Nucleic acids with bacterial and viral origins are recognized by toll like receptors (TLRs) that triggers mammalian innate immune system to secrete proinflammatory or inflammatory cytokines. Even though these ligands have a high potency to be used in clinical applications as a vaccine adjuvant or as an immunotherapeutic agent, the rapid clearance from the body by serum proteins, in vivo degradation via nucleases, consequently lead to poor in vivo stability and performance thus hampers their clinical applications.