- Mass production strategy for next-generation stem cell-derived extracellular vesicle (EV)-based therapeutics expected to enable applications in immunotherapy, vaccines, and other fields

A research paper titled “GENRISE-Induced Superior Extracellular Vesicles for Scalable Therapeutic Cargo Delivery,” jointly written by Professor Jong Bum Lee’s research team (first authors: Hyejin Kim and Sunghyun Moon) from the Department of Chemical Engineering at the University of Seoul and the research team of Professors Peter C W Lee and Jun-O Jin from the College of Medicine of the University of Ulsan (Asan Medical Center), has been accepted for publication in the prestigious journal Science Advances.

Science Advances, published by the American Association for the Advancement of Science (AAAS), is an open-access, multidisciplinary journal within the Science family. It is a top-tier journal with stringent review standards, accepting only about 10% of the approximately 20,000 papers submitted annually (5-year impact factor: 14.1).

The joint research team designed and engineered a novel mRNA granular condensate, “GENRISE,” to function as a “translation sponge” and a temporary intracellular vesicle. The research elucidated the principle whereby GENRISE induces localized translation activity and reversible ER stress signals, prompting cells to massively release “induced superior stem cell-derived extracellular vesicles (iSEVs)” rich in specific proteins. This demonstrated that a single RNA module can simultaneously control both the “cargo” and “production scale” of EVs without complex genetic engineering.

▶ Mass Production of Stem Cell-Derived Extracellular Vesicles and Anticancer Immunotherapy Outcomes

From a clinical application perspective, the research team administered iSEV-TRP2, manufactured using GENRISE expressing the melanoma antigen peptide (TRP2), to a tumor animal model. The results showed that tumor growth was significantly suppressed through an antigen-specific immune response, and a synergistic effect was observed when combined with the anti-PD-L1 immune checkpoint inhibitor.

This achievement was accomplished through collaborative research between the University of Seoul and Asan Medical Center, supported by the Ministry of Health and Welfare’s Non-Viral Delivery System Development Project and the Ministry of Science and ICT’s Mid-Career Researcher Support Program. This study is particularly significant as it offers a mass production strategy for next-generation stem cell-derived extracellular vesicle (EV)-based anticancer therapeutics for practical cancer treatment, while also effectively enhancing the loading and delivery efficiency of protein therapeutics.

Professor Jong Bum Lee stated, “This research has demonstrated that RNA alone can precisely control the production and cargo loading of stem cell-derived extracellular vesicles,” and added, “It has produced important findings, suggesting potential expansion into various fields, such as immunotherapy, vaccines, and precision medicine.”

▶ (L-R) Dr. Hyejin Kim (first author), Student Sunghyun Moon (first author), Professor Jong Bum Lee (University of Seoul), Professor Peter C W Lee (Asan Medical Center), Professor Jun-O Jin (Asan Medical Center)