GENETIC TREATMENT FOR ATHEROSCLEROSIS

动脉粥样硬化的基因治疗

• 批准号: 6194174
• 负责人: BA-BIE TENG
• 金额: $ 29.9万
• 依托单位: UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON
• 依托单位国家: 美国
• 财政年份: 1994
• 资助国家: 美国
• 起止时间: 1994-12-01 至 2004-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6194174
• 关键词: arteriosclerosis; disease /disorder model; gene therapy; genetic susceptibility; genetically modified animals; hypercholesterolemia; hyperlipidemia; in situ hybridization; laboratory mouse; model design /development; nonhuman therapy evaluation; ribozymes; tissue /cell culture

The objective of this proposed research is to define target gene(s) underlying predisposition to atherosclerosis and to develop human gene therapy for the treatment of hyperlipidemia. Studies will be carried out to define genetic factor(s) that contributes to atherosclerosis by developing dyslipidemia murine model. We will use these models to elucidate the molecular mechanisms of the disease and to evaluate novel therapeutics. The proposal seeks out to establish the effectiveness of using adeno-associated virus vector for gene delivery of ribozyme in diseased animals. Studies will also investigate the efficacy of using ribozyme as a potential therapeutic agent by generating transgenic mouse expressing ribozyme. Studies will also address new approaches for gene delivery of multiple genes together by using helper-dependent adenovirus vector in vivo to evaluate the synergistic effect of this strategy on the treatment for hyperlipidemia. Taken together, these studies will provide understanding of target(s) underlying predisposition to atherogenesis. The study will shed new insights to the understanding of the structure/function of the apoB mRNA hammerhead ribozyme, and the possible application of using this ribozyme as a therapeutic agent for the treatment of atherosclerosis.

本研究的目的是确定动脉粥样硬化易感基因的靶基因，并开发用于治疗高脂血症的人类基因疗法。将通过开发血脂异常小鼠模型进行研究，以确定导致动脉粥样硬化的遗传因素。 我们将使用这些模型来阐明疾病的分子机制，并评估新的治疗方法。该提案旨在建立使用腺相关病毒载体在患病动物中进行核酶基因递送的有效性。 研究还将通过产生表达核酶的转基因小鼠来研究使用核酶作为潜在治疗剂的功效。研究还将探讨通过使用辅助依赖性腺病毒载体在体内进行多基因联合基因递送的新方法，以评估该策略对高脂血症治疗的协同作用。总之，这些研究将提供对动脉粥样硬化形成的潜在易感性的靶点的理解。 本研究为进一步了解apoB mRNA锤头状核酶的结构和功能，以及利用该核酶作为治疗剂治疗动脉粥样硬化提供了新的思路。