{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,8,21]],"date-time":"2025-08-21T18:31:38Z","timestamp":1755801098318,"version":"3.44.0"},"reference-count":27,"publisher":"Danish Medical Association","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Ugeskr L\u00e6ger"],"abstract":"<jats:p>Severe haemoglobinopathies, including sickle cell disease and \u03b2-thalassaemia, represent significant global health burdens. CRISPR technology enables precise genetic editing of haematopoietic stem cells, with current therapies focused on boosting fetal haemoglobin production for a functional cure. This review finds that, while promising, ex vivo approaches require advanced facilities and substantial resources, limiting accessibility where the need is highest. Future development of in vivo methods may expand global access, addressing the urgent need for scalable and affordable treatments for these debilitating diseases.<\/jats:p>","DOI":"10.61409\/v12240888","type":"journal-article","created":{"date-parts":[[2025,6,10]],"date-time":"2025-06-10T06:16:15Z","timestamp":1749536175000},"page":"1-8","source":"Crossref","is-referenced-by-count":0,"title":["CRISPR as a functional cure for hemoglobinopathies"],"prefix":"10.61409","author":[{"given":"Andreas","family":"Glenth\u00f8j","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sarah Birgitte Ingemod Sand","family":"Carlsen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marianne","family":"Hoffmann","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eva Kannik","family":"Haastrup","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lisbeth Pernille","family":"Andersen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nina","family":"Toft","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Brian Thomas","family":"Kornblit","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jesper Brix","family":"Petersen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Henrik","family":"Hasle","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"arianne Rosenkrantz Segelcke","family":"Ifversen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"40208","published-online":{"date-parts":[[2025,5,26]]},"reference":[{"key":"ref0","doi-asserted-by":"publisher","unstructured":"Modell B, Darlison M. Global epidemiology of haemoglobin disorders and derived service indicators. Bull World Health Organ. 2008;86(6):480-7. https:\/\/doi.org\/10.2471\/BLT.06.036673","DOI":"10.2471\/BLT.06.036673"},{"key":"ref1","doi-asserted-by":"publisher","unstructured":"Gravholt EAE, J\u00f8rgensen FS, Holm C et al. Optimisation of the Danish national haemoglobinopathy screening programme: a prospective intervention study. EJHaem. (online 8. aug 2024). https:\/\/doi.org\/10.1002\/jha2.980","DOI":"10.1002\/jha2.980"},{"key":"ref2","doi-asserted-by":"publisher","unstructured":"Gravholt EAE, Petersen J, Mottelson M et al. The Danish national haemoglobinopathy screening programme: report from 16 years of screening in a low-prevalence, non-endemic region. Br J Haematol. 2024;204(1):329-336. https:\/\/doi.org\/10.1111\/bjh.19103","DOI":"10.1111\/bjh.19103"},{"key":"ref3","doi-asserted-by":"publisher","unstructured":"Pereira MDMM, Colombatti R, Alvarez F et al. Sickle cell disease landscape and challenges in the EU: the ERN-EuroBloodNet perspective. Lancet Haematol. 