We recently experienced the powers of a ground-breaking vaccine against COVID-19 thanks to mRNA technology, but it has even more potential to democratize access to bleeding-edge medical advancements. Messenger RNA or “mRNA” is a single-stranded RNA involved in protein synthesis. Although the blueprint for proteins in living cells was discovered six decades ago, its pharmaceutical potential was long overlooked. mRNA degradation prevention didn’t look promising; it was too unstable, not very effective, and inflammatory [1].
What does mRNA do?
Each mRNA messenger carries instructions to make a specific protein. These instructions act like a blueprint. mRNA then delivers these instructions for cells to put the protein together in a process known as translation. mRNA messengers carry protein building information from DNA in the cell’s nucleus all the way to the cell’s watery interior (cytoplasm), where our protein-producing machines read the mRNA sequences and translates each three-base mRNA codon (nucleotide triplets) into its corresponding amino acid inside a growing protein chain.
The future of mRNA
History of mRNA
Researchers have been experimenting with mRNA-based vaccines and treatments for several decades already. The first treatments were performed on rodents back in the early 1990s, for several diseases including diabetes and cancer. A first in medical history, the successful creation of the first mRNA vaccines against Covid-19 in 2020 was hailed as a triumph. The rapidly iterative advancements we mostly fueled by the independent contributions of scientists and researchers from all over the world. Researchers value mRNA for its adaptability and its capacity to activate the immune system. After the mRNA has been used to make protein, cells break it down naturally, usually within days to weeks [3].
The ability to deliver mRNA molecules to the proper immune cells in the body, as well as to increase its stability and effectiveness, were all things the medical world learned how to do. This
mRNA Therapy
mRNA is a platform for delivering instructions to cells; it is not one treatment for every infection. Researchers investigate different antigens, delivery systems and immune responses for tuberculosis, dengue and malaria. The cited tuberculosis commentary discusses research opportunities and obstacles; it does not establish vaccine efficacy or a current trial milestone for all three diseases. [4]
mRNA technology: Advantages and limitations
Sequence information and protein structure can help researchers choose vaccine targets. Target selection is only one step: an mRNA product must also deliver its instructions, produce a suitable immune response and be evaluated for safety and clinical protection. A commentary about tuberculosis vaccines is not a study validating a protein-structure prediction method.
Do mRNA Vaccines Contain Human Cells?
The Pfizer and Moderna pure mRNA synthesis do not not use any stem cells. The vaccines from AstraZeneca and Johnson & Johnson vaccines use adenovirus as a vehicle to deliver spike protein genes to the cells and these viruses need to grow in those cells. After culturing, the adenovirus is harvested from the cells and purified so that the final vaccine contains only the virus vehicle and no human cells. These adenovirus vaccines were linked to a rare but serious clotting disorder with low platelets, which in some cases caused clots in the brain and could increase risk of strokes. The initial cell line for AstraZeneca did come from human kidney cells. However, they were obtained over 50 years ago and the current iteration does not contain any human cells.
mRNA-Based Genetic Reprogramming
An mRNA vaccine can encode one or several antigens. This is different from testing a patient for a genetic abnormality. Research progress must be assessed for each product and disease; a promising target or an early study does not establish that a vaccine will prevent infection or eradicate the disease.
mRNA-based targeted cancer treatments, including personalized cancer vaccines, are being studied, mostly in early clinical trials, for cancers such as:
- Kidney Cancer
- Lung Cancer
- Liver Cancer
- Pleural mesothelioma
- Pancreatic Cancer
- Prostate Cancer
- Colorectal Cancer
- Multiple Myeloma
A potential benefit of mRNA cancer therapies is that they can be tailored to an individual patient’s tumor, prompting the immune system to attack the tumor cells. They are still being tested, often alongside other treatments, and while their side effects differ from the harmful side effects of traditional chemotherapy, they can cause side effects of their own, such as fever, fatigue and injection-site reactions.
The platform has already moved beyond COVID-19: MRESVIA, an mRNA RSV vaccine, received its first FDA approval in 2024. Other applications remain product-specific research questions. Approval of one vaccine does not approve other mRNA vaccines or therapies. [2]
- HIV
- Additional RSV vaccine research beyond the approved product
- Zika Virus
- Epstein-Barr virus
- Cystic Fibrosis
- Shingles
- Parkinson’s Therapy
- Flu
As research continues, mRNA technology may become more widely available and could affect many areas of medicine.
Published Clinical Citations
[1] ^Qin S, Tang X, Chen Y, Chen K, Fan N, Xiao W, Zheng Q, Li G, Teng Y, Wu M, Song X. mRNA-based therapeutics: powerful and versatile tools to combat diseases. Signal Transduct Target Ther. 2022 May 21;7(1):166. doi: 10.1038/s41392-022-01007-w. PMID: 35597779; PMCID: PMC9123296.
[2] ^ U.S. Food and Drug Administration. MRESVIA: product information and approval history. First approval: May 31, 2024.
[3] ^Coppin L, Leclerc J, Vincent A, Porchet N, Pigny P. Messenger RNA Life-Cycle in Cancer Cells: Emerging Role of Conventional and Non-Conventional RNA-Binding Proteins? Int J Mol Sci. 2018 Feb 25;19(3):650. doi: 10.3390/ijms19030650. PMID: 29495341; PMCID: PMC5877511.
[4] ^Fan XY, Lowrie DB. Where are the RNA vaccines for TB? Emerg Microbes Infect. 2021 Dec;10(1):1217-1218. doi: 10.1080/22221751.2021.1935328. PMID: 34036874; PMCID: PMC8216257.