DNA and mRNA vaccines
Updated onMartina Feichter studied biology with an elective subject pharmacy in Innsbruck and also immersed herself in the world of medicinal plants. From there it was not far to other medical topics that still captivate her to this day. She trained as a journalist at the Axel Springer Academy in Hamburg and has been working for since 2007 - first as an editor and since 2012 as a freelance writer.
More about the experts All content is checked by medical journalists.
DNA and mRNA vaccines represent a new generation of vaccines. They work in a completely different way than the well-known live and dead vaccines. Find out what that looks like and what advantages and potential risks DNA and mRNA vaccines bring with them here!
What are mRNA and DNA vaccines?
The so-called mRNA vaccines (short: RNA vaccines) and DNA vaccines belong to the new class of gene-based vaccines. Intensive research and testing has been carried out on them for several years. In the wake of the corona pandemic, mRNA vaccines were approved for the immunization of humans for the first time. Their principle of action differs from that of previous active ingredients.
Classic live and dead vaccines bring weakened or killed or inactivated pathogens or parts of them into the body.The immune system reacts by forming specific antibodies against these foreign substances, which are known as antigens. The vaccinated person then develops an immunity to the pathogen in question.
The new gene-based vaccines (DNA and mRNA vaccines) are different: They only smuggle the genetic blueprint for pathogen antigens into human cells. The cells then use these instructions to assemble the antigens themselves, which then trigger a specific immune response. In short: With gene-based vaccines, part of the complex vaccine production - the extraction of the antigens - is shifted from the laboratory to the human cells.
In addition to DNA and mRNA vaccines, the gene-based vaccines also include the so-called vector vaccines.
What are DNA and mRNA?
The abbreviation DNA stands for deoxyribonucleic acid. It is the carrier of genetic information in most organisms, including humans. The DNA is a double-stranded chain of four building blocks (called bases) arranged in pairs - similar to a rope ladder. The arrangement of the base pairs is a code for the blueprint, on the basis of which thousands of proteins are produced. They are the basis for the structure and function of the entire body.
In order to produce a certain protein, the cell first uses certain enzymes (polymerases) to create a "copy" of the DNA segment with the corresponding assembly instructions (gene) in the form of single-stranded mRNA (messenger ribonucleic acid). This process is called transcription. The mRNA leaves the nucleus and is read in the cell plasma (cytoplasm). The protein in question is assembled on the basis of these assembly instructions. This "translation" of a genetic blueprint into a protein is called translation.
How do DNA and mRNA vaccines work?
DNA vaccines contain the DNA blueprint (gene) for an antigen in a pathogen. In the case of mRNA vaccines, this antigen blueprint is already available in the form of mRNA. And this is how immunization using a DNA or mRNA vaccine works:
mRNA vaccine
The mRNA can be present "naked" in the vaccine. However, the unpackaged mRNA is very sensitive and fragile. The body also breaks them down quickly, especially if the vaccine is injected into the muscle. Therefore, the mRNA is at least stabilized, for example by special protein molecules.
Usually, however, the mRNA blueprint for a pathogen antigen is in a package. On the one hand, this protects the fragile mRNA and, on the other hand, it facilitates the absorption of the foreign genetic material into a body cell. The packaging can, for example, consist of lipid nanoparticles, or LNP for short (lipids = fats). Sometimes the foreign mRNA is also packaged in liposomes. These are small vesicles with an aqueous phase inside, which is surrounded by a lipid bilayer. This shell chemically resembles a cell membrane.
After the foreign mRNA has been taken up in a cell, it is "read" directly in the cytoplasm. The cell then produces the corresponding pathogen protein (antigen) and then presents this on its own cell surface. The immune system then recognizes the foreign structure and initiates the immune response. Among other things, the body now produces appropriate antibodies. This enables the body to react quickly to the pathogen itself in the event of a "real" infection. The vaccinated messenger RNA, in turn, is broken down again relatively quickly.
