GENRISE-induced superior extracellular vesicles for scalable therapeutic cargo delivery

Extracellular vesicles (EVs) demonstrate immense potential as naturally derived carriers of active therapeutics. To maximize their capacity, it is crucial to develop effective methods for manipulating cargo and ensuring scalability. To address this challenge, we propose that protein-free mRNA granule-like structures, named gene-encoded nanoparticle RNA for inducing superior EVs (GENRISE), can function as active translational sponge and as transient subcellular compartments. The overexpression of proteins in proximity to RNA assemblies stimulates parental cells to release excess exogenous proteins in induced superior EVs (iSEVs). The iSEV system enables the single-module-based enrichment of exogenous cargo in EVs with scalable manufacturing. By harnessing mass-produced iSEVs induced by GENRISEs, encoding an antigenic peptide, we have successfully demonstrated target-specific in vivo cancer immunotherapy. These findings suggest that the emerging iSEV platform shows considerable potential for biomedical applications by enabling the controlled production of cargo-specific EVs.

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Publication Details

Journal
Science Advances
Published
2025-10-22
DOI
https://doi.org/10.1126/sciadv.ady9680
Primary Topic
Extracellular vesicles in disease
Type
article
Field-Weighted Citation Impact
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article

GENRISE-induced superior extracellular vesicles for scalable therapeutic cargo delivery

Eun‐Koung An, Seon‐Mi Jin, Yoonbin Ji, In-ho Jeong et al.
Science Advances
Extracellular vesicles in disease
article

GENRISE-induced superior extracellular vesicles for scalable therapeutic cargo delivery

Eun‐Koung An, Seon‐Mi Jin, Yoonbin Ji, In-ho Jeong, Hae‐Bin Park, Hwankyu Lee, Eunji J. Lee, Young Jik Kwon, Jun‐O Jin, Ohsung Ko, Sunghyun Moon, Peter Chang-Whan Lee, Dajeong Kim, Jong Bum Lee, Hyejin Kim, Ju Hong Min
article en

Abstract

Extracellular vesicles (EVs) demonstrate immense potential as naturally derived carriers of active therapeutics. To maximize their capacity, it is crucial to develop effective methods for manipulating cargo and ensuring scalability. To address this challenge, we propose that protein-free mRNA granule-like structures, named gene-encoded nanoparticle RNA for inducing superior EVs (GENRISE), can function as active translational sponge and as transient subcellular compartments. The overexpression of proteins in proximity to RNA assemblies stimulates parental cells to release excess exogenous proteins in induced superior EVs (iSEVs). The iSEV system enables the single-module-based enrichment of exogenous cargo in EVs with scalable manufacturing. By harnessing mass-produced iSEVs induced by GENRISEs, encoding an antigenic peptide, we have successfully demonstrated target-specific in vivo cancer immunotherapy. These findings suggest that the emerging iSEV platform shows considerable potential for biomedical applications by enabling the controlled production of cargo-specific EVs.

Science AdvancesVol. 11(43)
Ulsan College (KR), University of Seoul (KR), University of California, Irvine (US), Asan Medical Center (KR), Gwangju Institute of Science and Technology (KR), University of Ulsan (KR), Korea University (JP), Dankook University (KR)
Openalex Percentile: Top 73%
Extracellular vesicles in disease
DOIOpen Access PDFOpenAlex
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