How mRNA and DNA vaccines could soon treat cancers, HIV, autoimmune disorders and genetic diseases

The idea of using genetic material to produce an immune response has opened up a world of research and potential medical uses far out of 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. We spoke to her about the future of mRNA vaccines.

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

This article is a repost which originally appeared on The Conversation
Deborah Fuller - January 6, 2022
Edited for content and readability - Images sourced from Pexels

Our Takeaways:

  • Nucleic acid vaccines are based on the idea that DNA makes RNA and then RNA makes proteins.
  • These vaccines are effective at inducing a T cell response.
  • For cancer, the goal is to make your body better able to recognize the very specific neoantigens the cancer cell has produced and destroy it.
  • For autoimmune disorders, the vaccine would suppress the T Cells to keep the immune system from attacking myelin

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.

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.

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.

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.

8 Surprisingly Easy Ways to De-Stress at Home, From a Longevity Doctor

8 Surprisingly Easy Ways to De-Stress at Home, From a Longevity Doctor

Hailey Welch

This article is a repost which originally appeared on The Beet

Edited for content.

Constant stress can gradually chip away at our health, creating inflammation in the body that ultimately leads to disease if we are not able to alleviate it. Every year, 120,000 people die of stress-related conditions, such as heart attack, high blood pressure, stroke, diabetes, and depression, according to the NIH, but this doctor believes we are each capable of avoiding these complications if we have the right tools and strategies. Here he shares his helpful tips to help you de-stress, avoid negatives emotions, and live a longer, happier life.

Dr. Kien Vuu specializes in longevity and his work focuses on helping his patients cope and manage their stress. “Getting rid of stress is the best medicine we can give ourselves,” he says, and he himself has had to manage his own stress-related disease, which he treated naturally, so he now wants to help others do so, without adding drugs into the equation.

Five years ago, Dr. Vuu had a wake-up call when he was diagnosed with early-stage diabetes. He realized his body was inflamed from unhealthy lifestyle choices and poor eating habits. The first thing he decided to do was to make mental health a top priority, as well as focus on changing his nutrition, sleep habit, and exercise routine. Through his journey, he taught himself to live a more purpose-driven life, improve his personal relationships, and in time, reduce his chronic stress, which he believes was fueling the disease. In six months, he reversed his symptoms without the use of medication, and now he teaches others how they can have a similar experience. In addition, Dr. Vuu ‘s, Thrive State, helps people reach their peak performance, optimize their health, and live longer.

Here’s how stress affects the body and mind

In our exclusive interview, Dr.Vuu explains how psychological changes happen in the body when we’re stressed since it had a place in our evolutionary survival when it allowed us to activate a “fight or flight” response when facing a perceived danger. Running from a saber tooth tiger may not be relevant today, but it’s the same response as when we think we’re going to get fired or experience conflict, and it helps people understand how stress, when it’s chronic rather than fleeting, can affect the body.

“When we run from something as scary and frightening as a saber tooth tiger, our heart rate goes up, and our blood thickens so just in case we get that flesh wound we don’t bleed out. This response makes our blood very sluggish. It diverts blood away from our visceral organs, such as our liver, kidney, gut, and into our skeletal muscles, so we can run away from the saber tooth tiger,” according to Dr. Vuu.

Then, he explained how this physiological feeling disrupts our body: “When we experience stressful situations, we’re not getting enough blood flow to the kidneys, which is an organ responsible for cleansing the blood. Our liver is also a detoxifying organ. Our gut is there to absorb nutrients. Under stress, we’re not going to detoxify very well. Your microbiome is going to be stressed, which might lead to a leaky gut. Inflammation in our body also increases,” said Dr.Vuu.

“If you get that flesh wound from the saber tooth tiger, we want to fight off all the infections and germs. It starts to heal that wound. But what happens in the chronic long term is that inflammation can attack part of your own body. Over time, this raises the risk of getting an autoimmune disease and basically sets the stage for every type of disease,” according to Dr. Vuu.

8 Surprising Ways to De-Stress from a Longevity Doctor

1. Gaze into the sky, soak up the sunshine: When you’re running from the saber tooth tiger your eyes get laser-sharp and your pupils start to constrict. If you start to relax your eyes, open them, allow your pupils to dilate and gaze at nature – that will then actually activate your parasympathetic state to counteract that stress.

2. Try a breathing technique: One of the best tricks to do is breathwork. If you need to run away from a tiger you normally taking very rapid, short, deep, shallow breaths. But if you were breathing long and slow that signals a state of calm, and activates both the vagus nerve and the parasympathetic system, which tells your body: ‘There’s no saber tooth tiger here.’ Slow your breathing to convince yourself that you are in a relaxed state. Breathe into the count of six, seven, eight, and out to one more count on the exhale to fully empty the lungs.

3. Move around: Just moving around is going to help detoxify your body. Stress raises antioxidants in your body and it can raise toxins that disrupt normal healthy cell function. When you have toxins, your immune system has to work overtime and when your cells start to show signs of wear and tear, the body needs to shunt them off for disposal, and your immune system would rather get busy fighting off bacteria and viral bugs. Moving around will shift the stress hormones by creating endorphins, which and will help you release stress and replace it with this natural feel-good chemical in your body.

4. Journal: Writing down your thoughts can help break the stress cycle when you get into a negative feedback loop. If you start to journal some of these thoughts, you may be able to get them down on paper, instead of having them stuck in your mind. You’re able to look at it and think ‘that’s a weird thought… Do I still want to keep this in my mind?’ It’s a way of gaining some control of how you want to think or how do you want to behave. Script the things that are going right in your life instead and put those into your mental process for repeating often.

