Reprogramming Exosomes for Biomedical Applications

重编程外泌体的生物医学应用

• 批准号: 10272635
• 负责人: Yong Zhang
• 金额: $ 52.76万
• 依托单位: UNIVERSITY OF SOUTHERN CALIFORNIA
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-09-01 至 2025-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10272635
• 关键词: Address; Antibodies; Antigens; Biogenesis; Biological; Biology; Blood Circulation; CD47 gene; Catalytic Domain; Cell physiology; Cells; Characteristics; Chemical Engineering; Chemicals; Chimeric Proteins; Coupling; Dendritic Cells; Development; Enzyme Inhibitor Drugs; Enzymes; Epidermal Growth Factor Receptor; Exhibits; Generations; Genetic; Genetic Engineering; Human; In Vitro; Investigation; Knowledge; Ligands; Mediating; Membrane; Membrane Fusion; Membrane Proteins; Methods; Modality; Modeling; Monoclonal Antibodies; Nature; OX40; Pathway interactions; Patients; Phagocytes; Platelet-Derived Growth Factor Receptor; Play; Property; Protein Engineering; Proteins; Research; Role; Series; Site; Sorting - Cell Movement; Specificity; Surface; Synthesis Chemistry; TNFSF4 gene; Technology; Therapeutic; Therapeutic Agents; Tissues; Transmembrane Domain; base; cell type; design; drug development; engineered exosomes; exosome; extracellular vesicles; immunogenic; immunogenicity; improved functioning; in vivo; inhibitor/antagonist; innovation; intercellular communication; interest; multidisciplinary; nanocarrier; nanomedicine; nanoparticle; new technology; next generation; novel; photoactivation; receptor; targeted delivery; therapeutic development; therapeutic protein; tool

Abstract Exosomes are extracellular vesicles secreted by many types of cells and play important roles in mediating intercellular communications. Endogenous exosomes have been emerging as a new and attractive class of therapeutics, owing to their unique and important characteristics. However, effective approaches remain limited for targeting exosomes to desired cells and tissues. And few methods are available for active loading of protein cargos into exosomes for cellular delivery. To address these challenges for broadening therapeutic utility of exosomes and unleashing their full potential, we propose to develop an innovative platform technology, termed synthetic multivalent antibodies retargeted exosomes (SMART-Exos). This will be achieved through genetically and chemically engineering exosomes with functional antibodies, ligands, and enzymes, combined with encapsulation of different types of therapeutic payloads. By integrating knowledge and technologies in exosome biology, protein engineering, synthetic chemistry, and enzyme inhibitor design, we aim to design and generate a series of SMART-Exos with new and/or enhanced functions and properties through distinct but complementary strategies. The resulting SMART-Exos are expected to redirect exosomes toward target cells in high specificity for modulating cellular functions and processes through receptor engagement and/or cargo delivery, leading to the development of a general and versatile platform technology for next-generation investigational and therapeutic exosomes.

摘要 外泌体是由多种类型细胞分泌的细胞外囊泡，在介导 细胞间通讯内源性外泌体已经成为一类新的和有吸引力的 治疗，由于其独特的和重要的特点。然而，有效的办法仍然有限 用于将外来体靶向至所需细胞和组织。而主动负载蛋白质的方法较少 货物进入外泌体用于细胞递送。为了解决这些挑战，以扩大治疗效用， 外泌体并释放其全部潜力，我们建议开发一种创新的平台技术，称为 合成的多价抗体重靶向外泌体（SMART-Exos）。这将通过基因工程来实现 以及用功能性抗体、配体和酶对外泌体进行化学工程改造， 封装不同类型的治疗有效载荷。通过整合外泌体中的知识和技术， 生物学，蛋白质工程，合成化学和酶抑制剂设计，我们的目标是设计和生成 通过独特但互补的方式，一系列具有新的和/或增强的功能和特性的SMART-Exo 战略布局预计所得SMART-Exos将以高特异性将外泌体重定向至靶细胞 用于通过受体接合和/或货物递送来调节细胞功能和过程，导致 为下一代研究开发通用的多功能平台技术， 治疗性外泌体