Molecular mechanisms governing exosome biogenesis, engineering strategies, and emerging role as cell-free...

Exosomes are nanosized extracellular vesicles that mediate intercellular communication by delivering functional cargo, including proteins, lipids, and regulatory nucleic acids. They overcome limitations of conventional cell-based therapies such as immune rejection, tumorigenicity, and poor engraftment, making them a promising tool for regenerative and precision medicine. Exosome engineering involves modifying exosomes through cargo enrichment, surface modification, hybrid vesicle design, and targeted delivery. It has revolutionized therapeutic strategies by enhancing tissue-specific targeting, stability in circulation, delivery efficiency of nucleic acids and drugs across biological barriers, and reducing off-target effects. These advances provide a clinically relevant platform for personalized treatments, offering safer and more efficient alternatives to traditional therapies. This review highlights the latest advances in exosome biology, including their biogenesis, cargo sorting, and engineering strategies for targeted delivery. Additionally, key therapeutic applications in regenerative and precision medicine are discussed, along with challenges in large-scale production, standardization, and clinical translation. This paper also highlights the transformative potential of exosome-based therapies and engineered platforms as next-generation, cell-free therapeutic strategies compared to conventional molecules such as liposomes.