Open AccessA system for multiplexed selection of aptamers with exquisite specificity without counterselection
Author(s) -
Alex M. Yoshikawa,
Leping Wan,
Liwei Zheng,
Michael Eisenstein,
H. Tom Soh
Publication year - 2022
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.011
H-Index - 771
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.2119945119
Subject(s) - aptamer , computational biology , analyte , systematic evolution of ligands by exponential enrichment , selection (genetic algorithm) , small molecule , computer science , biology , chemistry , genetics , artificial intelligence , rna , gene
Significance Aptamers have the capacity to discriminate between structurally similar small molecules. However, generating such highly specific aptamers has proven challenging using conventional processes based on counterselection against nontarget molecules. In this work, we describe a high-throughput screening platform that can characterize the specificity of millions of aptamers toward a group of structurally related molecules in a single experiment and generate exquisitely specific aptamers without any counterselection. As exemplars, we generated aptamers with high affinity and specificity toward three structurally related kynurenine metabolites using our platform. Our platform can be readily adapted to other small-molecule targets and should therefore accelerate the development of aptamer reagents with exquisite specificity.