Selection of nuclease-resistant XNA aptamers.

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Alex Taylor, V. B. Pinheiro, P. Holliger

Medical Research Council Laboratory of Molecular Biology, United Kingdom

We have recently engineered a set of polymerases that allow genetic information to be transferred to, and retrieved from, a variety of unnatural nucleic acids with distinct physicochemical properties (XNAs). These synthetic polymers are now accessible for evolutionary exploration. As a proof of principle, we have selected aptamers (functional nucleic acid structures) entirely composed of a nuclease-resistant XNA, anhydrohexitol nucleic acid (HNA), from a pool of random sequences. The evolved aptamers bind their targets, a protein (Hen Egg Lysozyme) and an RNA motif (HIV-TAR), with high affinity (nM) and specificity in several different assays, including when presented on the surface of cells. XNA has the potential to overcome problems associated with the use of RNA and DNA structures in biotechnology and medicine.