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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：
8874860
负责人：
DAVID M. MARGOLIS
金额：
$ 709.65万
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 2017-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8874860
关键词：
Acquired Immunodeficiency Syndrome Address Animal Model Area Biological Assay Biological Models Cell model Clinical Collaborations 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）在临床上取得了成功，但每天感染人类免疫缺陷病毒（HIV）的人比开始ART的人多。终身ART的困难-特别是在发展中国家-使得根除HIV势在必行。但是，清除接受抗逆转录病毒治疗的患者的逆转录病毒感染是一项艰巨的任务。尽管人们对艾滋病毒在ART治疗后的持续性了解很多，但仍然存在许多困惑。解决潜伏感染的新工具必须取代用于开发ART的范例和模型。代表体内HIV潜伏期的现有细胞和动物模型需要进一步开发，虽然潜伏前病毒可以在实验室中清除，但可测试的全面治疗策略还没有。因此，我们提议成立马丁·德莱尼合作实验室，以根除HIV-1感染，这是一个由21名杰出研究人员组成的密切合作，他们在过去10年中共同领导了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，以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，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，以描述病毒持续存在的基础。三个核心将协助药理学，分子测定，序列和表达分析的研究项目。一个行政核心将确保协调，并保持这个经验丰富和强大的团队对翻译产品开发的关注。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对于提供治疗进展至关重要。我们相信，我们将共同推动取得进展，最终导致根除艾滋病毒感染。

项目成果

期刊论文数量（22）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Latency reversal and viral clearance to cure HIV-1.

DOI：
10.1126/science.aaf6517
发表时间：
2016-07-22
期刊：
Science (New York, N.Y.)
影响因子：
0
作者：
Margolis DM;Garcia JV;Hazuda DJ;Haynes BF
通讯作者：
Haynes BF

The differential short- and long-term effects of HIV-1 latency-reversing agents on T cell function.

DOI：
10.1038/srep30749
发表时间：
2016-08-02
期刊：
Scientific reports
影响因子：
4.6
作者：
Clutton G;Xu Y;Baldoni PL;Mollan KR;Kirchherr J;Newhard W;Cox K;Kuruc JD;Kashuba A;Barnard R;Archin N;Gay CL;Hudgens MG;Margolis DM;Goonetilleke N
通讯作者：
Goonetilleke N

In vivo analysis of the effect of panobinostat on cell-associated HIV RNA and DNA levels and latent HIV infection.

DOI：
10.1186/s12977-016-0268-7
发表时间：
2016-05-21
期刊：
Retrovirology
影响因子：
3.3
作者：
Tsai P;Wu G;Baker CE;Thayer WO;Spagnuolo RA;Sanchez R;Barrett S;Howell B;Margolis D;Hazuda DJ;Archin NM;Garcia JV
通讯作者：
Garcia JV

Peripheral Vγ9Vδ2 T Cells Are a Novel Reservoir of Latent HIV Infection.

DOI：
10.1371/journal.ppat.1005201
发表时间：
2015-10
期刊：
PLoS pathogens
影响因子：
6.7
作者：
Soriano-Sarabia N;Archin NM;Bateson R;Dahl NP;Crooks AM;Kuruc JD;Garrido C;Margolis DM
通讯作者：
Margolis DM

Vorinostat Renders the Replication-Competent Latent Reservoir of Human Immunodeficiency Virus (HIV) Vulnerable to Clearance by CD8 T Cells.

DOI：
10.1016/j.ebiom.2017.07.019
发表时间：
2017-09
期刊：
EBioMedicine
影响因子：
11.1
作者：
Sung JA;Sholtis K;Kirchherr J;Kuruc JD;Gay CL;Nordstrom JL;Bollard CM;Archin NM;Margolis DM
通讯作者：
Margolis DM