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Illustration: Sarah Grillo/Axios

The blockbuster success of messenger RNA vaccines in the COVID-19 pandemic could give a boost to efforts to use the technology to tackle cancers, malaria and other intractable illnesses.

Why it matters: There's a pressing need for new ways to prevent infection from viruses like HIV and influenza that conventional vaccines have struggled to address and to treat rare genetic diseases and cancers that kill millions each year. Vaccines and therapies based on messenger RNA (mRNA) hold promise as a solution, but the technology is still in its infancy.

"The pandemic has alerted the world to how good this platform is," says Drew Weissman, an immunologist at the University of Pennsylvania whose research underpins the mRNA COVID-19 vaccines by Moderna and Pfizer-BioNTech.

  • "It will hopefully make future studies and approvals easier."

The basics: In every cell in your body, mRNA carries instructions for making proteins from one part of the cell to another.

  • Proteins — a broad class of molecules that includes antibodies, enzymes and some hormones — are at the center of the immune system's response to viral and bacterial invaders and, when a protein malfunctions, disease can result.
  • Vaccines and therapies that use mRNA can, in theory, be used to train the immune system to recognize invaders and aberrations and correct or restore proteins involved in a host of diseases.
  • But the technology faces hurdles around its delivery within the body, its effectiveness against some diseases and its production.

The list of diseases mRNA vaccine technology could be applied to is "enormous," Weissman says.

  • It includes infectious diseases like malaria and influenza. And cystic fibrosis, sickle cell anemia and cancers are all potential targets for mRNA-based therapies.
  • But some conditions — like diabetes, which results from misregulation of insulin in the body — may not be ripe for mRNA therapy because "we don't have control over how much protein is produced by the RNA," Weissman says.

How it works: Vaccines based on mRNA carry the instructions for making antigen proteins found on the surface of a virus into the body's cells. Those antigens are then made by the cells and in turn prime the immune system to protect the host if the virus attacks.

  • With mRNA therapies, the goal in cases like cystic fibrosis may be to restore the proper function of a protein, whereas in others, mRNA could be a way to deliver replacement proteins or gene-editing enzymes to treat genetic diseases before birth.

Where it stands: After decades of development and several setbacks for mRNA vaccines, two are now being actively deployed to fight COVID-19. And pharmaceutical companies are pursuing others.

The effectiveness and safety of COVID-19 mRNA vaccines and their delivery to millions of people during the pandemic have "tremendously accelerated" the technology, says Sarah Fortune, a professor of immunology and infectious disease at Harvard who studies tuberculosis.

  • She and others are taking advantage of the speed at which mRNA vaccines can be made by plugging in mRNA sequences to make vaccines that trigger different levels of immune response, allowing researchers to home in on sweet spots for diseases like TB where too strong an immune response can be dangerous.

What's next: Researchers are trying to use mRNA for therapies for noninfectious diseases that can't be prevented with a vaccine.

  • For cancer, mRNA is being investigated as a way to deliver to cells the code for proteins in a tumor, which could even be personalized to match an individual's cancer mutations. The cells then produce those proteins, training the immune system to recognize and destroy the cancer.
  • Some early results are promising, but its success has been limited in other studies.

The challenges: It can be difficult to direct mRNA to specific organs and types of cells, and for cancers and other noninfectious diseases, location matters.

  • Weissman told MIT Tech Review's Antonio Regalado he's come up with a solution to get the nanoparticles that carry mRNA to bone marrow stem cells and he hopes to use it to deliver gene therapy for sickle cell anemia.

More broadly, another challenge is likely to be tissue-level immunity, says Fortune, pointing to tuberculosis, an infection of the lungs, which "have many mechanisms to tamp down the immune response so it doesn’t go crazy. It's unclear whether mRNA vaccines will intersect with those tissue level immune regulatory systems."

  • The fragility of mRNA also means there can be strict manufacturing and storage needs.
  • And the full cost of treatments is unknown — large-scale manufacturing of mRNA vaccines is still being optimized and, despite their pandemic moment, "RNA vaccines might yet face financial headwinds," Elie Dolgin writes for Nature News.

The bottom line: There will be hurdles in getting mRNA technology to work in humans for different diseases, Weissman says. "There's a lot we don't know."

Editor's note: This post has been clarified to say that Moderna has 24 mRNA-based vaccines or therapies in development (not 24 mRNA vaccines).

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The latest: As many as 99 people are reported missing, Miami-Dade County's police director said, per the Miami Herald.

Biden strikes infrastructure deal with bipartisan group of senators

President Biden announced Thursday that he had agreed to a roughly $1 trillion infrastructure plan with a bipartisan group of ten senators, declaring: "We have a deal."

Why it matters: The agreement on the size and scope of an infrastructure package is a major achievement for Biden, who has long been a proponent of bipartisanship, but the compromise still faces serious hurdles in the House and Senate.

Pacific Northwest soon to be ground zero for record-shattering heat

Computer model projection showing the unusually strong heat dome over the Pacific Northwest on Sunday. (PivotalWeather).

A heat wave is bringing unprecedented high temperatures to the Pacific Northwest — a region of the country typically cooled by the ocean, rather than central air conditioning. The heat will begin Friday and last into early next week.

Why it matters: The heat wave will shatter monthly and all-time temperature records in the Pacific Northwest. Some of the records could break the old milestones by several degrees.