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光学成像在新药发现中的新语法。

Optical imaging for the new grammar of drug discovery.

机构信息

Global Imaging Group, Novartis Institutes for BioMedical Research, Cambridge, MA 02139, USA.

出版信息

Philos Trans A Math Phys Eng Sci. 2011 Nov 28;369(1955):4651-65. doi: 10.1098/rsta.2011.0300.

Abstract

Optical technologies used in biomedical research have undergone tremendous development in the last decade and enabled important insight into biochemical, cellular and physiological phenomena at the microscopic and macroscopic level. Historically in drug discovery, to increase throughput in screening, or increase efficiency through automation of image acquisition and analysis in pathology, efforts in imaging were focused on the reengineering of established microscopy solutions. However, with the emergence of the new grammar for drug discovery, other requirements and expectations have created unique opportunities for optical imaging. The new grammar of drug discovery provides rules for translating the wealth of genomic and proteomic information into targeted medicines with a focus on complex interactions of proteins. This paradigm shift requires highly specific and quantitative imaging at the molecular level with tools that can be used in cellular assays, animals and finally translated into patients. The development of fluorescent targeted and activatable 'smart' probes, fluorescent proteins and new reporter gene systems as functional and dynamic markers of molecular events in vitro and in vivo is therefore playing a pivotal role. An enabling optical imaging platform will combine optical hardware refinement with a strong emphasis on creating and validating highly specific chemical and biological tools.

摘要

在过去十年中,用于生物医学研究的光学技术取得了巨大的发展,使人们能够深入了解微观和宏观层面的生化、细胞和生理现象。在药物发现历史上,为了提高筛选的通量,或者通过病理学中图像采集和分析的自动化来提高效率,成像方面的努力集中在对现有显微镜解决方案的重新设计上。然而,随着新药发现语法的出现,其他需求和期望为光学成像创造了独特的机会。新药发现的新语法为将大量基因组和蛋白质组信息转化为靶向药物提供了规则,重点是蛋白质的复杂相互作用。这种范式转变需要在分子水平上进行高度特异性和定量的成像,使用可以在细胞测定、动物中使用并最终转化为患者的工具。因此,荧光靶向和可激活的“智能”探针、荧光蛋白和新的报告基因系统的发展正在作为体外和体内分子事件的功能和动态标记物发挥关键作用。一个可行的光学成像平台将结合光学硬件的改进,并强烈强调创建和验证高度特异性的化学和生物学工具。

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