RNA can be engineered for its intended therapeutic functions by in vitro transcription or solidsupport synthesis. Therapeutic mRNAs, which are translated in vivo to deliver a therapeutic or vaccine protein, require extensive replacement of uridine with 1-methylpseudouridine to decrease the immune response to the mRNA and improve the translation. ASOs and therapeutic siRNAs have phosphorothioate and 2'-ribose modifications to protect the RNA from degradation and to improve target specificity. Aptamers, whose 3-D structure rather than primary sequence determines their function, are heavily modified. For all RNAs, the degree of modification can be adjusted to enhance the effectiveness of the therapeutic RNA.