DNA vaccine
The DNA blueprint of a pathogen antigen is usually first built into a plasmid that cannot multiply. A plasmid is a small, circular DNA molecule that is typically found in bacteria.
The plasmid penetrates the body cells together with the antigen blueprint. With some DNA vaccines, this is supported by electroporation: At the puncture site, brief electrical pulses are used to briefly increase the permeability of the cell membranes, so that larger molecules such as foreign DNA can pass through more easily.
The DNA-antigen blueprint is then transcribed into mRNA in the cell nucleus. This leaves the nucleus and is translated into the corresponding antigen in the cytoplasm. Often it is a surface protein of the pathogen. It is then built into the shell of the cell. This foreign protein on the cell surface ultimately calls the immune system on the scene. It sets off a specific defense reaction. If the vaccinated person then becomes infected with the actual pathogen, the body can fight it faster.
Do vaccines save risks?
The main concern of some people is that mRNA and DNA vaccines could damage or alter the human genome. But so far there has been no evidence of this. There is also no evidence that the vaccinations can cause diseases such as cancer.
Can mRNA vaccines change the human genome?
It is almost impossible that mRNA vaccines could damage or change the human genome. There are several reasons for this:
>> mRNA does not get into the cell nucleus: On the one hand, the foreign mRNA that has been smuggled into cells and the human DNA reside in different places - the mRNA remains in the cell plasma, while the human DNA lies in the cell nucleus. This is separated from the cell by a membrane. It is true that there are nuclear pores through which mRNA from the cell nucleus enters the cell plasma. However, this is a complex process that only runs in one direction. There is no way back.
>> mRNA cannot be integrated into DNA: On the other hand, mRNA and DNA have different chemical structures. Therefore, an mRNA cannot be incorporated into the human genome at all. To do this, it would first have to be rewritten in DNA. This step requires special enzymes that have long been known from certain viruses (retroviruses), but also occur in human cells, as has been known for some time. So would it be conceivable that mRNA administered as a vaccine could be converted into DNA and then incorporated into the human genome?
Let us first consider the enzymes of retroviruses: These types of viruses (which also include the AIDS pathogen HIV) have the enzymes reverse transcriptase and integrase. With their help, the viruses can transcribe their RNA genome into DNA and then integrate it into the DNA genome of an infected human cell.
Theoretically, the following would be conceivable: If a person who is infected with such an RNA virus (e.g. HIV) happens to have vaccine mRNA and the virus in a body cell, the viral enzymes among the many human mRNA pieces that present in a cell at any time, of all things "fish out" the mRNA introduced as a vaccine and transcribe it into DNA.
In order for this to occur, which is very unlikely anyway, another factor would be necessary: The transcription of mRNA into DNA requires a genetic start sequence (called "primer"), which the RNA viruses themselves bring with them. However, this primer is designed in such a way that only the virus's own RNA genome is transcribed into DNA - and not any other mRNA that is present in the cell. And mRNA vaccines themselves do not contain a "primer".
It is therefore practically impossible that a vaccine mRNA is transcribed into DNA in this way and then incorporated into the human genome.
The same conclusion can be reached if one looks at human enzymes that can transcribe RNA into DNA: As mentioned at the beginning, the cell can use polymerase enzymes to translate DNA into mRNA, which then serves as a template for protein synthesis in the cell plasma. However, polymerases have other tasks as well: Before cell division, they duplicate the human DNA genome so that each daughter cell that is created then receives a complete set of genetic information. Polymerases can also repair DNA damage.
For a long time it was thought that polymerases could only rewrite DNA into mRNA and DNA into DNA. It is now known, however, that some polymerases can also transcribe RNA into DNA (such as the reverse transcriptase of retroviruses). Above all, the so-called polymerase theta has this ability. This enzyme's job is to repair DNA damage. If, for example, a piece is missing in one of the two strands of a DNA segment, polymerase theta can reassemble the missing piece using the complementary second single strand of DNA (i.e. DNA-DNA translation).
