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  1. Article ; Online: Extracellular vesicles as carriers of viruses.

    Troyer, Zach / Tilton, John C

    ExRNA

    2021  Volume 3

    Language English
    Publishing date 2021-12-30
    Publishing country England
    Document type Journal Article
    ISSN 2398-0060
    ISSN (online) 2398-0060
    DOI 10.21037/exrna-21-24
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Extracellular vesicles: The next generation in gene therapy delivery.

    Cecchin, Riccardo / Troyer, Zach / Witwer, Ken / Morris, Kevin V

    Molecular therapy : the journal of the American Society of Gene Therapy

    2023  Volume 31, Issue 5, Page(s) 1225–1230

    Abstract: Extracellular vesicles (EVs) are esteemed as a promising delivery vehicle for various genetic therapeutics. They are relatively inert, non-immunogenic, biodegradable, and biocompatible. At least in rodents, they can even transit challenging bodily ... ...

    Abstract Extracellular vesicles (EVs) are esteemed as a promising delivery vehicle for various genetic therapeutics. They are relatively inert, non-immunogenic, biodegradable, and biocompatible. At least in rodents, they can even transit challenging bodily hurdles such as the blood-brain barrier. Constitutively shed by all cells and with the potential to interact specifically with neighboring and distant targets, EVs can be engineered to carry and deliver therapeutic molecules such as proteins and RNAs. EVs are thus emerging as an elegant in vivo gene therapy vector. Deeper understanding of basic EV biology-including cellular production, EV loading, systemic distribution, and cell delivery-is still needed for effective harnessing of these endogenous cellular nanoparticles as next-generation nanodelivery tools. However, even a perfect EV product will be challenging to produce at clinical scale. In this regard, we propose that vector transduction technologies can be used to convert cells either ex vivo or directly in vivo into EV factories for stable, safe modulation of gene expression and function. Here, we extrapolate from the current EV state of the art to a bright potential future using EVs to treat genetic diseases that are refractory to current therapeutics.
    MeSH term(s) Extracellular Vesicles/metabolism ; RNA/metabolism ; Proteins/metabolism ; Nanoparticles ; Genetic Therapy
    Chemical Substances RNA (63231-63-0) ; Proteins
    Language English
    Publishing date 2023-01-25
    Publishing country United States
    Document type Journal Article ; Review ; Research Support, N.I.H., Extramural
    ZDB-ID 2010592-7
    ISSN 1525-0024 ; 1525-0016
    ISSN (online) 1525-0024
    ISSN 1525-0016
    DOI 10.1016/j.ymthe.2023.01.021
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Plant-Derived Vesicle-Like Nanoparticles as Promising Biotherapeutic Tools: Present and Future.

    Feng, Junjie / Xiu, Qi / Huang, Yiyao / Troyer, Zach / Li, Bo / Zheng, Lei

    Advanced materials (Deerfield Beach, Fla.)

    2023  Volume 35, Issue 24, Page(s) e2207826

    Abstract: Extracellular vesicles (EVs) are heterogeneous, phospholipid bilayer-enclosed biological particles that regulate cell communication by molecular cargo delivery and surface signaling. EVs are secreted by almost all living cells, including plant cells. ... ...

    Abstract Extracellular vesicles (EVs) are heterogeneous, phospholipid bilayer-enclosed biological particles that regulate cell communication by molecular cargo delivery and surface signaling. EVs are secreted by almost all living cells, including plant cells. Plant-derived vesicle-like nanoparticles (PDVLNs) is a generic term referring to vesicle-like nanostructure particles isolated from plants. Their low immunogenicity and wide availability make PDVLNs safer and more economical to be developed as therapeutic agents and drug carriers. Accumulating evidence indicates the key roles of PDVLNs in regulating interkingdom crosstalk between humans and plants. PDVLNs are capable of entering the human-body systemand delivering effector molecules to cells that modulate cell-signaling pathways. PDVLNs released by or obtained from plants thus have great influenceon human health and diseases. In this review, the biogenesis, detailed preparation methods, various physical and biochemical characteristics, biosafety, and preservation of PDVLNs are introduced, along with how these characteristics pertain to their biosafety and preservability. The potential applications of PDVLNs on different plant and mammalian diseases and PDVLN research standardization are then systematically discussed.
    MeSH term(s) Animals ; Humans ; Extracellular Vesicles/metabolism ; Plants ; Drug Carriers/metabolism ; Cell Communication ; Nanoparticles ; Mammals
    Chemical Substances Drug Carriers
    Language English
    Publishing date 2023-04-09
    Publishing country Germany
    Document type Journal Article ; Review
    ZDB-ID 1474949-X
    ISSN 1521-4095 ; 0935-9648
    ISSN (online) 1521-4095
    ISSN 0935-9648
    DOI 10.1002/adma.202207826
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  4. Article ; Online: HIV signaling through CD4 and CCR5 activates Rho family GTPases that are required for optimal infection of primary CD4+ T cells.

