This episode of Lifespan News features Emmett Short talking about a way to deliver collagen-producing mRNA through extracellular vesicles.
Script
New mRNA technology, like some Covid vaccines, can reduce wrinkles and eliminate signs of skin aging in mice. Wait a second… mRNA technology? Is this a government plot to make us all sexier?
Welcome to Lifespan News. I’m Emmett Short. Finding a good way to deliver molecular cargo into cells is big business. Why do you think there are so many dating apps?
The use of messenger ribonucleic acid, or mRNA, received a lot of attention during the COVID pandemic, but this technology has a lot more potential and is even tested for use in cancer treatments. You can learn more about this in our previous episode of Lifespan News, linked here and in the description.
Covid vaccines, like the mRNA-based ones from Moderna and Pfizer, use lipid nanoparticles to get their molecular cargo inside cells. These are bio-similar and sometimes cytotoxic, immunogenic and often not specific enough with the types of cells they go after. Hey, polyamory might work for some lipids but in my body, I’m looking for some commitment. I just want a lipid that really gets me, you know?
Enter EVs. Extracellular vesicles. These are nature’s nano-lipids! Cells create EVs, tiny droplets that permeate through cellular membranes passing molecular information without causing an immune reaction. Best of all they have what’s called inherent targeting, meaning they only have eyes for the cell type they were meant to be with. It’s so beautiful.
In this new study published in the journal Nature, researchers were able to pack mRNA inside these natural EVs. The mRNA encoded for a gene that creates collagen. It’s called collagen I alpha I, but let’s just call it “the collagen gene”.
Collagen gets depleted with age causing wrinkles. But it also affects your joints and ligaments and tendons. Many products and procedures claim to help with collagen deficiency. I drink it with my coffee because Jennifer Aniston told me to and she looks great, but none of the currently available technologies has been effective in achieving long-term collagen replacement. If this method is successful we’re talking about a natural mRNA vaccine for wrinkles and creaky joints. Gold mine!
How did they do it? The researchers used something called cellular nanoporation. They used an electrical field to create pores in cell membranes so the mRNA can get inside the EVs. Those EVs had 3,000 times more collagen genes than natural EVs. Then they injected these suped up EVs into aged fibroblasts, which are connective tissue cells that produce collagen proteins. These connective tissues, fibroblasts, started producing way more collagen but also new fibroblasts, which created even more collagen. It was like a collagen flywheel. It was nuts!
For their in vivo experiments, the researchers used a mouse model of UV-induced skin aging. Basically they gave the mice a lot of sunburns to cause wrinkles. I know what that looks like, but keep it clean guys. Ok? That is a mouse. Those are mice backs. I know it looks like a text message you’d have to report to HR but get your mind right. How dare you, this is science.
They pitted their EVs against healthy control mice with no wrinkles and a group that had been treated with lipid-nano particles that also had the collagen gene mRNA.
12 hours after receiving the EV treatment, Collagen gene mRNA peaked and had increased significantly, returning to baseline levels after four days. Both LNP and EV treatments led to decreases in wrinkle number and area, but the EV group had the biggest change. By day 28, the EV group had as few wrinkles as the healthy mice. LNP and EV treatments both resulted in higher elasticity and firmness. Basically these EV mice got way sexier. We’re talking firm, supple mouse backs.
The researchers also compared the immunogenic side effects of LNPs and EVs. 24 hours after injection, skin treated with LNPs showed redness, swelling, and recruitment of immune cells. But tissue treated with EVs did not exhibit a strong inflammatory reaction, showing that EVs cause much less of an immune response than LNPs.
Unfortunately, wrinkles did reappear about one week later, and about two months after the treatment the wrinkle number and area went back to pre-treatment levels. But they tried something new.
They repeated their experiments and instead of injection, they used microneedle patches treated with EVs. You put the patch on and then you take it off, but the microneedles stay in place.
Not only did this method cause wrinkle reduction to last twice as long, it also resulted in more even dispersion of collagen, so less clumping and more smooth, wrinkle-free skin. Throw a micro needle patch on your widow’s peaks once a month and you’re golden? Sign me up!
So, this proof-of-concept study showed us two things. MRNA delivery through Extracellular Vesicles delivers great results with less side effects, and microneedle application is an effective delivery system.
If you were excited by this and you want to learn more, make sure to subscribe and click the bell because it’s all happening right here. I’m Emmett Short, and we’ll see you next time on Lifespan News!
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