Genetically targeted adenovirus vector directed to CD40-expressing cells
Genetically targeted adenovirus vector directed to CD40-expressing cells
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DOI：
10.1128/jvi.77.21.11367-11377.2003
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发表时间：
2003-11-01
影响因子：
5.4
通讯作者：
Krasnykh, V
中科院分区：
文献类型：
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作者：
Belousova, N;Korokhov, N;Krasnykh, V
基因治疗的成功取决于治疗载体传递转基因的特异性。本研究描述了使用腺病毒（Ad）纤维替代策略将病毒基因靶向于多种病变组织表达的人类CD40。病毒的趋向性是通过将包含三种不同蛋白质结构域的蛋白质嵌合体掺入其衣壳来修饰的：Ad血清型5纤维、噬菌体T4纤维蛋白和人CD40配体（CD40L）。CD40L的肿瘤坏死因子样结构域在与嵌合体结合后保留其功能性三级结构，并允许病毒使用CD40作为进入细胞的替代受体。修饰后的Ad载体能够高效感染cd40阳性树突状细胞和肿瘤细胞，这使得该病毒成为遗传免疫和肿瘤靶向破坏治疗载体衍生的原型选择。
The success of gene therapy depends on the specificity of transgene delivery by therapeutic vectors. The present study describes the use of an adenovirus (Ad) fiber replacement strategy for genetic targeting of the virus to human CD40, which is expressed by a variety of diseased tissues. The tropism of the virus was modified by the incorporation into its capsid of a protein chimera comprising structural domains of three different proteins: the Ad serotype 5 fiber, phage T4 fibritin, and the human CD40 ligand (CD40L). The tumor necrosis factor-like domain of CD40L retains its functional tertiary structure upon incorporation into this chimera and allows the virus to use CD40 as a surrogate receptor for cell entry. The ability of the modified Ad vector to infect CD40-positive dendritic cells and tumor cells with a high efficiency makes this virus a prototype of choice for the derivation of therapeutic vectors for the genetic immunization and targeted destruction of tumors.