Exosome theranostics: Comparative analysis of P body and exosome proteins and their mutations for clinical applications.

ABSTRACT

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.