Enhanced liver gene transfer and evasion of preexisting humoral immunity with exosome-enveloped AAV vectors
Year: 2017
Type: article
Abstract: vector genomes per kilogram of exo-AAV8 vectors, a staggering ∼1 log increase in hF.IX transgene expression was observed, leading to superior correction of clotting time. Enhanced liver expression was also associated with an increase in the frequency of regulatory T cells in lymph nodes. The efficiency of exo- and standard AAV8 vectors in evading preexisting NAbs to the capsid was then evaluated in a passive immunization mouse model and in human sera. Exo-AAV8 gene delivery allowed for efficient transduction even in the presence of moderate NAb titers, thus potentially extending the proportion of subjects eligible for liver gene transfer. Exo-AAV vectors therefore represent a platform to improve the safety and efficacy of liver-directed gene transfer.
Source: Blood Advances
Authors: 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
Institutions: Inserm, Genethon (France), Université Pierre-et-Marie-Curie, Centre Hospitalier Universitaire de Rouen, Centre National de la Recherche Scientifique, Université de Bordeaux, Chimie et Biologie des Membranes et des Nanoobjects, Institut Polytechnique de Bordeaux, Physiopathologie, autoimmunité, maladies neuromusculaire et thérapie régénératrice, Université Paris-Sud, Harvard University, Harvard NeuroDiscovery Center, Massachusetts General Hospital
Language: English
Subfield: Genetics
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $3,800
OpenAlex ID: W2765408594