{"doi":"10.1126/sciadv.abb7107","title":"Supramolecular nanosubstrate–mediated delivery system enables CRISPR-Cas9 knockin of hemoglobin beta gene for hemoglobinopathies","abstract":"Leveraging the endogenous homology-directed repair (HDR) pathway, the CRISPR-Cas9 gene-editing system can be applied to knock in a therapeutic gene at a designated site in the genome, offering a general therapeutic solution for treating genetic diseases such as hemoglobinopathies. Here, a combined supramolecular nanoparticle (SMNP)/supramolecular nanosubstrate-mediated delivery (SNSMD) strategy is used to facilitate CRISPR-Cas9 knockin of the hemoglobin beta (HBB) gene into the adeno-associated virus integration site 1 (AAVS1) safe-harbor site of an engineered K562 3.21 cell line harboring the sickle cell disease mutation. Through stepwise treatments of the two SMNP vectors encapsulating a Cas9•single-guide RNA (sgRNA) complex and an HBB/green fluorescent protein (GFP)-encoding plasmid, CRISPR-Cas9 knockin was successfully achieved via HDR. Last, the HBB/GFP-knockin K562 3.21 cells were introduced into mice via intraperitoneal injection to show their in vivo proliferative potential. This proof-of-concept demonstration paves the way for general gene therapeutic solutions for treating hemoglobinopathies.","journal":"Science Advances","year":2020,"id":92596,"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":42,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9477,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":243902,"name":"Shih‐Jie Chou","orcid":null,"position":1,"is_corresponding":false},{"id":463215,"name":"Jindian Li","orcid":"0009-0004-1113-6760","position":2,"is_corresponding":false},{"id":320810,"name":"Wenqiao Hui","orcid":"0000-0002-1645-1311","position":3,"is_corresponding":false},{"id":320813,"name":"Wenfei Liu","orcid":"0000-0003-1338-7905","position":4,"is_corresponding":false},{"id":241793,"name":"Na Sun","orcid":"0000-0002-3282-4405","position":5,"is_corresponding":false},{"id":241795,"name":"Ryan Y. Zhang","orcid":"0000-0002-3122-4053","position":6,"is_corresponding":false},{"id":241821,"name":"Yazhen Zhu","orcid":"0000-0002-2130-8085","position":7,"is_corresponding":false},{"id":463216,"name":"Ming‐Long Tsai","orcid":"0000-0002-9957-923X","position":8,"is_corresponding":false},{"id":463217,"name":"Henkie Isahwan Ahmad Mulyadi Lai","orcid":"0000-0001-8516-743X","position":9,"is_corresponding":false},{"id":241801,"name":"Matthew Smalley","orcid":"0000-0002-0509-6502","position":10,"is_corresponding":false},{"id":463218,"name":"Xinyue Zhang","orcid":"0009-0009-1046-6828","position":11,"is_corresponding":false},{"id":463219,"name":"Jiayuan Chen","orcid":"0000-0003-2586-8626","position":12,"is_corresponding":false},{"id":463220,"name":"Zulema Romero","orcid":"0000-0001-8305-8184","position":13,"is_corresponding":false},{"id":463221,"name":"Dahai Liu","orcid":"0000-0001-6201-9776","position":14,"is_corresponding":false},{"id":463222,"name":"Zunfu Ke","orcid":"0000-0002-6251-7246","position":15,"is_corresponding":false},{"id":463223,"name":"Chang Zou","orcid":"0000-0002-2003-7834","position":16,"is_corresponding":false},{"id":463224,"name":"Chin‐Fa Lee","orcid":"0000-0003-0735-5691","position":17,"is_corresponding":false},{"id":233310,"name":"Steven J. Jonas","orcid":"0000-0002-8111-0249","position":18,"is_corresponding":false},{"id":320806,"name":"Qian Ban","orcid":"0000-0002-3520-1721","position":19,"is_corresponding":false},{"id":255732,"name":"Paul S. Weiss","orcid":"0000-0001-5527-6248","position":20,"is_corresponding":false},{"id":3656,"name":"Donald B. 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