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mRNA Is Here Forever - Stone - 03-31-2023
mRNA Is Here Forever
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Scientists have long-known that mRNA could hold the key to developing much-needed vaccines. The covid pandemic proved them right, spurring a boom in mRNA-based vaccine research that could soon upend medical prevention as we know it.
Scientists have long-known that mRNA could hold the key to developing much-needed vaccines. The covid pandemic proved them right, spurring a boom in mRNA-based vaccine research that could soon upend medical prevention as we know it.
TBP [adapted] | March 29, 2023
This is NOT a Covid article. It’s about mRNA. “They” have ginormous plans for mRNA technology. Eventually it will be used to treat everything except death. [...] The article ends with a commentary that the only thing now holding back all this healthy and safe progress is “bravery“. [...][/i]
How mRNA vaccines could target everything from cancer to the plague
Imagine visiting your doctor for a routine checkup, and on top of the usual shots — the annual flu or COVID vaccine—your doctor asks if you’d like to be vaccinated for cancer. All cancer— lung, skin, colon, you name it — with just one mildly uncomfortable jab in the arm.
That scenario, which sounds like something out of science fiction, might be closer than you think. And it’s mostly thanks to the COVID vaccine – which in a few short years has become the highest-profile of the increasingly influential family known as mRNA vaccines.
Indeed, mRNA vaccines designed to treat cancer (among other diseases) “are quite realistic,” says Anna Blakney, an RNA researcher at the University of British Columbia.
And cancer is just the tip of the iceberg. Earlier this month, scientists Edo Kon and and Dan Peer from Tel Aviv University and the Israel Institute for Biological Research announced that they’d created a single dose vaccine that could effectively protect people from Yersinia pestis bacterium. Haven’t heard of it? That’s because it’s better known (at least in the Middle Ages) as the plague — a disease that still kills thousands in Asia and parts of Africa each year.
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Anna Blakney, an RNA researcher at the University of British Columbia, says we are currently in the midst of an "mRNA renaissance."
The plague might not be something that keeps you up at night, but there are likely plenty of infectious diseases that do, and somewhere in the world, scientists are working (and getting amazingly close) to developing mRNA-based vaccines that could potentially make the disease you fear the most obsolete.
Blakney describes it as a RNAissance. ”Scientists are exploring the use of mRNA for many different applications,” she says, not just in treating cancer and COVID but “enzyme replacement therapies, immunotherapies, you name it.” These medicines “will be game changers in the years to come,” she says.
It may seem like these advances have arrived staggeringly fast, but researchers have been experimenting with mRNA treatments for decades. “Scientists first started studying mRNA vaccines in 1990,” says Blakney. “The first RNA vaccine clinical trial was started in 2009.”
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Dan Peer, a scientist at Tel Aviv University, is part of a team that developed a new mRNA-based vaccine that could help prevent plague.
But then came the pandemic, and its urgency meant “bureaucratic red tape was reduced,” says Keith Knutson, a professor of immunology at the Mayo Clinic who researches and develops cancer vaccines. “It resulted in critical re-evaluation of some of the rules, regulations, and procedures that guide drug development.”
We’re not talking about the types of regulatory mechanisms that protect the consumer from unsafe drugs, but rules around “how we get things done,” he says. “It forced us to do things better and more efficiently.” Adds Knutson, a specialist in ovarian and breast cancer immunotherapies, “the pandemic pushed RNA from an emerging star to a superstar.”
So how do mRNA vaccines work? Katalin Karikó, the Penn Medicine-scientist whose research laid the foundation for both the Pfizer and Moderna COVID vaccines, calls it a “middleman between information and action.” Unlike most vaccines, which inject part of a virus into the patient, mRNA gives our cells instructions on how to make the necessary protein (or antibodies) to fight off infectious agents.
“The technology could potentially target any abnormal protein” that leads to disease, says Lennard Lee, an oncologist at the University of Oxford. “We should move forwards and push the boundaries.”
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Oxford University Professor Leonard Lee says mRNA-based vaccines could potentially target any disease-causing protein.
Those boundaries are now being pushed in almost every type of deadly disease, from tuberculosis and malaria to high cholesterol and HIV. Promising advances are also being made for a universal flu vaccine, one that could protect against multiple strains of seasonal flu.
In the past, the effectiveness of flu vaccines varied from year to year — they were 39% effective in 2019-2020, but just 10% effective during the 2004-2005 flu season, according to CDC data. But a new vaccine being developed by University of Pennsylvania researchers “could include twenty strains of flu in a single mRNA vaccine,” says Blakney.
And that’s just the tip of the iceberg. Several mRNA vaccines are in the works that will tackle everything from ovarian, colorectal, lung and pancreatic cancers. Vaccines are even being developed for diseases that aren’t threatening humans — yet.
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Prof. Katalin Karikó from the University of Pennsylvania was part of the team whose mRNA research helped lead
to covid vaccine development by Pfizer and Moderna.
Manufacturers like Moderna, GSK and CSL Seqirus are currently working on a precautionary measure vaccine, for a new strain of avian flu called H5N1, which has killed millions of animals (including mammals like foes, raccoons and bears) but remains very rare, and almost never deadly, among people. At least for now.
