“I said, ‘I’m an RNA scientist. I can do anything with RNA,'” recalled Dr. Karikó to Dr. Weissman. He asked her: Could you make an HIV vaccine?
“Oh yes, oh yes, I can do it,” Dr. Karikó said.
Up until this point, commercial vaccines had delivered modified viruses, or parts thereof, into the body to train the immune system to attack invading microbes. An mRNA vaccine would instead contain instructions – encoded in mRNA – that would allow the body’s cells to churn out their own viral proteins. This approach, thought Dr. Weissman, would better mimic a real infection and elicit a more robust immune response than traditional vaccines.
It was a fringe idea that few scientists thought would work. A molecule as fragile as mRNA seemed an unlikely vaccine candidate. The reviewers weren’t impressed either. His lab had to be run with seed capital, which the university gives to new faculty members to get started.
At that time it was easy to synthesize mRNA in the laboratory to encode any protein. dr Weissman and Karikó inserted mRNA molecules into human cells growing in petri dishes, and as expected, the mRNA instructed the cells to make specific proteins. But when they injected mice with mRNA, the animals got sick.
“Their fur became ruffled, they crouched, they stopped eating, they stopped running,” said Dr. Weissman. “Nobody knew why.”
For seven years, the two studied how mRNA works. Countless attempts failed. They walked down one dead end after the other. Their problem was that the immune system saw the mRNA as part of an invading pathogen and attacked it, making the animals sick and destroying the mRNA.
Finally they solved the mystery. The researchers discovered that cells protect their own mRNA with a specific chemical modification. So the scientists tried to make the same change to mRNA that was made in the lab before injecting it into cells. It worked: the mRNA was taken up by cells without triggering an immune response.