Reprogramming Exosomes for Biomedical Applications

重编程外泌体的生物医学应用

基本信息

批准号：
10661042
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
项目类别：
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/10661042
关键词：
Address Antibodies Antigens Biogenesis Biological Biology CD47 gene Catalytic Domain Cell physiology Cells Characteristics Chemical Engineering Chemicals Chimeric Proteins Circulation Coupling Dendritic Cells Development Encapsulated Endosomes Enzyme Inhibitor Drugs Enzymes Epidermal Growth Factor Receptor Exhibits Generations Genetic Genetic Engineering Human Immunoglobulin Fragments In Vitro 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 Specificity Surface Synthesis Chemistry TNFSF4 gene Technology Therapeutic Therapeutic Agents Tissues Transmembrane Domain cell type chemical conjugate design drug development engineered exosomes exosome extracellular vesicles functional improvement immunogenic immunogenicity in vivo inhibitor innovation intercellular communication interest knowledge integration multidisciplinary nanocarrier nanomedicine nanoparticle new technology next generation novel photoactivation receptor targeted delivery technology platform therapeutic development therapeutic protein tool

项目摘要

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.

抽象的外泌体是多种细胞分泌的细胞外囊泡，在介导细胞间通讯。内源性外泌体已成为一类新的、有吸引力的外泌体。疗法，由于其独特而重要的特征。然而，有效的方法仍然有限用于将外泌体靶向所需的细胞和组织。可用于主动装载蛋白质的方法很少货物进入外泌体进行细胞递送。为了应对这些挑战，扩大药物的治疗效用外泌体并充分发挥其潜力，我们建议开发一种创新的平台技术，称为合成多价抗体重靶向外泌体（SMART-Exos）。这将通过基因来实现以及具有功能性抗体、配体和酶的化学工程外泌体，并结合封装不同类型的治疗有效负载。通过整合外泌体知识和技术生物学、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一系列 SMART-Exos 通过独特但互补的方式具有新的和/或增强的功能和特性策略。由此产生的 SMART-Exos 有望以高特异性将外泌体重定向至靶细胞通过受体参与和/或货物输送来调节细胞功能和过程，从而导致为下一代研究和开发通用且多功能的平台技术治疗性外泌体。