5. Pause when you have a negative thought and take 10 slow deep breaths: This is a technique that Dr. Vuu said he learned from a psychiatrist and Holocaust survivor, Victor Frankl who has seen so many devastating things in his life. Between stimulus and response, there’s space–in that space is our power to choose our response. And in that response, lies our freedom and growth.

Frankl has experienced and seen horrific things, but rather than react to them, he chooses how he wants to show up,” says Dr. Vuu. “If you could stop that negative pattern or way of thinking, or maybe that negative belief you have about yourself and choose how you want to show up, you can start this transformation process.

So when you find yourself feeling stressed or experience a negative emotion, pause and take 10 deep breaths in, through your nose, and out through your mouth very slowly. It will activate the vagus nerve (as we noted above) and as you do this breathing, notice that you’re creating space between that stimulus, and create a positive response instead.

6. Stand in a power pose: A person who’s feeling stressed or depressed often stands, breathes, and postures in a way that is tense, or defeated. They may be hunched over, their neck and head lowered down, or they may slouch. Emotional stress causes your body to carry itself differently than when you feel confident and in control. But if you change your posture, and stand in a power pose, it can make a huge difference and signal to the brain: I am here, I am in control and I am going to conquer whatever it is that’s in front of me.

A Harvard study showed how standing in a power pose for two minutes before delivering a speech in front of mock job interviewers, made the candidates more likely to be hired when videos of these people were shown to strangers. Just standing tall and expansively makes you more likely to seem confident and that translates into success.

Try moving in a power pose (upright, chest out, arms wide or out) to shift your physiology, Dr. Vuu suggests. How you choose to move, breathe, and gaze is a powerful physical technique for reducing stress in the body.

7. Try the ACT acronym to find joy and gratitude

If you’re feeling stressed because something ticked you off, or you were in an argument with a partner or spouse, use this acronym to help yourself calm down. Dr. Vuu uses the acronym A.C.T which helps people feel in control of their stress and manage it before it elevates into a bigger problem.

A–Awareness. If you have a negative feeling in your body, ask yourself to be aware of the trigger. By seeing patterns, you can head off the behavior that causes the stress before it happens.

C— Choice. You have the power of choice. What decision do you choose? Do you want to feel joy, gratitude, or happiness? The more you practice choosing happiness, the better you will be at feeling that emotion.

T—Take Action. What’s the next step you would do in this new stress-free version of yourself? Is it showing up with love, compassion, and gratitude? After a disagreement with a partner, you might say to yourself, I’m going to let that go and show up with love.

If you let yourself down, ask yourself: How can I show up with love for myself? Ate a whole tub if dairy-free ice cream? maybe it was your inner child and the trigger was something that could have been avoided next time if you took action.

“As you start to train to do this, what you’re doing is you’re training in new neuro networks so that you’re no longer a victim of your own trigger,” said Dr. Vuu. “You’re laying down new tracks to the emotions of love, joy gratitude,” he adds, which ultimately leads to healthier body function and anti-aging mechanisms to kick in.
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8. To make a positive change in your life, try Dr. Vuu’s H.E.R.O acronym

Dr. Vuu is on a mission is to help people achieve optimal health, longevity, and peak performance. Therefore, when his patients need to change something in their lives to reach these goals, he suggests using the H.E.R.O acronym to transform their lives. “You’re going to need a reason to make that change,” he adds. Each letter works in a way to motivate people to make a change, according to Dr. Vuu.

“H” stands for Hunger. The hunger is really your Why? It’s the thing that will compel you to do something even though your habits make you resistant to change.

If you are committed to something the impetus for change cannot come just for yourself. Realizing that you are doing something for other people allows you to access greater leverage for change. You might have to look outside yourself for that leverage point. Defining your life and why you need to make that change is going to put you in the right direction.

“E” stands for Energy. “I talk about the bioenergetic model for health,” says Dr. Vuus, which means the energy of your cells within the environment they are existing in. “Your longevity depends on your body’s optimal performance. The flip side of that is experiencing chronic disease. “We can thrive and heal when we are in an optimal state.” But if our cells are stressed, inflamed, it requires the immune system to react, and then that will set off a chain reaction so that our bodies will continuously be failing to support optimal health.

What determines whether our cells are in an optimal state is the energy that your brain signals to the body, which can be stress-driven or what Dr. Vuu calls a “Thrive State.” Stress can negatively impact your cells’ ability to replicate by harming the DNA, and when DNA gets off track that means you can get diseases such as heart disease, cancer, and more. If our cells are functioning at a 75 percent capacity, that will also prevent our kidneys or liver from performing their important detoxifying work.

For everything to function as smoothly as it can, we need to prioritize better sleep, eat nutrient-dense food, work on our emotional relationships, tame negative thoughts, and adopt a positive mindset. “I boil it down to those seven things and if you master them, your ability to perform at your very best and prevent and reverse chronic disease. Your longevity is going to improve dramatically. That’s what it means to master your bioenergetic state.

“R” is for reclaiming. This has to do with reclaiming your identity. It’s about shifting that voice in your head that tells you: You aren’t a healthy person. Instead, tell yourself that you are is a gift to the world. You need to be at your very best to serve yourself and others. Imagine yourself as this healthier version of yourself in order to reclaim your identity. Then understand what you need to do, in order to reach that level.

“O” stands for optimization. The H.E.R. part of the acronym can be done on your own. But the O will require a doctor’s visit to measure your markers and get a baseline checkup. There might be problem areas of your life that still need to be resolved, even if you’re working towards doing these seven other things. You could have a food allergy, a mineral deficiency, or a hormonal imbalance. Know your cholesterol and blood pressure, fasting blood sugar, to determine whether there are still conditions that need to be resolved or improved. There are really two main signals that our cells are constantly listening to: Are we in a stress mode? Or are we in a thriving state? You get to determine which one your body hears.