Katalin Karikó

Katalin Karikó
Institutions	University of Pennsylvania; BioNTech
Awards	Nobel Prize in Physiology or Medicine (2023)
Known for	mRNA therapy; nucleoside modification
Occupation	Biochemist
Notable works	Pseudouridine incorporation in mRNA
Notable contributions	Nucleoside-modified mRNA to evade innate immunity
Field	mRNA therapeutics; biochemistry
Wikidata	Q88608397

Katalin Karikó is a Hungarian-born biochemist whose pioneering work on messenger RNA (mRNA) revolutionized vaccine development. Her decades-long research showed how to make synthetic mRNA safe for use in humans, laying the foundation for the first mRNA vaccines – including the highly effective COVID-19 shots authorized in 2020. In collaboration with immunologist Drew Weissman, Karikó discovered that chemically modifying the nucleosides (the building blocks) of RNA prevents it from triggering harmful immune reactions. This breakthrough enabled clinicians to use mRNA as a therapeutic tool, a milestone that earned Karikó and Weissman the 2023 Nobel Prize in Physiology or Medicine.

Early life and education

Karikó was born on January 17, 1955, in Szolnok, Hungary. She grew up in a modest household in the rural town of Kisújszállás – her father was a butcher and the family’s home lacked running water and had only limited electricity. Despite these humble beginnings, Karikó showed a strong aptitude for science from a young age. She excelled in her studies and even traveled on her own as a teenager to attend national science competitions, winning accolades along the way.

Her passion for biology and medicine led her to the University of Szeged in the mid-1970s, where she studied biology/biochemistry. After earning her diploma, Karikó stayed at Szeged to pursue a Ph.D., which she completed in biochemistry in 1982. Her doctoral research focused on RNA, the molecule that carries genetic instructions from DNA to make proteins in cells.

From 1982 to 1985, Karikó continued as a researcher at the Hungarian Academy of Sciences in Szeged. Facing limited research funding in Hungary, she and her husband Béla Francia emigrated to the United States in 1985. There she took a postdoctoral fellowship at Temple University in Philadelphia, where she learned new molecular biology techniques and began experimenting with delivering genetic material into cells. In 1988 Karikó moved to the Uniformed Services University of the Health Sciences in Bethesda, Maryland, where she heard about a new delivery agent, Lipofectin, that could carry nucleic acids into cells via lipid (fat) particles.

In 1989 she was hired by the University of Pennsylvania (UPenn) in Philadelphia, working in the lab of Dr. Elliot Barnathan. As a research assistant professor (a non-tenure position), Karikó’s goal was ambitious: to use mRNA as a therapeutic tool. mRNA (messenger RNA) is a single-stranded molecule that cells naturally use to carry instructions (the “message”) from genes (DNA) to the cellular machinery that makes proteins. Karikó set out to create synthetic mRNA in the lab (“in vitro transcription”) and package it in lipid vesicles so that it could enter human cells and produce desired proteins. One project aimed to make an mRNA coding for an enzyme that breaks down blood clots, with the hope of treating heart attacks or strokes. In cell culture experiments, her team succeeded in getting human cells to produce large amounts of the target protein from the injected mRNA This showed that synthetic mRNA could, in principle, work as a drug.

However, Karikó and others encountered major obstacles. When synthetic mRNA was tested in animals, it proved unstable and was quickly destroyed or provoked an immune reaction. Early researchers found that injecting unmodified mRNA into animals often caused inflammation and immune activation. By the mid-1990s, many scientists had dismissed mRNA therapy as impractical because the body’s innate immune system sees foreign RNA as a threat. Toll-like receptors (proteins in immune cells) and enzymes like PKR detect and respond to external RNA by releasing inflammatory signaling molecules. In essence, immune cells treated lab-made mRNA as if it were an invading virus. With funding scarce and skepticism high, Karikó’s ambitious projects drew criticism. In 1995, when her initial funding ran out, Penn offered her the choice of leaving or taking a demotion. She chose to stay on in a lower-ranked position so she could continue her research.

