Nature sub-journal: A novel method of mRNA delivery using extracellular vesicles

A team of researchers led by the University of Texas MD Anderson Cancer Center has developed a novel messenger RNA (mRNA) delivery system
using extracellular vesicles (ev).
This new technology has the potential to overcome many of the delivery hurdles
faced by other promising mRNA therapeutics.

In the study, published in the journal Nature Biomedical Engineering, the researchers used ev-wrapped mRNA to initiate and maintain collagen production in photoaged skin cells in a laboratory model for several months
.
This is the first therapy to demonstrate this capability and represents a proof of concept
for deploying EV mRNA therapeutics.

"This is a completely new way of delivering mRNA," said corresponding author Betty Kim, a professor of neurosurgery
.
"We use it in our research to initiate collagen production in cells, but it has the potential to be a delivery system for many mRNA therapies that currently do not have a good delivery method
.
"

The genetic code for building a specific protein is contained in mRNA, but delivering mRNA in vivo is one of the biggest barriers to clinical adoption of
many mRNA-based therapies.

The current COVID-19 vaccine, which marks the first widespread application of mRNA therapeutics, uses lipid nanoparticles for delivery, and until now, other major delivery systems of genetic material have been virus-based
.
However, each approach has certain limitations and challenges
.

Extracellular vesicles are small structures produced by cells that transport biomolecules and nucleic acids
in the body.
These naturally occurring particles can be modified to carry mRNA, which makes them inherently biocompatible without triggering a strong immune response, allowing them to be used multiple times
.
In addition, their size allows them to carry even the largest human genes and proteins
.

In the current study, the team used EV mRNA therapy to deliver COL1A1-encoding collagen-encoding mRNA into skin cells
that mimic a laboratory model of aging damaged skin in humans.
EV mRNA is applied to the skin via patches, administered
using a microneedle delivery system.
This injection improved collagen production and reduced wrinkle formation in the target area for two months
.

Kim said that while initiating collagen production in cells is a notable achievement in itself, this study opens the door
to further evaluation of EV mRNA therapy as a viable platform for mRNA delivery.

"mRNA therapies have the potential to address many health problems, from protein loss with age to inherited diseases
in which beneficial genes or proteins are missing," Kim said.
"It's even possible to use tumor-suppressing mRNA as a cancer therapy, so finding a new pathway to deliver mRNA is exciting
.
" There is still a lot of work to be done to apply it to the clinic, but these early results are promising
.
”

The research was supported
by an institutional fund from MD Anderson.
A full list of co-authors and their disclosures can be found here
.