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Martin Delaney Collaboratory to Eradicate HIV-1 Infection

Martin Delaney 合作根除 HIV-1 感染

基本信息

批准号：
8707337
负责人：
DAVID M. MARGOLIS
金额：
$ 851.33万
依托单位：
UNIV OF NORTH CAROLINA CHAPEL HILL
依托单位国家：
美国
项目类别：
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/8707337
关键词：
Acquired Immunodeficiency Syndrome Address Animal Model Area Biological Assay Biological Models Cell model Clinical Collaborations Commit Communities Complement Contracts Development Disease Evaluation Genome Genomics Goals HIV HIV-1 Hand Human Immunohistochemistry In Situ Industry Infection Laboratories Laboratory Research Lead Medical Methods Minnesota Mission Modeling Molecular Patients Pharmacology Program Development Proviruses Reagent Research Research Infrastructure Research Personnel Research Project Grants Research Support Resources Scientist System T-Lymphocyte Testing Therapeutic Transcend Universities Utah Viral Virus Diseases Virus Latency Work antiretroviral therapy base collaboratory drug candidate drug discovery experience in vivo industry partner insight latent infection member mortality novel novel strategies pandemic disease phase 1 study prevent product development programs purge research clinical testing small molecule success tool verdin photosensitizer

项目摘要

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）：尽管抗逆转录病毒治疗（ART）取得了临床成功，但每天感染人类免疫缺陷病毒（HIV）的人数多于开始抗逆转录病毒治疗的人数。终生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。但对接受抗逆转录病毒治疗的患者来说，清除逆转录病毒感染是一项艰巨的任务。尽管人们对抗逆转录病毒治疗后艾滋病毒的持久性了解很多，但仍存在许多谜题。应对潜伏感染的新工具必须取代用于开发抗逆转录病毒药物的范例和模式。现有的代表HIV在体内潜伏期的细胞和动物模型需要进一步开发，虽然潜伏的原病毒可以在实验室中被清除，但目前还没有一种可测试的、全面的治疗策略。因此，我们建议建立Martin Delaney合作实验室，以根除HIV-1感染，这是21位杰出的研究人员的密切合作，他们在过去的10年里共同领导了HIV潜伏期领域。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，开发确定根除疗法所需的基础设施和系统，确定具有治疗潜力的新分子，并在动物模型中为基于小分子的根除策略提供概念验证。目的1将确定病毒持久性和潜伏期的分子机制；目的2将确定候选药物和治疗策略，以减少潜伏病毒库；目的3将建立信息性动物模型系统来评估潜伏期和测试治疗策略；最后。目标4将在人类中进行研究，以描述病毒持久性的基础。三个核心将协助研究项目与药理学，分子分析，序列和表达分析。行政核心将确保协调，并保持这一经验丰富和强有力的小组对转化产品开发的关注。作为一个团体，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将是提供治疗进步的关键。我们深信，我们将共同推动最终导致根除艾滋病毒感染的进展。