RNA vaccines have to be injected, which can be an obstacle for people who fear needles. The team hopes its new method could help people become more receptive to RNA vaccines by making them easier to tolerate.
The approach could also be used to deliver other kinds of therapeutic RNA or DNA directly to the digestive tract, which could allow for easier treatment of gastrointestinal disorders such as ulcers.
“Nucleic acids, in particular RNA, can be extremely sensitive 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 Matter, Traverso and his colleagues described how they showed ability to use the capsule to deliver up to 150 micrograms of RNA — more than the amount used in mRNA Covid vaccines, which have 30 to 100 micrograms — in 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, have been developing novel ways to deliver drugs to the gastrointestinal tract for years.
In 2019, the researchers designed a capsule 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 tortoise can right itself if it rolls onto its back, the capsule can orient itself so that its contents can be injected into the stomach lining.
Last year, they showed that they could use the capsule to deliver large molecules such as monoclonal antibodies in liquid form. Next, researchers decided to try to use the capsule to deliver nucleic acids, which are also large molecules.
As they are susceptible to degradation in the body, nucleic acids need to be carried by protective particles. The MIT team used a new type of polymeric nanoparticle for this study, recently developed in Langer and Traverso’s labs.
The particles, said to deliver RNA with high efficiency, are made from 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 study’s lead authors, explained that through making a library of branched hybrid poly(beta-amino esters), the team could reduce the total amount of nanoparticles administered.
To test the particles, researchers first injected them into the stomachs of mice without using the delivery capsule. The RNA that they delivered codes for 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 had been taken up in other organs and then carried to the liver which filters the blood.
Next, they freeze-dried the RNA-nanoparticle complexes and packaged them into their drug delivery capsules. Working with scientists at Novo Nordisk, they could load around 50 micrograms of mRNA per capsule, and delivered three capsules into pigs’ 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 nanoparticles’ composition or giving larger doses. However, co-lead author Alex Abramson said it may be possible to generate a strong immune response with delivery only to the stomach.
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.