Researchers at MIT have created an oral mRNA delivery system that could provide an alternative to injectable mRNA vaccines. It could also enable RNA or DNA therapies that are intended to treat gastrointestinal diseases.
mRNA has shown its therapeutic potential in spectacular fashion, providing the powerhouse behind some of the world’s most successful and ubiquitous COVID-19 vaccines. However, not everyone is a fan of injections and an oral delivery solution for these treatments would be most welcome. Oral delivery would also help in directly targeting the gastrointestinal tract with mRNA therapeutics, which is currently very difficult given the inhospitable nature of our gut and the delicate nature of mRNA.
“Nucleic acids, in particular RNA, can be extremely sensitive to degradation particularly in the digestive tract,” said Giovanni Traverso, one of the MIT scientists that created the new delivery system. “Overcoming this challenge opens up multiple approaches to therapy, including potential vaccination through the oral route.”
These researchers have developed domed capsules that can self-right in the stomach. This design was inspired by the steep domed shell of the leopard tortoise, which allows it to right itself if it falls onto its back. In the case of the capsule, this approach ensures that one side will always face the wall of the stomach, allowing the capsule to deliver milli-needle injections of the mRNA cargo into the stomach wall.
As mRNA is so delicate, the researchers incorporated it within polymeric nanoparticles that are encased within the swallowable capsule. So far, the researchers have tested the mRNA delivery system in mice and pigs. The delivered mRNA encoded a reporter protein, which let the researchers identify whether it had been successfully delivered to the cells of the stomach.
They loaded 50 micrograms of mRNA per capsule, and administered three capsules to each pig for a total of 150 micrograms. For context, conventional COVID-19 vaccine doses usually contain about 30–100 micrograms of mRNA. The cells in the pig stomach successfully demonstrated mRNA uptake, suggesting that the technique may be viable for mRNA-mediated vaccination.
Study in journal Matter: Oral mRNA delivery using capsule-mediated gastrointestinal tissue injections