{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T13:56:57Z","timestamp":1790517417047,"version":"4.1.0"},"reference-count":45,"publisher":"Springer Science and Business Media LLC","license":[{"start":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T00:00:00Z","timestamp":1790467200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.springernature.com\/gp\/researchers\/text-and-data-mining"},{"start":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T00:00:00Z","timestamp":1790467200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.springernature.com\/gp\/researchers\/text-and-data-mining"}],"funder":[{"name":"National Key Research and Development Program of China","award":["2024YFA0917302"],"award-info":[{"award-number":["2024YFA0917302"]}]},{"DOI":"10.13039\/501100013076","name":"National Major Science and Technology Projects of China","doi-asserted-by":"publisher","award":["2023ZD0500502"],"award-info":[{"award-number":["2023ZD0500502"]}],"id":[{"id":"10.13039\/501100013076","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Gene Ther"],"DOI":"10.1038\/s41434-026-00639-9","type":"journal-article","created":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T00:59:06Z","timestamp":1790470746000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Rational selection of SpCas9 and variant-derived adenine base editors for human genome editing"],"prefix":"10.1038","author":[{"given":"Jiahua","family":"Wang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leben","family":"He","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lin","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yujing","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuanyuan","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuejun","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zongming","family":"Song","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuanbo","family":"Liang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jin","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9600-8407","authenticated-orcid":false,"given":"Feng","family":"Gu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,9,27]]},"reference":[{"key":"639_CR1","doi-asserted-by":"publisher","first-page":"816","DOI":"10.1126\/science.1225829","volume":"337","author":"M Jinek","year":"2012","unstructured":"Jinek M, Chylinski K, Fonfara I, Hauer M, Doudna JA, Charpentier E. A programmable dual-RNA-guided DNA endonuclease in adaptive bacterial immunity. Science. 2012;337:816\u201321.","journal-title":"Science"},{"key":"639_CR2","doi-asserted-by":"publisher","first-page":"89","DOI":"10.1038\/nrd.2016.238","volume":"16","author":"C Fellmann","year":"2017","unstructured":"Fellmann C, Cowen BC, Lin PC, Doudna JA, Corn JE. Cornerstones of CRISPR-Cas in drug discovery and therapy. Nat Rev Drug Discov. 2017;16:89\u2013100.","journal-title":"Nat Rev Drug Discov"},{"key":"639_CR3","doi-asserted-by":"publisher","first-page":"661","DOI":"10.1038\/s41580-020-00288-9","volume":"21","author":"HC Zhu","year":"2020","unstructured":"Zhu HC, Li C, Gao CX. Applications of CRISPR-Cas in agriculture and plant biotechnology. Nat Rev Mol Cell Bio. 2020;21:661\u201377.","journal-title":"Nat Rev Mol Cell Bio"},{"key":"639_CR4","doi-asserted-by":"publisher","first-page":"419","DOI":"10.1038\/s41591-019-0343-4","volume":"25","author":"E Beyret","year":"2019","unstructured":"Beyret E, Liao HK, Yamamoto M, Hernandez-Benitez R, Fu YP, Erikson G, et al. Single-dose CRISPR-Cas9 therapy extends the lifespan of mice with Hutchinson-Gilford progeria syndrome. Nature Medicine. 