(549c) RNA Product Delivery Using 3D Printed Microfluidic Microarray Patches (MAPs)

The use of 3D printing technologies, particularly single-digit micron resolution Continuous Liquid Interface Production (CLIP) developed by the DeSimone Lab at Stanford University, has promises to revolutionize microarray patch (MAP) production for drug and vaccine delivery. An additional significant 3D printing development for MAP production is the emergence of injection CLIP (iCLIP) technology, which enables the production of microfluidic MAP devices with double-digit micron features. These microfluidic structures can be integrated into the needles and backing of MAPs allowing for the creation of microfluidic structures within MAPs, leading to novel functionalities and enhanced capabilities. Additionally, this allows for rapid and precise delivery of drugs and vaccines. This advancement not only improves the efficacy of delivery, but also enables the administration of doses that were previously unattainable with conventional MAP platforms.

Moreover, the microfluidic backing of MAPs serves as a reservoir for lyophilized products, offering enhanced stability for shelf-unstable drugs and vaccines. This feature allows for the simultaneous reconstitution and delivery of these products, thereby ensuring their efficacy and viability during transportation and storage. We have demonstrated the utility of this approach for RNA delivery, achieving comparable reporter gene expression to intramuscular or intradermal controls.

The utilization of emergent RNA technologies, such as self-amplifying RNA (saRNA) encapsulated in lipid nanoparticles (LNPs), has further expanded the capabilities of the microfluidic MAP platform. By lyophilizing saRNA-LNP complexes, their thermostability is enhanced, enabling reliable and accessible vaccine delivery even in challenging environments. The combination of microfluidic MAPs with saRNA delivery holds promise for achieving equivalent immune responses with lower doses of RNA and longer duration of immunity, thereby potentially reducing manufacturing costs and improving vaccine accessibility. Additionally, being able to deliver lower doses of RNA to achieve equivalent immune responses also means that lower lipid doses are needed and lower reactogenicity may be achieved.

In summary, the integration of 3D printing technologies, microfluidic structures, and emergent RNA delivery methods has paved the way for the development of a robust, reliable, and thermostable vaccine delivery platform. This innovative approach has the potential to revolutionize vaccine distribution by offering improved stability, enhanced efficacy, and increased accessibility, particularly in resource-limited settings.

*This work was supported by the Wellcome Leap R3 Program and the Gates Foundation.