Plasma exosomes can deliver exogenous short interfering RNA to monocytes and lymphocytes

Wahlgren, Jessica; Karlson, Tanya De L.; Brisslert, Mikael; Sani, Forugh Vaziri; Telemo, Esbjörn; Sunnerhagen, Per; Valadi, Hadi

doi:10.1093/nar/gks463

Cited by 615 publications

(484 citation statements)

References 31 publications

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“…Leaders in this research area, such as Alvarez‐Erviti et al, have transferred siRNA into EVs via electroporation; subsequent experiments have demonstrated that these electroporated EVs could significantly inhibit expression of the target gene ( Figure 9 ). 20 Electroporation to generate siRNA‐loaded EVs was successfully verified by follow‐up studies 119, 120. However, it appears that electroporation might not be efficacious for transferring all types of RNA directly into EVs without modifying the “source cells.”107 Simple electroporation might not be sufficiently efficient, and more in‐depth studies are needed 121.…”

Section: Modular Design Of Internal Contentsmentioning

confidence: 99%

Modularized Extracellular Vesicles: The Dawn of Prospective Personalized and Precision Medicine

2018

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Extracellular vesicles (EVs) are ubiquitous nanosized membrane vesicles consisting of a lipid bilayer enclosing proteins and nucleic acids, which are active in intercellular communications. EVs are increasingly seen as a vital component of many biological functions that were once considered to require the direct participation of stem cells. Consequently, transplantation of EVs is gradually becoming considered an alternative to stem cell transplantation due to their significant advantages, including their relatively low probability of neoplastic transformation and abnormal differentiation. However, as research has progressed, it is realized that EVs derived from native‐source cells may have various shortcomings, which can be corrected by modification and optimization. To date, attempts are made to modify or improve almost all the components of EVs, including the lipid bilayer, proteins, and nucleic acids, launching a new era of modularized EV therapy through the “modular design” of EV components. One high‐yield technique, generating EV mimetic nanovesicles, will help to make industrial production of modularized EVs a reality. These modularized EVs have highly customized “modular design” components related to biological function and targeted delivery and are proposed as a promising approach to achieve personalized and precision medicine.

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Section: Modular Design Of Internal Contentsmentioning

confidence: 99%

Modularized Extracellular Vesicles: The Dawn of Prospective Personalized and Precision Medicine

2018

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“…Load siRNA to MAPK-1 into exosomes Suppress MAPK-1 in monocytes and lymphocytes [24] Mouse M12.4 B lymphocyte…”

Section: Electroporation Of Hydrophilic Cargomentioning

confidence: 99%

“…Wahlgren et al compared the efficiency of two methods for loading plasmaderived exosomes with siRNA to MAPK-1 [24]. The two loading methods included chemical transfection using HiPerFect commercial transfection reagent and EP.…”

Section: Encapsulating Cargo In Exosomesmentioning

confidence: 99%

Post Isolation Modification of Exosomes for Nanomedicine Applications

Hood

2016

Nanomedicine (Lond.)

164

118

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Exosomes are extracellular nanovesicles. They innately possess ideal structural and biocompatible nanocarrier properties. Exosome components can be engineered at the cellular level. Alternatively, when exosome source cells are unavailable for customized exosome production, exosomes derived from a variety of biological origins can be modified post isolation which is the focus of this article. Modification of exosome surface structures allows for exosome imaging and tracking in vivo. Exosome membranes can be loaded with hydrophobic therapeutics to increase drug stability and efficacy. Hydrophilic therapeutics such as RNA can be encapsulated in exosomes to improve cellular delivery. Despite advances in post isolation exosome modification strategies, many challenges to effectively harnessing their therapeutic potential remain. Future topics of exploration include: matching exosome subtypes with nanomedicine applications, optimizing exosomal nanocarrier formulation and investigating how modified exosomes interface with the immune system. Research into these areas will greatly facilitate personalized exosome-based nanomedicine endeavors.

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“…Jian-Jun Wang 1 , Ze-You Wang 2 , Rui Chen 3 , Jing Xiong 4 , Yong-Liang Yao 1 , JianHong Wu 1 , Guang-Xin Li 3 * intercellular delivery of endogenous proteins and nucleic acids, and can also deliver exogenous pharmaceutical proteins and nucleic acids such as mRNAs, microRNAs (miRNAs) and siRNAs (Wahlgren et al, 2012;Chen et al, 2014). Exosome secretion of microvesicles transporting miRNAs, mRNAs, and proteins through bodily fluids facilitates intercellular communication and can elicit an immune response (McDonald et al, 2014).…”

Section: Macrophage-secreted Exosomes Delivering Mirna-21 Inhibitor Cmentioning

confidence: 99%

Macrophage-secreted Exosomes Delivering miRNA-21 Inhibitor can Regulate BGC-823 Cell Proliferation

Wang¹,

Wang²,

Chen³

et al. 2015

Asian Pacific Journal of Cancer Prevention

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Exosomes, membranous nanovesicles, naturally carry bio-macromolecules or miRNA and play impoetant roles in tumor pathogenesis. Here, we showed that macrophages cell-derived exosomes can function as vehicles to deliver exogenous miR-21 inhibitor into BGC-823 gastric cancer cells. Exosomes loaded with miR-21inhibitor significantly increased miR-21 levels in BGC-823, but miR-21inhibitor loaded in exosomes exerted an opposite effect. miRNA transfected with exosomes had less cellular toxicity to host cells compared to conventional transfection methods. The miR-21inhibitor loaded exosomes promoted the migration ability and reduced apoptosis of BGC-823 gastric cancer cells. These observations indicate that miR-21 acts as a tumor promoter by targeting the PDCD4 gene and preventing apoptosis of gastric cancer cells through inhibition of PDCD4 expression. Furthermore, exosome -mediated miR-21 inhibitor delivery resulted in functionally more efficient inhibition and less cellular toxicity compared to conventional transfection methods. Similar approaches could be useful in modification of target biomolecules in vitro and in vivo. These findings contribute to our understanding of the functions of miR-21 and exosomes as a carrier for therapy of gastric cancer.

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Plasma exosomes can deliver exogenous short interfering RNA to monocytes and lymphocytes

Cited by 615 publications

References 31 publications

Modularized Extracellular Vesicles: The Dawn of Prospective Personalized and Precision Medicine

Modularized Extracellular Vesicles: The Dawn of Prospective Personalized and Precision Medicine

Post Isolation Modification of Exosomes for Nanomedicine Applications

Macrophage-secreted Exosomes Delivering miRNA-21 Inhibitor can Regulate BGC-823 Cell Proliferation

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