Novel mRNA delivery method stimulates collagen repair and could replace fillers for skin wrinkles

summary: A novel mRNA delivery method uses extracellular vesicles that initiate collagen replacement in photodamaged skin. One injection increased collagen production and reduced wrinkle formation in the targeted areas for 2 months. Researchers say the new delivery method could be used to treat a number of disorders including disorders associated with protein loss associated with aging and genetic disorders 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 a study published today in The nature of biomedical engineeringIn laboratory models, researchers use EV-encapsulated mRNA to initiate and maintain collagen production for several months in photodamaged skin cells. It is the first treatment to demonstrate this ability and represents a proof of concept for dissemination of EV mRNA therapy.

“This is a completely new way to deliver mRNAs,” said corresponding author Betty Kim, MD, PhD, 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 way to deliver.”

mRNA contains the genetic code for building specific proteins, but delivery of mRNA within the body is one of the biggest hurdles for clinical applications of many mRNA-based therapies.

Current COVID-19 vaccines, which were the first large-scale use of an mRNA treatment, use lipid nanoparticles for delivery, and other primary delivery systems for genetic material to date have been virus-based. However, each of these methods comes with some limitations and challenges.

Extracellular vesicles are small structures created by cells that transport vital molecules and nucleic acids in the body. These naturally occurring particles can be modified to carry mRNAs, giving them the advantage of innate biocompatibility without triggering a strong immune response, allowing them to be administered multiple times. In addition, its size allows it to carry the largest human genes and proteins.

This shows a syringe drawing
This single injection improves collagen production and reduces wrinkle formation in the target area for 2 months. The image is in the public domain

In the current study, the research team used EV mRNA therapy to deliver COL1A1 mRNA, which encodes the collagen protein, into the skin cells of a laboratory model that mimics the skin damaged in aging in humans. EV mRNA was administered using a microneedle delivery system via a patch applied to the skin. This single injection improves collagen production and reduces wrinkle formation in the target area for 2 months.

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

“MRNA therapies have the potential to address a number of health issues, from protein loss as we age to genetic disorders where beneficial genes or proteins are missing,” Kim said. “There is also potential for delivering tumor suppressor mRNA as a treatment for cancer, so finding a new medium for mRNA delivery is exciting. There is still work to be done to bring this into the clinic, but these early results are promising.”

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

About this genetic research news

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

See also

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Original search: open access.
Intradermal delivery of mRNA-encapsulated extracellular vesicles for collagen replacement therapyWritten by Betty Kim et al. The nature of biomedical engineering


Summary

Intradermal delivery of mRNA-encapsulated extracellular vesicles for collagen replacement therapy

The success of mRNA therapies depends largely on the availability of delivery systems that enable safe, efficient, and stable translation of genetic material into functional proteins.

Here we show that extracellular vesicles (EVs) produced by cytokinesis of human dermal fibroblasts, encapsulation of an mRNA encoding extracellular collagen α1 type I (COL1A1) induced the formation of collagen protein grafts and reduced wrinkle formation in collagen-depleted dermal tissues. For mice with damaged skin.

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

Intradermal delivery of EV-based COL1A1 mRNA may lead to an effective protein replacement therapy for the treatment of photodamaged skin.

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