TY - JOUR
T1 - Microvesicle-associated AAV vector as a novel gene delivery system
AU - Maguire, Casey A.
AU - Balaj, Leonora
AU - Sivaraman, Sarada
AU - Crommentuijn, Matheus H.W.
AU - Ericsson, Maria
AU - Mincheva-Nilsson, Lucia
AU - Baranov, Vladimir
AU - Gianni, Davide
AU - Tannous, Bakhos A.
AU - Sena-Esteves, Miguel
AU - Breakefield, Xandra O.
AU - Skog, Johan
PY - 2012/2/7
Y1 - 2012/2/7
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84860526022&partnerID=8YFLogxK
U2 - 10.1038/mt.2011.303
DO - 10.1038/mt.2011.303
M3 - Article
C2 - 22314290
AN - SCOPUS:84860526022
VL - 20
SP - 960
EP - 971
JO - Molecular Therapy
JF - Molecular Therapy
SN - 1525-0016
IS - 5
ER -