{"doi":"10.1002/cbic.202200520","title":"Inverse <i>In Vitro</i> Selection Enables Comprehensive Analysis of Cross‐Chiral L‐Aptamer Interactions","abstract":"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\" in vitro 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 in vitro selection provides several opportunities to advance L-aptamer technology.","journal":"ChemBioChem","year":2022,"id":268116,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":6,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9476,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2022-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":657348,"name":"Xuan Han","orcid":"0000-0002-4685-8235","position":1,"is_corresponding":false},{"id":503694,"name":"Adam M. Kabza","orcid":null,"position":2,"is_corresponding":false},{"id":479666,"name":"Sougata Dey","orcid":"0000-0002-9588-9265","position":3,"is_corresponding":false},{"id":479667,"name":"Jonathan T. Sczepanski","orcid":"0000-0002-9275-2597","position":4,"is_corresponding":false},{"id":930307,"name":"Alexander T. Piwko","orcid":null,"position":0,"is_corresponding":true}],"reference_count":35,"raw_metadata":null,"created_at":"2026-07-19T00:27:10.233250Z","pmid":"36282114","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}