Noubar Afeyan, Bob Langer, Tim Springer, and a host of other Boston biotech luminaries have been sitting on a big secret. Today we’re going to out them.
Moderna Therapeutics, a stealthy startup in Cambridge, MA, is the subject of their considerable brainpower and experiments. The company is finally emerging from stealth, having raised $40 million to date from Flagship Ventures and private investors.
Here’s the idea: Instead of producing protein drugs using genetically engineered bacteria in dedicated manufacturing plants—the dominant biotech model of the past 30 years—why not enable the human body to produce its own protein drugs, on demand?
Much easier said than done, of course. The key is developing a technique that triggers cells to produce the drug proteins, without also making the body’s immune system go haywire. To that end, Moderna (pronounced “mode-UR-nuh”) starts by making a specially modified version of messenger RNA. Inject that messenger RNA into the body—so far the company has done tests in mice, rats, and monkeys—and the cells produce the drug proteins right in the body. (More on this below, but the gist is that mRNA, an important intermediary in the process that cells use to make proteins, can be produced using relatively cheap chemistry, whereas proteins themselves cannot.)
If the process works safely in human patients—always a huge “if” in biotech—it could be the biggest story since, well, probably the rise of Genentech and the entire industry in the late ‘70s and early ‘80s. But there’s a lot to be done before the company gets to that point.
“If we’re safe in man, this is crazy,” says Stéphane Bancel, the CEO of Moderna. “It will change the industry in several ways. One is how fast we’ll be able to bring new protein-based drugs to market, with a manufacturing process that’s much cheaper. Our technology can make any human protein.”
The back-story here is pretty interesting. Moderna’s technology was born in the lab of researcher Derrick Rossi at the Harvard Stem Cell Institute and Harvard Medical School. In 2010, Rossi’s team developed a method for modifying messenger RNA and injecting it into human cells as a way to produce cells that mimic embryonic stem cells, in that they can become any other kind of cell. The key advance: the method did not run the risk of triggering an immune-system response if the cells were used to treat patients. (The original technique for producing such stem cells used viruses, posing a risk of an immune response. It also earned its inventor, Shinya Yamanaka, a share of the Nobel Prize in physiology/medicine this year. Yamanaka’s Nobel lecture is this Friday.)
To commercialize his method, Rossi met with Tim Springer, an immune-disease expert also from Harvard Medical School; Springer is known for founding LeukoSite, which was bought by Millennium in 1999. They then hooked up with Bob Langer, the prolific MIT scientist and entrepreneur, and Ken Chien, a cardiology expert from Massachusetts General Hospital and Harvard Medical School. Together they had an idea to start a stem-cell company. Their first stop: venture capitalist Noubar Afeyan, the managing partner and CEO of Flagship Ventures.
Afeyan (pictured at left) knows his biochemical engineering and proteins, among other things, and he saw something very different in what they were showing him. For one thing, he didn’t want to invest in a stem-cell company—there would be too much biology risk. Instead, Afeyan asked the researchers if they could inject some of their messenger RNA, coded for a human protein (say, EPO, a hormone that regulates production of red blood cells), into a mouse and see if they find the human protein in the mouse’s blood.
Rossi went back to his lab and did the experiment—and it worked. Afeyan and the team recognized the significance of the result and filed
