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Protein & Cell

Protein & Cell

IF: 12.8
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Engineered extracellular vesicles enable high-efficient delivery of intracellular therapeutic proteins

Published:1 October 2024 DOI: 10.1093/procel/pwae015 PMID: 38518087
Ding Ma,?An Xie,?Jiahui Lv,?Xiaolin Min,?Xinye Zhang,?Qian Zhou,?Daxing Gao,?Enyu Wang,?Lei Gao,?Linzhao Cheng,?Senquan Liu

Abstract

Developing an intracellular delivery system is of key importance in the expansion of protein-based therapeutics acting on cytosolic or nuclear targets. Recently, extracellular vesicles (EVs) have been exploited as next-generation delivery modalities due to their natural role in intercellular communication and biocompatibility. However, fusion of protein of interest to a scaffold represents a widely used strategy for cargo enrichment in EVs, which could compromise the stability and functionality of cargo. Herein, we report intracellular delivery via EV-based approach (IDEA) that efficiently packages and delivers native proteins both in vitro and in vivo without the use of a scaffold. As a proof-of-concept, we applied the IDEA to deliver cyclic GMP-AMP synthase (cGAS), an innate immune sensor. The results showed that cGAS-carrying EVs activated interferon signaling and elicited enhanced antitumor immunity in multiple syngeneic tumor models. Combining cGAS EVs with immune checkpoint inhibition further synergistically boosted antitumor efficacy in vivo. Mechanistically, scRNA-seq demonstrated that cGAS EVs mediated significant remodeling of intratumoral microenvironment, revealing a pivotal role of infiltrating neutrophils in the antitumor immune milieu. Collectively, IDEA, as a universal and facile strategy, can be applied to expand and advance the development of protein-based therapeutics.

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Materials
Procduct Name CAS Molecular Formula Supplier Price
MG-132 133407-82-6 C26H41N3O5 427 suppliers $11.00-$9807.90
MG-132 133407-82-6 C26H41N3O5 427 suppliers $11.00-$9807.90
MG-132 133407-82-6 C26H41N3O5 427 suppliers $11.00-$9807.90
MG-132 133407-82-6 C26H41N3O5 427 suppliers $11.00-$9807.90
CHLOROQUINE 54-05-7 C18H26ClN3 219 suppliers $5.00-$1550.00
CHLOROQUINE 54-05-7 C18H26ClN3 219 suppliers $5.00-$1550.00
CHLOROQUINE 54-05-7 C18H26ClN3 219 suppliers $5.00-$1550.00
CHLOROQUINE 54-05-7 C18H26ClN3 219 suppliers $5.00-$1550.00
Dynasore 304448-55-3 C18H14N2O4 185 suppliers $12.00-$2755.00
Dynasore 304448-55-3 C18H14N2O4 185 suppliers $12.00-$2755.00

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