{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,28]],"date-time":"2026-08-28T23:59:34Z","timestamp":1787961574746,"version":"build-2784847793"},"reference-count":169,"publisher":"Elsevier BV","issue":"6","license":[{"start":{"date-parts":[[2025,6,1]],"date-time":"2025-06-01T00:00:00Z","timestamp":1748736000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2025,6,1]],"date-time":"2025-06-01T00:00:00Z","timestamp":1748736000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2026,6,4]],"date-time":"2026-06-04T00:00:00Z","timestamp":1780531200000},"content-version":"vor","delay-in-days":368,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100007470","name":"Shaqra University","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100007470","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000866","name":"Cardiff University","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000866","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100018948","name":"Saudi Arabian Cultural Bureau","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100018948","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["cell.com","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Molecular Therapy"],"published-print":{"date-parts":[[2025,6]]},"DOI":"10.1016\/j.ymthe.2025.01.031","type":"journal-article","created":{"date-parts":[[2025,1,18]],"date-time":"2025-01-18T03:30:22Z","timestamp":1737171022000},"page":"2645-2662","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":9,"title":["Treating genetic blood disorders in the era of CRISPR-mediated genome editing"],"prefix":"10.1016","volume":"33","author":[{"given":"Alhomidi","family":"Almotiri","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ahmed","family":"Abogosh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ali","family":"Abdelfattah","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dalya","family":"Alowaisy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1925-7733","authenticated-orcid":false,"given":"Neil P.","family":"Rodrigues","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.ymthe.2025.01.031_bib1","doi-asserted-by":"crossref","first-page":"1288","DOI":"10.1126\/science.2660260","article-title":"Altering the genome by homologous recombination","volume":"244","author":"Capecchi","year":"1989","journal-title":"Science"},{"key":"10.1016\/j.ymthe.2025.01.031_bib2","doi-asserted-by":"crossref","first-page":"319","DOI":"10.1038\/nbt788","article-title":"Homologous recombination in human embryonic stem cells","volume":"21","author":"Zwaka","year":"2003","journal-title":"Nat. Biotechnol."},{"key":"10.1016\/j.ymthe.2025.01.031_bib3","doi-asserted-by":"crossref","first-page":"1501","DOI":"10.1126\/science.1178817","article-title":"A simple cipher governs DNA recognition by TAL effectors","volume":"326","author":"Moscou","year":"2009","journal-title":"Science"},{"key":"10.1016\/j.ymthe.2025.01.031_bib4","doi-asserted-by":"crossref","first-page":"1169","DOI":"10.1093\/genetics\/161.3.1169","article-title":"Targeted chromosomal cleavage and mutagenesis in Drosophila using zinc-finger nucleases","volume":"161","author":"Bibikova","year":"2002","journal-title":"Genetics"},{"key":"10.1016\/j.ymthe.2025.01.031_bib5","doi-asserted-by":"crossref","DOI":"10.3390\/ijms21249604","article-title":"Various Aspects of a Gene Editing System-CRISPR-Cas9","volume":"21","author":"Janik","year":"2020","journal-title":"Int. J. Mol. Sci."},{"key":"10.1016\/j.ymthe.2025.01.031_bib6","doi-asserted-by":"crossref","first-page":"816","DOI":"10.1126\/science.1225829","article-title":"A programmable dual-RNA-guided DNA endonuclease in adaptive bacterial immunity","volume":"337","author":"Jinek","year":"2012","journal-title":"Science"},{"key":"10.1016\/j.ymthe.2025.01.031_bib7","doi-asserted-by":"crossref","first-page":"1262","DOI":"10.1016\/j.cell.2014.05.010","article-title":"Development and applications of CRISPR-Cas9 for genome engineering","volume":"157","author":"Hsu","year":"2014","journal-title":"Cell"},{"key":"10.1016\/j.ymthe.2025.01.031_bib8","doi-asserted-by":"crossref","first-page":"583","DOI":"10.1038\/nature14136","article-title":"Genome-scale transcriptional activation by an engineered CRISPR-Cas9 complex","volume":"517","author":"Konermann","year":"2015","journal-title":"Nature"},{"key":"10.1016\/j.ymthe.2025.01.031_bib9","doi-asserted-by":"crossref","first-page":"174","DOI":"10.1007\/s00239-004-0046-3","article-title":"Intervening sequences of regularly spaced prokaryotic repeats derive from foreign genetic elements","volume":"60","author":"Mojica","year":"2005","journal-title":"J. Mol. Evol."},{"key":"10.1016\/j.ymthe.2025.01.031_bib10","doi-asserted-by":"crossref","first-page":"653","DOI":"10.1099\/mic.0.27437-0","article-title":"CRISPR elements in Yersinia pestis acquire new repeats by preferential uptake of bacteriophage DNA, and provide additional tools for evolutionary studies","volume":"151","author":"Pourcel","year":"2005","journal-title":"Microbiology"},{"key":"10.1016\/j.ymthe.2025.01.031_bib11","doi-asserted-by":"crossref","first-page":"819","DOI":"10.1126\/science.1231143","article-title":"Multiplex genome engineering using CRISPR\/Cas systems","volume":"339","author":"Cong","year":"2013","journal-title":"Science"},{"key":"10.1016\/j.ymthe.2025.01.031_bib12","doi-asserted-by":"crossref","first-page":"823","DOI":"10.1126\/science.1232033","article-title":"RNA-guided human genome engineering via Cas9","volume":"339","author":"Mali","year":"2013","journal-title":"Science"},{"key":"10.1016\/j.ymthe.2025.01.031_bib13","doi-asserted-by":"crossref","first-page":"263","DOI":"10.1038\/nature13769","article-title":"Programmable RNA recognition and cleavage by CRISPR\/Cas9","volume":"516","author":"O'Connell","year":"2014","journal-title":"Nature"},{"key":"10.1016\/j.ymthe.2025.01.031_bib14","doi-asserted-by":"crossref","first-page":"385","DOI":"10.1016\/j.molcel.2015.10.008","article-title":"Discovery and Functional Characterization of Diverse Class 2 CRISPR-Cas Systems","volume":"60","author":"Shmakov","year":"2015","journal-title":"Mol. Cell"},{"key":"10.1016\/j.ymthe.2025.01.031_bib15","doi-asserted-by":"crossref","first-page":"290","DOI":"10.1126\/science.aba8853","article-title":"Unconstrained genome targeting with near-PAMless engineered CRISPR-Cas9 variants","volume":"368","author":"Walton","year":"2020","journal-title":"Science"},{"key":"10.1016\/j.ymthe.2025.01.031_bib16","doi-asserted-by":"crossref","first-page":"227","DOI":"10.1038\/nbt.2501","article-title":"Efficient genome editing in zebrafish using a CRISPR-Cas system","volume":"31","author":"Hwang","year":"2013","journal-title":"Nat. Biotechnol."