The successful success of messenger RNA vaccines in the COVID-19 pandemic could boost efforts to use the technology to tackle cancer, malaria and other serious diseases.
Why it matters: There is an urgent need for new ways to prevent infection by viruses such as HIV and influenza that have struggled to deal with conventional vaccines and to treat rare genetic diseases and cancers that kill millions annually. Vaccinations and therapies based on messenger RNA (mRNA) hold promise as a solution, but the technology is still in its infancy.
‘The pandemic has warned the world how good this platform is, ”says Drew Weissman, an immunologist at the University of Pennsylvania whose research supports the mRNA COVID-19 vaccines by Moderna and Pfizer-BioNTech.
- “It will hopefully facilitate future studies and approvals.”
The basics: 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 that include antibodies, enzymes and some hormones – are at the center of the immune system’s response to viral and bacterial invaders, and if a protein does not function, diseases can develop.
- Vaccinations and therapies using mRNA can in theory be used to train the immune system to recognize invaders and disorders and to correct or repair proteins involved in a variety of diseases.
- But technology faces obstacles around its delivery into the body, its effectiveness against some diseases and its production.
The list of diseases mRNA vaccine technology can be applied is ‘enormous’, says Weissman.
- These include infectious diseases such as malaria and influenza. And cystic fibrosis, sickle cell anemia, and cancers are all possible targets for mRNA-based therapies.
- But some conditions – such as diabetes, which is the result of insulin dysregulation in the body – may not be ripe for mRNA therapy because ‘we have no control over how much protein is produced by the RNA,’ says Weissman.
How it works: Vaccines based on mRNA contain the instructions for making antigenic proteins that occur on the surface of a virus in the body’s cells. Those antigens are then produced by the cells and in turn stimulate 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 recovery function of a protein, while mRNA may in other ways be a way to produce replacement proteins or gene-editing enzymes to treat genetic diseases before birth.
Where it says: After decades of development and several setbacks for mRNA vaccines, two are now being actively used to fight COVID-19. And pharmaceutical companies are chasing others.
- Moderna, for example, has 24 mRNA vaccines in development, and in January the company announced it was targeting three new vaccines: for HIV, seasonal flu and the Nipah virus, which causes encephalitis and has a mortality rate of as high as 75%.
- Clinical trials – one for a seasonal flu vaccine, one for a universal flu vaccine, one for genital herpes and two for HIV – are underway at Penn, Weissman said.
The efficiency and safety of COVID-19 mRNA vaccines and their delivery to millions of people during the pandemic “accelerated” the technology, says Sarah Fortune, a professor of immunology and infectious diseases at Harvard who studies tuberculosis.
- She and others use the speed at which mRNA vaccines can be made by plugging in mRNA sequences to make vaccines that cause different levels of immune response, enabling researchers to come up with sweet spots for diseases such as TB with a strong immune response. can be dangerous.
What’s next: Researchers are trying to use mRNA for therapies for non-communicable diseases that cannot be prevented with a vaccine.
- For cancer, mRNA is being investigated as a way to deliver the code for proteins in a tumor to cells, which can even be personalized to fit the individual’s cancer mutations. The cells then produce those proteins, which 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 direct mRNA to specific organs and cell types, and for cancers and other non-communicable diseases, it is important for location.
- Weissman told Antonio Regalado of MIT Tech Review that he came up with a solution to get the nanoparticles carrying mRNA to bone marrow stem cells and he hopes to use them to deliver gene therapy for sickle cell anemia.
Wider, another challenge is likely to be tissue-level immunity, says Fortune, pointing to tuberculosis, an infection in the lungs, which has many mechanisms to ease the immune response so that it does not go crazy. It is unclear whether mRNA vaccines cross with tissue-level immune regulatory systems. “
- The fragility of mRNA also means that there may be strict manufacturing and storage requirements.
- And the full cost of treatments is unknown – large-scale production of mRNA vaccines is still being optimized and, despite their pandemic moment, “RNA vaccines may still get financial wind, ”writes Elie Dolgin Nature News.
The conclusion: There will be obstacles to making mRNA technology work for different diseases in humans, says Weissman. “There’s a lot we do not know.”