(Image via @NobelPrize / X)

Volunteer Writer: Ryan Cadorette

Email: rcadorette@umassd.edu

Each year on December 10th, individuals from the science and research world assemble in Stockholm, Sweden, to celebrate scientific breakthroughs in the memory of Alfred Nobel. This year is no different, as some of the most impactful Nobel Prizes were awarded to notable individuals who made discoveries that have progressed humanity. 

The most notable Nobel Prize awarded is to Dr. Katalin Karikó and Dr. Drew Weissman of the University of Pennsylvania for their discovery of a method for safe mRNA modification, which gave rise to mRNA Vaccines during the COVID-19 pandemic. 

While mRNA synthesis has been used since the 1980s, the obstacle seen with synthesized mRNA is that human bodies can detect its injection. 

Immune systems have an innate detection system called Toll-Like Receptors (TLRs). These receptors will look for anything foreign, or not-self, in the body. They can recognize molecular patterns, like those found on the surface of bacteria, as well as DNA and/or mRNA. 

TLRs must be able to recognize molecular patterns because viruses inject their mRNA or DNA into cells to replicate and produce more viruses. 

They do this by hijacking the cell’s machinery for mRNA translation. Under normal conditions, cells make proteins by transcribing the DNA in the nucleus to mRNA. The mRNA then moves out of the nucleus to find a ribosome, which can translate mRNA into proteins. Viruses hijack this pathway by translating viral mRNA to proteins instead of the cell’s own mRNA translation. 

This leads to the creation of new viruses, which then bud out of the infected cell and search for a new cell to infect. 

TLRs exist to stop this from happening, but they are activated by anything they view as “not self,” such as viral DNA/RNA. Activation of these TLRs can lead to inflammation, which is the production of immune system signaling molecules. 

Through their research, Karikó and Weissman discovered a method for modifying mRNA that does not activate human TLRs.

They have achieved this by adding small changes to specific nucleosides on the mRNA of interest. As a result, the immune system does not respond significantly to the synthesized mRNA, and no inflammation occurs. 

This method was not mature when it was discovered in 2005. More testing was required to identify other potential side effects their mRNA modifications could have on the body’s immune system. However, by the time the COVID-19 pandemic began, enough testing had been conducted to use modified mRNA in the fight against the virus. 

Compared to classic vaccines, an mRNA vaccine does not contain the virus that gets you sick. Like viruses, it hijacks the cell’s machinery to produce a protein of interest from mRNA, which the immune system can respond to. 

For the COVID-19 vaccine, the mRNA encoded for the S protein, a coat protein found on the virus’s surface. 

When injected with the vaccine, cells will take in the mRNA. The mRNA will then locate a ribosome, and translation begins. The resulting S protein constructed from the mRNA is then presented on the cell’s surface, where immune cells can see them and create antibodies for the S protein. 

This type of vaccine, although relatively new, has the potential to help vaccinate against many kinds of pathogens and diseases. It diverges from classic vaccines, which usually involve the pathogen of interest, whether it be a weakened but alive form, a dead or inactivated form of the pathogen, or a single part of the pathogen. 

Both Pfizer and the Moderna COVID-19 vaccines are mRNA vaccines, which helped immensely to ease the world from a pandemic to a more normal day-to-day life. 

Karikó and Weissman’s impact through their discovery goes beyond beating the COVID-19 pandemic. 

Their methods and the subsequent vaccines that have come out of their discovery can be used in the fight against other detrimental diseases and illnesses, such as HIV/AIDS, cancer, or other conditions. 

The mRNA vaccine is here to stay, and interest in the technology is growing thanks to its effect on the COVID-19 pandemic. 

The significance of the development of DNA/RNA vaccines cannot be understated, and it was enabled through the dedicated research of Katilin Karikó and Drew Weissman.