},{"key":"10.1016\/j.ymthe.2025.01.031_bib17","doi-asserted-by":"crossref","first-page":"380","DOI":"10.1038\/nature13589","article-title":"CRISPR-mediated direct mutation of cancer genes in the mouse liver","volume":"514","author":"Xue","year":"2014","journal-title":"Nature"},{"key":"10.1016\/j.ymthe.2025.01.031_bib18","doi-asserted-by":"crossref","first-page":"428","DOI":"10.1177\/0192623315613160","article-title":"Meganucleases Revolutionize the Production of Genetically Engineered Pigs for the Study of Human Diseases","volume":"44","author":"Redel","year":"2016","journal-title":"Toxicol. Pathol."},{"key":"10.1016\/j.ymthe.2025.01.031_bib19","doi-asserted-by":"crossref","first-page":"384","DOI":"10.1038\/nature20134","article-title":"CRISPR\/Cas9 \u03b2-globin gene targeting in human haematopoietic stem cells","volume":"539","author":"Dever","year":"2016","journal-title":"Nature"},{"key":"10.1016\/j.ymthe.2025.01.031_bib20","doi-asserted-by":"crossref","first-page":"415","DOI":"10.1038\/nm.4313","article-title":"Refining strategies to translate genome editing to the clinic","volume":"23","author":"Cornu","year":"2017","journal-title":"Nat. Med."},{"key":"10.1016\/j.ymthe.2025.01.031_bib21","first-page":"239","article-title":"Structure-function relations of human hemoglobins","volume":"19","author":"Marengo-Rowe","year":"2006","journal-title":"Proc. (Bayl. Univ. Med. Cent.)"},{"key":"10.1016\/j.ymthe.2025.01.031_bib22","doi-asserted-by":"crossref","first-page":"64","DOI":"10.1126\/science.110.2846.64","article-title":"The Inheritance of Sickle Cell Anemia","volume":"110","author":"Neel","year":"1949","journal-title":"Science"},{"key":"10.1016\/j.ymthe.2025.01.031_bib23","first-page":"4","article-title":"Differences in the clinical and genotypic presentation of sickle cell disease around the world","volume":"15","author":"Saraf","year":"2014","journal-title":"Paediatr. Respir. Rev."},{"key":"10.1016\/j.ymthe.2025.01.031_bib24","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1001\/jama.2022.10233","article-title":"Sickle Cell Disease: A Review","volume":"328","author":"Kavanagh","year":"2022","journal-title":"JAMA"},{"key":"10.1016\/j.ymthe.2025.01.031_bib25","doi-asserted-by":"crossref","first-page":"237","DOI":"10.1111\/ejh.13430","article-title":"The vaso-occlusive pain crisis in sickle cell disease: Definition, pathophysiology, and management","volume":"105","author":"Darbari","year":"2020","journal-title":"Eur. J. Haematol."},{"key":"10.1016\/j.ymthe.2025.01.031_bib26","first-page":"229","article-title":"Hematopoietic stem cell transplantation in sickle cell disease: patient selection and special considerations","volume":"6","author":"Bhatia","year":"2015","journal-title":"J. Blood Med."},{"key":"10.1016\/j.ymthe.2025.01.031_bib27","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1080\/14656566.2024.2317336","article-title":"An update review of new therapies in sickle cell disease: the prospects for drug combinations","volume":"25","author":"Lugthart","year":"2024","journal-title":"Expert Opin. Pharmacother."},{"key":"10.1016\/j.ymthe.2025.01.031_bib28","doi-asserted-by":"crossref","first-page":"2555","DOI":"10.1182\/blood.V79.10.2555.2555","article-title":"Hydroxyurea: effects on hemoglobin F production in patients with sickle cell anemia","volume":"79","author":"Charache","year":"1992","journal-title":"Blood"},{"key":"10.1016\/j.ymthe.2025.01.031_bib29","doi-asserted-by":"crossref","first-page":"3774","DOI":"10.1021\/bi992691l","article-title":"Transposing sequences between fetal and adult hemoglobins indicates which subunits and regulatory molecule interfaces are functionally related","volume":"39","author":"Chen","year":"2000","journal-title":"Biochemistry"},{"key":"10.1016\/j.ymthe.2025.01.031_bib30","doi-asserted-by":"crossref","DOI":"10.1101\/cshperspect.a011643","article-title":"The switch from fetal to adult hemoglobin","volume":"3","author":"Sankaran","year":"2013","journal-title":"Cold Spring Harb. Perspect. Med."},{"key":"10.1016\/j.ymthe.2025.01.031_bib31","doi-asserted-by":"crossref","first-page":"2392","DOI":"10.1182\/blood.2020007645","article-title":"Fetal hemoglobin in sickle cell anemia","volume":"136","author":"Steinberg","year":"2020","journal-title":"Blood"},{"key":"10.1016\/j.ymthe.2025.01.031_bib32","doi-asserted-by":"crossref","first-page":"2146","DOI":"10.1002\/pbc.26161","article-title":"Decreased fetal hemoglobin over time among youth with sickle cell disease on hydroxyurea is associated with higher urgent hospital use","volume":"63","author":"Green","year":"2016","journal-title":"Pediatr. Blood Cancer"},{"key":"10.1016\/j.ymthe.2025.01.031_bib33","doi-asserted-by":"crossref","first-page":"62","DOI":"10.1182\/asheducation-2009.1.62","article-title":"Advances in the use of hydroxyurea","volume":"2009","author":"Ware","year":"2009","journal-title":"Hematol. Am. Soc. Hematol. Educ. Program"},{"key":"10.1016\/j.ymthe.2025.01.031_bib34","doi-asserted-by":"crossref","first-page":"1620","DOI":"10.1073\/pnas.0711566105","article-title":"Genome-wide association study shows BCL11A associated with persistent fetal hemoglobin and amelioration of the phenotype of beta-thalassemia","volume":"105","author":"Uda","year":"2008","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"10.1016\/j.ymthe.2025.01.031_bib35","doi-asserted-by":"crossref","first-page":"1839","DOI":"10.1126\/science.1165409","article-title":"Human fetal hemoglobin expression is regulated by the developmental stage-specific repressor BCL11A","volume":"322","author":"Sankaran","year":"2008","journal-title":"Science"},{"key":"10.1016\/j.ymthe.2025.01.031_bib36","doi-asserted-by":"crossref","first-page":"993","DOI":"10.1126\/science.1211053","article-title":"Correction of sickle cell disease in adult mice by interference with fetal hemoglobin silencing","volume":"334","author":"Xu","year":"2011","journal-title":"Science"},{"key":"10.1016\/j.ymthe.2025.01.031_bib37","doi-asserted-by":"crossref","first-page":"192","DOI":"10.1038\/nature15521","article-title":"BCL11A enhancer dissection by Cas9-mediated in situ saturating mutagenesis","volume":"527","author":"Canver","year":"2015","journal-title":"Nature"},{"key":"10.1016\/j.ymthe.2025.01.031_bib38","doi-asserted-by":"crossref","first-page":"498","DOI":"10.1038\/s41588-018-0085-0","article-title":"Natural regulatory mutations elevate the fetal globin gene via disruption of BCL11A or ZBTB7A binding","volume":"50","author":"Martyn","year":"2018","journal-title":"Nat. Genet."},{"key":"10.1016\/j.ymthe.2025.01.031_bib39","doi-asserted-by":"crossref","DOI":"10.1126\/sciadv.aay9392","article-title":"Editing a \u03b3-globin repressor binding site restores fetal hemoglobin synthesis and corrects the sickle cell disease phenotype","volume":"6","author":"Weber","year":"2020","journal-title":"Sci. Adv."