Martin Delaney Collaboratory to Eradicate HIV-1 Infection

Martin Delaney 合作根除 HIV-1 感染

• 批准号: 8298077
• 负责人: DAVID M. MARGOLIS
• 金额: $ 899.01万
• 依托单位: UNIV OF NORTH CAROLINA CHAPEL HILL
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-07-08 至 2016-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8298077
• 关键词: Martin; Delaney; Collaboratory; Eradicate; HIV

DESCRIPTION (provided by applicant): Despite the clinical success of antiretroviral therapy (ART), more people contract human immunodeficiency virus (HIV) infection daily than initiate ART. The difficulties of lifelong ART - particularly in the developing world - make the eradication of HIV imperative. But clearance of a retroviral infection for patients on ART is a herculean task. While much is known about HIV persistence despite ART, many puzzles remain. New tools to address latent infection must replace the paradigms and models used to develop ART. Existing cellular and animal models that represent HIV latency in vivo require further development, and while latent provirus can be purged in the laboratory, a testable, comprehensive therapeutic strategy is not at hand. Therefore we propose the Martin Delaney Collaboratory to Eradicate HIV-1 Infection, a close collaboration of 21 exceptional investigators who have collectively led the field of HIV latency over the last 10 years. To maximize success, we will work across four areas of research to develop the infrastructure and systems needed to define eradication therapies, identify new molecules with therapeutic potential and provide a proof-of-concept for a small molecule based eradication strategy in animal models. Objective 1 will identify the molecular mechanisms underlying viral persistence and latency; Objective 2 will identify drug candidates and therapeutic strategies to reduce the latent viral pool; Objective 3 will establish informative animal model systems to evaluate latency and test therapeutic strategies; and finally. Objective 4 will perform studies in humans to delineate the basis for viral persistence. Three cores will assist research projects with pharmacology, molecular assays, and sequence and expression analysis. An administrative core will assure coordination, and maintain the focus of this experienced and potent group towards translational product development. As a group, we are committed to pooling our resources and expertise to transcend the normal constraints of academic research. Of note, the expertise and durable commitment of Merck Research Laboratories will be critical to delivering therapeutic advances. We are convinced that together we will catalyze advances that will ultimately lead to the eradication of HIV infection.

描述（由申请人提供）：尽管抗逆转录病毒疗法 (ART) 在临床上取得了成功，但每天感染人类免疫缺陷病毒 (HIV) 的人数仍多于开始 ART 的人数。终身抗逆转录病毒治疗的困难——特别是在发展中国家——使得根除艾滋病毒势在必行。但对于接受 ART 的患者来说，清除逆转录病毒感染是一项艰巨的任务。尽管接受抗逆转录病毒疗法后，艾滋病毒的持续存在已广为人知，但仍然存在许多谜团。解决潜伏感染的新工具必须取代用于开发 ART 的范式和模型。代表 HIV 体内潜伏期的现有细胞和动物模型需要进一步开发，虽然潜伏原病毒可以在实验室中清除，但目前还没有可测试的综合治疗策略。 因此，我们提议建立 Martin Delaney 根除 HIV-1 感染合作实验室，该实验室由 21 名杰出研究人员密切合作，他们在过去 10 年里共同领导了 HIV 潜伏期领域的研究。为了最大限度地取得成功，我们将在四个研究领域开展工作，开发定义根除疗法所需的基础设施和系统，识别具有治疗潜力的新分子，并为动物模型中基于小分子的根除策略提供概念验证。目标 1 将确定病毒持续存在和潜伏期的分子机制；目标 2 将确定候选药物和治疗策略，以减少潜伏病毒库；目标3将建立信息丰富的动物模型系统来评估潜伏期并测试治疗策略；最后。目标 4 将在人体中进行研究，以确定病毒持续存在的基础。三个核心将协助药理学、分子测定以及序列和表达分析的研究项目。行政核心将确保协调，并保持这个经验丰富且强大的团队对转化产品开发的关注。作为一个团队，我们致力于汇集我们的资源和专业知识，以超越学术研究的正常限制。值得注意的是，默克研究实验室的专业知识和持久的承诺对于实现治疗进展至关重要。我们相信，我们将共同推动进步，最终消除艾滋病毒感染。