Microvesicle-associated AAV vector as a novel gene delivery system

Casey A. Maguire, Leonora Balaj, Sarada Sivaraman, Matheus H.W. Crommentuijn, Maria Ericsson, Lucia Mincheva-Nilsson, Vladimir Baranov, Davide Gianni, Bakhos A. Tannous, Miguel Sena-Esteves, Xandra O. Breakefield, Johan Skog*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

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.

Original languageEnglish
Pages (from-to)960-971
Number of pages12
JournalMolecular Therapy
Volume20
Issue number5
DOIs
Publication statusPublished - 7 Feb 2012

Cite this

Maguire, C. A., Balaj, L., Sivaraman, S., Crommentuijn, M. H. W., Ericsson, M., Mincheva-Nilsson, L., ... Skog, J. (2012). Microvesicle-associated AAV vector as a novel gene delivery system. Molecular Therapy, 20(5), 960-971. https://doi.org/10.1038/mt.2011.303