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Generation of high-affinity DNA aptamers using non-natural nucleotides

Non-natural nucleotides could be useful for generating high-affinity DNA aptamers. Libraries of DNA aptamers were generated using the four natural nucleotides plus the non-natural nucleotide 7-(2-thienyl)imidazo[4,5-b]pyridine. In vitro selection experiments against human VEGF-165 and interferon-g (IFNG; IFN-g) identified aptamers that bound to the proteins with subpicomolar and subnanomolar Kd values that were a 100-fold improvement over DNA aptamers made from only natural nucleotides. Next steps include using the technology to develop high-affinity aptamers against small molecules and cells (see Expanding the aptamer alphabet, page 7).

SciBX 6(15); doi:10.1038/scibx.2013.373
Published online April 18, 2013

Patent applications filed; available for licensing from TagCyx Biotechnologies

Kimoto, M. et al. Nat. Biotechnol.; published online April 7, 2013;
Contact: Ichiro Hirao, RIKEN Systems and Structural Biology Center, Kanagawa, Japan