2019;25:419\u201322.","journal-title":"Nature Medicine"},{"key":"639_CR5","doi-asserted-by":"publisher","first-page":"403","DOI":"10.1126\/science.aad5143","volume":"351","author":"CE Nelson","year":"2016","unstructured":"Nelson CE, Hakim CH, Ousterout DG, Thakore PI, Moreb EA, Rivera RMC, et al. In vivo genome editing improves muscle function in a mouse model of Duchenne muscular dystrophy. Science. 2016;351:403\u201307.","journal-title":"Science"},{"key":"639_CR6","doi-asserted-by":"publisher","first-page":"186","DOI":"10.1038\/nature14299","volume":"520","author":"FA Ran","year":"2015","unstructured":"Ran FA, Cong L, Yan WX, Scott DA, Gootenberg JS, Kriz AJ, et al. In vivo genome editing using Staphylococcus aureus Cas9. Nature. 2015;520:186\u201391.","journal-title":"Nature"},{"key":"639_CR7","first-page":"384","volume":"26","author":"N Zabaleta","year":"2018","unstructured":"Zabaleta N, Barberia M, Mart\u00edn-Higueras C, Zapata N, Betancor I, Rodr\u00edguez S, et al. CRISPR\/Cas9-mediated disruption of glycolate oxidase is an efficacious and safe treatment for primary hyperoxaluria type I. Molecular Therapy. 2018;26:384\u201385.","journal-title":"Molecular Therapy"},{"key":"639_CR8","doi-asserted-by":"publisher","first-page":"819","DOI":"10.1126\/science.1231143","volume":"339","author":"L Cong","year":"2013","unstructured":"Cong L, Ran FA, Cox D, Lin SL, Barretto R, Habib N, et al. Multiplex genome engineering using CRISPR\/Cas systems. Science. 2013;339:819\u201323.","journal-title":"Science"},{"key":"639_CR9","doi-asserted-by":"publisher","first-page":"827","DOI":"10.1038\/nbt.2647","volume":"31","author":"PD Hsu","year":"2013","unstructured":"Hsu PD, Scott DA, Weinstein JA, Ran FA, Konermann S, Agarwala V, et al. DNA targeting specificity of RNA-guided Cas9 nucleases. Nat Biotechnol. 2013;31:827\u201332.","journal-title":"Nat Biotechnol"},{"key":"639_CR10","doi-asserted-by":"publisher","first-page":"187","DOI":"10.1038\/nbt.3117","volume":"33","author":"SQ Tsai","year":"2015","unstructured":"Tsai SQ, Zheng Z, Nguyen NT, Liebers M, Topkar VV, Thapar V, et al. GUIDE-seq enables genome-wide profiling of off-target cleavage by CRISPR-Cas nucleases. Nat Biotechnol. 2015;33:187\u201397.","journal-title":"Nat Biotechnol"},{"key":"639_CR11","doi-asserted-by":"publisher","first-page":"1380","DOI":"10.1016\/j.cell.2013.08.021","volume":"154","author":"FA Ran","year":"2013","unstructured":"Ran FA, Hsu PD, Lin CY, Gootenberg JS, Konermann S, Trevino AE, et al. Double nicking by RNA-guided CRISPR Cas9 for enhanced genome editing specificity. Cell. 2013;154:1380\u201389.","journal-title":"Cell"},{"key":"639_CR12","doi-asserted-by":"publisher","first-page":"279","DOI":"10.1038\/nbt.2808","volume":"32","author":"YF Fu","year":"2014","unstructured":"Fu YF, Sander JD, Reyon D, Cascio VM, Joung JK. Improving CRISPR-Cas nuclease specificity using truncated guide RNAs. Nature Biotechnology. 2014;32:279\u201384.","journal-title":"Nature Biotechnology"},{"key":"639_CR13","doi-asserted-by":"publisher","first-page":"490","DOI":"10.1038\/nature16526","volume":"529","author":"BP Kleinstiver","year":"2016","unstructured":"Kleinstiver BP, Pattanayak V, Prew MS, Tsai SQ, Nguyen NT, Zheng ZL, et al. High-fidelity CRISPR-Cas9 nucleases with no detectable genome-wide off-target effects. Nature. 