How a messenger RNA drug became the first novel candidate to take on the COVID-19 pandemic.
In the world of vaccines, this was crazy fast.
The SARS-CoV2 coronavirus was sequenced on January 7. Scientists at Moderna and the National Institute of Allergy and Infectious Diseases (NIAID) selected a vaccine target on January 13. By February 7, Moderna had a vaccine candidate. After some safety testing, on February 23 the company shipped this “mRNA-1273” vaccine to the NIAID, which is now recruiting for a first clinical trial.*
Moderna is a pioneer of messenger RNA (mRNA) drugs, designed to generate exquisitely tailored therapeutic proteins within each patient’s body.
As you recall, the central dogma of molecular biology is that DNA makes RNA that makes protein. The mRNA drug candidates created by Moderna and a few other biotechs tap into those natural steps.
Once researchers design the desired therapeutic proteins, manufacturing for an mRNA drug starts with a DNA template for those proteins. The DNA is treated with a suite of biological players to generate mRNA. Next, the mRNA is purified and put inside a lipid nanoparticle built to let it slip inside cells. After quality controls, you get an injectable drug. Once it’s injected, the patient’s own cells churn out proteins that attack the disease—in the case of coronavirus, by mimicking the deadly disease to alert the immune system.
No mRNA drugs have been approved, but there’s a real chance they will become that rare beast, a genuine revolution in medicine. That’s what Juan Andres, chief technical operations and quality officer, told me last summer when I visited the company’s giant facility in Norwood, Massachusetts for a Nature story on flu vaccines.
Traditional biotech drugs go after extracellular proteins, because the drugs can’t enter cells. But mRNA drugs open the possibility of producing proteins inside the cell. Moreover, unlike gene therapies, “we are not touching the DNA,” Andres said. “We are not touching the hardware of the body.”
mRNA drug manufacture and delivery are also stunningly efficient, at least in theory. You’re not using cells at all, so you don’t need the giant bioreactor vats in traditional biotech factories. In fact, the main bioreactor in the Norwood plant was roughly the size of my home’s hot-water heater.
Unusually for a biotech startup, even one as well-heeled as Moderna, the company invested heavily to achieve fully integrated production, starting with raw materials, at Norwood. “We produce the active product ingredient, which is basically mRNA itself,” Andres said. “We formulate it, we fill into vials, we finish it, we do the quality control and we ship it into clinical sites.”
So one of Moderna’s potential manufacturing advantages is speed—especially crucial for vaccines for seasonal flu or for epidemics, where the clock is always ticking (or rather, alarms are ringing loudly). The technology also may offer other major benefits, eventually, in product quality, scalability and cost.
And mRNA drugs just may end up addressing a broad spectrum of medical need. Moderna is examining many opportunities for treatment, among them personalized cancer vaccines and localized regenerative medicine.
But the company’s most advanced programs are in preventive vaccines. So far it has chalked up positive results in phase 1 clinical trials for six vaccines, among them a cytomegalovirus vaccine combining no fewer than six mRNAs that has moved into a phase II trial.
Good safety signals from these early vaccine studies encouraged NIAID to launch the mRNA-1273 trial even before the vaccine was tested in animal studies.
It will be many months before trials can prove safety and efficacy for mRNA-1273, if indeed they do.
The desperate global need drove both quick funding for the novel vaccine from the Coalition for Epidemic Preparedness Innovations (yes, not the CDC) and the supercharged development. “There was a huge amount of motivation,” Andres commented at a Moderna online forum last week. “I have not seen this kind of energy anywhere before.”
* Volunteers received first injections on March 16.
Images courtesy Moderna.