    Lucera, Mark B / Fleissner, Zach / Tabler, Caroline O / Schlatzer, Daniela M / Troyer, Zach / Tilton, John C

    Retrovirology

    2017  Volume 14, Issue 1, Page(s) 4

    Abstract: Background: HIV-1 hijacks host cell machinery to ensure successful replication, including cytoskeletal components for intracellular trafficking, nucleoproteins for pre-integration complex import, and the ESCRT pathway for assembly and budding. It is ... ...

    Abstract Background: HIV-1 hijacks host cell machinery to ensure successful replication, including cytoskeletal components for intracellular trafficking, nucleoproteins for pre-integration complex import, and the ESCRT pathway for assembly and budding. It is widely appreciated that cellular post-translational modifications (PTMs) regulate protein activity within cells; however, little is known about how PTMs influence HIV replication. Previously, we reported that blocking deacetylation of tubulin using histone deacetylase inhibitors promoted the kinetics and efficiency of early post-entry viral events. To uncover additional PTMs that modulate entry and early post-entry stages in HIV infection, we employed a flow cytometric approach to assess a panel of small molecule inhibitors on viral fusion and LTR promoter-driven gene expression.
    Results: While viral fusion was not significantly affected, early post-entry viral events were modulated by drugs targeting multiple processes including histone deacetylation, methylation, and bromodomain inhibition. Most notably, we observed that inhibitors of the Rho GTPase family of cytoskeletal regulators-including RhoA, Cdc42, and Rho-associated kinase signaling pathways-significantly reduced viral infection. Using phosphoproteomics and a biochemical GTPase activation assay, we found that virion-induced signaling via CD4 and CCR5 activated Rho family GTPases including Rac1 and Cdc42 and led to widespread modification of GTPase signaling-associated factors.
    Conclusions: Together, these data demonstrate that HIV signaling activates members of the Rho GTPase family of cytoskeletal regulators that are required for optimal HIV infection of primary CD4+ T cells.
    MeSH term(s) CD4 Antigens/metabolism ; CD4-Positive T-Lymphocytes/virology ; Cells, Cultured ; HIV/physiology ; Host-Pathogen Interactions ; Humans ; Receptors, CCR5/metabolism ; Signal Transduction ; Virus Integration ; Virus Internalization ; rho GTP-Binding Proteins/metabolism
    Chemical Substances CCR5 protein, human ; CD4 Antigens ; Receptors, CCR5 ; rho GTP-Binding Proteins (EC 3.6.5.2)
    Language English
    Publishing date 2017-01-24
    Publishing country England
    Document type Journal Article
    ISSN 1742-4690
    ISSN (online) 1742-4690
    DOI 10.1186/s12977-017-0328-7
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: Chronic opioid use modulates human enteric microbiota and intestinal barrier integrity.

    Cruz-Lebrón, Angélica / Johnson, Ramona / Mazahery, Claire / Troyer, Zach / Joussef-Piña, Samira / Quiñones-Mateu, Miguel E / Strauch, Christopher M / Hazen, Stanley L / Levine, Alan D

    Gut microbes

    2021  Volume 13, Issue 1, Page(s) 1946368

    Abstract: Over the past three decades the United States has experienced a devastating opioid epidemic. One of the many debilitating side effects of chronic opioid use is opioid-induced bowel dysfunction. We investigated the impact of methadone maintenance ... ...

