The BUILDING THE FOUNDATION AWARD recognizes an individual(s) whose basic research discoveries played a pivotal role in the response to COVID-19.
Katalin Karikó, PhD, is Senior Vice President of BioNTech SE where she started to work in 2013. She is also Adjunct Associate Professor at the Perelman School of Medicine, University of Pennsylvania, where she worked for 24 years, between 1989 and 2013.
For four decades, her research has been focusing on RNA-mediated mechanisms with the ultimate goal of developing in vitro-transcribed (IVT) mRNA for protein therapy. She investigated RNA-mediated immune activation and together with Dr. Drew Weissman discovered that nucleoside modifications suppress immunogenicity of RNA. This groundbreaking work unlocked the opportunity for the therapeutic use of mRNA. Her patent, co-invented with Dr. Weissman on nucleoside-modified uridines of mRNA, was the foundation for the FDA-authorized anti-SARS-CoV-2 mRNA vaccines developed by BioNTech/Pfizer and Moderna/NIH that are crucial to ending the global pandemic.
She received her Ph.D. in biochemistry from University of Szeged, Hungary, in 1982. Her thesis work involved synthesis and antiviral evaluation of 2’-5’-linked oligoadenylates, called 2-5A, that is responsible for the interferon-induced antiviral mechanism. Her research focused on 2-5A generated with nucleoside analog, cordycepin. In 1985, after moving to Temple University, Philadelphia, she studied 2-5A molecules modified at their nucleosides. In 1989 she started to work at the University of Pennsylvania, where she used IVT mRNA to overexpress selected proteins in cultured cells. Her first success was when she demonstrated that functional highly processed proteins were generated from IVT mRNA transfected into cultured mammalian cells, suggesting that mRNA encoding therapeutic proteins have the potential for treating various diseases. However, she, together with Drew Weissman demonstrated that IVT mRNA is immunogenic and thus unfit for therapeutic use. They identified uridine as being responsible for this activation. After searching for years, they discovered that incorporating naturally-occurring modified nucleosides such as pseudouridine into the mRNA, the newly created mRNA was highly translatable and avoided activation of TLR7 and TLR8 in human immune cells. They also invented a purification procedure that further increased the translational capacity of the mRNA.
Together with her colleagues, she demonstrated functional use of nucleoside-modified mRNA encoding antibodies for the treatment of cancer and infectious diseases. In animal models of multiple sclerosis, they used autoantigen-encoding mRNA and proved that this mRNA technology can be applied for induction of tolerization, thus opening the possibility of treating autoimmune diseases. She also initiated a clinical study in which tumors of patients were injected with modified mRNAs encoding cytokines, thus promoting potent antitumor immunity and tumor eradication at local and remote sites. She is the co-inventor on 10 patents granted by US and related to application of non-immunogenic, nucleoside-modified RNA. Together with Dr. Weissman, she co-founded RNARx, a small biotech company dedicated to develop nucleoside-modified mRNA for therapy. She served as CEO of RNARx from 2006-2013. She is a founding member of the scientific planning committee for the International mRNA Health Conference, an annual non-profit meeting for advancements of mRNA technology, inaugurated in 2013. She was a guest editor of the Molecular Therapy special issue on mRNA Therapy, in 2019.