On October 2nd, the Nobel Assembly unveiled the recipients of the 2023 Nobel Prize in Physiology or Medicine: scientists Katalin Karikó and Drew Weissman. Their pioneering research in messenger ribonucleic acid (mRNA) has reshaped vaccine development, notably amid the COVID-19 pandemic. Their work has not only saved countless lives but has also alleviated the severity of cases, relieving pressure on healthcare systems and facilitating the global reopening of societies. To date, mRNA vaccines, administered over 13 billion times worldwide, have played a pivotal role in fighting the pandemic. Scientists have delved into mRNA’s potential for vaccine development since the 1990s.
The laureates’ work “revolutionized our comprehension of mRNA’s interaction with the immune system,” crucial in the swift creation of mRNA vaccines for SARS-CoV-2 during the ongoing global health crisis. These vaccines deliver the spike protein mRNA sequence into cells using lipid nanoparticles (LNPs) as carriers. This innovative method triggers protein production, activating immune cells and eliciting responses like the creation of neutralizing antibodies and antigen-specific T cells. mRNA-based SARS-CoV-2 vaccines boast rapid production and cost-effectiveness. By amplifying antigens through mRNA synthesis, high concentrations of neutralizing antibodies are achieved, enhancing vaccine efficacy.
In contrast, producing vaccines based on whole viruses or viral proteins necessitates extensive cell cultures, complicating rapid pandemic vaccine production. SARS-CoV-2 vaccine candidates underwent testing in animal models like ACE2 humanized mice, ferrets, and rhesus macaques. Exogenous mRNA corresponding to viral gene fragments enables host cells to produce viral proteins, stimulating immune responses and serving as vaccine candidates. Yet, extracellular mRNA production suffers from instability and inefficient delivery.
The laureates’ research showcased that modifying extracellular mRNA’s nucleotide bases could make the host “recognize” exogenous mRNA as self-mRNA. This modification reduces inflammatory reactions and boosts protein production after delivery, removing key hurdles in mRNA’s clinical application. This breakthrough paves the way for agile mRNA vaccine development for infectious diseases and holds potential for delivering therapeutic proteins and treating specific cancer types
However, mRNA is inherently unstable and prone to enzymatic degradation within the body. Another challenge lies in the potential for mRNA to trigger intense inflammatory responses, potentially harming cells and tissues. Despite skepticism and rejection, Karikó and Weissman persevered. In 2005, they published a groundbreaking paper addressing these challenges. By modifying mRNA’s building blocks, nucleotides, they enhanced stability and reduced immunogenicity. Additionally, they devised a method employing lipid nanoparticles to deliver mRNA into cells, safeguarding and transporting mRNA within minuscule lipid bubbles.
Karikó and Weissman’s work stands as a groundbreaking transformation in anti-SARS-CoV-2 candidates and public health, illustrating the potency of curiosity-driven science and resilience. Their achievements inspire researchers and innovators worldwide to explore mRNA technology’s potential in enhancing human health and well-being.
