Novel Viral Load Diagnostic for Resource-Limited Setting

描述（由申请人提供）：缺乏负担得起和实用的艾滋病毒诊断方法，包括监测艾滋病毒RNA水平（“病毒载量”）和诊断婴儿艾滋病毒感染的检测方法，已被确定为全球艾滋病毒护理的主要障碍。对于资源有限的环境，一种有用的HIV RNA诊断方法应该是简单、自动化和快速的，而且每次检测的成本不到10美元。我们建议使用BioScale的专有传感器格式开发一种符合这些规格的HIV病毒粒子检测方法。

DESCRIPTION (provided by applicant): The lack of affordable and practical HIV diagnostics, including assays to monitor HIV RNA levels ("viral load") and to diagnose HIV infection in infants, has been identified as a major barrier to HIV care worldwide. For resource-limited settings, a useful HIV RNA diagnostic assay would be simple, automated, and rapid and cost less than $10 per test. We propose to develop an HIV virion assay that meets these specifications using BioScale's proprietary sensor format. We hypothesize that capturing whole virions with specific physiological receptors (DC-SIGN, CD4) and/or new monoclonal antibodies against surface epitopes and integrating them into an assay on BioScale's detection platform will provide a sensitive new diagnostic that meets requirements of resource-poor setting. In the first year of the project, capture surfaces will be functionalized using recombinant soluble CD4, recombinant soluble DC-SIGN, and new anti-gp41 and anti-gp120 antibodies to create a novel system to capture and isolate HIV virions and anchor them to the sensor surface. In the second year, this new HIV virion assay will be optimized and validated for sensitivity and specificity compared to standard viral load measurements (i.e. RT-PCR) in 75 HIV-infected subjects. The successful completion of this proposal will demonstrate the feasibility of BioScale's HIV assay for resource-limited settings. The specific aims of the proposal are three-fold: A) To develop a method to capture HIV virions using magnetic beads coated with receptors and/or new monoclonal antibodies; B) To develop a bead capture surface on the BioScale biosensor and integrate it with HIV capture beads, to create an HIV virion assay; and C) To evaluate the qualitative and quantitative threshold of HIV detection in whole blood via HIV assay testing compared to RT-PCR in HIV-infected subjects. The Phase II of this proposal is anticipated to include beta-testing of the instrument, larger clinical testing, and preparation for instrument and assay kit manufacturing and deployment in resource-limited settings.