The success of messenger RNA vaccines in the COVID-19 pandemic could boost efforts to use the technology to tackle cancer, malaria and other intractable diseases.
Why it matters: There is an urgent need for new ways to prevent infection from viruses such as HIV and flu that have been difficult for conventional vaccines to tackle and to treat rare genetic diseases and cancers that kill millions every year. Messenger RNA (mRNA) -based vaccines and therapies hold great promise as a solution, but the technology is still in its infancy.
“The pandemic has warned the world how good this platform is, ”said Drew Weissman, an immunologist at the University of Pennsylvania whose research supports Moderna and Pfizer-BioNTech’s mRNA COVID-19 vaccines.
- “It will hopefully make future studies and approvals easier.”
The base: In every cell in your body, mRNA contains instructions for making proteins from one part of the cell to another.
- Proteins – a broad class of molecules containing antibodies, enzymes and some hormones – are at the heart of the immune system’s response to viral and bacterial invaders and, when a protein malfunctions, disease can result.
- Vaccines and therapies using mRNA can theoretically be used to train the immune system to recognize intruders and abnormalities and to correct or repair proteins involved in a wide variety of diseases.
- But the technology faces hurdles surrounding its delivery in the body, its effectiveness against some diseases, and its production.
The list of diseases The mRNA vaccine technology that can be applied is “huge,” says Weissman.
- It includes infectious diseases such as malaria and flu. And cystic fibrosis, sickle cell anemia, and cancers are all potential targets for mRNA-based therapies.
- But some conditions – such as diabetes, which result from the body’s insulin mismatch – may not be ripe for mRNA therapy because “we don’t control how much protein is produced by the RNA,” Weissman says.
How it works: MRNA-based vaccines contain the instructions for making antigen proteins that are found on the surface of a virus in the cells of the body. Those antigens are then produced by the cells and, in turn, ready 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 repair the right one function of a protein, while in others mRNA could be a way to deliver replacement proteins or gene editing enzymes to treat genetic diseases before birth.
Where it is: After decades of development and several setbacks for mRNA vaccines, two are now actively used to combat COVID-19. And pharmaceutical companies are chasing others.
- For example, Moderna has 24 mRNA vaccines in development, and in January the company announced that it was pursuing three new vaccines: for HIV, seasonal flu and the Nipah virus, which causes encephalitis and has a mortality rate of up to 75%.
- Clinical trials – one for a seasonal flu vaccine, another for a universal flu vaccine, a vaccine for genital herpes and two for HIV – are underway at Penn, Weissman says.
The effectiveness and safety COVID-19 mRNA vaccines and their delivery to millions of people during the pandemic have “greatly accelerated the technology,” said Sarah Fortune, a Harvard professor of immunology and infectious diseases 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 create vaccines that elicit different levels of immune response, allowing researchers to settle in sweet spots for diseases like TB, where an overly strong immune response is. can be dangerous.
What’s next: 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 to cells the code for proteins in a tumor, which can even be personalized to match an individual’s cancer mutations. The cells then produce those proteins and train the immune system to recognize and destroy the 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 location matters for cancers and other non-infectious diseases.
- Weissman told Antonio Regalado of MIT Tech Review that he has come up with a solution to get the nanoparticles that carry mRNA into bone marrow stem cells and he hopes to use it in gene therapy for sickle cell anemia.
WiderAnother challenge is likely to be tissue-level immunity, Fortune says, pointing to tuberculosis, an infection of the lungs that “ has lots of mechanisms to suppress the immune response so it doesn’t go crazy. It’s unclear whether mRNA vaccines will do that. intersect with those immune regulatory systems at the tissue level. “
- The vulnerability of mRNA also means that there can be strict production and storage needs.
- And the full costs of treatments are unknown – the large-scale production of mRNA vaccines is still being optimized and, despite their pandemic moment, RNA vaccines can still face financial headwinds, ”writes Elie Dolgin Nature News
It comes down to: There will be hurdles to making mRNA technology work in humans for a variety of diseases, Weissman says. “There is a lot we don’t know.”