The use of synthetic mRNA-based gene modification offers several advantages over traditional DNA based gene therapy including faster translational kinetics, transient expression and mitigation of risks associated with insertational mutagenesis and genomic integration. Accordingly, mRNA technology holds particular promise for applications in tissue engineering where spatiotemporal control of gene expression is crucial. Recent advances in non-viral delivery technologies have significantly increased the efficiency of intracellular delivery of synthetic mRNA by modulating mTOR signaling, which has been identified as a crucial player in mRNA translation. However, mTOR signaling is regulated by matrix stiffness through mechanotransductive pathways. Therefore, the mechanical properties of the engineered tissue must be tailored for optimal translation and expression of mRNA.