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Use of Lentiviral Particles As a Cell Membrane-Based mFasL Delivery System for In Vivo Treatment of Inflammatory Arthritis
During budding, lentiviral particles (LVP) incorporate cell membrane proteins in the viral envelope. We explored the possibility of harnessing this process to generate LVP-expressing membrane proteins of therapeutic interest and studied the potential of these tools to treat different pathologies. Fa...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5399037/ https://www.ncbi.nlm.nih.gov/pubmed/28484458 http://dx.doi.org/10.3389/fimmu.2017.00460 |
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author | Rodríguez-Frade, José M. Guedán, Anabel Lucas, Pilar Martínez-Muñoz, Laura Villares, Ricardo Criado, Gabriel Balomenos, Dimitri Reyburn, Hugh T. Mellado, Mario |
author_facet | Rodríguez-Frade, José M. Guedán, Anabel Lucas, Pilar Martínez-Muñoz, Laura Villares, Ricardo Criado, Gabriel Balomenos, Dimitri Reyburn, Hugh T. Mellado, Mario |
author_sort | Rodríguez-Frade, José M. |
collection | PubMed |
description | During budding, lentiviral particles (LVP) incorporate cell membrane proteins in the viral envelope. We explored the possibility of harnessing this process to generate LVP-expressing membrane proteins of therapeutic interest and studied the potential of these tools to treat different pathologies. Fas-mediated apoptosis is central to the maintenance of T cell homeostasis and prevention of autoimmune processes. We prepared LVP that express murine FasL on their surface. Our data indicate that mFasL-bearing LVP induce caspase 3 and 9 processing, cytochrome C release, and significantly more cell death than control LVP in vitro. This cytotoxicity is blocked by the caspase inhibitor Z-VAD. Analysis of the application of these reagents for the treatment of inflammatory arthritis in vivo suggests that FasL-expressing LVP could be useful for therapy in autoimmune diseases such as rheumatoid arthritis, where there is an excess of Fas-expressing activated T cells in the joint. LVP could be a vehicle not only for mFasL but also for other membrane-bound proteins that maintain their native conformation and might mediate biological activities. |
format | Online Article Text |
id | pubmed-5399037 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-53990372017-05-08 Use of Lentiviral Particles As a Cell Membrane-Based mFasL Delivery System for In Vivo Treatment of Inflammatory Arthritis Rodríguez-Frade, José M. Guedán, Anabel Lucas, Pilar Martínez-Muñoz, Laura Villares, Ricardo Criado, Gabriel Balomenos, Dimitri Reyburn, Hugh T. Mellado, Mario Front Immunol Immunology During budding, lentiviral particles (LVP) incorporate cell membrane proteins in the viral envelope. We explored the possibility of harnessing this process to generate LVP-expressing membrane proteins of therapeutic interest and studied the potential of these tools to treat different pathologies. Fas-mediated apoptosis is central to the maintenance of T cell homeostasis and prevention of autoimmune processes. We prepared LVP that express murine FasL on their surface. Our data indicate that mFasL-bearing LVP induce caspase 3 and 9 processing, cytochrome C release, and significantly more cell death than control LVP in vitro. This cytotoxicity is blocked by the caspase inhibitor Z-VAD. Analysis of the application of these reagents for the treatment of inflammatory arthritis in vivo suggests that FasL-expressing LVP could be useful for therapy in autoimmune diseases such as rheumatoid arthritis, where there is an excess of Fas-expressing activated T cells in the joint. LVP could be a vehicle not only for mFasL but also for other membrane-bound proteins that maintain their native conformation and might mediate biological activities. Frontiers Media S.A. 2017-04-21 /pmc/articles/PMC5399037/ /pubmed/28484458 http://dx.doi.org/10.3389/fimmu.2017.00460 Text en Copyright © 2017 Rodríguez-Frade, Guedán, Lucas, Martínez-Muñoz, Villares, Criado, Balomenos, Reyburn and Mellado. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Immunology Rodríguez-Frade, José M. Guedán, Anabel Lucas, Pilar Martínez-Muñoz, Laura Villares, Ricardo Criado, Gabriel Balomenos, Dimitri Reyburn, Hugh T. Mellado, Mario Use of Lentiviral Particles As a Cell Membrane-Based mFasL Delivery System for In Vivo Treatment of Inflammatory Arthritis |
title | Use of Lentiviral Particles As a Cell Membrane-Based mFasL Delivery System for In Vivo Treatment of Inflammatory Arthritis |
title_full | Use of Lentiviral Particles As a Cell Membrane-Based mFasL Delivery System for In Vivo Treatment of Inflammatory Arthritis |
title_fullStr | Use of Lentiviral Particles As a Cell Membrane-Based mFasL Delivery System for In Vivo Treatment of Inflammatory Arthritis |
title_full_unstemmed | Use of Lentiviral Particles As a Cell Membrane-Based mFasL Delivery System for In Vivo Treatment of Inflammatory Arthritis |
title_short | Use of Lentiviral Particles As a Cell Membrane-Based mFasL Delivery System for In Vivo Treatment of Inflammatory Arthritis |
title_sort | use of lentiviral particles as a cell membrane-based mfasl delivery system for in vivo treatment of inflammatory arthritis |
topic | Immunology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5399037/ https://www.ncbi.nlm.nih.gov/pubmed/28484458 http://dx.doi.org/10.3389/fimmu.2017.00460 |
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