Loading mRNA into extracellular vesicles reduces wrinkles in mice

Scientists at the University of Texas MD Anderson Cancer Center have shown that extracellular vesicles (EVs) can deliver mRNA to the skin of mice, advancing efforts to establish the delivery vehicle as an alternative to lipid nanoparticles (LNPs).

LNPs underpin mRNA COVID-19 vaccines and many investigational candidates based on the delivery of the nucleic acid. However, studies have linked LNPs to cytotoxicity, poor biodistribution, lack of target specificity and immunogenicity—potentially because of the use of surface PEGylation to improve half-life—and spurred interest in alternative ways of getting mRNA to target cells.

A team led by MD Anderson scientists shared details of their work on the problem in Nature Biomedical Engineering. The journal paper describes the production of EVs from human dermal fibroblasts using cellular nanoporation as well as the encapsulation of mRNA and testing of the resulting drug candidate. 

After loading EVs with human collagen I alpha I mRNA, the researchers tested the candidate in a mouse model of acute photoaging. In the first study, the scientists delivered the EVs to the dermis of mice via an insulin needle syringe. But, while the approach initially induced the formation of collagen-protein grafts and reduced wrinkle formation, wrinkles returned to baseline within one month of stopping treatment.

In a bid to boost durability, the collaborators formulated the mRNA-loaded EVs into microneedle patches and showed that the delivery format resulted in prolonged and more uniform synthesis and replacement of collagen. Buoyed by the findings, the team is eyeing other applications of the mRNA delivery system. 

“This is an entirely new modality for delivering mRNA,” Betty Kim, M.D., Ph.D., corresponding author and professor of neurosurgery at MD Anderson, said in a statement. “We used it in our study to initiate collagen production in cells, but it has the potential to be a delivery system for a number of mRNA therapies that currently have no good method for being delivered.”