Nucleic acids are enabling a new generation of therapeutics and vaccines to treat and prevent a range of diseases. While these therapies have typically been limited to parenteral dosing, patients and clinicians prefer oral dosage forms. Furthermore, oral delivery enables local transfection of cells in the gastrointestinal tract that are not easily targeted via parenteral administration.

To address these challenges, we synthesized and screened a library of branched hybrid poly(β-amino ester) mRNA nanoparticles for transfection efficiency. We then combined the highest-performing formulations with ingestible milli-injector capsules capable of delivering the formulations directly into gastric tissue.

We validated the performance of both the formulations and devices in rodents and pigs, demonstrating protein translation in delta, gastric, and parietal cells of the gastric mucosa, in addition to systemic uptake.

We anticipate that oral delivery of mRNA could facilitate the rapid deployment of episodic interventions, such as vaccines, while also supporting long-term therapies.