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基于融合球形核酸的仿生方法实现细胞膜的空间控制工程

A Biomimetic Approach for Spatially Controlled Cell Membrane Engineering Using Fusogenic Spherical Nucleic Acid.

机构信息

Institute of Chemical Biology and Nanomedicine, State Key Laboratory of Chemo/Biosensing and Chemometrics, Hunan Provincial Key Laboratory of Biomacromolecular Chemical Biology, College of Chemistry and Chemical Engineering, Hunan University, Changsha, 410082, China.

Institute of Chemical Biology and Nanomedicine, College of Biology, Hunan University, Changsha, 410082, China.

出版信息

Angew Chem Int Ed Engl. 2022 Jan 3;61(1):e202111647. doi: 10.1002/anie.202111647. Epub 2021 Nov 25.

DOI:10.1002/anie.202111647
PMID:34637590
Abstract

Engineering of the cell plasma membrane using functional DNA is important for studying and controlling cellular behaviors. However, most efforts to apply artificial DNA interactions on cells are limited to external membrane surface due to the lack of suitable synthetic tools to engineer the intracellular side, which impedes many applications in cell biology. Inspired by the natural extracellular vesicle-cell fusion process, we have developed a fusogenic spherical nucleic acid construct to realize robust DNA functionalization on both external and internal cell surfaces via liposome fusion-based transport (LiFT) strategy, which enables applications including the construction of heterotypic cell assembly for programmed signaling pathway and detection of intracellular metabolites. This approach can engineer cell membranes in a highly efficient and spatially controlled manner, allowing one to build anisotropic membrane structures with two orthogonal DNA functionalities.

摘要

利用功能性 DNA 对细胞膜进行工程改造对于研究和控制细胞行为非常重要。然而,由于缺乏合适的合成工具来对细胞内表面进行工程改造,大多数将人工 DNA 相互作用应用于细胞的努力都仅限于细胞膜表面,这阻碍了细胞生物学中的许多应用。受天然细胞外囊泡与细胞融合过程的启发,我们开发了一种融合球形核酸构建体,通过基于脂质体融合的转染(LiFT)策略,在外部和内部细胞表面实现强大的 DNA 功能化,这使得包括构建用于程序化信号通路的异型细胞组装体和检测细胞内代谢物在内的应用成为可能。这种方法可以高效且空间受控地对细胞膜进行工程改造,允许构建具有两个正交 DNA 功能的各向异性膜结构。

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