},{"key":"10.1016\/j.ymthe.2025.01.031_bib40","doi-asserted-by":"crossref","first-page":"285","DOI":"10.1126\/science.aad3312","article-title":"Transcription factors LRF and BCL11A independently repress expression of fetal hemoglobin","volume":"351","author":"Masuda","year":"2016","journal-title":"Science"},{"key":"10.1016\/j.ymthe.2025.01.031_bib41","doi-asserted-by":"crossref","first-page":"1649","DOI":"10.1056\/NEJMoa2309676","article-title":"Exagamglogene Autotemcel for Severe Sickle Cell Disease","volume":"390","author":"Frangoul","year":"2024","journal-title":"N. Engl. J. Med."},{"key":"10.1016\/j.ymthe.2025.01.031_bib42","doi-asserted-by":"crossref","first-page":"820","DOI":"10.1056\/NEJMoa2215643","article-title":"CRISPR-Cas9 Editing of the HBG1 and HBG2 Promoters to Treat Sickle Cell Disease","volume":"389","author":"Sharma","year":"2023","journal-title":"N. Engl. J. Med."},{"key":"10.1016\/j.ymthe.2025.01.031_bib43","doi-asserted-by":"crossref","first-page":"759","DOI":"10.1016\/j.cell.2015.09.038","article-title":"Cpf1 is a single RNA-guided endonuclease of a class 2 CRISPR-Cas system","volume":"163","author":"Zetsche","year":"2015","journal-title":"Cell"},{"key":"10.1016\/j.ymthe.2025.01.031_bib44","doi-asserted-by":"crossref","DOI":"10.1097\/01.HS9.0000967968.05170.e0","article-title":"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","volume":"7","author":"Hanna","year":"2023","journal-title":"Hemasphere"},{"key":"10.1016\/j.ymthe.2025.01.031_bib45","doi-asserted-by":"crossref","first-page":"1920","DOI":"10.1126\/science.1152092","article-title":"Treatment of sickle cell anemia mouse model with iPS cells generated from autologous skin","volume":"318","author":"Hanna","year":"2007","journal-title":"Science"},{"key":"10.1016\/j.ymthe.2025.01.031_bib46","doi-asserted-by":"crossref","first-page":"770","DOI":"10.1038\/s41576-018-0059-1","article-title":"Base editing: precision chemistry on the genome and transcriptome of living cells","volume":"19","author":"Rees","year":"2018","journal-title":"Nat. Rev. Genet."},{"key":"10.1016\/j.ymthe.2025.01.031_bib47","doi-asserted-by":"crossref","first-page":"1470","DOI":"10.1172\/JCI25398","article-title":"Understanding globin regulation in beta-thalassemia: it's as simple as alpha, beta, gamma, delta","volume":"115","author":"Bank","year":"2005","journal-title":"J. Clin. Invest."},{"key":"10.1016\/j.ymthe.2025.01.031_bib48","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0103020","article-title":"IthaGenes: an interactive database for haemoglobin variations and epidemiology","volume":"9","author":"Kountouris","year":"2014","journal-title":"PLoS One"},{"key":"10.1016\/j.ymthe.2025.01.031_bib49","doi-asserted-by":"crossref","DOI":"10.1101\/cshperspect.a011700","article-title":"The molecular basis of \u03b2-thalassemia","volume":"3","author":"Thein","year":"2013","journal-title":"Cold Spring Harb. Perspect. Med."},{"key":"10.1016\/j.ymthe.2025.01.031_bib50","doi-asserted-by":"crossref","first-page":"727","DOI":"10.1056\/NEJMra2021838","article-title":"\u03b2-Thalassemias","volume":"384","author":"Taher","year":"2021","journal-title":"N. Engl. J. Med."},{"key":"10.1016\/j.ymthe.2025.01.031_bib51","doi-asserted-by":"crossref","first-page":"300","DOI":"10.1016\/j.blre.2018.02.001","article-title":"A paradigm shift on beta-thalassaemia treatment: How will we manage this old disease with new therapies?","volume":"32","author":"Cappellini","year":"2018","journal-title":"Blood Rev."},{"key":"10.1016\/j.ymthe.2025.01.031_bib52","doi-asserted-by":"crossref","first-page":"1526","DOI":"10.1101\/gr.173427.114","article-title":"Seamless gene correction of \u03b2-thalassemia mutations in patient-specific iPSCs using CRISPR\/Cas9 and piggyBac","volume":"24","author":"Xie","year":"2014","journal-title":"Genome Res."},{"key":"10.1016\/j.ymthe.2025.01.031_bib53","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1002\/sctm.17-0066","article-title":"A Universal Approach to Correct Various HBB Gene Mutations in Human Stem Cells for Gene Therapy of Beta-Thalassemia and Sickle Cell Disease","volume":"7","author":"Cai","year":"2018","journal-title":"Stem Cell Transl. Med."},{"key":"10.1016\/j.ymthe.2025.01.031_bib54","doi-asserted-by":"crossref","first-page":"1663","DOI":"10.1056\/NEJMoa2309673","article-title":"Exagamglogene Autotemcel for Transfusion-Dependent \u03b2-Thalassemia","volume":"390","author":"Locatelli","year":"2024","journal-title":"N. Engl. J. Med."},{"key":"10.1016\/j.ymthe.2025.01.031_bib55","doi-asserted-by":"crossref","first-page":"4995","DOI":"10.1182\/blood-2023-186031","article-title":"Efficacy and Safety of Brl-101, CRISPR-Cas9-Mediated Gene Editing of the BCL11A Enhancer in Transfusion-Dependent \u03b2-Thalassemia","volume":"142","author":"Zheng","year":"2023","journal-title":"Blood"},{"key":"10.1016\/j.ymthe.2025.01.031_bib56","doi-asserted-by":"crossref","first-page":"10652","DOI":"10.1182\/blood-2022-166365","article-title":"Preliminary Safety and Efficacy Results of EDI001: An Investigator Initiated Trial on CRISPR\/Cas9-Modified Autologous CD34+ Hematopoietic Stem and Progenitor Cells for Patients with Transfusion Dependent \u03b2-Thalassemia","volume":"140","author":"Shi","year":"2022","journal-title":"Blood"},{"key":"10.1016\/j.ymthe.2025.01.031_bib57","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1007\/s40291-024-00696-z","article-title":"Exagamglogene Autotemcel: First Approval","volume":"28","author":"Hoy","year":"2024","journal-title":"Mol. Diagn. Ther."},{"key":"10.1016\/j.ymthe.2025.01.031_bib58","doi-asserted-by":"crossref","first-page":"617","DOI":"10.1056\/NEJMoa2117175","article-title":"Biologic and Clinical Efficacy of LentiGlobin for Sickle Cell Disease","volume":"386","author":"Kanter","year":"2022","journal-title":"N. Engl. J. Med."},{"key":"10.1016\/j.ymthe.2025.01.031_bib59","doi-asserted-by":"crossref","first-page":"399","DOI":"10.1016\/S0889-8588(18)30422-2","article-title":"Delta beta thalassemia and hereditary persistence of fetal hemoglobin","volume":"5","author":"Bollekens","year":"1991","journal-title":"Hematol. Oncol. Clin. North. Am."