One of the favorite things about Moderna co-founder Derrick Rossi is that there are three keys to life on Earth.
“DNA makes mRNA makes protein makes life,” he says.
The experimental technology behind the coronavirus vaccines from Moderna and Pfizer harnesses the power of one of these keys – messenger RNA or mRNA. These vaccines are the first medical products to use mRNA in this way, but they certainly won’t be the last. A COVID-19 vaccine is just one of the almost infinite possibilities that the technology offers, says Rossi.
Being able to control mRNA would allow scientists to manipulate life in surprising new ways. This may open the door to new treatments for diseases like cystic fibrosis, cancer and HIV. Now, supported by the apparent success of the COVID-19 vaccine, Rossi says that these other applications may soon materialize.
“Within 10 years, we will probably see dozens of mRNA therapies. In perhaps 15 years, we will see perhaps 50 or 60 mRNA therapies,” he says.
Before Rossi co-founded Moderna, he was a biologist at Harvard working on mRNA. DNA is often described as the building block of life, but DNA is essentially a database of information that cells need to create proteins. RNA is the molecule that actually does the job of creating these proteins.
The possibilities were limitless. You know, RNA can code for anything.
Timothy Springer, immunologist
For years, Rossi and other scientists have tried to design strands of mRNA that would force cells to produce specific proteins. But long before this technique created the highest profile vaccines in the world, they failed.
“It didn’t work out entirely,”Rossi says. “So what it looked like to the cell was that the mRNA was a virus. And the cell, like a good soldier, would elicit a very robust antiviral response. “
Each time Rossi tried to insert the mRNA, the cell would either destroy the molecule or kill itself – it was not what he wanted. He felt like he had hit a wall.
The solution came from another part of the cell – and two scientists at the University of Pennsylvania discovered it. Katalin Karikó, then a junior scientist at UPenn and now senior vice president of BioNTech, another company that developed a COVID-19 vaccine, was trying to do the same thing as Rossi – and it didn’t work either. But a UPenn colleague, Dr. Drew Weissman suggested Karikó to try to use modified chemical letters in his mRNA code.
“By modifying the RNA, it hides the RNA. It’s like giving a fake passport, ”says Timothy Springer, an immunologist at Boston Children’s Hospital and Harvard Medical School. “And it worked brilliantly.”
“An hour later, we put the mice in this machine and we could see this bright spot.”
Derrick Rossi
The modified chemical letters disguised the mRNA, making it appear more or less innocent to the cell. When Rossi read about the work of Karikó and Weissman, he immediately started to incorporate the technique into his own research.. In one experiment, he directed the cells to create proteins called Yamanaka factors, which converted mature cells into stem cells. In another, he injected mice with the mRNA encoded by the protein that makes fireflies ignite.
“And then you know, an hour later, we put the mice in this machine and we could see this bright spot,” says Rossi.
The experiments were working, and now Rossi knew how to control one of the three most fundamental keys in life. He took the new data to Springer, also a talented entrepreneur, and asked him to help start a company based on the new technology.
Springer jumped on board, becoming the company’s first investor. They called it Moderna – short for modified and RNA. Both still own shares in the company.
“The possibilities were limitless,” says Springer. “You know, RNA can code anything. They may be encoding a secreted protein or enzyme in the cell or a vaccine unit, you know, to protect against SARS-CoV-2. “
In the past decade, Moderna and other companies like BioNTech have studied modified mRNA technology as a way to develop treatments for a wide variety of diseases, including heart failure and chikungunya viruses. Other researchers have found ways to use the modified mRNA to make advances in anti-aging research.
“Technology offers an agile platform on which you can change things quickly.”
Dr. Cathy Wu, Dana Farber Cancer Institute
And the modified mRNA is particularly suitable for creating vaccines, says Springer. This is because, although these modified chemical letters allow the molecule to sneak through cellular defenses, the compound still looks a little suspicious.
“He doesn’t completely sneak. There is a little bit of interest. Perhaps the eyebrows of the immune system get excited, ”says Springer.
The mRNA in a vaccine carries the code for a pathogenic protein – like the coronavirus spike protein. When the cell starts executing the vaccine code and making that protein, the already cautious immune system kicks in and produces a particularly strong immune response. Springer says this may be one of the reasons why the modern and Pfizer coronavirus vaccines have been so effective in clinical trials.
This property, along with others, makes modified mRNA an attractive option for cancer vaccines, says Dr. Cathy Wu, an oncologist at the Dana Farber Cancer Institute. These vaccines train the immune system to attack tumors, but they are expensive and take a long time to create vaccines. This is a problem for cancer patients.
“If someone has advanced cancer, you can’t wait that long,” she says. “Being able to produce vaccines in a timely manner is probably what it will take to make this really work.”
And mRNA vaccines can be made quickly. All you need to do to create a new one is to rewrite the vaccine’s genetic code. The COVID-19 vaccine took only a few days to design, as the researchers obtained the genome of the new coronavirus. This can also be an advantage if the coronavirus mutates to make current vaccines less effective.
“The technology offers an agile platform where you can change things quickly,” says Wu.
Now that the COVID-19 vaccine is being produced on a large scale, Wu says it may also help to reduce some technology costs, as manufacturers find more efficient ways to make mRNA. The last remaining step for cancer vaccines is to be tested in large clinical studies.
This also applies to other applications of modified mRNA. Wu points out that with two COVID-19 mRNA vaccines in use, billions of dollars are going to the new technology. Other therapies are unlikely to be far behind.
This segment aired on January 11, 2021.