EV信号进行分析剖析并获得基本理解。
