Development of a library of regulated Actibodies

开发受监管的 Actibodies 库

• 批准号: 8227141
• 负责人: Wendy E Thomas
• 金额: $ 19.29万
• 依托单位: UNIVERSITY OF WASHINGTON
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-02-08 至 2014-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8227141
• 关键词: Address; Adhesions; Adhesives; Affinity; Allosteric Regulation; Antibodies; Binding; Biomedical Technology; Biotechnology; Characteristics; Contrast Media; Cues; Development; Devices; Diagnostic; Drug Delivery Systems; Effectiveness; Eligibility Determination; Escherichia coli; Exclusion; Goals; Image; In Vitro; Individual; Libraries; Ligand Binding; Ligands; Medicine; Methods; Molecular Target; Nucleic Acid Regulatory Sequences; Outcome; Procedures; Property; Protein Binding; Proteins; Recovery; Regulation; Response to stimulus physiology; Risk; Scaffolding Protein; Screening procedure; Side; Site-Directed Mutagenesis; Specificity; Surface; System; Technology; Testing; Therapeutic; Variant; Work; base; cost; high risk; improved; in vivo; interest; member; molecular imaging; novel; particle; scaffold

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.

描述（由申请人提供）：识别蛋白，例如抗体，在医学和生物技术中有许多应用。当识别蛋白与目标结合时，这些应用中的许多应用将受益于控制或激活的能力。该提案旨在开发和测试一个可激活的抗体启发识别蛋白或actibodies的库。具体而言，我们首先旨在将多样性引入受调节的蛋白质，并开发出适合该蛋白质的新显示系统和随附的筛选技术。然后，我们将确定以这种方式选择的单个变体可以识别目标分子。在我们的第二个目标中，我们将确定该库的成员是否确实是Actibodies，可以激活以绑定目标。这项工作将有助于我们了解新发现的变构调节类型，并确定它是否对于制造受调节的识别蛋白有用。由此产生的活性缩合技术应有助于一系列生物医学技术，包括靶向药物递送，分子成像，体外诊断和分离技术。特别是，激活结合的能力应增强在所有应用中仅具体识别正确目标的能力，并且还可以在体外应用中轻轻恢复目标。 公共卫生相关性：识别蛋白，例如抗体，在医学和生物技术中有许多应用。当识别蛋白与目标结合时，这些应用中的许多应用将受益于控制或激活的能力。该建议旨在开发和测试一个可活化抗体或actibodies的库。