Apart from Covid-19, mRNA Technology Could Fight Other Challenging Diseases

George J. Ziogas

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The first Covid-19 vaccines approved by western government agencies were based on what’s called messenger ribonucleic acid (mRNA) technology, a process never used before in licensed human vaccines. The vaccines’ rollout generated huge media coverage worldwide. That coverage, however, largely overshadowed the technology’s broader medical significance.

To appreciate that significance, it’s worth first looking at how the Covid-19 mRNA vaccines work. An enzyme called RNA polymerase reads the DNA base of the virus and transcribes it into mRNA. The vaccines made from this mRNA don’t contain any part of a virus, just a synthetic mRNA strand based on the part of the virus DNA responsible for what’s known as the spike protein.

When injected, the vaccine’s mRNA delivers its message to the person’s cell, prompting it to make the spike protein. The spike protein appears on the cell’s surface, and the immune system treats it like a real infection. It responds by generating targeted antibodies and T-cells to suppress it. Should the immune system encounter a real Covid-19 infection in the future, it’s primed and ready to neutralize it.

Even if a person hadn’t been vaccinated, the immune system would respond to the virus, but the response would typically be slow and weak and, in many cases, incapable of overcoming the virus. The vaccine’s secret is that it stimulates the immune system before an infection occurs. That gives the body a powerful head start, enabling it to defeat the viral attack in virtually every case.

So, if a targeted virus mutates enough to render the vaccine less efficacious, the laboratory can quickly make a new mRNA strand from the mutated virus’s DNA.

mRNA vaccines have many advantages over conventional ones. As well as not containing any part of a real virus, they’re highly adaptable and relatively quick to develop and manufacture. More adaptable means, among other things, that the scientists can tweak the manufacturing process relatively easily and quickly, unlike conventional vaccine platforms.

So, if a targeted virus mutates enough to render the vaccine less efficacious, the laboratory can quickly make a new mRNA strand from the mutated virus’s DNA. That adaptability also means that the same technology can be used to make vaccines for many types of infections. Scientists are even working on producing a single vaccine that targets all influenza strains simultaneously.

Some people have likened it to a garden spray gun. The same spray gun can be used to apply many different products — pesticides, fungicides, insecticides, etc. In the mRNA analogy, the most complex part was making the first spray gun. Once made, it’s ready to spray whatever product the gardener loads it with.

This flexibility is important for a number of reasons. For example, a future viral pandemic could be much more lethal than Covid-19, but science now has a proven technology that could produce a vaccine against such a pathogen, possibly in a matter of weeks.

Scientists have been experimenting with this kind of technology for decades. One of the most notable among them is Katalin Karikó, a Hungarian scientist now working with the German biotech company BioNTech, one of the companies that developed and brought to market an approved mRNA-based Covid-19 vaccine.

For decades, she worked on developing this technology at the University of Pennsylvania. Collaborating with Drew Weissman, professor of medicine at the university, she carried out early-stage clinical trials for a number of diseases, including rabies, Zika, and cytomegalovirus (CMV).

They encountered many problems initially, including limited immune response, inadvertent inflammation, and mRNA instability. They addressed all these problems in different ways.

For example, the instability issue was solved by enclosing the delicate mRNA strand in a lipid nanoparticle — a tiny fatty outer layer that protects the mRNA long enough after injection for it to deliver its message to the cell. The fatty enclosure is temperature-sensitive, however, which is why mRNA vaccines must be stored in freezers until they’re ready to be used.

So, the current mRNA vaccines for Covid-19 were not really created in about a year, after all. Decades of basic science research have been put into it.

For example, by using mRNA made from the DNA of a cancer patient’s tumor, doctors can make a unique vaccine specific to that patient’s cancer.

Apart from mRNA technology’s use in combatting viral infections, scientists are working on using it to fight many other diseases, including cancers. The European Mutanome Engineered RNA Immuno-Therapy project (MERIT), in which BioNTech is participating, is carrying out clinical trials on cancer patients using this technology.

Many scientists working in this field see great promise in personalized immunotherapy for treating cancers. As cancers are highly diverse and complicated disorders that behave differently in each case, scientists always strive for more effective personalized treatments. For example, by using mRNA made from the DNA of a cancer patient’s tumor, doctors can make a unique vaccine specific to that patient’s cancer.

Other scientists are working on mRNA therapies to combat other conditions, including cystic fibrosis, Duchenne muscular dystrophy, osteoarthritis, Alzheimer’s and Parkinson’s diseases, and autoimmune diseases.

Moderna, a U.S. company that developed a successful mRNA Covid-19 vaccine, is experimenting with using the technology to repair damaged coronary blood vessels. Their phase I clinical trial showed that mRNA technology successfully stimulated the vascular endothelial growth factor (VEGF), a protein that promotes blood vessel growth.

A terrible pandemic has caused widespread illness, suffering, and many deaths worldwide. Yet, it also prompted major advances in mRNA technology. Scientists expect those advances to be pivotal in the fight against a huge number of diseases in the future. The glory of science is that it’s constantly moving forward, even during a crisis.

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