Recent developments of mRNA vaccines to protect people from SARS-COV-2 are making headlines. The first two successful mRNA vaccines, the immunization jointly developed by Pfizer and BioNTech and a second vaccine developed by Moderna, are turning mRNA vaccines into a household topic. For many scientists, this is not only great news for public health but also a proof-of-concept that mRNA vaccines can work! Today, I'll share with you some significant scientific discoveries and principles that make mRNA vaccines possible.
What is mRNA?
mRNA is the abbreviation of Messenger RiboNucleic Acid. As the name suggests, it is responsible for relaying messages encoded in DNA molecules to protein production in cells.
The synthesis of mRNA, a process called transcription, is carried out by RNA polymerase. tRNA molecules help to bring in the bricks needed for protein synthesis. For mRNA vaccine production, mRNA synthesis starts with a DNA template, and the mRNA molecules are synthesized using a phage RNA polymerase.
How do mRNA vaccines work?
COVID mRNA vaccines function by delivering the mRNA that encodes spike proteins. Spike proteins are a protein on the surface of the SARS-COV-2 virus, and it plays an essential role in facilitating viruses to enter the cell. By delivering mRNA molecules that encode this protein into human bodies, cells inside the human body will synthesize this spike protein and prime the immune system accordingly. A diagram from Bloomberg news summarizes this well.
How is mRNA delivered?
Most of the mRNA vaccines encapsulate mRNA molecules in lipid nanoparticles. Other delivery methods in RNA therapeutics include using polymeric nanoparticles comprising of RNA and cationic polymer. For small interfering RNA (siRNA), conjugating RNA to N-acetylgalactosamine, which targets receptors on hepatocytes for uptake, is also an option.
What are the difficulties for mRNA vaccine development?
The hurdles for developing an effective mRNA vaccine can be divided into two parts: (1) mRNA cannot enter the cell intact, and (2) it cannot be translated into protein efficiently.
What are the scientific discoveries that help to overcome these problems?
Most of the work falls into two categories: (1) direct mRNA modifications and (2) optimization of delivery particles.
What are the differences between the Pfizer and Moderna vaccines?
Both vaccines use lipid nanoparticles to deliver mRNA that encodes SARS-COV-2's spike proteins. However, because specific formulations are secret, the exact differences are unknown. Yet, it is speculated the differences in the lipid components are the reason why Pfizer's vaccine needs to be preserved at an ultra-cold temperature. In contrast, Moderna's vaccine can be shipped in a regular freezer. The difference in lipid composition may also explain why the Pfizer vaccine results in fewer side effects.
What else to look for?
Moderna's mRNA vaccines against other infectious diseases, such as its Zika vaccine currently in clinical trials, are worth watching. It posted encouraging Phase I clinical trial data and may come to the market sometime in the future.
Other applications of mRNA vaccine technology include immunizations for cancer, such as a cancer vaccine jointly developed by Moderna and Merck that targets common mutations in KRAS, an oncogene that is often mutated in cancer patients.