LAUSR

Aptamers generated from natural and modified nucleo-tides are often prone to nuclease digestion, which limits their utility in many biomedical applications, including therapeutics. Here we describe the in vitro selection of an unnatural nucleic acid polymer system based on α-L-threofuranosyl nucleic acid (TNA) that is completely refractory to nuclease digestion. The use of an engi-neered TNA polymerase permitted the isolation of func-tional TNA aptamers that bind to HIV reverse transcrip-tase (HIV RT) with KD values of ~0.4 to 4.0 nM. The TNA aptamers remain active in the presence of strong nucle-olytic enzymes, where DNA and FANA aptamers rapidly degrade, and exhibit markedly higher thermal stability than monoclonal antibodies (mAbs), which irreversibly unfold at elevated temperatures. The combined proper-ties of biological stability, high target binding affinity, and thermal stability make TNA aptamers a powerful system for further development as future diagnostic and therapeutic agents.