EVALUATE EFFICACY OF ANGIOGENIC DELIVERY THERAPIES USING MICRO-CT

使用 MICRO-CT 评估血管生成疗法的疗效

• 批准号: 7956933
• 负责人: SECHIN CHO
• 金额: $ 0.82万
• 依托单位: DUKE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-07-01 至 2010-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7956933
• 关键词: Angiogenic Factor; Apoptosis; Apoptotic; Blood flow; Cardiovascular Diseases; Cells; Computer Retrieval of Information on Scientific Projects Database; DNA; DNA delivery; Endothelial Cells; Esters; Event; Funding; Genes; Grant; Hindlimb; Human; In Vitro; Injection of therapeutic agent; Institution; Ischemia; Limb structure; Lipids; Luciferases; Mediating; Mesenchymal Stem Cells; Microscopy; Modeling; Mus; Muscle; PTPN6 gene; Polymers; Process; Reporter; Research; Research Personnel; Resources; Signal Pathway; Small Interfering RNA; Source; System; Tissues; Treatment Efficacy; United States National Institutes of Health; Vascular Endothelial Growth Factors; angiogenesis; base; biocompatible polymer; gene delivery system; in vivo; muscle degeneration; prevent; protein expression; therapeutic angiogenesis; vector

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The overall objective of this study is to investigate therapeutic efficacy of our gene delivery systems in mouse hindlimb ischemic model. We have successfully demonstrated an efficient in vivo gene (DNA or siRNA) delivery using biocompatible polymers (poly ¿-amino ester for DNA delivery) and lipids (lipidoid for siRNA delivery) developed in Langer group. We are planning to investigate the in vivo feasibility of our gene delivery systems for treatment of cardiovascular diseases. 1. The first specific aim is to treat hindlimb ischemia with a lipid-mediated injection of siRNA for apoptotic molecules (e.g. SHP-1). Silencing of pro-apoptotic factors which are highly expressed in ischemic tissues could reduce cell apoptosis caused by no blood flow in ischemic tissues by blocking apoptotic signal pathway in the cells in ischemic regions, which may prevent limb muscle degeneration after ischemic event. 2. The second specific aim is to treat hindlimb ischemia with a polymer-mediated injection of angiogenic factor DNA (e.g. VEGF). Delivery of DNA for angiogenic factors could enhance angiogenesis process in ischemic limb muscle. However, our previous study showed that local injection of reporter DNA (luciferase) using the polymeric vectors into limb muscle did not show significant reporter protein expression in muscle tissues (Anderson et al., Proc Natl Acad Sci USA 2004;101:16028-16033). Thus, we are also considering the local injection of human endothelial cells or human mesenchymal stem cells in vitro genetically modified with VEGF DNA using our polymer-based delivery system as an alternative strategy for therapeutic angiogenesis.

该副本是使用众多研究子项目之一 由NIH/NCRR资助的中心赠款提供的资源。子弹和 调查员（PI）可能已经从其他NIH来源获得了主要资金， 因此可以在其他清晰的条目中代表。列出的机构是 对于中心，这是调查员的机构。 这项研究的总体目的是研究小鼠后肢缺血模型中基因递送系统的治疗效率。我们已经成功地证明了使用生物相容性聚合物（用于DNA递送的poly？氨基酯）和Langer组开发的脂质（用于siRNA递送的Lipidoid）的有效体内基因（DNA或siRNA）。我们计划调查我们基因输送系统治疗心血管疾病的体内可行性。 1。第一个具体目的是用脂质介导的siRNA对凋亡分子的siRNA（例如SHP-1）进行脂质介导的siRNA治疗后肢缺血。在缺血性组织中高度表达的促凋亡因子的沉默可以通过阻断缺血性区域的细胞凋亡信号途径而导致缺血性组织中没有血流引起的细胞凋亡，这可能会阻止肢体肌肉退化后缺血性事件。 2。第二个具体目的是用聚合物介导的血管生成因子DNA（例如VEGF）的注射来治疗后肢缺血。在缺血性肢体肌肉中递送DNA用于血管生成过程。但是，我们先前的研究表明，使用聚合物向量进入肢体肌肉的局部注射报告基因DNA（荧光素酶）在肌肉组织中没有显示出明显的报告蛋白表达（Anderson等，Proc Natl Acad Sci USA 2004; 101：16028-16033）。因此，我们还考虑使用基于聚合物的递送系统在体外注入人内皮细胞或人间质干细胞在体外用VEGF DNA修饰，作为治疗性血管生成的替代策略。