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）：尽管抗逆转录病毒疗法（ART）的临床成功，但每天都会感染人类免疫缺陷病毒（HIV）感染，而不是发起艺术。终身艺术的困难 - 尤其是在发展中国家中 - 消除了艾滋病毒的势在必行。但是，在ART上清除患者的逆转录病毒感染是一项艰巨的任务。尽管尽管艺术有许多谜题，但对艾滋病毒的持久性知之甚少，但仍然存在许多难题。解决潜在感染的新工具必须取代用于开发艺术的范例和模型。代表体内艾滋病毒潜伏期的现有细胞和动物模型需要进一步发育，尽管可以在实验室清除潜在的病毒，但目前却没有可检验，全面的治疗策略。因此，我们建议马丁·德莱尼（Martin Delaney）合作消除HIV-1感染，这是21名杰出调查人员的密切合作，他们在过去的10年中统治着艾滋病毒潜伏期领域。为了最大程度地提高成功，我们将在四个研究领域进行开发，以开发定义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，并为动物模型中基于小分子的消除策略提供了概念验证。目标1将确定病毒持续性和潜伏期的分子机制；目标2将确定候选药物和治疗策略，以减少潜在的病毒库；目标3将建立信息丰富的动物模型系统，以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。三个核心将通过药理学，分子测定以及序列和表达分析来协助研究项目。行政核心将确保协调，并保持这个经验丰富且有效的群体的重点转化为转化产品开发。作为一个小组，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。我们坚信，我们将共同促进进步，最终导致根除HIV感染。