A hybrid vector for ligand-directed tumor targeting and molecular imaging
A hybrid vector for ligand-directed tumor targeting and molecular imaging
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DOI：
10.1016/j.cell.2006.02.042
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发表时间：
2006-04-21
期刊：
影响因子：
64.5
通讯作者：
Arap, W
中科院分区：
文献类型：
--
作者：
Hajitou, A;Trepel, M;Arap, W
将肿瘤靶向和分子遗传成像合并到一个集成平台中受到缺乏策略的限制，这些策略可以实现特定转基因的系统性但配体定向的递送和成像。许多真核病毒用于转基因递送，但需要消除对哺乳动物细胞的天然向性;相反，原核病毒可以适于结合哺乳动物受体，但在其他方面是差的载体。在这里，我们介绍了一个系统包含顺式元件从腺相关病毒（AAV）和单链噬菌体。我们的AAV/噬菌体（AAVP）原型靶向整合素。我们表明AAVP提供了优于噬菌体的上级肿瘤转导，并且反向末端重复序列的掺入与递送的转基因的改善的命运相关。此外，我们表明，靶向AAVP介导的基因表达的时间动态和空间异质性可以通过正电子发射断层扫描监测。这类新的靶向杂交病毒颗粒将在生物学和医学中得到广泛的应用。
Merging tumor targeting and molecular-genetic imaging into an integrated platform is limited by lack of strategies to enable systemic yet ligand-directed delivery and imaging of specific transgenes. Many eukaryotic viruses serve for transgene delivery but require elimination of native tropism for mammalian cells; in contrast, prokaryotic viruses can be adapted to bind to mammalian receptors but are otherwise poor vehicles. Here we introduce a system containing cis-elements from adeno-associated virus (AAV) and single-stranded bacteriophage. Our AAV/phage (AAVP) prototype targets an integrin. We show that AAVP provides superior tumor transduction over phage and that incorporation of inverted terminal repeats is associated with improved fate of the delivered transgene. Moreover, we show that the temporal dynamics and spatial heterogeneity of gene expression mediated by targeted AAVP can be monitored by positron emission tomography. This new class of targeted hybrid viral particles will enable a wide range of applications in biology and medicine.