2016;529:490\u201395.","journal-title":"Nature"},{"key":"639_CR14","doi-asserted-by":"publisher","first-page":"265","DOI":"10.1038\/nbt.4066","volume":"36","author":"A Casini","year":"2018","unstructured":"Casini A, Olivieri M, Petris G, Montagna C, Reginato G, Maule G, et al. A highly specific SpCas9 variant is identified by screening in yeast. Nature Biotechnology. 2018;36:265\u201371.","journal-title":"Nature Biotechnology"},{"key":"639_CR15","doi-asserted-by":"publisher","first-page":"e3000747","DOI":"10.1371\/journal.pbio.3000747","volume":"18","author":"H Xie","year":"2020","unstructured":"Xie H, Ge X, Yang F, Wang B, Li S, Duan J, et al. High-fidelity SaCas9 identified by directional screening in human cells. PLoS Biol. 2020;18:e3000747.","journal-title":"PLoS Biol"},{"key":"639_CR16","doi-asserted-by":"publisher","first-page":"1259","DOI":"10.1126\/science.aas9129","volume":"361","author":"H Nishimasu","year":"2018","unstructured":"Nishimasu H, Shi X, Ishiguro S, Gao LY, Hirano S, Okazaki S, et al. Engineered CRISPR-Cas9 nuclease with expanded targeting space. Science. 2018;361:1259\u201362.","journal-title":"Science"},{"key":"639_CR17","doi-asserted-by":"publisher","first-page":"481","DOI":"10.1038\/nature14592","volume":"523","author":"BP Kleinstiver","year":"2015","unstructured":"Kleinstiver BP, Prew MS, Tsai SQ, Topkar VV, Nguyen NT, Zheng ZL, et al. Engineered CRISPR-Cas9 nucleases with altered PAM specificities. Nature. 2015;523:481\u201385.","journal-title":"Nature"},{"key":"639_CR18","doi-asserted-by":"publisher","first-page":"290","DOI":"10.1126\/science.aba8853","volume":"368","author":"RT Walton","year":"2020","unstructured":"Walton RT, Christie KA, Whittaker MN, Kleinstiver BP. Unconstrained genome targeting with near-PAMless engineered CRISPR-Cas9 variants. Science. 2020;368:290\u201396.","journal-title":"Science"},{"key":"639_CR19","doi-asserted-by":"publisher","first-page":"382","DOI":"10.1631\/jzus.B2100710","volume":"23","author":"J Ye","year":"2022","unstructured":"Ye J, Xi H, Chen Y, Chen Q, Lu X, Lv J, et al. Can SpRY recognize any PAM in human cells? J Zhejiang Univ Sci B. 2022;23:382\u201391.","journal-title":"J Zhejiang Univ Sci B"},{"key":"639_CR20","doi-asserted-by":"publisher","first-page":"464","DOI":"10.1038\/nature24644","volume":"551","author":"NM Gaudelli","year":"2017","unstructured":"Gaudelli NM, Komor AC, Rees HA, Packer MS, Badran AH, Bryson DI, et al. Programmable base editing of A\u2022T to G\u2022C in genomic DNA without DNA cleavage. Nature. 2017;551:464\u201371.","journal-title":"Nature"},{"key":"639_CR21","doi-asserted-by":"publisher","first-page":"420","DOI":"10.1038\/nature17946","volume":"533","author":"AC Komor","year":"2016","unstructured":"Komor AC, Kim YB, Packer MS, Zuris JA, Liu DR. Programmable editing of a target base in genomic DNA without double-stranded DNA cleavage. Nature. 2016;533:420\u201324.","journal-title":"Nature"},{"key":"639_CR22","doi-asserted-by":"publisher","first-page":"1414","DOI":"10.1038\/s41587-021-00938-z","volume":"39","author":"LW Koblan","year":"2021","unstructured":"Koblan LW, Arbab M, Shen MW, Hussmann JA, Anzalone AV, Doman JL, et al. Efficient C\u2022G-to-G\u2022C base editors developed using CRISPRi screens, target-library analysis, and machine learning. Nat Biotechnol. 