DNA virus as vectors for cardiovascular diseases

这一竞争性延期申请是在2010年第一周期取得实质性进展的基础上提出的。 这项赠款用于开发基因转移到心脏和肝脏治疗心脏病， 动脉粥样硬化赠款的结构在延长期间没有改变，包括以下项目： Drs. Wilson，Sweeney和Rader以及Vector，Cell Morphology和Administrative Cores。的 P01当前周期的目标已经实现，共发表了63篇文章。更新 应用程序建立在这一进展之上。更新补助金的总体目标是发展有效的 心血管疾病的基因治疗，可以通过靶向心脏和肝脏来实现。一个 更新的一个重要主题是，人们需要了解的生物学和发病机制， 为了实现这一目标，需要对所使用的病媒系统和目标疾病进行研究。在项目1中，威尔逊博士将 利用他们最近发现的广泛分布在非人类中的新的AAV家族， 灵长类动物群体，以创造更好的载体靶向心脏和肝脏，并了解更多关于 在使用AAV载体的情况下，天然AAV感染的生物学。斯威尼博士，在二号计划中 将开发用载体靶向心肌细胞的方法，以进一步确定机制， 扩张型心肌病的进展和心肌梗死后心力衰竭的基础 心肌梗死和在慢性压力超负荷的情况下发展的肥大。在项目3中， 博士雷德将利用肝脏定向基因转移技术来研究和治疗两种 含载脂蛋白B的脂蛋白疾病：家族性高胆固醇血症和无β脂蛋白血症。 将根据项目2和项目3的需要对项目1中开发的矢量进行评估。矢量 核心将生产和表征所有项目中使用的材料，而细胞形态核心将 为基因转移的体内分析和载体制剂的表征提供支持。

This competing renewal application builds on substantial progress that was made in the initial cycle of this grant in the development of gene transfer to heart and liver for treating heart disease and atherosclerosis. The structure of the grant has not changed in the renewal with includes projects by Drs. Wilson, Sweeney and Rader as well as Vector, Cell Morphology and Administrative Cores. The goals of the current cycle of this P01 have been realized resulting in 63 publications. The renewal application builds on this progress. The overall goal of the renewal grant is the development of effective gene therapy for cardiovascular disease, which can be achieved by targeting the heart and liver. An important theme in the renewal is that one needs to understand the biology and pathogenesis of the vectors systems used and the target diseases in order to realize this goal. In Project 1, Dr. Wilson will exploit their recent discovery of a new family of AAVs broadly distributed throughout non-human primate populations to create better vectors for targeting heart and liver and to learn more about the biology of natural AAV infections in the context of the use of AAV vectors. Dr. Sweeney, in Project 2, will develop methods to target cardiac myocytes with vectors to further define the mechanisms underlying the progressive development of dilated cardiomyopathy and failure following myocardial infarction and the hypertrophy that develops in the setting of chronic pressure overload. In Project 3, Dr. Rader will utilize techniques of liver directed gene transfer to study and potentially treat two diseases of apoB-containing lipoproteins: familial hypercholesterolemia and abetalipoproteinemia. Vectors developed in Project 1 will be evaluated in terms of the needs of Projects 2 and 3. The Vector Core will produce and characterize materials used in all projects while the Cell Morphology Core will provide support in the in vivo analysis of gene transfer and characterization of vector preparations.