International Journal of Molecular Medical Science, 2024, Vol.14, No.3, 193-202 http://medscipublisher.com/index.php/ijmms 200 Future research should focus on optimizing the efficiency and specificity of gene editing techniques to minimize off-target effects and ensure long-term safety and efficacy. Additionally, addressing the challenges of delivering gene-edited cells to patients, particularly in regions where SCA is endemic, is crucial. Further studies are needed to refine the protocols for clinical-scale production of gene-edited HSPCs and to evaluate the long-term outcomes of these therapies in clinical trials. The advancements in gene editing technologies offer a transformative potential for the treatment of SCA. The ability to correct the underlying genetic defect or to induce HbF expression provides a promising curative approach. The durability and effectiveness of these treatments in preclinical models and early-phase clinical trials are encouraging, suggesting that gene editing could become a universal curative option for SCA in the near future. Continued research and clinical development will be essential to bring these therapies to patients worldwide, offering hope for a definitive cure for SCA. Acknowledgments Thank you to the two anonymous peer reviewers for their feedback on the manuscript. Conflict of Interest Disclosure The authors affirm that this research was conducted without any commercial or financial relationships that could be construed as a potential conflict of interest. References Bak R., Dever D., and Porteus M., 2018, CRISPR/Cas9 genome editing in human hematopoietic stem cells, Nature Protocols, 13: 358-376. https://doi.org/10.1038/nprot.2017.143 PMid:29370156 PMCid:PMC5826598 Brendel C., and Williams D., 2020, Current and future gene therapies for hemoglobinopathies, Current Opinion in Hematology, 27(3): 149-154. https://doi.org/10.1097/MOH.0000000000000581 PMid:32205585 Chu S., Packer M., Rees H., Lam D., Yu Y., Marshall J., Cheng L., Lam D., Olins J., Ran F., Liquori A., Gantzer B., Decker J., Born D., Barrera L., Hartigan A., Gaudelli N., Ciaramella G., and Slaymaker I., 2021, Rationally designed base editors for precise editing of the sickle cell disease mutation, The CRISPR journal, 4(2): 169-177. https://doi.org/10.1089/crispr.2020.0144 PMid:33876959 Cisneros G., and Thein S., 2020, Recent advances in the treatment of sickle cell disease, Frontiers in Physiology, 11: 435. https://doi.org/10.3389/fphys.2020.00435 PMid:32508672 PMCid:PMC7252227 DeWitt M., Magis W., Bray N., Wang T., Berman J., Urbinati F., Heo S., Mitros T., Muñoz D., Boffelli D., Kohn D., Walters M., Carroll D., Martin D., and Corn J., 2016, Selection-free genome editing of the sickle mutation in human adult hematopoietic stem/progenitor cells, Science Translational Medicine, 8(360):134-360 https://doi.org/10.1126/scitranslmed.aaf9336 PMid:27733558 PMCid:PMC5500303 Ebens A., Curd A., Sim D., Quijano E., Tam F., Coull J., Huang L., Hayes M., Marshall F., Pearson R., Whoriskey S., Srivastava T., Li X., and Zhang Z., 2019, Identification of optimized peptide nucleic acid (PNA) designs for nuclease-free gene editing in sickle cell disease hematopoietic stem and progenitor cells (HSPCs), Blood, 134(1): 4645. https://doi.org/10.1182/blood-2019-127538 Frangoul H., Altshuler D., Cappellini M., Chen Y., Domm J., Eustace B., Foell J., Fuente J., Grupp S., Handgretinger R., Ho T., Kattamis A., Kernytsky A., Lekstrom-Himes J., Li A., Locatelli F., Mapara M., Montalembert M., Rondelli D., Sharma A., Sheth S., Soni S., Steinberg M., Wall D., Yen A., and Corbacioglu S., 2020, CRISPR-Cas9 gene editing for sickle cell disease and β-thalassemia, The New England journal of medicine, 384: 3. https://doi.org/10.1056/NEJMoa2031054 PMid:33283989 George A., Ravi N., Prasad K., Panigrahi L., Koikkara S., Rajendiran V., Devaraju N., Paul J., Pai A., Nakamura Y., Kurita R., Balasubramanian P., Thangavel S., Marepally S., Velayudhan S., Srivastava A., and Mohankumar K., 2022, Efficient and error-free correction of sickle mutation in human erythroid cells using prime editor-2. Frontiers in Genome Editing, 4: 1085111. https://doi.org/10.3389/fgeed.2022.1085111 PMid:36605051 PMCid:PMC9808041 Germino-Watnick P., Hinds M., Le A., Chu R., Liu X., and Uchida N., 2022, Hematopoietic stem cell gene-addition/editing therapy in sickle cell disease, Cells, 11(11): 1843. https://doi.org/10.3390/cells11111843
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