Throughout this period, Karikó remained committed to her vision that mRNA could become medicine. A crucial opportunity came in 1997 when she began collaborating with immunologist Drew Weissman, who had just joined Penn. Weissman had grants and interest in how immune cells respond to genetic material. Karikó and Weissman decided to investigate why synthetic mRNA triggered inflammation, whereas native mRNA (made by the body) did not. Their joint efforts would lead to the key discoveries for which they are now renowned.

Major works and ideas

Karikó’s major contributions center on understanding and solving the immune response problem of synthetic mRNA. She and Weissman asked: What makes one RNA cause a cytokine storm and another go unnoticed? To answer this, they compared different forms of RNA in cultured human immune cells, particularly dendritic cells (a type of immune cell that activates defenses). They knew that natural RNA in our cells is often chemically modified – various bases in ribosomal RNA and transfer RNA carry small chemical tags – but mRNA made in the lab lacked these tags. In a landmark series of experiments, Karikó and Weissman showed that these small differences mattered enormously.

Their strategy was simple and systematic: they made in vitro transcripts of mRNA in which they replaced one of the usual bases at a time with a modified version. For example, the RNA base uridine (one of the four nucleosides of RNA, abbreviated “U”) could be substituted with pseudouridine (often written Ψ), which is a naturally occurring modified version of uridine found in many human RNAs. It turned out that pseudouridine (and other analogous modifications) dramatically changed how immune cells saw the mRNA.

In 2005 Karikó and Weissman published a breakthrough result: mRNA molecules containing modified nucleosides triggered almost no immune response in human cells whereas unmodified mRNA did. In practical terms, they found that when dendritic cells were exposed to pseudouridine-containing mRNA, the usual inflammatory signaling (release of interferon and other cytokines) was “almost abolished” At the same time, cells translated the modified mRNA into protein very efficiently. In fact, adding modifications had two beneficial effects: it tamed the innate immune system and it increased protein output. The reason for the latter is that in normal immune signaling, an enzyme called PKR stops protein production when it detects foreign RNA. By avoiding immune detection, the modified mRNA faced no such block, so more protein could be made.

Karikó and Weissman detailed these findings in a 2005 paper in Immunity, and later showed more examples and proof-of-concept experiments. In 2008 they reported in Molecular Therapy that pseudouridine-containing mRNA not only avoided immunity but also had greater stability and translational capacity (it stayed intact longer and produced more protein) Their work provided a template for making any mRNA therapeutic: synthesize the RNA with modified bases (pseudouridine or N1-methylpseudouridine, for example), purify it, and deliver it in lipids.

Karikó’s team even tested the approach in animals. In one striking study, they delivered tiny amounts of pseudouridine-modified mRNA encoding the hormone erythropoietin (EPO) to mice. A single injection of only 100 nanograms of this modified mRNA raised blood EPO levels significantly within hours and maintained them for days, boosting red blood cell counts – all without inducing any inflammation By contrast, mRNA without modifications produced 10–100 times less EPO and only for about one day. This experiment in 2012 demonstrated the practical potential of the modified mRNA approach for therapeutic protein delivery.

In summary, Karikó’s major idea was to turn mRNA into a “gene-based drug” by chemically disguising it. She showed that by copying nature’s own strategy (many cellular RNAs carry modified nucleosides), synthetic mRNA could evade the alarm system until it has done its job of producing a protein. These discoveries removed the main barriers to using mRNA in medicine.

Method

Karikó’s work used a combination of molecular biology and immunology techniques to produce and test therapeutic mRNA. The method begins with in vitro transcription: an enzyme called RNA polymerase is used in a test tube to copy a DNA template into mRNA. The researcher supplies the polymerase with four nucleotide triphosphates (ATP, CTP, GTP, and a variant of UTP). The clever step is to replace the normal UTP with a modified version, such as pseudouridine triphosphate or N1-methylpseudouridine triphosphate. This causes the resulting RNA to contain the modified base wherever the DNA code calls for a U. By doing so for one or more of the four bases, the team can create RNA that carries these chemical marks throughout its length.

After synthesizing the mRNA, it must be purified to remove any contaminants. One concern is double-stranded RNA or other fragments that can form during transcription – these are also potent triggers of innate immunity. Karikó’s group used high-performance liquid chromatography (HPLC) and other purification steps to eliminate such impurities The final product is a clean, single-stranded mRNA molecule with the desired sequence and base modifications.