},{"key":"10.1016\/j.ymthe.2025.01.031_bib60","doi-asserted-by":"crossref","first-page":"481","DOI":"10.1182\/blood-2013-09-528067","article-title":"Fetal hemoglobin in sickle cell anemia: a glass half full?","volume":"123","author":"Steinberg","year":"2014","journal-title":"Blood"},{"key":"10.1016\/j.ymthe.2025.01.031_bib61","doi-asserted-by":"crossref","first-page":"343","DOI":"10.1038\/s41586-022-04786-y","article-title":"Clonal dynamics of haematopoiesis across the human lifespan","volume":"606","author":"Mitchell","year":"2022","journal-title":"Nature"},{"key":"10.1016\/j.ymthe.2025.01.031_bib62","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1016\/S0140-6736(15)01123-X","article-title":"The past and future of haemophilia: diagnosis, treatments, and its complications","volume":"388","author":"Peyvandi","year":"2016","journal-title":"Lancet"},{"key":"10.1016\/j.ymthe.2025.01.031_bib63","doi-asserted-by":"crossref","first-page":"1702","DOI":"10.3324\/haematol.2019.221093","article-title":"Hemophilia A and B: molecular and clinical similarities and differences","volume":"104","author":"Castaman","year":"2019","journal-title":"Haematologica"},{"key":"10.1016\/j.ymthe.2025.01.031_bib64","doi-asserted-by":"crossref","first-page":"1099","DOI":"10.1080\/14712598.2022.2002842","article-title":"Hemophilia A gene therapy: current and next-generation approaches","volume":"22","author":"Pipe","year":"2022","journal-title":"Expert Opin. Biol. Ther."},{"key":"10.1016\/j.ymthe.2025.01.031_bib65","doi-asserted-by":"crossref","first-page":"630","DOI":"10.1016\/S0140-6736(20)32722-7","article-title":"The changing treatment landscape in haemophilia: from standard half-life clotting factor concentrates to gene editing","volume":"397","author":"Mancuso","year":"2021","journal-title":"The Lancet"},{"key":"10.1016\/j.ymthe.2025.01.031_bib66","doi-asserted-by":"crossref","first-page":"2251","DOI":"10.1182\/blood-2017-08-742312","article-title":"Novel approaches to hemophilia therapy: successes and challenges","volume":"130","author":"Arruda","year":"2017","journal-title":"Blood"},{"key":"10.1016\/j.ymthe.2025.01.031_bib67","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1620\/tjem.256.197","article-title":"Current Therapies in Hemophilia: From Plasma-Derived Factor Modalities to CRISPR\/Cas Alternatives","volume":"256","author":"Jair Lara-Navarro","year":"2022","journal-title":"Tohoku J. Exp. Med."},{"key":"10.1016\/j.ymthe.2025.01.031_bib68","doi-asserted-by":"crossref","first-page":"e265","DOI":"10.1016\/S2352-3026(24)00006-1","article-title":"Etranacogene dezaparvovec gene therapy for haemophilia B (HOPE-B): 24-month post-hoc efficacy and safety data from a single-arm, multicentre, phase 3 trial","volume":"11","author":"Coppens","year":"2024","journal-title":"Lancet Haematol."},{"key":"10.1016\/j.ymthe.2025.01.031_bib69","doi-asserted-by":"crossref","first-page":"347","DOI":"10.1007\/s40265-023-01845-0","article-title":"Etranacogene Dezaparvovec: First Approval","volume":"83","author":"Heo","year":"2023","journal-title":"Drugs"},{"key":"10.1016\/j.ymthe.2025.01.031_bib70","doi-asserted-by":"crossref","first-page":"342","DOI":"10.1038\/nm1358","article-title":"Successful transduction of liver in hemophilia by AAV-Factor IX and limitations imposed by the host immune response","volume":"12","author":"Manno","year":"2006","journal-title":"Nat. Med."},{"key":"10.1016\/j.ymthe.2025.01.031_bib71","article-title":"Hemophilia A ameliorated in mice by CRISPR-based in vivo genome editing of human Factor VIII","volume":"9","author":"Chen","year":"2019","journal-title":"Sci. Rep."},{"key":"10.1016\/j.ymthe.2025.01.031_bib72","doi-asserted-by":"crossref","first-page":"128","DOI":"10.1016\/j.jconrel.2019.02.009","article-title":"Long-term correction of hemophilia B using adenoviral delivery of CRISPR\/Cas9","volume":"298","author":"Stephens","year":"2019","journal-title":"J. Control Release"},{"key":"10.1016\/j.ymthe.2025.01.031_bib73","doi-asserted-by":"crossref","first-page":"2745","DOI":"10.1182\/blood.2019000790","article-title":"CRISPR\/Cas9-mediated in vivo gene targeting corrects hemostasis in newborn and adult factor IX-knockout mice","volume":"133","author":"Wang","year":"2019","journal-title":"Blood"},{"key":"10.1016\/j.ymthe.2025.01.031_bib74","doi-asserted-by":"crossref","first-page":"1911","DOI":"10.1038\/s41467-018-04252-2","article-title":"The CRISPR tool kit for genome editing and beyond","volume":"9","author":"Adli","year":"2018","journal-title":"Nat. Commun."},{"key":"10.1016\/j.ymthe.2025.01.031_bib75","doi-asserted-by":"crossref","first-page":"822","DOI":"10.1038\/nbt.2623","article-title":"High-frequency off-target mutagenesis induced by CRISPR-Cas nucleases in human cells","volume":"31","author":"Fu","year":"2013","journal-title":"Nat. Biotechnol."},{"key":"10.1016\/j.ymthe.2025.01.031_bib76","doi-asserted-by":"crossref","first-page":"1328","DOI":"10.1002\/ijc.29626","article-title":"CRISPR-Cas9 systems: versatile cancer modelling platforms and promising therapeutic strategies","volume":"138","author":"Wen","year":"2016","journal-title":"Int. J. Cancer"},{"key":"10.1016\/j.ymthe.2025.01.031_bib77","doi-asserted-by":"crossref","first-page":"1200","DOI":"10.1038\/mt.2008.114","article-title":"Zinc-finger Nucleases: The Next Generation Emerges","volume":"16","author":"Cathomen","year":"2008","journal-title":"Mol. Ther."},{"key":"10.1016\/j.ymthe.2025.01.031_bib78","doi-asserted-by":"crossref","first-page":"316","DOI":"10.1038\/nchembio.1793","article-title":"Small molecule-triggered Cas9 protein with improved genome-editing specificity","volume":"11","author":"Davis","year":"2015","journal-title":"Nat. Chem. Biol."},{"key":"10.1016\/j.ymthe.2025.01.031_bib79","doi-asserted-by":"crossref","first-page":"980","DOI":"10.1038\/nchembio.2179","article-title":"A chemical-inducible CRISPR-Cas9 system for rapid control of genome editing","volume":"12","author":"Liu","year":"2016","journal-title":"Nat. Chem. Biol."},{"key":"10.1016\/j.ymthe.2025.01.031_bib80","doi-asserted-by":"crossref","first-page":"870","DOI":"10.1016\/j.tibtech.2019.01.009","article-title":"Improving CRISPR Genome Editing by Engineering Guide RNAs","volume":"37","author":"Moon","year":"2019","journal-title":"Trends Biotechnol."},{"key":"10.1016\/j.ymthe.2025.01.031_bib81","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1038\/nbt.3149","article-title":"A split-Cas9 architecture for inducible genome editing and transcription modulation","volume":"33","author":"Zetsche","year":"2015","journal-title":"Nat. Biotechnol."},{"key":"10.1016\/j.ymthe.2025.01.031_bib82","doi-asserted-by":"crossref","first-page":"6568","DOI":"10.1038\/s41467-022-34320-7","article-title":"A comprehensive Bioconductor ecosystem for the design of CRISPR guide RNAs across nucleases and technologies","volume":"13","author":"Hoberecht","year":"2022","journal-title":"Nat. Commun."