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What's the Difference Between a DNA and RNA Vaccine?

two vaccine vials
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Key Takeaways

  • DNA and RNA vaccines have the same goal as traditional vaccines, but they work slightly differently.
  • Instead of injecting a weakened form of a virus or bacteria into the body as with a traditional vaccine, DNA and RNA vaccines use part of the virus’ own genetic code to stimulate an immune response.
  • Several potential DNA and RNA COVID-19 vaccines are in clinical trials, meaning they are an important and promising area of vaccine development.

Researchers around the world are working on developing a safe and effective vaccine for COVID-19, the disease caused by the novel coronavirus. There are currently several global vaccine clinical trials taking place, including four major trials in the United States. Some of these potential COVID-19 vaccines are RNA and DNA vaccines, which is an emerging area of vaccine development. 

What Are DNA and RNA Vaccines?

Traditional vaccines, which expose the body to proteins made by a virus or bacteria, are often made by using weakened or inactive versions of that virus or bacteria. That’s how popular vaccines, like the measles, mumps, and rubella (MMR) vaccine and pneumococcal vaccine, work.

When you get the MMR vaccine, for example, your body is introduced to weakened forms of the measles, mumps and rubella viruses that do not cause disease. This triggers an immune response and causes your body to make antibodies like it would with a natural infection. These antibodies help recognize and fight the virus should you be exposed to it later on, helping prevent you from getting sick. 

A DNA or RNA vaccine has the same goal as traditional vaccines, but they work slightly differently. Instead of injecting a weakened form of a virus or bacteria into the body, DNA and RNA vaccines use part of the virus’ own genes to stimulate an immune response. In other words, they carry the genetic instructions for the host’s cells to make antigens.

“Both DNA and RNA vaccines deliver the message to the cell to create the desired protein so the immune system creates a response against this protein,” Angelica Cifuentes-Kottkamp, MD, an infectious diseases doctor at NYU Langone’s Vaccine Center, tells Verywell. “[Then the body] is ready to fight it once it sees it again.”

Research published last year in medical journal Frontiers in Immunology reports that “preclinical and clinical trials have shown that mRNA vaccines provide a safe and long-lasting immune response in animal models and humans.”

If an RNA or DNA COVID-19 vaccine makes it through clinical trials and is approved for use, it will be the first of its kind. 

“So far, there’s been no mass production of vaccines based on DNA or RNA,” Maria Gennaro, MD, a professor of medicine at the Rutgers New Jersey Medical School, tells Verywell. “So this is kind of new.” 

The Difference Between DNA and RNA Vaccines

DNA and RNA vaccines work the same way as each other, but have some differences. With a DNA vaccine, the virus’ genetic information “is transmitted to another molecule that is called the messenger RNA (mRNA),” Gennaro says. This means with an RNA or mRNA vaccine, you’re one step ahead of a DNA vaccine. 

COVID-19 vaccines in development by Moderna and Pfizer are mRNA vaccines.

“The mRNA goes into the cell, and the cell translates it into proteins…which are the ones that the organism sees and induces the immune response,” Gennaro says. 

Another difference between a DNA and RNA vaccine is that a DNA vaccine delivers the message via a small electrical pulse, which “literally pushes the message into the cell,” Cifuentes-Kottkamp says.

“The advantage is that this vaccine is very stable at higher temperatures. The disadvantage is that it requires a special device that provides the electrical pulse,” she says. 

Based on research so far, Cifuentes-Kottkamp says that it looks like both DNA and RNA vaccines induce similar immune responses. “But since both are under clinical trials, we still have a lot to learn from them,” she adds. 

Pros and Cons of DNA and RNA Vaccines

DNA and RNA vaccines are being touted for their cost effectiveness and ability to be developed more quickly than traditional, protein vaccines. Traditional vaccines often rely on actual viruses or viral proteins grown in eggs or cells, and can take years and years to develop. DNA and RNA vaccines, on the other hand, can theoretically be made more readily available because they rely on genetic code–not a live virus or bacteria. This also makes them cheaper to produce. 

“The advantage over protein vaccines—in principle, not necessarily in practice—is that if you know what protein you want to end up expressing in the body, it’s very easy to synthesize a messenger RNA and then inject it into people,” Gennaro says. “Proteins are a little more finicky as molecules, whereas the nucleic acid [DNA and RNA] is a much simpler structure.”

But with any health advancement comes potential risk. Gennaro says that with a DNA vaccine, there is always a risk it can cause a permanent change to the cell’s natural DNA sequence. 

“Usually, there are ways in which DNA vaccines are made that try to minimize this risk, but it’s a potential risk,” she says. “Instead, if you inject mRNA, it cannot get integrated into the genetic material of a cell. It is also ready to be translated into protein.”

Because no DNA or RNA vaccine is currently approved for human use, there is still much to learn about their effectiveness. Still, some of the genetic-based vaccines that are currently in clinical trials to protect against COVID-19 look promising, Gennaro says. The hope is that one will be approved for market use as soon as it’s shown to be safe and effective. 

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