Abstract
Exosomes, as key mediators of intercellular communication, have shown great potential in disease intervention and therapy in recent years. As natural nanocarriers, exosomes play a crucial role in transporting a wide array of cargo. Among these, miRNAs carried by exosomes are pivotal in gene regulation and the modulation of cellular signaling. Given that miRNAs are essential gene regulators, understanding how miRNAs are selectively loaded into exosomes is crucial for the development of novel diagnostic and therapeutic approaches. This review provides a detailed overview of the biogenesis and secretion mechanisms of exosomes, with a particular focus on the molecular mechanisms governing miRNA sorting into exosomes. Specifically, it highlights the miRNA motifs associated with exosomes enrichment (EXOmotifs), as well as those related to intracellular miRNA enrichment (CELLmotifs), along with RNA-binding proteins (RBPs) involved in sorting. We summarize the current progress in this field and discuss strategies for engineering Exosomes - such as gene editing, drug loading, and surface modification - to enhance their functionality and specificity. By exploring these mechanisms, this review offers a theoretical foundation for the application of engineered exosomes in disease treatment and outlines future research directions and potential applications.