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

Abstract

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.

Keywords

• cell dehydration
• extracellular vesicles
• gene editing
• nucleic acid loading
• size adjustment
• tumour vaccine