The box office success of RNA messenger vaccines in the COVID-19 pandemic could boost efforts to use technology to fight cancer, malaria and other intractable diseases.
Why it’s important: There is an urgent need for new ways to prevent virus infection such as HIV and the flu that conventional vaccines have struggled to address and to treat rare genetic diseases and cancers that kill millions each year. Vaccines and messenger RNA (mRNA) -based therapies are promising as a solution, but the technology is still in its infancy.
“The pandemic has alerted the world how good this platform is, ”says Drew Weissman, an immunologist at the University of Pennsylvania whose research supports Moderna and Pfizer-BioNTech’s COVID-19 mRNA vaccines.
- “We hope it will facilitate future studies and approvals.”
The basics: In all cells of the body, mRNA contains 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 malfunctions, 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 number of diseases.
- But technology faces obstacles around its distribution in the body, its effectiveness against some diseases, and its production.
The list of diseases Weissman says the mRNA vaccine technology is “huge.”
- It includes infectious diseases such as malaria and influenza. And cystic fibrosis, sickle cell anemia, and cancers are potential targets for mRNA-based therapies.
- But some diseases, such as diabetes, which result from poor regulation of insulin in the body, may not be ripe for mRNA therapy because “we have no control over the amount of protein that RNA produces. “says Weissman.
How it works: MRNA-based vaccines contain instructions for making antigen proteins that are on the surface of a virus in the body’s cells. These antigens are made by the cells and in turn cover the immune system to protect the host if the virus attacks.
- With mRNA therapies, the goal in cases such as cystic fibrosis may be to restore the correct function of one protein, while in others, mRNA could be a way to supply replacement proteins or gene editing enzymes to treat genetic diseases before birth.
Where is it: After decades of development and several setbacks for mRNA vaccines, two are being actively deployed to combat COVID-19. And pharmaceutical companies are chasing others.
- Modern, for example, has 24 mRNA vaccines in development, and in January the company announced it was pursuing three new vaccines: for HIV, seasonal flu, and the Nipah virus, which causes encephalitis and has a mortality rate. of 75%.
- At Penn, clinical trials are underway (one for a seasonal flu vaccine, another for a universal flu vaccine, a genital herpes vaccine, and two for HIV), according to Weissman.
Efficiency 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 Harvard professor of immunology and infectious diseases who studies tuberculosis.
- She and others take advantage of the speed with which mRNA vaccines can be made by connecting mRNA sequences to produce vaccines that trigger different levels of immune response, allowing researchers to welcome sweet spots for diseases such as tuberculosis where a too strong immune response can be dangerous.
What follows: Researchers are trying to use mRNA for therapies against non-infectious diseases that cannot be prevented with a vaccine.
- In the case of cancer, mRNA is being investigated as a way to deliver to cells the protein code of a tumor, which could even be customized to match the cancer mutations of a tumor. individual. Cells produce these proteins, training the immune system to recognize and destroy cancer.
- Some early 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, location is important.
- Weissman told Antonio Regalado of the MIT Tech Review that he found a solution to get the nanoparticles that carry the mRNA to the bone marrow stem cells and hopes to use it to administer gene therapy for sickle cell anemia. .
More broadly, another challenge is likely to be tissue-level immunity, according to Fortune, who points to tuberculosis, a lung infection, which “has many mechanisms to reduce the immune response and thus does not go crazy. It is unclear whether vaccines with mRNA they cross with these systems of tissue immune regulation “.
- The fragility of mRNA also means that there may be strict manufacturing and storage needs.
- And the total cost of treatments is unknown: large-scale manufacturing of mRNA vaccines is still being optimized and, despite its pandemic moment, “RNA vaccines can still suffer from financial winds, ”writes Elie Dolgin Nature News.
The summary: There will be obstacles to getting mRNA technology to work in humans for different diseases, Weissman says. “There are a lot of things we don’t know.”