Year: 2025
Type: article
Abstract: β-hemoglobinopathies, comprising sickle cell disease (SCD) and transfusion -dependent β-thalassemia (TDT), represent monogenetic disorders caused by mutations in the β-globin gene, resulting in aberrant hemoglobin synthesis and severe clinical complications. CRISPR-Cas9, a revolutionary genome-editing tool, offers promising potential for correcting these mutations at the genetic level. This review employs a literature review methodology to explore the therapeutic application of CRISPR-Cas9 in treating β-hemoglobinopathies, focusing on its molecular mechanisms, experimental progress and clinical challenges. Key investigations confirm that ex vivo CRISPR-Cas9 editing of hematopoietic stem cells can effectively restores physiological hemoglobin production. However, challenges such as off-target effects, long-term, and cost safety remain barriers to clinical translation. Preclinical data highlight the need for optimized delivery systems—such as lipid nanoparticle-mediated transfection—to enhance editing efficiency while minimizing genotoxicity. Future research should prioritize optimizing delivery systems, enhancing specificity, and addressing long-term safety. This review concludes that CRISPR-Cas9 holds transformative potential for curing β-hemoglobinopathies but requires further refinement for widespread therapeutic use.
Source: Theoretical and Natural Science
Author: Junzhe Zheng
Institution: Queen's University Belfast
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: hybrid
OpenAlex ID: W4412495359