Aptamer modification improves the adenoviral transduction of malignant glioma cells
Aptamer modification improves the adenoviral transduction of malignant glioma cells
复制标题
适体修饰改善恶性胶质瘤细胞的腺病毒转导
DOI：
10.1016/j.jbiotec.2013.10.024
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发表时间：
2013-12-01
影响因子：
4.1
通讯作者：
Mao, Qinwen
中科院分区：
文献类型：
--
作者：
Chen, Hao;Zheng, Xiaojing;Mao, Qinwen
腺病毒在胶质母细胞瘤的基因病毒治疗中显示出越来越大的前景，这种治疗策略依赖于将病毒或转基因传递到肿瘤细胞中。然而，由于胶质瘤细胞中柯萨奇病毒和腺病毒受体（CAR）的表达水平较低，腺病毒靶向人胶质母细胞瘤仍然是一个挑战。适体是小型且高度结构化的单链寡核苷酸，能够以高亲和力与靶分子结合，是靶向成像和治疗的良好候选者。在本研究中，为了构建适配体修饰的Ad5，我们首先通过生物素受体肽（BAP）对Ad六邻体的HVR5进行基因修饰，该肽在HEK293细胞中生产过程中会被代谢生物素化，然后通过亲和素-生物素结合将生物素标记的适配体附着到修饰的Ad上。本研究中使用的适配体包括AS1411和GBI-10。前者是一种DNA适体，可以与核仁素（癌细胞表面发现的一种核基质蛋白）结合。后者是一种DNA适体，可以识别人胶质母细胞瘤细胞表面的细胞外基质蛋白tenascin-C。为了检查六邻体蛋白的适体修饰是否可以提高腺病毒转导效率，用适体修饰的Ads转导胶质母细胞瘤细胞系U251。 AS1411或GBI-10修饰的Ad的转导效率比对照高约4.1倍或5.2倍。数据表明，适配体修饰的腺病毒将成为癌症基因治疗的有用工具。 (C) 2013 Elsevier B.V. 保留所有权利。
Adenovirus has shown increasing promise in the gene-viral therapy for glioblastoma, a treatment strategy that relies on the delivery of viruses or transgenes into tumor cells. However, targeting of adenovirus to human glioblastoma remains a challenge due to the low expression level of coxsackie and adenovirus receptor (CAR) in glioma cells. Aptamers are small and highly structured single-stranded oligonucleotides that bind at high affinity to a target molecule, and are good candidates for targeted imaging and therapy. In this study, to construct an aptamer-modified Ad5, we first genetically modified the HVR5 of Ad hexon by biotin acceptor peptide (BAP), which would be metabolically biotinylated during production in HEK293 cells, and then attached the biotin labeled aptamer to the modified Ad through avidin-biotin binding. The aptamers used in this study includes AS1411 and GBI-10. The former is a DNA aptamer that can bind to nucleolin, a nuclear matrix protein found on the surface of cancer cells. The latter is a DNA aptamer that can recognize the extracellular matrix protein tenascin-C on the surface of human glioblastoma cells. To examine if aptamer-modification of the hexon protein could improve the adenoviral transduction efficiency, a glioblastoma cell line, U251, was transduced with aptamer-modified Ads. The transduction efficiency of AS1411- or GBI-10-modified Ad was approximately 4.1-fold or 5.2-fold higher than that of the control. The data indicated that aptamer modified adenovirus would be a useful tool for cancer gene therapy. (C) 2013 Elsevier B.V. All rights reserved.