“I said, ‘I am an RNA scientist. I can do anything with RNA,’” Dr. Karikó recalled telling Dr. Weissman. He asked her: Could an H.I.V. be made? vaccine?
“Oh yeah, oh yeah, I can do it,” Dr. Karikó said.
Commercial vaccines have carried modified viruses or bits of them into the body in order to train the immune system against invading microbes. An mRNA vaccine would instead carry instructions — encoded in mRNA — that would allow the body’s cells to pump out their own viral proteins. Dr. Weissman felt that this approach would better mimic a real infection, and trigger a stronger immune response, than traditional vaccines.
It was a fringe idea that very few scientists believed would work. It seemed unlikely that a molecule as fragile and ineligible as mRNA would be a candidate for a vaccine. Grant reviewers weren’t impressed either. His lab was funded by seed money, which the university provides to new faculty members to start their careers.
It was possible to synthesize any type of mRNA in the laboratory at that time. Drs. 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. The mice got sick when they injected mRNA to them.
“Their fur got ruffled, they hunched up, they stopped eating, they stopped running,” Dr. Weissman said. “Nobody knew why.”
The pair worked together for seven years to study the mechanisms of mRNA. Numerous experiments were unsuccessful. They kept going down the same path. Their problem was that mRNA is seen by the immune system as an invading pathogen. It attacks it and makes animals sick.
They eventually solved the mystery. Researchers discovered that cells protect their mRNA using a particular chemical modification. The scientists then tried to make the same chemical modification to the mRNA in the lab before injecting it into the cells. It worked: The cells took up the mRNA without triggering an immune response.
Source: NY Times
