The messenger ribonucleic acid (mRNA) used in vaccines has transformed into a pill that prevents inflammation in the intestines. In animal experiments, a capsule containing the mRNA treatment successfully treated inflammatory bowel disease (IBD) by reaching the intestines without dissolving in stomach acid.
Researchers at Brigham and Women's Hospital, Harvard Medical School, noted on the 17th in the journal Science Translational Medicine that they succeeded in delivering an mRNA drug contained in a capsule called RNACap to the intestines of experimental animals.
Professor Wei Tao, who led the research, said, "The method of safely reaching the intestines itself has significant meaning" and added, "The mRNA contained in the capsule reached the intestinal mucosal cells and macrophages to directly produce anti-inflammatory proteins."
mRNA copies some information from genetic DNA to synthesize proteins in cells. This is also used in the novel coronavirus disease (COVID-19) vaccine. When injected, the mRNA in the body produces spike proteins of the coronavirus, inducing an immune response that generates antibodies.
The mRNA COVID vaccine gained attention for its rapid development speed and high efficacy compared to existing vaccine technologies, and it is continuing to evolve into various disease vaccines and treatments. However, it has been developed solely as an injection administered by medical personnel, limiting convenience for patients and accessibility to medical care.
The researchers at Brigham and Women's Hospital conducted research to convert the injectable formulation into an oral mRNA treatment. The key challenge was to ensure mRNA's stability in stomach acid, accurately deliver it to the target area in the intestines, and optimize cellular absorption.
The research team placed the mRNA that would produce therapeutic proteins into the RNACap capsule. The original component, which dissolves in water, was specially coated on its surface to prevent it from dissolving in acidic gastric juices. In the process of the capsule passing through the stomach to the intestines, this coating dissolves, and intestinal peristalsis causes the capsule to open, releasing the mRNA drug. Finally, the mRNA is absorbed by intestinal cells and produces therapeutic proteins to exert its effects.
The research team included mRNA capable of synthesizing a protein called "interleukin (IL)-10" in the capsule. IL-10 is a cytokine protein that regulates immune responses and has anti-inflammatory effects. After administering the capsule containing mRNA to mice and pigs with colitis, the researchers reported that inflammatory protein levels decreased and intestinal tissue damage was alleviated.
In particular, it was confirmed during the pig experiments that the RNACap capsule operates quickly in the intestines without being broken down in the stomach. Clear mRNA expression was observed in the intestinal tissues just 8.5 hours after dosing. The research team anticipates similar effects will appear in humans.
The researchers assessed that this technology could develop into an oral mRNA treatment applicable not only to inflammatory bowel diseases but also to various disease treatments. Professor Tao remarked, "The biggest advantage of mRNA capsules is that they can be taken as pills and are non-invasive, with no harm to the human body," adding, "This is especially beneficial for patients who require continuous medication, such as those with chronic diseases."
Jacob Becraft, CEO of Strand Therapeutics, a U.S. mRNA therapeutic development corporation, evaluated, "Oral mRNA treatments will change the landscape of gastrointestinal therapies." Dr. Joanna Melia, a gastroenterologist at Johns Hopkins Hospital, also noted, "The attempt to deliver mRNA directly to the intestines is very encouraging" and expressed hopes that this technology would evolve into a platform applicable for the treatment of various diseases.
However, there are hurdles to overcome before mRNA pills can be commercialized. mRNA drugs are challenging to store and have short shelf lives. mRNA vaccines must be kept in ultra-low temperature freezers (cold chain) at -70 degrees Celsius. The researchers at Brigham and Women's Hospital stated that they are developing a more stable mRNA treatment and will also pursue clinical trials involving people. Furthermore, they are conducting research to expand the oral capsule technology beyond mRNA treatments to include vaccines and other drugs.
References
Science Translational Medicine (2025), DOI: https://doi.org/10.1126/scitranslmed.adu1493