Search

Messenger RNA (mRNA) has emerged as an attractive therapeutic molecule for a range of clinical applications. Forin vivofunctionality, mRNA therapeutics require encapsulation into effective, stable, and safe delivery systems to protect the cargo from degradation and reduce immunogenicity. Here, we developed a bioengineering platform for efficient mRNA loading and functional delivery using naturally-derived nanoparticles, Extracellular Vesicles (EVs). By expressing the highly specific PUFe RNA-binding domain fused to CD63 in EV producer cells stably expressing the target mRNA, our system exceeds mRNA loading efficiencies by up to 4.5-fold over previously reported EV-based approaches. By combining with an mRNA-stabilizing protein, PABPc, and a fusogenic endosomal escape moiety, VSVg, functional mRNA deliveryin vivois achieved at doses substantially lower than clinically used lipid nanoparticles. Our technology solves substantial drawbacks currently associated with EV-based nucleic acid delivery systems and could enable new applications for mRNA therapeutics.