Department of Biological Sciences, Carnegie Mellon University, Pittsburgh, PA 15213, USA.
Gene Ther. 2013 Jun;20(6):589-96. doi: 10.1038/gt.2012.70. Epub 2012 Sep 20.
The development of effective strategies for gene therapy has been hampered by difficulties verifying transgene delivery in vivo and quantifying gene expression non-invasively. Magnetic resonance imaging (MRI) offers high spatial resolution and three-dimensional views, without tissue depth limitations. The iron-storage protein ferritin is a prototype MRI gene reporter. Ferritin forms a paramagnetic ferrihydrite core that can be detected by MRI via its effect on the local magnetic field experienced by water protons. In an effort to better characterize the ferritin reporter for central nervous system applications, we expressed ferritin in the mouse brain in vivo using a neurotropic herpes simplex virus type 1 (HSV-1). We computed three-dimensional maps of MRI transverse relaxation rates in the mouse brain with ascending doses of ferritin-expressing HSV-1. We established that the transverse relaxation rates correlate significantly to the number of inoculated infectious particles. Our results are potentially useful for quantitatively assessing limitations of ferritin reporters for gene therapy applications.
基因治疗中有效策略的发展受到难以在体内验证转基因的传递和非侵入性定量基因表达的阻碍。磁共振成像（MRI）提供了高空间分辨率和三维视图，没有组织深度限制。铁储存蛋白铁蛋白是 MRI 基因报告器的原型。铁蛋白形成顺磁的水铁矿核心，可通过 MRI 检测到，其通过对水质子所经历的局部磁场的影响来检测。为了更好地描述铁蛋白报告器在中枢神经系统应用中的特征，我们使用神经嗜性单纯疱疹病毒 1（HSV-1）在小鼠脑中表达铁蛋白。我们用递增剂量的表达铁蛋白的 HSV-1 计算了小鼠脑的 MRI 横向弛豫率的三维图谱。我们确定横向弛豫率与接种的感染性颗粒数显著相关。我们的结果对于定量评估铁蛋白报告器在基因治疗应用中的局限性具有潜在的应用价值。
