What You Need to Know About mRNA Vaccines

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The COVID-19 vaccines produced by Moderna and Pfizer are the first widely-implemented vaccines to utilize mRNA. Understandably, some people have some concerns and questions- What even is mRNA? Are these vaccines safe? Can they alter your DNA? – I’ll do my best to try and address some of those questions in this post.

What is mRNA?

To explain what mRNA is, we’re going to have to explain a process called protein synthesis.

Brief synopsis: proteins are molecules which are formed by stringing together smaller molecules called amino acids. This process of protein synthesis is completed by ribosomes within the cytoplasm of our cells. Proteins serve a variety of functions within our body, from structural components to enzymes (which facilitate different chemical reactions within or body). Pretty much every living organism is built in part and kept alive by proteins.

The human body consists of an estimated hundreds of thousands of different proteins- but these proteins have to come from somewhere. Something has to tell our bodies how to assemble the amino acids together.

That is part of the function of our DNA (deoxyribonucleic acid). I’m not going to go too much into the structure of DNA here, because it’s not hugely important for the subject at hand. In summary: DNA is another molecule, which is found within the nucleus of our cells. It consists of two strands of nucleotides (smaller molecules), which join together to form a double helix (sort of like if you took a ladder and twisted it).

One of the major functions of DNA is that it contains the instructions for building proteins. But there’s a problem- to build proteins, our ribosomes need the information found within our DNA, but the ribosomes are found outside the nucleus, while DNA is trapped inside the nucleus.

This is a simplified diagram of a human cell, featuring the components involved in protein synthesis. DNA (white) is found within the nucleus (dark brown). Proteins are assembled by the ribosomes (grey dots), which are found either attached to the endoplasmic reticulum (brown blobs) or freely floating in the cytoplasm (pink). mRNA (not shown) is a copy of a section of DNA which contains the instructions for building a single protein, and can move from the nucleus to the ribosomes within the cytoplasm.

That’s where mRNA comes in. RNA (ribonucleic acid) is similar to DNA, but consist of one nucleotide strand instead of 2 (which makes it less stable- that’s going to be important when we talk about the vaccines). There are different types of RNA, including mRNA (short for “messenger RNA”). The function of mRNA is to copy a small section of DNA in the nucleus (through a process called transcription). Because mRNA is much smaller than our DNA, it can leave the nucleus of the cell and travel to our ribosomes, which can read the information contained in mRNA and use it to build proteins (through a process called translation). [DNA and mRNA tell the ribosomes which amino acids to use to build the protein, and what order to put them in).

Here’s a more succinct summary:

  • DNA is trapped in the nucleus
  • A gene (section of DNA with the instructions for building a single protein) is copied (transcribed) into mRNA
  • mRNA leaves the nucleus and travels to a ribosome
  • The ribosome reads (translates) the mRNA to create the corresponding protein (by assembling specific amino acids together in a specific order)

I like to think of protein synthesis like building a LEGO set.

The goal is to build something (a LEGO set or protein) from individual pieces (LEGO blocks or amino acids). But you can’t just put the blocks together randomly- for it to work, they need to be assembled in a particular order and structure.

To do that, you need instructions. In the case of proteins, those instructions are found in our DNA (in the nucleus of our cells). In the case of LEGO sets, those instructions are found in LEGO’s databases. In either case, you can’t use the original copy- both because of its 1) physical location (DNA is in the nucleus, but protein synthesis occurs in the ribosomes found within our cytoplasm. In the case of LEGOs, you obviously cannot access the original file on LEGO’s servers from your home), and 2) as a safety precaution to keep the “originals” (DNA or files) safe from being damaged or corrupted.

When it comes to LEGO sets, you typically get a printed copy of the instructions telling you how to assemble the pieces together. Likewise, mRNA is a copy of a section of DNA explaining how to build a specific protein. This is often referred to as a gene. It is estimated that humans have roughly 30,000 genes.

How do mRNA Vaccines Work?

To understand how vaccines work, we need to understand how our immune system protects us from foreign microbes in the first place.

The Immune System

Our immune system consists of the organs and cells which help protect our body from pathogens (bacteria, fungi, viruses, etc.). There are three major components to the immune system:

  • Passive immune system: the passive immune system consists of physical barriers (such as skin) that help keep pathogens out of our body
  • Innate immune system: the innate immune system consists of mechanisms which are not specific to individual pathogens, such as fevers (which can be used to fight a variety of infections).
  • Adaptive immune system: when you think of “immunity,” this is what you’re thinking of. The adaptive immune system consists of a variety of cells which recognize, destroy, and remember specific pathogens.

The way the adaptive immune system works is complex, but here is a simplified/generalized summary of how it works:

  1. A microbe (virus, bacteria, etc.) enters the body and begins to reproduce.
  2. White blood cells ingest some of the microbes, then present proteins from the microbe on their cell surface (these foreign proteins are often referred to as antigens). Alternatively, the antigens may be released into the bloodstream.
  3. T cells recognize the antigen, which triggers a series of events resulting in the activation of B cells, which produce and secrete antibodies (highly specific protein which circulate in the blood and bind to antigens). Antibodies can function in many ways to help fight off a pathogen, including the neutralization of toxins, immobilizing microbes, etc.
  4. After activation, B cells clone themselves to produce other cells, including memory B cells, which are long-lived and facilitate a rapid response to the same microbe in the future.

