首页|Engineered extracellular vesicles enable high-efficient delivery of intracellular therapeutic proteins

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

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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.

extracellular vesiclesintracellular protein deliverycGAScancer immunotherapy

Ding Ma、An Xie、Jiahui Lv、Xiaolin Min、Xinye Zhang、Qian Zhou、Daxing Gao、Enyu Wang、Lei Gao、Linzhao Cheng、Senquan Liu

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Department of Hematology,The First Affiliated Hospital of USTC,Division of Life Sciences and Medicine,University of Science and Technology of China,Hefei 230001,China

Blood and Cell Therapy Institute,Anhui Provincial Key Laboratory of Blood Research and Applications,University of Science and Technology of China,Hefei 230036,China

School of Basic Medical Sciences,Division of Life Sciences and Medicine,University of Science and Technology of China,Hefei 230027,China

School of Biomedical Engineering,Division of Life Sciences and Medicine,University of Science and Technology of China,Hefei 230026,China

School of Biomedical Engineering,Division o

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2024

10.1093/procel/pwae015

蛋白质与细胞

蛋白质与细胞

CSTPCD
影响因子：0.645
ISSN：
年,卷(期)：2024.15(10)