Aptamers are short single-stranded DNA or RNA oligonucleotides (< 100 nt). They gained increasing importance in drug discovery due to their inherent ability to form defined three-dimensional structures that enables them to bind to various targets (e.g. proteins) with antibody-antigen-like affinity and specificity.
Aptamers with the highest binding affinity and specificity against a given target molecule are generated by an multi-step in vitro selection and enzymatic amplification process called "systematic evolution of ligands by exponential enrichment (SELEX) (for detailed information please refer to the references below[2,3]).
The main advantages of aptamers compared to antibodies are heat stability, the lack of immunogenicity and minimal interbatch variability. Their usage in diagnostics however, is often hampered by nuclease-mediated degradation.
Enzymatic incorporation of fluoro-, amino- or O-methyl- 2'-ribose-modified nucleotides (1) by generating an initially modified combinatorial library or (2) post-SELEX markedly improve the nuclease resistance of aptamers (Tab. 1) [3-12]. Furthermore, a number of modified nucleotides suitable for the selection of cross-linking capable aptamers (Photo-SELEX) are available as well (Tab. 1)[13-15].
 Jensen et al. (1995) Using in vitro selection to direct the covalent attachment of human immunodeficiency virus type 1 Rev protein to high-affinity RNA ligands. Proc. Natl. Acad. Sci. USA 92:12220.
 Park et al. (2008) Higher-Order Association States of Cellular ERBB3 Probed with Photo-Cross-Linkable Aptamers. Biochemistry 47 (46):11992.
 Crouzier et al. (2012) Efficient reverse transcription using locked nucleic acid nucleotides towards the evolution of nuclease resistant RNA aptamers. PLoS One. 7 (4):e35990.