Passive tumour targeting of polymer-coated adenovirus for cancer gene therapy
Passive tumour targeting of polymer-coated adenovirus for cancer gene therapy
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DOI：
10.1080/10611860701501014
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发表时间：
2007-01-01
影响因子：
4.5
通讯作者：
Seymour, Leonard W.
中科院分区：
文献类型：
--
作者：
Fisher, Kerry D.;Green, Nicola K.;Seymour, Leonard W.
腺病毒提供了许多机会，作为一种载体，用于交付细胞毒性基因的肿瘤。已知腺病毒的聚合物涂层增加其血浆循环动力学，从而提供主动和被动靶向投票的可能性。在这里，我们表明，聚合物包被腺病毒（pc病毒）废除其正常的体外感染性，也在肝脏静脉注射后。包被的病毒在固体皮下AB22间皮瘤中的积累比未修饰的病毒多40倍，并介导肿瘤内更高水平的转基因表达。这是第一次证明通过静脉注射施用的聚合物包被的腺病毒的被动转向靶向，也是第一次证明pc病毒在体内被动靶向肿瘤后具有感染性。该技术提供了一种有趣的选择，通过静脉注射将治疗性病毒递送至播散的肿瘤块。
Adenovirus provides many opportunities as a vector for delivery of cytotoxic genes to tumours. Polymer coating of adenovirus is known to increase its plasma circulation kinetics, affording the possibility of active and passive targeting to turnouts. Here we show that polymer-coating adenovirus (pc-virus) abrogates its normal infectivity in vitro and also in liver following intravenous injection. The coated virus accumulates within solid subcutaneous AB22 mesotheliorna turnouts 40-times more than unmodified virus, and mediates higher levels of transgene expression within tumours. This is the first demonstration of passive turnour targeting of polymer-coated adenoviruses administered by intravenous injection, and also the first time pc-virus has been shown to be infectious following passive targeting to tumours in vivo. This technology provides an interesting option for delivery of therapeutic viruses to disseminated tumour masses by intravenous injection.