A strategy of antigen incorporation into exosomes: Comparing cross-presentation levels of antigens delivered by engineered exosomes and by lentiviral virus-like particles

Lattanzi, Laura; Federico, Maurizio

doi:10.1016/j.vaccine.2012.10.010

Cited by 72 publications

(73 citation statements)

References 36 publications

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“…Methods published for encapsulating drugs in exosomes include electroporation, incubation, or transfection of donor cells 14, 18. It was also reported that catalase loaded into exosomes via sonication and extrusion, or permeabilization with saponin results in higher loading efficiency than simple incubation.…”

Section: Resultsmentioning

confidence: 99%

Exosome–Liposome Hybrid Nanoparticles Deliver CRISPR/Cas9 System in MSCs

et al. 2018

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Targeted delivery of clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR‐associated protein 9 (Cas9) system to the receptor cells is essential for in vivo gene editing. Exosomes are intensively studied as a promising targeted drug delivery carrier recently, while limited by their low efficiency in encapsulating of large nucleic acids. Here, a kind of hybrid exosomes with liposomes is developed via simple incubation. Different from the original exosomes, the resultant hybrid nanoparticles efficiently encapsulate large plasmids, including the CRISPR–Cas9 expression vectors, similarly as the liposomes. Moreover, the resultant hybrid nanoparticles can be endocytosed by and express the encapsulated genes in the mesenchymal stem cells (MSCs), which cannot be transfected by the liposome alone. Taken together, the exosome–liposome hybrid nanoparticles can deliver CRISPR–Cas9 system in MSCs and thus be promising in in vivo gene manipulation.

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Section: Resultsmentioning

confidence: 99%

Exosome–Liposome Hybrid Nanoparticles Deliver CRISPR/Cas9 System in MSCs

et al. 2018

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“…In their recent review Yin et al analyze and discuss the possible use of immature DC-derived exosomes as a subcellular vaccine in autoimmunity [72]. Finally, in a recent original paper, Lattanzi et al describe and propose a new method of incorporating protein antigens in exosomes, relying on the unique properties of a mutant of the HIV-1 Nef protein, a biologically inactive mutant they found by incorporating it into exosomes at high levels while also fusing at its C -terminus with foreign proteins [168]. …”

Section: Exosomes In Clinical Diagnostic and Therapeutic Approachesmentioning

confidence: 99%

Exosomes as Intercellular Signaling Organelles Involved in Health and Disease: Basic Science and Clinical Applications

Corrado

Raimondo

Chiesi³

et al. 2013

IJMS

351

319

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Cell to cell communication is essential for the coordination and proper organization of different cell types in multicellular systems. Cells exchange information through a multitude of mechanisms such as secreted growth factors and chemokines, small molecules (peptides, ions, bioactive lipids and nucleotides), cell-cell contact and the secretion of extracellular matrix components. Over the last few years, however, a considerable amount of experimental evidence has demonstrated the occurrence of a sophisticated method of cell communication based on the release of specialized membranous nano-sized vesicles termed exosomes. Exosome biogenesis involves the endosomal compartment, the multivesicular bodies (MVB), which contain internal vesicles packed with an extraordinary set of molecules including enzymes, cytokines, nucleic acids and different bioactive compounds. In response to stimuli, MVB fuse with the plasma membrane and vesicles are released in the extracellular space where they can interact with neighboring cells and directly induce a signaling pathway or affect the cellular phenotype through the transfer of new receptors or even genetic material. This review will focus on exosomes as intercellular signaling organelles involved in a number of physiological as well as pathological processes and their potential use in clinical diagnostics and therapeutics.

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“…12 To this end, C57 Bl/6 mice (four per group) were injected IM in each quadriceps with 50 µg of a vector expressing either wt Nef or Nef mut or with the empty vector. The inoculations were repeated 10 days later, and after an additional 10 days the mice were sacrificed.…”

Section: Lack Of Immunogenicity Of a Dna Vector Expressing The Wt Nefmentioning

confidence: 99%

“…12 This Nef mutant (referred to as Nef mut ) is defective for basically all Nef functions. Its efficiency of incorporation in nanovesicles does not change significantly when fused at its C-terminus with foreign proteins.…”

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confidence: 99%

Antitumor HPV E7-specific CTL activity elicited by in vivo engineered exosomes produced through DNA inoculation

Bonito¹,

Chiozzini²,

Arenaccio³

et al. 2017

IJN

Self Cite

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We recently proved that exosomes engineered in vitro to deliver high amounts of HPV E7 upon fusion with the Nef mut exosome-anchoring protein elicit an efficient anti-E7 cytotoxic T lymphocyte immune response. However, in view of a potential clinic application of this finding, our exosome-based immunization strategy was faced with possible technical difficulties including industrial manufacturing, cost of production, and storage. To overcome these hurdles, we designed an as yet unproven exosome-based immunization strategy relying on delivery by intramuscular inoculation of a DNA vector expressing Nef mut fused with HPV E7. In this way, we predicted that the expression of the Nef mut /E7 vector in muscle cells would result in a continuous source of endogenous (ie, produced by the inoculated host) engineered exosomes able to induce an E7-specific immune response. To assess this hypothesis, we first demonstrated that the injection of a Nef mut /green fluorescent protein-expressing vector led to the release of fluorescent exosomes, as detected in plasma of inoculated mice. Then, we observed that mice inoculated intramuscularly with a vector expressing Nef mut /E7 developed a CD8 + T-cell immune response against both Nef and E7. Conversely, no CD8 + T-cell responses were detected upon injection of vectors expressing either the wild-type Nef isoform of E7 alone, most likely a consequence of their inefficient exosome incorporation. The production of immunogenic exosomes in the DNA-injected mice was formally demonstrated by the E7-specific CD8 + T-cell immune response we detected in mice inoculated with exosomes isolated from plasma of mice inoculated with the Nef mut /E7 vector. Finally, we provide evidence that the injection of Nef mut /E7 DNA led to the generation of effective antigen-specific cytotoxic T lymphocytes whose activity was likely part of the potent, therapeutic antitumor effect we observed in mice implanted with TC-1 tumor cells. In summary, we established a novel method to generate immunogenic exosomes in vivo by the intramuscular inoculation of DNA vectors expressing the exosome-anchoring protein Nef mut and its derivatives.

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A strategy of antigen incorporation into exosomes: Comparing cross-presentation levels of antigens delivered by engineered exosomes and by lentiviral virus-like particles

Cited by 72 publications

References 36 publications

Exosome–Liposome Hybrid Nanoparticles Deliver CRISPR/Cas9 System in MSCs

Exosome–Liposome Hybrid Nanoparticles Deliver CRISPR/Cas9 System in MSCs

Exosomes as Intercellular Signaling Organelles Involved in Health and Disease: Basic Science and Clinical Applications

Antitumor HPV E7-specific CTL activity elicited by in vivo engineered exosomes produced through DNA inoculation

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