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Biotechnology and health

The next generation of mRNA vaccines is on its way

Adding a photocopier gene to mRNA vaccines could make them last longer and curb side effects.

syringe in front of a strand of RNA that is larger at the right than at the left
Stephanie Arnett/MITTR | Envato

This article first appeared in The Checkup, MIT Technology Review's weekly biotech newsletter. To receive it in your inbox every Thursday, and read articles like this first, sign up here.

Welcome back to The Checkup! Today I want to talk about … mRNA vaccines.

I can hear the collective groan from here, but wait—hear me out! I know you’ve heard a lot about mRNA vaccines, but Japan recently approved a new one for covid. And this one is pretty exciting. Just like the mRNA vaccines you know and love, it delivers the instructions for making the virus’s spike protein. But here’s what makes it novel: it also tells the body how to make more mRNA. Essentially, it provides instructions for making more instructions. It’s self-amplifying.

I’ll wait while your head explodes.

Self-amplifying RNA vaccines (saRNA) offer a couple of important advantages over conventional mRNA vaccines, at least in theory. Because saRNA vaccines come with a built-in photocopier, the dose can be much lower. One team of researchers tested both an mRNA vaccine and an saRNA vaccine in mice and found that they could achieve equivalent levels of protection against influenza with just 1/64th the dose. Second, it’s possible that saRNA vaccines will induce a more durable immune response because the RNA keeps copying itself and  sticks around longer. While mRNA might last a day or two, self-amplifying RNA can persist for a month.

Lest you think that this is just a tweaked version of conventional mRNA, It’s not. “saRNA is a totally different beast,” Anna Blakney, a bioengineer at the University of British Columbia, told Nature. (Blakney was one of our 35 Innovators Under 35 in 2023.)

What makes it a different beast? Conventional mRNA vaccines consist of messenger RNA that carries the genetic code for covid’s spike protein. Once that mRNA enters the body, it gets translated into proteins by the same cellular machinery that translates our own messenger RNA. 

Self-amplifying mRNA vaccines contain a gene that encodes the spike protein as well as viral genes that code for replicase, the enzyme that serves as a photocopier. So one self-amplifying mRNA molecule can produce many more. The idea of a vaccine that copies itself in the body might sound a little, well, unnerving. But there are a few things I should make clear. Although the genes that give these vaccines the ability to self-amplify come from viruses, they don’t encode the information needed to make the virus itself. So saRNA vaccines can’t produce new viruses. And just like mRNA, saRNA degrades quickly in the body. It lasts longer than mRNA, but it doesn’t amplify forever. 

Japan approved the new vaccine, called LUNAR-COV19, in late November on the basis of results from a 16,000-person trial in Vietnam. Last month researchers published results of a head-to-head comparison between LUNAR-COV19 and Comirnaty, the mRNA vaccine from Pfizer-BioNTech. In that 800-person study, vaccinated participants received either five  micrograms of LUNAR-COV19 or 30 micrograms of Comirnaty as a fourth dose booster. Reactions to both shots tended to be mild and resolve quickly. But the self-amplifying mRNA shot did elicit antibodies in a greater percentage of people than Comirnaty. And a month out, antibody levels against Omicron BA.4/5 were higher in people who received LUNAR-COV19. That could be a signal of increased durability.

The company has already filed for approval in Europe. It’s also working on a self-amplifying mRNA vaccine for flu, both seasonal and pandemic. Other companies are exploring the possibility that self-amplifying mRNA might be useful in rare genetic conditions to replace missing proteins. It’s an mRNA bonanza that will hopefully lead to better vaccines and new therapies. 

Another thing

Babies and AI learn language in very different ways. The former rely on a relatively small set of experiences. The latter relies on data sets that encompass a trillion words. But this week I wrote about a new study that shows AI can learn language like a baby—at least some aspects of language. The researchers found that a neural network trained on things a single child saw and heard over the course of a year and a half could learn to match words to the objects they represent. Here’s the story. 

Read more from MIT Technology Review’s archive

mRNA vaccines helped tackle covid, but they can help with so much more—malaria, HIV, TB, Zika, even cancer. Jessica Hamzelou wrote about their potential in January, and I followed up with a story after two mRNA researchers won a Nobel Prize. 

Using self-amplifying RNA isn’t the only way to make mRNA vaccines more powerful. Researchers are tweaking them in other ways that might help boost the immune response, writes Anne Trafton

From around the web

Elon Musk says his company Neuralink has implanted a brain chip in a person for the first time. The device is designed to allow people to control external devices like smartphones and computers with their thoughts. (Washington Post)

In August I  wrote about Vertex’s quest to develop a non-opioid pain pill. This week the company announced positive results from phase 3 trials. The company expects to seek regulatory approval in the coming months, and if approved, the drug is likely to become a blockbuster. (Stat)

In some rare cases, it appears that Alzheimer’s can be transmitted from one person to another. That’s the conclusion of a new study: it found that eight people who received growth hormone from the brains of cadavers before the 1980s had sticky beta-amyloid plaques in their brains, a hallmark of the disease. The growth hormone they received also contained these proteins. And when researchers injected these proteins into mice, the mice also developed amyloid plaques. (Science)

Correction: A previous version of this article mischaracterized the therapy Arcturus is developing for ornithine transcarbamylase deficiency as using saRNA. It involves regular mRNA.

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