by
Dr. Adaeze Ekwe, PhD
Junior Associate Editor
ISCT ESP Leadership Development Program
Arguably one of the most anticipated awards in the scientific community is the Nobel Prize in Physiology or Medicine. Dr. Katalin Karikó PhD and Dr. Drew Weissman PHD were decorated with this year's honours for their discoveries on “nucleoside base modifications that enabled the development of effective mRNA vaccines against COVID-19”. The Laureates identified a way to modify messenger RNA (mRNA) to enable its safe introduction into cells and prevent the immune system from launching an inflammatory response against in vitro-produced mRNA [1 – 3].
These pioneering findings which laid the foundation for the rapid development of the mRNA vaccine against the SARS-CoV-2 virus have revolutionised medicine and has inspired a new generation of innovative medical treatments. Three mRNA vaccine candidates for protection against HIV infection are currently in clinical trials (NCT05217641) [4]. Beyond infectious diseases, mRNA technology also has potential applications in cell and gene immunotherapeutics for inherited immune disorders, autoimmune diseases as well as cancer [5]. Some of such examples include correction of the genetic mutations that cause sickle cell anaemia with gene-edited mRNA delivered to hematopoietic stem cells [6]. mRNA-based vaccines encoding for autoantigens successfully induced antigen-specific tolerance in experimental model of multiple sclerosis [7]. In addition, several studies and clinical trials are underway on the use of mRNA vaccines (NCT01066390) or mRNA transfected T cells encoding chimeric antigen receptor (CAR) for various types of cancers (NCT01355965, NCT04503278, 2019-004323-20) [8 – 9].
The advances and revolution that mRNA-centered medical intervention has birthed will in no small measure inspire more revolutionary discoveries that will give humanity a fighting chance against hitherto uncurable illnesses. These possibilities make the current applications feel like scratching the surface. However, to create that future we imagine, the government and corporate organizations need to do more in funding and supporting fundamental scientific research. It should not take another pandemic for the world to see the need to fund scientific breakthroughs. There are already numerous health crisis that have defied existing interventions and yearning for new ones. While looking forward with renewed optimism and hoping that the lessons of the pandemic will not be forgotten, like Dr Karikó, “let us not dwell on the problem” but rather "focus on the things (we) can change".
Congratulations and thank you to Katalin Karikó and Drew Weissman for their hard work, persistence, and for turning their curiosity and passion for science into a groundbreaking invention that saved the human race from a hungry pandemic that would have devoured much more.
References
- Karikó, Katalin et al. “Suppression of RNA recognition by Toll-like receptors: the impact of nucleoside modification and the evolutionary origin of RNA.” Immunity vol. 23,2 (2005): 165-75. doi:10.1016/j.immuni.2005.06.008.
- Karikó, Katalin et al. “Incorporation of pseudouridine into mRNA yields superior nonimmunogenic vector with increased translational capacity and biological stability.” Molecular therapy : the journal of the American Society of Gene Therapy vol. 16,11 (2008): 1833-40. doi:10.1038/mt.2008.200.
- Weissman, Drew, and Katalin Karikó. “mRNA: Fulfilling the Promise of Gene Therapy.” Molecular therapy : the journal of the American Society of Gene Therapy vol. 23,9 (2015): 1416-7. doi:10.1038/mt.2015.138.
- Laura Breda et al., In vivo hematopoietic stem cell modification by mRNA delivery.Science381,436-443(2023).DOI:10.1126/science.ade6967.
- Krienke, Christina et al. “A noninflammatory mRNA vaccine for treatment of experimental autoimmune encephalomyelitis.” Science (New York, N.Y.) vol. 371,6525 (2021): 145-153. doi:10.1126/science.aay3638.
- Beatty, Gregory L et al. “Mesothelin-specific chimeric antigen receptor mRNA-engineered T cells induce anti-tumor activity in solid malignancies.” Cancer immunology research vol. 2,2 (2014): 112-20. doi:10.1158/2326-6066.CIR-13-0170.
- Wilgenhof, S et al. “A phase IB study on intravenous synthetic mRNA electroporated dendritic cell immunotherapy in pretreated advanced melanoma patients.” Annals of oncology : official journal of the European Society for Medical Oncology vol. 24,10 (2013): 2686-2693. doi:10.1093/annonc/mdt245.
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