Pioneers of mRNA Vaccine Technology

Katalin Karikó and Dr. Drew Weissman, the recipients of this year’s Nobel Prize in physiology or medicine, embarked on their groundbreaking journey in the realm of messenger RNA (mRNA) technology at a chance encounter near a photocopy machine at the University of Pennsylvania in the 1990s. Their collaborative efforts would eventually revolutionize the world of medicine, playing a pivotal role in the development of mRNA-based vaccines, notably the Pfizer-BioNTech and Moderna COVID-19 vaccines. The Nobel committee acknowledged their contributions for saving countless lives during the pandemic.

Before the advent of mRNA technology, vaccines were traditionally crafted from inactive or benign viral materials. This approach often involved laborious cell culturing processes that extended the vaccine development timeline to more than a decade. However, scientists had long pondered the potential of mRNA, a cellular molecule, in expediting vaccine development.

Dr. Weissman expressed, “We knew from the beginning that RNA had incredible potential; we just didn’t know when.” The breakthrough came in the 1980s when researchers discovered a method for producing mRNA outside of cell culture, known as in vitro transcription. Nevertheless, mRNA synthesized through this method tended to trigger immune responses, leading to inflammation and inefficient protein production in the body.

It was Katalin Karikó and Dr. Drew Weissman who overcame these formidable obstacles. They collaborated on an innovative experiment involving the injection of mRNA into dendritic cells, a crucial component of the immune system. The result was a revelation: the mRNA triggered protein production. However, the initial excitement was tempered by an unexpected inflammatory response, as the cells perceived the mRNA as a foreign intruder.

The breakthrough occurred when they modified the basic components, or nucleosides, of mRNA, effectively rendering it “immune silent.” This modification allowed the mRNA to enter cells without triggering an inflammatory response, significantly boosting protein production.

In 2005, Karikó and Weissman published their groundbreaking findings, anticipating substantial interest from the scientific community and biotechnology companies. However, they encountered disappointment and limited recognition.

Katalin Karikó faced setbacks in her career at Penn in the mid-1990s when her mRNA research failed to secure adequate funding. Additionally, their startup venture did not gain significant traction. Undeterred, they remained committed to advancing their groundbreaking work, persevering in the face of adversity.

Their pioneering mRNA technology was patented by the University of Pennsylvania and subsequently licensed to biotechnology giants Moderna and BioNTech. These companies now pay royalties to Penn based on sales of their mRNA vaccines, marking a remarkable journey from initial skepticism to global recognition.

Dr. Drew Weissman received the news of his Nobel Prize win in a 4 a.m. phone call, underscoring the significance of their contributions to science and medicine.

Katalin Karikó served as Senior Vice President at BioNTech from 2013 until 2022 and continues to advise the company. She is also a professor at the University of Szeged in her native Hungary and an adjunct professor at the University of Pennsylvania. Dr. Drew Weissman holds a professorship at the University of Pennsylvania.

Winners of the Nobel Prize in physiology or medicine receive 11 million Swedish kronor, equivalent to approximately $1 million. The recognition of Karikó and Weissman’s pioneering work not only highlights their dedication to science but also opens doors to a promising future for mRNA technology in addressing a wide range of diseases, including influenza and cancer.

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