Viscoelastic flow Mechanoporation for Scalable mRNA Delivery in Therapeutic Applications

초록

Intracellular mRNA delivery is crucial for advancing gene therapy, cell therapy, and vaccine development. Conventional methods, such as polymer-based carriers, electroporation, and viral vectors, face challenges including cytotoxicity, high cost, scalability, and inconsistent efficiency. To overcome these issues, microfluidic technology has introduced mechanoporation for more controlled and efficient delivery. Despite its promise, mechanoporation suffers from frequent clogging in microfluidic channels, affecting reproducibility. In this study, we used wider microfluidic channels and viscoelastic fluids to mitigate clogging and enable consistent mRNA delivery. We demonstrated that delivery efficiency can be optimized by controlling key parameters, including flow rate, cross-sectional area of channel, and the length and angle of the squeeze zone in a microfluidic channel. Our findings indicate that optimized flow rate and cross-sectional area of channel allow rapid processing of higher cell concentrations and delivery efficiency and cell viability can be enhanced by optimizing the concentration of viscoelastic material and the length and angle of the squeeze zone in a microfluidic channel. Overall, our approach enhances the scalability and consistency of intracellular mRNA delivery, supporting high-throughput cell processing and broad application in research.