Highly efficient mRNA delivery with nonlinear microfluidic cell stretching for cellular engineering.

In the past few years, messenger RNA (mRNA) has emerged as a promising therapeutic agent for the treatment and prevention of various diseases. Clinically, mRNA-based drugs have been used for cancer immunotherapy, infectious diseases, and genomic disorders. To maximize the therapeutic efficacy of mRNA, the exact amount of mRNAs must be delivered to the target locations without degradation; however, traditional delivery modalities, such as lipid carriers and electroporation, are suboptimal because of their high cost, cell-type sensitivity, low scalability, transfection/delivery inconsistency, and/or loss of cell functionality. Therefore, new effective and stable delivery methods are required. Accordingly, we present a novel nonlinear microfluidic cell stretching (μ-cell stretcher) platform that leverages viscoelastic fluids,