Intravascular MRI-Enchanced Vascular Gene Transfer

描述（来自申请人摘要的逐字）：血管基因疗法是 动脉粥样硬化性心血管疾病治疗的前沿领域 疾病迄今为止，血管基因治疗的成像方法还没有被发现。 探讨了心血管磁共振成像，其突出的优势， 血管壁的高分辨率图像和多种诊断评价 器官功能和形态以及多个图像平面，无风险 电离辐射，是一种独特的成像方式，通过它来监测和 控制血管基因治疗。在这个项目中，我们将探索一种新的 通过三种新血管内磁共振血管基因治疗方法 技术：1）使用我们的无环MR天线作为独特的血管内 射频加热源，以增强血管基因转染; 2）使用我们的 血管内MR引导介入技术精确引导血管 基因递送;以及3）创建对比增强的血管内高分辨率 基因/热靶向血管壁MR成像监测血管基因 疗法这些技术的发展将首先在体外测试使用细胞 模型和人尸体动脉，然后在国内进行体内验证 猪和尤卡坦小型猪的髂动脉粥样硬化狭窄。 我们将使用第三代慢病毒载体作为主要的血管基因 在我们的体外和体内研究中，另外我们 将比较慢病毒与其他病毒/非病毒的作用， 载体，如腺病毒和脂质体以及质粒DNA， 血管基因转移的MR/RF加热增强。我们坚信 这一项目的成功将为未来的全球经济发展开辟新的途径。 基于MR的心血管缺血性疾病的综合管理 形式，即，使用术前和术后MR血管造影和功能 MR成像，以验证基于MR的血管内干预的成功， 基因治疗在一个单一的设置，在一个磁共振扫描仪。这也将有助于 临床接受度，因此MR方法的临床应用更加广泛， 提高心血管疾病诊断和治疗水平。

DESCRIPTION (Verbatim from the Applicant's Abstract): Vascular gene therapy is an exciting frontier in the treatment of atherosclerotic cardiovascular disease. To date, methods of imaging vascular gene therapy have not been explored. Cardiovascular MR imaging, with its prominent advantages of high-resolution images of the vessel wall and multiple diagnostic evaluations of organ function and morphology as well as multiple image planes with no risk of ionizing radiation, is a unique imaging modality by which to monitor and control vascular gene therapy. In this project, we will explore a new methodology of intravascular MR-based vascular gene therapy through three novel techniques: 1) using our loopless MR antenna as a unique endovascular RF-heating source to enhance vascular gene transfection; 2) using our intravascular MR-guided interventional technique to precisely guide vascular gene delivery; and 3) creating contrast-enhanced intravascular high-resolution MR imaging of the gene/heat-targeted vessel wall to monitor vascular gene therapy. These technical developments will be first tested in vitro using cell phantoms and human cadaveric arteries, and then validated in vivo in domestic pigs and Yucatan minipigs with atherosclerotic stenoses of the iliac arteries. We will use a third-generation lentiviral vector as the primary vascular gene delivery vector in our in vitro and in vivo investigations. In addition, we will compare the role of the lentivirus with that of other viraVnon-viral vectors, such as adenovirus and liposome as well as plasmid DNA, in the MR/RF-heating enhancement of vascular gene transfer. We firmly believe that the success of this project will open up new avenues for the future global comprehensive management of cardiovascular ischemic disorders using MR-based modalities, i.e., using pre- and post-operative MR angiography and functional MR imaging to validate the success of intravascular MR-based interventions and gene therapy in a single setting, in an MR scanner. This should also facilitate clinical acceptance and therefore more extensive clinical use of MR methods to improve tbe diagnosis and management of cardiovascular disorders.