Inverse In Vitro Selection Enables Comprehensive Analysis of Cross-Chiral L-Aptamer Interactions. Academic Article uri icon


  • Aptamers composed of mirror-image L-(deoxy)ribose nucleic acids, referred to as L-aptamers, are a promising class of RNA-binding reagents. Yet, the selectivity of cross-chiral interactions between L-aptamers and their RNA targets remain poorly characterized, limiting the potential utility of this approach for applications in biological systems. Herein, we carried out the first comprehensive analysis of cross-chiral L-aptamer selectivity using a newly developed "inverse" invitro selection approach that exploits the genetic nature of the D-RNA ligand. By employing a library of more than a million target-derived sequences, we determined the RNA sequence and structural preference of a model L-aptamer and revealed previously unidentified and potentially broad off-target RNA binding behaviors. These results provide valuable information for assessing the likelihood and consequences of potential off-target interactions and reveal strategies to mitigate these effects. Thus, inverse invitro selection provides several opportunities to advance L-aptamer technology.

published proceedings

  • Chembiochem

altmetric score

  • 0.75

author list (cited authors)

  • Piwko, A. T., Han, X., Kabza, A. M., Dey, S., & Sczepanski, J. T.

citation count

  • 0

complete list of authors

  • Piwko, Alexander T||Han, Xuan||Kabza, Adam M||Dey, Sougata||Sczepanski, Jonathan T

publication date

  • December 2022