Adenovirus-microbead conjugates possess enhanced infectivity: A new strategy for localized gene delivery
Adenovirus-microbead conjugates possess enhanced infectivity: A new strategy for localized gene delivery
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DOI：
10.1006/viro.2002.1510
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发表时间：
2002-08-01
期刊：
影响因子：
3.7
通讯作者：
Sano, T
中科院分区：
文献类型：
--
作者：
Pandori, MW;Hobson, DA;Sano, T
我们已经创造了一种新的方法，用于将腺病毒载体偶联到固体微珠上，这种方法不会对所连接的病毒粒子的感染性产生不利影响。该方法利用蛋白质链霉亲和素与其配体生物素之间的极其紧密的相互作用作为将病毒颗粒拴系到微珠的手段。所产生的腺病毒-微珠缀合物作为完全感染性实体起作用，并且与游离的、未修饰的病毒颗粒相比具有若干功能优势。腺病毒-微珠缀合物具有增强的在培养物中粘附靶细胞的能力。对于高度允许性质的靶细胞，这种感染性的增加是适度的。然而，对于中到低渗透率的靶细胞，转导效率的增强是实质性的。腺病毒载体以前不能感染特定的结肠癌细胞系，当作为固相缀合物递送时，在相同的细胞系上完全具有感染性。此外，固相腺病毒-微珠缀合物在溶液中显示出高度有限的扩散，允许病毒载体仅集中递送至与缀合物接触的细胞。当病毒颗粒附着的固相具有顺磁性时，通过使用策略性放置的磁体，病毒感染的位置可以通过磁力严格控制。(C)2002 Elsevier Science（美国）。
We have created a novel method for coupling adenoviral vectors to solid microbeads in a way that does not adversely affect the infectivity of the attached virions. This method utilizes the extremely tight interaction between the protein streptavidin and its ligand biotin as a means of tethering viral particles to microbeads. The adenovirus-microbead conjugates that were created functioned as fully infectious entities and possessed several functional advantages over free, unmodified viral particles. The adenovirus-microbead conjugates possessed enhanced ability to transduce target cells in culture. For target cells of a highly permissive nature, this increase in infectivity was modest. However for target cells of moderate to low permissivity, the enhancement of transduction efficiency was substantial. Adenoviral vectors, previously incapable of infecting a particular colon cancer cell line, were made fully infectious on the same cell line when delivered as solid-phase conjugates. Additionally, solid-phase adenovirus-microbead conjugates showed highly limited diffusion in solution, allowing for focused delivery of viral vectors only to cells that come into contact with the conjugates. When the solid phase to which the viral particles were attached had paramagnetic properties, the location of viral infections was tightly controllable by magnetic force through the use of strategically placed magnets. (C) 2002 Elsevier Science (USA).