Over the last decade, advances in genome engineering, viral vectors, and stem cell biology have massively expanded the therapeutic potential of engineered cells. An expanding array of cell-based therapeutics is entering clinical trials for treatment of cancers 1, 2, 3, neurodegenerative disease [4], diabetes 5, 6, and blood disorders 7, 8. Achieving the best safety and performance for gene and cell-based therapies requires tools for tuning, tailoring, and controlling expression of transgenes. Tapping into information-rich streams within the cell provides the potential to coordinate synthetic and native genetic programs and to build both autonomous and clinician-mediated control of gene and cell-based therapies. As a highly compact, modular, portable, and programmable substrate, RNA serves an ideal medium for interfacing native and synthetic programs to extract information and to program cellular responses for optimal control of gene and cell-based therapies (Figure 1).