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Meliani A, Boisgerault F, Fitzpatrick Z, et al. Enhanced liver gene transfer and evasion of preexisting humoral immunity with exosome-enveloped AAV vectors. Blood Adv. 2017;1(23):2019-2031doi: 10.1182/bloodadvances.2017010181.
Meliani, A., Boisgerault, F., Fitzpatrick, Z., Marmier, S., Leborgne, C., Collaud, F., Simon Sola, M., Charles, S., Ronzitti, G., Vignaud, A., van Wittenberghe, L., Marolleau, B., Jouen, F., Tan, S., Boyer, O., Christophe, O., Brisson, A. R., Maguire, C. A., & Mingozzi, F. (2017). Enhanced liver gene transfer and evasion of preexisting humoral immunity with exosome-enveloped AAV vectors. Blood advances, 1(23), 2019-2031. https://doi.org/10.1182/bloodadvances.2017010181
Meliani, Amine, et al. "Enhanced liver gene transfer and evasion of preexisting humoral immunity with exosome-enveloped AAV vectors." Blood advances vol. 1,23 (2017): 2019-2031. doi: https://doi.org/10.1182/bloodadvances.2017010181
Meliani A, Boisgerault F, Fitzpatrick Z, Marmier S, Leborgne C, Collaud F, Simon Sola M, Charles S, Ronzitti G, Vignaud A, van Wittenberghe L, Marolleau B, Jouen F, Tan S, Boyer O, Christophe O, Brisson AR, Maguire CA, Mingozzi F. Enhanced liver gene transfer and evasion of preexisting humoral immunity with exosome-enveloped AAV vectors. Blood Adv. 2017 Oct 16;1(23):2019-2031. doi: 10.1182/bloodadvances.2017010181. eCollection 2017 Oct 24. PMID: 29296848; PMCID: PMC5728288.
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Blood Adv. 2017 Oct 16;1(23):2019-2031. doi: 10.1182/bloodadvances.2017010181. eCollection 2017 Oct 24.

Enhanced liver gene transfer and evasion of preexisting humoral immunity with exosome-enveloped AAV vectors.

Blood advances

Amine Meliani, Florence Boisgerault, Zachary Fitzpatrick, Solenne Marmier, Christian Leborgne, Fanny Collaud, Marcelo Simon Sola, Severine Charles, Giuseppe Ronzitti, Alban Vignaud, Laetitia van Wittenberghe, Beatrice Marolleau, Fabienne Jouen, Sisareuth Tan, Olivier Boyer, Olivier Christophe, Alain R Brisson, Casey A Maguire, Federico Mingozzi

Affiliations

  1. University Pierre and Marie Curie-Paris 6 and INSERM U974, Paris, France.
  2. Genethon, Evry, France.
  3. Unité Mixte de Recherche (UMR)-951, Evry, France.
  4. Centre Hospitalier Universitaire Hôpitaux de Rouen, Rouen, France.
  5. UMR-5248 Chimie and Biologie des Membranes and des Nano-objets, Centre National de la Recherche Scientifique, University of Bordeaux, Institut Polytechnique de Bordeaux, Pessac, France.
  6. Normandie University, UNIROUEN, Pathophysiology and Biotherapy of Inflammatory and Autoimmune Diseases, INSERM U905, Rouen, France.
  7. INSERM U1176 and UMR S1176, Université Paris-Sud-Kremlin-bicetre, Paris, France; and.
  8. Department of Neurology, The Massachusetts General Hospital and NeuroDiscovery Center, Harvard Medical School, Boston, MA.

PMID: 29296848 PMCID: PMC5728288 DOI: 10.1182/bloodadvances.2017010181

Abstract

Results from clinical trials of liver gene transfer for hemophilia demonstrate the potential of the adeno-associated virus (AAV) vector platform. However, to achieve therapeutic transgene expression, in some cases high vector doses are required, which are associated with a higher risk of triggering anti-capsid cytotoxic T-cell responses. Additionally, anti-AAV preexisting immunity can prevent liver transduction even at low neutralizing antibody (NAb) titers. Here, we describe the use of exosome-associated AAV (exo-AAV) vectors as a robust liver gene delivery system that allows the therapeutic vector dose to be decreased while protecting from preexisting humoral immunity to the capsid. The in vivo efficiency of liver targeting of standard AAV8 or AAV5 and exo-AAV8 or exo-AAV5 vectors expressing human coagulation factor IX (hF.IX) was evaluated. A significant enhancement of transduction efficiency was observed, and in hemophilia B mice treated with 4 × 10

Conflict of interest statement

Conflict-of-interest disclosure: C.A.M. has filed patent applications related to the exo-AAV technology, and is a founder of, and scientific advisor for, Chameleon Biosciences, Inc, a gene therapy com

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