Introduction Gene therapy encompasses a set of therapeutic modalities intended to treat genetic and acquired diseases, by directly administering nucleic acids to replace defective genes or alter gene expression. Currently, gene therapies exhibit low payload, resulting in expensive manufacturing costs, high dosage requirements, and adverse immune responses in patients. To overcome these limitations and increase the restorative capacity of gene therapy, previous studies sought to engineer promoter regions of the genome, mainly to enhance transcription machinery or modify expression levels across various cell types. However, these studies rarely capitalize upon the potential of engineering 5’ untranslated regions (UTRs), sections of mRNA stationed upstream of the start codon responsible for translation initiation. 5’ UTRs primarily contribute to the post-transcriptional regulation of gene expression, specifically, the modulation of translation efficiency and mRNA stability. Thus, identifying target features of 5’ UTRs provides insight into prospective mechanisms to optimize protein expression across various cell types.