Leveraging microRNAs for cellular therapy

•Cellular therapy, in particular T cell therapy, has demonstrated remarkable clinical success.•Cellular therapies are rapidly becoming programmable therapeutics.•Versatile and ever more precise genome engineering tools and synthetic biology approaches catalyze the next generation of engineered cellular therapies.•microRNAs and by extension other non-coding RNAs should be included in cellular engineering. Owing to Karl Landsteiner's discovery of blood groups, blood transfusions became safe cellular therapies in the early 1900s. Since then, cellular therapy made great advances from transfusions with unmodified cells to today's commercially available chimeric antigen receptor (CAR) T cells requiring complex manufacturing. Modern cellular therapy products can be improved using basic knowledge of cell biology and molecular genetics. Emerging genome engineering tools are becoming ever more versatile and precise and thus catalyze rapid progress towards programmable therapeutic cells that compute input and respond with defined output. Despite a large body of literature describing important functions of non-coding RNAs including microRNAs (miRNAs), the vast majority of cell engineering efforts focuses on proteins. However, miRNAs form an important layer of posttranscriptional regulation of gene expression. Here, we highlight examples of how miRNAs can successfully be incorporated into engineered cellular therapies. [Display omitted]