RNA, particularly small interfering RNA (siRNA), is linked to gastrointestinal disorders. siRNA aims at genes that are involved with gastrointestinal diseases such as inflammatory bowel disease, celiac, and esophageal scarring, therefore, introducing it into the digestive tract is one step taken to cure such diseases. However, as simple and easy as this method seems, doctors find it difficult to get this nucleic acid into the gastrointestinal environment. This is because this environment is unpleasantly rough to nucleic acids (particularly RNA) as it causes their degradation. This prompted scientists to go into research to find a way around it.
The research team at MIT’s Koch Institute for Integrative Cancer Research was one of those that began this research, and they found a remedy: they thought of introducing RNA into the digestive tract in form of a drug. So, they designed a capsule in a way that has a protective coating for the nucleic acid when ingested into the digestive tract.
The research team employed knowledge from the discovery made by researchers at Langer’s and Traverso’s labs. In 2019, the latter designed a capsule that could introduce insulin into the stomach’s lining after being swallowed; and in 2021, showed that large molecules like monoclonal antibodies (in liquid form) and nucleic acids, can also be taken into the body via capsules. However, they did not produce capsules that could protect the nucleic acids while in the digestive tract for a longer period. This was done by the former.
The MIT research team worked on improving the protective coating for nucleic acids. They further developed the protective particles made by Langer’s and Traverso’s labs, by designing a new type of nanoparticle – the protective coating for the nucleic acid. Made from a polymer known as poly beta-amino ester, this particle is highly efficient at delivering RNA into the body. They found that using the branched structures of this polymer works more effectively than its linear counterpart; and that using two instead of one polymer for the design of the particle, does a better job at protecting nucleic acids.
They tested the newly-improved nanoparticle on mice and pigs: to the mice, they injected the particles into their stomachs barely without the capsule; into the pig’s stomachs, they delivered three capsules, each containing 50mg of the RNA-nanoparticle complex. The RNA contained in the capsule codes for a reporter protein which is easily detected via the tissues of the animals when taken up by their cells.
After a while, they noticed that reporter proteins were present both in the stomach and liver of the mice. They concluded that the RNA was also taken up by other organs of the body since the protein was found also in the liver. In the pigs’ stomachs, they noticed the reporter proteins were fully taken up by their cells and were not present at any other organ. They are currently working on increasing the uptake of RNA by other organs, even while delivered via the capsules.
Also, the study shows that the immune system can be better stimulated if RNA vaccines, in form of capsules (designed with the knowledge from this study), were to be introduced into the gastrointestinal tract since many immune cells are present in the gastrointestinal tract.
This study is of utmost importance as it unravels the mystery behind RNA survival in the digestive tract. This solved puzzle has opened the door to solving gastrointestinal disorders by introducing siRNAs. In addition, people who shy away from vaccines due to the fear of injections can now receive vaccines in form of pills.
If this research is implemented then in the future doctors could use RNA-based treatments for diseases of the digestive tract, via easy-to-swallow pills.