Modular immunoconjugates

模块化免疫偶联物

• 批准号: 7826125
• 负责人: Vaughn Vasil Smider
• 金额: $ 50万
• 依托单位: SCRIPPS RESEARCH INSTITUTE, THE
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-09-30 至 2011-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7826125
• 关键词: Amino Acids; Animal Model; Animals; Base Pairing; Binding; Biocompatible Materials; Bispecific Antibodies; Cells; Complement; Coupled; Coupling; DNA; Data; Diagnostic; Disease; Engineering; Future; Genetic; Goals; Image; Immunoconjugates; Immunoglobulin Constant Region; Immunoglobulin Fragments; In Vitro; Label; Link; Medicine; Muromonab-CD3; Nucleic Acids; Oligonucleotides; Positioning Attribute; Process; Proteins; Site; Specificity; Technetium; Techniques; Technology; Testing; Therapeutic; Therapeutic Agents; Toxin; base; combinatorial; design; efficacy testing; in vivo; killings; neoplastic cell; novel; public health relevance; single molecule; single photon emission computed tomography; success; therapeutic protein; tumor

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.

描述（由申请人提供）：（13）Smart Biomaterials - 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治疗剂的设计和生产是困难的。在单个分子中连接结合、效应和成像成分的能力将是一个显著的优势。我们建议开发非天然氨基酸寡核苷酸技术（UAA-oligo），以精确控制模块化治疗和诊断的形成。在单个位置上工程的非天然氨基酸将允许寡核苷酸的位点特异性偶联。然后可以将寡核苷酸杂交到其偶联到第二个模块蛋白的补体上。DNA的碱基配对规则将允许产生更高阶的异二聚体、三聚体、四聚体和其他多聚体。这一策略将允许诊断和治疗模块在单个分子中耦合，从而产生“治疗药物”。