Ahmed Rehab, Alghamdi Wafa N, Alharbi Fetun R, Alatawi Huda D, Alenezi Kawthar M, Alanazi Turki F, Elsherbiny Nehal M
Division of Microbiology, Immunology and Biotechnology, Department of Natural Products and Alternative Medicine, Faculty of Pharmacy, University of Tabuk, Tabuk, Saudi Arabia.
Pharm D Program, Faculty of Pharmacy, University of Tabuk, Tabuk, 71491, Saudi Arabia.
Mol Biotechnol. 2025 Jan 10. doi: 10.1007/s12033-025-01368-x.
Clustered, regularly interspaced short palindromic repeats (CRISPR)-CRISPR-associated protein (Cas) system is a new gene editing tool that represents a revolution in gene therapy. This study aimed to review the clinical trials conducted to evaluate the efficacy and safety of the CRISPR/Cas9 system in treating thalassemia and sickle cell disease (SCD). We searched relevant literature using "CRISPR Cas", "thalassemia", "sickle cell" and "clinical trial" as subject terms in PubMed, Cochrane, Web of Science, and Google Scholar up to December 3rd, 2023. Following the PIO format (Patients, Intervention, Outcome), PRISMA guidelines were followed in the study selection, data extraction, and quality assessment processes. Out of 110 publications, 6 studies met our eligibility criteria with a total of 115 patients involved. CRISPR/Cas9 system was used to disrupt BCL11A gene enhancer in 4 studies and to disrupt γ-globin gene promoters in 2 studies. Patients demonstrated significant activation of fetal hemoglobin, elevated total hemoglobin, transfusion independence in thalassemia, and repression of vaso-occlusive episodes in SCD. Using CRISPR/Cas9 system to directly disrupt genes provides a safe and potential one-time functional cure for thalassemia and SCD, suggesting CRISPR/Cas9 as a potential therapeutic tool for the treatment of inherited hematological disorders.
成簇规律间隔短回文重复序列（CRISPR）-CRISPR相关蛋白（Cas）系统是一种新的基因编辑工具，代表了基因治疗领域的一场革命。本研究旨在综述为评估CRISPR/Cas9系统治疗地中海贫血和镰状细胞病（SCD）的疗效和安全性而开展的临床试验。我们在PubMed、Cochrane、科学网和谷歌学术中以“CRISPR Cas”、“地中海贫血”、“镰状细胞”和“临床试验”作为主题词检索了截至2023年12月3日的相关文献。按照PIO格式（患者、干预措施、结果），在研究选择、数据提取和质量评估过程中遵循PRISMA指南。在110篇出版物中，有6项研究符合我们的纳入标准，共涉及115例患者。在4项研究中使用CRISPR/Cas9系统破坏BCL11A基因增强子，在2项研究中破坏γ-珠蛋白基因启动子。患者表现出胎儿血红蛋白显著激活、总血红蛋白升高、地中海贫血患者实现输血独立以及SCD患者血管闭塞性发作受到抑制。使用CRISPR/Cas9系统直接破坏基因可为地中海贫血和SCD提供一种安全且有潜力的一次性功能性治愈方法，这表明CRISPR/Cas9是治疗遗传性血液疾病的一种潜在治疗工具。
