Microvesicle-associated AAV Vector as a Novel Gene Delivery System
Microvesicle-associated AAV Vector as a Novel Gene Delivery System
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DOI：
10.1038/mt.2011.303
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发表时间：
2012-05-01
影响因子：
12.4
通讯作者：
Skog, Johan
中科院分区：
文献类型：
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作者：
Maguire, Casey A.;Balaj, Leonora;Skog, Johan
腺相关病毒（AAV）载体在培养细胞和人类疾病动物模型中表现出显著的基因传递效率。然而，静脉转移后AAV载体基因转移存在局限性，包括脱靶基因递送（如肝脏）和靶组织的低转导。在这里，我们发现在生产过程中，一小部分AAV载体与微囊泡/外泌体相关，称为囊泡体（载体外泌体）。利用电子显微镜观察与微泡表面和内部相关的AAV衣壳。在培养的细胞中，静脉泌体的转导效率优于常规纯化的AAV载体。我们发现，与常规纯化的AAV相比，纯化的vexosomes对中和的抗AAV抗体更具抗性。最后，我们表明，在培养的细胞中，与磁珠结合的体体可以被吸引到磁化区域。静脉泌体是一种独特的实体，它为改善基因传递提供了一种有前途的策略。
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.