Innovative approach to mRNA delivery

A group of scientists spearheaded by The University of Texas MD Anderson Cancer Center has created a unique messenger RNA (mRNA) delivery system utilizing extracellular vesicles (EVs). The new method has the capability to circumvent many of the delivery challenges that other promising mRNA therapies have encountered.

Innovative approach to mRNA delivery
Betty Kim MD, PhD. Image Credit: The University of Texas MD Anderson Cancer Center

The scientists used EV-encapsulated mRNA to start and sustain collagen production in photoaged skin cells in laboratory models for several months in the work. The study was published in the journal Nature Biomedical Engineering. It is the first therapy to display this capability and serves as proof-of-concept for the use of EV mRNA therapy.

This is an entirely new modality for delivering mRNA. 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.”

Betty Kim MD PhD, Study Corresponding Author and Professor, Neurosurgery, The University of Texas MD Anderson Cancer Center

Although mRNA contains the genetic code for building specific proteins, clinical applications of many mRNA-based therapies face significant challenges in transferring mRNA within the body.

The current COVID-19 vaccines, which were the first widely used mRNA therapy, use lipid nanoparticles for delivery, while all prior key delivery mechanisms for genetic materials have been viral. Each of these approaches, however, has challenges and limitations.

Cells produce extracellular vesicles, which are tiny structures that transport chemicals and nucleic acids throughout the body. These naturally present particles can be engineered to transport mRNAs, allowing them to be administered several times without eliciting a severe immune response. Furthermore, their size enables them to transport even the largest human genes and proteins.

The researchers employed EV mRNA therapy to transfer COL1A1 mRNA, which expresses the collagen protein, into the skin cells of a laboratory model that mirrors aging-damaged skin in humans in the current study. The EV mRNA was delivered via a skin patch utilizing a microneedle delivery system. For two months, this single injection increased collagen production and reduced wrinkle formation in the specified site.

While initiating collagen formation in cells is a significant accomplishment, Kim believes that this discovery opens the door for further investigation of EV mRNA therapy as a potential platform for mRNA delivery.

mRNA therapies have the potential to address a number of health issues, from protein loss as we age to hereditary disorders where beneficial genes or proteins are missing. There is even the potential for delivering tumor-suppressing mRNA as a cancer therapy, so finding a new avenue to deliver mRNA is exciting. There is still work to be done to bring this to the clinic, but these early results are promising.”

Betty Kim MD PhD, Study Corresponding Author and Professor, Neurosurgery, The University of Texas MD Anderson Cancer Center

Source:
Journal reference:

You, Y., et al. (2023) Intradermally delivered mRNA-encapsulating extracellular vesicles for collagen-replacement therapy. Nature Biomedical Engineering. doi.org/10.1038/s41551-022-00989-w.

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