},{"key":"10.1016\/j.ymthe.2025.01.031_bib83","doi-asserted-by":"crossref","first-page":"706","DOI":"10.1038\/s41592-023-01840-z","article-title":"Improving the sensitivity of in vivo CRISPR off-target detection with DISCOVER-Seq","volume":"20","author":"Zou","year":"2023","journal-title":"Nat. Methods"},{"key":"10.1016\/j.ymthe.2025.01.031_bib84","doi-asserted-by":"crossref","first-page":"607","DOI":"10.1038\/nmeth.4278","article-title":"CIRCLE-seq: a highly sensitive in vitro screen for genome-wide CRISPR-Cas9 nuclease off-targets","volume":"14","author":"Tsai","year":"2017","journal-title":"Nat. Methods"},{"key":"10.1016\/j.ymthe.2025.01.031_bib85","doi-asserted-by":"crossref","first-page":"600","DOI":"10.1038\/nmeth.4284","article-title":"Mapping the genomic landscape of CRISPR-Cas9 cleavage","volume":"14","author":"Cameron","year":"2017","journal-title":"Nat. Methods"},{"key":"10.1016\/j.ymthe.2025.01.031_bib86","doi-asserted-by":"crossref","first-page":"1894","DOI":"10.1101\/gr.236620.118","article-title":"DIG-seq: a genome-wide CRISPR off-target profiling method using chromatin DNA","volume":"28","author":"Kim","year":"2018","journal-title":"Genome Res."},{"key":"10.1016\/j.ymthe.2025.01.031_bib87","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1038\/nbt.3117","article-title":"GUIDE-seq enables genome-wide profiling of off-target cleavage by CRISPR-Cas nucleases","volume":"33","author":"Tsai","year":"2015","journal-title":"Nat. Biotechnol."},{"key":"10.1016\/j.ymthe.2025.01.031_bib88","doi-asserted-by":"crossref","first-page":"84","DOI":"10.1126\/science.aad5227","article-title":"Rationally engineered Cas9 nucleases with improved specificity","volume":"351","author":"Slaymaker","year":"2016","journal-title":"Science"},{"key":"10.1016\/j.ymthe.2025.01.031_bib89","doi-asserted-by":"crossref","first-page":"490","DOI":"10.1038\/nature16526","article-title":"High-fidelity CRISPR-Cas9 nucleases with no detectable genome-wide off-target effects","volume":"529","author":"Kleinstiver","year":"2016","journal-title":"Nature"},{"key":"10.1016\/j.ymthe.2025.01.031_bib90","doi-asserted-by":"crossref","first-page":"543","DOI":"10.1038\/nbt.3198","article-title":"Increasing the efficiency of homology-directed repair for CRISPR-Cas9-induced precise gene editing in mammalian cells","volume":"33","author":"Chu","year":"2015","journal-title":"Nat. Biotechnol."},{"key":"10.1016\/j.ymthe.2025.01.031_bib91","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1038\/nbt.4021","article-title":"Inhibition of 53BP1 favors homology-dependent DNA repair and increases CRISPR-Cas9 genome-editing efficiency","volume":"36","author":"Canny","year":"2018","journal-title":"Nat. Biotechnol."},{"key":"10.1016\/j.ymthe.2025.01.031_bib92","doi-asserted-by":"crossref","DOI":"10.1038\/ncomms10548","article-title":"RS-1 enhances CRISPR\/Cas9- and TALEN-mediated knock-in efficiency","volume":"7","author":"Song","year":"2016","journal-title":"Nat. Commun."},{"key":"10.1016\/j.ymthe.2025.01.031_bib93","doi-asserted-by":"crossref","first-page":"888","DOI":"10.1038\/nbt.4194","article-title":"Optimized base editors enable efficient editing in cells, organoids and mice","volume":"36","author":"Zafra","year":"2018","journal-title":"Nat. Biotechnol."},{"key":"10.1016\/j.ymthe.2025.01.031_bib94","doi-asserted-by":"crossref","first-page":"1041","DOI":"10.1038\/s41587-019-0236-6","article-title":"CRISPR DNA base editors with reduced RNA off-target and self-editing activities","volume":"37","author":"Gr\u00fcnewald","year":"2019","journal-title":"Nat. Biotechnol."},{"key":"10.1016\/j.ymthe.2025.01.031_bib95","doi-asserted-by":"crossref","first-page":"856","DOI":"10.1038\/s41587-020-0527-y","article-title":"Dual base editor catalyzes both cytosine and adenine base conversions in human cells","volume":"38","author":"Zhang","year":"2020","journal-title":"Nat. Biotechnol."},{"key":"10.1016\/j.ymthe.2025.01.031_bib96","doi-asserted-by":"crossref","first-page":"295","DOI":"10.1038\/s41586-021-03609-w","article-title":"Base editing of haematopoietic stem cells rescues sickle cell disease in mice","volume":"595","author":"Newby","year":"2021","journal-title":"Nature"},{"key":"10.1016\/j.ymthe.2025.01.031_bib97","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1038\/s41586-019-1711-4","article-title":"Search-and-replace genome editing without double-strand breaks or donor DNA","volume":"576","author":"Anzalone","year":"2019","journal-title":"Nature"},{"key":"10.1016\/j.ymthe.2025.01.031_bib98","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1038\/s41576-022-00541-1","article-title":"Prime editing for precise and highly versatile genome manipulation","volume":"24","author":"Chen","year":"2023","journal-title":"Nat. Rev. Genet."},{"key":"10.1016\/j.ymthe.2025.01.031_bib99","doi-asserted-by":"crossref","DOI":"10.26508\/lsa.202000940","article-title":"Evaluating CRISPR-based prime editing for cancer modeling and CFTR repair in organoids","volume":"4","author":"Geurts","year":"2021","journal-title":"Life Sci. Alliance"},{"key":"10.1016\/j.ymthe.2025.01.031_bib100","doi-asserted-by":"crossref","first-page":"402","DOI":"10.1038\/s41587-021-01039-7","article-title":"Engineered pegRNAs improve prime editing efficiency","volume":"40","author":"Nelson","year":"2022","journal-title":"Nat. Biotechnol."},{"key":"10.1016\/j.ymthe.2025.01.031_bib101","doi-asserted-by":"crossref","first-page":"639","DOI":"10.1038\/s41586-024-07259-6","article-title":"Improving prime editing with an endogenous small RNA-binding protein","volume":"628","author":"Yan","year":"2024","journal-title":"Nature"},{"key":"10.1016\/j.ymthe.2025.01.031_bib102","article-title":"Click editing enables programmable genome writing using DNA polymerases and HUH endonucleases","author":"Ferreira da Silva","year":"2024","journal-title":"Nat. Biotechnol."},{"key":"10.1016\/j.ymthe.2025.01.031_bib103","doi-asserted-by":"crossref","first-page":"1039","DOI":"10.1038\/s41587-023-01947-w","article-title":"Targeted genome editing with a DNA-dependent DNA polymerase and exogenous DNA-containing templates","volume":"42","author":"Liu","year":"2024","journal-title":"Nat. Biotechnol."},{"key":"10.1016\/j.ymthe.2025.01.031_bib104","doi-asserted-by":"crossref","first-page":"234","DOI":"10.1021\/acs.biochem.8b01202","article-title":"Precision Control of CRISPR-Cas9 Using Small Molecules and Light","volume":"58","author":"Gangopadhyay","year":"2019","journal-title":"Biochemistry"},{"key":"10.1016\/j.ymthe.2025.01.031_bib105","doi-asserted-by":"crossref","first-page":"156","DOI":"10.1126\/science.aav2440","article-title":"Anti-CRISPRs on the march","volume":"362","author":"Koonin","year":"2018","journal-title":"Science"},{"key":"10.1016\/j.ymthe.2025.01.031_bib106","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1038\/nrmicro.2017.120","article-title":"Anti-CRISPR: discovery, mechanism and function","volume":"16","author":"Pawluk","year":"2018","journal-title":"Nat. Rev. Microbiol."