News broke on October 2 that the 2023 Nobel Prize in Physiology or Medicine has been awarded to 2022 Tang Prize laureates Dr. Katalin Kariko and Dr. Drew Weissman “for their discoveries concerning nucleoside based modifications that enabled the development of effective mRNA vaccines against COVID-19.” It marked the third time that Tang Prize recipients were named Nobel laureates, a history made in 2018 when 2014 Tang Prize recipients Dr. James P. Allison and Dr. Tasuku Honjo won the Nobel Prize in Medicine, then repeated in 2020 when the Nobel Prize in Chemistry went to 2016 Tang Prize winners Dr. Emmanuelle Charpentier and Dr. Jennifer A. Doudna.
Upon hearing this good news, CEO of the Tang Prize Foundation Dr. Jenn-Chuan Chern immediately sent his congratulations to both laureates on behalf of the founder of the Tang Prize Dr. Samuel Yin. He also expressed his sincere gratitude to the independent Tang Prize selection committee, thanking its professional and visionary members for ensuring that Tang Prize laureates are all scientists who have influenced and made substantive contributions to the world. The recognition from the Nobel Committee is yet another proof that the lauretes’ breakthrough discoveries and the ingenious approaches they pioneered are key to the rapid and successful development of SARS-CoV-2 vaccine. These techniques not only revolutionized vaccinology but also signaled a paradigm shift in protein therapy, ushering in the era of RNA-based therapies.
Unlike traditional protein therapies that are usually time-consuming and expensive, these new mRNA techniques turn cells into factories where proteins that serve as antigens or therapeutic molecules can be produced. Manufacturing vaccines in large quantity and at relatively low cost became possible, thus making it easier for especially people in developing countries to access quality healthcare. In addition, they can be applied to tackle a variety of diseases, such as to develop vaccines against other viruses, and even tailored-made vaccines against cancer.
The two laureates were in Taiwan this August to attend the 5th Tang Prize award ceremony and other Tang Prize Week events, including Laureates’ Lectures and the Tang Prize Taiwan Biotechnology Forum. In addition, the Tang Prize Foundation arranged for Dr. Kariko to give a talk at the Taipei First Girls High School (TFG) to more than two hundred students from TFG, Taipei Municipal Jianguo High School (JGHS), Affiliated Senior High School of National Taiwan Normal University (HSNU), and Taipei Municipal Chenggong High School. Titled “Developing mRNA for Therapy: My Journey,” the talk featured Dr. Kariko’s life story, a journey of realizing her dreams that was full of ups and downs. She also told the young minds in the room that they should be passionate about what they do, have faith in themselves, learn how to handle stress, never stop learning and aspire to be a scientist.
Devoting his life to vaccine research and development, Dr. Weissman emphasized in his acceptance speech “the immense potential of mRNA-LNPs in transforming the landscape of medicine.” Moreover, winning the prize has enabled him to “reach out to lower income countries and regions and help them develop their own academic mRNA research infrastructure followed by building GMP production centers.” So far, “this has been completely in 18 locations, including Pune, Ukraine and Brazil.” Dr. Weissman believes that “this is an important manner to address the unequal access to new medicines and vaccines and allow the development of treatments needed in certain locations.”
During the three years since the coronavirus emerged in November 2019, the COVID pandemic caused tragic numbers of hospitalizations and deaths in many parts of the world and severely battered the global economy. The World Health Organization’s statistics show that up to September 2022, more than 600 million COVID infections and about 6.5 million deaths have been recorded globally. Fortunately, it took Pfizer/BioNTech and Moderna less than 12 months to successfully develop vaccines against SARS-CoV-2. As a result, millions of lives have been saved. This public health miracle would not have happened if Dr. Kariko and Dr. Weissman had not figured out how to reduce the immunogenicity of mRNA.
There are two major challenges when it comes to delivering RNA into the human body. First, RNA triggers innate immune responses. Second, it is easily degradable, and hence difficult to reach the target cells or organs. The new platform developed by these two laureates is a nucleoside-modified mRNA-based vaccine that can evade the immune system, thus preventing the severe inflammation which occurs when in vitro-transcribed mRNA is recognized by immune cells. When these mRNA molecules are delivered into the cells, they instruct the cell’s machinery to produce harmless pieces of spike protein found on the surface of the coronavirus and initiate a series of adaptive immune responses such as triggering B cells to produce antibodies and training T cells to attack infected cells.
Dr. Kariko was educated in Hungary and moved to the US in 1985. She was especially interested in RNA and its chemical synthesis for efficient protein expression in cells in vitro and in vivo. With systematic rigor, she has solved several problems related to the use of RNA in vaccinology and therapy. During the 1990s, as a research associate professor at the University of Pennsylvania, she devoted herself to the development of in vitro-transcribed messenger RNA (mRNA) for protein therapies. For that, she needed to understand the mechanism of the immune response mediated by RNAs. Together with her colleague, Dr. Weissman, she showed that mRNA is recognized by Toll-like receptors, thus participating in the innate immune response, and the injection of mRNA into animals caused severe inflammation. However, they found that if the nucleosides of the mRNA were modified like selected nucleosides in naturally occurring RNA, the mRNA did not elicit such responses. Eventually, they were able to identify key modifications. This critical finding enabled them to create stealth RNAs that do not cause inflammation.
Dr. Weissman is an expert in immunology and the Roberts Family Professor in Vaccine Research at the University of Pennsylvania, where he started his laboratory in 1997 to develop vaccine against HIV. Prior to that, he worked at America’s National Institutes of Health (NIH) on HIV-related research. In collaboration with Dr. Kariko, he started studying RNA as vaccines. In 2005, they published their pivotal discovery that nucleoside-modified RNAs are non-immunogenic. Since then, Dr. Weissman has been actively engaged in the application of this technology to the development of RNA vaccines against infections by viruses such as HIV and Zika virus. Dr. Weissman and Dr. Kariko has been working together for more than two decades and has reached many important milestones during their scientific adventures. Together, they hold the U.S. patent for the application of the non-immunogenic, nucleoside-modified RNA.
About the Tang Prize
With the advent of globalization, mankind has been able to enjoy the convenience brought forth by the advancement of human civilization and science. Yet a multitude of challenges, such as climate change, the emergence of new infectious diseases, wealth gap, and moral degradation, have surfaced along the way. Against this backdrop, Dr. Samuel Yin established the Tang Prize in December 2012. It consists of four award categories, namely Sustainable Development, Biopharmaceutical Science, Sinology, and Rule of Law. Every other year, four independent and professional selection committees, made up of many internationally experts and scholars, including Nobel laureates, choose as Tang Prize recipient people who with great influence and great contributions to the world, regardless of ethnicity, nationality or gender. A cash prize of NT$50 million (approx. US$1.7 million) is allocated to each category, of which NT$10 million (approx. US$ 0.35 million) is designated as a research grant to support educational projects chosen by laureates, so as to prompt people to pay more attention to mankind’s most urgent needs in the 21st century, and to become leading forces behind the development of human society through their outstanding research and active civic engagement.
