Piffoux Max, Volatron Jeanne, Silva Amanda K A, Gazeau Florence
Centre Léon Bérard, Department of Medical Oncology, 69003 Lyon, France.
INSERM UMR 1197-Interaction Cellules Souches-Niches: Physiologie, Tumeurs et Réparation Tissulaire, 94800 Villejuif, France.
Pharmaceutics. 2021 Nov 15;13(11):1931. doi: 10.3390/pharmaceutics13111931.
Extracellular vesicles (EVs) are 50-1000 nm vesicles secreted by virtually any cell type in the body. They are expected to transfer information from one cell or tissue to another in a short- or long-distance way. RNA-based transfer of information via EVs at long distances is an interesting well-worn hypothesis which is ~15 years old. We review from a quantitative point of view the different facets of this hypothesis, ranging from natural RNA loading in EVs, EV pharmacokinetic modeling, EV targeting, endosomal escape and RNA delivery efficiency. Despite the unique intracellular delivery properties endowed by EVs, we show that the transfer of RNA naturally present in EVs might be limited in a physiological context and discuss the lessons we can learn from this example to design efficient RNA-loaded engineered EVs for biotherapies. We also discuss other potential EV mediated information transfer mechanisms, among which are ligand-receptor mechanisms.
细胞外囊泡（EVs）是由体内几乎任何细胞类型分泌的50 - 1000纳米的囊泡。它们有望以短距离或长距离的方式将信息从一个细胞或组织传递到另一个细胞或组织。基于RNA通过EVs进行的长距离信息传递是一个有趣且由来已久的假说，已有约15年历史。我们从定量的角度回顾这一假说的不同方面，包括EVs中天然RNA的装载、EVs的药代动力学建模、EVs的靶向、内体逃逸以及RNA传递效率。尽管EVs具有独特的细胞内递送特性，但我们表明，在生理环境中，EVs中天然存在的RNA的传递可能受到限制，并讨论我们可以从这个例子中学到什么，以设计用于生物治疗的高效装载RNA的工程化EVs。我们还讨论了其他潜在的EV介导的信息传递机制，其中包括配体 - 受体机制。
