This technology creates stable, inhalable dry powders of mRNA-polymer complexes using thin-film freeze-drying, enabling room-temperature storage and efficient pulmonary delivery of RNA therapeutics, including CRISPR, for treating lung diseases without the need for cold chain logistics.
Messenger RNA (mRNA) therapeutics represent a transformative medical field, offering rapid and transient protein expression without the risks of DNA integration. This makes mRNA highly attractive for vaccination, gene editing, and protein replacement therapies. A particularly promising area is pulmonary delivery, which targets treatments directly to the lungs for respiratory diseases. To maximize clinical impact, there is a critical need for delivery systems that are effective, portable, and patient-friendly, ensuring treatments can be easily administered outside specialized clinical settings.
Despite this potential, current pulmonary mRNA delivery methods face significant logistical and functional hurdles. Existing formulations primarily rely on liquid mRNA-polyplex suspensions, which suffer from severe instability and are highly sensitive to freezing-induced aggregation. Consequently, these liquids mandate strict, costly cold chain storage. Furthermore, administering these therapies requires nebulizers. Nebulization is inherently time-consuming, heavily device-dependent, and often yields inconsistent aerosolization efficiency. The reliance on bulky nebulizer equipment restricts patient mobility and convenience, ultimately leading to poor patient compliance and limiting the widespread viability of current pulmonary RNA treatments.
This technology provides inhalable dry powders of messenger RNA (mRNA)-polymer polyplexes, created through a specialized thin-film freeze-drying (TFFD) process. Engineered for highly efficient pulmonary delivery, the optimized formulations incorporate a specific blend of trehalose, maltitol, and leucine. This composition achieves a delivered fine particle fraction of 71% and a mass median aerodynamic diameter of 1.6 μm for optimal lung penetration. The platform supports high RNA loading capacities by maintaining low polymer-to-excipient ratios. Highly versatile, the technology is validated across multiple RNA modalities, including CRISPR components, making it a robust vehicle for targeted respiratory therapies.
This solution is differentiated by its ability to overcome the severe limitations of traditional liquid mRNA formulations. Unlike conventional liquid polyplexes that require strict cold chain storage, these dry powders remain stable at room temperature for at least three months. Furthermore, the technology eliminates the need for bulky, time-consuming nebulizers, offering a portable alternative with consistent aerosolization. Uniquely, contrary to typical TFFD powders, increasing the solid content in this formulation actually improves its aerosol performance. By preserving the biological activity of the polyplexes without requiring refrigeration, this platform significantly advances the accessibility and commercial viability of pulmonary RNA therapeutics.
These inhalable dry powders of mRNA-polymer polyplexes are produced via thin-film freeze-drying. They maintain structural integrity at room temperature for over three months, eliminating cold chain requirements. Optimized with trehalose, maltitol, and leucine, the formulation achieves a 71% fine particle fraction and 1.6 μm aerodynamic diameter. Higher solid content uniquely improves aerosol performance. This technology enables efficient pulmonary delivery of RNA modalities, including CRISPR components.
Provisional Patent 64/023,636 filed 03/31/2026