How mRNA and DNA Vaccines Could Soon Treat Cancer, HIV, Genetic Diseases, and More

Messenger RNA mRNA Strand

Nucleic acid vaccines use mRNA to give cells instructions on how to produce a desired protein.

The two most successful coronavirus vaccines developed in the U.S. – the Pfizer and Moderna vaccines – are both mRNA vaccines. The idea of using genetic material to produce an immune response has opened up a world of research and potential medical uses that are far out of the reach of traditional vaccines. Deborah Fuller is a microbiologist at the University of Washington who has been studying genetic vaccines for more than 20 years. The Conversation spoke to her about the future of mRNA vaccines for The Conversation Weekly podcast.

Below are excerpts from that conversation which have been edited for length and clarity.

How long have gene-based vaccines been in development?

This type of vaccine has been in the works for about 30 years. Nucleic acid vaccines are based on the idea that DNA makes RNA and then RNA makes proteins. For any given protein, once we know the genetic sequence or code, we can design an mRNA or DNA molecule that prompts a person’s cells to start making it.

When we first thought about this idea of putting a genetic code into somebody’s cells, we were studying both DNA and RNA. The mRNA vaccines did not work very well at first. They were unstable and they caused pretty strong immune responses that were not necessarily desirable. For a very long time DNA vaccines took the front seat, and the very first clinical trials were with a DNA vaccine.

But about seven or eight years ago, mRNA vaccines started to take the lead. Researchers solved a lot of the problems – notably the instability – and discovered new technologies to deliver mRNA into cells and ways of modifying the coding sequence to make the vaccines a lot more safe to use in humans.

Once those problems were solved, the technology was really poised to become a revolutionary tool for medicine. This was just when COVID-19 hit.

T Cell Colorized Scanning Electron Micrograph

DNA and mRNA vaccines are much better at producing T cells than are normal vaccines. Credit: NIAID

What makes nucleic acid vaccines different from traditional vaccines?

Most vaccines induce antibody responses. Antibodies are the primary immune mechanism that blocks infections. As we began to study nucleic acid vaccines, we discovered that because these vaccines are expressed within our cells, they were also very effective at inducing a T cell response. This discovery really prompted additional thinking about how researchers could use nucleic acid vaccines not just for infectious diseases, but also for immunotherapy to treat cancers and chronic infectious diseases – like HIV, hepatitis B and herpes – as well as autoimmune disorders and even for gene therapy.

How can a vaccine treat cancers or chronic infectious diseases?

T cell responses are very important for identifying cells infected with chronic diseases and aberrant cancer cells. They also play a big role in eliminating these cells from the body.

When a cell becomes cancerous, it starts producing neoantigens. In normal cases, the immune system detects these neoantigens, recognizes that something’s wrong with the cell and eliminates it. The reason some people get tumors is that their immune system isn’t quite capable of eliminating the tumor cells, so the cells propagate.

With an mRNA or DNA vaccine, the goal is to make your body better able to recognize the very specific neoantigens the cancer cell has produced. If your immune system can recognize and see those better, it will attack the cancer cells and eliminate them from the body.

This same strategy can be applied to the elimination of chronic infections like HIV, hepatitis B and herpes. These viruses infect the human body and stay in the body forever unless the immune system eliminates them. Similar to the way nucleic acid vaccines can train the immune system to eliminate cancer cells, they can be used to train our immune cells to recognize and eliminate chronically infected cells.

Vaccine Needle Vial

There are dozens of ongoing trials testing the efficacy of mRNA or DNA vaccines to treat cancers or chronic diseases.

What is the status of these vaccines?

Some of the very first clinical trials of nucleic acid vaccines happened in the 1990s and were for cancer, particularly for melanoma.

Today, there are a number of ongoing mRNA clinical trials for the treatment of melanoma, prostate cancer, ovarian cancer, breast cancer, leukemia, glioblastoma and others, and there have been some promising outcomes. Moderna recently announced promising results with its phase 1 trial using mRNA to treat solid tumors and lymphoma

There are also a lot of ongoing trials looking at cancer DNA vaccines, because DNA vaccines are particularly effective in inducing T cell responses. A company called Inovio recently demonstrated a significant impact on cervical cancer caused by human papilloma virus in women using a DNA vaccine.

Can nucleic acid vaccines treat autoimmune disorders?

Autoimmune disorders occur when a person’s immune cells are actually attacking a part of the person’s own body. An example of this is multiple sclerosis. If you have multiple sclerosis, your own immune cells are attacking myelin, a protein that coats the nerve cells in your muscles.

