Chemical Modifications for a Next Generation of Nucleic Acid Aptamers

In the past three decades, in vitro systematic evolution of ligands by exponential enrichment (SELEX) has yielded many aptamers for translational applications in both research and clinical settings. Despite their promise as an alternative to antibodies, the low success rate of SELEX (similar to 30 %) has been a major bottleneck that hampers the further development of aptamers. One hurdle is the lack of chemical diversity in nucleic acids. To address this, the aptamer chemical repertoire has been extended by introducing exotic chemical groups, which provide novel binding functionalities. This review will focus on how modified aptamers can be selected and evolved, with illustration of some successful examples. In particular, unique chemistries are exemplified. Various strategies of incorporating modified building blocks into the standard SELEX protocol are highlighted, with a comparison of the differences between pre-SELEX and post-SELEX modifications. Nucleic acid aptamers with extended functionality evolved from non-natural chemistries will open up new vistas for function and application of nucleic acids.

Automated summary

In the past three decades, in vitro systematic evolution of ligands by exponential enrichment (SELEX) has been used to select many aptamers for translational applications. However, the low success rate of SELEX has hindered the further development of aptamers, with one major obstacle being the lack of chemical diversity in nucleic acids. To overcome this, exotic chemical groups have been introduced to expand the chemical repertoire of aptamers.