News & Events

Most people are aware of the quick rollout of the COVID-19 vaccines. Developed, tested for safety, and deployed in record time, the first round of COVID-19 vaccines partially owe their speedy development to the use of a molecule called “messenger RNA,” or mRNA for short. Scientists had been studying mRNA for its potential as a vaccine against coronaviruses since the SARS-1 pandemic that began in 2002. Likewise, we have seen progress related the use of mRNA for vaccines since the release of COVID-19 vaccines. For example, an mRNA vaccine that protects against respiratory syncytial virus (RSV) was licensed and approved for use earlier in 2024. While more mRNA vaccines are likely to be developed, vaccines are not the only potential use for mRNA. In this article, we describe the biology of mRNA, discuss the history of understanding and working with mRNA, and share updates on three exciting potential uses for mRNA technology beyond vaccines.
 

mRNA: The basics

mRNA is made from DNA, and it is produced in every cell of every living thing. Once generated, mRNA is used make proteins. Each piece of mRNA is like a “recipe” for a specific protein. Cells have machinery in the cytoplasm that reads these “recipes” to make the proteins needed to accomplish tasks in the cell and throughout the body. These tasks include processes like making hormones, repairing damage to the cell, and fighting off invading microbes. In order to control the quantities of protein in a cell, mRNA  is designed to limit how much of a particular protein is made from it before it breaks down and is disposed. As a result, mRNA does not have a long lifespan in the cell. Scientists have discovered how to use these characteristics of mRNA to our advantage, so that the limited amounts of a protein needed for protective or therapeutic purposes can be made by our cells based on the design of the mRNA that is delivered.
 

Using mRNA technology: A brief history 

Although mRNA technology recently came into global prominence, the history of scientific study of mRNA is long. Scientists have been working on understanding and using mRNA ever since its discovery more than 60 years ago. mRNA molecules were first generated in the lab in 1984. From there, mRNA produced in the lab was used to test its therapeutic potential in cell culture and later in animal models. Once proven safe in animals, clinical trials evaluated the use of mRNA-based therapies and preventions, such as for treating cancer or preventing infections through vaccination. Although none of the previous mRNA-based therapies were licensed for use in people, it was not for reasons of safety. Rather, in the case of cancer treatment therapies, low frequencies of the cancers being studied means it can take time to accumulate enough data to show whether the treatment is effective in a population. In the case of vaccines, the data did not demonstrate that the vaccines were effective in preventing disease, so larger trials were not pursued. 

Some scientists, like Dr. Katalin Karikó, have dedicated their lives to the study of mRNA and its potential uses in human health. Dr. Karikó’s work with immunologist Dr. Drew Weissman began when they met at a copy machine at the University of Pennsylvania in 1997. Theirs is a classic story of the importance of scientific collaboration. Dr. Karikó was an expert on mRNA, and Dr. Weissman was an immunologist.  As a result, their respective areas of expertise and their joint effort to understand the immune response to mRNA ultimately led to mRNA vaccine technology being used to combat the COVID-19 pandemic, earning them the 2023 Nobel Prize in Physiology and Medicine. 
 

Using mRNA technology: Vaccines and beyond

mRNA technology offers two key benefits that give it potential in a litany of applications. First, scientists can make mRNA molecules that serve as the recipe for any given protein that we might want cells to make, including proteins that an individual’s body may not make sufficient quantities of due to disease. Indeed, many diseases and other health problems can result from someone’s cells making the wrong proteins at the wrong times or failing to make important proteins effectively. By delivering the mRNA recipes for the proteins involved in a disease state, the individual’s cells can make the correct form of the protein, helping restore that person to health. 

Second, the mRNA for particular proteins can be developed relatively quickly and easily – like a series of recipes that all use the same ingredients. This makes mRNA technology an attractive tool with great potential for tackling a variety of health problems. Let’s take a closer look at three possible applications that scientists are researching now.