},{"key":"10.1016\/j.ymthe.2025.01.031_bib107","doi-asserted-by":"crossref","first-page":"150","DOI":"10.1016\/j.cell.2016.12.009","article-title":"Inhibition of CRISPR-Cas9 with Bacteriophage Proteins","volume":"168","author":"Rauch","year":"2017","journal-title":"Cell"},{"key":"10.1016\/j.ymthe.2025.01.031_bib108","article-title":"BindCraft: one-shot design of functional protein binders","author":"Pacesa","year":"2024","journal-title":"bioRxiv"},{"key":"10.1016\/j.ymthe.2025.01.031_bib109","doi-asserted-by":"crossref","first-page":"1224","DOI":"10.1016\/j.cell.2017.07.037","article-title":"A Broad-Spectrum Inhibitor of CRISPR-Cas9","volume":"170","author":"Harrington","year":"2017","journal-title":"Cell"},{"key":"10.1016\/j.ymthe.2025.01.031_bib110","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1146\/annurev-pharmtox-010715-103507","article-title":"Targeted Protein Degradation by Small Molecules","volume":"57","author":"Bondeson","year":"2017","journal-title":"Annu. Rev. Pharmacol. Toxicol."},{"key":"10.1016\/j.ymthe.2025.01.031_bib111","doi-asserted-by":"crossref","DOI":"10.1126\/sciadv.abh2358","article-title":"A far-red light-inducible CRISPR-Cas12a platform for remote-controlled genome editing and gene activation","volume":"7","author":"Wang","year":"2021","journal-title":"Sci. Adv."},{"key":"10.1016\/j.ymthe.2025.01.031_bib112","article-title":"Design of highly functional genome editors by modeling the universe of CRISPR-Cas sequences","author":"Ruffolo","year":"2024","journal-title":"bioRxiv"},{"key":"10.1016\/j.ymthe.2025.01.031_bib113","article-title":"Development of safer gene delivery systems to minimize the risk of insertional mutagenesis-related malignancies: a critical issue for the field of gene therapy","volume":"2012","author":"Romano","year":"2012","journal-title":"ISRN Oncol."},{"key":"10.1016\/j.ymthe.2025.01.031_bib114","doi-asserted-by":"crossref","first-page":"458","DOI":"10.1007\/s11427-017-9033-0","article-title":"Non-viral and viral delivery systems for CRISPR-Cas9 technology in the biomedical field","volume":"60","author":"He","year":"2017","journal-title":"Sci. China. Life Sci."},{"key":"10.1016\/j.ymthe.2025.01.031_bib115","doi-asserted-by":"crossref","first-page":"387","DOI":"10.2174\/1566523054546224","article-title":"Altering the tropism of lentiviral vectors through pseudotyping","volume":"5","author":"Cronin","year":"2005","journal-title":"Curr. Gene Ther."},{"key":"10.1016\/j.ymthe.2025.01.031_bib116","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1002\/bit.20562","article-title":"PEG conjugation moderately protects adeno-associated viral vectors against antibody neutralization","volume":"92","author":"Lee","year":"2005","journal-title":"Biotechnol. Bioeng."},{"key":"10.1016\/j.ymthe.2025.01.031_bib117","doi-asserted-by":"crossref","first-page":"1287","DOI":"10.1038\/nbt.1708","article-title":"A robust system for production of minicircle DNA vectors","volume":"28","author":"Kay","year":"2010","journal-title":"Nat. Biotechnol."},{"key":"10.1016\/j.ymthe.2025.01.031_bib118","doi-asserted-by":"crossref","first-page":"889","DOI":"10.1038\/s41551-017-0137-2","article-title":"Nanoparticle delivery of Cas9 ribonucleoprotein and donor DNA in vivo induces homology-directed DNA repair","volume":"1","author":"Lee","year":"2017","journal-title":"Nat. Biomed. Eng."},{"key":"10.1016\/j.ymthe.2025.01.031_bib119","doi-asserted-by":"crossref","first-page":"252","DOI":"10.1056\/NEJMoa2031054","article-title":"CRISPR-Cas9 Gene Editing for Sickle Cell Disease and \u03b2-Thalassemia","volume":"384","author":"Frangoul","year":"2021","journal-title":"N. Engl. J. Med."},{"key":"10.1016\/j.ymthe.2025.01.031_bib120","doi-asserted-by":"crossref","first-page":"616","DOI":"10.1038\/s41551-023-01026-0","article-title":"Ex vivo prime editing of patient haematopoietic stem cells rescues sickle-cell disease phenotypes after engraftment in mice","volume":"7","author":"Everette","year":"2023","journal-title":"Nat. Biomed. Eng."},{"key":"10.1016\/j.ymthe.2025.01.031_bib121","article-title":"Lipid nanoparticle-mediated mRNA delivery to CD34(+) cells in rhesus monkeys","author":"Kim","year":"2024","journal-title":"Nat. Biotechnol."},{"key":"10.1016\/j.ymthe.2025.01.031_bib122","doi-asserted-by":"crossref","first-page":"3360","DOI":"10.1002\/cbic.202100359","article-title":"Exosomes as Targeted Delivery Platform of CRISPR\/Cas9 for Therapeutic Genome Editing","volume":"22","author":"Duan","year":"2021","journal-title":"Chembiochem"},{"key":"10.1016\/j.ymthe.2025.01.031_bib123","doi-asserted-by":"crossref","first-page":"2777","DOI":"10.7150\/thno.92133","article-title":"Small extracellular vesicles (sEVs)-based gene delivery platform for cell-specific CRISPR\/Cas9 genome editing","volume":"14","author":"Dubey","year":"2024","journal-title":"Theranostics"},{"key":"10.1016\/j.ymthe.2025.01.031_bib124","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1038\/nature13404","article-title":"Accurate design of co-assembling multi-component protein nanomaterials","volume":"510","author":"King","year":"2014","journal-title":"Nature"},{"key":"10.1016\/j.ymthe.2025.01.031_bib125","doi-asserted-by":"crossref","first-page":"357","DOI":"10.1038\/s41586-023-05870-7","article-title":"Programmable protein delivery with a bacterial contractile injection system","volume":"616","author":"Kreitz","year":"2023","journal-title":"Nature"},{"key":"10.1016\/j.ymthe.2025.01.031_bib126","article-title":"Directed evolution of engineered virus-like particles with improved production and transduction efficiencies","author":"Raguram","year":"2024","journal-title":"Nat. Biotechnol."},{"key":"10.1016\/j.ymthe.2025.01.031_bib127","doi-asserted-by":"crossref","first-page":"1526","DOI":"10.1038\/s41587-023-02078-y","article-title":"Engineered virus-like particles for transient delivery of prime editor ribonucleoprotein complexes in vivo","volume":"42","author":"An","year":"2024","journal-title":"Nat. Biotechnol."},{"key":"10.1016\/j.ymthe.2025.01.031_bib128","doi-asserted-by":"crossref","first-page":"250","DOI":"10.1016\/j.cell.2021.12.021","article-title":"Engineered virus-like particles for efficient in vivo delivery of therapeutic proteins","volume":"185","author":"Banskota","year":"2022","journal-title":"Cell"},{"key":"10.1016\/j.ymthe.2025.01.031_bib129","doi-asserted-by":"crossref","first-page":"358","DOI":"10.1038\/s41573-019-0012-9","article-title":"Adeno-associated virus vector as a platform for gene therapy delivery","volume":"18","author":"Wang","year":"2019","journal-title":"Nat. Rev. Drug Discov."},{"key":"10.1016\/j.ymthe.2025.01.031_bib130","doi-asserted-by":"crossref","first-page":"1408","DOI":"10.1016\/j.yexcr.2010.03.003","article-title":"Commensal pathogens, with a focus on Streptococcus pneumoniae, and interactions with the human host","volume":"316","author":"Henriques-Normark","year":"2010","journal-title":"Exp. Cell Res."