Drug intelligence / Profile preview

EV-HNF4α mRNA

Development stage
Preclinical
Lead developer
Southeast University
Modality
mRNA Therapeutics → RNA Therapeutics → Nucleic Acid Therapeutics, Lipid-based Nanoparticles → Nanoparticles → Drug Delivery Systems
Administration
Intravenous
01

Overview

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.

Other names
EV-Hnf4α mRNAendogenous HNF4α mRNA-loaded EVsHNF4α mRNA-loaded EVs
02

Targets

HNF4A (Hepatocyte nuclear factor 4 alpha)TIM-1 (T-cell immunoglobulin and mucin domain-containing protein 1)LCN2 (Lipocalin-2)

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