Insertion of an RGD motif into the HI loop of adenovirus fiber protein alters the distribution of transgene expression of the systemically administered vector
Insertion of an RGD motif into the HI loop of adenovirus fiber protein alters the distribution of transgene expression of the systemically administered vector
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DOI：
10.1038/sj.gt.3300941
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发表时间：
1999-07-01
期刊：
影响因子：
5.1
通讯作者：
Curiel, DT
中科院分区：
文献类型：
--
作者：
Reynolds, PN;Dimitriev, I;Curiel, DT
腺病毒载体是有吸引力的基因递送载体，但其体内效用由于缺乏细胞特异性感染而降低。通过衣壳蛋白的遗传操作对病毒粒子进行嗜性修饰是实现靶向转导的有吸引力的策略。然而，还没有遗传靶向策略显示出在系统施用载体后改变转基因表达的分布。如果这些方法要成为进一步发展病媒的基础，这是一项基本要求。在这份报告中，我们目前的数据显示，插入一个RGD基序到HI环的腺病毒纤维球的结果在转基因表达谱的显着变化后，静脉内给药。当全身施用时，Hl环中的基序可用于细胞相互作用的关键发现意味着可以合理地将这种修饰视为基础，在此基础上可以叠加进一步的遗传修饰用于靶向全身基因治疗。
Adenoviral vectors are attractive gene delivery vehicles, but their in vivo utility is reduced by lack of cell-specific infection. Tropism modification of the virion by genetic manipulation of capsid proteins is an attractive strategy to achieve targeted transduction. However, no genetic targeting strategies have yet been shown to modify the distribution of transgene expression following systemic administration of vector. This is an essential requirement if such approaches are to form a basis for further vector development. In this report we present data showing that insertion of a RGD motif into the HI loop of the adenoviral fiber knob results in a significant change in transgene expression profile following intravenous administration. The key finding that a motif in the HI loop is available for cellular interaction when administered systemically means that such modifications can be rationally considered as a foundation upon which further genetic modifications can be superimposed for targeted systemic gene therapy.