    Abstract Over the past three decades the United States has experienced a devastating opioid epidemic. One of the many debilitating side effects of chronic opioid use is opioid-induced bowel dysfunction. We investigated the impact of methadone maintenance treatment (MMT) on the gut microbiome, the gut bacterial metabolite profile, and intestinal barrier integrity. An imbalance in key bacterial communities required for production of short-chain fatty acids (SCFAs), mucus degradation, and maintenance of barrier integrity was identified. Consistent with dysbiosis, levels of fecal SCFAs were reduced in MMT. We demonstrated that metabolites synthesized by
    MeSH term(s) Adult ; Analgesics, Opioid/adverse effects ; Analgesics, Opioid/therapeutic use ; Animals ; Dysbiosis/chemically induced ; Dysbiosis/physiopathology ; Female ; Gastrointestinal Microbiome/drug effects ; Healthy Volunteers ; Humans ; Male ; Methadone/therapeutic use ; Middle Aged ; Opioid-Related Disorders/drug therapy ; Opioid-Related Disorders/epidemiology ; Opioid-Related Disorders/physiopathology ; United States
    Chemical Substances Analgesics, Opioid ; Methadone (UC6VBE7V1Z)
    Language English
    Publishing date 2021-07-27
    Publishing country United States
    Document type Comparative Study ; Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ISSN 1949-0984
    ISSN (online) 1949-0984
    DOI 10.1080/19490976.2021.1946368
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article: Extracellular vesicles carry SARS-CoV-2 spike protein and serve as decoys for neutralizing antibodies.

    Troyer, Zach / Alhusaini, Najwa / Tabler, Caroline O / Sweet, Thomas / de Carvalho, Karina Inacio Ladislau / Schlatzer, Daniela M / Carias, Lenore / King, Christopher L / Matreyek, Kenneth / Tilton, John C

    Journal of extracellular vesicles

    2021  Volume 10, Issue 8, Page(s) e12112

    Abstract: In late 2019, a novel coronavirus named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in Wuhan, China. SARS-CoV-2 and the disease it causes, coronavirus disease 2019 (COVID-19), spread rapidly and became a global pandemic in early ... ...

    Abstract In late 2019, a novel coronavirus named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in Wuhan, China. SARS-CoV-2 and the disease it causes, coronavirus disease 2019 (COVID-19), spread rapidly and became a global pandemic in early 2020. SARS-CoV-2 spike protein is responsible for viral entry and binds to angiotensin converting enzyme 2 (ACE2) on host cells, making it a major target of the immune system - particularly neutralizing antibodies (nAbs) that are induced by infection or vaccines. Extracellular vesicles (EVs) are small membraned particles constitutively released by cells, including virally-infected cells. EVs and viruses enclosed within lipid membranes share some characteristics: they are small, sub-micron particles and they overlap in cellular biogenesis and egress routes. Given their shared characteristics, we hypothesized that EVs released from spike-expressing cells could carry spike and serve as decoys for anti-spike nAbs, promoting viral infection. Here, using mass spectrometry and nanoscale flow cytometry (NFC) approaches, we demonstrate that SARS-CoV-2 spike protein can be incorporated into EVs. Furthermore, we show that spike-carrying EVs act as decoy targets for convalescent patient serum-derived nAbs, reducing their effectiveness in blocking viral entry. These findings have important implications for the pathogenesis of SARS-CoV-2 infection in vivo and highlight the complex interplay between viruses, extracellular vesicles, and the immune system that occurs during viral infections.
    MeSH term(s) Antibodies, Neutralizing/immunology ; COVID-19/immunology ; COVID-19/therapy ; COVID-19/virology ; Extracellular Vesicles/chemistry ; Flow Cytometry ; HEK293 Cells ; Humans ; Immunization, Passive ; Protein Binding ; SARS-CoV-2/physiology ; Spike Glycoprotein, Coronavirus/analysis ; Spike Glycoprotein, Coronavirus/metabolism
    Chemical Substances Antibodies, Neutralizing ; Spike Glycoprotein, Coronavirus ; spike protein, SARS-CoV-2
    Language English
    Publishing date 2021-06-18
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural
    ZDB-ID 2683797-3
    ISSN 2001-3078
    ISSN 2001-3078
    DOI 10.1002/jev2.12112
    Database MEDical Literature Analysis and Retrieval System OnLINE

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