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The success of the Pfizer/BioNTech and Moderna COVID-19 mRNA vaccines has galvanized research on mRNA therapeutics. Rather than use mRNA to make antigens, the objective of mRNA therapeutics is to make proteins on demand inside patients’ cells within a tissue of interest at a level and duration sufficient to achieve treatment benefit. Applications are many and varied: enzyme replacement therapy for rare diseases, hormone production, monoclonal antibodies or immunostimulatory proteins for cancer, cytokines or transcription factors to treat autoimmunity. Linear mRNA is the template of choice, but it has drawbacks. Synthetic mRNA must be heavily modified to resist nuclease degradation and to avoid innate immune stimulation. Such mRNAs are inefficient to manufacture, difficult to properly incorporate into lipid nanoparticle carriers, and expensive. And modified linear mRNA is still relatively short-lived, limiting the amount of therapeutic protein produced per molecule delivered.