Development of next-generation exosome-based combination therapy for the treatment of the metabolically challenging disease mash

□ DGIST (President Kunwoo Lee) Department of New Biology Professor Yea Kyungmoo and his research team have developed a next-generation exosome-based drug-delivery technology to effectively treat metabolic dysfunction-associated steatohepatitis (MASH), an incurable metabolic disease, in collaboration with Professor Baek Moon-chang of Kyungpook National University School of Medicine.

□ MASH is a complex disease that accompanies various metabolic diseases, such as obesity and diabetes, and existing therapies are limited in their effectiveness since they target only a single pathological mechanism. Some candidates have either failed clinical trials or are delayed in approval due to cardiovascular side effects or long-term use concerns. Such circumstances demonstrate the need for safer and more effective combination treatment strategies.

□ To address these challenges, Professor Yea’s research team achieved the simultaneous engineering of the interior and the surface of extracellular vesicles (exosomes), biologically derived particles that play a vital role in delivering signals between cells, to formulate a bifunctional drug-delivery system that is specific to the treatment of pathologically complex MASH.

□ Exosomes, which carry various molecules including proteins, lipids, and genetic materials, are produced naturally in the body and are considered a promising next-generation drug-delivery system because they have higher biocompatibility, lower toxicity, and fewer side effects than existing lipid-based drug-delivery systems (such as COVID-19 vaccines).

□ The research is designed to regulate metabolic abnormalities, inflammation, and fibrosis simultaneously, the main pathological mechanisms of MASH, by attaching the potent fat-burning protein Fibroblast Growth Factor 21 (FGF21) to the surface of the exosomes, and enclosing miRNA-223, which is effective for regulating inflammation and fibrosis. In particular, the exosomes may be delivered explicitly to liver tissues, maximizing treatment efficiency.

□ “This research is the first to demonstrate a novel combination treatment concept utilizing exosomes for MASH, a metabolic disease that is difficult to treat. It sheds light on the potential to overcome the limitations of existing treatment strategies,” Professor Yea said. “We hope to establish a mass production system in the future that will lead to actual drug development.”

□ This research is funded by the Ministry of Science and ICT and DGIST’s D-GRIP, and the findings are published in Biomaterials, a leading international journal in biomaterials.

- Corresponding Author E-mail Address : ykm31@dgist.ac.kr