2021;39:1414\u201325.","journal-title":"Nat Biotechnol"},{"key":"639_CR23","doi-asserted-by":"publisher","first-page":"41","DOI":"10.1038\/s41587-020-0609-x","volume":"39","author":"IC Kurt","year":"2021","unstructured":"Kurt IC, Zhou R, Iyer S, Garcia SP, Miller BR, Langner LM, et al. CRISPR C-to-G base editors for inducing targeted DNA transversions in human cells. Nat Biotechnol. 2021;39:41\u20136.","journal-title":"Nat Biotechnol"},{"key":"639_CR24","doi-asserted-by":"publisher","first-page":"D862","DOI":"10.1093\/nar\/gkv1222","volume":"44","author":"MJ Landrum","year":"2016","unstructured":"Landrum MJ, Lee JM, Benson M, Brown G, Chao C, Chitipiralla S, et al. ClinVar: public archive of interpretations of clinically relevant variants. Nucleic Acids Research. 2016;44:D862\u2013D68.","journal-title":"Nucleic Acids Research"},{"key":"639_CR25","doi-asserted-by":"publisher","first-page":"883","DOI":"10.1038\/s41587-020-0453-z","volume":"38","author":"MF Richter","year":"2020","unstructured":"Richter MF, Zhao KT, Eton E, Lapinaite A, Newby GA, Thuronyi BW, et al. Phage-assisted evolution of an adenine base editor with improved Cas domain compatibility and activity. Nat Biotechnol. 2020;38:883\u201391.","journal-title":"Nat Biotechnol"},{"key":"639_CR26","doi-asserted-by":"publisher","first-page":"892","DOI":"10.1038\/s41587-020-0491-6","volume":"38","author":"NM Gaudelli","year":"2020","unstructured":"Gaudelli NM, Lam DK, Rees HA, Sol\u00e1-Esteves NM, Barrera LA, Born DA, et al. Directed evolution of adenine base editors with increased activity and therapeutic application. Nature Biotechnology. 2020;38:892\u2013900.","journal-title":"Nature Biotechnology"},{"key":"639_CR27","doi-asserted-by":"crossref","unstructured":"Xiao YL, Wu Y, Tang W. An adenine base editor variant expands context compatibility. Nat Biotechnol. 2024;42:1442\u201353.","DOI":"10.1038\/s41587-023-01994-3"},{"key":"639_CR28","doi-asserted-by":"publisher","first-page":"101","DOI":"10.1038\/s41589-022-01163-8","volume":"19","author":"L Chen","year":"2023","unstructured":"Chen L, Zhang S, Xue N, Hong M, Zhang X, Zhang D, et al. Engineering a precise adenine base editor with minimal bystander editing. Nat Chem Biol. 2023;19:101\u201310.","journal-title":"Nat Chem Biol"},{"key":"639_CR29","doi-asserted-by":"crossref","unstructured":"Fu JH, Li Q, Liu XY, Tu TX, Lv XJ, Yin XD, et al. Human cell-based directed evolution of adenine base editors with improved efficiency. Nat Commun. 2021;12:5897.","DOI":"10.1038\/s41467-021-26211-0"},{"key":"639_CR30","doi-asserted-by":"publisher","DOI":"10.1186\/s13059-017-1325-9","volume":"18","author":"D Zhang","year":"2017","unstructured":"Zhang D, Zhang H, Li T, Chen K, Qiu JL, Gao C. Perfectly matched 20-nucleotide guide RNA sequences enable robust genome editing using high-fidelity SpCas9 nucleases. Genome Biol. 2017;18:191.","journal-title":"Genome Biol"},{"key":"639_CR31","doi-asserted-by":"publisher","first-page":"2933","DOI":"10.1016\/j.ymthe.2022.07.010","volume":"30","author":"TX Tu","year":"2022","unstructured":"Tu TX, Song ZM, Liu XY, Wang SX, He XX, Xi HT, et al. A precise and efficient adenine base editor. Molecular Therapy. 