How mRNA vaccines were made: Stopping progress and happy accidents

“I said, ‘I’m an RNA researcher.’ I can do anything with RNA, ”Dr. Karikó recalled telling Dr. Weissman. He asked him: Could you get an HIV vaccine?

“Oh yeah, oh, I can do it,” Dr. Karikó said.

Until then, commercial vaccines had carried modified viruses or pieces of them into the body to train the immune system to attack invading microbes. Instead, the mRNA vaccine would have instructions encoded in the mRNA that would allow the body’s cells to pump out their own viral proteins. This approach, Dr. Weissman thought, better mimics the actual infection and would elicit a more effective immune response than traditional vaccines.

It was an edge idea that few scientists believed would work. A fragile molecule similar to MRNA appeared to be an unlikely vaccine candidate. The evaluators of the grants were not impressed either. His lab had to be used with seed money that the university would give to new faculty members to get started.

Until then, mRNA was easily synthesized in the laboratory to encode any protein. Drs. Weissman and Karikó inserted mRNA molecules into human cells growing in petri dishes and, as expected, mRNA instructed the cells to produce specific proteins. But when they injected mRNA into mice, the animals became ill.

“Their fur was ruffled, they bent down, they stopped eating and running,” Dr. Weissman said. “No one knew why.”

For seven years, the couple studied the function of mRNA. Countless experiments failed. They wandered one dead end after another. Their problem was that the immune system sees the mRNA invading the piece of the pathogen and attacks it, making the animals sick while destroying the mRNA.

In the end, they solved the mystery. The researchers found that cells protect their own mRNA with a certain chemical modification. So the researchers tried to make the same change to the mRNA made in the lab before injecting it into the cells. It worked: the cells received the mRNA without an immune response.

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