Transcriptomic Analysis Reveals the Inability of Recombinant AAV8 to Activate Human Monocyte-Derived Dendritic Cells
In: ISSN: 1661-6596, 2023
Online
academicJournal
Zugriff:
International audience ; Recombinant Adeno-Associated Virus (rAAV) is considered as one of the most successful and widely used viral vectors for in vivo gene therapy. However, host immune responses to the vector and/or the transgene product remain a major hurdle to successful AAV gene transfer. In contrast to antivector adaptive immunity, the initiation of the innate immunity towards rAAV is still poorly understood but is directly dependent on the interaction between the viral vector and innate immune cells. Here, we used a quantitative transcriptomic-based approach to determine the activation of inflammatory and anti-viral pathways after rAAV8-based infection of monocyte-derived dendritic cells (moDCs) obtained from 12 healthy human donors. We have shown that rAAV8 particles are efficiently internalized, but that this uptake does not induce any detectable transcriptomic change in moDCs in contrast to an adenoviral infection, which upregulates anti-viral pathways. These findings suggest an immunologically favorable profile for rAAV8 serotype with regard to in vitro activation of moDC model. Transcriptomic analysis of rAAV-infected innate immune cells is a powerful method to determine the ability of the viral vector to be seen by these sensor cells, which remains of great importance to better understand the immunogenicity of rAAV vectors and to design immune-stealth products.
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Transcriptomic Analysis Reveals the Inability of Recombinant AAV8 to Activate Human Monocyte-Derived Dendritic Cells
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Autor/in / Beteiligte Person: | Masri, Samer ; Carré, Laure ; Jaulin, Nicolas ; Vandamme, Céline ; Couzinié, Célia ; Guy-Duché, Aurélien ; Dupont, Jean-Baptiste ; Pereira, Allwyn ; Charpentier, Eric ; David, Laurent ; Gernoux, Gwladys ; Guilbaud, Mickaël ; Adjali, Oumeya ; Laboratoire de Thérapie Génique Translationnelle des Maladies Génétiques / Translational Research in Gene Therapy - UMR_S 1089 (TARGET) ; Institut National de la Santé et de la Recherche Médicale (INSERM)-Nantes Université - UFR de Médecine et des Techniques Médicales (Nantes Univ - UFR MEDECINE) ; Nantes Université - pôle Santé ; Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Nantes Université - pôle Santé ; Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ) ; Centre Hospitalier Universitaire de Nantes = Nantes University Hospital (CHU Nantes) ; Structure fédérative de recherche François Bonamy (Nantes Univ - SFR François Bonamy) ; Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Nantes Université (Nantes Univ) ; Centre de Recherche en Transplantation et Immunologie - Center for Research in Transplantation and Translational Immunology (U1064 Inserm - CR2TI) ; ANR-10-IBHU-0005,CESTI (TSI-IHU),Centre Européen des Sciences de la Transplantation et de l'Immunothérapie (TSI-IHU)(2010) ; ANR-17-CE17-0007,TOLGEN,Transfert de gène dans le muscle squelettique à l'aide d'AAV: Décryptage de la réponse immune de l'hôte(2017) |
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Zeitschrift: | ISSN: 1661-6596, 2023 |
Veröffentlichung: | HAL CCSD ; MDPI, 2023 |
Medientyp: | academicJournal |
DOI: | 10.3390/ijms241310447 |
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