GENRISE-induced superior extracellular vesicles for scalable therapeutic cargo delivery.

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.