Nucleic acids offer an ideal building material for the development of therapeutic nucleic acids because they are biocompatible and can be programmed as or functionalized with antisense oligonucleotides, small interfering RNA (siRNAs), microRNAs (miRNAs), aptamers, and decoy sequence. New research shows that nucleic acid composition can be designed for enhanced stability, targeted cellular delivery, and optimal activation or abrogation of immune responses.