mRNA technology—using messenger RNA, essentially a sequence of biological code, to deliver instructions to the body's cells and train the immune system to recognize and attack specific mutations or foreign invaders, such as cancer cells or viruses—has been under development for decades. But its medical application became much more practical through Nobel Prize-winning
research by Katalin Karikó and Drew Weissman of the University of Pennsylvania, who in 2005 discovered a way to introduce mRNA into the body without triggering a destructive immune response.
With that advance, Karikó and Weissman unlocked the two massive medical advantages of mRNA: customization and speed.
"The trick to this is that mRNAs are natural parts of the human body, and they pass away from the body very quickly," Jeff Coller, a professor of RNA biology and therapeutics at Johns Hopkins University, told
TMD. "That's really important because you don't want a drug to be permanent. You don't want to take a drug, and then constantly in your body have Tylenol, for example." Instead, he explained, mRNA technology enables targeted, temporary treatments for diseases such as cancer and rare genetic disorders at the individual level.
Vaccine development is also accelerated by mRNA technology. "As soon as we understand the sequence of the virus and what we have to target, usually the envelope proteins, then we can quickly make vaccines," Akiko Iwasaki, a professor of immunobiology at the Yale University School of Medicine, told
TMD. During the COVID-19 pandemic, mRNA technology enabled Moderna researchers to finalize the design of their vaccine only
two days after Chinese scientists released the COVID-19 genome to the world. Traditional vaccine development can take months or even years.
"The real advantage of using mRNA is when speed is really important," Amesh Adalja, a senior scholar at the Johns Hopkins Center for Health Security, told
TMD.Conyngham took full advantage of both kinds of breakthroughs to help his dog Rosie. Distraught by the fact that chemotherapy for his dog was failing to work, he paid for a research team at the University of New South Wales to sequence Rosie's DNA, then used AlphaFold—an AI system that predicts the structure of proteins—to suggest a way to attack his dog's cancer cells using mRNA. Her advanced tumors have now halved in size, according to Rachel Allavena, a canine immunotherapy professor at the University of Queensland's veterinary school, whose research team administered the vaccine.
For dogs, mRNA treatments like these are novel. "I haven't come across anything like it," Allavena told
TMD. "The fact that she had such advanced disease and she got such a good response makes me very, very hopeful." But while Conyngham's specific AI expertise and dogged initiative certainly helped develop the vaccine, Allavena noted that Rosie's treatment was a group effort that still relied on highly specialized scientific expertise. "It's not a basement vaccine … it's a really high-tech vaccine," she said.
More than 100
clinical trials for similar vaccines using mRNA to target a variety of human cancers have been conducted. "On the human side, they're much more advanced," David Vail, a doctor who studies the comparative treatment of cancer in animals and humans at the University of Wisconsin School of Veterinary Medicine, told
TMD. While off-the-shelf cancer vaccines for both dogs and humans already exist, custom mRNA vaccines offer the advantage of tailored formulations for each patient's tumors.
For all their promise, mRNA treatments have real limitations. Not all cancers respond to mRNA vaccines, and the vaccines are most effective when used as part of a larger battery of therapies. "Probably less than 10 percent of people that are given just an mRNA personalized vaccine will have a robust response," Vail said, adding that the treatments should be used in combination with other established treatments.
Cost is also a major concern. "Personalized immunotherapy for a single patient is presently an expensive option, both for humans and for dogs," Mark Mamula, a professor at the Yale School of Medicine and the founder of
TheraJan, a company developing a canine cancer vaccine, told
TMD.
Bringing costs down will likely also require the Food and Drug Administration to rethink its approach to approving individualized therapies. "Commercialization in the marketplace just breaks down because we're used to the FDA approving, testing, and marketing drugs at scale," Coller explained, making the cost of each custom therapy inordinately expensive for the average person. For the tens of millions of Americans who have one of the roughly 10,000 documented
rare diseases, "we don't have a way to bring those therapies forward in a way that the cost is less than, like, $3 million per patient," Coller said.
The Trump administration doesn't appear poised to ease regulatory burdens on companies working on this technology. In August, Health and Human Services (HHS) Secretary Robert F. Kennedy Jr. announced the cancellation of $500 million in HHS contracts that supported mRNA vaccine research through the Biomedical Advanced Research and Development Authority (BARDA). Then, in early February, the FDA's top vaccine regulator
refused to review an application for approval of Moderna's mRNA-based flu vaccine, which had entered the final stages of trials before Kennedy's appointment, in a rare reversal on a study the agency had already agreed to. Only a White House
intervention convinced the FDA to allow the final approval process to go forward.
The Department of Defense's Joint Program Executive Office for Chemical, Biological, Radiological, and Nuclear Defense—which was already funding multiple mRNA vaccine projects—
stepped in to at least partially cover the shortfalls for some projects defunded by Kennedy's HHS. The U.S. Department of Agriculture also provides funding for mRNA vaccines targeting diseases that affect livestock. But this only covers a fraction of what BARDA offered to researchers. And while some other governments, like the
European Union, and private nonprofits, like the
Gates Foundation, have ramped up broader vaccine funding—some of which has benefited stalled mRNA projects—their investments weren't designed to replace BARDA's targeted support for the technology and haven't done so. Pharmaceutical companies can't fill the gap either, Adalja told
TMD: "When it comes to infectious disease countermeasures for biothreats, [the funding cut] was basically a fatal blow."
Richard H. Hughes IV, a member at the law firm Epstein Becker Green and a former executive at Moderna, told
TMD that the message sent by the government's decision, not just the money lost, is critical. "I can tell you that years and years of effort went into developing that technology, with and without government partnership … because they believed they would have a market; that there would be a recognized public health need, that regulators would act in good faith," he said. "What you're seeing are very clear signals that the opposite is becoming true."
Others in the industry seem to agree. "You cannot make a return on investment if you don't have access to the U.S. market," Moderna CEO Stéphane Bancel
said at the World Economic Forum in January, while announcing that his company had no plans to invest in new late-stage infectious disease vaccine trials.
"I think the U.S. risks a future when the cutting edge of biotech innovation no longer runs through San Francisco or Boston, but through Beijing and Shanghai," Sam Howell, an associate fellow with the Technology and National Security Program at the Center for a New American Security, told
TMD.
Even though they currently face political headwinds, mRNA vaccines and therapies offer immense promise. Though Rosie the dog isn't cancer-free, Conyngham says she now enjoys a far higher quality of life, able to
walk around and
appear on daytime TV. For humans, last year 6-month-old
KJ Muldoon began receiving a bespoke CRISPR gene-editing treatment, delivered via mRNA, at the Children's Hospital of Philadelphia for a rare metabolic condition known as severe carbamoyl phosphate synthetase 1 deficiency, which kills half of all babies who suffer from it in their early infancy and causes severe developmental delays and liver problems in others. Nearly a year later, "Baby KJ" is healthy and thriving.
"You've got a whole population of scientists around the world who are inspired to start using this technology to do all sorts of interesting interventions," Coller said. "But they're experiencing significant headwinds in the United States because of the federal landscape. That's just the reality."
No comments:
Post a Comment