Hope amidst chaos: the revolution started by the mRNA vaccines
In early 2020, the COVID-19 pandemic caught the world off guard. After two years, the pandemic has affected hundreds of millions of lives worldwide and forced entire countries into lockdowns, wrecking economies and affecting multiple spheres of society through its cascading effects. Amidst the chaos, we were surprised by the production of surprisingly effective vaccines in record-breaking time. Until then, the fastest-ever vaccine created, for mumps in 1967, had taken four years to become available. The secret behind this unprecedented success lies in a technological novelty that brought an idea worthy of science fiction into reality: giving our cells the recipe to make our bodies develop immunity.
The Pfizer-Biontech Pfizer-BioNTech COVID-19 Vaccine was the first mRNA vaccine in history to be approved for human use.
DNA is widely recognized as the source code that determines the development and functioning of our organisms through its sequences of nucleic bases. While that is true, the outstanding role of DNA on what we are may draw the public view away from a significant cell co-star: the RNA or ribonucleic acid. The RNA is a polymer that serves as an intermediate between the information encoded by the DNA and the resulting proteins produced in the cell. If a cell were a kitchen, the DNA would be a recipes book kept in a safe, cell components called ribosomes would be a cook, and each mRNA would be a photocopy of a specific recipe from the book.
“DNA Transcription (Basic)”
Because the DNA is an enormous and irreplaceable structure for the cell, it rests safely into a specific chamber, the nuclei, for most of the cell lifecycle. However, the actual builders in charge of executing the DNA’s commands – the ribosomes – stay outside the nuclei. To bridge this gap, we have the messenger RNA (a.k.a. mRNA), which transcribes specific segments of the DNA in the nucleic and pass the instructions on to the ribosomes.
“mRNA Translation (Basic)”
So, how does all that apply to the development of vaccines?
When a pathogen (e.g., a virus or bacteria) invades our body, our immune system detects it through specific molecules called antigens. Traditionally, vaccines are inactivated or weakened forms of pathogens, which allow our bodies to get in touch with their antigens without developing the disease. As a result, our bodies produce antibodies to detect and combat those pathogens, developing immunity to the disease. mRNA vaccines are strands of mRNA in lipid capsules that carry the recipe for the antigens of the target pathogen. Once absorbed by our cells, a ribosome uses the mRNA the same way it would if it was mRNA coming from the nuclei and produces the antigen encoded on it. After that, the cell destroys the mRNA, and the antigen becomes available to our body, setting the immune system in motion. Contrary to rumors spread through anti-vaccination groups, the mRNA from the vaccine does not interact in any way with our cell DNA, which stays inside the cell nuclei. Additionally, the mRNA is destroyed right after been used by a ribosome, so it does not affect the cell after that.
mRNA vaccines have several advantages over conventional vaccines, ranging from biosafety to logistics. Traditional methods to produce vaccines typically involve collecting, adapting, and growing large quantities of pathogens or pieces of them. These complex and time-consuming processes create economic and logistic constraints to the production and development of vaccines. On the other hand, mRNA is made from a DNA template, requiring just the information on the correct sequence of bases to be produced. An experimental batch of an mRNA vaccine takes as little as one week to be ready. Additionally, the production process of mRNA vaccines enables changing the sequence encoded to target different variants or even pathogens with minimal changes, which facilitates scaling and standardizing their production.
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Although the COVID-19 vaccines were the first mRNA vaccines in history to be approved to use in humans, the idea of using RNA to give direct instructions to our bodies is far from a novelty in itself. Pathogens like viruses use this strategy to make their host cells build copies of themselves. Scientists have known and been inspired by this for many years. However, because of the potential threat that attending orders from foreign RNA strands can represent to our organism, our body has evolved mechanisms to recognize and promptly destroy these molecules once inside the cell. Finding a way to come around this was until recently the main challenge holding scientists back.
Katalin Karikó, a pioneer on the research of RNA, and one of the scientists responsible for the development of the mRNA vaccines.
Dr. Katalin Karikó is a Hungarian biochemist responsible for laying the scientific foundation for the mRNA vaccines. She has been working on this topic since 1989 and has advocated for the potential of what has now become known as the “software of life” or “operating system” for medicine. In 2004, working with Dr. Drew Weissman at the University of Pennsylvania, Dr. Karikó managed to engineer synthetic mRNA molecules that were not rejected by the body’s defenses. This breakthrough finally made all the theoretical possibilities of the RNA technology accessible to humankind, and in its debut application, the COVID-19 vaccines already saved hundreds of thousands of lives.
Now, mRNA is the center of attention of scientists worldwide, and the possibilities ahead of us are revolutionary. Through the mRNA, we can send all types of instructions the DNA could, which in the case of the COVID-19 vaccines is to make a viral antigen, but can also be many other things, like a cancer-blocking molecule, or new tissues, for example. Because the production of mRNA is so much easier than conventional methods, it allows for faster advancements into developing vaccines for fast mutating pathogens like the common flu, which kills over 300,000 people every year, or HIV. The production process for mRNA is so simple that Dr. Harris Makatsoris, from King’s College London, is even working on a prototype for an mRNA printer, which would be the equivalent of an entire vaccine fabric fitting on a single desk.
As of now, it is still hard to grasp the impact this new technology can have on our lives. Perhaps the most impactful application for this technology is yet to be discovered. However, with the prospect of applications for treating cancer, protein replacement, repairing tissues, immune engineering, and even slowing aging itself, the future could not be more promising.