Noninvasive imaging of transcriptionally restricted transgene expression following intratumoral injection of an adenovirus in which the COX-2 promoter drives a reporter gene
Noninvasive imaging of transcriptionally restricted transgene expression following intratumoral injection of an adenovirus in which the COX-2 promoter drives a reporter gene
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DOI：
10.1016/j.mibio.2004.09.002
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发表时间：
2004-11-01
影响因子：
3.1
通讯作者：
Herschman, HR
中科院分区：
文献类型：
--
作者：
Liang, QW;Yamamoto, M;Herschman, HR
目的：通过对报告基因表达的重复、非侵入性光学成像，观察双特异性重组分子(I)对依赖于柯萨奇病毒和腺病毒受体(CAR)的正常组织的非转导靶向感染能力和(II)对特定靶细胞的感染能力。疤痕部分与病毒结合，阻止CAR依赖腺病毒感染。EGF部分与细胞内的EGF受体结合。我们使用萤火虫荧光素酶的非侵入性光学成像，在活体动物中重复监测SCAR-EGF(I)从正常组织系统地注射Ad.CMVfLuc的能力，Ad.CMVfLuc是一种从正常组织中组成地表达荧光素酶的腺病毒，以及(Ii)将小鼠的腺病毒感染“转导重定向”到表达升高的表皮生长因子(EGF)受体水平的异种移植瘤。结果：系统注射从CMV早期启动子表达萤火虫荧光素酶的SCAR-EGF“包衣”腺病毒，结论：利用荧光素酶报告基因可以对重组SCAR-EGF重组腺病毒的肝脏“非靶向”和肿瘤“重定向”进行非侵入性成像。(C)2004 Elsevier Inc.保留所有权利。
PURPOSE: To demonstrate the efficacy of repeated, non-invasive optical imaging of reporter gene expression in monitoring the ability of bi-specific recombinant molecules (i) to "transductionally untarget" adenovirus from Coxsackie and Adenovirus Receptor (CAR)dependent infection of normal tissue and (ii) to "transductionally retarget" infection to specific target cells.PROCEDURES: sCAR-EGF is a recombinant, bi-specific molecule containing the soluble portion of CAR fused to Epidermal Growth Factor. The sCAR moiety binds to the virus and blocks CAR dependent adenovirus infection. The EGF moity binds to cellular EGF receptors. We used non-invasive optical imaging of firefly luciferase to repeatedly monitor, in living animals, the ability of sCAR-EGF (i) to "transductionally untarget" systemically administered Ad.CMVfLuc, an adenovirus that constitutively expresses luciferase, from normal tissues and (ii) to "transductionally redirect" adenovirus infection in mice to xenograft tumors that express elevated epidermal growth factor (EGF) receptor levels.RESULTS: Systemic injection of sCAR-EGF "coated" adenovirus expressing firefly luciferase from the CMV early promoter, reduces expression of the reporter gene in the liver and facilitates expression of the reporter gene in tumor xenografts expressing high levels of the EGF-receptor.CONCLUSION: Both liver "untargeting" and tumor "retargeting" of adenovirus by recombinant sCAR-EGF can be imaged non-invasively using a luciferase reporter gene. (C) 2004 Elsevier Inc. All rights reserved.