New mRNA delivery method induces collagen repair and could replace fillers for skin wrinkles
Resume: A new mRNA delivery method using extracellular vesicles initiates collagen replacement in photoaged skin. A single injection increased collagen production and reduced wrinkle formation in targeted areas for two months. The researchers say the new delivery method could be used to treat a number of disorders, including those associated with protein loss associated with aging and inherited disorders in which genes and proteins are missing.
Font: MD Anderson Cancer Center
A team of researchers led by the University of Texas MD Anderson Cancer Center has developed a new messenger RNA (mRNA) delivery system using extracellular vesicles (EVs). The new technique has the potential to overcome many of the obstacles faced by other promising mRNA therapies.
In the study, published today in Nature Biomedical Engineering, researchers use EV-encapsulated mRNA to initiate and maintain collagen production for several months in photoaged skin cells in laboratory models. It is the first therapy to demonstrate this capability and represents a proof of concept for implementing EV mRNA therapy.
“This is a completely new modality for mRNA delivery,” said corresponding author Betty Kim, MD, Ph.D., professor of neurosurgery.
“We used it in our study to initiate collagen production in cells, but it has the potential to be a delivery system for various mRNA therapies that currently do not have a good delivery method.”
The genetic code to build specific proteins is contained in mRNA, but mRNA delivery within the body is one of the biggest obstacles facing 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 delivery systems for genetic materials have so far been virus-based. However, each of these approaches comes with certain limitations and challenges.
Extracellular vesicles are small structures created by cells that transport biomolecules and nucleic acids in the body. These naturally occurring particles can be engineered to carry mRNA, giving them the benefit of innate biocompatibility without triggering a strong immune response, allowing them to be administered multiple times. Furthermore, their size allows them to carry even the largest human genes and proteins.
In the current study, the research team used EV mRNA therapy to deliver COL1A1 mRNA, encoding the collagen protein, in skin cells from a laboratory model that mimics skin damaged by aging in humans. EV mRNA was delivered using a microneedle delivery system through a patch applied to the skin. This single injection improved collagen production and reduced wrinkle formation in the targeted area for two months.
While initiating collagen production in cells is a remarkable 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 problems, from protein loss as we age to inherited disorders in which beneficial genes or proteins are missing,” Kim said. “There is even the possibility of delivering tumor suppressor mRNA as a cancer therapy, so finding a new route to deliver mRNA is exciting. There is still work to be done to bring this to the clinic, but these early results are promising.”
Money: This research was supported by an institutional fund from MD Anderson.
About this genetic research news
Author: aubrey flower
Font: MD Anderson Cancer Cancer
Contact: Aubrey Bloom–MD Anderson Cancer Center
Picture: The image is in the public domain.
original research: Open access.
“Extracellular vesicles encapsulating mRNA delivered intradermally for collagen replacement therapy” by Betty Kim et al. Nature Biomedical Engineering
Extracellular vesicles encapsulating mRNA delivered intradermally for collagen replacement therapy
The success of messenger RNA therapies is highly dependent on the availability of delivery systems that allow safe, efficient, and stable translation of genetic material into functional proteins.
Here we show that extracellular vesicles (EVs) produced via cell nanoporation from human dermal fibroblasts and encapsulation of mRNA encoding extracellular matrix collagen type I α1 (COL1A1) induced the formation of collagen protein grafts. and reduced wrinkle formation in collagen-depleted dermal tissue of mice with photoaged skin.
We also show that intradermal delivery of mRNA-loaded EVs via a microneedle array led to prolonged and more uniform collagen synthesis and replacement in the dermis of animals.
Intradermal delivery of EV-based COL1A1 mRNA may become an effective protein replacement therapy for the treatment of photoaged skin.