A pill-like capsule could be used to deliver therapeutic mRNA into the stomach lining as an alternative to injection, a new study by MIT researchers published in the journal Matter has suggested. “We see this as a potential way to treat different diseases that are present in the gastrointestinal tract,” said co-lead author Alex Abramson in a statement. The pill, called the self-orienting millimeter-scale applicator (SOMA), was unveiled in 2019 as a potential new method to administer insulin. In 2021, a study in Nature Biotechnology demonstrated that it could be used to administer monoclonal antibodies. The capsules have an unlikely inspiration: tortoises. “Similar to a leopard tortoise or a weeble-wobble toy, the pill only possesses one stable configuration in which the injection mechanism faces toward the tissue wall,” the authors explain in the paper. “Once the pill self-orients, a hydration-triggered actuator releases a spring-based injection mechanism that propels a needle into the tissue.” The gastrointestinal tract is not currently the ideal route for administering mRNA. The researchers explain in their paper that “nucleic acids are generally administered intravenously or subcutaneously because the gastrointestinal (GI) tract naturally prohibits biomacromolecule uptake. When administered orally, nucleic acids rapidly degrade after ingestion, thus limiting cellular permeation and reducing bioavailability.” “To enable oral delivery, these therapeutics must avoid enzymatic degradation and bypass physical tissue barriers in the gastrointestinal tract” To bypass this obstacle, the team developed new nanoparticles made of polymers to encapsulate and protect the mRNA. The researchers then gave the capsules to three pigs. Each pig was given three pills containing 50 micrograms of mRNA coding for an enzyme called Cre. A day later, the swine were euthanized and tissue from the stomach injection site and the liver were collected. The Cre enzyme was observed in the stomachs of two pigs, but not the third. None of the liver samples showed Cre expression. “The absence of Cre translation in one of the three swine was more likely due to variations in the transfection of the mRNA particles into cells rather than a device malfunction,” the study authors say. “There are many immune cells in the gastrointestinal tract, and stimulating the immune system of the gastrointestinal tract is a known way of creating an immune response,” explained Abramson. In future studies, the researchers aim to investigate whether delivering mRNA into the stomach with SOMA only stimulates an immune response in the stomach, or if an immune response happens throughout the rest of the body. If the capsules cause a systemic immune response, they could be used to vaccinate people afraid of needles, with the researchers explaining in their paper that “Nucleic acid therapeutics and vaccines, such as the COVID-19 vaccine, are only available as injectable formulations because these therapeutic molecules cannot survive passage through the gastrointestinal tract.” “Injectable formulations often result in low acceptance and […] adherence by patients because they cause discomfort and require a trained professional for administration.” Source
