Extracellular vesicles to mediate RNA therapies

Graphical AbstractDifferent methods of vascular endothelial growth factor (VEGF) therapy have utilized the molecule in three distinct forms: protein, DNA, and mRNA, each varying in application methods, sites, efficacy, and associated risks. Protein delivery involves direct administration of recombinant VEGF-A protein, but challenges such as short half-life and instability limit its therapeutic efficacy. DNA delivery introduces VEGF-A genes via plasmids or adeno-associated virus (AAV) vectors, but carries risks of low transfection efficiency, immune responses, and potential genomic integration, raising concerns about long-term effects such as tumour stimulation. mRNA delivery, especially using lipid nanoparticles (LNPs), offers transient expression but may cause immune activation due to synthetic components, while naked mRNA application showed rapid degradation. The use of extracellular vesicles (EVs) to deliver VEGF-A mRNA addresses these limitations by providing a biocompatible, low-immunogenicity alternative that enhances efficacy. EVs-mediated mRNA delivery protects the mRNA cargo, allows efficient uptake by target cells, and enables repeated dosing without strong immune activation, offering a promising approach for therapeutic angiogenesis in ischaemic vascular diseases.Open in new tabDownload slide