Of all the vaccine candidates to prevent covid-19, those developed by Pfizer / BioNTech and Moderna are the ones that (for now) are winning the race.
What characterizes both vaccines is that they are messenger RNA vaccines. This technique is not new to scientists, but it is the first time it has been used in humans on a large scale.
Traditional vaccines consist of inoculating the person with an attenuated pathogen (capable of infecting and multiplying, but not causing disease), an inactivated pathogen (that cannot infect), or virus proteins to stimulate the immune system. The goal is the same: to develop an immune response that protects against future infections.
Messenger RNA vaccines differ from the previous ones in that no pathogen or fragments thereof are inoculated. Instead, scientists create synthetic messenger RNA in the laboratory, which contains a copy of part of the viral genetic code. This messenger RNA will be introduced into our cells and will allow the cellular machinery to manufacture the viral protein directly, which will be presented in the cell membrane and will stimulate the immune system.
Being a relatively new vaccine, it is normal that doubts arise. Especially in social networks, where the content that is shared is not always verified.
One of the most widespread rumors says that RNA vaccines can modify our genome and cause unknown and irreparable damage. However, the truth is that it is not possible that this type of vaccine can alter our DNA. The reasons are not few.
1. Natural infection does the same
The first thing to keep in mind is that each time the virus naturally infects a cell, millions of messenger RNAs are produced. However, this does not pose any risk to our DNA.
2. Messenger RNA disappears very easily
The RNA molecule is very fragile – so much so that these vaccines have to be kept at very low temperatures – and the time it remains in cells is very short (hours).
Therefore, this RNA is not going to stay inside the cell long enough to be able to do more than make the virus protein and disappear.
3. RNA never meets DNA
Imagine that this messenger RNA can magically stay inside cells for an indeterminate time. The next step to be able to alter our DNA would be to be able to interact with it and this does not happen. Why? Well, simply because there is a physical separation between them: the DNA is in the nucleus of the cell and the RNA would be in the cytoplasm.
It is true that there are certain RNAs that can travel to the nucleus, such as those of the influenza virus, but for this they should contain certain genetic information that would allow the participation of very specific proteins, something that has nothing to do with the RNAs used in these types of vaccines.
4. Messenger RNA cannot integrate into DNA
Let’s imagine that this RNA is able to travel to the nucleus and come face to face with our genome. Nothing would happen either, because the messenger RNA sequence used in the vaccine cannot be integrated into the genome. For this, the RNA would have to be converted into DNA, which is only possible by means of a special enzyme called reverse transcriptase.
This enzyme is mainly found in retroviruses such as human acquired immunodeficiency virus or HIV, retrotransposons (self-replicating stretches of our genome) or telomerases (enzymes that replicate DNA at the ends of our chromosomes). Here you can find a fairly detailed explanation of how they work and the differences between them, but the most important message is that these enzymes are very specific and require very special conditions to function.
At this point I would like to dwell a bit on the presence of retrotransposons in the human genome because it is something that is often used as an argument against these types of vaccines.
Retrotransposons are a type of mobile genetic sequence found in the genome of many eukaryotic organisms and can copy themselves and stick to other parts of the genome. There is a wide diversity of mobile genetic elements or transposons (formerly known as “jumping genes” for their ability to jump in the genome).
As I said, these “jumping genes” are very abundant. In fact, about 42% of the human genome is made up of retrotransposons. These mobile elements have accompanied living organisms during their evolution and their contribution to the genetic changes that have taken place has been decisive.
What characterizes retrotransposons and differentiates them from other transposons is their transposition strategy (the way they jump). To do this, before integrating into another site in the genome, they first become RNA and then are transformed back into DNA using the aforementioned reverse transcriptase.
Knowing this, one might think that there is a possibility that the RNA of the vaccine was converted into DNA using the tools available to genetic elements such as retrotransposons or even endogenous retroviruses (yes, we also have retrovirus sequences in our genome. In fact , up to 5-8% of the human genome is comprised of endogenous retroviruses ). However, this is not possible because a primer and specific sequences are required for reverse transcription to take place that are not found in the RNA of the vaccine.
In short, any RNA that is found with a reverse transcriptase is not going to become DNA. Therefore, if the RNA from the vaccine were to meet our genome, it would not be able to integrate.
6. If the RNA from the vaccine could be inserted into the genome, the cell would not last long.
Imagine that the messenger RNA from the vaccine was finally able to become DNA, travel to the nucleus, and integrate with the genome. What would most likely happen is that we would have a cell that would begin to produce the SARS-CoV-2 protein used as an antigen so it would be recognized by the immune system and destroyed immediately.
7. If it could be done it would be a great discovery
If we really found out how to modify our genome simply by injecting messenger RNA sequences it would be a breakthrough in the field of gene therapy.
In summary, there is no scientific evidence based on what we know about molecular biology that the messenger RNA used in vaccines against COVID-19 may have the ability to alter our genome. The problem comes when incomplete or simply not true information is used and shared.
Jose M Jimenez Guardeño, Researcher in the Department of Infectious Diseases, King’s College London and Ana María Ortega-Prieto, Postdoctoral research associate, King’s College London
This article was originally published on The Conversation. Read the original.
