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.

随着高度活跃的抗逆转录病毒疗法（HAART）的出现，在 在艾滋病毒感染的个体中控制病毒复制和无艾滋病生存的延长。然而， 当前的治疗方式不能有效地靶向或消除潜在的病毒储存库。结果，病毒 停止治疗后通常会反弹。由于 长期多药疗法的必要性。因此，抗HIV疗法的最终目标应该是 消除病毒学，即治愈HIV感染。迄今为止，消除病毒学的可行性仅是 在一名HIV感染患者中证明了来自A的同种异体造血细胞移植（HCT） CCR5DELTA32纯合供体。尽管这是一项重要的概念证明研究，但 使用HLA匹配和CCR5DELTA32纯合供体作为一般治疗方法是遥远的。这 该U19应用程序的总体目标是探索策略，以在主机和 前病毒DNA靶向并消除潜在的HIV储量。该核心的目的是提供全面 支持非人类灵长类动物模型中的概念验证研究。这个目标将通过 执行以下特定目的：（1）。提供动物资源，畜牧业和 在非人类灵长类动物中研究灵长类动病毒感染所需的生物安全遏制设施 模型; （2）为实施非人类灵长类动物研究提供技术和临床支持 该U19应用程序中的协议； （3）为监视提供实验室专业知识和分析支持 猕猴中的Shiv感染； （4）为进行科学和行政监督 非人类灵长类动物研究。该核心将与该U19的所有项目和核心进行互动。