{"doi":"10.1101/2023.10.20.563154","title":"<i>In vivo</i> affinity maturation of murine B cells reprogrammed to express human antibodies","abstract":"Abstract CRISPR-edited murine B cells engineered to express human antibody variable chains proliferate, class switch, and secrete these antibodies in vaccinated mice. However, current strategies disrupt the heavy-chain locus, resulting in inefficient somatic hypermutation without functional affinity maturation. Here we show that recombined murine heavy- and kappa-variable genes can be directly and simultaneously overwritten, using Cas12a-mediated cuts at their 3’-most J segments and 5’ homology arms complementary to distal V segments. Cells edited in this way to express the HIV-1 broadly neutralizing antibodies 10-1074 or VRC26.25-y robustly hypermutated and generated potent neutralizing plasma in vaccinated recipient mice. 10-1074 variants isolated from these mice bound and neutralized HIV-1 envelope glycoprotein more efficiently than wild-type 10-1074 while maintaining or improving its already low polyreactivity and long in vivo half-life. We further validated this approach by generating substantially broader and more potent variants of the anti-SARS-CoV-2 antibodies ZCB11 and S309. Thus, B cells edited at their native loci affinity mature, facilitating development of broad, potent, and bioavailable antibodies and expanding the potential applications of engineered B cells.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2023,"id":401279,"datarank":0.10397207708399181,"base_score":0.6931471805599453,"endowment":0.6931471805599453,"self_citation_contribution":0.10397207708399181,"citation_network_contribution":0.0,"self_endowment_contribution":0.10397207708399181,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":1,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9456,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1074029,"name":"Yan Guo","orcid":"0000-0001-7674-758X","position":1,"is_corresponding":false},{"id":1177939,"name":"Yuxuan Jiang","orcid":"0000-0001-7660-8029","position":2,"is_corresponding":false},{"id":106933,"name":"Brian D. Quinlan","orcid":"0000-0003-2719-731X","position":3,"is_corresponding":false},{"id":459266,"name":"Haiyong Peng","orcid":"0000-0003-0312-1337","position":4,"is_corresponding":false},{"id":511333,"name":"Gogce Crynen","orcid":"0000-0001-6066-9900","position":5,"is_corresponding":false},{"id":559549,"name":"Wenhui He","orcid":"0000-0002-3176-1385","position":6,"is_corresponding":false},{"id":106928,"name":"Lizhou Zhang","orcid":"0000-0002-2637-9712","position":7,"is_corresponding":false},{"id":621942,"name":"Tianling Ou","orcid":"0000-0002-5119-2239","position":8,"is_corresponding":false},{"id":381176,"name":"Charles C. Bailey","orcid":"0000-0003-0200-3523","position":9,"is_corresponding":false},{"id":104360,"name":"Michael Farzan","orcid":"0000-0002-2990-5319","position":10,"is_corresponding":false},{"id":717227,"name":"Yiming Yin","orcid":"0000-0003-0087-2784","position":0,"is_corresponding":true}],"reference_count":65,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-19T01:20:08.195423Z","pmid":"37961481","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":[]}