Researchers at Harvard Medical School and Brigham and Women’s Hospital have developed an innovative oral delivery system known as RNACap, which enables the administration of liquid mRNA therapeutics specifically targeting intestinal diseases. This MSAD™ platform technology fundamentally changes the treatment space by eliminating painful and inconvenient needle injection procedures. It provides a sexier, more patient-friendly approach for something like colitis.
Unlike traditional pH sensors, the RNACap is based on next-generation pH-sensitive coatings. It adds release membranes that rupture under pressure to prevent the capsule from opening in the stomach. After it arrives in the intestines, the capsule releases its payload of liquid mRNA and allows the mRNA to enter intestinal epithelial cells directly. Beyond the creativity and artistic design, thoughtful design, and engineering expertise, the success of RNACap is a leap forward in the emerging field of oral mRNA therapeutics.
Engineering Breakthroughs in mRNA Delivery
RNACap design incorporates nanoparticles patterned with G0-C14/PLGA/PEG-lipid components. Together these structural features are key to improving mucus penetration and promoting endosomal escape, enabling efficient cellular uptake of mRNA. In formalized studies, RNACap showed highest transfection efficiency in vitro with 5% DMPE-PEG formulation.
Across animal trials with both Sprague-Dawley rats and Yorkshire swine, RNACap achieved successful intracellular delivery of interleukin-10 (IL-10) mRNA. This translated into increased IL-10 protein levels in both serum and colonic tissue. This fourth finding indicates that the delivery system may be powerful in clinical applications.
“Oral delivery of liquid mRNA therapeutics by an engineered capsule for treatment of preclinical intestinal disease,” – Xiangang Huang et al
Promising Results in Preclinical Models
The efficacy of RNACap was further validated in preclinical models of colitis. In these studies, the intraluminal delivery of RNACap produced quantifiable mRNA expression as early as 8.5 hours. Elutec treatment not only led to the drastic suppression of proinflammatory cytokines, but restored proper in vivo healing in dextran sodium sulfate-induced colitis models.
Serum cytokine levels were consistently low after dosing and only minor increases were observed for IL-1Ra, IL-5 and IL-6. Together, these results suggest that RNACap achieves efficient systemic delivery of therapeutic mRNA. Further, it would be less likely to induce the inflammatory responses typically associated with the standard of care.
Implications for Future Therapeutics
RNACap could serve as a compelling platform for the oral delivery of mRNA therapeutics, especially for treating intestinal diseases. With this technology, we are in a unique position to change how treatments are delivered. The subcutaneous administration route improves patient comfort and compliance by removing the need for painful injections.
The research behind RNACap was recently published in the prestigious journal Science Translational Medicine, signaling the importance of this work to the medical community. These results highlight the promise that this new technology holds to change therapeutic approaches for a wide range of diseases far beyond those of the intestine.