Nonhuman Primate Core

非人类灵长类核心

• 批准号: 8202348
• 负责人: Shiu-Lok Hu
• 金额: $ 108.48万
• 依托单位: FRED HUTCHINSON CANCER RESEARCH CENTER
• 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/8202348
• 关键词: AIDS/HIV problem; Acquired Immunodeficiency Syndrome; Adverse effects; Allogenic; Animal Husbandry; Anti-HIV Therapy; CCR5 gene; Cell Transplants; Clinical; Complementary DNA; Containment; DNA; DNA Sequencing Facility; Dendrimers; Drug resistance; Engineering; Fingers; Goals; HIV; HIV Infections; HIV-1; Hematopoietic; Highly Active Antiretroviral Therapy; Homing; Immunology; In Vitro; Individual; Infection; Laboratories; Lentivirus Infections; Macaca; Messenger RNA; Modality; Modeling; Modification; Monitor; Patients; Primate Lentiviruses; Protocols documentation; Rosa; Sequence Analysis; Site-Directed Mutagenesis; Stem cells; Therapeutic; Tissue Sample; Transplantation; Viral; Virus; animal resource; aptamer; endonuclease; in vivo; nonhuman primate; nuclease; purge; simian human immunodeficiency virus

With the advent of highly active anti-retroviral therapy (HAART), significant progress has been achieved in the control of viral replication and prolongation of AIDS-free survival in HIV infected individuals. However, current therapeutic modalities do not effectively target or eliminate latent viral reservoirs. As a result, virus often rebounds after cessation of therapy. Significant side effects and drug-resistance are common due to the necessity for long-term multidrug therapy. An ultimate goal for anti-HIV therapy should therefore be virological eradication, i.e., to cure HIV infection. To date, the feasibility of virologic eradication has only been demonstrated in one HIV-infected patient given an allogeneic hematopoietic cell transplant (HCT) from a CCR5delta32 homozygous donor. Although this is an important proof-of-concept study, the likelihood of using HLA-matched and CCR5delta32 homozygous donor as a general therapeutic approach is remote. The overall objective of this U19 application is to explore strategies to introduce specific modifications in host and proviral DNA to target and eliminate latent HIV reservoir. The goal of this Core is to provide comprehensive support for the proof-of-concept studies in non-human primate models. This goal will be achieved through the execution of the following Specific Aims: (1). To provide animal resources, animal husbandry, and biosafety containment facilities necessary for the study of primate lentivirus infection in a non-human primate model; (2) To provide technical and clinical support for the implementation of non-human primate study protocols in this U19 application; (3) To provide laboratory expertise and analytical support for the monitoring of SHIV infection in macaques; and (4) To provide scientific and administrative oversight for the conduct of non-human primate studies. This Core will interact with all Projects and Cores of this U19.

随着高效抗逆转录病毒疗法（HAART）的出现， 控制病毒复制和延长HIV感染者的无艾滋病生存期。然而，在这方面， 目前的治疗方式不能有效地靶向或消除潜伏的病毒储库。因此，病毒 经常在治疗停止后反弹。严重的副作用和耐药性是常见的， 长期多药治疗的必要性。因此，抗HIV治疗的最终目标应该是 病毒学根除，即，来治愈艾滋病病毒感染到目前为止，病毒学根除的可行性仅为 在一名接受异基因造血细胞移植（HCT）的HIV感染患者中证实， CCR 5 δ 32纯合供体。尽管这是一项重要的概念验证研究， 使用HLA匹配和CCR 5 δ 32纯合供体作为一般治疗方法是遥远的。的 本U19申请的总体目标是探索在宿主中引入特定修饰的策略， 前病毒DNA靶向并消除潜伏的HIV宿主。本核心的目标是提供全面的 支持非人类灵长类动物模型的概念验证研究。这一目标将通过 实现以下具体目标：（1）。提供动物资源，畜牧业， 研究非人灵长类动物中灵长类慢病毒感染所需的生物安全防护设施 为开展非人灵长类动物研究提供技术和临床支持 本U19应用程序中的协议;（3）为监测提供实验室专业知识和分析支持 （4）为猕猴的SHIV感染提供科学和行政监督， 非人类灵长类动物研究。此核心将与此U19的所有项目和核心进行交互。