GENETIC TREATMENT FOR ATHEROSCLEROSIS

动脉粥样硬化的基因治疗

• 批准号: 6612557
• 负责人: BA-BIE TENG
• 金额: $ 33.43万
• 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 2005-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6612557
• 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.

这项拟议的研究的目的是定义靶基因对动脉粥样硬化的易感性，并开发人类基因治疗以治疗高脂血症。将进行研究以定义遗传因子，这些因素通过发展血脂异常模型来促进动脉粥样硬化。 我们将使用这些模型来阐明该疾病的分子机制并评估新的治疗疗法。该提案旨在确定使用腺相关病毒载体在患病动物中递送核酶的有效性。 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疗效。研究还将通过在体内使用辅助腺病毒载体来评估该策略对高脂血症治疗的协同作用，从而解决多个基因基因递送的新方法。综上所述，这些研究将提供对动脉粥样硬化倾向的靶标的理解。 这项研究将为理解Apob mRNA锤头核酶的结构/功能提供新的见解，并可能应用将此核酶作为治疗动脉粥样硬化的治疗剂。

项目成果

Mutational analysis of apolipoprotein B mRNA editing enzyme (APOBEC1). structure-function relationships of RNA editing and dimerization.

• 发表时间: 1999-04
• 期刊: Journal of lipid research
• 影响因子: 6.5
• 作者: B. Teng;S. Ochsner;Q. Zhang;K. Soman;P. Lau;L. Chan

Hammerhead ribozyme cleavage of apolipoprotein B mRNA generates a truncated protein.

锤头核酶切割载脂蛋白 B mRNA 产生截短的蛋白质。

• DOI: 10.1074/jbc.274.34.24161
• 发表时间: 1999
• 期刊: The Journal of biological chemistry
• 作者: Wang,JP;Enjoji,M;Tiebel,M;Ochsner,S;Chan,L;Teng,BB
• 通讯作者: Teng,BB

Simultaneous expression of apolipoprotein B mRNA editing enzyme and scavenger receptor BI mediated by a therapeutic gene expression system.

由治疗基因表达系统介导的载脂蛋白 B mRNA 编辑酶和清道夫受体 BI 的同时表达。

• DOI: 10.1016/j.atherosclerosis.2005.04.017
• 发表时间: 2006
• 期刊: Atherosclerosis
• 影响因子: 5.3
• 作者: Zhong,Shumei;Liu,Chichi;Haviland,David;Doris,PeterA;Teng,Ba-Bie
• 通讯作者: Teng,Ba-Bie

Effective lowering of plasma, LDL, and esterified cholesterol in LDL receptor-knockout mice by adenovirus-mediated gene delivery of ApoB mRNA editing enzyme (Apobec1).

通过腺病毒介导的 ApoB mRNA 编辑酶 (Apobec1) 基因传递，有效降低 LDL 受体敲除小鼠的血浆、LDL 和酯化胆固醇。

• DOI: 10.1161/01.atv.17.5.889
• 发表时间: 1997
• 期刊: Arteriosclerosis, thrombosis, and vascular biology
• 作者: Teng,B;Ishida,B;Forte,TM;Blumenthal,S;Song,LZ;GottoJr,AM;Chan,L
• 通讯作者: Chan,L

The recombinant adeno-associated virus vector (rAAV2)-mediated apolipoprotein B mRNA-specific hammerhead ribozyme: a self-complementary AAV2 vector improves the gene expression.

重组腺相关病毒载体 (rAAV2) 介导的载脂蛋白 B mRNA 特异性锤头核酶：自我互补的 AAV2 载体可改善基因表达。

• DOI: 10.1186/1479-0556-2-5
• 发表时间: 2004
• 期刊: Genetic vaccines and therapy
• 作者: Zhong,Shumei;Sun,Shihua;Teng,Ba-Bie
• 通讯作者: Teng,Ba-Bie