Decentralized Biomanufacturing of Circular RNA Vaccines

RNA therapeutics offer public health systems the ability to rapidly design and deliver protection against infectious disease, as seen with the COVID-19 pandemic. In addition, the precision of RNA offers new possibilities for treating cancer and neurological disorders with personalized medicine. Despite this potential, the technologies driving this revolution remain costly, relying on centralized manufacturing centers, and requiring cold-chain distribution, limiting their accessibility worldwide. We have developed a portable device designed for manufacturing protein-based drugs and laboratory reagents capable of synthesis and purification. This MANGO (MANufacturing on the GO) device successfully manufactured enzymes and during a four month diagnostic trial in South America, demonstrating the value of accessible biomanufacturing. We propose to adapt the MANGO device for automated biomanufacturing of RNA therapeutics (MANGO-R), integrating on-device RNA quality control and encapsulation in lipid nanoparticles (LNPs) for vaccine delivery. The objectives of this research are to optimize the in-vitro transcription and purification of a SARS-CoV-2 circular RNA (circRNA) vaccine prior to packaging circRNA into LNPs. Once reactions are optimized for on-demand manufacturing, they will be integrated into the MANGO-R device. Although RNA medicine holds tremendous promise, efficient delivery of therapeutics remains a critical barrier. This proof-of-concept, portable RNA vaccine manufacturing with the MANGO-R device could significantly improve personal and public health readiness.