期刊
MOLECULAR THERAPY
卷 20, 期 5, 页码 960-971出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/mt.2011.303
关键词
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资金
- NCI [P50 CA86355, P01 CA069246, RO1 CA141150]
- NIH/NINDS [P30NS045776]
- American Brain Tumor Association
- NINDS [P30NS4577]
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.
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