Tackling intrinsic instability of mRNA vaccine by a rapid onsite microfluidic assembly (ROMA) technology

Despite achieving unprecedented success, current mRNA vaccines face significant challenges, including thermo-instability, degradation, and infrastructure-dependence, making customizable supply a distant goal. Here, we describe a Rapid Onsite Microfluidic Assembly (ROMA) technology capable of generating ready-to-inject mRNA vaccines with a real-time quality inspection as a solution. Diverging from traditional manufacturing mechanism of directly assembling mRNA and lipids into mRNA-LNPs, ROMA technology utilizes mRNA and pre-made empty LNPs to form mRNA-LNPs that exhibit equivalent physiochemical parameters and in vivo expressions compared to conventional ones. Our ROMA prototype offers personalized options for mRNA vaccines, including lipid nanoparticle (LNP) sizes, compositions, mRNA types, and dosages tailored to individual needs, at a throughput of 200 doses/hour (∼100 µg mRNA/dose) with scalable potential. Crucially, ROMA mRNA vaccine, immediately deployable without the need for storage, fundamentally avoids the intrinsic thermal instability and degradation risks associated with conventional ones. This transformative ROMA technology offers unparalleled user-end convenience, unlocking the translational potential for personalized mRNA vaccines and treatments, thereby significantly expanding the scope of mRNA-based therapeutics.