Health Secretary Robert F. Kennedy Jr. has repeatedly questioned the safety of mRNA vaccines against Covid-19. Funding scientists from the National Institutes of Health were advised to scrub grants for any reference to mRNA. Nationally, state legislatures are considering bills banning or restricting such vaccines, describing them as weapons of mass destruction.
mRNAs, or messenger RNAs, have gained widespread attention in recent years, but scientists first discovered them in 1961. They have studied it, prevented infections and have since investigated its promise in treating cancer and rare diseases.
What is mRNA?
mRNA, a large molecule found in all of our cells, is used to make all the proteins that our DNA tells us to build our bodies. This does so by transporting information from DNA in the nucleus to the cell's protein production machinery. Jeff Koller, a professor of RNA biology and therapy at Johns Hopkins University and co-founder of an RNA therapy company, can use a single mRNA molecule to make many copies of a protein, but is naturally programmed to die in the end.
How do mRNA vaccines work?
Currently, older adults have three FDA-approved vaccines that use mRNA and three FDA-approved vaccines that use mRNA. These vaccines are made up of strands of mRNA encoding specific viral proteins.
Suppose you get a Covid-19 vaccine. The mRNA chains packaged in small fat particles enter the muscles and immune cells, said Robert Alexander Wesselhoif, director of the RNA Therapy Institute at Mass General Brigham's Institute of Genetic and Cell Therapy. Intracellular protein factories receive instructions from mRNA to produce proteins like those found on the surface of Covid-19 viruses. Your body recognizes that protein as a foreign body and acquires an immune response.
Most of the mRNA disappears within a few days, but the body retains “memory” in the form of antibodies, Dr. Koller said. Like other types of vaccines, immunity will evolve over time into new variants.
Why are mRNA vaccines in use now?
In the mid-2000s, University of Pennsylvania scientists found a way to put foreign mRNA into human cells without first degradation. This allowed researchers to develop it for use in vaccines.
The main use of such vaccines today is to prevent infectious diseases like Covid-19 and RSV, according to Dr. Wesselhoeft, who founded a company that develops RNA therapy. mRNA vaccines can be created very quickly, as all components other than RNA sequences remain the same between different vaccines.
This feature could help develop an annual flu vaccine, said Florian Krammer, a virologist at Icahn School of Medicine in Sinai Mountain, who once consulted Pfizer and Curevac about mRNA therapy. Typically, scientists will determine in February or March which strains of influenza virus will be included in vaccines rolled out in the US in September. But by then another strain may prevail. Because mRNA vaccines can be manufactured more quickly than current shots of flu, scientists can wait until May or June to see which strains are circulating, increasing the likelihood that the vaccine will be effective, Dr. Krammer said.
Are these vaccines at risk?
A common question patients ask is whether mRNA vaccines can affect DNA, Dr. Boucher said. The answer is no. Our cells cannot convert mRNA into DNA. In other words, it cannot be integrated into the genome.
Covid-19 vaccines can cause muscle pain and thin symptoms, but these are generally expected to have side effects from the vaccine, Dr. Krammer said.
Dr. Adam Ratner, a New York pediatric infection expert, said it has been more than four years since the Covid-19 vaccine was first rolled out with “no long-term safety signals.” Many parents were worried about myocarditis, an inflammation of the myocardium, which was reported as a possible side effect of the vaccine. However, Dr. Ratner said the risk of such inflammation from actual Covid-19 infections, or the risk of long Covid or multi-system inflammatory syndromes in children, was much greater.
What else can mRNA be used for?
mRNA-based vaccines currently incorporate a wide range of diseases, including cancer, cardiovascular disease, autoimmune diseases such as type 1 diabetes, and rare diseases such as cystic fibrosis.
In cancer, the idea is that mRNA encodes tumor proteins that the immune system recognizes as foreign bodies, and instructs the body to attack the tumor. In genetic disorders like cystic fibrosis, it encodes a functional version of a missing protein, replacing the failed protein and restores mucus to a healthy state.
A Nature Journal paper earlier this year showed that experimental mRNA vaccines for pancreatic cancer caused immune responses in some patients after undergoing cancer surgery. Patients who experienced that immune response lived longer than those who did not.
Another recent paper showed that in monkeys, inhaled mRNA therapy may produce the proteins needed to form cilia. This is the pole structure that moves mucus alongside the airways. These proteins are dysfunction in debilitating respiratory disorders called primary cilia dyskinesia.
This research is still in its early stages. The Phase I trial, Pancreatic Cancer Study, only 16 patients included, and there could have been other differences between the two groups accounting for different survival times. Dr. Stephen Rosenberg, chief of the Surgery Division at the National Cancer Institute and cancer immunotherapy expert, has a long history of research showing that interventions can actually lead to immune responses without changing patient outcomes.
Dr. Richard Boucher, a pulmonary scientist at the University of North Carolina, Chapel Hill, noted that for lung disease, it is extremely difficult to make mRNA-carrying particles safe to the correct cells accurately.
In general, Dr. Ratner said mRNA vaccines are “exciting” and “stimulating” in that they provide hope for treatment of diseases where previous technologies have failed. However, mRNA therapy remains a drug technology similar to others. With some illnesses, he said, it is likely to work.
