Innovative Exosome-Based Combination Therapy Offers New Hope for Treating Metabolic Liver Disease MASH

Researchers from Daegu Gyeongbuk Institute of Science and Technology (DGIST), led by Professor Yea Kyungmoo, have developed a groundbreaking exosome-based drug delivery system aimed at effectively treating metabolic dysfunction-associated steatohepatitis (MASH). This complex, currently incurable liver disease often coexists with obesity and diabetes, posing significant treatment challenges. The team's innovative approach involves engineering extracellular vesicles, or exosomes, to carry therapeutic agents directly to liver tissues.

Exosomes are natural particles produced by cells that transport proteins, lipids, and genetic materials, playing essential roles in cell communication. Their inherent biocompatibility, low toxicity, and minimal side effects make them promising carriers for targeted drug delivery, especially compared to traditional lipid-based systems.

The engineered exosomes are designed to address the key pathological mechanisms of MASH by simultaneously regulating metabolic abnormalities, inflammation, and fibrosis. The surface of these exosomes is modified to display Fibroblast Growth Factor 21 (FGF21), a potent protein that enhances fat burning. Inside, they carry microRNA-223, which effectively modulates inflammation and fibrosis. This dual-function system enables precise delivery to liver tissues, maximizing therapeutic effects.

This innovative strategy marks the first time an exosome-based combination treatment has been proposed for MASH, showcasing potential advantages over conventional therapies that often target single pathways and face issues like adverse cardiovascular effects or long-term safety concerns. The research team aims to establish scalable production methods to facilitate future drug development and clinical application.

The study, published in the journal Biomaterials, underscores the potential of bioengineered exosomes as a versatile platform for tackling complex metabolic diseases. As MASH represents a significant unmet medical need, this novel approach opens new avenues for safer and more effective treatments.

For more details, see the full publication: Hanchae Cho et al, "Engineered extracellular vesicles with surface FGF21 and enclosed miR-223 for treating metabolic dysfunction-associated steatohepatitis," Biomaterials, 2025. DOI: 10.1016/j.biomaterials.2025.123321