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EV-HNF4α mRNA is an experimental engineered extracellular vesicle (EV) therapy designed to deliver hepatocyte nuclear factor 4α (HNF4α) mRNA for hepato-renal protection. Developed by researchers at Southeast University, the system utilizes an in vivo EV engineering platform based on a minimal 144-amino acid scaffold protein, EN-144 (derived from ENPP1), fused to an L7Ae RNA-binding domain. This scaffold, when co-delivered with C/D box-modified Hnf4α mRNA into hepatocytes, promotes the selective incorporation of the mRNA into newly generated endogenous EVs. These engineered EVs facilitate targeted delivery of functional HNF4α mRNA to renal tubular epithelial cells and hepatocytes, significantly increasing HNF4α expression. In preclinical models of cisplatin-induced acute kidney injury (AKI) with hepatic injury, treatment with EV-HNF4α mRNA attenuated tissue damage, reduced serum biomarkers of renal and hepatic injury (such as creatinine, blood urea nitrogen, and AST), suppressed TNF-α-associated inflammatory signaling, and improved survival.
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