Scientists have been experimenting with mRNA since the 1990s. Their theory was that it would instruct cells to make proteins used by viruses, triggering an immune response that could then fight off the actual virus. This new technology is also used to target rare genetic disorders and cancer.
Since Edward Jenner created the world’s first vaccine in 1796 against smallpox, virtually all vaccines have been developed using actual bits of viruses to trigger our immune systems. That could change, thanks to mRNA technology. mRNA, or messenger RNA, already exists in our bodies and carries a “message” that directs cells to produce proteins. mRNA vaccines deliver this same message to the cells, and they make the proteins that would be made if the real virus invaded the body. This triggers the immune system to respond by producing antibodies, which can fight any future infection from that particular strain of virus. The mRNA technology also works as an anti-tumor therapy by instructing a patient’s cancerous cells to produce unique pieces of protein not found in healthy tissue. That prompts the immune system to find and attack the tumor cells. This approach has shown promise in melanoma and other skin cancers, as well as in leukemia and other blood and solid cancers. Because mRNA vaccines require less time to develop than conventional vaccines, they can be produced more quickly. Scientists are working on mRNA vaccines for peanut allergies and heart failure by targeting the liver genes with excessive cholesterol and reducing conditions such as fibrosis in the kidneys, lungs, and liver.
A COVID-19 vaccine developed at unprecedented speed using mRNA has already saved lives, but the technology’s impact will extend far beyond that one disease. mRNA’s ability to rapidly trigger cells to produce a specific protein will also allow it to be used in other vaccines to treat conditions like cancer, immune-mediated diseases, and rare disorders caused by insufficient proteins. Despite years of promising lab experiments, mRNA’s promise was largely overlooked until 2021, when it became clear the global need for a vaccine during the coronavirus pandemic would force researchers to accelerate the process. The resulting vaccines produced by Moderna and Pfizer-BioNTech are now being tested on patients in clinical trials.
mRNA, or messenger RNA, already exists in our cells and carries the instructions that direct our cells to make proteins. But to make a vaccine, scientists must first package mRNA into a delivery vehicle that allows it to enter cells without rejection. This enables mRNA to teach our immune cells to produce antibodies against specific diseases. When the COVID-19 pandemic began, researchers rushed to develop mRNA vaccines to fight it. These experimental vaccines use mRNA to tell our cells to make copies of the spike protein on the surface of the coronavirus. This prompts our immune system to recognize the spike protein as a foreign pathogen and dispatch defenders to destroy it. Other mRNA-based vaccines are in clinical trials to treat cancer, including head and neck, melanoma, and lung cancer. For these, mRNA is delivered to a patient’s dendritic cells, which then present the mRNA to our immune systems. Our immune systems then create antibodies against the mRNA, which help attack the cancer cells and keep them from growing.
Over the past 30 years, scientists have been learning how to make stable mRNA that could be delivered into the body, where it would instruct cells to build proteins that mimicked viral molecules. When these mRNA-based vaccines come into contact with actual viruses or tumor cells, the immune system creates antibodies that recognize them as foreign and destroy them. This technology has given rise to two mRNA-based vaccines against COVID-19 that are now available: the Pfizer-BioNTech vaccine and Moderna’s. Both work by injecting mRNA that tells the body’s cells to make copies of the virus’s spike protein. When these proteins are present in intact viruses or cancer cells, the immune system creates antibodies to attack and destroy them. Researchers also use mRNA vaccines to target specific tumor cells by delivering collections of neoantigens—the abnormal molecular features that distinguish cancer from healthy tissue. These mRNA-based cancer vaccines are now in clinical trials, with promising early results. The success of mRNA vaccines against COVID-19 opens the door to exploring the use of mRNA in vaccines against other diseases, such as multiple sclerosis and cancer.
People with rare diseases often face medical misdiagnosis, treatment delays and a lack of research. We’re working to change that. A towering figure in drug-delivery technology, Langer’s office walls are covered with 250 major awards – including the Charles Stark Draper Prize, considered the equivalent of the Nobel Prize for engineers. But when he heard Rossi talk about using mRNA to cloak cells and slip into them to produce proteins, he knew he’d stumbled upon something much bigger than a better way to create stem cells. Every strand of mRNA is made up of four molecular building blocks called nucleosides. Kariko and Weissman realized that one of those nucleosides was acting like a misaligned wheel, alerting the body’s immune system to war. They swapped it out for a different nucleoside, creating a hybrid form of mRNA that could sneak into cells without alarming the body’s defenses. mRNA vaccines are being developed to fight rabies, influenza and Ebola; the technology is also being tested in cancer treatments. Unlike traditional vaccines, mRNA doesn’t force the body to produce viruses’ proteins, making it simpler and cheaper.