'mRNA' in Amazing Science

Tags
Current selected tag: 'mRNA'. Clear

COVID-19 and Flu-Ravaged Lungs Could Be Repaired with mRNA Therapy | Amazing Science | Scoop.it

From www.genengnews.com - February 19, 3:04 AM

Viral infection can lead to acute respiratory distress syndrome that damages the lungs and is often lethal. Zhao et al. show that the TGF-β receptor 2 (TGF-βR2) is important for lung endothelial cells to recover after injury due to influenza virus or SARS-CoV-2 infection. The researchers used mice, human organoids, and human endothelial cells to demonstrate how TGF-βR2 interacts with VEGFA specifically in endothelial lung cells to promote tissue regeneration after viral injury. They also developed lung-targeted nanoparticles to deliver Vegfa mRNA to promote lung healing in mice lacking TGF-βR2. This study highlights the potential for targeting TGF-βR2 signaling in lung endothelial cells as a treatment for acute respiratory distress syndrome.

Disruption of pulmonary vascular homeostasis is a central feature of viral pneumonia, wherein endothelial cell (EC) death and subsequent angiogenic responses are critical determinants of the outcome of severe lung injury. A more granular understanding of the fundamental mechanisms driving reconstitution of lung endothelium is necessary to facilitate therapeutic vascular repair.

Now a team of scientists demonstrated that TGF-β signaling through TGF-βR2 (transforming growth factor–β receptor 2) is activated in pulmonary ECs upon influenza infection, and mice deficient in endothelial Tgfbr2 exhibited prolonged injury and diminished vascular repair. Loss of endothelial Tgfbr2 prevented autocrine Vegfa (vascular endothelial growth factor α) expression, reduced endothelial proliferation, and impaired renewal of aerocytes thought to be critical for alveolar gas exchange.

Angiogenic responses through TGF-βR2 were attributable to leucine-rich α-2-glycoprotein 1, a proangiogenic factor that counterbalances canonical angiostatic TGF-β signaling. Further, the scientists developed a lipid nanoparticle that targets the pulmonary endothelium, Lung-LNP (LuLNP). Delivery of Vegfa mRNA, a critical TGF-βR2 downstream effector, by LuLNPs improved the impaired regeneration phenotype of EC Tgfbr2 deficiency during influenza injury.

These studies defined a role for TGF-βR2 in lung endothelial repair and demonstrated efficacy of an efficient and safe endothelial-targeted LNP capable of delivering therapeutic mRNA cargo for vascular repair in influenza infection.

Via Juan Lama

Pioneers of mRNA COVID Vaccines Win Nobel Prize for Medicine | Amazing Science | Scoop.it

From www.nature.com - October 6, 2023 2:23 PM

Katalin Karikó and Drew Weissman laid the groundwork for immunizations that were rolled out during the pandemic at record-breaking speed. This year’s Nobel Prize in Physiology or Medicine has been awarded to biochemist Katalin Karikó and immunologist Drew Weissman for discoveries that enabled the development of mRNA vaccines against COVID-19. The vaccines have been administered more than 13 billion times, saved millions of lives and prevented millions of cases of severe COVID-19, said the Nobel committee. Karikó, who is at Szeged University in Hungary, and Weissman, at the University of Pennsylvania in Philadelphia (UPenn), paved the way for the vaccines’ development by finding a way to deliver genetic material called messenger RNA into cells without triggering an unwanted immune response. They will each receive an equal share of the prize, which totals 11 million Swedish krona (US$1 million). Karikó is the 13th female scientist to win a Nobel Prize in medicine or physiology. She was born in Hungary, and moved to the United States in the 1980s. “Hopefully, this prize will inspire women and immigrants and all of the young ones to persevere and be resilient. That’s what I hope,” she tells Nature.

A new chapter

The COVID-19 vaccines developed by Moderna and the Pfizer–BioNTech collaboration deliver mRNA that instructs cells to create copies of a protein that is found on SARS-CoV-2 virus particles, called the spike protein. This stimulates the body to make antibodies that target the protein, as well as triggering other immune responses. For decades, mRNA vaccines were considered unfeasible because the injection of mRNA into the body triggered an immune reaction that immediately broke down the mRNA. In the mid-2000s, working at UPenn, Karikó and Weissman demonstrated that swapping one type of molecule in mRNA, called uridine, with a similar one called pseudouridine bypasses the cells’ innate immune defences[1].

“I’m delighted to see them recognized,” says Robin Shattock, a vaccine scientist at Imperial College London, who has worked on mRNA vaccines. “Their contribution was really fundamental in the success of the COVID-19 vaccines, and I think will underlie RNA technology for some time to come.” “They demonstrated that changing the type of the RNA nucleotides within the vaccine altered the way in which cells see it,” said John Tregoning, a vaccine immunologist at Imperial College London, in a press statement for the UK Science Media Centre. “This increased the amount of vaccine protein made following the injection of the RNA, effectively increasing the efficiency of the vaccination: more response for less RNA. This discovery has opened a new chapter for medicine,” said Nobel committee member Qiang Pan Hammarström, an immunologist at the Karolinska Institute in Stockholm, at a press conference after the prize announcement. “Investment in long-term basic research is very important.”

Vaccine revolution

There are now mRNA vaccines in development for a number of other diseases, including influenza, HIV, malaria and Zika. “It’s really like a revolution starting since the COVID pandemic,” says Rein Verbeke, an mRNA vaccine researcher at the Ghent University in Belgium. He adds that Karikó and Weissman’s contributions were essential to the vaccines’ success during the pandemic, and beyond. “Their part was really crucial to the development of this platform.” A COVID-19 mRNA vaccine containing unmodified RNA, developed by CureVac, based in Tübingen, Germany, was widely seen as a flop after its mediocre performance in clinical trials. Another key component of COVID-19 mRNA vaccines was the lipid nanoparticles (LNPs) that surround the modified RNA and ease its entry into cells.

Numerous scientists contributed to the development of LNPs, says Verbeke, and it would have been nice if the Nobel committee had also recognized their contributions to mRNA vaccines. The modification of mRNA and the development of LNPs “were the two major steps that were necessary to have mRNA vaccines working”, he says. Many people were involved in developing LNPs, however, and it would be difficult to single out any one contribution, says Pierre Meulien, who worked on using mRNA to trigger immune responses in the 1990s at Transgène, a small biotech firm near Strasbourg in France. Karikó and Weissman “really created the key to success of the whole enterprise around mRNA vaccines”, he adds. The development of mRNA vaccines and therapeutics is still in its infancy, says Shattock.

Scientists and biotechnology companies are busy coming up with new applications for mRNA technology, from cancer treatments to next-generation COVID-19 vaccines. Many teams are also working on improved ways of delivering mRNA. “What we see used today is not what’s going to be used in the future,” he says. “We’re at the beginning of an RNA revolution.” Although COVID-19 jabs put mRNA vaccines on the map, the technology’s impact is likely to reach far and wide, says Karikó. “It is just limitless.”

https://doi.org/10.1038/d41586-023-03046-x

Via Juan Lama

COVID-19 and Flu-Ravaged Lungs Could Be Repaired with mRNA Therapy

Pioneers of mRNA COVID Vaccines Win Nobel Prize for Medicine

A new chapter

Vaccine revolution