Dependence of click-SELEX performance on the nature and average number of modified nucleotides.

The click-SELEX procedure enables the identification of nucleobase-modified aptamers in which chemical entities are introduced by a copper(i)-catalysed alkyne-azide 'click' reaction. Here we report on the impact of modified nucleobases on PCR conditions and the average amount of modified nucleobases on click-SELEX performance. We demonstrate click-SELEX being strongly dependent on which and on how many modifications are used.

A SARS-CoV-2 Spike Binding DNA Aptamer that Inhibits Pseudovirus Infection by an RBD-Independent Mechanism.

The receptor binding domain (RBD) of the spike glycoprotein of the coronavirus SARS-CoV-2 (CoV2-S) binds to the human angiotensin-converting enzyme 2 (ACE2) representing the initial contact point for leveraging the infection cascade. We used an automated selection process and identified an aptamer that specifically interacts with CoV2-S. The aptamer does not bind to the RBD of CoV2-S and does not block the interaction of CoV2-S with ACE2.

Dynamic changes in DNA populations revealed by split-combine selection.

Clickmers are chemically modified aptamers representing an innovative reagent class for developing binders for biomolecules with great impact on therapeutic and diagnostic applications. To establish a novel layer for screening various chemical entities, we developed a split-combine selection strategy simultaneously enriching for clickmers having different modifications. Due to the inherent design of this strategy, dynamic changes of DNA populations are traceable at an individual sequence level.