{"doi":"10.1038/s42003-021-02565-5","title":"In vivo pharmacokinetic enhancement of monomeric Fc and monovalent bispecific designs through structural guidance","abstract":"In a biologic therapeutic landscape that requires versatility in targeting specificity, valency and half-life modulation, the monomeric Fc fusion platform holds exciting potential for the creation of a class of monovalent protein therapeutics that includes fusion proteins and bispecific targeting molecules. Here we report a structure-guided approach to engineer monomeric Fc molecules to adapt multiple versions of half-life extension modifications. Co-crystal structures of these monomeric Fc variants with Fc neonatal receptor (FcRn) shed light into the binding interactions that could serve as a guide for engineering the half-life of antibody Fc fragments. These engineered monomeric Fc molecules also enabled the generation of a novel monovalent bispecific molecular design, which translated the FcRn binding enhancement to improvement of in vivo serum half-life.","journal":"Communications Biology","year":2021,"id":185521,"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":8,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9519,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":742068,"name":"Nydia van Dyk","orcid":"0000-0003-2034-7688","position":1,"is_corresponding":false},{"id":570600,"name":"Nantaporn Haskins","orcid":null,"position":2,"is_corresponding":false},{"id":742701,"name":"Kimberly M. Cook","orcid":null,"position":3,"is_corresponding":false},{"id":742702,"name":"Kim L. Rosenthal","orcid":null,"position":4,"is_corresponding":false},{"id":289050,"name":"Ronit Mazor","orcid":"0000-0002-5456-1247","position":5,"is_corresponding":false},{"id":501931,"name":"Sonia Dragulin-Otto","orcid":null,"position":6,"is_corresponding":false},{"id":742069,"name":"Yu Jiang","orcid":"0000-0002-9741-6787","position":7,"is_corresponding":false},{"id":742703,"name":"Herren Wu","orcid":null,"position":8,"is_corresponding":false},{"id":742704,"name":"William F. Dall’Acqua","orcid":null,"position":9,"is_corresponding":false},{"id":742070,"name":"M. Jack Borrok","orcid":"0000-0002-1477-6649","position":10,"is_corresponding":false},{"id":742071,"name":"Melissa Damschroder","orcid":"0000-0001-9453-6532","position":11,"is_corresponding":false},{"id":742072,"name":"Vaheh Oganesyan","orcid":"0000-0001-8910-9202","position":12,"is_corresponding":false},{"id":742067,"name":"Lu Shan","orcid":"0000-0003-2334-9216","position":0,"is_corresponding":true}],"reference_count":50,"raw_metadata":null,"created_at":"2026-07-18T23:48:38.805613Z","pmid":"34497355","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":[]}