Next, the mRNA needs a delivery system to get into cells. Karikó and colleagues wrapped the mRNA molecules in lipid nanoparticles (LNPs). These are tiny vesicles made of fat-like molecules that serve two purposes: they protect the fragile RNA from enzymes in the body, and they fuse with cell membranes to deliver the mRNA inside cells During her early career, Karikó learned about these lipids (for example, Lipofectin) at the Bethesda lab, and later at BioNTech she helped optimize the LNP formulations. The mRNA is also engineered with a “cap” structure at one end and a long poly-A tail at the other – natural modifications that stabilize the molecule and help cells recognize it for translation.

To test the efficacy of a given mRNA design, Karikó’s team employed cell culture assays. They would transfect dendritic cells or other human cells with the LNP-encapsulated mRNA and measure two things: the amount of protein produced, and the level of immune signaling. For protein output, they could encode a reporter (like luciferase enzyme) or a human protein (like EPO) and quantify it by biochemical assays. For immune activation, they measured cytokines (such as interferons and interleukins) released into the culture medium. The experiments showed that cells receiving pseudouridine-mRNAs made more protein and released far fewer cytokines than cells given unmodified mRNA.

Finally, Karikó tested the modified mRNA in animals (mice and monkeys). For example, in the EPO study, she injected mice with LNP-formulated EPO mRNA containing pseudouridine Blood tests confirmed that the mice’s EPO levels and hematocrit (the proportion of red blood cells) rose dramatically, while blood samples showed no sign of an inflammatory response. Parallel tests in macaques (monkeys) showed similar success. These animal experiments validated that HPLC-purified, nucleoside-modified mRNA could alert the host cells to produce a protein in a living organism without provoking harmful inflammation.

In summary, Karikó’s methodological approach combined advanced RNA chemistry (base modifications and purification) with modern delivery systems (lipid nanoparticles) and careful immunological assays. Her rigorous work demonstrated each step of the process needed to translate an mRNA sequence into a functioning therapy.

Influence

Karikó’s discoveries have had profound influence on medicine and biotechnology, especially during the COVID-19 pandemic. When the SARS-CoV-2 coronavirus spread globally in early 2020, there was an urgent race to create effective vaccines. The groundwork that Karikó and Weissman had laid allowed companies to respond with unprecedented speed. BioNTech (Germany) and Moderna (USA) quickly designed vaccine candidates using synthetic mRNA coding for the viral spike protein, fully incorporating the nucleoside modification principles from Karikó’s research.

In proof-of-concept studies, these mRNA vaccines showed roughly 95% efficacy at preventing symptomatic COVID-19 infection – far exceeding expectations The vaccines’ safety profiles were good: most recipients experienced only mild side effects (sore arm, fever, fatigue) and serious reactions were extremely rare. Thanks to these results, regulators authorized the Pfizer–BioNTech and Moderna vaccines by December 2020, just 11 months after the viral genome was published. This was the fastest vaccine development in history. Globally, hundreds of millions of people received mRNA vaccines by 2021, and more than 13 billion doses have been administered so far Public health experts estimate that mRNA and other COVID vaccines prevented millions of deaths and allowed many parts of the world to reopen safely.

Beyond COVID, Karikó’s influence is evident in the surge of interest in mRNA therapies. Researchers and companies around the world are now pursuing mRNA vaccines for other infectious diseases. Influenza (the seasonal flu) is a prime target; traditional flu shots are only 30–60% effective each year, and take months to produce. Several mRNA flu vaccines are in late-stage trials, with the hope they will be faster to update and more protective. Vaccines against HIV, Zika, dengue, and even malaria and Ebola are in development. The flexibility of mRNA means that once the technology is in place, a new vaccine can be engineered by swapping out the mRNA sequence – much like installing new software. As one biotech leader put it, mRNA therapy has become the “software of life” or “operating system for medicine,” because changing the sequence allows rapid redesign for different diseases.

