AUTHOR=Rodríguez-Frade José M. , Guedán Anabel , Lucas Pilar , Martínez-Muñoz Laura , Villares Ricardo , Criado Gabriel , Balomenos Dimitri , Reyburn Hugh T. , Mellado Mario TITLE=Use of Lentiviral Particles As a Cell Membrane-Based mFasL Delivery System for In Vivo Treatment of Inflammatory Arthritis JOURNAL=Frontiers in Immunology VOLUME=Volume 8 - 2017 YEAR=2017 URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2017.00460 DOI=10.3389/fimmu.2017.00460 ISSN=1664-3224 ABSTRACT=

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.