There is one application in addition to vaccines, however, where brief exposure to messenger RNA could have effects lasting years, or even a lifetime.
In late 2019, before covid-19, the US National Institutes of Health and the Bill and Melinda Gates Foundation announced they would spend $200 million developing affordable gene therapies for use in sub-Saharan Africa. The top targets: HIV and sickle-cell disease, which are widespread there.
Gates and the NIH didn’t say how they would make such cutting-edge treatments cheap and easy to use, but Weissman told me that the plan may depend on using messenger RNA to add instructions for gene-editing tools like CRISPR to a person’s body, making permanent changes to the genome. Think of mass vaccination campaigns, says Weissman, except with gene editing to correct inherited disease.
Right now, gene therapy is complex and expensive. Since 2017, several types have been approved in the US and Europe. One, a treatment for blindness, in which viruses carry a new gene to the retina, costs $425,000 per eye.
A startup called Intellia Therapeutics is testing a treatment that packages CRISPR into RNA and then into a nanoparticle, with which it hopes to cure a painful inherited liver disease. The aim is to make the gene scissors appear in a person’s cells, cut out the problem gene, and then fade away. The company tested the drug on a patient for the first time in 2020.
It’s not a coincidence that Intellia is treating a liver disease. When dripped into the bloodstream through an IV, lipid nanoparticles tend to all end up in the liver—the body’s house-cleaning organ. “If you want to treat a liver disease, great—anything else, you have a problem,” says Weissman.
But Weissman says he’s figured out how to target the nanoparticles so that they wind up inside bone marrow, which constantly manufactures all red blood cells and immune cells. That would be a hugely valuable trick—so valuable that Weissman wouldn’t tell me how he does it. It’s a secret, he says, “until we get the patents filed.”
He intends to use this technique to try to cure sickle-cell disease by sending new instructions into the cells of the body’s blood factory. He’s also working with researchers who are ready to test on monkeys whether immune cells called T cells can be engineered to go on a seek-and-destroy mission after HIV and cure that infection, once and for all.
What all this means is that the fatty particles of messenger RNA may become a way to edit genomes at massive scales, and on the cheap. A drip drug that allows engineering of the blood system could become a public health boon as significant as vaccines. The burden of sickle-cell, an inherited disease that shortens lives by decades (or, in poor regions, kills during childhood), falls most heavily on Black people in equatorial Africa, Brazil, and the US. HIV has also become a lingering scourge: about two-thirds of people living with the virus, or dying from it, are in Africa.
Moderna and BioNTech have been selling their covid-19 vaccine shots for $20 to $40 a dose. What if that were the cost of genetic modification, too? “We could correct sickle-cell with a single shot,” Weissman says. “We think that is groundbreaking new therapy.”
There are fantastic fortunes to be made in mRNA technology. At least five people connected to Moderna and BioNTech are now billionaires, including Bancel. Weissman is not one of them, though he stands to get patent royalties. He says he prefers academia, where people are less likely to tell him what to research—or, just as important, what not to. He’s always looking for the next great scientific challenge: “It’s not that the vaccine is old news, but it was obvious they were going to work.” Messenger RNA, he says, “has an incredible future.”