Development of a library of regulated Actibodies

描述（由申请人提供）：识别蛋白，如抗体，在医学和生物技术中有许多应用。这些应用中的许多应用将受益于控制或激活识别蛋白何时与靶标结合的能力。该提案旨在开发和测试可活化抗体激发的识别蛋白或活性体的文库。具体来说，我们的目标首先是将多样性引入到受调控的蛋白质中，并开发适合于该蛋白质的新的展示系统和伴随的筛选技术。然后，我们将确定以这种方式选择的个体变体能够识别靶分子的程度。在我们的第二个目标中，我们将确定该文库的成员是否确实是可以被激活以结合靶标的活性体。这项工作将帮助我们了解一种新发现的变构调节类型，并确定它是否有助于制造受调节的识别蛋白。由此产生的活性体技术应该有助于一系列生物医学技术，包括靶向药物输送、分子成像、体外诊断和分离技术。特别地，激活结合的能力应当增强在所有应用中仅特异性鉴定正确靶标的能力，并且还将允许在体外应用中温和地回收靶标。 公共卫生相关性：识别蛋白，如抗体，在医学和生物技术中有许多应用。这些应用中的许多应用将受益于控制或激活识别蛋白何时与靶标结合的能力。该提议寻求开发和测试可活化抗体或活性体的文库。

DESCRIPTION (provided by applicant): Recognition proteins, such as antibodies, have many applications in medicine and biotechnology. Many of these applications would benefit from the ability to control, or activate, when the recognition protein binds to the target. This proposal seeks to develop and test a library of activatable antibody-inspired recognition proteins, or actibodies. Specifically, we first aim to introduce diversity into a regulated protein and develop a new display system and accompanying screening technology that is appropriate for this protein. We will then determine how well individual variants selected in this fashion can recognize the target molecules. In our second aim, we will determine whether members of this library are indeed actibodies, that can be activated to bind the target. This work will help us understand a newly discovered type of allosteric regulation, and determine whether it is useful for making regulated recognition proteins. The resulting actibody technology should contribute to a range of biomedical technologies, including targeted drug delivery, molecular imaging, in vitro diagnostics, and separation technologies. In particular, the ability to activate binding should enhance the ability to specifically identify only the correct target in all applications, and would also allow for gentle recovery of the target in the in vitro applications. PUBLIC HEALTH RELEVANCE: Recognition proteins, such as antibodies, have many applications in medicine and biotechnology. Many of these applications would benefit from the ability to control, or activate, when the recognition protein binds to the target. This proposal seeks to develop and test a library of activatable antibodies, or actibodies.