Engineered Antibodies for Imaging Gene Expression

描述(申请人提供)：观察转基因细胞的表达 生命系统中的基因，在最小的干扰下，对未来很重要 基因治疗的发展。我们提出了一种方法，它拥有许多 该领域最新进展的最佳特征，但扩展了成像的力量 在新的方向上。金属元素具有各种有用的物理特性 这些属性使它们成为有价值的探测器。其中包括放射性物质 用于伽马或PET成像的光子辐射，放射性辐射 用于治疗的粒子，用于MRI对比度的顺磁性，用于光学的发光 用于在生物医学中利用这些特性的化学 应用是影像技术进一步发展的基础 仪器和技术。我们将演示成像的可行性 利用金属络合物通过设计抗体进行基因表达，使其 表达为金属螯合物的细胞表面受体，受 一个可诱导的转录单位。当在细胞表面表达时，这种新的 受体将捕获标记的螯合物，并最终提供 表达受体的转化细胞群。第二阶段将重点放在 开发新产品，将这项技术应用于一组有用的 金属元素和成像技术。 建议的商业应用： 癌细胞中基因表达的高分辨率成像对未来的科学很重要 和癌症治疗技术。我们准备的分子工具将允许 金属元素的物理性质将以新的方式使用。他们会找到用处的 在各种高科技成像应用中，无论是在研究中还是(最终) 临床应用。

DESCRIPTION (Provided by Applicant): Observing the expression of transfected genes in a living system, with minimal disturbance, is important for the future development of gene therapy. We propose an approach that possesses many of the best features of recent advances in this area, but extends the power of imaging in new directions. The metallic elements possess a variety of useful physical properties that make them valuable as probes. These include radioactive emissions of photons for gamma or PET imaging, radioactive emissions of particles for therapy, paramagnetism for MRI contrast, luminescence for optical imaging, etc. Chemistry for making use of these properties in biomedical applications is fundamental to the further development of imaging instrumentation and technology. We will demonstrate the feasibility of imaging gene expression with metal chelates by engineering an antibody so that it is expressed as a cell-surface receptor for metal chelates, under the control of an inducible transcription unit. When expressed on the cell surface, this new receptor will capture labeled chelates and ultimately provide an image of the cluster of transformed cells that express the receptor. Phase 2 will focus on development of new products that apply this technology to a useful set of metallic elements and imaging techniques. PROPOSED COMMERCIAL APPLICATION: High-resolution imaging of gene expression in cancer cells is important to the future science and technology of cancer treatment. The molecular tools that we prepare will allow the physical properties of metallic elements to be employed in new ways. They will find uses in a variety of high-technology imaging applications, in both research and (ultimately) clinical applications.