2022;30:2933\u201341.","journal-title":"Molecular Therapy"},{"key":"639_CR32","doi-asserted-by":"publisher","first-page":"949","DOI":"10.1038\/s41587-021-00933-4","volume":"39","author":"T Rothgangl","year":"2021","unstructured":"Rothgangl T, Dennis MK, Lin PJC, Oka R, Witzigmann D, Villiger L, et al. In vivo adenine base editing of PCSK9 in macaques reduces LDL cholesterol levels. Nat Biotechnol. 2021;39:949\u201357.","journal-title":"Nat Biotechnol"},{"key":"639_CR33","doi-asserted-by":"publisher","DOI":"10.1186\/s13059-017-1355-3","volume":"18","author":"S Kim","year":"2017","unstructured":"Kim S, Bae T, Hwang J, Kim JS. Rescue of high-specificity Cas9 variants using sgRNAs with matched 5\u2019 nucleotides. Genome Biol. 2017;18:218.","journal-title":"Genome Biol"},{"key":"639_CR34","doi-asserted-by":"publisher","first-page":"252","DOI":"10.1056\/NEJMoa2031054","volume":"384","author":"H Frangoul","year":"2021","unstructured":"Frangoul H, Altshuler D, Cappellini MD, Chen YS, Domm J, Eustace BK, et al. CRISPR-Cas9 gene editing for sickle cell disease and beta-thalassemia. N Engl J Med. 2021;384:252\u201360.","journal-title":"N Engl J Med"},{"key":"639_CR35","doi-asserted-by":"publisher","first-page":"11933","DOI":"10.1073\/pnas.95.20.11933","volume":"95","author":"T Li","year":"1998","unstructured":"Li T, Sandberg MA, Pawlyk BS, Rosner B, Hayes KC, Dryja TP, et al. Effect of vitamin A supplementation on rhodopsin mutants threonine-17 \u2013> methionine and proline-347 \u2013> serine in transgenic mice and in cell cultures. Proc Natl Acad Sci USA 1998;95:11933\u20138.","journal-title":"Proc Natl Acad Sci USA"},{"key":"639_CR36","doi-asserted-by":"crossref","unstructured":"Daiger SP, Bowne SJ, Sullivan LS. Genes and mutations causing autosomal dominant retinitis pigmentosa. Cold Spring Harb Perspect Med. 2015;5:a017129.","DOI":"10.1101\/cshperspect.a017129"},{"key":"639_CR37","doi-asserted-by":"publisher","first-page":"3101","DOI":"10.1016\/j.ymthe.2025.03.021","volume":"33","author":"X He","year":"2025","unstructured":"He X, Yan T, Song Z, Xiang L, Xiang J, Yang Y, et al. Correcting a patient-specific Rhodopsin mutation with an adenine base editor in a mouse model. Mol Ther. 2025;33:3101\u201313.","journal-title":"Mol Ther"},{"key":"639_CR38","doi-asserted-by":"publisher","first-page":"2933","DOI":"10.1016\/j.ymthe.2022.07.010","volume":"30","author":"T Tu","year":"2022","unstructured":"Tu T, Song Z, Liu X, Wang S, He X, Xi H, et al. A precise and efficient adenine base editor. Mol Ther. 2022;30:2933\u201341.","journal-title":"Mol Ther"},{"key":"639_CR39","doi-asserted-by":"publisher","DOI":"10.1186\/s13059-025-03586-7","volume":"26","author":"L Kissling","year":"2025","unstructured":"Kissling L, Mollaysa A, Janjuha S, Mathis N, Marquart KF, Weber Y, et al. Predicting adenine base editing efficiencies in different cellular contexts by deep learning. Genome Biol. 2025;26:115.","journal-title":"Genome Biol"},{"key":"639_CR40","doi-asserted-by":"publisher","first-page":"275","DOI":"10.1080\/21541264.2017.1322170","volume":"8","author":"Z Gao","year":"2017","unstructured":"Gao Z, Harwig A, Berkhout B, Herrera-Carrillo E. Mutation of nucleotides around the +1 position of type 3 polymerase III promoters: the effect on transcriptional activity and start site usage. Transcription. 2017;8:275\u201387.","journal-title":"Transcription"},{"key":"639_CR41","doi-asserted-by":"publisher","first-page":"1089","DOI":"10.1038\/s41596-020-00450-9","volume":"16","author":"TP Huang","year":"2021","unstructured":"Huang TP, Newby GA, Liu DR. Precision genome editing using cytosine and adenine base editors in mammalian cells. Nat Protoc. 