If messenger-RNA vaccines are the breakthrough of the epidemic, then the small lipid spheres that bring them to human cells are the undisputed heroes.
The world desperately needs both.
Consider BioNTech, which until a year ago was buying a few grams of lipids to support a drug development program that most people thought had not been mainstream for years. Major German chemical companies such as Merck and Evonik Industries are now boosting their production, which could be a big step if they գործընկեր partner Pfizer Inc. are ready for their COVID-19 vaccine 2 this year. billion dose delivery programs. ,
“We need those pounds and pounds,” said Cierk Poetting, chief financial officer of BioNTech, citing lipids as one of his most pressing needs.
Manufacturers benefit. On Thursday, Merck forecast record earnings for this year, citing strong demand for vaccine developers, among other supplies, a lipid-producing unit.
Lipids have topped the list of the world’s top healthcare providers, as other vaccines developed by Pfizer-BioNTech և Moderna as well as CureVac և Sanofi cannot do without them. Messenger RNA, the genetic material underlying these vaccines, needs a protective membrane made up of four different types of fatty material, called lipid nanoparticles, to be able to successfully pass from plant to human and then enter. human cells
Governments looking to turbocharge Covid vaccines are learning from officials that making more lipids is not easy.
“This is an incredibly difficult process,” President Biden said as he toured the Michigan plant last month with Pfizer CEO Albert Burla, who promised to produce more lipids, along with mRNA, as part of a vaccine duplication. Biden was amazed at the close collaboration between machine technicians, chemists, and biologists, who were “advanced technologies that, in less than a year, far exceeded theories and aspirations.”
For Bob Langer, those aspirations last much longer. Back in the 1970s, he was trying to prove that you could capture, move large, complex molecules, such as DNA, RNA inside small particles without destroying them.
“Everyone told me it was impossible,” he recalled in a telephone interview. “I turned down my first nine grants. I could not get a job at the faculty. “
It turns out that it was possible, և Langer was not unemployed for a long time. Today, the professor at the Massachusetts Institute of Technology has a chemical engineering lab named after him, focused on the intersection of biotechnology and material science. After decades of development, in 2010 Langer founded Moderna, where he still serves on the board. The company, like BioNTech և CureVac, develops mRNA vaccines for infectious diseases beyond Covid, as well as treatments for cancer and rare diseases.
“I do not think people have realized how important delivery systems can be for all kinds of drugs,” Langer said. “If you get more and more complex drugs, like RNA, DNA, things like that, you’ll see more and more work on delivery systems, more and more problems will be solved. Lipid nanoparticles will be a big part of the arsenal. ”
The drug delivery industry was at a watershed in 2018 when the Food and Drug Administration approved new therapy from Alnylam Pharmaceuticals Inc. This drug, Onpattro, treats a rare genetic disease that causes nerve and heart damage. Although it works a little differently than mRNA treatment, it is delivered via lipid nanoparticles. This meant that regulators had at least some level of comfort with the idea of an epidemic.
Thomas Madden has worked with Alnylam for years to develop these pioneering lipids. Upon confirmation, he had long since reorganized his Vancouver-based company, Acuitas Therapy, into what he considered to be the most promising area of mRNA. He recalls the Eureka moment around 2011, when he read a scientific article detailing recent progress in the field, concluding that companies need even better delivery tools. This is because the body is full of enzymes that are designed to directly cut the mRNA found outside the cells.
To prevent this from happening, Covid shot mRNA sits inside a membrane of four lipids. After protecting the mRNA during human travel, the nanoparticle is transported to the cell. There, the positively charged lipid helps the mRNA to come out. Once in the cell’s cytoplasm, the mRNA instructs the cell to make copies of the coronavirus stem protein, stimulating the body’s immune system to build defenses.
Moderna designed its recharged lipids, while Acuitas licensed its delivery technology to BioNTech և CureVac. Each of these companies was involved in early clinical trials of mRNA treatment prior to the epidemic.
When covid-19 appeared, Madden flew to Germany to talk to regulators և BioNTech officials about how they could most quickly begin clinical trials of mRNA wall shots. They decided to reuse the lipid nanoparticle from the rabies vaccine developed by CureVac because it was already effective for humans.
“The package really does not care what is inside,” explains Madden. “It will just deliver.”
In addition to Pfizer 2 BioNTech’s 2 billion doses, Moderna plans to produce 1 billion shots, while CureVac targets և 300 million. These other companies are also moving fast to develop other mRNA products in their pipelines, increasing the unprecedented demand for lipid nanoparticles.
Considered major chemical manufacturers of drugs. In early February, German Merck agreed to speed up the supply of lipids to BioNTech, while Evonik backed down from that example a week later.
Evonik rebuilds tanks and ships at two German plants, buys new tools in the cleaning process.
“Usually in the pharmaceutical industry, this process takes a year or two,” said Thomas Riermayer, head of the company’s healthcare department, in an interview. “It takes more or less a few months to do that.”