The way to eliminate an autoimmune disorder is to modulate your immune cells to prevent them from attacking your own proteins. In contrast to vaccines, whose goal is to stimulate the immune system to better recognize something, treatment for autoimmune diseases seeks to dampen the immune system so that it stops attacking something it shouldn’t. Recently, researchers created an mRNA vaccine encoding a myelin protein with slightly tweaked genetic instructions to prevent it from stimulating immune responses. Instead of activating normal T cells that increase immune responses, the vaccine caused the body to produce T regulatory cells that specifically suppressed only the T cells that were attacking myelin.

DNA mRNA Protein

Many diseases result when people have mutations or are missing certain genes, and nucleic acid vaccines could act as temporary replacements for the missing genes.

Any other applications of the new vaccine technology?

The last application is actually one of the very first things that researchers thought about using DNA and mRNA vaccines for: gene therapy. Some people are born missing certain genes. The goal with gene therapy is to supply cells with the missing instructions they need to produce an important protein.

A great example of this is cystic fibrosis, a genetic disease caused by mutations in a single gene. Using DNA or an mRNA vaccine, researchers are investigating the feasibility of essentially replacing the missing gene and allowing someone’s body to transiently produce the missing protein. Once the protein is present, the symptoms could disappear, at least temporarily. The mRNA would not persist very long in the human body, nor would it integrate into people’s genomes or change the genome in any way. So additional doses would be needed as the effect wore off.

Research has shown that this concept is feasible, but it still needs some work.

Written by Deborah Fuller, Professor of Microbiology, School of Medicine, University of Washington.

This article was first published in The Conversation.The Conversation

7 Comments on "How mRNA and DNA Vaccines Could Soon Treat Cancer, HIV, Genetic Diseases, and More"

  1. Very Innteresting.

    When solving a Jigsaw Puzzle , which is complex , All the Pieces need to fit together perfectly.

    Looks like the Jigsaw puzzle is beginning to fall into Place.

    Now if the dream is to banish all diseases from Huamanity , there are some more problems to be solved.

    For example, how does body develop resistance to the human ecosystem normal functioninng.

    Take Insulin for example. Why is the ablity of Insulin to nullify the sugars in the blood stream impaired. The structure of Insulin is known.

    The structure of the Blood Cells carrying the digested carbohydrate and stored as starch, which can provide energy aa sugars —-which provides energy to the cells in the human ecosystem is also known . The Structure of the Cells in the Human Ecosystem is also known.

    Now, if the Hippocratic Oath is followed in letter and spirit , then problems such as these need to be solved in both lletter and spirit. In my opinion Type-II Diabetes shoulld not even exist. Neither should Autoimmune Diseaes. We need to figure out what triggers this impairment.

    Similarly ,many other Diseaes which exist as a result of various factors which impair the ability of the normal human body to function at its peak efficiency, needs to be addressed. I am personally convinced that Diet has a major role to play in the solution of this puzzle.
    Also introduction of various unwanted substances through ingestion from the polluted environment (unwillingly) and also as a result of Hedonist tendencies for a High drives the introductionof such substaces. Many are addictive. . Lysergic …. Acid (LSD) has been around since I was a kid!!!

    Views expressed are personal and not binding on anyone.

  2. In addition to above post, remember reading about research from Kangaroo Country about Benign turning Unfriendly. Recent findings.

    May be a Clue and also help us figure out how to avoid such reactions.

    Views expressed are personal and not binding on anyone.

  3. Pfizer was made by biontech in Germany. Off course Pfizer mass produced it and it might be more intricate.However, it would be good to at least be fair with the attributions as a journalist/article writer

  4. BioNTech, From Germany, is the originator of the Pfizer vaccine.

  5. These vaccines killed or injured over one million innocent souls. To label them the most successful is callous and shameful.

  6. Our healthcare system is about to experience a tsunami! Potential side effects of jabs include chronic inflammation, because the vaccine continuously stimulates the immune system to produce antibodies. Other concerns include the possible integration of plasmid DNA into the body’s host genome, resulting in mutations, problems with DNA replication, triggering of autoimmune responses, and activation of cancer-causing genes. Alternative COVID cures exist. Ivermectin is one of them. While Ivermectin is very effective curing COVID symptoms, it has also been shown to eliminate certain cancers. Do not get the poison jab. Get your Ivermectin while you still can

  7. There appears to be a lot of misinformation here in these comments. Be very careful what you read, and especially what you believe. Until science finds a better way, the vaccines are simply the best thing we have to combat this virus. Yes there have been a few people that have had negative reactions to the vaccines, which is true about almost every medication out there. This number is very small compared to the millions upon millions of folks that have received the vaccine, with no side effects except maybe a bit of a sore arm.

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