Exploring mRNA in the fight against cancer

One of the ongoing issues when treating cancer is that the drugs used in chemotherapy are indiscriminate in their attack, killing both healthy and cancerous cells. Newer strategies for fighting cancer, like CAR T-cells, overcome this indiscriminate killing, but they involve an intensive treatment regimen for patients and are prohibitively expensive.

mRNA technology offers the ability for treatments to be both targeted and economical. In addition to using mRNA technology to avoid the negative side effects of untargeted chemotherapy, researchers are also focusing on regulatory proteins that are missing from cancer cells in some cases, hoping to deliver mRNA that can reinstate these checks and balances that normally prevent cancer from developing. Scientists are also hopeful that mRNA technology will make it easier to personalize treatment to an individual patient’s unique cancer. 

Exploring mRNA in the fight against HIV

Treatment for HIV infection has evolved in the 40 years since the virus was discovered. We now have medications that can both suppress the virus and prevent it from spreading. Unfortunately, patients with HIV need to take these medications for the rest of their lives to stay healthy — a cumbersome and often expensive effort, especially in low-income countries. 

HIV has been particularly difficult because the virus “hides” inside a person’s white blood cells. However, because the infected cells are not producing the virus, they’re difficult to target with medication. HIV researchers see a lot of potential in mRNA technology because the mRNA is delivered in lipid nanoparticles that can, themselves, be designed to target a specific kind of cell, such as the white blood cells that HIV infects. Once the nanoparticles reach the correct cell type, they can deliver mRNA that will provoke the cells to produce the virus, causing them to come to the attention of other immune system cells, so the infected cells can be cleared from the body. 

Exploring mRNA in treatment for sickle cell disease

Sickle cell disease is an inheritable blood disorder that affects eight million people worldwide. Sickle cell disease occurs when hemoglobin, the protein that our red blood cells use to carry oxygen around the body, is made incorrectly due to an error in the gene for that protein. When the gene is passed from one generation to the next, the disease is also experienced by the next generation. Red blood cells with affected hemoglobin are crescent-shaped, making them easy to detect in a blood test. Because of their altered shape, red blood cells do not efficiently carry oxygen, causing affected individuals to experience fatigue, cold hands and feet, shortness of breath and dizziness, , among other symptoms. Currently, people with sickle cell disease require regular blood transfusions and costly medications. The disease can be cured by getting a bone marrow transplant, but this procedure is expensive and comes with risks. As a result, many people with sickle cell disease do not have the option for a transplant.

Sickle cell researchers hope that mRNA technology might provide an opportunity to cure this disease in a less expensive and less risky way. For example, mRNA technology may be able to help by delivering mRNA that enables affected individuals to make hemoglobin in its most biologically efficient shape. Early studies in animals and experimental cell lines have successfully demonstrated that  mRNA delivery can prompt the red blood cells to produce the correct hemoglobin protein. Other researchers have been working on using mRNA technology to improve the process of bone marrow transplantation. Right now, removing the old bone marrow that makes sickled red blood cells involves taking medications that cause severe side effects. By instead delivering mRNA that makes a protein that can help with clearing out the deficient bone marrow, patients would not need to take these medications before the healthy marrow is introduced, making the procedure easier and safer. 
 

mRNA: The hope of future therapies

Now that we know mRNA technology can be used safely and effectively, we have started to see a variety of ways that scientists are trying to apply it to improve existing options or create new ones for patients around the globe.  

mRNA technology isn’t a one-size-fits-all solution to human health and there will be many problems that the technology won’t be able to fix. But mRNA technology also shows us the promise and potential of science — just a decade ago, even mRNA experts couldn’t have predicted how powerful a tool it would become. Now, we can continue to refine our recipes and expand our cookbook as we tackle the challenges of today and prepare for the obstacles of tomorrow.
 

Acknowledgements

We would like to thank Dr. Ravi Amaravadi at the Abramson Cancer Center, Dr. Edward Kreider at the University of Pennsylvania Institute for RNA Innovation, and Dr. Stefano Rivella at the Children’s Hospital of Philadelphia for their helpful conversations during preparation of this article.

For more information about mRNA technology, check out the University of Pennsylvania Institute for RNA Innovation video and website.