Dept of Biochemistry and Molecular Biology, Central University of Kerala, Krishna building, Periye, Kasargod, 671316, Kerala, India.
Funct Integr Genomics. 2024 Jul 12;24(4):124. doi: 10.1007/s10142-024-01404-0.
Exosomes are lipid-bilayered vesicles, originating from early endosomes that capture cellular proteins and genetic materials to form multi-vesicular bodies. These exosomes are secreted into extracellular fluids such as cerebrospinal fluid, blood, urine, and cell culture supernatants. They play a key role in intercellular communication by carrying active molecules like lipids, cytokines, growth factors, metabolites, proteins, and RNAs. Recently, the potential of exosomal delivery for therapeutic purposes has been explored due to their low immunogenicity, nano-scale size, and ability to cross cellular barriers. This review comprehensively examines the biogenesis of exosomes, their isolation techniques, and their diverse applications in theranostics. We delve into the mechanisms and methods for loading exosomes with mRNA, miRNA, proteins, and drugs, highlighting their transformative role in delivering therapeutic payloads. Additionally, the utility of exosomes in stem cell therapy is discussed, showcasing their potential in regenerative medicine. Insights into exosome cargo using pre- or post-loading techniques are critical for exosome theranostics. We review exosome databases such as ExoCarta, Expedia, and ExoBCD, which document exosome cargo. From these databases, we identified 25 proteins common to both exosomes and P-bodies, known for mutations in the COSMIC database. Exosome databases do not integrate with mutation analysis programs; hence, we performed mutation analysis using additional databases. Accounting for the mutation status of parental cells and exosomal cargo is crucial in exosome theranostics. This review provides a comprehensive report on exosome databases, proteins common to exosomes and P-bodies, and their mutation analysis, along with the latest studies on exosome-engineered theranostics.
外泌体是由早期内涵体捕获细胞蛋白和遗传物质形成多泡体的双层脂质囊泡。这些外泌体被分泌到细胞外液中，如脑脊液、血液、尿液和细胞培养上清液。它们通过携带脂质、细胞因子、生长因子、代谢物、蛋白质和 RNA 等活性分子在细胞间通讯中发挥关键作用。最近，由于其免疫原性低、纳米级尺寸和穿过细胞屏障的能力，外泌体的传递治疗潜力得到了探索。本综述全面考察了外泌体的生物发生、分离技术及其在治疗学中的多种应用。我们深入探讨了用 mRNA、miRNA、蛋白质和药物装载外泌体的机制和方法，强调了它们在递呈治疗有效载荷方面的变革作用。此外，还讨论了外泌体在干细胞治疗中的应用，展示了它们在再生医学中的潜力。使用预加载或后加载技术对外泌体货物进行分析对于外泌体治疗学至关重要。我们回顾了 ExoCarta、Expedia 和 ExoBCD 等外泌体数据库，这些数据库记录了外泌体货物。从这些数据库中，我们确定了 25 种在 COSMIC 数据库中已知突变的外泌体和 P 体共有的蛋白质。外泌体数据库与突变分析程序不集成；因此，我们使用其他数据库进行了突变分析。考虑到亲本细胞和外泌体货物的突变状态在外泌体治疗学中至关重要。本综述提供了对外泌体数据库、外泌体和 P 体共有的蛋白质及其突变分析的全面报告，以及外泌体工程治疗学的最新研究。
