MOLECULAR PROBES TO IMAGE DNA DAMAGE IN BRAIN CELLS

用于脑细胞 DNA 损伤成像的分子探针

• 批准号: 6015398
• 负责人: BenXiao Zhang
• 金额: $ 23.93万
• 依托单位: MOLECULAR THERAPEUTICS, INC.
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-09-01 至 2003-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6015398
• 关键词: DNA damage; animal tissue; apoptosis; bioimaging /biomedical imaging; brain cell; fluorescence resonance energy transfer; fluorescent dye /probe; histochemistry /cytochemistry; histology; human tissue; imaging /visualization /scanning; laboratory rat; magnetic resonance imaging; nucleic acid probes; technology /technique development

A novel approach is proposed for detection and analysis of apoptotic DNA damage in tissue sections, as well as in vivo. The technology is based on it situ ligation of DNA probes that will uniquely bind to characteristic DNA breaks, which other and we have demonstrated are a specific signature for apoptosis. Preliminary results using the first generation of the probes documented higher specificity for apoptosis detection compared with the currently used terminal transferase-based labeling (TUNEL), thus demonstrating the potential for development into a marketable kit for use in tissue sections. Probes under development include loopless hairpin oligoprobes with greater specificity and less background staining, as well as probes utilizing Fluorescence Resonance Energy Transfer (FRET) technology, which change color upon successful ligation. A much more powerful application of technology is related to in vivo imaging of apoptosis. In preliminary experiments we have tested the modification of the approach allowing it to detect specific DNA damage in vivo. Using this modified approach, we will develop a marketable in vivo detection procedure for analysis of apoptotic damage in brain, with visualization utilizing magnetic resonance imaging (MRI). PROPOSED COMMERCIAL APPLICATION: NOT AVAILABLE

提出了一种新的检测和分析方法， 组织切片中以及体内的凋亡DNA损伤。该技术 基于DNA探针的原位连接， 特征性DNA断裂，我们已经证明了这是一个特定的 细胞凋亡的标志。使用第一代的初步结果 探针记录了更高的特异性凋亡检测相比， 目前使用的基于末端转移酶的标记（TUNEL），从而证明 开发成用于组织切片的可销售试剂盒的潜力。 正在开发的探针包括具有更大的 特异性和较少的背景染色，以及利用 荧光共振能量转移（FRET）技术， 在成功结扎后。一个更强大的技术应用是 与凋亡的体内成像相关。在初步实验中，我们测试了 该方法的改进使其能够检测体内特异性DNA损伤。使用 这种改进的方法，我们将开发一种可销售的体内检测程序， 利用磁共振可视化分析脑中的凋亡损伤 成像（MRI）。 拟议商业应用：不可用