Evaluation of the specificity and sensitivity of ferritin as an MRI reporter gene in the mouse brain using lentiviral and adeno-associated viral vectors
Evaluation of the specificity and sensitivity of ferritin as an MRI reporter gene in the mouse brain using lentiviral and adeno-associated viral vectors
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DOI：
10.1038/gt.2011.2
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发表时间：
2011-06-01
期刊：
影响因子：
5.1
通讯作者：
Baekelandt, V.
中科院分区：
文献类型：
--
作者：
Vande Velde, G.;Rangarajan, J. R.;Baekelandt, V.
开发体内成像方案以可靠地跟踪移植细胞或报告基因表达对于（预）临床细胞和基因治疗方案中的治疗监测至关重要。因此，我们评估了慢病毒载体（LV）和腺相关病毒载体（AAV）在啮齿动物大脑中表达磁共振成像（MRI）报告基因铁蛋白的潜力。首先，我们比较了免疫缺陷和免疫功能正常小鼠中两种载体系统的背景 MRI 对比度的诱导。左心室注射导致注射部位 T-2/T-2*（自旋-自旋弛豫时间）加权 MRI 对比出现低信号（即暗）变化，这可以部分解释为针对载体注射的炎症反应。与 LV 相比，AAV 注射导致背景对比度降低。此外，AAV 介导的铁蛋白过度表达导致 T-2* 加权 MRI 上的背景对比度显着增强。尽管与铁蛋白报告基因相关的灵敏度仍然较低，但 AAV 似乎是体内 MRI 报告基因成像最有前途的载体系统。基因治疗 (2011) 18, 594-605; doi：10.1038/gt.2011.2； 2011 年 2 月 24 日在线发布
The development of in vivo imaging protocols to reliably track transplanted cells or to report on gene expression is critical for treatment monitoring in (pre) clinical cell and gene therapy protocols. Therefore, we evaluated the potential of lentiviral vectors (LVs) and adeno-associated viral vectors (AAVs) to express the magnetic resonance imaging (MRI) reporter gene ferritin in the rodent brain. First, we compared the induction of background MRI contrast for both vector systems in immune-deficient and immune-competent mice. LV injection resulted in hypointense (that is, dark) changes of T-2/T-2* (spin-spin relaxation time)weighted MRI contrast at the injection site, which can be partially explained by an inflammatory response against the vector injection. In contrast to LVs, AAV injection resulted in reduced background contrast. Moreover, AAV-mediated ferritin overexpression resulted in significantly enhanced contrast to background on T-2*-weighted MRI. Although sensitivity associated with the ferritin reporter remains modest, AAVs seem to be the most promising vector system for in vivo MRI reporter gene imaging. Gene Therapy (2011) 18, 594-605; doi: 10.1038/gt.2011.2; published online 24 February 2011