/ mRNA Vaccine Technology: Discarded Idea Became Mainstay in the Fight Against Covid-19

Matías Saavedra
Patent Engineer
Alessandri Abogados

Health sustainability in the world depends to a great extent on the virtuous interaction between science and industry to adapt and develop innovative solutions. In this interaction, industrial property tools play a key role in making new knowledge public and making the risk-taking inherent to innovation activities viable. The generation of scientific knowledge, often without any foreseen application or value, combined with business activities that transform such knowledge into concrete products and services available to society, are a fundamental pillar in the generation of lasting welfare for mankind.

The history of messenger RNA (mRNA) technology is a tale of scientific perseverance and innovation that revolutionized vaccine development. Once dismissed as a secondary technology, synthetic mRNA finally emerged as a powerful tool not only in the fight against the Covid-19 pandemic, but in the sustainability of human health and well-being. However, turning scientific promise into medical reality was a more difficult path than many assumed. The story began three decades ago, with one persevering scientist.

Before messenger RNA technology became a multi-billion dollar idea, it was an apparent dead end in the career of Katalin Karikó, a Hungarian-born scientist responsible for a key discovery in its further development.

Katalin Karikó held the following idea: in the natural world, the body depends on millions of tiny proteins to stay alive and healthy and uses mRNA molecules to tell cells which proteins to make. If one could design one’s own mRNA, a synthetic mRNA, one could, in theory, “hack” that process and create any protein one desired: antibodies to vaccinate against an infection, enzymes to reverse a rare disease, or growth agents to repair damaged heart tissue, among countless possibilities. By injecting a synthetic mRNA molecule into a human being with precise and deliberate adjustments, any cell in the body could be transformed into an on-demand drug factory.

Despite the potential of her line of research, Katalin Karikó received no support or funding, with consequences for her academic career.

The development of the medical use of mRNA was accompanied by significant difficulties and challenges: synthetic mRNA is a molecule that is highly vulnerable to the body’s natural defenses, which means that it is likely to be destroyed long before it reaches the target cells. Worse still, the synthetic mRNA is recognized by the body as a foreign agent and thus may provoke an intense and disproportionate immune response that would make any therapy an obvious health risk for patients.

However, Katalin Karikó persevered in the search for a solution. After more than a decade of research at the University of Pennsylvania, Karikó, together with her close collaborator, immunologist Drew Weissman, discovered a solution to the Achilles’ heel of mRNA. By making some changes to its components, they succeeded in creating a synthetic hybrid mRNA capable of entering cells without alerting the body’s defenses, and thus without creating a dangerous immune response.

Contrary to what one might think, this discovery, described in a series of scientific papers published from 2005 onwards, went unnoticed, without generating enthusiasm in the scientific community. Despite this, Karikó and Weissman again persevered and decided to protect their development through invention patents, founding a company called RNARx in 2006 to exploit them. Unfortunately for them, the persistent lack of interest in the scientific and business environment for the incipient technology caused the early closure of the company due to lack of funding.

Over time, the knowledge generated by Karikó and Weissman eventually found its way into the hands of three key scientists, who continued its development: Derrick Rossi, a 39-year-old post-doctoral researcher at Stanford University (USA) and the couple formed by Ugur Sahin and Özlem Türeci, two German medical researchers and entrepreneurs of Turkish origin.

Rossi was instrumental in founding the US biotech company Moderna (in 2010), and the Sahin-Türeci couple created the German company BioNTech in 2008, which later partnered with Pfizer. Both companies acquired licenses to Karikó’s and Weissman’s patents and ended up creating and commercializing viable mRNA-based vaccines, key in the fight against the COVID19 (Coronavirus Disease Year 2019) pandemic generated by the SARS-Cov2 (Severe Acute Respiratory Syndrome Coronavirus 2) virus, the Moderna and Pfizer-BioNTech vaccines. These vaccines, based on mRNA technology, allow patients’ own cells to manufacture a harmless protein present on the surface of the SARS-CoV-2 virus, known as “spike”, which is recognized by the immune system, generating a functional and effective immune response that attenuates the effects of the disease and reduces the probability of contagion.

The idea of synthetic mRNA, once dismissed by both the scientific community and the financial and business world, has become a success story, one of those that, along with other notable examples, can contribute to the interest of children in pursuing STEM (science, technology, engineering and mathematics) careers.

As a result of their remarkable contribution to global health, Katalin Karikó and Drew Weissman won the Nobel Prize in Medicine 2023.