CRISPR-mediated gene modification of hematopoietic stem cells with beta-thalassemia IVS-1-110 mutation

Gabr, Hala; Ghamrawy, Mona K. El; Almaeen, Abdulrahman H.; Abdelhafiz, Ahmed Samir; Hassan, Aya; Sissy, Maha Hamdi El

doi:10.1186/s13287-020-01876-4

Cited by 10 publications

(7 citation statements)

References 41 publications

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“…The corrected CD34+ cells gained the wild-type HBB and then were subjected for differentiation by culturing them in complete media containing erythropoietin. This study supported the existing studies for the application of CRISPR/Cas9 to treat β-thalassemia ( 48 ).…”

Section: Genome Manipulation Strategiessupporting

confidence: 86%

Genetic Manipulation Strategies for β-Thalassemia: A Review

Zakaria

Bahar²,

Abdullah³

et al. 2022

Front. Pediatr.

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Thalassemias are monogenic hematologic diseases that are classified as α- or β-thalassemia according to its quantitative abnormalities of adult α- or β-globin chains. β-thalassemia has widely spread throughout the world especially in Mediterranean countries, the Middle East, Central Asia, India, Southern China, and the Far East as well as countries along the north coast of Africa and in South America. The one and the only cure for β-thalassemia is allogenic hematopoietic stem cell transplantations (HSCT). Nevertheless, the difficulty to find matched donors has hindered the availability of this therapeutic option. Therefore, this present review explored the alternatives for β-thalassemia treatment such as RNA manipulation therapy, splice-switching, genome editing and generation of corrected induced pluripotent stem cells (iPSCs). Manipulation of β-globin RNA is mediated by antisense oligonucleotides (ASOs) or splice-switching oligonucleotides (SSOs), which redirect pre-mRNA splicing to significantly restore correct β-globin pre-mRNA splicing and gene product in cultured erythropoietic cells. Zinc finger nucleases (ZFNs), transcription activator-like effector nucleases (TALENs) and clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated 9 (Cas9) are designer proteins that can alter the genome precisely by creating specific DNA double-strand breaks. The treatment of β-thalassemia patient-derived iPSCs with TALENs have been found to correct the β-globin gene mutations, implying that TALENs could be used as a therapy option for β-thalassemia. Additionally, CRISPR technologies using Cas9 have been used to fix mutations in the β-globin gene in cultured cells as well as induction of hereditary persistence of fetal hemoglobin (HPFH), and α-globin gene deletions have proposed a possible therapeutic option for β-thalassemia. Overall, the accumulated research evidence demonstrated the potential of ASOs-mediated aberrant splicing correction of β-thalassemia mutations and the advancements of genome therapy approaches using ZFNs, TALENs, and CRISPR/Cas9 that provided insights in finding the permanent cure of β-thalassemia.

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Section: Genome Manipulation Strategiessupporting

confidence: 86%

Genetic Manipulation Strategies for β-Thalassemia: A Review

Zakaria

Bahar²,

Abdullah³

et al. 2022

Front. Pediatr.

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“…Genome editing (GE) can be considered among the most promising strategies to correct hereditary alterations in a variety of monogenic diseases, including hematopoietic pathologies [ 34 , 35 ]. Figure 2 depicts how CRISPR-Cas9 gene editing can be applied to β-thalassemia [ 34 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 ]. CRISPR-Cas9 gene editing can be proposed for efficient correction of the NM_000518.5:c.118C>T thalassemia variant (HGVS nomenclature, β 0 39C>T traditional nomenclature) [ 45 ].…”

Section: The Impact Of Changes In the Expression Of Alpha-globin Gene...mentioning

confidence: 99%

Impact of α-Globin Gene Expression and α-Globin Modifiers on the Phenotype of β-Thalassemia and Other Hemoglobinopathies: Implications for Patient Management

Traeger-Synodinos,

Vrettou,

Sofocleous

et al. 2024

IJMS

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In this short review, we presented and discussed studies on the expression of globin genes in β-thalassemia, focusing on the impact of α-globin gene expression and α-globin modifiers on the phenotype and clinical severity of β-thalassemia. We first discussed the impact of the excess of free α-globin on the phenotype of β-thalassemia. We then reviewed studies focusing on the expression of α-globin-stabilizing protein (AHSP), as a potential strategy of counteracting the effects of the excess of free α-globin on erythroid cells. Alternative processes controlling α-globin excess were also considered, including the activation of autophagy by β-thalassemia erythroid cells. Altogether, the studies reviewed herein are expected to have a potential impact on the management of patients with β-thalassemia and other hemoglobinopathies for which reduction in α-globin excess is clinically beneficial.

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“…Furthermore, one recent study has employed he CRISPR/Cas9 system as gene-editing tools to target the enhancer region of B-cell lymphoma/leukemia 11 A (BCL11A) gene in hematopoietic stem and progenitor cells (HSPCs) to treat SCD [91]. Likewise, the CRISPR/Cas9 system is also capable of correcting the human hemoglobin beta (HBB) gene mutations, which are major causing agents of β-thalassemia [92]. Mutation of the factor VIII (F8) gene generally gives rise to monogenic disease Hemophilia A, of which symptoms can be ameliorated in mice through the CRISPR-based therapeutic treatment [93].…”

Section: Gene Therapymentioning

confidence: 99%

Recent advances of the biological and biomedical applications of CRISPR/Cas systems

Wang

Zhao

2022

Mol Biol Rep

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It has also been reported that about 40% of spacers from lactic acid bacteria, namely Streptococcus thermophiles, have a homologue corresponding to either phage or plasmid DNA sequences among the isolated and sequenced phage's genome [3]. Thus, the spacers are proposed to be derived from foreign DNA including phage and plasmids. Bacteria generally acquire new spacers once they are exposed to new viruses in order to confer resistance to the cognate virus. Therefore, spacers present in a certain bacterium typically reveal the historical record of phages that the bacterium has been exposed to [4]. The leader sequence is commonly located 5' to the CRISPR locus and is rich in AT nucleotides. However, it has been demonstrated that the leader sequence is incapable of encoding RNAs or proteins, and that it is located next to the short repeats. Apart from the leader sequence, the genes encoding Cas proteins are found to be localized either upstream or downstream of the CRISPR locus.The CRISPR/Cas system is postulated to be formed in three stages. In the adaption stage, bacterial cells acquire sequences derived from foreign DNA such as viral DNA, and then incorporate them into the bacterial CRISPR array. During the expression stage, precursor CRISPR RNA (crRNA)

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CRISPR-mediated gene modification of hematopoietic stem cells with beta-thalassemia IVS-1-110 mutation

Cited by 10 publications

References 41 publications

Genetic Manipulation Strategies for β-Thalassemia: A Review

Genetic Manipulation Strategies for β-Thalassemia: A Review

Impact of α-Globin Gene Expression and α-Globin Modifiers on the Phenotype of β-Thalassemia and Other Hemoglobinopathies: Implications for Patient Management

Recent advances of the biological and biomedical applications of CRISPR/Cas systems

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