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Two scientists who developed technology used in COVID-19 mRNA vaccines received a $ 3 million prize.
Now in their 10th year, the Breakthrough Prizes recognize leading researchers in the fields of fundamental physics, life sciences and mathematics. Each prize is accompanied by a $ 3 million award, provided by the founding sponsors of the foundation, Sergey Brin, Priscilla Chan and Mark Zuckerberg, Yuri and Julia Milner, and Anne Wojcicki. This year, one of the three awards in the Life Sciences category will go to Katalin Karikó and Dr Drew Weissman, whose work over the past decades has led to the development of the technology needed to introduce mRNA into cells. , paving the way for today’s COVID. -19 vaccines, in particular those produced by Pfizer-BioNTech and Moderna.
Essentially, Karikó and Weissman figured out how to silence the alarms of the immune system long enough for the synthetic messenger RNA to slip into cells, send commands to cells to make proteins, and be broken down safely after these instructions are given. This process enabled the Vaccines against covid-19 that have been given to more than 360 million people in the United States, the United States alone, and millions more around the world – and the technology could pave the way for gene therapies and treatments against cancer in the future.
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“The innovative vaccines developed by Pfizer / BioNTech and Moderna that have been shown to be effective against the virus build on decades of work by Katalin Karikó and Drew Weissman,” the Breakthrough Foundation wrote in a statement. “Convinced of the promise of mRNA-based therapies despite widespread skepticism, they created a technology that is not only vital in the fight against coronavirus today, but which also holds great promise for future vaccines and treatments for a wide range of diseases, including HIV, cancer, autoimmune diseases. and genetic diseases. “
“There is huge potential for the future of modified RNA,” Weissman, immunologist and vaccine research professor at the Perelman School of Medicine at the University of Pennsylvania, told Live Science.
For example, before the coronavirus pandemic, Weissman’s group had initiated clinical trials of mRNA vaccines to prevent genital herpes, influenza, and HIV; in 2020, they began work on a pan-coronavirus vaccine capable of foiling any beta coronavirus, of which SARS-CoV-2 is just one example. They are also working on an RNA-based gene therapy for sickle cell anemia, which is said to target stem cells in the bone marrow.
Meanwhile, Karikó, assistant professor of neurosurgery at Perelman School of Medicine and senior vice president of BioNTech, is working with the German biotech company to develop mRNA therapies to combat Cancer and autoimmune diseases such as multiple sclerosis.
To understand why the platform is so powerful, it helps to know how RNA molecules help direct activity in our cells.
In every living being, DNA and RNA work together to make proteins. The genes in DNA contain instructions for building proteins, but the DNA remains locked in the nucleus, away from the sites of the cell’s protein construction, the ribosomes. To get the information in our genes from point A to point B, the cell builds a molecule called messenger RNA (mRNA), which rushes in, copies the relevant bits of the genetic code, and zooms in on a ribosome. From there, the ribosomes work with a second molecule, “transfer RNA” (tRNA), to transform this genetic code into a new shine. protein.
RNA vaccines and therapies work very similar to natural RNA, except that scientists build their own personalized RNA molecules in the lab. The synthesized RNA can then be delivered to specific cells in the body, which use the RNA’s instructions to build proteins. When Karikó and Weissman started working together in the 1990s, they experimented with methods of delivering RNA into dendritic cells – immune cells that trigger alarm signals when they detect foreign invaders, such as virus. Vaccines target these cells in order to trigger an immune response and train the body to recognize specific pathogens.
But in this early work, “we found that RNA strongly activates the immune system, possibly because many viruses are RNA and our bodies are continually fighting against them,” Weissman said. In their experiments, the team still managed to get the dendritic cells to build the proteins they wanted, but their synthetic RNA also triggered serious inflammation in cells. “So the work that Kati [Karikó] and I did that for the first seven years or so, was figuring out what made RNA so immunogenic, so activating, and how to get rid of it. “
Eventually, they figured out that they could prevent inflammation by replacing one of the building blocks of mRNA – uridine – with a very similar element called pseudouridin. In human cells, pseudouridin can be found in tRNA, Weissman said. This critical discovery, published in 2005 in the journal Immunity, would be the key to any development of mRNA vaccines in the future, New statistics reported.
After resolving the inflammation issue, the team still faced “a lot of obstacles,” Weissman said. For example, they had to design the best method to get mRNA into cells in the first place. They eventually found that lipid nanoparticles, which are basically tiny bubbles of fat, did the best job of protecting RNA from enzymes that could break it down while circulating the molecules in cells, he said.
All of this work laid the groundwork for the advent of Pfizer and Moderna’s COVID-19 vaccines, which trick cells into building the spike protein characteristic of the coronavirus. And these vaccines can be easily updated to target new coronavirus variants, thanks to the adaptability of the RNA platform. Perhaps in the future, mRNA could form the basis of the first pan-coronavirus vaccine, along with a myriad of other medical treatments.
“The potential is huge,” Weissman said. “My lab is currently working with 150 different labs around the world, developing different mRNA-based vaccines and therapies, so interest in it is increasing day by day.”
Originally posted on Live Science.
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