Researchers have developed a groundbreaking method using mRNA and extracellular vesicles to stimulate collagen production, offering a safer and more effective alternative to Botox for wrinkle reduction and paving the way for innovative mRNA-based medical treatments.

Botox has long been the go-to solution for individuals seeking smoother skin. However, its mode of action is far from perfect. Botox paralyses muscles, leading to potential side effects such as muscle weakness, vision and breathing difficulties, speech problems, swallowing issues, and even loss of bladder control.

Recognising these drawbacks, the research team at MD Anderson Cancer Center set out to develop a safer and more effective alternative.

The future of wrinkle reduction?

Instead of paralysing muscles, these DNA injections utilise mRNA to stimulate collagen production. To test their approach, researchers conducted experiments on a bald experimental model, exposing them to UV radiation for 60 days to induce wrinkles.

Subsequently, mRNA was injected into the irradiated experimental model's skin using microneedles for 15 minutes in a single session. After just 28 days of single-dose mRNA injection, the treated experimental model displayed the same wrinkle count as those not exposed to UV radiation. Additionally, the injection sustained enhanced collagen production in the targeted area for nearly 2 months.

Central to this breakthrough research is the first successful application of extracellular vesicles (EVs) derived from human skin fibroblasts as a pharmaceutical therapy. This study used EVs to carry mRNA for a protein called COL1A1. Then, researchers used a special patch with needles made of hyaluronic acid (HA) to deliver these mRNA-loaded EVs to the skin.

Betty Kim, MD, PhD, the corresponding author of the MD Anderson study and a professor of neurosurgery, emphasised the significance of this new modality for mRNA delivery. In the MD Anderson press release about the study, Dr. Kim said, “This [EV] 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 several therapies that currently have no good delivery method.”

Overcoming challenges in mRNA medicine

While mRNA holds tremendous promise for medical applications, its fragile nature presents a significant challenge. However, the successful deployment of mRNA vaccines in the fight against COVID-19 has illuminated a path forward. As the MD Anderson researchers explained in their article, delivering mRNA into target cells requires a protective carrier, which has traditionally been a synthetic fat like lipid nanoparticles (LNPs).

Although LNPs are the primary method for transporting mRNA, they have drawbacks, such as potential toxicity to cells, limited ability to reach target receptors, and occasional immunological reactions. Scientists are actively exploring alternative options, like EVs, in response to these limitations. EVs are naturally produced in our bodies within fibroblasts and are less likely to cause any potential adverse events.

Additional uses of mRNA therapies

Dr. Kim envisions a bright future for mRNA in medicine: “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,” she said.

“There is even the potential for delivering tumour-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.”

- Dr. Kim

Future prospects

In prior research endeavours, the MD Anderson research team successfully pioneered a technique known as cellular nanoporation (CNP). This method involves the creation of temporary nanoscale openings on the surface of donor cells, facilitating the extensive loading of full-length mRNA transcripts into secreted EVs. Future research studies can apply this CNP technology to craft clinically useful pharmacological therapies.

Disclaimer: This story is contributed by Alpana Mohta and is a part of our Global Content Initiative, where we feature selected stories from our Global network which we believe would be most useful and informative to our doctor members.