The blockbuster success of messenger RNA vaccines in the COVID-19 pandemic could boost 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 such as HIV and the flu that conventional vaccines have strived to address and treat rare genetic diseases and cancers that kill millions of people each year. Vaccines and therapies based on messenger RNA (mRNA) 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 is based on COVID-19 mRNA vaccines by Moderna and Pfizer-BioNTech.
- “We hope it will facilitate future studies and approvals.”
The basics: In every cell in your body, mRNA contains instructions for making proteins from one side of the cell to the other.
- Proteins – a broad class of molecules that include 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 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 delivery to the body, its effectiveness against disease and its production.
List of diseases The mRNA vaccine technology that could be applied is “enormous,” says Weissman.
- It includes infectious diseases such as malaria and influenza. 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 improper regulation of insulin in the body – may not be ripe for mRNA therapy because “we have no control over the amount of protein produced by RNA,” says Weissman. .
How it works: MRNA-based vaccines carry instructions for transforming antigenic proteins found on the surface of a virus into body cells. These antigens are then produced by the cells and, in turn, prioritize the immune system to protect the host if the virus attacks.
- With mRNA therapies, the goal in cases such as cystic fibrosis may be correct recovery function of one protein, while in others, mRNA could be a way to provide replacement proteins or gene editing enzymes to treat genetic diseases before birth.
Where is it: After decades of development and several failures for mRNA vaccines, two are now actively underway to combat COVID-19. And pharmaceutical companies are pursuing others.
- Modern, for example, has 24 mRNA vaccines under development, and in January the company announced that it is targeting three new vaccines: for HIV, seasonal flu and 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, one genital herpes vaccine and two for HIV – are underway at Penn, says Weissman.
Effectiveness and safety COVID-19 mRNA vaccines and their delivery to millions of people during the pandemic have “greatly accelerated” the technology, says Sarah Fortune, a professor of immunology and infectious diseases at Harvard who studies tuberculosis.
- She and others take 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 be in sweet spots for diseases such as TB where too strong an immune response 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 provide cells with the protein code in a tumor, which could even be customized to fit an individual’s cancer mutations. The cells then produce these proteins, causing the immune system to recognize and destroy the cancer.
- Some early results are promising, but its success has been limited in other studies.
Challenges: It can be difficult to target mRNA to specific organs and cell types, and for cancer and other non-infectious diseases, location matters.
- Weissman told Antonio Regalado of the MIT Tech Review that he came up with a solution to obtain nanoparticles that carry mRNA to bone marrow stem cells and hopes to use it to provide gene therapy for sickle cell disease.
Larger, another challenge is probably tissue immunity, says Fortune, pointing to tuberculosis, an infection of the lungs, which “has many mechanisms to reduce the immune response so as not to go crazy. It is unclear whether mRNA vaccines will intersect with those tissue-regulated immune systems.
- Fragility of mRNA also means that there may be strict production and storage requirements.
- And the total cost of treatments is unknown – large-scale manufacturing of mRNA vaccines is still optimized and, despite their pandemic momentum, “RNA vaccines could still face financial winds, “Elie Dolgin writes for Nature news.
Bottom line: Weissman says there will be obstacles to getting mRNA technology to work in humans for various diseases. “There are many we don’t know.”