Memory B cells (along with Memory T cells) are specific to individual pathogens. Once we have developed these cells, our immune system will have a stronger, faster response if exposed to the same pathogen in the future (which can help prevent us from getting sick).

Key takeaway: in order to develop immunity to a disease, you have to be exposed and develop an immune response to the pathogen that causes it.

Vaccines

Normally, developing immunity requires you to become infected with a pathogen, which takes time and carries the risk that you may not survive.

The concept behind vaccines is simple: instead of waiting to get infected to gain immunity, why not try and trigger an immune response by exposing the immune system to antigens associated with a pathogen? This could quickly activate the immune system without the risks associated from the actual disease.

Most “traditional” vaccines work by injecting antigens in the form of weakened pathogen, pathogen proteins, etc. into our bodies. Our immune system recognizes the contents of the vaccine as foreign, and mounts an immune response to the antigens. This allows us to develop immunity to a disease and produce antibodies without necessarily having to get sick with it. (By the way, there’s no scientific evidence that vaccines cause autism, but that’s a post for another day.)

Here’s a short video explaining how the immune system and vaccines work: (it mentions DNA vaccines, which are similar to mRNA vaccines, but aren’t exactly the same. The differences are beyond the scope of this post)

With mRNA vaccines, you aren’t injected with proteins, pathogen fragments, or weakened pathogens at all. Instead, you are injected with copies of mRNA from the pathogen. Eventually, these pieces of mRNA make their way to our ribosomes, which results in the production of proteins associated with that pathogen. Although our body built the proteins, our immune system can tell that they didn’t come from our DNA, recognizing them as antigens and triggering the immune response. Once the proteins are produced, the mRNA is broken down by normal cellular processes.

When we think about the COVID-19 vaccines, they are specifically designed to produce a “spike protein” normally found on the surface of the COVID-19 virus. This protein is harmless, but triggers an adaptive immune response, eventually granting immunity from COVID-19.

This Isn’t New Technology

The technology for mRNA vaccines has existed for decades– The first study using mRNA vaccines was published in 1990.

There are essentially two reasons an mRNA vaccine has not been previously approved by the FDA:

  • Efficacy: human trials of most previous mRNA vaccines have had “somewhat modest” results
  • Logistics: as I mentioned earlier, mRNA is not very stable. This poses problems for both storage and delivery of the vaccines (both of which have improved in recent years. The super cold storage requirements still pose logistical issues for distribution though.)

Advantages of mRNA Vaccines

There are quite a few advantages of mRNA vaccines, especially for a new virus like COVID-19. (Summarized in this paper.)

  • It is non-infectious; You can’t potentially get sick like you can from a weakened virus
  • mRNA is degraded by normal cellular processes after translation
  • They have the potential for rapid, inexpensive, and scalable manufacturing. (In summary, producing genetic material is much faster, easier, and cheaper than proteins, weakened virus, etc. It’s no accident that the first two COVID-19 vaccines were both mRNA vaccines; the process of developing and producing them is easier and faster than traditional vaccines.)

For anyone who is concerned about the safety of these vaccines- tens of thousands of people have received both the Pfizer and Moderna vaccines already. If they weren’t safe, they would not have received emergency use authorization (but that’s a topic for another post). It is worth noting that trials on children and pregnant individuals have not been conducted yet, as they normally follow trials for the overall population. Those trials for the Pfizer and Moderna vaccines should hopefully begin within a month.

Can mRNA from COVID-19 Vaccines Enter our DNA?

In short, almost definitely no.

The process by which foreign DNA is inserted into our own DNA is called insertional mutagenesis. Insertional mutagenesis can happen with certain kinds of vaccines, mainly DNA-based vaccines. However, this is virtually impossible with mRNA vaccines (which is actually considered to be one of their advantages).

Aside from the fact that mRNA is quickly broken down by normal cellular processes following protein synthesis, there are several hurdles that would need to be overcome for mRNA to become integrated into our DNA:

The first requirement would be for the mRNA to move from our cells into the nucleus, for which it would need something called a nuclear localization signal. In short, the mRNA in the COVID-19 vaccines doesn’t have such a signal, so it can’t enter the nucleus. (Strike 1)

The second requirement would be converting the mRNA fragments into DNA. That requires an enzyme called reverse transcriptase. Our bodies don’t make reverse transcriptase, and it isn’t found in the COVID-19 vaccines. (Strike 2)

Lastly, the vaccine would have to contain an enzyme called integrase, which would allow the DNA fragment to be spliced into the genome. This also is not found naturally in our bodies or the COVID-19 vaccines. (Strike 3)

Final Thoughts

Regarding references: This post doesn’t contain as much primary scientific research as some of my other posts, for a good reason: the process of protein synthesis and the function of vaccines/the immune system are well understood- you can find a fair amount of this information in basically any biology textbook. If anyone is skeptical of my references, these are the textbooks I referred to:

Biology: the Dynamic Science by Russell et al.

Molecular Biology of the Cell by Alberts et al.

There are a lot more things that are worth discussing about the COVID-19 vaccines, and I am doing my best to write blog posts about them. But if you’re concerned that mRNA in these vaccines could fundamentally and permanently alter your DNA- don’t be.

I’m sure that I have missed something. Please feel free to leave any thoughts or questions below- I only ask that you take some time to fact-check before you post.

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