Today, the story of Katalin Kariko's multi-decade-long struggle to prove that messenger RNA can be successfully used in medicine is well-known. The world has now learned a lot about mRNA technology in just two years. It can respond quickly when needed, and holds many promises for future applications. The ride was bumpy and long, as is the case for “instant hits” science. But more later.
What's mRNA?
In simple words, messenger ribonucleic acid (or mRNAs) is the body's natural method to transmit messages from our DNA into our cells. It tells cells which proteins to produce in order to ensure everything works as it should. It can be viewed as an IKEA user manual, where all the instructions are created from the combination of four nucleotides which make up the “letters” in the RNA.
What is it doing in a vaccine?
The mRNA vaccines are different from other vaccines in that they introduce the body to the actual pathogen (living or dead [parts]). Instead of introducing the body directly to the pathogen, they contain instructions that allow our bodies to make a small but important part of it. This is the COVID vaccine's famous spike protein.
Why is it so good?
The body can create the antibody that will fight the disease by replicating the COVID spike protein, even if it is not infected. Our immune system is already trained to recognize and fight the virus by the time it reaches us.
This illustration will help you understand the concept. Although it has only ever encountered a small part of the pathogen it was still trained to fight it.
Not a new thing
Our knowledge of the purpose and existence of mRNA was first discovered in the 1960s. Scientists have struggled to understand how this messenger molecule could be used for medicine despite its long history.
In 1990, scientists were able to successfully inject mRNA into mice's bodies and produce certain proteins. This was the first attempt. It proved that the technology was possible, but they had to overcome two obstacles: 1. The instability of the mRNA molecules in the body (so they don't disappear within minutes), and 2. its tendency to trigger inflammatory reactions.
Now, fast forward 15 years to 2005. (Note that we were in 44th year of mRNA research at this point – so much the myth about the vaccine created in haste). Kariko's team made a major breakthrough when they found a way to “wrap” mRNA in the right type of lipid coating. This solved both of the major hurdles. It took 30+ years to find the right lipid nanoparticles, but that story is another story.
Yet, 15 more years pass with constant research until 2020 when the COVID pandemic will stop the world like nothing else.
This novel crisis presented an unprecedented opportunity for the mRNA technology, diverting never-before-possible funds and opportunities to the field. The neglected and long-detailed research segment of mRNA became the favorite, creating new vaccines almost instantly.
The success of the mRNA vaccinations and the pandemic gave tremendous momentum for possible applications. These are the things we can expect for the near, mid-, and longer-term.
What's next? The short-term future: Combinated flu shots
Moderna began the human trial of a combined mRNA flu shot mid-2021. It promises that the technology can be made much faster than traditional flu vaccines. This means the jab will be closer to actual year-specific pathogens. Moderna isn't the only one with similar ventures. Sanofi, Pfizer BioNTech and Translate Bio also have similar ventures.
With the combined flu shots, we aim to create a vaccine which prepares patients for all types of respiratory pathogens in just one shot.
Infectious Diseases: Malaria
Pfizer-BioNTech stated in 2021 that part of their profits would be used to develop a malaria vaccine using the exact same mRNA technology.
Ugur Sahin, BioNTech's Chief Executive Officer and cofounder, said that Malaria is a complicated infection that is resistant to the immune system. He also stated that the goal of developing a vaccine that will make the parasite visible and attackable right from the beginning is the goal.
Although initial reports suggested clinical testing for malaria mRNA vaccines in 2022, there have been no recent developments.
According to reports, the company has started construction of an mRNA vaccine manufacturing plant in Rwanda. This is the first such facility on the African continent. The company is planning to follow this up with the establishment of additional factories in Senegal, South Africa and other African countries. The published information states that the plants will produce HIV mRNA vaccines for COVID, Malaria, and HIV in the future.
Infectious Diseases: HIV
According to a posting in the National Institutes of Health's clinical trials registry, “Two of Moderna’s mRNA-based HIV vaccinations could begin human trials this week.” This 2021 report stated that the Phase I study would assess vaccine safety and collect basic data to determine if they induce immunity. However, Phase II and III would still be required to verify their effectiveness.
Although human trials are a bit later than expected, they are ongoing. In-Africa clinical trials for the future vaccine began in May 2022.
Breast cancer, advanced melanoma and other solid tumours
After a successful trial with mice, BioNTech was joined by Sanofi to test the safety of a 4-mRNA mixture on 231 subjects. These preliminary results showed no side effects and were published here.
The treatment is not suitable for tumors located near the surface of the body at the moment, as the mRNAs need to be directly injected into them.
Pancreatic Cancer
A new vaccine that uses the same mRNA technology used in the Pfizer jab against COVID-19 may be a breakthrough in fighting pancreatic cancer. BioNTech reported that half of patients who had their tumors removed and received the jabs remained cancer-free for 18 months. This was in June 2022.
The vaccine was shown to be able to train the immune system and kill pancreatic cancer cells. It also boosts immune cells that target the tumours. Each patient received eight doses each of the individualized vaccine based on the mRNA genetic code from their respective tumours.
Vaccines preventing skin cancer
Another fascinating line of research is from Oregon State University. This research was inspired by TR1, a protein in the thioredoxin antioxidant system. This protein is thought to be capable of protecting melanocytes from oxidative stress. These cells are damaged by UV radiation.
Researchers used mice to study the effects of TR1 on melanocyte protection. The researchers found that melanocyte proliferation was reduced when TR1 was removed from their antioxidant systems. The researchers concluded that TR1 directly affected melanocytes. These cells are responsible for protecting skin cancer prevention. A vaccine that could produce more TR1s could also protect against sun-induced UV damage.
Perhaps we will soon be able to get an annual vaccination for additional sun protection.
Individual with inherited genetic issues
A clinical trial to determine if an mRNA injection could be used to instruct the body to produce the protein missing in patients with certain metabolic diseases is currently underway.
“Moderna is researching the use mRNA to treat the metabolic disorder Glycogen Store Disease Type Ia (GSDIa), which results in the liver not breaking down glycogen into glucose. This causes blood sugar levels to drop.”
What's the situation?
We can see the immense potential of mRNA technology. In the last two years, billions of doses of mRNA vaccinations were administered around the world. This has helped to accelerate the field by a few decades.
The Medical Futurist published the post mRNA vaccines: From treating cancer to tackling pandemics.
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By: Andrea Koncz
Title: mRNA Vaccines: From Tackling Pandemic To Treating Cancer
Sourced From: medicalfuturist.com/mrna-vaccines-from-tackling-pandemic-to-treating-cancer
Published Date: Tue, 12 Jul 2022 08:00:00 +0000
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