Extracellular vesicles (EVs) have been found to be a viable alternative to lipid nanoparticles for the delivery of mRNA to mice’s skin, according to researchers at the University of Texas MD Anderson Cancer Center.
Numerous research possibilities relying on mRNA COVID-19 vaccine delivery are grounded in LNPs. However, the application of surface PEGylation to increase LNPs’ half-lives has been related to cytotoxicity, poor biodistribution, a lack of target selectivity, and immunogenicity, leading researchers to seek out alternate methods of delivering mRNA to their intended cells.
Scientists from MD Anderson led a team that published their findings in Nature Biomedical Engineering. The process of creating EVs from dermal fibroblasts of humans through cellular nanoporation, including mRNA encapsulation and testing, is detailed in the aforementioned journal article.
The candidate was put to the test in a mouse model of acute photoaging after EVs were loaded with human collagen I alpha I mRNA. Researchers injected EVs into the skin of mice with an insulin needle in the first trial. The method did minimize wrinkle formation in the short term and led to the production of collagen-protein grafts. However, after the treatment was discontinued, wrinkles returned to pre-treatment levels within a month.
The researchers demonstrated that microneedle patch administration of mRNA-loaded EVs led to sustained and more even collagen synthesis and replacement, both of which are important for tissue integrity and longevity. The results have given the scientists confidence to consider expanding the mRNA delivery method to additional areas.
“This is an entirely new modality for delivering mRNA,” Betty Kim, M.D., the corresponding author stated. “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.”
One potential drawback of LNPs is that they are known to trigger inflammatory responses. It’s hard to target a specific tissue because they aren’t always biocompatible. Although these limitations do not pose a serious threat to the use of LNPs for vaccinations, they can restrict the delivery of other treatments.
Two medications delivered through viral vectors, specifically adeno-associated viruses (AAV), have received US Food and Drug Administration (FDA) approval. The limitations of AAV delivery, in contrast to LNPs, include immunogenicity, toxicity, and a small cargo capacity. However, the majority of human genes are too big to be packaged into an AAV.
Many of the challenges faced by prospective mRNA therapies may be surmounted by delivering the mRNA in EVs. Unlike LNPs and AAVs, EVs – such as exosomes and micro-vesicles – are naturally occurring in the body and serve a biological purpose by transporting a wide range of biomolecules. That’s why they’re naturally biocompatible and able to pass through all sorts of biological barriers. Because of this, they can be given multiple times without causing any sort of inflammatory response.
Moreover, EVs are large enough to carry even the biggest human genes and proteins, and they can be manufactured from cells in an easy and inexpensive way to make them in considerable quantities.