The mRNA vaccine has gained a reputation in the fight against COVID-19, and the scientific community has studied it beyond that.
On Jan. 31, Cell Press's flagship journal in the field of materials, Matter, published online a study by researchers from the Massachusetts Institute of Technology (MIT) and global biopharmaceutical company Novo Nordisk, who developed a way to pack RNA into a special capsule that can be swallowed. In addition to being used to increase public acceptance of the vaccine, the research team hopes that this approach could be used to deliver other therapeutic RNA or DNA directly to the digestive tract, making it easier to treat gastrointestinal disorders such as ulcers.
"Nucleic acids, especially RNA, are very sensitive to degradation, especially in the digestive tract. Overcoming this challenge opened up a variety of treatments, including the possibility of oral vaccination. Giovanni Traverso, an assistant professor in the Department of Mechanical Engineering at MIT and a gastroenterologist at the Women's and People's Hospital, said.
Traverso is one of the study's corresponding authors, and the other is Robert Lange, the first person in the field of global tissue engineering. Lange is one of only 12 college professors at MIT, and the youngest member of the American Academy of Sciences, the Academy of Engineering, and the College of Medicine.
For several years, Langer and Travelso's lab has been developing new ways to deliver drugs to the gastrointestinal tract. In 2019, researchers designed a capsule that, when swallowed, delivered solid drugs such as insulin to the lining of the stomach. In 2021, researchers continue to demonstrate that they can use this capsule to deliver macromolecules such as monoclonal antibodies in liquid form. Next, the researchers decided to try using capsules to deliver nucleic acids.
As mentioned above, nucleic acids are easily degraded after entering the human body and therefore need to be carried by protective particles. For the study, the MIT team used a novel polymer nanoparticle recently developed by Langer and The Travelso lab. These particles, which can efficiently deliver RNA, are made from a polymer called poly (β-amino ester).
To test the particles, the research team first injected them into the stomach sacs of mice without using delivery capsules. If cells successfully absorb RNA, the RNA-encoded reporter proteins they deliver can be detected in tissues. The researchers found the reporter protein in the stomach and liver of the mice, suggesting that the RNA had been absorbed by other organs of the body and then carried to the liver that filtered the blood.
Next, the researchers lyophilized the RNA-nanoparticle complex and loaded it into drug delivery capsules, a study further coordinated with scientists at Novo Nordisk. The research team was able to fill about 50 micrograms of mRNA in each capsule and put 3 capsules into the stomach of the pig, for a total of 150 micrograms of mRNA. That's more mRNA than the COVID-19 vaccines currently in use, which contain 30 to 100 micrograms of mRNA.
In studies of pigs, the researchers found that the reporting protein was successfully produced by stomach cells, but was not detected elsewhere in the body. They mentioned that in future work, it is hoped to increase the uptake of RNA by changing the composition of nanoparticles or increasing the dose.
However, Abramson also said that it is also possible to produce a strong immune response if only the stomach is given. "There are many immune cells in the gastrointestinal tract, and stimulating the immune system of the gastrointestinal tract is a known method of generating an immune response."
The research team plans to further investigate whether they can produce a systemic immune response by delivering mRNA vaccines in capsules, including activating B cells and T cells. This approach can also be used to create targeted therapies for gastrointestinal disorders that are difficult to treat with traditional subcutaneous injection therapy. "We see this as a potential way to treat different diseases present in the gastrointestinal tract." Abramson said.
Https://www.cell.com/matter/fulltext/S2590-2385(21)00680-9?_returnURL=https%3A%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2FS2590238521006809%3Fshowall%3Dtrue#% 20