Most SARS-CoV-2 vaccines elicit an immune response that targets the coronavirus ear protein, which is found on the surface of the virus. Messenger RNA vaccinations encode segments of the vein protein, and those mRNA sequences are much easier to generate in the laboratory than the vein protein itself. Credit: Image: Christine Daniloff, MIT; and stock images
Many years of research have enabled scientists to synthesize rapidly RNA vaccines and deliver them in cells.
The development and testing of a new vaccine usually takes at least 12 to 18 months. Just over ten months after the genetic sequence of the EARS-CoV-2 virus, two pharmaceutical companies have applied for FDA authorization for vaccines that appear to be very effective against the virus.
Both vaccines are made from messenger RNA, the molecule that cells naturally use to carry DNAinstructions to cells’ protein-building machinery. A vaccine based on mRNA has never been approved by the FDA before. However, many years of research have been done on RNA vaccines, which is one of the reasons why scientists were able to start testing such vaccines against Covid-19 so quickly. After the viral series was announced in January, it took pharmaceutical companies Moderna and Pfizer, along with its German partner BioNTech, just days to generate candidates for mRNA vaccine.
‘What is particularly unique about mRNA is the ability to quickly generate vaccines against new diseases. I think this is one of the most exciting stories behind this technology, ”says Daniel Anderson, a professor of chemical engineering at MIT and a member of MIT’s Koch Institute for Integrative Cancer Research and Institute of Medical Engineering and Science.
Most traditional vaccines consist of killed or attenuated forms of a virus or bacterium. It triggers an immune response with which the body can later fight the actual pathogen.
Instead of delivering a virus or a viral protein, RNA vaccines provide genetic information that enables the body’s own cells to produce a viral protein. Synthetic mRNA encoding a viral protein can borrow this machinery to produce many copies of the protein. These proteins stimulate the immune system to get a response, without posing any risk of infection.
An important advantage of mRNA is that it is easy to synthesize once researchers know the sequence of the viral protein they want to target. Most vaccines for SARS-CoV-2 elicit an immune response that targets the coronavirus ear protein, which occurs on the surface of the virus and gives the virus its characteristic prickly shape. Messenger RNA vaccinations encode segments of the vein protein, and those mRNA sequences are much easier to generate in the laboratory than the vein protein itself.
‘With traditional vaccines, you have to develop a lot. You need a large factory to produce the protein or virus, and it takes a long time to grow it, ‘says Robert Langer, professor at the David H. Koch Institute at MIT, a member of the Koch Institute, and one of the founders of Moderna. ‘The beauty of mRNA is that you do not need it. If you inject nanocapsulated mRNA into a person, it goes into the cells and then the body is your factory. From there, the body takes care of everything else. ”
For decades, Langer has been developing new ways of delivering drugs, including therapeutic nucleic acids such as RNA and DNA. In the 1970s, he published the first study showing that it is possible to encapsulate nucleic acids, as well as other large molecules, in small particles and deliver them into the body. (The work by Professor Phillip Sharp of the MIT Institute and others on RNA cleavage, which also laid the foundation for today’s mRNA vaccines, also began in the 1970s.)
“It was very controversial at the time,” Langer recalls. “Everyone told us it was impossible, and my first nine grants were rejected. I worked on it for about two years and I found over 200 ways to make it work. But in the end, I finally found a way to make it work. ‘
That paper, which in Earth in 1976 showed that small particles of synthetic polymers can safely carry and release large molecules such as proteins and nucleic acids. Later, Langer and others showed that when polyethylene glycol (PEG) is added to the surface of nanoparticles, they can last longer in the body, instead of being destroyed almost immediately.
In the following years, Langer, Anderson and other fatty molecules called lipid nanoparticles developed, which are also very effective at delivering nucleic acids. These carriers protect RNA from degradation in the body and help it transport cell membranes. Both the Moderna and Pfizer RNA vaccines are carried by lipid nanoparticles with PEG.
Messenger RNA is a large hydrophilic molecule. It does not enter cells on its own, and therefore these vaccines are wrapped in nanoparticles that facilitate their delivery into the cells. It allows the RNA inside cells and then translates it into proteins, ‘says Anderson.
In 2018, the FDA approved the first lipid nanoparticle carrier for RNA, developed by Alnylam Pharmaceuticals to produce a type of RNA called siRNA. Unlike mRNA, siRNA silences its target genes, which can benefit patients by eliminating mutated genes that cause disease.
One disadvantage of mRNA vaccines is that they can degrade at high temperatures, and therefore the current vaccines are stored at such cold temperatures. Pfizer’s SARS-CoV-2 vaccine should be stored at -70 degrees Celsius (-94 degrees Fahrenheit), and the Moderna vaccine at -20 C (-4 F). One way to make RNA vaccines more stable, Anderson points out, is to add stabilizers and remove water from the vaccine through a process called lyophilization, which has shown that some mRNA vaccines are refrigerated instead of ‘ a freezer can be stored.
The striking efficacy of both of these Covid-19 vaccines in phase 3 clinical trials (approximately 95 percent) offers hope that these vaccines will not only help end the current pandemic, but also help RNA vaccines in the future. in the fight against other diseases such as HIV and cancer, says Anderson.
‘People in the field, including me, have seen a lot of promise in technology, but you do not really know until you get human data. ‘To see that the level of protection, not only with the Pfizer vaccine, but also with Moderna, really validates the potential of the technology – not only for Covid, but also for all these other diseases that people are working on,’ says he. “I think this is an important moment for the field.”