2021;16:1089\u2013128.","journal-title":"Nat Protoc"},{"key":"639_CR42","doi-asserted-by":"publisher","first-page":"9308","DOI":"10.1074\/jbc.RA119.007791","volume":"294","author":"X He","year":"2019","unstructured":"He X, Wang Y, Yang F, Wang B, Xie H, Gu L, et al. Boosting activity of high-fidelity CRISPR\/Cas9 variants using a tRNA(Gln)-processing system in human cells. J Biol Chem. 2019;294:9308\u201315.","journal-title":"J Biol Chem"},{"key":"639_CR43","doi-asserted-by":"publisher","DOI":"10.1038\/srep18341","volume":"5","author":"S Yoshioka","year":"2015","unstructured":"Yoshioka S, Fujii W, Ogawa T, Sugiura K, Naito K. Development of a mono-promoter-driven CRISPR\/Cas9 system in mammalian cells. Sci Rep. 2015;5:18341.","journal-title":"Sci Rep"},{"key":"639_CR44","doi-asserted-by":"publisher","unstructured":"Perrotta RM, Vinke S, Ferreira R, Moret M, Mahas A, Chiappino-Pepe A, et al. Engineered base editors with reduced bystander editing through directed evolution. Nat Biotechnol. 2025. https:\/\/doi.org\/10.1038\/s41587-025-02937-w. Online ahead of print.","DOI":"10.1038\/s41587-025-02937-w"},{"key":"639_CR45","doi-asserted-by":"publisher","unstructured":"Lazzarotto CR, Katta V, Li Y, Manquen G, Wood RK, Chyr J, et al. Sensitive and unbiased genome-wide profiling of base-editor-induced off-target activity using CHANGE-seq-BE. Nat Biotechnol. 2026. https:\/\/doi.org\/10.1038\/s41587-025-02948-7. Online ahead of print.","DOI":"10.1038\/s41587-025-02948-7"}],"container-title":["Gene Therapy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41434-026-00639-9.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41434-026-00639-9","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41434-026-00639-9.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T13:02:28Z","timestamp":1790514148000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41434-026-00639-9"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,27]]},"references-count":45,"alternative-id":["639"],"URL":"https:\/\/doi.org\/10.1038\/s41434-026-00639-9","relation":{},"ISSN":["0969-7128","1476-5462"],"issn-type":[{"value":"0969-7128","type":"print"},{"value":"1476-5462","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,27]]},"assertion":[{"value":"11 February 2026","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"30 July 2026","order":2,"name":"revised","label":"Revised","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"9 August 2026","order":3,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"27 September 2026","order":4,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing interests.","order":1,"name":"Ethics","label":"Competing interests","group":{"name":"EthicsHeading","label":"Ethics"}},{"value":"All methods were performed in accordance with the relevant guidelines and regulations. This study used only established HEK-293 and HEK-293-derived cell lines; the HEK-293 cell line was obtained from the American Type Culture Collection (ATCC; CRL-1573). No human participants, newly collected human biological samples, live vertebrate animals, or identifiable personal data were involved.","order":2,"name":"Ethics","label":"Ethics approval and consent to participate","group":{"name":"EthicsHeading","label":"Ethics"}}]}}