Cell Sub-journal: Preparation Of Swallowable RNA Vaccine, Capsule Delivery Of MRNA Vaccine Is Expected To Achieve
Mar 28, 2022
Contact: Audrey Hu Whatsapp/hp: 0086 13880143964 Email: audrey.hu@wecistanche.com
mRNA vaccines have become famous in the fight against the new crown, and the scientific community's research on them does not stop there.
On January 31, Matter, the flagship journal of Cell Press in the field of materials, published a study online by researchers from the Massachusetts Institute of Technology (MIT), global biopharmaceutical company Novo Nordisk and other teams. They developed an A method of packing 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 RNAs or DNA directly into the digestive tract, making it easier to treat gastrointestinal conditions such as ulcers

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"Nucleic acids, especially RNA, are very sensitive to degradation, especially in the digestive tract. Overcoming this challenge opens up a variety of therapeutic approaches, including the possibility of vaccination via the oral route." Brigham, assistant professor in MIT's Department of Mechanical Engineering and Women's Hospital gastroenterologist Giovanni Traverso said.
Traverso is one of the corresponding authors of the study, and the other corresponding author is Robert Lange, the first person in the field of global tissue engineering. According to the official website, Lange is one of only 12 college professors at MIT, and the youngest member of the American Academy of Sciences, Engineering, and Medicine.
For several years, Langer and Traverso's labs have been developing new ways to deliver drugs to the gastrointestinal tract. In 2019, researchers designed a capsule that, when swallowed, could deliver solid drugs such as insulin to the lining of the stomach. In 2021, the researchers went on to demonstrate that they could use the capsule to deliver macromolecules such as monoclonal antibodies in liquid form. Next, the researchers decided to try using capsules to deliver nucleic acids.

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As mentioned above, nucleic acids are easily degraded after entering the human body, so they need to be carried by protective particles. For this study, the MIT team used a new type of polymer nanoparticles recently developed in the Langer and Traverso labs. These particles, which deliver RNA efficiently, are made of a polymer called poly(beta-aminoester).
To test the particles, the research team first injected them into the stomachs of mice without using a delivery capsule. If the cells successfully took up the RNA, the reporter protein encoded by the RNA they delivered could be detected in the tissue. The researchers found reporter proteins in the mice's stomachs and livers, suggesting that the RNA had been taken up by other organs in the body and taken to the liver, which filters the blood.

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Next, the researchers lyophilized the RNA-nanoparticle complexes and loaded them into drug-delivery capsules, a study further collaboration with scientists from Novo Nordisk. The research team was able to pack about 50 micrograms of mRNA into each capsule and put three capsules into the pig's stomach for a total of 150 micrograms of mRNA. That's more mRNA than currently used Covid-19 vaccines, which contain 30 to 100 micrograms of mRNA.

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In studies with pigs, the researchers found that the reporter protein was successfully produced by stomach cells, but not detected elsewhere in the body. They mentioned that in future work, they hope to increase RNA uptake by other organs by changing the composition of the nanoparticles or increasing the dose.
However, Abramson also said that it is also possible to generate a strong immune response when given to the stomach alone. "There are many immune cells in the gastrointestinal tract, and stimulating the immune system in the gastrointestinal tract is a known way to generate an immune response."
The research team plans to further investigate whether they can deliver the mRNA vaccine via capsules to generate a systemic immune response, including activation of B and T cells. This approach could also be used to create targeted treatments for gastrointestinal disorders that are difficult to treat with traditional subcutaneous injections. "We think this is a potential way to treat different diseases that exist in the gastrointestinal tract," Abramson said.







