The success of messenger RNA vaccines in the pandemic COVID-19 could spur efforts to use technology to fight cancer, malaria and other intractable diseases.
Why does it matter: There is an urgent need for new ways to prevent infection with viruses like HIV and influenza that conventional vaccines have endeavored to address and treat rare genetic diseases and cancers that kill millions each year. Vaccines and therapies based on messenger RNA (mRNA) promise to be a solution, but the technology is still in its infancy.
“The pandemic has alerted the world about how good this platform is, “says Drew Weissman, an immunologist at the University of Pennsylvania, whose research underlies the COVID-19 mRNA vaccines from Moderna and Pfizer-BioNTech.
- “This will make future studies and approvals easier.”
The basic: In each 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 include antibodies, enzymes and some hormones – are at the center of the immune system’s response to viral and bacterial invaders, and when a protein doesn’t work well, disease can occur.
- Vaccines and therapies that use mRNA can, in theory, be used to train the immune system to recognize invaders and aberrations and to correct or restore proteins involved in a range of diseases.
- But the technology faces obstacles around its delivery within the body, its effectiveness against some diseases and its production.
The list of diseases The technology of the mRNA vaccine that could be applied is “huge,” says Weissman.
- It includes infectious diseases like malaria and flu. And cystic fibrosis, sickle cell anemia and cancers are all potential targets for mRNA-based therapies.
- But some conditions – like diabetes, which results from poor insulin regulation in the body – may not be ripe for mRNA therapy because “we have no control over how much protein is produced by RNA,” says Weissman.
How it works: MRNA-based vaccines carry the instructions for making proteins from the antigen found on the surface of a virus in the cells of the body. These antigens are then produced by the cells and, in turn, prepare the immune system to protect the host if the virus attacks.
- With mRNA therapies, the goal in cases such as cystic fibrosis can be to restore the function of a protein, while in others, mRNA could be a way to deliver replacement proteins or gene-editing enzymes to treat genetic disorders before birth.
Where is it: After decades of development and several setbacks for mRNA vaccines, two are now being actively deployed to combat COVID-19. And pharmaceutical companies are looking for others.
- Moderna, for example, has 24 mRNA vaccines under development and, in January, the company announced that it was looking for three new vaccines: for HIV, seasonal flu and Nipah virus, which causes encephalitis and has a lethality of up to 75%.
- Clinical trials – one for a seasonal flu vaccine, one for a universal flu vaccine, a vaccine for genital herpes and two for HIV – are underway at Penn, says Weissman.
Efficiency and safety of COVID-19 mRNA vaccines and their delivery to millions of people during the pandemic has “tremendously accelerated” the technology, says Sarah Fortune, professor of immunology and infectious diseases at Harvard who studies tuberculosis.
- She and others are taking advantage of the speed with which mRNA vaccines can be made by connecting mRNA sequences to make vaccines that trigger different levels of immune response, allowing researchers to focus on sweet spots for diseases like TB, where a response very strong immune system can be dangerous.
What is the next: The researchers are trying to use mRNA for therapies for non-infectious diseases that cannot be prevented with a vaccine.
- For cancer, mRNA is being investigated as a way to deliver the protein code in a tumor to cells, which could even be customized to match an individual’s cancer mutations. The cells then produce these proteins, training the immune system to recognize and destroy the cancer.
- Some initial results are promising, but their success has been limited in other studies.
The challenges: It can be difficult to target mRNA to specific organs and cell types, and for cancers and other non-infectious diseases, localization is important.
- Weissman told Antonio Regalado of MIT Tech Review that he came up with a solution to obtain the nanoparticles that carry mRNA for bone marrow stem cells and he hopes to use it to provide gene therapy for sickle cell anemia.
Most widely, another challenge is likely to be tissue-level immunity, says Fortune, pointing to tuberculosis, an infection of the lungs, “which has many mechanisms to contain the immune response so it doesn’t go crazy. It is unclear whether mRNA vaccines will intersect with tissue-level immune regulatory systems. “
- The fragility of the mRNA also means that there may be strict manufacturing and storage needs.
- And the total cost of treatments is unknown – the large-scale manufacture of mRNA vaccines is still being optimized and, despite its pandemic moment, “RNA vaccines can still face financial headwinds, “writes Elie Dolgin to Nature News.
The end result: There will be obstacles to making mRNA technology work in humans for different diseases, says Weissman. “There is a lot that we don’t know.”