Optical Chip Test for T Cell Function in HIV Patients

HIV 患者 T 细胞功能的光学芯片测试

• 批准号: 6843406
• 负责人: Bernard H. Schneider
• 金额: $ 83.62万
• 依托单位: NGIMAT COMPANY
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-07-01 至 2006-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6843406
• 关键词: HIV infections; biomedical equipment development; cell component structure /function; cell differentiation; cell sorting; cytotoxic T lymphocyte; disease /disorder model; fluid flow; gene expression; human tissue; laboratory mouse; microarray technology; microorganism immunology; nucleic acid amplification techniques; optics; silicon; temperature; time resolved data; virus load; virus replication

DESCRIPTION (provided by applicant): This proposal is targeted at the development of a novel research platform for analyzing immune cell gene expression as a result of HIV infection that is based on the on-chip real-time amplification detection (OCRAD) method that came out of the Phase I program. Current methods for performing gene expression analysis require lengthy and complex protocols, involving separate RNA amplification, hybridization, washing and label read-out steps. OCRAD employs a refractometric integrated optic chip (IOC) sensor to perform multiplex on-chip nucleic acid amplification. This combination of on-chip amplification and real-time detection will create a platform with the features necessary to make a significant advancement in the ability of researchers to perform gene expression measurements in a more rapid, simple and less expensive format. Gene expression analysis is an important tool for understanding a cell's differentiation state and may be useful in a clinical setting as a diagnostic or predictive tool. CD8 T cells are critical for the control of many viral infections and are the target of vaccine efforts for HIV. However, during HIV infection immune control by CD8 T cells eventually fails leading to AIDS. Considerable evidence suggests that CD8 T cells in HIV patients undergo an inappropriate differentiation process leading to impaired function, although the molecular signature of this process in humans is not well defined. Using a small gene set profile based on previous gene expression studies using mouse models of viral infection, OCRAD will be applied to analyzing gene expression in CD8 T cell subsets from HIV- healthy patients, HIV+ patients with suppressed viral load and HIV+ patients with viremia. It is believed that this analysis should provide a better understanding of the molecular profile of CD8 T cells during HIV infection. This may ultimately lead to improved diagnostic and/or predictive clinical tools and may uncover important biological pathways that can be used as targets for therapeutic intervention.

描述（由申请人提供）：该提案针对的是开发一个新的研究平台，用于分析基于I阶段计划的芯片实时扩增检测检测（OCRAD）方法，用于分析免疫细胞基因表达。进行基因表达分析的当前方法需要冗长而复杂的方案，涉及单独的RNA扩增，杂交，洗涤和标签读出步骤。 Ocrad采用折射率集成的光学芯片（IOC）传感器来执行多重芯片核酸扩增。片上放大和实时检测的这种组合将创建一个平台，具有必要的功能，以在研究人员以更快，简单且较便宜的格式进行基因表达测量的能力方面取得了重大进步。基因表达分析是理解细胞分化状态的重要工具，并且在临床环境中可能是诊断或预测工具的重要工具。 CD8 T细胞对于控制许多病毒感染至关重要，并且是HIV疫苗努力的靶标。但是，在HIV感染期间，CD8 T细胞免疫控制最终会导致艾滋病。大量证据表明，艾滋病毒患者中的CD8 T细胞经历了不适当的分化过程，导致功能受损，尽管该过程在人类中的分子特征尚未得到很好的定义。使用基于先前的基因表达研究使用病毒感染的小鼠模型，将使用小基因集谱图，将OCRAD用于分析来自HIV健康患者的CD8 T细胞亚群中的基因表达，HIV+患有病毒载量的HIV+患者和病毒性血症HIV+患者。据信，该分析应更好地了解HIV感染期间CD8 T细胞的分子谱。这最终可能会改善诊断和/或预测性临床工具，并可能发现重要的生物学途径，可以用作治疗干预的靶标。