Karikó’s work also opened doors beyond vaccines. Biotech firms are testing mRNA for cancer immunotherapy, creating personalized cancer vaccines that coax the immune system to attack tumors. Early trials in melanoma and other cancers are ongoing. mRNA can also deliver proteins for gene therapy: for instance, replacing a missing hormone or enzyme. In one idea, infants born with rare genetic disorders might one day receive injections of the correct protein made from mRNA rather than lifelong enzyme replacement therapy. Karikó herself demonstrated the concept by raising EPO levels in animals. Another application is using mRNA instructions to reprogram cells; the Nobel-winning induced-pluripotent stem cell technique in 2010 used modified mRNA to turn adult cells into stem cells, a strategy that grew out of Karikó’s findings.

Her influence extends even to the biotechnology industry’s structure. Before the pandemic, neither BioNTech nor Moderna had an approved product, but both believed strongly in mRNA. After the COVID-19 success, pharmaceutical companies large and small have invested heavily in mRNA. The field is growing like a gold rush: Moderna has more than two dozen mRNA vaccine programs, and BioNTech has over eight in development Other giants have struck partnerships (Sanofi with Translate Bio, GSK with CureVac, etc.) to get on the mRNA train.

Finally, Karikó’s story has inspired a generation of scientists. Her persistence – often pushing her vision years ahead of her peers – serves as a powerful example. Colleagues describe her as an “evangelist” for RNA who could see the possibilities that others doubted As student Norbert Pardi recalled, Karikó once scolded him for underestimating what mRNA could do. By the time she won the Nobel, she had become a celebrity of sorts; her interview requests soared. Many young scientists, especially women and researchers from underrepresented countries, cite Karikó as a role model for overcoming obstacles and standing by a bold idea.

Critiques

While Karikó’s work is widely celebrated, there are cautions and critiques associated with mRNA technology that are worth noting. One category of concern relates to safety and regulatory issues. Any new class of medicines must undergo rigorous testing. The COVID-19 mRNA vaccines were fast-tracked due to the emergency, so experts emphasize continued monitoring of their long-term safety. For example, it is known that mRNA vaccines can very rarely cause mild myocarditis (heart inflammation) in young men; researchers adjusted dosage intervals or advised monitoring in response. These events are still quite uncommon, however, and they pale in comparison to the risks from COVID-19 itself. Scientists point out that thorough surveillance will be needed for any future mRNA treatments, but so far no unmanageable safety problems have emerged.

Another issue is that mRNA vaccines require special handling. The lipid nanoparticles and synthetic RNA are not as stable as traditional vaccines, so many mRNA vaccines need ultra-cold storage (e.g. –70°C). This complicates distribution, especially in warmer or poorer regions. New formulations are easing this problem (recent mRNA vaccines can be stored at fridge temperatures for months), but it remains a logistical concern for global use.

There have also been debates about equity and patents. Initially, wealthy countries secured most mRNA vaccine doses, leaving low-income countries short of supply. Critics argue this shows a flaw in the system: that cutting-edge technology wasn’t shared widely. Patent disputes have also drawn attention; Moderna filed a lawsuit against Pfizer-BioNTech in 2022, each accusing the other of using proprietary mRNA technology. While legal battles rage, some feel that urgent public health needs should override patent barriers. In response, there are initiatives to transfer mRNA vaccine know-how to manufacturers in Africa, Asia, and elsewhere, but building this capacity will take time.

Scientifically, not everyone is convinced that mRNA is a cure-all. Some experts caution that its success may vary by disease. For example, influenza viruses mutate constantly, so making an mRNA vaccine is only part of the solution (it must be updated regularly to match circulating strains). Viruses like HIV are notoriously difficult to vaccinate against for reasons beyond just antigen design, so hopes for an HIV mRNA vaccine are still cautious. In the cancer field, mRNA vaccines are promising but have not yet demonstrated a survival benefit in large trials (research is ongoing).

Overall, however, essential criticisms of Karikó’s contribution are few. Most “critics” of mRNA tend to be groups skeptical of vaccines or rapid vaccine rollout, but these criticisms do not challenge the scientific merits of her work. Within the scientific community, the general view is that Karikó addressed the key objections to mRNA (immunogenicity and stability). Remaining challenges are seen as engineering or deployment issues rather than flaws in her fundamental discovery. In fact, the Nobel Committee highlighted that her and Weissman’s work “fundamentally changed our understanding” of mRNA in cells and “paved the way” for new therapies.

