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细胞脱水可实现具有治疗功能的工程化膜泡的大规模生产。

Cell dehydration enables massive production of engineered membrane vesicles with therapeutic functions.

机构信息

School of Life Sciences, Faculty of Medicine, Tianjin University, Tianjin, PR China.

Hangzhou Institute of Medicine (HIM), University of Chinese Academy of Sciences (Zhejiang Cancer Hospital), Chinese Academy of Sciences, Hangzhou, Zhejiang, PR China.

出版信息

J Extracell Vesicles. 2024 Jul;13(7):e12483. doi: 10.1002/jev2.12483.

Abstract

Extracellular vesicles (EVs) have emerged as promising biomaterials for the treatment of different disease. However, only handful types of EVs with clinical transformation potential have been reported to date, and their preparation on a large scale under biosafety-controlled conditions is limited. In this study, we characterize a novel type of EV with promising clinical application potential: dehydration-induced extracellular vesicles (DIMVs). DIMV is a type of micron-diameter cell vesicle that contains more bioactive molecules, such as proteins and RNA, but not DNA, than previously reported cell vesicles. The preparation of DIMV is extraordinarily straightforward, which possesses a high level of biosafety, and the protein utilization ratio is roughly 600 times greater than that of naturally secreted EVs. Additional experiments demonstrate the viability of pre- or post-isolation DIMV modification, including gene editing, nucleic acid encapsulation or surface anchoring, size adjustment. Finally, on animal models, we directly show the biosafety and immunogenicity of DIMV, and investigate its potential application as tumour vaccine or drug carrier in cancer treatment.

摘要

细胞外囊泡 (EVs) 已成为治疗各种疾病的有前途的生物材料。然而,迄今为止,仅有少数几种具有临床转化潜力的 EV 被报道,并且在生物安全控制条件下大规模制备它们受到限制。在这项研究中,我们描述了一种具有有前途的临床应用潜力的新型 EV:脱水诱导的细胞外囊泡 (DIMV)。DIMV 是一种微米级直径的细胞囊泡,比以前报道的细胞囊泡含有更多的生物活性分子,如蛋白质和 RNA,但不含 DNA。制备 DIMV 非常简单,具有高度的生物安全性,并且蛋白质利用率比天然分泌的 EV 大约高 600 倍。此外的实验证明了 DIMV 修饰的可行性,包括基因编辑、核酸封装或表面锚定、大小调整。最后,在动物模型上,我们直接展示了 DIMV 的生物安全性和免疫原性,并研究了其作为肿瘤疫苗或药物载体在癌症治疗中的潜在应用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1cdd/11270585/8e9943816ad5/JEV2-13-e12483-g001.jpg

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