Biomolecular Medicine, Division of Biomolecular and Cellular Medicine, Department of Laboratory Medicine, Karolinska Institutet, 141 57 Huddinge, Sweden.
Biomolecular Medicine, Division of Biomolecular and Cellular Medicine, Department of Laboratory Medicine, Karolinska Institutet, 141 57 Huddinge, Sweden; Department of Paediatrics, University of Oxford, Oxford OX3 9DU, UK.
Mol Ther. 2023 May 3;31(5):1231-1250. doi: 10.1016/j.ymthe.2023.02.013. Epub 2023 Feb 20.
Extracellular vesicles (EVs) are gaining increasing attention for diagnostic and therapeutic applications in various diseases. These natural nanoparticles benefit from favorable safety profiles and unique biodistribution capabilities, rendering them attractive drug-delivery modalities over synthetic analogs. However, the widespread use of EVs is limited by technological shortcomings and biological knowledge gaps that fail to unravel their heterogeneity. An in-depth understanding of their biogenesis is crucial to unlocking their full therapeutic potential. Here, we explore how knowledge about EV biogenesis can be exploited for EV bioengineering to load therapeutic protein or nucleic acid cargos into or onto EVs. We summarize more than 75 articles and discuss their findings on the formation and composition of exosomes and microvesicles, revealing multiple pathways that may be stimulation and/or cargo dependent. Our analysis further identifies key regulators of natural EV cargo loading and we discuss how this knowledge is integrated to develop engineered EV biotherapeutics.
细胞外囊泡 (EVs) 在各种疾病的诊断和治疗应用中越来越受到关注。这些天然纳米颗粒具有良好的安全性和独特的生物分布能力，相对于合成类似物，它们是更有吸引力的药物传递方式。然而，EV 的广泛应用受到技术缺陷和生物知识空白的限制，这些缺陷无法揭示其异质性。深入了解它们的生物发生对于释放它们的全部治疗潜力至关重要。在这里，我们探讨了如何利用 EV 生物发生的知识来进行 EV 生物工程，将治疗性蛋白质或核酸有效负载装入或装入 EV 中。我们总结了超过 75 篇文章，并讨论了它们关于外泌体和微泡形成和组成的发现，揭示了可能依赖于刺激和/或有效负载的多种途径。我们的分析还确定了天然 EV 有效负载加载的关键调节剂，我们讨论了如何整合这些知识来开发工程 EV 生物疗法。
