Derrick Rossi doesn’t see it that way, but he somehow saved the world.
In 2008, he began researching messenger RNA (mRNA), building on the long-ignored work of Hungarian researcher Catalin Kariko and Drew Weissman, an immunologist at the University of Pennsylvania. In 2010, his discovery that modified mRNA, the molecule that gives DNA instructions on how to behave, could be inserted into cells to produce proteins, opened up a world of possibilities for the medical use of mRNA technology.
It was a discovery big enough to raise capital that allowed him to start a biotechnology company in Cambridge, Massachusetts, with Timothy Springer, who, like Rossi, was a professor at Harvard Medical School, and Robert Langer, an inventor and professor at MIT.
Thinking of a company name, Rossi plays with synonyms for “messenger”
He eventually learned that he had a name under his nose since 2008, when his lab staff began experimenting with modified mRNA and briefly referred to it as “fashion RNA.” Modern.
The first days of Modern
Rossi, 55, a native of Canada, is still based in Cambridge, but left Modern in 2014 to focus on his academic research. He never lost faith in the promise of mRNA. “DNA makes RNA makes proteins makes life. So wherever there is life, which is in the whole pathology of the disease, mRNA can potentially play a role, ”he explains.
“We had our fingers on one of the really key levers of almost every aspect of the disease, all aspects of life. “I imagined it would become a major therapeutic paradigm,” he said. One of the biggest challenges we had when we started the company was that there are so many different things we can work on. ”Thousands of genetic diseases, not to mention cancer, could potentially be treated with mRNA technology. .
But what Rossi did not imagine when Moderna launched was that the world would know about mRNA through a vaccine. “Vaccines weren’t even on the table in the early days of business,” he said.
One reason, he says, is that vaccines don’t usually make a lot of money. That is, unless billions of doses are needed at once to end the pandemic, which is not exactly the model on which you would like to rest your new biotech business.
The other reason was more resonant for the scientists in it: Vaccines just aren’t that exciting. “You have to give someone a dose once or twice and then let the immune system take over. So it’s nice and easy, “he says. “You don’t even have to deliver it to a specific place. You do an intramuscular shot in the arm and the system can do it, it can do the job. “
Instead, Rossi was interested in using mRNA technology to treat rare genetic diseases that could not be cured otherwise.
The pandemic accelerator
Because the potential of mRNA technology was so huge, for years research has focused on more complex applications. Moderna focuses on therapeutic agents, including regenerative medicine (for example, helping cells produce tissue to heal from events such as cardiac arrest) and genetic diseases. Later, BioNTech, an immunotherapy company founded in Germany in 2008, also began publishing research on mRNA-based immunotherapy after licensing the same technology that led Rossi to its discovery.
As is usual with new therapeutic research, none of the companies have had an approved product for years, which casts doubt on the potential of mRNA – and the viability of the companies working on it. However, in 2013, Moderna provided $ 240 million in funding from AstraZeneca to work on mRNA-based treatments for heart disease and went public in 2018, raising $ 621 million and presenting its plans for mRNA testing for treatment. of cancer.
Before 2020, the company, which employs more than 1,300 people, received promising animal test results for its candidates for mRNA-based drugs to treat cardiovascular disease and cancer, but it is still far from having products approved for human consumption.
Then Covid-19 happened and Moderna managed to produce a vaccine candidate a little over a month after Chinese scientists published the sequencing of the virus. About a month later, BioNTech partnered with Pfizer to work on the Covid-19 vaccine – and the companies set out to make history.
In a matter of months, Moderna went from an unknown company to a world-renowned brand, and mRNA from obscure technology to perhaps the most exciting medical innovation in decades. “For a new therapeutic modality, it’s actually pretty fast, given that hundreds of millions of people now receive an mRNA product,” Rossi said.
Rossi has always thought it was only a matter of time before the mRNA proved its worth. The pandemic, of course, has dramatically accelerated progress, but in the future, Rossi believes it makes sense for vaccines to be the first approved mRNA treatment. “It’s a very low technical band. You have mRNA for an antigen that someone has never been exposed to, and you can measure antibody levels very quickly in the peripheral blood, ”he says. “You have to dose it once or twice, it’s not like you dose it every day for five years before you start seeing clinical results.”
In fact, it’s so easy, Rossi believes, that eventually the entire vaccine industry will use mRNA technology.
What can mRNA treat next?
It took more than a decade, but the scientific community is finally realizing the potential of mRNA. “When we published our initial study, which started the whole thing in 2010, I actually expected the whole world of science to start making mRNA, because it had that kind of power, and I was a little surprised it didn’t happen,” Rossi said.
Although many potential applications will use mRNA to instruct the immune system to behave in a certain way, he believes that mRNA technology will quickly transcend conventional vaccines that target an external pathogen. MRNA therapies may soon be adapted to instruct the human immune system to fight its specific type of cancer or to target protein deficiency in certain organs without the toxic side effects of traditional medicines. “We know exactly what it does (mRNA),” says Rossi. “I like biology, which is nice and simple that way.”
“There is a new mRNA company that sprouts like mushrooms every day on the planet. So there will literally be hundreds in five years. And they will all have different programs working on different things. And I can tell you that there will be no vaccines. That would be ridiculous because there is not enough room for everyone to get vaccinated, “he said.
He predicts that we will receive the first non-vaccine mRNA therapeutic drug in five years and there will be 25 or 30 approved ones in the next decade.
Cancer, poisons and other lunar images
Given the virtuous excitement caused by his 2010 publication on mRNA, Rossi would have reason to believe that he played a role in saving humanity. Yet he is as humble as you would expect him to be. “I’m happy to have been an important lever in starting mRNA therapy, that’s for sure. But you know, we built on the shoulders of others who passed before us, and many people also followed us. That’s the nature of science, “he said.
Although he no longer participates in Modern and has retired from academia full-time, Rossi continues to participate in various areas of medical research and is involved in the management of several companies, including those working with multiple sclerosis and oncology. “I just can’t say no to good science,” he says.
And as for his personal mRNA boundary, his Holy Grail, he does not cure cancer or autoimmune disease. “My personal shot is snake venom and antinomies for snake bites,” he says.
Acute poisoning, he says, is something that mRNA can target effectively because it can act very quickly. “You inject it into a person and within hours, the protein you want is expressed,” he explains. The end product of such a study, as he imagines it, would be an antidote that could act on the deadliest species in a given area, delivered in a way that can be preserved for a long time in very remote areas – such as dust that can to be stored for long periods of time and to dissolve rapidly.
“You will be surprised at how many people die each year from a snake bite because there is no antibody available or they are in very remote areas. So this is something that I think is completely addressable and I don’t think anyone is working on it, “Rossi said. Accurate estimates of snake bite deaths are difficult because many countries do not report them, but the number can reach nearly 100,000 a year.
Cancer, pathogens, autoimmune disease – with the possible scope of application, will we finally be able to cure the mRNA on our way to immortality? Rossi doesn’t think so.
“Immortality is not something that will ever be achieved,” he said. “We’re falling apart too completely.”