New mRNA delivery method induces collagen repair and may replace skin wrinkle fillers

Overview: A new mRNA delivery method using extracellular vesicles initiates collagen replacement in slightly aged skin. A single injection increased collagen production and reduced wrinkle formation in the targeted areas for two months. Researchers say the new delivery method could be used to treat a number of conditions, including those related to protein loss associated with aging and inherited conditions where genes and proteins are missing.

Source: MD Anderson Cancer Center

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 (EVs). The new technique has the potential to overcome many of the delivery hurdles faced by other promising mRNA therapies.

In the study, published today in Nature Biomedical Technology, the researchers use EV-encapsulated mRNA to initiate and sustain collagen production in the cells of photo-aged skin in laboratory models for several months. It is the first therapy to demonstrate this ability and represents a proof-of-concept for deploying EV mRNA therapy.

“This is an entirely new modality for mRNA delivery,” says corresponding author Betty Kim, MD, Ph.D., professor of neurosurgery.

“We used it in our study to kick-start collagen production in cells, but it has the potential to be a delivery system for a number of mRNA therapies that currently don’t have a good method of delivery.”

The genetic code for building specific proteins is contained in mRNA, but delivering mRNA into the body is one of the major hurdles to clinical applications of many mRNA-based therapies.

Current COVID-19 vaccines, which marked the first widespread use of mRNA therapy, use lipid nanoparticles for delivery, and the other primary genetic material delivery systems to date have been virus-based. However, each of these approaches has certain limitations and challenges.

Extracellular vesicles are small structures made by cells that transport biomolecules and nucleic acids in the body. These naturally occurring particles can be modified to carry mRNAs, giving them the advantage of innate biocompatibility without eliciting a strong immune response, allowing multiple administrations. In addition, their size allows them to carry even the largest human genes and proteins.

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This single injection improved collagen production and reduced wrinkle formation in the targeted area for two months. The image is in the public domain

In the current study, the research team used EV mRNA therapy to deliver COL1A1 mRNA, which codes for the collagen protein, in the skin cells of a lab model that mimics aging-damaged skin in humans. The EV mRNA was administered using a microneedle delivery system via a patch applied to the skin. This single injection improved collagen production and reduced wrinkle formation in the targeted area for two months.

While triggering collagen production in cells is a remarkable achievement in itself, this study opens the door for further evaluation of EV mRNA therapy as a viable platform for mRNA delivery, Kim said.

“MRNA therapies have the potential to address a number of health problems, from protein loss as we age to inherited conditions where beneficial genes or proteins are missing,” Kim said. “There’s even the potential to deliver tumor suppressive mRNA as a cancer therapy, so it’s exciting to find a new avenue to deliver mRNA. There’s still work to be done to bring this to the clinic, but this first results are promising.”

financing: This research was supported by an institutional fund from MD Anderson.

About this genetics research news

Writer: Aubrey Bloom
Source: MD Anderson Cancer Cancer
Contact: Aubrey Bloom – MD Anderson Cancer Center
Image: The image is in the public domain

Also see

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Original research: Open access.
“Intradermally delivered mRNA-encapsulating extracellular vesicles for collagen replacement therapy” by Betty Kim et al. Nature Biomedical Technology


Abstract

Intradermally delivered mRNA-encapsulating extracellular vesicles for collagen replacement therapy

The success of messenger RNA therapeutics largely depends on the availability of delivery systems that enable the safe, effective and stable translation of genetic material into functional proteins.

Here we show that extracellular vesicles (EVs) produced via cellular nanoporation of human dermal fibroblasts and encapsulation of mRNA encoding extracellular matrix α1 type-I collagen (COL1A1) induced the formation of collagen protein grafts and reduced collagen wrinkling. depleted skin tissue from mice with photoaged skin.

We also show that the intradermal delivery of the mRNA-loaded EVs via a microneedle array led to the prolonged and more uniform synthesis and replacement of collagen in the dermis of the animals.

The intradermal administration of EV-based COL1A1 mRNA may be an effective protein replacement therapy for the treatment of photoaged skin.

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