Modular immunoconjugates

描述(由申请人提供)：(13)智能生物材料-Theranostics 13-EB-101*Theranostics：诊断和治疗药物的联合输送。多聚体多特异性蛋白质疗法很难设计和生产。在单个分子中将结合、效应器和成像组件连接在一起的能力将是一个显著的优势。我们建议发展非天然氨基酸-寡核苷酸技术(UAA-OGO)，以精确控制模块化治疗和诊断的形成。在单一位置设计的非天然氨基酸将允许寡核苷酸的特定部位偶联。然后，寡核苷酸可以与它的补体杂交，补体与第二个模块蛋白连接。DNA的碱基配对规则将允许生产更高阶杂二聚体、三聚体、四聚体和其他多聚体。这一战略将允许诊断和治疗模块耦合在单个分子中，以产生一种“Theranostic”。 与公共卫生相关：创造模块化蛋白质疗法的能力，使得新的结合蛋白、效应物和诊断蛋白可以结合在一个单一的“治疗”中，这在医学上具有相当重要的意义。具体地说，这项提议旨在为发现此类分子以及方便地构建它们创造平台。我们将使用寡核苷酸和非天然氨基酸通过核酸的互补碱基配对将两个或更多蛋白质特异性地连接在一起。我们创造的分子可以通过成像、结合和毒素模块同时检测、结合和杀死肿瘤细胞。这种“乐高”模块组装过程将允许创建大量的组合蛋白质治疗模块，并针对无数种疾病进行评估。

DESCRIPTION (provided by applicant): (13) Smart Biomaterials - Theranostics 13-EB-101*Theranostics: Combined delivery of diagnostic and therapeutic agents. Multimeric polyspecific protein therapeutics are difficult to design and produce. The ability to link binding, effector, and imaging components together in a single molecule would be a significant advantage. We propose to develop unnatural amino acid- oligonucleotide technology (UAA-oligo) in order to precisely control formation of modular therapeutics and diagnostics. An unnatural amino acid engineered in a single position will allow site-specific coupling of an oligonucleotide. The oligonucleotide can then be hybridized to its complement which is conjugated to a second modular protein. The base-pairing rules of DNA will allow higher order heterodimers, trimers, tetramers, and other multimers to be produced. This strategy will allow diagnostic and therapeutic modules to be coupled in a single molecule to produce a "Theranostic". PUBLIC HEALTH RELEVANCE: The ability to create modular protein therapeutics, such that novel binding, effector, and diagnostic proteins can be combined in a single "theranostic" has considerable importance in medicine. Specifically, this proposal aims to create the platform for discovery of such molecules as well as for their facile construction. We will use oligonucleotides and unnatural amino acids to site specifically link two or more proteins together through the complementary base pairing of nucleic acids. Molecules that we create could simultaneously detect, bind, and kill tumor cells through imaging, binding, and toxin modules. This "lego" block assembly process will allow a vast array of combinatorial protein theranostic modules to be created and evaluated against a myriad of diseases.