Capsule coffee-inspired customizable production of nucleic acid medicine using a rapid on-site microfluidic assembly (ROMA) technology

Abstract The emergence of nucleic acid medicine (NAM) has profoundly addressed global infectious disease challenges1 and revolutionized cancer therapy2 and gene-editing3. However, current NAM, such as mRNA vaccine, remains distant from customizable supply and is fraught with hurdles of thermo-instability and infrastructure dependence. Drawing inspiration from the efficiency of capsule coffee machines, we introduce a Rapid On-site Microfluidic Assembly (ROMA) prototype capable of generating ready-to-inject mRNA vaccines at a throughput of 180 doses/hour (∼100 µg mRNA/dose). Analogous to the varied flavors of capsule coffee, our ROMA prototype offers personalized options for mRNA vaccines, including lipid nanoparticle (LNP) sizes, compositions, mRNA types, and dosages tailored to individual needs. Diverging from traditional mechanism of directly assembling mRNA and lipids into mRNA-LNPs, ROMA technology utilizes mRNA and pre-made empty LNPs to form mRNA-LNPs. Nevertheless, ROMA mRNA vaccine exhibits equivalent physiochemical parameters and in-vivo expressions compared to conventional ones, with a benefit of lower toxicity. Crucially, ROMA mRNA vaccine, immediately deployable without the need for storage, fundamentally avoids the thermal instability and degradation risks associated with conventional mRNA vaccines. This transformative ROMA technology offers unparalleled user-end convenience, unlocking the potential for personalized mRNA vaccines and treatments, thereby significantly expanding the scope of NAM therapeutics.