DNA virus as vectors for cardiovascular diseases

DNA病毒作为心血管疾病的载体

• 批准号: 7822199
• 负责人: James M Wilson
• 金额: $ 2.84万
• 依托单位: UNIVERSITY OF PENNSYLVANIA
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-06-01 至 2010-10-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7822199
• 关键词: DNA; virus; vectors; cardiovascular; diseases

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.

这种竞争的续订应用程序建立在最初的最初周期中取得的重大进展 这项在基因转移到心脏和肝脏的发展中的赠款用于治疗心脏病和 动脉粥样硬化。赠款的结构在续签中没有改变，包括 博士。威尔逊，斯威尼和拉德以及向量，细胞形态和行政核心。这 该P01当前周期的目标已实现，导致63个出版物。更新 应用程序基于此进度。更新赠款的总体目标是发展有效 用于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 更新的重要主题是，需要了解的生物学和发病机理 为了实现这一目标，使用的向量系统和目标疾病。在项目1中，威尔逊博士将 利用他们最近发现的一个新的AAV家族，广泛分布在非人类 灵长类动物种群为靶向心脏和肝脏创建更好的向量，并了解更多有关 在使用AAV载体的背景下，天然AAV感染的生物学。 Sweeney博士，项目2， 将开发使用载体靶向心肌细胞的方法，以进一步定义机制 心肌后扩张性心肌病和衰竭的逐步发展的基础 在慢性压力超负荷的情况下，梗塞和肥大。在项目3中 Rader博士将利用肝脏定向基因转移技术来研究并可能治疗两个 含APOB的脂蛋白的疾病：家族性高胆固醇血症和降低脂蛋白血症。 项目1中开发的向量将根据项目2和3的需求进行评估。 核心将产生并表征所有项目中使用的材料，而细胞形态核心将 在基因转移和载体制剂表征的体内分析中提供支持。