2023;10(8):e687-e694. https:\/\/doi.org\/10.1016\/S2352-3026(23)00182-5","DOI":"10.1016\/S2352-3026(23)00182-5"},{"key":"ref4","doi-asserted-by":"publisher","unstructured":"Piel FB, Steinberg MH, Rees DC. Sickle cell disease. N Engl J Med. 2017;376(16):1561-1573. https:\/\/doi.org\/10.1056\/NEJMra1510865","DOI":"10.1056\/NEJMra1510865"},{"key":"ref5","doi-asserted-by":"publisher","unstructured":"Farmakis D, Porter J, Taher A et al. 2021 Thalassaemia International Federation guidelines for the management of transfusion-dependent thalassemia. Hemasphere. 2022;6(8):e732. https:\/\/doi.org\/10.1097\/HS9.0000000000000732","DOI":"10.1097\/HS9.0000000000000732"},{"key":"ref6","doi-asserted-by":"publisher","unstructured":"Pennings G, Schots R, Liebaers I. Ethical considerations on preimplantation genetic diagnosis for HLA typing to match a future child as a donor of haematopoietic stem cells to a sibling. Hum Reprod. 2002;17(3):534-538. https:\/\/doi.org\/10.1093\/humrep\/17.3.534","DOI":"10.1093\/humrep\/17.3.534"},{"key":"ref7","doi-asserted-by":"publisher","unstructured":"Kountouris P, Lederer CW, Fanis P et al. IthaGenes: an interactive database for haemoglobin variations and epidemiology. PLoS One. 2014;9(7):e103020. https:\/\/doi.org\/10.1371\/journal.pone.0103020","DOI":"10.1371\/journal.pone.0103020"},{"key":"ref8","doi-asserted-by":"publisher","unstructured":"Nardo-Marino A, Petersen J, Brewin JN et al. Oxygen gradient ektacytometry does not predict pain in children with sickle cell anaemia. Br J Haematol. 2022;197(5):609-617. https:\/\/doi.org\/10.1111\/bjh.17975","DOI":"10.1111\/bjh.17975"},{"key":"ref9","doi-asserted-by":"publisher","unstructured":"Krishnamurti L. Hematopoietic cell transplantation for sickle cell disease: updates and future directions. Hematology Am Soc Hematol Educ Program. 2021;2021(1):181-189. https:\/\/doi.org\/10.1182\/hematology.2021000251","DOI":"10.1182\/hematology.2021000251"},{"key":"ref10","doi-asserted-by":"publisher","unstructured":"Kanter J, Walters MC, Krishnamurti L et al. Biologic and clinical efficacy of LentiGlobin for sickle cell disease. N Engl J Med. 2022;386(7):617-628. https:\/\/doi.org\/10.1056\/NEJMoa2117175","DOI":"10.1056\/NEJMoa2117175"},{"key":"ref11","doi-asserted-by":"publisher","unstructured":"Locatelli F, Thompson AA, Kwiatkowski JL et al. Betibeglogene autotemcel gene therapy for non-\u03b20\/\u03b20 genotype \u03b2-thalassemia. N Engl J Med. 2022;386(5):415-427. https:\/\/doi.org\/10.1056\/NEJMoa2113206","DOI":"10.1056\/NEJMoa2113206"},{"key":"ref12","doi-asserted-by":"publisher","unstructured":"Yi Y, Noh MJ, Lee KH. Current advances in retroviral gene therapy. Curr Gene Ther. 2011;11(3):218-28. https:\/\/doi.org\/10.2174\/156652311795684740","DOI":"10.2174\/156652311795684740"},{"key":"ref13","doi-asserted-by":"publisher","unstructured":"Goyal S, Tisdale J, Schmidt M et al. Acute myeloid leukemia case after gene therapy for sickle cell disease. N Engl J Med. 2022;386(2):138-147. https:\/\/doi.org\/10.1056\/NEJMoa2109167","DOI":"10.1056\/NEJMoa2109167"},{"key":"ref14","doi-asserted-by":"publisher","unstructured":"Sharma A. How I treat sickle cell disease with gene therapy. Blood. 2024;144(26):2693-2705. https:\/\/doi.org\/10.1182\/blood.2024024519","DOI":"10.1182\/blood.2024024519"},{"key":"ref15","doi-asserted-by":"publisher","unstructured":"Yen A, Zappala Z, Fine RS et al. Specificity of CRISPR-Cas9 editing in exagamglogene autotemcel. N Engl J Med. 2024;390(18):1723-1725. https:\/\/doi.org\/10.1056\/NEJMc2313119","DOI":"10.1056\/NEJMc2313119"},{"key":"ref16","doi-asserted-by":"publisher","unstructured":"Locatelli F, Lang P, Wall D et al. Exagamglogene autotemcel for transfusion-dependent \u03b2-thalassemia. N Engl J Med. 