Antiviral Laboratory

抗病毒实验室

基本信息

批准号：
7480231
负责人：
Shirley Li Dong
金额：
$ 14.06万
依托单位：
BECKMAN RESEARCH INSTITUTE/CITY OF HOPE
依托单位国家：
美国
项目类别：
财政年份：
资助国家：
美国
起止时间：
至
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/7480231
关键词：
Acquired Immunodeficiency Syndrome Antiviral Agents Biological Assay Blood Blood Cells Blood specimen Cell Line Clinical Clinical Data Clinical Trials Core Facility DNA Data Set Development Evaluation Genetic Genetic Recombination HIV HIV Infections HIV-1 Human immunodeficiency virus test In Vitro Laboratories Learning Lentivirus Vector Life Macaca Mails Modeling Monitor Operative Surgical Procedures Peripheral Blood Mononuclear Cell Phase Phase I Clinical Trials Polymerase Chain Reaction Process Productivity RNA Interference Research Subjects Resistance Screening procedure Services Shipping Ships Specimen Specimen Handling Subfamily lentivirinae T-Lymphocyte Testing Time Transfection Variant Viral Virus design expression vector gene therapy inhibitor/antagonist isopentenyl methylenediphosphonate p27 Cell Cycle Protein p27 Enzyme Inhibitor pre-clinical programs research study simian human immunodeficiency virus vector

项目摘要

The AIDS lab, under the direction of Dr. S. Li, will perform all confirmatory antiviral analyses for the scientific Projects 1 and 2 involving anti-HIV inhibitory activity of new antiviral RNAi designs. In addition, the Core will provide the initial assessment of in vitro antiviral effects of the SHIV vector to be tested in the macaque model in Project 3. The Core will provide HIV isolation and analysis for the clinical trial that will monitor HIV isolation and assessment of HIV sequences during the phase 1 trial. Finally, this Core will be responsible for the release testing for all lots of new lentivirus vectors prepared in Project 2 prior to use in the other laboratory projects and of the RCL testing in the clinical trial. The specific aims are: Specific Aim 1: To assist Projects 1-3 in evaluation of new anti-HIV constructs for potential anti-HIV effect in vitro by performing transient co-transfection assays and post transduction HIV or SHIV infectivity challenges. The laboratory will perform RT, p24 or p27, and post challenge PBMC survival assays as confirmation of the new vector development experimentation. Specific Aim 2: To assist the clinical trial in Project 4 by performing all HIV-1 isolation required by the study and to coordinate the processing of all clinical specimens. HIV-1 isolates will be evaluated for resistance to RNAi by monitoring sequence variation within the RNAi targeted region of rev. Specific Aim 3: To perform the release tests for replication competent lentivirus on laboratory grade vectors produced in Projects 1 and 2, and to evaluate HIV-1 isolates from pHIV7-shlI vector-treated research subjects for the presence of recombination with the pHIV7-shII sequences.

在S. Li博士的指导下，艾滋病实验室将对涉及新抗病毒RNAi设计的抗HIV抑制活性的科学项目1和2进行所有确认性抗病毒分析。此外，核心将提供对项目3中猕猴模型中的SHIV载体的体外抗病毒效应的初步评估。核心将为临床试验提供HIV隔离和分析，该试验将监测1期试验期间HIV隔离和评估HIV序列的HIV隔离和评估。最后，该核心将负责在项目2中在其他实验室项目中使用和临床试验中的RCL测试之前在项目2中制备的所有新慢病毒矢量的发布测试。具体目的是：具体目标1：通过执行瞬态共染料转染测定法和转染后HIV或SHIV感染挑战，以1-3评估新的抗HIV构建体，以在体外进行潜在的抗HIV效应。这实验室将执行RT，P24或P27，并在挑战PBMC生存测定后作为新矢量发展实验的确认。具体目标2：通过执行研究要求的所有HIV-1隔离和协调所有临床标本的处理。 HIV-1分离株将通过监测RNNI靶向区域内的序列变化来评估对RNAi的抗性。特定目的3：对项目1和2中产生的实验室矢量进行复制的释放测试，并评估来自PHIV7-SHLI矢量处理的研究对象的HIV-1分离株，以与PHIV7-SHII序列重组有关。