A team of researchers at the Massachusetts Institute of Technology (MIT) has developed a method to deliver RNA in a capsule that can be swallowed.
RNA vaccines have to be injected, which can be an obstacle for people who are afraid of needles. The team hopes the new method can help people become more receptive to RNA vaccines by making them easier to tolerate.
The approach could also be used to deliver other types of therapeutic RNA or DNA directly into the digestive tract, allowing for easier treatment of gastrointestinal conditions such as ulcers.
“Nucleic acids, especially RNA, can be extremely susceptible to degradation, particularly in the digestive tract,” said Giovanni Traverso, the Karl van Tassel Career Development Assistant Professor of Mechanical Engineering at MIT and a gastroenterologist at Brigham and Women’s Hospital.
In a study published in the journal MatterTraverso and his colleagues described how they demonstrated the ability to use the capsule to deliver up to 150 micrograms of RNA — more than the amount used in mRNA Covid vaccines, which contain 30 to 100 micrograms — into the stomach of pigs.
Senior authors of the study Traverso and Robert Langer, the David H. Koch Institute Professor at MIT and a member of MIT’s Koch Institute for Integrative Cancer Research, spent years developing new ways of delivering drugs to the gastrointestinal tract.
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In 2019, the researchers designed a capsule that designed a capsule that can place solid drugs such as insulin into the lining of the stomach after being swallowed.
The pill is about the size of a blueberry and has a high, steep ‘dome’ inspired by the leopard tortoise. Just as the turtle can erect itself when it rolls onto its back, the capsule can orient itself so that its contents can be injected into the gastric mucosa.
Last year they showed that they can use the capsule to deliver large molecules such as monoclonal antibodies in liquid form. Next, researchers decided to use the capsule to deliver nucleic acids, which are also large molecules.
Because they are prone to breakdown in the body, nucleic acids must be carried by protective particles. For this study, the MIT team used a new type of polymer nanoparticle, recently developed in the labs of Langer and Traverso.
The particles, said to release RNA with high efficiency, are made of a type of polymer called poly(beta-amino esters). The team’s previous work showed that branched versions of these polymers are more effective than linear polymers at protecting nucleic acids and getting them into cells. They also showed that using two polymers together is more effective than just one.
Ameya Kirtane, one of the lead authors of the study, explained that by creating a library of branched hybrid poly(beta-amino esters) the team was able to reduce the total amount of nanoparticles administered.
To test the particles, researchers first injected them into the stomachs of mice without using the administration capsule. The RNA they delivered encodes a reporter protein that can be detected in tissue if cells successfully take up the RNA. Researchers found the reporter protein in the stomachs and liver of mice, suggesting that RNA was taken up in other organs and then transported to the liver which filters the blood.
They then freeze-dried the RNA-nanoparticle complexes and packaged them in their drug delivery capsules. Working with scientists at Novo Nordisk, they were able to load about 50 micrograms of mRNA per capsule and deliver three capsules into pig stomachs.
In these studies, researchers found that the reporter protein was successfully produced by the cells of the stomach, but did not see it elsewhere in the body. In future work, they hope to increase RNA uptake in other organs by changing the composition of the nanoparticles or giving larger doses. However, co-lead author Alex Abramson said it is possible to generate a strong immune response with delivery to the stomach alone.
Researchers now plan to investigate whether they can create a systemic immune response, including activation of B and T cells, by delivering mRNA vaccines using their capsule.
