Aptamer Array Finds Metabolic Change from Hepatotoxicity

适体阵列发现肝毒性引起的代谢变化

• 批准号: 6657868
• 负责人: EUGENE C AQUINO
• 金额: $ 23.92万
• 依托单位: AMERICAN RESEARCH CORP OF VIRGINIA
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-04-01 至 2005-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6657868
• 关键词: biomedical equipment development; cytotoxicity; gene expression; hepatotoxin; lasers; liver metabolism; method development; monitoring device; oligonucleotides; proteomics; toxicology

DESCRIPTION (provided by applicant): In order to reduce the costs of drug development and improve methods of detecting environmental effects of xeniobiotics, there is a need for in vitro methods of xeniobiotics identifying toxicity of materials to specific organs that do not require a whole-animal model. In particular, methods capable of identifying hepatotoxicity either require extensive animal studies or do not take into account differences in metabolic pathways that cannot be predicted by genomic approaches. American Research Corporation of Virginia (ARCOVA) proposes the development of a novel sensitive aptamer array that is capable of differentiating multiple metabolic products on a real-time basis through metabonomics. This proposal is innovative in developing an aptamer array having improved selectivity and sensitivity to changes of low molecular weight metabolic products resulting from hepatotoxicity in the cell culture. Phase I specific aims include preparation of liver metabolite-specific capture aptamers and capture aptamer-analyte probe aptamers for fabrication of surface-sensitive diode laser (SSDL) array elements, modification of SSDL aptamer array to improve sensitivity and reproducibility, design and fabrication of experimental workstation for the characterization of an engineering model SSDL array sensor head and acquisition of families of test data from an SSDL array and optimization of an engineering model for the metabolic monitor. In Phase II of the program, a prototype strip panel will be constructed and field-tested in preparation for commercialization during Phase III of the program. Successful completion of the Phase I program will result in an SSDL-based aptamer array for detection of hepatotoxicity-related metabolic products. The aptamer array will find commercial use in biomedical point-of-care monitoring, evaluation of treatment protocols and veterinary medicine.

描述（由申请人提供）： 为了降低药物开发成本并改进检测异生素环境影响的方法，需要一种不需要全动物模型的异生素体外鉴定材料对特定器官毒性的方法。特别是，能够识别肝毒性的方法要么需要广泛的动物研究，要么没有考虑基因组方法无法预测的代谢途径的差异。弗吉尼亚美国研究公司 (ARCOVA) 提议开发一种新型敏感适体阵列，能够通过代谢组学实时区分多种代谢产物。该提案在开发适体阵列方面具有创新性，该适体阵列对细胞培养物中肝毒性引起的低分子量代谢产物的变化具有更高的选择性和敏感性。第一阶段的具体目标包括制备肝脏代谢物特异性捕获适体和捕获适体-分析物探针适体，用于制造表面敏感二极管激光（SSDL）阵列元件，修改SSDL适体阵列以提高灵敏度和重现性，设计和制造实验工作站，用于表征工程模型 SSDL 阵列传感器头、从 SSDL 阵列采集测试数据族以及优化代谢监测仪的工程模型。在该计划的第二阶段，将建造一个带状面板原型并进行现场测试，为该计划第三阶段的商业化做准备。第一阶段计划的成功完成将产生基于 SSDL 的适体阵列，用于检测肝毒性相关的代谢产物。该适体阵列将在生物医学现场监测、治疗方案评估和兽医学方面找到商业用途。