Legacy

Katalin Karikó’s legacy is already profound and will only grow. In science and medicine, she is credited as a co-architect of the mRNA age. By the time she won the Nobel Prize in 2023, she had received many other honors: in 2021 she and Weissman won the prestigious Lasker Award and the Breakthrough Prize in Life Sciences for mRNA research She has published dozens of papers with thousands of citations, and she holds patents on mRNA modifications and delivery methods.

Beyond formal accolades, Karikó’s personal story of perseverance resonates widely. Media accounts often portray her as “the scientist who wouldn’t quit,” pointing out that she survived demotion, grant rejections, and even a cancer diagnosis while pressing on with her mRNA work. Even her former university, UPenn, which once doubted her, publicly celebrated her Nobel win (though some commentators urged Penn to acknowledge its earlier mistakes). This narrative is inspiring to many young researchers: it highlights the unpredictable path of discovery and the value of standing by a bold idea. Karikó herself often notes that she took the demotion because “the experiments were working,” illustrating her commitment to the science over titles or prestige.

In Hungary, Karikó is celebrated as a national hero. After winning the Nobel, she went on tour in the country, and the President congratulated her work. She took a professorship at the University of Szeged in 2021, returning to the city where she trained, and still holds an adjunct position at Penn’s medical school. Through these roles she mentors new scientists and helps ensure the mRNA revolution benefits global health.

The impact of her achievements is visible in the labs and hospitals of the world. Many vaccine research programs now carry the “RNA” stamp, and new mRNA therapies entering clinical trials for cancer, genetic diseases, and infectious threats are traced to her foundational research. Observers expect that in the coming decades, mRNA therapeutics will become a standard part of the medical toolkit – much as recombinant DNA and monoclonal antibodies did in past eras – and Karikó will be credited as a trailblazer of this paradigm.

In a broader sense, Karikó’s career underscores the importance of supporting basic research. Her most important experiments were done in the lab, often without immediate application, and yet they yielded a technology that reshaped an entire industry and saved lives during a crisis. The Nobel recognition acknowledges not just her specific discoveries but the model of scientific persistence they represent. In summary, Katalin Karikó’s legacy lies in unlocking the potential of RNA as medicine. Her work has inaugurated likely decades of innovation: in vaccines, in gene therapy, and in how we respond to future pandemics. As experts now say, we have entered an mRNA vaccine age – and Karikó’s early vision has, at last, come to fruition.

Selected works

Karikó K., Buckstein M., Ni H., Weissman D. (2005). Suppression of RNA recognition by Toll-like receptors: the impact of nucleoside modification. Immunity 23(2): 165–175.
Karikó K., Muramatsu H., Welsh F.A., Ludwig J., Kato H., Akira S., Weissman D. (2008). Incorporation of pseudouridine into mRNA yields superior nonimmunogenic vector with increased translational capacity and biological stability. Molecular Therapy 16(11): 1833–1840.
Anderson B.R., Muramatsu H., Nallagatla S.R., Bevilacqua P.C., Sansing L.H., Weissman D., Karikó K. (2010). Incorporation of pseudouridine into mRNA enhances translation by diminishing PKR activation. Nucleic Acids Research 38(21): 5884–5892.

Timeline

1955 – Born in Szolnok, Hungary.
1978 – Graduated from the University of Szeged (degree in biology/biochemistry).
1982 – Earned PhD in biochemistry from the University of Szeged.
1985 – Moved to the United States for postdoctoral research (Temple University, Philadelphia).
1989 – Joined the University of Pennsylvania as a research assistant professor.
1997 – Began collaborative work with Drew Weissman on mRNA and immune response.
2005 – Published discovery (in Immunity) that mRNA with chemically modified bases avoids immune activation.
2008 – Demonstrated (in Molecular Therapy) that pseudouridine-containing mRNA greatly increases protein production and stability.
2013 – Joined BioNTech RNA Pharmaceuticals (Germany) as a senior scientist to develop mRNA therapies.
2020 – Two mRNA COVID-19 vaccines (Pfizer–BioNTech and Moderna) based on her technology received emergency use authorization.
2023 – Awarded the Nobel Prize in Physiology or Medicine (shared with Drew Weissman) for the development of mRNA vaccines.