Like most vaccines, mRNA vaccines need to be injected with syringes, which can be an obstacle for people who are afraid of needles. If the mRNA vaccine can be delivered orally, it will undoubtedly help people to accept it more easily.

However, nucleic acid is easy to degrade, and RNA in particular, not to mention in the digestive tract. If the problem of nucleic acid degradation in the digestive tract can be overcome, in addition to oral mRNA vaccine, it can also be used to deliver RNA or DNA drugs directly to the digestive tract, thus making it easier to treat gastrointestinal diseases.

Recently, Professor Robert Langer and Professor Giovanni Traverso of the Massachusetts Institute of Technology (MIT) published a research paper entitled Oral mRNA delivery using capsule-mediated gastrointestinal tissue injections in the journal Matter.

The team developed a new way to deliver the mRNA vaccine through an oral capsule, and tested it in pigs. The capsule can deliver up to 150 micrograms of mRNA to the stomach of pigs, more than the mRNA in mRNA COVID-19 vaccine. The team believes that oral administration of mRNA can facilitate the rapid deployment of intermittent interventions such as vaccines and support long-term treatment.

Over the past few years, Professors Robert Langer and Giovanni Traverso have been developing new ways to deliver drugs to the gastrointestinal tract.

They developed a blueberry-sized capsule that lowers blood sugar by injecting insulin into the stomach wall after oral administration. Importantly, the capsule can correct direction by itself and ensure accurate injection.

In the capsule, the needle is connected to the compression spring, which is fixed in place by a disc made of sugar. After the capsule is swallowed, the water in the stomach dissolves the sugar disc, releasing the spring and injecting the needle into the stomach wall. Because there is no pain receptor in the stomach wall, the patient cannot feel the pain caused by the injection. To ensure that the drug is injected into the stomach wall, the researchers designed a capsule that won’t be dissolved until arriving at the stomach, and the needle may come into contact with the inner wall of the stomach.

Once the tip of the needle is injected into the stomach wall, the insulin dissolves at a controlled rate. In this study, it took about an hour for all insulin to be fully released into the bloodstream.

The team said the inspiration came from the self-positioning characteristics of a species of tortoise called the leopard tortoise. The tortoise, found in Africa, has a high, steep dome in its shell that allows it to tumble and quickly return to normal posture. The research team used computer modeling to design the shape and structure of the capsules so that they can also be repositioned in the dynamic environment of the stomach to ensure the accuracy of the injection.

In 2021, the team showed that the capsules could also be used to deliver protein macromolecules, such as monoclonal antibodies, in liquid form. Next, they began to experiment on nucleic acid delivery with the capsule.

It is well known that nucleic acids are easily degraded after entering the human body, so they need to be carried by protective particles. Professors LRobert Langer and Giovanni Traverso recently developed a new type of polymer nanoparticles that can efficiently deliver RNA. The nanoparticles were made of poly (β-amino ester), and they found that the branched form of the polymer protected nucleic acids better than the linear form and allowed them to enter the cell.

The team first tested the effect of the branched poly (β-amino ester) nanoparticles. The experimental results showed that after injection, the mRNA carried by the nanoparticles was delivered to stomach, liver and other organs, and was effectively expressed.

Next, the team freeze-dried the mRNA-nanoparticle complex and packaged it in a capsule. Working with Novo Nord scientists, they loaded about 50 micrograms of mRNA in each capsule and delivered three capsules orally to the stomach of pigs at a time. This delivery amount exceeds the currently used mRNA in COVID-19 vaccine, which contains about 30-100 micrograms of mRNA at a time.

In the study of pigs, the team found that pig stomach cells successfully produced reporter proteins, but other organs and tissues didn’t. The team said that in follow-up studies, the composition of nanoparticles would be improved or higher doses would be given to increase the absorption of mRNA delivered to other organs. It is also possible that simply delivering mRNA to the stomach is enough to induce a strong immune response, because there are many immune cells in the gastrointestinal tract that can stimulate the immune system, the team said.