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DNA and mRNA Vaccines: A Side-by-Side Comparison

Posted by The Protein Man on Nov 2, 2021 2:00:00 PM
The Protein Man

What’s the difference between DNA and mRNA vaccines and how do they work? Are they better than traditional vaccines? With all the exciting life-saving possibilities these modern technologies offer, it’s time to take a closer look.

No one can deny the fact that COVID-19 changed the way we live our lives, perhaps forever. However, if there’s one good thing that came out of this world-changing event, it would be the development of new technologies such as the mRNA and DNA vaccines at record pace.

DNA and mRNA Vaccines: A Side-by-Side Comparison

Unlike conventional vaccines that stimulate the immune system through the use of a weakened, damaged, or inactivated version of a pathogen (virus or bacteria), DNA and mRNA vaccines use genetic materials that code for the pathogen’s spike protein to trigger an immune response. Specifically, DNA vaccines use small DNA molecules (plasmids), while mRNA vaccines use the pathogen’s messenger RNA to do the job.

Despite the similarities, DNA and mRNA vaccines have several notable differences. Aside from the genetic material used in producing the actual vaccines, they also differ in terms of mode of action and administration as well as storage and transportation requirements.

Mode of action

DNA vaccines, such as the recently developed ZyCoV-D vaccine in India, make use of plasmids that carry the gene coding for the SARS-CoV-2 spike protein. Upon entering the human cell, the plasmid should successfully penetrate the cytoplasm and nuclear membrane before it can gain entry to the cell nucleus.

Once it is inside the nucleus, the genetic material carried by the plasmid is converted into messenger RNA (mRNA) which then travels back to the cytoplasm where it is converted into viral or bacterial protein. Because the immune system doesn’t recognize this particular protein, it raises a warning signal to stimulate the production of antibodies designed to fight the foreign material.

Since vaccination promotes the formation of memory immune cells, the immune system can launch the corresponding response and provide the necessary protection when a vaccinated person is exposed to these viruses or bacteria.

While DNA vaccines need to enter the nucleus and go all the way back to the cytoplasm to synthesize the necessary viral or bacterial proteins, mRNA vaccines require a shorter route. Basically, they just need to reach the cytoplasm, the component of the cell that contains the enzymes necessary for the synthesis of the bacterial or viral proteins.

As a result, mRNA vaccines produce a higher immune response, which may or may not be a good thing, depending on how you look at it. On one hand, it may provide a higher level of protection against infection but the resulting side effects may also limit their application.


DNA vaccines deliver the genetic code of the pathogen into the cell through a small electrical pulse using a specialized device while mRNA vaccines are administered via injection.

Storage and transportation requirements

DNA vaccines are significantly more temperature-stable compared to mRNA vaccines. Between the two, plasmid DNA vaccines are more stable and are easier to store and transport, while mRNA vaccines have stringent storage and transportation requirements, which significantly hamper the distribution process to poorer nations.

Advantages and Disadvantages

DNA and mRNA vaccines have numerous advantages over conventional vaccines.

  • They provide a stronger immune response. Since traditional vaccines use weakened or inactivated bacteria or viruses to stimulate an immune response, they produce a weaker response and may require several booster shots to maintain the level of protection they provide. On the contrary, DNA and mRNA vaccines produce a stronger immune response by activating all the components of the immune system.
  • They are more economical to produce. Compared to conventional vaccines, the production process is simpler, faster, and more straightforward. Rather than cultivating the actual viral proteins (which may take years to develop), the necessary DNA or RNA strands can be synthesized through a chemical process, making it easier to adapt as the need arise (e.g., in response to a new variant, an emerging disease, or a pandemic). Moreover, the manufacturing process is also considerably more cost-effective compared to that of traditional and recombinant subunit vaccines.

While these vaccines have great potentials in treating cancer and addressing other infectious diseases such as SARS-CoV-2, HIV, dengue, and malaria, they are not inherently risk-free. Though studies are promising, any new technology means are still a lot of unknowns regards the long-term safety and efficacy of these vaccines.

Topics: Molecular Biology

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