{"id":"doi:10.1038/s41467-018-06621-3","kind":"article","title":"Antigen-selective modulation of AAV immunogenicity with tolerogenic rapamycin nanoparticles enables successful vector re-administration","authors":["Amine Meliani","Florence Boisgérault","Romain Hardet","Solenne Marmier","Fanny Collaud","Giuseppe Ronzitti","Christian Leborgne","Helena Costa Verdera","Marcelo Simon Sola","Séverine Charles","Alban Vignaud","Laetitia van Wittenberghe","Giorgia Manni","Olivier D. Christophe","Francesca Fallarino","Christopher J. Roy","Alicia M. Michaud","Petr O. Ilyinskii","Takashi Kishimoto","Federico Mingozzi"],"author_count":20,"year":2018,"published":"2018-10-01","venue":"Nature Communications","cited_by":265,"doi":"10.1038/s41467-018-06621-3","arxiv_id":null,"nct_id":null,"source_url":"https://doi.org/10.1038/s41467-018-06621-3","archive_url":"https://space-kitty.com/papers/doi:10.1038/s41467-018-06621-3","updated":null,"pmid":"30291246","pmcid":null,"openalex_id":"W2894600652","pdf_url":"https://www.nature.com/articles/s41467-018-06621-3.pdf","abstract":"Abstract Gene therapy mediated by recombinant adeno-associated virus (AAV) vectors is a promising treatment for systemic monogenic diseases. However, vector immunogenicity represents a major limitation to gene transfer with AAV vectors, particularly for vector re-administration. Here, we demonstrate that synthetic vaccine particles encapsulating rapamycin (SVP[Rapa]), co-administered with AAV vectors, prevents the induction of anti-capsid humoral and cell-mediated responses. This allows successful vector re-administration in mice and nonhuman primates. SVP[Rapa] dosed with AAV vectors reduces B and T cell activation in an antigen-selective manner, inhibits CD8+ T cell infiltration in the liver, and efficiently blocks memory T cell responses. SVP[Rapa] immunomodulatory effects can be transferred from treated to naive mice by adoptive transfer of splenocytes, and is inhibited by depletion of CD25+ T cells, suggesting a role for regulatory T cells. Co-administration of SVP[Rapa] with AAV vector represents a powerful strategy to modulate vector immunogenicity and enable effective vector re-administration.","abstract_license":"CC-BY (publisher license, via OpenAlex)","license":"cc-by","is_open_access":true,"retracted":false,"peer_reviewed":null,"categories":["Virus-based gene therapy research"],"details":null,"provenance":"openalex","attribution":"Abstract of \"Antigen-selective modulation of AAV immunogenicity with tolerogenic rapamycin nanoparticles enables successful vector re-administration\" by Amine Meliani, Florence Boisgérault, Romain Hardet et al., https://doi.org/10.1038/s41467-018-06621-3, used under its Creative Commons Attribution license (CC-BY); markup removed, otherwise unmodified.","topics":[{"slug":"gene-cell-therapy","name":"Gene & Cell Therapy","domain_slug":"medicine"}],"cited_in_dossiers":[]}