As has recently been found out, this enzyme can also use RNA as a template and translate it into DNA - even more efficiently and with fewer errors than it can copy DNA. The polymerase theta may even prefer to use mRNA transcripts as a template to repair DNA damage.
So could the enzyme also transcribe the mRNA administered as a vaccine into DNA? From the point of view of experts, this is unlikely, and for the same reason why the virus enzyme reverse transcriptase is not able to do this - the necessary genetic start sequence ("primer") is missing.
Can DNA vaccines change the human genome?
The situation is somewhat different with so-called DNA vaccines. The structure corresponds to that of human DNA. However, experts consider it extremely unlikely that they could actually be accidentally incorporated into the human genome: Years of experiments and experience with DNA vaccines that have already been approved in veterinary medicine have provided no evidence of this.
Can mRNA and DNA vaccines cause autoimmune diseases?
The danger here does not seem to be any higher than with the classic live and dead vaccines. Any form of vaccination has an activating effect on the immune system. In very rare cases, this can actually lead to an autoimmune reaction. After the swine flu vaccination, around 1,600 people later developed narcolepsy. In view of the many millions of inoculated doses of the vaccine, the risk seems negligible. In addition, viral diseases can themselves lead to an autoimmune disease.
Can mRNA and DNA vaccines damage the germ line?
No. According to the current state of knowledge, the active ingredients of the vaccination do not reach egg cells and sperm.
The benefits of DNA and mRNA vaccines
The fact that the pharmaceutical industry has invested a lot of work and money in the development of DNA and mRNA vaccines for years is due, among other things, to the fact that they can be produced more cheaply and, above all, much faster than conventional live and dead vaccines. For the latter, it is first necessary to cultivate pathogens in a laborious manner and in large quantities, and then to obtain their antigens.
In the case of gene-based vaccines such as DNA and mRNA vaccines, the body of the person vaccinated takes on the task of producing the antigen itself. The genetic antigen blueprints administered as a vaccination can be produced in sufficient quantities relatively quickly and easily and - if the pathogen is genetically modified (mutated) - quickly adapted.
Another advantage is that the transferred foreign genetic material does not remain in the body permanently. It is broken down by the body or disappears when the cells break down naturally. The foreign antigens are therefore only produced for a short time. However, this period of time is sufficient for an immune response.
If you compare DNA and mRNA vaccines with one another, the latter have several advantages: Accidental incorporation into the human genome is even less likely than with DNA vaccines. In addition, DNA vaccines usually have to be supplemented with potent enhancers (adjuvants) so that they trigger an effective immune response.
DNA and mRNA Vaccines: Current Research
Scientists have been researching the development of DNA and mRNA vaccines for several years or even decades. As part of the coronavirus pandemic, the responsible authorities - in the EU this is the European Medicines Agency EMA - finally approved mRNA vaccines for use on humans for the first time.
In addition to the vaccines already available from BioNTech / Pfizer and Moderna, other mRNA-based vaccines are also being tested. Some projects again focus on a DNA vaccine against corona.
But not only DNA and mRNA vaccines are on the list of potential vaccine candidates against Sars-CoV-2. Scientists and pharmaceutical companies are also working on vector vaccines, as well as conventional live and dead vaccines. You can also find out everything you need to know in our article "Coronavirus Vaccination".
In addition, pharmaceutical companies are currently working on DNA vaccines against around 20 different diseases, including flu, AIDS, hepatitis B, hepatitis C and cervical cancer (usually caused by infection with HPV viruses). This also includes therapeutic vaccine candidates, i.e. those that can already be administered to sick people (e.g. cancer patients).
Various mRNA vaccines, for example against flu, rabies and the Zika virus, are also being worked on intensively.
Tags: news drugs skin