},{"key":"10.1016\/j.ymthe.2025.01.031_bib131","doi-asserted-by":"crossref","first-page":"675","DOI":"10.1038\/nrmicro.2017.104","article-title":"The commensal lifestyle of Staphylococcus aureus and its interactions with the nasal microbiota","volume":"15","author":"Krismer","year":"2017","journal-title":"Nat. Rev. Microbiol."},{"key":"10.1016\/j.ymthe.2025.01.031_bib132","doi-asserted-by":"crossref","first-page":"1117","DOI":"10.1128\/CVI.00506-09","article-title":"Levels of antibody against 11 Staphylococcus aureus antigens in a healthy population","volume":"17","author":"Colque-Navarro","year":"2010","journal-title":"Clin. Vaccine Immunol."},{"key":"10.1016\/j.ymthe.2025.01.031_bib133","doi-asserted-by":"crossref","first-page":"830","DOI":"10.1093\/infdis\/jiv128","article-title":"The Fall of a Dogma? Unexpected High T-Cell Memory Response to Staphylococcus aureus in Humans","volume":"212","author":"Kolata","year":"2015","journal-title":"J. Infect. Dis."},{"key":"10.1016\/j.ymthe.2025.01.031_bib134","doi-asserted-by":"crossref","first-page":"868","DOI":"10.1038\/nmeth.3993","article-title":"A multifunctional AAV-CRISPR-Cas9 and its host response","volume":"13","author":"Chew","year":"2016","journal-title":"Nat. Methods"},{"key":"10.1016\/j.ymthe.2025.01.031_bib135","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1038\/s41591-018-0326-x","article-title":"Identification of preexisting adaptive immunity to Cas9 proteins in humans","volume":"25","author":"Charlesworth","year":"2019","journal-title":"Nat. Med."},{"key":"10.1016\/j.ymthe.2025.01.031_bib136","doi-asserted-by":"crossref","first-page":"3497","DOI":"10.1038\/s41467-018-05843-9","article-title":"Cas9 immunity creates challenges for CRISPR gene editing therapies","volume":"9","author":"Crudele","year":"2018","journal-title":"Nat. Commun."},{"key":"10.1016\/j.ymthe.2025.01.031_bib137","doi-asserted-by":"crossref","first-page":"549","DOI":"10.1038\/s41434-021-00232-2","article-title":"Cas9-directed immune tolerance in humans-a model to evaluate regulatory T cells in gene therapy?","volume":"28","author":"Wagner","year":"2021","journal-title":"Gene Ther."},{"key":"10.1016\/j.ymthe.2025.01.031_bib138","doi-asserted-by":"crossref","first-page":"2605","DOI":"10.1182\/blood-2014-12-570200","article-title":"Hematopoietic stem cells: concepts, definitions, and the new reality","volume":"125","author":"Eaves","year":"2015","journal-title":"Blood"},{"key":"10.1016\/j.ymthe.2025.01.031_bib139","doi-asserted-by":"crossref","first-page":"799","DOI":"10.1016\/j.molmed.2017.07.003","article-title":"HSC Niche Biology and HSC Expansion Ex Vivo","volume":"23","author":"Kumar","year":"2017","journal-title":"Trends Mol. Med."},{"key":"10.1016\/j.ymthe.2025.01.031_bib140","doi-asserted-by":"crossref","first-page":"542","DOI":"10.1089\/hum.2020.049","article-title":"Adeno-Associated Virus and Hematopoietic Stem Cells: The Potential of Adeno-Associated Virus Hematopoietic Stem Cells in Genetic Medicines","volume":"31","author":"Chatterjee","year":"2020","journal-title":"Hum. Gene Ther."},{"key":"10.1016\/j.ymthe.2025.01.031_bib141","doi-asserted-by":"crossref","first-page":"679","DOI":"10.1016\/j.omtm.2020.07.010","article-title":"Purification of Human CD34+CD90+ HSCs Reduces Target Cell Population and Improves Lentiviral Transduction for Gene Therapy","volume":"18","author":"Radtke","year":"2020","journal-title":"Mol. Ther. Methods Clin. Dev."},{"key":"10.1016\/j.ymthe.2025.01.031_bib142","doi-asserted-by":"crossref","first-page":"977","DOI":"10.1016\/j.stemcr.2017.02.010","article-title":"Efficient Ex Vivo Engineering and Expansion of Highly Purified Human Hematopoietic Stem and Progenitor Cell Populations for Gene Therapy","volume":"8","author":"Zonari","year":"2017","journal-title":"Stem Cell Rep."},{"key":"10.1016\/j.ymthe.2025.01.031_bib143","doi-asserted-by":"crossref","first-page":"2163","DOI":"10.1016\/j.ymthe.2017.05.023","article-title":"Improving Gene Therapy Efficiency through the Enrichment of Human Hematopoietic Stem Cells","volume":"25","author":"Masiuk","year":"2017","journal-title":"Mol. Ther."},{"key":"10.1016\/j.ymthe.2025.01.031_bib144","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1016\/j.celrep.2019.06.008","article-title":"Environmental Optimization Enables Maintenance of Quiescent Hematopoietic Stem Cells Ex Vivo","volume":"28","author":"Kobayashi","year":"2019","journal-title":"Cell Rep."},{"key":"10.1016\/j.ymthe.2025.01.031_bib145","doi-asserted-by":"crossref","first-page":"284","DOI":"10.1002\/stem.2935","article-title":"Improving Gene Editing Outcomes in Human Hematopoietic Stem and Progenitor Cells by Temporal Control of DNA Repair","volume":"37","author":"Lomova","year":"2019","journal-title":"Stem cells (Dayton, Ohio)"},{"key":"10.1016\/j.ymthe.2025.01.031_bib146","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1016\/j.omtm.2023.02.014","article-title":"An improved medium formulation for efficient ex vivo gene editing, expansion and engraftment of hematopoietic stem and progenitor cells","volume":"29","author":"Rai","year":"2023","journal-title":"Mol. Ther. Methods Clin. Dev."},{"key":"10.1016\/j.ymthe.2025.01.031_bib147","doi-asserted-by":"crossref","DOI":"10.1016\/j.exphem.2023.12.001","article-title":"Ex vivo hematopoietic stem cell expansion technologies: recent progress, applications, and open questions","volume":"130","author":"Meaker","year":"2024","journal-title":"Exp. Hematol."},{"key":"10.1016\/j.ymthe.2025.01.031_bib148","doi-asserted-by":"crossref","first-page":"3205","DOI":"10.1016\/j.ymthe.2021.09.001","article-title":"Understanding and overcoming adverse consequences of genome editing on hematopoietic stem and progenitor cells","volume":"29","author":"Lee","year":"2021","journal-title":"Mol. Ther."},{"key":"10.1016\/j.ymthe.2025.01.031_bib149","doi-asserted-by":"crossref","first-page":"765","DOI":"10.1038\/nbt.4192","article-title":"Repair of double-strand breaks induced by CRISPR-Cas9 leads to large deletions and complex rearrangements","volume":"36","author":"Kosicki","year":"2018","journal-title":"Nat. Biotechnol."},{"key":"10.1016\/j.ymthe.2025.01.031_bib150","doi-asserted-by":"crossref","DOI":"10.3389\/fonc.2024.1308709","article-title":"The dark side of stemness - the role of hematopoietic stem cells in development of blood malignancies","volume":"14","author":"Filipek-Gorza\u0142a","year":"2024","journal-title":"Front. Oncol."},{"key":"10.1016\/j.ymthe.2025.01.031_bib151","doi-asserted-by":"crossref","first-page":"3175","DOI":"10.1038\/s41591-023-02636-6","article-title":"Clonal selection of hematopoietic stem cells after gene therapy for sickle cell disease","volume":"29","author":"Spencer Chapman","year":"2023","journal-title":"Nat. Med."