{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,8]],"date-time":"2026-11-08T01:18:50Z","timestamp":1794100730369,"version":"4.8.0"},"reference-count":36,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2025,1,7]],"date-time":"2025-01-07T00:00:00Z","timestamp":1736208000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"},{"start":{"date-parts":[[2025,1,7]],"date-time":"2025-01-07T00:00:00Z","timestamp":1736208000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Nat Commun"],"DOI":"10.1038\/s41467-025-55873-3","type":"journal-article","created":{"date-parts":[[2025,1,7]],"date-time":"2025-01-07T06:44:05Z","timestamp":1736232245000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["High frequency CCR5 editing in human hematopoietic stem progenitor cells protects xenograft mice from HIV infection"],"prefix":"10.1038","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2091-1456","authenticated-orcid":false,"given":"Daniel T.","family":"Claiborne","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2218-7334","authenticated-orcid":false,"given":"Zachary","family":"Detwiler","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3771-5504","authenticated-orcid":false,"given":"Steffen S.","family":"Docken","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Todd D.","family":"Borland","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5276-5094","authenticated-orcid":false,"given":"Deborah","family":"Cromer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amanda","family":"Simkhovich","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9443-1538","authenticated-orcid":false,"given":"Youdiil","family":"Ophinni","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ken","family":"Okawa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Timothy","family":"Bateson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tao","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wesley","family":"Hudson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Radiana","family":"Trifonova","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4751-1831","authenticated-orcid":false,"given":"Miles P.","family":"Davenport","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tony W.","family":"Ho","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-4715-6920","authenticated-orcid":false,"given":"Christian L.","family":"Boutwell","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Todd M.","family":"Allen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,1,7]]},"reference":[{"key":"55873_CR1","doi-asserted-by":"publisher","first-page":"727","DOI":"10.1038\/nm880","volume":"9","author":"JD Siliciano","year":"2003","unstructured":"Siliciano, J. D. et al. Long-term follow-up studies confirm the stability of the latent reservoir for HIV-1 in resting CD4+ T cells. Nat. Med. 9, 727\u2013728 (2003).","journal-title":"Nat. Med."},{"key":"55873_CR2","doi-asserted-by":"publisher","first-page":"E4987","DOI":"10.1073\/pnas.1308313110","volume":"110","author":"L Josefsson","year":"2013","unstructured":"Josefsson, L. et al. The HIV-1 reservoir in eight patients on long-term suppressive antiretroviral therapy is stable with few genetic changes over time. Proc. Natl. Acad. Sci. USA 110, E4987\u2013E4996 (2013).","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"55873_CR3","doi-asserted-by":"publisher","first-page":"1312","DOI":"10.1093\/cid\/ciu585","volume":"59","author":"GJ Besson","year":"2014","unstructured":"Besson, G. J. et al. HIV-1 DNA decay dynamics in blood during more than a decade of suppressive antiretroviral therapy. Clin. Infect. Dis. 59, 1312\u20131321 (2014).","journal-title":"Clin. Infect. Dis."},{"key":"55873_CR4","doi-asserted-by":"publisher","first-page":"596","DOI":"10.1093\/infdis\/jiv092","volume":"212","author":"S von Stockenstrom","year":"2015","unstructured":"von Stockenstrom, S. et al. Longitudinal genetic characterization reveals that cell proliferation maintains a persistent HIV type 1 DNA pool during effective HIV therapy. J. Infect. Dis. 212, 596\u2013607 (2015).","journal-title":"J. Infect. Dis."},{"key":"55873_CR5","doi-asserted-by":"publisher","first-page":"e18889","DOI":"10.7554\/eLife.18889","volume":"5","author":"J Brodin","year":"2016","unstructured":"Brodin, J. et al. Establishment and stability of the latent HIV-1 DNA reservoir. Elife 5, e18889 (2016).","journal-title":"Elife"},{"key":"55873_CR6","doi-asserted-by":"publisher","first-page":"872","DOI":"10.1016\/j.immuni.2018.04.030","volume":"48","author":"S Sengupta","year":"2018","unstructured":"Sengupta, S. & Siliciano, R. F. Targeting the latent reservoir for HIV-1. Immunity 48, 872\u2013895 (2018).","journal-title":"Immunity"},{"key":"55873_CR7","doi-asserted-by":"publisher","first-page":"1443","DOI":"10.3390\/v12121443","volume":"12","author":"I Moranguinho","year":"2020","unstructured":"Moranguinho, I. & Valente, S. T. Block-and-lock: new horizons for a cure for HIV-1. Viruses 12, 1443 (2020).","journal-title":"Viruses"},{"key":"55873_CR8","doi-asserted-by":"publisher","first-page":"692","DOI":"10.1056\/NEJMoa0802905","volume":"360","author":"G Hutter","year":"2009","unstructured":"Hutter, G. et al. Long-term control of HIV by CCR5 Delta32\/Delta32 stem-cell transplantation. N. Engl. J. Med. 360, 692\u2013698 (2009).","journal-title":"N. Engl. J. Med."},{"key":"55873_CR9","doi-asserted-by":"publisher","first-page":"244","DOI":"10.1038\/s41586-019-1027-4","volume":"568","author":"RK Gupta","year":"2019","unstructured":"Gupta, R. K. et al. HIV-1 remission following CCR5Delta32\/Delta32 haematopoietic stem-cell transplantation. Nature 568, 244\u2013248 (2019).","journal-title":"Nature"},{"key":"55873_CR10","doi-asserted-by":"publisher","first-page":"583","DOI":"10.1038\/s41591-023-02213-x","volume":"29","author":"BO Jensen","year":"2023","unstructured":"Jensen, B. O. et al. In-depth virological and immunological characterization of HIV-1 cure after CCR5Delta32\/Delta32 allogeneic hematopoietic stem cell transplantation. Nat. Med. 29, 583\u2013587 (2023).","journal-title":"Nat. Med."},{"key":"55873_CR11","doi-asserted-by":"publisher","first-page":"319","DOI":"10.7326\/M14-1027","volume":"161","author":"TJ Henrich","year":"2014","unstructured":"Henrich, T. J. et al. Antiretroviral-free HIV-1 remission and viral rebound after allogeneic stem cell transplantation: report of 2 cases. Ann. Intern. Med. 161, 319\u2013327 (2014).","journal-title":"Ann. Intern. Med."},{"key":"55873_CR12","doi-asserted-by":"publisher","first-page":"1694","DOI":"10.1093\/infdis\/jit086","volume":"207","author":"TJ Henrich","year":"2013","unstructured":"Henrich, T. J. et al. Long-term reduction in peripheral blood HIV type 1 reservoirs following reduced-intensity conditioning allogeneic stem cell transplantation. J. Infect. Dis. 207, 1694\u20131702 (2013).","journal-title":"J. Infect. Dis."},{"key":"55873_CR13","doi-asserted-by":"publisher","first-page":"674","DOI":"10.7326\/M18-0759","volume":"169","author":"M Salgado","year":"2018","unstructured":"Salgado, M. et al. Mechanisms that contribute to a profound reduction of the HIV-1 reservoir after allogeneic stem cell transplant. Ann. Intern. Med. 169, 674\u2013683, (2018).","journal-title":"Ann. Intern. Med."},{"key":"55873_CR14","doi-asserted-by":"publisher","first-page":"1240","DOI":"10.1056\/NEJMoa1817426","volume":"381","author":"L Xu","year":"2019","unstructured":"Xu, L. et al. CRISPR-edited stem cells in a patient with HIV and acute lymphocytic leukemia. N. Engl. J. Med. 381, 1240\u20131247 (2019).","journal-title":"N. Engl. J. Med."},{"key":"55873_CR15","doi-asserted-by":"publisher","first-page":"432","DOI":"10.1172\/JCI80563","volume":"126","author":"DR Kuritzkes","year":"2016","unstructured":"Kuritzkes, D. R. Hematopoietic stem cell transplantation for HIV cure. J. Clin. Investig. 126, 432\u2013437 (2016).","journal-title":"J. Clin. Investig."},{"key":"55873_CR16","doi-asserted-by":"publisher","first-page":"100","DOI":"10.1038\/ng0597-100","volume":"16","author":"JJ Martinson","year":"1997","unstructured":"Martinson, J. J., Chapman, N. H., Rees, D. C., Liu, Y. T. & Clegg, J. B. Global distribution of the CCR5 gene 32-basepair deletion. Nat. Genet. 16, 100\u2013103 (1997).","journal-title":"Nat. Genet."},{"key":"55873_CR17","doi-asserted-by":"publisher","first-page":"25","DOI":"10.3390\/biotech11030025","volume":"11","author":"JJ Freen-van Heeren","year":"2022","unstructured":"Freen-van Heeren, J. J. Closing the door with CRISPR: genome editing of CCR5 and CXCR4 as a potential curative solution for HIV. BioTechnology 11, 25 (2022).","journal-title":"BioTechnology"},{"key":"55873_CR18","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2217887120","volume":"120","author":"PK Dash","year":"2023","unstructured":"Dash, P. K. et al. CRISPR editing of CCR5 and HIV-1 facilitates viral elimination in antiretroviral drug-suppressed virus-infected humanized mice. Proc. Natl. Acad. Sci. USA 120, e2217887120 (2023).","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"55873_CR19","doi-asserted-by":"publisher","first-page":"235","DOI":"10.1038\/nature13420","volume":"510","author":"P Genovese","year":"2014","unstructured":"Genovese, P. et al. Targeted genome editing in human repopulating haematopoietic stem cells. Nature 510, 235\u2013240 (2014).","journal-title":"Nature"},{"key":"55873_CR20","doi-asserted-by":"publisher","first-page":"45","DOI":"10.1038\/s41577-018-0085-4","volume":"19","author":"MP Davenport","year":"2019","unstructured":"Davenport, M. P. et al. Functional cure of HIV: the scale of the challenge. Nat. Rev. Immunol. 19, 45\u201354 (2019).","journal-title":"Nat. Rev. Immunol."},{"key":"55873_CR21","doi-asserted-by":"publisher","first-page":"252","DOI":"10.1056\/NEJMoa2031054","volume":"384","author":"H Frangoul","year":"2021","unstructured":"Frangoul, H. et al. CRISPR-Cas9 gene editing for sickle cell disease and beta-thalassemia. N. Engl. J. Med. 384, 252\u2013260 (2021).","journal-title":"N. Engl. J. Med."},{"key":"55873_CR22","doi-asserted-by":"publisher","first-page":"171","DOI":"10.1016\/j.stemcr.2014.12.005","volume":"4","author":"BE McIntosh","year":"2015","unstructured":"McIntosh, B. E. et al. Nonirradiated NOD, B6.SCID Il2rgamma-\/- Kit(W41\/W41) (NBSGW) mice support multilineage engraftment of human hematopoietic cells. Stem Cell Rep. 4, 171\u2013180 (2015).","journal-title":"Stem Cell Rep."},{"key":"55873_CR23","doi-asserted-by":"publisher","first-page":"916","DOI":"10.1182\/bloodadvances.2023011371","volume":"8","author":"S Choo","year":"2024","unstructured":"Choo, S. et al. Choosing the right mouse model: comparison of humanized NSG and NBSGW mice for in vivo HSC gene therapy. Blood Adv. 8, 916\u2013926 (2024).","journal-title":"Blood Adv."},{"key":"55873_CR24","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-019-11962-8","volume":"10","author":"N Gomez-Ospina","year":"2019","unstructured":"Gomez-Ospina, N. et al. Human genome-edited hematopoietic stem cells phenotypically correct Mucopolysaccharidosis type I. Nat. Commun. 10, 4045 (2019).","journal-title":"Nat. Commun."},{"key":"55873_CR25","doi-asserted-by":"publisher","first-page":"1389","DOI":"10.1016\/j.ymthe.2019.05.014","volume":"27","author":"Z Romero","year":"2019","unstructured":"Romero, Z. et al. Editing the sickle cell disease mutation in human hematopoietic stem cells: comparison of endonucleases and homologous donor templates. Mol. Ther. 27, 1389\u20131406 (2019).","journal-title":"Mol. Ther."},{"key":"55873_CR26","doi-asserted-by":"publisher","first-page":"1782","DOI":"10.1016\/j.ymthe.2017.04.027","volume":"25","author":"L Xu","year":"2017","unstructured":"Xu, L. et al. CRISPR\/Cas9-mediated CCR5 ablation in human hematopoietic stem\/progenitor cells confers HIV-1 resistance in vivo. Mol. Ther. 25, 1782\u20131789 (2017).","journal-title":"Mol. Ther."},{"key":"55873_CR27","doi-asserted-by":"publisher","first-page":"e1006956","DOI":"10.1371\/journal.ppat.1006956","volume":"14","author":"CW Peterson","year":"2018","unstructured":"Peterson, C. W. et al. Differential impact of transplantation on peripheral and tissue-associated viral reservoirs: implications for HIV gene therapy. PLoS Pathog. 14, e1006956 (2018).","journal-title":"PLoS Pathog."},{"key":"55873_CR28","doi-asserted-by":"publisher","first-page":"e57646","DOI":"10.7554\/eLife.57646","volume":"10","author":"EF Cardozo-Ojeda","year":"2021","unstructured":"Cardozo-Ojeda, E. F. et al. Thresholds for post-rebound SHIV control after CCR5 gene-edited autologous hematopoietic cell transplantation. Elife 10, e57646 (2021).","journal-title":"Elife"},{"key":"55873_CR29","doi-asserted-by":"publisher","first-page":"e1005000","DOI":"10.1371\/journal.ppat.1005000","volume":"11","author":"M Pinkevych","year":"2015","unstructured":"Pinkevych, M. et al. HIV reactivation from latency after treatment interruption occurs on average every 5\u20138 days\u2013implications for HIV remission. PLoS Pathog. 11, e1005000 (2015).","journal-title":"PLoS Pathog."},{"key":"55873_CR30","doi-asserted-by":"publisher","first-page":"901","DOI":"10.1056\/NEJMoa1300662","volume":"370","author":"P Tebas","year":"2014","unstructured":"Tebas, P. et al. Gene editing of CCR5 in autologous CD4 T cells of persons infected with HIV. N. Engl. J. Med. 370, 901\u2013910 (2014).","journal-title":"N. Engl. J. Med."},{"key":"55873_CR31","doi-asserted-by":"publisher","first-page":"e144486","DOI":"10.1172\/JCI144486","volume":"131","author":"P Tebas","year":"2021","unstructured":"Tebas, P. et al. CCR5-edited CD4+ T cells augment HIV-specific immunity to enable post-rebound control of HIV replication. J. Clin. Investig. 131, e144486 (2021).","journal-title":"J. Clin. Investig."},{"key":"55873_CR32","doi-asserted-by":"publisher","first-page":"839","DOI":"10.1038\/nbt.1663","volume":"28","author":"N Holt","year":"2010","unstructured":"Holt, N. et al. Human hematopoietic stem\/progenitor cells modified by zinc-finger nucleases targeted to CCR5 control HIV-1 in vivo. Nat. Biotechnol. 28, 839\u2013847 (2010).","journal-title":"Nat. Biotechnol."},{"key":"55873_CR33","doi-asserted-by":"publisher","first-page":"e2102404118","DOI":"10.1073\/pnas.2102404118","volume":"118","author":"MG Morvan","year":"2021","unstructured":"Morvan, M. G. et al. Genetically edited CD34(+) cells derived from human iPS cells in vivo but not in vitro engraft and differentiate into HIV-resistant cells. Proc. Natl. Acad. Sci. USA 118, e2102404118 (2021).","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"55873_CR34","first-page":"2085","volume":"141","author":"C Li","year":"2023","unstructured":"Li, C. et al. In vivo HSC prime editing rescues sickle cell disease in a mouse model. Blood 141, 2085\u20132099 (2023).","journal-title":"Blood"},{"key":"55873_CR35","doi-asserted-by":"publisher","first-page":"2460","DOI":"10.1128\/JVI.01970-08","volume":"83","author":"CL Boutwell","year":"2009","unstructured":"Boutwell, C. L., Rowley, C. F. & Essex, M. Reduced viral replication capacity of human immunodeficiency virus type 1 subtype C caused by cytotoxic-T-lymphocyte escape mutations in HLA-B57 epitopes of capsid protein. J. Virol. 83, 2460\u20132468 (2009).","journal-title":"J. Virol."},{"key":"55873_CR36","doi-asserted-by":"publisher","first-page":"1776","DOI":"10.1038\/s41591-020-1039-5","volume":"26","author":"CR Maldini","year":"2020","unstructured":"Maldini, C. R. et al. Dual CD4-based CAR T cells with distinct costimulatory domains mitigate HIV pathogenesis in vivo. Nat. Med. 26, 1776\u20131787 (2020).","journal-title":"Nat. Med."}],"container-title":["Nature Communications"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41467-025-55873-3.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41467-025-55873-3","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41467-025-55873-3.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,1,7]],"date-time":"2025-01-07T07:03:47Z","timestamp":1736233427000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41467-025-55873-3"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,1,7]]},"references-count":36,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2025,12]]}},"alternative-id":["55873"],"URL":"https:\/\/doi.org\/10.1038\/s41467-025-55873-3","relation":{},"ISSN":["2041-1723"],"issn-type":[{"value":"2041-1723","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,1,7]]},"assertion":[{"value":"13 May 2024","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"2 January 2025","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"7 January 2025","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"ZD is a current employee, holds stock and stock options in CRISPR Therapeutics AG. TB and TH are former employees and shareholders of CRISPR Therapeutics AG. The other authors declare no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"446"}}