2024;390(18):1663-1676. https:\/\/doi.org\/10.1056\/NEJMoa2309673","DOI":"10.1056\/NEJMoa2309673"},{"key":"ref17","doi-asserted-by":"publisher","unstructured":"Frangoul H, Locatelli F, Sharma A et al. Exagamglogene autotemcel for severe sickle cell disease. N Engl J Med. 2024;390(18):1649-1662. https:\/\/doi.org\/10.1056\/NEJMoa2309676","DOI":"10.1056\/NEJMoa2309676"},{"key":"ref18","doi-asserted-by":"publisher","unstructured":"Hanna R, Frangoul H, McKinney C, Pineiro L. S264: EDIT-301 shows promising preliminary safety and efficacy results in the phase I\/II clinical trial (RUBY) of patients with severe sickle cell disease using highly specific and efficient AsCas12a enzyme. HemaSphere. 2023;7(S3):e05170e0. https:\/\/doi.org\/10.1097\/01.HS9.0000967968.05170.e0","DOI":"10.1097\/01.HS9.0000967968.05170.e0"},{"key":"ref19","doi-asserted-by":"publisher","unstructured":"Sharma A, Boelens JJ, Cancio M et al. CRISPR-Cas9 editing of the HBG1 and HBG2 promoters to treat sickle cell disease. N Engl J Med. 2023;389(9):820-832. https:\/\/doi.org\/10.1056\/NEJMoa2215643","DOI":"10.1056\/NEJMoa2215643"},{"key":"ref20","doi-asserted-by":"publisher","unstructured":"Carvalho T. Discontinued CRISPR gene therapy for sickle-cell disease improves symptoms. Nat Med. 2023;29(11):2669-2670. https:\/\/doi.org\/10.1038\/d41591-023-00088-6","DOI":"10.1038\/d41591-023-00088-6"},{"key":"ref21","unstructured":"Ifversen MS, Masmas TN, Kornblit B et al. Behandling af monogene sygdomme ved viral transduktion af h\u00e6matopoietiske stamceller. Ugeskr L\u00e6ger. 2020;182:V06200458. https:\/\/ugeskriftet.dk\/videnskab\/behandling-af-monogene-sygdomme-ved-viral-transduktion-af-haematopoietiske-stamceller"},{"key":"ref22","unstructured":"Glenth\u00f8j A, Samson M, Toft N et al. Det danske screeningsprogram for h\u00e6moglobinopatier. Ugeskr L\u00e6ger. 2021;183:V07200536. https:\/\/ugeskriftet.dk\/videnskab\/det-danske-screeningsprogram-haemoglobinopatier"},{"key":"ref23","doi-asserted-by":"publisher","unstructured":"Pauling L, Itano H, Singer S et al. Sickle cell anemia, a molecular disease. Science. 1949;110(2865):543-8. https:\/\/doi.org\/10.1126\/science.110.2865.543","DOI":"10.1126\/science.110.2865.543"},{"key":"ref24","doi-asserted-by":"publisher","unstructured":"Jinek M, Chylinski K, Fonfara I et al. A programmable dual-RNA-guided DNA endonuclease in adaptive bacterial immunity. Science. 2012;337(6096):816-21. https:\/\/doi.org\/10.1126\/science.1225829","DOI":"10.1126\/science.1225829"},{"key":"ref25","doi-asserted-by":"publisher","unstructured":"Breda L, Papp TE, Triebwasser MP et al. In vivo hematopoietic stem cell modification by mRNA delivery. Science. 2023;381(6656):436-443. https:\/\/doi.org\/10.1126\/science.ade6967","DOI":"10.1126\/science.ade6967"},{"key":"ref26","doi-asserted-by":"publisher","unstructured":"Li C, Georgakopoulou A, Newby GA et al. In vivo HSC prime editing rescues sickle cell disease in a mouse model. Blood. 2023;141(17):2085-2099. https:\/\/doi.org\/10.1182\/blood.2022018252","DOI":"10.1182\/blood.2022018252"}],"container-title":["Ugeskrift for L\u00e6ger"],"original-title":[],"deposited":{"date-parts":[[2025,8,20]],"date-time":"2025-08-20T13:18:51Z","timestamp":1755695931000},"score":1,"resource":{"primary":{"URL":"https:\/\/ugeskriftet.dk\/videnskab\/V12240888"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,5,26]]},"references-count":27,"URL":"https:\/\/doi.org\/10.61409\/v12240888","relation":{},"ISSN":["0041-5782","1603-6824"],"issn-type":[{"type":"print","value":"0041-5782"},{"type":"electronic","value":"1603-6824"}],"subject":[],"published":{"date-parts":[[2025,5,26]]}}}