},{"key":"10.1016\/j.ymthe.2025.01.031_bib152","doi-asserted-by":"crossref","first-page":"138","DOI":"10.1056\/NEJMoa2109167","article-title":"Acute Myeloid Leukemia Case after Gene Therapy for Sickle Cell Disease","volume":"386","author":"Goyal","year":"2022","journal-title":"N. Engl. J. Med."},{"key":"10.1016\/j.ymthe.2025.01.031_bib153","doi-asserted-by":"crossref","first-page":"1597","DOI":"10.1182\/blood-2017-05-783233","article-title":"Increased risk of leukemia among sickle cell disease patients in California","volume":"130","author":"Brunson","year":"2017","journal-title":"Blood"},{"key":"10.1016\/j.ymthe.2025.01.031_bib154","doi-asserted-by":"crossref","first-page":"584","DOI":"10.1038\/nrclinonc.2015.105","article-title":"Inflammation and cancer: advances and new agents","volume":"12","author":"Crusz","year":"2015","journal-title":"Nat. Rev. Clin. Oncol."},{"key":"10.1016\/j.ymthe.2025.01.031_bib155","doi-asserted-by":"crossref","first-page":"2058","DOI":"10.1182\/bloodadvances.2019001330","article-title":"Myelodysplastic syndrome unrelated to lentiviral vector in a patient treated with gene therapy for sickle cell disease","volume":"4","author":"Hsieh","year":"2020","journal-title":"Blood Adv."},{"key":"10.1016\/j.ymthe.2025.01.031_bib156","doi-asserted-by":"crossref","first-page":"209","DOI":"10.1016\/j.stem.2024.10.014","article-title":"BCL11A +58\/+55 enhancer-editing facilitates HSPC engraftment and HbF induction in rhesus macaques conditioned with a CD45 antibody-drug conjugate","volume":"32","author":"Demirci","year":"2024","journal-title":"Cell Stem Cell"},{"key":"10.1016\/j.ymthe.2025.01.031_bib157","first-page":"2085","article-title":"In vivo HSC prime editing rescues sickle cell disease in a mouse model","volume":"141","author":"Li","year":"2023","journal-title":"Blood"},{"key":"10.1016\/j.ymthe.2025.01.031_bib158","doi-asserted-by":"crossref","first-page":"2039","DOI":"10.1182\/blood.2023019922","article-title":"The promise of in vivo HSC prime editing","volume":"141","author":"Sweeney","year":"2023","journal-title":"Blood"},{"key":"10.1016\/j.ymthe.2025.01.031_bib159","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1016\/bs.pmbts.2018.05.001","article-title":"Different Methods of Delivering CRISPR\/Cas9 Into Cells","volume":"159","author":"Chandrasekaran","year":"2018","journal-title":"Prog. Mol. Biol. Transl. Sci."},{"key":"10.1016\/j.ymthe.2025.01.031_bib160","article-title":"Revolutionizing genetic disease treatment: The case of exagamglogene autotemcel","volume":"5","author":"Rao","year":"2024","journal-title":"Innovation"},{"key":"10.1016\/j.ymthe.2025.01.031_bib161","doi-asserted-by":"crossref","first-page":"747","DOI":"10.1038\/s41434-023-00392-3","article-title":"Towards affordable CRISPR genomic therapies: a task force convened by the Innovative Genomics Institute","volume":"30","author":"Witkowsky","year":"2023","journal-title":"Gene Ther."},{"key":"10.1016\/j.ymthe.2025.01.031_bib162","doi-asserted-by":"crossref","first-page":"874","DOI":"10.2105\/AJPH.2023.307315","article-title":"CRISPR in Public Health: The Health Equity Implications and Role of Community in Gene-Editing Research and Applications","volume":"113","author":"Subica","year":"2023","journal-title":"Am. J. Public Health"},{"key":"10.1016\/j.ymthe.2025.01.031_bib163","doi-asserted-by":"crossref","first-page":"220","DOI":"10.1089\/crispr.2024.0042","article-title":"Affordable Pricing of CRISPR Treatments is a Pressing Ethical Imperative","volume":"7","author":"Rueda","year":"2024","journal-title":"CRISPR J."},{"key":"10.1016\/j.ymthe.2025.01.031_bib164","doi-asserted-by":"crossref","first-page":"307","DOI":"10.1038\/s41586-024-07800-7","article-title":"A roadmap for affordable genetic medicines","volume":"634","author":"Kliegman","year":"2024","journal-title":"Nature"},{"key":"10.1016\/j.ymthe.2025.01.031_bib165","doi-asserted-by":"crossref","first-page":"3103","DOI":"10.1016\/j.ymthe.2021.10.019","article-title":"Imagine CRISPR cures","volume":"29","author":"Urnov","year":"2021","journal-title":"Mol. Ther."},{"key":"10.1016\/j.ymthe.2025.01.031_bib166","doi-asserted-by":"crossref","first-page":"753","DOI":"10.1089\/hum.2018.178","article-title":"Innovative Curative Treatment of Beta Thalassemia: Cost-Efficacy Analysis of Gene Therapy Versus Allogenic Hematopoietic Stem-Cell Transplantation","volume":"30","author":"Coquerelle","year":"2019","journal-title":"Hum. Gene Ther."},{"key":"10.1016\/j.ymthe.2025.01.031_bib167","doi-asserted-by":"crossref","first-page":"4089","DOI":"10.1182\/bloodadvances.2024012757","article-title":"A simplified G-CSF-free procedure allows for in vivo HSC gene therapy of sickle cell disease in a mouse model","volume":"8","author":"Li","year":"2024","journal-title":"Blood Adv."},{"key":"10.1016\/j.ymthe.2025.01.031_bib168","doi-asserted-by":"crossref","first-page":"3543","DOI":"10.1007\/s12325-023-02545-7","article-title":"Economic and Clinical Burden of Managing Sickle Cell Disease with Recurrent Vaso-Occlusive Crises in the United States","volume":"40","author":"Udeze","year":"2023","journal-title":"Adv. Ther."},{"key":"10.1016\/j.ymthe.2025.01.031_bib169","doi-asserted-by":"crossref","DOI":"10.1001\/jamanetworkopen.2023.14070","article-title":"Examining Mental Health, Education, Employment, and Pain in Sickle Cell Disease","volume":"6","author":"Harris","year":"2023","journal-title":"JAMA Netw. Open"}],"container-title":["Molecular Therapy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S1525001625000358?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S1525001625000358?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2026,6,4]],"date-time":"2026-06-04T01:04:04Z","timestamp":1780535044000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S1525001625000358"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,6]]},"references-count":169,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2025,6]]}},"alternative-id":["S1525001625000358"],"URL":"https:\/\/doi.org\/10.1016\/j.ymthe.2025.01.031","relation":{},"ISSN":["1525-0016"],"issn-type":[{"value":"1525-0016","type":"print"}],"subject":[],"published":{"date-parts":[[2025,6]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Treating genetic blood disorders in the era of CRISPR-mediated genome editing","name":"articletitle","label":"Article Title"},{"value":"Molecular Therapy","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.ymthe.2025.01.031","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2025 Published by Elsevier Inc. on behalf of The American Society of Gene and Cell Therapy.","name":"copyright","label":"Copyright"}]}}