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Microvesicle-associated AAV vector as a novel gene delivery system.
Maguire, Casey A; Balaj, Leonora; Sivaraman, Sarada; Crommentuijn, Matheus H W; Ericsson, Maria; Mincheva-Nilsson, Lucia; Baranov, Vladimir; Gianni, Davide; Tannous, Bakhos A; Sena-Esteves, Miguel; Breakefield, Xandra O; Skog, Johan.
Afiliación
  • Maguire CA; Department of Neurology, Massachusetts General Hospital, and Neuroscience Program, Harvard Medical School, Boston, Massachusetts, USA.
Mol Ther ; 20(5): 960-71, 2012 May.
Article en En | MEDLINE | ID: mdl-22314290
Adeno-associated virus (AAV) vectors have shown remarkable efficiency for gene delivery to cultured cells and in animal models of human disease. However, limitations to AAV vectored gene transfer exist after intravenous transfer, including off-target gene delivery (e.g., liver) and low transduction of target tissue. Here, we show that during production, a fraction of AAV vectors are associated with microvesicles/exosomes, termed vexosomes (vector-exosomes). AAV capsids associated with the surface and in the interior of microvesicles were visualized using electron microscopy. In cultured cells, vexosomes outperformed conventionally purified AAV vectors in transduction efficiency. We found that purified vexosomes were more resistant to a neutralizing anti-AAV antibody compared to conventionally purified AAV. Finally, we show that vexosomes bound to magnetic beads can be attracted to a magnetized area in cultured cells. Vexosomes represent a unique entity which offers a promising strategy to improve gene delivery.
Asunto(s)

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Técnicas de Transferencia de Gen / Dependovirus Tipo de estudio: Risk_factors_studies Límite: Humans Idioma: En Revista: Mol Ther Asunto de la revista: BIOLOGIA MOLECULAR / TERAPEUTICA Año: 2012 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Técnicas de Transferencia de Gen / Dependovirus Tipo de estudio: Risk_factors_studies Límite: Humans Idioma: En Revista: Mol Ther Asunto de la revista: BIOLOGIA MOLECULAR / TERAPEUTICA Año: 2012 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos