Katalin Kariko, RNA Hero, Future Nobel Prize

The development of the Pfizer-BioNTech coronavirus vaccine, the first approved jab in the West, is the crowning achievement of decades of work for Hungarian biochemist Katalin Kariko, who fled to the US from communist rule in the 1980s.

When trials found the Pfizer-BioNTech coronavirus vaccine to be safe and 95 percent effective in November, it was the crowning achievement of Katalin Kariko’s 40 years of research on the genetic code RNA (ribonucleic acid). Her first reaction was a sense of “redemption,” Kariko told The Daily Telegraph.

I was grabbing the air, I got so excited I was afraid that I might die or something,” she said from her home in Philadelphia. “When I am knocked down I know how to pick myself up, but I always enjoyed working… I imagined all of the diseases I could treat.”

Born in January 1955 in a Christian family in the town of Szolnok in central Hungary – a year before the doomed heroism of the uprising against the Soviet-backed communist regimeKariko grew up in nearby Kisujszellas on the Great Hungarian Plain, where her father was a butcher. Fascinated by science from a young age, Kariko began her career at the age of 23 at the University of Szeged’s Biological Research Centre, where she obtained her PhD.

It was there that she first developed her interest in RNA. But communist Hungary’s laboratories lacked resources, and in 1985 the university sacked her. Consequently, Kariko looked for work abroad, getting a job at Temple University in Philadelphia the same year. Hungarians were forbidden from taking money out of the country, so she sold the family car and hid the proceeds in her 2-year-old daughter’s teddy bear. “It was a one-way ticket,” she told Business Insider. “We didn’t know anybody.”

Not everything went as planned after Kariko’s escape from communism. At the end of the 1980s, the scientific community was focused on DNA, which was seen as the key to understanding how to develop treatments for diseases such as cancer. But Kariko’s main interest was RNA, the genetic code that gives cells instructions on how to make proteins.

At the time, research into RNA attracted criticism because the body’s immune system sees it as an intruder, meaning that it often provokes strong inflammatory reactions. In 1995, Kariko was about to be made a professor at the University of Pennsylvania, but instead she was consigned to the rank of researcher.

Usually, at that point, people just say goodbye and leave because it’s so horrible,” Kariko told medical publication Stat. She went through a cancer scare at the time, while her husband was stuck in Hungary trying to sort out visa issues. “I tried to imagine: Everything is here, and I just have to do better experiments,” she continued. Kariko was also on the receiving end of sexism, with colleagues asking her the name of her supervisor when she was running her own lab.

Kariko persisted in the face of these difficulties. “From outside, it seemed crazy, struggling, but I was happy in the lab,” she told Business Insider. “My husband always, even today, says, ‘This is entertainment for you.’ I don’t say that I go to work. It is like play.” Thanks to Kariko’s position at the University of Pennsylvania, she was able to send her daughter Susan Francia there for a quarter of the tuition costs. Francia won gold on the US rowing team in the 2008 and 2012 Olympics.

It was a serendipitous meeting in front of a photocopier in 1997 that turbocharged Kariko’s career. She met immunologist Drew Weissman, who was working on an HIV vaccine. They decided to collaborate to develop a way of allowing synthetic RNA to go unrecognised by the body’s immune system – an endeavour that succeeded to widespread acclaim in 2005. The duo continued their research and succeeded in placing RNA in lipid nanoparticles, a coating that prevents them from degrading too quickly and facilitates their entry into cells.

The researchers behind the Pfizer-BioNTech and Moderna jabs used these techniques to develop their vaccines.

Source: https://www.france24.com/

Secure Nano-Carrier Delivers Medications Directly To Cells

Medications often have unwanted side-effects. One reason is that they reach not only the unhealthy cells for which they are intended, but also reach and have an impact on healthy cells. Researchers at the Technical University of Munich (TUM), working together with the KTH Royal Institute of Technology in Stockholm, have developed a stable nano-carrier for medications. A special mechanism makes sure the drugs are only released in diseased cells.

The human body is made up of billions of cells. In the case of cancer, the genome of several of these cells is changed pathologically so that the cells divide in an uncontrolled manner. The cause of virus infections is also found within the affected cells. During chemotherapy for example, drugs are used to try to destroy these cells. However, the therapy impacts the entire body, damaging healthy cells as well and resulting in side effects which are sometimes quite serious.

A team of researchers led by Prof. Oliver Lieleg, Professor of Biomechanics and a member of the TUM Munich School of BioEngineering, and Prof. Thomas Crouzier of the KTH has developed a transport system which releases the active agents of medications in affected cells only.

The drug carriers are accepted by all the cells,” Lieleg explains. “But only the diseased cells should be able to trigger the release of the active agent.”

The scientists have now shown that the mechanism functions in tumor model systems based on cell cultures. First they packaged the active ingredients. For this purpose, they used so-called mucins, the main ingredient of the mucus found for example on the mucus membranes of the mouth, stomach and intestines. Mucins consist of a protein background to which sugar molecules are docked. “Since mucins occur naturally in the body, opened mucin particles can later be broken down by the cells,” Lieleg says.

Another important part of the package also occurs naturally in the body: deoxyribonucleic acid (DNA), the carrier of our genetic information. The researchers synthetically created DNA structures with the properties they desired and chemically bonded these structures to the mucins. If glycerol is now added to the solution containing the mucin DNA molecules and the active ingredient, the solubility of the mucins decreases, they fold up and enclose the active agent. The DNA strands bond to one another and thus stabilize the structure so that the mucins can no longer unfold themselves.

The DNA-stabilized particles can only be opened by the rightkey” in order to once again release the encapsulated active agent molecules. Here the researchers use what are called microRNA molecules. RNA or ribonucleic acid has a structure very similar to that of DNA and plays a major role in the body’s synthesis of proteins; it can also regulate other cell processes.

Cancer cells contain microRNA strands whose structure we know precisely,” explains Ceren Kimna, lead author of the study. “In order to use them as keys, we modified the lock accordingly by meticulously designing the synthetic DNA strands which stabilize our medication carrier particles.” The DNA strands are structured in such a way that the microRNA can bind to them and as a result break down the existing bonds which are stabilizing the structure. The synthetic DNA strands in the particles can also be adapted to microRNA structures which occur with other diseases such as diabetes or hepatitis.

Source: https://www.tum.de/

Why RNA Is A Better Measure Of A Patient’s Current Health Than DNA

By harnessing the combined power of NGS, machine learning and the dynamic nature of RNA we’re able to accurately measure the dynamic immune response and capture a more comprehensive picture of what’s happening at the site of the solid tumor. In the beginning, there was RNA – the first genetic molecule.

In the primordial soup of chemicals that represented the beginning of life, ribonucleic acid (RNA) had the early job of storing information, likely with the support of peptides. Today, RNA’s cousin – deoxyribonucleic acid – or DNA, has taken over most of the responsibilities of passing down genetic information from cell-to-cell, generation-to-generation. As a result, most early health technologies were developed to analyze DNA. But, RNA is a powerful force. And its role in storing information, while different from its early years, has no less of an impact on human health and is gaining more mindshare in our industry.

RNA is often considered a messenger molecule, taking the information coded in our DNA and transcribing it into cellular directives that result in downstream biological signals and proteinslevel changes.  And for this reason, RNA is becoming known not only as a drug target but perhaps more importantly, as a barometer of health.

3d illustration of a part of RNA chain from which the deoxyribonucleic acid or DNA is composed

How and why is RNA so useful? First, RNA is labile — changing in both sequence and abundance in response to genetic and epigenetic changes, but also external factors such as disease, therapy, exercise, and more. This is in contrast to DNA, which is generally static, changing little after conception.

Next, RNA is a more accurate snapshot of disease progression. When mutations do occur at the DNA level, these do not always result in downstream biological changes. Often, the body is able to compensate by repairing the mutation or overcome it by using redundancies in the pathway in which the gene resides. By instead evaluating RNA, we get one step closer to understanding the real impact disease is imparting on our body.

Finally, RNA is abundant. In most human cells, while only two copies of DNA are present, hundreds of thousands of mRNA molecules are present,representing more than 10,000 different species of RNA. Because even rare transcripts are present in multiple copies, biological signals can be confidently detected in RNA when the right technology is used.

Source: https://medcitynews.com/