mRNA vaccines have been used in clinical studies since 2001
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With the advent of the SARS-CoV-2 pandemic, the public has been presented with many unfamiliar scientific terms. Some worry that because they have not heard of mRNA technology, it is a brand new field, and scientists have acted hastily to produce a vaccine. In reality, mRNA technology was shown to be viable in animal models over 30 years ago, followed in 2001 with human trials. In contrast to their mRNA counterparts, conventional vaccines are time-consuming and labor-intensive to produce. While all you need to make an mRNA vaccine is the nucleotide sequence of interest, and they are easy to make in mass quantities. In the last decade, mRNA vaccines were used as immunotherapeutic agents for the treatment of cancer. This is an exciting time for this burgeoning field that was precipitated by a global tragedy. Accordingly, funding is increasing to use these treatments against other infectious diseases, solid tumors, and muscular dystrophy. In this clip, Dr. Roger Seheult and Dr. Rhonda Patrick explain the history and future potential of technology.
Dr. Seheult: The other aspect of this that is tossed around is that this is new technology. Now, I know that Dr. Patrick knows more about the technology in terms of the history, but I will just give you a very short timeline. Back in the 1990s, we injected for the first time mRNA into the muscle cells of a mouse, for the very first time. By 2005, we had modified the nucleotides, which are the signaling in that mRNA vaccine to get around early destruction. So the problem early on was that we couldn't allow these messenger RNA molecules to last long enough to make the protein product. The problem wasn't that they lasted forever. It was that they didn't last long enough, but they were able to finally figure out how to do that. And by 2013, they started working on medications that were based on mRNA. And then finally, we have the vaccines. Here is a paper that was published in 1990, so over 30 years ago, that was for the first time showing that this technology actually had viability. And so this technology is not new. It's been around for 30 years, and it's been looked at. And with that, I'll turn it over to Dr. Patrick. I think she has some more details on this.
Dr. Patrick: Yes. I do. You know, in addition to this technology not being new in the sense that everyone...most people think this is the first time it's actually been used in humans, just to kind of speak to your point about the acceleration of the process of getting this vaccine into people, and you were talking about all the money that's available for building the factories, I think another really important thing to point out is the difference between this vaccine and our history of vaccines in terms of how we make them. For the mRNA vaccines, all you need is the sequence. That's all you need to make it. And it's so easy to make in mass, mass, mass quantities versus having to actually grow vaccine in some kind of animal cell type. And like, I mean, you're limited. There's a limitation in how much of it you can make, physically, limitation. So, just going back to the actual history of mRNA vaccines and this mRNA technology in humans. In 2001, we have the first clinical trial of this mRNA technology that was made. It was mRNA-induced dendritic cells. In 2009, we have another clinical trial where mRNA was used as a therapeutic. In 2014, there's the first mRNA vaccine in terms of immunotherapy for cancer, so trying to treat cancer with mRNA vaccines. These are all in humans. In 2017, there were 2 clinical trials, one for mRNA-based vaccine for influenza, and another one for mRNA technology used to treat patients with heart...basically had heart failure, and they were injecting mRNA vaccines into their heart. So, we've got a lot of clinical data dating back to 2001 where we've been using this technology in humans, you know. So this is not the new technology that people in their minds they think that this is the first time it's ever been used in humans and how scary that is. It dates back to decades, well, you know, a couple of decades being used in humans.
To kind of add to that, I really...moving forward, it's amazing how this field has exploded in terms of all the clinical trials now being started and planned for this mRNA technology. There is so much interest, and there's a lot of funding now to understand this technology as a therapeutic for infectious diseases in addition to the SARS-CoV-2 virus for other ones. There are now clinical studies that are now starting to look at this technology to treat genetic disorders like muscular dystrophy where there's no treatment that exists. Can you imagine being the parent of a son that has muscular dystrophy and knowing there is no treatment and having to watch your son degenerate and die? I mean, we may see a treatment for muscular dystrophy in our lifetime because of this. It's accelerated and exploded this clinical arena where now we're seeing tons and tons of trials for mRNA vaccines as immunotherapy for cancers where they're going to be injecting this mRNA technology into a variety of different types of solid tumors. And again, we may very well in our lifetime now see a cure for different types of solid tumors. Solid tumors are the type of cancers that are hardest to treat with chemotherapy because they often grow far away from blood vessels. And so blood vessels, you need them to be close to the cancer site because that's how the chemotherapeutic gets, you know, delivered to the tumor site. And so you'll get these tumors growing far away from them. They're what's called hypoxic. They're growing far away from blood vessels. And so it's one of the reasons why many different solid tumors are resistant to many types of chemotherapeutic treatments. So imagine being able to directly inject the tumor with this mRNA technology where we're going to, you know, test a variety of different immune generating, you know, molecules and things that are going to activate the immune system to go right directly to that tumor and kill it. It's a very exciting time, and I understand that people are scared because it's new to them. And it's always scary when something, you know, is new, and there's change. But there's a bright side, and that bright side is, is that science is moving forward at an accelerated rate. And we are witnessing something that would have not have happened otherwise without this terrible pandemic that obviously a lot of bad has come out of. But, you know, to try to see the silver lining here, the good out of it is that the science has really catapulted forward, and there's some exciting stuff going on with the mRNA technology.
The end stage of heart disease, characterized by reduced capacity of the heart muscle to pump blood. Also referred to as heart failure, it represents the culmination of all forms of cardiovascular disease and affects nearly 65 million people worldwide.
A form of RNA, transcribed from a single strand of DNA, that carries genetic information required for protein synthesis from DNA to the ribosomes.
A type of vaccine that contains the genetic material to encode a single viral protein that, when injected into the body, induces antibody production against the target protein. Because mRNA degrades easily, it must be encapsulated in lipid nanoparticles in order to be absorbed by cells and often must be delivered in multiple injections to promote optimal immune response.
One of four nitrogen-containing molecules that comprise DNA. A nucleotide consists of one of four chemicals, called a “base,” plus one molecule of sugar and one molecule of phosphoric acid. Nucleotides are typically identified by the first letter of their base names: adenine (A), cytosine (C), guanine (G), and thymine (T). They form specific pairs (A with T, and G with C), and their bonds provide the helical structure of the DNA strand.
The virus that causes severe acute respiratory syndrome, or SARS. First identified in China in 2002, SARS-CoV-2 is a type of coronavirus. It was responsible for an epidemic that killed nearly 800 people worldwide.
The virus that causes COVID-19. SARS-CoV-2 is one of seven coronaviruses known to infect humans. Others include SARS-CoV-1 (which causes severe acute respiratory syndrome, or SARS) and MERS-CoV (which causes Middle East respiratory syndrome, or MERS). SARS-CoV2 exploits the angiotensin-converting enzyme 2, or ACE2, receptor to gain entry into cells. The ACE2 receptor is widely distributed among the body's tissues but is particularly abundant in lung alveolar epithelial cells and small intestine enterocytes. SARS-CoV-2 binds to a cell's ACE2 receptor and injects its genetic material (RNA) into the cytosol. Once inside, the viral RNA molecules are translated to produce RNA-dependent RNA polymerase, also known as replicase, the enzyme critical for the reproduction of RNA viruses. The viral RNA is then packaged into infective virion particles and released from the cell to infect neighboring cells.
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