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Advances in genome editing: the technology of choice for precise and efficient β-thalassemia treatment

Abstract

Beta (β)-thalassemia is one of the most significant hemoglobinopathy worldwide. The high prevalence of the β-thalassemia carriers aggravates the disease burden for patients and national economies in the developing world. The survival of β-thalassemia patients solely relies on repeated transfusions, which eventually results into multi-organ damage. The fetal γ-globin genes are ordinarily silenced at birth and replaced by the adult β-globin genes. However, mutations that cause lifelong persistence of fetal γ-globin, ameliorate the debilitating effects of β-globin mutations. Therefore, therapeutically reactivating the fetal γ-globin gene is a prime focus of researchers. CRISPR/Cas9 is the most common approach to correct disease causative mutations or to enhance or disrupt the expression of proteins to mitigate the effects of the disease. CRISPR/cas9 and prime gene editing to correct mutations in hematopoietic stem cells of β-thalassemia patients has been considered a novel therapeutic approach for effective hemoglobin production. However, genome-editing technologies, along with all advantages, have shown some disadvantages due to either random insertions or deletions at the target site of edition or non-specific targeting in genome. Therefore, the focus of this review is to compare pros and cons of these editing technologies and to elaborate the retrospective scope of gene therapy for β-thalassemia patients.

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Fig. 1: Gene Editing and β-thallasemia.
Fig. 2: The Human Globin Locus and Its Developmental Regulation.
Fig. 3: Summary of genome-editing strategies and known molecular mechanisms within the β-globin locus.

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This work was supported by funding from the University of Health Sciences Lahore.

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Ali, G., Tariq, M.A., Shahid, K. et al. Advances in genome editing: the technology of choice for precise and efficient β-thalassemia treatment. Gene Ther 28, 6–15 (2021). https://doi.org/10.1038/s41434-020-0153-9

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