UNA (unlocked nucleic acid): a flexible RNA mimic that allows engineering of nucleic acid duplex stability.

UNA (unlocked nucleic acid) monomers are acyclic derivatives of RNA lacking the C2'-C3'-bond of the ribose ring of RNA. Synthesis of phosphoramidite UNA building blocks of the nucleobases adenine, cytosine, guanine, and uracil is described herein together with their incorporation into RNA strands. UNA monomers additively decrease nucleic acid duplex stability and can be positioned strategically to induce either lack of discrimination of mismatches, that is, universal base behavior, or increased discrimination of mismatches, that is, improved hybridization specificity. UNA-modified RNA duplexes are shown to structurally mimic unmodified RNA duplexes by CD spectroscopy.