Summary: A new method of mRNA delivery that uses 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 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-based therapies.
In the study, published today in Nature Biomedical Engineering, researchers are using mRNA encapsulated in EV 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 proof of concept for the deployment of EV mRNA therapy.
“This is an entirely new modality of 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 a number of mRNA therapies that currently have no good method of delivery. administration.”
The genetic code for building specific proteins is contained in mRNA, but delivering mRNA into the body is one of the biggest hurdles facing the clinical applications of many mRNA therapies.
Current COVID-19 vaccines, which marked the first widespread use of mRNA therapy, use lipid nanoparticles for delivery, and other primary delivery systems for genetic material have so far been virus-based. . However, each of these approaches has certain limitations and challenges.
Extracellular vesicles are small structures created by cells that transport biomolecules and nucleic acids around the body. These naturally occurring particles can be engineered to transport mRNAs, giving them the advantage of innate biocompatibility without triggering a strong immune response, allowing them to be administered multiple times. Moreover, 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, which encodes the protein collagen, in skin cells of a laboratory model that mimics skin damaged by aging in humans. EV mRNA was administered using a micro-needle 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 initiating collagen production in cells is a remarkable achievement in itself, Kim said, this study opens the door to further evaluation of EV mRNA therapy as a viable platform for delivery. of mRNA.
“mRNA therapies have the potential to address a number of health issues, from protein loss with age to hereditary disorders where beneficial genes or proteins are missing,” Kim said. “There is even the possibility of delivering tumor-suppressing mRNA as a cancer treatment, so finding a new way to deliver mRNA is exciting. There is still work to be done to bring this to 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 Cancer
Contact: Aubrey Bloom – MD Anderson Cancer Center
Picture: Image is in public domain
Original research: Free access.
“Extracellular Vesicles Encapsulating mRNA Intradermally Administered 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 largely depends on the availability of delivery systems that allow the safe, efficient, and stable translation of genetic material into functional proteins.
Here, we show that extracellular vesicles (EVs) produced by cellular nanoporation from human dermal fibroblasts and encapsulation of mRNA encoding extracellular matrix type I collagen α1 (COL1A1) induced graft formation. of collagen-protein and reduces the formation of wrinkles in collagen. depleted dermal tissue from mice with photoaged skin.
We also show that intradermal delivery of mRNA-charged EVs via an array of microneedles led to prolonged and more uniform collagen synthesis and replacement in animal dermis.
Intradermal delivery of EV-based COL1A1 mRNA may be an effective protein replacement therapy for the treatment of photoaged skin.