Molecular Neurogenetics Unit, Department of Neurology and Center for Molecular Imaging Research, Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
Department of Oncology, University of Turin, Candiolo, Italy.
Nat Rev Mol Cell Biol. 2020 Oct;21(10):585-606. doi: 10.1038/s41580-020-0251-y. Epub 2020 May 26.
The term 'extracellular vesicles' refers to a heterogeneous population of vesicular bodies of cellular origin that derive either from the endosomal compartment (exosomes) or as a result of shedding from the plasma membrane (microvesicles, oncosomes and apoptotic bodies). Extracellular vesicles carry a variety of cargo, including RNAs, proteins, lipids and DNA, which can be taken up by other cells, both in the direct vicinity of the source cell and at distant sites in the body via biofluids, and elicit a variety of phenotypic responses. Owing to their unique biology and roles in cell-cell communication, extracellular vesicles have attracted strong interest, which is further enhanced by their potential clinical utility. Because extracellular vesicles derive their cargo from the contents of the cells that produce them, they are attractive sources of biomarkers for a variety of diseases. Furthermore, studies demonstrating phenotypic effects of specific extracellular vesicle-associated cargo on target cells have stoked interest in extracellular vesicles as therapeutic vehicles. There is particularly strong evidence that the RNA cargo of extracellular vesicles can alter recipient cell gene expression and function. During the past decade, extracellular vesicles and their RNA cargo have become better defined, but many aspects of extracellular vesicle biology remain to be elucidated. These include selective cargo loading resulting in substantial differences between the composition of extracellular vesicles and source cells; heterogeneity in extracellular vesicle size and composition; and undefined mechanisms for the uptake of extracellular vesicles into recipient cells and the fates of their cargo. Further progress in unravelling the basic mechanisms of extracellular vesicle biogenesis, transport, and cargo delivery and function is needed for successful clinical implementation. This Review focuses on the current state of knowledge pertaining to packaging, transport and function of RNAs in extracellular vesicles and outlines the progress made thus far towards their clinical applications.
术语“细胞外囊泡”是指源自细胞的囊泡体的异质群体,其源自内体区室(外泌体)或作为质膜脱落的结果(微囊泡、肿瘤小体和凋亡小体)。细胞外囊泡携带多种货物,包括 RNA、蛋白质、脂质和 DNA,这些货物可被其他细胞摄取,包括来源细胞的直接邻近细胞和体内远处部位的细胞,通过生物体液摄取,并引发各种表型反应。由于其独特的生物学特性及其在细胞间通讯中的作用,细胞外囊泡引起了强烈的兴趣,而其在临床应用中的潜力则进一步增强了这种兴趣。由于细胞外囊泡的货物源自产生它们的细胞的内容物,因此它们是各种疾病生物标志物的有吸引力的来源。此外,研究表明特定细胞外囊泡相关货物对靶细胞的表型效应,激发了将细胞外囊泡作为治疗载体的兴趣。有特别强有力的证据表明,细胞外囊泡的 RNA 货物可以改变受体细胞的基因表达和功能。在过去十年中,细胞外囊泡及其 RNA 货物的定义更加明确,但细胞外囊泡生物学的许多方面仍有待阐明。这些方面包括选择性货物装载导致细胞外囊泡与来源细胞的组成之间存在显著差异;细胞外囊泡大小和组成的异质性;以及受体细胞摄取细胞外囊泡及其货物命运的未定义机制。为了成功进行临床应用,需要进一步深入研究细胞外囊泡生物发生、运输和货物传递和功能的基本机制。这篇综述重点介绍了与 RNA 在细胞外囊泡中的包装、运输和功能相关的当前知识状态,并概述了迄今为止在其临床应用方面取得的进展。
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