The big one, of course, remains cancer. In fact, years before COVID became public enemy number one, the primary focus of mRNA researchers was creating a vaccine to treat cancer.
COVID was in many ways easier because it was more straightforward. “The protein target is clear and distinct from any of the proteins on a human cell,” explains Blakney. “For cancer vaccines, we’re targeting human cells that may or may not have completely distinct proteins, or the proteins may be found on other tissues, so it’s important and sometimes challenging to make sure they’re very specific to only the cancer cells.”
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Dr. Nora Disis, director of the University of Washington’s Cancer Vaccine Institute, suggests diseases now considered "death sentences" will soon be preventable via vaccines.
In other words, with COVID, they were aiming for a clear bullseye. For cancer, every target is different—“because every person’s cancers are different,” says Blakney—and the bullseye changes from patient to patient, and never looks quite the same.
But while cancer is a very different enemy than COVID, the lessons learned from the creation of COVID vaccines have served as a sort of canary in the coal mine for the entire arena of mRNA vaccine research. And the lighting speed in which COVID vaccines were introduced could soon seem like a turtle’s pace compared to what’s coming next.
Just last month, the FDA granted breakthrough therapy designation to a new experimental vaccine for advanced stage melanoma, the result of a collaboration between pharmaceutical companies Moderna and Merck. In clinical trials—which lasted for a year and involved 157 patients—the risk of dying from cancer dropped by as much as 44%. Phase 3 trials, with an even larger group of cancer patients, is planned for this year. A vaccine for skin cancer may not just become a reality in our lifetimes, but it could be just around the corner.
Knutson, the Mayo Clinic professor, is also currently overseeing five different clinical trials testing different vaccines for breast or ovarian cancer—vaccines that don’t just prevent cancer but also stop it from recurring. Although the data remains preliminary, he’s cautiously optimistic about their potential. Some treatments, he says, “are closer than others in becoming a reality.” And that’s mostly because cancer is so frustratingly diverse.
“Breast cancer for example, is subdivided into smaller subtypes,” he says. “It’s different in many ways from lung cancer or ovarian cancer. They all have different antigens.” If they manage to find the winning formula for a breast cancer vaccine, that doesn’t mean cancer patients everywhere should rejoice.
“A one-size-fits-all vaccine is likely not possible,” Knutson says.
But if we need more vaccines that target more cancers, that just means we have to speed up trials and continue the pace that started with COVID, says Lee. And even more than that, we need more cooperation like the type that helped advance the COVID vaccine so rapidly.
“Research requires hospitals to work together,” he says. This is exactly what’s happening in the U.K., with the January announcement of a Cancer Vaccine Launch Pad, in which the National Health Service has joined forces with BioNTech—the German firm that worked with Pfizer to manufacture the COVID vaccine—to fast-track cancer vaccines.
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The rapid-fire approval of covid vaccines by Pfizer and other pharmaceutical giants has led to a fast-tracking
of subsequent mRNA-based medical preventions.
“It aims to rapidly identify large numbers of patients who could be eligible for cancer vaccine trials,” Lee says. “It will explore potential vaccines across multiple types of cancer and could start as early as autumn 2023, with up to 10,000 treatments being delivered.”
That’s a big difference from what Lee calls “old-school, pre-pandemic clinical trials,” which typically took a decade or more to complete. “The NHS-Galleri study [in 2022] recruited 140,000 to test a revolutionary new blood test for cancer. This was achieved in less than a year,” Lee says. In the case of COVID, “the Oxford-Astrazeneca vaccine trials (of 2020) recruited 30,000 in less than a year. This is different from the hospital-by-hospital approach taken in the US.”
Ultimately, drugs enter the marketplace based on the speed of clinical trials, and Lee insists that it’s entirely in our control. “How many hospitals volunteer to run cancer vaccine trials, how many doctors/nurses will support the studies and how many patients will come forward?” he says. “I feel positive that there is strong grass-root support to get these new products tested rapidly.”
Just over a year ago, the BBC was wondering if mRNA vaccines could make us “superhuman.” We likely won’t get to that point, says Nora Disis, director of the University of Washington’s Cancer Vaccine Institute. But, she adds, “I don’t think we need ‘superhuman’ immunity, just good strong immunity.
There are vaccines being developed for opioid addiction, to prevent smoking, to treat Alzheimer’s, autoimmune disease, and many others.” There will come a time, perhaps sooner than expected, when many diseases that are essentially a death sentence today “can be treated and prevented with vaccines,” Disis adds.
The key will be maintaining this momentum. “The pandemic took humanity to the brink and we had to innovate to survive,” Lee says. “We were lucky and developed a tool that saved tens of millions of lives. The only thing holding us back from using the same tool to save many more is just . . . bravery.”
We need to be brave enough to collectively leap again with more clinical trials into more diseases, he says. “The legacy of the pandemic is that we don’t say, ‘Let’s wait another decade’ to complete research. We say, ‘Let’s act to hyper-accelerate this research field across the world.’ ”
Of course, no one knows for sure when — or even if — this will truly happen. But with the rapid pace of mRNA vaccines increasingly becoming the standard, we could very well live to see a day when we roll up our sleeves for a cancer vaccine, and it becomes one less thing we have to worry about.
SOURCE: NY (com)Post