{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,19]],"date-time":"2026-10-19T20:03:28Z","timestamp":1792440208547,"version":"4.5.0"},"reference-count":204,"publisher":"Cambridge University Press (CUP)","license":[{"start":{"date-parts":[[2025,3,31]],"date-time":"2025-03-31T00:00:00Z","timestamp":1743379200000},"content-version":"unspecified","delay-in-days":89,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["cambridge.org"],"crossmark-restriction":true},"short-container-title":["Expert Rev. Mol. Med."],"published-print":{"date-parts":[[2025]]},"abstract":"<jats:title>Abstract<\/jats:title>\n\t  <jats:p>Genome editing has recently evolved from a theoretical concept to a powerful and versatile set of tools. The discovery and implementation of CRISPR-Cas9 technology have propelled the field further into a new era. This RNA-guided system allows for specific modification of target genes, offering high accuracy and efficiency. Encouraging results are being announced in clinical trials employed in conditions like sickle cell disease (SCD) and transfusion-dependent beta-thalassaemia (TDT). The path finally led the way to the recent FDA approval of the first gene therapy drug utilising the CRISPR\/Cas9 system to edit autologous CD34+ haematopoietic stem cells in SCD patients (Casgevy). Ongoing research explores the potential of CRISPR technology for cancer therapies, HIV treatment and other complex diseases. Despite its remarkable potential, CRISPR technology faces challenges such as off-target effects, suboptimal delivery systems, long-term safety concerns, scalability, ethical dilemmas and potential repercussions of genetic alterations, particularly in the case of germline editing. Here, we examine the transformative role of CRISPR technologies, including base editing and prime editing approaches, in modifying the genetic and epigenetic codes in the human genome and provide a comprehensive focus, particularly on relevant clinical applications, to unlock the full potential and challenges of gene editing.<\/jats:p>","DOI":"10.1017\/erm.2025.10","type":"journal-article","created":{"date-parts":[[2025,3,31]],"date-time":"2025-03-31T05:12:16Z","timestamp":1743397936000},"update-policy":"https:\/\/doi.org\/10.1017\/policypage","source":"Crossref","is-referenced-by-count":74,"title":["Advancing CRISPR genome editing into gene therapy clinical trials: progress and future prospects"],"prefix":"10.1017","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9644-7610","authenticated-orcid":false,"given":"Busra","family":"Cetin","sequence":"first","affiliation":[{"name":"Akdeniz University"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fulya","family":"Erendor","sequence":"additional","affiliation":[{"name":"Akdeniz University"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yunus Emre","family":"Eksi","sequence":"additional","affiliation":[{"name":"Akdeniz University"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ahter D.","family":"Sanlioglu","sequence":"additional","affiliation":[{"name":"Akdeniz University"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8379-5678","authenticated-orcid":false,"given":"Salih","family":"Sanlioglu","sequence":"additional","affiliation":[{"name":"Akdeniz University"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"56","published-online":{"date-parts":[[2025,3,31]]},"reference":[{"key":"S1462399425000109_r154","doi-asserted-by":"publisher","DOI":"10.1016\/j.omtn.2024.102124"},{"key":"S1462399425000109_r76","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-022-05531-1"},{"key":"S1462399425000109_r14","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-018-04252-2"},{"key":"S1462399425000109_r178","doi-asserted-by":"crossref","unstructured":"178. Vijayraghavan, S and Kantor, B (2017) A Protocol for the Production of Integrase-deficient Lentiviral Vectors for CRISPR\/Cas9-mediated gene knockout in dividing cells. Journal of Visualized Experiments (130), 56915.","DOI":"10.3791\/56915"},{"key":"S1462399425000109_r34","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymthe.2020.09.028"},{"key":"S1462399425000109_r117","unstructured":"117. Sabih, A , Leslie, SW (2023) Complicated Urinary Tract Infections [Updated 2024 Dec 7]. 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Verve Therapeutics (2022) Verve Therapeutics doses first human with an investigational in vivo Base Editing Medicine, VERVE-101, as a potential treatment for Heterozygous Familial Hypercholesterolemia [press release]. July 12, 2022."},{"key":"S1462399425000109_r109","doi-asserted-by":"publisher","DOI":"10.1016\/j.iac.2022.10.012"},{"key":"S1462399425000109_r39","first-page":"e32491","article-title":"Thalassemia: A review of the challenges to the families and caregivers","volume":"14","author":"Yousuf","year":"2022","journal-title":"Cureus"},{"key":"S1462399425000109_r77","doi-asserted-by":"publisher","DOI":"10.3390\/ijms241512317"},{"key":"S1462399425000109_r134","unstructured":"134. Verve Therapeutics (2024) Verve Therapeutics announces pipeline progress and reports Third Quarter 2024 Financial Results [press release] November 5, 2024."},{"key":"S1462399425000109_r20","doi-asserted-by":"publisher","DOI":"10.3390\/ijms23115992"},{"key":"S1462399425000109_r123","unstructured":"123. Anderson, H (2022) CRISPR Clinical Trials: A 2022 Update Available at https:\/\/innovativegenomics.org\/news\/crispr-clinical-trials-2022\/."},{"key":"S1462399425000109_r23","doi-asserted-by":"publisher","DOI":"10.3390\/ijms21176240"},{"key":"S1462399425000109_r202","doi-asserted-by":"publisher","DOI":"10.1016\/j.forsciint.2022.111274"},{"key":"S1462399425000109_r139","unstructured":"139. 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Prime Medicine (2024) Prime Medicine announces (2024) FDA clearance of Investigational New Drug (IND) application for PM359 for the treatment of Chronic Granulomatous Disease (CGD) [press release]. 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Editas Medicine (2022) Editas Medicine announces clinical data demonstrating proof of concept of EDIT-101 from Phase 1\/2 BRILLIANCE Trial [press release]. November 17, 2022."},{"key":"S1462399425000109_r149","doi-asserted-by":"publisher","DOI":"10.1126\/science.aam9321"},{"key":"S1462399425000109_r193","doi-asserted-by":"publisher","DOI":"10.1016\/j.biomaterials.2019.119711"},{"key":"S1462399425000109_r63","unstructured":"63. Beam Therapeutics (2024) Beam Therapeutics announces new data from BEACON Phase 1\/2 Clinical Trial of BEAM-101 in Sickle Cell Disease at American Society of Hematology (ASH) Annual Meeting [press release]. 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