ANTI-HIV-1 TAT HUMAN SFV INTRABODY GENE THERAPY AGAINST SHIV IN RHESUS MACAQUES

抗 HIV-1 TAT 人类 SFV 体内针对恒河猴 SHIV 的基因治疗

• 批准号: 7958299
• 负责人: Wayne A. Marasco
• 金额: $ 11.19万
• 依托单位: HARVARD MEDICAL SCHOOL
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-05-01 至 2010-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7958299
• 关键词: Acquired Immunodeficiency Syndrome; Adult; Animals; Antibodies; Architecture; Axillary lymph node group; CD4 Lymphocyte Count; CD4 Positive T Lymphocytes; Cells; Computer Retrieval of Information on Scientific Projects Database; Development; Funding; Genes; Grant; HIV; Human; Infusion procedures; Institution; Macaca; Macaca mulatta; Modeling; Monitor; New England; Plasma; Primates; RNA; Research; Research Personnel; Resources; Sampling; Source; Technetium Tc 99m ciprofloxacin; Therapeutic; Time; Transgenes; United States National Institutes of Health; Virus Diseases; base; cellular transduction; gene therapy; research study; simian human immunodeficiency virus

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. To study protection effects of an HIV Tat specific intracellular antibody against viral infection, adult rhesus monkeys (Macaca mulatta) served as a model for gene therapy experiments against HIV-1-infecton and the development of AIDS. Following re-infusion of ex-vivo MLV transduced CD4+-enriched (CD8-depleted) cells, expressing an irrelevant intrabody (A3H5-Flag) and a therapeutic anti-tat sFv intrabody (hutat2-HA), animals were challenged intravenously with a pathogenic SHIV strain. Survival of transduced CD4+ cells and gene marking of the A3H5 or sFv hutat2 transgenes were analyzed, respectively, by FACS and real-time PCR. Levels of SHIV plasma RNA and CD4 counts in the treated macaques were also monitored. In addition, CTLs and/or antibodies against the A3H5 or hutat2 intrabodies will also be monitored. Axillary lymph nodes will be sampled serially and evaluated histopathologic for LN architecture. Finally, transduced cells will also be identified by IF for intracellular A3H5 or sFvhutat2 expression.

这个子项目是众多研究子项目之一